Viraferon

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 1 million IU/ml powder and solvent for solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One vial of powder contains 1 million IU of interferon alfa-2b produced in E.coli by recombinant DNA 
technology. 
After reconstitution, 1 ml contains 1 million IU of interferon alfa-2b. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection 
 
White to cream coloured powder.  
Clear and colourless solvent.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Chronic Hepatitis B: Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis B 
viral replication (presence of HBV-DNA and HBeAg), elevated alanine aminotransferase (ALT) and 
histologically proven active liver inflammation and/or fibrosis. 
 
Chronic Hepatitis C:  
Adult patients:  
Viraferon is indicated for the treatment of adult patients with chronic hepatitis C who have elevated 
transaminases without liver decompensation and who are positive for serum HCV-RNA or anti-HCV (see 
section 4.4). 
 
The best way to use Viraferon in this indication is in combination with ribavirin. 
 
Chidren and adolescents: 
Viraferon is intended for use, in a combination regimen with ribavirin, for the treatment of children and 
adolescents 3 years of age and older, who have chronic hepatitis C, not previously treated, without liver 
decompensation, and who are positive for serum HCV-RNA. The decision to treat should be made on a case 
by case basis, taking into account any evidence of disease progression such as hepatic inflammation and 
fibrosis, as well as prognostic factors for response, HCV genotype and viral load. The expected benefit of 
treatment should be weighed against the safety findings observed for paediatric subjects in the clinical trials 
(see sections 4.4, 4.8 and 5.1). 
 
4.2 Posology and method of administration 
 
Treatment must be initiated by a physician experienced in the management of the disease. 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 



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If adverse events develop during the course of treatment with Viraferon for any indication, modify the dosage 
or discontinue therapy temporarily until the adverse events abate. If persistent or recurrent intolerance 
develops following adequate dosage adjustment, or disease progresses, discontinue treatment with Viraferon. 
At the discretion of the physician, the patient may self-administer the dose for maintenance dosage regimens 
administered subcutaneously. 
 
Chronic Hepatitis B: The recommended dosage is in the range 5 to 10 million IU administered 
subcutaneously three times a week (every other day) for a period of 4 to 6 months. 
 
The administered dose should be reduced by 50 % in case of occurrence of haematological disorders (white 
blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3). Treatment should be 
discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe 
thrombocytopaenia (< 70,000/mm3). 
 
For all patients, if no improvement on serum HBV-DNA is observed after 3 to 4 months of treatment (at the 
maximum tolerated dose), discontinue Viraferon therapy. 
 
Chronic Hepatitis C: Viraferon is administered subcutaneously at a dose of 3 million IU three times a week 
(every other day) to adult patients, whether administered as monotherapy or in combination with ribavirin. 
 
Children 3 years of age or older and adolescents: Interferon alfa-2b 3 MIU/m2 is administered 
subcutaneously 3 times a week (every other day) in combination with ribavirin capsules or oral solution 
administered orally in two divided doses daily with food (morning and evening).  
 
(See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination 
therapy. For paediatric patients who weigh < 47 kg or cannot swallow capsules, see ribavirin oral solution 
SPC).  
 
Relapse patients (adults): 
Viraferon is given in combination with ribavirin. 
 
Based on the results of clinical trials, in which data are available for 6 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for 6 months. 
 
Naïve patients: 
Adults: The efficacy of Viraferon is enhanced when given in combination with ribavirin. Viraferon should be 
given alone mainly in case of intolerance or contraindication to ribavirin. 
 
Viraferon in combination with ribavirin: 
Based on the results of clinical trials, in which data are available for 12 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for at least 6 months. 
 
Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit 
negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and 
high pre-treatment viral load. 
 
Other negative prognostic factors (age > 40 years, male gender, bridging fibrosis) should be taken into 
account in order to extend therapy to 12 months. 
 
During clinical trials, patients who failed to show a virologic response after 6 months of treatment (HCV-
RNA below lower limit of detection) did not become sustained virologic responders (HCV-RNA below lower 
limit of detection six months after withdrawal of treatment). 
 
Viraferon alone: 



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The optimal duration of therapy with Viraferon alone is not yet fully established, but a therapy of between 
12 and 18 months is advised. 
 
It is recommended that patients be treated with Viraferon alone for at least 3 to 4 months, at which point 
HCV-RNA status should be determined. Treatment should be continued in patients who exhibit negative 
HCV-RNA. 
 
Children and adolescents: The efficacy and safety of Viraferon in combination with ribavirin has been 
studied in children and adolescents who have not been previously treated for chronic hepatitis C.  
 
Genotype 1: The recommended duration of treatment is one year. Patients who fail to achieve virological 
response at 12 weeks are highly unlikely to become sustained virological responders (negative predictive 
value 96 %). Virological response is defined as absence of detectable HCV-RNA at Week 12. Treatment 
should be discontinued in these patients. 
Genotype 2/3: The recommended duration of treatment is 24 weeks. 
 
Virological responses after 1 year of treatment and 6 months of follow-up were 36 % for genotype 1 and 
81 % for genotype 2/3/4. 
 
Viraferon may be administered using either glass or plastic disposable injection syringes. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients. 
- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure, recent 

myocardial infarction, severe arrhythmic disorders.  
- Severe renal or hepatic dysfunction; including that caused by metastases. 
- Epilepsy and/or compromised central nervous system (CNS) function (see section 4.4). 
- Chronic hepatitis with decompensated cirrhosis of the liver. 
- Chronic hepatitis in patients who are being or have been treated recently with immunosuppressive 

agents excluding short term corticosteroid withdrawal. 
- Autoimmune hepatitis; or history of autoimmune disease; immunosuppressed transplant recipients. 
- Pre-existing thyroid disease unless it can be controlled with conventional treatment. 
 
Children and adolescents: 
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal 

ideation or suicide attempt. 
 

Combination therapy with ribavirin: Also see ribavirin SPC if interferon alfa-2b is to be administered in 
combination with ribavirin in patients with chronic hepatitis C. 
 
4.4 Special warnings and precautions for use 
 
For all patients: 
Psychiatric and central nervous system (CNS): Severe CNS effects, particularly depression, suicidal ideation 
and attempted suicide have been observed in some patients during Viraferon therapy, and even after 
treatment discontinuation mainly during the 6-month follow-up periodand in the follow-up period. Among 
children and adolescents treated with Viraferon in combination with ribavirin, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6-month 
follow-up after treatment. As in adult patients, children and adolescents experienced other psychiatric adverse 
events (e.g., depression, emotional lability, and somnolence). Other CNS effects including aggressive behaviour 
(sometimes directed against others), confusion and alterations of mental status have been observed with alpha 
interferons. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such 
symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the 
prescribing physician and the need for adequate therapeutic management should be considered. If psychiatric 



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symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with 
Viraferon be discontinued, and the patient followed, with psychiatric intervention as appropriate. 
 
Patients with existence of or history of severe psychiatric conditions: 
If a treatment with interferon alfa-2b is judged necessary in adult patients with existence or history of severe 
psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and 
therapeutic management of the psychiatric condition. The use of interferon alfa-2b in children and adolescents 
with existence of or history of severe psychiatric conditions is contraindicated (see section 4.3). 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Moderate to severe adverse experiences may require modification of the patient's dosage regimen, or in some 
cases, termination of Viraferon therapy. Any patient developing liver function abnormalities during treatment 
with Viraferon must be monitored closely and treatment discontinued if signs and symptoms progress. 
 
Hypotension may occur during Viraferon therapy or up to two days post-therapy and may require supportive 
treatment. 
 
Adequate hydration must be maintained in patients undergoing Viraferon therapy since hypotension related 
to fluid depletion has been seen in some patients. Fluid replacement may be necessary. 
 
While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, 
other causes of persistent fever must be ruled out. 
 
Viraferon must be used cautiously in patients with debilitating medical conditions, such as those with a 
history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to 
ketoacidosis. Caution must be observed also in patients with coagulation disorders (e.g., thrombophlebitis, 
pulmonary embolism) or severe myelosuppression. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.5). Any patient developing fever, cough, 
dyspnea or other respiratory symptoms must have a chest X-ray taken. If the chest X-ray shows pulmonary 
infiltrates or there is evidence of pulmonary function impairment, the patient is to be monitored closely, and, 
if appropriate, discontinue interferon alpha. While this has been reported more often in patients with chronic 
hepatitis C treated with interferon alpha, it has also been reported in patients with oncologic diseases treated 
with interferon alpha. Prompt discontinuation of interferon alpha administration and treatment with 
corticosteroids appear to be associated with resolution of pulmonary adverse events. 
 
Ocular adverse events (see section 4.8) including retinal haemorrhages, cotton wool spots, and retinal artery 
or vein obstruction have been reported in rare instance after treatment with alpha interferons. All patients 
should have a baseline eye examination. Any patient complaining of changes in visual acuity or visual fields, 
or reporting other ophthalmologic symptoms during treatment with Viraferon, must have a prompt and 
complete eye examination. Periodic visual examinations during Viraferon therapy are recommended 
particularly in patients with disorders that may be associated with retinopathy, such as diabetes mellitus or 
hypertension. Discontinuation of Viraferon should be considered in patients who develop new or worsening 
ophthalmological disorders. 



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More significant obtundation and coma, including cases of encephalopathy, have been observed in some 
patients, usually elderly, treated at higher doses. While these effects are generally reversible, in a few patients 
full resolution took up to three weeks. Very rarely, seizures have occurred with high doses of Viraferon. 
 
Adult patients with a history of congestive heart failure, myocardial infarction and/or previous or current 
arrhythmic disorders, who require Viraferon therapy, must be closely monitored. It is recommended that 
those patients who have pre-existing cardiac abnormalities and/or are in advanced stages of cancer have 
electrocardiograms taken prior to and during the course of treatment. Cardiac arrhythmias (primarily 
supraventricular) usually respond to conventional therapy but may require discontinuation of Viraferon 
therapy. There are no data in children or adolescents with a history of cardiac disease. 
 
Hypertriglyceridemia and aggravation of hypertriglyceridemia, sometimes severe, have been observed. 
Monitoring of lipid levels is, therefore, recommended. 
 
Due to reports of interferon alpha exacerbating pre-existing psoriatic disease and sarcoidosis, use of 
Viraferon in patients with psoriasis or sarcoidosis is recommended only if the potential benefit justifies the 
potential risk. 
 
Preliminary data indicates that interferon alpha therapy may be associated with an increased rate of kidney 
graft rejection. Liver graft rejection has also been reported. 
 
The development of auto-antibodies and autoimmune disorders has been reported during treatment with alpha 
interferons. Patients predisposed to the development of autoimmune disorders may be at increased risk. 
Patients with signs or symptoms compatible with autoimmune disorders should be evaluated carefully, and 
the benefit-risk of continued interferon therapy should be reassessed (see also section 4.4 Chronic hepatitis C, 
Monotherapy (thyroid abnormalities) and section 4.8). 
Cases of Vogt-Koyanagi-Harada (VKH) syndrome have been reported in patients with chronic hepatitis C 
treated with interferon. This syndrome is a granulomatous inflammatory disorder affecting the eyes, auditory 
system, meninges, and skin. If VKH syndrome is suspected, antiviral treatment should be withdrawn and 
corticosteroid therapy discussed (see section 4.8). 
 
Discontinue treatment with Viraferon in patients with chronic hepatitis who develop prolongation of 
coagulation markers which might indicate liver decompensation. 
 
Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of 
human plasma-derived albumin. 
 
Standard measures to prevent infections resulting from the use of medicinal products prepared from human 
blood or plasma include selection of donors, screening of individual donations and plasma pools for specific 
markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of 
viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the 
possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or 
emerging viruses and other pathogens. 
 
There are no reports of virus transmissions with albumin manufactured to European Pharmacopoeia 
specifications by established processes. 
 
It is strongly recommended that every time that Viraferon is administered to a patient, the name and batch 
number of the product are recorded in order to maintain a link between the patient and the batch of the 
product. 
 
Chronic Hepatitis C: 
Combination therapy with ribavirin: Also see ribavirin SPC if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 



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All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i.e. 
patients with genotype 2 and 3), treatment may be possible without histological confirmation. Current 
treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing 
treatment. 
 
Monotherapy: Infrequently, adult patients treated for chronic hepatitis C with Viraferon developed thyroid 
abnormalities, either hypothyroidism or hyperthyroidism. In clinical trials using Viraferon therapy, 2.8 % 
patients overall developed thyroid abnormalities. The abnormalities were controlled by conventional therapy 
for thyroid dysfunction. The mechanism by which Viraferon may alter thyroid status is unknown. Prior to 
initiation of Viraferon therapy for the treatment of chronic hepatitis C, evaluate serum thyroid-stimulating 
hormone (TSH) levels. Any thyroid abnormality detected at that time must be treated with conventional 
therapy. Viraferon treatment may be initiated if TSH levels can be maintained in the normal range by 
medication. Determine TSH levels if, during the course of Viraferon therapy, a patient develops symptoms 
consistent with possible thyroid dysfunction. In the presence of thyroid dysfunction, Viraferon treatment may 
be continued if TSH levels can be maintained in the normal range by medication. Discontinuation of 
Viraferon therapy has not reversed thyroid dysfunction occurring during treatment (also see Children and 
adolescents, Thyroid monitoring). 
 
Supplemental monitoring specific for children and adolescents 
Thyroid Monitoring: Approximately 12 % of children treated with interferon alfa-2b and ribavirin developed 
increase in TSH. Another 4 % had a transient decrease below the lower limit of normal. Prior to initiation of 
Viraferon therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be 
treated with conventional therapy. Viraferon therapy may be initiated if TSH levels can be maintained in the 
normal range by medication. Thyroid dysfunction during treatment with interferon alfa-2b and ribavirin has 
been observed. If thyroid abnormalities are detected, the patient’s thyroid status should be evaluated and 
treated as clinically appropriate. Children and adolescents should be monitored every 3 months for evidence 
of thyroid dysfunction (e.g. TSH). 
 
Growth and Development: During a 1-year course of therapy there was a decrease in the rate of linear growth 
(mean percentile decrease of 9 %) and a decrease in the rate of weight gain (mean percentile decrease of 
13 %). A general reversal of these trends was noted during the 6 months follow-up post treatment. However, 
based on interim data from a long-term follow-up study, 12 (14 %) of 84 children had a > 15 percentile 
decrease in rate of linear growth, of whom 5 (6 %) children had a > 30 percentile decrease despite being off 
treatment for more than 1 year. In addition, preclicinal juvenile toxicity results have demonstrated a minor, 
dose-related decrease in overall growth in neonatal rats dosed with ribavirin (see section 5.3). Therefore, the 
risk/benefit of the combined use of interferon alfa-2b and ribavirin should be assessed in young children prior 
to the initiation of therapy. Physicians are advised to monitor the growth of children taking ribavirin in 
combination with interferon alfa-2b. There are no data on long term effects on growth and development and 
on sexual maturation. 
 
HCV/HIV Coinfection: Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy 
(HAART) may be at increased risk of developing lactic acidosis. Caution should be used when adding Viraferon 
and ribavirin to HAART therapy (see ribavirin SPC). Patients treated with Viraferon and ribavirin combination 
therapy and zidovudine could be at increased risk of developing anaemia. 
Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic 
decompensation and death. Adding treatment with alfa interferons alone or in combination with ribavirin may 
increase the risk in this patient subset.  
 
Dental and periodontal disorders: Dental and periodontal disorders, which may lead to loss of teeth, have 
been reported in patients receiving Viraferon and ribavirin combination therapy. In addition, dry mouth could 
have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the 
combination of Viraferon and ribavirin. Patients should brush their teeth thoroughly twice daily and have 
regular dental examinations. In addition some patients may experience vomiting. If this reaction occurs, they 
should be advised to rinse out their mouth thoroughly afterwards. 



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Laboratory Tests:  
Standard haematological tests and blood chemistries (complete blood count and differential, platelet count, 
electrolytes, liver enzymes, serum protein, serum bilirubin and serum creatinine) are to be conducted in all 
patients prior to and periodically during systemic treatment with Viraferon. 
 
During treatment for hepatitis B or C the recommended testing schedule is at weeks 1, 2, 4, 8, 12, 16, and 
every other month, thereafter, throughout treatment. If ALT flares during Viraferon therapy to greater than or 
equal to 2 times baseline, Viraferon therapy may be continued unless signs and symptoms of liver failure are 
observed. During ALT flare, liver function tests: ALT, prothrombin time, alkaline phosphatase, albumin and 
bilirubin must be monitored at two-week intervals. 
 
Effect on fertility: Interferon may impair fertility (see section 4.6 and section 5.3). 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with 
Viraferon. 
 
Interactions between Viraferon and other medicinal products have not been fully evaluated. Caution must be 
exercised when administering Viraferon in combination with other potentially myelosuppressive agents. 
 
Interferons may affect the oxidative metabolic process. This must be considered during concomitant therapy 
with medicinal products metabolised by this route, such as the xanthine derivatives theophylline or 
aminophylline. During concomitant therapy with xanthine agents, serum theophylline levels must be 
monitored and dosage adjusted if necessary. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.4). 
 
(Also see ribavirin SPC if Viraferon is to be administered in combination with ribavirin in patients with 
chronic hepatitis C). 
 
4.6 Pregnancy and lactation 
 
Women of childbearing potential have to use effective contraception during treatment. Viraferon must be 
used with caution in fertile men. Decreased serum estradiol and progesterone concentrations have been 
reported in women treated with human leukocyte interferon. 
 
There are no adequate data from the use of interferon alfa-2b in pregnant women.Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Viraferon is to be 
used during pregnancy only if the potential benefit justifies the potential risk to the foetus. 
 
It is not known whether the components of this medicinal product are excreted in human milk. Because of the 
potential for adverse reactions in nursing infants, nursing should be discontinued prior to initiation of 
treatment. 
 
Combination therapy with ribavirin: Ribavirin causes serious birth defects when administered during 
pregnancy. Ribavirin therapy is contraindicated in women who are pregnant. Extreme care must be taken to 
avoid pregnancy in female patients or in partners of male patients taking Viraferon in combination with 
ribavirin. Females of childbearing potential and their partners must each use an effective contraceptive during 
treatment and for 4 months after treatment has been concluded. Male patients and their female partners must 



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each use an effective contraceptive during treatment and for 7 months after treatment has been concluded (see 
ribavirin SPC). 
 
4.7 Effects on ability to drive and use machines 
 
Patients are to be advised that they may develop fatigue, somnolence, or confusion during treatment with 
Viraferon, and therefore it is recommended that they avoid driving or operating machinery. 
 
4.8 Undesirable effects 
 
See ribavirin SPC for ribavirin-related undesirable effects if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
In clinical trials conducted in a broad range of indications and at a wide range of doses (from 6 MIU/m2/week 
in hairy cell leukaemia up to 100 MIU/m2/week in melanoma), the most commonly reported undesirable 
effects were fever, fatigue, headache and myalgia. Fever and fatigue were often reversible within 72 hours of 
interruption or cessation of treatment. 
 
In clinical trials conducted in the hepatitis C population, patients were treated with Viraferon alone or in 
combination with ribavirin for one year. All patients in these trials received 3 MIU of Viraferon three times a 
week. In Table 1 the frequency of patients reporting (treatment related) undesirable effects is presented from 
clinical trials in naïve patients treated for one year. Severity was generally mild to moderate. The adverse 
reactions listed in Table 1 are based on experience from clinical trials and post-marketing. Within the organ 
system classes, adverse reactions are listed under headings of frequency using the following categories: very 
common (≥1/10); common (≥1/100, <1/10); rarely (≥1/10,000, <1/1,000); very rarely (<1/10,000); not 
known. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

Table 1. Adverse reactions reported during clinical trials or following the marketing use of Viraferon 
alone or in combination with ribavirin 

System Organ Class Adverse Reactions 
Infections and infestations 
Very common: 
Common: 
Rarely:  

 
Pharyngitis*, infection viral* 
Bronchitis, sinusitis, herpes simplex (resistance), rhinitis 
Pneumonia§ 

Blood and lymphatic system disorders 
Very common: 
Common: 
Very rarely:  
Not known:  

 
Leukopaenia 
Thrombocytopaenia, lymphadenopathy, lymphopenia 
Aplastic anaemia 
Pure red cell aplasia, idiopathic thrombocytopenic purpura, 
thrombotic thrombocytopenic purpura  

Immune system disorders§ 
Very rarely:  
Not known: 

 
Sarcoidosis, exacerbation of sarcoidosis 
Systemic lupus erythematosus, vasculitis, rheumatoid 
arthritis (new or aggravated), Vogt-Koyanagi-Harada 
syndrome, acute hypersensitivity reactions including 
urticaria, angioedema, bronchoconstriction, anaphylaxis§ 

Endocrine disorders 
Common: 
Very rarely:  

 
Hypothyroidism§, hyperthyroidism§ 
Diabetes, aggravated diabetes 

Metabolism and nutrition disorders 
Very common: 
Common:  
Very rarely:  

 
Anorexia 
Hypocalcaemia, dehydration, hyperuricemia, thirst 
Hyperglycaemia, hypertriglyceridaemia§, increased appetite 

Psychiatric disorders§  



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Very common: 
 
Common: 
Rarely:  
Very rarely: 
 
Not known: 

Depression, insomnia, anxiety, emotional lability*, 
agitation, nervousness 
Confusion, sleep disorder, libido decreased 
Suicide ideation 
Suicide, suicide attempts, aggressive behaviour (sometimes 
directed against others), psychosis including hallucinations 
Mental status change§ 

Nervous system disorders§ 
Very common: 
Common: 
 
Very rarely:  
 
 
Not known: 

 
Dizziness, headache, concentration impaired, mouth dry 
Tremor, paresthesia, hypoesthesia, migraine, flushing, 
somnolence, taste perversion 
Cerebrovascular haemorrhage, cerbrovascular ischaemia, 
seizure, impaired consciousness, encephalopathy, 
neuropathy, polyneuropathy 
Mononeuropathies, coma§ 

Eye disorders 
Very common: 
Common: 
 
Rarely:  

 
Vision blurred 
Conjunctivitis, vision abnormal, lacrimal gland disorder, eye 
pain 
Retinal haemorrhages§, retinopathies (including macular 
oedema), retinal artery or vein obstruction§, optic neuritis, 
papilloedema, loss of visual acuity or visual field, cotton-
wool spots§  

Ear and labyrinth 
Common: 
Very rarely:  

 
Vertigo, tinnitus 
Hearing loss, hearing disorder 

Cardiac disorders 
Common: 
Rarely: 
Very rarely: 
Not known: 

 
Palpitation, tachycardia 
Cardiomyopathy 
Myocardial infarction, cardiac ischaemia  
Arrhythmia  

Vascular disorders 
Common: 
Very rarely:  

 
Hypertension 
Peripheral ischaemia, hypotension§ 

Respiratory, thoracic and mediastinal 
disorders 
Very common: 
Common: 
 
Very rarely:  

 
 
Dyspnoea*, coughing* 
Epistaxis, respiratory disorder, nasal congestion, rhinorrhea, 
cough nonproductive 
Pulmonary infiltrates§, pneumonitis§ 

Gastrointestinal disorders 
Very common: 
 
Common: 
 
Very rarely:  
 
Not known: 

 
Nausea/vomiting, abdominal pain, diarrhoea, stomatitis, 
dyspepsia 
Stomatitis ulcerative, right upper quadrant pain, glossitis, 
gingivitis, constipation, loose stools 
Pancreatitis, ischaemic colitis, ulcerative colitis, gingival 
bleeding 
Periodontal disorder NOS, dental disorder NOS§ 

Hepatobiliary disorders 
Common: 
Very rarely:  

 
Hepatomegaly 
Hepatotoxicity, (including fatality) 

Skin and subcutaneous tissue disorders 
Very common: 
Common: 

 
Alopecia, pruritus*, skin dry*, rash*, sweating increased 
Psoriasis (new or aggravated)§, rash maculopapular, rash 



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Very rarely:  

erythematous, eczema, erythema, skin disorder 
Stevens Johnson syndrome, toxic epidermal necrolysis, 
erythema multiforme 

Musculoskeletal and connective tissue 
disorders 
Very common:  
Common: 
Very rarely: 

 
 
Myalgia, arthralgia, musculoskeletal pain 
Arthritis 
Rhabdomyolysis, myositis, leg cramps, back pain 

Renal and urinary disorders 
Common: 
Very rarely:  

 
Micturition frequency 
Renal failure, renal insufficiency, nephrotic syndrome 

Reproductive system and breast 
disorders 
Common: 

 
 
Amenorrhea, breast pain, dysmenorrhea, menorrhagia, 
menstrual disorder, vaginal disorder 

General disorders and administration 
site conditions 
Very common: 
 
 
Common: 
Very rarely: 

 
 
Injection site inflammation, injection site reaction*, fatigue, 
rigors, fever§, flu-like symptoms§, asthenia, irritability, chest 
pain, malaise 
Injection site pain 
Injection site necrosis, face oedema 

Investigations 
Very common: 

 
Weight decrease 

*These events were only common with Viraferon alone 
§See section 4.4 
 
These undesirable effects have also been reported with Viraferon alone. 
 
Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-
existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4). Cardiomyopathy, that may 
be reversible upon discontinuation of interferon alpha, has been reported rarely in patients without prior 
evidence of cardiac disease (see section 4.4).  
 
A wide variety of autoimmune and immune-mediated disorders have been reported with alpha interferons 
including thyroid disorders, systemic lupus erythematosus, rheumatoid arthritis (new or aggravated), 
idiopathic and thrombotic thrombocytopenic purpura, vasculitis, neuropathies including mononeuropathies 
(see also section 4.4).  
 
Clinically significant laboratory abnormalities, most frequently occurring at doses greater than 10 million IU 
daily, include reduction in granulocyte and white blood cell counts; decreases in haemoglobin level and 
platelet count; increases in alkaline phosphatase, LDH, serum creatinine and serum urea nitrogen levels. 
Increase in serum ALT/AST (SGPT/SGOT) levels have been noted as an abnormality in some non-hepatitis 
subjects and also in some patients with chronic hepatitis B coincident with clearance of viral DNAp. 
 
For safety with respect to transmissible agents, see section 4.4. 
 
Paediatric population 
 
Children and adolescents – Chronic Hepatitis C 
In clinical trials of 118 children or adolescents 3 to 16 years of age, 6 % discontinued therapy due to adverse 
events. In general, the adverse event profile in the limited paediatric population studied was similar to that 
observed in adults, although there is a paediatric specific concern regarding growth inhibition as decrease in 
height (mean percentile decrease of growth velocity of 9 %) and weight (mean percentile decrease of 13 %) 



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percentile were observed during treatment (see section 4.4). Furthermore, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6 month 
follow-up after treatment. As in adult patients, children and adolescents also experienced other psychiatric 
adverse events (e.g., depression, emotional lability, and somnolence) (see section 4.4). In addition, injection 
site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in children and 
adolescents compared to adult patients. Dose modifications were required in 30 % of patients, most 
commonly for anaemia and neutropaenia. 
 
The adverse reactions listed in Table 2 are based on experience from paediatric clinical trials.  
Within the organ system classes, adverse reactions are listed under headings of frequency using the following 
categories: very common (≥1/10); common (≥1/100, <1/10). Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness. 
 
Table 2  Adverse reactions very commonly and commonly reported in paediatric clinical trials  

Very common (≥1/10) - Common (≥1/100, <1/10) 
System Organ Class Adverse Reactions 
Infection and infestations 
Very common: 
Common: 

 
Viral infection, pharyngitis 
Fungal infection, bacterial infection, pulmonary infection, otitis 
media, tooth abscess, herpes simplex, urinary tract infection, 
vaginitis, gastroenteritis 

Neoplasms benign, malignant 
and unspecified (including 
cysts and polyps) 
Common: 

 
 
 
Neoplasm (unspecified) 

Blood and lymphatic system 
disorders 
Very common: 
Common: 

 
 
Anaemia, neutropaenia 
Thrombocytopaenia, lymphadenopathy 

Endocrine disorders 
Very common: 
Common: 

 
Hypothyroidism§,  
Hyperthyroidism§, virilism 

Metabolism and nutrition 
disorders 
Very common: 
Common: 

 
 
Anorexia 
Hypertriglyceridemia§, hyperuricemia, increased appetite 

Psychiatric disorders§ 
Very common: 
Common: 

 
Depression, emotional lability, insomnia 
Suicidal ideation, aggressive reaction, confusion, behaviour 
disorder, agitation, somnambulism, anxiety, nervousness, sleep 
disorder, abnormal dreaming, apathy 

Nervous system disorders§ 
Very common: 
Common: 

 
Headache, dizziness 
Hyperkinesia, tremor, dysphonia, paresthaesia, hypoaesthesia, 
hyperaesthesia, concentration impaired, somnolence 

Eye disorders 
Common: 

 
Conjunctivitis, eye pain, abnormal vision, lacrimal gland disorder 

Vascular disorders 
Common: 

 
Raynaud’s disease, flushing, pallor 

Respiratory, thoracic and 
mediastinal disorders 
Common: 

 
 
Dyspnoea, tachypnea, epistaxis, coughing, nasal congestion, nasal 
irritation, rhinorrhea, sneezing 

Gastrointestinal disorders  



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Very common: 
Common: 

Diarrhoea, vomiting, nausea, abdominal pain 
Mouth ulceration, stomatitis ulcerative, stomatitis, right upper 
quadrant pain, dyspepsia, glossitis, gastroesophogeal reflux, rectal 
disorder, gastrointestinal disorder, constipation, loose stools, 
toothache, tooth disorder 

Hepatobiliary disorders 
Common: 

 
Hepatic function abnormal 

Skin and subcutaneous tissue 
disorders  
Very common: 
Common: 

 
 
Alopecia, rash 
Photosensitivity reaction, maculopapular rash, eczema, acne, skin 
disorder, nail disorder, skin discolouration, pruritus, dry skin, 
erythema, bruise, sweating increased 

Musculoskeletal and 
connective tissue disorders 
Very common: 

 
 
Arthralgia, myalgia, musculoskeletal pain  

Renal and urinary disorders 
Common: 

 
Enuresis, micturition disorder, urinary incontinence 

Reproductive system and 
breast disorders 
Common: 

 
 
Female: amenorrhea, menorrhagia, menstrual disorder, vaginal 
disorder 
Male: testicular pain 

General disorders and 
administration site 
conditions 
Very common: 
 
Common: 

 
 
 
Injection site inflammation, injection site reaction, fatigue, rigors, 
fever§, influenza-like symptoms§, malaise, irritability 
Chest pain, asthenia, oedema, injection site pain 

Investigations 
Very common: 

 
Growth rate decrease (height and/or weight decrease for age)§  

Injury and poisoning 
Common: 

 
Skin laceration 

§See section 4.4 
 
4.9 Overdose 
 
No case of overdose has been reported that has led to acute clinical manifestations. However, as for any 
pharmacologically active compound, symptomatic treatment with frequent monitoring of vital signs and close 
observation of the patient is indicated. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunostimulants, cytokines and immunomodulators, interferons, interferon 
alfa-2b, ATC code: L03A B05 
 
Viraferon is a sterile, stable, formulation of highly purified interferon alfa-2b produced by recombinant DNA 
techniques. Recombinant interferon alfa-2b is a water-soluble protein with a molecular weight of 
approximately 19,300 daltons. It is obtained from a clone of E. coli, which harbours a genetically engineered 
plasmid hybrid encompassing an interferon alfa-2b gene from human leukocytes. 
 



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The activity of Viraferon is expressed in terms of IU, with 1 mg of recombinant interferon alfa-2b protein 
corresponding to 2.6 x l08 IU. International Units are determined by comparison of the activity of the 
recombinant interferon alfa-2b with the activity of the international reference preparation of human leukocyte 
interferon established by the World Health Organisation. 
 
The interferons are a family of small protein molecules with molecular weights of approximately 15,000 to 
21,000 daltons. They are produced and secreted by cells in response to viral infections or various synthetic 
and biological inducers. Three major classes of interferons have been identified: alpha, beta and gamma. 
These three main classes are themselves not homogeneous and may contain several different molecular 
species of interferon. More than 14 genetically distinct human alpha interferons have been identified. 
Viraferon has been classified as recombinant interferon alfa-2b. 
 
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. 
Human interferon receptors, as isolated from human lymphoblastoid (Daudi) cells, appear to be highly 
asymmetric proteins. They exhibit selectivity for human but not murine interferons, suggesting species 
specificity. Studies with other interferons have demonstrated species specificity. However, certain monkey 
species, eg, rhesus monkeys, are susceptible to pharmacodynamic stimulation upon exposure to human type 
1 interferons. 
 
The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex 
sequence of intracellular events that include the induction of certain enzymes. It is thought that this process, 
at least in part, is responsible for the various cellular responses to interferon, including inhibition of virus 
replication in virus-infected cells, suppression of cell proliferation and such immunomodulating activities as 
enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of 
lymphocytes for target cells. Any or all of these activities may contribute to interferon's therapeutic effects. 
 
Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and 
human cell culture systems as well as human tumour xenografts in animals. It has demonstrated significant 
immunomodulatory activity in vitro. 
 
Recombinant interferon alfa-2b also inhibits viral replication in vitro and in vivo. Although the exact antiviral 
mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism. 
This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell. 
 
Chronic hepatitis B: 
Current clinical experience in patients who remain on interferon alfa-2b for 4 to 6 months indicates that 
therapy can produce clearance of serum HBV-DNA. An improvement in liver histology has been observed. 
In adult patients with loss of HBeAg and HBV-DNA, a significant reduction in morbidity and mortality has 
been observed. 
 
Interferon alfa-2b (6 MIU/m2 3 times a week for 6 months) has been given to children with chronic active 
hepatitis B. Because of a methodological flaw, efficacy could not be demonstrated. Moreover children treated 
with interferon alfa-2b experienced a reduced rate of growth and some cases of depression were observed. 
 
Chronic hepatitis C: 
In adult patients receiving interferon in combination with ribavirin, the achieved sustained response rate is 
47 %. Superior efficacy has been demonstrated with the combination of pegylated interferon with ribavirin 
(sustained response rate of 61 % achieved in a study performed in naïve patients with a ribavirin dose 
> 10.6 mg/kg, p < 0.01). 
 
Adult patients: Viraferon alone or in combination with ribavirin has been studied in 4 randomised Phase III 
clinical trials in 2,552 interferon-naïve patients with chronic hepatitis C. The trials compared the efficacy of 
Viraferon used alone or in combination with ribavirin. Efficacy was defined as sustained virologic response, 
6 months after the end of treatment. Eligible patients for these trials had chronic hepatitis C confirmed by a 
positive HCV-RNA polymerase chain reaction assay (PCR) (> 100 copies/ml), a liver biopsy consistent with 



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a histologic diagnosis of chronic hepatitis with no other cause for the chronic hepatitis, and abnormal serum 
ALT. 
 
Viraferon was administered at a dose of 3 MIU 3 times a week as monotherapy or in combination with 
ribavirin. The majority of patients in these clinical trials were treated for one year. All patients were followed 
for an additional 6 months after the end of treatment for the determination of sustained virologic response. 
Sustained virologic response rates for treatment groups treated for one year with Viraferon alone or in 
combination with ribavirin (from two studies) are shown in Table 3. 
 
Co-administration of Viraferon with ribavirin increased the efficacy of Viraferon by at least two fold for the 
treatment of chronic heptatitis C in naïve patients. HCV genotype and baseline virus load are prognostic 
factors which are known to affect response rates. The increased response rate to the combination of Viraferon + 
ribavirin, compared with Viraferon alone, is maintained across all subgroups. The relative benefit of combination 
therapy with Viraferon + ribavirin is particularly significant in the most difficult to treat subgroup of patients 
(genotype 1 and high virus load) (Table 3). 
 
Response rates in these trials were increased with compliance. Regardless of genotype, patients who received 
Viraferon in combination with ribavirin and received ≥ 80 % of their treatment had a higher sustained 
response 6 months after 1 year of treatment than those who took < 80 % of their treatment (56 % vs. 32 % in 
trial C/I98-580).  



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Table 3 Sustained virologic response rates with Viraferon + ribavirin (one year of 

treatment) by genotype and viral load 
 

HCV Genotype  
 

I 
N=503 

C95-132/I95-143 

I/R 
N=505 

C95-132/I95-143 

I/R 
N=505 

C/I98-580 
 
All Genotypes 

 
16 % 

 
41 % 

 
47 % 

 
 
Genotype 1 

 
9 % 

 
29 % 

 
33 % 

 
Genotype 1  
≤ 2 million 
copies/ml 

 
25 % 

 
33 % 

 
45 % 

 
Genotype 1 
> 2 million 
copies/ml 

 
3 % 

 
27 % 

 

 
29 % 

 
Genotype 2/3 

 
31 % 

 
65 % 

 
79 % 

I Viraferon (3 MIU 3 times a week) 
I/R Viraferon (3 MIU 3 times a week) + ribavirin (1,000/1,200 mg/day) 
 
HCV/HIV Co-infected patients  
Two trials have been conducted in patients co-infected with HIV and HCV. Overall, in both studies, patients 
who received Viraferon plus ribavirin, were less likely to respond than patients who received pegylated 
interferon alfa-2b with ribavirin. The response to treatment in both of these trials is presented in Table 4. 
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 412 previously untreated 
adult patients with chronic hepatitis C who were co-infected with HIV. Patients were randomized to receive 
either pegylated interferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800 mg/day) or Viraferon (3 MIU TIW) 
plus ribavirin (800 mg/day) for 48 weeks with a follow-up period of 6 months. Study 2 (P02080) was a 
randomized, single centre study that enrolled 95 previously untreated adult patients with chronic hepatitis C 
who were co-infected with HIV. Patients were randomized to receive either pegylated interferon alfa-2b (100 
or 150 µg /week based on weight) plus ribavirin (800-1,200 mg/day based on weight) or Viraferon (3 MIU 
TIW) plus ribavirin (800-1,200 mg/day based on weight). The duration of therapy was 48 weeks with a 
follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load 
< 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6-month follow-up period.  



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Table 4 Sustained virological response based on genotype after Viraferon in combination with 

ribavirin versus pegylated interferon alfa-2b in combination with ribavirin in 
HCV/HIV co-infected patients 

 Study 11 Study 22 
 

pegylated 
interferon 

alfa-2b  
(1.5 µg/kg/ 

week) + 
ribavirin  
(800 mg) 

Viraferon  
(3 MIU TIW) +  

ribavirin  
(800 mg) 

p 
valuea 

pegylated 
interferon 

alfa-2b (100 
or  

150c µg/week) 
+ ribavirin 

(800- 
1,200 mg)d 

Viraferon  
(3 MIU TIW) 

+ ribavirin 
(800- 

1,200 mg)d 
p 

valueb 
All 27 % (56/205) 20 % (41/205) 0.047 44 % (23/52) 21 % (9/43) 0.017 
Genotype 1, 

4 
17 % (21/125) 6 % (8/129) 0.006 38 % (12/32) 7 % (2/27) 0.007 

Genotype 2, 
3 

44 % (35/80) 43 % (33/76) 0.88 53 % (10/19) 47 % (7/15) 0.730 

MIU = million international units; TIW = three times a week. 
a:  p value based on Cochran-Mantel Haenszel Chi square test. 
b:  p value based on chi-square test. 
c:  subjects < 75 kg received 100 µg/week pegylated interferon alfa-2b and subjects ≥ 75 kg received 150 µg/week pegylated 

interferon alfa-2b. 
d: ribavirin dosing was 800 mg for patients < 60 kg, 1,000 mg for patients 60-75 kg, and 1,200 mg for patients > 75 kg. 
 

1Carrat F, Bani-Sadr F, Pol S et al.  JAMA 2004; 292(23): 2839-2848. 
2 Laguno M, Murillas J, Blanco J.L et al.  AIDS 2004; 18(13): F27-F36. 
 
 
Relapse patients: A total of 345 interferon alpha relapse patients were treated in two clinical trials with 
Viraferon monotherapy or in combination with ribavirin. In these patients, the addition of ribavirin to 
Viraferon increased by as much as 10-fold the efficacy of Viraferon used alone in the treatment of chronic 
hepatitis C (48.6 % vs. 4.7 %). This enhancement in efficacy included loss of serum HCV (< 100 copies/ml 
by PCR), improvement in hepatic inflammation, and normalisation of ALT, and was sustained when 
measured 6 months after the end of treatment. 
 
Long-Term efficacy data 
In a large study, 1,071 patients were enrolled after treatment in a prior non pegylated interferon alfa-2b or 
non pegylated interferon alfa-2b/ribavirin study to evaluate the durability of sustained virologic response and 
assess the impact of continued viral negativity on clinical outcomes. 462 patients completed at least 5 years 
of long-term follow-up and only 12 sustained responders' out of 492 relapsed during this study.  
The Kaplan-Meier estimate for continued sustained response over 5 years for all patients is 97 % with a 95 % 
Confidence Interval of [95 %, 99 %].  
SVR after treatment of chronic HCV with non pegylated interferon alfa-2b (with or without ribavirin) results 
in long-term clearance of the virus providing resolution of the hepatic infection and clinical 'cure' from 
chronic HCV. However, this does not preclude the occurrence of hepatic events in patients with cirrhosis 
(including hepatocarcinoma). 
 
Clinical trials in paediatric patients with chronic hepatitis C: 
Children and adolescents 3 to 16 years of age with compensated chronic hepatitis C and detectable HCV-
RNA (assessed by a central laboratory using a research-based RT-PCR assay) were enrolled in two 
multicentre trials and received Viraferon 3 MIU/m2 3 times a week plus ribavirin 15 mg/kg per day for 1 year 
followed by 6 months follow-up after-treatment. A total of 118 patients were enrolled: 57 % male, 80 % 
Caucasian, and 78 % genotype 1,64 % ≤ 12 years of age. The population enrolled mainly consisted in 
children with mild to moderate hepatitis C. Sustained virological response rates in children and adolescents 



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were similar to those in adults. Due to the lack of data in children with severe progression of the disease, and 
the potential for undesirable effects, the benefit/risk of the combination of ribavirin and interferon alfa-2b 
needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8). 
 
Study results are summarized in Table 5. 
 
Table 5. Virological response in previously untreated paediatric patients 
 Viraferon 3 MIU/m2 3 times a week   

+ 
ribavirin 15 mg/kg/day 

Overall Response1 (n=118) 54 (46 %)* 

Genotype 1 (n=92) 33 (36 %)* 

Genotype 2/3/4 (n=26) 21 (81 %)* 

*Number (%) of patients 
1. Defined as HCV-RNA below limit of detection using a research based RT-PCR assay at end of treatment and during follow-up 
period 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of Viraferon were studied in healthy volunteers following single 5 million IU/m2 and 
10 million IU doses administered subcutaneously, at 5 million IU/m2 administered intramuscularly and as a 
30-minute intravenous infusion. The mean serum interferon concentrations following subcutaneous and 
intramuscular injections were comparable. Cmax occurred three to 12 hours after the lower dose and six to 
eight hours after the higher dose. The elimination half-lives of interferon injections were approximately two 
to three hours, and six to seven hours, respectively. Serum levels were below the detection limit 16 and 
24 hours, respectively, post-injection. Both subcutaneous and intramuscular administration resulted in 
bioavailabilities greater than 100 %. 
 
After intravenous administration, serum interferon levels peaked (135 to 273 IU/ml) by the end of the 
infusion, then declined at a slightly more rapid rate than after subcutaneous or intramuscular administration 
of medicinal product, becoming undetectable four hours after the infusion. The elimination half-life was 
approximately two hours. 
 
Urine levels of interferon were below the detection limit following each of the three routes of administration. 
 
Children and adolescents: Multiple-dose pharmacokinetic properties for Viraferon injection and ribavirin 
capsules in children and adolescents with chronic hepatitis C, between 5 and 16 years of age, are summarized 
in Table 6. The pharmacokinetics of Viraferon and ribavirin (dose-normalized) are similar in adults and 
children or adolescents. 



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Table 6. Mean (% CV) multiple-dose pharmacokinetic parameters for Viraferon and ribavirin 

capsules when administered to children or adolescents with chronic hepatitis C 
Parameter Ribavirin 

15 mg/kg/day as 2 divided 
doses 

(n = 17) 

Viraferon 
3 MIU/m2 3 times a week 

(n = 54) 

Tmax (hr) 1.9 (83) 5.9 (36) 
Cmax (ng/ml) 3,275 (25) 51 (48) 

AUC* 29,774 (26) 622 (48) 
Apparent clearance l/hr/kg 0.27 (27) Not done 

*AUC12 (ng.hr/ml) for ribavirin; AUC0-24 (IU.hr/ml) for Viraferon 
 
Interferon neutralising factor assays were performed on serum samples of patients who received Viraferon in 
Schering-Plough monitored clinical trials. Interferon neutralising factors are antibodies which neutralise the 
antiviral activity of interferon. The clinical incidence of neutralising factors developing in cancer patients 
treated systemically is 2.9 % and in chronic hepatitis patients is 6.2 %. The detectable titres are low in almost 
all cases and have not been regularly associated with loss of response or any other autoimmune phenomenon. 
In patients with hepatitis, no loss of response was observed apparently due to the low titres. 
 
5.3 Preclinical safety data 
 
Although interferon is generally recognised as being species specific, toxicity studies in animals were 
conducted. Injections of human recombinant interferon alfa-2b for up to three months have shown no 
evidence of toxicity in mice, rats, and rabbits. Daily dosing of cynomolgus monkeys with 20 x 106 IU/kg/day 
for 3 months caused no remarkable toxicity. Toxicity was demonstrated in monkeys given 
100 x 106 IU/kg/day for 3 months. 
 
In studies of interferon use in non-human primates, abnormalities of the menstrual cycle have been observed 
(see section 4.4). 
 
Results of animal reproduction studies indicate that recombinant interferon alfa-2b was not teratogenic in rats 
or rabbits, nor did it adversely affect pregnancy, foetal development or reproductive capacity in offspring of 
treated rats. Interferon alfa-2b has been shown to have abortifacient effects in Macaca mulatta (rhesus 
monkeys) at 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2. 
Abortion was observed in all dose groups (7.5 million, 15 million and 30 million IU/kg), and was statistically 
significant versus control at the mid- and high-dose groups (corresponding to 90 and 180 times the 
recommended intramuscular or subcutaneous dose of 2 million IU/m2). High doses of other forms of 
interferons alpha and beta are known to produce dose-related anovulatory and abortifacient effects in rhesus 
monkeys. 
 
Mutagenicity studies with interferon alfa-2b revealed no adverse events. 
 
No studies have been conducted in juvenile animals to examine the effects of treatment with interferon alfa-
2b on growth, development, sexual maturation, and behaviour (see section 4.4 and Rebetol SPC if Viraferon 
is to be administered in combination with ribavirin). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Glycine,  
Disodium phosphate anhydrous,  



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Sodium dihydrogen phosphate monohydrate, 
Human albumin solution. 
 
Solvent: water for injections 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
3 years 
 
After reconstitution: An immediate use is recommended. However, the chemical and physical in-use stability 
has been demonstrated for 24 hours at 25ºC. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C).  
Do not freeze.  
Within its shelf-life, for the purpose of transport and/or to facilitate ambulatory use the non-reconstituted 
product can be kept at or below 25°C for a period up to four weeks before use. If the product is not 
reconstituted during the four-week period, it cannot be put back in the refrigerator for a new storage period 
and must be discarded. 
 
6.5 Nature and contents of container 
 
24 mg of powder (corresponding to 1 MIU) in a vial (type I glass), with a stopper (butyl rubber) in a flip-off 
seal (aluminium) with a bonnet (polypropylene) 
and 1 ml water for injections in an ampoule (type I glass) 
with 1 injection syringe, 2 injection needles and 1 cleansing swab.  
Pack sizes of 1. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
Reconstitution of Viraferon, powder for solution for injection, for parenteral administration: Viraferon is 
supplied as a powder at strengths of 1 million IU/ml for single-dose use. Vials must be reconstituted with 
1 ml of water for injections. The reconstituted solutions are isotonic for parenteral administration. 
 
Proper precautions should be taken during reconstitution to prevent microbial contamination (refer to package 
leaflet).  
 
Using a sterilised injection syringe and injection needle, inject 1 ml water for injections into the vial of 
Viraferon. Agitate gently to facilitate complete dissolution of the powder. The appropriate dose can then be 
withdrawn with a sterile injection syringe and injected. 
 
As for all parenteral medicinal products, inspect the reconstituted solution visually for particulate matter and 
discoloration prior to administration. The reconstituted solution should be clear and colourless. 
 



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Detailed instructions for the subcutaneous use of the product are provided with the package leaflet (refer to 
“How to self inject Viraferon”). 
 
Any unused product must be discarded after withdrawal of the dose. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
SP Europe 
73, rue de Stalle 
B-1180 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBER 
 
EU/1/99/128/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation : 9 March 2000 
Date of last renewal : 23 May 2005 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu/ 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 3 million IU/ml powder and solvent for solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One vial of powder contains 3 million IU of interferon alfa-2b produced in E.coli by recombinant DNA 
technology. 
After reconstitution, 1 ml contains 3 million IU of interferon alfa-2b. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection 
 
White to cream coloured powder.  
Clear and colourless solvent. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Chronic Hepatitis B: Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis B 
viral replication (presence of HBV-DNA and HBeAg), elevated alanine aminotransferase (ALT) and 
histologically proven active liver inflammation and/or fibrosis. 
 
Chronic Hepatitis C:  
Adult patients:  
Viraferon is indicated for the treatment of adult patients with chronic hepatitis C who have elevated 
transaminases without liver decompensation and who are positive for serum HCV-RNA or anti-HCV (see 
section 4.4). 
 
The best way to use Viraferon in this indication is in combination with ribavirin. 
 
Chidren and adolescents: 
Viraferon is intended for use, in a combination regimen with ribavirin, for the treatment of children and 
adolescents 3 years of age and older, who have chronic hepatitis C, not previously treated, without liver 
decompensation, and who are positive for serum HCV-RNA. The decision to treat should be made on a case 
by case basis, taking into account any evidence of disease progression such as hepatic inflammation and 
fibrosis, as well as prognostic factors for response, HCV genotype and viral load. The expected benefit of 
treatment should be weighed against the safety findings observed for paediatric subjects in the clinical trials 
(see sections 4.4, 4.8 and 5.1). 
 
4.2 Posology and method of administration 
 
Treatment must be initiated by a physician experienced in the management of the disease. 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 



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If adverse events develop during the course of treatment with Viraferon for any indication, modify the dosage 
or discontinue therapy temporarily until the adverse events abate. If persistent or recurrent intolerance 
develops following adequate dosage adjustment, or disease progresses, discontinue treatment with Viraferon. 
At the discretion of the physician, the patient may self-administer the dose for maintenance dosage regimens 
administered subcutaneously. 
 
Chronic Hepatitis B: The recommended dosage is in the range 5 to 10 million IU administered 
subcutaneously three times a week (every other day) for a period of 4 to 6 months. 
 
The administered dose should be reduced by 50 % in case of occurrence of haematological disorders (white 
blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3). Treatment should be 
discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe 
thrombocytopaenia (< 70,000/mm3). 
 
For all patients, if no improvement on serum HBV-DNA is observed after 3 to 4 months of treatment (at the 
maximum tolerated dose), discontinue Viraferon therapy. 
 
Chronic Hepatitis C: Viraferon is administered subcutaneously at a dose of 3 million IU three times a week 
(every other day) to adult patients, whether administered as monotherapy or in combination with ribavirin. 
 
Children 3 years of age or older and adolescents: Interferon alfa-2b 3 MIU/m2 is administered 
subcutaneously 3 times a week (every other day) in combination with ribavirin capsules or oral solution 
administered orally in two divided doses daily with food (morning and evening).  
 
(See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination 
therapy. For paediatric patients who weigh < 47 kg or cannot swallow capsules, see ribavirin oral solution 
SPC).  
 
Relapse patients (adults): 
Viraferon is given in combination with ribavirin. 
 
Based on the results of clinical trials, in which data are available for 6 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for 6 months. 
 
Naïve patients: 
Adults: The efficacy of Viraferon is enhanced when given in combination with ribavirin. Viraferon should be 
given alone mainly in case of intolerance or contraindication to ribavirin. 
 
Viraferon in combination with ribavirin: 
Based on the results of clinical trials, in which data are available for 12 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for at least 6 months. 
 
Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit 
negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and 
high pre-treatment viral load. 
 
Other negative prognostic factors (age > 40 years, male gender, bridging fibrosis) should be taken into 
account in order to extend therapy to 12 months. 
 
During clinical trials, patients who failed to show a virologic response after 6 months of treatment (HCV-
RNA below lower limit of detection) did not become sustained virologic responders (HCV-RNA below lower 
limit of detection six months after withdrawal of treatment). 
 
Viraferon alone: 



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The optimal duration of therapy with Viraferon alone is not yet fully established, but a therapy of between 
12 and 18 months is advised. 
 
It is recommended that patients be treated with Viraferon alone for at least 3 to 4 months, at which point 
HCV-RNA status should be determined. Treatment should be continued in patients who exhibit negative 
HCV-RNA. 
 
Children and adolescents: The efficacy and safety of Viraferon in combination with ribavirin has been 
studied in children and adolescents who have not been previously treated for chronic hepatitis C.  
 
Genotype 1: The recommended duration of treatment is one year. Patients who fail to achieve virological 
response at 12 weeks are highly unlikely to become sustained virological responders (negative predictive 
value 96 %). Virological response is defined as absence of detectable HCV-RNA at Week 12. Treatment 
should be discontinued in these patients. 
Genotype 2/3: The recommended duration of treatment is 24 weeks. 
 
Virological responses after 1 year of treatment and 6 months of follow-up were 36 % for genotype 1 and 
81 % for genotype 2/3/4. 
 
Viraferon may be administered using either glass or plastic disposable injection syringes. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients. 
- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure, recent 

myocardial infarction, severe arrhythmic disorders.  
- Severe renal or hepatic dysfunction; including that caused by metastases. 
- Epilepsy and/or compromised central nervous system (CNS) function (see section 4.4). 
- Chronic hepatitis with decompensated cirrhosis of the liver. 
- Chronic hepatitis in patients who are being or have been treated recently with immunosuppressive 

agents excluding short term corticosteroid withdrawal. 
- Autoimmune hepatitis; or history of autoimmune disease; immunosuppressed transplant recipients. 
- Pre-existing thyroid disease unless it can be controlled with conventional treatment. 
 
Children and adolescents: 
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal 

ideation or suicide attempt. 
 

Combination therapy with ribavirin: Also see ribavirin SPC if interferon alfa-2b is to be administered in 
combination with ribavirin in patients with chronic hepatitis C. 
 
4.4 Special warnings and precautions for use 
 
For all patients: 
Psychiatric and central nervous system (CNS): Severe CNS effects, particularly depression, suicidal ideation 
and attempted suicide have been observed in some patients during Viraferon therapy, and even after 
treatment discontinuation mainly during the 6-month follow-up periodand in the follow-up period. Among 
children and adolescents treated with Viraferon in combination with ribavirin, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6-month 
follow-up after treatment. As in adult patients, children and adolescents experienced other psychiatric adverse 
events (e.g., depression, emotional lability, and somnolence). Other CNS effects including aggressive behaviour 
(sometimes directed against others), confusion and alterations of mental status have been observed with alpha 
interferons. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such 
symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the 
prescribing physician and the need for adequate therapeutic management should be considered. If psychiatric 



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symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with 
Viraferon be discontinued, and the patient followed, with psychiatric intervention as appropriate. 
 
Patients with existence of or history of severe psychiatric conditions: 
If a treatment with interferon alfa-2b is judged necessary in adult patients with existence or history of severe 
psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and 
therapeutic management of the psychiatric condition. The use of interferon alfa-2b in children and adolescents 
with existence of or history of severe psychiatric conditions is contraindicated (see section 4.3). 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Moderate to severe adverse experiences may require modification of the patient's dosage regimen, or in some 
cases, termination of Viraferon therapy. Any patient developing liver function abnormalities during treatment 
with Viraferon must be monitored closely and treatment discontinued if signs and symptoms progress. 
 
Hypotension may occur during Viraferon therapy or up to two days post-therapy and may require supportive 
treatment. 
 
Adequate hydration must be maintained in patients undergoing Viraferon therapy since hypotension related 
to fluid depletion has been seen in some patients. Fluid replacement may be necessary. 
 
While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, 
other causes of persistent fever must be ruled out. 
 
Viraferon must be used cautiously in patients with debilitating medical conditions, such as those with a 
history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to 
ketoacidosis. Caution must be observed also in patients with coagulation disorders (e.g., thrombophlebitis, 
pulmonary embolism) or severe myelosuppression. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.5). Any patient developing fever, cough, 
dyspnea or other respiratory symptoms must have a chest X-ray taken. If the chest X-ray shows pulmonary 
infiltrates or there is evidence of pulmonary function impairment, the patient is to be monitored closely, and, 
if appropriate, discontinue interferon alpha. While this has been reported more often in patients with chronic 
hepatitis C treated with interferon alpha, it has also been reported in patients with oncologic diseases treated 
with interferon alpha. Prompt discontinuation of interferon alpha administration and treatment with 
corticosteroids appear to be associated with resolution of pulmonary adverse events. 
 
Ocular adverse events (see section 4.8) including retinal haemorrhages, cotton wool spots, and retinal artery 
or vein obstruction have been reported in rare instance after treatment with alpha interferons. All patients 
should have a baseline eye examination. Any patient complaining of changes in visual acuity or visual fields, 
or reporting other ophthalmologic symptoms during treatment with Viraferon, must have a prompt and 
complete eye examination. Periodic visual examinations during Viraferon therapy are recommended 
particularly in patients with disorders that may be associated with retinopathy, such as diabetes mellitus or 
hypertension. Discontinuation of Viraferon should be considered in patients who develop new or worsening 
ophthalmological disorders. 



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More significant obtundation and coma, including cases of encephalopathy, have been observed in some 
patients, usually elderly, treated at higher doses. While these effects are generally reversible, in a few patients 
full resolution took up to three weeks. Very rarely, seizures have occurred with high doses of Viraferon. 
 
Adult patients with a history of congestive heart failure, myocardial infarction and/or previous or current 
arrhythmic disorders, who require Viraferon therapy, must be closely monitored. It is recommended that 
those patients who have pre-existing cardiac abnormalities and/or are in advanced stages of cancer have 
electrocardiograms taken prior to and during the course of treatment. Cardiac arrhythmias (primarily 
supraventricular) usually respond to conventional therapy but may require discontinuation of Viraferon 
therapy. There are no data in children or adolescents with a history of cardiac disease. 
 
Hypertriglyceridemia and aggravation of hypertriglyceridemia, sometimes severe, have been observed. 
Monitoring of lipid levels is, therefore, recommended. 
 
Due to reports of interferon alpha exacerbating pre-existing psoriatic disease and sarcoidosis, use of 
Viraferon in patients with psoriasis or sarcoidosis is recommended only if the potential benefit justifies the 
potential risk. 
 
Preliminary data indicates that interferon alpha therapy may be associated with an increased rate of kidney 
graft rejection. Liver graft rejection has also been reported. 
 
The development of auto-antibodies and autoimmune disorders has been reported during treatment with alpha 
interferons. Patients predisposed to the development of autoimmune disorders may be at increased risk. 
Patients with signs or symptoms compatible with autoimmune disorders should be evaluated carefully, and 
the benefit-risk of continued interferon therapy should be reassessed (see also section 4.4 Chronic hepatitis C, 
Monotherapy (thyroid abnormalities) and section 4.8). 
Cases of Vogt-Koyanagi-Harada (VKH) syndrome have been reported in patients with chronic hepatitis C 
treated with interferon. This syndrome is a granulomatous inflammatory disorder affecting the eyes, auditory 
system, meninges, and skin. If VKH syndrome is suspected, antiviral treatment should be withdrawn and 
corticosteroid therapy discussed (see section 4.8). 
 
Discontinue treatment with Viraferon in patients with chronic hepatitis who develop prolongation of 
coagulation markers which might indicate liver decompensation. 
 
Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of 
human plasma-derived albumin. 
 
Standard measures to prevent infections resulting from the use of medicinal products prepared from human 
blood or plasma include selection of donors, screening of individual donations and plasma pools for specific 
markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of 
viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the 
possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or 
emerging viruses and other pathogens. 
 
There are no reports of virus transmissions with albumin manufactured to European Pharmacopoeia 
specifications by established processes. 
 
It is strongly recommended that every time that Viraferon is administered to a patient, the name and batch 
number of the product are recorded in order to maintain a link between the patient and the batch of the 
product. 
 
Chronic Hepatitis C: 
Combination therapy with ribavirin: Also see ribavirin SPC if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 



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All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i.e. 
patients with genotype 2 and 3), treatment may be possible without histological confirmation. Current 
treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing 
treatment. 
 
Monotherapy: Infrequently, adult patients treated for chronic hepatitis C with Viraferon developed thyroid 
abnormalities, either hypothyroidism or hyperthyroidism. In clinical trials using Viraferon therapy, 2.8 % 
patients overall developed thyroid abnormalities. The abnormalities were controlled by conventional therapy 
for thyroid dysfunction. The mechanism by which Viraferon may alter thyroid status is unknown. Prior to 
initiation of Viraferon therapy for the treatment of chronic hepatitis C, evaluate serum thyroid-stimulating 
hormone (TSH) levels. Any thyroid abnormality detected at that time must be treated with conventional 
therapy. Viraferon treatment may be initiated if TSH levels can be maintained in the normal range by 
medication. Determine TSH levels if, during the course of Viraferon therapy, a patient develops symptoms 
consistent with possible thyroid dysfunction. In the presence of thyroid dysfunction, Viraferon treatment may 
be continued if TSH levels can be maintained in the normal range by medication. Discontinuation of 
Viraferon therapy has not reversed thyroid dysfunction occurring during treatment (also see Children and 
adolescents, Thyroid monitoring). 
 
Supplemental monitoring specific for children and adolescents 
Thyroid Monitoring: Approximately 12 % of children treated with interferon alfa-2b and ribavirin developed 
increase in TSH. Another 4 % had a transient decrease below the lower limit of normal. Prior to initiation of 
Viraferon therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be 
treated with conventional therapy. Viraferon therapy may be initiated if TSH levels can be maintained in the 
normal range by medication. Thyroid dysfunction during treatment with interferon alfa-2b and ribavirin has 
been observed. If thyroid abnormalities are detected, the patient’s thyroid status should be evaluated and 
treated as clinically appropriate. Children and adolescents should be monitored every 3 months for evidence 
of thyroid dysfunction (e.g. TSH). 
 
Growth and Development: During a 1-year course of therapy there was a decrease in the rate of linear growth 
(mean percentile decrease of 9 %) and a decrease in the rate of weight gain (mean percentile decrease of 
13 %). A general reversal of these trends was noted during the 6 months follow-up post treatment. However, 
based on interim data from a long-term follow-up study, 12 (14 %) of 84 children had a > 15 percentile 
decrease in rate of linear growth, of whom 5 (6 %) children had a > 30 percentile decrease despite being off 
treatment for more than 1 year. In addition, preclicinal juvenile toxicity results have demonstrated a minor, 
dose-related decrease in overall growth in neonatal rats dosed with ribavirin (see section 5.3). Therefore, the 
risk/benefit of the combined use of interferon alfa-2b and ribavirin should be assessed in young children prior 
to the initiation of therapy. Physicians are advised to monitor the growth of children taking ribavirin in 
combination with interferon alfa-2b. There are no data on long term effects on growth and development and 
on sexual maturation. 
 
HCV/HIV Coinfection: Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy 
(HAART) may be at increased risk of developing lactic acidosis. Caution should be used when adding Viraferon 
and ribavirin to HAART therapy (see ribavirin SPC). Patients treated with Viraferon and ribavirin combination 
therapy and zidovudine could be at increased risk of developing anaemia. 
Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic 
decompensation and death. Adding treatment with alfa interferons alone or in combination with ribavirin may 
increase the risk in this patient subset.  
 
Dental and periodontal disorders: Dental and periodontal disorders, which may lead to loss of teeth, have 
been reported in patients receiving Viraferon and ribavirin combination therapy. In addition, dry mouth could 
have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the 
combination of Viraferon and ribavirin. Patients should brush their teeth thoroughly twice daily and have 
regular dental examinations. In addition some patients may experience vomiting. If this reaction occurs, they 
should be advised to rinse out their mouth thoroughly afterwards. 



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Laboratory Tests:  
Standard haematological tests and blood chemistries (complete blood count and differential, platelet count, 
electrolytes, liver enzymes, serum protein, serum bilirubin and serum creatinine) are to be conducted in all 
patients prior to and periodically during systemic treatment with Viraferon. 
 
During treatment for hepatitis B or C the recommended testing schedule is at weeks 1, 2, 4, 8, 12, 16, and 
every other month, thereafter, throughout treatment. If ALT flares during Viraferon therapy to greater than or 
equal to 2 times baseline, Viraferon therapy may be continued unless signs and symptoms of liver failure are 
observed. During ALT flare, liver function tests: ALT, prothrombin time, alkaline phosphatase, albumin and 
bilirubin must be monitored at two-week intervals. 
 
Effect on fertility: Interferon may impair fertility (see section 4.6 and section 5.3). 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with 
Viraferon. 
 
Interactions between Viraferon and other medicinal products have not been fully evaluated. Caution must be 
exercised when administering Viraferon in combination with other potentially myelosuppressive agents. 
 
Interferons may affect the oxidative metabolic process. This must be considered during concomitant therapy 
with medicinal products metabolised by this route, such as the xanthine derivatives theophylline or 
aminophylline. During concomitant therapy with xanthine agents, serum theophylline levels must be 
monitored and dosage adjusted if necessary. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.4). 
 
(Also see ribavirin SPC if Viraferon is to be administered in combination with ribavirin in patients with 
chronic hepatitis C). 
 
4.6 Pregnancy and lactation 
 
Women of childbearing potential have to use effective contraception during treatment. Viraferon must be 
used with caution in fertile men. Decreased serum estradiol and progesterone concentrations have been 
reported in women treated with human leukocyte interferon. 
 
There are no adequate data from the use of interferon alfa-2b in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Viraferon is to be 
used during pregnancy only if the potential benefit justifies the potential risk to the foetus. 
 
It is not known whether the components of this medicinal product are excreted in human milk. Because of the 
potential for adverse reactions in nursing infants, nursing should be discontinued prior to initiation of 
treatment. 
 
Combination therapy with ribavirin: Ribavirin causes serious birth defects when administered during 
pregnancy. Ribavirin therapy is contraindicated in women who are pregnant. Extreme care must be taken to 
avoid pregnancy in female patients or in partners of male patients taking Viraferon in combination with 
ribavirin. Females of childbearing potential and their partners must each use an effective contraceptive during 
treatment and for 4 months after treatment has been concluded. Male patients and their female partners must 



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each use an effective contraceptive during treatment and for 7 months after treatment has been concluded (see 
ribavirin SPC). 
 
4.7 Effects on ability to drive and use machines 
 
Patients are to be advised that they may develop fatigue, somnolence, or confusion during treatment with 
Viraferon, and therefore it is recommended that they avoid driving or operating machinery. 
 
4.8 Undesirable effects 
 
See ribavirin SPC for ribavirin-related undesirable effects if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
In clinical trials conducted in a broad range of indications and at a wide range of doses (from 6 MIU/m2/week 
in hairy cell leukaemia up to 100 MIU/m2/week in melanoma), the most commonly reported undesirable 
effects were fever, fatigue, headache and myalgia. Fever and fatigue were often reversible within 72 hours of 
interruption or cessation of treatment. 
 
In clinical trials conducted in the hepatitis C population, patients were treated with Viraferon alone or in 
combination with ribavirin for one year. All patients in these trials received 3 MIU of Viraferon three times a 
week. In Table 1 the frequency of patients reporting (treatment related) undesirable effects is presented from 
clinical trials in naïve patients treated for one year. Severity was generally mild to moderate. The adverse 
reactions listed in Table 1 are based on experience from clinical trials and post-marketing. Within the organ 
system classes, adverse reactions are listed under headings of frequency using the following categories: very 
common (≥1/10); common (≥1/100, <1/10); rarely (≥1/10,000, <1/1,000); very rarely (<1/10,000); not 
known. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

Table 1. Adverse reactions reported during clinical trials or following the marketing use of Viraferon 
alone or in combination with ribavirin 

System Organ Class Adverse Reactions 
Infections and infestations 
Very common: 
Common: 
Rarely:  

 
Pharyngitis*, infection viral* 
Bronchitis, sinusitis, herpes simplex (resistance), rhinitis 
Pneumonia§ 

Blood and lymphatic system disorders 
Very common: 
Common: 
Very rarely:  
Not known:  

 
Leukopaenia 
Thrombocytopaenia, lymphadenopathy, lymphopenia 
Aplastic anaemia 
Pure red cell aplasia, idiopathic thrombocytopenic purpura, 
thrombotic thrombocytopenic purpura  

Immune system disorders§ 
Very rarely:  
Not known: 

 
Sarcoidosis, exacerbation of sarcoidosis 
Systemic lupus erythematosus, vasculitis, rheumatoid 
arthritis (new or aggravated), Vogt-Koyanagi-Harada 
syndrome, acute hypersensitivity reactions including 
urticaria, angioedema, bronchoconstriction, anaphylaxis§ 

Endocrine disorders 
Common: 
Very rarely:  

 
Hypothyroidism§, hyperthyroidism§ 
Diabetes, aggravated diabetes 

Metabolism and nutrition disorders 
Very common: 
Common:  
Very rarely:  

 
Anorexia 
Hypocalcaemia, dehydration, hyperuricemia, thirst 
Hyperglycaemia, hypertriglyceridaemia§, increased appetite 

Psychiatric disorders§  



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Very common: 
 
Common: 
Rarely:  
Very rarely: 
 
Not known: 

Depression, insomnia, anxiety, emotional lability*, 
agitation, nervousness 
Confusion, sleep disorder, libido decreased 
Suicide ideation 
Suicide, suicide attempts, aggressive behaviour (sometimes 
directed against others), psychosis including hallucinations 
Mental status change§ 

Nervous system disorders§ 
Very common: 
Common: 
 
Very rarely:  
 
 
Not known: 

 
Dizziness, headache, concentration impaired, mouth dry 
Tremor, paresthesia, hypoesthesia, migraine, flushing, 
somnolence, taste perversion 
Cerebrovascular haemorrhage, cerbrovascular ischaemia, 
seizure, impaired consciousness, encephalopathy, 
neuropathy, polyneuropathy 
Mononeuropathies, coma§ 

Eye disorders 
Very common: 
Common: 
 
Rarely:  

 
Vision blurred 
Conjunctivitis, vision abnormal, lacrimal gland disorder, eye 
pain 
Retinal haemorrhages§, retinopathies (including macular 
oedema), retinal artery or vein obstruction§, optic neuritis, 
papilloedema, loss of visual acuity or visual field, cotton-
wool spots§  

Ear and labyrinth 
Common: 
Very rarely:  

 
Vertigo, tinnitus 
Hearing loss, hearing disorder 

Cardiac disorders 
Common: 
Rarely: 
Very rarely: 
Not known: 

 
Palpitation, tachycardia 
Cardiomyopathy 
Myocardial infarction, cardiac ischaemia  
Arrhythmia  

Vascular disorders 
Common: 
Very rarely:  

 
Hypertension 
Peripheral ischaemia, hypotension§ 

Respiratory, thoracic and mediastinal 
disorders 
Very common: 
Common: 
 
Very rarely:  

 
 
Dyspnoea*, coughing* 
Epistaxis, respiratory disorder, nasal congestion, rhinorrhea, 
cough nonproductive 
Pulmonary infiltrates§, pneumonitis§ 

Gastrointestinal disorders 
Very common: 
 
Common: 
 
Very rarely:  
 
Not known: 

 
Nausea/vomiting, abdominal pain, diarrhoea, stomatitis, 
dyspepsia 
Stomatitis ulcerative, right upper quadrant pain, glossitis, 
gingivitis, constipation, loose stools 
Pancreatitis, ischaemic colitis, ulcerative colitis, gingival 
bleeding 
Periodontal disorder NOS, dental disorder NOS§ 

Hepatobiliary disorders 
Common: 
Very rarely:  

 
Hepatomegaly 
Hepatotoxicity, (including fatality) 

Skin and subcutaneous tissue disorders 
Very common: 
Common: 

 
Alopecia, pruritus*, skin dry*, rash*, sweating increased 
Psoriasis (new or aggravated)§, rash maculopapular, rash 



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Very rarely:  

erythematous, eczema, erythema, skin disorder 
Stevens Johnson syndrome, toxic epidermal necrolysis, 
erythema multiforme 

Musculoskeletal and connective tissue 
disorders 
Very common:  
Common: 
Very rarely: 

 
 
Myalgia, arthralgia, musculoskeletal pain 
Arthritis 
Rhabdomyolysis, myositis, leg cramps, back pain 

Renal and urinary disorders 
Common: 
Very rarely:  

 
Micturition frequency 
Renal failure, renal insufficiency, nephrotic syndrome 

Reproductive system and breast 
disorders 
Common: 

 
 
Amenorrhea, breast pain, dysmenorrhea, menorrhagia, 
menstrual disorder, vaginal disorder 

General disorders and administration 
site conditions 
Very common: 
 
 
Common: 
Very rarely: 

 
 
Injection site inflammation, injection site reaction*, fatigue, 
rigors, fever§, flu-like symptoms§, asthenia, irritability, chest 
pain, malaise 
Injection site pain 
Injection site necrosis, face oedema 

Investigations 
Very common: 

 
Weight decrease 

*These events were only common with Viraferon alone 
§See section 4.4 
 
These undesirable effects have also been reported with Viraferon alone. 
 
Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-
existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4). Cardiomyopathy, that may 
be reversible upon discontinuation of interferon alpha, has been reported rarely in patients without prior 
evidence of cardiac disease (see section 4.4).  
 
A wide variety of autoimmune and immune-mediated disorders have been reported with alpha interferons 
including thyroid disorders, systemic lupus erythematosus, rheumatoid arthritis (new or aggravated), 
idiopathic and thrombotic thrombocytopenic purpura, vasculitis, neuropathies including mononeuropathies 
(see also section 4.4).  
 
Clinically significant laboratory abnormalities, most frequently occurring at doses greater than 10 million IU 
daily, include reduction in granulocyte and white blood cell counts; decreases in haemoglobin level and 
platelet count; increases in alkaline phosphatase, LDH, serum creatinine and serum urea nitrogen levels. 
Increase in serum ALT/AST (SGPT/SGOT) levels have been noted as an abnormality in some non-hepatitis 
subjects and also in some patients with chronic hepatitis B coincident with clearance of viral DNAp. 
 
For safety with respect to transmissible agents, see section 4.4. 
 
Paediatric population 
 
Children and adolescents – Chronic Hepatitis C 
In clinical trials of 118 children or adolescents 3 to 16 years of age, 6 % discontinued therapy due to adverse 
events. In general, the adverse event profile in the limited paediatric population studied was similar to that 
observed in adults, although there is a paediatric specific concern regarding growth inhibition as decrease in 
height (mean percentile decrease of growth velocity of 9 %) and weight (mean percentile decrease of 13 %) 



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percentile were observed during treatment (see section 4.4). Furthermore, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6 month 
follow-up after treatment. As in adult patients, children and adolescents also experienced other psychiatric 
adverse events (e.g., depression, emotional lability, and somnolence) (see section 4.4). In addition, injection 
site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in children and 
adolescents compared to adult patients. Dose modifications were required in 30 % of patients, most 
commonly for anaemia and neutropaenia. 
 
The adverse reactions listed in Table 2 are based on experience from paediatric clinical trials.  
Within the organ system classes, adverse reactions are listed under headings of frequency using the following 
categories: very common (≥1/10); common (≥1/100, <1/10). Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness. 
 
Table 2  Adverse reactions very commonly and commonly reported in paediatric clinical trials  

Very common (≥1/10) - Common (≥1/100, <1/10) 
System Organ Class Adverse Reactions 
Infection and infestations 
Very common: 
Common: 

 
Viral infection, pharyngitis 
Fungal infection, bacterial infection, pulmonary infection, otitis 
media, tooth abscess, herpes simplex, urinary tract infection, 
vaginitis, gastroenteritis 

Neoplasms benign, malignant 
and unspecified (including 
cysts and polyps) 
Common: 

 
 
 
Neoplasm (unspecified) 

Blood and lymphatic system 
disorders 
Very common: 
Common: 

 
 
Anaemia, neutropaenia 
Thrombocytopaenia, lymphadenopathy 

Endocrine disorders 
Very common: 
Common: 

 
Hypothyroidism§,  
Hyperthyroidism§, virilism 

Metabolism and nutrition 
disorders 
Very common: 
Common: 

 
 
Anorexia 
Hypertriglyceridemia§, hyperuricemia, increased appetite 

Psychiatric disorders§ 
Very common: 
Common: 

 
Depression, emotional lability, insomnia 
Suicidal ideation, aggressive reaction, confusion, behaviour 
disorder, agitation, somnambulism, anxiety, nervousness, sleep 
disorder, abnormal dreaming, apathy 

Nervous system disorders§ 
Very common: 
Common: 

 
Headache, dizziness 
Hyperkinesia, tremor, dysphonia, paresthaesia, hypoaesthesia, 
hyperaesthesia, concentration impaired, somnolence 

Eye disorders 
Common: 

 
Conjunctivitis, eye pain, abnormal vision, lacrimal gland disorder 

Vascular disorders 
Common: 

 
Raynaud’s disease, flushing, pallor 

Respiratory, thoracic and 
mediastinal disorders 
Common: 

 
 
Dyspnoea, tachypnea, epistaxis, coughing, nasal congestion, nasal 
irritation, rhinorrhea, sneezing 

Gastrointestinal disorders  



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Very common: 
Common: 

Diarrhoea, vomiting, nausea, abdominal pain 
Mouth ulceration, stomatitis ulcerative, stomatitis, right upper 
quadrant pain, dyspepsia, glossitis, gastroesophogeal reflux, rectal 
disorder, gastrointestinal disorder, constipation, loose stools, 
toothache, tooth disorder 

Hepatobiliary disorders 
Common: 

 
Hepatic function abnormal 

Skin and subcutaneous tissue 
disorders  
Very common: 
Common: 

 
 
Alopecia, rash 
Photosensitivity reaction, maculopapular rash, eczema, acne, skin 
disorder, nail disorder, skin discolouration, pruritus, dry skin, 
erythema, bruise, sweating increased 

Musculoskeletal and 
connective tissue disorders 
Very common: 

 
 
Arthralgia, myalgia, musculoskeletal pain  

Renal and urinary disorders 
Common: 

 
Enuresis, micturition disorder, urinary incontinence 

Reproductive system and 
breast disorders 
Common: 

 
 
Female: amenorrhea, menorrhagia, menstrual disorder, vaginal 
disorder 
Male: testicular pain 

General disorders and 
administration site 
conditions 
Very common: 
 
Common: 

 
 
 
Injection site inflammation, injection site reaction, fatigue, rigors, 
fever§, influenza-like symptoms§, malaise, irritability 
Chest pain, asthenia, oedema, injection site pain 

Investigations 
Very common: 

 
Growth rate decrease (height and/or weight decrease for age)§  

Injury and poisoning 
Common: 

 
Skin laceration 

§See section 4.4 
 
4.9 Overdose 
 
No case of overdose has been reported that has led to acute clinical manifestations. However, as for any 
pharmacologically active compound, symptomatic treatment with frequent monitoring of vital signs and close 
observation of the patient is indicated. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunostimulants, cytokines and immunomodulators, interferons, interferon 
alfa-2b, ATC code: L03A B05 
 
Viraferon is a sterile, stable, formulation of highly purified interferon alfa-2b produced by recombinant DNA 
techniques. Recombinant interferon alfa-2b is a water-soluble protein with a molecular weight of 
approximately 19,300 daltons. It is obtained from a clone of E. coli, which harbours a genetically engineered 
plasmid hybrid encompassing an interferon alfa-2b gene from human leukocytes. 
 



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The activity of Viraferon is expressed in terms of IU, with 1 mg of recombinant interferon alfa-2b protein 
corresponding to 2.6 x l08 IU. International Units are determined by comparison of the activity of the 
recombinant interferon alfa-2b with the activity of the international reference preparation of human leukocyte 
interferon established by the World Health Organisation. 
 
The interferons are a family of small protein molecules with molecular weights of approximately 15,000 to 
21,000 daltons. They are produced and secreted by cells in response to viral infections or various synthetic 
and biological inducers. Three major classes of interferons have been identified: alpha, beta and gamma. 
These three main classes are themselves not homogeneous and may contain several different molecular 
species of interferon. More than 14 genetically distinct human alpha interferons have been identified. 
Viraferon has been classified as recombinant interferon alfa-2b. 
 
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. 
Human interferon receptors, as isolated from human lymphoblastoid (Daudi) cells, appear to be highly 
asymmetric proteins. They exhibit selectivity for human but not murine interferons, suggesting species 
specificity. Studies with other interferons have demonstrated species specificity. However, certain monkey 
species, eg, rhesus monkeys, are susceptible to pharmacodynamic stimulation upon exposure to human type 
1 interferons. 
 
The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex 
sequence of intracellular events that include the induction of certain enzymes. It is thought that this process, 
at least in part, is responsible for the various cellular responses to interferon, including inhibition of virus 
replication in virus-infected cells, suppression of cell proliferation and such immunomodulating activities as 
enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of 
lymphocytes for target cells. Any or all of these activities may contribute to interferon's therapeutic effects. 
 
Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and 
human cell culture systems as well as human tumour xenografts in animals. It has demonstrated significant 
immunomodulatory activity in vitro. 
 
Recombinant interferon alfa-2b also inhibits viral replication in vitro and in vivo. Although the exact antiviral 
mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism. 
This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell. 
 
Chronic hepatitis B: 
Current clinical experience in patients who remain on interferon alfa-2b for 4 to 6 months indicates that 
therapy can produce clearance of serum HBV-DNA. An improvement in liver histology has been observed. 
In adult patients with loss of HBeAg and HBV-DNA, a significant reduction in morbidity and mortality has 
been observed. 
 
Interferon alfa-2b (6 MIU/m2 3 times a week for 6 months) has been given to children with chronic active 
hepatitis B. Because of a methodological flaw, efficacy could not be demonstrated. Moreover children treated 
with interferon alfa-2b experienced a reduced rate of growth and some cases of depression were observed. 
 
Chronic hepatitis C: 
In adult patients receiving interferon in combination with ribavirin, the achieved sustained response rate is 
47 %. Superior efficacy has been demonstrated with the combination of pegylated interferon with ribavirin 
(sustained response rate of 61 % achieved in a study performed in naïve patients with a ribavirin dose 
> 10.6 mg/kg, p < 0.01). 
 
Adult patients: Viraferon alone or in combination with ribavirin has been studied in 4 randomised Phase III 
clinical trials in 2,552 interferon-naïve patients with chronic hepatitis C. The trials compared the efficacy of 
Viraferon used alone or in combination with ribavirin. Efficacy was defined as sustained virologic response, 
6 months after the end of treatment. Eligible patients for these trials had chronic hepatitis C confirmed by a 
positive HCV-RNA polymerase chain reaction assay (PCR) (> 100 copies/ml), a liver biopsy consistent with 



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a histologic diagnosis of chronic hepatitis with no other cause for the chronic hepatitis, and abnormal serum 
ALT. 
 
Viraferon was administered at a dose of 3 MIU 3 times a week as monotherapy or in combination with 
ribavirin. The majority of patients in these clinical trials were treated for one year. All patients were followed 
for an additional 6 months after the end of treatment for the determination of sustained virologic response. 
Sustained virologic response rates for treatment groups treated for one year with Viraferon alone or in 
combination with ribavirin (from two studies) are shown in Table 3. 
 
Co-administration of Viraferon with ribavirin increased the efficacy of Viraferon by at least two fold for the 
treatment of chronic heptatitis C in naïve patients. HCV genotype and baseline virus load are prognostic 
factors which are known to affect response rates. The increased response rate to the combination of Viraferon + 
ribavirin, compared with Viraferon alone, is maintained across all subgroups. The relative benefit of combination 
therapy with Viraferon + ribavirin is particularly significant in the most difficult to treat subgroup of patients 
(genotype 1 and high virus load) (Table 3). 
 
Response rates in these trials were increased with compliance. Regardless of genotype, patients who received 
Viraferon in combination with ribavirin and received ≥ 80 % of their treatment had a higher sustained 
response 6 months after 1 year of treatment than those who took < 80 % of their treatment (56 % vs. 32 % in 
trial C/I98-580).  



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Table 3 Sustained virologic response rates with Viraferon + ribavirin (one year of 

treatment) by genotype and viral load 
 

HCV Genotype  
 

I 
N=503 

C95-132/I95-143 

I/R 
N=505 

C95-132/I95-143 

I/R 
N=505 

C/I98-580 
 
All Genotypes 

 
16 % 

 
41 % 

 
47 % 

 
 
Genotype 1 

 
9 % 

 
29 % 

 
33 % 

 
Genotype 1  
≤ 2 million 
copies/ml 

 
25 % 

 
33 % 

 
45 % 

 
Genotype 1 
> 2 million 
copies/ml 

 
3 % 

 
27 % 

 

 
29 % 

 
Genotype 2/3 

 
31 % 

 
65 % 

 
79 % 

I Viraferon (3 MIU 3 times a week) 
I/R Viraferon (3 MIU 3 times a week) + ribavirin (1,000/1,200 mg/day) 
 
HCV/HIV Co-infected patients  
Two trials have been conducted in patients co-infected with HIV and HCV. Overall, in both studies, patients 
who received Viraferon plus ribavirin, were less likely to respond than patients who received pegylated 
interferon alfa-2b with ribavirin. The response to treatment in both of these trials is presented in Table 4. 
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 412 previously untreated 
adult patients with chronic hepatitis C who were co-infected with HIV. Patients were randomized to receive 
either pegylated interferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800 mg/day) or Viraferon (3 MIU TIW) 
plus ribavirin (800 mg/day) for 48 weeks with a follow-up period of 6 months. Study 2 (P02080) was a 
randomized, single centre study that enrolled 95 previously untreated adult patients with chronic hepatitis C 
who were co-infected with HIV. Patients were randomized to receive either pegylated interferon alfa-2b (100 
or 150 µg /week based on weight) plus ribavirin (800-1,200 mg/day based on weight) or Viraferon (3 MIU 
TIW) plus ribavirin (800-1,200 mg/day based on weight). The duration of therapy was 48 weeks with a 
follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load 
< 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6-month follow-up period.  



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Table 4 Sustained virological response based on genotype after Viraferon in combination with 

ribavirin versus pegylated interferon alfa-2b in combination with ribavirin in 
HCV/HIV co-infected patients 

 Study 11 Study 22 
 

pegylated 
interferon 

alfa-2b  
(1.5 µg/kg/ 

week) + 
ribavirin  
(800 mg) 

Viraferon  
(3 MIU TIW) +  

ribavirin  
(800 mg) 

p 
valuea 

pegylated 
interferon 

alfa-2b (100 
or  

150c µg/week) 
+ ribavirin 

(800- 
1,200 mg)d 

Viraferon  
(3 MIU TIW) 

+ ribavirin 
(800- 

1,200 mg)d 
p 

valueb 
All 27 % (56/205) 20 % (41/205) 0.047 44 % (23/52) 21 % (9/43) 0.017 
Genotype 1, 

4 
17 % (21/125) 6 % (8/129) 0.006 38 % (12/32) 7 % (2/27) 0.007 

Genotype 2, 
3 

44 % (35/80) 43 % (33/76) 0.88 53 % (10/19) 47 % (7/15) 0.730 

MIU = million international units; TIW = three times a week. 
a:  p value based on Cochran-Mantel Haenszel Chi square test. 
b:  p value based on chi-square test. 
c:  subjects < 75 kg received 100 µg/week pegylated interferon alfa-2b and subjects ≥ 75 kg received 150 µg/week pegylated 

interferon alfa-2b. 
d: ribavirin dosing was 800 mg for patients < 60 kg, 1,000 mg for patients 60-75 kg, and 1,200 mg for patients > 75 kg. 
 

1Carrat F, Bani-Sadr F, Pol S et al.  JAMA 2004; 292(23): 2839-2848. 
2 Laguno M, Murillas J, Blanco J.L et al.  AIDS 2004; 18(13): F27-F36. 
 
 
Relapse patients: A total of 345 interferon alpha relapse patients were treated in two clinical trials with 
Viraferon monotherapy or in combination with ribavirin. In these patients, the addition of ribavirin to 
Viraferon increased by as much as 10-fold the efficacy of Viraferon used alone in the treatment of chronic 
hepatitis C (48.6 % vs. 4.7 %). This enhancement in efficacy included loss of serum HCV (< 100 copies/ml 
by PCR), improvement in hepatic inflammation, and normalisation of ALT, and was sustained when 
measured 6 months after the end of treatment. 
 
Long-Term efficacy data 
In a large study, 1,071 patients were enrolled after treatment in a prior non pegylated interferon alfa-2b or 
non pegylated interferon alfa-2b/ribavirin study to evaluate the durability of sustained virologic response and 
assess the impact of continued viral negativity on clinical outcomes. 462 patients completed at least 5 years 
of long-term follow-up and only 12 sustained responders' out of 492 relapsed during this study.  
The Kaplan-Meier estimate for continued sustained response over 5 years for all patients is 97 % with a 95 % 
Confidence Interval of [95 %, 99 %].  
SVR after treatment of chronic HCV with non pegylated interferon alfa-2b (with or without ribavirin) results 
in long-term clearance of the virus providing resolution of the hepatic infection and clinical 'cure' from 
chronic HCV. However, this does not preclude the occurrence of hepatic events in patients with cirrhosis 
(including hepatocarcinoma). 
 
Clinical trials in paediatric patients with chronic hepatitis C: 
Children and adolescents 3 to 16 years of age with compensated chronic hepatitis C and detectable HCV-
RNA (assessed by a central laboratory using a research-based RT-PCR assay) were enrolled in two 
multicentre trials and received Viraferon 3 MIU/m2 3 times a week plus ribavirin 15 mg/kg per day for 1 year 
followed by 6 months follow-up after-treatment. A total of 118 patients were enrolled: 57 % male, 80 % 
Caucasian, and 78 % genotype 1,64 % ≤ 12 years of age. The population enrolled mainly consisted in 
children with mild to moderate hepatitis C. Sustained virological response rates in children and adolescents 



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were similar to those in adults. Due to the lack of data in children with severe progression of the disease, and 
the potential for undesirable effects, the benefit/risk of the combination of ribavirin and interferon alfa-2b 
needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8). 
 
Study results are summarized in Table 5. 
 
Table 5. Virological response in previously untreated paediatric patients 
 Viraferon 3 MIU/m2 3 times a week   

+ 
ribavirin 15 mg/kg/day 

Overall Response1 (n=118) 54 (46 %)* 

Genotype 1 (n=92) 33 (36 %)* 

Genotype 2/3/4 (n=26) 21 (81 %)* 

*Number (%) of patients 
1. Defined as HCV-RNA below limit of detection using a research based RT-PCR assay at end of treatment and during follow-up 
period 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of Viraferon were studied in healthy volunteers following single 5 million IU/m2 and 
10 million IU doses administered subcutaneously, at 5 million IU/m2 administered intramuscularly and as a 
30-minute intravenous infusion. The mean serum interferon concentrations following subcutaneous and 
intramuscular injections were comparable. Cmax occurred three to 12 hours after the lower dose and six to 
eight hours after the higher dose. The elimination half-lives of interferon injections were approximately two 
to three hours, and six to seven hours, respectively. Serum levels were below the detection limit 16 and 
24 hours, respectively, post-injection. Both subcutaneous and intramuscular administration resulted in 
bioavailabilities greater than 100 %. 
 
After intravenous administration, serum interferon levels peaked (135 to 273 IU/ml) by the end of the 
infusion, then declined at a slightly more rapid rate than after subcutaneous or intramuscular administration 
of medicinal product, becoming undetectable four hours after the infusion. The elimination half-life was 
approximately two hours. 
 
Urine levels of interferon were below the detection limit following each of the three routes of administration. 
 
Children and adolescents: Multiple-dose pharmacokinetic properties for Viraferon injection and ribavirin 
capsules in children and adolescents with chronic hepatitis C, between 5 and 16 years of age, are summarized 
in Table 6. The pharmacokinetics of Viraferon and ribavirin (dose-normalized) are similar in adults and 
children or adolescents. 



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Table 6. Mean (% CV) multiple-dose pharmacokinetic parameters for Viraferon and ribavirin 

capsules when administered to children or adolescents with chronic hepatitis C 
Parameter Ribavirin 

15 mg/kg/day as 2 divided 
doses 

(n = 17) 

Viraferon 
3 MIU/m2 3 times a week 

(n = 54) 

Tmax (hr) 1.9 (83) 5.9 (36) 
Cmax (ng/ml) 3,275 (25) 51 (48) 

AUC* 29,774 (26) 622 (48) 
Apparent clearance l/hr/kg 0.27 (27) Not done 

*AUC12 (ng.hr/ml) for ribavirin; AUC0-24 (IU.hr/ml) for Viraferon 
 
Interferon neutralising factor assays were performed on serum samples of patients who received Viraferon in 
Schering-Plough monitored clinical trials. Interferon neutralising factors are antibodies which neutralise the 
antiviral activity of interferon. The clinical incidence of neutralising factors developing in cancer patients 
treated systemically is 2.9 % and in chronic hepatitis patients is 6.2 %. The detectable titres are low in almost 
all cases and have not been regularly associated with loss of response or any other autoimmune phenomenon. 
In patients with hepatitis, no loss of response was observed apparently due to the low titres. 
 
5.3 Preclinical safety data 
 
Although interferon is generally recognised as being species specific, toxicity studies in animals were 
conducted. Injections of human recombinant interferon alfa-2b for up to three months have shown no 
evidence of toxicity in mice, rats, and rabbits. Daily dosing of cynomolgus monkeys with 20 x 106 IU/kg/day 
for 3 months caused no remarkable toxicity. Toxicity was demonstrated in monkeys given 
100 x 106 IU/kg/day for 3 months. 
 
In studies of interferon use in non-human primates, abnormalities of the menstrual cycle have been observed 
(see section 4.4). 
 
Results of animal reproduction studies indicate that recombinant interferon alfa-2b was not teratogenic in rats 
or rabbits, nor did it adversely affect pregnancy, foetal development or reproductive capacity in offspring of 
treated rats. Interferon alfa-2b has been shown to have abortifacient effects in Macaca mulatta (rhesus 
monkeys) at 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2. 
Abortion was observed in all dose groups (7.5 million, 15 million and 30 million IU/kg), and was statistically 
significant versus control at the mid- and high-dose groups (corresponding to 90 and 180 times the 
recommended intramuscular or subcutaneous dose of 2 million IU/m2). High doses of other forms of 
interferons alpha and beta are known to produce dose-related anovulatory and abortifacient effects in rhesus 
monkeys. 
 
Mutagenicity studies with interferon alfa-2b revealed no adverse events. 
 
No studies have been conducted in juvenile animals to examine the effects of treatment with interferon alfa-
2b on growth, development, sexual maturation, and behaviour (see section 4.4 and Rebetol SPC if Viraferon 
is to be administered in combination with ribavirin). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Glycine,  
Disodium phosphate anhydrous,  



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Sodium dihydrogen phosphate monohydrate, 
Human albumin solution. 
 
Solvent: water for injections 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
3 years 
 
After reconstitution: An immediate use is recommended. However, the chemical and physical in-use stability 
has been demonstrated for 24 hours at 25ºC. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C).  
Do not freeze.  
Within its shelf-life, for the purpose of transport and/or to facilitate ambulatory use the non-reconstituted 
product can be kept at or below 25°C for a period up to four weeks before use. If the product is not 
reconstituted during the four-week period, it cannot be put back in the refrigerator for a new storage period 
and must be discarded. 
 
6.5 Nature and contents of container 
 
24 mg of powder (corresponding to 3 MIU) in a vial (type I glass), with a stopper (butyl rubber) in a flip-off 
seal (aluminium) with a bonnet (polypropylene) 
and 1 ml of water for injections in an ampoule (type I glass) 
with 1 injection syringe, 2 injection needles and 1 cleansing swab. 
Pack sizes of 1 
 
Or 
 
24 mg of powder (corresponding to 3 MIU) in a vial (type I glass), with a stopper (butyl rubber) in a flip-off 
seal (aluminium) with a bonnet (polypropylene) 
and 1 ml of water for injections in an ampoule (type I glass) 
Pack sizes of 6 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
Reconstitution of Viraferon, powder for solution for injection, for parenteral administration: Viraferon is 
supplied as a powder at strengths of 3 million IU/ml for single-dose use. Vials must be reconstituted with 
1 ml of water for injections. The reconstituted solutions are isotonic for parenteral administration. 
 
Proper precautions should be taken during reconstitution to prevent microbial contamination (refer to package 
leaflet).  
 



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Using a sterilised injection syringe and injection needle, inject 1 ml water for injections into the vial of 
Viraferon. Agitate gently to facilitate complete dissolution of the powder. The appropriate dose can then be 
withdrawn with a sterile injection syringe and injected. 
 
As for all parenteral medicinal products, inspect the reconstituted solution visually for particulate matter and 
discoloration prior to administration. The reconstituted solution should be clear and colourless. 
 
Detailed instructions for the subcutaneous use of the product are provided with the package leaflet (refer to 
“How to self inject Viraferon”). 
 
Any unused product must be discarded after withdrawal of the dose. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
SP Europe 
73, rue de Stalle 
B-1180 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/99/128/002 
EU/1/99/128/003 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation : 9 March 2000 
Date of last renewal : 23 May 2005 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu/ 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 5 million IU/ml powder and solvent for solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One vial of powder contains 5 million IU of interferon alfa-2b produced in E.coli by recombinant DNA 
technology. 
After reconstitution, 1 ml contains 5 million IU of interferon alfa-2b. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection 
 
White to cream coloured powder.  
Clear and colourless solvent. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Chronic Hepatitis B: Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis B 
viral replication (presence of HBV-DNA and HBeAg), elevated alanine aminotransferase (ALT) and 
histologically proven active liver inflammation and/or fibrosis. 
 
Chronic Hepatitis C:  
Adult patients:  
Viraferon is indicated for the treatment of adult patients with chronic hepatitis C who have elevated 
transaminases without liver decompensation and who are positive for serum HCV-RNA or anti-HCV (see 
section 4.4). 
 
The best way to use Viraferon in this indication is in combination with ribavirin. 
 
Chidren and adolescents: 
Viraferon is intended for use, in a combination regimen with ribavirin, for the treatment of children and 
adolescents 3 years of age and older, who have chronic hepatitis C, not previously treated, without liver 
decompensation, and who are positive for serum HCV-RNA. The decision to treat should be made on a case 
by case basis, taking into account any evidence of disease progression such as hepatic inflammation and 
fibrosis, as well as prognostic factors for response, HCV genotype and viral load. The expected benefit of 
treatment should be weighed against the safety findings observed for paediatric subjects in the clinical trials 
(see sections 4.4, 4.8 and 5.1). 
 
4.2 Posology and method of administration 
 
Treatment must be initiated by a physician experienced in the management of the disease. 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 



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If adverse events develop during the course of treatment with Viraferon for any indication, modify the dosage 
or discontinue therapy temporarily until the adverse events abate. If persistent or recurrent intolerance 
develops following adequate dosage adjustment, or disease progresses, discontinue treatment with Viraferon. 
At the discretion of the physician, the patient may self-administer the dose for maintenance dosage regimens 
administered subcutaneously. 
 
Chronic Hepatitis B: The recommended dosage is in the range 5 to 10 million IU administered 
subcutaneously three times a week (every other day) for a period of 4 to 6 months. 
 
The administered dose should be reduced by 50 % in case of occurrence of haematological disorders (white 
blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3). Treatment should be 
discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe 
thrombocytopaenia (< 70,000/mm3). 
 
For all patients, if no improvement on serum HBV-DNA is observed after 3 to 4 months of treatment (at the 
maximum tolerated dose), discontinue Viraferon therapy. 
 
Chronic Hepatitis C: Viraferon is administered subcutaneously at a dose of 3 million IU three times a week 
(every other day) to adult patients, whether administered as monotherapy or in combination with ribavirin. 
 
Children 3 years of age or older and adolescents: Interferon alfa-2b 3 MIU/m2 is administered 
subcutaneously 3 times a week (every other day) in combination with ribavirin capsules or oral solution 
administered orally in two divided doses daily with food (morning and evening).  
 
(See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination 
therapy. For paediatric patients who weigh < 47 kg or cannot swallow capsules, see ribavirin oral solution 
SPC).  
 
Relapse patients (adults): 
Viraferon is given in combination with ribavirin. 
 
Based on the results of clinical trials, in which data are available for 6 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for 6 months. 
 
Naïve patients: 
Adults: The efficacy of Viraferon is enhanced when given in combination with ribavirin. Viraferon should be 
given alone mainly in case of intolerance or contraindication to ribavirin. 
 
Viraferon in combination with ribavirin: 
Based on the results of clinical trials, in which data are available for 12 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for at least 6 months. 
 
Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit 
negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and 
high pre-treatment viral load. 
 
Other negative prognostic factors (age > 40 years, male gender, bridging fibrosis) should be taken into 
account in order to extend therapy to 12 months. 
 
During clinical trials, patients who failed to show a virologic response after 6 months of treatment (HCV-
RNA below lower limit of detection) did not become sustained virologic responders (HCV-RNA below lower 
limit of detection six months after withdrawal of treatment). 
 
Viraferon alone: 



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The optimal duration of therapy with Viraferon alone is not yet fully established, but a therapy of between 
12 and 18 months is advised. 
 
It is recommended that patients be treated with Viraferon alone for at least 3 to 4 months, at which point 
HCV-RNA status should be determined. Treatment should be continued in patients who exhibit negative 
HCV-RNA. 
 
Children and adolescents: The efficacy and safety of Viraferon in combination with ribavirin has been 
studied in children and adolescents who have not been previously treated for chronic hepatitis C.  
 
Genotype 1: The recommended duration of treatment is one year. Patients who fail to achieve virological 
response at 12 weeks are highly unlikely to become sustained virological responders (negative predictive 
value 96 %). Virological response is defined as absence of detectable HCV-RNA at Week 12. Treatment 
should be discontinued in these patients. 
Genotype 2/3: The recommended duration of treatment is 24 weeks. 
 
Virological responses after 1 year of treatment and 6 months of follow-up were 36 % for genotype 1 and 
81 % for genotype 2/3/4. 
 
Viraferon may be administered using either glass or plastic disposable injection syringes. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients. 
- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure, recent 

myocardial infarction, severe arrhythmic disorders.  
- Severe renal or hepatic dysfunction; including that caused by metastases. 
- Epilepsy and/or compromised central nervous system (CNS) function (see section 4.4). 
- Chronic hepatitis with decompensated cirrhosis of the liver. 
- Chronic hepatitis in patients who are being or have been treated recently with immunosuppressive 

agents excluding short term corticosteroid withdrawal. 
- Autoimmune hepatitis; or history of autoimmune disease; immunosuppressed transplant recipients. 
- Pre-existing thyroid disease unless it can be controlled with conventional treatment. 
 
Children and adolescents: 
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal 

ideation or suicide attempt. 
 

Combination therapy with ribavirin: Also see ribavirin SPC if interferon alfa-2b is to be administered in 
combination with ribavirin in patients with chronic hepatitis C. 
 
4.4 Special warnings and precautions for use 
 
For all patients: 
Psychiatric and central nervous system (CNS): Severe CNS effects, particularly depression, suicidal ideation 
and attempted suicide have been observed in some patients during Viraferon therapy, and even after 
treatment discontinuation mainly during the 6-month follow-up periodand in the follow-up period. Among 
children and adolescents treated with Viraferon in combination with ribavirin, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6-month 
follow-up after treatment. As in adult patients, children and adolescents experienced other psychiatric adverse 
events (e.g., depression, emotional lability, and somnolence). Other CNS effects including aggressive behaviour 
(sometimes directed against others), confusion and alterations of mental status have been observed with alpha 
interferons. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such 
symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the 
prescribing physician and the need for adequate therapeutic management should be considered. If psychiatric 



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symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with 
Viraferon be discontinued, and the patient followed, with psychiatric intervention as appropriate. 
 
Patients with existence of or history of severe psychiatric conditions: 
If a treatment with interferon alfa-2b is judged necessary in adult patients with existence or history of severe 
psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and 
therapeutic management of the psychiatric condition. The use of interferon alfa-2b in children and adolescents 
with existence of or history of severe psychiatric conditions is contraindicated (see section 4.3). 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Moderate to severe adverse experiences may require modification of the patient's dosage regimen, or in some 
cases, termination of Viraferon therapy. Any patient developing liver function abnormalities during treatment 
with Viraferon must be monitored closely and treatment discontinued if signs and symptoms progress. 
 
Hypotension may occur during Viraferon therapy or up to two days post-therapy and may require supportive 
treatment. 
 
Adequate hydration must be maintained in patients undergoing Viraferon therapy since hypotension related 
to fluid depletion has been seen in some patients. Fluid replacement may be necessary. 
 
While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, 
other causes of persistent fever must be ruled out. 
 
Viraferon must be used cautiously in patients with debilitating medical conditions, such as those with a 
history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to 
ketoacidosis. Caution must be observed also in patients with coagulation disorders (e.g., thrombophlebitis, 
pulmonary embolism) or severe myelosuppression. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.5). Any patient developing fever, cough, 
dyspnea or other respiratory symptoms must have a chest X-ray taken. If the chest X-ray shows pulmonary 
infiltrates or there is evidence of pulmonary function impairment, the patient is to be monitored closely, and, 
if appropriate, discontinue interferon alpha. While this has been reported more often in patients with chronic 
hepatitis C treated with interferon alpha, it has also been reported in patients with oncologic diseases treated 
with interferon alpha. Prompt discontinuation of interferon alpha administration and treatment with 
corticosteroids appear to be associated with resolution of pulmonary adverse events. 
 
Ocular adverse events (see section 4.8) including retinal haemorrhages, cotton wool spots, and retinal artery 
or vein obstruction have been reported in rare instance after treatment with alpha interferons. All patients 
should have a baseline eye examination. Any patient complaining of changes in visual acuity or visual fields, 
or reporting other ophthalmologic symptoms during treatment with Viraferon, must have a prompt and 
complete eye examination. Periodic visual examinations during Viraferon therapy are recommended 
particularly in patients with disorders that may be associated with retinopathy, such as diabetes mellitus or 
hypertension. Discontinuation of Viraferon should be considered in patients who develop new or worsening 
ophthalmological disorders. 



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More significant obtundation and coma, including cases of encephalopathy, have been observed in some 
patients, usually elderly, treated at higher doses. While these effects are generally reversible, in a few patients 
full resolution took up to three weeks. Very rarely, seizures have occurred with high doses of Viraferon. 
 
Adult patients with a history of congestive heart failure, myocardial infarction and/or previous or current 
arrhythmic disorders, who require Viraferon therapy, must be closely monitored. It is recommended that 
those patients who have pre-existing cardiac abnormalities and/or are in advanced stages of cancer have 
electrocardiograms taken prior to and during the course of treatment. Cardiac arrhythmias (primarily 
supraventricular) usually respond to conventional therapy but may require discontinuation of Viraferon 
therapy. There are no data in children or adolescents with a history of cardiac disease. 
 
Hypertriglyceridemia and aggravation of hypertriglyceridemia, sometimes severe, have been observed. 
Monitoring of lipid levels is, therefore, recommended. 
 
Due to reports of interferon alpha exacerbating pre-existing psoriatic disease and sarcoidosis, use of 
Viraferon in patients with psoriasis or sarcoidosis is recommended only if the potential benefit justifies the 
potential risk. 
 
Preliminary data indicates that interferon alpha therapy may be associated with an increased rate of kidney 
graft rejection. Liver graft rejection has also been reported. 
 
The development of auto-antibodies and autoimmune disorders has been reported during treatment with alpha 
interferons. Patients predisposed to the development of autoimmune disorders may be at increased risk. 
Patients with signs or symptoms compatible with autoimmune disorders should be evaluated carefully, and 
the benefit-risk of continued interferon therapy should be reassessed (see also section 4.4 Chronic hepatitis C, 
Monotherapy (thyroid abnormalities) and section 4.8). 
Cases of Vogt-Koyanagi-Harada (VKH) syndrome have been reported in patients with chronic hepatitis C 
treated with interferon. This syndrome is a granulomatous inflammatory disorder affecting the eyes, auditory 
system, meninges, and skin. If VKH syndrome is suspected, antiviral treatment should be withdrawn and 
corticosteroid therapy discussed (see section 4.8). 
 
Discontinue treatment with Viraferon in patients with chronic hepatitis who develop prolongation of 
coagulation markers which might indicate liver decompensation. 
 
Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of 
human plasma-derived albumin. 
 
Standard measures to prevent infections resulting from the use of medicinal products prepared from human 
blood or plasma include selection of donors, screening of individual donations and plasma pools for specific 
markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of 
viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the 
possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or 
emerging viruses and other pathogens. 
 
There are no reports of virus transmissions with albumin manufactured to European Pharmacopoeia 
specifications by established processes. 
 
It is strongly recommended that every time that Viraferon is administered to a patient, the name and batch 
number of the product are recorded in order to maintain a link between the patient and the batch of the 
product. 
 
Chronic Hepatitis C: 
Combination therapy with ribavirin: Also see ribavirin SPC if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 



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All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i.e. 
patients with genotype 2 and 3), treatment may be possible without histological confirmation. Current 
treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing 
treatment. 
 
Monotherapy: Infrequently, adult patients treated for chronic hepatitis C with Viraferon developed thyroid 
abnormalities, either hypothyroidism or hyperthyroidism. In clinical trials using Viraferon therapy, 2.8 % 
patients overall developed thyroid abnormalities. The abnormalities were controlled by conventional therapy 
for thyroid dysfunction. The mechanism by which Viraferon may alter thyroid status is unknown. Prior to 
initiation of Viraferon therapy for the treatment of chronic hepatitis C, evaluate serum thyroid-stimulating 
hormone (TSH) levels. Any thyroid abnormality detected at that time must be treated with conventional 
therapy. Viraferon treatment may be initiated if TSH levels can be maintained in the normal range by 
medication. Determine TSH levels if, during the course of Viraferon therapy, a patient develops symptoms 
consistent with possible thyroid dysfunction. In the presence of thyroid dysfunction, Viraferon treatment may 
be continued if TSH levels can be maintained in the normal range by medication. Discontinuation of 
Viraferon therapy has not reversed thyroid dysfunction occurring during treatment (also see Children and 
adolescents, Thyroid monitoring). 
 
Supplemental monitoring specific for children and adolescents 
Thyroid Monitoring: Approximately 12 % of children treated with interferon alfa-2b and ribavirin developed 
increase in TSH. Another 4 % had a transient decrease below the lower limit of normal. Prior to initiation of 
Viraferon therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be 
treated with conventional therapy. Viraferon therapy may be initiated if TSH levels can be maintained in the 
normal range by medication. Thyroid dysfunction during treatment with interferon alfa-2b and ribavirin has 
been observed. If thyroid abnormalities are detected, the patient’s thyroid status should be evaluated and 
treated as clinically appropriate. Children and adolescents should be monitored every 3 months for evidence 
of thyroid dysfunction (e.g. TSH). 
 
Growth and Development: During a 1-year course of therapy there was a decrease in the rate of linear growth 
(mean percentile decrease of 9 %) and a decrease in the rate of weight gain (mean percentile decrease of 
13 %). A general reversal of these trends was noted during the 6 months follow-up post treatment. However, 
based on interim data from a long-term follow-up study, 12 (14 %) of 84 children had a > 15 percentile 
decrease in rate of linear growth, of whom 5 (6 %) children had a > 30 percentile decrease despite being off 
treatment for more than 1 year. In addition, preclicinal juvenile toxicity results have demonstrated a minor, 
dose-related decrease in overall growth in neonatal rats dosed with ribavirin (see section 5.3). Therefore, the 
risk/benefit of the combined use of interferon alfa-2b and ribavirin should be assessed in young children prior 
to the initiation of therapy. Physicians are advised to monitor the growth of children taking ribavirin in 
combination with interferon alfa-2b. There are no data on long term effects on growth and development and 
on sexual maturation. 
 
HCV/HIV Coinfection: Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy 
(HAART) may be at increased risk of developing lactic acidosis. Caution should be used when adding Viraferon 
and ribavirin to HAART therapy (see ribavirin SPC). Patients treated with Viraferon and ribavirin combination 
therapy and zidovudine could be at increased risk of developing anaemia. 
Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic 
decompensation and death. Adding treatment with alfa interferons alone or in combination with ribavirin may 
increase the risk in this patient subset.  
 
Dental and periodontal disorders: Dental and periodontal disorders, which may lead to loss of teeth, have 
been reported in patients receiving Viraferon and ribavirin combination therapy. In addition, dry mouth could 
have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the 
combination of Viraferon and ribavirin. Patients should brush their teeth thoroughly twice daily and have 
regular dental examinations. In addition some patients may experience vomiting. If this reaction occurs, they 
should be advised to rinse out their mouth thoroughly afterwards. 



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Laboratory Tests:  
Standard haematological tests and blood chemistries (complete blood count and differential, platelet count, 
electrolytes, liver enzymes, serum protein, serum bilirubin and serum creatinine) are to be conducted in all 
patients prior to and periodically during systemic treatment with Viraferon. 
 
During treatment for hepatitis B or C the recommended testing schedule is at weeks 1, 2, 4, 8, 12, 16, and 
every other month, thereafter, throughout treatment. If ALT flares during Viraferon therapy to greater than or 
equal to 2 times baseline, Viraferon therapy may be continued unless signs and symptoms of liver failure are 
observed. During ALT flare, liver function tests: ALT, prothrombin time, alkaline phosphatase, albumin and 
bilirubin must be monitored at two-week intervals. 
 
Effect on fertility: Interferon may impair fertility (see section 4.6 and section 5.3). 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with 
Viraferon. 
 
Interactions between Viraferon and other medicinal products have not been fully evaluated. Caution must be 
exercised when administering Viraferon in combination with other potentially myelosuppressive agents. 
 
Interferons may affect the oxidative metabolic process. This must be considered during concomitant therapy 
with medicinal products metabolised by this route, such as the xanthine derivatives theophylline or 
aminophylline. During concomitant therapy with xanthine agents, serum theophylline levels must be 
monitored and dosage adjusted if necessary. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.4). 
 
(Also see ribavirin SPC if Viraferon is to be administered in combination with ribavirin in patients with 
chronic hepatitis C). 
 
4.6 Pregnancy and lactation 
 
Women of childbearing potential have to use effective contraception during treatment. Viraferon must be 
used with caution in fertile men. Decreased serum estradiol and progesterone concentrations have been 
reported in women treated with human leukocyte interferon. 
 
There are no adequate data from the use of interferon alfa-2b in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Viraferon is to be 
used during pregnancy only if the potential benefit justifies the potential risk to the foetus. 
 
It is not known whether the components of this medicinal product are excreted in human milk. Because of the 
potential for adverse reactions in nursing infants, nursing should be discontinued prior to initiation of 
treatment. 
 
Combination therapy with ribavirin: Ribavirin causes serious birth defects when administered during 
pregnancy. Ribavirin therapy is contraindicated in women who are pregnant. Extreme care must be taken to 
avoid pregnancy in female patients or in partners of male patients taking Viraferon in combination with 
ribavirin. Females of childbearing potential and their partners must each use an effective contraceptive during 
treatment and for 4 months after treatment has been concluded. Male patients and their female partners must 



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each use an effective contraceptive during treatment and for 7 months after treatment has been concluded (see 
ribavirin SPC). 
 
4.7 Effects on ability to drive and use machines 
 
Patients are to be advised that they may develop fatigue, somnolence, or confusion during treatment with 
Viraferon, and therefore it is recommended that they avoid driving or operating machinery. 
 
4.8 Undesirable effects 
 
See ribavirin SPC for ribavirin-related undesirable effects if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
In clinical trials conducted in a broad range of indications and at a wide range of doses (from 6 MIU/m2/week 
in hairy cell leukaemia up to 100 MIU/m2/week in melanoma), the most commonly reported undesirable 
effects were fever, fatigue, headache and myalgia. Fever and fatigue were often reversible within 72 hours of 
interruption or cessation of treatment. 
 
In clinical trials conducted in the hepatitis C population, patients were treated with Viraferon alone or in 
combination with ribavirin for one year. All patients in these trials received 3 MIU of Viraferon three times a 
week. In Table 1 the frequency of patients reporting (treatment related) undesirable effects is presented from 
clinical trials in naïve patients treated for one year. Severity was generally mild to moderate. The adverse 
reactions listed in Table 1 are based on experience from clinical trials and post-marketing. Within the organ 
system classes, adverse reactions are listed under headings of frequency using the following categories: very 
common (≥1/10); common (≥1/100, <1/10); rarely (≥1/10,000, <1/1,000); very rarely (<1/10,000); not 
known. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

Table 1. Adverse reactions reported during clinical trials or following the marketing use of Viraferon 
alone or in combination with ribavirin 

System Organ Class Adverse Reactions 
Infections and infestations 
Very common: 
Common: 
Rarely:  

 
Pharyngitis*, infection viral* 
Bronchitis, sinusitis, herpes simplex (resistance), rhinitis 
Pneumonia§ 

Blood and lymphatic system disorders 
Very common: 
Common: 
Very rarely:  
Not known:  

 
Leukopaenia 
Thrombocytopaenia, lymphadenopathy, lymphopenia 
Aplastic anaemia 
Pure red cell aplasia, idiopathic thrombocytopenic purpura, 
thrombotic thrombocytopenic purpura  

Immune system disorders§ 
Very rarely:  
Not known: 

 
Sarcoidosis, exacerbation of sarcoidosis 
Systemic lupus erythematosus, vasculitis, rheumatoid 
arthritis (new or aggravated), Vogt-Koyanagi-Harada 
syndrome, acute hypersensitivity reactions including 
urticaria, angioedema, bronchoconstriction, anaphylaxis§ 

Endocrine disorders 
Common: 
Very rarely:  

 
Hypothyroidism§, hyperthyroidism§ 
Diabetes, aggravated diabetes 

Metabolism and nutrition disorders 
Very common: 
Common:  
Very rarely:  

 
Anorexia 
Hypocalcaemia, dehydration, hyperuricemia, thirst 
Hyperglycaemia, hypertriglyceridaemia§, increased appetite 

Psychiatric disorders§  



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Very common: 
 
Common: 
Rarely:  
Very rarely: 
 
Not known: 

Depression, insomnia, anxiety, emotional lability*, 
agitation, nervousness 
Confusion, sleep disorder, libido decreased 
Suicide ideation 
Suicide, suicide attempts, aggressive behaviour (sometimes 
directed against others), psychosis including hallucinations 
Mental status change§ 

Nervous system disorders§ 
Very common: 
Common: 
 
Very rarely:  
 
 
Not known: 

 
Dizziness, headache, concentration impaired, mouth dry 
Tremor, paresthesia, hypoesthesia, migraine, flushing, 
somnolence, taste perversion 
Cerebrovascular haemorrhage, cerbrovascular ischaemia, 
seizure, impaired consciousness, encephalopathy, 
neuropathy, polyneuropathy 
Mononeuropathies, coma§ 

Eye disorders 
Very common: 
Common: 
 
Rarely:  

 
Vision blurred 
Conjunctivitis, vision abnormal, lacrimal gland disorder, eye 
pain 
Retinal haemorrhages§, retinopathies (including macular 
oedema), retinal artery or vein obstruction§, optic neuritis, 
papilloedema, loss of visual acuity or visual field, cotton-
wool spots§  

Ear and labyrinth 
Common: 
Very rarely:  

 
Vertigo, tinnitus 
Hearing loss, hearing disorder 

Cardiac disorders 
Common: 
Rarely: 
Very rarely: 
Not known: 

 
Palpitation, tachycardia 
Cardiomyopathy 
Myocardial infarction, cardiac ischaemia  
Arrhythmia  

Vascular disorders 
Common: 
Very rarely:  

 
Hypertension 
Peripheral ischaemia, hypotension§ 

Respiratory, thoracic and mediastinal 
disorders 
Very common: 
Common: 
 
Very rarely:  

 
 
Dyspnoea*, coughing* 
Epistaxis, respiratory disorder, nasal congestion, rhinorrhea, 
cough nonproductive 
Pulmonary infiltrates§, pneumonitis§ 

Gastrointestinal disorders 
Very common: 
 
Common: 
 
Very rarely:  
 
Not known: 

 
Nausea/vomiting, abdominal pain, diarrhoea, stomatitis, 
dyspepsia 
Stomatitis ulcerative, right upper quadrant pain, glossitis, 
gingivitis, constipation, loose stools 
Pancreatitis, ischaemic colitis, ulcerative colitis, gingival 
bleeding 
Periodontal disorder NOS, dental disorder NOS§ 

Hepatobiliary disorders 
Common: 
Very rarely:  

 
Hepatomegaly 
Hepatotoxicity, (including fatality) 

Skin and subcutaneous tissue disorders 
Very common: 
Common: 

 
Alopecia, pruritus*, skin dry*, rash*, sweating increased 
Psoriasis (new or aggravated)§, rash maculopapular, rash 



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Very rarely:  

erythematous, eczema, erythema, skin disorder 
Stevens Johnson syndrome, toxic epidermal necrolysis, 
erythema multiforme 

Musculoskeletal and connective tissue 
disorders 
Very common:  
Common: 
Very rarely: 

 
 
Myalgia, arthralgia, musculoskeletal pain 
Arthritis 
Rhabdomyolysis, myositis, leg cramps, back pain 

Renal and urinary disorders 
Common: 
Very rarely:  

 
Micturition frequency 
Renal failure, renal insufficiency, nephrotic syndrome 

Reproductive system and breast 
disorders 
Common: 

 
 
Amenorrhea, breast pain, dysmenorrhea, menorrhagia, 
menstrual disorder, vaginal disorder 

General disorders and administration 
site conditions 
Very common: 
 
 
Common: 
Very rarely: 

 
 
Injection site inflammation, injection site reaction*, fatigue, 
rigors, fever§, flu-like symptoms§, asthenia, irritability, chest 
pain, malaise 
Injection site pain 
Injection site necrosis, face oedema 

Investigations 
Very common: 

 
Weight decrease 

*These events were only common with Viraferon alone 
§See section 4.4 
 
These undesirable effects have also been reported with Viraferon alone. 
 
Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-
existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4). Cardiomyopathy, that may 
be reversible upon discontinuation of interferon alpha, has been reported rarely in patients without prior 
evidence of cardiac disease (see section 4.4).  
 
A wide variety of autoimmune and immune-mediated disorders have been reported with alpha interferons 
including thyroid disorders, systemic lupus erythematosus, rheumatoid arthritis (new or aggravated), 
idiopathic and thrombotic thrombocytopenic purpura, vasculitis, neuropathies including mononeuropathies 
(see also section 4.4).  
 
Clinically significant laboratory abnormalities, most frequently occurring at doses greater than 10 million IU 
daily, include reduction in granulocyte and white blood cell counts; decreases in haemoglobin level and 
platelet count; increases in alkaline phosphatase, LDH, serum creatinine and serum urea nitrogen levels. 
Increase in serum ALT/AST (SGPT/SGOT) levels have been noted as an abnormality in some non-hepatitis 
subjects and also in some patients with chronic hepatitis B coincident with clearance of viral DNAp. 
 
For safety with respect to transmissible agents, see section 4.4. 
 
Paediatric population 
 
Children and adolescents – Chronic Hepatitis C 
In clinical trials of 118 children or adolescents 3 to 16 years of age, 6 % discontinued therapy due to adverse 
events. In general, the adverse event profile in the limited paediatric population studied was similar to that 
observed in adults, although there is a paediatric specific concern regarding growth inhibition as decrease in 
height (mean percentile decrease of growth velocity of 9 %) and weight (mean percentile decrease of 13 %) 



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percentile were observed during treatment (see section 4.4). Furthermore, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6 month 
follow-up after treatment. As in adult patients, children and adolescents also experienced other psychiatric 
adverse events (e.g., depression, emotional lability, and somnolence) (see section 4.4). In addition, injection 
site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in children and 
adolescents compared to adult patients. Dose modifications were required in 30 % of patients, most 
commonly for anaemia and neutropaenia. 
 
The adverse reactions listed in Table 2 are based on experience from paediatric clinical trials.  
Within the organ system classes, adverse reactions are listed under headings of frequency using the following 
categories: very common (≥1/10); common (≥1/100, <1/10). Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness. 
 
Table 2  Adverse reactions very commonly and commonly reported in paediatric clinical trials  

Very common (≥1/10) - Common (≥1/100, <1/10) 
System Organ Class Adverse Reactions 
Infection and infestations 
Very common: 
Common: 

 
Viral infection, pharyngitis 
Fungal infection, bacterial infection, pulmonary infection, otitis 
media, tooth abscess, herpes simplex, urinary tract infection, 
vaginitis, gastroenteritis 

Neoplasms benign, malignant 
and unspecified (including 
cysts and polyps) 
Common: 

 
 
 
Neoplasm (unspecified) 

Blood and lymphatic system 
disorders 
Very common: 
Common: 

 
 
Anaemia, neutropaenia 
Thrombocytopaenia, lymphadenopathy 

Endocrine disorders 
Very common: 
Common: 

 
Hypothyroidism§,  
Hyperthyroidism§, virilism 

Metabolism and nutrition 
disorders 
Very common: 
Common: 

 
 
Anorexia 
Hypertriglyceridemia§, hyperuricemia, increased appetite 

Psychiatric disorders§ 
Very common: 
Common: 

 
Depression, emotional lability, insomnia 
Suicidal ideation, aggressive reaction, confusion, behaviour 
disorder, agitation, somnambulism, anxiety, nervousness, sleep 
disorder, abnormal dreaming, apathy 

Nervous system disorders§ 
Very common: 
Common: 

 
Headache, dizziness 
Hyperkinesia, tremor, dysphonia, paresthaesia, hypoaesthesia, 
hyperaesthesia, concentration impaired, somnolence 

Eye disorders 
Common: 

 
Conjunctivitis, eye pain, abnormal vision, lacrimal gland disorder 

Vascular disorders 
Common: 

 
Raynaud’s disease, flushing, pallor 

Respiratory, thoracic and 
mediastinal disorders 
Common: 

 
 
Dyspnoea, tachypnea, epistaxis, coughing, nasal congestion, nasal 
irritation, rhinorrhea, sneezing 

Gastrointestinal disorders  



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Very common: 
Common: 

Diarrhoea, vomiting, nausea, abdominal pain 
Mouth ulceration, stomatitis ulcerative, stomatitis, right upper 
quadrant pain, dyspepsia, glossitis, gastroesophogeal reflux, rectal 
disorder, gastrointestinal disorder, constipation, loose stools, 
toothache, tooth disorder 

Hepatobiliary disorders 
Common: 

 
Hepatic function abnormal 

Skin and subcutaneous tissue 
disorders  
Very common: 
Common: 

 
 
Alopecia, rash 
Photosensitivity reaction, maculopapular rash, eczema, acne, skin 
disorder, nail disorder, skin discolouration, pruritus, dry skin, 
erythema, bruise, sweating increased 

Musculoskeletal and 
connective tissue disorders 
Very common: 

 
 
Arthralgia, myalgia, musculoskeletal pain  

Renal and urinary disorders 
Common: 

 
Enuresis, micturition disorder, urinary incontinence 

Reproductive system and 
breast disorders 
Common: 

 
 
Female: amenorrhea, menorrhagia, menstrual disorder, vaginal 
disorder 
Male: testicular pain 

General disorders and 
administration site 
conditions 
Very common: 
 
Common: 

 
 
 
Injection site inflammation, injection site reaction, fatigue, rigors, 
fever§, influenza-like symptoms§, malaise, irritability 
Chest pain, asthenia, oedema, injection site pain 

Investigations 
Very common: 

 
Growth rate decrease (height and/or weight decrease for age)§  

Injury and poisoning 
Common: 

 
Skin laceration 

§See section 4.4 
 
4.9 Overdose 
 
No case of overdose has been reported that has led to acute clinical manifestations. However, as for any 
pharmacologically active compound, symptomatic treatment with frequent monitoring of vital signs and close 
observation of the patient is indicated. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunostimulants, cytokines and immunomodulators, interferons, interferon 
alfa-2b, ATC code: L03A B05 
 
Viraferon is a sterile, stable, formulation of highly purified interferon alfa-2b produced by recombinant DNA 
techniques. Recombinant interferon alfa-2b is a water-soluble protein with a molecular weight of 
approximately 19,300 daltons. It is obtained from a clone of E. coli, which harbours a genetically engineered 
plasmid hybrid encompassing an interferon alfa-2b gene from human leukocytes. 
 



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The activity of Viraferon is expressed in terms of IU, with 1 mg of recombinant interferon alfa-2b protein 
corresponding to 2.6 x l08 IU. International Units are determined by comparison of the activity of the 
recombinant interferon alfa-2b with the activity of the international reference preparation of human leukocyte 
interferon established by the World Health Organisation. 
 
The interferons are a family of small protein molecules with molecular weights of approximately 15,000 to 
21,000 daltons. They are produced and secreted by cells in response to viral infections or various synthetic 
and biological inducers. Three major classes of interferons have been identified: alpha, beta and gamma. 
These three main classes are themselves not homogeneous and may contain several different molecular 
species of interferon. More than 14 genetically distinct human alpha interferons have been identified. 
Viraferon has been classified as recombinant interferon alfa-2b. 
 
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. 
Human interferon receptors, as isolated from human lymphoblastoid (Daudi) cells, appear to be highly 
asymmetric proteins. They exhibit selectivity for human but not murine interferons, suggesting species 
specificity. Studies with other interferons have demonstrated species specificity. However, certain monkey 
species, eg, rhesus monkeys, are susceptible to pharmacodynamic stimulation upon exposure to human type 
1 interferons. 
 
The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex 
sequence of intracellular events that include the induction of certain enzymes. It is thought that this process, 
at least in part, is responsible for the various cellular responses to interferon, including inhibition of virus 
replication in virus-infected cells, suppression of cell proliferation and such immunomodulating activities as 
enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of 
lymphocytes for target cells. Any or all of these activities may contribute to interferon's therapeutic effects. 
 
Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and 
human cell culture systems as well as human tumour xenografts in animals. It has demonstrated significant 
immunomodulatory activity in vitro. 
 
Recombinant interferon alfa-2b also inhibits viral replication in vitro and in vivo. Although the exact antiviral 
mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism. 
This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell. 
 
Chronic hepatitis B: 
Current clinical experience in patients who remain on interferon alfa-2b for 4 to 6 months indicates that 
therapy can produce clearance of serum HBV-DNA. An improvement in liver histology has been observed. 
In adult patients with loss of HBeAg and HBV-DNA, a significant reduction in morbidity and mortality has 
been observed. 
 
Interferon alfa-2b (6 MIU/m2 3 times a week for 6 months) has been given to children with chronic active 
hepatitis B. Because of a methodological flaw, efficacy could not be demonstrated. Moreover children treated 
with interferon alfa-2b experienced a reduced rate of growth and some cases of depression were observed. 
 
Chronic hepatitis C: 
In adult patients receiving interferon in combination with ribavirin, the achieved sustained response rate is 
47 %. Superior efficacy has been demonstrated with the combination of pegylated interferon with ribavirin 
(sustained response rate of 61 % achieved in a study performed in naïve patients with a ribavirin dose 
> 10.6 mg/kg, p < 0.01). 
 
Adult patients: Viraferon alone or in combination with ribavirin has been studied in 4 randomised Phase III 
clinical trials in 2,552 interferon-naïve patients with chronic hepatitis C. The trials compared the efficacy of 
Viraferon used alone or in combination with ribavirin. Efficacy was defined as sustained virologic response, 
6 months after the end of treatment. Eligible patients for these trials had chronic hepatitis C confirmed by a 
positive HCV-RNA polymerase chain reaction assay (PCR) (> 100 copies/ml), a liver biopsy consistent with 



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a histologic diagnosis of chronic hepatitis with no other cause for the chronic hepatitis, and abnormal serum 
ALT. 
 
Viraferon was administered at a dose of 3 MIU 3 times a week as monotherapy or in combination with 
ribavirin. The majority of patients in these clinical trials were treated for one year. All patients were followed 
for an additional 6 months after the end of treatment for the determination of sustained virologic response. 
Sustained virologic response rates for treatment groups treated for one year with Viraferon alone or in 
combination with ribavirin (from two studies) are shown in Table 3. 
 
Co-administration of Viraferon with ribavirin increased the efficacy of Viraferon by at least two fold for the 
treatment of chronic heptatitis C in naïve patients. HCV genotype and baseline virus load are prognostic 
factors which are known to affect response rates. The increased response rate to the combination of Viraferon + 
ribavirin, compared with Viraferon alone, is maintained across all subgroups. The relative benefit of combination 
therapy with Viraferon + ribavirin is particularly significant in the most difficult to treat subgroup of patients 
(genotype 1 and high virus load) (Table 3). 
 
Response rates in these trials were increased with compliance. Regardless of genotype, patients who received 
Viraferon in combination with ribavirin and received ≥ 80 % of their treatment had a higher sustained 
response 6 months after 1 year of treatment than those who took < 80 % of their treatment (56 % vs. 32 % in 
trial C/I98-580).  



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Table 3 Sustained virologic response rates with Viraferon + ribavirin (one year of 

treatment) by genotype and viral load 
 

HCV Genotype  
 

I 
N=503 

C95-132/I95-143 

I/R 
N=505 

C95-132/I95-143 

I/R 
N=505 

C/I98-580 
 
All Genotypes 

 
16 % 

 
41 % 

 
47 % 

 
 
Genotype 1 

 
9 % 

 
29 % 

 
33 % 

 
Genotype 1  
≤ 2 million 
copies/ml 

 
25 % 

 
33 % 

 
45 % 

 
Genotype 1 
> 2 million 
copies/ml 

 
3 % 

 
27 % 

 

 
29 % 

 
Genotype 2/3 

 
31 % 

 
65 % 

 
79 % 

I Viraferon (3 MIU 3 times a week) 
I/R Viraferon (3 MIU 3 times a week) + ribavirin (1,000/1,200 mg/day) 
 
HCV/HIV Co-infected patients  
Two trials have been conducted in patients co-infected with HIV and HCV. Overall, in both studies, patients 
who received Viraferon plus ribavirin, were less likely to respond than patients who received pegylated 
interferon alfa-2b with ribavirin. The response to treatment in both of these trials is presented in Table 4. 
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 412 previously untreated 
adult patients with chronic hepatitis C who were co-infected with HIV. Patients were randomized to receive 
either pegylated interferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800 mg/day) or Viraferon (3 MIU TIW) 
plus ribavirin (800 mg/day) for 48 weeks with a follow-up period of 6 months. Study 2 (P02080) was a 
randomized, single centre study that enrolled 95 previously untreated adult patients with chronic hepatitis C 
who were co-infected with HIV. Patients were randomized to receive either pegylated interferon alfa-2b (100 
or 150 µg /week based on weight) plus ribavirin (800-1,200 mg/day based on weight) or Viraferon (3 MIU 
TIW) plus ribavirin (800-1,200 mg/day based on weight). The duration of therapy was 48 weeks with a 
follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load 
< 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6-month follow-up period.  



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Table 4 Sustained virological response based on genotype after Viraferon in combination with 

ribavirin versus pegylated interferon alfa-2b in combination with ribavirin in 
HCV/HIV co-infected patients 

 Study 11 Study 22 
 

pegylated 
interferon 

alfa-2b  
(1.5 µg/kg/ 

week) + 
ribavirin  
(800 mg) 

Viraferon  
(3 MIU TIW) +  

ribavirin  
(800 mg) 

p 
valuea 

pegylated 
interferon 

alfa-2b (100 
or  

150c µg/week) 
+ ribavirin 

(800- 
1,200 mg)d 

Viraferon  
(3 MIU TIW) 

+ ribavirin 
(800- 

1,200 mg)d 
p 

valueb 
All 27 % (56/205) 20 % (41/205) 0.047 44 % (23/52) 21 % (9/43) 0.017 
Genotype 1, 

4 
17 % (21/125) 6 % (8/129) 0.006 38 % (12/32) 7 % (2/27) 0.007 

Genotype 2, 
3 

44 % (35/80) 43 % (33/76) 0.88 53 % (10/19) 47 % (7/15) 0.730 

MIU = million international units; TIW = three times a week. 
a:  p value based on Cochran-Mantel Haenszel Chi square test. 
b:  p value based on chi-square test. 
c:  subjects < 75 kg received 100 µg/week pegylated interferon alfa-2b and subjects ≥ 75 kg received 150 µg/week pegylated 

interferon alfa-2b. 
d: ribavirin dosing was 800 mg for patients < 60 kg, 1,000 mg for patients 60-75 kg, and 1,200 mg for patients > 75 kg. 
 

1Carrat F, Bani-Sadr F, Pol S et al.  JAMA 2004; 292(23): 2839-2848. 
2 Laguno M, Murillas J, Blanco J.L et al.  AIDS 2004; 18(13): F27-F36. 
 
 
Relapse patients: A total of 345 interferon alpha relapse patients were treated in two clinical trials with 
Viraferon monotherapy or in combination with ribavirin. In these patients, the addition of ribavirin to 
Viraferon increased by as much as 10-fold the efficacy of Viraferon used alone in the treatment of chronic 
hepatitis C (48.6 % vs. 4.7 %). This enhancement in efficacy included loss of serum HCV (< 100 copies/ml 
by PCR), improvement in hepatic inflammation, and normalisation of ALT, and was sustained when 
measured 6 months after the end of treatment. 
 
Long-Term efficacy data 
In a large study, 1,071 patients were enrolled after treatment in a prior non pegylated interferon alfa-2b or 
non pegylated interferon alfa-2b/ribavirin study to evaluate the durability of sustained virologic response and 
assess the impact of continued viral negativity on clinical outcomes. 462 patients completed at least 5 years 
of long-term follow-up and only 12 sustained responders' out of 492 relapsed during this study.  
The Kaplan-Meier estimate for continued sustained response over 5 years for all patients is 97 % with a 95 % 
Confidence Interval of [95 %, 99 %].  
SVR after treatment of chronic HCV with non pegylated interferon alfa-2b (with or without ribavirin) results 
in long-term clearance of the virus providing resolution of the hepatic infection and clinical 'cure' from 
chronic HCV. However, this does not preclude the occurrence of hepatic events in patients with cirrhosis 
(including hepatocarcinoma). 
 
Clinical trials in paediatric patients with chronic hepatitis C: 
Children and adolescents 3 to 16 years of age with compensated chronic hepatitis C and detectable HCV-
RNA (assessed by a central laboratory using a research-based RT-PCR assay) were enrolled in two 
multicentre trials and received Viraferon 3 MIU/m2 3 times a week plus ribavirin 15 mg/kg per day for 1 year 
followed by 6 months follow-up after-treatment. A total of 118 patients were enrolled: 57 % male, 80 % 
Caucasian, and 78 % genotype 1,64 % ≤ 12 years of age. The population enrolled mainly consisted in 
children with mild to moderate hepatitis C. Sustained virological response rates in children and adolescents 



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were similar to those in adults. Due to the lack of data in children with severe progression of the disease, and 
the potential for undesirable effects, the benefit/risk of the combination of ribavirin and interferon alfa-2b 
needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8). 
 
Study results are summarized in Table 5. 
 
Table 5. Virological response in previously untreated paediatric patients 
 Viraferon 3 MIU/m2 3 times a week   

+ 
ribavirin 15 mg/kg/day 

Overall Response1 (n=118) 54 (46 %)* 

Genotype 1 (n=92) 33 (36 %)* 

Genotype 2/3/4 (n=26) 21 (81 %)* 

*Number (%) of patients 
1. Defined as HCV-RNA below limit of detection using a research based RT-PCR assay at end of treatment and during follow-up 
period 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of Viraferon were studied in healthy volunteers following single 5 million IU/m2 and 
10 million IU doses administered subcutaneously, at 5 million IU/m2 administered intramuscularly and as a 
30-minute intravenous infusion. The mean serum interferon concentrations following subcutaneous and 
intramuscular injections were comparable. Cmax occurred three to 12 hours after the lower dose and six to 
eight hours after the higher dose. The elimination half-lives of interferon injections were approximately two 
to three hours, and six to seven hours, respectively. Serum levels were below the detection limit 16 and 
24 hours, respectively, post-injection. Both subcutaneous and intramuscular administration resulted in 
bioavailabilities greater than 100 %. 
 
After intravenous administration, serum interferon levels peaked (135 to 273 IU/ml) by the end of the 
infusion, then declined at a slightly more rapid rate than after subcutaneous or intramuscular administration 
of medicinal product, becoming undetectable four hours after the infusion. The elimination half-life was 
approximately two hours. 
 
Urine levels of interferon were below the detection limit following each of the three routes of administration. 
 
Children and adolescents: Multiple-dose pharmacokinetic properties for Viraferon injection and ribavirin 
capsules in children and adolescents with chronic hepatitis C, between 5 and 16 years of age, are summarized 
in Table 6. The pharmacokinetics of Viraferon and ribavirin (dose-normalized) are similar in adults and 
children or adolescents. 



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Table 6. Mean (% CV) multiple-dose pharmacokinetic parameters for Viraferon and ribavirin 

capsules when administered to children or adolescents with chronic hepatitis C 
Parameter Ribavirin 

15 mg/kg/day as 2 divided 
doses 

(n = 17) 

Viraferon 
3 MIU/m2 3 times a week 

(n = 54) 

Tmax (hr) 1.9 (83) 5.9 (36) 
Cmax (ng/ml) 3,275 (25) 51 (48) 

AUC* 29,774 (26) 622 (48) 
Apparent clearance l/hr/kg 0.27 (27) Not done 

*AUC12 (ng.hr/ml) for ribavirin; AUC0-24 (IU.hr/ml) for Viraferon 
 
Interferon neutralising factor assays were performed on serum samples of patients who received Viraferon in 
Schering-Plough monitored clinical trials. Interferon neutralising factors are antibodies which neutralise the 
antiviral activity of interferon. The clinical incidence of neutralising factors developing in cancer patients 
treated systemically is 2.9 % and in chronic hepatitis patients is 6.2 %. The detectable titres are low in almost 
all cases and have not been regularly associated with loss of response or any other autoimmune phenomenon. 
In patients with hepatitis, no loss of response was observed apparently due to the low titres. 
 
5.3 Preclinical safety data 
 
Although interferon is generally recognised as being species specific, toxicity studies in animals were 
conducted. Injections of human recombinant interferon alfa-2b for up to three months have shown no 
evidence of toxicity in mice, rats, and rabbits. Daily dosing of cynomolgus monkeys with 20 x 106 IU/kg/day 
for 3 months caused no remarkable toxicity. Toxicity was demonstrated in monkeys given 
100 x 106 IU/kg/day for 3 months. 
 
In studies of interferon use in non-human primates, abnormalities of the menstrual cycle have been observed 
(see section 4.4). 
 
Results of animal reproduction studies indicate that recombinant interferon alfa-2b was not teratogenic in rats 
or rabbits, nor did it adversely affect pregnancy, foetal development or reproductive capacity in offspring of 
treated rats. Interferon alfa-2b has been shown to have abortifacient effects in Macaca mulatta (rhesus 
monkeys) at 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2. 
Abortion was observed in all dose groups (7.5 million, 15 million and 30 million IU/kg), and was statistically 
significant versus control at the mid- and high-dose groups (corresponding to 90 and 180 times the 
recommended intramuscular or subcutaneous dose of 2 million IU/m2). High doses of other forms of 
interferons alpha and beta are known to produce dose-related anovulatory and abortifacient effects in rhesus 
monkeys. 
 
Mutagenicity studies with interferon alfa-2b revealed no adverse events. 
 
No studies have been conducted in juvenile animals to examine the effects of treatment with interferon alfa-
2b on growth, development, sexual maturation, and behaviour (see section 4.4 and Rebetol SPC if Viraferon 
is to be administered in combination with ribavirin). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Glycine,  
Disodium phosphate anhydrous,  



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Sodium dihydrogen phosphate monohydrate, 
Human albumin solution. 
 
Solvent: water for injections 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
3 years 
 
After reconstitution: An immediate use is recommended. However, the chemical and physical in-use stability 
has been demonstrated for 24 hours at 25ºC. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C).  
Do not freeze.  
Within its shelf-life, for the purpose of transport and/or to facilitate ambulatory use the non-reconstituted 
product can be kept at or below 25°C for a period up to four weeks before use. If the product is not 
reconstituted during the four-week period, it cannot be put back in the refrigerator for a new storage period 
and must be discarded. 
 
6.5 Nature and contents of container 
 
24 mg of powder (corresponding to 5 MIU) in a vial (type I glass), with a stopper (butyl rubber) in a flip-off 
seal (aluminium) with a bonnet (polypropylene) 
and 1 ml water for injections in an ampoule (type I glass) 
with 1 injection syringe, 2 injection needles and 1 cleansing swab. 
Pack sizes of 1 
 
Or 
 
24 mg of powder (corresponding to 5 MIU) in a vial (type I glass), with a stopper (butyl rubber) in a flip-off 
seal (aluminium) with a bonnet (polypropylene) 
and 1 ml water for injections in an ampoule (type I glass) 
Pack sizes of 6 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
Reconstitution of Viraferon, powder for solution for injection, for parenteral administration: Viraferon is 
supplied as a powder at strengths of 5 million IU/ml for single-dose use. Vials must be reconstituted with 
1 ml of water for injections. The reconstituted solutions are isotonic for parenteral administration. 
 
Proper precautions should be taken during reconstitution to prevent microbial contamination (refer to package 
leaflet).  
 



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Using a sterilised injection syringe and injection needle, inject 1 ml water for injections into the vial of 
Viraferon. Agitate gently to facilitate complete dissolution of the powder. The appropriate dose can then be 
withdrawn with a sterile injection syringe and injected. 
 
As for all parenteral medicinal products, inspect the reconstituted solution visually for particulate matter and 
discoloration prior to administration. The reconstituted solution should be clear and colourless. 
 
Detailed instructions for the subcutaneous use of the product are provided with the package leaflet (refer to 
“How to self inject Viraferon”).  
 
Any unused product must be discarded after withdrawal of the dose. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
SP Europe 
73, rue de Stalle 
B-1180 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/99/128/004 
EU/1/99/128/005 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation : 9 March 2000 
Date of last renewal : 23 May 2005 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu/ 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 10 million IU/ml powder and solvent for solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One vial of powder contains 10 million IU of interferon alfa-2b produced in E.coli by recombinant DNA 
technology. 
After reconstitution, 1 ml contains 10 million IU of interferon alfa-2b. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection 
 
White to cream coloured powder.  
Clear and colourless solvent. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Chronic Hepatitis B: Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis B 
viral replication (presence of HBV-DNA and HBeAg), elevated alanine aminotransferase (ALT) and 
histologically proven active liver inflammation and/or fibrosis. 
 
Chronic Hepatitis C:  
Adult patients:  
Viraferon is indicated for the treatment of adult patients with chronic hepatitis C who have elevated 
transaminases without liver decompensation and who are positive for serum HCV-RNA or anti-HCV (see 
section 4.4). 
 
The best way to use Viraferon in this indication is in combination with ribavirin. 
 
Chidren and adolescents: 
Viraferon is intended for use, in a combination regimen with ribavirin, for the treatment of children and 
adolescents 3 years of age and older, who have chronic hepatitis C, not previously treated, without liver 
decompensation, and who are positive for serum HCV-RNA. The decision to treat should be made on a case 
by case basis, taking into account any evidence of disease progression such as hepatic inflammation and 
fibrosis, as well as prognostic factors for response, HCV genotype and viral load. The expected benefit of 
treatment should be weighed against the safety findings observed for paediatric subjects in the clinical trials 
(see sections 4.4, 4.8 and 5.1). 
 
4.2 Posology and method of administration 
 
Treatment must be initiated by a physician experienced in the management of the disease. 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 



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If adverse events develop during the course of treatment with Viraferon for any indication, modify the dosage 
or discontinue therapy temporarily until the adverse events abate. If persistent or recurrent intolerance 
develops following adequate dosage adjustment, or disease progresses, discontinue treatment with Viraferon. 
At the discretion of the physician, the patient may self-administer the dose for maintenance dosage regimens 
administered subcutaneously. 
 
Chronic Hepatitis B: The recommended dosage is in the range 5 to 10 million IU administered 
subcutaneously three times a week (every other day) for a period of 4 to 6 months. 
 
The administered dose should be reduced by 50 % in case of occurrence of haematological disorders (white 
blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3). Treatment should be 
discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe 
thrombocytopaenia (< 70,000/mm3). 
 
For all patients, if no improvement on serum HBV-DNA is observed after 3 to 4 months of treatment (at the 
maximum tolerated dose), discontinue Viraferon therapy. 
 
Chronic Hepatitis C: Viraferon is administered subcutaneously at a dose of 3 million IU three times a week 
(every other day) to adult patients, whether administered as monotherapy or in combination with ribavirin. 
 
Children 3 years of age or older and adolescents: Interferon alfa-2b 3 MIU/m2 is administered 
subcutaneously 3 times a week (every other day) in combination with ribavirin capsules or oral solution 
administered orally in two divided doses daily with food (morning and evening).  
 
(See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination 
therapy. For paediatric patients who weigh < 47 kg or cannot swallow capsules, see ribavirin oral solution 
SPC).  
 
Relapse patients (adults): 
Viraferon is given in combination with ribavirin. 
 
Based on the results of clinical trials, in which data are available for 6 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for 6 months. 
 
Naïve patients: 
Adults: The efficacy of Viraferon is enhanced when given in combination with ribavirin. Viraferon should be 
given alone mainly in case of intolerance or contraindication to ribavirin. 
 
Viraferon in combination with ribavirin: 
Based on the results of clinical trials, in which data are available for 12 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for at least 6 months. 
 
Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit 
negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and 
high pre-treatment viral load. 
 
Other negative prognostic factors (age > 40 years, male gender, bridging fibrosis) should be taken into 
account in order to extend therapy to 12 months. 
 
During clinical trials, patients who failed to show a virologic response after 6 months of treatment (HCV-
RNA below lower limit of detection) did not become sustained virologic responders (HCV-RNA below lower 
limit of detection six months after withdrawal of treatment). 
 
Viraferon alone: 



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The optimal duration of therapy with Viraferon alone is not yet fully established, but a therapy of between 
12 and 18 months is advised. 
 
It is recommended that patients be treated with Viraferon alone for at least 3 to 4 months, at which point 
HCV-RNA status should be determined. Treatment should be continued in patients who exhibit negative 
HCV-RNA. 
 
Children and adolescents: The efficacy and safety of Viraferon in combination with ribavirin has been 
studied in children and adolescents who have not been previously treated for chronic hepatitis C.  
 
Genotype 1: The recommended duration of treatment is one year. Patients who fail to achieve virological 
response at 12 weeks are highly unlikely to become sustained virological responders (negative predictive 
value 96 %). Virological response is defined as absence of detectable HCV-RNA at Week 12. Treatment 
should be discontinued in these patients. 
Genotype 2/3: The recommended duration of treatment is 24 weeks. 
 
Virological responses after 1 year of treatment and 6 months of follow-up were 36 % for genotype 1 and 
81 % for genotype 2/3/4. 
 
Viraferon may be administered using either glass or plastic disposable injection syringes. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients. 
- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure, recent 

myocardial infarction, severe arrhythmic disorders.  
- Severe renal or hepatic dysfunction; including that caused by metastases. 
- Epilepsy and/or compromised central nervous system (CNS) function (see section 4.4). 
- Chronic hepatitis with decompensated cirrhosis of the liver. 
- Chronic hepatitis in patients who are being or have been treated recently with immunosuppressive 

agents excluding short term corticosteroid withdrawal. 
- Autoimmune hepatitis; or history of autoimmune disease; immunosuppressed transplant recipients. 
- Pre-existing thyroid disease unless it can be controlled with conventional treatment. 
 
Children and adolescents: 
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal 

ideation or suicide attempt. 
 

Combination therapy with ribavirin: Also see ribavirin SPC if interferon alfa-2b is to be administered in 
combination with ribavirin in patients with chronic hepatitis C. 
 
4.4 Special warnings and precautions for use 
 
For all patients: 
Psychiatric and central nervous system (CNS): Severe CNS effects, particularly depression, suicidal ideation 
and attempted suicide have been observed in some patients during Viraferon therapy, and even after 
treatment discontinuation mainly during the 6-month follow-up periodand in the follow-up period. Among 
children and adolescents treated with Viraferon in combination with ribavirin, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6-month 
follow-up after treatment. As in adult patients, children and adolescents experienced other psychiatric adverse 
events (e.g., depression, emotional lability, and somnolence). Other CNS effects including aggressive behaviour 
(sometimes directed against others), confusion and alterations of mental status have been observed with alpha 
interferons. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such 
symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the 
prescribing physician and the need for adequate therapeutic management should be considered. If psychiatric 



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symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with 
Viraferon be discontinued, and the patient followed, with psychiatric intervention as appropriate. 
 
Patients with existence of or history of severe psychiatric conditions: 
If a treatment with interferon alfa-2b is judged necessary in adult patients with existence or history of severe 
psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and 
therapeutic management of the psychiatric condition. The use of interferon alfa-2b in children and adolescents 
with existence of or history of severe psychiatric conditions is contraindicated (see section 4.3). 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Moderate to severe adverse experiences may require modification of the patient's dosage regimen, or in some 
cases, termination of Viraferon therapy. Any patient developing liver function abnormalities during treatment 
with Viraferon must be monitored closely and treatment discontinued if signs and symptoms progress. 
 
Hypotension may occur during Viraferon therapy or up to two days post-therapy and may require supportive 
treatment. 
 
Adequate hydration must be maintained in patients undergoing Viraferon therapy since hypotension related 
to fluid depletion has been seen in some patients. Fluid replacement may be necessary. 
 
While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, 
other causes of persistent fever must be ruled out. 
 
Viraferon must be used cautiously in patients with debilitating medical conditions, such as those with a 
history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to 
ketoacidosis. Caution must be observed also in patients with coagulation disorders (e.g., thrombophlebitis, 
pulmonary embolism) or severe myelosuppression. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.5). Any patient developing fever, cough, 
dyspnea or other respiratory symptoms must have a chest X-ray taken. If the chest X-ray shows pulmonary 
infiltrates or there is evidence of pulmonary function impairment, the patient is to be monitored closely, and, 
if appropriate, discontinue interferon alpha. While this has been reported more often in patients with chronic 
hepatitis C treated with interferon alpha, it has also been reported in patients with oncologic diseases treated 
with interferon alpha. Prompt discontinuation of interferon alpha administration and treatment with 
corticosteroids appear to be associated with resolution of pulmonary adverse events. 
 
Ocular adverse events (see section 4.8) including retinal haemorrhages, cotton wool spots, and retinal artery 
or vein obstruction have been reported in rare instance after treatment with alpha interferons. All patients 
should have a baseline eye examination. Any patient complaining of changes in visual acuity or visual fields, 
or reporting other ophthalmologic symptoms during treatment with Viraferon, must have a prompt and 
complete eye examination. Periodic visual examinations during Viraferon therapy are recommended 
particularly in patients with disorders that may be associated with retinopathy, such as diabetes mellitus or 
hypertension. Discontinuation of Viraferon should be considered in patients who develop new or worsening 
ophthalmological disorders. 



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More significant obtundation and coma, including cases of encephalopathy, have been observed in some 
patients, usually elderly, treated at higher doses. While these effects are generally reversible, in a few patients 
full resolution took up to three weeks. Very rarely, seizures have occurred with high doses of Viraferon. 
 
Adult patients with a history of congestive heart failure, myocardial infarction and/or previous or current 
arrhythmic disorders, who require Viraferon therapy, must be closely monitored. It is recommended that 
those patients who have pre-existing cardiac abnormalities and/or are in advanced stages of cancer have 
electrocardiograms taken prior to and during the course of treatment. Cardiac arrhythmias (primarily 
supraventricular) usually respond to conventional therapy but may require discontinuation of Viraferon 
therapy. There are no data in children or adolescents with a history of cardiac disease. 
 
Hypertriglyceridemia and aggravation of hypertriglyceridemia, sometimes severe, have been observed. 
Monitoring of lipid levels is, therefore, recommended. 
 
Due to reports of interferon alpha exacerbating pre-existing psoriatic disease and sarcoidosis, use of 
Viraferon in patients with psoriasis or sarcoidosis is recommended only if the potential benefit justifies the 
potential risk. 
 
Preliminary data indicates that interferon alpha therapy may be associated with an increased rate of kidney 
graft rejection. Liver graft rejection has also been reported. 
 
The development of auto-antibodies and autoimmune disorders has been reported during treatment with alpha 
interferons. Patients predisposed to the development of autoimmune disorders may be at increased risk. 
Patients with signs or symptoms compatible with autoimmune disorders should be evaluated carefully, and 
the benefit-risk of continued interferon therapy should be reassessed (see also section 4.4 Chronic hepatitis C, 
Monotherapy (thyroid abnormalities) and section 4.8). 
Cases of Vogt-Koyanagi-Harada (VKH) syndrome have been reported in patients with chronic hepatitis C 
treated with interferon. This syndrome is a granulomatous inflammatory disorder affecting the eyes, auditory 
system, meninges, and skin. If VKH syndrome is suspected, antiviral treatment should be withdrawn and 
corticosteroid therapy discussed (see section 4.8). 
 
Discontinue treatment with Viraferon in patients with chronic hepatitis who develop prolongation of 
coagulation markers which might indicate liver decompensation. 
 
Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of 
human plasma-derived albumin. 
 
Standard measures to prevent infections resulting from the use of medicinal products prepared from human 
blood or plasma include selection of donors, screening of individual donations and plasma pools for specific 
markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of 
viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the 
possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or 
emerging viruses and other pathogens. 
 
There are no reports of virus transmissions with albumin manufactured to European Pharmacopoeia 
specifications by established processes. 
 
It is strongly recommended that every time that Viraferon is administered to a patient, the name and batch 
number of the product are recorded in order to maintain a link between the patient and the batch of the 
product. 
 
Chronic Hepatitis C: 
Combination therapy with ribavirin: Also see ribavirin SPC if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 



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All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i.e. 
patients with genotype 2 and 3), treatment may be possible without histological confirmation. Current 
treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing 
treatment. 
 
Monotherapy: Infrequently, adult patients treated for chronic hepatitis C with Viraferon developed thyroid 
abnormalities, either hypothyroidism or hyperthyroidism. In clinical trials using Viraferon therapy, 2.8 % 
patients overall developed thyroid abnormalities. The abnormalities were controlled by conventional therapy 
for thyroid dysfunction. The mechanism by which Viraferon may alter thyroid status is unknown. Prior to 
initiation of Viraferon therapy for the treatment of chronic hepatitis C, evaluate serum thyroid-stimulating 
hormone (TSH) levels. Any thyroid abnormality detected at that time must be treated with conventional 
therapy. Viraferon treatment may be initiated if TSH levels can be maintained in the normal range by 
medication. Determine TSH levels if, during the course of Viraferon therapy, a patient develops symptoms 
consistent with possible thyroid dysfunction. In the presence of thyroid dysfunction, Viraferon treatment may 
be continued if TSH levels can be maintained in the normal range by medication. Discontinuation of 
Viraferon therapy has not reversed thyroid dysfunction occurring during treatment (also see Children and 
adolescents, Thyroid monitoring). 
 
Supplemental monitoring specific for children and adolescents 
Thyroid Monitoring: Approximately 12 % of children treated with interferon alfa-2b and ribavirin developed 
increase in TSH. Another 4 % had a transient decrease below the lower limit of normal. Prior to initiation of 
Viraferon therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be 
treated with conventional therapy. Viraferon therapy may be initiated if TSH levels can be maintained in the 
normal range by medication. Thyroid dysfunction during treatment with interferon alfa-2b and ribavirin has 
been observed. If thyroid abnormalities are detected, the patient’s thyroid status should be evaluated and 
treated as clinically appropriate. Children and adolescents should be monitored every 3 months for evidence 
of thyroid dysfunction (e.g. TSH). 
 
Growth and Development: During a 1-year course of therapy there was a decrease in the rate of linear growth 
(mean percentile decrease of 9 %) and a decrease in the rate of weight gain (mean percentile decrease of 
13 %). A general reversal of these trends was noted during the 6 months follow-up post treatment. However, 
based on interim data from a long-term follow-up study, 12 (14 %) of 84 children had a > 15 percentile 
decrease in rate of linear growth, of whom 5 (6 %) children had a > 30 percentile decrease despite being off 
treatment for more than 1 year. In addition, preclicinal juvenile toxicity results have demonstrated a minor, 
dose-related decrease in overall growth in neonatal rats dosed with ribavirin (see section 5.3). Therefore, the 
risk/benefit of the combined use of interferon alfa-2b and ribavirin should be assessed in young children prior 
to the initiation of therapy. Physicians are advised to monitor the growth of children taking ribavirin in 
combination with interferon alfa-2b. There are no data on long term effects on growth and development and 
on sexual maturation. 
 
HCV/HIV Coinfection: Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy 
(HAART) may be at increased risk of developing lactic acidosis. Caution should be used when adding Viraferon 
and ribavirin to HAART therapy (see ribavirin SPC). Patients treated with Viraferon and ribavirin combination 
therapy and zidovudine could be at increased risk of developing anaemia. 
Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic 
decompensation and death. Adding treatment with alfa interferons alone or in combination with ribavirin may 
increase the risk in this patient subset.  
 
Dental and periodontal disorders: Dental and periodontal disorders, which may lead to loss of teeth, have 
been reported in patients receiving Viraferon and ribavirin combination therapy. In addition, dry mouth could 
have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the 
combination of Viraferon and ribavirin. Patients should brush their teeth thoroughly twice daily and have 
regular dental examinations. In addition some patients may experience vomiting. If this reaction occurs, they 
should be advised to rinse out their mouth thoroughly afterwards. 



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Laboratory Tests:  
Standard haematological tests and blood chemistries (complete blood count and differential, platelet count, 
electrolytes, liver enzymes, serum protein, serum bilirubin and serum creatinine) are to be conducted in all 
patients prior to and periodically during systemic treatment with Viraferon. 
 
During treatment for hepatitis B or C the recommended testing schedule is at weeks 1, 2, 4, 8, 12, 16, and 
every other month, thereafter, throughout treatment. If ALT flares during Viraferon therapy to greater than or 
equal to 2 times baseline, Viraferon therapy may be continued unless signs and symptoms of liver failure are 
observed. During ALT flare, liver function tests: ALT, prothrombin time, alkaline phosphatase, albumin and 
bilirubin must be monitored at two-week intervals. 
 
Effect on fertility: Interferon may impair fertility (see section 4.6 and section 5.3). 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with 
Viraferon. 
 
Interactions between Viraferon and other medicinal products have not been fully evaluated. Caution must be 
exercised when administering Viraferon in combination with other potentially myelosuppressive agents. 
 
Interferons may affect the oxidative metabolic process. This must be considered during concomitant therapy 
with medicinal products metabolised by this route, such as the xanthine derivatives theophylline or 
aminophylline. During concomitant therapy with xanthine agents, serum theophylline levels must be 
monitored and dosage adjusted if necessary. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.4). 
 
(Also see ribavirin SPC if Viraferon is to be administered in combination with ribavirin in patients with 
chronic hepatitis C). 
 
4.6 Pregnancy and lactation 
 
Women of childbearing potential have to use effective contraception during treatment. Viraferon must be 
used with caution in fertile men. Decreased serum estradiol and progesterone concentrations have been 
reported in women treated with human leukocyte interferon. 
 
There are no adequate data from the use of interferon alfa-2b in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Viraferon is to be 
used during pregnancy only if the potential benefit justifies the potential risk to the foetus. 
 
It is not known whether the components of this medicinal product are excreted in human milk. Because of the 
potential for adverse reactions in nursing infants, nursing should be discontinued prior to initiation of 
treatment. 
 
Combination therapy with ribavirin: Ribavirin causes serious birth defects when administered during 
pregnancy. Ribavirin therapy is contraindicated in women who are pregnant. Extreme care must be taken to 
avoid pregnancy in female patients or in partners of male patients taking Viraferon in combination with 
ribavirin. Females of childbearing potential and their partners must each use an effective contraceptive during 
treatment and for 4 months after treatment has been concluded. Male patients and their female partners must 



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each use an effective contraceptive during treatment and for 7 months after treatment has been concluded (see 
ribavirin SPC). 
 
4.7 Effects on ability to drive and use machines 
 
Patients are to be advised that they may develop fatigue, somnolence, or confusion during treatment with 
Viraferon, and therefore it is recommended that they avoid driving or operating machinery. 
 
4.8 Undesirable effects 
 
See ribavirin SPC for ribavirin-related undesirable effects if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
In clinical trials conducted in a broad range of indications and at a wide range of doses (from 6 MIU/m2/week 
in hairy cell leukaemia up to 100 MIU/m2/week in melanoma), the most commonly reported undesirable 
effects were fever, fatigue, headache and myalgia. Fever and fatigue were often reversible within 72 hours of 
interruption or cessation of treatment. 
 
In clinical trials conducted in the hepatitis C population, patients were treated with Viraferon alone or in 
combination with ribavirin for one year. All patients in these trials received 3 MIU of Viraferon three times a 
week. In Table 1 the frequency of patients reporting (treatment related) undesirable effects is presented from 
clinical trials in naïve patients treated for one year. Severity was generally mild to moderate. The adverse 
reactions listed in Table 1 are based on experience from clinical trials and post-marketing. Within the organ 
system classes, adverse reactions are listed under headings of frequency using the following categories: very 
common (≥1/10); common (≥1/100, <1/10); rarely (≥1/10,000, <1/1,000); very rarely (<1/10,000); not 
known. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

Table 1. Adverse reactions reported during clinical trials or following the marketing use of Viraferon 
alone or in combination with ribavirin 

System Organ Class Adverse Reactions 
Infections and infestations 
Very common: 
Common: 
Rarely:  

 
Pharyngitis*, infection viral* 
Bronchitis, sinusitis, herpes simplex (resistance), rhinitis 
Pneumonia§ 

Blood and lymphatic system disorders 
Very common: 
Common: 
Very rarely:  
Not known:  

 
Leukopaenia 
Thrombocytopaenia, lymphadenopathy, lymphopenia 
Aplastic anaemia 
Pure red cell aplasia, idiopathic thrombocytopenic purpura, 
thrombotic thrombocytopenic purpura  

Immune system disorders§ 
Very rarely:  
Not known: 

 
Sarcoidosis, exacerbation of sarcoidosis 
Systemic lupus erythematosus, vasculitis, rheumatoid 
arthritis (new or aggravated), Vogt-Koyanagi-Harada 
syndrome, acute hypersensitivity reactions including 
urticaria, angioedema, bronchoconstriction, anaphylaxis§ 

Endocrine disorders 
Common: 
Very rarely:  

 
Hypothyroidism§, hyperthyroidism§ 
Diabetes, aggravated diabetes 

Metabolism and nutrition disorders 
Very common: 
Common:  
Very rarely:  

 
Anorexia 
Hypocalcaemia, dehydration, hyperuricemia, thirst 
Hyperglycaemia, hypertriglyceridaemia§, increased appetite 

Psychiatric disorders§  



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Very common: 
 
Common: 
Rarely:  
Very rarely: 
 
Not known: 

Depression, insomnia, anxiety, emotional lability*, 
agitation, nervousness 
Confusion, sleep disorder, libido decreased 
Suicide ideation 
Suicide, suicide attempts, aggressive behaviour (sometimes 
directed against others), psychosis including hallucinations 
Mental status change§ 

Nervous system disorders§ 
Very common: 
Common: 
 
Very rarely:  
 
 
Not known: 

 
Dizziness, headache, concentration impaired, mouth dry 
Tremor, paresthesia, hypoesthesia, migraine, flushing, 
somnolence, taste perversion 
Cerebrovascular haemorrhage, cerbrovascular ischaemia, 
seizure, impaired consciousness, encephalopathy, 
neuropathy, polyneuropathy 
Mononeuropathies, coma§ 

Eye disorders 
Very common: 
Common: 
 
Rarely:  

 
Vision blurred 
Conjunctivitis, vision abnormal, lacrimal gland disorder, eye 
pain 
Retinal haemorrhages§, retinopathies (including macular 
oedema), retinal artery or vein obstruction§, optic neuritis, 
papilloedema, loss of visual acuity or visual field, cotton-
wool spots§  

Ear and labyrinth 
Common: 
Very rarely:  

 
Vertigo, tinnitus 
Hearing loss, hearing disorder 

Cardiac disorders 
Common: 
Rarely: 
Very rarely: 
Not known: 

 
Palpitation, tachycardia 
Cardiomyopathy 
Myocardial infarction, cardiac ischaemia  
Arrhythmia  

Vascular disorders 
Common: 
Very rarely:  

 
Hypertension 
Peripheral ischaemia, hypotension§ 

Respiratory, thoracic and mediastinal 
disorders 
Very common: 
Common: 
 
Very rarely:  

 
 
Dyspnoea*, coughing* 
Epistaxis, respiratory disorder, nasal congestion, rhinorrhea, 
cough nonproductive 
Pulmonary infiltrates§, pneumonitis§ 

Gastrointestinal disorders 
Very common: 
 
Common: 
 
Very rarely:  
 
Not known: 

 
Nausea/vomiting, abdominal pain, diarrhoea, stomatitis, 
dyspepsia 
Stomatitis ulcerative, right upper quadrant pain, glossitis, 
gingivitis, constipation, loose stools 
Pancreatitis, ischaemic colitis, ulcerative colitis, gingival 
bleeding 
Periodontal disorder NOS, dental disorder NOS§ 

Hepatobiliary disorders 
Common: 
Very rarely:  

 
Hepatomegaly 
Hepatotoxicity, (including fatality) 

Skin and subcutaneous tissue disorders 
Very common: 
Common: 

 
Alopecia, pruritus*, skin dry*, rash*, sweating increased 
Psoriasis (new or aggravated)§, rash maculopapular, rash 



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Very rarely:  

erythematous, eczema, erythema, skin disorder 
Stevens Johnson syndrome, toxic epidermal necrolysis, 
erythema multiforme 

Musculoskeletal and connective tissue 
disorders 
Very common:  
Common: 
Very rarely: 

 
 
Myalgia, arthralgia, musculoskeletal pain 
Arthritis 
Rhabdomyolysis, myositis, leg cramps, back pain 

Renal and urinary disorders 
Common: 
Very rarely:  

 
Micturition frequency 
Renal failure, renal insufficiency, nephrotic syndrome 

Reproductive system and breast 
disorders 
Common: 

 
 
Amenorrhea, breast pain, dysmenorrhea, menorrhagia, 
menstrual disorder, vaginal disorder 

General disorders and administration 
site conditions 
Very common: 
 
 
Common: 
Very rarely: 

 
 
Injection site inflammation, injection site reaction*, fatigue, 
rigors, fever§, flu-like symptoms§, asthenia, irritability, chest 
pain, malaise 
Injection site pain 
Injection site necrosis, face oedema 

Investigations 
Very common: 

 
Weight decrease 

*These events were only common with Viraferon alone 
§See section 4.4 
 
These undesirable effects have also been reported with Viraferon alone. 
 
Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-
existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4). Cardiomyopathy, that may 
be reversible upon discontinuation of interferon alpha, has been reported rarely in patients without prior 
evidence of cardiac disease (see section 4.4).  
 
A wide variety of autoimmune and immune-mediated disorders have been reported with alpha interferons 
including thyroid disorders, systemic lupus erythematosus, rheumatoid arthritis (new or aggravated), 
idiopathic and thrombotic thrombocytopenic purpura, vasculitis, neuropathies including mononeuropathies 
(see also section 4.4).  
 
Clinically significant laboratory abnormalities, most frequently occurring at doses greater than 10 million IU 
daily, include reduction in granulocyte and white blood cell counts; decreases in haemoglobin level and 
platelet count; increases in alkaline phosphatase, LDH, serum creatinine and serum urea nitrogen levels. 
Increase in serum ALT/AST (SGPT/SGOT) levels have been noted as an abnormality in some non-hepatitis 
subjects and also in some patients with chronic hepatitis B coincident with clearance of viral DNAp. 
 
For safety with respect to transmissible agents, see section 4.4. 
 
Paediatric population 
 
Children and adolescents – Chronic Hepatitis C 
In clinical trials of 118 children or adolescents 3 to 16 years of age, 6 % discontinued therapy due to adverse 
events. In general, the adverse event profile in the limited paediatric population studied was similar to that 
observed in adults, although there is a paediatric specific concern regarding growth inhibition as decrease in 
height (mean percentile decrease of growth velocity of 9 %) and weight (mean percentile decrease of 13 %) 



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percentile were observed during treatment (see section 4.4). Furthermore, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6 month 
follow-up after treatment. As in adult patients, children and adolescents also experienced other psychiatric 
adverse events (e.g., depression, emotional lability, and somnolence) (see section 4.4). In addition, injection 
site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in children and 
adolescents compared to adult patients. Dose modifications were required in 30 % of patients, most 
commonly for anaemia and neutropaenia. 
 
The adverse reactions listed in Table 2 are based on experience from paediatric clinical trials.  
Within the organ system classes, adverse reactions are listed under headings of frequency using the following 
categories: very common (≥1/10); common (≥1/100, <1/10). Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness. 
 
Table 2  Adverse reactions very commonly and commonly reported in paediatric clinical trials  

Very common (≥1/10) - Common (≥1/100, <1/10) 
System Organ Class Adverse Reactions 
Infection and infestations 
Very common: 
Common: 

 
Viral infection, pharyngitis 
Fungal infection, bacterial infection, pulmonary infection, otitis 
media, tooth abscess, herpes simplex, urinary tract infection, 
vaginitis, gastroenteritis 

Neoplasms benign, malignant 
and unspecified (including 
cysts and polyps) 
Common: 

 
 
 
Neoplasm (unspecified) 

Blood and lymphatic system 
disorders 
Very common: 
Common: 

 
 
Anaemia, neutropaenia 
Thrombocytopaenia, lymphadenopathy 

Endocrine disorders 
Very common: 
Common: 

 
Hypothyroidism§,  
Hyperthyroidism§, virilism 

Metabolism and nutrition 
disorders 
Very common: 
Common: 

 
 
Anorexia 
Hypertriglyceridemia§, hyperuricemia, increased appetite 

Psychiatric disorders§ 
Very common: 
Common: 

 
Depression, emotional lability, insomnia 
Suicidal ideation, aggressive reaction, confusion, behaviour 
disorder, agitation, somnambulism, anxiety, nervousness, sleep 
disorder, abnormal dreaming, apathy 

Nervous system disorders§ 
Very common: 
Common: 

 
Headache, dizziness 
Hyperkinesia, tremor, dysphonia, paresthaesia, hypoaesthesia, 
hyperaesthesia, concentration impaired, somnolence 

Eye disorders 
Common: 

 
Conjunctivitis, eye pain, abnormal vision, lacrimal gland disorder 

Vascular disorders 
Common: 

 
Raynaud’s disease, flushing, pallor 

Respiratory, thoracic and 
mediastinal disorders 
Common: 

 
 
Dyspnoea, tachypnea, epistaxis, coughing, nasal congestion, nasal 
irritation, rhinorrhea, sneezing 

Gastrointestinal disorders  



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Very common: 
Common: 

Diarrhoea, vomiting, nausea, abdominal pain 
Mouth ulceration, stomatitis ulcerative, stomatitis, right upper 
quadrant pain, dyspepsia, glossitis, gastroesophogeal reflux, rectal 
disorder, gastrointestinal disorder, constipation, loose stools, 
toothache, tooth disorder 

Hepatobiliary disorders 
Common: 

 
Hepatic function abnormal 

Skin and subcutaneous tissue 
disorders  
Very common: 
Common: 

 
 
Alopecia, rash 
Photosensitivity reaction, maculopapular rash, eczema, acne, skin 
disorder, nail disorder, skin discolouration, pruritus, dry skin, 
erythema, bruise, sweating increased 

Musculoskeletal and 
connective tissue disorders 
Very common: 

 
 
Arthralgia, myalgia, musculoskeletal pain  

Renal and urinary disorders 
Common: 

 
Enuresis, micturition disorder, urinary incontinence 

Reproductive system and 
breast disorders 
Common: 

 
 
Female: amenorrhea, menorrhagia, menstrual disorder, vaginal 
disorder 
Male: testicular pain 

General disorders and 
administration site 
conditions 
Very common: 
 
Common: 

 
 
 
Injection site inflammation, injection site reaction, fatigue, rigors, 
fever§, influenza-like symptoms§, malaise, irritability 
Chest pain, asthenia, oedema, injection site pain 

Investigations 
Very common: 

 
Growth rate decrease (height and/or weight decrease for age)§  

Injury and poisoning 
Common: 

 
Skin laceration 

§See section 4.4 
 
4.9 Overdose 
 
No case of overdose has been reported that has led to acute clinical manifestations. However, as for any 
pharmacologically active compound, symptomatic treatment with frequent monitoring of vital signs and close 
observation of the patient is indicated. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunostimulants, cytokines and immunomodulators, interferons, interferon 
alfa-2b, ATC code: L03A B05 
 
Viraferon is a sterile, stable, formulation of highly purified interferon alfa-2b produced by recombinant DNA 
techniques. Recombinant interferon alfa-2b is a water-soluble protein with a molecular weight of 
approximately 19,300 daltons. It is obtained from a clone of E. coli, which harbours a genetically engineered 
plasmid hybrid encompassing an interferon alfa-2b gene from human leukocytes. 
 



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The activity of Viraferon is expressed in terms of IU, with 1 mg of recombinant interferon alfa-2b protein 
corresponding to 2.6 x l08 IU. International Units are determined by comparison of the activity of the 
recombinant interferon alfa-2b with the activity of the international reference preparation of human leukocyte 
interferon established by the World Health Organisation. 
 
The interferons are a family of small protein molecules with molecular weights of approximately 15,000 to 
21,000 daltons. They are produced and secreted by cells in response to viral infections or various synthetic 
and biological inducers. Three major classes of interferons have been identified: alpha, beta and gamma. 
These three main classes are themselves not homogeneous and may contain several different molecular 
species of interferon. More than 14 genetically distinct human alpha interferons have been identified. 
Viraferon has been classified as recombinant interferon alfa-2b. 
 
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. 
Human interferon receptors, as isolated from human lymphoblastoid (Daudi) cells, appear to be highly 
asymmetric proteins. They exhibit selectivity for human but not murine interferons, suggesting species 
specificity. Studies with other interferons have demonstrated species specificity. However, certain monkey 
species, eg, rhesus monkeys, are susceptible to pharmacodynamic stimulation upon exposure to human type 
1 interferons. 
 
The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex 
sequence of intracellular events that include the induction of certain enzymes. It is thought that this process, 
at least in part, is responsible for the various cellular responses to interferon, including inhibition of virus 
replication in virus-infected cells, suppression of cell proliferation and such immunomodulating activities as 
enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of 
lymphocytes for target cells. Any or all of these activities may contribute to interferon's therapeutic effects. 
 
Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and 
human cell culture systems as well as human tumour xenografts in animals. It has demonstrated significant 
immunomodulatory activity in vitro. 
 
Recombinant interferon alfa-2b also inhibits viral replication in vitro and in vivo. Although the exact antiviral 
mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism. 
This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell. 
 
Chronic hepatitis B: 
Current clinical experience in patients who remain on interferon alfa-2b for 4 to 6 months indicates that 
therapy can produce clearance of serum HBV-DNA. An improvement in liver histology has been observed. 
In adult patients with loss of HBeAg and HBV-DNA, a significant reduction in morbidity and mortality has 
been observed. 
 
Interferon alfa-2b (6 MIU/m2 3 times a week for 6 months) has been given to children with chronic active 
hepatitis B. Because of a methodological flaw, efficacy could not be demonstrated. Moreover children treated 
with interferon alfa-2b experienced a reduced rate of growth and some cases of depression were observed. 
 
Chronic hepatitis C: 
In adult patients receiving interferon in combination with ribavirin, the achieved sustained response rate is 
47 %. Superior efficacy has been demonstrated with the combination of pegylated interferon with ribavirin 
(sustained response rate of 61 % achieved in a study performed in naïve patients with a ribavirin dose 
> 10.6 mg/kg, p < 0.01). 
 
Adult patients: Viraferon alone or in combination with ribavirin has been studied in 4 randomised Phase III 
clinical trials in 2,552 interferon-naïve patients with chronic hepatitis C. The trials compared the efficacy of 
Viraferon used alone or in combination with ribavirin. Efficacy was defined as sustained virologic response, 
6 months after the end of treatment. Eligible patients for these trials had chronic hepatitis C confirmed by a 
positive HCV-RNA polymerase chain reaction assay (PCR) (> 100 copies/ml), a liver biopsy consistent with 



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a histologic diagnosis of chronic hepatitis with no other cause for the chronic hepatitis, and abnormal serum 
ALT. 
 
Viraferon was administered at a dose of 3 MIU 3 times a week as monotherapy or in combination with 
ribavirin. The majority of patients in these clinical trials were treated for one year. All patients were followed 
for an additional 6 months after the end of treatment for the determination of sustained virologic response. 
Sustained virologic response rates for treatment groups treated for one year with Viraferon alone or in 
combination with ribavirin (from two studies) are shown in Table 3. 
 
Co-administration of Viraferon with ribavirin increased the efficacy of Viraferon by at least two fold for the 
treatment of chronic heptatitis C in naïve patients. HCV genotype and baseline virus load are prognostic 
factors which are known to affect response rates. The increased response rate to the combination of Viraferon + 
ribavirin, compared with Viraferon alone, is maintained across all subgroups. The relative benefit of combination 
therapy with Viraferon + ribavirin is particularly significant in the most difficult to treat subgroup of patients 
(genotype 1 and high virus load) (Table 3). 
 
Response rates in these trials were increased with compliance. Regardless of genotype, patients who received 
Viraferon in combination with ribavirin and received ≥ 80 % of their treatment had a higher sustained 
response 6 months after 1 year of treatment than those who took < 80 % of their treatment (56 % vs. 32 % in 
trial C/I98-580).  



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Table 3 Sustained virologic response rates with Viraferon + ribavirin (one year of 

treatment) by genotype and viral load 
 

HCV Genotype  
 

I 
N=503 

C95-132/I95-143 

I/R 
N=505 

C95-132/I95-143 

I/R 
N=505 

C/I98-580 
 
All Genotypes 

 
16 % 

 
41 % 

 
47 % 

 
 
Genotype 1 

 
9 % 

 
29 % 

 
33 % 

 
Genotype 1  
≤ 2 million 
copies/ml 

 
25 % 

 
33 % 

 
45 % 

 
Genotype 1 
> 2 million 
copies/ml 

 
3 % 

 
27 % 

 

 
29 % 

 
Genotype 2/3 

 
31 % 

 
65 % 

 
79 % 

I Viraferon (3 MIU 3 times a week) 
I/R Viraferon (3 MIU 3 times a week) + ribavirin (1,000/1,200 mg/day) 
 
HCV/HIV Co-infected patients  
Two trials have been conducted in patients co-infected with HIV and HCV. Overall, in both studies, patients 
who received Viraferon plus ribavirin, were less likely to respond than patients who received pegylated 
interferon alfa-2b with ribavirin. The response to treatment in both of these trials is presented in Table 4. 
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 412 previously untreated 
adult patients with chronic hepatitis C who were co-infected with HIV. Patients were randomized to receive 
either pegylated interferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800 mg/day) or Viraferon (3 MIU TIW) 
plus ribavirin (800 mg/day) for 48 weeks with a follow-up period of 6 months. Study 2 (P02080) was a 
randomized, single centre study that enrolled 95 previously untreated adult patients with chronic hepatitis C 
who were co-infected with HIV. Patients were randomized to receive either pegylated interferon alfa-2b (100 
or 150 µg /week based on weight) plus ribavirin (800-1,200 mg/day based on weight) or Viraferon (3 MIU 
TIW) plus ribavirin (800-1,200 mg/day based on weight). The duration of therapy was 48 weeks with a 
follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load 
< 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6-month follow-up period.  



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Table 4 Sustained virological response based on genotype after Viraferon in combination with 

ribavirin versus pegylated interferon alfa-2b in combination with ribavirin in 
HCV/HIV co-infected patients 

 Study 11 Study 22 
 

pegylated 
interferon 

alfa-2b  
(1.5 µg/kg/ 

week) + 
ribavirin  
(800 mg) 

Viraferon  
(3 MIU TIW) +  

ribavirin  
(800 mg) 

p 
valuea 

pegylated 
interferon 

alfa-2b (100 
or  

150c µg/week) 
+ ribavirin 

(800- 
1,200 mg)d 

Viraferon  
(3 MIU TIW) 

+ ribavirin 
(800- 

1,200 mg)d 
p 

valueb 
All 27 % (56/205) 20 % (41/205) 0.047 44 % (23/52) 21 % (9/43) 0.017 
Genotype 1, 

4 
17 % (21/125) 6 % (8/129) 0.006 38 % (12/32) 7 % (2/27) 0.007 

Genotype 2, 
3 

44 % (35/80) 43 % (33/76) 0.88 53 % (10/19) 47 % (7/15) 0.730 

MIU = million international units; TIW = three times a week. 
a:  p value based on Cochran-Mantel Haenszel Chi square test. 
b:  p value based on chi-square test. 
c:  subjects < 75 kg received 100 µg/week pegylated interferon alfa-2b and subjects ≥ 75 kg received 150 µg/week pegylated 

interferon alfa-2b. 
d: ribavirin dosing was 800 mg for patients < 60 kg, 1,000 mg for patients 60-75 kg, and 1,200 mg for patients > 75 kg. 
 

1Carrat F, Bani-Sadr F, Pol S et al.  JAMA 2004; 292(23): 2839-2848. 
2 Laguno M, Murillas J, Blanco J.L et al.  AIDS 2004; 18(13): F27-F36. 
 
 
Relapse patients: A total of 345 interferon alpha relapse patients were treated in two clinical trials with 
Viraferon monotherapy or in combination with ribavirin. In these patients, the addition of ribavirin to 
Viraferon increased by as much as 10-fold the efficacy of Viraferon used alone in the treatment of chronic 
hepatitis C (48.6 % vs. 4.7 %). This enhancement in efficacy included loss of serum HCV (< 100 copies/ml 
by PCR), improvement in hepatic inflammation, and normalisation of ALT, and was sustained when 
measured 6 months after the end of treatment. 
 
Long-Term efficacy data 
In a large study, 1,071 patients were enrolled after treatment in a prior non pegylated interferon alfa-2b or 
non pegylated interferon alfa-2b/ribavirin study to evaluate the durability of sustained virologic response and 
assess the impact of continued viral negativity on clinical outcomes. 462 patients completed at least 5 years 
of long-term follow-up and only 12 sustained responders' out of 492 relapsed during this study.  
The Kaplan-Meier estimate for continued sustained response over 5 years for all patients is 97 % with a 95 % 
Confidence Interval of [95 %, 99 %].  
SVR after treatment of chronic HCV with non pegylated interferon alfa-2b (with or without ribavirin) results 
in long-term clearance of the virus providing resolution of the hepatic infection and clinical 'cure' from 
chronic HCV. However, this does not preclude the occurrence of hepatic events in patients with cirrhosis 
(including hepatocarcinoma). 
 
Clinical trials in paediatric patients with chronic hepatitis C: 
Children and adolescents 3 to 16 years of age with compensated chronic hepatitis C and detectable HCV-
RNA (assessed by a central laboratory using a research-based RT-PCR assay) were enrolled in two 
multicentre trials and received Viraferon 3 MIU/m2 3 times a week plus ribavirin 15 mg/kg per day for 1 year 
followed by 6 months follow-up after-treatment. A total of 118 patients were enrolled: 57 % male, 80 % 
Caucasian, and 78 % genotype 1,64 % ≤ 12 years of age. The population enrolled mainly consisted in 
children with mild to moderate hepatitis C. Sustained virological response rates in children and adolescents 



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were similar to those in adults. Due to the lack of data in children with severe progression of the disease, and 
the potential for undesirable effects, the benefit/risk of the combination of ribavirin and interferon alfa-2b 
needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8). 
 
Study results are summarized in Table 5. 
 
Table 5. Virological response in previously untreated paediatric patients 
 Viraferon 3 MIU/m2 3 times a week   

+ 
ribavirin 15 mg/kg/day 

Overall Response1 (n=118) 54 (46 %)* 

Genotype 1 (n=92) 33 (36 %)* 

Genotype 2/3/4 (n=26) 21 (81 %)* 

*Number (%) of patients 
1. Defined as HCV-RNA below limit of detection using a research based RT-PCR assay at end of treatment and during follow-up 
period 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of Viraferon were studied in healthy volunteers following single 5 million IU/m2 and 
10 million IU doses administered subcutaneously, at 5 million IU/m2 administered intramuscularly and as a 
30-minute intravenous infusion. The mean serum interferon concentrations following subcutaneous and 
intramuscular injections were comparable. Cmax occurred three to 12 hours after the lower dose and six to 
eight hours after the higher dose. The elimination half-lives of interferon injections were approximately two 
to three hours, and six to seven hours, respectively. Serum levels were below the detection limit 16 and 
24 hours, respectively, post-injection. Both subcutaneous and intramuscular administration resulted in 
bioavailabilities greater than 100 %. 
 
After intravenous administration, serum interferon levels peaked (135 to 273 IU/ml) by the end of the 
infusion, then declined at a slightly more rapid rate than after subcutaneous or intramuscular administration 
of medicinal product, becoming undetectable four hours after the infusion. The elimination half-life was 
approximately two hours. 
 
Urine levels of interferon were below the detection limit following each of the three routes of administration. 
 
Children and adolescents: Multiple-dose pharmacokinetic properties for Viraferon injection and ribavirin 
capsules in children and adolescents with chronic hepatitis C, between 5 and 16 years of age, are summarized 
in Table 6. The pharmacokinetics of Viraferon and ribavirin (dose-normalized) are similar in adults and 
children or adolescents. 



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Table 6. Mean (% CV) multiple-dose pharmacokinetic parameters for Viraferon and ribavirin 

capsules when administered to children or adolescents with chronic hepatitis C 
Parameter Ribavirin 

15 mg/kg/day as 2 divided 
doses 

(n = 17) 

Viraferon 
3 MIU/m2 3 times a week 

(n = 54) 

Tmax (hr) 1.9 (83) 5.9 (36) 
Cmax (ng/ml) 3,275 (25) 51 (48) 

AUC* 29,774 (26) 622 (48) 
Apparent clearance l/hr/kg 0.27 (27) Not done 

*AUC12 (ng.hr/ml) for ribavirin; AUC0-24 (IU.hr/ml) for Viraferon 
 
Interferon neutralising factor assays were performed on serum samples of patients who received Viraferon in 
Schering-Plough monitored clinical trials. Interferon neutralising factors are antibodies which neutralise the 
antiviral activity of interferon. The clinical incidence of neutralising factors developing in cancer patients 
treated systemically is 2.9 % and in chronic hepatitis patients is 6.2 %. The detectable titres are low in almost 
all cases and have not been regularly associated with loss of response or any other autoimmune phenomenon. 
In patients with hepatitis, no loss of response was observed apparently due to the low titres. 
 
5.3 Preclinical safety data 
 
Although interferon is generally recognised as being species specific, toxicity studies in animals were 
conducted. Injections of human recombinant interferon alfa-2b for up to three months have shown no 
evidence of toxicity in mice, rats, and rabbits. Daily dosing of cynomolgus monkeys with 20 x 106 IU/kg/day 
for 3 months caused no remarkable toxicity. Toxicity was demonstrated in monkeys given 
100 x 106 IU/kg/day for 3 months. 
 
In studies of interferon use in non-human primates, abnormalities of the menstrual cycle have been observed 
(see section 4.4). 
 
Results of animal reproduction studies indicate that recombinant interferon alfa-2b was not teratogenic in rats 
or rabbits, nor did it adversely affect pregnancy, foetal development or reproductive capacity in offspring of 
treated rats. Interferon alfa-2b has been shown to have abortifacient effects in Macaca mulatta (rhesus 
monkeys) at 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2. 
Abortion was observed in all dose groups (7.5 million, 15 million and 30 million IU/kg), and was statistically 
significant versus control at the mid- and high-dose groups (corresponding to 90 and 180 times the 
recommended intramuscular or subcutaneous dose of 2 million IU/m2). High doses of other forms of 
interferons alpha and beta are known to produce dose-related anovulatory and abortifacient effects in rhesus 
monkeys. 
 
Mutagenicity studies with interferon alfa-2b revealed no adverse events. 
 
No studies have been conducted in juvenile animals to examine the effects of treatment with interferon alfa-
2b on growth, development, sexual maturation, and behaviour (see section 4.4 and Rebetol SPC if Viraferon 
is to be administered in combination with ribavirin). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Glycine,  
Disodium phosphate anhydrous,  



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Sodium dihydrogen phosphate monohydrate, 
Human albumin solution. 
 
Solvent: water for injections 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
3 years 
 
After reconstitution: An immediate use is recommended. However, the chemical and physical in-use stability 
has been demonstrated for 24 hours at 25ºC. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C).  
Do not freeze.  
Within its shelf-life, for the purpose of transport and/or to facilitate ambulatory use the non-reconstituted 
product can be kept at or below 25°C for a period up to four weeks before use. If the product is not 
reconstituted during the four-week period, it cannot be put back in the refrigerator for a new storage period 
and must be discarded. 
 
6.5 Nature and contents of container 
 
24 mg of powder (corresponding to 10 MIU) in a vial (type I glass), with a stopper (butyl rubber) in a flip-off 
seal (aluminium) with a bonnet (polypropylene) 
and 1 ml water for injections in an ampoule (type I glass) 
with 1 injection syringe, 2 injection needles and 1 cleansing swab. 
Pack sizes of 1 and 10 
 
Or 
 
24 mg of powder (corresponding to 10 MIU) in a vial (type I glass), with a stopper (butyl rubber) in a flip-off 
seal (aluminium) with a bonnet (polypropylene) 
and 1 ml water for injections in an ampoule (type I glass). 
Pack sizes of 6 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
Reconstitution of Viraferon, powder for solution for injection, for parenteral administration: Viraferon is 
supplied as a powder at strengths of 10 million IU/ml for single-dose use. Vials must be reconstituted with 
1 ml of water for injections. The reconstituted solutions are isotonic for parenteral administration. 
 
Proper precautions should be taken during reconstitution to prevent microbial contamination (refer to package 
leaflet).  
 



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Using a sterilised injection syringe and injection needle, inject 1 ml water for injections into the vial of 
Viraferon. Agitate gently to facilitate complete dissolution of the powder. The appropriate dose can then be 
withdrawn with a sterile injection syringe and injected. 
 
As for all parenteral medicinal products, inspect the reconstituted solution visually for particulate matter and 
discoloration prior to administration. The reconstituted solution should be clear and colourless. 
 
Detailed instructions for the subcutaneous use of the product are provided with the package leaflet (refer to 
“How to self inject Viraferon”). 
 
Any unused product must be discarded after withdrawal of the dose. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
SP Europe 
73, rue de Stalle 
B-1180 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/99/128/006 
EU/1/99/128/007 
EU/1/99/128/008 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation : 9 March 2000 
Date of last renewal : 23 May 2005 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu/ 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 3 million IU/0.5 ml solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One vial of Viraferon solution for injection, single dose vial, contains 3 million IU of recombinant interferon 
alfa-2b produced in E.coli by recombinant DNA technology, in 0.5 ml of solution. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection 
Solution is clear and colourless. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Chronic Hepatitis B: Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis B 
viral replication (presence of HBV-DNA and HBeAg), elevated alanine aminotransferase (ALT) and 
histologically proven active liver inflammation and/or fibrosis. 
 
Chronic Hepatitis C:  
Adult patients:  
Viraferon is indicated for the treatment of adult patients with chronic hepatitis C who have elevated 
transaminases without liver decompensation and who are positive for serum HCV-RNA or anti-HCV (see 
section 4.4). 
 
The best way to use Viraferon in this indication is in combination with ribavirin. 
 
Chidren and adolescents: 
Viraferon is intended for use, in a combination regimen with ribavirin, for the treatment of children and 
adolescents 3 years of age and older, who have chronic hepatitis C, not previously treated, without liver 
decompensation, and who are positive for serum HCV-RNA. The decision to treat should be made on a case 
by case basis, taking into account any evidence of disease progression such as hepatic inflammation and 
fibrosis, as well as prognostic factors for response, HCV genotype and viral load. The expected benefit of 
treatment should be weighed against the safety findings observed for paediatric subjects in the clinical trials 
(see sections 4.4, 4.8 and 5.1). 
 
4.2 Posology and method of administration 
 
Treatment must be initiated by a physician experienced in the management of the disease. 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
If adverse events develop during the course of treatment with Viraferon for any indication, modify the dosage 
or discontinue therapy temporarily until the adverse events abate. If persistent or recurrent intolerance 
develops following adequate dosage adjustment, or disease progresses, discontinue treatment with Viraferon. 



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At the discretion of the physician, the patient may self-administer the dose for maintenance dosage regimens 
administered subcutaneously. 
 
Chronic Hepatitis B: The recommended dosage is in the range 5 to 10 million IU administered 
subcutaneously three times a week (every other day) for a period of 4 to 6 months. 
 
The administered dose should be reduced by 50 % in case of occurrence of haematological disorders (white 
blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3). Treatment should be 
discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe 
thrombocytopaenia (< 70,000/mm3). 
 
For all patients, if no improvement on serum HBV-DNA is observed after 3 to 4 months of treatment (at the 
maximum tolerated dose), discontinue Viraferon therapy. 
 
Chronic Hepatitis C: Viraferon is administered subcutaneously at a dose of 3 million IU three times a week 
(every other day) to adult patients, whether administered as monotherapy or in combination with ribavirin. 
 
Children 3 years of age or older and adolescents: Interferon alfa-2b 3 MIU/m2 is administered 
subcutaneously 3 times a week (every other day) in combination with ribavirin capsules or oral solution 
administered orally in two divided doses daily with food (morning and evening).  
 
(See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination 
therapy. For paediatric patients who weigh < 47 kg or cannot swallow capsules, see ribavirin oral solution 
SPC).  
 
Relapse patients (adults): 
Viraferon is given in combination with ribavirin. 
 
Based on the results of clinical trials, in which data are available for 6 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for 6 months. 
 
Naïve patients: 
Adults: The efficacy of Viraferon is enhanced when given in combination with ribavirin. Viraferon should be 
given alone mainly in case of intolerance or contraindication to ribavirin. 
 
Viraferon in combination with ribavirin: 
Based on the results of clinical trials, in which data are available for 12 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for at least 6 months. 
 
Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit 
negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and 
high pre-treatment viral load. 
 
Other negative prognostic factors (age > 40 years, male gender, bridging fibrosis) should be taken into 
account in order to extend therapy to 12 months. 
 
During clinical trials, patients who failed to show a virologic response after 6 months of treatment (HCV-
RNA below lower limit of detection) did not become sustained virologic responders (HCV-RNA below lower 
limit of detection six months after withdrawal of treatment). 
 
Viraferon alone: 
The optimal duration of therapy with Viraferon alone is not yet fully established, but a therapy of between 
12 and 18 months is advised. 
 



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It is recommended that patients be treated with Viraferon alone for at least 3 to 4 months, at which point 
HCV-RNA status should be determined. Treatment should be continued in patients who exhibit negative 
HCV-RNA. 
 
Children and adolescents: The efficacy and safety of Viraferon in combination with ribavirin has been 
studied in children and adolescents who have not been previously treated for chronic hepatitis C.  
 
Genotype 1: The recommended duration of treatment is one year. Patients who fail to achieve virological 
response at 12 weeks are highly unlikely to become sustained virological responders (negative predictive 
value 96 %). Virological response is defined as absence of detectable HCV-RNA at Week 12. Treatment 
should be discontinued in these patients. 
Genotype 2/3: The recommended duration of treatment is 24 weeks. 
 
Virological responses after 1 year of treatment and 6 months of follow-up were 36 % for genotype 1 and 
81 % for genotype 2/3/4. 
 
Viraferon may be administered using either glass or plastic disposable injection syringes. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients. 
- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure, recent 

myocardial infarction, severe arrhythmic disorders.  
- Severe renal or hepatic dysfunction; including that caused by metastases. 
- Epilepsy and/or compromised central nervous system (CNS) function (see section 4.4). 
- Chronic hepatitis with decompensated cirrhosis of the liver. 
- Chronic hepatitis in patients who are being or have been treated recently with immunosuppressive 

agents excluding short term corticosteroid withdrawal. 
- Autoimmune hepatitis; or history of autoimmune disease; immunosuppressed transplant recipients. 
- Pre-existing thyroid disease unless it can be controlled with conventional treatment. 
 
Children and adolescents: 
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal 

ideation or suicide attempt. 
 

Combination therapy with ribavirin: Also see ribavirin SPC if interferon alfa-2b is to be administered in 
combination with ribavirin in patients with chronic hepatitis C. 
 
4.4 Special warnings and precautions for use 
 
For all patients: 
Psychiatric and central nervous system (CNS): Severe CNS effects, particularly depression, suicidal ideation 
and attempted suicide have been observed in some patients during Viraferon therapy, and even after 
treatment discontinuation mainly during the 6-month follow-up periodand in the follow-up period. Among 
children and adolescents treated with Viraferon in combination with ribavirin, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6-month 
follow-up after treatment. As in adult patients, children and adolescents experienced other psychiatric adverse 
events (e.g., depression, emotional lability, and somnolence). Other CNS effects including aggressive behaviour 
(sometimes directed against others), confusion and alterations of mental status have been observed with alpha 
interferons. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such 
symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the 
prescribing physician and the need for adequate therapeutic management should be considered. If psychiatric 
symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with 
Viraferon be discontinued, and the patient followed, with psychiatric intervention as appropriate. 
 



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Patients with existence of or history of severe psychiatric conditions: 
If a treatment with interferon alfa-2b is judged necessary in adult patients with existence or history of severe 
psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and 
therapeutic management of the psychiatric condition. The use of interferon alfa-2b in children and adolescents 
with existence of or history of severe psychiatric conditions is contraindicated (see section 4.3). 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Moderate to severe adverse experiences may require modification of the patient's dosage regimen, or in some 
cases, termination of Viraferon therapy. Any patient developing liver function abnormalities during treatment 
with Viraferon must be monitored closely and treatment discontinued if signs and symptoms progress. 
 
Hypotension may occur during Viraferon therapy or up to two days post-therapy and may require supportive 
treatment. 
 
Adequate hydration must be maintained in patients undergoing Viraferon therapy since hypotension related 
to fluid depletion has been seen in some patients. Fluid replacement may be necessary. 
 
While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, 
other causes of persistent fever must be ruled out. 
 
Viraferon must be used cautiously in patients with debilitating medical conditions, such as those with a 
history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to 
ketoacidosis. Caution must be observed also in patients with coagulation disorders (e.g., thrombophlebitis, 
pulmonary embolism) or severe myelosuppression. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.5). Any patient developing fever, cough, 
dyspnea or other respiratory symptoms must have a chest X-ray taken. If the chest X-ray shows pulmonary 
infiltrates or there is evidence of pulmonary function impairment, the patient is to be monitored closely, and, 
if appropriate, discontinue interferon alpha. While this has been reported more often in patients with chronic 
hepatitis C treated with interferon alpha, it has also been reported in patients with oncologic diseases treated 
with interferon alpha. Prompt discontinuation of interferon alpha administration and treatment with 
corticosteroids appear to be associated with resolution of pulmonary adverse events. 
 
Ocular adverse events (see section 4.8) including retinal haemorrhages, cotton wool spots, and retinal artery 
or vein obstruction have been reported in rare instance after treatment with alpha interferons. All patients 
should have a baseline eye examination. Any patient complaining of changes in visual acuity or visual fields, 
or reporting other ophthalmologic symptoms during treatment with Viraferon, must have a prompt and 
complete eye examination. Periodic visual examinations during Viraferon therapy are recommended 
particularly in patients with disorders that may be associated with retinopathy, such as diabetes mellitus or 
hypertension. Discontinuation of Viraferon should be considered in patients who develop new or worsening 
ophthalmological disorders. 
 



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More significant obtundation and coma, including cases of encephalopathy, have been observed in some 
patients, usually elderly, treated at higher doses. While these effects are generally reversible, in a few patients 
full resolution took up to three weeks. Very rarely, seizures have occurred with high doses of Viraferon. 
 
Adult patients with a history of congestive heart failure, myocardial infarction and/or previous or current 
arrhythmic disorders, who require Viraferon therapy, must be closely monitored. It is recommended that 
those patients who have pre-existing cardiac abnormalities and/or are in advanced stages of cancer have 
electrocardiograms taken prior to and during the course of treatment. Cardiac arrhythmias (primarily 
supraventricular) usually respond to conventional therapy but may require discontinuation of Viraferon 
therapy. There are no data in children or adolescents with a history of cardiac disease. 
 
Hypertriglyceridemia and aggravation of hypertriglyceridemia, sometimes severe, have been observed. 
Monitoring of lipid levels is, therefore, recommended. 
 
Due to reports of interferon alpha exacerbating pre-existing psoriatic disease and sarcoidosis, use of 
Viraferon in patients with psoriasis or sarcoidosis is recommended only if the potential benefit justifies the 
potential risk. 
 
Preliminary data indicates that interferon alpha therapy may be associated with an increased rate of kidney 
graft rejection. Liver graft rejection has also been reported. 
 
The development of auto-antibodies and autoimmune disorders has been reported during treatment with alpha 
interferons. Patients predisposed to the development of autoimmune disorders may be at increased risk. 
Patients with signs or symptoms compatible with autoimmune disorders should be evaluated carefully, and 
the benefit-risk of continued interferon therapy should be reassessed (see also section 4.4 Chronic hepatitis C, 
Monotherapy (thyroid abnormalities) and section 4.8). 
Cases of Vogt-Koyanagi-Harada (VKH) syndrome have been reported in patients with chronic hepatitis C 
treated with interferon. This syndrome is a granulomatous inflammatory disorder affecting the eyes, auditory 
system, meninges, and skin. If VKH syndrome is suspected, antiviral treatment should be withdrawn and 
corticosteroid therapy discussed (see section 4.8). 
 
Discontinue treatment with Viraferon in patients with chronic hepatitis who develop prolongation of 
coagulation markers which might indicate liver decompensation. 
 
Chronic Hepatitis C: 
Combination therapy with ribavirin: Also see ribavirin SPC if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i.e. 
patients with genotype 2 and 3), treatment may be possible without histological confirmation. Current 
treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing 
treatment. 
 
Monotherapy: Infrequently, adult patients treated for chronic hepatitis C with Viraferon developed thyroid 
abnormalities, either hypothyroidism or hyperthyroidism. In clinical trials using Viraferon therapy, 2.8 % 
patients overall developed thyroid abnormalities. The abnormalities were controlled by conventional therapy 
for thyroid dysfunction. The mechanism by which Viraferon may alter thyroid status is unknown. Prior to 
initiation of Viraferon therapy for the treatment of chronic hepatitis C, evaluate serum thyroid-stimulating 
hormone (TSH) levels. Any thyroid abnormality detected at that time must be treated with conventional 
therapy. Viraferon treatment may be initiated if TSH levels can be maintained in the normal range by 
medication. Determine TSH levels if, during the course of Viraferon therapy, a patient develops symptoms 
consistent with possible thyroid dysfunction. In the presence of thyroid dysfunction, Viraferon treatment may 
be continued if TSH levels can be maintained in the normal range by medication. Discontinuation of 
Viraferon therapy has not reversed thyroid dysfunction occurring during treatment (also see Children and 
adolescents, Thyroid monitoring). 



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Supplemental monitoring specific for children and adolescents 
Thyroid Monitoring: Approximately 12 % of children treated with interferon alfa-2b and ribavirin developed 
increase in TSH. Another 4 % had a transient decrease below the lower limit of normal. Prior to initiation of 
Viraferon therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be 
treated with conventional therapy. Viraferon therapy may be initiated if TSH levels can be maintained in the 
normal range by medication. Thyroid dysfunction during treatment with interferon alfa-2b and ribavirin has 
been observed. If thyroid abnormalities are detected, the patient’s thyroid status should be evaluated and 
treated as clinically appropriate. Children and adolescents should be monitored every 3 months for evidence 
of thyroid dysfunction (e.g. TSH). 
 
Growth and Development: During a 1-year course of therapy there was a decrease in the rate of linear growth 
(mean percentile decrease of 9 %) and a decrease in the rate of weight gain (mean percentile decrease of 
13 %). A general reversal of these trends was noted during the 6 months follow-up post treatment. However, 
based on interim data from a long-term follow-up study, 12 (14 %) of 84 children had a > 15 percentile 
decrease in rate of linear growth, of whom 5 (6 %) children had a > 30 percentile decrease despite being off 
treatment for more than 1 year. In addition, preclicinal juvenile toxicity results have demonstrated a minor, 
dose-related decrease in overall growth in neonatal rats dosed with ribavirin (see section 5.3). Therefore, the 
risk/benefit of the combined use of interferon alfa-2b and ribavirin should be assessed in young children prior 
to the initiation of therapy. Physicians are advised to monitor the growth of children taking ribavirin in 
combination with interferon alfa-2b. There are no data on long term effects on growth and development and 
on sexual maturation. 
 
HCV/HIV Coinfection: Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy 
(HAART) may be at increased risk of developing lactic acidosis. Caution should be used when adding Viraferon 
and ribavirin to HAART therapy (see ribavirin SPC). Patients treated with Viraferon and ribavirin combination 
therapy and zidovudine could be at increased risk of developing anaemia. 
Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic 
decompensation and death. Adding treatment with alfa interferons alone or in combination with ribavirin may 
increase the risk in this patient subset.  
 
Dental and periodontal disorders: Dental and periodontal disorders, which may lead to loss of teeth, have 
been reported in patients receiving Viraferon and ribavirin combination therapy. In addition, dry mouth could 
have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the 
combination of Viraferon and ribavirin. Patients should brush their teeth thoroughly twice daily and have 
regular dental examinations. In addition some patients may experience vomiting. If this reaction occurs, they 
should be advised to rinse out their mouth thoroughly afterwards. 
 
Laboratory Tests:  
Standard haematological tests and blood chemistries (complete blood count and differential, platelet count, 
electrolytes, liver enzymes, serum protein, serum bilirubin and serum creatinine) are to be conducted in all 
patients prior to and periodically during systemic treatment with Viraferon. 
 
During treatment for hepatitis B or C the recommended testing schedule is at weeks 1, 2, 4, 8, 12, 16, and 
every other month, thereafter, throughout treatment. If ALT flares during Viraferon therapy to greater than or 
equal to 2 times baseline, Viraferon therapy may be continued unless signs and symptoms of liver failure are 
observed. During ALT flare, liver function tests: ALT, prothrombin time, alkaline phosphatase, albumin and 
bilirubin must be monitored at two-week intervals. 
 
Effect on fertility: Interferon may impair fertility (see section 4.6 and section 5.3). 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with 
Viraferon. 



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Interactions between Viraferon and other medicinal products have not been fully evaluated. Caution must be 
exercised when administering Viraferon in combination with other potentially myelosuppressive agents. 
 
Interferons may affect the oxidative metabolic process. This must be considered during concomitant therapy 
with medicinal products metabolised by this route, such as the xanthine derivatives theophylline or 
aminophylline. During concomitant therapy with xanthine agents, serum theophylline levels must be 
monitored and dosage adjusted if necessary. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.4). 
 
(Also see ribavirin SPC if Viraferon is to be administered in combination with ribavirin in patients with 
chronic hepatitis C). 
 
4.6 Pregnancy and lactation 
 
Women of childbearing potential have to use effective contraception during treatment. Viraferon must be 
used with caution in fertile men. Decreased serum estradiol and progesterone concentrations have been 
reported in women treated with human leukocyte interferon. 
 
There are no adequate data from the use of interferon alfa-2b in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Viraferon is to be 
used during pregnancy only if the potential benefit justifies the potential risk to the foetus. 
 
It is not known whether the components of this medicinal product are excreted in human milk. Because of the 
potential for adverse reactions in nursing infants, nursing should be discontinued prior to initiation of 
treatment. 
 
Combination therapy with ribavirin: Ribavirin causes serious birth defects when administered during 
pregnancy. Ribavirin therapy is contraindicated in women who are pregnant. Extreme care must be taken to 
avoid pregnancy in female patients or in partners of male patients taking Viraferon in combination with 
ribavirin. Females of childbearing potential and their partners must each use an effective contraceptive during 
treatment and for 4 months after treatment has been concluded. Male patients and their female partners must 
each use an effective contraceptive during treatment and for 7 months after treatment has been concluded (see 
ribavirin SPC). 
 
4.7 Effects on ability to drive and use machines 
 
Patients are to be advised that they may develop fatigue, somnolence, or confusion during treatment with 
Viraferon, and therefore it is recommended that they avoid driving or operating machinery. 
 
4.8 Undesirable effects 
 
See ribavirin SPC for ribavirin-related undesirable effects if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
In clinical trials conducted in a broad range of indications and at a wide range of doses (from 6 MIU/m2/week 
in hairy cell leukaemia up to 100 MIU/m2/week in melanoma), the most commonly reported undesirable 
effects were fever, fatigue, headache and myalgia. Fever and fatigue were often reversible within 72 hours of 
interruption or cessation of treatment. 
 



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In clinical trials conducted in the hepatitis C population, patients were treated with Viraferon alone or in 
combination with ribavirin for one year. All patients in these trials received 3 MIU of Viraferon three times a 
week. In Table 1 the frequency of patients reporting (treatment related) undesirable effects is presented from 
clinical trials in naïve patients treated for one year. Severity was generally mild to moderate. The adverse 
reactions listed in Table 1 are based on experience from clinical trials and post-marketing. Within the organ 
system classes, adverse reactions are listed under headings of frequency using the following categories: very 
common (≥1/10); common (≥1/100, <1/10); rarely (≥1/10,000, <1/1,000); very rarely (<1/10,000); not 
known. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

Table 1. Adverse reactions reported during clinical trials or following the marketing use of Viraferon 
alone or in combination with ribavirin 

System Organ Class Adverse Reactions 
Infections and infestations 
Very common: 
Common: 
Rarely:  

 
Pharyngitis*, infection viral* 
Bronchitis, sinusitis, herpes simplex (resistance), rhinitis 
Pneumonia§ 

Blood and lymphatic system disorders 
Very common: 
Common: 
Very rarely:  
Not known:  

 
Leukopaenia 
Thrombocytopaenia, lymphadenopathy, lymphopenia 
Aplastic anaemia 
Pure red cell aplasia, idiopathic thrombocytopenic purpura, 
thrombotic thrombocytopenic purpura  

Immune system disorders§ 
Very rarely:  
Not known: 

 
Sarcoidosis, exacerbation of sarcoidosis 
Systemic lupus erythematosus, vasculitis, rheumatoid 
arthritis (new or aggravated), Vogt-Koyanagi-Harada 
syndrome, acute hypersensitivity reactions including 
urticaria, angioedema, bronchoconstriction, anaphylaxis§ 

Endocrine disorders 
Common: 
Very rarely:  

 
Hypothyroidism§, hyperthyroidism§ 
Diabetes, aggravated diabetes 

Metabolism and nutrition disorders 
Very common: 
Common:  
Very rarely:  

 
Anorexia 
Hypocalcaemia, dehydration, hyperuricemia, thirst 
Hyperglycaemia, hypertriglyceridaemia§, increased appetite 

Psychiatric disorders§ 
Very common: 
 
Common: 
Rarely:  
Very rarely: 
 
Not known: 

 
Depression, insomnia, anxiety, emotional lability*, 
agitation, nervousness 
Confusion, sleep disorder, libido decreased 
Suicide ideation 
Suicide, suicide attempts, aggressive behaviour (sometimes 
directed against others), psychosis including hallucinations 
Mental status change§ 

Nervous system disorders§ 
Very common: 
Common: 
 
Very rarely:  
 
 
Not known: 

 
Dizziness, headache, concentration impaired, mouth dry 
Tremor, paresthesia, hypoesthesia, migraine, flushing, 
somnolence, taste perversion 
Cerebrovascular haemorrhage, cerbrovascular ischaemia, 
seizure, impaired consciousness, encephalopathy, 
neuropathy, polyneuropathy 
Mononeuropathies, coma§ 

Eye disorders 
Very common: 
Common: 

 
Vision blurred 
Conjunctivitis, vision abnormal, lacrimal gland disorder, eye 



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Rarely:  

pain 
Retinal haemorrhages§, retinopathies (including macular 
oedema), retinal artery or vein obstruction§, optic neuritis, 
papilloedema, loss of visual acuity or visual field, cotton-
wool spots§  

Ear and labyrinth 
Common: 
Very rarely:  

 
Vertigo, tinnitus 
Hearing loss, hearing disorder 

Cardiac disorders 
Common: 
Rarely: 
Very rarely: 
Not known: 

 
Palpitation, tachycardia 
Cardiomyopathy 
Myocardial infarction, cardiac ischaemia  
Arrhythmia  

Vascular disorders 
Common: 
Very rarely:  

 
Hypertension 
Peripheral ischaemia, hypotension§ 

Respiratory, thoracic and mediastinal 
disorders 
Very common: 
Common: 
 
Very rarely:  

 
 
Dyspnoea*, coughing* 
Epistaxis, respiratory disorder, nasal congestion, rhinorrhea, 
cough nonproductive 
Pulmonary infiltrates§, pneumonitis§ 

Gastrointestinal disorders 
Very common: 
 
Common: 
 
Very rarely:  
 
Not known: 

 
Nausea/vomiting, abdominal pain, diarrhoea, stomatitis, 
dyspepsia 
Stomatitis ulcerative, right upper quadrant pain, glossitis, 
gingivitis, constipation, loose stools 
Pancreatitis, ischaemic colitis, ulcerative colitis, gingival 
bleeding 
Periodontal disorder NOS, dental disorder NOS§ 

Hepatobiliary disorders 
Common: 
Very rarely:  

 
Hepatomegaly 
Hepatotoxicity, (including fatality) 

Skin and subcutaneous tissue disorders 
Very common: 
Common: 
 
Very rarely:  

 
Alopecia, pruritus*, skin dry*, rash*, sweating increased 
Psoriasis (new or aggravated)§, rash maculopapular, rash 
erythematous, eczema, erythema, skin disorder 
Stevens Johnson syndrome, toxic epidermal necrolysis, 
erythema multiforme 

Musculoskeletal and connective tissue 
disorders 
Very common:  
Common: 
Very rarely: 

 
 
Myalgia, arthralgia, musculoskeletal pain 
Arthritis 
Rhabdomyolysis, myositis, leg cramps, back pain 

Renal and urinary disorders 
Common: 
Very rarely:  

 
Micturition frequency 
Renal failure, renal insufficiency, nephrotic syndrome 

Reproductive system and breast 
disorders 
Common: 

 
 
Amenorrhea, breast pain, dysmenorrhea, menorrhagia, 
menstrual disorder, vaginal disorder 

General disorders and administration 
site conditions 
Very common: 

 
 
Injection site inflammation, injection site reaction*, fatigue, 



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Common: 
Very rarely: 

rigors, fever§, flu-like symptoms§, asthenia, irritability, chest 
pain, malaise 
Injection site pain 
Injection site necrosis, face oedema 

Investigations 
Very common: 

 
Weight decrease 

*These events were only common with Viraferon alone 
§See section 4.4 
 
These undesirable effects have also been reported with Viraferon alone. 
 
Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-
existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4). Cardiomyopathy, that may 
be reversible upon discontinuation of interferon alpha, has been reported rarely in patients without prior 
evidence of cardiac disease (see section 4.4).  
 
A wide variety of autoimmune and immune-mediated disorders have been reported with alpha interferons 
including thyroid disorders, systemic lupus erythematosus, rheumatoid arthritis (new or aggravated), 
idiopathic and thrombotic thrombocytopenic purpura, vasculitis, neuropathies including mononeuropathies 
(see also section 4.4).  
 
Clinically significant laboratory abnormalities, most frequently occurring at doses greater than 10 million IU 
daily, include reduction in granulocyte and white blood cell counts; decreases in haemoglobin level and 
platelet count; increases in alkaline phosphatase, LDH, serum creatinine and serum urea nitrogen levels. 
Increase in serum ALT/AST (SGPT/SGOT) levels have been noted as an abnormality in some non-hepatitis 
subjects and also in some patients with chronic hepatitis B coincident with clearance of viral DNAp. 
 
Paediatric population 
 
Children and adolescents – Chronic Hepatitis C 
In clinical trials of 118 children or adolescents 3 to 16 years of age, 6 % discontinued therapy due to adverse 
events. In general, the adverse event profile in the limited paediatric population studied was similar to that 
observed in adults, although there is a paediatric specific concern regarding growth inhibition as decrease in 
height (mean percentile decrease of growth velocity of 9 %) and weight (mean percentile decrease of 13 %) 
percentile were observed during treatment (see section 4.4). Furthermore, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6 month 
follow-up after treatment. As in adult patients, children and adolescents also experienced other psychiatric 
adverse events (e.g., depression, emotional lability, and somnolence) (see section 4.4). In addition, injection 
site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in children and 
adolescents compared to adult patients. Dose modifications were required in 30 % of patients, most 
commonly for anaemia and neutropaenia. 
 
The adverse reactions listed in Table 2 are based on experience from paediatric clinical trials.  
Within the organ system classes, adverse reactions are listed under headings of frequency using the following 
categories: very common (≥1/10); common (≥1/100, <1/10). Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness. 
 
Table 2  Adverse reactions very commonly and commonly reported in paediatric clinical trials  

Very common (≥1/10) - Common (≥1/100, <1/10) 
System Organ Class Adverse Reactions 
Infection and infestations 
Very common: 
Common: 

 
Viral infection, pharyngitis 
Fungal infection, bacterial infection, pulmonary infection, otitis 
media, tooth abscess, herpes simplex, urinary tract infection, 



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vaginitis, gastroenteritis 
Neoplasms benign, malignant 
and unspecified (including 
cysts and polyps) 
Common: 

 
 
 
Neoplasm (unspecified) 

Blood and lymphatic system 
disorders 
Very common: 
Common: 

 
 
Anaemia, neutropaenia 
Thrombocytopaenia, lymphadenopathy 

Endocrine disorders 
Very common: 
Common: 

 
Hypothyroidism§,  
Hyperthyroidism§, virilism 

Metabolism and nutrition 
disorders 
Very common: 
Common: 

 
 
Anorexia 
Hypertriglyceridemia§, hyperuricemia, increased appetite 

Psychiatric disorders§ 
Very common: 
Common: 

 
Depression, emotional lability, insomnia 
Suicidal ideation, aggressive reaction, confusion, behaviour 
disorder, agitation, somnambulism, anxiety, nervousness, sleep 
disorder, abnormal dreaming, apathy 

Nervous system disorders§ 
Very common: 
Common: 

 
Headache, dizziness 
Hyperkinesia, tremor, dysphonia, paresthaesia, hypoaesthesia, 
hyperaesthesia, concentration impaired, somnolence 

Eye disorders 
Common: 

 
Conjunctivitis, eye pain, abnormal vision, lacrimal gland disorder 

Vascular disorders 
Common: 

 
Raynaud’s disease, flushing, pallor 

Respiratory, thoracic and 
mediastinal disorders 
Common: 

 
 
Dyspnoea, tachypnea, epistaxis, coughing, nasal congestion, nasal 
irritation, rhinorrhea, sneezing 

Gastrointestinal disorders 
Very common: 
Common: 

 
Diarrhoea, vomiting, nausea, abdominal pain 
Mouth ulceration, stomatitis ulcerative, stomatitis, right upper 
quadrant pain, dyspepsia, glossitis, gastroesophogeal reflux, rectal 
disorder, gastrointestinal disorder, constipation, loose stools, 
toothache, tooth disorder 

Hepatobiliary disorders 
Common: 

 
Hepatic function abnormal 

Skin and subcutaneous tissue 
disorders  
Very common: 
Common: 

 
 
Alopecia, rash 
Photosensitivity reaction, maculopapular rash, eczema, acne, skin 
disorder, nail disorder, skin discolouration, pruritus, dry skin, 
erythema, bruise, sweating increased 

Musculoskeletal and 
connective tissue disorders 
Very common: 

 
 
Arthralgia, myalgia, musculoskeletal pain  

Renal and urinary disorders 
Common: 

 
Enuresis, micturition disorder, urinary incontinence 

Reproductive system and 
breast disorders 

 
 



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Common: Female: amenorrhea, menorrhagia, menstrual disorder, vaginal 
disorder 
Male: testicular pain 

General disorders and 
administration site 
conditions 
Very common: 
 
Common: 

 
 
 
Injection site inflammation, injection site reaction, fatigue, rigors, 
fever§, influenza-like symptoms§, malaise, irritability 
Chest pain, asthenia, oedema, injection site pain 

Investigations 
Very common: 

 
Growth rate decrease (height and/or weight decrease for age)§  

Injury and poisoning 
Common: 

 
Skin laceration 

§See section 4.4 
 
4.9 Overdose 
 
No case of overdose has been reported that has led to acute clinical manifestations. However, as for any 
pharmacologically active compound, symptomatic treatment with frequent monitoring of vital signs and close 
observation of the patient is indicated. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunostimulants, cytokines and immunomodulators, interferons, interferon 
alfa-2b, ATC code: L03A B05 
 
Viraferon is a sterile, stable, formulation of highly purified interferon alfa-2b produced by recombinant DNA 
techniques. Recombinant interferon alfa-2b is a water-soluble protein with a molecular weight of 
approximately 19,300 daltons. It is obtained from a clone of E. coli, which harbours a genetically engineered 
plasmid hybrid encompassing an interferon alfa-2b gene from human leukocytes. 
 
The activity of Viraferon is expressed in terms of IU, with 1 mg of recombinant interferon alfa-2b protein 
corresponding to 2.6 x l08 IU. International Units are determined by comparison of the activity of the 
recombinant interferon alfa-2b with the activity of the international reference preparation of human leukocyte 
interferon established by the World Health Organisation. 
 
The interferons are a family of small protein molecules with molecular weights of approximately 15,000 to 
21,000 daltons. They are produced and secreted by cells in response to viral infections or various synthetic 
and biological inducers. Three major classes of interferons have been identified: alpha, beta and gamma. 
These three main classes are themselves not homogeneous and may contain several different molecular 
species of interferon. More than 14 genetically distinct human alpha interferons have been identified. 
Viraferon has been classified as recombinant interferon alfa-2b. 
 
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. 
Human interferon receptors, as isolated from human lymphoblastoid (Daudi) cells, appear to be highly 
asymmetric proteins. They exhibit selectivity for human but not murine interferons, suggesting species 
specificity. Studies with other interferons have demonstrated species specificity. However, certain monkey 
species, eg, rhesus monkeys, are susceptible to pharmacodynamic stimulation upon exposure to human type 
1 interferons. 
 



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The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex 
sequence of intracellular events that include the induction of certain enzymes. It is thought that this process, 
at least in part, is responsible for the various cellular responses to interferon, including inhibition of virus 
replication in virus-infected cells, suppression of cell proliferation and such immunomodulating activities as 
enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of 
lymphocytes for target cells. Any or all of these activities may contribute to interferon's therapeutic effects. 
 
Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and 
human cell culture systems as well as human tumour xenografts in animals. It has demonstrated significant 
immunomodulatory activity in vitro. 
 
Recombinant interferon alfa-2b also inhibits viral replication in vitro and in vivo. Although the exact antiviral 
mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism. 
This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell. 
 
Chronic hepatitis B: 
Current clinical experience in patients who remain on interferon alfa-2b for 4 to 6 months indicates that 
therapy can produce clearance of serum HBV-DNA. An improvement in liver histology has been observed. 
In adult patients with loss of HBeAg and HBV-DNA, a significant reduction in morbidity and mortality has 
been observed. 
 
Interferon alfa-2b (6 MIU/m2 3 times a week for 6 months) has been given to children with chronic active 
hepatitis B. Because of a methodological flaw, efficacy could not be demonstrated. Moreover children treated 
with interferon alfa-2b experienced a reduced rate of growth and some cases of depression were observed. 
 
Chronic hepatitis C: 
In adult patients receiving interferon in combination with ribavirin, the achieved sustained response rate is 
47 %. Superior efficacy has been demonstrated with the combination of pegylated interferon with ribavirin 
(sustained response rate of 61 % achieved in a study performed in naïve patients with a ribavirin dose 
> 10.6 mg/kg, p < 0.01). 
 
Adult patients: Viraferon alone or in combination with ribavirin has been studied in 4 randomised Phase III 
clinical trials in 2,552 interferon-naïve patients with chronic hepatitis C. The trials compared the efficacy of 
Viraferon used alone or in combination with ribavirin. Efficacy was defined as sustained virologic response, 
6 months after the end of treatment. Eligible patients for these trials had chronic hepatitis C confirmed by a 
positive HCV-RNA polymerase chain reaction assay (PCR) (> 100 copies/ml), a liver biopsy consistent with 
a histologic diagnosis of chronic hepatitis with no other cause for the chronic hepatitis, and abnormal serum 
ALT. 
 
Viraferon was administered at a dose of 3 MIU 3 times a week as monotherapy or in combination with 
ribavirin. The majority of patients in these clinical trials were treated for one year. All patients were followed 
for an additional 6 months after the end of treatment for the determination of sustained virologic response. 
Sustained virologic response rates for treatment groups treated for one year with Viraferon alone or in 
combination with ribavirin (from two studies) are shown in Table 3. 
 
Co-administration of Viraferon with ribavirin increased the efficacy of Viraferon by at least two fold for the 
treatment of chronic heptatitis C in naïve patients. HCV genotype and baseline virus load are prognostic 
factors which are known to affect response rates. The increased response rate to the combination of Viraferon + 
ribavirin, compared with Viraferon alone, is maintained across all subgroups. The relative benefit of combination 
therapy with Viraferon + ribavirin is particularly significant in the most difficult to treat subgroup of patients 
(genotype 1 and high virus load) (Table 3). 
 
Response rates in these trials were increased with compliance. Regardless of genotype, patients who received 
Viraferon in combination with ribavirin and received ≥ 80 % of their treatment had a higher sustained 



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response 6 months after 1 year of treatment than those who took < 80 % of their treatment (56 % vs. 32 % in 
trial C/I98-580).  
 

Table 3 Sustained virologic response rates with Viraferon + ribavirin (one year of 
treatment) by genotype and viral load 

 
HCV Genotype  
 

I 
N=503 

C95-132/I95-143 

I/R 
N=505 

C95-132/I95-143 

I/R 
N=505 

C/I98-580 
 
All Genotypes 

 
16 % 

 
41 % 

 
47 % 

 
 
Genotype 1 

 
9 % 

 
29 % 

 
33 % 

 
Genotype 1  
≤ 2 million 
copies/ml 

 
25 % 

 
33 % 

 
45 % 

 
Genotype 1 
> 2 million 
copies/ml 

 
3 % 

 
27 % 

 

 
29 % 

 
Genotype 2/3 

 
31 % 

 
65 % 

 
79 % 

I Viraferon (3 MIU 3 times a week) 
I/R Viraferon (3 MIU 3 times a week) + ribavirin (1,000/1,200 mg/day) 
 
HCV/HIV Co-infected patients  
Two trials have been conducted in patients co-infected with HIV and HCV. Overall, in both studies, patients 
who received Viraferon plus ribavirin, were less likely to respond than patients who received pegylated 
interferon alfa-2b with ribavirin. The response to treatment in both of these trials is presented in Table 4. 
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 412 previously untreated 
adult patients with chronic hepatitis C who were co-infected with HIV. Patients were randomized to receive 
either pegylated interferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800 mg/day) or Viraferon (3 MIU TIW) 
plus ribavirin (800 mg/day) for 48 weeks with a follow-up period of 6 months. Study 2 (P02080) was a 
randomized, single centre study that enrolled 95 previously untreated adult patients with chronic hepatitis C 
who were co-infected with HIV. Patients were randomized to receive either pegylated interferon alfa-2b (100 
or 150 µg /week based on weight) plus ribavirin (800-1,200 mg/day based on weight) or Viraferon (3 MIU 
TIW) plus ribavirin (800-1,200 mg/day based on weight). The duration of therapy was 48 weeks with a 
follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load 
< 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6-month follow-up period.  
           
Table 4 Sustained virological response based on genotype after Viraferon in combination with 

ribavirin versus pegylated interferon alfa-2b in combination with ribavirin in 
HCV/HIV co-infected patients 

 Study 11 Study 22 
 

pegylated 
interferon 

alfa-2b  
(1.5 µg/kg/ 

week) + 
ribavirin  
(800 mg) 

Viraferon  
(3 MIU TIW) +  

ribavirin  
(800 mg) 

p 
valuea 

pegylated 
interferon 

alfa-2b (100 
or  

150c µg/week) 
+ ribavirin 

(800- 
1,200 mg)d 

Viraferon  
(3 MIU TIW) 

+ ribavirin 
(800- 

1,200 mg)d 
p 

valueb 



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All 27 % (56/205) 20 % (41/205) 0.047 44 % (23/52) 21 % (9/43) 0.017 
Genotype 1, 

4 
17 % (21/125) 6 % (8/129) 0.006 38 % (12/32) 7 % (2/27) 0.007 

Genotype 2, 
3 

44 % (35/80) 43 % (33/76) 0.88 53 % (10/19) 47 % (7/15) 0.730 

MIU = million international units; TIW = three times a week. 
a:  p value based on Cochran-Mantel Haenszel Chi square test. 
b:  p value based on chi-square test. 
c:  subjects < 75 kg received 100 µg/week pegylated interferon alfa-2b and subjects ≥ 75 kg received 150 µg/week pegylated 

interferon alfa-2b. 
d: ribavirin dosing was 800 mg for patients < 60 kg, 1,000 mg for patients 60-75 kg, and 1,200 mg for patients > 75 kg. 
 

1Carrat F, Bani-Sadr F, Pol S et al.  JAMA 2004; 292(23): 2839-2848. 
2 Laguno M, Murillas J, Blanco J.L et al.  AIDS 2004; 18(13): F27-F36. 
 
 
Relapse patients: A total of 345 interferon alpha relapse patients were treated in two clinical trials with 
Viraferon monotherapy or in combination with ribavirin. In these patients, the addition of ribavirin to 
Viraferon increased by as much as 10-fold the efficacy of Viraferon used alone in the treatment of chronic 
hepatitis C (48.6 % vs. 4.7 %). This enhancement in efficacy included loss of serum HCV (< 100 copies/ml 
by PCR), improvement in hepatic inflammation, and normalisation of ALT, and was sustained when 
measured 6 months after the end of treatment. 
 
Long-Term efficacy data 
In a large study, 1,071 patients were enrolled after treatment in a prior non pegylated interferon alfa-2b or 
non pegylated interferon alfa-2b/ribavirin study to evaluate the durability of sustained virologic response and 
assess the impact of continued viral negativity on clinical outcomes. 462 patients completed at least 5 years 
of long-term follow-up and only 12 sustained responders' out of 492 relapsed during this study.  
The Kaplan-Meier estimate for continued sustained response over 5 years for all patients is 97 % with a 95 % 
Confidence Interval of [95 %, 99 %].  
SVR after treatment of chronic HCV with non pegylated interferon alfa-2b (with or without ribavirin) results 
in long-term clearance of the virus providing resolution of the hepatic infection and clinical 'cure' from 
chronic HCV. However, this does not preclude the occurrence of hepatic events in patients with cirrhosis 
(including hepatocarcinoma). 
 
Clinical trials in paediatric patients with chronic hepatitis C: 
Children and adolescents 3 to 16 years of age with compensated chronic hepatitis C and detectable HCV-
RNA (assessed by a central laboratory using a research-based RT-PCR assay) were enrolled in two 
multicentre trials and received Viraferon 3 MIU/m2 3 times a week plus ribavirin 15 mg/kg per day for 1 year 
followed by 6 months follow-up after-treatment. A total of 118 patients were enrolled: 57 % male, 80 % 
Caucasian, and 78 % genotype 1,64 % ≤ 12 years of age. The population enrolled mainly consisted in 
children with mild to moderate hepatitis C. Sustained virological response rates in children and adolescents 
were similar to those in adults. Due to the lack of data in children with severe progression of the disease, and 
the potential for undesirable effects, the benefit/risk of the combination of ribavirin and interferon alfa-2b 
needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8). 
 
Study results are summarized in Table 5. 
 
Table 5. Virological response in previously untreated paediatric patients 
 Viraferon 3 MIU/m2 3 times a week   

+ 
ribavirin 15 mg/kg/day 

Overall Response1 (n=118) 54 (46 %)* 



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Genotype 1 (n=92) 33 (36 %)* 

Genotype 2/3/4 (n=26) 21 (81 %)* 

*Number (%) of patients 
1. Defined as HCV-RNA below limit of detection using a research based RT-PCR assay at end of treatment and during follow-up 
period 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of Viraferon were studied in healthy volunteers following single 5 million IU/m2 and 
10 million IU doses administered subcutaneously, at 5 million IU/m2 administered intramuscularly and as a 
30-minute intravenous infusion. The mean serum interferon concentrations following subcutaneous and 
intramuscular injections were comparable. Cmax occurred three to 12 hours after the lower dose and six to 
eight hours after the higher dose. The elimination half-lives of interferon injections were approximately two 
to three hours, and six to seven hours, respectively. Serum levels were below the detection limit 16 and 
24 hours, respectively, post-injection. Both subcutaneous and intramuscular administration resulted in 
bioavailabilities greater than 100 %. 
 
After intravenous administration, serum interferon levels peaked (135 to 273 IU/ml) by the end of the 
infusion, then declined at a slightly more rapid rate than after subcutaneous or intramuscular administration 
of medicinal product, becoming undetectable four hours after the infusion. The elimination half-life was 
approximately two hours. 
 
Urine levels of interferon were below the detection limit following each of the three routes of administration. 
 
Children and adolescents: Multiple-dose pharmacokinetic properties for Viraferon injection and ribavirin 
capsules in children and adolescents with chronic hepatitis C, between 5 and 16 years of age, are summarized 
in Table 6. The pharmacokinetics of Viraferon and ribavirin (dose-normalized) are similar in adults and 
children or adolescents. 
 

Table 6. Mean (% CV) multiple-dose pharmacokinetic parameters for Viraferon and ribavirin 
capsules when administered to children or adolescents with chronic hepatitis C 

Parameter Ribavirin 
15 mg/kg/day as 2 divided 

doses 
(n = 17) 

Viraferon 
3 MIU/m2 3 times a week 

(n = 54) 

Tmax (hr) 1.9 (83) 5.9 (36) 
Cmax (ng/ml) 3,275 (25) 51 (48) 

AUC* 29,774 (26) 622 (48) 
Apparent clearance l/hr/kg 0.27 (27) Not done 

*AUC12 (ng.hr/ml) for ribavirin; AUC0-24 (IU.hr/ml) for Viraferon 
 
Interferon neutralising factor assays were performed on serum samples of patients who received Viraferon in 
Schering-Plough monitored clinical trials. Interferon neutralising factors are antibodies which neutralise the 
antiviral activity of interferon. The clinical incidence of neutralising factors developing in cancer patients 
treated systemically is 2.9 % and in chronic hepatitis patients is 6.2 %. The detectable titres are low in almost 
all cases and have not been regularly associated with loss of response or any other autoimmune phenomenon. 
In patients with hepatitis, no loss of response was observed apparently due to the low titres. 
 
5.3 Preclinical safety data 
 
Although interferon is generally recognised as being species specific, toxicity studies in animals were 
conducted. Injections of human recombinant interferon alfa-2b for up to three months have shown no 
evidence of toxicity in mice, rats, and rabbits. Daily dosing of cynomolgus monkeys with 20 x 106 IU/kg/day 



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for 3 months caused no remarkable toxicity. Toxicity was demonstrated in monkeys given 
100 x 106 IU/kg/day for 3 months. 
 
In studies of interferon use in non-human primates, abnormalities of the menstrual cycle have been observed 
(see section 4.4). 
 
Results of animal reproduction studies indicate that recombinant interferon alfa-2b was not teratogenic in rats 
or rabbits, nor did it adversely affect pregnancy, foetal development or reproductive capacity in offspring of 
treated rats. Interferon alfa-2b has been shown to have abortifacient effects in Macaca mulatta (rhesus 
monkeys) at 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2. 
Abortion was observed in all dose groups (7.5 million, 15 million and 30 million IU/kg), and was statistically 
significant versus control at the mid- and high-dose groups (corresponding to 90 and 180 times the 
recommended intramuscular or subcutaneous dose of 2 million IU/m2). High doses of other forms of 
interferons alpha and beta are known to produce dose-related anovulatory and abortifacient effects in rhesus 
monkeys. 
 
Mutagenicity studies with interferon alfa-2b revealed no adverse events. 
 
No studies have been conducted in juvenile animals to examine the effects of treatment with interferon alfa-
2b on growth, development, sexual maturation, and behaviour (see section 4.4 and Rebetol SPC if Viraferon 
is to be administered in combination with ribavirin). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Disodium phosphate anhydrous,  
Sodium dihydrogen phosphate monohydrate,  
Edetate disodium,  
Sodium chloride,  
M-cresol,  
Polysorbate 80, 
Water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
18 months 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C).  
Do not freeze.  
Within its shelf-life, for the purpose of transport, the solution can be kept at or below 25ºC for a period up to 
seven days before use. Viraferon can be put back in the refrigerator at any time during this seven-day period. 
If the product is not used during the seven-day period, it cannot be put back in the refrigerator for a new 
storage period and must be discarded. 
 
6.5 Nature and contents of container 
 



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0.5 ml of solution (corresponding to 3 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in an 
flip-off seal (aluminium) with a bonnet (polypropylene). 
Pack sizes of 1 
 
Or 
 
0.5 ml of solution (corresponding to 3 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in an 
flip-off seal (aluminium) with a bonnet (polypropylene). 
with 1 injection syringe, 1 injection needle and 1 cleansing swab.  
Packs sizes of 1, 6 or 12. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
Viraferon solution for injection, may be injected directly after withdrawal of the appropriate doses from the 
vial with a sterile injection syringe. 
 
As with all parenteral medicinal products, prior to administration inspect Viraferon, solution for injection, 
visually for particulate matter and discolouration. The solution should be clear and colourless. 
 
Detailed instructions for the subcutaneous use of the product are provided with the package leaflet (refer to 
“How to self inject Viraferon”). 
 
Any unused product must be discarded after withdrawal of the dose. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
SP Europe 
73, rue de Stalle 
B-1180 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/99/128/009 
EU/1/99/128/010 
EU/1/99/128/011 
EU/1/99/128/012 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation : 9 March 2000 
Date of last renewal : 23 May 2005 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 



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Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu/ 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 5 million IU/0.5 ml solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One vial of Viraferon solution for injection, single dose vial, contains 5 million IU of recombinant interferon 
alfa-2b produced in E.coli by recombinant DNA technology, in 0.5 ml of solution. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection 
Solution is clear and colourless. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Chronic Hepatitis B: Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis B 
viral replication (presence of HBV-DNA and HBeAg), elevated alanine aminotransferase (ALT) and 
histologically proven active liver inflammation and/or fibrosis. 
 
Chronic Hepatitis C:  
Adult patients:  
Viraferon is indicated for the treatment of adult patients with chronic hepatitis C who have elevated 
transaminases without liver decompensation and who are positive for serum HCV-RNA or anti-HCV (see 
section 4.4). 
 
The best way to use Viraferon in this indication is in combination with ribavirin. 
 
Chidren and adolescents: 
Viraferon is intended for use, in a combination regimen with ribavirin, for the treatment of children and 
adolescents 3 years of age and older, who have chronic hepatitis C, not previously treated, without liver 
decompensation, and who are positive for serum HCV-RNA. The decision to treat should be made on a case 
by case basis, taking into account any evidence of disease progression such as hepatic inflammation and 
fibrosis, as well as prognostic factors for response, HCV genotype and viral load. The expected benefit of 
treatment should be weighed against the safety findings observed for paediatric subjects in the clinical trials 
(see sections 4.4, 4.8 and 5.1). 
 
4.2 Posology and method of administration 
 
Treatment must be initiated by a physician experienced in the management of the disease. 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
If adverse events develop during the course of treatment with Viraferon for any indication, modify the dosage 
or discontinue therapy temporarily until the adverse events abate. If persistent or recurrent intolerance 
develops following adequate dosage adjustment, or disease progresses, discontinue treatment with Viraferon. 



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At the discretion of the physician, the patient may self-administer the dose for maintenance dosage regimens 
administered subcutaneously. 
 
Chronic Hepatitis B: The recommended dosage is in the range 5 to 10 million IU administered 
subcutaneously three times a week (every other day) for a period of 4 to 6 months. 
 
The administered dose should be reduced by 50 % in case of occurrence of haematological disorders (white 
blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3). Treatment should be 
discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe 
thrombocytopaenia (< 70,000/mm3). 
 
For all patients, if no improvement on serum HBV-DNA is observed after 3 to 4 months of treatment (at the 
maximum tolerated dose), discontinue Viraferon therapy. 
 
Chronic Hepatitis C: Viraferon is administered subcutaneously at a dose of 3 million IU three times a week 
(every other day) to adult patients, whether administered as monotherapy or in combination with ribavirin. 
 
Children 3 years of age or older and adolescents: Interferon alfa-2b 3 MIU/m2 is administered 
subcutaneously 3 times a week (every other day) in combination with ribavirin capsules or oral solution 
administered orally in two divided doses daily with food (morning and evening).  
 
(See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination 
therapy. For paediatric patients who weigh < 47 kg or cannot swallow capsules, see ribavirin oral solution 
SPC).  
 
Relapse patients (adults): 
Viraferon is given in combination with ribavirin. 
 
Based on the results of clinical trials, in which data are available for 6 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for 6 months. 
 
Naïve patients: 
Adults: The efficacy of Viraferon is enhanced when given in combination with ribavirin. Viraferon should be 
given alone mainly in case of intolerance or contraindication to ribavirin. 
 
Viraferon in combination with ribavirin: 
Based on the results of clinical trials, in which data are available for 12 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for at least 6 months. 
 
Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit 
negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and 
high pre-treatment viral load. 
 
Other negative prognostic factors (age > 40 years, male gender, bridging fibrosis) should be taken into 
account in order to extend therapy to 12 months. 
 
During clinical trials, patients who failed to show a virologic response after 6 months of treatment (HCV-
RNA below lower limit of detection) did not become sustained virologic responders (HCV-RNA below lower 
limit of detection six months after withdrawal of treatment). 
 
Viraferon alone: 
The optimal duration of therapy with Viraferon alone is not yet fully established, but a therapy of between 
12 and 18 months is advised. 
 



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It is recommended that patients be treated with Viraferon alone for at least 3 to 4 months, at which point 
HCV-RNA status should be determined. Treatment should be continued in patients who exhibit negative 
HCV-RNA. 
 
Children and adolescents: The efficacy and safety of Viraferon in combination with ribavirin has been 
studied in children and adolescents who have not been previously treated for chronic hepatitis C.  
 
Genotype 1: The recommended duration of treatment is one year. Patients who fail to achieve virological 
response at 12 weeks are highly unlikely to become sustained virological responders (negative predictive 
value 96 %). Virological response is defined as absence of detectable HCV-RNA at Week 12. Treatment 
should be discontinued in these patients. 
Genotype 2/3: The recommended duration of treatment is 24 weeks. 
 
Virological responses after 1 year of treatment and 6 months of follow-up were 36 % for genotype 1 and 
81 % for genotype 2/3/4. 
 
Viraferon may be administered using either glass or plastic disposable injection syringes. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients. 
- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure, recent 

myocardial infarction, severe arrhythmic disorders.  
 Severe renal or hepatic dysfunction; including that caused by metastases. 
- Epilepsy and/or compromised central nervous system (CNS) function (see section 4.4). 
- Chronic hepatitis with decompensated cirrhosis of the liver. 
- Chronic hepatitis in patients who are being or have been treated recently with immunosuppressive 

agents excluding short term corticosteroid withdrawal. 
- Autoimmune hepatitis; or history of autoimmune disease; immunosuppressed transplant recipients. 
- Pre-existing thyroid disease unless it can be controlled with conventional treatment. 
 
Children and adolescents: 
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal 

ideation or suicide attempt. 
 

Combination therapy with ribavirin: Also see ribavirin SPC if interferon alfa-2b is to be administered in 
combination with ribavirin in patients with chronic hepatitis C. 
 
4.4 Special warnings and precautions for use 
 
For all patients: 
Psychiatric and central nervous system (CNS): Severe CNS effects, particularly depression, suicidal ideation 
and attempted suicide have been observed in some patients during Viraferon therapy, and even after 
treatment discontinuation mainly during the 6-month follow-up periodand in the follow-up period. Among 
children and adolescents treated with Viraferon in combination with ribavirin, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6-month 
follow-up after treatment. As in adult patients, children and adolescents experienced other psychiatric adverse 
events (e.g., depression, emotional lability, and somnolence). Other CNS effects including aggressive behaviour 
(sometimes directed against others), confusion and alterations of mental status have been observed with alpha 
interferons. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such 
symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the 
prescribing physician and the need for adequate therapeutic management should be considered. If psychiatric 
symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with 
Viraferon be discontinued, and the patient followed, with psychiatric intervention as appropriate. 
 



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Patients with existence of or history of severe psychiatric conditions: 
If a treatment with interferon alfa-2b is judged necessary in adult patients with existence or history of severe 
psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and 
therapeutic management of the psychiatric condition. The use of interferon alfa-2b in children and adolescents 
with existence of or history of severe psychiatric conditions is contraindicated (see section 4.3). 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Moderate to severe adverse experiences may require modification of the patient's dosage regimen, or in some 
cases, termination of Viraferon therapy. Any patient developing liver function abnormalities during treatment 
with Viraferon must be monitored closely and treatment discontinued if signs and symptoms progress. 
 
Hypotension may occur during Viraferon therapy or up to two days post-therapy and may require supportive 
treatment. 
 
Adequate hydration must be maintained in patients undergoing Viraferon therapy since hypotension related 
to fluid depletion has been seen in some patients. Fluid replacement may be necessary. 
 
While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, 
other causes of persistent fever must be ruled out. 
 
Viraferon must be used cautiously in patients with debilitating medical conditions, such as those with a 
history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to 
ketoacidosis. Caution must be observed also in patients with coagulation disorders (e.g., thrombophlebitis, 
pulmonary embolism) or severe myelosuppression. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.5). Any patient developing fever, cough, 
dyspnea or other respiratory symptoms must have a chest X-ray taken. If the chest X-ray shows pulmonary 
infiltrates or there is evidence of pulmonary function impairment, the patient is to be monitored closely, and, 
if appropriate, discontinue interferon alpha. While this has been reported more often in patients with chronic 
hepatitis C treated with interferon alpha, it has also been reported in patients with oncologic diseases treated 
with interferon alpha. Prompt discontinuation of interferon alpha administration and treatment with 
corticosteroids appear to be associated with resolution of pulmonary adverse events. 
 
Ocular adverse events (see section 4.8) including retinal haemorrhages, cotton wool spots, and retinal artery 
or vein obstruction have been reported in rare instance after treatment with alpha interferons. All patients 
should have a baseline eye examination. Any patient complaining of changes in visual acuity or visual fields, 
or reporting other ophthalmologic symptoms during treatment with Viraferon, must have a prompt and 
complete eye examination. Periodic visual examinations during Viraferon therapy are recommended 
particularly in patients with disorders that may be associated with retinopathy, such as diabetes mellitus or 
hypertension. Discontinuation of Viraferon should be considered in patients who develop new or worsening 
ophthalmological disorders. 
 



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More significant obtundation and coma, including cases of encephalopathy, have been observed in some 
patients, usually elderly, treated at higher doses. While these effects are generally reversible, in a few patients 
full resolution took up to three weeks. Very rarely, seizures have occurred with high doses of Viraferon. 
 
Adult patients with a history of congestive heart failure, myocardial infarction and/or previous or current 
arrhythmic disorders, who require Viraferon therapy, must be closely monitored. It is recommended that 
those patients who have pre-existing cardiac abnormalities and/or are in advanced stages of cancer have 
electrocardiograms taken prior to and during the course of treatment. Cardiac arrhythmias (primarily 
supraventricular) usually respond to conventional therapy but may require discontinuation of Viraferon 
therapy. There are no data in children or adolescents with a history of cardiac disease. 
 
Hypertriglyceridemia and aggravation of hypertriglyceridemia, sometimes severe, have been observed. 
Monitoring of lipid levels is, therefore, recommended. 
 
Due to reports of interferon alpha exacerbating pre-existing psoriatic disease and sarcoidosis, use of 
Viraferon in patients with psoriasis or sarcoidosis is recommended only if the potential benefit justifies the 
potential risk. 
 
Preliminary data indicates that interferon alpha therapy may be associated with an increased rate of kidney 
graft rejection. Liver graft rejection has also been reported. 
 
The development of auto-antibodies and autoimmune disorders has been reported during treatment with alpha 
interferons. Patients predisposed to the development of autoimmune disorders may be at increased risk. 
Patients with signs or symptoms compatible with autoimmune disorders should be evaluated carefully, and 
the benefit-risk of continued interferon therapy should be reassessed (see also section 4.4 Chronic hepatitis C, 
Monotherapy (thyroid abnormalities) and section 4.8). 
Cases of Vogt-Koyanagi-Harada (VKH) syndrome have been reported in patients with chronic hepatitis C 
treated with interferon. This syndrome is a granulomatous inflammatory disorder affecting the eyes, auditory 
system, meninges, and skin. If VKH syndrome is suspected, antiviral treatment should be withdrawn and 
corticosteroid therapy discussed (see section 4.8). 
 
Discontinue treatment with Viraferon in patients with chronic hepatitis who develop prolongation of 
coagulation markers which might indicate liver decompensation. 
 
Chronic Hepatitis C: 
Combination therapy with ribavirin: Also see ribavirin SPC if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i.e. 
patients with genotype 2 and 3), treatment may be possible without histological confirmation. Current 
treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing 
treatment. 
 
Monotherapy: Infrequently, adult patients treated for chronic hepatitis C with Viraferon developed thyroid 
abnormalities, either hypothyroidism or hyperthyroidism. In clinical trials using Viraferon therapy, 2.8 % 
patients overall developed thyroid abnormalities. The abnormalities were controlled by conventional therapy 
for thyroid dysfunction. The mechanism by which Viraferon may alter thyroid status is unknown. Prior to 
initiation of Viraferon therapy for the treatment of chronic hepatitis C, evaluate serum thyroid-stimulating 
hormone (TSH) levels. Any thyroid abnormality detected at that time must be treated with conventional 
therapy. Viraferon treatment may be initiated if TSH levels can be maintained in the normal range by 
medication. Determine TSH levels if, during the course of Viraferon therapy, a patient develops symptoms 
consistent with possible thyroid dysfunction. In the presence of thyroid dysfunction, Viraferon treatment may 
be continued if TSH levels can be maintained in the normal range by medication. Discontinuation of 
Viraferon therapy has not reversed thyroid dysfunction occurring during treatment (also see Children and 
adolescents, Thyroid monitoring). 



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Supplemental monitoring specific for children and adolescents 
Thyroid Monitoring: Approximately 12 % of children treated with interferon alfa-2b and ribavirin developed 
increase in TSH. Another 4 % had a transient decrease below the lower limit of normal. Prior to initiation of 
Viraferon therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be 
treated with conventional therapy. Viraferon therapy may be initiated if TSH levels can be maintained in the 
normal range by medication. Thyroid dysfunction during treatment with interferon alfa-2b and ribavirin has 
been observed. If thyroid abnormalities are detected, the patient’s thyroid status should be evaluated and 
treated as clinically appropriate. Children and adolescents should be monitored every 3 months for evidence 
of thyroid dysfunction (e.g. TSH). 
 
Growth and Development: During a 1-year course of therapy there was a decrease in the rate of linear growth 
(mean percentile decrease of 9 %) and a decrease in the rate of weight gain (mean percentile decrease of 
13 %). A general reversal of these trends was noted during the 6 months follow-up post treatment. However, 
based on interim data from a long-term follow-up study, 12 (14 %) of 84 children had a > 15 percentile 
decrease in rate of linear growth, of whom 5 (6 %) children had a > 30 percentile decrease despite being off 
treatment for more than 1 year. In addition, preclicinal juvenile toxicity results have demonstrated a minor, 
dose-related decrease in overall growth in neonatal rats dosed with ribavirin (see section 5.3). Therefore, the 
risk/benefit of the combined use of interferon alfa-2b and ribavirin should be assessed in young children prior 
to the initiation of therapy. Physicians are advised to monitor the growth of children taking ribavirin in 
combination with interferon alfa-2b. There are no data on long term effects on growth and development and 
on sexual maturation. 
 
HCV/HIV Coinfection: Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy 
(HAART) may be at increased risk of developing lactic acidosis. Caution should be used when adding Viraferon 
and ribavirin to HAART therapy (see ribavirin SPC). Patients treated with Viraferon and ribavirin combination 
therapy and zidovudine could be at increased risk of developing anaemia. 
Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic 
decompensation and death. Adding treatment with alfa interferons alone or in combination with ribavirin may 
increase the risk in this patient subset.  
 
Dental and periodontal disorders: Dental and periodontal disorders, which may lead to loss of teeth, have 
been reported in patients receiving Viraferon and ribavirin combination therapy. In addition, dry mouth could 
have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the 
combination of Viraferon and ribavirin. Patients should brush their teeth thoroughly twice daily and have 
regular dental examinations. In addition some patients may experience vomiting. If this reaction occurs, they 
should be advised to rinse out their mouth thoroughly afterwards. 
 
Laboratory Tests:  
Standard haematological tests and blood chemistries (complete blood count and differential, platelet count, 
electrolytes, liver enzymes, serum protein, serum bilirubin and serum creatinine) are to be conducted in all 
patients prior to and periodically during systemic treatment with Viraferon. 
 
During treatment for hepatitis B or C the recommended testing schedule is at weeks 1, 2, 4, 8, 12, 16, and 
every other month, thereafter, throughout treatment. If ALT flares during Viraferon therapy to greater than or 
equal to 2 times baseline, Viraferon therapy may be continued unless signs and symptoms of liver failure are 
observed. During ALT flare, liver function tests: ALT, prothrombin time, alkaline phosphatase, albumin and 
bilirubin must be monitored at two-week intervals. 
 
Effect on fertility: Interferon may impair fertility (see section 4.6 and section 5.3). 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with 
Viraferon. 



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Interactions between Viraferon and other medicinal products have not been fully evaluated. Caution must be 
exercised when administering Viraferon in combination with other potentially myelosuppressive agents. 
 
Interferons may affect the oxidative metabolic process. This must be considered during concomitant therapy 
with medicinal products metabolised by this route, such as the xanthine derivatives theophylline or 
aminophylline. During concomitant therapy with xanthine agents, serum theophylline levels must be 
monitored and dosage adjusted if necessary. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.4). 
 
(Also see ribavirin SPC if Viraferon is to be administered in combination with ribavirin in patients with 
chronic hepatitis C). 
 
4.6 Pregnancy and lactation 
 
Women of childbearing potential have to use effective contraception during treatment. Viraferon must be 
used with caution in fertile men. Decreased serum estradiol and progesterone concentrations have been 
reported in women treated with human leukocyte interferon. 
 
There are no adequate data from the use of interferon alfa-2b in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Viraferon is to be 
used during pregnancy only if the potential benefit justifies the potential risk to the foetus. 
 
It is not known whether the components of this medicinal product are excreted in human milk. Because of the 
potential for adverse reactions in nursing infants, nursing should be discontinued prior to initiation of 
treatment. 
 
Combination therapy with ribavirin: Ribavirin causes serious birth defects when administered during 
pregnancy. Ribavirin therapy is contraindicated in women who are pregnant. Extreme care must be taken to 
avoid pregnancy in female patients or in partners of male patients taking Viraferon in combination with 
ribavirin. Females of childbearing potential and their partners must each use an effective contraceptive during 
treatment and for 4 months after treatment has been concluded. Male patients and their female partners must 
each use an effective contraceptive during treatment and for 7 months after treatment has been concluded (see 
ribavirin SPC). 
 
4.7 Effects on ability to drive and use machines 
 
Patients are to be advised that they may develop fatigue, somnolence, or confusion during treatment with 
Viraferon, and therefore it is recommended that they avoid driving or operating machinery. 
 
4.8 Undesirable effects 
 
See ribavirin SPC for ribavirin-related undesirable effects if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
In clinical trials conducted in a broad range of indications and at a wide range of doses (from 6 MIU/m2/week 
in hairy cell leukaemia up to 100 MIU/m2/week in melanoma), the most commonly reported undesirable 
effects were fever, fatigue, headache and myalgia. Fever and fatigue were often reversible within 72 hours of 
interruption or cessation of treatment. 
 



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In clinical trials conducted in the hepatitis C population, patients were treated with Viraferon alone or in 
combination with ribavirin for one year. All patients in these trials received 3 MIU of Viraferon three times a 
week. In Table 1 the frequency of patients reporting (treatment related) undesirable effects is presented from 
clinical trials in naïve patients treated for one year. Severity was generally mild to moderate. The adverse 
reactions listed in Table 1 are based on experience from clinical trials and post-marketing. Within the organ 
system classes, adverse reactions are listed under headings of frequency using the following categories: very 
common (≥1/10); common (≥1/100, <1/10); rarely (≥1/10,000, <1/1,000); very rarely (<1/10,000); not 
known. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

Table 1. Adverse reactions reported during clinical trials or following the marketing use of Viraferon 
alone or in combination with ribavirin 

System Organ Class Adverse Reactions 
Infections and infestations 
Very common: 
Common: 
Rarely:  

 
Pharyngitis*, infection viral* 
Bronchitis, sinusitis, herpes simplex (resistance), rhinitis 
Pneumonia§ 

Blood and lymphatic system disorders 
Very common: 
Common: 
Very rarely:  
Not known:  

 
Leukopaenia 
Thrombocytopaenia, lymphadenopathy, lymphopenia 
Aplastic anaemia 
Pure red cell aplasia, idiopathic thrombocytopenic purpura, 
thrombotic thrombocytopenic purpura  

Immune system disorders§ 
Very rarely:  
Not known: 

 
Sarcoidosis, exacerbation of sarcoidosis 
Systemic lupus erythematosus, vasculitis, rheumatoid 
arthritis (new or aggravated), Vogt-Koyanagi-Harada 
syndrome, acute hypersensitivity reactions including 
urticaria, angioedema, bronchoconstriction, anaphylaxis§ 

Endocrine disorders 
Common: 
Very rarely:  

 
Hypothyroidism§, hyperthyroidism§ 
Diabetes, aggravated diabetes 

Metabolism and nutrition disorders 
Very common: 
Common:  
Very rarely:  

 
Anorexia 
Hypocalcaemia, dehydration, hyperuricemia, thirst 
Hyperglycaemia, hypertriglyceridaemia§, increased appetite 

Psychiatric disorders§ 
Very common: 
 
Common: 
Rarely:  
Very rarely: 
 
Not known: 

 
Depression, insomnia, anxiety, emotional lability*, 
agitation, nervousness 
Confusion, sleep disorder, libido decreased 
Suicide ideation 
Suicide, suicide attempts, aggressive behaviour (sometimes 
directed against others), psychosis including hallucinations 
Mental status change§ 

Nervous system disorders§ 
Very common: 
Common: 
 
Very rarely:  
 
 
Not known: 

 
Dizziness, headache, concentration impaired, mouth dry 
Tremor, paresthesia, hypoesthesia, migraine, flushing, 
somnolence, taste perversion 
Cerebrovascular haemorrhage, cerbrovascular ischaemia, 
seizure, impaired consciousness, encephalopathy, 
neuropathy, polyneuropathy 
Mononeuropathies, coma§ 

Eye disorders 
Very common: 
Common: 

 
Vision blurred 
Conjunctivitis, vision abnormal, lacrimal gland disorder, eye 



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Rarely:  

pain 
Retinal haemorrhages§, retinopathies (including macular 
oedema), retinal artery or vein obstruction§, optic neuritis, 
papilloedema, loss of visual acuity or visual field, cotton-
wool spots§  

Ear and labyrinth 
Common: 
Very rarely:  

 
Vertigo, tinnitus 
Hearing loss, hearing disorder 

Cardiac disorders 
Common: 
Rarely: 
Very rarely: 
Not known: 

 
Palpitation, tachycardia 
Cardiomyopathy 
Myocardial infarction, cardiac ischaemia  
Arrhythmia  

Vascular disorders 
Common: 
Very rarely:  

 
Hypertension 
Peripheral ischaemia, hypotension§ 

Respiratory, thoracic and mediastinal 
disorders 
Very common: 
Common: 
 
Very rarely:  

 
 
Dyspnoea*, coughing* 
Epistaxis, respiratory disorder, nasal congestion, rhinorrhea, 
cough nonproductive 
Pulmonary infiltrates§, pneumonitis§ 

Gastrointestinal disorders 
Very common: 
 
Common: 
 
Very rarely:  
 
Not known: 

 
Nausea/vomiting, abdominal pain, diarrhoea, stomatitis, 
dyspepsia 
Stomatitis ulcerative, right upper quadrant pain, glossitis, 
gingivitis, constipation, loose stools 
Pancreatitis, ischaemic colitis, ulcerative colitis, gingival 
bleeding 
Periodontal disorder NOS, dental disorder NOS§ 

Hepatobiliary disorders 
Common: 
Very rarely:  

 
Hepatomegaly 
Hepatotoxicity, (including fatality) 

Skin and subcutaneous tissue disorders 
Very common: 
Common: 
 
Very rarely:  

 
Alopecia, pruritus*, skin dry*, rash*, sweating increased 
Psoriasis (new or aggravated)§, rash maculopapular, rash 
erythematous, eczema, erythema, skin disorder 
Stevens Johnson syndrome, toxic epidermal necrolysis, 
erythema multiforme 

Musculoskeletal and connective tissue 
disorders 
Very common:  
Common: 
Very rarely: 

 
 
Myalgia, arthralgia, musculoskeletal pain 
Arthritis 
Rhabdomyolysis, myositis, leg cramps, back pain 

Renal and urinary disorders 
Common: 
Very rarely:  

 
Micturition frequency 
Renal failure, renal insufficiency, nephrotic syndrome 

Reproductive system and breast 
disorders 
Common: 

 
 
Amenorrhea, breast pain, dysmenorrhea, menorrhagia, 
menstrual disorder, vaginal disorder 

General disorders and administration 
site conditions 
Very common: 

 
 
Injection site inflammation, injection site reaction*, fatigue, 



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Common: 
Very rarely: 

rigors, fever§, flu-like symptoms§, asthenia, irritability, chest 
pain, malaise 
Injection site pain 
Injection site necrosis, face oedema 

Investigations 
Very common: 

 
Weight decrease 

*These events were only common with Viraferon alone 
§See section 4.4 
 
These undesirable effects have also been reported with Viraferon alone. 
 
Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-
existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4). Cardiomyopathy, that may 
be reversible upon discontinuation of interferon alpha, has been reported rarely in patients without prior 
evidence of cardiac disease (see section 4.4).  
 
A wide variety of autoimmune and immune-mediated disorders have been reported with alpha interferons 
including thyroid disorders, systemic lupus erythematosus, rheumatoid arthritis (new or aggravated), 
idiopathic and thrombotic thrombocytopenic purpura, vasculitis, neuropathies including mononeuropathies 
(see also section 4.4).  
 
Clinically significant laboratory abnormalities, most frequently occurring at doses greater than 10 million IU 
daily, include reduction in granulocyte and white blood cell counts; decreases in haemoglobin level and 
platelet count; increases in alkaline phosphatase, LDH, serum creatinine and serum urea nitrogen levels. 
Increase in serum ALT/AST (SGPT/SGOT) levels have been noted as an abnormality in some non-hepatitis 
subjects and also in some patients with chronic hepatitis B coincident with clearance of viral DNAp. 
 
Paediatric population 
 
Children and adolescents – Chronic Hepatitis C 
In clinical trials of 118 children or adolescents 3 to 16 years of age, 6 % discontinued therapy due to adverse 
events. In general, the adverse event profile in the limited paediatric population studied was similar to that 
observed in adults, although there is a paediatric specific concern regarding growth inhibition as decrease in 
height (mean percentile decrease of growth velocity of 9 %) and weight (mean percentile decrease of 13 %) 
percentile were observed during treatment (see section 4.4). Furthermore, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6 month 
follow-up after treatment. As in adult patients, children and adolescents also experienced other psychiatric 
adverse events (e.g., depression, emotional lability, and somnolence) (see section 4.4). In addition, injection 
site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in children and 
adolescents compared to adult patients. Dose modifications were required in 30 % of patients, most 
commonly for anaemia and neutropaenia. 
 
The adverse reactions listed in Table 2 are based on experience from paediatric clinical trials.  
Within the organ system classes, adverse reactions are listed under headings of frequency using the following 
categories: very common (≥1/10); common (≥1/100, <1/10). Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness. 
 
Table 2  Adverse reactions very commonly and commonly reported in paediatric clinical trials  

Very common (≥1/10) - Common (≥1/100, <1/10) 
System Organ Class Adverse Reactions 
Infection and infestations 
Very common: 
Common: 

 
Viral infection, pharyngitis 
Fungal infection, bacterial infection, pulmonary infection, otitis 
media, tooth abscess, herpes simplex, urinary tract infection, 



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vaginitis, gastroenteritis 
Neoplasms benign, malignant 
and unspecified (including 
cysts and polyps) 
Common: 

 
 
 
Neoplasm (unspecified) 

Blood and lymphatic system 
disorders 
Very common: 
Common: 

 
 
Anaemia, neutropaenia 
Thrombocytopaenia, lymphadenopathy 

Endocrine disorders 
Very common: 
Common: 

 
Hypothyroidism§,  
Hyperthyroidism§, virilism 

Metabolism and nutrition 
disorders 
Very common: 
Common: 

 
 
Anorexia 
Hypertriglyceridemia§, hyperuricemia, increased appetite 

Psychiatric disorders§ 
Very common: 
Common: 

 
Depression, emotional lability, insomnia 
Suicidal ideation, aggressive reaction, confusion, behaviour 
disorder, agitation, somnambulism, anxiety, nervousness, sleep 
disorder, abnormal dreaming, apathy 

Nervous system disorders§ 
Very common: 
Common: 

 
Headache, dizziness 
Hyperkinesia, tremor, dysphonia, paresthaesia, hypoaesthesia, 
hyperaesthesia, concentration impaired, somnolence 

Eye disorders 
Common: 

 
Conjunctivitis, eye pain, abnormal vision, lacrimal gland disorder 

Vascular disorders 
Common: 

 
Raynaud’s disease, flushing, pallor 

Respiratory, thoracic and 
mediastinal disorders 
Common: 

 
 
Dyspnoea, tachypnea, epistaxis, coughing, nasal congestion, nasal 
irritation, rhinorrhea, sneezing 

Gastrointestinal disorders 
Very common: 
Common: 

 
Diarrhoea, vomiting, nausea, abdominal pain 
Mouth ulceration, stomatitis ulcerative, stomatitis, right upper 
quadrant pain, dyspepsia, glossitis, gastroesophogeal reflux, rectal 
disorder, gastrointestinal disorder, constipation, loose stools, 
toothache, tooth disorder 

Hepatobiliary disorders 
Common: 

 
Hepatic function abnormal 

Skin and subcutaneous tissue 
disorders  
Very common: 
Common: 

 
 
Alopecia, rash 
Photosensitivity reaction, maculopapular rash, eczema, acne, skin 
disorder, nail disorder, skin discolouration, pruritus, dry skin, 
erythema, bruise, sweating increased 

Musculoskeletal and 
connective tissue disorders 
Very common: 

 
 
Arthralgia, myalgia, musculoskeletal pain  

Renal and urinary disorders 
Common: 

 
Enuresis, micturition disorder, urinary incontinence 

Reproductive system and 
breast disorders 

 
 



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Common: Female: amenorrhea, menorrhagia, menstrual disorder, vaginal 
disorder 
Male: testicular pain 

General disorders and 
administration site 
conditions 
Very common: 
 
Common: 

 
 
 
Injection site inflammation, injection site reaction, fatigue, rigors, 
fever§, influenza-like symptoms§, malaise, irritability 
Chest pain, asthenia, oedema, injection site pain 

Investigations 
Very common: 

 
Growth rate decrease (height and/or weight decrease for age)§  

Injury and poisoning 
Common: 

 
Skin laceration 

§See section 4.4 
 
4.9 Overdose 
 
No case of overdose has been reported that has led to acute clinical manifestations. However, as for any 
pharmacologically active compound, symptomatic treatment with frequent monitoring of vital signs and close 
observation of the patient is indicated. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunostimulants, cytokines and immunomodulators, interferons, interferon 
alfa-2b, ATC code: L03A B05 
 
Viraferon is a sterile, stable, formulation of highly purified interferon alfa-2b produced by recombinant DNA 
techniques. Recombinant interferon alfa-2b is a water-soluble protein with a molecular weight of 
approximately 19,300 daltons. It is obtained from a clone of E. coli, which harbours a genetically engineered 
plasmid hybrid encompassing an interferon alfa-2b gene from human leukocytes. 
 
The activity of Viraferon is expressed in terms of IU, with 1 mg of recombinant interferon alfa-2b protein 
corresponding to 2.6 x l08 IU. International Units are determined by comparison of the activity of the 
recombinant interferon alfa-2b with the activity of the international reference preparation of human leukocyte 
interferon established by the World Health Organisation. 
 
The interferons are a family of small protein molecules with molecular weights of approximately 15,000 to 
21,000 daltons. They are produced and secreted by cells in response to viral infections or various synthetic 
and biological inducers. Three major classes of interferons have been identified: alpha, beta and gamma. 
These three main classes are themselves not homogeneous and may contain several different molecular 
species of interferon. More than 14 genetically distinct human alpha interferons have been identified. 
Viraferon has been classified as recombinant interferon alfa-2b. 
 
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. 
Human interferon receptors, as isolated from human lymphoblastoid (Daudi) cells, appear to be highly 
asymmetric proteins. They exhibit selectivity for human but not murine interferons, suggesting species 
specificity. Studies with other interferons have demonstrated species specificity. However, certain monkey 
species, eg, rhesus monkeys, are susceptible to pharmacodynamic stimulation upon exposure to human type 
1 interferons. 
 



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The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex 
sequence of intracellular events that include the induction of certain enzymes. It is thought that this process, 
at least in part, is responsible for the various cellular responses to interferon, including inhibition of virus 
replication in virus-infected cells, suppression of cell proliferation and such immunomodulating activities as 
enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of 
lymphocytes for target cells. Any or all of these activities may contribute to interferon's therapeutic effects. 
 
Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and 
human cell culture systems as well as human tumour xenografts in animals. It has demonstrated significant 
immunomodulatory activity in vitro. 
 
Recombinant interferon alfa-2b also inhibits viral replication in vitro and in vivo. Although the exact antiviral 
mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism. 
This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell. 
 
Chronic hepatitis B: 
Current clinical experience in patients who remain on interferon alfa-2b for 4 to 6 months indicates that 
therapy can produce clearance of serum HBV-DNA. An improvement in liver histology has been observed. 
In adult patients with loss of HBeAg and HBV-DNA, a significant reduction in morbidity and mortality has 
been observed. 
 
Interferon alfa-2b (6 MIU/m2 3 times a week for 6 months) has been given to children with chronic active 
hepatitis B. Because of a methodological flaw, efficacy could not be demonstrated. Moreover children treated 
with interferon alfa-2b experienced a reduced rate of growth and some cases of depression were observed. 
 
Chronic hepatitis C: 
In adult patients receiving interferon in combination with ribavirin, the achieved sustained response rate is 
47 %. Superior efficacy has been demonstrated with the combination of pegylated interferon with ribavirin 
(sustained response rate of 61 % achieved in a study performed in naïve patients with a ribavirin dose 
> 10.6 mg/kg, p < 0.01). 
 
Adult patients: Viraferon alone or in combination with ribavirin has been studied in 4 randomised Phase III 
clinical trials in 2,552 interferon-naïve patients with chronic hepatitis C. The trials compared the efficacy of 
Viraferon used alone or in combination with ribavirin. Efficacy was defined as sustained virologic response, 
6 months after the end of treatment. Eligible patients for these trials had chronic hepatitis C confirmed by a 
positive HCV-RNA polymerase chain reaction assay (PCR) (> 100 copies/ml), a liver biopsy consistent with 
a histologic diagnosis of chronic hepatitis with no other cause for the chronic hepatitis, and abnormal serum 
ALT. 
 
Viraferon was administered at a dose of 3 MIU 3 times a week as monotherapy or in combination with 
ribavirin. The majority of patients in these clinical trials were treated for one year. All patients were followed 
for an additional 6 months after the end of treatment for the determination of sustained virologic response. 
Sustained virologic response rates for treatment groups treated for one year with Viraferon alone or in 
combination with ribavirin (from two studies) are shown in Table 3. 
 
Co-administration of Viraferon with ribavirin increased the efficacy of Viraferon by at least two fold for the 
treatment of chronic heptatitis C in naïve patients. HCV genotype and baseline virus load are prognostic 
factors which are known to affect response rates. The increased response rate to the combination of Viraferon + 
ribavirin, compared with Viraferon alone, is maintained across all subgroups. The relative benefit of combination 
therapy with Viraferon + ribavirin is particularly significant in the most difficult to treat subgroup of patients 
(genotype 1 and high virus load) (Table 3). 
 
Response rates in these trials were increased with compliance. Regardless of genotype, patients who received 
Viraferon in combination with ribavirin and received ≥ 80 % of their treatment had a higher sustained 



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response 6 months after 1 year of treatment than those who took < 80 % of their treatment (56 % vs. 32 % in 
trial C/I98-580).  
 

Table 3 Sustained virologic response rates with Viraferon + ribavirin (one year of 
treatment) by genotype and viral load 

 
HCV Genotype  
 

I 
N=503 

C95-132/I95-143 

I/R 
N=505 

C95-132/I95-143 

I/R 
N=505 

C/I98-580 
 
All Genotypes 

 
16 % 

 
41 % 

 
47 % 

 
 
Genotype 1 

 
9 % 

 
29 % 

 
33 % 

 
Genotype 1  
≤ 2 million 
copies/ml 

 
25 % 

 
33 % 

 
45 % 

 
Genotype 1 
> 2 million 
copies/ml 

 
3 % 

 
27 % 

 

 
29 % 

 
Genotype 2/3 

 
31 % 

 
65 % 

 
79 % 

I Viraferon (3 MIU 3 times a week) 
I/R Viraferon (3 MIU 3 times a week) + ribavirin (1,000/1,200 mg/day) 
 
HCV/HIV Co-infected patients  
Two trials have been conducted in patients co-infected with HIV and HCV. Overall, in both studies, patients 
who received Viraferon plus ribavirin, were less likely to respond than patients who received pegylated 
interferon alfa-2b with ribavirin. The response to treatment in both of these trials is presented in Table 4. 
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 412 previously untreated 
adult patients with chronic hepatitis C who were co-infected with HIV. Patients were randomized to receive 
either pegylated interferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800 mg/day) or Viraferon (3 MIU TIW) 
plus ribavirin (800 mg/day) for 48 weeks with a follow-up period of 6 months. Study 2 (P02080) was a 
randomized, single centre study that enrolled 95 previously untreated adult patients with chronic hepatitis C 
who were co-infected with HIV. Patients were randomized to receive either pegylated interferon alfa-2b (100 
or 150 µg /week based on weight) plus ribavirin (800-1,200 mg/day based on weight) or Viraferon (3 MIU 
TIW) plus ribavirin (800-1,200 mg/day based on weight). The duration of therapy was 48 weeks with a 
follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load 
< 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6-month follow-up period.  
           
Table 4 Sustained virological response based on genotype after Viraferon in combination with 

ribavirin versus pegylated interferon alfa-2b in combination with ribavirin in 
HCV/HIV co-infected patients 

 Study 11 Study 22 
 

pegylated 
interferon 

alfa-2b  
(1.5 µg/kg/ 

week) + 
ribavirin  
(800 mg) 

Viraferon  
(3 MIU TIW) +  

ribavirin  
(800 mg) 

p 
valuea 

pegylated 
interferon 

alfa-2b (100 
or  

150c µg/week) 
+ ribavirin 

(800- 
1,200 mg)d 

Viraferon  
(3 MIU TIW) 

+ ribavirin 
(800- 

1,200 mg)d 
p 

valueb 



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All 27 % (56/205) 20 % (41/205) 0.047 44 % (23/52) 21 % (9/43) 0.017 
Genotype 1, 

4 
17 % (21/125) 6 % (8/129) 0.006 38 % (12/32) 7 % (2/27) 0.007 

Genotype 2, 
3 

44 % (35/80) 43 % (33/76) 0.88 53 % (10/19) 47 % (7/15) 0.730 

MIU = million international units; TIW = three times a week. 
a:  p value based on Cochran-Mantel Haenszel Chi square test. 
b:  p value based on chi-square test. 
c:  subjects < 75 kg received 100 µg/week pegylated interferon alfa-2b and subjects ≥ 75 kg received 150 µg/week pegylated 

interferon alfa-2b. 
d: ribavirin dosing was 800 mg for patients < 60 kg, 1,000 mg for patients 60-75 kg, and 1,200 mg for patients > 75 kg. 
 

1Carrat F, Bani-Sadr F, Pol S et al.  JAMA 2004; 292(23): 2839-2848. 
2 Laguno M, Murillas J, Blanco J.L et al.  AIDS 2004; 18(13): F27-F36. 
 
 
Relapse patients: A total of 345 interferon alpha relapse patients were treated in two clinical trials with 
Viraferon monotherapy or in combination with ribavirin. In these patients, the addition of ribavirin to 
Viraferon increased by as much as 10-fold the efficacy of Viraferon used alone in the treatment of chronic 
hepatitis C (48.6 % vs. 4.7 %). This enhancement in efficacy included loss of serum HCV (< 100 copies/ml 
by PCR), improvement in hepatic inflammation, and normalisation of ALT, and was sustained when 
measured 6 months after the end of treatment. 
 
Long-Term efficacy data 
In a large study, 1,071 patients were enrolled after treatment in a prior non pegylated interferon alfa-2b or 
non pegylated interferon alfa-2b/ribavirin study to evaluate the durability of sustained virologic response and 
assess the impact of continued viral negativity on clinical outcomes. 462 patients completed at least 5 years 
of long-term follow-up and only 12 sustained responders' out of 492 relapsed during this study.  
The Kaplan-Meier estimate for continued sustained response over 5 years for all patients is 97 % with a 95 % 
Confidence Interval of [95 %, 99 %].  
SVR after treatment of chronic HCV with non pegylated interferon alfa-2b (with or without ribavirin) results 
in long-term clearance of the virus providing resolution of the hepatic infection and clinical 'cure' from 
chronic HCV. However, this does not preclude the occurrence of hepatic events in patients with cirrhosis 
(including hepatocarcinoma). 
 
Clinical trials in paediatric patients with chronic hepatitis C: 
Children and adolescents 3 to 16 years of age with compensated chronic hepatitis C and detectable HCV-
RNA (assessed by a central laboratory using a research-based RT-PCR assay) were enrolled in two 
multicentre trials and received Viraferon 3 MIU/m2 3 times a week plus ribavirin 15 mg/kg per day for 1 year 
followed by 6 months follow-up after-treatment. A total of 118 patients were enrolled: 57 % male, 80 % 
Caucasian, and 78 % genotype 1,64 % ≤ 12 years of age. The population enrolled mainly consisted in 
children with mild to moderate hepatitis C. Sustained virological response rates in children and adolescents 
were similar to those in adults. Due to the lack of data in children with severe progression of the disease, and 
the potential for undesirable effects, the benefit/risk of the combination of ribavirin and interferon alfa-2b 
needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8). 
 
Study results are summarized in Table 5. 
 
Table 5. Virological response in previously untreated paediatric patients 
 Viraferon 3 MIU/m2 3 times a week   

+ 
ribavirin 15 mg/kg/day 

Overall Response1 (n=118) 54 (46 %)* 



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Genotype 1 (n=92) 33 (36 %)* 

Genotype 2/3/4 (n=26) 21 (81 %)* 

*Number (%) of patients 
1. Defined as HCV-RNA below limit of detection using a research based RT-PCR assay at end of treatment and during follow-up 
period 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of Viraferon were studied in healthy volunteers following single 5 million IU/m2 and 
10 million IU doses administered subcutaneously, at 5 million IU/m2 administered intramuscularly and as a 
30-minute intravenous infusion. The mean serum interferon concentrations following subcutaneous and 
intramuscular injections were comparable. Cmax occurred three to 12 hours after the lower dose and six to 
eight hours after the higher dose. The elimination half-lives of interferon injections were approximately two 
to three hours, and six to seven hours, respectively. Serum levels were below the detection limit 16 and 
24 hours, respectively, post-injection. Both subcutaneous and intramuscular administration resulted in 
bioavailabilities greater than 100 %. 
 
After intravenous administration, serum interferon levels peaked (135 to 273 IU/ml) by the end of the 
infusion, then declined at a slightly more rapid rate than after subcutaneous or intramuscular administration 
of medicinal product, becoming undetectable four hours after the infusion. The elimination half-life was 
approximately two hours. 
 
Urine levels of interferon were below the detection limit following each of the three routes of administration. 
 
Children and adolescents: Multiple-dose pharmacokinetic properties for Viraferon injection and ribavirin 
capsules in children and adolescents with chronic hepatitis C, between 5 and 16 years of age, are summarized 
in Table 6. The pharmacokinetics of Viraferon and ribavirin (dose-normalized) are similar in adults and 
children or adolescents. 
 

Table 6. Mean (% CV) multiple-dose pharmacokinetic parameters for Viraferon and ribavirin 
capsules when administered to children or adolescents with chronic hepatitis C 
Parameter Ribavirin 

15 mg/kg/day as 2 divided 
doses 

(n = 17) 

Viraferon 
3 MIU/m2 3 times a week 

(n = 54) 

Tmax (hr) 1.9 (83) 5.9 (36) 
Cmax (ng/ml) 3,275 (25) 51 (48) 

AUC* 29,774 (26) 622 (48) 
Apparent clearance l/hr/kg 0.27 (27) Not done 

*AUC12 (ng.hr/ml) for ribavirin; AUC0-24 (IU.hr/ml) for Viraferon 
 
Interferon neutralising factor assays were performed on serum samples of patients who received Viraferon in 
Schering-Plough monitored clinical trials. Interferon neutralising factors are antibodies which neutralise the 
antiviral activity of interferon. The clinical incidence of neutralising factors developing in cancer patients 
treated systemically is 2.9 % and in chronic hepatitis patients is 6.2 %. The detectable titres are low in almost 
all cases and have not been regularly associated with loss of response or any other autoimmune phenomenon. 
In patients with hepatitis, no loss of response was observed apparently due to the low titres. 
 
5.3 Preclinical safety data 
 
Although interferon is generally recognised as being species specific, toxicity studies in animals were 
conducted. Injections of human recombinant interferon alfa-2b for up to three months have shown no 
evidence of toxicity in mice, rats, and rabbits. Daily dosing of cynomolgus monkeys with 20 x 106 IU/kg/day 



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for 3 months caused no remarkable toxicity. Toxicity was demonstrated in monkeys given 
100 x 106 IU/kg/day for 3 months. 
 
In studies of interferon use in non-human primates, abnormalities of the menstrual cycle have been observed 
(see section 4.4). 
 
Results of animal reproduction studies indicate that recombinant interferon alfa-2b was not teratogenic in rats 
or rabbits, nor did it adversely affect pregnancy, foetal development or reproductive capacity in offspring of 
treated rats. Interferon alfa-2b has been shown to have abortifacient effects in Macaca mulatta (rhesus 
monkeys) at 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2. 
Abortion was observed in all dose groups (7.5 million, 15 million and 30 million IU/kg), and was statistically 
significant versus control at the mid- and high-dose groups (corresponding to 90 and 180 times the 
recommended intramuscular or subcutaneous dose of 2 million IU/m2). High doses of other forms of 
interferons alpha and beta are known to produce dose-related anovulatory and abortifacient effects in rhesus 
monkeys. 
 
Mutagenicity studies with interferon alfa-2b revealed no adverse events. 
 
No studies have been conducted in juvenile animals to examine the effects of treatment with interferon alfa-
2b on growth, development, sexual maturation, and behaviour (see section 4.4 and Rebetol SPC if Viraferon 
is to be administered in combination with ribavirin). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Disodium phosphate anhydrous,  
Sodium dihydrogen phosphate monohydrate,  
Edetate disodium,  
Eodium chloride,  
M-cresol,  
Polysorbate 80, 
Water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
18 months 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C).  
Do not freeze.  
Within its shelf-life, for the purpose of transport, the solution can be kept at or below 25ºC for a period up to 
seven days before use. Viraferon can be put back in the refrigerator at any time during this seven-day period. 
If the product is not used during the seven-day period, it cannot be put back in the refrigerator for a new 
storage period and must be discarded. 
 
6.5 Nature and contents of container 
 



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0.5 ml of solution (corresponding to 5 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in a 
flip-off seal (aluminium) with a bonnet (polypropylene) 
Pack sizes of 1 
 
Or 
 
0.5 ml of solution (corresponding to 5 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in a 
flip-off seal (aluminium) with a bonnet (polypropylene) 
with 1 injection syringe, 1 injection needle and 1 cleansing swab.  
Packs sizes of 1, 6 or 12. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
Viraferon solution for injection, may be injected directly after withdrawal of the appropriate doses from the 
vial with a sterile injection syringe. 
 
As with all parenteral medicinal products, prior to administration inspect Viraferon, solution for injection, 
visually for particulate matter and discolouration. The solution should be clear and colourless. 
 
Detailed instructions for the subcutaneous use of the product are provided with the package leaflet (refer to 
“How to self inject Viraferon”). 
 
Any unused product must be discarded after withdrawal of the dose. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
SP Europe 
73, rue de Stalle 
B-1180 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBERS  
 
EU/1/99/128/013 
EU/1/99/128/014 
EU/1/99/128/015 
EU/1/99/128/016 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation : 9 March 2000 
Date of last renewal : 23 May 2005 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 



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Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu/ 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 10 million IU/ml solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One vial of Viraferon solution for injection, single dose vial, contains 10 million IU of recombinant 
interferon alfa-2b produced in E.coli by recombinant DNA technology, in 1 ml of solution. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection 
Solution is clear and colourless. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Chronic Hepatitis B: Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis B 
viral replication (presence of HBV-DNA and HBeAg), elevated alanine aminotransferase (ALT) and 
histologically proven active liver inflammation and/or fibrosis. 
 
Chronic Hepatitis C:  
Adult patients:  
Viraferon is indicated for the treatment of adult patients with chronic hepatitis C who have elevated 
transaminases without liver decompensation and who are positive for serum HCV-RNA or anti-HCV (see 
section 4.4). 
 
The best way to use Viraferon in this indication is in combination with ribavirin. 
 
Chidren and adolescents: 
Viraferon is intended for use, in a combination regimen with ribavirin, for the treatment of children and 
adolescents 3 years of age and older, who have chronic hepatitis C, not previously treated, without liver 
decompensation, and who are positive for serum HCV-RNA. The decision to treat should be made on a case 
by case basis, taking into account any evidence of disease progression such as hepatic inflammation and 
fibrosis, as well as prognostic factors for response, HCV genotype and viral load. The expected benefit of 
treatment should be weighed against the safety findings observed for paediatric subjects in the clinical trials 
(see sections 4.4, 4.8 and 5.1). 
 
4.2 Posology and method of administration 
 
Treatment must be initiated by a physician experienced in the management of the disease. 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
If adverse events develop during the course of treatment with Viraferon for any indication, modify the dosage 
or discontinue therapy temporarily until the adverse events abate. If persistent or recurrent intolerance 
develops following adequate dosage adjustment, or disease progresses, discontinue treatment with Viraferon. 



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At the discretion of the physician, the patient may self-administer the dose for maintenance dosage regimens 
administered subcutaneously. 
 
Chronic Hepatitis B: The recommended dosage is in the range 5 to 10 million IU administered 
subcutaneously three times a week (every other day) for a period of 4 to 6 months. 
 
The administered dose should be reduced by 50 % in case of occurrence of haematological disorders (white 
blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3). Treatment should be 
discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe 
thrombocytopaenia (< 70,000/mm3). 
 
For all patients, if no improvement on serum HBV-DNA is observed after 3 to 4 months of treatment (at the 
maximum tolerated dose), discontinue Viraferon therapy. 
 
Chronic Hepatitis C: Viraferon is administered subcutaneously at a dose of 3 million IU three times a week 
(every other day) to adult patients, whether administered as monotherapy or in combination with ribavirin. 
 
Children 3 years of age or older and adolescents: Interferon alfa-2b 3 MIU/m2 is administered 
subcutaneously 3 times a week (every other day) in combination with ribavirin capsules or oral solution 
administered orally in two divided doses daily with food (morning and evening).  
 
(See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination 
therapy. For paediatric patients who weigh < 47 kg or cannot swallow capsules, see ribavirin oral solution 
SPC).  
 
Relapse patients (adults): 
Viraferon is given in combination with ribavirin. 
 
Based on the results of clinical trials, in which data are available for 6 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for 6 months. 
 
Naïve patients: 
Adults: The efficacy of Viraferon is enhanced when given in combination with ribavirin. Viraferon should be 
given alone mainly in case of intolerance or contraindication to ribavirin. 
 
Viraferon in combination with ribavirin: 
Based on the results of clinical trials, in which data are available for 12 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for at least 6 months. 
 
Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit 
negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and 
high pre-treatment viral load. 
 
Other negative prognostic factors (age > 40 years, male gender, bridging fibrosis) should be taken into 
account in order to extend therapy to 12 months. 
 
During clinical trials, patients who failed to show a virologic response after 6 months of treatment (HCV-
RNA below lower limit of detection) did not become sustained virologic responders (HCV-RNA below lower 
limit of detection six months after withdrawal of treatment). 
 
Viraferon alone: 
The optimal duration of therapy with Viraferon alone is not yet fully established, but a therapy of between 
12 and 18 months is advised. 
 



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It is recommended that patients be treated with Viraferon alone for at least 3 to 4 months, at which point 
HCV-RNA status should be determined. Treatment should be continued in patients who exhibit negative 
HCV-RNA. 
 
Children and adolescents: The efficacy and safety of Viraferon in combination with ribavirin has been 
studied in children and adolescents who have not been previously treated for chronic hepatitis C.  
 
Genotype 1: The recommended duration of treatment is one year. Patients who fail to achieve virological 
response at 12 weeks are highly unlikely to become sustained virological responders (negative predictive 
value 96 %). Virological response is defined as absence of detectable HCV-RNA at Week 12. Treatment 
should be discontinued in these patients. 
Genotype 2/3: The recommended duration of treatment is 24 weeks. 
 
Virological responses after 1 year of treatment and 6 months of follow-up were 36 % for genotype 1 and 
81 % for genotype 2/3/4. 
 
Viraferon may be administered using either glass or plastic disposable injection syringes. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients. 
- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure, recent 

myocardial infarction, severe arrhythmic disorders.  
- Severe renal or hepatic dysfunction; including that caused by metastases. 
- Epilepsy and/or compromised central nervous system (CNS) function (see section 4.4). 
- Chronic hepatitis with decompensated cirrhosis of the liver. 
- Chronic hepatitis in patients who are being or have been treated recently with immunosuppressive 

agents excluding short term corticosteroid withdrawal. 
- Autoimmune hepatitis; or history of autoimmune disease; immunosuppressed transplant recipients. 
- Pre-existing thyroid disease unless it can be controlled with conventional treatment. 
 
Children and adolescents: 
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal 

ideation or suicide attempt. 
 

Combination therapy with ribavirin: Also see ribavirin SPC if interferon alfa-2b is to be administered in 
combination with ribavirin in patients with chronic hepatitis C. 
 
4.4 Special warnings and precautions for use 
 
For all patients: 
Psychiatric and central nervous system (CNS): Severe CNS effects, particularly depression, suicidal ideation 
and attempted suicide have been observed in some patients during Viraferon therapy, and even after 
treatment discontinuation mainly during the 6-month follow-up periodand in the follow-up period. Among 
children and adolescents treated with Viraferon in combination with ribavirin, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6-month 
follow-up after treatment. As in adult patients, children and adolescents experienced other psychiatric adverse 
events (e.g., depression, emotional lability, and somnolence). Other CNS effects including aggressive behaviour 
(sometimes directed against others), confusion and alterations of mental status have been observed with alpha 
interferons. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such 
symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the 
prescribing physician and the need for adequate therapeutic management should be considered. If psychiatric 
symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with 
Viraferon be discontinued, and the patient followed, with psychiatric intervention as appropriate. 
 



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Patients with existence of or history of severe psychiatric conditions: 
If a treatment with interferon alfa-2b is judged necessary in adult patients with existence or history of severe 
psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and 
therapeutic management of the psychiatric condition. The use of interferon alfa-2b in children and adolescents 
with existence of or history of severe psychiatric conditions is contraindicated (see section 4.3). 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Moderate to severe adverse experiences may require modification of the patient's dosage regimen, or in some 
cases, termination of Viraferon therapy. Any patient developing liver function abnormalities during treatment 
with Viraferon must be monitored closely and treatment discontinued if signs and symptoms progress. 
 
Hypotension may occur during Viraferon therapy or up to two days post-therapy and may require supportive 
treatment. 
 
Adequate hydration must be maintained in patients undergoing Viraferon therapy since hypotension related 
to fluid depletion has been seen in some patients. Fluid replacement may be necessary. 
 
While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, 
other causes of persistent fever must be ruled out. 
 
Viraferon must be used cautiously in patients with debilitating medical conditions, such as those with a 
history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to 
ketoacidosis. Caution must be observed also in patients with coagulation disorders (e.g., thrombophlebitis, 
pulmonary embolism) or severe myelosuppression. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.5). Any patient developing fever, cough, 
dyspnea or other respiratory symptoms must have a chest X-ray taken. If the chest X-ray shows pulmonary 
infiltrates or there is evidence of pulmonary function impairment, the patient is to be monitored closely, and, 
if appropriate, discontinue interferon alpha. While this has been reported more often in patients with chronic 
hepatitis C treated with interferon alpha, it has also been reported in patients with oncologic diseases treated 
with interferon alpha. Prompt discontinuation of interferon alpha administration and treatment with 
corticosteroids appear to be associated with resolution of pulmonary adverse events. 
 
Ocular adverse events (see section 4.8) including retinal haemorrhages, cotton wool spots, and retinal artery 
or vein obstruction have been reported in rare instance after treatment with alpha interferons. All patients 
should have a baseline eye examination. Any patient complaining of changes in visual acuity or visual fields, 
or reporting other ophthalmologic symptoms during treatment with Viraferon, must have a prompt and 
complete eye examination. Periodic visual examinations during Viraferon therapy are recommended 
particularly in patients with disorders that may be associated with retinopathy, such as diabetes mellitus or 
hypertension. Discontinuation of Viraferon should be considered in patients who develop new or worsening 
ophthalmological disorders. 
 



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More significant obtundation and coma, including cases of encephalopathy, have been observed in some 
patients, usually elderly, treated at higher doses. While these effects are generally reversible, in a few patients 
full resolution took up to three weeks. Very rarely, seizures have occurred with high doses of Viraferon. 
 
Adult patients with a history of congestive heart failure, myocardial infarction and/or previous or current 
arrhythmic disorders, who require Viraferon therapy, must be closely monitored. It is recommended that 
those patients who have pre-existing cardiac abnormalities and/or are in advanced stages of cancer have 
electrocardiograms taken prior to and during the course of treatment. Cardiac arrhythmias (primarily 
supraventricular) usually respond to conventional therapy but may require discontinuation of Viraferon 
therapy. There are no data in children or adolescents with a history of cardiac disease. 
 
Hypertriglyceridemia and aggravation of hypertriglyceridemia, sometimes severe, have been observed. 
Monitoring of lipid levels is, therefore, recommended. 
 
Due to reports of interferon alpha exacerbating pre-existing psoriatic disease and sarcoidosis, use of 
Viraferon in patients with psoriasis or sarcoidosis is recommended only if the potential benefit justifies the 
potential risk. 
 
Preliminary data indicates that interferon alpha therapy may be associated with an increased rate of kidney 
graft rejection. Liver graft rejection has also been reported. 
 
The development of auto-antibodies and autoimmune disorders has been reported during treatment with alpha 
interferons. Patients predisposed to the development of autoimmune disorders may be at increased risk. 
Patients with signs or symptoms compatible with autoimmune disorders should be evaluated carefully, and 
the benefit-risk of continued interferon therapy should be reassessed (see also section 4.4 Chronic hepatitis C, 
Monotherapy (thyroid abnormalities) and section 4.8). 
Cases of Vogt-Koyanagi-Harada (VKH) syndrome have been reported in patients with chronic hepatitis C 
treated with interferon. This syndrome is a granulomatous inflammatory disorder affecting the eyes, auditory 
system, meninges, and skin. If VKH syndrome is suspected, antiviral treatment should be withdrawn and 
corticosteroid therapy discussed (see section 4.8). 
 
Discontinue treatment with Viraferon in patients with chronic hepatitis who develop prolongation of 
coagulation markers which might indicate liver decompensation. 
 
Chronic Hepatitis C: 
Combination therapy with ribavirin: Also see ribavirin SPC if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i.e. 
patients with genotype 2 and 3), treatment may be possible without histological confirmation. Current 
treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing 
treatment. 
 
Monotherapy: Infrequently, adult patients treated for chronic hepatitis C with Viraferon developed thyroid 
abnormalities, either hypothyroidism or hyperthyroidism. In clinical trials using Viraferon therapy, 2.8 % 
patients overall developed thyroid abnormalities. The abnormalities were controlled by conventional therapy 
for thyroid dysfunction. The mechanism by which Viraferon may alter thyroid status is unknown. Prior to 
initiation of Viraferon therapy for the treatment of chronic hepatitis C, evaluate serum thyroid-stimulating 
hormone (TSH) levels. Any thyroid abnormality detected at that time must be treated with conventional 
therapy. Viraferon treatment may be initiated if TSH levels can be maintained in the normal range by 
medication. Determine TSH levels if, during the course of Viraferon therapy, a patient develops symptoms 
consistent with possible thyroid dysfunction. In the presence of thyroid dysfunction, Viraferon treatment may 
be continued if TSH levels can be maintained in the normal range by medication. Discontinuation of 
Viraferon therapy has not reversed thyroid dysfunction occurring during treatment (also see Children and 
adolescents, Thyroid monitoring). 



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Supplemental monitoring specific for children and adolescents 
Thyroid Monitoring: Approximately 12 % of children treated with interferon alfa-2b and ribavirin developed 
increase in TSH. Another 4 % had a transient decrease below the lower limit of normal. Prior to initiation of 
Viraferon therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be 
treated with conventional therapy. Viraferon therapy may be initiated if TSH levels can be maintained in the 
normal range by medication. Thyroid dysfunction during treatment with interferon alfa-2b and ribavirin has 
been observed. If thyroid abnormalities are detected, the patient’s thyroid status should be evaluated and 
treated as clinically appropriate. Children and adolescents should be monitored every 3 months for evidence 
of thyroid dysfunction (e.g. TSH). 
 
Growth and Development: During a 1-year course of therapy there was a decrease in the rate of linear growth 
(mean percentile decrease of 9 %) and a decrease in the rate of weight gain (mean percentile decrease of 
13 %). A general reversal of these trends was noted during the 6 months follow-up post treatment. However, 
based on interim data from a long-term follow-up study, 12 (14 %) of 84 children had a > 15 percentile 
decrease in rate of linear growth, of whom 5 (6 %) children had a > 30 percentile decrease despite being off 
treatment for more than 1 year. In addition, preclicinal juvenile toxicity results have demonstrated a minor, 
dose-related decrease in overall growth in neonatal rats dosed with ribavirin (see section 5.3). Therefore, the 
risk/benefit of the combined use of interferon alfa-2b and ribavirin should be assessed in young children prior 
to the initiation of therapy. Physicians are advised to monitor the growth of children taking ribavirin in 
combination with interferon alfa-2b. There are no data on long term effects on growth and development and 
on sexual maturation. 
 
HCV/HIV Coinfection: Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy 
(HAART) may be at increased risk of developing lactic acidosis. Caution should be used when adding Viraferon 
and ribavirin to HAART therapy (see ribavirin SPC). Patients treated with Viraferon and ribavirin combination 
therapy and zidovudine could be at increased risk of developing anaemia. 
Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic 
decompensation and death. Adding treatment with alfa interferons alone or in combination with ribavirin may 
increase the risk in this patient subset.  
 
Dental and periodontal disorders: Dental and periodontal disorders, which may lead to loss of teeth, have 
been reported in patients receiving Viraferon and ribavirin combination therapy. In addition, dry mouth could 
have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the 
combination of Viraferon and ribavirin. Patients should brush their teeth thoroughly twice daily and have 
regular dental examinations. In addition some patients may experience vomiting. If this reaction occurs, they 
should be advised to rinse out their mouth thoroughly afterwards. 
 
Laboratory Tests:  
Standard haematological tests and blood chemistries (complete blood count and differential, platelet count, 
electrolytes, liver enzymes, serum protein, serum bilirubin and serum creatinine) are to be conducted in all 
patients prior to and periodically during systemic treatment with Viraferon. 
 
During treatment for hepatitis B or C the recommended testing schedule is at weeks 1, 2, 4, 8, 12, 16, and 
every other month, thereafter, throughout treatment. If ALT flares during Viraferon therapy to greater than or 
equal to 2 times baseline, Viraferon therapy may be continued unless signs and symptoms of liver failure are 
observed. During ALT flare, liver function tests: ALT, prothrombin time, alkaline phosphatase, albumin and 
bilirubin must be monitored at two-week intervals. 
 
Effect on fertility: Interferon may impair fertility (see section 4.6 and section 5.3). 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with 
Viraferon. 



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Interactions between Viraferon and other medicinal products have not been fully evaluated. Caution must be 
exercised when administering Viraferon in combination with other potentially myelosuppressive agents. 
 
Interferons may affect the oxidative metabolic process. This must be considered during concomitant therapy 
with medicinal products metabolised by this route, such as the xanthine derivatives theophylline or 
aminophylline. During concomitant therapy with xanthine agents, serum theophylline levels must be 
monitored and dosage adjusted if necessary. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.4). 
 
(Also see ribavirin SPC if Viraferon is to be administered in combination with ribavirin in patients with 
chronic hepatitis C). 
 
4.6 Pregnancy and lactation 
 
Women of childbearing potential have to use effective contraception during treatment. Viraferon must be 
used with caution in fertile men. Decreased serum estradiol and progesterone concentrations have been 
reported in women treated with human leukocyte interferon. 
 
There are no adequate data from the use of interferon alfa-2b in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Viraferon is to be 
used during pregnancy only if the potential benefit justifies the potential risk to the foetus. 
 
It is not known whether the components of this medicinal product are excreted in human milk. Because of the 
potential for adverse reactions in nursing infants, nursing should be discontinued prior to initiation of 
treatment. 
 
Combination therapy with ribavirin: Ribavirin causes serious birth defects when administered during 
pregnancy. Ribavirin therapy is contraindicated in women who are pregnant. Extreme care must be taken to 
avoid pregnancy in female patients or in partners of male patients taking Viraferon in combination with 
ribavirin. Females of childbearing potential and their partners must each use an effective contraceptive during 
treatment and for 4 months after treatment has been concluded. Male patients and their female partners must 
each use an effective contraceptive during treatment and for 7 months after treatment has been concluded (see 
ribavirin SPC). 
 
4.7 Effects on ability to drive and use machines 
 
Patients are to be advised that they may develop fatigue, somnolence, or confusion during treatment with 
Viraferon, and therefore it is recommended that they avoid driving or operating machinery. 
 
4.8 Undesirable effects 
 
See ribavirin SPC for ribavirin-related undesirable effects if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
In clinical trials conducted in a broad range of indications and at a wide range of doses (from 6 MIU/m2/week 
in hairy cell leukaemia up to 100 MIU/m2/week in melanoma), the most commonly reported undesirable 
effects were fever, fatigue, headache and myalgia. Fever and fatigue were often reversible within 72 hours of 
interruption or cessation of treatment. 
 



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In clinical trials conducted in the hepatitis C population, patients were treated with Viraferon alone or in 
combination with ribavirin for one year. All patients in these trials received 3 MIU of Viraferon three times a 
week. In Table 1 the frequency of patients reporting (treatment related) undesirable effects is presented from 
clinical trials in naïve patients treated for one year. Severity was generally mild to moderate. The adverse 
reactions listed in Table 1 are based on experience from clinical trials and post-marketing. Within the organ 
system classes, adverse reactions are listed under headings of frequency using the following categories: very 
common (≥1/10); common (≥1/100, <1/10); rarely (≥1/10,000, <1/1,000); very rarely (<1/10,000); not 
known. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 
 

Table 1. Adverse reactions reported during clinical trials or following the marketing use of Viraferon 
alone or in combination with ribavirin 

System Organ Class Adverse Reactions 
Infections and infestations 
Very common: 
Common: 
Rarely:  

 
Pharyngitis*, infection viral* 
Bronchitis, sinusitis, herpes simplex (resistance), rhinitis 
Pneumonia§ 

Blood and lymphatic system disorders 
Very common: 
Common: 
Very rarely:  
Not known:  

 
Leukopaenia 
Thrombocytopaenia, lymphadenopathy, lymphopenia 
Aplastic anaemia 
Pure red cell aplasia, idiopathic thrombocytopenic purpura, 
thrombotic thrombocytopenic purpura  

Immune system disorders§ 
Very rarely:  
Not known: 

 
Sarcoidosis, exacerbation of sarcoidosis 
Systemic lupus erythematosus, vasculitis, rheumatoid 
arthritis (new or aggravated), Vogt-Koyanagi-Harada 
syndrome, acute hypersensitivity reactions including 
urticaria, angioedema, bronchoconstriction, anaphylaxis§ 

Endocrine disorders 
Common: 
Very rarely:  

 
Hypothyroidism§, hyperthyroidism§ 
Diabetes, aggravated diabetes 

Metabolism and nutrition disorders 
Very common: 
Common:  
Very rarely:  

 
Anorexia 
Hypocalcaemia, dehydration, hyperuricemia, thirst 
Hyperglycaemia, hypertriglyceridaemia§, increased appetite 

Psychiatric disorders§ 
Very common: 
 
Common: 
Rarely:  
Very rarely: 
 
Not known: 

 
Depression, insomnia, anxiety, emotional lability*, 
agitation, nervousness 
Confusion, sleep disorder, libido decreased 
Suicide ideation 
Suicide, suicide attempts, aggressive behaviour (sometimes 
directed against others), psychosis including hallucinations 
Mental status change§ 

Nervous system disorders§ 
Very common: 
Common: 
 
Very rarely:  
 
 
Not known: 

 
Dizziness, headache, concentration impaired, mouth dry 
Tremor, paresthesia, hypoesthesia, migraine, flushing, 
somnolence, taste perversion 
Cerebrovascular haemorrhage, cerbrovascular ischaemia, 
seizure, impaired consciousness, encephalopathy, 
neuropathy, polyneuropathy 
Mononeuropathies, coma§ 

Eye disorders 
Very common: 

 
Vision blurred 



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Common: 
 
Rarely:  

Conjunctivitis, vision abnormal, lacrimal gland disorder, eye 
pain 
Retinal haemorrhages§, retinopathies (including macular 
oedema), retinal artery or vein obstruction§, optic neuritis, 
papilloedema, loss of visual acuity or visual field, cotton-
wool spots§  

Ear and labyrinth 
Common: 
Very rarely:  

 
Vertigo, tinnitus 
Hearing loss, hearing disorder 

Cardiac disorders 
Common: 
Rarely: 
Very rarely: 
Not known: 

 
Palpitation, tachycardia 
Cardiomyopathy 
Myocardial infarction, cardiac ischaemia  
Arrhythmia  

Vascular disorders 
Common: 
Very rarely:  

 
Hypertension 
Peripheral ischaemia, hypotension§ 

Respiratory, thoracic and mediastinal 
disorders 
Very common: 
Common: 
 
Very rarely:  

 
 
Dyspnoea*, coughing* 
Epistaxis, respiratory disorder, nasal congestion, rhinorrhea, 
cough nonproductive 
Pulmonary infiltrates§, pneumonitis§ 

Gastrointestinal disorders 
Very common: 
 
Common: 
 
Very rarely:  
 
Not known: 

 
Nausea/vomiting, abdominal pain, diarrhoea, stomatitis, 
dyspepsia 
Stomatitis ulcerative, right upper quadrant pain, glossitis, 
gingivitis, constipation, loose stools 
Pancreatitis, ischaemic colitis, ulcerative colitis, gingival 
bleeding 
Periodontal disorder NOS, dental disorder NOS§ 

Hepatobiliary disorders 
Common: 
Very rarely:  

 
Hepatomegaly 
Hepatotoxicity, (including fatality) 

Skin and subcutaneous tissue disorders 
Very common: 
Common: 
 
Very rarely:  

 
Alopecia, pruritus*, skin dry*, rash*, sweating increased 
Psoriasis (new or aggravated)§, rash maculopapular, rash 
erythematous, eczema, erythema, skin disorder 
Stevens Johnson syndrome, toxic epidermal necrolysis, 
erythema multiforme 

Musculoskeletal and connective tissue 
disorders 
Very common:  
Common: 
Very rarely: 

 
 
Myalgia, arthralgia, musculoskeletal pain 
Arthritis 
Rhabdomyolysis, myositis, leg cramps, back pain 

Renal and urinary disorders 
Common: 
Very rarely:  

 
Micturition frequency 
Renal failure, renal insufficiency, nephrotic syndrome 

Reproductive system and breast 
disorders 
Common: 

 
 
Amenorrhea, breast pain, dysmenorrhea, menorrhagia, 
menstrual disorder, vaginal disorder 

General disorders and administration 
site conditions 

 
 



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Very common: 
 
 
Common: 
Very rarely: 

Injection site inflammation, injection site reaction*, fatigue, 
rigors, fever§, flu-like symptoms§, asthenia, irritability, chest 
pain, malaise 
Injection site pain 
Injection site necrosis, face oedema 

Investigations 
Very common: 

 
Weight decrease 

*These events were only common with Viraferon alone 
§See section 4.4 
 
These undesirable effects have also been reported with Viraferon alone. 
 
Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-
existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4). Cardiomyopathy, that may 
be reversible upon discontinuation of interferon alpha, has been reported rarely in patients without prior 
evidence of cardiac disease (see section 4.4).  
 
A wide variety of autoimmune and immune-mediated disorders have been reported with alpha interferons 
including thyroid disorders, systemic lupus erythematosus, rheumatoid arthritis (new or aggravated), 
idiopathic and thrombotic thrombocytopenic purpura, vasculitis, neuropathies including mononeuropathies 
(see also section 4.4).  
 
Clinically significant laboratory abnormalities, most frequently occurring at doses greater than 10 million IU 
daily, include reduction in granulocyte and white blood cell counts; decreases in haemoglobin level and 
platelet count; increases in alkaline phosphatase, LDH, serum creatinine and serum urea nitrogen levels. 
Increase in serum ALT/AST (SGPT/SGOT) levels have been noted as an abnormality in some non-hepatitis 
subjects and also in some patients with chronic hepatitis B coincident with clearance of viral DNAp. 
 
Paediatric population 
 
Children and adolescents – Chronic Hepatitis C 
In clinical trials of 118 children or adolescents 3 to 16 years of age, 6 % discontinued therapy due to adverse 
events. In general, the adverse event profile in the limited paediatric population studied was similar to that 
observed in adults, although there is a paediatric specific concern regarding growth inhibition as decrease in 
height (mean percentile decrease of growth velocity of 9 %) and weight (mean percentile decrease of 13 %) 
percentile were observed during treatment (see section 4.4). Furthermore, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6 month 
follow-up after treatment. As in adult patients, children and adolescents also experienced other psychiatric 
adverse events (e.g., depression, emotional lability, and somnolence) (see section 4.4). In addition, injection 
site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in children and 
adolescents compared to adult patients. Dose modifications were required in 30 % of patients, most 
commonly for anaemia and neutropaenia. 
 
The adverse reactions listed in Table 2 are based on experience from paediatric clinical trials.  
Within the organ system classes, adverse reactions are listed under headings of frequency using the following 
categories: very common (≥1/10); common (≥1/100, <1/10). Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness. 
 
Table 2  Adverse reactions very commonly and commonly reported in paediatric clinical trials  

Very common (≥1/10) - Common (≥1/100, <1/10) 
System Organ Class Adverse Reactions 
Infection and infestations 
Very common: 
Common: 

 
Viral infection, pharyngitis 
Fungal infection, bacterial infection, pulmonary infection, otitis 



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media, tooth abscess, herpes simplex, urinary tract infection, 
vaginitis, gastroenteritis 

Neoplasms benign, malignant 
and unspecified (including 
cysts and polyps) 
Common: 

 
 
 
Neoplasm (unspecified) 

Blood and lymphatic system 
disorders 
Very common: 
Common: 

 
 
Anaemia, neutropaenia 
Thrombocytopaenia, lymphadenopathy 

Endocrine disorders 
Very common: 
Common: 

 
Hypothyroidism§,  
Hyperthyroidism§, virilism 

Metabolism and nutrition 
disorders 
Very common: 
Common: 

 
 
Anorexia 
Hypertriglyceridemia§, hyperuricemia, increased appetite 

Psychiatric disorders§ 
Very common: 
Common: 

 
Depression, emotional lability, insomnia 
Suicidal ideation, aggressive reaction, confusion, behaviour 
disorder, agitation, somnambulism, anxiety, nervousness, sleep 
disorder, abnormal dreaming, apathy 

Nervous system disorders§ 
Very common: 
Common: 

 
Headache, dizziness 
Hyperkinesia, tremor, dysphonia, paresthaesia, hypoaesthesia, 
hyperaesthesia, concentration impaired, somnolence 

Eye disorders 
Common: 

 
Conjunctivitis, eye pain, abnormal vision, lacrimal gland disorder 

Vascular disorders 
Common: 

 
Raynaud’s disease, flushing, pallor 

Respiratory, thoracic and 
mediastinal disorders 
Common: 

 
 
Dyspnoea, tachypnea, epistaxis, coughing, nasal congestion, nasal 
irritation, rhinorrhea, sneezing 

Gastrointestinal disorders 
Very common: 
Common: 

 
Diarrhoea, vomiting, nausea, abdominal pain 
Mouth ulceration, stomatitis ulcerative, stomatitis, right upper 
quadrant pain, dyspepsia, glossitis, gastroesophogeal reflux, rectal 
disorder, gastrointestinal disorder, constipation, loose stools, 
toothache, tooth disorder 

Hepatobiliary disorders 
Common: 

 
Hepatic function abnormal 

Skin and subcutaneous tissue 
disorders  
Very common: 
Common: 

 
 
Alopecia, rash 
Photosensitivity reaction, maculopapular rash, eczema, acne, skin 
disorder, nail disorder, skin discolouration, pruritus, dry skin, 
erythema, bruise, sweating increased 

Musculoskeletal and 
connective tissue disorders 
Very common: 

 
 
Arthralgia, myalgia, musculoskeletal pain  

Renal and urinary disorders 
Common: 

 
Enuresis, micturition disorder, urinary incontinence 

Reproductive system and  



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breast disorders 
Common: 

 
Female: amenorrhea, menorrhagia, menstrual disorder, vaginal 
disorder 
Male: testicular pain 

General disorders and 
administration site 
conditions 
Very common: 
 
Common: 

 
 
 
Injection site inflammation, injection site reaction, fatigue, rigors, 
fever§, influenza-like symptoms§, malaise, irritability 
Chest pain, asthenia, oedema, injection site pain 

Investigations 
Very common: 

 
Growth rate decrease (height and/or weight decrease for age)§  

Injury and poisoning 
Common: 

 
Skin laceration 

§See section 4.4 
 
4.9 Overdose 
 
No case of overdose has been reported that has led to acute clinical manifestations. However, as for any 
pharmacologically active compound, symptomatic treatment with frequent monitoring of vital signs and close 
observation of the patient is indicated. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunostimulants, cytokines and immunomodulators, interferons, interferon 
alfa-2b, ATC code: L03A B05 
 
Viraferon is a sterile, stable, formulation of highly purified interferon alfa-2b produced by recombinant DNA 
techniques. Recombinant interferon alfa-2b is a water-soluble protein with a molecular weight of 
approximately 19,300 daltons. It is obtained from a clone of E. coli, which harbours a genetically engineered 
plasmid hybrid encompassing an interferon alfa-2b gene from human leukocytes. 
 
The activity of Viraferon is expressed in terms of IU, with 1 mg of recombinant interferon alfa-2b protein 
corresponding to 2.6 x l08 IU. International Units are determined by comparison of the activity of the 
recombinant interferon alfa-2b with the activity of the international reference preparation of human leukocyte 
interferon established by the World Health Organisation. 
 
The interferons are a family of small protein molecules with molecular weights of approximately 15,000 to 
21,000 daltons. They are produced and secreted by cells in response to viral infections or various synthetic 
and biological inducers. Three major classes of interferons have been identified: alpha, beta and gamma. 
These three main classes are themselves not homogeneous and may contain several different molecular 
species of interferon. More than 14 genetically distinct human alpha interferons have been identified. 
Viraferon has been classified as recombinant interferon alfa-2b. 
 
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. 
Human interferon receptors, as isolated from human lymphoblastoid (Daudi) cells, appear to be highly 
asymmetric proteins. They exhibit selectivity for human but not murine interferons, suggesting species 
specificity. Studies with other interferons have demonstrated species specificity. However, certain monkey 
species, eg, rhesus monkeys, are susceptible to pharmacodynamic stimulation upon exposure to human type 
1 interferons. 
 



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The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex 
sequence of intracellular events that include the induction of certain enzymes. It is thought that this process, 
at least in part, is responsible for the various cellular responses to interferon, including inhibition of virus 
replication in virus-infected cells, suppression of cell proliferation and such immunomodulating activities as 
enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of 
lymphocytes for target cells. Any or all of these activities may contribute to interferon's therapeutic effects. 
 
Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and 
human cell culture systems as well as human tumour xenografts in animals. It has demonstrated significant 
immunomodulatory activity in vitro. 
 
Recombinant interferon alfa-2b also inhibits viral replication in vitro and in vivo. Although the exact antiviral 
mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism. 
This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell. 
 
Chronic hepatitis B: 
Current clinical experience in patients who remain on interferon alfa-2b for 4 to 6 months indicates that 
therapy can produce clearance of serum HBV-DNA. An improvement in liver histology has been observed. 
In adult patients with loss of HBeAg and HBV-DNA, a significant reduction in morbidity and mortality has 
been observed. 
 
Interferon alfa-2b (6 MIU/m2 3 times a week for 6 months) has been given to children with chronic active 
hepatitis B. Because of a methodological flaw, efficacy could not be demonstrated. Moreover children treated 
with interferon alfa-2b experienced a reduced rate of growth and some cases of depression were observed. 
 
Chronic hepatitis C: 
In adult patients receiving interferon in combination with ribavirin, the achieved sustained response rate is 
47 %. Superior efficacy has been demonstrated with the combination of pegylated interferon with ribavirin 
(sustained response rate of 61 % achieved in a study performed in naïve patients with a ribavirin dose 
> 10.6 mg/kg, p < 0.01). 
 
Adult patients: Viraferon alone or in combination with ribavirin has been studied in 4 randomised Phase III 
clinical trials in 2,552 interferon-naïve patients with chronic hepatitis C. The trials compared the efficacy of 
Viraferon used alone or in combination with ribavirin. Efficacy was defined as sustained virologic response, 
6 months after the end of treatment. Eligible patients for these trials had chronic hepatitis C confirmed by a 
positive HCV-RNA polymerase chain reaction assay (PCR) (> 100 copies/ml), a liver biopsy consistent with 
a histologic diagnosis of chronic hepatitis with no other cause for the chronic hepatitis, and abnormal serum 
ALT. 
 
Viraferon was administered at a dose of 3 MIU 3 times a week as monotherapy or in combination with 
ribavirin. The majority of patients in these clinical trials were treated for one year. All patients were followed 
for an additional 6 months after the end of treatment for the determination of sustained virologic response. 
Sustained virologic response rates for treatment groups treated for one year with Viraferon alone or in 
combination with ribavirin (from two studies) are shown in Table 3. 
 
Co-administration of Viraferon with ribavirin increased the efficacy of Viraferon by at least two fold for the 
treatment of chronic heptatitis C in naïve patients. HCV genotype and baseline virus load are prognostic 
factors which are known to affect response rates. The increased response rate to the combination of Viraferon + 
ribavirin, compared with Viraferon alone, is maintained across all subgroups. The relative benefit of combination 
therapy with Viraferon + ribavirin is particularly significant in the most difficult to treat subgroup of patients 
(genotype 1 and high virus load) (Table 3). 
 
Response rates in these trials were increased with compliance. Regardless of genotype, patients who received 
Viraferon in combination with ribavirin and received ≥ 80 % of their treatment had a higher sustained 



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response 6 months after 1 year of treatment than those who took < 80 % of their treatment (56 % vs. 32 % in 
trial C/I98-580).  
 

Table 3 Sustained virologic response rates with Viraferon + ribavirin (one year of 
treatment) by genotype and viral load 

 
HCV Genotype  
 

I 
N=503 

C95-132/I95-143 

I/R 
N=505 

C95-132/I95-143 

I/R 
N=505 

C/I98-580 
 
All Genotypes 

 
16 % 

 
41 % 

 
47 % 

 
 
Genotype 1 

 
9 % 

 
29 % 

 
33 % 

 
Genotype 1  
≤ 2 million 
copies/ml 

 
25 % 

 
33 % 

 
45 % 

 
Genotype 1 
> 2 million 
copies/ml 

 
3 % 

 
27 % 

 

 
29 % 

 
Genotype 2/3 

 
31 % 

 
65 % 

 
79 % 

I Viraferon (3 MIU 3 times a week) 
I/R Viraferon (3 MIU 3 times a week) + ribavirin (1,000/1,200 mg/day) 
 
HCV/HIV Co-infected patients  
Two trials have been conducted in patients co-infected with HIV and HCV. Overall, in both studies, patients 
who received Viraferon plus ribavirin, were less likely to respond than patients who received pegylated 
interferon alfa-2b with ribavirin. The response to treatment in both of these trials is presented in Table 4. 
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 412 previously untreated 
adult patients with chronic hepatitis C who were co-infected with HIV. Patients were randomized to receive 
either pegylated interferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800 mg/day) or Viraferon (3 MIU TIW) 
plus ribavirin (800 mg/day) for 48 weeks with a follow-up period of 6 months. Study 2 (P02080) was a 
randomized, single centre study that enrolled 95 previously untreated adult patients with chronic hepatitis C 
who were co-infected with HIV. Patients were randomized to receive either pegylated interferon alfa-2b (100 
or 150 µg /week based on weight) plus ribavirin (800-1,200 mg/day based on weight) or Viraferon (3 MIU 
TIW) plus ribavirin (800-1,200 mg/day based on weight). The duration of therapy was 48 weeks with a 
follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load 
< 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6-month follow-up period.  
           
Table 4 Sustained virological response based on genotype after Viraferon in combination with 

ribavirin versus pegylated interferon alfa-2b in combination with ribavirin in 
HCV/HIV co-infected patients 

 Study 11 Study 22 
 

pegylated 
interferon 

alfa-2b  
(1.5 µg/kg/ 

week) + 
ribavirin  
(800 mg) 

Viraferon  
(3 MIU TIW) +  

ribavirin  
(800 mg) 

p 
valuea 

pegylated 
interferon 

alfa-2b (100 
or  

150c µg/week) 
+ ribavirin 

(800- 
1,200 mg)d 

Viraferon  
(3 MIU TIW) 

+ ribavirin 
(800- 

1,200 mg)d 
p 

valueb 



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All 27 % (56/205) 20 % (41/205) 0.047 44 % (23/52) 21 % (9/43) 0.017 
Genotype 1, 

4 
17 % (21/125) 6 % (8/129) 0.006 38 % (12/32) 7 % (2/27) 0.007 

Genotype 2, 
3 

44 % (35/80) 43 % (33/76) 0.88 53 % (10/19) 47 % (7/15) 0.730 

MIU = million international units; TIW = three times a week. 
a:  p value based on Cochran-Mantel Haenszel Chi square test. 
b:  p value based on chi-square test. 
c:  subjects < 75 kg received 100 µg/week pegylated interferon alfa-2b and subjects ≥ 75 kg received 150 µg/week pegylated 

interferon alfa-2b. 
d: ribavirin dosing was 800 mg for patients < 60 kg, 1,000 mg for patients 60-75 kg, and 1,200 mg for patients > 75 kg. 
 

1Carrat F, Bani-Sadr F, Pol S et al.  JAMA 2004; 292(23): 2839-2848. 
2 Laguno M, Murillas J, Blanco J.L et al.  AIDS 2004; 18(13): F27-F36. 
 
 
Relapse patients: A total of 345 interferon alpha relapse patients were treated in two clinical trials with 
Viraferon monotherapy or in combination with ribavirin. In these patients, the addition of ribavirin to 
Viraferon increased by as much as 10-fold the efficacy of Viraferon used alone in the treatment of chronic 
hepatitis C (48.6 % vs. 4.7 %). This enhancement in efficacy included loss of serum HCV (< 100 copies/ml 
by PCR), improvement in hepatic inflammation, and normalisation of ALT, and was sustained when 
measured 6 months after the end of treatment. 
 
Long-Term efficacy data 
In a large study, 1,071 patients were enrolled after treatment in a prior non pegylated interferon alfa-2b or 
non pegylated interferon alfa-2b/ribavirin study to evaluate the durability of sustained virologic response and 
assess the impact of continued viral negativity on clinical outcomes. 462 patients completed at least 5 years 
of long-term follow-up and only 12 sustained responders' out of 492 relapsed during this study.  
The Kaplan-Meier estimate for continued sustained response over 5 years for all patients is 97 % with a 95 % 
Confidence Interval of [95 %, 99 %].  
SVR after treatment of chronic HCV with non pegylated interferon alfa-2b (with or without ribavirin) results 
in long-term clearance of the virus providing resolution of the hepatic infection and clinical 'cure' from 
chronic HCV. However, this does not preclude the occurrence of hepatic events in patients with cirrhosis 
(including hepatocarcinoma). 
 
Clinical trials in paediatric patients with chronic hepatitis C: 
Children and adolescents 3 to 16 years of age with compensated chronic hepatitis C and detectable HCV-
RNA (assessed by a central laboratory using a research-based RT-PCR assay) were enrolled in two 
multicentre trials and received Viraferon 3 MIU/m2 3 times a week plus ribavirin 15 mg/kg per day for 1 year 
followed by 6 months follow-up after-treatment. A total of 118 patients were enrolled: 57 % male, 80 % 
Caucasian, and 78 % genotype 1,64 % ≤ 12 years of age. The population enrolled mainly consisted in 
children with mild to moderate hepatitis C. Sustained virological response rates in children and adolescents 
were similar to those in adults. Due to the lack of data in children with severe progression of the disease, and 
the potential for undesirable effects, the benefit/risk of the combination of ribavirin and interferon alfa-2b 
needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8). 
 
Study results are summarized in Table 5. 
 
Table 5. Virological response in previously untreated paediatric patients 
 Viraferon 3 MIU/m2 3 times a week   

+ 
ribavirin 15 mg/kg/day 

Overall Response1 (n=118) 54 (46 %)* 



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Genotype 1 (n=92) 33 (36 %)* 

Genotype 2/3/4 (n=26) 21 (81 %)* 

*Number (%) of patients 
1. Defined as HCV-RNA below limit of detection using a research based RT-PCR assay at end of treatment and during follow-up 
period 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of Viraferon were studied in healthy volunteers following single 5 million IU/m2 and 
10 million IU doses administered subcutaneously, at 5 million IU/m2 administered intramuscularly and as a 
30-minute intravenous infusion. The mean serum interferon concentrations following subcutaneous and 
intramuscular injections were comparable. Cmax occurred three to 12 hours after the lower dose and six to 
eight hours after the higher dose. The elimination half-lives of interferon injections were approximately two 
to three hours, and six to seven hours, respectively. Serum levels were below the detection limit 16 and 
24 hours, respectively, post-injection. Both subcutaneous and intramuscular administration resulted in 
bioavailabilities greater than 100 %. 
 
After intravenous administration, serum interferon levels peaked (135 to 273 IU/ml) by the end of the 
infusion, then declined at a slightly more rapid rate than after subcutaneous or intramuscular administration 
of medicinal product, becoming undetectable four hours after the infusion. The elimination half-life was 
approximately two hours. 
 
Urine levels of interferon were below the detection limit following each of the three routes of administration. 
 
Children and adolescents: Multiple-dose pharmacokinetic properties for Viraferon injection and ribavirin 
capsules in children and adolescents with chronic hepatitis C, between 5 and 16 years of age, are summarized 
in Table 6. The pharmacokinetics of Viraferon and ribavirin (dose-normalized) are similar in adults and 
children or adolescents. 
 

Table 6. Mean (% CV) multiple-dose pharmacokinetic parameters for Viraferon and ribavirin 
capsules when administered to children or adolescents with chronic hepatitis C 
Parameter Ribavirin 

15 mg/kg/day as 2 divided 
doses 

(n = 17) 

Viraferon 
3 MIU/m2 3 times a week 

(n = 54) 

Tmax (hr) 1.9 (83) 5.9 (36) 
Cmax (ng/ml) 3,275 (25) 51 (48) 

AUC* 29,774 (26) 622 (48) 
Apparent clearance l/hr/kg 0.27 (27) Not done 

*AUC12 (ng.hr/ml) for ribavirin; AUC0-24 (IU.hr/ml) for Viraferon 
 
Interferon neutralising factor assays were performed on serum samples of patients who received Viraferon in 
Schering-Plough monitored clinical trials. Interferon neutralising factors are antibodies which neutralise the 
antiviral activity of interferon. The clinical incidence of neutralising factors developing in cancer patients 
treated systemically is 2.9 % and in chronic hepatitis patients is 6.2 %. The detectable titres are low in almost 
all cases and have not been regularly associated with loss of response or any other autoimmune phenomenon. 
In patients with hepatitis, no loss of response was observed apparently due to the low titres. 
 
5.3 Preclinical safety data 
 
Although interferon is generally recognised as being species specific, toxicity studies in animals were 
conducted. Injections of human recombinant interferon alfa-2b for up to three months have shown no 
evidence of toxicity in mice, rats, and rabbits. Daily dosing of cynomolgus monkeys with 20 x 106 IU/kg/day 



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for 3 months caused no remarkable toxicity. Toxicity was demonstrated in monkeys given 
100 x 106 IU/kg/day for 3 months. 
 
In studies of interferon use in non-human primates, abnormalities of the menstrual cycle have been observed 
(see section 4.4). 
 
Results of animal reproduction studies indicate that recombinant interferon alfa-2b was not teratogenic in rats 
or rabbits, nor did it adversely affect pregnancy, foetal development or reproductive capacity in offspring of 
treated rats. Interferon alfa-2b has been shown to have abortifacient effects in Macaca mulatta (rhesus 
monkeys) at 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2. 
Abortion was observed in all dose groups (7.5 million, 15 million and 30 million IU/kg), and was statistically 
significant versus control at the mid- and high-dose groups (corresponding to 90 and 180 times the 
recommended intramuscular or subcutaneous dose of 2 million IU/m2). High doses of other forms of 
interferons alpha and beta are known to produce dose-related anovulatory and abortifacient effects in rhesus 
monkeys. 
 
Mutagenicity studies with interferon alfa-2b revealed no adverse events. 
 
No studies have been conducted in juvenile animals to examine the effects of treatment with interferon alfa-
2b on growth, development, sexual maturation, and behaviour (see section 4.4 and Rebetol SPC if Viraferon 
is to be administered in combination with ribavirin). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Disodium phosphate anhydrous,  
Sodium dihydrogen phosphate monohydrate,  
Edetate disodium,  
Sodium chloride,  
M-cresol,  
Polysorbate 80, 
Water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
18 months 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C).  
Do not freeze.  
Within its shelf-life, for the purpose of transport, the solution can be kept at or below 25ºC for a period up to 
seven days before use. Viraferon can be put back in the refrigerator at any time during this seven-day period. 
If the product is not used during the seven-day period, it cannot be put back in the refrigerator for a new 
storage period and must be discarded. 
 
6.5 Nature and contents of container 
 



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1 ml of solution (corresponding to 10 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in a flip-
off seal (aluminium) with a bonnet (polypropylene) 
Pack sizes of 1 
 
Or 
 
1 ml of solution (corresponding to 10 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in a flip-
off seal (aluminium) with a bonnet (polypropylene) 
with 1 injection syringe, 1 injection needle and 1 cleansing swab.  
Packs sizes of 1, 6 or 12 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
Viraferon solution for injection, may be injected directly after withdrawal of the appropriate doses from the 
vial with a sterile injection syringe. 
 
As with all parenteral medicinal products, prior to administration inspect Viraferon, solution for injection, 
visually for particulate matter and discolouration. The solution should be clear and colourless. 
 
Detailed instructions for the subcutaneous use of the product are provided with the package leaflet (refer to 
“How to self inject Viraferon”). 
 
Any unused product must be discarded after withdrawal of the dose. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
SP Europe 
73, rue de Stalle 
B-1180 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/99/128/017 
EU/1/99/128/018 
EU/1/99/128/019 
EU/1/99/128/020 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation : 9 March 2000 
Date of last renewal : 23 May 2005 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 



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Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu/ 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 18 million IU/3 ml solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One vial of Viraferon solution for injection, multiple dose vial, contains 18 million IU of recombinant 
interferon alfa-2b produced in E.coli by recombinant DNA technology, in 3 ml of solution. 
 
One ml of solution contains 6 million IU of interferon alfa-2b. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection 
Solution is clear and colourless. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Chronic Hepatitis B: Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis B 
viral replication (presence of HBV-DNA and HBeAg), elevated alanine aminotransferase (ALT) and 
histologically proven active liver inflammation and/or fibrosis. 
 
Chronic Hepatitis C:  
Adult patients:  
Viraferon is indicated for the treatment of adult patients with chronic hepatitis C who have elevated 
transaminases without liver decompensation and who are positive for serum HCV-RNA or anti-HCV (see 
section 4.4). 
 
The best way to use Viraferon in this indication is in combination with ribavirin. 
 
Chidren and adolescents: 
Viraferon is intended for use, in a combination regimen with ribavirin, for the treatment of children and 
adolescents 3 years of age and older, who have chronic hepatitis C, not previously treated, without liver 
decompensation, and who are positive for serum HCV-RNA. The decision to treat should be made on a case 
by case basis, taking into account any evidence of disease progression such as hepatic inflammation and 
fibrosis, as well as prognostic factors for response, HCV genotype and viral load. The expected benefit of 
treatment should be weighed against the safety findings observed for paediatric subjects in the clinical trials 
(see sections 4.4, 4.8 and 5.1). 
 
4.2 Posology and method of administration 
 
Treatment must be initiated by a physician experienced in the management of the disease. 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
If adverse events develop during the course of treatment with Viraferon for any indication, modify the dosage 
or discontinue therapy temporarily until the adverse events abate. If persistent or recurrent intolerance 



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develops following adequate dosage adjustment, or disease progresses, discontinue treatment with Viraferon. 
At the discretion of the physician, the patient may self-administer the dose for maintenance dosage regimens 
administered subcutaneously. 
 
Chronic Hepatitis B: The recommended dosage is in the range 5 to 10 million IU administered 
subcutaneously three times a week (every other day) for a period of 4 to 6 months. 
 
The administered dose should be reduced by 50 % in case of occurrence of haematological disorders (white 
blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3). Treatment should be 
discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe 
thrombocytopaenia (< 70,000/mm3). 
 
For all patients, if no improvement on serum HBV-DNA is observed after 3 to 4 months of treatment (at the 
maximum tolerated dose), discontinue Viraferon therapy. 
 
Chronic Hepatitis C: Viraferon is administered subcutaneously at a dose of 3 million IU three times a week 
(every other day) to adult patients, whether administered as monotherapy or in combination with ribavirin. 
 
Children 3 years of age or older and adolescents: Interferon alfa-2b 3 MIU/m2 is administered 
subcutaneously 3 times a week (every other day) in combination with ribavirin capsules or oral solution 
administered orally in two divided doses daily with food (morning and evening).  
 
(See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination 
therapy. For paediatric patients who weigh < 47 kg or cannot swallow capsules, see ribavirin oral solution 
SPC).  
 
Relapse patients (adults): 
Viraferon is given in combination with ribavirin. 
 
Based on the results of clinical trials, in which data are available for 6 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for 6 months. 
 
Naïve patients: 
Adults: The efficacy of Viraferon is enhanced when given in combination with ribavirin. Viraferon should be 
given alone mainly in case of intolerance or contraindication to ribavirin. 
 
Viraferon in combination with ribavirin: 
Based on the results of clinical trials, in which data are available for 12 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for at least 6 months. 
 
Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit 
negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and 
high pre-treatment viral load. 
 
Other negative prognostic factors (age > 40 years, male gender, bridging fibrosis) should be taken into 
account in order to extend therapy to 12 months. 
 
During clinical trials, patients who failed to show a virologic response after 6 months of treatment (HCV-
RNA below lower limit of detection) did not become sustained virologic responders (HCV-RNA below lower 
limit of detection six months after withdrawal of treatment). 
 
Viraferon alone: 
The optimal duration of therapy with Viraferon alone is not yet fully established, but a therapy of between 
12 and 18 months is advised. 
 



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It is recommended that patients be treated with Viraferon alone for at least 3 to 4 months, at which point 
HCV-RNA status should be determined. Treatment should be continued in patients who exhibit negative 
HCV-RNA. 
 
Children and adolescents: The efficacy and safety of Viraferon in combination with ribavirin has been 
studied in children and adolescents who have not been previously treated for chronic hepatitis C.  
 
Genotype 1: The recommended duration of treatment is one year. Patients who fail to achieve virological 
response at 12 weeks are highly unlikely to become sustained virological responders (negative predictive 
value 96 %). Virological response is defined as absence of detectable HCV-RNA at Week 12. Treatment 
should be discontinued in these patients. 
Genotype 2/3: The recommended duration of treatment is 24 weeks. 
 
Virological responses after 1 year of treatment and 6 months of follow-up were 36 % for genotype 1 and 
81 % for genotype 2/3/4. 
 
Viraferon may be administered using either glass or plastic disposable injection syringes. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients. 
- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure, recent 

myocardial infarction, severe arrhythmic disorders.  
- Severe renal or hepatic dysfunction; including that caused by metastases. 
- Epilepsy and/or compromised central nervous system (CNS) function (see section 4.4). 
- Chronic hepatitis with decompensated cirrhosis of the liver. 
- Chronic hepatitis in patients who are being or have been treated recently with immunosuppressive 

agents excluding short term corticosteroid withdrawal. 
- Autoimmune hepatitis; or history of autoimmune disease; immunosuppressed transplant recipients. 
- Pre-existing thyroid disease unless it can be controlled with conventional treatment. 
 
Children and adolescents: 
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal 

ideation or suicide attempt. 
 

Combination therapy with ribavirin: Also see ribavirin SPC if interferon alfa-2b is to be administered in 
combination with ribavirin in patients with chronic hepatitis C. 
 
4.4 Special warnings and precautions for use 
 
For all patients: 
Psychiatric and central nervous system (CNS): Severe CNS effects, particularly depression, suicidal ideation 
and attempted suicide have been observed in some patients during Viraferon therapy, and even after 
treatment discontinuation mainly during the 6-month follow-up periodand in the follow-up period. Among 
children and adolescents treated with Viraferon in combination with ribavirin, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6-month 
follow-up after treatment. As in adult patients, children and adolescents experienced other psychiatric adverse 
events (e.g., depression, emotional lability, and somnolence). Other CNS effects including aggressive behaviour 
(sometimes directed against others), confusion and alterations of mental status have been observed with alpha 
interferons. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such 
symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the 
prescribing physician and the need for adequate therapeutic management should be considered. If psychiatric 
symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with 
Viraferon be discontinued, and the patient followed, with psychiatric intervention as appropriate. 
 



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Patients with existence of or history of severe psychiatric conditions: 
If a treatment with interferon alfa-2b is judged necessary in adult patients with existence or history of severe 
psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and 
therapeutic management of the psychiatric condition. The use of interferon alfa-2b in children and adolescents 
with existence of or history of severe psychiatric conditions is contraindicated (see section 4.3). 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Moderate to severe adverse experiences may require modification of the patient's dosage regimen, or in some 
cases, termination of Viraferon therapy. Any patient developing liver function abnormalities during treatment 
with Viraferon must be monitored closely and treatment discontinued if signs and symptoms progress. 
 
Hypotension may occur during Viraferon therapy or up to two days post-therapy and may require supportive 
treatment. 
 
Adequate hydration must be maintained in patients undergoing Viraferon therapy since hypotension related 
to fluid depletion has been seen in some patients. Fluid replacement may be necessary. 
 
While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, 
other causes of persistent fever must be ruled out. 
 
Viraferon must be used cautiously in patients with debilitating medical conditions, such as those with a 
history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to 
ketoacidosis. Caution must be observed also in patients with coagulation disorders (e.g., thrombophlebitis, 
pulmonary embolism) or severe myelosuppression. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.5). Any patient developing fever, cough, 
dyspnea or other respiratory symptoms must have a chest X-ray taken. If the chest X-ray shows pulmonary 
infiltrates or there is evidence of pulmonary function impairment, the patient is to be monitored closely, and, 
if appropriate, discontinue interferon alpha. While this has been reported more often in patients with chronic 
hepatitis C treated with interferon alpha, it has also been reported in patients with oncologic diseases treated 
with interferon alpha. Prompt discontinuation of interferon alpha administration and treatment with 
corticosteroids appear to be associated with resolution of pulmonary adverse events. 
 
Ocular adverse events (see section 4.8) including retinal haemorrhages, cotton wool spots, and retinal artery 
or vein obstruction have been reported in rare instance after treatment with alpha interferons. All patients 
should have a baseline eye examination. Any patient complaining of changes in visual acuity or visual fields, 
or reporting other ophthalmologic symptoms during treatment with Viraferon, must have a prompt and 
complete eye examination. Periodic visual examinations during Viraferon therapy are recommended 
particularly in patients with disorders that may be associated with retinopathy, such as diabetes mellitus or 
hypertension. Discontinuation of Viraferon should be considered in patients who develop new or worsening 
ophthalmological disorders. 
 



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More significant obtundation and coma, including cases of encephalopathy, have been observed in some 
patients, usually elderly, treated at higher doses. While these effects are generally reversible, in a few patients 
full resolution took up to three weeks. Very rarely, seizures have occurred with high doses of Viraferon. 
 
Adult patients with a history of congestive heart failure, myocardial infarction and/or previous or current 
arrhythmic disorders, who require Viraferon therapy, must be closely monitored. It is recommended that 
those patients who have pre-existing cardiac abnormalities and/or are in advanced stages of cancer have 
electrocardiograms taken prior to and during the course of treatment. Cardiac arrhythmias (primarily 
supraventricular) usually respond to conventional therapy but may require discontinuation of Viraferon 
therapy. There are no data in children or adolescents with a history of cardiac disease. 
 
Hypertriglyceridemia and aggravation of hypertriglyceridemia, sometimes severe, have been observed. 
Monitoring of lipid levels is, therefore, recommended. 
 
Due to reports of interferon alpha exacerbating pre-existing psoriatic disease and sarcoidosis, use of 
Viraferon in patients with psoriasis or sarcoidosis is recommended only if the potential benefit justifies the 
potential risk. 
 
Preliminary data indicates that interferon alpha therapy may be associated with an increased rate of kidney 
graft rejection. Liver graft rejection has also been reported. 
 
The development of auto-antibodies and autoimmune disorders has been reported during treatment with alpha 
interferons. Patients predisposed to the development of autoimmune disorders may be at increased risk. 
Patients with signs or symptoms compatible with autoimmune disorders should be evaluated carefully, and 
the benefit-risk of continued interferon therapy should be reassessed (see also section 4.4 Chronic hepatitis C, 
Monotherapy (thyroid abnormalities) and section 4.8). 
Cases of Vogt-Koyanagi-Harada (VKH) syndrome have been reported in patients with chronic hepatitis C 
treated with interferon. This syndrome is a granulomatous inflammatory disorder affecting the eyes, auditory 
system, meninges, and skin. If VKH syndrome is suspected, antiviral treatment should be withdrawn and 
corticosteroid therapy discussed (see section 4.8). 
 
Discontinue treatment with Viraferon in patients with chronic hepatitis who develop prolongation of 
coagulation markers which might indicate liver decompensation. 
 
Chronic Hepatitis C: 
Combination therapy with ribavirin: Also see ribavirin SPC if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i.e. 
patients with genotype 2 and 3), treatment may be possible without histological confirmation. Current 
treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing 
treatment. 
 
Monotherapy: Infrequently, adult patients treated for chronic hepatitis C with Viraferon developed thyroid 
abnormalities, either hypothyroidism or hyperthyroidism. In clinical trials using Viraferon therapy, 2.8 % 
patients overall developed thyroid abnormalities. The abnormalities were controlled by conventional therapy 
for thyroid dysfunction. The mechanism by which Viraferon may alter thyroid status is unknown. Prior to 
initiation of Viraferon therapy for the treatment of chronic hepatitis C, evaluate serum thyroid-stimulating 
hormone (TSH) levels. Any thyroid abnormality detected at that time must be treated with conventional 
therapy. Viraferon treatment may be initiated if TSH levels can be maintained in the normal range by 
medication. Determine TSH levels if, during the course of Viraferon therapy, a patient develops symptoms 
consistent with possible thyroid dysfunction. In the presence of thyroid dysfunction, Viraferon treatment may 
be continued if TSH levels can be maintained in the normal range by medication. Discontinuation of 
Viraferon therapy has not reversed thyroid dysfunction occurring during treatment (also see Children and 
adolescents, Thyroid monitoring). 



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Supplemental monitoring specific for children and adolescents 
Thyroid Monitoring: Approximately 12 % of children treated with interferon alfa-2b and ribavirin developed 
increase in TSH. Another 4 % had a transient decrease below the lower limit of normal. Prior to initiation of 
Viraferon therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be 
treated with conventional therapy. Viraferon therapy may be initiated if TSH levels can be maintained in the 
normal range by medication. Thyroid dysfunction during treatment with interferon alfa-2b and ribavirin has 
been observed. If thyroid abnormalities are detected, the patient’s thyroid status should be evaluated and 
treated as clinically appropriate. Children and adolescents should be monitored every 3 months for evidence 
of thyroid dysfunction (e.g. TSH). 
 
Growth and Development: During a 1-year course of therapy there was a decrease in the rate of linear growth 
(mean percentile decrease of 9 %) and a decrease in the rate of weight gain (mean percentile decrease of 
13 %). A general reversal of these trends was noted during the 6 months follow-up post treatment. However, 
based on interim data from a long-term follow-up study, 12 (14 %) of 84 children had a > 15 percentile 
decrease in rate of linear growth, of whom 5 (6 %) children had a > 30 percentile decrease despite being off 
treatment for more than 1 year. In addition, preclicinal juvenile toxicity results have demonstrated a minor, 
dose-related decrease in overall growth in neonatal rats dosed with ribavirin (see section 5.3). Therefore, the 
risk/benefit of the combined use of interferon alfa-2b and ribavirin should be assessed in young children prior 
to the initiation of therapy. Physicians are advised to monitor the growth of children taking ribavirin in 
combination with interferon alfa-2b. There are no data on long term effects on growth and development and 
on sexual maturation. 
 
HCV/HIV Coinfection: Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy 
(HAART) may be at increased risk of developing lactic acidosis. Caution should be used when adding Viraferon 
and ribavirin to HAART therapy (see ribavirin SPC). Patients treated with Viraferon and ribavirin combination 
therapy and zidovudine could be at increased risk of developing anaemia. 
Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic 
decompensation and death. Adding treatment with alfa interferons alone or in combination with ribavirin may 
increase the risk in this patient subset.  
 
Dental and periodontal disorders: Dental and periodontal disorders, which may lead to loss of teeth, have 
been reported in patients receiving Viraferon and ribavirin combination therapy. In addition, dry mouth could 
have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the 
combination of Viraferon and ribavirin. Patients should brush their teeth thoroughly twice daily and have 
regular dental examinations. In addition some patients may experience vomiting. If this reaction occurs, they 
should be advised to rinse out their mouth thoroughly afterwards. 
 
Laboratory Tests:  
Standard haematological tests and blood chemistries (complete blood count and differential, platelet count, 
electrolytes, liver enzymes, serum protein, serum bilirubin and serum creatinine) are to be conducted in all 
patients prior to and periodically during systemic treatment with Viraferon. 
 
During treatment for hepatitis B or C the recommended testing schedule is at weeks 1, 2, 4, 8, 12, 16, and 
every other month, thereafter, throughout treatment. If ALT flares during Viraferon therapy to greater than or 
equal to 2 times baseline, Viraferon therapy may be continued unless signs and symptoms of liver failure are 
observed. During ALT flare, liver function tests: ALT, prothrombin time, alkaline phosphatase, albumin and 
bilirubin must be monitored at two-week intervals. 
 
Effect on fertility: Interferon may impair fertility (see section 4.6 and section 5.3). 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with 
Viraferon. 



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Interactions between Viraferon and other medicinal products have not been fully evaluated. Caution must be 
exercised when administering Viraferon in combination with other potentially myelosuppressive agents. 
 
Interferons may affect the oxidative metabolic process. This must be considered during concomitant therapy 
with medicinal products metabolised by this route, such as the xanthine derivatives theophylline or 
aminophylline. During concomitant therapy with xanthine agents, serum theophylline levels must be 
monitored and dosage adjusted if necessary. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.4). 
 
(Also see ribavirin SPC if Viraferon is to be administered in combination with ribavirin in patients with 
chronic hepatitis C). 
 
4.6 Pregnancy and lactation 
 
Women of childbearing potential have to use effective contraception during treatment. Viraferon must be 
used with caution in fertile men. Decreased serum estradiol and progesterone concentrations have been 
reported in women treated with human leukocyte interferon. 
 
There are no adequate data from the use of interferon alfa-2b in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Viraferon is to be 
used during pregnancy only if the potential benefit justifies the potential risk to the foetus. 
 
It is not known whether the components of this medicinal product are excreted in human milk. Because of the 
potential for adverse reactions in nursing infants, nursing should be discontinued prior to initiation of 
treatment. 
 
Combination therapy with ribavirin: Ribavirin causes serious birth defects when administered during 
pregnancy. Ribavirin therapy is contraindicated in women who are pregnant. Extreme care must be taken to 
avoid pregnancy in female patients or in partners of male patients taking Viraferon in combination with 
ribavirin. Females of childbearing potential and their partners must each use an effective contraceptive during 
treatment and for 4 months after treatment has been concluded. Male patients and their female partners must 
each use an effective contraceptive during treatment and for 7 months after treatment has been concluded (see 
ribavirin SPC). 
 
4.7 Effects on ability to drive and use machines 
 
Patients are to be advised that they may develop fatigue, somnolence, or confusion during treatment with 
Viraferon, and therefore it is recommended that they avoid driving or operating machinery. 
 
4.8 Undesirable effects 
 
See ribavirin SPC for ribavirin-related undesirable effects if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
In clinical trials conducted in a broad range of indications and at a wide range of doses (from 6 MIU/m2/week 
in hairy cell leukaemia up to 100 MIU/m2/week in melanoma), the most commonly reported undesirable 
effects were fever, fatigue, headache and myalgia. Fever and fatigue were often reversible within 72 hours of 
interruption or cessation of treatment. 
 



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In clinical trials conducted in the hepatitis C population, patients were treated with Viraferon alone or in 
combination with ribavirin for one year. All patients in these trials received 3 MIU of Viraferon three times a 
week. In Table 1 the frequency of patients reporting (treatment related) undesirable effects is presented from 
clinical trials in naïve patients treated for one year. Severity was generally mild to moderate. The adverse 
reactions listed in Table 1 are based on experience from clinical trials and post-marketing. Within the organ 
system classes, adverse reactions are listed under headings of frequency using the following categories: very 
common (≥1/10); common (≥1/100, <1/10); rarely (≥1/10,000, <1/1,000); very rarely (<1/10,000); not 
known. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 
 

Table 1. Adverse reactions reported during clinical trials or following the marketing use of Viraferon 
alone or in combination with ribavirin 

System Organ Class Adverse Reactions 
Infections and infestations 
Very common: 
Common: 
Rarely:  

 
Pharyngitis*, infection viral* 
Bronchitis, sinusitis, herpes simplex (resistance), rhinitis 
Pneumonia§ 

Blood and lymphatic system disorders 
Very common: 
Common: 
Very rarely:  
Not known:  

 
Leukopaenia 
Thrombocytopaenia, lymphadenopathy, lymphopenia 
Aplastic anaemia 
Pure red cell aplasia, idiopathic thrombocytopenic purpura, 
thrombotic thrombocytopenic purpura  

Immune system disorders§ 
Very rarely:  
Not known: 

 
Sarcoidosis, exacerbation of sarcoidosis 
Systemic lupus erythematosus, vasculitis, rheumatoid 
arthritis (new or aggravated), Vogt-Koyanagi-Harada 
syndrome, acute hypersensitivity reactions including 
urticaria, angioedema, bronchoconstriction, anaphylaxis§ 

Endocrine disorders 
Common: 
Very rarely:  

 
Hypothyroidism§, hyperthyroidism§ 
Diabetes, aggravated diabetes 

Metabolism and nutrition disorders 
Very common: 
Common:  
Very rarely:  

 
Anorexia 
Hypocalcaemia, dehydration, hyperuricemia, thirst 
Hyperglycaemia, hypertriglyceridaemia§, increased appetite 

Psychiatric disorders§ 
Very common: 
 
Common: 
Rarely:  
Very rarely: 
 
Not known: 

 
Depression, insomnia, anxiety, emotional lability*, 
agitation, nervousness 
Confusion, sleep disorder, libido decreased 
Suicide ideation 
Suicide, suicide attempts, aggressive behaviour (sometimes 
directed against others), psychosis including hallucinations 
Mental status change§ 

Nervous system disorders§ 
Very common: 
Common: 
 
Very rarely:  
 
 
Not known: 

 
Dizziness, headache, concentration impaired, mouth dry 
Tremor, paresthesia, hypoesthesia, migraine, flushing, 
somnolence, taste perversion 
Cerebrovascular haemorrhage, cerbrovascular ischaemia, 
seizure, impaired consciousness, encephalopathy, 
neuropathy, polyneuropathy 
Mononeuropathies, coma§ 

Eye disorders 
Very common: 

 
Vision blurred 



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Common: 
 
Rarely:  

Conjunctivitis, vision abnormal, lacrimal gland disorder, eye 
pain 
Retinal haemorrhages§, retinopathies (including macular 
oedema), retinal artery or vein obstruction§, optic neuritis, 
papilloedema, loss of visual acuity or visual field, cotton-
wool spots§  

Ear and labyrinth 
Common: 
Very rarely:  

 
Vertigo, tinnitus 
Hearing loss, hearing disorder 

Cardiac disorders 
Common: 
Rarely: 
Very rarely: 
Not known: 

 
Palpitation, tachycardia 
Cardiomyopathy 
Myocardial infarction, cardiac ischaemia  
Arrhythmia  

Vascular disorders 
Common: 
Very rarely:  

 
Hypertension 
Peripheral ischaemia, hypotension§ 

Respiratory, thoracic and mediastinal 
disorders 
Very common: 
Common: 
 
Very rarely:  

 
 
Dyspnoea*, coughing* 
Epistaxis, respiratory disorder, nasal congestion, rhinorrhea, 
cough nonproductive 
Pulmonary infiltrates§, pneumonitis§ 

Gastrointestinal disorders 
Very common: 
 
Common: 
 
Very rarely:  
 
Not known: 

 
Nausea/vomiting, abdominal pain, diarrhoea, stomatitis, 
dyspepsia 
Stomatitis ulcerative, right upper quadrant pain, glossitis, 
gingivitis, constipation, loose stools 
Pancreatitis, ischaemic colitis, ulcerative colitis, gingival 
bleeding 
Periodontal disorder NOS, dental disorder NOS§ 

Hepatobiliary disorders 
Common: 
Very rarely:  

 
Hepatomegaly 
Hepatotoxicity, (including fatality) 

Skin and subcutaneous tissue disorders 
Very common: 
Common: 
 
Very rarely:  

 
Alopecia, pruritus*, skin dry*, rash*, sweating increased 
Psoriasis (new or aggravated)§, rash maculopapular, rash 
erythematous, eczema, erythema, skin disorder 
Stevens Johnson syndrome, toxic epidermal necrolysis, 
erythema multiforme 

Musculoskeletal and connective tissue 
disorders 
Very common:  
Common: 
Very rarely: 

 
 
Myalgia, arthralgia, musculoskeletal pain 
Arthritis 
Rhabdomyolysis, myositis, leg cramps, back pain 

Renal and urinary disorders 
Common: 
Very rarely:  

 
Micturition frequency 
Renal failure, renal insufficiency, nephrotic syndrome 

Reproductive system and breast 
disorders 
Common: 

 
 
Amenorrhea, breast pain, dysmenorrhea, menorrhagia, 
menstrual disorder, vaginal disorder 

General disorders and administration 
site conditions 

 
 



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Very common: 
 
 
Common: 
Very rarely: 

Injection site inflammation, injection site reaction*, fatigue, 
rigors, fever§, flu-like symptoms§, asthenia, irritability, chest 
pain, malaise 
Injection site pain 
Injection site necrosis, face oedema 

Investigations 
Very common: 

 
Weight decrease 

*These events were only common with Viraferon alone 
§See section 4.4 
 
These undesirable effects have also been reported with Viraferon alone. 
 
Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-
existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4). Cardiomyopathy, that may 
be reversible upon discontinuation of interferon alpha, has been reported rarely in patients without prior 
evidence of cardiac disease (see section 4.4).  
 
A wide variety of autoimmune and immune-mediated disorders have been reported with alpha interferons 
including thyroid disorders, systemic lupus erythematosus, rheumatoid arthritis (new or aggravated), 
idiopathic and thrombotic thrombocytopenic purpura, vasculitis, neuropathies including mononeuropathies 
(see also section 4.4).  
 
Clinically significant laboratory abnormalities, most frequently occurring at doses greater than 10 million IU 
daily, include reduction in granulocyte and white blood cell counts; decreases in haemoglobin level and 
platelet count; increases in alkaline phosphatase, LDH, serum creatinine and serum urea nitrogen levels. 
Increase in serum ALT/AST (SGPT/SGOT) levels have been noted as an abnormality in some non-hepatitis 
subjects and also in some patients with chronic hepatitis B coincident with clearance of viral DNAp. 
 
Paediatric population 
 
Children and adolescents – Chronic Hepatitis C 
In clinical trials of 118 children or adolescents 3 to 16 years of age, 6 % discontinued therapy due to adverse 
events. In general, the adverse event profile in the limited paediatric population studied was similar to that 
observed in adults, although there is a paediatric specific concern regarding growth inhibition as decrease in 
height (mean percentile decrease of growth velocity of 9 %) and weight (mean percentile decrease of 13 %) 
percentile were observed during treatment (see section 4.4). Furthermore, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6 month 
follow-up after treatment. As in adult patients, children and adolescents also experienced other psychiatric 
adverse events (e.g., depression, emotional lability, and somnolence) (see section 4.4). In addition, injection 
site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in children and 
adolescents compared to adult patients. Dose modifications were required in 30 % of patients, most 
commonly for anaemia and neutropaenia. 
 
The adverse reactions listed in Table 2 are based on experience from paediatric clinical trials.  
Within the organ system classes, adverse reactions are listed under headings of frequency using the following 
categories: very common (≥1/10); common (≥1/100, <1/10). Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness. 
 
Table 2  Adverse reactions very commonly and commonly reported in paediatric clinical trials  

Very common (≥1/10) - Common (≥1/100, <1/10) 
System Organ Class Adverse Reactions 
Infection and infestations 
Very common: 
Common: 

 
Viral infection, pharyngitis 
Fungal infection, bacterial infection, pulmonary infection, otitis 



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media, tooth abscess, herpes simplex, urinary tract infection, 
vaginitis, gastroenteritis 

Neoplasms benign, malignant 
and unspecified (including 
cysts and polyps) 
Common: 

 
 
 
Neoplasm (unspecified) 

Blood and lymphatic system 
disorders 
Very common: 
Common: 

 
 
Anaemia, neutropaenia 
Thrombocytopaenia, lymphadenopathy 

Endocrine disorders 
Very common: 
Common: 

 
Hypothyroidism§,  
Hyperthyroidism§, virilism 

Metabolism and nutrition 
disorders 
Very common: 
Common: 

 
 
Anorexia 
Hypertriglyceridemia§, hyperuricemia, increased appetite 

Psychiatric disorders§ 
Very common: 
Common: 

 
Depression, emotional lability, insomnia 
Suicidal ideation, aggressive reaction, confusion, behaviour 
disorder, agitation, somnambulism, anxiety, nervousness, sleep 
disorder, abnormal dreaming, apathy 

Nervous system disorders§ 
Very common: 
Common: 

 
Headache, dizziness 
Hyperkinesia, tremor, dysphonia, paresthaesia, hypoaesthesia, 
hyperaesthesia, concentration impaired, somnolence 

Eye disorders 
Common: 

 
Conjunctivitis, eye pain, abnormal vision, lacrimal gland disorder 

Vascular disorders 
Common: 

 
Raynaud’s disease, flushing, pallor 

Respiratory, thoracic and 
mediastinal disorders 
Common: 

 
 
Dyspnoea, tachypnea, epistaxis, coughing, nasal congestion, nasal 
irritation, rhinorrhea, sneezing 

Gastrointestinal disorders 
Very common: 
Common: 

 
Diarrhoea, vomiting, nausea, abdominal pain 
Mouth ulceration, stomatitis ulcerative, stomatitis, right upper 
quadrant pain, dyspepsia, glossitis, gastroesophogeal reflux, rectal 
disorder, gastrointestinal disorder, constipation, loose stools, 
toothache, tooth disorder 

Hepatobiliary disorders 
Common: 

 
Hepatic function abnormal 

Skin and subcutaneous tissue 
disorders  
Very common: 
Common: 

 
 
Alopecia, rash 
Photosensitivity reaction, maculopapular rash, eczema, acne, skin 
disorder, nail disorder, skin discolouration, pruritus, dry skin, 
erythema, bruise, sweating increased 

Musculoskeletal and 
connective tissue disorders 
Very common: 

 
 
Arthralgia, myalgia, musculoskeletal pain  

Renal and urinary disorders 
Common: 

 
Enuresis, micturition disorder, urinary incontinence 

Reproductive system and  



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breast disorders 
Common: 

 
Female: amenorrhea, menorrhagia, menstrual disorder, vaginal 
disorder 
Male: testicular pain 

General disorders and 
administration site 
conditions 
Very common: 
 
Common: 

 
 
 
Injection site inflammation, injection site reaction, fatigue, rigors, 
fever§, influenza-like symptoms§, malaise, irritability 
Chest pain, asthenia, oedema, injection site pain 

Investigations 
Very common: 

 
Growth rate decrease (height and/or weight decrease for age)§  

Injury and poisoning 
Common: 

 
Skin laceration 

§See section 4.4 
 
4.9 Overdose 
 
No case of overdose has been reported that has led to acute clinical manifestations. However, as for any 
pharmacologically active compound, symptomatic treatment with frequent monitoring of vital signs and close 
observation of the patient is indicated. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunostimulants, cytokines and immunomodulators, interferons, interferon 
alfa-2b, ATC code: L03A B05 
 
Viraferon is a sterile, stable, formulation of highly purified interferon alfa-2b produced by recombinant DNA 
techniques. Recombinant interferon alfa-2b is a water-soluble protein with a molecular weight of 
approximately 19,300 daltons. It is obtained from a clone of E. coli, which harbours a genetically engineered 
plasmid hybrid encompassing an interferon alfa-2b gene from human leukocytes. 
 
The activity of Viraferon is expressed in terms of IU, with 1 mg of recombinant interferon alfa-2b protein 
corresponding to 2.6 x l08 IU. International Units are determined by comparison of the activity of the 
recombinant interferon alfa-2b with the activity of the international reference preparation of human leukocyte 
interferon established by the World Health Organisation. 
 
The interferons are a family of small protein molecules with molecular weights of approximately 15,000 to 
21,000 daltons. They are produced and secreted by cells in response to viral infections or various synthetic 
and biological inducers. Three major classes of interferons have been identified: alpha, beta and gamma. 
These three main classes are themselves not homogeneous and may contain several different molecular 
species of interferon. More than 14 genetically distinct human alpha interferons have been identified. 
Viraferon has been classified as recombinant interferon alfa-2b. 
 
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. 
Human interferon receptors, as isolated from human lymphoblastoid (Daudi) cells, appear to be highly 
asymmetric proteins. They exhibit selectivity for human but not murine interferons, suggesting species 
specificity. Studies with other interferons have demonstrated species specificity. However, certain monkey 
species, eg, rhesus monkeys, are susceptible to pharmacodynamic stimulation upon exposure to human type 
1 interferons. 
 



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The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex 
sequence of intracellular events that include the induction of certain enzymes. It is thought that this process, 
at least in part, is responsible for the various cellular responses to interferon, including inhibition of virus 
replication in virus-infected cells, suppression of cell proliferation and such immunomodulating activities as 
enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of 
lymphocytes for target cells. Any or all of these activities may contribute to interferon's therapeutic effects. 
 
Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and 
human cell culture systems as well as human tumour xenografts in animals. It has demonstrated significant 
immunomodulatory activity in vitro. 
 
Recombinant interferon alfa-2b also inhibits viral replication in vitro and in vivo. Although the exact antiviral 
mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism. 
This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell. 
 
Chronic hepatitis B: 
Current clinical experience in patients who remain on interferon alfa-2b for 4 to 6 months indicates that 
therapy can produce clearance of serum HBV-DNA. An improvement in liver histology has been observed. 
In adult patients with loss of HBeAg and HBV-DNA, a significant reduction in morbidity and mortality has 
been observed. 
 
Interferon alfa-2b (6 MIU/m2 3 times a week for 6 months) has been given to children with chronic active 
hepatitis B. Because of a methodological flaw, efficacy could not be demonstrated. Moreover children treated 
with interferon alfa-2b experienced a reduced rate of growth and some cases of depression were observed. 
 
Chronic hepatitis C: 
In adult patients receiving interferon in combination with ribavirin, the achieved sustained response rate is 
47 %. Superior efficacy has been demonstrated with the combination of pegylated interferon with ribavirin 
(sustained response rate of 61 % achieved in a study performed in naïve patients with a ribavirin dose 
> 10.6 mg/kg, p < 0.01). 
 
Adult patients: Viraferon alone or in combination with ribavirin has been studied in 4 randomised Phase III 
clinical trials in 2,552 interferon-naïve patients with chronic hepatitis C. The trials compared the efficacy of 
Viraferon used alone or in combination with ribavirin. Efficacy was defined as sustained virologic response, 
6 months after the end of treatment. Eligible patients for these trials had chronic hepatitis C confirmed by a 
positive HCV-RNA polymerase chain reaction assay (PCR) (> 100 copies/ml), a liver biopsy consistent with 
a histologic diagnosis of chronic hepatitis with no other cause for the chronic hepatitis, and abnormal serum 
ALT. 
 
Viraferon was administered at a dose of 3 MIU 3 times a week as monotherapy or in combination with 
ribavirin. The majority of patients in these clinical trials were treated for one year. All patients were followed 
for an additional 6 months after the end of treatment for the determination of sustained virologic response. 
Sustained virologic response rates for treatment groups treated for one year with Viraferon alone or in 
combination with ribavirin (from two studies) are shown in Table 3. 
 
Co-administration of Viraferon with ribavirin increased the efficacy of Viraferon by at least two fold for the 
treatment of chronic heptatitis C in naïve patients. HCV genotype and baseline virus load are prognostic 
factors which are known to affect response rates. The increased response rate to the combination of Viraferon + 
ribavirin, compared with Viraferon alone, is maintained across all subgroups. The relative benefit of combination 
therapy with Viraferon + ribavirin is particularly significant in the most difficult to treat subgroup of patients 
(genotype 1 and high virus load) (Table 3). 
 
Response rates in these trials were increased with compliance. Regardless of genotype, patients who received 
Viraferon in combination with ribavirin and received ≥ 80 % of their treatment had a higher sustained 



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response 6 months after 1 year of treatment than those who took < 80 % of their treatment (56 % vs. 32 % in 
trial C/I98-580).  
 

Table 3 Sustained virologic response rates with Viraferon + ribavirin (one year of 
treatment) by genotype and viral load 

 
HCV Genotype  
 

I 
N=503 

C95-132/I95-143 

I/R 
N=505 

C95-132/I95-143 

I/R 
N=505 

C/I98-580 
 
All Genotypes 

 
16 % 

 
41 % 

 
47 % 

 
 
Genotype 1 

 
9 % 

 
29 % 

 
33 % 

 
Genotype 1  
≤ 2 million 
copies/ml 

 
25 % 

 
33 % 

 
45 % 

 
Genotype 1 
> 2 million 
copies/ml 

 
3 % 

 
27 % 

 

 
29 % 

 
Genotype 2/3 

 
31 % 

 
65 % 

 
79 % 

I Viraferon (3 MIU 3 times a week) 
I/R Viraferon (3 MIU 3 times a week) + ribavirin (1,000/1,200 mg/day) 
 
HCV/HIV Co-infected patients  
Two trials have been conducted in patients co-infected with HIV and HCV. Overall, in both studies, patients 
who received Viraferon plus ribavirin, were less likely to respond than patients who received pegylated 
interferon alfa-2b with ribavirin. The response to treatment in both of these trials is presented in Table 4. 
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 412 previously untreated 
adult patients with chronic hepatitis C who were co-infected with HIV. Patients were randomized to receive 
either pegylated interferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800 mg/day) or Viraferon (3 MIU TIW) 
plus ribavirin (800 mg/day) for 48 weeks with a follow-up period of 6 months. Study 2 (P02080) was a 
randomized, single centre study that enrolled 95 previously untreated adult patients with chronic hepatitis C 
who were co-infected with HIV. Patients were randomized to receive either pegylated interferon alfa-2b (100 
or 150 µg /week based on weight) plus ribavirin (800-1,200 mg/day based on weight) or Viraferon (3 MIU 
TIW) plus ribavirin (800-1,200 mg/day based on weight). The duration of therapy was 48 weeks with a 
follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load 
< 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6-month follow-up period.  
           
Table 4 Sustained virological response based on genotype after Viraferon in combination with 

ribavirin versus pegylated interferon alfa-2b in combination with ribavirin in 
HCV/HIV co-infected patients 

 Study 11 Study 22 
 

pegylated 
interferon 

alfa-2b  
(1.5 µg/kg/ 

week) + 
ribavirin  
(800 mg) 

Viraferon  
(3 MIU TIW) +  

ribavirin  
(800 mg) 

p 
valuea 

pegylated 
interferon 

alfa-2b (100 
or  

150c µg/week) 
+ ribavirin 

(800- 
1,200 mg)d 

Viraferon  
(3 MIU TIW) 

+ ribavirin 
(800- 

1,200 mg)d 
p 

valueb 



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All 27 % (56/205) 20 % (41/205) 0.047 44 % (23/52) 21 % (9/43) 0.017 
Genotype 1, 

4 
17 % (21/125) 6 % (8/129) 0.006 38 % (12/32) 7 % (2/27) 0.007 

Genotype 2, 
3 

44 % (35/80) 43 % (33/76) 0.88 53 % (10/19) 47 % (7/15) 0.730 

MIU = million international units; TIW = three times a week. 
a:  p value based on Cochran-Mantel Haenszel Chi square test. 
b:  p value based on chi-square test. 
c:  subjects < 75 kg received 100 µg/week pegylated interferon alfa-2b and subjects ≥ 75 kg received 150 µg/week pegylated 

interferon alfa-2b. 
d: ribavirin dosing was 800 mg for patients < 60 kg, 1,000 mg for patients 60-75 kg, and 1,200 mg for patients > 75 kg. 
 

1Carrat F, Bani-Sadr F, Pol S et al.  JAMA 2004; 292(23): 2839-2848. 
2 Laguno M, Murillas J, Blanco J.L et al.  AIDS 2004; 18(13): F27-F36. 
 
 
Relapse patients: A total of 345 interferon alpha relapse patients were treated in two clinical trials with 
Viraferon monotherapy or in combination with ribavirin. In these patients, the addition of ribavirin to 
Viraferon increased by as much as 10-fold the efficacy of Viraferon used alone in the treatment of chronic 
hepatitis C (48.6 % vs. 4.7 %). This enhancement in efficacy included loss of serum HCV (< 100 copies/ml 
by PCR), improvement in hepatic inflammation, and normalisation of ALT, and was sustained when 
measured 6 months after the end of treatment. 
 
Long-Term efficacy data 
In a large study, 1,071 patients were enrolled after treatment in a prior non pegylated interferon alfa-2b or 
non pegylated interferon alfa-2b/ribavirin study to evaluate the durability of sustained virologic response and 
assess the impact of continued viral negativity on clinical outcomes. 462 patients completed at least 5 years 
of long-term follow-up and only 12 sustained responders' out of 492 relapsed during this study.  
The Kaplan-Meier estimate for continued sustained response over 5 years for all patients is 97 % with a 95 % 
Confidence Interval of [95 %, 99 %].  
SVR after treatment of chronic HCV with non pegylated interferon alfa-2b (with or without ribavirin) results 
in long-term clearance of the virus providing resolution of the hepatic infection and clinical 'cure' from 
chronic HCV. However, this does not preclude the occurrence of hepatic events in patients with cirrhosis 
(including hepatocarcinoma). 
 
Clinical trials in paediatric patients with chronic hepatitis C: 
Children and adolescents 3 to 16 years of age with compensated chronic hepatitis C and detectable HCV-
RNA (assessed by a central laboratory using a research-based RT-PCR assay) were enrolled in two 
multicentre trials and received Viraferon 3 MIU/m2 3 times a week plus ribavirin 15 mg/kg per day for 1 year 
followed by 6 months follow-up after-treatment. A total of 118 patients were enrolled: 57 % male, 80 % 
Caucasian, and 78 % genotype 1,64 % ≤ 12 years of age. The population enrolled mainly consisted in 
children with mild to moderate hepatitis C. Sustained virological response rates in children and adolescents 
were similar to those in adults. Due to the lack of data in children with severe progression of the disease, and 
the potential for undesirable effects, the benefit/risk of the combination of ribavirin and interferon alfa-2b 
needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8). 
 
Study results are summarized in Table 5. 
 
Table 5. Virological response in previously untreated paediatric patients 
 Viraferon 3 MIU/m2 3 times a week   

+ 
ribavirin 15 mg/kg/day 

Overall Response1 (n=118) 54 (46 %)* 



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Genotype 1 (n=92) 33 (36 %)* 

Genotype 2/3/4 (n=26) 21 (81 %)* 

*Number (%) of patients 
1. Defined as HCV-RNA below limit of detection using a research based RT-PCR assay at end of treatment and during follow-up 
period 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of Viraferon were studied in healthy volunteers following single 5 million IU/m2 and 
10 million IU doses administered subcutaneously, at 5 million IU/m2 administered intramuscularly and as a 
30-minute intravenous infusion. The mean serum interferon concentrations following subcutaneous and 
intramuscular injections were comparable. Cmax occurred three to 12 hours after the lower dose and six to 
eight hours after the higher dose. The elimination half-lives of interferon injections were approximately two 
to three hours, and six to seven hours, respectively. Serum levels were below the detection limit 16 and 
24 hours, respectively, post-injection. Both subcutaneous and intramuscular administration resulted in 
bioavailabilities greater than 100 %. 
 
After intravenous administration, serum interferon levels peaked (135 to 273 IU/ml) by the end of the 
infusion, then declined at a slightly more rapid rate than after subcutaneous or intramuscular administration 
of medicinal product, becoming undetectable four hours after the infusion. The elimination half-life was 
approximately two hours. 
 
Urine levels of interferon were below the detection limit following each of the three routes of administration. 
 
Children and adolescents: Multiple-dose pharmacokinetic properties for Viraferon injection and ribavirin 
capsules in children and adolescents with chronic hepatitis C, between 5 and 16 years of age, are summarized 
in Table 6. The pharmacokinetics of Viraferon and ribavirin (dose-normalized) are similar in adults and 
children or adolescents. 
 

Table 6. Mean (% CV) multiple-dose pharmacokinetic parameters for Viraferon and ribavirin 
capsules when administered to children or adolescents with chronic hepatitis C 
Parameter Ribavirin 

15 mg/kg/day as 2 divided 
doses 

(n = 17) 

Viraferon 
3 MIU/m2 3 times a week 

(n = 54) 

Tmax (hr) 1.9 (83) 5.9 (36) 
Cmax (ng/ml) 3,275 (25) 51 (48) 

AUC* 29,774 (26) 622 (48) 
Apparent clearance l/hr/kg 0.27 (27) Not done 

*AUC12 (ng.hr/ml) for ribavirin; AUC0-24 (IU.hr/ml) for Viraferon 
 
Interferon neutralising factor assays were performed on serum samples of patients who received Viraferon in 
Schering-Plough monitored clinical trials. Interferon neutralising factors are antibodies which neutralise the 
antiviral activity of interferon. The clinical incidence of neutralising factors developing in cancer patients 
treated systemically is 2.9 % and in chronic hepatitis patients is 6.2 %. The detectable titres are low in almost 
all cases and have not been regularly associated with loss of response or any other autoimmune phenomenon. 
In patients with hepatitis, no loss of response was observed apparently due to the low titres. 
 
5.3 Preclinical safety data 
 
Although interferon is generally recognised as being species specific, toxicity studies in animals were 
conducted. Injections of human recombinant interferon alfa-2b for up to three months have shown no 
evidence of toxicity in mice, rats, and rabbits. Daily dosing of cynomolgus monkeys with 20 x 106 IU/kg/day 



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for 3 months caused no remarkable toxicity. Toxicity was demonstrated in monkeys given 
100 x 106 IU/kg/day for 3 months. 
 
In studies of interferon use in non-human primates, abnormalities of the menstrual cycle have been observed 
(see section 4.4). 
 
Results of animal reproduction studies indicate that recombinant interferon alfa-2b was not teratogenic in rats 
or rabbits, nor did it adversely affect pregnancy, foetal development or reproductive capacity in offspring of 
treated rats. Interferon alfa-2b has been shown to have abortifacient effects in Macaca mulatta (rhesus 
monkeys) at 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2. 
Abortion was observed in all dose groups (7.5 million, 15 million and 30 million IU/kg), and was statistically 
significant versus control at the mid- and high-dose groups (corresponding to 90 and 180 times the 
recommended intramuscular or subcutaneous dose of 2 million IU/m2). High doses of other forms of 
interferons alpha and beta are known to produce dose-related anovulatory and abortifacient effects in rhesus 
monkeys. 
 
Mutagenicity studies with interferon alfa-2b revealed no adverse events. 
 
No studies have been conducted in juvenile animals to examine the effects of treatment with interferon alfa-
2b on growth, development, sexual maturation, and behaviour (see section 4.4 and Rebetol SPC if Viraferon 
is to be administered in combination with ribavirin). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Disodium phosphate anhydrous,  
Sodium dihydrogen phosphate monohydrate,  
Edetate disodium,  
Sodium chloride,  
M-cresol,  
Polysorbate 80, 
Water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
2 years 
 
After first opening the container: Chemical and physical in-use stability has been demonstrated for 28 days at 
2ºC – 8ºC. 
From a microbiological point of view, once opened, the product may be stored for a maximum of 28 days at 
2ºC – 8ºC. Other in-use storage times and conditions are the responsibility of the user. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C).  
Do not freeze.  
Within its shelf-life, for the purpose of transport, the solution can be kept at or below 25ºC for a period up to 
seven days before use. Viraferon can be put back in the refrigerator at any time during this seven-day period. 



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If the product is not used during the seven-day period, it cannot be put back in the refrigerator for a new 
storage period and must be discarded. 
 
6.5 Nature and contents of container 
 
3 ml of solution (corresponding to 18 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in a flip-
off seal (aluminium) with a bonnet (polypropylene). 
Pack sizes of 1, 2 or 12 
 
Or 
 
3 ml of solution (corresponding to 18 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in a flip-
off seal (aluminium) with a bonnet (polypropylene) 
with 6 injection syringes, 6 injection needles and 12 cleansing swabs. 
Pack sizes of 1  
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
Viraferon solution for injection, may be injected directly after withdrawal of the appropriate doses from the 
vial with a sterile injection syringe. 
 
As with all parenteral medicinal products, prior to administration inspect Viraferon, solution for injection, 
visually for particulate matter and discolouration. The solution should be clear and colourless. 
 
Detailed instructions for the subcutaneous use of the product are provided with the package leaflet (refer to 
“How to self inject Viraferon”). 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
SP Europe 
73, rue de Stalle 
B-1180 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/99/128/021 
EU/1/99/128/022 
EU/1/99/128/023 
EU/1/99/128/024 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation : 9 March 2000 
Date of last renewal : 23 May 2005 
 
 
10. DATE OF REVISION OF THE TEXT 



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Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu/ 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 25 million IU/2.5 ml solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One vial of Viraferon solution for injection, multiple dose vial, contains 25 million IU of recombinant 
interferon alfa-2b produced in E.coli by recombinant DNA technology, in 2.5 ml of solution. 
 
One ml of solution contains 10 million IU of interferon alfa-2b. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection 
Solution is clear and colourless. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Chronic Hepatitis B: Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis B 
viral replication (presence of HBV-DNA and HBeAg), elevated alanine aminotransferase (ALT) and 
histologically proven active liver inflammation and/or fibrosis. 
 
Chronic Hepatitis C:  
Adult patients:  
Viraferon is indicated for the treatment of adult patients with chronic hepatitis C who have elevated 
transaminases without liver decompensation and who are positive for serum HCV-RNA or anti-HCV (see 
section 4.4). 
 
The best way to use Viraferon in this indication is in combination with ribavirin. 
 
Chidren and adolescents: 
Viraferon is intended for use, in a combination regimen with ribavirin, for the treatment of children and 
adolescents 3 years of age and older, who have chronic hepatitis C, not previously treated, without liver 
decompensation, and who are positive for serum HCV-RNA. The decision to treat should be made on a case 
by case basis, taking into account any evidence of disease progression such as hepatic inflammation and 
fibrosis, as well as prognostic factors for response, HCV genotype and viral load. The expected benefit of 
treatment should be weighed against the safety findings observed for paediatric subjects in the clinical trials 
(see sections 4.4, 4.8 and 5.1). 
 
4.2 Posology and method of administration 
 
Treatment must be initiated by a physician experienced in the management of the disease. 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
If adverse events develop during the course of treatment with Viraferon for any indication, modify the dosage 
or discontinue therapy temporarily until the adverse events abate. If persistent or recurrent intolerance 



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develops following adequate dosage adjustment, or disease progresses, discontinue treatment with Viraferon. 
At the discretion of the physician, the patient may self-administer the dose for maintenance dosage regimens 
administered subcutaneously. 
 
Chronic Hepatitis B: The recommended dosage is in the range 5 to 10 million IU administered 
subcutaneously three times a week (every other day) for a period of 4 to 6 months. 
 
The administered dose should be reduced by 50 % in case of occurrence of haematological disorders (white 
blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3). Treatment should be 
discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe 
thrombocytopaenia (< 70,000/mm3). 
 
For all patients, if no improvement on serum HBV-DNA is observed after 3 to 4 months of treatment (at the 
maximum tolerated dose), discontinue Viraferon therapy. 
 
Chronic Hepatitis C: Viraferon is administered subcutaneously at a dose of 3 million IU three times a week 
(every other day) to adult patients, whether administered as monotherapy or in combination with ribavirin. 
 
Children 3 years of age or older and adolescents: Interferon alfa-2b 3 MIU/m2 is administered 
subcutaneously 3 times a week (every other day) in combination with ribavirin capsules or oral solution 
administered orally in two divided doses daily with food (morning and evening).  
 
(See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination 
therapy. For paediatric patients who weigh < 47 kg or cannot swallow capsules, see ribavirin oral solution 
SPC).  
 
Relapse patients (adults): 
Viraferon is given in combination with ribavirin. 
 
Based on the results of clinical trials, in which data are available for 6 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for 6 months. 
 
Naïve patients: 
Adults: The efficacy of Viraferon is enhanced when given in combination with ribavirin. Viraferon should be 
given alone mainly in case of intolerance or contraindication to ribavirin. 
 
Viraferon in combination with ribavirin: 
Based on the results of clinical trials, in which data are available for 12 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for at least 6 months. 
 
Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit 
negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and 
high pre-treatment viral load. 
 
Other negative prognostic factors (age > 40 years, male gender, bridging fibrosis) should be taken into 
account in order to extend therapy to 12 months. 
 
During clinical trials, patients who failed to show a virologic response after 6 months of treatment (HCV-
RNA below lower limit of detection) did not become sustained virologic responders (HCV-RNA below lower 
limit of detection six months after withdrawal of treatment). 
 
Viraferon alone: 
The optimal duration of therapy with Viraferon alone is not yet fully established, but a therapy of between 
12 and 18 months is advised. 
 



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It is recommended that patients be treated with Viraferon alone for at least 3 to 4 months, at which point 
HCV-RNA status should be determined. Treatment should be continued in patients who exhibit negative 
HCV-RNA. 
 
Children and adolescents: The efficacy and safety of Viraferon in combination with ribavirin has been 
studied in children and adolescents who have not been previously treated for chronic hepatitis C.  
 
Genotype 1: The recommended duration of treatment is one year. Patients who fail to achieve virological 
response at 12 weeks are highly unlikely to become sustained virological responders (negative predictive 
value 96 %). Virological response is defined as absence of detectable HCV-RNA at Week 12. Treatment 
should be discontinued in these patients. 
Genotype 2/3: The recommended duration of treatment is 24 weeks. 
 
Virological responses after 1 year of treatment and 6 months of follow-up were 36 % for genotype 1 and 
81 % for genotype 2/3/4. 
 
Viraferon may be administered using either glass or plastic disposable injection syringes. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients. 
- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure, recent 

myocardial infarction, severe arrhythmic disorders.  
- Severe renal or hepatic dysfunction; including that caused by metastases. 
- Epilepsy and/or compromised central nervous system (CNS) function (see section 4.4). 
- Chronic hepatitis with decompensated cirrhosis of the liver. 
- Chronic hepatitis in patients who are being or have been treated recently with immunosuppressive 

agents excluding short term corticosteroid withdrawal. 
- Autoimmune hepatitis; or history of autoimmune disease; immunosuppressed transplant recipients. 
- Pre-existing thyroid disease unless it can be controlled with conventional treatment. 
 
Children and adolescents: 
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal 

ideation or suicide attempt. 
 

Combination therapy with ribavirin: Also see ribavirin SPC if interferon alfa-2b is to be administered in 
combination with ribavirin in patients with chronic hepatitis C. 
 
4.4 Special warnings and precautions for use 
 
For all patients: 
Psychiatric and central nervous system (CNS): Severe CNS effects, particularly depression, suicidal ideation 
and attempted suicide have been observed in some patients during Viraferon therapy, and even after 
treatment discontinuation mainly during the 6-month follow-up periodand in the follow-up period. Among 
children and adolescents treated with Viraferon in combination with ribavirin, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6-month 
follow-up after treatment. As in adult patients, children and adolescents experienced other psychiatric adverse 
events (e.g., depression, emotional lability, and somnolence). Other CNS effects including aggressive behaviour 
(sometimes directed against others), confusion and alterations of mental status have been observed with alpha 
interferons. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such 
symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the 
prescribing physician and the need for adequate therapeutic management should be considered. If psychiatric 
symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with 
Viraferon be discontinued, and the patient followed, with psychiatric intervention as appropriate. 
 



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Patients with existence of or history of severe psychiatric conditions: 
If a treatment with interferon alfa-2b is judged necessary in adult patients with existence or history of severe 
psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and 
therapeutic management of the psychiatric condition. The use of interferon alfa-2b in children and adolescents 
with existence of or history of severe psychiatric conditions is contraindicated (see section 4.3). 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Moderate to severe adverse experiences may require modification of the patient's dosage regimen, or in some 
cases, termination of Viraferon therapy. Any patient developing liver function abnormalities during treatment 
with Viraferon must be monitored closely and treatment discontinued if signs and symptoms progress. 
 
Hypotension may occur during Viraferon therapy or up to two days post-therapy and may require supportive 
treatment. 
 
Adequate hydration must be maintained in patients undergoing Viraferon therapy since hypotension related 
to fluid depletion has been seen in some patients. Fluid replacement may be necessary. 
 
While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, 
other causes of persistent fever must be ruled out. 
 
Viraferon must be used cautiously in patients with debilitating medical conditions, such as those with a 
history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to 
ketoacidosis. Caution must be observed also in patients with coagulation disorders (e.g., thrombophlebitis, 
pulmonary embolism) or severe myelosuppression. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.5). Any patient developing fever, cough, 
dyspnea or other respiratory symptoms must have a chest X-ray taken. If the chest X-ray shows pulmonary 
infiltrates or there is evidence of pulmonary function impairment, the patient is to be monitored closely, and, 
if appropriate, discontinue interferon alpha. While this has been reported more often in patients with chronic 
hepatitis C treated with interferon alpha, it has also been reported in patients with oncologic diseases treated 
with interferon alpha. Prompt discontinuation of interferon alpha administration and treatment with 
corticosteroids appear to be associated with resolution of pulmonary adverse events. 
 
Ocular adverse events (see section 4.8) including retinal haemorrhages, cotton wool spots, and retinal artery 
or vein obstruction have been reported in rare instance after treatment with alpha interferons. All patients 
should have a baseline eye examination. Any patient complaining of changes in visual acuity or visual fields, 
or reporting other ophthalmologic symptoms during treatment with Viraferon, must have a prompt and 
complete eye examination. Periodic visual examinations during Viraferon therapy are recommended 
particularly in patients with disorders that may be associated with retinopathy, such as diabetes mellitus or 
hypertension. Discontinuation of Viraferon should be considered in patients who develop new or worsening 
ophthalmological disorders. 
 



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More significant obtundation and coma, including cases of encephalopathy, have been observed in some 
patients, usually elderly, treated at higher doses. While these effects are generally reversible, in a few patients 
full resolution took up to three weeks. Very rarely, seizures have occurred with high doses of Viraferon. 
 
Adult patients with a history of congestive heart failure, myocardial infarction and/or previous or current 
arrhythmic disorders, who require Viraferon therapy, must be closely monitored. It is recommended that 
those patients who have pre-existing cardiac abnormalities and/or are in advanced stages of cancer have 
electrocardiograms taken prior to and during the course of treatment. Cardiac arrhythmias (primarily 
supraventricular) usually respond to conventional therapy but may require discontinuation of Viraferon 
therapy. There are no data in children or adolescents with a history of cardiac disease. 
 
Hypertriglyceridemia and aggravation of hypertriglyceridemia, sometimes severe, have been observed. 
Monitoring of lipid levels is, therefore, recommended. 
 
Due to reports of interferon alpha exacerbating pre-existing psoriatic disease and sarcoidosis, use of 
Viraferon in patients with psoriasis or sarcoidosis is recommended only if the potential benefit justifies the 
potential risk. 
 
Preliminary data indicates that interferon alpha therapy may be associated with an increased rate of kidney 
graft rejection. Liver graft rejection has also been reported. 
 
The development of auto-antibodies and autoimmune disorders has been reported during treatment with alpha 
interferons. Patients predisposed to the development of autoimmune disorders may be at increased risk. 
Patients with signs or symptoms compatible with autoimmune disorders should be evaluated carefully, and 
the benefit-risk of continued interferon therapy should be reassessed (see also section 4.4 Chronic hepatitis C, 
Monotherapy (thyroid abnormalities) and section 4.8). 
Cases of Vogt-Koyanagi-Harada (VKH) syndrome have been reported in patients with chronic hepatitis C 
treated with interferon. This syndrome is a granulomatous inflammatory disorder affecting the eyes, auditory 
system, meninges, and skin. If VKH syndrome is suspected, antiviral treatment should be withdrawn and 
corticosteroid therapy discussed (see section 4.8). 
 
Discontinue treatment with Viraferon in patients with chronic hepatitis who develop prolongation of 
coagulation markers which might indicate liver decompensation. 
 
Chronic Hepatitis C: 
Combination therapy with ribavirin: Also see ribavirin SPC if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i.e. 
patients with genotype 2 and 3), treatment may be possible without histological confirmation. Current 
treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing 
treatment. 
 
Monotherapy: Infrequently, adult patients treated for chronic hepatitis C with Viraferon developed thyroid 
abnormalities, either hypothyroidism or hyperthyroidism. In clinical trials using Viraferon therapy, 2.8 % 
patients overall developed thyroid abnormalities. The abnormalities were controlled by conventional therapy 
for thyroid dysfunction. The mechanism by which Viraferon may alter thyroid status is unknown. Prior to 
initiation of Viraferon therapy for the treatment of chronic hepatitis C, evaluate serum thyroid-stimulating 
hormone (TSH) levels. Any thyroid abnormality detected at that time must be treated with conventional 
therapy. Viraferon treatment may be initiated if TSH levels can be maintained in the normal range by 
medication. Determine TSH levels if, during the course of Viraferon therapy, a patient develops symptoms 
consistent with possible thyroid dysfunction. In the presence of thyroid dysfunction, Viraferon treatment may 
be continued if TSH levels can be maintained in the normal range by medication. Discontinuation of 
Viraferon therapy has not reversed thyroid dysfunction occurring during treatment (also see Children and 
adolescents, Thyroid monitoring). 



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Supplemental monitoring specific for children and adolescents 
Thyroid Monitoring: Approximately 12 % of children treated with interferon alfa-2b and ribavirin developed 
increase in TSH. Another 4 % had a transient decrease below the lower limit of normal. Prior to initiation of 
Viraferon therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be 
treated with conventional therapy. Viraferon therapy may be initiated if TSH levels can be maintained in the 
normal range by medication. Thyroid dysfunction during treatment with interferon alfa-2b and ribavirin has 
been observed. If thyroid abnormalities are detected, the patient’s thyroid status should be evaluated and 
treated as clinically appropriate. Children and adolescents should be monitored every 3 months for evidence 
of thyroid dysfunction (e.g. TSH). 
 
Growth and Development: During a 1-year course of therapy there was a decrease in the rate of linear growth 
(mean percentile decrease of 9 %) and a decrease in the rate of weight gain (mean percentile decrease of 
13 %). A general reversal of these trends was noted during the 6 months follow-up post treatment. However, 
based on interim data from a long-term follow-up study, 12 (14 %) of 84 children had a > 15 percentile 
decrease in rate of linear growth, of whom 5 (6 %) children had a > 30 percentile decrease despite being off 
treatment for more than 1 year. In addition, preclicinal juvenile toxicity results have demonstrated a minor, 
dose-related decrease in overall growth in neonatal rats dosed with ribavirin (see section 5.3). Therefore, the 
risk/benefit of the combined use of interferon alfa-2b and ribavirin should be assessed in young children prior 
to the initiation of therapy. Physicians are advised to monitor the growth of children taking ribavirin in 
combination with interferon alfa-2b. There are no data on long term effects on growth and development and 
on sexual maturation. 
 
HCV/HIV Coinfection: Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy 
(HAART) may be at increased risk of developing lactic acidosis. Caution should be used when adding Viraferon 
and ribavirin to HAART therapy (see ribavirin SPC). Patients treated with Viraferon and ribavirin combination 
therapy and zidovudine could be at increased risk of developing anaemia. 
Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic 
decompensation and death. Adding treatment with alfa interferons alone or in combination with ribavirin may 
increase the risk in this patient subset.  
 
Dental and periodontal disorders: Dental and periodontal disorders, which may lead to loss of teeth, have 
been reported in patients receiving Viraferon and ribavirin combination therapy. In addition, dry mouth could 
have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the 
combination of Viraferon and ribavirin. Patients should brush their teeth thoroughly twice daily and have 
regular dental examinations. In addition some patients may experience vomiting. If this reaction occurs, they 
should be advised to rinse out their mouth thoroughly afterwards. 
 
Laboratory Tests:  
Standard haematological tests and blood chemistries (complete blood count and differential, platelet count, 
electrolytes, liver enzymes, serum protein, serum bilirubin and serum creatinine) are to be conducted in all 
patients prior to and periodically during systemic treatment with Viraferon. 
 
During treatment for hepatitis B or C the recommended testing schedule is at weeks 1, 2, 4, 8, 12, 16, and 
every other month, thereafter, throughout treatment. If ALT flares during Viraferon therapy to greater than or 
equal to 2 times baseline, Viraferon therapy may be continued unless signs and symptoms of liver failure are 
observed. During ALT flare, liver function tests: ALT, prothrombin time, alkaline phosphatase, albumin and 
bilirubin must be monitored at two-week intervals. 
 
Effect on fertility: Interferon may impair fertility (see section 4.6 and section 5.3). 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with 
Viraferon. 



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Interactions between Viraferon and other medicinal products have not been fully evaluated. Caution must be 
exercised when administering Viraferon in combination with other potentially myelosuppressive agents. 
 
Interferons may affect the oxidative metabolic process. This must be considered during concomitant therapy 
with medicinal products metabolised by this route, such as the xanthine derivatives theophylline or 
aminophylline. During concomitant therapy with xanthine agents, serum theophylline levels must be 
monitored and dosage adjusted if necessary. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.4). 
 
(Also see ribavirin SPC if Viraferon is to be administered in combination with ribavirin in patients with 
chronic hepatitis C). 
 
4.6 Pregnancy and lactation 
 
Women of childbearing potential have to use effective contraception during treatment. Viraferon must be 
used with caution in fertile men. Decreased serum estradiol and progesterone concentrations have been 
reported in women treated with human leukocyte interferon. 
 
There are no adequate data from the use of interferon alfa-2b in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Viraferon is to be 
used during pregnancy only if the potential benefit justifies the potential risk to the foetus. 
 
It is not known whether the components of this medicinal product are excreted in human milk. Because of the 
potential for adverse reactions in nursing infants, nursing should be discontinued prior to initiation of 
treatment. 
 
Combination therapy with ribavirin: Ribavirin causes serious birth defects when administered during 
pregnancy. Ribavirin therapy is contraindicated in women who are pregnant. Extreme care must be taken to 
avoid pregnancy in female patients or in partners of male patients taking Viraferon in combination with 
ribavirin. Females of childbearing potential and their partners must each use an effective contraceptive during 
treatment and for 4 months after treatment has been concluded. Male patients and their female partners must 
each use an effective contraceptive during treatment and for 7 months after treatment has been concluded (see 
ribavirin SPC). 
 
4.7 Effects on ability to drive and use machines 
 
Patients are to be advised that they may develop fatigue, somnolence, or confusion during treatment with 
Viraferon, and therefore it is recommended that they avoid driving or operating machinery. 
 
4.8 Undesirable effects 
 
See ribavirin SPC for ribavirin-related undesirable effects if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
In clinical trials conducted in a broad range of indications and at a wide range of doses (from 6 MIU/m2/week 
in hairy cell leukaemia up to 100 MIU/m2/week in melanoma), the most commonly reported undesirable 
effects were fever, fatigue, headache and myalgia. Fever and fatigue were often reversible within 72 hours of 
interruption or cessation of treatment. 
 



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In clinical trials conducted in the hepatitis C population, patients were treated with Viraferon alone or in 
combination with ribavirin for one year. All patients in these trials received 3 MIU of Viraferon three times a 
week. In Table 1 the frequency of patients reporting (treatment related) undesirable effects is presented from 
clinical trials in naïve patients treated for one year. Severity was generally mild to moderate. The adverse 
reactions listed in Table 1 are based on experience from clinical trials and post-marketing. Within the organ 
system classes, adverse reactions are listed under headings of frequency using the following categories: very 
common (≥1/10); common (≥1/100, <1/10); rarely (≥1/10,000, <1/1,000); very rarely (<1/10,000); not 
known. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

Table 1. Adverse reactions reported during clinical trials or following the marketing use of Viraferon 
alone or in combination with ribavirin 

System Organ Class Adverse Reactions 
Infections and infestations 
Very common: 
Common: 
Rarely:  

 
Pharyngitis*, infection viral* 
Bronchitis, sinusitis, herpes simplex (resistance), rhinitis 
Pneumonia§ 

Blood and lymphatic system disorders 
Very common: 
Common: 
Very rarely:  
Not known:  

 
Leukopaenia 
Thrombocytopaenia, lymphadenopathy, lymphopenia 
Aplastic anaemia 
Pure red cell aplasia, idiopathic thrombocytopenic purpura, 
thrombotic thrombocytopenic purpura  

Immune system disorders§ 
Very rarely:  
Not known: 

 
Sarcoidosis, exacerbation of sarcoidosis 
Systemic lupus erythematosus, vasculitis, rheumatoid 
arthritis (new or aggravated), Vogt-Koyanagi-Harada 
syndrome, acute hypersensitivity reactions including 
urticaria, angioedema, bronchoconstriction, anaphylaxis§ 

Endocrine disorders 
Common: 
Very rarely:  

 
Hypothyroidism§, hyperthyroidism§ 
Diabetes, aggravated diabetes 

Metabolism and nutrition disorders 
Very common: 
Common:  
Very rarely:  

 
Anorexia 
Hypocalcaemia, dehydration, hyperuricemia, thirst 
Hyperglycaemia, hypertriglyceridaemia§, increased appetite 

Psychiatric disorders§ 
Very common: 
 
Common: 
Rarely:  
Very rarely: 
 
Not known: 

 
Depression, insomnia, anxiety, emotional lability*, 
agitation, nervousness 
Confusion, sleep disorder, libido decreased 
Suicide ideation 
Suicide, suicide attempts, aggressive behaviour (sometimes 
directed against others), psychosis including hallucinations 
Mental status change§ 

Nervous system disorders§ 
Very common: 
Common: 
 
Very rarely:  
 
 
Not known: 

 
Dizziness, headache, concentration impaired, mouth dry 
Tremor, paresthesia, hypoesthesia, migraine, flushing, 
somnolence, taste perversion 
Cerebrovascular haemorrhage, cerbrovascular ischaemia, 
seizure, impaired consciousness, encephalopathy, 
neuropathy, polyneuropathy 
Mononeuropathies, coma§ 

Eye disorders 
Very common: 
Common: 

 
Vision blurred 
Conjunctivitis, vision abnormal, lacrimal gland disorder, eye 



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Rarely:  

pain 
Retinal haemorrhages§, retinopathies (including macular 
oedema), retinal artery or vein obstruction§, optic neuritis, 
papilloedema, loss of visual acuity or visual field, cotton-
wool spots§  

Ear and labyrinth 
Common: 
Very rarely:  

 
Vertigo, tinnitus 
Hearing loss, hearing disorder 

Cardiac disorders 
Common: 
Rarely: 
Very rarely: 
Not known: 

 
Palpitation, tachycardia 
Cardiomyopathy 
Myocardial infarction, cardiac ischaemia  
Arrhythmia  

Vascular disorders 
Common: 
Very rarely:  

 
Hypertension 
Peripheral ischaemia, hypotension§ 

Respiratory, thoracic and mediastinal 
disorders 
Very common: 
Common: 
 
Very rarely:  

 
 
Dyspnoea*, coughing* 
Epistaxis, respiratory disorder, nasal congestion, rhinorrhea, 
cough nonproductive 
Pulmonary infiltrates§, pneumonitis§ 

Gastrointestinal disorders 
Very common: 
 
Common: 
 
Very rarely:  
 
Not known: 

 
Nausea/vomiting, abdominal pain, diarrhoea, stomatitis, 
dyspepsia 
Stomatitis ulcerative, right upper quadrant pain, glossitis, 
gingivitis, constipation, loose stools 
Pancreatitis, ischaemic colitis, ulcerative colitis, gingival 
bleeding 
Periodontal disorder NOS, dental disorder NOS§ 

Hepatobiliary disorders 
Common: 
Very rarely:  

 
Hepatomegaly 
Hepatotoxicity, (including fatality) 

Skin and subcutaneous tissue disorders 
Very common: 
Common: 
 
Very rarely:  

 
Alopecia, pruritus*, skin dry*, rash*, sweating increased 
Psoriasis (new or aggravated)§, rash maculopapular, rash 
erythematous, eczema, erythema, skin disorder 
Stevens Johnson syndrome, toxic epidermal necrolysis, 
erythema multiforme 

Musculoskeletal and connective tissue 
disorders 
Very common:  
Common: 
Very rarely: 

 
 
Myalgia, arthralgia, musculoskeletal pain 
Arthritis 
Rhabdomyolysis, myositis, leg cramps, back pain 

Renal and urinary disorders 
Common: 
Very rarely:  

 
Micturition frequency 
Renal failure, renal insufficiency, nephrotic syndrome 

Reproductive system and breast 
disorders 
Common: 

 
 
Amenorrhea, breast pain, dysmenorrhea, menorrhagia, 
menstrual disorder, vaginal disorder 

General disorders and administration 
site conditions 
Very common: 

 
 
Injection site inflammation, injection site reaction*, fatigue, 



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Common: 
Very rarely: 

rigors, fever§, flu-like symptoms§, asthenia, irritability, chest 
pain, malaise 
Injection site pain 
Injection site necrosis, face oedema 

Investigations 
Very common: 

 
Weight decrease 

*These events were only common with Viraferon alone 
§See section 4.4 
 
These undesirable effects have also been reported with Viraferon alone. 
 
Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-
existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4). Cardiomyopathy, that may 
be reversible upon discontinuation of interferon alpha, has been reported rarely in patients without prior 
evidence of cardiac disease (see section 4.4).  
 
A wide variety of autoimmune and immune-mediated disorders have been reported with alpha interferons 
including thyroid disorders, systemic lupus erythematosus, rheumatoid arthritis (new or aggravated), 
idiopathic and thrombotic thrombocytopenic purpura, vasculitis, neuropathies including mononeuropathies 
(see also section 4.4).  
 
Clinically significant laboratory abnormalities, most frequently occurring at doses greater than 10 million IU 
daily, include reduction in granulocyte and white blood cell counts; decreases in haemoglobin level and 
platelet count; increases in alkaline phosphatase, LDH, serum creatinine and serum urea nitrogen levels. 
Increase in serum ALT/AST (SGPT/SGOT) levels have been noted as an abnormality in some non-hepatitis 
subjects and also in some patients with chronic hepatitis B coincident with clearance of viral DNAp. 
 
Paediatric population 
 
Children and adolescents – Chronic Hepatitis C 
In clinical trials of 118 children or adolescents 3 to 16 years of age, 6 % discontinued therapy due to adverse 
events. In general, the adverse event profile in the limited paediatric population studied was similar to that 
observed in adults, although there is a paediatric specific concern regarding growth inhibition as decrease in 
height (mean percentile decrease of growth velocity of 9 %) and weight (mean percentile decrease of 13 %) 
percentile were observed during treatment (see section 4.4). Furthermore, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6 month 
follow-up after treatment. As in adult patients, children and adolescents also experienced other psychiatric 
adverse events (e.g., depression, emotional lability, and somnolence) (see section 4.4). In addition, injection 
site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in children and 
adolescents compared to adult patients. Dose modifications were required in 30 % of patients, most 
commonly for anaemia and neutropaenia. 
 
The adverse reactions listed in Table 2 are based on experience from paediatric clinical trials.  
Within the organ system classes, adverse reactions are listed under headings of frequency using the following 
categories: very common (≥1/10); common (≥1/100, <1/10). Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness. 
 
Table 2  Adverse reactions very commonly and commonly reported in paediatric clinical trials  

Very common (≥1/10) - Common (≥1/100, <1/10) 
System Organ Class Adverse Reactions 
Infection and infestations 
Very common: 
Common: 

 
Viral infection, pharyngitis 
Fungal infection, bacterial infection, pulmonary infection, otitis 
media, tooth abscess, herpes simplex, urinary tract infection, 



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vaginitis, gastroenteritis 
Neoplasms benign, malignant 
and unspecified (including 
cysts and polyps) 
Common: 

 
 
 
Neoplasm (unspecified) 

Blood and lymphatic system 
disorders 
Very common: 
Common: 

 
 
Anaemia, neutropaenia 
Thrombocytopaenia, lymphadenopathy 

Endocrine disorders 
Very common: 
Common: 

 
Hypothyroidism§,  
Hyperthyroidism§, virilism 

Metabolism and nutrition 
disorders 
Very common: 
Common: 

 
 
Anorexia 
Hypertriglyceridemia§, hyperuricemia, increased appetite 

Psychiatric disorders§ 
Very common: 
Common: 

 
Depression, emotional lability, insomnia 
Suicidal ideation, aggressive reaction, confusion, behaviour 
disorder, agitation, somnambulism, anxiety, nervousness, sleep 
disorder, abnormal dreaming, apathy 

Nervous system disorders§ 
Very common: 
Common: 

 
Headache, dizziness 
Hyperkinesia, tremor, dysphonia, paresthaesia, hypoaesthesia, 
hyperaesthesia, concentration impaired, somnolence 

Eye disorders 
Common: 

 
Conjunctivitis, eye pain, abnormal vision, lacrimal gland disorder 

Vascular disorders 
Common: 

 
Raynaud’s disease, flushing, pallor 

Respiratory, thoracic and 
mediastinal disorders 
Common: 

 
 
Dyspnoea, tachypnea, epistaxis, coughing, nasal congestion, nasal 
irritation, rhinorrhea, sneezing 

Gastrointestinal disorders 
Very common: 
Common: 

 
Diarrhoea, vomiting, nausea, abdominal pain 
Mouth ulceration, stomatitis ulcerative, stomatitis, right upper 
quadrant pain, dyspepsia, glossitis, gastroesophogeal reflux, rectal 
disorder, gastrointestinal disorder, constipation, loose stools, 
toothache, tooth disorder 

Hepatobiliary disorders 
Common: 

 
Hepatic function abnormal 

Skin and subcutaneous tissue 
disorders  
Very common: 
Common: 

 
 
Alopecia, rash 
Photosensitivity reaction, maculopapular rash, eczema, acne, skin 
disorder, nail disorder, skin discolouration, pruritus, dry skin, 
erythema, bruise, sweating increased 

Musculoskeletal and 
connective tissue disorders 
Very common: 

 
 
Arthralgia, myalgia, musculoskeletal pain  

Renal and urinary disorders 
Common: 

 
Enuresis, micturition disorder, urinary incontinence 

Reproductive system and 
breast disorders 

 
 



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Common: Female: amenorrhea, menorrhagia, menstrual disorder, vaginal 
disorder 
Male: testicular pain 

General disorders and 
administration site 
conditions 
Very common: 
 
Common: 

 
 
 
Injection site inflammation, injection site reaction, fatigue, rigors, 
fever§, influenza-like symptoms§, malaise, irritability 
Chest pain, asthenia, oedema, injection site pain 

Investigations 
Very common: 

 
Growth rate decrease (height and/or weight decrease for age)§  

Injury and poisoning 
Common: 

 
Skin laceration 

§See section 4.4 
 
4.9 Overdose 
 
No case of overdose has been reported that has led to acute clinical manifestations. However, as for any 
pharmacologically active compound, symptomatic treatment with frequent monitoring of vital signs and close 
observation of the patient is indicated. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunostimulants, cytokines and immunomodulators, interferons, interferon 
alfa-2b, ATC code: L03A B05 
 
Viraferon is a sterile, stable, formulation of highly purified interferon alfa-2b produced by recombinant DNA 
techniques. Recombinant interferon alfa-2b is a water-soluble protein with a molecular weight of 
approximately 19,300 daltons. It is obtained from a clone of E. coli, which harbours a genetically engineered 
plasmid hybrid encompassing an interferon alfa-2b gene from human leukocytes. 
 
The activity of Viraferon is expressed in terms of IU, with 1 mg of recombinant interferon alfa-2b protein 
corresponding to 2.6 x l08 IU. International Units are determined by comparison of the activity of the 
recombinant interferon alfa-2b with the activity of the international reference preparation of human leukocyte 
interferon established by the World Health Organisation. 
 
The interferons are a family of small protein molecules with molecular weights of approximately 15,000 to 
21,000 daltons. They are produced and secreted by cells in response to viral infections or various synthetic 
and biological inducers. Three major classes of interferons have been identified: alpha, beta and gamma. 
These three main classes are themselves not homogeneous and may contain several different molecular 
species of interferon. More than 14 genetically distinct human alpha interferons have been identified. 
Viraferon has been classified as recombinant interferon alfa-2b. 
 
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. 
Human interferon receptors, as isolated from human lymphoblastoid (Daudi) cells, appear to be highly 
asymmetric proteins. They exhibit selectivity for human but not murine interferons, suggesting species 
specificity. Studies with other interferons have demonstrated species specificity. However, certain monkey 
species, eg, rhesus monkeys, are susceptible to pharmacodynamic stimulation upon exposure to human type 
1 interferons. 
 



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The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex 
sequence of intracellular events that include the induction of certain enzymes. It is thought that this process, 
at least in part, is responsible for the various cellular responses to interferon, including inhibition of virus 
replication in virus-infected cells, suppression of cell proliferation and such immunomodulating activities as 
enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of 
lymphocytes for target cells. Any or all of these activities may contribute to interferon's therapeutic effects. 
 
Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and 
human cell culture systems as well as human tumour xenografts in animals. It has demonstrated significant 
immunomodulatory activity in vitro. 
 
Recombinant interferon alfa-2b also inhibits viral replication in vitro and in vivo. Although the exact antiviral 
mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism. 
This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell. 
 
Chronic hepatitis B: 
Current clinical experience in patients who remain on interferon alfa-2b for 4 to 6 months indicates that 
therapy can produce clearance of serum HBV-DNA. An improvement in liver histology has been observed. 
In adult patients with loss of HBeAg and HBV-DNA, a significant reduction in morbidity and mortality has 
been observed. 
 
Interferon alfa-2b (6 MIU/m2 3 times a week for 6 months) has been given to children with chronic active 
hepatitis B. Because of a methodological flaw, efficacy could not be demonstrated. Moreover children treated 
with interferon alfa-2b experienced a reduced rate of growth and some cases of depression were observed. 
 
Chronic hepatitis C: 
In adult patients receiving interferon in combination with ribavirin, the achieved sustained response rate is 
47 %. Superior efficacy has been demonstrated with the combination of pegylated interferon with ribavirin 
(sustained response rate of 61 % achieved in a study performed in naïve patients with a ribavirin dose 
> 10.6 mg/kg, p < 0.01). 
 
Adult patients: Viraferon alone or in combination with ribavirin has been studied in 4 randomised Phase III 
clinical trials in 2,552 interferon-naïve patients with chronic hepatitis C. The trials compared the efficacy of 
Viraferon used alone or in combination with ribavirin. Efficacy was defined as sustained virologic response, 
6 months after the end of treatment. Eligible patients for these trials had chronic hepatitis C confirmed by a 
positive HCV-RNA polymerase chain reaction assay (PCR) (> 100 copies/ml), a liver biopsy consistent with 
a histologic diagnosis of chronic hepatitis with no other cause for the chronic hepatitis, and abnormal serum 
ALT. 
 
Viraferon was administered at a dose of 3 MIU 3 times a week as monotherapy or in combination with 
ribavirin. The majority of patients in these clinical trials were treated for one year. All patients were followed 
for an additional 6 months after the end of treatment for the determination of sustained virologic response. 
Sustained virologic response rates for treatment groups treated for one year with Viraferon alone or in 
combination with ribavirin (from two studies) are shown in Table 3. 
 
Co-administration of Viraferon with ribavirin increased the efficacy of Viraferon by at least two fold for the 
treatment of chronic heptatitis C in naïve patients. HCV genotype and baseline virus load are prognostic 
factors which are known to affect response rates. The increased response rate to the combination of Viraferon + 
ribavirin, compared with Viraferon alone, is maintained across all subgroups. The relative benefit of combination 
therapy with Viraferon + ribavirin is particularly significant in the most difficult to treat subgroup of patients 
(genotype 1 and high virus load) (Table 3). 
 
Response rates in these trials were increased with compliance. Regardless of genotype, patients who received 
Viraferon in combination with ribavirin and received ≥ 80 % of their treatment had a higher sustained 



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response 6 months after 1 year of treatment than those who took < 80 % of their treatment (56 % vs. 32 % in 
trial C/I98-580).  
 

Table 3 Sustained virologic response rates with Viraferon + ribavirin (one year of 
treatment) by genotype and viral load 

 
HCV Genotype  
 

I 
N=503 

C95-132/I95-143 

I/R 
N=505 

C95-132/I95-143 

I/R 
N=505 

C/I98-580 
 
All Genotypes 

 
16 % 

 
41 % 

 
47 % 

 
 
Genotype 1 

 
9 % 

 
29 % 

 
33 % 

 
Genotype 1  
≤ 2 million 
copies/ml 

 
25 % 

 
33 % 

 
45 % 

 
Genotype 1 
> 2 million 
copies/ml 

 
3 % 

 
27 % 

 

 
29 % 

 
Genotype 2/3 

 
31 % 

 
65 % 

 
79 % 

I Viraferon (3 MIU 3 times a week) 
I/R Viraferon (3 MIU 3 times a week) + ribavirin (1,000/1,200 mg/day) 
 
HCV/HIV Co-infected patients  
Two trials have been conducted in patients co-infected with HIV and HCV. Overall, in both studies, patients 
who received Viraferon plus ribavirin, were less likely to respond than patients who received pegylated 
interferon alfa-2b with ribavirin. The response to treatment in both of these trials is presented in Table 4. 
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 412 previously untreated 
adult patients with chronic hepatitis C who were co-infected with HIV. Patients were randomized to receive 
either pegylated interferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800 mg/day) or Viraferon (3 MIU TIW) 
plus ribavirin (800 mg/day) for 48 weeks with a follow-up period of 6 months. Study 2 (P02080) was a 
randomized, single centre study that enrolled 95 previously untreated adult patients with chronic hepatitis C 
who were co-infected with HIV. Patients were randomized to receive either pegylated interferon alfa-2b (100 
or 150 µg /week based on weight) plus ribavirin (800-1,200 mg/day based on weight) or Viraferon (3 MIU 
TIW) plus ribavirin (800-1,200 mg/day based on weight). The duration of therapy was 48 weeks with a 
follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load 
< 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6-month follow-up period.  
           
Table 4 Sustained virological response based on genotype after Viraferon in combination with 

ribavirin versus pegylated interferon alfa-2b in combination with ribavirin in 
HCV/HIV co-infected patients 

 Study 11 Study 22 
 

pegylated 
interferon 

alfa-2b  
(1.5 µg/kg/ 

week) + 
ribavirin  
(800 mg) 

Viraferon  
(3 MIU TIW) +  

ribavirin  
(800 mg) 

p 
valuea 

pegylated 
interferon 

alfa-2b (100 
or  

150c µg/week) 
+ ribavirin 

(800- 
1,200 mg)d 

Viraferon  
(3 MIU TIW) 

+ ribavirin 
(800- 

1,200 mg)d 
p 

valueb 



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All 27 % (56/205) 20 % (41/205) 0.047 44 % (23/52) 21 % (9/43) 0.017 
Genotype 1, 

4 
17 % (21/125) 6 % (8/129) 0.006 38 % (12/32) 7 % (2/27) 0.007 

Genotype 2, 
3 

44 % (35/80) 43 % (33/76) 0.88 53 % (10/19) 47 % (7/15) 0.730 

MIU = million international units; TIW = three times a week. 
a:  p value based on Cochran-Mantel Haenszel Chi square test. 
b:  p value based on chi-square test. 
c:  subjects < 75 kg received 100 µg/week pegylated interferon alfa-2b and subjects ≥ 75 kg received 150 µg/week pegylated 

interferon alfa-2b. 
d: ribavirin dosing was 800 mg for patients < 60 kg, 1,000 mg for patients 60-75 kg, and 1,200 mg for patients > 75 kg. 
 

1Carrat F, Bani-Sadr F, Pol S et al.  JAMA 2004; 292(23): 2839-2848. 
2 Laguno M, Murillas J, Blanco J.L et al.  AIDS 2004; 18(13): F27-F36. 
 
 
Relapse patients: A total of 345 interferon alpha relapse patients were treated in two clinical trials with 
Viraferon monotherapy or in combination with ribavirin. In these patients, the addition of ribavirin to 
Viraferon increased by as much as 10-fold the efficacy of Viraferon used alone in the treatment of chronic 
hepatitis C (48.6 % vs. 4.7 %). This enhancement in efficacy included loss of serum HCV (< 100 copies/ml 
by PCR), improvement in hepatic inflammation, and normalisation of ALT, and was sustained when 
measured 6 months after the end of treatment. 
 
Long-Term efficacy data 
In a large study, 1,071 patients were enrolled after treatment in a prior non pegylated interferon alfa-2b or 
non pegylated interferon alfa-2b/ribavirin study to evaluate the durability of sustained virologic response and 
assess the impact of continued viral negativity on clinical outcomes. 462 patients completed at least 5 years 
of long-term follow-up and only 12 sustained responders' out of 492 relapsed during this study.  
The Kaplan-Meier estimate for continued sustained response over 5 years for all patients is 97 % with a 95 % 
Confidence Interval of [95 %, 99 %].  
SVR after treatment of chronic HCV with non pegylated interferon alfa-2b (with or without ribavirin) results 
in long-term clearance of the virus providing resolution of the hepatic infection and clinical 'cure' from 
chronic HCV. However, this does not preclude the occurrence of hepatic events in patients with cirrhosis 
(including hepatocarcinoma). 
 
Clinical trials in paediatric patients with chronic hepatitis C: 
Children and adolescents 3 to 16 years of age with compensated chronic hepatitis C and detectable HCV-
RNA (assessed by a central laboratory using a research-based RT-PCR assay) were enrolled in two 
multicentre trials and received Viraferon 3 MIU/m2 3 times a week plus ribavirin 15 mg/kg per day for 1 year 
followed by 6 months follow-up after-treatment. A total of 118 patients were enrolled: 57 % male, 80 % 
Caucasian, and 78 % genotype 1,64 % ≤ 12 years of age. The population enrolled mainly consisted in 
children with mild to moderate hepatitis C. Sustained virological response rates in children and adolescents 
were similar to those in adults. Due to the lack of data in children with severe progression of the disease, and 
the potential for undesirable effects, the benefit/risk of the combination of ribavirin and interferon alfa-2b 
needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8). 
 
Study results are summarized in Table 5. 
 
Table 5. Virological response in previously untreated paediatric patients 
 Viraferon 3 MIU/m2 3 times a week   

+ 
ribavirin 15 mg/kg/day 

Overall Response1 (n=118) 54 (46 %)* 



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Genotype 1 (n=92) 33 (36 %)* 

Genotype 2/3/4 (n=26) 21 (81 %)* 

*Number (%) of patients 
1. Defined as HCV-RNA below limit of detection using a research based RT-PCR assay at end of treatment and during follow-up 
period 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of Viraferon were studied in healthy volunteers following single 5 million IU/m2 and 
10 million IU doses administered subcutaneously, at 5 million IU/m2 administered intramuscularly and as a 
30-minute intravenous infusion. The mean serum interferon concentrations following subcutaneous and 
intramuscular injections were comparable. Cmax occurred three to 12 hours after the lower dose and six to 
eight hours after the higher dose. The elimination half-lives of interferon injections were approximately two 
to three hours, and six to seven hours, respectively. Serum levels were below the detection limit 16 and 
24 hours, respectively, post-injection. Both subcutaneous and intramuscular administration resulted in 
bioavailabilities greater than 100 %. 
 
After intravenous administration, serum interferon levels peaked (135 to 273 IU/ml) by the end of the 
infusion, then declined at a slightly more rapid rate than after subcutaneous or intramuscular administration 
of medicinal product, becoming undetectable four hours after the infusion. The elimination half-life was 
approximately two hours. 
 
Urine levels of interferon were below the detection limit following each of the three routes of administration. 
 
Children and adolescents: Multiple-dose pharmacokinetic properties for Viraferon injection and ribavirin 
capsules in children and adolescents with chronic hepatitis C, between 5 and 16 years of age, are summarized 
in Table 6. The pharmacokinetics of Viraferon and ribavirin (dose-normalized) are similar in adults and 
children or adolescents. 
 

Table 6. Mean (% CV) multiple-dose pharmacokinetic parameters for Viraferon and ribavirin 
capsules when administered to children or adolescents with chronic hepatitis C 
Parameter Ribavirin 

15 mg/kg/day as 2 divided 
doses 

(n = 17) 

Viraferon 
3 MIU/m2 3 times a week 

(n = 54) 

Tmax (hr) 1.9 (83) 5.9 (36) 
Cmax (ng/ml) 3,275 (25) 51 (48) 

AUC* 29,774 (26) 622 (48) 
Apparent clearance l/hr/kg 0.27 (27) Not done 

*AUC12 (ng.hr/ml) for ribavirin; AUC0-24 (IU.hr/ml) for Viraferon 
 
Interferon neutralising factor assays were performed on serum samples of patients who received Viraferon in 
Schering-Plough monitored clinical trials. Interferon neutralising factors are antibodies which neutralise the 
antiviral activity of interferon. The clinical incidence of neutralising factors developing in cancer patients 
treated systemically is 2.9 % and in chronic hepatitis patients is 6.2 %. The detectable titres are low in almost 
all cases and have not been regularly associated with loss of response or any other autoimmune phenomenon. 
In patients with hepatitis, no loss of response was observed apparently due to the low titres. 
 
5.3 Preclinical safety data 
 
Although interferon is generally recognised as being species specific, toxicity studies in animals were 
conducted. Injections of human recombinant interferon alfa-2b for up to three months have shown no 
evidence of toxicity in mice, rats, and rabbits. Daily dosing of cynomolgus monkeys with 20 x 106 IU/kg/day 



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for 3 months caused no remarkable toxicity. Toxicity was demonstrated in monkeys given 
100 x 106 IU/kg/day for 3 months. 
 
In studies of interferon use in non-human primates, abnormalities of the menstrual cycle have been observed 
(see section 4.4). 
 
Results of animal reproduction studies indicate that recombinant interferon alfa-2b was not teratogenic in rats 
or rabbits, nor did it adversely affect pregnancy, foetal development or reproductive capacity in offspring of 
treated rats. Interferon alfa-2b has been shown to have abortifacient effects in Macaca mulatta (rhesus 
monkeys) at 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2. 
Abortion was observed in all dose groups (7.5 million, 15 million and 30 million IU/kg), and was statistically 
significant versus control at the mid- and high-dose groups (corresponding to 90 and 180 times the 
recommended intramuscular or subcutaneous dose of 2 million IU/m2). High doses of other forms of 
interferons alpha and beta are known to produce dose-related anovulatory and abortifacient effects in rhesus 
monkeys. 
 
Mutagenicity studies with interferon alfa-2b revealed no adverse events. 
 
No studies have been conducted in juvenile animals to examine the effects of treatment with interferon alfa-
2b on growth, development, sexual maturation, and behaviour ((see section 4.4 and Rebetol SPC if Viraferon 
is to be administered in combination with ribavirin). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Disodium phosphate anhydrous,  
Sodium dihydrogen phosphate monohydrate,  
Edetate disodium,  
Sodium chloride,  
M-cresol,  
Polysorbate 80, 
Water for injections. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
2 years 
 
After first opening the container: Chemical and physical in-use stability has been demonstrated for 28 days at 
2ºC – 8ºC. 
From a microbiological point of view, once opened, the product may be stored for a maximum of 28 days at 
2ºC – 8ºC. Other in-use storage times and conditions are the responsibility of the user. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C).  
Do not freeze.  
Within its shelf-life, for the purpose of transport, the solution can be kept at or below 25ºC for a period up to 
seven days before use. Viraferon can be put back in the refrigerator at any time during this seven-day period. 



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If the product is not used during the seven-day period, it cannot be put back in the refrigerator for a new 
storage period and must be discarded. 
 
6.5 Nature and contents of container 
 
2.5 ml of solution (corresponding to 25 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in a 
flip-off seal (aluminium) with a bonnet (polypropylene). 
Pack sizes of 1, 2 or 12 
 
Or 
 
2.5 ml of solution (corresponding to 25 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in a 
flip-off seal (aluminium) with a bonnet (polypropylene) 
with 6 injection syringes, 6 injection needles and 12 cleansing swabs. 
Pack sizes of 1 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
Viraferon solution for injection, may be injected directly after withdrawal of the appropriate doses from the 
vial with a sterile injection syringe. 

 
As with all parenteral medicinal products, prior to administration inspect Viraferon, solution for injection, 
visually for particulate matter and discolouration. The solution should be clear and colourless. 
 
Detailed instructions for the subcutaneous use of the product are provided with the package leaflet (refer to 
“How to self inject Viraferon”). 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
SP Europe 
73, rue de Stalle 
B-1180 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/99/128/025 
EU/1/99/128/026 
EU/1/99/128/027 
EU/1/99/128/028 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation : 9 March 2000 
Date of last renewal : 23 May 2005 
 
 
10. DATE OF REVISION OF THE TEXT 



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Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu/ 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 18 million IU solution for injection, multidose pen 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One cartridge contains 18 million IU of recombinant interferon alfa-2b produced in E.coli by recombinant 
DNA technology, in 1.2 ml. 
 
One ml contains 15 million IU of interferon alfa-2b. 
 
The pen is designed to deliver its contents of 18 million IU in doses ranging from 1.5 to 6 million IU. The 
pen will deliver a maximum of 12 doses of 1.5 million IU over a period not to exceed 4 weeks. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection 
Solution is clear and colourless. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Chronic Hepatitis B: Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis B 
viral replication (presence of HBV-DNA and HBeAg), elevated alanine aminotransferase (ALT) and 
histologically proven active liver inflammation and/or fibrosis. 
 
Chronic Hepatitis C:  
Adult patients:  
Viraferon is indicated for the treatment of adult patients with chronic hepatitis C who have elevated 
transaminases without liver decompensation and who are positive for serum HCV-RNA or anti-HCV (see 
section 4.4). 
 
The best way to use Viraferon in this indication is in combination with ribavirin. 
 
Chidren and adolescents: 
Viraferon is intended for use, in a combination regimen with ribavirin, for the treatment of children and 
adolescents 3 years of age and older, who have chronic hepatitis C, not previously treated, without liver 
decompensation, and who are positive for serum HCV-RNA. The decision to treat should be made on a case 
by case basis, taking into account any evidence of disease progression such as hepatic inflammation and 
fibrosis, as well as prognostic factors for response, HCV genotype and viral load. The expected benefit of 
treatment should be weighed against the safety findings observed for paediatric subjects in the clinical trials 
(see sections 4.4, 4.8 and 5.1). 
 
4.2 Posology and method of administration 
 
Treatment must be initiated by a physician experienced in the management of the disease. 
 
Multidose presentations must be for individual patient use only. 
 



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Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
If adverse events develop during the course of treatment with Viraferon for any indication, modify the dosage 
or discontinue therapy temporarily until the adverse events abate. If persistent or recurrent intolerance 
develops following adequate dosage adjustment, or disease progresses, discontinue treatment with Viraferon. 
At the discretion of the physician, the patient may self-administer the dose for maintenance dosage regimens 
administered subcutaneously. 
 
Chronic Hepatitis B: The recommended dosage is in the range 5 to 10 million IU administered 
subcutaneously three times a week (every other day) for a period of 4 to 6 months. 
 
The administered dose should be reduced by 50 % in case of occurrence of haematological disorders (white 
blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3). Treatment should be 
discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe 
thrombocytopaenia (< 70,000/mm3). 
 
For all patients, if no improvement on serum HBV-DNA is observed after 3 to 4 months of treatment (at the 
maximum tolerated dose), discontinue Viraferon therapy. 
 
Chronic Hepatitis C: Viraferon is administered subcutaneously at a dose of 3 million IU three times a week 
(every other day) to adult patients, whether administered as monotherapy or in combination with ribavirin. 
 
Children 3 years of age or older and adolescents: Interferon alfa-2b 3 MIU/m2 is administered 
subcutaneously 3 times a week (every other day) in combination with ribavirin capsules or oral solution 
administered orally in two divided doses daily with food (morning and evening).  
 
(See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination 
therapy. For paediatric patients who weigh < 47 kg or cannot swallow capsules, see ribavirin oral solution 
SPC).  
 
Relapse patients (adults): 
Viraferon is given in combination with ribavirin. 
 
Based on the results of clinical trials, in which data are available for 6 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for 6 months. 
 
Naïve patients: 
Adults: The efficacy of Viraferon is enhanced when given in combination with ribavirin. Viraferon should be 
given alone mainly in case of intolerance or contraindication to ribavirin. 
 
Viraferon in combination with ribavirin: 
Based on the results of clinical trials, in which data are available for 12 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for at least 6 months. 
 
Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit 
negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and 
high pre-treatment viral load. 
 
Other negative prognostic factors (age > 40 years, male gender, bridging fibrosis) should be taken into 
account in order to extend therapy to 12 months. 
 
During clinical trials, patients who failed to show a virologic response after 6 months of treatment (HCV-
RNA below lower limit of detection) did not become sustained virologic responders (HCV-RNA below lower 
limit of detection six months after withdrawal of treatment). 



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Viraferon alone: 
The optimal duration of therapy with Viraferon alone is not yet fully established, but a therapy of between 
12 and 18 months is advised. 
 
It is recommended that patients be treated with Viraferon alone for at least 3 to 4 months, at which point 
HCV-RNA status should be determined. Treatment should be continued in patients who exhibit negative 
HCV-RNA. 
 
Children and adolescents: The efficacy and safety of Viraferon in combination with ribavirin has been 
studied in children and adolescents who have not been previously treated for chronic hepatitis C.  
 
Genotype 1: The recommended duration of treatment is one year. Patients who fail to achieve virological 
response at 12 weeks are highly unlikely to become sustained virological responders (negative predictive 
value 96 %). Virological response is defined as absence of detectable HCV-RNA at Week 12. Treatment 
should be discontinued in these patients. 
Genotype 2/3: The recommended duration of treatment is 24 weeks. 
 
Virological responses after 1 year of treatment and 6 months of follow-up were 36 % for genotype 1 and 
81 % for genotype 2/3/4. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients. 
- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure, recent 

myocardial infarction, severe arrhythmic disorders.  
- Severe renal or hepatic dysfunction; including that caused by metastases. 
- Epilepsy and/or compromised central nervous system (CNS) function (see section 4.4). 
- Chronic hepatitis with decompensated cirrhosis of the liver. 
- Chronic hepatitis in patients who are being or have been treated recently with immunosuppressive 

agents excluding short term corticosteroid withdrawal. 
- Autoimmune hepatitis; or history of autoimmune disease; immunosuppressed transplant recipients. 
- Pre-existing thyroid disease unless it can be controlled with conventional treatment. 
 
Children and adolescents: 
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal 

ideation or suicide attempt. 
 

Combination therapy with ribavirin: Also see ribavirin SPC if interferon alfa-2b is to be administered in 
combination with ribavirin in patients with chronic hepatitis C. 
 
4.4 Special warnings and precautions for use 
 
For all patients: 
Psychiatric and central nervous system (CNS): Severe CNS effects, particularly depression, suicidal ideation 
and attempted suicide have been observed in some patients during Viraferon therapy, and even after 
treatment discontinuation mainly during the 6-month follow-up periodand in the follow-up period. Among 
children and adolescents treated with Viraferon in combination with ribavirin, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6-month 
follow-up after treatment. As in adult patients, children and adolescents experienced other psychiatric adverse 
events (e.g., depression, emotional lability, and somnolence). Other CNS effects including aggressive behaviour 
(sometimes directed against others), confusion and alterations of mental status have been observed with alpha 
interferons. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such 
symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the 
prescribing physician and the need for adequate therapeutic management should be considered. If psychiatric 



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symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with 
Viraferon be discontinued, and the patient followed, with psychiatric intervention as appropriate. 
 
Patients with existence of or history of severe psychiatric conditions: 
If a treatment with interferon alfa-2b is judged necessary in adult patients with existence or history of severe 
psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and 
therapeutic management of the psychiatric condition. The use of interferon alfa-2b in children and adolescents 
with existence of or history of severe psychiatric conditions is contraindicated (see section 4.3). 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Moderate to severe adverse experiences may require modification of the patient's dosage regimen, or in some 
cases, termination of Viraferon therapy. Any patient developing liver function abnormalities during treatment 
with Viraferon must be monitored closely and treatment discontinued if signs and symptoms progress. 
 
Hypotension may occur during Viraferon therapy or up to two days post-therapy and may require supportive 
treatment. 
 
Adequate hydration must be maintained in patients undergoing Viraferon therapy since hypotension related 
to fluid depletion has been seen in some patients. Fluid replacement may be necessary. 
 
While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, 
other causes of persistent fever must be ruled out. 
 
Viraferon must be used cautiously in patients with debilitating medical conditions, such as those with a 
history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to 
ketoacidosis. Caution must be observed also in patients with coagulation disorders (e.g., thrombophlebitis, 
pulmonary embolism) or severe myelosuppression. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.5). Any patient developing fever, cough, 
dyspnea or other respiratory symptoms must have a chest X-ray taken. If the chest X-ray shows pulmonary 
infiltrates or there is evidence of pulmonary function impairment, the patient is to be monitored closely, and, 
if appropriate, discontinue interferon alpha. While this has been reported more often in patients with chronic 
hepatitis C treated with interferon alpha, it has also been reported in patients with oncologic diseases treated 
with interferon alpha. Prompt discontinuation of interferon alpha administration and treatment with 
corticosteroids appear to be associated with resolution of pulmonary adverse events. 
 
Ocular adverse events (see section 4.8) including retinal haemorrhages, cotton wool spots, and retinal artery 
or vein obstruction have been reported in rare instance after treatment with alpha interferons. All patients 
should have a baseline eye examination. Any patient complaining of changes in visual acuity or visual fields, 
or reporting other ophthalmologic symptoms during treatment with Viraferon, must have a prompt and 
complete eye examination. Periodic visual examinations during Viraferon therapy are recommended 
particularly in patients with disorders that may be associated with retinopathy, such as diabetes mellitus or 
hypertension. Discontinuation of Viraferon should be considered in patients who develop new or worsening 
ophthalmological disorders. 



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More significant obtundation and coma, including cases of encephalopathy, have been observed in some 
patients, usually elderly, treated at higher doses. While these effects are generally reversible, in a few patients 
full resolution took up to three weeks. Very rarely, seizures have occurred with high doses of Viraferon. 
 
Adult patients with a history of congestive heart failure, myocardial infarction and/or previous or current 
arrhythmic disorders, who require Viraferon therapy, must be closely monitored. It is recommended that 
those patients who have pre-existing cardiac abnormalities and/or are in advanced stages of cancer have 
electrocardiograms taken prior to and during the course of treatment. Cardiac arrhythmias (primarily 
supraventricular) usually respond to conventional therapy but may require discontinuation of Viraferon 
therapy. There are no data in children or adolescents with a history of cardiac disease. 
 
Hypertriglyceridemia and aggravation of hypertriglyceridemia, sometimes severe, have been observed. 
Monitoring of lipid levels is, therefore, recommended. 
 
Due to reports of interferon alpha exacerbating pre-existing psoriatic disease and sarcoidosis, use of 
Viraferon in patients with psoriasis or sarcoidosis is recommended only if the potential benefit justifies the 
potential risk. 
 
Preliminary data indicates that interferon alpha therapy may be associated with an increased rate of kidney 
graft rejection. Liver graft rejection has also been reported. 
 
The development of auto-antibodies and autoimmune disorders has been reported during treatment with alpha 
interferons. Patients predisposed to the development of autoimmune disorders may be at increased risk. 
Patients with signs or symptoms compatible with autoimmune disorders should be evaluated carefully, and 
the benefit-risk of continued interferon therapy should be reassessed (see also section 4.4 Chronic hepatitis C, 
Monotherapy (thyroid abnormalities) and section 4.8). 
Cases of Vogt-Koyanagi-Harada (VKH) syndrome have been reported in patients with chronic hepatitis C 
treated with interferon. This syndrome is a granulomatous inflammatory disorder affecting the eyes, auditory 
system, meninges, and skin. If VKH syndrome is suspected, antiviral treatment should be withdrawn and 
corticosteroid therapy discussed (see section 4.8). 
 
Discontinue treatment with Viraferon in patients with chronic hepatitis who develop prolongation of 
coagulation markers which might indicate liver decompensation. 
 
Chronic Hepatitis C: 
Combination therapy with ribavirin: Also see ribavirin SPC if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i.e. 
patients with genotype 2 and 3), treatment may be possible without histological confirmation. Current 
treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing 
treatment. 
 
Monotherapy: Infrequently, adult patients treated for chronic hepatitis C with Viraferon developed thyroid 
abnormalities, either hypothyroidism or hyperthyroidism. In clinical trials using Viraferon therapy, 2.8 % 
patients overall developed thyroid abnormalities. The abnormalities were controlled by conventional therapy 
for thyroid dysfunction. The mechanism by which Viraferon may alter thyroid status is unknown. Prior to 
initiation of Viraferon therapy for the treatment of chronic hepatitis C, evaluate serum thyroid-stimulating 
hormone (TSH) levels. Any thyroid abnormality detected at that time must be treated with conventional 
therapy. Viraferon treatment may be initiated if TSH levels can be maintained in the normal range by 
medication. Determine TSH levels if, during the course of Viraferon therapy, a patient develops symptoms 
consistent with possible thyroid dysfunction. In the presence of thyroid dysfunction, Viraferon treatment may 
be continued if TSH levels can be maintained in the normal range by medication. Discontinuation of 



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Viraferon therapy has not reversed thyroid dysfunction occurring during treatment (also see Children and 
adolescents, Thyroid monitoring). 
 
Supplemental monitoring specific for children and adolescents 
Thyroid Monitoring: Approximately 12 % of children treated with interferon alfa-2b and ribavirin developed 
increase in TSH. Another 4 % had a transient decrease below the lower limit of normal. Prior to initiation of 
Viraferon therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be 
treated with conventional therapy. Viraferon therapy may be initiated if TSH levels can be maintained in the 
normal range by medication. Thyroid dysfunction during treatment with interferon alfa-2b and ribavirin has 
been observed. If thyroid abnormalities are detected, the patient’s thyroid status should be evaluated and 
treated as clinically appropriate. Children and adolescents should be monitored every 3 months for evidence 
of thyroid dysfunction (e.g. TSH). 
 
Growth and Development: During a 1-year course of therapy there was a decrease in the rate of linear growth 
(mean percentile decrease of 9 %) and a decrease in the rate of weight gain (mean percentile decrease of 
13 %). A general reversal of these trends was noted during the 6 months follow-up post treatment. However, 
based on interim data from a long-term follow-up study, 12 (14 %) of 84 children had a > 15 percentile 
decrease in rate of linear growth, of whom 5 (6 %) children had a > 30 percentile decrease despite being off 
treatment for more than 1 year. In addition, preclicinal juvenile toxicity results have demonstrated a minor, 
dose-related decrease in overall growth in neonatal rats dosed with ribavirin (see section 5.3). Therefore, the 
risk/benefit of the combined use of interferon alfa-2b and ribavirin should be assessed in young children prior 
to the initiation of therapy. Physicians are advised to monitor the growth of children taking ribavirin in 
combination with interferon alfa-2b. There are no data on long term effects on growth and development and 
on sexual maturation. 
 
HCV/HIV Coinfection: Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy 
(HAART) may be at increased risk of developing lactic acidosis. Caution should be used when adding Viraferon 
and ribavirin to HAART therapy (see ribavirin SPC). Patients treated with Viraferon and ribavirin combination 
therapy and zidovudine could be at increased risk of developing anaemia. 
Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic 
decompensation and death. Adding treatment with alfa interferons alone or in combination with ribavirin may 
increase the risk in this patient subset.  
 
Dental and periodontal disorders: Dental and periodontal disorders, which may lead to loss of teeth, have 
been reported in patients receiving Viraferon and ribavirin combination therapy. In addition, dry mouth could 
have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the 
combination of Viraferon and ribavirin. Patients should brush their teeth thoroughly twice daily and have 
regular dental examinations. In addition some patients may experience vomiting. If this reaction occurs, they 
should be advised to rinse out their mouth thoroughly afterwards. 
 
Laboratory Tests:  
Standard haematological tests and blood chemistries (complete blood count and differential, platelet count, 
electrolytes, liver enzymes, serum protein, serum bilirubin and serum creatinine) are to be conducted in all 
patients prior to and periodically during systemic treatment with Viraferon. 
 
During treatment for hepatitis B or C the recommended testing schedule is at weeks 1, 2, 4, 8, 12, 16, and 
every other month, thereafter, throughout treatment. If ALT flares during Viraferon therapy to greater than or 
equal to 2 times baseline, Viraferon therapy may be continued unless signs and symptoms of liver failure are 
observed. During ALT flare, liver function tests: ALT, prothrombin time, alkaline phosphatase, albumin and 
bilirubin must be monitored at two-week intervals. 
 
Effect on fertility: Interferon may impair fertility (see section 4.6 and section 5.3). 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 



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Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with 
Viraferon. 
 
Interactions between Viraferon and other medicinal products have not been fully evaluated. Caution must be 
exercised when administering Viraferon in combination with other potentially myelosuppressive agents. 
 
Interferons may affect the oxidative metabolic process. This must be considered during concomitant therapy 
with medicinal products metabolised by this route, such as the xanthine derivatives theophylline or 
aminophylline. During concomitant therapy with xanthine agents, serum theophylline levels must be 
monitored and dosage adjusted if necessary. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.4). 
 
(Also see ribavirin SPC if Viraferon is to be administered in combination with ribavirin in patients with 
chronic hepatitis C). 
 
4.6 Pregnancy and lactation 
 
Women of childbearing potential have to use effective contraception during treatment. Viraferon must be 
used with caution in fertile men. Decreased serum estradiol and progesterone concentrations have been 
reported in women treated with human leukocyte interferon. 
 
There are no adequate data from the use of interferon alfa-2b in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Viraferon is to be 
used during pregnancy only if the potential benefit justifies the potential risk to the foetus. 
 
It is not known whether the components of this medicinal product are excreted in human milk. Because of the 
potential for adverse reactions in nursing infants, nursing should be discontinued prior to initiation of 
treatment. 
 
Combination therapy with ribavirin: Ribavirin causes serious birth defects when administered during 
pregnancy. Ribavirin therapy is contraindicated in women who are pregnant. Extreme care must be taken to 
avoid pregnancy in female patients or in partners of male patients taking Viraferon in combination with 
ribavirin. Females of childbearing potential and their partners must each use an effective contraceptive during 
treatment and for 4 months after treatment has been concluded. Male patients and their female partners must 
each use an effective contraceptive during treatment and for 7 months after treatment has been concluded (see 
ribavirin SPC). 
 
4.7 Effects on ability to drive and use machines 
 
Patients are to be advised that they may develop fatigue, somnolence, or confusion during treatment with 
Viraferon, and therefore it is recommended that they avoid driving or operating machinery. 
 
4.8 Undesirable effects 
 
See ribavirin SPC for ribavirin-related undesirable effects if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
In clinical trials conducted in a broad range of indications and at a wide range of doses (from 6 MIU/m2/week 
in hairy cell leukaemia up to 100 MIU/m2/week in melanoma), the most commonly reported undesirable 
effects were fever, fatigue, headache and myalgia. Fever and fatigue were often reversible within 72 hours of 
interruption or cessation of treatment. 



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In clinical trials conducted in the hepatitis C population, patients were treated with Viraferon alone or in 
combination with ribavirin for one year. All patients in these trials received 3 MIU of Viraferon three times a 
week. In Table 1 the frequency of patients reporting (treatment related) undesirable effects is presented from 
clinical trials in naïve patients treated for one year. Severity was generally mild to moderate. The adverse 
reactions listed in Table 1 are based on experience from clinical trials and post-marketing. Within the organ 
system classes, adverse reactions are listed under headings of frequency using the following categories: very 
common (≥1/10); common (≥1/100, <1/10); rarely (≥1/10,000, <1/1,000); very rarely (<1/10,000); not 
known. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

Table 1. Adverse reactions reported during clinical trials or following the marketing use of Viraferon 
alone or in combination with ribavirin 

System Organ Class Adverse Reactions 
Infections and infestations 
Very common: 
Common: 
Rarely:  

 
Pharyngitis*, infection viral* 
Bronchitis, sinusitis, herpes simplex (resistance), rhinitis 
Pneumonia§ 

Blood and lymphatic system disorders 
Very common: 
Common: 
Very rarely:  
Not known:  

 
Leukopaenia 
Thrombocytopaenia, lymphadenopathy, lymphopenia 
Aplastic anaemia 
Pure red cell aplasia, idiopathic thrombocytopenic purpura, 
thrombotic thrombocytopenic purpura  

Immune system disorders§ 
Very rarely:  
Not known: 

 
Sarcoidosis, exacerbation of sarcoidosis 
Systemic lupus erythematosus, vasculitis, rheumatoid 
arthritis (new or aggravated), Vogt-Koyanagi-Harada 
syndrome, acute hypersensitivity reactions including 
urticaria, angioedema, bronchoconstriction, anaphylaxis§ 

Endocrine disorders 
Common: 
Very rarely:  

 
Hypothyroidism§, hyperthyroidism§ 
Diabetes, aggravated diabetes 

Metabolism and nutrition disorders 
Very common: 
Common:  
Very rarely:  

 
Anorexia 
Hypocalcaemia, dehydration, hyperuricemia, thirst 
Hyperglycaemia, hypertriglyceridaemia§, increased appetite 

Psychiatric disorders§ 
Very common: 
 
Common: 
Rarely:  
Very rarely: 
 
Not known: 

 
Depression, insomnia, anxiety, emotional lability*, 
agitation, nervousness 
Confusion, sleep disorder, libido decreased 
Suicide ideation 
Suicide, suicide attempts, aggressive behaviour (sometimes 
directed against others), psychosis including hallucinations 
Mental status change§ 

Nervous system disorders§ 
Very common: 
Common: 
 
Very rarely:  
 
 
Not known: 

 
Dizziness, headache, concentration impaired, mouth dry 
Tremor, paresthesia, hypoesthesia, migraine, flushing, 
somnolence, taste perversion 
Cerebrovascular haemorrhage, cerbrovascular ischaemia, 
seizure, impaired consciousness, encephalopathy, 
neuropathy, polyneuropathy 
Mononeuropathies, coma§ 

Eye disorders 
Very common: 

 
Vision blurred 



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Common: 
 
Rarely:  

Conjunctivitis, vision abnormal, lacrimal gland disorder, eye 
pain 
Retinal haemorrhages§, retinopathies (including macular 
oedema), retinal artery or vein obstruction§, optic neuritis, 
papilloedema, loss of visual acuity or visual field, cotton-
wool spots§  

Ear and labyrinth 
Common: 
Very rarely:  

 
Vertigo, tinnitus 
Hearing loss, hearing disorder 

Cardiac disorders 
Common: 
Rarely: 
Very rarely: 
Not known: 

 
Palpitation, tachycardia 
Cardiomyopathy 
Myocardial infarction, cardiac ischaemia  
Arrhythmia  

Vascular disorders 
Common: 
Very rarely:  

 
Hypertension 
Peripheral ischaemia, hypotension§ 

Respiratory, thoracic and mediastinal 
disorders 
Very common: 
Common: 
 
Very rarely:  

 
 
Dyspnoea*, coughing* 
Epistaxis, respiratory disorder, nasal congestion, rhinorrhea, 
cough nonproductive 
Pulmonary infiltrates§, pneumonitis§ 

Gastrointestinal disorders 
Very common: 
 
Common: 
 
Very rarely:  
 
Not known: 

 
Nausea/vomiting, abdominal pain, diarrhoea, stomatitis, 
dyspepsia 
Stomatitis ulcerative, right upper quadrant pain, glossitis, 
gingivitis, constipation, loose stools 
Pancreatitis, ischaemic colitis, ulcerative colitis, gingival 
bleeding 
Periodontal disorder NOS, dental disorder NOS§ 

Hepatobiliary disorders 
Common: 
Very rarely:  

 
Hepatomegaly 
Hepatotoxicity, (including fatality) 

Skin and subcutaneous tissue disorders 
Very common: 
Common: 
 
Very rarely:  

 
Alopecia, pruritus*, skin dry*, rash*, sweating increased 
Psoriasis (new or aggravated)§, rash maculopapular, rash 
erythematous, eczema, erythema, skin disorder 
Stevens Johnson syndrome, toxic epidermal necrolysis, 
erythema multiforme 

Musculoskeletal and connective tissue 
disorders 
Very common:  
Common: 
Very rarely: 

 
 
Myalgia, arthralgia, musculoskeletal pain 
Arthritis 
Rhabdomyolysis, myositis, leg cramps, back pain 

Renal and urinary disorders 
Common: 
Very rarely:  

 
Micturition frequency 
Renal failure, renal insufficiency, nephrotic syndrome 

Reproductive system and breast 
disorders 
Common: 

 
 
Amenorrhea, breast pain, dysmenorrhea, menorrhagia, 
menstrual disorder, vaginal disorder 

General disorders and administration 
site conditions 

 
 



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Very common: 
 
 
Common: 
Very rarely: 

Injection site inflammation, injection site reaction*, fatigue, 
rigors, fever§, flu-like symptoms§, asthenia, irritability, chest 
pain, malaise 
Injection site pain 
Injection site necrosis, face oedema 

Investigations 
Very common: 

 
Weight decrease 

*These events were only common with Viraferon alone 
§See section 4.4 
 
These undesirable effects have also been reported with Viraferon alone. 
 
Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-
existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4). Cardiomyopathy, that may 
be reversible upon discontinuation of interferon alpha, has been reported rarely in patients without prior 
evidence of cardiac disease (see section 4.4).  
 
A wide variety of autoimmune and immune-mediated disorders have been reported with alpha interferons 
including thyroid disorders, systemic lupus erythematosus, rheumatoid arthritis (new or aggravated), 
idiopathic and thrombotic thrombocytopenic purpura, vasculitis, neuropathies including mononeuropathies 
(see also section 4.4).  
 
Clinically significant laboratory abnormalities, most frequently occurring at doses greater than 10 million IU 
daily, include reduction in granulocyte and white blood cell counts; decreases in haemoglobin level and 
platelet count; increases in alkaline phosphatase, LDH, serum creatinine and serum urea nitrogen levels. 
Increase in serum ALT/AST (SGPT/SGOT) levels have been noted as an abnormality in some non-hepatitis 
subjects and also in some patients with chronic hepatitis B coincident with clearance of viral DNAp. 
 
Paediatric population 
 
Children and adolescents – Chronic Hepatitis C 
In clinical trials of 118 children or adolescents 3 to 16 years of age, 6 % discontinued therapy due to adverse 
events. In general, the adverse event profile in the limited paediatric population studied was similar to that 
observed in adults, although there is a paediatric specific concern regarding growth inhibition as decrease in 
height (mean percentile decrease of growth velocity of 9 %) and weight (mean percentile decrease of 13 %) 
percentile were observed during treatment (see section 4.4). Furthermore, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6 month 
follow-up after treatment. As in adult patients, children and adolescents also experienced other psychiatric 
adverse events (e.g., depression, emotional lability, and somnolence) (see section 4.4). In addition, injection 
site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in children and 
adolescents compared to adult patients. Dose modifications were required in 30 % of patients, most 
commonly for anaemia and neutropaenia. 
 
The adverse reactions listed in Table 2 are based on experience from paediatric clinical trials.  
Within the organ system classes, adverse reactions are listed under headings of frequency using the following 
categories: very common (≥1/10); common (≥1/100, <1/10). Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness. 
 
Table 2  Adverse reactions very commonly and commonly reported in paediatric clinical trials  

Very common (≥1/10) - Common (≥1/100, <1/10) 
System Organ Class Adverse Reactions 
Infection and infestations 
Very common: 
Common: 

 
Viral infection, pharyngitis 
Fungal infection, bacterial infection, pulmonary infection, otitis 



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media, tooth abscess, herpes simplex, urinary tract infection, 
vaginitis, gastroenteritis 

Neoplasms benign, malignant 
and unspecified (including 
cysts and polyps) 
Common: 

 
 
 
Neoplasm (unspecified) 

Blood and lymphatic system 
disorders 
Very common: 
Common: 

 
 
Anaemia, neutropaenia 
Thrombocytopaenia, lymphadenopathy 

Endocrine disorders 
Very common: 
Common: 

 
Hypothyroidism§,  
Hyperthyroidism§, virilism 

Metabolism and nutrition 
disorders 
Very common: 
Common: 

 
 
Anorexia 
Hypertriglyceridemia§, hyperuricemia, increased appetite 

Psychiatric disorders§ 
Very common: 
Common: 

 
Depression, emotional lability, insomnia 
Suicidal ideation, aggressive reaction, confusion, behaviour 
disorder, agitation, somnambulism, anxiety, nervousness, sleep 
disorder, abnormal dreaming, apathy 

Nervous system disorders§ 
Very common: 
Common: 

 
Headache, dizziness 
Hyperkinesia, tremor, dysphonia, paresthaesia, hypoaesthesia, 
hyperaesthesia, concentration impaired, somnolence 

Eye disorders 
Common: 

 
Conjunctivitis, eye pain, abnormal vision, lacrimal gland disorder 

Vascular disorders 
Common: 

 
Raynaud’s disease, flushing, pallor 

Respiratory, thoracic and 
mediastinal disorders 
Common: 

 
 
Dyspnoea, tachypnea, epistaxis, coughing, nasal congestion, nasal 
irritation, rhinorrhea, sneezing 

Gastrointestinal disorders 
Very common: 
Common: 

 
Diarrhoea, vomiting, nausea, abdominal pain 
Mouth ulceration, stomatitis ulcerative, stomatitis, right upper 
quadrant pain, dyspepsia, glossitis, gastroesophogeal reflux, rectal 
disorder, gastrointestinal disorder, constipation, loose stools, 
toothache, tooth disorder 

Hepatobiliary disorders 
Common: 

 
Hepatic function abnormal 

Skin and subcutaneous tissue 
disorders  
Very common: 
Common: 

 
 
Alopecia, rash 
Photosensitivity reaction, maculopapular rash, eczema, acne, skin 
disorder, nail disorder, skin discolouration, pruritus, dry skin, 
erythema, bruise, sweating increased 

Musculoskeletal and 
connective tissue disorders 
Very common: 

 
 
Arthralgia, myalgia, musculoskeletal pain  

Renal and urinary disorders 
Common: 

 
Enuresis, micturition disorder, urinary incontinence 

Reproductive system and  



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breast disorders 
Common: 

 
Female: amenorrhea, menorrhagia, menstrual disorder, vaginal 
disorder 
Male: testicular pain 

General disorders and 
administration site 
conditions 
Very common: 
 
Common: 

 
 
 
Injection site inflammation, injection site reaction, fatigue, rigors, 
fever§, influenza-like symptoms§, malaise, irritability 
Chest pain, asthenia, oedema, injection site pain 

Investigations 
Very common: 

 
Growth rate decrease (height and/or weight decrease for age)§  

Injury and poisoning 
Common: 

 
Skin laceration 

§See section 4.4 
 
4.9 Overdose 
 
No case of overdose has been reported that has led to acute clinical manifestations. However, as for any 
pharmacologically active compound, symptomatic treatment with frequent monitoring of vital signs and close 
observation of the patient is indicated. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunostimulants, cytokines and immunomodulators, interferons, interferon 
alfa-2b, ATC code: L03A B05 
 
Viraferon is a sterile, stable, formulation of highly purified interferon alfa-2b produced by recombinant DNA 
techniques. Recombinant interferon alfa-2b is a water-soluble protein with a molecular weight of 
approximately 19,300 daltons. It is obtained from a clone of E. coli, which harbours a genetically engineered 
plasmid hybrid encompassing an interferon alfa-2b gene from human leukocytes. 
 
The activity of Viraferon is expressed in terms of IU, with 1 mg of recombinant interferon alfa-2b protein 
corresponding to 2.6 x l08 IU. International Units are determined by comparison of the activity of the 
recombinant interferon alfa-2b with the activity of the international reference preparation of human leukocyte 
interferon established by the World Health Organisation. 
 
The interferons are a family of small protein molecules with molecular weights of approximately 15,000 to 
21,000 daltons. They are produced and secreted by cells in response to viral infections or various synthetic 
and biological inducers. Three major classes of interferons have been identified: alpha, beta and gamma. 
These three main classes are themselves not homogeneous and may contain several different molecular 
species of interferon. More than 14 genetically distinct human alpha interferons have been identified. 
Viraferon has been classified as recombinant interferon alfa-2b. 
 
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. 
Human interferon receptors, as isolated from human lymphoblastoid (Daudi) cells, appear to be highly 
asymmetric proteins. They exhibit selectivity for human but not murine interferons, suggesting species 
specificity. Studies with other interferons have demonstrated species specificity. However, certain monkey 
species, eg, rhesus monkeys, are susceptible to pharmacodynamic stimulation upon exposure to human type 
1 interferons. 
 



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The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex 
sequence of intracellular events that include the induction of certain enzymes. It is thought that this process, 
at least in part, is responsible for the various cellular responses to interferon, including inhibition of virus 
replication in virus-infected cells, suppression of cell proliferation and such immunomodulating activities as 
enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of 
lymphocytes for target cells. Any or all of these activities may contribute to interferon's therapeutic effects. 
 
Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and 
human cell culture systems as well as human tumour xenografts in animals. It has demonstrated significant 
immunomodulatory activity in vitro. 
 
Recombinant interferon alfa-2b also inhibits viral replication in vitro and in vivo. Although the exact antiviral 
mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism. 
This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell. 
 
Chronic hepatitis B: 
Current clinical experience in patients who remain on interferon alfa-2b for 4 to 6 months indicates that 
therapy can produce clearance of serum HBV-DNA. An improvement in liver histology has been observed. 
In adult patients with loss of HBeAg and HBV-DNA, a significant reduction in morbidity and mortality has 
been observed. 
 
Interferon alfa-2b (6 MIU/m2 3 times a week for 6 months) has been given to children with chronic active 
hepatitis B. Because of a methodological flaw, efficacy could not be demonstrated. Moreover children treated 
with interferon alfa-2b experienced a reduced rate of growth and some cases of depression were observed. 
 
Chronic hepatitis C: 
In adult patients receiving interferon in combination with ribavirin, the achieved sustained response rate is 
47 %. Superior efficacy has been demonstrated with the combination of pegylated interferon with ribavirin 
(sustained response rate of 61 % achieved in a study performed in naïve patients with a ribavirin dose 
> 10.6 mg/kg, p < 0.01). 
 
Adult patients: Viraferon alone or in combination with ribavirin has been studied in 4 randomised Phase III 
clinical trials in 2,552 interferon-naïve patients with chronic hepatitis C. The trials compared the efficacy of 
Viraferon used alone or in combination with ribavirin. Efficacy was defined as sustained virologic response, 
6 months after the end of treatment. Eligible patients for these trials had chronic hepatitis C confirmed by a 
positive HCV-RNA polymerase chain reaction assay (PCR) (> 100 copies/ml), a liver biopsy consistent with 
a histologic diagnosis of chronic hepatitis with no other cause for the chronic hepatitis, and abnormal serum 
ALT. 
 
Viraferon was administered at a dose of 3 MIU 3 times a week as monotherapy or in combination with 
ribavirin. The majority of patients in these clinical trials were treated for one year. All patients were followed 
for an additional 6 months after the end of treatment for the determination of sustained virologic response. 
Sustained virologic response rates for treatment groups treated for one year with Viraferon alone or in 
combination with ribavirin (from two studies) are shown in Table 3. 
 
Co-administration of Viraferon with ribavirin increased the efficacy of Viraferon by at least two fold for the 
treatment of chronic heptatitis C in naïve patients. HCV genotype and baseline virus load are prognostic 
factors which are known to affect response rates. The increased response rate to the combination of Viraferon + 
ribavirin, compared with Viraferon alone, is maintained across all subgroups. The relative benefit of combination 
therapy with Viraferon + ribavirin is particularly significant in the most difficult to treat subgroup of patients 
(genotype 1 and high virus load) (Table 3). 
 
Response rates in these trials were increased with compliance. Regardless of genotype, patients who received 
Viraferon in combination with ribavirin and received ≥ 80 % of their treatment had a higher sustained 



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response 6 months after 1 year of treatment than those who took < 80 % of their treatment (56 % vs. 32 % in 
trial C/I98-580).  
 

Table 3 Sustained virologic response rates with Viraferon + ribavirin (one year of 
treatment) by genotype and viral load 

 
HCV Genotype  
 

I 
N=503 

C95-132/I95-143 

I/R 
N=505 

C95-132/I95-143 

I/R 
N=505 

C/I98-580 
 
All Genotypes 

 
16 % 

 
41 % 

 
47 % 

 
 
Genotype 1 

 
9 % 

 
29 % 

 
33 % 

 
Genotype 1  
≤ 2 million 
copies/ml 

 
25 % 

 
33 % 

 
45 % 

 
Genotype 1 
> 2 million 
copies/ml 

 
3 % 

 
27 % 

 

 
29 % 

 
Genotype 2/3 

 
31 % 

 
65 % 

 
79 % 

I Viraferon (3 MIU 3 times a week) 
I/R Viraferon (3 MIU 3 times a week) + ribavirin (1,000/1,200 mg/day) 
 
HCV/HIV Co-infected patients  
Two trials have been conducted in patients co-infected with HIV and HCV. Overall, in both studies, patients 
who received Viraferon plus ribavirin, were less likely to respond than patients who received pegylated 
interferon alfa-2b with ribavirin. The response to treatment in both of these trials is presented in Table 4. 
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 412 previously untreated 
adult patients with chronic hepatitis C who were co-infected with HIV. Patients were randomized to receive 
either pegylated interferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800 mg/day) or Viraferon (3 MIU TIW) 
plus ribavirin (800 mg/day) for 48 weeks with a follow-up period of 6 months. Study 2 (P02080) was a 
randomized, single centre study that enrolled 95 previously untreated adult patients with chronic hepatitis C 
who were co-infected with HIV. Patients were randomized to receive either pegylated interferon alfa-2b (100 
or 150 µg /week based on weight) plus ribavirin (800-1,200 mg/day based on weight) or Viraferon (3 MIU 
TIW) plus ribavirin (800-1,200 mg/day based on weight). The duration of therapy was 48 weeks with a 
follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load 
< 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6-month follow-up period.  
           
Table 4 Sustained virological response based on genotype after Viraferon in combination with 

ribavirin versus pegylated interferon alfa-2b in combination with ribavirin in 
HCV/HIV co-infected patients 

 Study 11 Study 22 
 

pegylated 
interferon 

alfa-2b  
(1.5 µg/kg/ 

week) + 
ribavirin  
(800 mg) 

Viraferon  
(3 MIU TIW) +  

ribavirin  
(800 mg) 

p 
valuea 

pegylated 
interferon 

alfa-2b (100 
or  

150c µg/week) 
+ ribavirin 

(800- 
1,200 mg)d 

Viraferon  
(3 MIU TIW) 

+ ribavirin 
(800- 

1,200 mg)d 
p 

valueb 



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All 27 % (56/205) 20 % (41/205) 0.047 44 % (23/52) 21 % (9/43) 0.017 
Genotype 1, 

4 
17 % (21/125) 6 % (8/129) 0.006 38 % (12/32) 7 % (2/27) 0.007 

Genotype 2, 
3 

44 % (35/80) 43 % (33/76) 0.88 53 % (10/19) 47 % (7/15) 0.730 

MIU = million international units; TIW = three times a week. 
a:  p value based on Cochran-Mantel Haenszel Chi square test. 
b:  p value based on chi-square test. 
c:  subjects < 75 kg received 100 µg/week pegylated interferon alfa-2b and subjects ≥ 75 kg received 150 µg/week pegylated 

interferon alfa-2b. 
d: ribavirin dosing was 800 mg for patients < 60 kg, 1,000 mg for patients 60-75 kg, and 1,200 mg for patients > 75 kg. 
 

1Carrat F, Bani-Sadr F, Pol S et al.  JAMA 2004; 292(23): 2839-2848. 
2 Laguno M, Murillas J, Blanco J.L et al.  AIDS 2004; 18(13): F27-F36. 
 
 
Relapse patients: A total of 345 interferon alpha relapse patients were treated in two clinical trials with 
Viraferon monotherapy or in combination with ribavirin. In these patients, the addition of ribavirin to 
Viraferon increased by as much as 10-fold the efficacy of Viraferon used alone in the treatment of chronic 
hepatitis C (48.6 % vs. 4.7 %). This enhancement in efficacy included loss of serum HCV (< 100 copies/ml 
by PCR), improvement in hepatic inflammation, and normalisation of ALT, and was sustained when 
measured 6 months after the end of treatment. 
 
Long-Term efficacy data 
In a large study, 1,071 patients were enrolled after treatment in a prior non pegylated interferon alfa-2b or 
non pegylated interferon alfa-2b/ribavirin study to evaluate the durability of sustained virologic response and 
assess the impact of continued viral negativity on clinical outcomes. 462 patients completed at least 5 years 
of long-term follow-up and only 12 sustained responders' out of 492 relapsed during this study.  
The Kaplan-Meier estimate for continued sustained response over 5 years for all patients is 97 % with a 95 % 
Confidence Interval of [95 %, 99 %].  
SVR after treatment of chronic HCV with non pegylated interferon alfa-2b (with or without ribavirin) results 
in long-term clearance of the virus providing resolution of the hepatic infection and clinical 'cure' from 
chronic HCV. However, this does not preclude the occurrence of hepatic events in patients with cirrhosis 
(including hepatocarcinoma). 
 
Clinical trials in paediatric patients with chronic hepatitis C: 
Children and adolescents 3 to 16 years of age with compensated chronic hepatitis C and detectable HCV-
RNA (assessed by a central laboratory using a research-based RT-PCR assay) were enrolled in two 
multicentre trials and received Viraferon 3 MIU/m2 3 times a week plus ribavirin 15 mg/kg per day for 1 year 
followed by 6 months follow-up after-treatment. A total of 118 patients were enrolled: 57 % male, 80 % 
Caucasian, and 78 % genotype 1,64 % ≤ 12 years of age. The population enrolled mainly consisted in 
children with mild to moderate hepatitis C. Sustained virological response rates in children and adolescents 
were similar to those in adults. Due to the lack of data in children with severe progression of the disease, and 
the potential for undesirable effects, the benefit/risk of the combination of ribavirin and interferon alfa-2b 
needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8). 
 
Study results are summarized in Table 5. 
 
Table 5. Virological response in previously untreated paediatric patients 
 Viraferon 3 MIU/m2 3 times a week   

+ 
ribavirin 15 mg/kg/day 

Overall Response1 (n=118) 54 (46 %)* 



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Genotype 1 (n=92) 33 (36 %)* 

Genotype 2/3/4 (n=26) 21 (81 %)* 

*Number (%) of patients 
1. Defined as HCV-RNA below limit of detection using a research based RT-PCR assay at end of treatment and during follow-up 
period 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of Viraferon were studied in healthy volunteers following single 5 million IU/m2 and 
10 million IU doses administered subcutaneously, at 5 million IU/m2 administered intramuscularly and as a 
30-minute intravenous infusion. The mean serum interferon concentrations following subcutaneous and 
intramuscular injections were comparable. Cmax occurred three to 12 hours after the lower dose and six to 
eight hours after the higher dose. The elimination half-lives of interferon injections were approximately two 
to three hours, and six to seven hours, respectively. Serum levels were below the detection limit 16 and 
24 hours, respectively, post-injection. Both subcutaneous and intramuscular administration resulted in 
bioavailabilities greater than 100 %. 
 
After intravenous administration, serum interferon levels peaked (135 to 273 IU/ml) by the end of the 
infusion, then declined at a slightly more rapid rate than after subcutaneous or intramuscular administration 
of medicinal product, becoming undetectable four hours after the infusion. The elimination half-life was 
approximately two hours. 
 
Urine levels of interferon were below the detection limit following each of the three routes of administration. 
 
Children and adolescents: Multiple-dose pharmacokinetic properties for Viraferon injection and ribavirin 
capsules in children and adolescents with chronic hepatitis C, between 5 and 16 years of age, are summarized 
in Table 6. The pharmacokinetics of Viraferon and ribavirin (dose-normalized) are similar in adults and 
children or adolescents. 
 

Table 6. Mean (% CV) multiple-dose pharmacokinetic parameters for Viraferon and ribavirin 
capsules when administered to children or adolescents with chronic hepatitis C 
Parameter Ribavirin 

15 mg/kg/day as 2 divided 
doses 

(n = 17) 

Viraferon 
3 MIU/m2 3 times a week 

(n = 54) 

Tmax (hr) 1.9 (83) 5.9 (36) 
Cmax (ng/ml) 3,275 (25) 51 (48) 

AUC* 29,774 (26) 622 (48) 
Apparent clearance l/hr/kg 0.27 (27) Not done 

*AUC12 (ng.hr/ml) for ribavirin; AUC0-24 (IU.hr/ml) for Viraferon 
 
Interferon neutralising factor assays were performed on serum samples of patients who received Viraferon in 
Schering-Plough monitored clinical trials. Interferon neutralising factors are antibodies which neutralise the 
antiviral activity of interferon. The clinical incidence of neutralising factors developing in cancer patients 
treated systemically is 2.9 % and in chronic hepatitis patients is 6.2 %. The detectable titres are low in almost 
all cases and have not been regularly associated with loss of response or any other autoimmune phenomenon. 
In patients with hepatitis, no loss of response was observed apparently due to the low titres. 
 
5.3 Preclinical safety data 
 
Although interferon is generally recognised as being species specific, toxicity studies in animals were 
conducted. Injections of human recombinant interferon alfa-2b for up to three months have shown no 
evidence of toxicity in mice, rats, and rabbits. Daily dosing of cynomolgus monkeys with 20 x 106 IU/kg/day 



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for 3 months caused no remarkable toxicity. Toxicity was demonstrated in monkeys given 
100 x 106 IU/kg/day for 3 months. 
 
In studies of interferon use in non-human primates, abnormalities of the menstrual cycle have been observed 
(see section 4.4). 
 
Results of animal reproduction studies indicate that recombinant interferon alfa-2b was not teratogenic in rats 
or rabbits, nor did it adversely affect pregnancy, foetal development or reproductive capacity in offspring of 
treated rats. Interferon alfa-2b has been shown to have abortifacient effects in Macaca mulatta (rhesus 
monkeys) at 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2. 
Abortion was observed in all dose groups (7.5 million, 15 million and 30 million IU/kg), and was statistically 
significant versus control at the mid- and high-dose groups (corresponding to 90 and 180 times the 
recommended intramuscular or subcutaneous dose of 2 million IU/m2). High doses of other forms of 
interferons alpha and beta are known to produce dose-related anovulatory and abortifacient effects in rhesus 
monkeys. 
 
Mutagenicity studies with interferon alfa-2b revealed no adverse events. 
 
No studies have been conducted in juvenile animals to examine the effects of treatment with interferon alfa-
2b on growth, development, sexual maturation, and behaviour (see section 4.4 and Rebetol SPC if Viraferon 
is to be administered in combination with ribavirin). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Disodium phosphate anhydrous,  
Sodium dihydrogen phosphate monohydrate,  
Edetate disodium,  
Sodium chloride,  
M-cresol,  
Polysorbate 80,  
Water for injections q.s.  
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
15 months 
 
Chemical and physical in-use stability has been demonstrated for 27 days at 2ºC – 8ºC. 
From a microbiological point of view, once opened, the product may be stored for a maximum of 27 days at 
2ºC – 8ºC. Other in-use storage times and conditions are the responsibility of the user. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C).  
Do not freeze. 
 
6.5 Nature and contents of container 
 



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1.2 ml of solution (corresponding to 18 MIU) in a pen made of a cartridge (type I glass) sealed at one end 
with an cap (aluminium) containing a liner (bromobutyl rubber) and at the other end by a plunger 
(bromobutyl rubber)  
with 12 injection needles and12 cleansing swabs 
Pack sizes of 1, 2 or 8 
Not all pack sizes may be marketed. 
 
The pen is designed to deliver its contents of 18 million IU in doses ranging from 1.5 to 6 million IU. The 
pen will deliver a maximum of 12 doses of 1.5 million IU over a period not to exceed 4 weeks. 
 
6.6 Special precautions for disposal 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
Viraferon, solution for injection, multidose pen is injected subcutaneously after attaching an injection needle 
and dialing the prescribed dose. 
 
Remove the pen from the refrigerator approximately 30 minutes before administration to allow the injectable 
solution to reach room temperature (not more than 25°C). 
 
Detailed instructions for the subcutaneous use of the product are provided with the package leaflet (refer to 
“How to self inject Viraferon”). 
 
Each pen is intended for a maximum four-week use period and must then be discarded. A new injection 
needle must be used for each dose. After each use, the injection needle must be discarded safely and the pen 
must be returned immediately to the refrigerator. A maximum of 48 hours (two days) of exposure to 25°C is 
permitted over the four-week use period to cover accidental delays in returning the pen to the refrigerator. 
Sufficient needles and swabs are provided to use the Viraferon pen for administering the smallest measurable 
doses. Instruct the patient that any extra needles and swabs that remain after the final dose has been taken 
from the pen, must be discarded appropriately and safely. 
 
As with all parenteral medicinal products, prior to administration inspect Viraferon, solution for injection, 
visually for particulate matter and discolouration. The solution should be clear and colourless. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
SP Europe 
73, rue de Stalle 
B-1180 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/99/128/029 
EU/1/99/128/030 
EU/1/99/128/031 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation : 9 March 2000 
Date of last renewal : 23 May 2005 



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10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu/ 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 30 million IU solution for injection, multidose pen 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One cartridge contains 30 million IU of recombinant interferon alfa-2b produced in E.coli by recombinant 
DNA technology, in 1.2 ml. 
 
One ml contains 25 million IU of interferon alfa-2b. 
 
The pen is designed to deliver its contents of 30 million IU in doses ranging from 2.5 to 10 million IU. The 
pen will deliver a maximum of 12 doses of 2.5 million IU over a period not to exceed 4 weeks. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection 
Solution is clear and colourless. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Chronic Hepatitis B: Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis B 
viral replication (presence of HBV-DNA and HBeAg), elevated alanine aminotransferase (ALT) and 
histologically proven active liver inflammation and/or fibrosis. 
 
Chronic Hepatitis C:  
Adult patients:  
Viraferon is indicated for the treatment of adult patients with chronic hepatitis C who have elevated 
transaminases without liver decompensation and who are positive for serum HCV-RNA or anti-HCV (see 
section 4.4). 
 
The best way to use Viraferon in this indication is in combination with ribavirin. 
 
Chidren and adolescents: 
Viraferon is intended for use, in a combination regimen with ribavirin, for the treatment of children and 
adolescents 3 years of age and older, who have chronic hepatitis C, not previously treated, without liver 
decompensation, and who are positive for serum HCV-RNA. The decision to treat should be made on a case 
by case basis, taking into account any evidence of disease progression such as hepatic inflammation and 
fibrosis, as well as prognostic factors for response, HCV genotype and viral load. The expected benefit of 
treatment should be weighed against the safety findings observed for paediatric subjects in the clinical trials 
(see sections 4.4, 4.8 and 5.1). 
 
4.2 Posology and method of administration 
 
Treatment must be initiated by a physician experienced in the management of the disease. 
 
Multidose presentations must be for individual patient use only. 
 



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Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
If adverse events develop during the course of treatment with Viraferon for any indication, modify the dosage 
or discontinue therapy temporarily until the adverse events abate. If persistent or recurrent intolerance 
develops following adequate dosage adjustment, or disease progresses, discontinue treatment with Viraferon. 
At the discretion of the physician, the patient may self-administer the dose for maintenance dosage regimens 
administered subcutaneously. 
 
Chronic Hepatitis B: The recommended dosage is in the range 5 to 10 million IU administered 
subcutaneously three times a week (every other day) for a period of 4 to 6 months. 
 
The administered dose should be reduced by 50 % in case of occurrence of haematological disorders (white 
blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3). Treatment should be 
discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe 
thrombocytopaenia (< 70,000/mm3). 
 
For all patients, if no improvement on serum HBV-DNA is observed after 3 to 4 months of treatment (at the 
maximum tolerated dose), discontinue Viraferon therapy. 
 
Chronic Hepatitis C: Viraferon is administered subcutaneously at a dose of 3 million IU three times a week 
(every other day) to adult patients, whether administered as monotherapy or in combination with ribavirin. 
 
Children 3 years of age or older and adolescents: Interferon alfa-2b 3 MIU/m2 is administered 
subcutaneously 3 times a week (every other day) in combination with ribavirin capsules or oral solution 
administered orally in two divided doses daily with food (morning and evening).  
 
(See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination 
therapy. For paediatric patients who weigh < 47 kg or cannot swallow capsules, see ribavirin oral solution 
SPC).  
 
Relapse patients (adults): 
Viraferon is given in combination with ribavirin. 
 
Based on the results of clinical trials, in which data are available for 6 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for 6 months. 
 
Naïve patients: 
Adults: The efficacy of Viraferon is enhanced when given in combination with ribavirin. Viraferon should be 
given alone mainly in case of intolerance or contraindication to ribavirin. 
 
Viraferon in combination with ribavirin: 
Based on the results of clinical trials, in which data are available for 12 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for at least 6 months. 
 
Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit 
negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and 
high pre-treatment viral load. 
 
Other negative prognostic factors (age > 40 years, male gender, bridging fibrosis) should be taken into 
account in order to extend therapy to 12 months. 
 
During clinical trials, patients who failed to show a virologic response after 6 months of treatment (HCV-
RNA below lower limit of detection) did not become sustained virologic responders (HCV-RNA below lower 
limit of detection six months after withdrawal of treatment). 



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Viraferon alone: 
The optimal duration of therapy with Viraferon alone is not yet fully established, but a therapy of between 
12 and 18 months is advised. 
 
It is recommended that patients be treated with Viraferon alone for at least 3 to 4 months, at which point 
HCV-RNA status should be determined. Treatment should be continued in patients who exhibit negative 
HCV-RNA. 
 
Children and adolescents: The efficacy and safety of Viraferon in combination with ribavirin has been 
studied in children and adolescents who have not been previously treated for chronic hepatitis C.  
 
Genotype 1: The recommended duration of treatment is one year. Patients who fail to achieve virological 
response at 12 weeks are highly unlikely to become sustained virological responders (negative predictive 
value 96 %). Virological response is defined as absence of detectable HCV-RNA at Week 12. Treatment 
should be discontinued in these patients. 
Genotype 2/3: The recommended duration of treatment is 24 weeks. 
 
Virological responses after 1 year of treatment and 6 months of follow-up were 36 % for genotype 1 and 
81 % for genotype 2/3/4. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients. 
- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure, recent 

myocardial infarction, severe arrhythmic disorders.  
- Severe renal or hepatic dysfunction; including that caused by metastases. 
- Epilepsy and/or compromised central nervous system (CNS) function (see section 4.4). 
- Chronic hepatitis with decompensated cirrhosis of the liver. 
- Chronic hepatitis in patients who are being or have been treated recently with immunosuppressive 

agents excluding short term corticosteroid withdrawal. 
- Autoimmune hepatitis; or history of autoimmune disease; immunosuppressed transplant recipients. 
- Pre-existing thyroid disease unless it can be controlled with conventional treatment. 
 
Children and adolescents: 
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal 

ideation or suicide attempt. 
 

Combination therapy with ribavirin: Also see ribavirin SPC if interferon alfa-2b is to be administered in 
combination with ribavirin in patients with chronic hepatitis C. 
 
4.4 Special warnings and precautions for use 
 
For all patients: 
Psychiatric and central nervous system (CNS): Severe CNS effects, particularly depression, suicidal ideation 
and attempted suicide have been observed in some patients during Viraferon therapy, and even after 
treatment discontinuation mainly during the 6-month follow-up periodand in the follow-up period. Among 
children and adolescents treated with Viraferon in combination with ribavirin, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6-month 
follow-up after treatment. As in adult patients, children and adolescents experienced other psychiatric adverse 
events (e.g., depression, emotional lability, and somnolence). Other CNS effects including aggressive behaviour 
(sometimes directed against others), confusion and alterations of mental status have been observed with alpha 
interferons. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such 
symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the 
prescribing physician and the need for adequate therapeutic management should be considered. If psychiatric 



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symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with 
Viraferon be discontinued, and the patient followed, with psychiatric intervention as appropriate. 
 
Patients with existence of or history of severe psychiatric conditions: 
If a treatment with interferon alfa-2b is judged necessary in adult patients with existence or history of severe 
psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and 
therapeutic management of the psychiatric condition. The use of interferon alfa-2b in children and adolescents 
with existence of or history of severe psychiatric conditions is contraindicated (see section 4.3). 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Moderate to severe adverse experiences may require modification of the patient's dosage regimen, or in some 
cases, termination of Viraferon therapy. Any patient developing liver function abnormalities during treatment 
with Viraferon must be monitored closely and treatment discontinued if signs and symptoms progress. 
 
Hypotension may occur during Viraferon therapy or up to two days post-therapy and may require supportive 
treatment. 
 
Adequate hydration must be maintained in patients undergoing Viraferon therapy since hypotension related 
to fluid depletion has been seen in some patients. Fluid replacement may be necessary. 
 
While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, 
other causes of persistent fever must be ruled out. 
 
Viraferon must be used cautiously in patients with debilitating medical conditions, such as those with a 
history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to 
ketoacidosis. Caution must be observed also in patients with coagulation disorders (e.g., thrombophlebitis, 
pulmonary embolism) or severe myelosuppression. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.5). Any patient developing fever, cough, 
dyspnea or other respiratory symptoms must have a chest X-ray taken. If the chest X-ray shows pulmonary 
infiltrates or there is evidence of pulmonary function impairment, the patient is to be monitored closely, and, 
if appropriate, discontinue interferon alpha. While this has been reported more often in patients with chronic 
hepatitis C treated with interferon alpha, it has also been reported in patients with oncologic diseases treated 
with interferon alpha. Prompt discontinuation of interferon alpha administration and treatment with 
corticosteroids appear to be associated with resolution of pulmonary adverse events. 
 
Ocular adverse events (see section 4.8) including retinal haemorrhages, cotton wool spots, and retinal artery 
or vein obstruction have been reported in rare instance after treatment with alpha interferons. All patients 
should have a baseline eye examination. Any patient complaining of changes in visual acuity or visual fields, 
or reporting other ophthalmologic symptoms during treatment with Viraferon, must have a prompt and 
complete eye examination. Periodic visual examinations during Viraferon therapy are recommended 
particularly in patients with disorders that may be associated with retinopathy, such as diabetes mellitus or 
hypertension. Discontinuation of Viraferon should be considered in patients who develop new or worsening 
ophthalmological disorders. 



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More significant obtundation and coma, including cases of encephalopathy, have been observed in some 
patients, usually elderly, treated at higher doses. While these effects are generally reversible, in a few patients 
full resolution took up to three weeks. Very rarely, seizures have occurred with high doses of Viraferon. 
 
Adult patients with a history of congestive heart failure, myocardial infarction and/or previous or current 
arrhythmic disorders, who require Viraferon therapy, must be closely monitored. It is recommended that 
those patients who have pre-existing cardiac abnormalities and/or are in advanced stages of cancer have 
electrocardiograms taken prior to and during the course of treatment. Cardiac arrhythmias (primarily 
supraventricular) usually respond to conventional therapy but may require discontinuation of Viraferon 
therapy. There are no data in children or adolescents with a history of cardiac disease. 
 
Hypertriglyceridemia and aggravation of hypertriglyceridemia, sometimes severe, have been observed. 
Monitoring of lipid levels is, therefore, recommended. 
 
Due to reports of interferon alpha exacerbating pre-existing psoriatic disease and sarcoidosis, use of 
Viraferon in patients with psoriasis or sarcoidosis is recommended only if the potential benefit justifies the 
potential risk. 
 
Preliminary data indicates that interferon alpha therapy may be associated with an increased rate of kidney 
graft rejection. Liver graft rejection has also been reported. 
 
The development of auto-antibodies and autoimmune disorders has been reported during treatment with alpha 
interferons. Patients predisposed to the development of autoimmune disorders may be at increased risk. 
Patients with signs or symptoms compatible with autoimmune disorders should be evaluated carefully, and 
the benefit-risk of continued interferon therapy should be reassessed (see also section 4.4 Chronic hepatitis C, 
Monotherapy (thyroid abnormalities) and section 4.8). 
Cases of Vogt-Koyanagi-Harada (VKH) syndrome have been reported in patients with chronic hepatitis C 
treated with interferon. This syndrome is a granulomatous inflammatory disorder affecting the eyes, auditory 
system, meninges, and skin. If VKH syndrome is suspected, antiviral treatment should be withdrawn and 
corticosteroid therapy discussed (see section 4.8). 
 
Discontinue treatment with Viraferon in patients with chronic hepatitis who develop prolongation of 
coagulation markers which might indicate liver decompensation. 
 
Chronic Hepatitis C: 
Combination therapy with ribavirin: Also see ribavirin SPC if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i.e. 
patients with genotype 2 and 3), treatment may be possible without histological confirmation. Current 
treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing 
treatment. 
 
Monotherapy: Infrequently, adult patients treated for chronic hepatitis C with Viraferon developed thyroid 
abnormalities, either hypothyroidism or hyperthyroidism. In clinical trials using Viraferon therapy, 2.8 % 
patients overall developed thyroid abnormalities. The abnormalities were controlled by conventional therapy 
for thyroid dysfunction. The mechanism by which Viraferon may alter thyroid status is unknown. Prior to 
initiation of Viraferon therapy for the treatment of chronic hepatitis C, evaluate serum thyroid-stimulating 
hormone (TSH) levels. Any thyroid abnormality detected at that time must be treated with conventional 
therapy. Viraferon treatment may be initiated if TSH levels can be maintained in the normal range by 
medication. Determine TSH levels if, during the course of Viraferon therapy, a patient develops symptoms 
consistent with possible thyroid dysfunction. In the presence of thyroid dysfunction, Viraferon treatment may 
be continued if TSH levels can be maintained in the normal range by medication. Discontinuation of 



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Viraferon therapy has not reversed thyroid dysfunction occurring during treatment (also see Children and 
adolescents, Thyroid monitoring). 
 
Supplemental monitoring specific for children and adolescents 
Thyroid Monitoring: Approximately 12 % of children treated with interferon alfa-2b and ribavirin developed 
increase in TSH. Another 4 % had a transient decrease below the lower limit of normal. Prior to initiation of 
Viraferon therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be 
treated with conventional therapy. Viraferon therapy may be initiated if TSH levels can be maintained in the 
normal range by medication. Thyroid dysfunction during treatment with interferon alfa-2b and ribavirin has 
been observed. If thyroid abnormalities are detected, the patient’s thyroid status should be evaluated and 
treated as clinically appropriate. Children and adolescents should be monitored every 3 months for evidence 
of thyroid dysfunction (e.g. TSH). 
 
Growth and Development: During a 1-year course of therapy there was a decrease in the rate of linear growth 
(mean percentile decrease of 9 %) and a decrease in the rate of weight gain (mean percentile decrease of 
13 %). A general reversal of these trends was noted during the 6 months follow-up post treatment. However, 
based on interim data from a long-term follow-up study, 12 (14 %) of 84 children had a > 15 percentile 
decrease in rate of linear growth, of whom 5 (6 %) children had a > 30 percentile decrease despite being off 
treatment for more than 1 year. In addition, preclicinal juvenile toxicity results have demonstrated a minor, 
dose-related decrease in overall growth in neonatal rats dosed with ribavirin (see section 5.3). Therefore, the 
risk/benefit of the combined use of interferon alfa-2b and ribavirin should be assessed in young children prior 
to the initiation of therapy. Physicians are advised to monitor the growth of children taking ribavirin in 
combination with interferon alfa-2b. There are no data on long term effects on growth and development and 
on sexual maturation. 
 
HCV/HIV Coinfection: Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy 
(HAART) may be at increased risk of developing lactic acidosis. Caution should be used when adding Viraferon 
and ribavirin to HAART therapy (see ribavirin SPC). Patients treated with Viraferon and ribavirin combination 
therapy and zidovudine could be at increased risk of developing anaemia. 
Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic 
decompensation and death. Adding treatment with alfa interferons alone or in combination with ribavirin may 
increase the risk in this patient subset.  
 
Dental and periodontal disorders: Dental and periodontal disorders, which may lead to loss of teeth, have 
been reported in patients receiving Viraferon and ribavirin combination therapy. In addition, dry mouth could 
have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the 
combination of Viraferon and ribavirin. Patients should brush their teeth thoroughly twice daily and have 
regular dental examinations. In addition some patients may experience vomiting. If this reaction occurs, they 
should be advised to rinse out their mouth thoroughly afterwards. 
 
Laboratory Tests:  
Standard haematological tests and blood chemistries (complete blood count and differential, platelet count, 
electrolytes, liver enzymes, serum protein, serum bilirubin and serum creatinine) are to be conducted in all 
patients prior to and periodically during systemic treatment with Viraferon. 
 
During treatment for hepatitis B or C the recommended testing schedule is at weeks 1, 2, 4, 8, 12, 16, and 
every other month, thereafter, throughout treatment. If ALT flares during Viraferon therapy to greater than or 
equal to 2 times baseline, Viraferon therapy may be continued unless signs and symptoms of liver failure are 
observed. During ALT flare, liver function tests: ALT, prothrombin time, alkaline phosphatase, albumin and 
bilirubin must be monitored at two-week intervals. 
 
Effect on fertility: Interferon may impair fertility (see section 4.6 and section 5.3). 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 



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Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with 
Viraferon. 
 
Interactions between Viraferon and other medicinal products have not been fully evaluated. Caution must be 
exercised when administering Viraferon in combination with other potentially myelosuppressive agents. 
 
Interferons may affect the oxidative metabolic process. This must be considered during concomitant therapy 
with medicinal products metabolised by this route, such as the xanthine derivatives theophylline or 
aminophylline. During concomitant therapy with xanthine agents, serum theophylline levels must be 
monitored and dosage adjusted if necessary. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.4). 
 
(Also see ribavirin SPC if Viraferon is to be administered in combination with ribavirin in patients with 
chronic hepatitis C). 
 
4.6 Pregnancy and lactation 
 
Women of childbearing potential have to use effective contraception during treatment. Viraferon must be 
used with caution in fertile men. Decreased serum estradiol and progesterone concentrations have been 
reported in women treated with human leukocyte interferon. 
 
There are no adequate data from the use of interferon alfa-2b in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Viraferon is to be 
used during pregnancy only if the potential benefit justifies the potential risk to the foetus. 
 
It is not known whether the components of this medicinal product are excreted in human milk. Because of the 
potential for adverse reactions in nursing infants, nursing should be discontinued prior to initiation of 
treatment. 
 
Combination therapy with ribavirin: Ribavirin causes serious birth defects when administered during 
pregnancy. Ribavirin therapy is contraindicated in women who are pregnant. Extreme care must be taken to 
avoid pregnancy in female patients or in partners of male patients taking Viraferon in combination with 
ribavirin. Females of childbearing potential and their partners must each use an effective contraceptive during 
treatment and for 4 months after treatment has been concluded. Male patients and their female partners must 
each use an effective contraceptive during treatment and for 7 months after treatment has been concluded (see 
ribavirin SPC). 
 
4.7 Effects on ability to drive and use machines 
 
Patients are to be advised that they may develop fatigue, somnolence, or confusion during treatment with 
Viraferon, and therefore it is recommended that they avoid driving or operating machinery. 
 
4.8 Undesirable effects 
 
See ribavirin SPC for ribavirin-related undesirable effects if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
In clinical trials conducted in a broad range of indications and at a wide range of doses (from 6 MIU/m2/week 
in hairy cell leukaemia up to 100 MIU/m2/week in melanoma), the most commonly reported undesirable 
effects were fever, fatigue, headache and myalgia. Fever and fatigue were often reversible within 72 hours of 
interruption or cessation of treatment. 



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In clinical trials conducted in the hepatitis C population, patients were treated with Viraferon alone or in 
combination with ribavirin for one year. All patients in these trials received 3 MIU of Viraferon three times a 
week. In Table 1 the frequency of patients reporting (treatment related) undesirable effects is presented from 
clinical trials in naïve patients treated for one year. Severity was generally mild to moderate. The adverse 
reactions listed in Table 1 are based on experience from clinical trials and post-marketing. Within the organ 
system classes, adverse reactions are listed under headings of frequency using the following categories: very 
common (≥1/10); common (≥1/100, <1/10); rarely (≥1/10,000, <1/1,000); very rarely (<1/10,000); not 
known. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 
 

Table 1. Adverse reactions reported during clinical trials or following the marketing use of Viraferon 
alone or in combination with ribavirin 

System Organ Class Adverse Reactions 
Infections and infestations 
Very common: 
Common: 
Rarely:  

 
Pharyngitis*, infection viral* 
Bronchitis, sinusitis, herpes simplex (resistance), rhinitis 
Pneumonia§ 

Blood and lymphatic system disorders 
Very common: 
Common: 
Very rarely:  
Not known:  

 
Leukopaenia 
Thrombocytopaenia, lymphadenopathy, lymphopenia 
Aplastic anaemia 
Pure red cell aplasia, idiopathic thrombocytopenic purpura, 
thrombotic thrombocytopenic purpura  

Immune system disorders§ 
Very rarely:  
Not known: 

 
Sarcoidosis, exacerbation of sarcoidosis 
Systemic lupus erythematosus, vasculitis, rheumatoid 
arthritis (new or aggravated), Vogt-Koyanagi-Harada 
syndrome, acute hypersensitivity reactions including 
urticaria, angioedema, bronchoconstriction, anaphylaxis§ 

Endocrine disorders 
Common: 
Very rarely:  

 
Hypothyroidism§, hyperthyroidism§ 
Diabetes, aggravated diabetes 

Metabolism and nutrition disorders 
Very common: 
Common:  
Very rarely:  

 
Anorexia 
Hypocalcaemia, dehydration, hyperuricemia, thirst 
Hyperglycaemia, hypertriglyceridaemia§, increased appetite 

Psychiatric disorders§ 
Very common: 
 
Common: 
Rarely:  
Very rarely: 
 
Not known: 

 
Depression, insomnia, anxiety, emotional lability*, 
agitation, nervousness 
Confusion, sleep disorder, libido decreased 
Suicide ideation 
Suicide, suicide attempts, aggressive behaviour (sometimes 
directed against others), psychosis including hallucinations 
Mental status change§ 

Nervous system disorders§ 
Very common: 
Common: 
 
Very rarely:  
 
 
Not known: 

 
Dizziness, headache, concentration impaired, mouth dry 
Tremor, paresthesia, hypoesthesia, migraine, flushing, 
somnolence, taste perversion 
Cerebrovascular haemorrhage, cerbrovascular ischaemia, 
seizure, impaired consciousness, encephalopathy, 
neuropathy, polyneuropathy 
Mononeuropathies, coma§ 

Eye disorders  



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Very common: 
Common: 
 
Rarely:  

Vision blurred 
Conjunctivitis, vision abnormal, lacrimal gland disorder, eye 
pain 
Retinal haemorrhages§, retinopathies (including macular 
oedema), retinal artery or vein obstruction§, optic neuritis, 
papilloedema, loss of visual acuity or visual field, cotton-
wool spots§  

Ear and labyrinth 
Common: 
Very rarely:  

 
Vertigo, tinnitus 
Hearing loss, hearing disorder 

Cardiac disorders 
Common: 
Rarely: 
Very rarely: 
Not known: 

 
Palpitation, tachycardia 
Cardiomyopathy 
Myocardial infarction, cardiac ischaemia  
Arrhythmia  

Vascular disorders 
Common: 
Very rarely:  

 
Hypertension 
Peripheral ischaemia, hypotension§ 

Respiratory, thoracic and mediastinal 
disorders 
Very common: 
Common: 
 
Very rarely:  

 
 
Dyspnoea*, coughing* 
Epistaxis, respiratory disorder, nasal congestion, rhinorrhea, 
cough nonproductive 
Pulmonary infiltrates§, pneumonitis§ 

Gastrointestinal disorders 
Very common: 
 
Common: 
 
Very rarely:  
 
Not known: 

 
Nausea/vomiting, abdominal pain, diarrhoea, stomatitis, 
dyspepsia 
Stomatitis ulcerative, right upper quadrant pain, glossitis, 
gingivitis, constipation, loose stools 
Pancreatitis, ischaemic colitis, ulcerative colitis, gingival 
bleeding 
Periodontal disorder NOS, dental disorder NOS§ 

Hepatobiliary disorders 
Common: 
Very rarely:  

 
Hepatomegaly 
Hepatotoxicity, (including fatality) 

Skin and subcutaneous tissue disorders 
Very common: 
Common: 
 
Very rarely:  

 
Alopecia, pruritus*, skin dry*, rash*, sweating increased 
Psoriasis (new or aggravated)§, rash maculopapular, rash 
erythematous, eczema, erythema, skin disorder 
Stevens Johnson syndrome, toxic epidermal necrolysis, 
erythema multiforme 

Musculoskeletal and connective tissue 
disorders 
Very common:  
Common: 
Very rarely: 

 
 
Myalgia, arthralgia, musculoskeletal pain 
Arthritis 
Rhabdomyolysis, myositis, leg cramps, back pain 

Renal and urinary disorders 
Common: 
Very rarely:  

 
Micturition frequency 
Renal failure, renal insufficiency, nephrotic syndrome 

Reproductive system and breast 
disorders 
Common: 

 
 
Amenorrhea, breast pain, dysmenorrhea, menorrhagia, 
menstrual disorder, vaginal disorder 

General disorders and administration  



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site conditions 
Very common: 
 
 
Common: 
Very rarely: 

 
Injection site inflammation, injection site reaction*, fatigue, 
rigors, fever§, flu-like symptoms§, asthenia, irritability, chest 
pain, malaise 
Injection site pain 
Injection site necrosis, face oedema 

Investigations 
Very common: 

 
Weight decrease 

*These events were only common with Viraferon alone 
§See section 4.4 
 
These undesirable effects have also been reported with Viraferon alone. 
 
Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-
existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4). Cardiomyopathy, that may 
be reversible upon discontinuation of interferon alpha, has been reported rarely in patients without prior 
evidence of cardiac disease (see section 4.4).  
 
A wide variety of autoimmune and immune-mediated disorders have been reported with alpha interferons 
including thyroid disorders, systemic lupus erythematosus, rheumatoid arthritis (new or aggravated), 
idiopathic and thrombotic thrombocytopenic purpura, vasculitis, neuropathies including mononeuropathies 
(see also section 4.4).  
 
Clinically significant laboratory abnormalities, most frequently occurring at doses greater than 10 million IU 
daily, include reduction in granulocyte and white blood cell counts; decreases in haemoglobin level and 
platelet count; increases in alkaline phosphatase, LDH, serum creatinine and serum urea nitrogen levels. 
Increase in serum ALT/AST (SGPT/SGOT) levels have been noted as an abnormality in some non-hepatitis 
subjects and also in some patients with chronic hepatitis B coincident with clearance of viral DNAp. 
 
Paediatric population 
 
Children and adolescents – Chronic Hepatitis C 
In clinical trials of 118 children or adolescents 3 to 16 years of age, 6 % discontinued therapy due to adverse 
events. In general, the adverse event profile in the limited paediatric population studied was similar to that 
observed in adults, although there is a paediatric specific concern regarding growth inhibition as decrease in 
height (mean percentile decrease of growth velocity of 9 %) and weight (mean percentile decrease of 13 %) 
percentile were observed during treatment (see section 4.4). Furthermore, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6 month 
follow-up after treatment. As in adult patients, children and adolescents also experienced other psychiatric 
adverse events (e.g., depression, emotional lability, and somnolence) (see section 4.4). In addition, injection 
site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in children and 
adolescents compared to adult patients. Dose modifications were required in 30 % of patients, most 
commonly for anaemia and neutropaenia. 
 
The adverse reactions listed in Table 2 are based on experience from paediatric clinical trials.  
Within the organ system classes, adverse reactions are listed under headings of frequency using the following 
categories: very common (≥1/10); common (≥1/100, <1/10). Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness. 
 
Table 2  Adverse reactions very commonly and commonly reported in paediatric clinical trials  

Very common (≥1/10) - Common (≥1/100, <1/10) 
System Organ Class Adverse Reactions 
Infection and infestations 
Very common: 

 
Viral infection, pharyngitis 



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Common: Fungal infection, bacterial infection, pulmonary infection, otitis 
media, tooth abscess, herpes simplex, urinary tract infection, 
vaginitis, gastroenteritis 

Neoplasms benign, malignant 
and unspecified (including 
cysts and polyps) 
Common: 

 
 
 
Neoplasm (unspecified) 

Blood and lymphatic system 
disorders 
Very common: 
Common: 

 
 
Anaemia, neutropaenia 
Thrombocytopaenia, lymphadenopathy 

Endocrine disorders 
Very common: 
Common: 

 
Hypothyroidism§,  
Hyperthyroidism§, virilism 

Metabolism and nutrition 
disorders 
Very common: 
Common: 

 
 
Anorexia 
Hypertriglyceridemia§, hyperuricemia, increased appetite 

Psychiatric disorders§ 
Very common: 
Common: 

 
Depression, emotional lability, insomnia 
Suicidal ideation, aggressive reaction, confusion, behaviour 
disorder, agitation, somnambulism, anxiety, nervousness, sleep 
disorder, abnormal dreaming, apathy 

Nervous system disorders§ 
Very common: 
Common: 

 
Headache, dizziness 
Hyperkinesia, tremor, dysphonia, paresthaesia, hypoaesthesia, 
hyperaesthesia, concentration impaired, somnolence 

Eye disorders 
Common: 

 
Conjunctivitis, eye pain, abnormal vision, lacrimal gland disorder 

Vascular disorders 
Common: 

 
Raynaud’s disease, flushing, pallor 

Respiratory, thoracic and 
mediastinal disorders 
Common: 

 
 
Dyspnoea, tachypnea, epistaxis, coughing, nasal congestion, nasal 
irritation, rhinorrhea, sneezing 

Gastrointestinal disorders 
Very common: 
Common: 

 
Diarrhoea, vomiting, nausea, abdominal pain 
Mouth ulceration, stomatitis ulcerative, stomatitis, right upper 
quadrant pain, dyspepsia, glossitis, gastroesophogeal reflux, rectal 
disorder, gastrointestinal disorder, constipation, loose stools, 
toothache, tooth disorder 

Hepatobiliary disorders 
Common: 

 
Hepatic function abnormal 

Skin and subcutaneous tissue 
disorders  
Very common: 
Common: 

 
 
Alopecia, rash 
Photosensitivity reaction, maculopapular rash, eczema, acne, skin 
disorder, nail disorder, skin discolouration, pruritus, dry skin, 
erythema, bruise, sweating increased 

Musculoskeletal and 
connective tissue disorders 
Very common: 

 
 
Arthralgia, myalgia, musculoskeletal pain  

Renal and urinary disorders 
Common: 

 
Enuresis, micturition disorder, urinary incontinence 



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Reproductive system and 
breast disorders 
Common: 

 
 
Female: amenorrhea, menorrhagia, menstrual disorder, vaginal 
disorder 
Male: testicular pain 

General disorders and 
administration site 
conditions 
Very common: 
 
Common: 

 
 
 
Injection site inflammation, injection site reaction, fatigue, rigors, 
fever§, influenza-like symptoms§, malaise, irritability 
Chest pain, asthenia, oedema, injection site pain 

Investigations 
Very common: 

 
Growth rate decrease (height and/or weight decrease for age)§  

Injury and poisoning 
Common: 

 
Skin laceration 

§See section 4.4 
 
4.9 Overdose 
 
No case of overdose has been reported that has led to acute clinical manifestations. However, as for any 
pharmacologically active compound, symptomatic treatment with frequent monitoring of vital signs and close 
observation of the patient is indicated. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunostimulants, cytokines and immunomodulators, interferons, interferon 
alfa-2b, ATC code: L03A B05 
 
Viraferon is a sterile, stable, formulation of highly purified interferon alfa-2b produced by recombinant DNA 
techniques. Recombinant interferon alfa-2b is a water-soluble protein with a molecular weight of 
approximately 19,300 daltons. It is obtained from a clone of E. coli, which harbours a genetically engineered 
plasmid hybrid encompassing an interferon alfa-2b gene from human leukocytes. 
 
The activity of Viraferon is expressed in terms of IU, with 1 mg of recombinant interferon alfa-2b protein 
corresponding to 2.6 x l08 IU. International Units are determined by comparison of the activity of the 
recombinant interferon alfa-2b with the activity of the international reference preparation of human leukocyte 
interferon established by the World Health Organisation. 
 
The interferons are a family of small protein molecules with molecular weights of approximately 15,000 to 
21,000 daltons. They are produced and secreted by cells in response to viral infections or various synthetic 
and biological inducers. Three major classes of interferons have been identified: alpha, beta and gamma. 
These three main classes are themselves not homogeneous and may contain several different molecular 
species of interferon. More than 14 genetically distinct human alpha interferons have been identified. 
Viraferon has been classified as recombinant interferon alfa-2b. 
 
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. 
Human interferon receptors, as isolated from human lymphoblastoid (Daudi) cells, appear to be highly 
asymmetric proteins. They exhibit selectivity for human but not murine interferons, suggesting species 
specificity. Studies with other interferons have demonstrated species specificity. However, certain monkey 
species, eg, rhesus monkeys, are susceptible to pharmacodynamic stimulation upon exposure to human type 
1 interferons. 



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The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex 
sequence of intracellular events that include the induction of certain enzymes. It is thought that this process, 
at least in part, is responsible for the various cellular responses to interferon, including inhibition of virus 
replication in virus-infected cells, suppression of cell proliferation and such immunomodulating activities as 
enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of 
lymphocytes for target cells. Any or all of these activities may contribute to interferon's therapeutic effects. 
 
Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and 
human cell culture systems as well as human tumour xenografts in animals. It has demonstrated significant 
immunomodulatory activity in vitro. 
 
Recombinant interferon alfa-2b also inhibits viral replication in vitro and in vivo. Although the exact antiviral 
mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism. 
This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell. 
 
Chronic hepatitis B: 
Current clinical experience in patients who remain on interferon alfa-2b for 4 to 6 months indicates that 
therapy can produce clearance of serum HBV-DNA. An improvement in liver histology has been observed. 
In adult patients with loss of HBeAg and HBV-DNA, a significant reduction in morbidity and mortality has 
been observed. 
 
Interferon alfa-2b (6 MIU/m2 3 times a week for 6 months) has been given to children with chronic active 
hepatitis B. Because of a methodological flaw, efficacy could not be demonstrated. Moreover children treated 
with interferon alfa-2b experienced a reduced rate of growth and some cases of depression were observed. 
 
Chronic hepatitis C: 
In adult patients receiving interferon in combination with ribavirin, the achieved sustained response rate is 
47 %. Superior efficacy has been demonstrated with the combination of pegylated interferon with ribavirin 
(sustained response rate of 61 % achieved in a study performed in naïve patients with a ribavirin dose 
> 10.6 mg/kg, p < 0.01). 
 
Adult patients: Viraferon alone or in combination with ribavirin has been studied in 4 randomised Phase III 
clinical trials in 2,552 interferon-naïve patients with chronic hepatitis C. The trials compared the efficacy of 
Viraferon used alone or in combination with ribavirin. Efficacy was defined as sustained virologic response, 
6 months after the end of treatment. Eligible patients for these trials had chronic hepatitis C confirmed by a 
positive HCV-RNA polymerase chain reaction assay (PCR) (> 100 copies/ml), a liver biopsy consistent with 
a histologic diagnosis of chronic hepatitis with no other cause for the chronic hepatitis, and abnormal serum 
ALT. 
 
Viraferon was administered at a dose of 3 MIU 3 times a week as monotherapy or in combination with 
ribavirin. The majority of patients in these clinical trials were treated for one year. All patients were followed 
for an additional 6 months after the end of treatment for the determination of sustained virologic response. 
Sustained virologic response rates for treatment groups treated for one year with Viraferon alone or in 
combination with ribavirin (from two studies) are shown in Table 3. 
 
Co-administration of Viraferon with ribavirin increased the efficacy of Viraferon by at least two fold for the 
treatment of chronic heptatitis C in naïve patients. HCV genotype and baseline virus load are prognostic 
factors which are known to affect response rates. The increased response rate to the combination of Viraferon + 
ribavirin, compared with Viraferon alone, is maintained across all subgroups. The relative benefit of combination 
therapy with Viraferon + ribavirin is particularly significant in the most difficult to treat subgroup of patients 
(genotype 1 and high virus load) (Table 3). 
 
Response rates in these trials were increased with compliance. Regardless of genotype, patients who received 
Viraferon in combination with ribavirin and received ≥ 80 % of their treatment had a higher sustained 



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response 6 months after 1 year of treatment than those who took < 80 % of their treatment (56 % vs. 32 % in 
trial C/I98-580).  
 

Table 3 Sustained virologic response rates with Viraferon + ribavirin (one year of 
treatment) by genotype and viral load 

 
HCV Genotype  
 

I 
N=503 

C95-132/I95-143 

I/R 
N=505 

C95-132/I95-143 

I/R 
N=505 

C/I98-580 
 
All Genotypes 

 
16 % 

 
41 % 

 
47 % 

 
 
Genotype 1 

 
9 % 

 
29 % 

 
33 % 

 
Genotype 1  
≤ 2 million 
copies/ml 

 
25 % 

 
33 % 

 
45 % 

 
Genotype 1 
> 2 million 
copies/ml 

 
3 % 

 
27 % 

 

 
29 % 

 
Genotype 2/3 

 
31 % 

 
65 % 

 
79 % 

I Viraferon (3 MIU 3 times a week) 
I/R Viraferon (3 MIU 3 times a week) + ribavirin (1,000/1,200 mg/day) 
 
HCV/HIV Co-infected patients  
Two trials have been conducted in patients co-infected with HIV and HCV. Overall, in both studies, patients 
who received Viraferon plus ribavirin, were less likely to respond than patients who received pegylated 
interferon alfa-2b with ribavirin. The response to treatment in both of these trials is presented in Table 4. 
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 412 previously untreated 
adult patients with chronic hepatitis C who were co-infected with HIV. Patients were randomized to receive 
either pegylated interferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800 mg/day) or Viraferon (3 MIU TIW) 
plus ribavirin (800 mg/day) for 48 weeks with a follow-up period of 6 months. Study 2 (P02080) was a 
randomized, single centre study that enrolled 95 previously untreated adult patients with chronic hepatitis C 
who were co-infected with HIV. Patients were randomized to receive either pegylated interferon alfa-2b (100 
or 150 µg /week based on weight) plus ribavirin (800-1,200 mg/day based on weight) or Viraferon (3 MIU 
TIW) plus ribavirin (800-1,200 mg/day based on weight). The duration of therapy was 48 weeks with a 
follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load 
< 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6-month follow-up period.  
           
Table 4 Sustained virological response based on genotype after Viraferon in combination with 

ribavirin versus pegylated interferon alfa-2b in combination with ribavirin in 
HCV/HIV co-infected patients 

 Study 11 Study 22 
 

pegylated 
interferon 

alfa-2b  
(1.5 µg/kg/ 

week) + 
ribavirin  
(800 mg) 

Viraferon  
(3 MIU TIW) +  

ribavirin  
(800 mg) 

p 
valuea 

pegylated 
interferon 

alfa-2b (100 
or  

150c µg/week) 
+ ribavirin 

(800- 
1,200 mg)d 

Viraferon  
(3 MIU TIW) 

+ ribavirin 
(800- 

1,200 mg)d 
p 

valueb 



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All 27 % (56/205) 20 % (41/205) 0.047 44 % (23/52) 21 % (9/43) 0.017 
Genotype 1, 

4 
17 % (21/125) 6 % (8/129) 0.006 38 % (12/32) 7 % (2/27) 0.007 

Genotype 2, 
3 

44 % (35/80) 43 % (33/76) 0.88 53 % (10/19) 47 % (7/15) 0.730 

MIU = million international units; TIW = three times a week. 
a:  p value based on Cochran-Mantel Haenszel Chi square test. 
b:  p value based on chi-square test. 
c:  subjects < 75 kg received 100 µg/week pegylated interferon alfa-2b and subjects ≥ 75 kg received 150 µg/week pegylated 

interferon alfa-2b. 
d: ribavirin dosing was 800 mg for patients < 60 kg, 1,000 mg for patients 60-75 kg, and 1,200 mg for patients > 75 kg. 
 

1Carrat F, Bani-Sadr F, Pol S et al.  JAMA 2004; 292(23): 2839-2848. 
2 Laguno M, Murillas J, Blanco J.L et al.  AIDS 2004; 18(13): F27-F36. 
 
 
Relapse patients: A total of 345 interferon alpha relapse patients were treated in two clinical trials with 
Viraferon monotherapy or in combination with ribavirin. In these patients, the addition of ribavirin to 
Viraferon increased by as much as 10-fold the efficacy of Viraferon used alone in the treatment of chronic 
hepatitis C (48.6 % vs. 4.7 %). This enhancement in efficacy included loss of serum HCV (< 100 copies/ml 
by PCR), improvement in hepatic inflammation, and normalisation of ALT, and was sustained when 
measured 6 months after the end of treatment. 
 
Long-Term efficacy data 
In a large study, 1,071 patients were enrolled after treatment in a prior non pegylated interferon alfa-2b or 
non pegylated interferon alfa-2b/ribavirin study to evaluate the durability of sustained virologic response and 
assess the impact of continued viral negativity on clinical outcomes. 462 patients completed at least 5 years 
of long-term follow-up and only 12 sustained responders' out of 492 relapsed during this study.  
The Kaplan-Meier estimate for continued sustained response over 5 years for all patients is 97 % with a 95 % 
Confidence Interval of [95 %, 99 %].  
SVR after treatment of chronic HCV with non pegylated interferon alfa-2b (with or without ribavirin) results 
in long-term clearance of the virus providing resolution of the hepatic infection and clinical 'cure' from 
chronic HCV. However, this does not preclude the occurrence of hepatic events in patients with cirrhosis 
(including hepatocarcinoma). 
 
Clinical trials in paediatric patients with chronic hepatitis C: 
Children and adolescents 3 to 16 years of age with compensated chronic hepatitis C and detectable HCV-
RNA (assessed by a central laboratory using a research-based RT-PCR assay) were enrolled in two 
multicentre trials and received Viraferon 3 MIU/m2 3 times a week plus ribavirin 15 mg/kg per day for 1 year 
followed by 6 months follow-up after-treatment. A total of 118 patients were enrolled: 57 % male, 80 % 
Caucasian, and 78 % genotype 1,64 % ≤ 12 years of age. The population enrolled mainly consisted in 
children with mild to moderate hepatitis C. Sustained virological response rates in children and adolescents 
were similar to those in adults. Due to the lack of data in children with severe progression of the disease, and 
the potential for undesirable effects, the benefit/risk of the combination of ribavirin and interferon alfa-2b 
needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8). 
 
Study results are summarized in Table 5. 
 
Table 5. Virological response in previously untreated paediatric patients 
 Viraferon 3 MIU/m2 3 times a week   

+ 
ribavirin 15 mg/kg/day 

Overall Response1 (n=118) 54 (46 %)* 



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Genotype 1 (n=92) 33 (36 %)* 

Genotype 2/3/4 (n=26) 21 (81 %)* 

*Number (%) of patients 
1. Defined as HCV-RNA below limit of detection using a research based RT-PCR assay at end of treatment and during follow-up 
period 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of Viraferon were studied in healthy volunteers following single 5 million IU/m2 and 
10 million IU doses administered subcutaneously, at 5 million IU/m2 administered intramuscularly and as a 
30-minute intravenous infusion. The mean serum interferon concentrations following subcutaneous and 
intramuscular injections were comparable. Cmax occurred three to 12 hours after the lower dose and six to 
eight hours after the higher dose. The elimination half-lives of interferon injections were approximately two 
to three hours, and six to seven hours, respectively. Serum levels were below the detection limit 16 and 
24 hours, respectively, post-injection. Both subcutaneous and intramuscular administration resulted in 
bioavailabilities greater than 100 %. 
 
After intravenous administration, serum interferon levels peaked (135 to 273 IU/ml) by the end of the 
infusion, then declined at a slightly more rapid rate than after subcutaneous or intramuscular administration 
of medicinal product, becoming undetectable four hours after the infusion. The elimination half-life was 
approximately two hours. 
 
Urine levels of interferon were below the detection limit following each of the three routes of administration. 
 
Children and adolescents: Multiple-dose pharmacokinetic properties for Viraferon injection and ribavirin 
capsules in children and adolescents with chronic hepatitis C, between 5 and 16 years of age, are summarized 
in Table 6. The pharmacokinetics of Viraferon and ribavirin (dose-normalized) are similar in adults and 
children or adolescents. 
 

Table 6. Mean (% CV) multiple-dose pharmacokinetic parameters for Viraferon and ribavirin 
capsules when administered to children or adolescents with chronic hepatitis C 
Parameter Ribavirin 

15 mg/kg/day as 2 divided 
doses 

(n = 17) 

Viraferon 
3 MIU/m2 3 times a week 

(n = 54) 

Tmax (hr) 1.9 (83) 5.9 (36) 
Cmax (ng/ml) 3,275 (25) 51 (48) 

AUC* 29,774 (26) 622 (48) 
Apparent clearance l/hr/kg 0.27 (27) Not done 

*AUC12 (ng.hr/ml) for ribavirin; AUC0-24 (IU.hr/ml) for Viraferon 
 
Interferon neutralising factor assays were performed on serum samples of patients who received Viraferon in 
Schering-Plough monitored clinical trials. Interferon neutralising factors are antibodies which neutralise the 
antiviral activity of interferon. The clinical incidence of neutralising factors developing in cancer patients 
treated systemically is 2.9 % and in chronic hepatitis patients is 6.2 %. The detectable titres are low in almost 
all cases and have not been regularly associated with loss of response or any other autoimmune phenomenon. 
In patients with hepatitis, no loss of response was observed apparently due to the low titres. 
 
5.3 Preclinical safety data 
 
Although interferon is generally recognised as being species specific, toxicity studies in animals were 
conducted. Injections of human recombinant interferon alfa-2b for up to three months have shown no 
evidence of toxicity in mice, rats, and rabbits. Daily dosing of cynomolgus monkeys with 20 x 106 IU/kg/day 



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for 3 months caused no remarkable toxicity. Toxicity was demonstrated in monkeys given 
100 x 106 IU/kg/day for 3 months. 
 
In studies of interferon use in non-human primates, abnormalities of the menstrual cycle have been observed 
(see section 4.4). 
 
Results of animal reproduction studies indicate that recombinant interferon alfa-2b was not teratogenic in rats 
or rabbits, nor did it adversely affect pregnancy, foetal development or reproductive capacity in offspring of 
treated rats. Interferon alfa-2b has been shown to have abortifacient effects in Macaca mulatta (rhesus 
monkeys) at 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2. 
Abortion was observed in all dose groups (7.5 million, 15 million and 30 million IU/kg), and was statistically 
significant versus control at the mid- and high-dose groups (corresponding to 90 and 180 times the 
recommended intramuscular or subcutaneous dose of 2 million IU/m2). High doses of other forms of 
interferons alpha and beta are known to produce dose-related anovulatory and abortifacient effects in rhesus 
monkeys. 
 
Mutagenicity studies with interferon alfa-2b revealed no adverse events. 
 
No studies have been conducted in juvenile animals to examine the effects of treatment with interferon alfa-
2b on growth, development, sexual maturation, and behaviour (see section 4.4 and Rebetol SPC if Viraferon 
is to be administered in combination with ribavirin). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Disodium phosphate anhydrous,  
Sodium dihydrogen phosphate monohydrate,  
Edetate disodium,  
Sodium chloride,  
M-cresol,  
Polysorbate 80,  
Water for injections q.s.  
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
15 months 
 
Chemical and physical in-use stability has been demonstrated for 27 days at 2ºC – 8ºC. 
From a microbiological point of view, once opened, the product may be stored for a maximum of 27 days at 
2ºC – 8ºC. Other in-use storage times and conditions are the responsibility of the user. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C).  
Do not freeze. 
 
6.5 Nature and contents of container 
 



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1.2 ml of solution (corresponding to 30 MIU) in a pen made of a cartridge (type I glass) sealed at one end 
with an cap (aluminium) containing a liner (bromobutyl rubber) and at the other end by a plunger 
(bromobutyl rubber)  
with 12 injection needles and12 cleansing swabs 
Pack sizes of 1, 2 or 8 
Not all pack sizes may be marketed. 
 
The pen is designed to deliver its contents of 30 million IU in doses ranging from 2.5 to 10 million IU. The 
pen will deliver a maximum of 12 doses of 2.5 million IU over a period not to exceed 4 weeks. 
 
6.6 Special precautions for disposal 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
Viraferon, solution for injection, multidose pen is injected subcutaneously after attaching an injection needle 
and dialing the prescribed dose. 
 
Remove the pen from the refrigerator approximately 30 minutes before administration to allow the injectable 
solution to reach room temperature (not more than 25°C). 
 
Detailed instructions for the subcutaneous use of the product are provided with the package leaflet (refer to 
“How to self inject Viraferon”). 
 
Each pen is intended for a maximum four-week use period and must then be discarded. A new injection 
needle must be used for each dose. After each use, the injection needle must be discarded safely and the pen 
must be returned immediately to the refrigerator. A maximum of 48 hours (two days) of exposure to 25°C is 
permitted over the four-week use period to cover accidental delays in returning the pen to the refrigerator. 
Sufficient needles and swabs are provided to use the Viraferon pen for administering the smallest measurable 
doses. Instruct the patient that any extra needles and swabs that remain after the final dose has been taken 
from the pen, must be discarded appropriately and safely. 
 
As with all parenteral medicinal products, prior to administration inspect Viraferon, solution for injection, 
visually for particulate matter and discolouration. The solution should be clear and colourless. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
SP Europe 
73, rue de Stalle 
B-1180 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBERS  
 
EU/1/99/128/032 
EU/1/99/128/033 
EU/1/99/128/034 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation : 9 March 2000 
Date of last renewal : 23 May 2005 



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10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu/ 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 60 million IU solution for injection, multidose pen 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One cartridge contains 60 million IU of recombinant interferon alfa-2b produced in E.coli by recombinant 
DNA technology, in 1.2 ml. 
 
One ml contains 50 million IU of interferon alfa-2b. 
 
The pen is designed to deliver its contents of 60 million IU in doses ranging from 5 to 20 million IU. The pen 
will deliver a maximum of 12 doses of 5 million IU over a period not to exceed 4 weeks. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection 
Solution is clear and colourless. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Chronic Hepatitis B: Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis B 
viral replication (presence of HBV-DNA and HBeAg), elevated alanine aminotransferase (ALT) and 
histologically proven active liver inflammation and/or fibrosis. 
 
Chronic Hepatitis C:  
Adult patients:  
Viraferon is indicated for the treatment of adult patients with chronic hepatitis C who have elevated 
transaminases without liver decompensation and who are positive for serum HCV-RNA or anti-HCV (see 
section 4.4). 
 
The best way to use Viraferon in this indication is in combination with ribavirin. 
 
Chidren and adolescents: 
Viraferon is intended for use, in a combination regimen with ribavirin, for the treatment of children and 
adolescents 3 years of age and older, who have chronic hepatitis C, not previously treated, without liver 
decompensation, and who are positive for serum HCV-RNA. The decision to treat should be made on a case 
by case basis, taking into account any evidence of disease progression such as hepatic inflammation and 
fibrosis, as well as prognostic factors for response, HCV genotype and viral load. The expected benefit of 
treatment should be weighed against the safety findings observed for paediatric subjects in the clinical trials 
(see sections 4.4, 4.8 and 5.1). 
 
4.2 Posology and method of administration 
 
Treatment must be initiated by a physician experienced in the management of the disease. 
 
Multidose presentations must be for individual patient use only. 
 



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Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
If adverse events develop during the course of treatment with Viraferon for any indication, modify the dosage 
or discontinue therapy temporarily until the adverse events abate. If persistent or recurrent intolerance 
develops following adequate dosage adjustment, or disease progresses, discontinue treatment with Viraferon. 
At the discretion of the physician, the patient may self-administer the dose for maintenance dosage regimens 
administered subcutaneously. 
 
Chronic Hepatitis B: The recommended dosage is in the range 5 to 10 million IU administered 
subcutaneously three times a week (every other day) for a period of 4 to 6 months. 
 
The administered dose should be reduced by 50 % in case of occurrence of haematological disorders (white 
blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3). Treatment should be 
discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe 
thrombocytopaenia (< 70,000/mm3). 
 
For all patients, if no improvement on serum HBV-DNA is observed after 3 to 4 months of treatment (at the 
maximum tolerated dose), discontinue Viraferon therapy. 
 
Chronic Hepatitis C: Viraferon is administered subcutaneously at a dose of 3 million IU three times a week 
(every other day) to adult patients, whether administered as monotherapy or in combination with ribavirin. 
 
Children 3 years of age or older and adolescents: Interferon alfa-2b 3 MIU/m2 is administered 
subcutaneously 3 times a week (every other day) in combination with ribavirin capsules or oral solution 
administered orally in two divided doses daily with food (morning and evening).  
 
(See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination 
therapy. For paediatric patients who weigh < 47 kg or cannot swallow capsules, see ribavirin oral solution 
SPC).  
 
Relapse patients (adults): 
Viraferon is given in combination with ribavirin. 
 
Based on the results of clinical trials, in which data are available for 6 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for 6 months. 
 
Naïve patients: 
Adults: The efficacy of Viraferon is enhanced when given in combination with ribavirin. Viraferon should be 
given alone mainly in case of intolerance or contraindication to ribavirin. 
 
Viraferon in combination with ribavirin: 
Based on the results of clinical trials, in which data are available for 12 months of treatment, it is 
recommended that patients be treated with Viraferon in combination with ribavirin for at least 6 months. 
 
Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit 
negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and 
high pre-treatment viral load. 
 
Other negative prognostic factors (age > 40 years, male gender, bridging fibrosis) should be taken into 
account in order to extend therapy to 12 months. 
 
During clinical trials, patients who failed to show a virologic response after 6 months of treatment (HCV-
RNA below lower limit of detection) did not become sustained virologic responders (HCV-RNA below lower 
limit of detection six months after withdrawal of treatment). 



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Viraferon alone: 
The optimal duration of therapy with Viraferon alone is not yet fully established, but a therapy of between 
12 and 18 months is advised. 
 
It is recommended that patients be treated with Viraferon alone for at least 3 to 4 months, at which point 
HCV-RNA status should be determined. Treatment should be continued in patients who exhibit negative 
HCV-RNA. 
 
Children and adolescents: The efficacy and safety of Viraferon in combination with ribavirin has been 
studied in children and adolescents who have not been previously treated for chronic hepatitis C.  
 
Genotype 1: The recommended duration of treatment is one year. Patients who fail to achieve virological 
response at 12 weeks are highly unlikely to become sustained virological responders (negative predictive 
value 96 %). Virological response is defined as absence of detectable HCV-RNA at Week 12. Treatment 
should be discontinued in these patients. 
Genotype 2/3: The recommended duration of treatment is 24 weeks. 
 
Virological responses after 1 year of treatment and 6 months of follow-up were 36 % for genotype 1 and 
81 % for genotype 2/3/4. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients. 
- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure, recent 

myocardial infarction, severe arrhythmic disorders.  
- Severe renal or hepatic dysfunction; including that caused by metastases. 
- Epilepsy and/or compromised central nervous system (CNS) function (see section 4.4). 
- Chronic hepatitis with decompensated cirrhosis of the liver. 
- Chronic hepatitis in patients who are being or have been treated recently with immunosuppressive 

agents excluding short term corticosteroid withdrawal. 
- Autoimmune hepatitis; or history of autoimmune disease; immunosuppressed transplant recipients. 
- Pre-existing thyroid disease unless it can be controlled with conventional treatment. 
 
Children and adolescents: 
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal 

ideation or suicide attempt. 
 

Combination therapy with ribavirin: Also see ribavirin SPC if interferon alfa-2b is to be administered in 
combination with ribavirin in patients with chronic hepatitis C. 
 
4.4 Special warnings and precautions for use 
 
For all patients: 
Psychiatric and central nervous system (CNS): Severe CNS effects, particularly depression, suicidal ideation 
and attempted suicide have been observed in some patients during Viraferon therapy, and even after 
treatment discontinuation mainly during the 6-month follow-up periodand in the follow-up period. Among 
children and adolescents treated with Viraferon in combination with ribavirin, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6-month 
follow-up after treatment. As in adult patients, children and adolescents experienced other psychiatric adverse 
events (e.g., depression, emotional lability, and somnolence). Other CNS effects including aggressive behaviour 
(sometimes directed against others), confusion and alterations of mental status have been observed with alpha 
interferons. Patients should be closely monitored for any signs or symptoms of psychiatric disorders. If such 
symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the 
prescribing physician and the need for adequate therapeutic management should be considered. If psychiatric 



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symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with 
Viraferon be discontinued, and the patient followed, with psychiatric intervention as appropriate. 
 
Patients with existence of or history of severe psychiatric conditions: 
If a treatment with interferon alfa-2b is judged necessary in adult patients with existence or history of severe 
psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and 
therapeutic management of the psychiatric condition. The use of interferon alfa-2b in children and adolescents 
with existence of or history of severe psychiatric conditions is contraindicated (see section 4.3). 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon 
alfa-2b have been observed rarely during Viraferon therapy. If such a reaction develops, discontinue the 
medication and institute appropriate medical therapy. Transient rashes do not necessitate interruption of 
treatment. 
 
Moderate to severe adverse experiences may require modification of the patient's dosage regimen, or in some 
cases, termination of Viraferon therapy. Any patient developing liver function abnormalities during treatment 
with Viraferon must be monitored closely and treatment discontinued if signs and symptoms progress. 
 
Hypotension may occur during Viraferon therapy or up to two days post-therapy and may require supportive 
treatment. 
 
Adequate hydration must be maintained in patients undergoing Viraferon therapy since hypotension related 
to fluid depletion has been seen in some patients. Fluid replacement may be necessary. 
 
While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, 
other causes of persistent fever must be ruled out. 
 
Viraferon must be used cautiously in patients with debilitating medical conditions, such as those with a 
history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to 
ketoacidosis. Caution must be observed also in patients with coagulation disorders (e.g., thrombophlebitis, 
pulmonary embolism) or severe myelosuppression. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.5). Any patient developing fever, cough, 
dyspnea or other respiratory symptoms must have a chest X-ray taken. If the chest X-ray shows pulmonary 
infiltrates or there is evidence of pulmonary function impairment, the patient is to be monitored closely, and, 
if appropriate, discontinue interferon alpha. While this has been reported more often in patients with chronic 
hepatitis C treated with interferon alpha, it has also been reported in patients with oncologic diseases treated 
with interferon alpha. Prompt discontinuation of interferon alpha administration and treatment with 
corticosteroids appear to be associated with resolution of pulmonary adverse events. 
 
Ocular adverse events (see section 4.8) including retinal haemorrhages, cotton wool spots, and retinal artery 
or vein obstruction have been reported in rare instance after treatment with alpha interferons. All patients 
should have a baseline eye examination. Any patient complaining of changes in visual acuity or visual fields, 
or reporting other ophthalmologic symptoms during treatment with Viraferon, must have a prompt and 
complete eye examination. Periodic visual examinations during Viraferon therapy are recommended 
particularly in patients with disorders that may be associated with retinopathy, such as diabetes mellitus or 
hypertension. Discontinuation of Viraferon should be considered in patients who develop new or worsening 
ophthalmological disorders. 



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More significant obtundation and coma, including cases of encephalopathy, have been observed in some 
patients, usually elderly, treated at higher doses. While these effects are generally reversible, in a few patients 
full resolution took up to three weeks. Very rarely, seizures have occurred with high doses of Viraferon. 
 
Adult patients with a history of congestive heart failure, myocardial infarction and/or previous or current 
arrhythmic disorders, who require Viraferon therapy, must be closely monitored. It is recommended that 
those patients who have pre-existing cardiac abnormalities and/or are in advanced stages of cancer have 
electrocardiograms taken prior to and during the course of treatment. Cardiac arrhythmias (primarily 
supraventricular) usually respond to conventional therapy but may require discontinuation of Viraferon 
therapy. There are no data in children or adolescents with a history of cardiac disease. 
 
Hypertriglyceridemia and aggravation of hypertriglyceridemia, sometimes severe, have been observed. 
Monitoring of lipid levels is, therefore, recommended. 
 
Due to reports of interferon alpha exacerbating pre-existing psoriatic disease and sarcoidosis, use of 
Viraferon in patients with psoriasis or sarcoidosis is recommended only if the potential benefit justifies the 
potential risk. 
 
Preliminary data indicates that interferon alpha therapy may be associated with an increased rate of kidney 
graft rejection. Liver graft rejection has also been reported. 
 
The development of auto-antibodies and autoimmune disorders has been reported during treatment with alpha 
interferons. Patients predisposed to the development of autoimmune disorders may be at increased risk. 
Patients with signs or symptoms compatible with autoimmune disorders should be evaluated carefully, and 
the benefit-risk of continued interferon therapy should be reassessed (see also section 4.4 Chronic hepatitis C, 
Monotherapy (thyroid abnormalities) and section 4.8). 
Cases of Vogt-Koyanagi-Harada (VKH) syndrome have been reported in patients with chronic hepatitis C 
treated with interferon. This syndrome is a granulomatous inflammatory disorder affecting the eyes, auditory 
system, meninges, and skin. If VKH syndrome is suspected, antiviral treatment should be withdrawn and 
corticosteroid therapy discussed (see section 4.8). 
 
Discontinue treatment with Viraferon in patients with chronic hepatitis who develop prolongation of 
coagulation markers which might indicate liver decompensation. 
 
Chronic Hepatitis C: 
Combination therapy with ribavirin: Also see ribavirin SPC if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i.e. 
patients with genotype 2 and 3), treatment may be possible without histological confirmation. Current 
treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing 
treatment. 
 
Monotherapy: Infrequently, adult patients treated for chronic hepatitis C with Viraferon developed thyroid 
abnormalities, either hypothyroidism or hyperthyroidism. In clinical trials using Viraferon therapy, 2.8 % 
patients overall developed thyroid abnormalities. The abnormalities were controlled by conventional therapy 
for thyroid dysfunction. The mechanism by which Viraferon may alter thyroid status is unknown. Prior to 
initiation of Viraferon therapy for the treatment of chronic hepatitis C, evaluate serum thyroid-stimulating 
hormone (TSH) levels. Any thyroid abnormality detected at that time must be treated with conventional 
therapy. Viraferon treatment may be initiated if TSH levels can be maintained in the normal range by 
medication. Determine TSH levels if, during the course of Viraferon therapy, a patient develops symptoms 
consistent with possible thyroid dysfunction. In the presence of thyroid dysfunction, Viraferon treatment may 
be continued if TSH levels can be maintained in the normal range by medication. Discontinuation of 



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Viraferon therapy has not reversed thyroid dysfunction occurring during treatment (also see Children and 
adolescents, Thyroid monitoring). 
 
Supplemental monitoring specific for children and adolescents 
Thyroid Monitoring: Approximately 12 % of children treated with interferon alfa-2b and ribavirin developed 
increase in TSH. Another 4 % had a transient decrease below the lower limit of normal. Prior to initiation of 
Viraferon therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be 
treated with conventional therapy. Viraferon therapy may be initiated if TSH levels can be maintained in the 
normal range by medication. Thyroid dysfunction during treatment with interferon alfa-2b and ribavirin has 
been observed. If thyroid abnormalities are detected, the patient’s thyroid status should be evaluated and 
treated as clinically appropriate. Children and adolescents should be monitored every 3 months for evidence 
of thyroid dysfunction (e.g. TSH). 
 
Growth and Development: During a 1-year course of therapy there was a decrease in the rate of linear growth 
(mean percentile decrease of 9 %) and a decrease in the rate of weight gain (mean percentile decrease of 
13 %). A general reversal of these trends was noted during the 6 months follow-up post treatment. However, 
based on interim data from a long-term follow-up study, 12 (14 %) of 84 children had a > 15 percentile 
decrease in rate of linear growth, of whom 5 (6 %) children had a > 30 percentile decrease despite being off 
treatment for more than 1 year. In addition, preclicinal juvenile toxicity results have demonstrated a minor, 
dose-related decrease in overall growth in neonatal rats dosed with ribavirin (see section 5.3). Therefore, the 
risk/benefit of the combined use of interferon alfa-2b and ribavirin should be assessed in young children prior 
to the initiation of therapy. Physicians are advised to monitor the growth of children taking ribavirin in 
combination with interferon alfa-2b. There are no data on long term effects on growth and development and 
on sexual maturation. 
 
HCV/HIV Coinfection: Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy 
(HAART) may be at increased risk of developing lactic acidosis. Caution should be used when adding Viraferon 
and ribavirin to HAART therapy (see ribavirin SPC). Patients treated with Viraferon and ribavirin combination 
therapy and zidovudine could be at increased risk of developing anaemia. 
Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic 
decompensation and death. Adding treatment with alfa interferons alone or in combination with ribavirin may 
increase the risk in this patient subset.  
 
Dental and periodontal disorders: Dental and periodontal disorders, which may lead to loss of teeth, have 
been reported in patients receiving Viraferon and ribavirin combination therapy. In addition, dry mouth could 
have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the 
combination of Viraferon and ribavirin. Patients should brush their teeth thoroughly twice daily and have 
regular dental examinations. In addition some patients may experience vomiting. If this reaction occurs, they 
should be advised to rinse out their mouth thoroughly afterwards. 
 
Laboratory Tests:  
Standard haematological tests and blood chemistries (complete blood count and differential, platelet count, 
electrolytes, liver enzymes, serum protein, serum bilirubin and serum creatinine) are to be conducted in all 
patients prior to and periodically during systemic treatment with Viraferon. 
 
During treatment for hepatitis B or C the recommended testing schedule is at weeks 1, 2, 4, 8, 12, 16, and 
every other month, thereafter, throughout treatment. If ALT flares during Viraferon therapy to greater than or 
equal to 2 times baseline, Viraferon therapy may be continued unless signs and symptoms of liver failure are 
observed. During ALT flare, liver function tests: ALT, prothrombin time, alkaline phosphatase, albumin and 
bilirubin must be monitored at two-week intervals. 
 
Effect on fertility: Interferon may impair fertility (see section 4.6 and section 5.3). 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 



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Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with 
Viraferon. 
 
Interactions between Viraferon and other medicinal products have not been fully evaluated. Caution must be 
exercised when administering Viraferon in combination with other potentially myelosuppressive agents. 
 
Interferons may affect the oxidative metabolic process. This must be considered during concomitant therapy 
with medicinal products metabolised by this route, such as the xanthine derivatives theophylline or 
aminophylline. During concomitant therapy with xanthine agents, serum theophylline levels must be 
monitored and dosage adjusted if necessary. 
 
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed 
rarely in interferon alpha treated patients, including those treated with Viraferon. The aetiology has not been 
defined. These symptoms have been reported more frequently when shosaikoto, a Chinese herbal medicine, is 
administered concomitantly with interferon alpha (see section 4.4). 
 
(Also see ribavirin SPC if Viraferon is to be administered in combination with ribavirin in patients with 
chronic hepatitis C). 
 
4.6 Pregnancy and lactation 
 
Women of childbearing potential have to use effective contraception during treatment. Viraferon must be 
used with caution in fertile men. Decreased serum estradiol and progesterone concentrations have been 
reported in women treated with human leukocyte interferon. 
 
There are no adequate data from the use of interferon alfa-2b in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Viraferon is to be 
used during pregnancy only if the potential benefit justifies the potential risk to the foetus. 
 
It is not known whether the components of this medicinal product are excreted in human milk. Because of the 
potential for adverse reactions in nursing infants, nursing should be discontinued prior to initiation of 
treatment. 
 
Combination therapy with ribavirin: Ribavirin causes serious birth defects when administered during 
pregnancy. Ribavirin therapy is contraindicated in women who are pregnant. Extreme care must be taken to 
avoid pregnancy in female patients or in partners of male patients taking Viraferon in combination with 
ribavirin. Females of childbearing potential and their partners must each use an effective contraceptive during 
treatment and for 4 months after treatment has been concluded. Male patients and their female partners must 
each use an effective contraceptive during treatment and for 7 months after treatment has been concluded (see 
ribavirin SPC). 
 
4.7 Effects on ability to drive and use machines 
 
Patients are to be advised that they may develop fatigue, somnolence, or confusion during treatment with 
Viraferon, and therefore it is recommended that they avoid driving or operating machinery. 
 
4.8 Undesirable effects 
 
See ribavirin SPC for ribavirin-related undesirable effects if Viraferon is to be administered in combination 
with ribavirin in patients with chronic hepatitis C. 
 
In clinical trials conducted in a broad range of indications and at a wide range of doses (from 6 MIU/m2/week 
in hairy cell leukaemia up to 100 MIU/m2/week in melanoma), the most commonly reported undesirable 
effects were fever, fatigue, headache and myalgia. Fever and fatigue were often reversible within 72 hours of 
interruption or cessation of treatment. 



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In clinical trials conducted in the hepatitis C population, patients were treated with Viraferon alone or in 
combination with ribavirin for one year. All patients in these trials received 3 MIU of Viraferon three times a 
week. In Table 1 the frequency of patients reporting (treatment related) undesirable effects is presented from 
clinical trials in naïve patients treated for one year. Severity was generally mild to moderate. The adverse 
reactions listed in Table 1 are based on experience from clinical trials and post-marketing. Within the organ 
system classes, adverse reactions are listed under headings of frequency using the following categories: very 
common (≥1/10); common (≥1/100, <1/10); rarely (≥1/10,000, <1/1,000); very rarely (<1/10,000); not 
known. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

Table 1. Adverse reactions reported during clinical trials or following the marketing use of Viraferon 
alone or in combination with ribavirin 

System Organ Class Adverse Reactions 
Infections and infestations 
Very common: 
Common: 
Rarely:  

 
Pharyngitis*, infection viral* 
Bronchitis, sinusitis, herpes simplex (resistance), rhinitis 
Pneumonia§ 

Blood and lymphatic system disorders 
Very common: 
Common: 
Very rarely:  
Not known:  

 
Leukopaenia 
Thrombocytopaenia, lymphadenopathy, lymphopenia 
Aplastic anaemia 
Pure red cell aplasia, idiopathic thrombocytopenic purpura, 
thrombotic thrombocytopenic purpura  

Immune system disorders§ 
Very rarely:  
Not known: 

 
Sarcoidosis, exacerbation of sarcoidosis 
Systemic lupus erythematosus, vasculitis, rheumatoid 
arthritis (new or aggravated), Vogt-Koyanagi-Harada 
syndrome, acute hypersensitivity reactions including 
urticaria, angioedema, bronchoconstriction, anaphylaxis§ 

Endocrine disorders 
Common: 
Very rarely:  

 
Hypothyroidism§, hyperthyroidism§ 
Diabetes, aggravated diabetes 

Metabolism and nutrition disorders 
Very common: 
Common:  
Very rarely:  

 
Anorexia 
Hypocalcaemia, dehydration, hyperuricemia, thirst 
Hyperglycaemia, hypertriglyceridaemia§, increased appetite 

Psychiatric disorders§ 
Very common: 
 
Common: 
Rarely:  
Very rarely: 
 
Not known: 

 
Depression, insomnia, anxiety, emotional lability*, 
agitation, nervousness 
Confusion, sleep disorder, libido decreased 
Suicide ideation 
Suicide, suicide attempts, aggressive behaviour (sometimes 
directed against others), psychosis including hallucinations 
Mental status change§ 

Nervous system disorders§ 
Very common: 
Common: 
 
Very rarely:  
 
 
Not known: 

 
Dizziness, headache, concentration impaired, mouth dry 
Tremor, paresthesia, hypoesthesia, migraine, flushing, 
somnolence, taste perversion 
Cerebrovascular haemorrhage, cerbrovascular ischaemia, 
seizure, impaired consciousness, encephalopathy, 
neuropathy, polyneuropathy 
Mononeuropathies, coma§ 

Eye disorders 
Very common: 

 
Vision blurred 



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Common: 
 
Rarely:  

Conjunctivitis, vision abnormal, lacrimal gland disorder, eye 
pain 
Retinal haemorrhages§, retinopathies (including macular 
oedema), retinal artery or vein obstruction§, optic neuritis, 
papilloedema, loss of visual acuity or visual field, cotton-
wool spots§  

Ear and labyrinth 
Common: 
Very rarely:  

 
Vertigo, tinnitus 
Hearing loss, hearing disorder 

Cardiac disorders 
Common: 
Rarely: 
Very rarely: 
Not known: 

 
Palpitation, tachycardia 
Cardiomyopathy 
Myocardial infarction, cardiac ischaemia  
Arrhythmia  

Vascular disorders 
Common: 
Very rarely:  

 
Hypertension 
Peripheral ischaemia, hypotension§ 

Respiratory, thoracic and mediastinal 
disorders 
Very common: 
Common: 
 
Very rarely:  

 
 
Dyspnoea*, coughing* 
Epistaxis, respiratory disorder, nasal congestion, rhinorrhea, 
cough nonproductive 
Pulmonary infiltrates§, pneumonitis§ 

Gastrointestinal disorders 
Very common: 
 
Common: 
 
Very rarely:  
 
Not known: 

 
Nausea/vomiting, abdominal pain, diarrhoea, stomatitis, 
dyspepsia 
Stomatitis ulcerative, right upper quadrant pain, glossitis, 
gingivitis, constipation, loose stools 
Pancreatitis, ischaemic colitis, ulcerative colitis, gingival 
bleeding 
Periodontal disorder NOS, dental disorder NOS§ 

Hepatobiliary disorders 
Common: 
Very rarely:  

 
Hepatomegaly 
Hepatotoxicity, (including fatality) 

Skin and subcutaneous tissue disorders 
Very common: 
Common: 
 
Very rarely:  

 
Alopecia, pruritus*, skin dry*, rash*, sweating increased 
Psoriasis (new or aggravated)§, rash maculopapular, rash 
erythematous, eczema, erythema, skin disorder 
Stevens Johnson syndrome, toxic epidermal necrolysis, 
erythema multiforme 

Musculoskeletal and connective tissue 
disorders 
Very common:  
Common: 
Very rarely: 

 
 
Myalgia, arthralgia, musculoskeletal pain 
Arthritis 
Rhabdomyolysis, myositis, leg cramps, back pain 

Renal and urinary disorders 
Common: 
Very rarely:  

 
Micturition frequency 
Renal failure, renal insufficiency, nephrotic syndrome 

Reproductive system and breast 
disorders 
Common: 

 
 
Amenorrhea, breast pain, dysmenorrhea, menorrhagia, 
menstrual disorder, vaginal disorder 

General disorders and administration 
site conditions 

 
 



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Very common: 
 
 
Common: 
Very rarely: 

Injection site inflammation, injection site reaction*, fatigue, 
rigors, fever§, flu-like symptoms§, asthenia, irritability, chest 
pain, malaise 
Injection site pain 
Injection site necrosis, face oedema 

Investigations 
Very common: 

 
Weight decrease 

*These events were only common with Viraferon alone 
§See section 4.4 
 
These undesirable effects have also been reported with Viraferon alone. 
 
Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-
existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4). Cardiomyopathy, that may 
be reversible upon discontinuation of interferon alpha, has been reported rarely in patients without prior 
evidence of cardiac disease (see section 4.4).  
 
A wide variety of autoimmune and immune-mediated disorders have been reported with alpha interferons 
including thyroid disorders, systemic lupus erythematosus, rheumatoid arthritis (new or aggravated), 
idiopathic and thrombotic thrombocytopenic purpura, vasculitis, neuropathies including mononeuropathies 
(see also section 4.4). 
 
Clinically significant laboratory abnormalities, most frequently occurring at doses greater than 10 million IU 
daily, include reduction in granulocyte and white blood cell counts; decreases in haemoglobin level and 
platelet count; increases in alkaline phosphatase, LDH, serum creatinine and serum urea nitrogen levels. 
Increase in serum ALT/AST (SGPT/SGOT) levels have been noted as an abnormality in some non-hepatitis 
subjects and also in some patients with chronic hepatitis B coincident with clearance of viral DNAp. 
 
Paediatric population 
 
Children and adolescents – Chronic Hepatitis C 
In clinical trials of 118 children or adolescents 3 to 16 years of age, 6 % discontinued therapy due to adverse 
events. In general, the adverse event profile in the limited paediatric population studied was similar to that 
observed in adults, although there is a paediatric specific concern regarding growth inhibition as decrease in 
height (mean percentile decrease of growth velocity of 9 %) and weight (mean percentile decrease of 13 %) 
percentile were observed during treatment (see section 4.4). Furthermore, suicidal ideation or attempts were 
reported more frequently compared to adult patients (2.4 % vs 1 %) during treatment and during the 6 month 
follow-up after treatment. As in adult patients, children and adolescents also experienced other psychiatric 
adverse events (e.g., depression, emotional lability, and somnolence) (see section 4.4). In addition, injection 
site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in children and 
adolescents compared to adult patients. Dose modifications were required in 30 % of patients, most 
commonly for anaemia and neutropaenia. 
 
The adverse reactions listed in Table 2 are based on experience from paediatric clinical trials.  
Within the organ system classes, adverse reactions are listed under headings of frequency using the following 
categories: very common (≥1/10); common (≥1/100, <1/10). Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness. 
 
Table 2  Adverse reactions very commonly and commonly reported in paediatric clinical trials  

Very common (≥1/10) - Common (≥1/100, <1/10) 
System Organ Class Adverse Reactions 
Infection and infestations 
Very common: 
Common: 

 
Viral infection, pharyngitis 
Fungal infection, bacterial infection, pulmonary infection, otitis 



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media, tooth abscess, herpes simplex, urinary tract infection, 
vaginitis, gastroenteritis 

Neoplasms benign, malignant 
and unspecified (including 
cysts and polyps) 
Common: 

 
 
 
Neoplasm (unspecified) 

Blood and lymphatic system 
disorders 
Very common: 
Common: 

 
 
Anaemia, neutropaenia 
Thrombocytopaenia, lymphadenopathy 

Endocrine disorders 
Very common: 
Common: 

 
Hypothyroidism§,  
Hyperthyroidism§, virilism 

Metabolism and nutrition 
disorders 
Very common: 
Common: 

 
 
Anorexia 
Hypertriglyceridemia§, hyperuricemia, increased appetite 

Psychiatric disorders§ 
Very common: 
Common: 

 
Depression, emotional lability, insomnia 
Suicidal ideation, aggressive reaction, confusion, behaviour 
disorder, agitation, somnambulism, anxiety, nervousness, sleep 
disorder, abnormal dreaming, apathy 

Nervous system disorders§ 
Very common: 
Common: 

 
Headache, dizziness 
Hyperkinesia, tremor, dysphonia, paresthaesia, hypoaesthesia, 
hyperaesthesia, concentration impaired, somnolence 

Eye disorders 
Common: 

 
Conjunctivitis, eye pain, abnormal vision, lacrimal gland disorder 

Vascular disorders 
Common: 

 
Raynaud’s disease, flushing, pallor 

Respiratory, thoracic and 
mediastinal disorders 
Common: 

 
 
Dyspnoea, tachypnea, epistaxis, coughing, nasal congestion, nasal 
irritation, rhinorrhea, sneezing 

Gastrointestinal disorders 
Very common: 
Common: 

 
Diarrhoea, vomiting, nausea, abdominal pain 
Mouth ulceration, stomatitis ulcerative, stomatitis, right upper 
quadrant pain, dyspepsia, glossitis, gastroesophogeal reflux, rectal 
disorder, gastrointestinal disorder, constipation, loose stools, 
toothache, tooth disorder 

Hepatobiliary disorders 
Common: 

 
Hepatic function abnormal 

Skin and subcutaneous tissue 
disorders  
Very common: 
Common: 

 
 
Alopecia, rash 
Photosensitivity reaction, maculopapular rash, eczema, acne, skin 
disorder, nail disorder, skin discolouration, pruritus, dry skin, 
erythema, bruise, sweating increased 

Musculoskeletal and 
connective tissue disorders 
Very common: 

 
 
Arthralgia, myalgia, musculoskeletal pain  

Renal and urinary disorders 
Common: 

 
Enuresis, micturition disorder, urinary incontinence 

Reproductive system and  



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breast disorders 
Common: 

 
Female: amenorrhea, menorrhagia, menstrual disorder, vaginal 
disorder 
Male: testicular pain 

General disorders and 
administration site 
conditions 
Very common: 
 
Common: 

 
 
 
Injection site inflammation, injection site reaction, fatigue, rigors, 
fever§, influenza-like symptoms§, malaise, irritability 
Chest pain, asthenia, oedema, injection site pain 

Investigations 
Very common: 

 
Growth rate decrease (height and/or weight decrease for age)§  

Injury and poisoning 
Common: 

 
Skin laceration 

§See section 4.4 
 
4.9 Overdose 
 
No case of overdose has been reported that has led to acute clinical manifestations. However, as for any 
pharmacologically active compound, symptomatic treatment with frequent monitoring of vital signs and close 
observation of the patient is indicated. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunostimulants, cytokines and immunomodulators, interferons, interferon 
alfa-2b, ATC code: L03A B05 
 
Viraferon is a sterile, stable, formulation of highly purified interferon alfa-2b produced by recombinant DNA 
techniques. Recombinant interferon alfa-2b is a water-soluble protein with a molecular weight of 
approximately 19,300 daltons. It is obtained from a clone of E. coli, which harbours a genetically engineered 
plasmid hybrid encompassing an interferon alfa-2b gene from human leukocytes. 
 
The activity of Viraferon is expressed in terms of IU, with 1 mg of recombinant interferon alfa-2b protein 
corresponding to 2.6 x l08 IU. International Units are determined by comparison of the activity of the 
recombinant interferon alfa-2b with the activity of the international reference preparation of human leukocyte 
interferon established by the World Health Organisation. 
 
The interferons are a family of small protein molecules with molecular weights of approximately 15,000 to 
21,000 daltons. They are produced and secreted by cells in response to viral infections or various synthetic 
and biological inducers. Three major classes of interferons have been identified: alpha, beta and gamma. 
These three main classes are themselves not homogeneous and may contain several different molecular 
species of interferon. More than 14 genetically distinct human alpha interferons have been identified. 
Viraferon has been classified as recombinant interferon alfa-2b. 
 
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. 
Human interferon receptors, as isolated from human lymphoblastoid (Daudi) cells, appear to be highly 
asymmetric proteins. They exhibit selectivity for human but not murine interferons, suggesting species 
specificity. Studies with other interferons have demonstrated species specificity. However, certain monkey 
species, eg, rhesus monkeys, are susceptible to pharmacodynamic stimulation upon exposure to human type 
1 interferons. 
 



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The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex 
sequence of intracellular events that include the induction of certain enzymes. It is thought that this process, 
at least in part, is responsible for the various cellular responses to interferon, including inhibition of virus 
replication in virus-infected cells, suppression of cell proliferation and such immunomodulating activities as 
enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of 
lymphocytes for target cells. Any or all of these activities may contribute to interferon's therapeutic effects. 
 
Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and 
human cell culture systems as well as human tumour xenografts in animals. It has demonstrated significant 
immunomodulatory activity in vitro. 
 
Recombinant interferon alfa-2b also inhibits viral replication in vitro and in vivo. Although the exact antiviral 
mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism. 
This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell. 
 
Chronic hepatitis B: 
Current clinical experience in patients who remain on interferon alfa-2b for 4 to 6 months indicates that 
therapy can produce clearance of serum HBV-DNA. An improvement in liver histology has been observed. 
In adult patients with loss of HBeAg and HBV-DNA, a significant reduction in morbidity and mortality has 
been observed. 
 
Interferon alfa-2b (6 MIU/m2 3 times a week for 6 months) has been given to children with chronic active 
hepatitis B. Because of a methodological flaw, efficacy could not be demonstrated. Moreover children treated 
with interferon alfa-2b experienced a reduced rate of growth and some cases of depression were observed. 
 
Chronic hepatitis C: 
In adult patients receiving interferon in combination with ribavirin, the achieved sustained response rate is 
47 %. Superior efficacy has been demonstrated with the combination of pegylated interferon with ribavirin 
(sustained response rate of 61 % achieved in a study performed in naïve patients with a ribavirin dose 
> 10.6 mg/kg, p < 0.01). 
 
Adult patients: Viraferon alone or in combination with ribavirin has been studied in 4 randomised Phase III 
clinical trials in 2,552 interferon-naïve patients with chronic hepatitis C. The trials compared the efficacy of 
Viraferon used alone or in combination with ribavirin. Efficacy was defined as sustained virologic response, 
6 months after the end of treatment. Eligible patients for these trials had chronic hepatitis C confirmed by a 
positive HCV-RNA polymerase chain reaction assay (PCR) (> 100 copies/ml), a liver biopsy consistent with 
a histologic diagnosis of chronic hepatitis with no other cause for the chronic hepatitis, and abnormal serum 
ALT. 
 
Viraferon was administered at a dose of 3 MIU 3 times a week as monotherapy or in combination with 
ribavirin. The majority of patients in these clinical trials were treated for one year. All patients were followed 
for an additional 6 months after the end of treatment for the determination of sustained virologic response. 
Sustained virologic response rates for treatment groups treated for one year with Viraferon alone or in 
combination with ribavirin (from two studies) are shown in Table 3. 
 
Co-administration of Viraferon with ribavirin increased the efficacy of Viraferon by at least two fold for the 
treatment of chronic heptatitis C in naïve patients. HCV genotype and baseline virus load are prognostic 
factors which are known to affect response rates. The increased response rate to the combination of Viraferon + 
ribavirin, compared with Viraferon alone, is maintained across all subgroups. The relative benefit of combination 
therapy with Viraferon + ribavirin is particularly significant in the most difficult to treat subgroup of patients 
(genotype 1 and high virus load) (Table 3). 
 
Response rates in these trials were increased with compliance. Regardless of genotype, patients who received 
Viraferon in combination with ribavirin and received ≥ 80 % of their treatment had a higher sustained 



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response 6 months after 1 year of treatment than those who took < 80 % of their treatment (56 % vs. 32 % in 
trial C/I98-580).  
 

Table 3 Sustained virologic response rates with Viraferon + ribavirin (one year of 
treatment) by genotype and viral load 

 
HCV Genotype  
 

I 
N=503 

C95-132/I95-143 

I/R 
N=505 

C95-132/I95-143 

I/R 
N=505 

C/I98-580 
 
All Genotypes 

 
16 % 

 
41 % 

 
47 % 

 
 
Genotype 1 

 
9 % 

 
29 % 

 
33 % 

 
Genotype 1  
≤ 2 million 
copies/ml 

 
25 % 

 
33 % 

 
45 % 

 
Genotype 1 
> 2 million 
copies/ml 

 
3 % 

 
27 % 

 

 
29 % 

 
Genotype 2/3 

 
31 % 

 
65 % 

 
79 % 

I Viraferon (3 MIU 3 times a week) 
I/R Viraferon (3 MIU 3 times a week) + ribavirin (1,000/1,200 mg/day) 
 
HCV/HIV Co-infected patients  
Two trials have been conducted in patients co-infected with HIV and HCV. Overall, in both studies, patients 
who received Viraferon plus ribavirin, were less likely to respond than patients who received pegylated 
interferon alfa-2b with ribavirin. The response to treatment in both of these trials is presented in Table 4. 
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 412 previously untreated 
adult patients with chronic hepatitis C who were co-infected with HIV. Patients were randomized to receive 
either pegylated interferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800 mg/day) or Viraferon (3 MIU TIW) 
plus ribavirin (800 mg/day) for 48 weeks with a follow-up period of 6 months. Study 2 (P02080) was a 
randomized, single centre study that enrolled 95 previously untreated adult patients with chronic hepatitis C 
who were co-infected with HIV. Patients were randomized to receive either pegylated interferon alfa-2b (100 
or 150 µg /week based on weight) plus ribavirin (800-1,200 mg/day based on weight) or Viraferon (3 MIU 
TIW) plus ribavirin (800-1,200 mg/day based on weight). The duration of therapy was 48 weeks with a 
follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load 
< 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6-month follow-up period.  
           
Table 4 Sustained virological response based on genotype after Viraferon in combination with 

ribavirin versus pegylated interferon alfa-2b in combination with ribavirin in 
HCV/HIV co-infected patients 

 Study 11 Study 22 
 

pegylated 
interferon 

alfa-2b  
(1.5 µg/kg/ 

week) + 
ribavirin  
(800 mg) 

Viraferon  
(3 MIU TIW) +  

ribavirin  
(800 mg) 

p 
valuea 

pegylated 
interferon 

alfa-2b (100 
or  

150c µg/week) 
+ ribavirin 

(800- 
1,200 mg)d 

Viraferon  
(3 MIU TIW) 

+ ribavirin 
(800- 

1,200 mg)d 
p 

valueb 



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All 27 % (56/205) 20 % (41/205) 0.047 44 % (23/52) 21 % (9/43) 0.017 
Genotype 1, 

4 
17 % (21/125) 6 % (8/129) 0.006 38 % (12/32) 7 % (2/27) 0.007 

Genotype 2, 
3 

44 % (35/80) 43 % (33/76) 0.88 53 % (10/19) 47 % (7/15) 0.730 

MIU = million international units; TIW = three times a week. 
a:  p value based on Cochran-Mantel Haenszel Chi square test. 
b:  p value based on chi-square test. 
c:  subjects < 75 kg received 100 µg/week pegylated interferon alfa-2b and subjects ≥ 75 kg received 150 µg/week pegylated 

interferon alfa-2b. 
d: ribavirin dosing was 800 mg for patients < 60 kg, 1,000 mg for patients 60-75 kg, and 1,200 mg for patients > 75 kg. 
 

1Carrat F, Bani-Sadr F, Pol S et al.  JAMA 2004; 292(23): 2839-2848. 
2 Laguno M, Murillas J, Blanco J.L et al.  AIDS 2004; 18(13): F27-F36. 
 
 
Relapse patients: A total of 345 interferon alpha relapse patients were treated in two clinical trials with 
Viraferon monotherapy or in combination with ribavirin. In these patients, the addition of ribavirin to 
Viraferon increased by as much as 10-fold the efficacy of Viraferon used alone in the treatment of chronic 
hepatitis C (48.6 % vs. 4.7 %). This enhancement in efficacy included loss of serum HCV (< 100 copies/ml 
by PCR), improvement in hepatic inflammation, and normalisation of ALT, and was sustained when 
measured 6 months after the end of treatment. 
 
Long-Term efficacy data 
In a large study, 1,071 patients were enrolled after treatment in a prior non pegylated interferon alfa-2b or 
non pegylated interferon alfa-2b/ribavirin study to evaluate the durability of sustained virologic response and 
assess the impact of continued viral negativity on clinical outcomes. 462 patients completed at least 5 years 
of long-term follow-up and only 12 sustained responders' out of 492 relapsed during this study.  
The Kaplan-Meier estimate for continued sustained response over 5 years for all patients is 97 % with a 95 % 
Confidence Interval of [95 %, 99 %].  
SVR after treatment of chronic HCV with non pegylated interferon alfa-2b (with or without ribavirin) results 
in long-term clearance of the virus providing resolution of the hepatic infection and clinical 'cure' from 
chronic HCV. However, this does not preclude the occurrence of hepatic events in patients with cirrhosis 
(including hepatocarcinoma). 
 
Clinical trials in paediatric patients with chronic hepatitis C: 
Children and adolescents 3 to 16 years of age with compensated chronic hepatitis C and detectable HCV-
RNA (assessed by a central laboratory using a research-based RT-PCR assay) were enrolled in two 
multicentre trials and received Viraferon 3 MIU/m2 3 times a week plus ribavirin 15 mg/kg per day for 1 year 
followed by 6 months follow-up after-treatment. A total of 118 patients were enrolled: 57 % male, 80 % 
Caucasian, and 78 % genotype 1,64 % ≤ 12 years of age. The population enrolled mainly consisted in 
children with mild to moderate hepatitis C. Sustained virological response rates in children and adolescents 
were similar to those in adults. Due to the lack of data in children with severe progression of the disease, and 
the potential for undesirable effects, the benefit/risk of the combination of ribavirin and interferon alfa-2b 
needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8). 
 
Study results are summarized in Table 5. 
 
Table 5. Virological response in previously untreated paediatric patients 
 Viraferon 3 MIU/m2 3 times a week   

+ 
ribavirin 15 mg/kg/day 

Overall Response1 (n=118) 54 (46 %)* 



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Genotype 1 (n=92) 33 (36 %)* 

Genotype 2/3/4 (n=26) 21 (81 %)* 

*Number (%) of patients 
1. Defined as HCV-RNA below limit of detection using a research based RT-PCR assay at end of treatment and during follow-up 
period 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of Viraferon were studied in healthy volunteers following single 5 million IU/m2 and 
10 million IU doses administered subcutaneously, at 5 million IU/m2 administered intramuscularly and as a 
30-minute intravenous infusion. The mean serum interferon concentrations following subcutaneous and 
intramuscular injections were comparable. Cmax occurred three to 12 hours after the lower dose and six to 
eight hours after the higher dose. The elimination half-lives of interferon injections were approximately two 
to three hours, and six to seven hours, respectively. Serum levels were below the detection limit 16 and 
24 hours, respectively, post-injection. Both subcutaneous and intramuscular administration resulted in 
bioavailabilities greater than 100 %. 
 
After intravenous administration, serum interferon levels peaked (135 to 273 IU/ml) by the end of the 
infusion, then declined at a slightly more rapid rate than after subcutaneous or intramuscular administration 
of medicinal product, becoming undetectable four hours after the infusion. The elimination half-life was 
approximately two hours. 
 
Urine levels of interferon were below the detection limit following each of the three routes of administration. 
 
Children and adolescents: Multiple-dose pharmacokinetic properties for Viraferon injection and ribavirin 
capsules in children and adolescents with chronic hepatitis C, between 5 and 16 years of age, are summarized 
in Table 6. The pharmacokinetics of Viraferon and ribavirin (dose-normalized) are similar in adults and 
children or adolescents. 
 

Table 6. Mean (% CV) multiple-dose pharmacokinetic parameters for Viraferon and ribavirin 
capsules when administered to children or adolescents with chronic hepatitis C 
Parameter Ribavirin 

15 mg/kg/day as 2 divided 
doses 

(n = 17) 

Viraferon 
3 MIU/m2 3 times a week 

(n = 54) 

Tmax (hr) 1.9 (83) 5.9 (36) 
Cmax (ng/ml) 3,275 (25) 51 (48) 

AUC* 29,774 (26) 622 (48) 
Apparent clearance l/hr/kg 0.27 (27) Not done 

*AUC12 (ng.hr/ml) for ribavirin; AUC0-24 (IU.hr/ml) for Viraferon 
 
Interferon neutralising factor assays were performed on serum samples of patients who received Viraferon in 
Schering-Plough monitored clinical trials. Interferon neutralising factors are antibodies which neutralise the 
antiviral activity of interferon. The clinical incidence of neutralising factors developing in cancer patients 
treated systemically is 2.9 % and in chronic hepatitis patients is 6.2 %. The detectable titres are low in almost 
all cases and have not been regularly associated with loss of response or any other autoimmune phenomenon. 
In patients with hepatitis, no loss of response was observed apparently due to the low titres. 
 
5.3 Preclinical safety data 
 
Although interferon is generally recognised as being species specific, toxicity studies in animals were 
conducted. Injections of human recombinant interferon alfa-2b for up to three months have shown no 
evidence of toxicity in mice, rats, and rabbits. Daily dosing of cynomolgus monkeys with 20 x 106 IU/kg/day 



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for 3 months caused no remarkable toxicity. Toxicity was demonstrated in monkeys given 
100 x 106 IU/kg/day for 3 months. 
 
In studies of interferon use in non-human primates, abnormalities of the menstrual cycle have been observed 
(see section 4.4). 
 
Results of animal reproduction studies indicate that recombinant interferon alfa-2b was not teratogenic in rats 
or rabbits, nor did it adversely affect pregnancy, foetal development or reproductive capacity in offspring of 
treated rats. Interferon alfa-2b has been shown to have abortifacient effects in Macaca mulatta (rhesus 
monkeys) at 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2. 
Abortion was observed in all dose groups (7.5 million, 15 million and 30 million IU/kg), and was statistically 
significant versus control at the mid- and high-dose groups (corresponding to 90 and 180 times the 
recommended intramuscular or subcutaneous dose of 2 million IU/m2). High doses of other forms of 
interferons alpha and beta are known to produce dose-related anovulatory and abortifacient effects in rhesus 
monkeys. 
 
Mutagenicity studies with interferon alfa-2b revealed no adverse events. 
 
No studies have been conducted in juvenile animals to examine the effects of treatment with interferon alfa-
2b on growth, development, sexual maturation, and behaviour (see section 4.4 and Rebetol SPC if Viraferon 
is to be administered in combination with ribavirin). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Disodium phosphate anhydrous,  
Sodium dihydrogen phosphate monohydrate,  
Edetate disodium,  
Sodium chloride,  
M-cresol,  
Polysorbate 80,  
Water for injections q.s.  
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
15 months 
 
Chemical and physical in-use stability has been demonstrated for 27 days at 2ºC – 8ºC. 
From a microbiological point of view, once opened, the product may be stored for a maximum of 27 days at 
2ºC – 8ºC. Other in-use storage times and conditions are the responsibility of the user. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C).  
Do not freeze. 
 
6.5 Nature and contents of container 
 



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1.2 ml of solution (corresponding to 60 MIU) in a pen made of a cartridge (type I glass) sealed at one end 
with an cap (aluminium) containing a liner (bromobutyl rubber) and at the other end by a plunger 
(bromobutyl rubber)  
with 12 injection needles and12 cleansing swabs 
Pack sizes of 1, 2 or 8 
Not all pack sizes may be marketed. 
 
The pen is designed to deliver its contents of 60 million IU in doses ranging from 5 to 20 million IU. The pen 
will deliver a maximum of 12 doses of 5 million IU over a period not to exceed 4 weeks. 
 
6.6 Special precautions for disposal 
 
Not all dosage forms and strengths are appropriate for some indications. Please make sure to select an 
appropriate dosage form and strength. 
 
Viraferon, solution for injection, multidose pen is injected subcutaneously after attaching an injection needle 
and dialing the prescribed dose. 
 
Remove the pen from the refrigerator approximately 30 minutes before administration to allow the injectable 
solution to reach room temperature (not more than 25°C). 
 
Detailed instructions for the subcutaneous use of the product are provided with the package leaflet (refer to 
“How to self inject Viraferon”). 
 
Each pen is intended for a maximum four-week use period and must then be discarded. A new injection 
needle must be used for each dose. After each use, the injection needle must be discarded safely and the pen 
must be returned immediately to the refrigerator. A maximum of 48 hours (two days) of exposure to 25°C is 
permitted over the four-week use period to cover accidental delays in returning the pen to the refrigerator. 
Sufficient needles and swabs are provided to use the Viraferon pen for administering the smallest measurable 
doses. Instruct the patient that any extra needles and swabs that remain after the final dose has been taken 
from the pen, must be discarded appropriately and safely. 
 
As with all parenteral medicinal products, prior to administration inspect Viraferon, solution for injection, 
visually for particulate matter and discolouration. The solution should be clear and colourless. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
SP Europe 
73, rue de Stalle 
B-1180 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/99/128/035 
EU/1/99/128/036 
EU/1/99/128/037 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation : 9 March 2000 
Date of last renewal : 23 May 2005 



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10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMEA) http://www.emea.europa.eu/ 



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ANNEX II 

 
A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 

SUBSTANCE AND MANUFACTURING AUTHORISATION 
HOLDER RESPONSIBLE FOR BATCH RELEASE 

 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 



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A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
SP (Brinny) Company 
Innishannon - County Cork 
Ireland 
 
Name and address of the manufacturer responsible for batch release 
 
SP Labo N.V. 
Industriepark 30 
B-2220 Heist-op-den-Berg 
Belgium 
 
 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 

• CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON THE 
MARKETING AUTHORISATION HOLDER 

 
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 
Characteristics, 4.2). 
 
• CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE OF 

THE MEDICINAL PRODUCT 
 
Not applicable. 



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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



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A. LABELLING 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Outer carton 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 1 million IU/ml powder and solvent for solution for injection 
interferon alfa-2b 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial of powder contains 1 million IU of interferon alfa-2b and provides 1 million IU per ml of interferon 
alfa-2b when reconstituted as recommended. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: glycine, disodium phosphate anhydrous, Sodium dihydrogen phosphate monohydrate, and human 
albumin solution 
One ampoule of solvent contains 1 ml of water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
1 million IU/ml powder and solvent for solution for injection 
1 vial of powder, 1 ampoule of solvent, 1 injection syringe, 2 injection needles and 1 cleansing swab 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
After reconstitution, use the reconstituted solution immediately or within 24 hours when stored in a 
refrigerator (2°C - 8°C). 
 
 



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9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
After withdrawal of the dose, any remaining solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SP Europe, 73, rue de Stalle, B-1180 Bruxelles, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/128/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Viraferon 1 MIU powder 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Viraferon 1 million IU/ml powder for injection 
interferon alfa-2b 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 million IU/ml 
 
 
6. OTHER 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Outer carton 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 3 million IU/ml powder and solvent for solution for injection 
interferon alfa-2b 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial of powder contains 3 million IU of interferon alfa-2b and provides 3 million IU per ml of interferon 
alfa-2b when reconstituted as recommended. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: glycine, disodium phosphate anhydrous sodium dihydrogen phosphate monohydrate, and human 
albumin solution 
One ampoule of solvent contains 1 ml of water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
3 million IU/ml powder and solvent for solution for injection 
1 vial of powder, 1 ampoule of solvent, 1 injection syringe, 2 injection needles and 1 cleansing swab  
6 vials of powder and 6 ampoules of solvent  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
After reconstitution, use the reconstituted solution immediately or within 24 hours when stored in a 
refrigerator (2°C - 8°C). 
 
 



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9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
After withdrawal of the dose, any remaining solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SP Europe, 73, rue de Stalle, B-1180 Bruxelles, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/128/002 1 vial of powder 
EU/1/99/128/003 6 vials of powder 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Viraferon 3 MIU powder 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Viraferon 3 million IU/ml powder for injection 
interferon alfa-2b 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 million IU/ml 
 
 
6. OTHER 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
 
Outer carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 5 million IU/ml powder and solvent for solution for injection 
interferon alfa-2b 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial of powder contains 5 million IU of interferon alfa-2b and provides 5 million IU per ml of interferon 
alfa-2b when reconstituted as recommended. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: glycine, disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, and human 
albumin solution 
One ampoule of solvent contains 1 ml of water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
5 million IU/ml powder and solvent for solution for injection 
1 vial of powder, 1 ampoule of solvent, 1 injection syringe, 2 injection needles and 1 cleansing swab  
6 vials of powder and 6 ampoules of solvent  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
After reconstitution, use the reconstituted solution immediately or within 24 hours when stored in a 
refrigerator (2°C - 8°C). 
 



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9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
After withdrawal of the dose, any remaining solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SP Europe, 73, rue de Stalle, B-1180 Bruxelles, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/128/004 1 vial of powder 
EU/1/99/128/005 6 vials of powder  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Viraferon 5 MIU powder 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Viraferon 5 million IU/ml powder for injection 
interferon alfa-2b 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 million IU/ml 
 
 
6. OTHER 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
 
Outer carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 10 million IU/ml powder and solvent for solution for injection 
interferon alfa-2b 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial of powder contains 10 million IU of interferon alfa-2b and provides 10 million IU per ml of 
interferon alfa-2b when reconstituted as recommended. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: glycine, disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, and human 
albumin solution 
One ampoule of solvent contains 1 ml of water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
10 million IU/ml powder and solvent for solution for injection 
1 vial of powder, 1 ampoule of solvent, 1 injection syringe, 2 injection needles and 1 cleansing swab  
6 vials of powder and 6 ampoules of solvent 
10 vials of powder, 10 ampoules of solvent, 10 injection syringes, 20 injection needles and 10 cleansing 
swabs 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
After reconstitution, use the reconstituted solution immediately or within 24 hours when stored in a 



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refrigerator (2°C - 8°C). 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
After withdrawal of the dose, any remaining solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SP Europe, 73, rue de Stalle, B-1180 Bruxelles, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/128/006 1 vial of powder 
EU/1/99/128/007 6 vials of powder  
EU/1/99/128/008 10 vials of powder 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Viraferon 10 MIU powder 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Viraferon 10 million IU/ml powder for injection 
interferon alfa-2b 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
10 million IU/ml 
 
 
6. OTHER 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial label, ampoule of solvent 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for Viraferon 
Water for injections 
 
 
2. METHOD OF ADMINISTRATION 
 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 ml 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
 
Outer carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 3 million IU/0.5 ml solution for injection 
interferon alfa-2b 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial contains 3 million IU of interferon alfa-2b in 0.5 ml of solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, edetate disodium, 
sodium chloride, m-cresol, polysorbate 80 and water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
3 million IU/0.5 ml solution for injection 
1 single dose vial 
1 single dose vial, 1 injection syringe, 1 injection needle and 1 cleansing swab 
6 single dose vials, 6 injection syringes, 6 injection needles and 6 cleansing swabs 
12 single dose vials, 12 injection syringes, 12 injection needles and 12 cleansing swabs 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 



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Store in a refrigerator. Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
After withdrawal of the dose, any remaining solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SP Europe, 73, rue de Stalle, B-1180 Bruxelles, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/128/009 1 single dose vial 
EU/1/99/128/010 1 single dose vial, 1 injection syringe, 1 injection needle and 1 cleansing swab 
EU/1/99/128/011 6 single dose vials 
EU/1/99/128/012 12 single dose vials 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Viraferon 3 MIU solution 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Viraferon 3 million IU/0.5 ml solution for injection 
interferon alfa-2b 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 million IU/0.5 ml 
 
 
6. OTHER 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
 
Outer carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 5 million IU/0.5 ml solution for injection 
interferon alfa-2b 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial contains 5 million IU of interferon alfa-2b in 0.5 ml of solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, edetate disodium, 
sodium chloride, m-cresol, polysorbate 80 and water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
5 million IU/0.5 ml solution for injection 
1 single dose vial 
1 single dose vial, 1 injection syringe, 1 injection needle and 1 cleansing swab 
6 single dose vials, 6 injection syringes, 6 injection needles and 6 cleansing swabs 
12 single dose vials, 12 injection syringes, 12 injection needles and 12 cleansing swabs 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 



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Store in a refrigerator. Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
After withdrawal of the dose, any remaining solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SP Europe, 73, rue de Stalle, B-1180 Bruxelles, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/128/013 1 single dose vial 
EU/1/99/128/014 1 single dose vial, 1 injection syringe, 1 injection needle and 1 cleansing swab 
EU/1/99/128/015 6 single dose vials 
EU/1/99/128/016 12 single dose vials 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Viraferon 5 MIU solution 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Viraferon 5 million IU/0.5 ml solution for injection 
interferon alfa-2b 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 million IU/0.5 ml 
 
 
6. OTHER 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
 
Outer carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 10 million IU/ml solution for injection 
interferon alfa-2b 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial contains 10 million IU of interferon alfa-2b in 1 ml of solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, edetate disodium, 
sodium chloride, m-cresol, polysorbate 80 and water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
10 million IU/ml solution for injection 
1 single dose vial 
1 single dose vial, 1 injection syringe, 1 injection needle and 1 cleansing swab 
6 single dose vials, 6 injection syringes, 6 injection needles and 6 cleansing swabs 
12 single dose vials, 12 injection syringes, 12 injection needles and 12 cleansing swabs 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 



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Store in a refrigerator. Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
After withdrawal of the dose, any remaining solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SP Europe, 73, rue de Stalle, B-1180 Bruxelles, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/128/017 1 single dose vial 
EU/1/99/128/018 1 single dose vial, 1 injection syringe, 1 injection needle and 1 cleansing swab 
EU/1/99/128/019 6 single dose vials  
EU/1/99/128/020 12 single dose vials 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Viraferon 10 MIU solution 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Viraferon 10 million IU/ml solution for injection 
interferon alfa-2b 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
10 million IU/1 ml 
 
 
6. OTHER 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
 
Outer carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 18 million IU/3 ml solution for injection 
interferon alfa-2b 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial contains 18 million IU of interferon alfa-2b in 3 ml of solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, edetate disodium, 
sodium chloride, m-cresol, polysorbate 80 and water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
18 million IU/3 ml solution for injection 
1 multiple dose vial 
1 multiple dose vial, 6 injection syringes, 6 injection needles and 12 cleansing swabs 
2 multiple dose vials 
12 multiple dose vials 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 



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Store in a refrigerator. Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SP Europe, 73, rue de Stalle, B-1180 Bruxelles, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/128/021 1 multiple dose vial 
EU/1/99/128/022 1 multiple dose vial, 6 injection syringes, 6 injection needles and 12 cleansing swabs 
EU/1/99/128/023 2 multiple dose vials 
EU/1/99/128/024 12 multiple dose vials 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Viraferon 18 MIU solution 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Viraferon 18 million IU/3 ml solution for injection 
interferon alfa-2b 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
18 million IU/3 ml  
 
 
6. OTHER 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
 
Outer carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 25 million IU/2.5 ml solution for injection 
interferon alfa-2b 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One vial contains 25 million IU of interferon alfa-2b in 2.5 ml of solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, edetate disodium, 
sodium chloride, m-cresol, polysorbate 80 and water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
25 million IU/2.5 ml solution for injection 
1 multiple dose vial 
1 multiple dose vial, 6 injection syringes, 6 injection needles and 12 cleansing swabs 
2 multiple dose vials 
12 multiple dose vials 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 



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Store in a refrigerator. Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SP Europe, 73, rue de Stalle, B-1180 Bruxelles, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/128/025 1 multiple dose vial 
EU/1/99/128/026 1 multiple dose vial, 6 injection syringes, 6 injection needles and 12 cleansing swabs 
EU/1/99/128/027 2 multiple dose vials 
EU/1/99/128/028 12 multiple dose vials 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Viraferon 25 MIU solution 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Viraferon 25 million IU/2.5 ml solution for injection 
interferon alfa-2b 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
25 million IU/2.5 ml  
 
 
6. OTHER 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
 
Outer carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 18 million IU solution for injection multidose pen 
interferon alfa-2b 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pen contains 18 million IU of interferon alfa-2b in 1.2 ml of solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, edetate disodium, 
sodium chloride, m-cresol, polysorbate 80 and water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
18 million IU solution for injection multidose pen 
1 pen, 12 injection needles and 12 cleansing swabs 
2 pens, 24 injection needles and 24 cleansing swabs 
8 pens, 96 injection needles and 96 cleansing swabs 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



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Store in a refrigerator. Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SP Europe, 73, rue de Stalle, B-1180 Bruxelles, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/128/029 1 pen 
EU/1/99/128/030 2 pens 
EU/1/99/128/031 8 pens 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Viraferon 18 MIU pen 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Pen label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Viraferon 18 million IU solution for injection multidose pen 
interferon alfa-2b 
Subcutaneous use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
18 million IU/pen 
 
 
6. OTHER 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
 
Outer carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 30 million IU solution for injection multidose pen 
interferon alfa-2b 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pen contains 30 million IU of interferon alfa-2b in 1.2 ml of solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, edetate disodium, 
sodium chloride, m-cresol, polysorbate 80 and water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 million IU solution for injection multidose pen 
1 pen, 12 injection needles and 12 cleansing swabs 
2 pens, 24 injection needles and 24 cleansing swabs 
8 pens, 96 injection needles and 96 cleansing swabs 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



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Store in a refrigerator. Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SP Europe, 73, rue de Stalle, B-1180 Bruxelles, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/128/032 1 pen 
EU/1/99/128/033 2 pens 
EU/1/99/128/034 8 pens 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Viraferon 30 MIU pen 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Pen label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Viraferon 30 million IU solution for injection multidose pen 
interferon alfa-2b 
Subcutaneous use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
30 million IU/pen  
 
 
6. OTHER 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
 
Outer carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Viraferon 60 million IU solution for injection multidose pen 
interferon alfa-2b 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pen contains 60 million IU of interferon alfa-2b in 1.2 ml of solution. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, edetate disodium, 
sodium chloride, m-cresol, polysorbate 80 and water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 million IU solution for injection multidose pen 
1 pen, 12 injection needles and 12 cleansing swabs 
2 pens, 24 injection needles and 24 cleansing swabs 
8 pens, 96 injection needles and 96 cleansing swabs 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



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Store in a refrigerator. Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SP Europe, 73, rue de Stalle, B-1180 Bruxelles, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/99/128/035 1 pen 
EU/1/99/128/036 2 pens 
EU/1/99/128/037 8 pens 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Viraferon 60 MIU pen 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Pen label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Viraferon 60 million IU solution for injection multidose pen 
interferon alfa-2b 
Subcutaneous use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
60 million IU/pen 
 
 
6. OTHER 



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B. PACKAGE LEAFLET 
 
 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Viraferon, 1 million IU/ml powder and solvent for solution for injection 
Interferon alfa-2b 

 
Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Viraferon is and what it is used for 
2. Before you use Viraferon 
3. How to use Viraferon 
4. Possible side effects 
5. How to store Viraferon 
6. Further information 
 
 
1. WHAT VIRAFERON IS AND WHAT IT IS USED FOR 
 
Viraferon (interferon alfa-2b) modifies the response of the body's immune system to help fight infections and 
severe diseases. Viraferon is used in adult patients for the treatment of chronic hepatitis B or C, which are viral 
infections of the liver. 
 
Viraferon is used in combination with ribavirin in children and adolescents 3 years of age and older who have 
previously untreated chronic hepatitis C. 
 
 
2. BEFORE YOU USE VIRAFERON 
 
Do not use Viraferon 
- if you are allergic (hypersensitive) to interferon or any of the other ingredients of Viraferon. 
- if you have severe heart disease. 
- if you have poor kidney or liver function. 
- if you have advanced decompensated (uncontrolled) liver disease. 
- if you have hepatitis and have been treated recently with medications that suppress the immune system 

(other than short-term treatment with cortisone-type medicine). 
- if you have a history of seizures (convulsions). 
- if you have a history of autoimmune disease, or have had an organ transplant and are taking medicine that 

suppresses your immune system (your immune system helps protect you from infection). 
- if you have thyroid disease that is not well controlled. 
Children and adolescents: 
- if you have had serious nervous or mental problems, such as severe depression or thoughts of suicide. 
 
Take special care with Viraferon 
- if you are pregnant or planning to become pregnant (see Pregnancy). 
- if you have had a severe nervous or mental disorder. The use of interferon alfa-2b in children and 

adolescents with existence of or history of severe psychiatric conditions is contraindicated (see “Do not use 
Viraferon”) 

- if you have ever had depression or develop symptoms associated with depression (e.g. feelings of sadness, 
dejection, etc.) while on treatment with Viraferon (see section 4). 



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- if you have psoriasis, it may get worse during treatment with Viraferon. 
- when receiving Viraferon, you may temporarily have a greater risk of getting an infection. Check with 

your doctor if you think you are getting an infection. 
- if you develop symptoms associated with a cold or other respiratory infection, such as fever, cough, or any 

difficulty in breathing, tell your doctor. 
- if you notice unusual bleeding or bruising check with your doctor immediately. 
- if you develop symptoms of a severe allergic reaction (such as difficulty in breathing, wheezing, or hives) 

while on this medication seek medical help immediately. 
- if you are also being treated for HIV, please see Using other medicines. 
- if you have received an organ transplant, either kidney or liver, interferon treatment may increase the risk 

of rejection. Be sure to discuss this with your doctor. 
 
Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving Viraferon 
and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and 
membranes of the mouth during long-term treatment with the combination of Viraferon with ribavirin. You 
should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some 
patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly 
afterwards. 
 
During the one year of treatment, many children did not grow or gain weight as much as expected. However, 
during the 6 months after treatment, this trend was generally reversed, although a few children did not return 
to their previous rate of growth within the first year after completing treatment. 
 
Tell your doctor if you have ever had a heart attack or a heart problem; if you have a history of breathing 
irregularities or pneumonia, problems with blood clotting, liver condition, thyroid problems, diabetes, or high 
or low blood pressure. 
 
Tell your doctor if you have ever been treated for depression or any other psychiatric disorder; confusion; 
unconsciousness; thoughts of suicide or attempted suicide. 
 
Be sure to tell your doctor if you are taking the Chinese herbal medication Shosaikoto. 
 
Using other medicines 
Viraferon will add to the effects of substances that slow down your nervous system, possibly causing 
drowsiness. Therefore, check with your doctor or pharmacist about drinking alcoholic beverages, or taking 
sleeping pills, sedatives or strong pain medications.  
 
Tell your doctor if you are taking theophylline or aminophylline for asthma, and about all other medication 
you are taking, or have taken recently, even those not prescribed, as the dose of some medications may have 
to be adjusted while you are treated with Viraferon. 

 
Patients who also have HIV infection: Lactic acidosis and worsening liver function are side effects associated 
with Highly Active Anti-Retroviral Therapy (HAART), an HIV treatment. If you are receiving HAART, the 
addition of Viraferon and ribavirin may increase your risk of lactic acidosis and of liver failure. Your doctor 
will monitor you for signs and symptoms of these conditions (Please be sure to read the ribavirin Patient 
Leaflet also). Additionally, patients treated with Viraferon and ribavirin combination therapy and zidovudine 
could be at increased risk of developing anaemia (low number of red blood cells). 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. 
 
Using Viraferon with food and drink 
While being treated with Viraferon, your doctor may want you to drink extra fluids to help prevent low blood 
pressure. 
 



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Pregnancy and breast-feeding 
Ask your doctor or pharmacist for advice before taking any medicine. In studies in pregnant animals, 
interferons have sometimes caused miscarriage. The effect on human pregnancy is not known. 
If you are prescribed Viraferon in combination with ribavirin, ribavirin can be very damaging to an unborn 
baby, thus both female and male patients must take special precautions in their sexual activity if there is any 
chance for pregnancy to occur: 
- if you are a girl or a woman of childbearing age, you must have a negative pregnancy test before treatment, 
each month during treatment, and for the 4 months after treatment is stopped. You and your partner must 
each use an effective contraceptive during the time you are taking ribavirin and for 4 months after stopping 
treatment. This can be discussed with your doctor.  
- if you are a man who is taking ribavirin, do not have sex with a pregnant woman unless you use a condom. 
This will lessen the chance for ribavirin to be left in the woman’s body. If your female partner is not pregnant 
now but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 
7 months after treatment has stopped. This can be discussed with your doctor. If you are a male patient, you 
and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 
7 months after stopping treatment. This can be discussed with your doctor. 
 
It is not known whether this product is present in human milk. Therefore, do not breast-feed an infant if you 
are taking Viraferon. In combination therapy with ribavirin, take notice of the respective informing texts of 
ribavirin containing medicinal products. 
 
Driving and using machines 
Do not drive or use machinery if you become drowsy, tired, or confused from this medicine. 
 
Important information about some of the ingredients of Viraferon 
Your doctor may recommend that you consider vaccination against hepatitis A and B if you 
regularly/repeatedly receive human plasma-derived albumin. 
 
This medicine contains human albumin solution as an excipient. When medicines are made from human blood 
or plasma, certain measures are put in place to prevent infections being passed on to patients. These include 
careful selection of blood and plasma donors to make sure those at risk of carrying infections are excluded, 
and the testing of each donation and pools of plasma for signs of virus/infections. Manufacturers of these 
products also include steps in the processing of the blood or plasma that can inactivate or remove viruses. 
Despite these measures, when medicines prepared from human blood or plasma are administered, the 
possibility of passing on infection cannot be totally excluded. This also applies to any unknown or emerging 
viruses or other types of infections. 
 
There are no reports of virus infections with albumin manufactured to European Pharmacopoeia 
specifications by established processes. 
 
It is strongly recommended that every time you receive a dose of Viraferon the name and batch number of the 
product are recorded in order to maintain a record of the batches used. 
 
 
3. HOW TO USE VIRAFERON 
 
Your doctor has prescribed Viraferon specifically for you and your current condition; do not share this medicine 
with anyone else. 
 
Your doctor has determined the exact dosage for administration of Viraferon according to your individual needs. 
The dosage will vary according to the disease being treated. 
 
If you are injecting Viraferon yourself, please be sure that the dose that has been prescribed for you is clearly 
provided with the package of medicine you receive. Dosages that are to be administered 3 times a week are best 
given every other day. 



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The usual starting dose for each condition follows; however, individual doses may vary, and the doctor may 
change your dose based on your specific needs: 
 
Chronic hepatitis B: 5 to 10 million IU 3 times a week (every other day) injected subcutaneously (under the skin). 
 
Chronic hepatitis C: Adults - 3 million IU 3 times a week (every other day) injected subcutaneously (under the 
skin) in combination with ribavirin or alone. Children 3 years of age and older and adolescents - 
3 million IU/m2 3 times a week (every other day) injected subcutaneously (under the skin) in combination with 
ribavirin (Please also see ribavirin package leaflet).  
 
Your doctor may prescribe a different dose of Viraferon alone or in combination with other medicines (e.g. 
ribavirin). If you are prescribed Viraferon in combination with another medicine, please refer also to the Package 
Leaflet of the medicine to be used in combination. Your doctor will determine the exact dosage schedule and 
regimen according to your needs. If you have the impression that the effect of Viraferon is too strong or too 
weak, talk to your doctor or pharmacist. 
 
Subcutaneous use: 
Viraferon is usually intended for subcutaneous use. This means that Viraferon is injected with a short needle into 
the fatty tissue just under the skin. If you are injecting this medicine yourself, you will be instructed how to 
prepare and give the injection. Detailed instructions for subcutaneous administration are provided with this leaflet 
(see HOW TO SELF INJECT VIRAFERON at the end of the leaflet). 
 
One dose of Viraferon is given on each scheduled day. Viraferon is given three times a week, every other day, for 
example on Monday, Wednesday, and Friday. Interferons may cause unusual tiredness; if you are injecting this 
medicine yourself, or giving it to a child, use it at bedtime. 
 
Use Viraferon exactly as prescribed by your doctor. Do not exceed the recommended dosage, and take Viraferon 
for as long as prescribed. 
 
If you use more Viraferon than you should 
Contact your doctor or healthcare professional as soon as possible. 
 
If you forget to take Viraferon 
If you are self-administering treatment, or if you are the caregiver of a child taking Viraferon in combination 
with ribavirin, inject the recommended dose as soon as you remember and continue treatment as usual. Do 
not take a double dose to make up for a forgotten dose. If you are scheduled to inject this product every day, 
and you accidentally missed a full day’s dose, continue treatment at the usual dose the following day. Contact 
your doctor or pharmacist if needed. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Viraferon can cause side effects, although not everybody gets them. Although not all of 
these side effects may occur, they may need medical attention if they do. 
 
Some people get depressed when taking Viraferon alone or in combination treatment with ribavirin, and in some 
cases people had suicidal thoughts or aggressive behaviour (sometimes directed against others). Some patients have 
actually committed suicide. Be sure to seek emergency care if you notice that you are becoming depressed or have 
suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend 
to help you stay alert to signs of depression or changes in your behaviour. 
 
Paediatric Use: Children are particularly prone to develop depression when being treated with Viraferon and 
ribavirin. Immediately contact the doctor or seek emergency care if they display any unusual behavioural 
symptoms, feel depressed, or feel they want to harm themselves or others. 



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If any of the following side effects happen, stop taking Viraferon and tell your doctor immediately or go to 
the casualty department at your nearest hospital: 
• swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in 

swallowing or breathing; hives; fainting. 
These are all very serious side effects. If you have them, you may have had a serious allergic reaction to 
Viraferon. You may need urgent medical attention or hospitalisation. These very serious side effects are very 
rare. 
 
Check with your doctor immediately if any of the following side effects occur: 
• chest pain or persistent and severe cough; irregular or rapid heartbeat; shortness of breath, confusion, 

difficulty remaining alert, numbness or tingling sensation or pain in hands or feet; seizure 
(convulsions); trouble sleeping, thinking or concentrating; altered mental state; suicidal thoughts, 
suicide attempt, changed behaviour or aggressive behaviour (sometimes directed against others), 
hallucinations; severe stomach pain; black or tar like stools; blood in stool or urine, severe 
nosebleed; waxy pallor, high sugar level in blood, fever or chills beginning after a few weeks of 
treatment, lower back or side pain, difficult urination, problems with your eyes or your eyesight or 
hearing, loss of hearing, severe or painful reddening or sores on your skin or mucous membrane. 

These may signal serious side effects that may need urgent medical attention. Your doctor will test your 
blood to ensure that your white blood cell (cells that fight infection) and red blood cell (cells that carry iron 
and oxygen) counts, platelets (blood clotting cells) and other laboratory values are at acceptable levels. 
 
At the beginning of treatment with Viraferon, you may experience a flu-like reaction, with fever, fatigue, 
headache, muscle ache, joint pain and chills/rigors. Your doctor may recommend that you take paracetamol if 
you develop these symptoms. 
 
Other side effects that may occur include: 
 
Very commonly reported side effects (at least 1 in every 10 patients):  
pain, swelling and redness or skin damage at site of injection, hair loss, dizziness, changes in appetite, 
stomach or abdominal pains, diarrhoea, nausea (feeling sick), viral infection, depression, emotional lability, 
insomnia, anxiety, sore throat and painful swallowing, fatigue, chills/rigors, fever, flu-like reaction, feeling 
of general discomfort, headaches, weight loss, vomiting, irritability, weakness, mood swings, coughing 
(sometimes severe), shortness of breath, itching, dry skin, rash, sudden and severe muscle pain, joint pain, 
musculoskeletal pain, changes in laboratory blood values including decreased white blood cell count. Some 
children have had a decrease in their rate of growth (height and weight). 
 
Commonly reported side effects (at least 1 in every 100 patients, but less than 1 in every 10 patients): 
thirst, dehydration, high blood pressure, migraines, swollen glands, flushing, menstrual problems, 
decreased sexual drive, vaginal problem, breast pain, pain in testicle, problems with thyroid gland, red 
gums, dry mouth, red or sore mouth or tongue, tooth ache or tooth disorder, herpes simplex (fever blisters), 
taste change, upset stomach, dyspepsia (heartburn), constipation, enlargement of liver (liver problems, 
sometimes severe), loose stools, bedwetting in children, inflammation of the sinuses, bronchitis, eye pain, 
problem with your tear ducts, conjunctivitis (“pink eye”), agitation, sleepiness, sleepwalking, problem with 
behaviour, nervousness, stuffy or runny nose, sneezing, rapid breathing, pale or reddened skin, bruising, 
fingers and toes very sensitive to cold, problem with skin or nails, psoriasis (new or worsened), increased 
sweating, increased need to pass urine, fine shaking movements, decreased sensitivity to touch, arthritis.  
 
Rarely reported side effects (at least 1 in every 10,000 patients, but less than 1 in every 1,000 patients): 
pneumonia 
 
Very rarely reported side effects (less than 1 in every 10,000 patients): 
low blood pressure, puffy face, diabetes, leg cramps, back pain, kidney problems, nerve damage, bleeding 
gums, aplastic anaemia. Pure red cell aplasia, a condition where the body stopped or reduced the production 



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of red blood cells, has been reported. This causes severe anaemia, symptoms of which would include unusual 
tiredness and a lack of energy. 
 
Very rarely sarcoidosis, (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin 
lesions and swollen glands) has been reported. Loss of consciousness has occurred very rarely, mostly in 
elderly patients treated at high doses. Cases of stroke (cerebrovascular events) have been reported. Check 
with your doctor immediately if you have any of these symptoms.  
Periodontal (affecting gums) and dental disorders, altered mental status, loss of consciousness, acute 
hypersensitivity reactions including urticaria (hives), angioedema (swelling of the hands, feet, ankles, face, 
lips, mouth, or throat which may cause difficulty in swallowing or breathing), bronchoconstriction and 
anaphylaxis (a severe, whole-body allergic reaction) have been reported, but their frequency is unknown.  
 
Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin 
and the membranes of the ears, brain and spinal cord) has been reported with Viraferon use. 
 
Other side effects not listed above may also occur in some patients. If any of the side effects gets serious, or if you 
notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. 
 
 
5. HOW TO STORE VIRAFERON 
 
Keep out of the reach and sight of children. 
 
Store in a refrigerator (2°C - 8°C).  
Do not freeze.  
For short term travelling, the non-reconstituted product can be kept out of the refrigerator at or below 25°C 
for a period up to four weeks before use. If the product is not used during this four-week period, it should be 
discarded. 
 
The solution should be used immediately after reconstitution. If not used immediately, it must be stored at 
2°C - 8°C in the refrigerator and used within 24 hours. 
 
Do not use Viraferon after the expiry date which is stated on the package. 
 
Do not use Viraferon if you notice changes in the appearance of Viraferon. 
 
Any unused product must be discarded after withdrawal of the dose. 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose 
of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What Viraferon contains 
 
- The active substance is recombinant interferon alfa-2b, 1 million IU/ml. 
- The other ingredients are glycine, disodium phosphate anhydrous, sodium dihydrogen phosphate 

monohydrate, and human albumin solution. 
- Solvent: water for injections 1 ml/ampoule 
 
What Viraferon looks like and contents of the pack 
 
Viraferon is presented as a powder and solvent for solution for injection 
The white to cream coloured powder is contained in a 2 ml glass vial and the clear and colourless solvent is 
presented in a 2 ml glass ampoule with 1 injection syringe, 2 injection needles and 1 cleansing swab.  



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Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: Manufacturer: 
SP Europe SP Labo N.V. 
73, rue de Stalle Industriepark 30 
B-1180 Bruxelles B-2220 Heist-op-den-Berg 
Belgium Belgium 
 
For any information about this medicinal product, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Rue de Stalle/Stallestraat 73 
B-1180 Bruxelles/Brussel/Brüssel 
Tél/Tel: + 32-(0)2 370 92 11 
 

Luxembourg/Luxemburg 
Rue de Stalle 73 
B-1180 Bruxelles/Brüssel 
Belgique/Belgien 
Tél/Tel: + 32-(0)2 370 92 11 
 

България 
ул. "Проф. Милко Бичев" № 7, ет.3 
BG-София 1504  
Тел.: +359 2 944 1073 

Magyarország 
Alkotás u. 53. 
H-1123 Budapest 
Tel.: + 36 1 457-8500 
 

Česká republika 
Na Příkopě 25 
CZ-110 00 Praha 1 
Tel: + 420 221771250 
 

Malta 
168 Christopher Street 
MT-VLT02 Valletta 
Tel: + 356-21 23 21 75 
 

Danmark 
Lautrupbjerg 2 
DK-2750 Ballerup 
Tlf: + 45-44 39 50 00 
 

Nederland 
Maarssenbroeksedijk 4 
NL-3542 DN Utrecht 
Tel: + 31-(0)800 778 78 78 

Deutschland 
Thomas-Dehler-Straße 27 
D-81737 München  
Tel: + 49-(0)89 627 31-0 
 

Norge 
Pb. 398 
N-1326 Lysaker 
Tlf: + 47 67 16 64 50 
 



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Eesti 
Järvevana tee 9 
EE-11314 Tallinn 
Tel: + 372 654 96 86 
 

Österreich 
Badener Strasse 23 
A-2514 Traiskirchen 
Tel: + 43-(0)2252 502-0 
 

Ελλάδα 
Αγίου Δημητρίου 63 
GR-174 55 Άλιμος  
Tηλ: + 30-210 98 97 300 
 

Polska 
Al. Jerozolimskie 195a 
PL-02-222 Warszawa 
Tel.: + 48-(0)22 478 41 50 
 

España 
Km. 36, Ctra. Nacional I 
E-28750 San Agustín de Guadalix – Madrid 
Tel: + 34-91 848 85 00 
 

Portugal 
Rua Agualva dos Açores 16 
P-2735-557 Agualva-Cacém 
Tel: + 351-21 433 93 00 
 

France 
92 rue Baudin  
F-92300 Levallois-Perret 
Tél: + 33-(0)1 41 06 35 00 
 

România 
Şos. Bucureşti-Ploieşti, nr. 17-21,  
Băneasa Center, et. 8, sector 1 
RO-013682 Bucureşti 
Tel. + 40 21 233 35 30 

Ireland 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW 
Tel: + 44-(0)1 707 363 636 
 

Slovenija 
Dunajska 22 
SI-1000 Ljubljana 
Tel. + 386 01 3001070 
 

Ísland 
Hörgatún 2 
IS-210 Garðabær 
Sími: + 354 535 70 00 
 

Slovenská republika 
Strakova 5 
SK-811 01 Bratislava 
Tel: + 421 (2) 5920 2712 
 

Italia 
Via fratelli Cervi snc, 
Centro Direzionale Milano Due 
Palazzo Borromini 
I-20090 Segrate (Milano) 
Tel: + 39-02 21018.1 
 

Suomi/Finland 
PL 3/PB 3 
FIN-02201 Espoo/Esbo 
Puh/Tel: + 358-(0)20-7570 300 
 

Κύπρος 
Οδός Αγίου Νικολάου, 8 
CY-1055 Λευκωσία 
Τηλ: + 357-22 757188 
 

Sverige 
Box 6185 
S-102 33 Stockholm 
Tel: + 46-(0)8 522 21 500 
 

Latvija 
Bauskas 58a -401 
Rīga, LV-1004  
Tel: + 371-7 21 38 25 
 

United Kingdom 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW - UK 
Tel: + 44-(0)1 707 363 636 
 



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Lietuva 
Kęstučio g. 65/40 
LT-08124 Vilnius 
Tel. + 370 52 101868 
 

 

 
 
This leaflet was last approved on 
 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: 
http://www.emea.europa.eu/ 
 



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HOW TO SELF INJECT VIRAFERON 
 
The following instructions explain how to inject Viraferon yourself. Please read the instructions carefully and 
follow them step by step. Your doctor or his/her assistant will instruct you how to self-inject Viraferon. Do 
not attempt to inject yourself unless you are sure you understand the procedure and requirement of self-
injection. 
 
Preparation 
Collect necessary items before you begin: 
- a vial of Viraferon powder for injection; 
- an ampoule of solvent for Viraferon (water for injections 1 ml); 
- a 2 ml syringe; 
- a long needle (for example 0.8 × 40 mm [21 gauge 1.5 inch]) to be used to add water for injections to 

the Viraferon powder vial; 
- a short needle (for example 0.3 × 13 mm [30 gauge 0.5 inch]) for the subcutaneous injection; 
- a cleansing swab. 
Wash your hands carefully. 
 
Reconstituting Viraferon powder for injection 
Remove the protective cap from the Viraferon vial. Clean the rubber top of the vial with a cleansing swab. 
You can save the swab to clean the skin area where you will inject the dose. Remove the syringe from the 
wrapping. Do not touch the tip of the syringe. Take the long needle and place it firmly onto the tip of the 
syringe. Remove the needle guard without touching the needle and keep the syringe with the needle in your 
hand. Tap the top of the ampoule of solvent gently to make sure that all the liquid is at the bottom of the 
ampoule. Break the top of the ampoule of solvent. Insert the needle in the ampoule of solvent and withdraw 
the total amount of solvent. 
 
To prepare the Viraferon solution insert the needle through the rubber top of the Viraferon vial and gently 
place the needle tip against the glass wall of the vial without touching the cleaned top of the vial with your 
hands. 
Slowly inject the diluent, aiming the stream of liquid at the glass wall of the vial in order to avoid production 
of air bubbles. Do not aim the stream at the white powder at the bottom of the vial. To dissolve the white 
contents, swirl the Viraferon vial with a gentle rotary motion leaving the syringe needle in the vial, until the 
contents are completely dissolved. Do not shake. If air bubbles do form, wait until the solution has settled and 
all bubbles have risen to the top of the solution and disappeared before withdrawing your dose from the vial. 
The solution should be used immediately after reconstitution. If not used immediately, it must be stored at 
2°C - 8°C in the refrigerator and used within 24 hours. 
 
Measuring the dose of Viraferon from the reconstituted powder for injection 
Turn the vial and the syringe upside down in one hand. Be sure the tip of needle is in the Viraferon 
reconstituted solution. Your other hand will be free to move the plunger. Pull back on the plunger slowly to 
draw the correct dose as prescribed by your doctor into the syringe. 
Hold the syringe with the needle in the vial pointing up, remove the syringe from the long needle leaving the 
needle in the vial and without touching the tip of the syringe. Take the short needle and place it firmly onto 
the tip of the syringe. Remove the needle guard from the syringe needle and check for air bubbles in the 
syringe. If you see any bubbles, pull the plunger slightly back; tap the syringe gently, with the needle 
pointing up, until the bubbles disappear. Push up the plunger slowly back to the correct dose. Replace the 
needle guard and place the syringe with the needle on a flat surface. 
 
Be sure the solution is at room temperature up to 25°C. If the solution is cold, warm the syringe between your 
palms. Examine the reconstituted solution prior to administration: it should be clear and colourless. Do not 
use if discolouration or particulate matter is present. You are now ready to inject the dose. 



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Injecting the solution 
Select the injection site. The best sites for injection are tissues with a layer of fat between skin and muscle: 
thigh, outer surface of the upper arm (you may need the assistance of another person to use this site), 
abdomen (except the navel or waistline). If you are exceptionally thin, use only the thigh or outer surface of 
the arm for injection. 
Change your injection site each time. 
 
Cleanse and disinfect the skin where the injection is to be made. Wait for the area to dry. Remove the needle 
guard.With one hand, pinch a fold of loose skin. With your other hand hold the syringe as you would a 
pencil. Insert the needle into the pinched skin at an angle of 45° to 90°. Inject the solution by pushing the 
plunger all the way down gently. 
Pull the needle straight out of the skin. Press the injection site with a small bandage or sterile gauze if 
necessary for several seconds. Do not massage the injection site. If there is bleeding, cover with an adhesive 
bandage. 
The vial, ampoule and injection materials intended for single use must be discarded. Dispose of the syringe 
and needles safely in a closed container. 
 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Viraferon, 3 million IU/ml powder and solvent for solution for injection 
Interferon alfa-2b 

 
Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Viraferon is and what it is used for 
2. Before you use Viraferon 
3. How to use Viraferon 
4. Possible side effects 
5. How to store Viraferon 
6. Further information 
 
 
1. WHAT VIRAFERON IS AND WHAT IT IS USED FOR 
 
Viraferon (interferon alfa-2b) modifies the response of the body's immune system to help fight infections and 
severe diseases. Viraferon is used in adult patients for the treatment of chronic hepatitis B or C, which are viral 
infections of the liver. 
 
Viraferon is used in combination with ribavirin in children and adolescents 3 years of age and older who have 
previously untreated chronic hepatitis C. 
 
 
2. BEFORE YOU USE VIRAFERON 
 
Do not use Viraferon 
- if you are allergic (hypersensitive) to interferon or any of the other ingredients of Viraferon. 
- if you have severe heart disease. 
- if you have poor kidney or liver function. 
- if you have advanced decompensated (uncontrolled) liver disease. 
- if you have hepatitis and have been treated recently with medications that suppress the immune system 

(other than short-term treatment with cortisone-type medicine). 
- if you have a history of seizures (convulsions). 
- if you have a history of autoimmune disease, or have had an organ transplant and are taking medicine that 

suppresses your immune system (your immune system helps protect you from infection). 
- if you have thyroid disease that is not well controlled. 
Children and adolescents: 
- if you have had serious nervous or mental problems, such as severe depression or thoughts of suicide. 
 
Take special care with Viraferon 
- if you are pregnant or planning to become pregnant (see Pregnancy). 
- if you have had a severe nervous or mental disorder. The use of interferon alfa-2b in children and 

adolescents with existence of or history of severe psychiatric conditions is contraindicated (see “Do not use 
Viraferon”) 

- if you have ever had depression or develop symptoms associated with depression (e.g. feelings of sadness, 
dejection, etc.) while on treatment with Viraferon (see section 4). 



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- if you have psoriasis, it may get worse during treatment with Viraferon. 
- when receiving Viraferon, you may temporarily have a greater risk of getting an infection. Check with 

your doctor if you think you are getting an infection. 
- if you develop symptoms associated with a cold or other respiratory infection, such as fever, cough, or any 

difficulty in breathing, tell your doctor. 
- if you notice unusual bleeding or bruising check with your doctor immediately. 
- if you develop symptoms of a severe allergic reaction (such as difficulty in breathing, wheezing, or hives) 

while on this medication seek medical help immediately. 
- if you are also being treated for HIV, please see Using other medicines. 
- if you have received an organ transplant, either kidney or liver, interferon treatment may increase the risk 

of rejection. Be sure to discuss this with your doctor. 
 
Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving Viraferon 
and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and 
membranes of the mouth during long-term treatment with the combination of Viraferon with ribavirin. You 
should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some 
patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly 
afterwards. 
 
During the one year of treatment, many children did not grow or gain weight as much as expected. However, 
during the 6 months after treatment, this trend was generally reversed, although a few children did not return 
to their previous rate of growth within the first year after completing treatment. 
 
Tell your doctor if you have ever had a heart attack or a heart problem; if you have a history of breathing 
irregularities or pneumonia, problems with blood clotting, liver condition, thyroid problems, diabetes, or high 
or low blood pressure. 
 
Tell your doctor if you have ever been treated for depression or any other psychiatric disorder; confusion; 
unconsciousness; thoughts of suicide or attempted suicide. 
 
Be sure to tell your doctor if you are taking the Chinese herbal medication Shosaikoto. 
 
Using other medicines 
Viraferon will add to the effects of substances that slow down your nervous system, possibly causing 
drowsiness. Therefore, check with your doctor or pharmacist about drinking alcoholic beverages, or taking 
sleeping pills, sedatives or strong pain medications.  
 
Tell your doctor if you are taking theophylline or aminophylline for asthma, and about all other medication 
you are taking, or have taken recently, even those not prescribed, as the dose of some medications may have 
to be adjusted while you are treated with Viraferon. 

 
Patients who also have HIV infection: Lactic acidosis and worsening liver function are side effects associated 
with Highly Active Anti-Retroviral Therapy (HAART), an HIV treatment. If you are receiving HAART, the 
addition of Viraferon and ribavirin may increase your risk of lactic acidosis and of liver failure. Your doctor 
will monitor you for signs and symptoms of these conditions (Please be sure to read the ribavirin Patient 
Leaflet also). Additionally, patients treated with Viraferon and ribavirin combination therapy and zidovudine 
could be at increased risk of developing anaemia (low number of red blood cells). 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. 
 
Using Viraferon with food and drink 
While being treated with Viraferon, your doctor may want you to drink extra fluids to help prevent low blood 
pressure. 
 



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Pregnancy and breast-feeding 
Ask your doctor or pharmacist for advice before taking any medicine. In studies in pregnant animals, 
interferons have sometimes caused miscarriage. The effect on human pregnancy is not known. 
If you are prescribed Viraferon in combination with ribavirin, ribavirin can be very damaging to an unborn 
baby, thus both female and male patients must take special precautions in their sexual activity if there is any 
chance for pregnancy to occur: 
- if you are a girl or a woman of childbearing age, you must have a negative pregnancy test before treatment, 
each month during treatment, and for the 4 months after treatment is stopped. You and your partner must 
each use an effective contraceptive during the time you are taking ribavirin and for 4 months after stopping 
treatment. This can be discussed with your doctor.  
- if you are a man who is taking ribavirin, do not have sex with a pregnant woman unless you use a condom. 
This will lessen the chance for ribavirin to be left in the woman’s body. If your female partner is not pregnant 
now but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 
7 months after treatment has stopped. This can be discussed with your doctor. If you are a male patient, you 
and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 
7 months after stopping treatment. This can be discussed with your doctor. 
 
It is not known whether this product is present in human milk. Therefore, do not breast-feed an infant if you 
are taking Viraferon. In combination therapy with ribavirin, take notice of the respective informing texts of 
ribavirin containing medicinal products. 
 
Driving and using machines 
Do not drive or use machinery if you become drowsy, tired, or confused from this medicine. 
 
Important information about some of the ingredients of Viraferon 
Your doctor may recommend that you consider vaccination against hepatitis A and B if you 
regularly/repeatedly receive human plasma-derived albumin. 
 
This medicine contains human albumin solution as an excipient. When medicines are made from human blood 
or plasma, certain measures are put in place to prevent infections being passed on to patients. These include 
careful selection of blood and plasma donors to make sure those at risk of carrying infections are excluded, 
and the testing of each donation and pools of plasma for signs of virus/infections. Manufacturers of these 
products also include steps in the processing of the blood or plasma that can inactivate or remove viruses. 
Despite these measures, when medicines prepared from human blood or plasma are administered, the 
possibility of passing on infection cannot be totally excluded. This also applies to any unknown or emerging 
viruses or other types of infections. 
 
There are no reports of virus infections with albumin manufactured to European Pharmacopoeia 
specifications by established processes. 
 
It is strongly recommended that every time you receive a dose of Viraferon the name and batch number of the 
product are recorded in order to maintain a record of the batches used. 
 
 
3. HOW TO USE VIRAFERON 
 
Your doctor has prescribed Viraferon specifically for you and your current condition; do not share this medicine 
with anyone else. 
 
Your doctor has determined the exact dosage for administration of Viraferon according to your individual needs. 
The dosage will vary according to the disease being treated. 
 
If you are injecting Viraferon yourself, please be sure that the dose that has been prescribed for you is clearly 
provided with the package of medicine you receive. Dosages that are to be administered 3 times a week are best 
given every other day. 



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The usual starting dose for each condition follows; however, individual doses may vary, and the doctor may 
change your dose based on your specific needs: 
 
Chronic hepatitis B: 5 to 10 million IU 3 times a week (every other day) injected subcutaneously (under the skin). 
 
Chronic hepatitis C: Adults - 3 million IU 3 times a week (every other day) injected subcutaneously (under the 
skin) in combination with ribavirin or alone. Children 3 years of age and older and adolescents - 
3 million IU/m2 3 times a week (every other day) injected subcutaneously (under the skin) in combination with 
ribavirin (Please also see ribavirin package leaflet).  
 
Your doctor may prescribe a different dose of Viraferon alone or in combination with other medicines (e.g. 
ribavirin). If you are prescribed Viraferon in combination with another medicine, please refer also to the Package 
Leaflet of the medicine to be used in combination. Your doctor will determine the exact dosage schedule and 
regimen according to your needs. If you have the impression that the effect of Viraferon is too strong or too 
weak, talk to your doctor or pharmacist. 
 
Subcutaneous use: 
Viraferon is usually intended for subcutaneous use. This means that Viraferon is injected with a short needle into 
the fatty tissue just under the skin. If you are injecting this medicine yourself, you will be instructed how to 
prepare and give the injection. Detailed instructions for subcutaneous administration are provided with this leaflet 
(see HOW TO SELF INJECT VIRAFERON at the end of the leaflet). 
 
One dose of Viraferon is given on each scheduled day. Viraferon is given three times a week, every other day, for 
example on Monday, Wednesday, and Friday. Interferons may cause unusual tiredness; if you are injecting this 
medicine yourself, or giving it to a child, use it at bedtime. 
 
Use Viraferon exactly as prescribed by your doctor. Do not exceed the recommended dosage, and take Viraferon 
for as long as prescribed. 
 
If you use more Viraferon than you should 
Contact your doctor or healthcare professional as soon as possible. 
 
If you forget to take Viraferon 
If you are self-administering treatment, or if you are the caregiver of a child taking Viraferon in combination 
with ribavirin, inject the recommended dose as soon as you remember and continue treatment as usual. Do 
not take a double dose to make up for a forgotten dose. If you are scheduled to inject this product every day, 
and you accidentally missed a full day’s dose, continue treatment at the usual dose the following day. Contact 
your doctor or pharmacist if needed. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Viraferon can cause side effects, although not everybody gets them. Although not all of 
these side effects may occur, they may need medical attention if they do. 
 
Some people get depressed when taking Viraferon alone or in combination treatment with ribavirin, and in some 
cases people had suicidal thoughts or aggressive behaviour (sometimes directed against others). Some patients have 
actually committed suicide. Be sure to seek emergency care if you notice that you are becoming depressed or have 
suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend 
to help you stay alert to signs of depression or changes in your behaviour. 
 
Paediatric Use: Children are particularly prone to develop depression when being treated with Viraferon and 
ribavirin. Immediately contact the doctor or seek emergency care if they display any unusual behavioural 
symptoms, feel depressed, or feel they want to harm themselves or others. 



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If any of the following side effects happen, stop taking Viraferon and tell your doctor immediately or go to 
the casualty department at your nearest hospital: 
• swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in 

swallowing or breathing; hives; fainting. 
These are all very serious side effects. If you have them, you may have had a serious allergic reaction to 
Viraferon. You may need urgent medical attention or hospitalisation. These very serious side effects are very 
rare. 
 
Check with your doctor immediately if any of the following side effects occur: 
• chest pain or persistent and severe cough; irregular or rapid heartbeat; shortness of breath, confusion, 

difficulty remaining alert, numbness or tingling sensation or pain in hands or feet; seizure 
(convulsions); trouble sleeping, thinking or concentrating; altered mental state; suicidal thoughts, 
suicide attempt, changed behaviour or aggressive behaviour (sometimes directed against others), 
hallucinations; severe stomach pain; black or tar like stools; blood in stool or urine, severe 
nosebleed; waxy pallor, high sugar level in blood, fever or chills beginning after a few weeks of 
treatment, lower back or side pain, difficult urination, problems with your eyes or your eyesight or 
hearing, loss of hearing, severe or painful reddening or sores on your skin or mucous membrane. 

These may signal serious side effects that may need urgent medical attention. Your doctor will test your 
blood to ensure that your white blood cell (cells that fight infection) and red blood cell (cells that carry iron 
and oxygen) counts, platelets (blood clotting cells) and other laboratory values are at acceptable levels. 
 
At the beginning of treatment with Viraferon, you may experience a flu-like reaction, with fever, fatigue, 
headache, muscle ache, joint pain and chills/rigors. Your doctor may recommend that you take paracetamol if 
you develop these symptoms. 
 
Other side effects that may occur include: 
 
Very commonly reported side effects (at least 1 in every 10 patients):  
pain, swelling and redness or skin damage at site of injection, hair loss, dizziness, changes in appetite, 
stomach or abdominal pains, diarrhoea, nausea (feeling sick), viral infection, depression, emotional lability, 
insomnia, anxiety, sore throat and painful swallowing, fatigue, chills/rigors, fever, flu-like reaction, feeling 
of general discomfort, headaches, weight loss, vomiting, irritability, weakness, mood swings, coughing 
(sometimes severe), shortness of breath, itching, dry skin, rash, sudden and severe muscle pain, joint pain, 
musculoskeletal pain, changes in laboratory blood values including decreased white blood cell count. Some 
children have had a decrease in their rate of growth (height and weight). 
 
Commonly reported side effects (at least 1 in every 100 patients, but less than 1 in every 10 patients): 
thirst, dehydration, high blood pressure, migraines, swollen glands, flushing, menstrual problems, 
decreased sexual drive, vaginal problem, breast pain, pain in testicle, problems with thyroid gland, red 
gums, dry mouth, red or sore mouth or tongue, tooth ache or tooth disorder, herpes simplex (fever blisters), 
taste change, upset stomach, dyspepsia (heartburn), constipation, enlargement of liver (liver problems, 
sometimes severe), loose stools, bedwetting in children, inflammation of the sinuses, bronchitis, eye pain, 
problem with your tear ducts, conjunctivitis (“pink eye”), agitation, sleepiness, sleepwalking, problem with 
behaviour, nervousness, stuffy or runny nose, sneezing, rapid breathing, pale or reddened skin, bruising, 
fingers and toes very sensitive to cold, problem with skin or nails, psoriasis (new or worsened), increased 
sweating, increased need to pass urine, fine shaking movements, decreased sensitivity to touch, arthritis.  
 
Rarely reported side effects (at least 1 in every 10,000 patients, but less than 1 in every 1,000 patients): 
pneumonia 
 
Very rarely reported side effects (less than 1 in every 10,000 patients): 
low blood pressure, puffy face, diabetes, leg cramps, back pain, kidney problems, nerve damage, bleeding 
gums, aplastic anaemia. Pure red cell aplasia, a condition where the body stopped or reduced the production 



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of red blood cells, has been reported. This causes severe anaemia, symptoms of which would include unusual 
tiredness and a lack of energy. 
 
Very rarely sarcoidosis, (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin 
lesions and swollen glands) has been reported. Loss of consciousness has occurred very rarely, mostly in 
elderly patients treated at high doses. Cases of stroke (cerebrovascular events) have been reported. Check 
with your doctor immediately if you have any of these symptoms.  
Periodontal (affecting gums) and dental disorders, altered mental status, loss of consciousness, acute 
hypersensitivity reactions including urticaria (hives), angioedema (swelling of the hands, feet, ankles, face, 
lips, mouth, or throat which may cause difficulty in swallowing or breathing), bronchoconstriction and 
anaphylaxis (a severe, whole-body allergic reaction) have been reported, but their frequency is unknown.  
 
Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin 
and the membranes of the ears, brain and spinal cord) has been reported with Viraferon use. 
 
Other side effects not listed above may also occur in some patients. If any of the side effects gets serious, or if you 
notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. 
 
 
5. HOW TO STORE VIRAFERON 
 
Keep out of the reach and sight of children. 
 
Store in a refrigerator (2°C - 8°C).  
Do not freeze.  
For short term travelling, the non-reconstituted product can be kept out of the refrigerator at or below 25°C 
for a period up to four weeks before use. If the product is not used during this four-week period, it should be 
discarded. 
 
The solution should be used immediately after reconstitution. If not used immediately, it must be stored at 
2°C - 8°C in the refrigerator and used within 24 hours. 
 
Do not use Viraferon after the expiry date which is stated on the package. 
 
Do not use Viraferon if you notice changes in the appearance of Viraferon. 
 
Any unused product must be discarded after withdrawal of the dose. 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose 
of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What Viraferon contains 
 
- The active substance is recombinant interferon alfa-2b, 3 million IU/ml. 
- The other ingredients are glycine, disodium phosphate anhydrous, sodium dihydrogen phosphate 

monohydrate, and human albumin solution. 
- Solvent: water for injections 1 ml/ampoule 
 
What Viraferon looks like and contents of the pack 
 
Viraferon is presented as a powder and solvent for solution for injection 
The white to cream coloured powder is contained in a 2 ml glass vial and the clear and colourless solvent is 
presented in a 2 ml glass ampoule. 



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Viraferon is available in two different pack sizes: 
- Pack of 1 vial of powder for solution for injection, 1 ampoule of water for injections, 1 injection 

syringe, 2 injection needles and 1 cleansing swab 
- Pack of 6 vials of powder for solution for injection and 6 ampoules of water for injections 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: Manufacturer: 
SP Europe SP Labo N.V. 
73, rue de Stalle Industriepark 30 
B-1180 Bruxelles B-2220 Heist-op-den-Berg 
Belgium Belgium 
 
For any information about this medicinal product, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Rue de Stalle/Stallestraat 73 
B-1180 Bruxelles/Brussel/Brüssel 
Tél/Tel: + 32-(0)2 370 92 11 
 

Luxembourg/Luxemburg 
Rue de Stalle 73 
B-1180 Bruxelles/Brüssel 
Belgique/Belgien 
Tél/Tel: + 32-(0)2 370 92 11 
 

България 
ул. "Проф. Милко Бичев" № 7, ет.3 
BG-София 1504  
Тел.: +359 2 944 1073 

Magyarország 
Alkotás u. 53. 
H-1123 Budapest 
Tel.: + 36 1 457-8500 
 

Česká republika 
Na Příkopě 25 
CZ-110 00 Praha 1 
Tel: + 420 221771250 
 

Malta 
168 Christopher Street 
MT-VLT02 Valletta 
Tel: + 356-21 23 21 75 
 

Danmark 
Lautrupbjerg 2 
DK-2750 BallerupTlf: + 45-44 39 50 00 
 

Nederland 
Maarssenbroeksedijk 4 
NL-3542 DN Utrecht 
Tel: + 31-(0)800 778 78 78 



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Deutschland 
Thomas-Dehler-Straße 27 
D-81737 München  
Tel: + 49-(0)89 627 31-0 
 

Norge 
Pb. 398 
N-1326 Lysaker 
Tlf: + 47 67 16 64 50 
 

Eesti 
Järvevana tee 9 
EE-11314 Tallinn 
Tel: + 372 654 96 86 
 

Österreich 
Badener Strasse 23 
A-2514 Traiskirchen 
Tel: + 43-(0)2252 502-0 
 

Ελλάδα 
Αγίου Δημητρίου 63 
GR-174 55 Άλιμος  
Tηλ: + 30-210 98 97 300 
 

Polska 
Al. Jerozolimskie 195a 
PL-02-222 Warszawa 
Tel.: + 48-(0)22 478 41 50 
 

España 
Km. 36, Ctra. Nacional I 
E-28750 San Agustín de Guadalix – Madrid 
Tel: + 34-91 848 85 00 
 

Portugal 
Rua Agualva dos Açores 16 
P-2735-557 Agualva-Cacém 
Tel: + 351-21 433 93 00 
 

France 
92 rue Baudin  
F-92300 Levallois-Perret 
Tél: + 33-(0)1 41 06 35 00 
 

România 
Şos. Bucureşti-Ploieşti, nr. 17-21,  
Băneasa Center, et. 8, sector 1 
RO-013682 Bucureşti 
Tel. + 40 21 233 35 30 

Ireland 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW 
Tel: + 44-(0)1 707 363 636 
 

Slovenija 
Dunajska 22 
SI-1000 Ljubljana 
Tel. + 386 01 3001070 
 

Ísland 
Hörgatún 2 
IS-210 Garðabær 
Sími: + 354 535 70 00 
 

Slovenská republika 
Strakova 5 
SK-811 01 Bratislava 
Tel: + 421 (2) 5920 2712 
 

Italia 
Via fratelli Cervi snc, 
Centro Direzionale Milano Due 
Palazzo Borromini 
I-20090 Segrate (Milano) 
Tel: + 39-02 21018.1 
 

Suomi/Finland 
PL 3/PB 3 
FIN-02201 Espoo/Esbo 
Puh/Tel: + 358-(0)20-7570 300 
 



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Κύπρος 
Οδός Αγίου Νικολάου, 8 
CY-1055 Λευκωσία 
Τηλ: + 357-22 757188 
 

Sverige 
Box 6185 
S-102 33 Stockholm 
Tel: + 46-(0)8 522 21 500 
 

Latvija 
Bauskas 58a -401 
Rīga, LV-1004  
Tel: + 371-7 21 38 25 
 

United Kingdom 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW - UK 
Tel: + 44-(0)1 707 363 636 
 

Lietuva 
Kęstučio g. 65/40 
LT-08124 Vilnius 
Tel. + 370 52 101868 

 

 
 
This leaflet was last approved on 
 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: 
http://www.emea.europa.eu/ 



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HOW TO SELF INJECT VIRAFERON 
 
The following instructions explain how to inject Viraferon yourself. Please read the instructions carefully and 
follow them step by step. Your doctor or his/her assistant will instruct you how to self-inject Viraferon. Do 
not attempt to inject yourself unless you are sure you understand the procedure and requirement of self-
injection. 
 
Preparation 
Collect necessary items before you begin: 
- a vial of Viraferon powder for injection; 
- an ampoule of solvent for Viraferon (water for injections 1 ml); 
- a 2 ml syringe; 
- a long needle (for example 0.8 × 40 mm [21 gauge 1.5 inch]) to be used to add water for injections to 

the Viraferon powder vial; 
- a short needle (for example 0.3 × 13 mm [30 gauge 0.5 inch]) for the subcutaneous injection; 
- a cleansing swab. 
Wash your hands carefully. 
 
Reconstituting Viraferon powder for injection 
Remove the protective cap from the Viraferon vial. Clean the rubber top of the vial with a cleansing swab. 
You can save the swab to clean the skin area where you will inject the dose. Remove the syringe from the 
wrapping. Do not touch the tip of the syringe. Take the long needle and place it firmly onto the tip of the 
syringe. Remove the needle guard without touching the needle and keep the syringe with the needle in your 
hand. Tap the top of the ampoule of solvent gently to make sure that all the liquid is at the bottom of the 
ampoule. Break the top of the ampoule of solvent. Insert the needle in the ampoule of solvent and withdraw 
the total amount of solvent. 
 
To prepare the Viraferon solution insert the needle through the rubber top of the Viraferon vial and gently 
place the needle tip against the glass wall of the vial without touching the cleaned top of the vial with your 
hands. 
Slowly inject the diluent, aiming the stream of liquid at the glass wall of the vial in order to avoid production 
of air bubbles. Do not aim the stream at the white powder at the bottom of the vial. To dissolve the white 
contents, swirl the Viraferon vial with a gentle rotary motion leaving the syringe needle in the vial, until the 
contents are completely dissolved. Do not shake. If air bubbles do form, wait until the solution has settled and 
all bubbles have risen to the top of the solution and disappeared before withdrawing your dose from the vial. 
The solution should be used immediately after reconstitution. If not used immediately, it must be stored at 
2°C - 8°C in the refrigerator and used within 24 hours. 
 
Measuring the dose of Viraferon from the reconstituted powder for injection 
Turn the vial and the syringe upside down in one hand. Be sure the tip of needle is in the Viraferon 
reconstituted solution. Your other hand will be free to move the plunger. Pull back on the plunger slowly to 
draw the correct dose as prescribed by your doctor into the syringe. 
Hold the syringe with the needle in the vial pointing up, remove the syringe from the long needle leaving the 
needle in the vial and without touching the tip of the syringe. Take the short needle and place it firmly onto 
the tip of the syringe. Remove the needle guard from the syringe needle and check for air bubbles in the 
syringe. If you see any bubbles, pull the plunger slightly back; tap the syringe gently, with the needle 
pointing up, until the bubbles disappear. Push up the plunger slowly back to the correct dose. Replace the 
needle guard and place the syringe with the needle on a flat surface. 
 
Be sure the solution is at room temperature up to 25°C. If the solution is cold, warm the syringe between your 
palms. Examine the reconstituted solution prior to administration: it should be clear and colourless. Do not 
use if discolouration or particulate matter is present. You are now ready to inject the dose. 



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Injecting the solution 
Select the injection site. The best sites for injection are tissues with a layer of fat between skin and muscle: 
thigh, outer surface of the upper arm (you may need the assistance of another person to use this site), 
abdomen (except the navel or waistline). If you are exceptionally thin, use only the thigh or outer surface of 
the arm for injection. 
Change your injection site each time. 
 
Cleanse and disinfect the skin where the injection is to be made. Wait for the area to dry. Remove the needle 
guard.With one hand, pinch a fold of loose skin. With your other hand hold the syringe as you would a 
pencil. Insert the needle into the pinched skin at an angle of 45° to 90°. Inject the solution by pushing the 
plunger all the way down gently. 
Pull the needle straight out of the skin. Press the injection site with a small bandage or sterile gauze if 
necessary for several seconds. Do not massage the injection site. If there is bleeding, cover with an adhesive 
bandage. 
The vial, ampoule and injection materials intended for single use must be discarded. Dispose of the syringe 
and needles safely in a closed container. 
 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Viraferon, 5 million IU/ml powder and solvent for solution for injection 
Interferon alfa-2b 

 
Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Viraferon is and what it is used for 
2. Before you use Viraferon 
3. How to use Viraferon 
4. Possible side effects 
5. How to store Viraferon 
6. Further information 
 
 
1. WHAT VIRAFERON IS AND WHAT IT IS USED FOR 
 
Viraferon (interferon alfa-2b) modifies the response of the body's immune system to help fight infections and 
severe diseases. Viraferon is used in adult patients for the treatment of chronic hepatitis B or C, which are viral 
infections of the liver. 
 
Viraferon is used in combination with ribavirin in children and adolescents 3 years of age and older who have 
previously untreated chronic hepatitis C. 
 
 
2. BEFORE YOU USE VIRAFERON 
 
Do not use Viraferon 
- if you are allergic (hypersensitive) to interferon or any of the other ingredients of Viraferon. 
- if you have severe heart disease. 
- if you have poor kidney or liver function. 
- if you have advanced decompensated (uncontrolled) liver disease. 
- if you have hepatitis and have been treated recently with medications that suppress the immune system 

(other than short-term treatment with cortisone-type medicine). 
- if you have a history of seizures (convulsions). 
- if you have a history of autoimmune disease, or have had an organ transplant and are taking medicine that 

suppresses your immune system (your immune system helps protect you from infection). 
- if you have thyroid disease that is not well controlled. 
Children and adolescents: 
- if you have had serious nervous or mental problems, such as severe depression or thoughts of suicide. 
 
Take special care with Viraferon 
- if you are pregnant or planning to become pregnant (see Pregnancy). 
- if you have had a severe nervous or mental disorder. The use of interferon alfa-2b in children and 

adolescents with existence of or history of severe psychiatric conditions is contraindicated (see “Do not use 
Viraferon”) 

- if you have ever had depression or develop symptoms associated with depression (e.g. feelings of sadness, 
dejection, etc.) while on treatment with Viraferon (see section 4). 



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- if you have psoriasis, it may get worse during treatment with Viraferon. 
- when receiving Viraferon, you may temporarily have a greater risk of getting an infection. Check with 

your doctor if you think you are getting an infection. 
- if you develop symptoms associated with a cold or other respiratory infection, such as fever, cough, or any 

difficulty in breathing, tell your doctor. 
- if you notice unusual bleeding or bruising check with your doctor immediately. 
- if you develop symptoms of a severe allergic reaction (such as difficulty in breathing, wheezing, or hives) 

while on this medication seek medical help immediately. 
- if you are also being treated for HIV, please see Using other medicines. 
- if you have received an organ transplant, either kidney or liver, interferon treatment may increase the risk 

of rejection. Be sure to discuss this with your doctor. 
 
Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving Viraferon 
and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and 
membranes of the mouth during long-term treatment with the combination of Viraferon with ribavirin. You 
should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some 
patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly 
afterwards. 
 
During the one year of treatment, many children did not grow or gain weight as much as expected. However, 
during the 6 months after treatment, this trend was generally reversed, although a few children did not return 
to their previous rate of growth within the first year after completing treatment. 
 
Tell your doctor if you have ever had a heart attack or a heart problem; if you have a history of breathing 
irregularities or pneumonia, problems with blood clotting, liver condition, thyroid problems, diabetes, or high 
or low blood pressure. 
 
Tell your doctor if you have ever been treated for depression or any other psychiatric disorder; confusion; 
unconsciousness; thoughts of suicide or attempted suicide. 
 
Be sure to tell your doctor if you are taking the Chinese herbal medication Shosaikoto. 
 
Using other medicines 
Viraferon will add to the effects of substances that slow down your nervous system, possibly causing 
drowsiness. Therefore, check with your doctor or pharmacist about drinking alcoholic beverages, or taking 
sleeping pills, sedatives or strong pain medications.  
 
Tell your doctor if you are taking theophylline or aminophylline for asthma, and about all other medication 
you are taking, or have taken recently, even those not prescribed, as the dose of some medications may have 
to be adjusted while you are treated with Viraferon. 

 
Patients who also have HIV infection: Lactic acidosis and worsening liver function are side effects associated 
with Highly Active Anti-Retroviral Therapy (HAART), an HIV treatment. If you are receiving HAART, the 
addition of Viraferon and ribavirin may increase your risk of lactic acidosis and of liver failure. Your doctor 
will monitor you for signs and symptoms of these conditions (Please be sure to read the ribavirin Patient 
Leaflet also). Additionally, patients treated with Viraferon and ribavirin combination therapy and zidovudine 
could be at increased risk of developing anaemia (low number of red blood cells). 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. 
 
Using Viraferon with food and drink 
While being treated with Viraferon, your doctor may want you to drink extra fluids to help prevent low blood 
pressure. 
 



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Pregnancy and breast-feeding 
Ask your doctor or pharmacist for advice before taking any medicine. In studies in pregnant animals, 
interferons have sometimes caused miscarriage. The effect on human pregnancy is not known. 
If you are prescribed Viraferon in combination with ribavirin, ribavirin can be very damaging to an unborn 
baby, thus both female and male patients must take special precautions in their sexual activity if there is any 
chance for pregnancy to occur: 
- if you are a girl or a woman of childbearing age, you must have a negative pregnancy test before treatment, 
each month during treatment, and for the 4 months after treatment is stopped. You and your partner must 
each use an effective contraceptive during the time you are taking ribavirin and for 4 months after stopping 
treatment. This can be discussed with your doctor.  
- if you are a man who is taking ribavirin, do not have sex with a pregnant woman unless you use a condom. 
This will lessen the chance for ribavirin to be left in the woman’s body. If your female partner is not pregnant 
now but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 
7 months after treatment has stopped. This can be discussed with your doctor. If you are a male patient, you 
and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 
7 months after stopping treatment. This can be discussed with your doctor. 
 
It is not known whether this product is present in human milk. Therefore, do not breast-feed an infant if you 
are taking Viraferon. In combination therapy with ribavirin, take notice of the respective informing texts of 
ribavirin containing medicinal products. 
 
Driving and using machines 
Do not drive or use machinery if you become drowsy, tired, or confused from this medicine. 
 
Important information about some of the ingredients of Viraferon 
Your doctor may recommend that you consider vaccination against hepatitis A and B if you 
regularly/repeatedly receive human plasma-derived albumin. 
 
This medicine contains human albumin solution as an excipient. When medicines are made from human blood 
or plasma, certain measures are put in place to prevent infections being passed on to patients. These include 
careful selection of blood and plasma donors to make sure those at risk of carrying infections are excluded, 
and the testing of each donation and pools of plasma for signs of virus/infections. Manufacturers of these 
products also include steps in the processing of the blood or plasma that can inactivate or remove viruses. 
Despite these measures, when medicines prepared from human blood or plasma are administered, the 
possibility of passing on infection cannot be totally excluded. This also applies to any unknown or emerging 
viruses or other types of infections. 
 
There are no reports of virus infections with albumin manufactured to European Pharmacopoeia 
specifications by established processes. 
 
It is strongly recommended that every time you receive a dose of Viraferon the name and batch number of the 
product are recorded in order to maintain a record of the batches used. 
 
 
3. HOW TO USE VIRAFERON 
 
Your doctor has prescribed Viraferon specifically for you and your current condition; do not share this medicine 
with anyone else. 
 
Your doctor has determined the exact dosage for administration of Viraferon according to your individual needs. 
The dosage will vary according to the disease being treated. 
 
If you are injecting Viraferon yourself, please be sure that the dose that has been prescribed for you is clearly 
provided with the package of medicine you receive. Dosages that are to be administered 3 times a week are best 
given every other day. 



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The usual starting dose for each condition follows; however, individual doses may vary, and the doctor may 
change your dose based on your specific needs: 
 
Chronic hepatitis B: 5 to 10 million IU 3 times a week (every other day) injected subcutaneously (under the skin). 
 
Chronic hepatitis C: Adults - 3 million IU 3 times a week (every other day) injected subcutaneously (under the 
skin) in combination with ribavirin or alone. Children 3 years of age and older and adolescents - 
3 million IU/m2 3 times a week (every other day) injected subcutaneously (under the skin) in combination with 
ribavirin (Please also see ribavirin package leaflet).  
 
Your doctor may prescribe a different dose of Viraferon alone or in combination with other medicines (e.g. 
ribavirin). If you are prescribed Viraferon in combination with another medicine, please refer also to the Package 
Leaflet of the medicine to be used in combination. Your doctor will determine the exact dosage schedule and 
regimen according to your needs. If you have the impression that the effect of Viraferon is too strong or too 
weak, talk to your doctor or pharmacist. 
 
Subcutaneous use: 
Viraferon is usually intended for subcutaneous use. This means that Viraferon is injected with a short needle into 
the fatty tissue just under the skin. If you are injecting this medicine yourself, you will be instructed how to 
prepare and give the injection. Detailed instructions for subcutaneous administration are provided with this leaflet 
(see HOW TO SELF INJECT VIRAFERON at the end of the leaflet). 
 
One dose of Viraferon is given on each scheduled day. Viraferon is given three times a week, every other day, for 
example on Monday, Wednesday, and Friday. Interferons may cause unusual tiredness; if you are injecting this 
medicine yourself, or giving it to a child, use it at bedtime. 
 
Use Viraferon exactly as prescribed by your doctor. Do not exceed the recommended dosage, and take Viraferon 
for as long as prescribed. 
 
If you use more Viraferon than you should 
Contact your doctor or healthcare professional as soon as possible. 
 
If you forget to take Viraferon 
If you are self-administering treatment, or if you are the caregiver of a child taking Viraferon in combination 
with ribavirin, inject the recommended dose as soon as you remember and continue treatment as usual Do not 
take a double dose to make up for a forgotten dose. If you are scheduled to inject this product every day, and 
you accidentally missed a full day’s dose, continue treatment at the usual dose the following day. Contact 
your doctor or pharmacist if needed. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Viraferon can cause side effects, although not everybody gets them. Although not all of 
these side effects may occur, they may need medical attention if they do. 
 
Some people get depressed when taking Viraferon alone or in combination treatment with ribavirin, and in some 
cases people had suicidal thoughts or aggressive behaviour (sometimes directed against others). Some patients have 
actually committed suicide. Be sure to seek emergency care if you notice that you are becoming depressed or have 
suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend 
to help you stay alert to signs of depression or changes in your behaviour. 
 
Paediatric Use: Children are particularly prone to develop depression when being treated with Viraferon and 
ribavirin. Immediately contact the doctor or seek emergency care if they display any unusual behavioural 
symptoms, feel depressed, or feel they want to harm themselves or others. 



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If any of the following side effects happen, stop taking Viraferon and tell your doctor immediately or go to 
the casualty department at your nearest hospital: 
• swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in 

swallowing or breathing; hives; fainting. 
These are all very serious side effects. If you have them, you may have had a serious allergic reaction to 
Viraferon. You may need urgent medical attention or hospitalisation. These very serious side effects are very 
rare. 
 
Check with your doctor immediately if any of the following side effects occur: 
• chest pain or persistent and severe cough; irregular or rapid heartbeat; shortness of breath, confusion, 

difficulty remaining alert, numbness or tingling sensation or pain in hands or feet; seizure 
(convulsions); trouble sleeping, thinking or concentrating; altered mental state; suicidal thoughts, 
suicide attempt, changed behaviour or aggressive behaviour (sometimes directed against others), 
hallucinations; severe stomach pain; black or tar like stools; blood in stool or urine, severe 
nosebleed; waxy pallor, high sugar level in blood, fever or chills beginning after a few weeks of 
treatment, lower back or side pain, difficult urination, problems with your eyes or your eyesight or 
hearing, loss of hearing, severe or painful reddening or sores on your skin or mucous membrane. 

These may signal serious side effects that may need urgent medical attention. Your doctor will test your 
blood to ensure that your white blood cell (cells that fight infection) and red blood cell (cells that carry iron 
and oxygen) counts, platelets (blood clotting cells) and other laboratory values are at acceptable levels. 
 
At the beginning of treatment with Viraferon, you may experience a flu-like reaction, with fever, fatigue, 
headache, muscle ache, joint pain and chills/rigors. Your doctor may recommend that you take paracetamol if 
you develop these symptoms. 
 
Other side effects that may occur include: 
 
Very commonly reported side effects (at least 1 in every 10 patients):  
pain, swelling and redness or skin damage at site of injection, hair loss, dizziness, changes in appetite, 
stomach or abdominal pains, diarrhoea, nausea (feeling sick), viral infection, depression, emotional lability, 
insomnia, anxiety, sore throat and painful swallowing, fatigue, chills/rigors, fever, flu-like reaction, feeling 
of general discomfort, headaches, weight loss, vomiting, irritability, weakness, mood swings, coughing 
(sometimes severe), shortness of breath, itching, dry skin, rash, sudden and severe muscle pain, joint pain, 
musculoskeletal pain, changes in laboratory blood values including decreased white blood cell count. Some 
children have had a decrease in their rate of growth (height and weight). 
 
Commonly reported side effects (at least 1 in every 100 patients, but less than 1 in every 10 patients): 
thirst, dehydration, high blood pressure, migraines, swollen glands, flushing, menstrual problems, 
decreased sexual drive, vaginal problem, breast pain, pain in testicle, problems with thyroid gland, red 
gums, dry mouth, red or sore mouth or tongue, tooth ache or tooth disorder, herpes simplex (fever blisters), 
taste change, upset stomach, dyspepsia (heartburn), constipation, enlargement of liver (liver problems, 
sometimes severe), loose stools, bedwetting in children, inflammation of the sinuses, bronchitis, eye pain, 
problem with your tear ducts, conjunctivitis (“pink eye”), agitation, sleepiness, sleepwalking, problem with 
behaviour, nervousness, stuffy or runny nose, sneezing, rapid breathing, pale or reddened skin, bruising, 
fingers and toes very sensitive to cold, problem with skin or nails, psoriasis (new or worsened), increased 
sweating, increased need to pass urine, fine shaking movements, decreased sensitivity to touch, arthritis.  
 
Rarely reported side effects (at least 1 in every 10,000 patients, but less than 1 in every 1,000 patients): 
pneumonia 
 
Very rarely reported side effects (less than 1 in every 10,000 patients): 
low blood pressure, puffy face, diabetes, leg cramps, back pain, kidney problems, nerve damage, bleeding 
gums, aplastic anaemia. Pure red cell aplasia, a condition where the body stopped or reduced the production 



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of red blood cells, has been reported. This causes severe anaemia, symptoms of which would include unusual 
tiredness and a lack of energy. 
 
Very rarely sarcoidosis, (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin 
lesions and swollen glands) has been reported. Loss of consciousness has occurred very rarely, mostly in 
elderly patients treated at high doses. Cases of stroke (cerebrovascular events) have been reported. Check 
with your doctor immediately if you have any of these symptoms.  
Periodontal (affecting gums) and dental disorders, altered mental status, loss of consciousness, acute 
hypersensitivity reactions including urticaria (hives), angioedema (swelling of the hands, feet, ankles, face, 
lips, mouth, or throat which may cause difficulty in swallowing or breathing), bronchoconstriction and 
anaphylaxis (a severe, whole-body allergic reaction) have been reported, but their frequency is unknown.  
 
Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin 
and the membranes of the ears, brain and spinal cord) has been reported with Viraferon use. 
 
Other side effects not listed above may also occur in some patients. If any of the side effects gets serious, or if you 
notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. 
 
 
5. HOW TO STORE VIRAFERON 
 
Keep out of the reach and sight of children. 
 
Store in a refrigerator (2°C - 8°C).  
Do not freeze.  
For short term travelling, the non-reconstituted product can be kept out of the refrigerator at or below 25°C 
for a period up to four weeks before use. If the product is not used during this four-week period, it should be 
discarded. 
 
The solution should be used immediately after reconstitution. If not used immediately, it must be stored at 
2°C - 8°C in the refrigerator and used within 24 hours. 
 
Do not use Viraferon after the expiry date which is stated on the package. 
 
Do not use Viraferon if you notice changes in the appearance of Viraferon. 
 
Any unused product must be discarded after withdrawal of the dose. 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose 
of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What Viraferon contains 
 
- The active substance is recombinant interferon alfa-2b, 5 million IU/ml. 
- The other ingredients are glycine, disodium phosphate anhydrous, sodium dihydrogen phosphate 

monohydrate, and human albumin solution. 
- Solvent: water for injections 1 ml/ampoule 
 
What Viraferon looks like and contents of the pack 
 
Viraferon is presented as a powder and solvent for solution for injection 
The white to cream coloured powder is contained in a 2 ml glass vial and the clear and colourless solvent is 
presented in a 2 ml glass ampoule. 



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Viraferon is available in two different pack sizes: 
- Pack of 1 vial of powder for solution for injection, 1 ampoule of water for injections, 1 injection 

syringe, 2 injection needles and 1 cleansing swab 
- Pack of 6 vials of powder for solution for injection and 6 ampoules of water for injections 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: Manufacturer: 
SP Europe SP Labo N.V. 
73, rue de Stalle Industriepark 30 
B-1180 Bruxelles B-2220 Heist-op-den-Berg 
Belgium Belgium 
 
For any information about this medicinal product, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Rue de Stalle/Stallestraat 73 
B-1180 Bruxelles/Brussel/Brüssel 
Tél/Tel: + 32-(0)2 370 92 11 
 

Luxembourg/Luxemburg 
Rue de Stalle 73 
B-1180 Bruxelles/Brüssel 
Belgique/Belgien 
Tél/Tel: + 32-(0)2 370 92 11 
 

България 
ул. "Проф. Милко Бичев" № 7, ет.3 
BG-София 1504  
Тел.: +359 2 944 1073 

Magyarország 
Alkotás u. 53. 
H-1123 Budapest 
Tel.: + 36 1 457-8500 

Česká republika 
Na Příkopě 25 
CZ-110 00 Praha 1 
Tel: + 420 221771250 
 

Malta 
168 Christopher Street 
MT-VLT02 Valletta 
Tel: + 356-21 23 21 75 
 

Danmark 
Lautrupbjerg 2 
DK-2750 BallerupTlf: + 45-44 39 50 00 

Nederland 
Maarssenbroeksedijk 4 
NL-3542 DN Utrecht 
Tel: + 31-(0)800 778 78 78 

Deutschland 
Thomas-Dehler-Straße 27 
D-81737 München  
Tel: + 49-(0)89 627 31-0 
 

Norge 
Pb. 398 
N-1326 Lysaker 
Tlf: + 47 67 16 64 50 
 

Eesti 
Järvevana tee 9 
EE-11314 Tallinn 
Tel: + 372 654 96 86 
 

Österreich 
Badener Strasse 23 
A-2514 Traiskirchen 
Tel: + 43-(0)2252 502-0 
 

Ελλάδα 
Αγίου Δημητρίου 63 
GR-174 55 Άλιμος  
Tηλ: + 30-210 98 97 300 
 

Polska 
Al. Jerozolimskie 195a 
PL-02-222 Warszawa 
Tel.: + 48-(0)22 478 41 50 
 

España 
Km. 36, Ctra. Nacional I 
E-28750 San Agustín de Guadalix – Madrid 
Tel: + 34-91 848 85 00 
 

Portugal 
Rua Agualva dos Açores 16 
P-2735-557 Agualva-Cacém 
Tel: + 351-21 433 93 00 
 



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France 
92 rue Baudin  
F-92300 Levallois-Perret 
Tél: + 33-(0)1 41 06 35 00 
 

România 
Şos. Bucureşti-Ploieşti, nr. 17-21,  
Băneasa Center, et. 8, sector 1 
RO-013682 Bucureşti 
Tel. + 40 21 233 35 30 
 

Ireland 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW 
Tel: + 44-(0)1 707 363 636 
 

Slovenija 
Dunajska 22 
SI-1000 Ljubljana 
Tel. + 386 01 3001070 
 

Ísland 
Hörgatún 2 
IS-210 Garðabær 
Sími: + 354 535 70 00 
 

Slovenská republika 
Strakova 5 
SK-811 01 Bratislava 
Tel: + 421 (2) 5920 2712 
 

Italia 
Via fratelli Cervi snc, 
Centro Direzionale Milano Due 
Palazzo Borromini 
I-20090 Segrate (Milano) 
Tel: + 39-02 21018.1 
 

Suomi/Finland 
PL 3/PB 3 
FIN-02201 Espoo/Esbo 
Puh/Tel: + 358-(0)20-7570 300 
 

Κύπρος 
Οδός Αγίου Νικολάου, 8 
CY-1055 Λευκωσία 
Τηλ: + 357-22 757188 
 

Sverige 
Box 6185 
S-102 33 Stockholm 
Tel: + 46-(0)8 522 21 500 
 

Latvija 
Bauskas 58a -401 
Rīga, LV-1004  
Tel: + 371-7 21 38 25 
 

United Kingdom 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW - UK 
Tel: + 44-(0)1 707 363 636 
 



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Lietuva 
Kęstučio g. 65/40 
LT-08124 Vilnius 
Tel. + 370 52 101868 

 

 
 
This leaflet was last approved on 
 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: 
http://www.emea.europa.eu/ 



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HOW TO SELF INJECT VIRAFERON 
 
The following instructions explain how to inject Viraferon yourself. Please read the instructions carefully and 
follow them step by step. Your doctor or his/her assistant will instruct you how to self-inject Viraferon. Do 
not attempt to inject yourself unless you are sure you understand the procedure and requirement of self-
injection. 
 
Preparation 
Collect necessary items before you begin: 
- a vial of Viraferon powder for injection; 
- an ampoule of solvent for Viraferon (water for injections 1 ml); 
- a 2 ml syringe; 
- a long needle (for example 0.8 × 40 mm [21 gauge 1.5 inch]) to be used to add water for injections to 

the Viraferon powder vial; 
- a short needle (for example 0.3 × 13 mm [30 gauge 0.5 inch]) for the subcutaneous injection; 
- a cleansing swab. 
Wash your hands carefully. 
 
Reconstituting Viraferon powder for injection 
Remove the protective cap from the Viraferon vial. Clean the rubber top of the vial with a cleansing swab. 
You can save the swab to clean the skin area where you will inject the dose. Remove the syringe from the 
wrapping. Do not touch the tip of the syringe. Take the long needle and place it firmly onto the tip of the 
syringe. Remove the needle guard without touching the needle and keep the syringe with the needle in your 
hand. Tap the top of the ampoule of solvent gently to make sure that all the liquid is at the bottom of the 
ampoule. Break the top of the ampoule of solvent. Insert the needle in the ampoule of solvent and withdraw 
the total amount of solvent. 
 
To prepare the Viraferon solution insert the needle through the rubber top of the Viraferon vial and gently 
place the needle tip against the glass wall of the vial without touching the cleaned top of the vial with your 
hands. 
Slowly inject the diluent, aiming the stream of liquid at the glass wall of the vial in order to avoid production 
of air bubbles. Do not aim the stream at the white powder at the bottom of the vial. To dissolve the white 
contents, swirl the Viraferon vial with a gentle rotary motion leaving the syringe needle in the vial, until the 
contents are completely dissolved. Do not shake. If air bubbles do form, wait until the solution has settled and 
all bubbles have risen to the top of the solution and disappeared before withdrawing your dose from the vial. 
The solution should be used immediately after reconstitution. If not used immediately, it must be stored at 
2°C - 8°C in the refrigerator and used within 24 hours. 
 
Measuring the dose of Viraferon from the reconstituted powder for injection 
Turn the vial and the syringe upside down in one hand. Be sure the tip of needle is in the Viraferon 
reconstituted solution. Your other hand will be free to move the plunger. Pull back on the plunger slowly to 
draw the correct dose as prescribed by your doctor into the syringe. 
Hold the syringe with the needle in the vial pointing up, remove the syringe from the long needle leaving the 
needle in the vial and without touching the tip of the syringe. Take the short needle and place it firmly onto 
the tip of the syringe. Remove the needle guard from the syringe needle and check for air bubbles in the 
syringe. If you see any bubbles, pull the plunger slightly back; tap the syringe gently, with the needle 
pointing up, until the bubbles disappear. Push up the plunger slowly back to the correct dose. Replace the 
needle guard and place the syringe with the needle on a flat surface. 
 
Be sure the solution is at room temperature up to 25°C. If the solution is cold, warm the syringe between your 
palms. Examine the reconstituted solution prior to administration: it should be clear and colourless. Do not 
use if discolouration or particulate matter is present. You are now ready to inject the dose. 



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Injecting the solution 
Select the injection site. The best sites for injection are tissues with a layer of fat between skin and muscle: 
thigh, outer surface of the upper arm (you may need the assistance of another person to use this site), 
abdomen (except the navel or waistline). If you are exceptionally thin, use only the thigh or outer surface of 
the arm for injection. 
Change your injection site each time. 
 
Cleanse and disinfect the skin where the injection is to be made. Wait for the area to dry. Remove the needle 
guard.With one hand, pinch a fold of loose skin. With your other hand hold the syringe as you would a 
pencil. Insert the needle into the pinched skin at an angle of 45° to 90°. Inject the solution by pushing the 
plunger all the way down gently. 
Pull the needle straight out of the skin. Press the injection site with a small bandage or sterile gauze if 
necessary for several seconds. Do not massage the injection site. If there is bleeding, cover with an adhesive 
bandage. 
The vial, ampoule and injection materials intended for single use must be discarded. Dispose of the syringe 
and needles safely in a closed container. 
 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Viraferon, 10 million IU/ml powder and solvent for solution for injection 
Interferon alfa-2b 

 
Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Viraferon is and what it is used for 
2. Before you use Viraferon 
3. How to use Viraferon 
4. Possible side effects 
5. How to store Viraferon 
6. Further information 
 
 
1. WHAT VIRAFERON IS AND WHAT IT IS USED FOR 
 
Viraferon (interferon alfa-2b) modifies the response of the body's immune system to help fight infections and 
severe diseases. Viraferon is used in adult patients for the treatment of chronic hepatitis B or C, which are viral 
infections of the liver. 
 
Viraferon is used in combination with ribavirin in children and adolescents 3 years of age and older who have 
previously untreated chronic hepatitis C. 
 
 
2. BEFORE YOU USE VIRAFERON 
 
Do not use Viraferon 
- if you are allergic (hypersensitive) to interferon or any of the other ingredients of Viraferon. 
- if you have severe heart disease. 
- if you have poor kidney or liver function. 
- if you have advanced decompensated (uncontrolled) liver disease. 
- if you have hepatitis and have been treated recently with medications that suppress the immune system 

(other than short-term treatment with cortisone-type medicine). 
- if you have a history of seizures (convulsions). 
- if you have a history of autoimmune disease, or have had an organ transplant and are taking medicine that 

suppresses your immune system (your immune system helps protect you from infection). 
- if you have thyroid disease that is not well controlled. 
Children and adolescents: 
- if you have had serious nervous or mental problems, such as severe depression or thoughts of suicide. 
 
Take special care with Viraferon 
- if you are pregnant or planning to become pregnant (see Pregnancy). 
- if you have had a severe nervous or mental disorder. The use of interferon alfa-2b in children and 

adolescents with existence of or history of severe psychiatric conditions is contraindicated (see “Do not use 
Viraferon”) 

- if you have ever had depression or develop symptoms associated with depression (e.g. feelings of sadness, 
dejection, etc.) while on treatment with Viraferon (see section 4). 



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- if you have psoriasis, it may get worse during treatment with Viraferon. 
- when receiving Viraferon, you may temporarily have a greater risk of getting an infection. Check with 

your doctor if you think you are getting an infection. 
- if you develop symptoms associated with a cold or other respiratory infection, such as fever, cough, or any 

difficulty in breathing, tell your doctor. 
- if you notice unusual bleeding or bruising check with your doctor immediately. 
- if you develop symptoms of a severe allergic reaction (such as difficulty in breathing, wheezing, or hives) 

while on this medication seek medical help immediately. 
- if you are also being treated for HIV, please see Using other medicines. 
- if you have received an organ transplant, either kidney or liver, interferon treatment may increase the risk 

of rejection. Be sure to discuss this with your doctor. 
 
Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving Viraferon 
and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and 
membranes of the mouth during long-term treatment with the combination of Viraferon with ribavirin. You 
should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some 
patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly 
afterwards. 
 
During the one year of treatment, many children did not grow or gain weight as much as expected. However, 
during the 6 months after treatment, this trend was generally reversed, although a few children did not return 
to their previous rate of growth within the first year after completing treatment. 
 
Tell your doctor if you have ever had a heart attack or a heart problem; if you have a history of breathing 
irregularities or pneumonia, problems with blood clotting, liver condition, thyroid problems, diabetes, or high 
or low blood pressure. 
 
Tell your doctor if you have ever been treated for depression or any other psychiatric disorder; confusion; 
unconsciousness; thoughts of suicide or attempted suicide. 
 
Be sure to tell your doctor if you are taking the Chinese herbal medication Shosaikoto. 
 
Using other medicines 
Viraferon will add to the effects of substances that slow down your nervous system, possibly causing 
drowsiness. Therefore, check with your doctor or pharmacist about drinking alcoholic beverages, or taking 
sleeping pills, sedatives or strong pain medications.  
 
Tell your doctor if you are taking theophylline or aminophylline for asthma, and about all other medication 
you are taking, or have taken recently, even those not prescribed, as the dose of some medications may have 
to be adjusted while you are treated with Viraferon. 

 
Patients who also have HIV infection: Lactic acidosis and worsening liver function are side effects associated 
with Highly Active Anti-Retroviral Therapy (HAART), an HIV treatment. If you are receiving HAART, the 
addition of Viraferon and ribavirin may increase your risk of lactic acidosis and of liver failure. Your doctor 
will monitor you for signs and symptoms of these conditions (Please be sure to read the ribavirin Patient 
Leaflet also). Additionally, patients treated with Viraferon and ribavirin combination therapy and zidovudine 
could be at increased risk of developing anaemia (low number of red blood cells). 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. 
 
Using Viraferon with food and drink 
While being treated with Viraferon, your doctor may want you to drink extra fluids to help prevent low blood 
pressure. 
 



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Pregnancy and breast-feeding 
Ask your doctor or pharmacist for advice before taking any medicine. In studies in pregnant animals, 
interferons have sometimes caused miscarriage. The effect on human pregnancy is not known. 
If you are prescribed Viraferon in combination with ribavirin, ribavirin can be very damaging to an unborn 
baby, thus both female and male patients must take special precautions in their sexual activity if there is any 
chance for pregnancy to occur: 
- if you are a girl or a woman of childbearing age, you must have a negative pregnancy test before treatment, 
each month during treatment, and for the 4 months after treatment is stopped. You and your partner must 
each use an effective contraceptive during the time you are taking ribavirin and for 4 months after stopping 
treatment. This can be discussed with your doctor.  
- if you are a man who is taking ribavirin, do not have sex with a pregnant woman unless you use a condom. 
This will lessen the chance for ribavirin to be left in the woman’s body. If your female partner is not pregnant 
now but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 
7 months after treatment has stopped. This can be discussed with your doctor. If you are a male patient, you 
and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 
7 months after stopping treatment. This can be discussed with your doctor. 
 
It is not known whether this product is present in human milk. Therefore, do not breast-feed an infant if you 
are taking Viraferon. In combination therapy with ribavirin, take notice of the respective informing texts of 
ribavirin containing medicinal products. 
 
Driving and using machines 
Do not drive or use machinery if you become drowsy, tired, or confused from this medicine. 
 
Important information about some of the ingredients of Viraferon 
Your doctor may recommend that you consider vaccination against hepatitis A and B if you 
regularly/repeatedly receive human plasma-derived albumin. 
 
This medicine contains human albumin solution as an excipient. When medicines are made from human blood 
or plasma, certain measures are put in place to prevent infections being passed on to patients. These include 
careful selection of blood and plasma donors to make sure those at risk of carrying infections are excluded, 
and the testing of each donation and pools of plasma for signs of virus/infections. Manufacturers of these 
products also include steps in the processing of the blood or plasma that can inactivate or remove viruses. 
Despite these measures, when medicines prepared from human blood or plasma are administered, the 
possibility of passing on infection cannot be totally excluded. This also applies to any unknown or emerging 
viruses or other types of infections. 
 
There are no reports of virus infections with albumin manufactured to European Pharmacopoeia 
specifications by established processes. 
 
It is strongly recommended that every time you receive a dose of Viraferon the name and batch number of the 
product are recorded in order to maintain a record of the batches used. 
 
 
3. HOW TO USE VIRAFERON 
 
Your doctor has prescribed Viraferon specifically for you and your current condition; do not share this medicine 
with anyone else. 
 
Your doctor has determined the exact dosage for administration of Viraferon according to your individual needs. 
The dosage will vary according to the disease being treated. 
 
If you are injecting Viraferon yourself, please be sure that the dose that has been prescribed for you is clearly 
provided with the package of medicine you receive. Dosages that are to be administered 3 times a week are best 
given every other day. 



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The usual starting dose for each condition follows; however, individual doses may vary, and the doctor may 
change your dose based on your specific needs: 
 
Chronic hepatitis B: 5 to 10 million IU 3 times a week (every other day) injected subcutaneously (under the skin). 
 
Chronic hepatitis C: Adults - 3 million IU 3 times a week (every other day) injected subcutaneously (under the 
skin) in combination with ribavirin or alone. Children 3 years of age and older and adolescents - 
3 million IU/m2 3 times a week (every other day) injected subcutaneously (under the skin) in combination with 
ribavirin (Please also see ribavirin package leaflet).  
 
Your doctor may prescribe a different dose of Viraferon alone or in combination with other medicines (e.g. 
ribavirin). If you are prescribed Viraferon in combination with another medicine, please refer also to the Package 
Leaflet of the medicine to be used in combination. Your doctor will determine the exact dosage schedule and 
regimen according to your needs. If you have the impression that the effect of Viraferon is too strong or too 
weak, talk to your doctor or pharmacist. 
 
Subcutaneous use: 
Viraferon is usually intended for subcutaneous use. This means that Viraferon is injected with a short needle into 
the fatty tissue just under the skin. If you are injecting this medicine yourself, you will be instructed how to 
prepare and give the injection. Detailed instructions for subcutaneous administration are provided with this leaflet 
(see HOW TO SELF INJECT VIRAFERON at the end of the leaflet). 
 
One dose of Viraferon is given on each scheduled day. Viraferon is given three times a week, every other day, for 
example on Monday, Wednesday, and Friday. Interferons may cause unusual tiredness; if you are injecting this 
medicine yourself, or giving it to a child, use it at bedtime. 
 
Use Viraferon exactly as prescribed by your doctor. Do not exceed the recommended dosage, and take Viraferon 
for as long as prescribed. 
 
If you use more Viraferon than you should 
Contact your doctor or healthcare professional as soon as possible. 
 
If you forget to take Viraferon 
If you are self-administering treatment, or if you are the caregiver of a child taking Viraferon in combination 
with ribavirin, inject the recommended dose as soon as you remember and continue treatment as usual. Do 
not take a double dose to make up for a forgotten dose. If you are scheduled to inject this product every day, 
and you accidentally missed a full day’s dose, continue treatment at the usual dose the following day. Contact 
your doctor or pharmacist if needed. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Viraferon can cause side effects, although not everybody gets them. Although not all of 
these side effects may occur, they may need medical attention if they do. 
 
Some people get depressed when taking Viraferon alone or in combination treatment with ribavirin, and in some 
cases people had suicidal thoughts or aggressive behaviour (sometimes directed against others). Some patients have 
actually committed suicide. Be sure to seek emergency care if you notice that you are becoming depressed or have 
suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend 
to help you stay alert to signs of depression or changes in your behaviour. 
 
Paediatric Use: Children are particularly prone to develop depression when being treated with Viraferon and 
ribavirin. Immediately contact the doctor or seek emergency care if they display any unusual behavioural 
symptoms, feel depressed, or feel they want to harm themselves or others. 



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If any of the following side effects happen, stop taking Viraferon and tell your doctor immediately or go to 
the casualty department at your nearest hospital: 
• swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in 

swallowing or breathing; hives; fainting. 
These are all very serious side effects. If you have them, you may have had a serious allergic reaction to 
Viraferon. You may need urgent medical attention or hospitalisation. These very serious side effects are very 
rare. 
 
Check with your doctor immediately if any of the following side effects occur: 
• chest pain or persistent and severe cough; irregular or rapid heartbeat; shortness of breath, confusion, 

difficulty remaining alert, numbness or tingling sensation or pain in hands or feet; seizure 
(convulsions); trouble sleeping, thinking or concentrating; altered mental state; suicidal thoughts, 
suicide attempt, changed behaviour or aggressive behaviour (sometimes directed against others), 
hallucinations; severe stomach pain; black or tar like stools; blood in stool or urine, severe 
nosebleed; waxy pallor, high sugar level in blood, fever or chills beginning after a few weeks of 
treatment, lower back or side pain, difficult urination, problems with your eyes or your eyesight or 
hearing, loss of hearing, severe or painful reddening or sores on your skin or mucous membrane. 

These may signal serious side effects that may need urgent medical attention. Your doctor will test your 
blood to ensure that your white blood cell (cells that fight infection) and red blood cell (cells that carry iron 
and oxygen) counts, platelets (blood clotting cells) and other laboratory values are at acceptable levels. 
 
At the beginning of treatment with Viraferon, you may experience a flu-like reaction, with fever, fatigue, 
headache, muscle ache, joint pain and chills/rigors. Your doctor may recommend that you take paracetamol if 
you develop these symptoms. 
 
Other side effects that may occur include: 
 
Very commonly reported side effects (at least 1 in every 10 patients):  
pain, swelling and redness or skin damage at site of injection, hair loss, dizziness, changes in appetite, 
stomach or abdominal pains, diarrhoea, nausea (feeling sick), viral infection, depression, emotional lability, 
insomnia, anxiety, sore throat and painful swallowing, fatigue, chills/rigors, fever, flu-like reaction, feeling 
of general discomfort, headaches, weight loss, vomiting, irritability, weakness, mood swings, coughing 
(sometimes severe), shortness of breath, itching, dry skin, rash, sudden and severe muscle pain, joint pain, 
musculoskeletal pain, changes in laboratory blood values including decreased white blood cell count. Some 
children have had a decrease in their rate of growth (height and weight). 
 
Commonly reported side effects (at least 1 in every 100 patients, but less than 1 in every 10 patients): 
thirst, dehydration, high blood pressure, migraines, swollen glands, flushing, menstrual problems, 
decreased sexual drive, vaginal problem, breast pain, pain in testicle, problems with thyroid gland, red 
gums, dry mouth, red or sore mouth or tongue, tooth ache or tooth disorder, herpes simplex (fever blisters), 
taste change, upset stomach, dyspepsia (heartburn), constipation, enlargement of liver (liver problems, 
sometimes severe), loose stools, bedwetting in children, inflammation of the sinuses, bronchitis, eye pain, 
problem with your tear ducts, conjunctivitis (“pink eye”), agitation, sleepiness, sleepwalking, problem with 
behaviour, nervousness, stuffy or runny nose, sneezing, rapid breathing, pale or reddened skin, bruising, 
fingers and toes very sensitive to cold, problem with skin or nails, psoriasis (new or worsened), increased 
sweating, increased need to pass urine, fine shaking movements, decreased sensitivity to touch, arthritis.  
 
Rarely reported side effects (at least 1 in every 10,000 patients, but less than 1 in every 1,000 patients): 
pneumonia 
 
Very rarely reported side effects (less than 1 in every 10,000 patients): 
low blood pressure, puffy face, diabetes, leg cramps, back pain, kidney problems, nerve damage, bleeding 
gums, aplastic anaemia. Pure red cell aplasia, a condition where the body stopped or reduced the production 



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of red blood cells, has been reported. This causes severe anaemia, symptoms of which would include unusual 
tiredness and a lack of energy. 
 
Very rarely sarcoidosis, (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin 
lesions and swollen glands) has been reported. Loss of consciousness has occurred very rarely, mostly in 
elderly patients treated at high doses. Cases of stroke (cerebrovascular events) have been reported. Check 
with your doctor immediately if you have any of these symptoms.  
Periodontal (affecting gums) and dental disorders, altered mental status, loss of consciousness, acute 
hypersensitivity reactions including urticaria (hives), angioedema (swelling of the hands, feet, ankles, face, 
lips, mouth, or throat which may cause difficulty in swallowing or breathing), bronchoconstriction and 
anaphylaxis (a severe, whole-body allergic reaction) have been reported, but their frequency is unknown.  
 
Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin 
and the membranes of the ears, brain and spinal cord) has been reported with Viraferon use. 
 
Other side effects not listed above may also occur in some patients. If any of the side effects gets serious, or if you 
notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. 
 
 
5. HOW TO STORE VIRAFERON 
 
Keep out of the reach and sight of children. 
 
Store in a refrigerator (2°C - 8°C).  
Do not freeze.  
For short term travelling, the non-reconstituted product can be kept out of the refrigerator at or below 25°C 
for a period up to four weeks before use. If the product is not used during this four-week period, it should be 
discarded. 
 
The solution should be used immediately after reconstitution. If not used immediately, it must be stored at 
2°C - 8°C in the refrigerator and used within 24 hours. 
 
Do not use Viraferon after the expiry date which is stated on the package. 
 
Do not use Viraferon if you notice changes in the appearance of Viraferon. 
 
Any unused product must be discarded after withdrawal of the dose. 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose 
of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What Viraferon contains 
 
- The active substance is recombinant interferon alfa-2b, 10 million IU/ml. 
- The other ingredients are glycine, disodium phosphate anhydrous, sodium dihydrogen phosphate 

monohydrate, and human albumin solution. 
- Solvent: water for injections 1 ml/ampoule 
 
What Viraferon looks like and contents of the pack 
 
Viraferon is presented as a powder and solvent for solution for injection 
The white to cream coloured powder is contained in a 2 ml glass vial and the clear and colourless solvent is 
presented in a 2 ml glass ampoule. 



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Viraferon is available in three different pack sizes: 
- Pack of 1 vial of powder for solution for injection, 1 ampoule of water for injections, 1 injection 

syringe, 2 injection needles and 1 cleansing swab 
- Pack of 6 vials of powder for solution for injection and 6 ampoules of water for injections 
- Pack of 10 vials of powder for solution for injection, 10 ampoules of water for injections, 10 injection 

syringes, 20 injection needles and 10 cleansing swabs 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: Manufacturer: 
SP Europe SP Labo N.V. 
73, rue de Stalle Industriepark 30 
B-1180 Bruxelles B-2220 Heist-op-den-Berg 
Belgium Belgium 
 
For any information about this medicinal product, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Rue de Stalle/Stallestraat 73 
B-1180 Bruxelles/Brussel/Brüssel 
Tél/Tel: + 32-(0)2 370 92 11 
 

Luxembourg/Luxemburg 
Rue de Stalle 73 
B-1180 Bruxelles/Brüssel 
Belgique/Belgien 
Tél/Tel: + 32-(0)2 370 92 11 
 

България 
ул. "Проф. Милко Бичев" № 7, ет.3 
BG-София 1504  
Тел.: +359 2 944 1073 

Magyarország 
Alkotás u. 53. 
H-1123 Budapest 
Tel.: + 36 1 457-8500 

Česká republika 
Na Příkopě 25 
CZ-110 00 Praha 1 
Tel: + 420 221771250 
 

Malta 
168 Christopher Street 
MT-VLT02 Valletta 
Tel: + 356-21 23 21 75 
 

Danmark 
Lautrupbjerg 2 
DK-2750 Ballerup 
Tlf: + 45-44 39 50 00 
 

Nederland 
Maarssenbroeksedijk 4 
NL-3542 DN Utrecht 
Tel: + 31-(0)800 778 78 78 



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Deutschland 
Thomas-Dehler-Straße 27 
D-81737 München  
Tel: + 49-(0)89 627 31-0 
 

Norge 
Pb. 398 
N-1326 Lysaker 
Tlf: + 47 67 16 64 50 
 

Eesti 
Järvevana tee 9 
EE-11314 Tallinn 
Tel: + 372 654 96 86 
 

Österreich 
Badener Strasse 23 
A-2514 Traiskirchen 
Tel: + 43-(0)2252 502-0 
 

Ελλάδα 
Αγίου Δημητρίου 63 
GR-174 55 Άλιμος  
Tηλ: + 30-210 98 97 300 
 

Polska 
Al. Jerozolimskie 195a 
PL-02-222 Warszawa 
Tel.: + 48-(0)22 478 41 50 
 

España 
Km. 36, Ctra. Nacional I 
E-28750 San Agustín de Guadalix – Madrid 
Tel: + 34-91 848 85 00 
 

Portugal 
Rua Agualva dos Açores 16 
P-2735-557 Agualva-Cacém 
Tel: + 351-21 433 93 00 
 

France 
92 rue Baudin  
F-92300 Levallois-Perret 
Tél: + 33-(0)1 41 06 35 00 
 

România 
Şos. Bucureşti-Ploieşti, nr. 17-21,  
Băneasa Center, et. 8, sector 1 
RO-013682 Bucureşti 
Tel. + 40 21 233 35 30 

Ireland 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW 
Tel: + 44-(0)1 707 363 636 
 

Slovenija 
Dunajska 22 
SI-1000 Ljubljana 
Tel. + 386 01 3001070 
 

Ísland 
Hörgatún 2 
IS-210 Garðabær 
Sími: + 354 535 70 00 
 

Slovenská republika 
Strakova 5 
SK-811 01 Bratislava 
Tel: + 421 (2) 5920 2712 
 

Italia 
Via fratelli Cervi snc, 
Centro Direzionale Milano Due 
Palazzo Borromini 
I-20090 Segrate (Milano) 
Tel: + 39-02 21018.1 
 

Suomi/Finland 
PL 3/PB 3 
FIN-02201 Espoo/Esbo 
Puh/Tel: + 358-(0)20-7570 300 
 



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Κύπρος 
Οδός Αγίου Νικολάου, 8 
CY-1055 Λευκωσία 
Τηλ: + 357-22 757188 
 

Sverige 
Box 6185 
S-102 33 Stockholm 
Tel: + 46-(0)8 522 21 500 
 

Latvija 
Bauskas 58a -401 
Rīga, LV-1004  
Tel: + 371-7 21 38 25 
 

United Kingdom 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW - UK 
Tel: + 44-(0)1 707 363 636 
 

Lietuva 
Kęstučio g. 65/40 
LT-08124 Vilnius 
Tel. + 370 52 101868 

 

 
 
This leaflet was last approved on 
 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: 
http://www.emea.europa.eu/ 
 



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HOW TO SELF INJECT VIRAFERON 
 
The following instructions explain how to inject Viraferon yourself. Please read the instructions carefully and 
follow them step by step. Your doctor or his/her assistant will instruct you how to self-inject Viraferon. Do 
not attempt to inject yourself unless you are sure you understand the procedure and requirement of self-
injection. 
 
Preparation 
Collect necessary items before you begin: 
- a vial of Viraferon powder for injection; 
- an ampoule of solvent for Viraferon (water for injections 1 ml); 
- a 2 ml syringe; 
- a long needle (for example 0.8 × 40 mm [21 gauge 1.5 inch]) to be used to add water for injections to 

the Viraferon powder vial; 
- a short needle (for example 0.3 × 13 mm [30 gauge 0.5 inch]) for the subcutaneous injection; 
- a cleansing swab. 
Wash your hands carefully. 
 
Reconstituting Viraferon powder for injection 
Remove the protective cap from the Viraferon vial. Clean the rubber top of the vial with a cleansing swab. 
You can save the swab to clean the skin area where you will inject the dose. Remove the syringe from the 
wrapping. Do not touch the tip of the syringe. Take the long needle and place it firmly onto the tip of the 
syringe. Remove the needle guard without touching the needle and keep the syringe with the needle in your 
hand. Tap the top of the ampoule of solvent gently to make sure that all the liquid is at the bottom of the 
ampoule. Break the top of the ampoule of solvent. Insert the needle in the ampoule of solvent and withdraw 
the total amount of solvent. 
 
To prepare the Viraferon solution insert the needle through the rubber top of the Viraferon vial and gently 
place the needle tip against the glass wall of the vial without touching the cleaned top of the vial with your 
hands. 
Slowly inject the diluent, aiming the stream of liquid at the glass wall of the vial in order to avoid production 
of air bubbles. Do not aim the stream at the white powder at the bottom of the vial. To dissolve the white 
contents, swirl the Viraferon vial with a gentle rotary motion leaving the syringe needle in the vial, until the 
contents are completely dissolved. Do not shake. If air bubbles do form, wait until the solution has settled and 
all bubbles have risen to the top of the solution and disappeared before withdrawing your dose from the vial. 
The solution should be used immediately after reconstitution. If not used immediately, it must be stored at 
2°C - 8°C in the refrigerator and used within 24 hours. 
 
Measuring the dose of Viraferon from the reconstituted powder for injection 
Turn the vial and the syringe upside down in one hand. Be sure the tip of needle is in the Viraferon 
reconstituted solution. Your other hand will be free to move the plunger. Pull back on the plunger slowly to 
draw the correct dose as prescribed by your doctor into the syringe. 
Hold the syringe with the needle in the vial pointing up, remove the syringe from the long needle leaving the 
needle in the vial and without touching the tip of the syringe. Take the short needle and place it firmly onto 
the tip of the syringe. Remove the needle guard from the syringe needle and check for air bubbles in the 
syringe. If you see any bubbles, pull the plunger slightly back; tap the syringe gently, with the needle 
pointing up, until the bubbles disappear. Push up the plunger slowly back to the correct dose. Replace the 
needle guard and place the syringe with the needle on a flat surface. 
 
Be sure the solution is at room temperature up to 25°C. If the solution is cold, warm the syringe between your 
palms. Examine the reconstituted solution prior to administration: it should be clear and colourless. Do not 
use if discolouration or particulate matter is present. You are now ready to inject the dose. 



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Injecting the solution 
Select the injection site. The best sites for injection are tissues with a layer of fat between skin and muscle: 
thigh, outer surface of the upper arm (you may need the assistance of another person to use this site), 
abdomen (except the navel or waistline). If you are exceptionally thin, use only the thigh or outer surface of 
the arm for injection. 
Change your injection site each time. 
 
Cleanse and disinfect the skin where the injection is to be made. Wait for the area to dry. Remove the needle 
guard.With one hand, pinch a fold of loose skin. With your other hand hold the syringe as you would a 
pencil. Insert the needle into the pinched skin at an angle of 45° to 90°. Inject the solution by pushing the 
plunger all the way down gently. 
Pull the needle straight out of the skin. Press the injection site with a small bandage or sterile gauze if 
necessary for several seconds. Do not massage the injection site. If there is bleeding, cover with an adhesive 
bandage. 
The vial, ampoule and injection materials intended for single use must be discarded. Dispose of the syringe 
and needles safely in a closed container. 
 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Viraferon, 3 million IU/0.5 ml solution for injection 
Interferon alfa-2b 

 
Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Viraferon is and what it is used for 
2. Before you use Viraferon 
3. How to use Viraferon 
4. Possible side effects 
5. How to store Viraferon 
6. Further information 
 
 
1. WHAT VIRAFERON IS AND WHAT IT IS USED FOR 
 
Viraferon (interferon alfa-2b) modifies the response of the body's immune system to help fight infections and 
severe diseases. Viraferon is used in adult patients for the treatment of chronic hepatitis B or C, which are viral 
infections of the liver. 
 
Viraferon is used in combination with ribavirin in children and adolescents 3 years of age and older who have 
previously untreated chronic hepatitis C. 
 
 
2. BEFORE YOU USE VIRAFERON 
 
Do not use Viraferon 
- if you are allergic (hypersensitive) to interferon or any of the other ingredients of Viraferon. 
- if you have severe heart disease. 
- if you have poor kidney or liver function. 
- if you have advanced decompensated (uncontrolled) liver disease. 
- if you have hepatitis and have been treated recently with medications that suppress the immune system 

(other than short-term treatment with cortisone-type medicine). 
- if you have a history of seizures (convulsions). 
- if you have a history of autoimmune disease, or have had an organ transplant and are taking medicine that 

suppresses your immune system (your immune system helps protect you from infection). 
- if you have thyroid disease that is not well controlled. 
Children and adolescents: 
- if you have had serious nervous or mental problems, such as severe depression or thoughts of suicide. 
 
Take special care with Viraferon 
- if you are pregnant or planning to become pregnant (see Pregnancy). 
- if you have had a severe nervous or mental disorder. The use of interferon alfa-2b in children and 

adolescents with existence of or history of severe psychiatric conditions is contraindicated (see “Do not use 
Viraferon”) 

- if you have ever had depression or develop symptoms associated with depression (e.g. feelings of sadness, 
dejection, etc.) while on treatment with Viraferon (see section 4). 



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- if you have psoriasis, it may get worse during treatment with Viraferon. 
- when receiving Viraferon, you may temporarily have a greater risk of getting an infection. Check with 

your doctor if you think you are getting an infection. 
- if you develop symptoms associated with a cold or other respiratory infection, such as fever, cough, or any 

difficulty in breathing, tell your doctor. 
- if you notice unusual bleeding or bruising check with your doctor immediately. 
- if you develop symptoms of a severe allergic reaction (such as difficulty in breathing, wheezing, or hives) 

while on this medication seek medical help immediately. 
- if you are also being treated for HIV, please see Using other medicines. 
- if you have received an organ transplant, either kidney or liver, interferon treatment may increase the risk 

of rejection. Be sure to discuss this with your doctor. 
 
Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving Viraferon 
and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and 
membranes of the mouth during long-term treatment with the combination of Viraferon with ribavirin. You 
should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some 
patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly 
afterwards. 
 
During the one year of treatment, many children did not grow or gain weight as much as expected. However, 
during the 6 months after treatment, this trend was generally reversed, although a few children did not return 
to their previous rate of growth within the first year after completing treatment. 
 
Tell your doctor if you have ever had a heart attack or a heart problem; if you have a history of breathing 
irregularities or pneumonia, problems with blood clotting, liver condition, thyroid problems, diabetes, or high 
or low blood pressure. 
 
Tell your doctor if you have ever been treated for depression or any other psychiatric disorder; confusion; 
unconsciousness; thoughts of suicide or attempted suicide. 
 
Be sure to tell your doctor if you are taking the Chinese herbal medication Shosaikoto. 
 
Using other medicines 
Viraferon will add to the effects of substances that slow down your nervous system, possibly causing 
drowsiness. Therefore, check with your doctor or pharmacist about drinking alcoholic beverages, or taking 
sleeping pills, sedatives or strong pain medications.  
 
Tell your doctor if you are taking theophylline or aminophylline for asthma, and about all other medication 
you are taking, or have taken recently, even those not prescribed, as the dose of some medications may have 
to be adjusted while you are treated with Viraferon. 

 
Patients who also have HIV infection: Lactic acidosis and worsening liver function are side effects associated 
with Highly Active Anti-Retroviral Therapy (HAART), an HIV treatment. If you are receiving HAART, the 
addition of Viraferon and ribavirin may increase your risk of lactic acidosis and of liver failure. Your doctor 
will monitor you for signs and symptoms of these conditions (Please be sure to read the ribavirin Patient 
Leaflet also). Additionally, patients treated with Viraferon and ribavirin combination therapy and zidovudine 
could be at increased risk of developing anaemia (low number of red blood cells). 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. 
 
Using Viraferon with food and drink 
While being treated with Viraferon, your doctor may want you to drink extra fluids to help prevent low blood 
pressure. 
 



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Pregnancy and breast-feeding 
Ask your doctor or pharmacist for advice before taking any medicine. In studies in pregnant animals, 
interferons have sometimes caused miscarriage. The effect on human pregnancy is not known. 
If you are prescribed Viraferon in combination with ribavirin, ribavirin can be very damaging to an unborn 
baby, thus both female and male patients must take special precautions in their sexual activity if there is any 
chance for pregnancy to occur: 
- if you are a girl or a woman of childbearing age, you must have a negative pregnancy test before treatment, 
each month during treatment, and for the 4 months after treatment is stopped. You and your partner must 
each use an effective contraceptive during the time you are taking ribavirin and for 4 months after stopping 
treatment. This can be discussed with your doctor.  
- if you are a man who is taking ribavirin, do not have sex with a pregnant woman unless you use a condom. 
This will lessen the chance for ribavirin to be left in the woman’s body. If your female partner is not pregnant 
now but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 
7 months after treatment has stopped. This can be discussed with your doctor. If you are a male patient, you 
and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 
7 months after stopping treatment. This can be discussed with your doctor. 
 
It is not known whether this product is present in human milk. Therefore, do not breast-feed an infant if you 
are taking Viraferon. In combination therapy with ribavirin, take notice of the respective informing texts of 
ribavirin containing medicinal products. 
 
Driving and using machines 
Do not drive or use machinery if you become drowsy, tired, or confused from this medicine. 
 
 
3. HOW TO USE VIRAFERON 
 
Your doctor has prescribed Viraferon specifically for you and your current condition; do not share this medicine 
with anyone else. 
 
Your doctor has determined the exact dosage for administration of Viraferon according to your individual needs. 
The dosage will vary according to the disease being treated. 
 
If you are injecting Viraferon yourself, please be sure that the dose that has been prescribed for you is clearly 
provided with the package of medicine you receive. Dosages that are to be administered 3 times a week are best 
given every other day. 
 
The usual starting dose for each condition follows; however, individual doses may vary, and the doctor may 
change your dose based on your specific needs: 
 
Chronic hepatitis B: 5 to 10 million IU 3 times a week (every other day) injected subcutaneously (under the skin). 
 
Chronic hepatitis C: Adults - 3 million IU 3 times a week (every other day) injected subcutaneously (under the 
skin) in combination with ribavirin or alone. Children 3 years of age and older and adolescents - 
3 million IU/m2 3 times a week (every other day) injected subcutaneously (under the skin) in combination with 
ribavirin (Please also see ribavirin package leaflet).  
 
Your doctor may prescribe a different dose of Viraferon alone or in combination with other medicines (e.g. 
ribavirin). If you are prescribed Viraferon in combination with another medicine, please refer also to the Package 
Leaflet of the medicine to be used in combination. Your doctor will determine the exact dosage schedule and 
regimen according to your needs. If you have the impression that the effect of Viraferon is too strong or too 
weak, talk to your doctor or pharmacist. 
 
Subcutaneous use: 



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Viraferon is usually intended for subcutaneous use. This means that Viraferon is injected with a short needle into 
the fatty tissue just under the skin. If you are injecting this medicine yourself, you will be instructed how to 
prepare and give the injection. Detailed instructions for subcutaneous administration are provided with this leaflet 
(see HOW TO SELF INJECT VIRAFERON at the end of the leaflet). 
 
One dose of Viraferon is given on each scheduled day. Viraferon is given three times a week, every other day, for 
example on Monday, Wednesday, and Friday. Interferons may cause unusual tiredness; if you are injecting this 
medicine yourself, or giving it to a child, use it at bedtime. 
 
Use Viraferon exactly as prescribed by your doctor. Do not exceed the recommended dosage, and take Viraferon 
for as long as prescribed. 
 
If you use more Viraferon than you should 
Contact your doctor or healthcare professional as soon as possible. 
 
If you forget to take Viraferon 
If you are self-administering treatment, or if you are the caregiver of a child taking Viraferon in combination 
with ribavirin, inject the recommended dose as soon as you remember and continue treatment as usual Do not 
take a double dose to make up for a forgotten dose. If you are scheduled to inject this product every day, and 
you accidentally missed a full day’s dose, continue treatment at the usual dose the following day. Contact 
your doctor or pharmacist if needed. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Viraferon can cause side effects, although not everybody gets them. Although not all of 
these side effects may occur, they may need medical attention if they do. 
 
Some people get depressed when taking Viraferon alone or in combination treatment with ribavirin, and in some 
cases people had suicidal thoughts or aggressive behaviour (sometimes directed against others). Some patients have 
actually committed suicide. Be sure to seek emergency care if you notice that you are becoming depressed or have 
suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend 
to help you stay alert to signs of depression or changes in your behaviour. 
 
Paediatric Use: Children are particularly prone to develop depression when being treated with Viraferon and 
ribavirin. Immediately contact the doctor or seek emergency care if they display any unusual behavioural 
symptoms, feel depressed, or feel they want to harm themselves or others. 
 
If any of the following side effects happen, stop taking Viraferon and tell your doctor immediately or go to 
the casualty department at your nearest hospital: 
• swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in 

swallowing or breathing; hives; fainting. 
These are all very serious side effects. If you have them, you may have had a serious allergic reaction to 
Viraferon. You may need urgent medical attention or hospitalisation. These very serious side effects are very 
rare. 
 
Check with your doctor immediately if any of the following side effects occur: 
• chest pain or persistent and severe cough; irregular or rapid heartbeat; shortness of breath, confusion, 

difficulty remaining alert, numbness or tingling sensation or pain in hands or feet; seizure 
(convulsions); trouble sleeping, thinking or concentrating; altered mental state; suicidal thoughts, 
suicide attempt, changed behaviour or aggressive behaviour (sometimes directed against others), 
hallucinations; severe stomach pain; black or tar like stools; blood in stool or urine, severe 
nosebleed; waxy pallor, high sugar level in blood, fever or chills beginning after a few weeks of 



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treatment, lower back or side pain, difficult urination, problems with your eyes or your eyesight or 
hearing, loss of hearing, severe or painful reddening or sores on your skin or mucous membrane. 

These may signal serious side effects that may need urgent medical attention. Your doctor will test your 
blood to ensure that your white blood cell (cells that fight infection) and red blood cell (cells that carry iron 
and oxygen) counts, platelets (blood clotting cells) and other laboratory values are at acceptable levels. 
 
At the beginning of treatment with Viraferon, you may experience a flu-like reaction, with fever, fatigue, 
headache, muscle ache, joint pain and chills/rigors. Your doctor may recommend that you take paracetamol if 
you develop these symptoms. 
 
Other side effects that may occur include: 
 
Very commonly reported side effects (at least 1 in every 10 patients):  
pain, swelling and redness or skin damage at site of injection, hair loss, dizziness, changes in appetite, 
stomach or abdominal pains, diarrhoea, nausea (feeling sick), viral infection, depression, emotional lability, 
insomnia, anxiety, sore throat and painful swallowing, fatigue, chills/rigors, fever, flu-like reaction, feeling 
of general discomfort, headaches, weight loss, vomiting, irritability, weakness, mood swings, coughing 
(sometimes severe), shortness of breath, itching, dry skin, rash, sudden and severe muscle pain, joint pain, 
musculoskeletal pain, changes in laboratory blood values including decreased white blood cell count. Some 
children have had a decrease in their rate of growth (height and weight). 
 
Commonly reported side effects (at least 1 in every 100 patients, but less than 1 in every 10 patients): 
thirst, dehydration, high blood pressure, migraines, swollen glands, flushing, menstrual problems, 
decreased sexual drive, vaginal problem, breast pain, pain in testicle, problems with thyroid gland, red 
gums, dry mouth, red or sore mouth or tongue, tooth ache or tooth disorder, herpes simplex (fever blisters), 
taste change, upset stomach, dyspepsia (heartburn), constipation, enlargement of liver (liver problems, 
sometimes severe), loose stools, bedwetting in children, inflammation of the sinuses, bronchitis, eye pain, 
problem with your tear ducts, conjunctivitis (“pink eye”), agitation, sleepiness, sleepwalking, problem with 
behaviour, nervousness, stuffy or runny nose, sneezing, rapid breathing, pale or reddened skin, bruising, 
fingers and toes very sensitive to cold, problem with skin or nails, psoriasis (new or worsened), increased 
sweating, increased need to pass urine, fine shaking movements, decreased sensitivity to touch, arthritis.  
 
Rarely reported side effects (at least 1 in every 10,000 patients, but less than 1 in every 1,000 patients): 
pneumonia 
 
Very rarely reported side effects (less than 1 in every 10,000 patients): 
low blood pressure, puffy face, diabetes, leg cramps, back pain, kidney problems, nerve damage, bleeding 
gums, aplastic anaemia. Pure red cell aplasia, a condition where the body stopped or reduced the production 
of red blood cells, has been reported. This causes severe anaemia, symptoms of which would include unusual 
tiredness and a lack of energy. 
 
Very rarely sarcoidosis, (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin 
lesions and swollen glands) has been reported. Loss of consciousness has occurred very rarely, mostly in 
elderly patients treated at high doses. Cases of stroke (cerebrovascular events) have been reported. Check 
with your doctor immediately if you have any of these symptoms.  
Periodontal (affecting gums) and dental disorders, altered mental status, loss of consciousness, acute 
hypersensitivity reactions including urticaria (hives), angioedema (swelling of the hands, feet, ankles, face, 
lips, mouth, or throat which may cause difficulty in swallowing or breathing), bronchoconstriction and 
anaphylaxis (a severe, whole-body allergic reaction) have been reported, but their frequency is unknown.  
 
Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin 
and the membranes of the ears, brain and spinal cord) has been reported with Viraferon use. 
 
Other side effects not listed above may also occur in some patients. If any of the side effects gets serious, or if you 
notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. 



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5. HOW TO STORE VIRAFERON 
 
Keep out of the reach and sight of children. 
 
Store in a refrigerator (2°C - 8°C).  
Do not freeze.  
For short term travelling, the solution can be kept out of the refrigerator at or below 25°C for a period up to 
seven days before use. Viraferon can be put back in the refrigerator at any time during this seven-day period. 
If the product is not used during the seven-day period, it should be discarded. 
 
Do not use Viraferon after the expiry date which is stated on the package. 
 
Do not use Viraferon if you notice changes in the appearance of Viraferon. 
 
Any unused product must be discarded after withdrawal of the dose. 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose 
of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What Viraferon contains 
 
- The active substance is recombinant interferon alfa-2b, 3 million IU in a single dose vial 
- The other ingredients are disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, 

edetate disodium, sodium chloride, m-cresol, polysorbate 80 and water for injections. 
 
What Viraferon looks like and contents of the pack 
 
Viraferon is presented as a solution for injection 
- The clear and colourless solution is contained in a glass vial with 1 injection syringe, 1 injection 

needle and 1 cleansing swab. Pack of 1, 6 or 12. Vial alone is also available. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: Manufacturer: 
SP Europe SP Labo N.V. 
73, rue de Stalle Industriepark 30 
B-1180 Bruxelles B-2220 Heist-op-den-Berg 
Belgium Belgium 
 
For any information about this medicinal product, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Rue de Stalle/Stallestraat 73 
B-1180 Bruxelles/Brussel/Brüssel 
Tél/Tel: + 32-(0)2 370 92 11 
 

Luxembourg/Luxemburg 
Rue de Stalle 73 
B-1180 Bruxelles/Brüssel 
Belgique/Belgien 
Tél/Tel: + 32-(0)2 370 92 11 
 

България 
ул. "Проф. Милко Бичев" № 7, ет.3 
BG-София 1504  
Тел.: +359 2 944 1073 

Magyarország 
Alkotás u. 53. 
H-1123 Budapest 
Tel.: + 36 1 457-8500 



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Česká republika 
Na Příkopě 25 
CZ-110 00 Praha 1 
Tel: + 420 221771250 
 

Malta 
168 Christopher Street 
MT-VLT02 Valletta 
Tel: + 356-21 23 21 75 
 

Danmark 
Lautrupbjerg 2 
DK-2750 BallerupTlf: + 45-44 39 50 00 
 

Nederland 
Maarssenbroeksedijk 4 
NL-3542 DN Utrecht 
Tel: + 31-(0)800 778 78 78 

Deutschland 
Thomas-Dehler-Straße 27 
D-81737 München  
Tel: + 49-(0)89 627 31-0 
 

Norge 
Pb. 398 
N-1326 Lysaker 
Tlf: + 47 67 16 64 50 
 

Eesti 
Järvevana tee 9 
EE-11314 Tallinn 
Tel: + 372 654 96 86 
 

Österreich 
Badener Strasse 23 
A-2514 Traiskirchen 
Tel: + 43-(0)2252 502-0 
 

Ελλάδα 
Αγίου Δημητρίου 63 
GR-174 55 Άλιμος  
Tηλ: + 30-210 98 97 300 
 

Polska 
Al. Jerozolimskie 195a 
PL-02-222 Warszawa 
Tel.: + 48-(0)22 478 41 50 
 

España 
Km. 36, Ctra. Nacional I 
E-28750 San Agustín de Guadalix – Madrid 
Tel: + 34-91 848 85 00 
 

Portugal 
Rua Agualva dos Açores 16 
P-2735-557 Agualva-Cacém 
Tel: + 351-21 433 93 00 
 

France 
92 rue Baudin  
F-92300 Levallois-Perret 
Tél: + 33-(0)1 41 06 35 00 
 

România 
Şos. Bucureşti-Ploieşti, nr. 17-21,  
Băneasa Center, et. 8, sector 1 
RO-013682 Bucureşti 
Tel. + 40 21 233 35 30 



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Ireland 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW 
Tel: + 44-(0)1 707 363 636 
 

Slovenija 
Dunajska 22 
SI-1000 Ljubljana 
Tel. + 386 01 3001070 
 

Ísland 
Hörgatún 2 
IS-210 Garðabær 
Sími: + 354 535 70 00 
 

Slovenská republika 
Strakova 5 
SK-811 01 Bratislava 
Tel: + 421 (2) 5920 2712 
 

Italia 
Via fratelli Cervi snc, 
Centro Direzionale Milano Due 
Palazzo Borromini 
I-20090 Segrate (Milano) 
Tel: + 39-02 21018.1 
 

Suomi/Finland 
PL 3/PB 3 
FIN-02201 Espoo/Esbo 
Puh/Tel: + 358-(0)20-7570 300 
 

Κύπρος 
Οδός Αγίου Νικολάου, 8 
CY-1055 Λευκωσία 
Τηλ: + 357-22 757188 
 

Sverige 
Box 6185 
S-102 33 Stockholm 
Tel: + 46-(0)8 522 21 500 
 

Latvija 
Bauskas 58a -401 
Rīga, LV-1004  
Tel: + 371-7 21 38 25 
 

United Kingdom 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW - UK 
Tel: + 44-(0)1 707 363 636 
 

Lietuva 
Kęstučio g. 65/40 
LT-08124 Vilnius 
Tel. + 370 52 101868 

 

 
 
This leaflet was last approved on 
 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: 
http://www.emea.europa.eu/ 
 



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HOW TO SELF INJECT VIRAFERON 
 
The following instructions explain how to inject Viraferon yourself. Please read the instructions carefully and 
follow them step by step. Your doctor or his/her assistant will instruct you how to self-inject Viraferon. Do 
not attempt to inject yourself unless you are sure you understand the procedure and requirement of self-
injection. 
 
Preparation 
Collect necessary items before you begin: 
- a vial of Viraferon solution for injection; 
- a 1 ml syringe; 
- a needle for the subcutaneous injection (for example 0.4 × 13 mm [27 gauge 0.5 inch]); 
- a cleansing swab. 
Wash your hands carefully. 
 
Measuring the dose of Viraferon 
Remove the cap from the vial. If this is a multidose vial, you will only have to remove the cap when 
preparing the first dose. Clean the rubber stopper on the top of the vial containing the Viraferon solution with 
a cleansing swab. 
Remove the syringe from the wrapping. Do not touch the tip of the syringe. Take the needle and place it 
firmly onto the tip of the syringe. 
Remove the needle guard without touching the needle, and fill the syringe with air by pulling the plunger to 
the level that represents your dose as prescribed by your doctor. 
Hold the Viraferon vial upright without touching the cleaned top of the vial with your hands. 
Insert the needle into the vial containing the Viraferon solution and inject air into the vial. 
Turn the vial and the syringe upside down in one hand. Be sure the tip of needle is in the Viraferon solution. 
Your other hand will be free to move the plunger. Pull back on the plunger slowly to draw the correct dose as 
prescribed by your doctor into the syringe. 
Remove the needle from the vial and check for air bubbles in the syringe. If you see any bubbles, pull the 
plunger slightly back; tap the syringe gently, with the needle pointing up, until the bubbles disappear. Push 
up the plunger slowly back to the correct dose. Replace the needle guard and place the syringe with the 
needle on a flat surface. 
 
Be sure the solution is at room temperature up to 25°C. If the solution is cold, warm the syringe between your 
palms. Examine the solution prior to administration: it should be clear and colourless. Do not use if 
discolouration or particulate matter is present. You are now ready to inject the dose. 
 
Injecting the solution 
Select the injection site. The best sites for injection are tissues with a layer of fat between skin and muscle: 
thigh, outer surface of the upper arm (you may need the assistance of another person to use this site), 
abdomen (except the navel or waistline). If you are exceptionally thin, use only the thigh or outer surface of 
the arm for injection. 
Change your injection site each time. 
 
Cleanse and disinfect the skin where the injection is to be made. Wait for the area to dry. Remove the needle 
guard. With one hand, pinch a fold of loose skin. With your other hand hold the syringe as you would a 
pencil. Insert the needle into the pinched skin at an angle of 45° to 90°. Inject the solution by pushing the 
plunger all the way down gently. Pull the needle straight out of the skin. Press the injection site with a small 
bandage or sterile gauze if necessary for several seconds. Do not massage the injection site. If there is 
bleeding, cover with an adhesive bandage. 
The vial and injection materials intended for single use must be discarded. Dispose of the syringe and needle 
safely in a closed container. For multidose vials, be sure to return the vial to the refrigerator. 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Viraferon, 5 million IU/0.5 ml solution for injection 
Interferon alfa-2b 

 
Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Viraferon is and what it is used for 
2. Before you use Viraferon 
3. How to use Viraferon 
4. Possible side effects 
5. How to store Viraferon 
6. Further information 
 
 
1. WHAT VIRAFERON IS AND WHAT IT IS USED FOR 
 
Viraferon (interferon alfa-2b) modifies the response of the body's immune system to help fight infections and 
severe diseases. Viraferon is used in adult patients for the treatment of chronic hepatitis B or C, which are viral 
infections of the liver. 
 
Viraferon is used in combination with ribavirin in children and adolescents 3 years of age and older who have 
previously untreated chronic hepatitis C. 
 
 
2. BEFORE YOU USE VIRAFERON 
 
Do not use Viraferon 
- if you are allergic (hypersensitive) to interferon or any of the other ingredients of Viraferon. 
- if you have severe heart disease. 
- if you have poor kidney or liver function. 
- if you have advanced decompensated (uncontrolled) liver disease. 
- if you have hepatitis and have been treated recently with medications that suppress the immune system 

(other than short-term treatment with cortisone-type medicine). 
- if you have a history of seizures (convulsions). 
- if you have a history of autoimmune disease, or have had an organ transplant and are taking medicine that 

suppresses your immune system (your immune system helps protect you from infection). 
- if you have thyroid disease that is not well controlled. 
Children and adolescents: 
- if you have had serious nervous or mental problems, such as severe depression or thoughts of suicide. 
 
Take special care with Viraferon 
- if you are pregnant or planning to become pregnant (see Pregnancy). 
- if you have had a severe nervous or mental disorder. The use of interferon alfa-2b in children and 

adolescents with existence of or history of severe psychiatric conditions is contraindicated (see “Do not use 
Viraferon”) 

- if you have ever had depression or develop symptoms associated with depression (e.g. feelings of sadness, 
dejection, etc.) while on treatment with Viraferon (see section 4). 



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- if you have psoriasis, it may get worse during treatment with Viraferon. 
- when receiving Viraferon, you may temporarily have a greater risk of getting an infection. Check with 

your doctor if you think you are getting an infection. 
- if you develop symptoms associated with a cold or other respiratory infection, such as fever, cough, or any 

difficulty in breathing, tell your doctor. 
- if you notice unusual bleeding or bruising check with your doctor immediately. 
- if you develop symptoms of a severe allergic reaction (such as difficulty in breathing, wheezing, or hives) 

while on this medication seek medical help immediately. 
- if you are also being treated for HIV, please see Using other medicines. 
- if you have received an organ transplant, either kidney or liver, interferon treatment may increase the risk 

of rejection. Be sure to discuss this with your doctor. 
 
Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving Viraferon 
and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and 
membranes of the mouth during long-term treatment with the combination of Viraferon with ribavirin. You 
should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some 
patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly 
afterwards. 
 
During the one year of treatment, many children did not grow or gain weight as much as expected. However, 
during the 6 months after treatment, this trend was generally reversed, although a few children did not return 
to their previous rate of growth within the first year after completing treatment. 
 
Tell your doctor if you have ever had a heart attack or a heart problem; if you have a history of breathing 
irregularities or pneumonia, problems with blood clotting, liver condition, thyroid problems, diabetes, or high 
or low blood pressure. 
 
Tell your doctor if you have ever been treated for depression or any other psychiatric disorder; confusion; 
unconsciousness; thoughts of suicide or attempted suicide. 
 
Be sure to tell your doctor if you are taking the Chinese herbal medication Shosaikoto. 
 
Using other medicines 
Viraferon will add to the effects of substances that slow down your nervous system, possibly causing 
drowsiness. Therefore, check with your doctor or pharmacist about drinking alcoholic beverages, or taking 
sleeping pills, sedatives or strong pain medications.  
 
Tell your doctor if you are taking theophylline or aminophylline for asthma, and about all other medication 
you are taking, or have taken recently, even those not prescribed, as the dose of some medications may have 
to be adjusted while you are treated with Viraferon. 

 
Patients who also have HIV infection: Lactic acidosis and worsening liver function are side effects associated 
with Highly Active Anti-Retroviral Therapy (HAART), an HIV treatment. If you are receiving HAART, the 
addition of Viraferon and ribavirin may increase your risk of lactic acidosis and of liver failure. Your doctor 
will monitor you for signs and symptoms of these conditions (Please be sure to read the ribavirin Patient 
Leaflet also). Additionally, patients treated with Viraferon and ribavirin combination therapy and zidovudine 
could be at increased risk of developing anaemia (low number of red blood cells). 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. 
 
Using Viraferon with food and drink 
While being treated with Viraferon, your doctor may want you to drink extra fluids to help prevent low blood 
pressure. 
 



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Pregnancy and breast-feeding 
Ask your doctor or pharmacist for advice before taking any medicine. In studies in pregnant animals, 
interferons have sometimes caused miscarriage. The effect on human pregnancy is not known. 
If you are prescribed Viraferon in combination with ribavirin, ribavirin can be very damaging to an unborn 
baby, thus both female and male patients must take special precautions in their sexual activity if there is any 
chance for pregnancy to occur: 
- if you are a girl or a woman of childbearing age, you must have a negative pregnancy test before treatment, 
each month during treatment, and for the 4 months after treatment is stopped. You and your partner must 
each use an effective contraceptive during the time you are taking ribavirin and for 4 months after stopping 
treatment. This can be discussed with your doctor.  
- if you are a man who is taking ribavirin, do not have sex with a pregnant woman unless you use a condom. 
This will lessen the chance for ribavirin to be left in the woman’s body. If your female partner is not pregnant 
now but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 
7 months after treatment has stopped. This can be discussed with your doctor. If you are a male patient, you 
and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 
7 months after stopping treatment. This can be discussed with your doctor. 
 
It is not known whether this product is present in human milk. Therefore, do not breast-feed an infant if you 
are taking Viraferon. In combination therapy with ribavirin, take notice of the respective informing texts of 
ribavirin containing medicinal products. 
 
Driving and using machines 
Do not drive or use machinery if you become drowsy, tired, or confused from this medicine. 
 
 
3. HOW TO USE VIRAFERON 
 
Your doctor has prescribed Viraferon specifically for you and your current condition; do not share this medicine 
with anyone else. 
 
Your doctor has determined the exact dosage for administration of Viraferon according to your individual needs. 
The dosage will vary according to the disease being treated. 
 
If you are injecting Viraferon yourself, please be sure that the dose that has been prescribed for you is clearly 
provided with the package of medicine you receive. Dosages that are to be administered 3 times a week are best 
given every other day. 
 
The usual starting dose for each condition follows; however, individual doses may vary, and the doctor may 
change your dose based on your specific needs: 
 
Chronic hepatitis B: 5 to 10 million IU 3 times a week (every other day) injected subcutaneously (under the skin). 
 
Chronic hepatitis C: Adults - 3 million IU 3 times a week (every other day) injected subcutaneously (under the 
skin) in combination with ribavirin or alone. Children 3 years of age and older and adolescents - 
3 million IU/m2 3 times a week (every other day) injected subcutaneously (under the skin) in combination with 
ribavirin (Please also see ribavirin package leaflet).  
 
Your doctor may prescribe a different dose of Viraferon alone or in combination with other medicines (e.g. 
ribavirin). If you are prescribed Viraferon in combination with another medicine, please refer also to the Package 
Leaflet of the medicine to be used in combination. Your doctor will determine the exact dosage schedule and 
regimen according to your needs. If you have the impression that the effect of Viraferon is too strong or too 
weak, talk to your doctor or pharmacist. 
 
Subcutaneous use: 



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Viraferon is usually intended for subcutaneous use. This means that Viraferon is injected with a short needle into 
the fatty tissue just under the skin. If you are injecting this medicine yourself, you will be instructed how to 
prepare and give the injection. Detailed instructions for subcutaneous administration are provided with this leaflet 
(see HOW TO SELF INJECT VIRAFERON at the end of the leaflet). 
 
One dose of Viraferon is given on each scheduled day. Viraferon is given three times a week, every other day, for 
example on Monday, Wednesday, and Friday. Interferons may cause unusual tiredness; if you are injecting this 
medicine yourself, or giving it to a child, use it at bedtime. 
 
Use Viraferon exactly as prescribed by your doctor. Do not exceed the recommended dosage, and take Viraferon 
for as long as prescribed. 
 
If you use more Viraferon than you should 
Contact your doctor or healthcare professional as soon as possible. 
 
If you forget to take Viraferon 
If you are self-administering treatment, or if you are the caregiver of a child taking Viraferon in combination 
with ribavirin, inject the recommended dose as soon as you remember and continue treatment as usual Do not 
take a double dose to make up for a forgotten dose. If you are scheduled to inject this product every day, and 
you accidentally missed a full day’s dose, continue treatment at the usual dose the following day. Contact 
your doctor or pharmacist if needed. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Viraferon can cause side effects, although not everybody gets them. Although not all of 
these side effects may occur, they may need medical attention if they do. 
 
Some people get depressed when taking Viraferon alone or in combination treatment with ribavirin, and in some 
cases people had suicidal thoughts or aggressive behaviour (sometimes directed against others). Some patients have 
actually committed suicide. Be sure to seek emergency care if you notice that you are becoming depressed or have 
suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend 
to help you stay alert to signs of depression or changes in your behaviour. 
 
Paediatric Use: Children are particularly prone to develop depression when being treated with Viraferon and 
ribavirin. Immediately contact the doctor or seek emergency care if they display any unusual behavioural 
symptoms, feel depressed, or feel they want to harm themselves or others. 
 
If any of the following side effects happen, stop taking Viraferon and tell your doctor immediately or go to 
the casualty department at your nearest hospital: 
• swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in 

swallowing or breathing; hives; fainting. 
These are all very serious side effects. If you have them, you may have had a serious allergic reaction to 
Viraferon. You may need urgent medical attention or hospitalisation. These very serious side effects are very 
rare. 
 
Check with your doctor immediately if any of the following side effects occur: 
• chest pain or persistent and severe cough; irregular or rapid heartbeat; shortness of breath, confusion, 

difficulty remaining alert, numbness or tingling sensation or pain in hands or feet; seizure 
(convulsions); trouble sleeping, thinking or concentrating; altered mental state; suicidal thoughts, 
suicide attempt, changed behaviour or aggressive behaviour (sometimes directed against others), 
hallucinations; severe stomach pain; black or tar like stools; blood in stool or urine, severe 
nosebleed; waxy pallor, high sugar level in blood, fever or chills beginning after a few weeks of 



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treatment, lower back or side pain, difficult urination, problems with your eyes or your eyesight or 
hearing, loss of hearing, severe or painful reddening or sores on your skin or mucous membrane. 

These may signal serious side effects that may need urgent medical attention. Your doctor will test your 
blood to ensure that your white blood cell (cells that fight infection) and red blood cell (cells that carry iron 
and oxygen) counts, platelets (blood clotting cells) and other laboratory values are at acceptable levels. 
 
At the beginning of treatment with Viraferon, you may experience a flu-like reaction, with fever, fatigue, 
headache, muscle ache, joint pain and chills/rigors. Your doctor may recommend that you take paracetamol if 
you develop these symptoms. 
 
Other side effects that may occur include: 
 
Very commonly reported side effects (at least 1 in every 10 patients):  
pain, swelling and redness or skin damage at site of injection, hair loss, dizziness, changes in appetite, 
stomach or abdominal pains, diarrhoea, nausea (feeling sick), viral infection, depression, emotional lability, 
insomnia, anxiety, sore throat and painful swallowing, fatigue, chills/rigors, fever, flu-like reaction, feeling 
of general discomfort, headaches, weight loss, vomiting, irritability, weakness, mood swings, coughing 
(sometimes severe), shortness of breath, itching, dry skin, rash, sudden and severe muscle pain, joint pain, 
musculoskeletal pain, changes in laboratory blood values including decreased white blood cell count. Some 
children have had a decrease in their rate of growth (height and weight). 
 
Commonly reported side effects (at least 1 in every 100 patients, but less than 1 in every 10 patients): 
thirst, dehydration, high blood pressure, migraines, swollen glands, flushing, menstrual problems, 
decreased sexual drive, vaginal problem, breast pain, pain in testicle, problems with thyroid gland, red 
gums, dry mouth, red or sore mouth or tongue, tooth ache or tooth disorder, herpes simplex (fever blisters), 
taste change, upset stomach, dyspepsia (heartburn), constipation, enlargement of liver (liver problems, 
sometimes severe), loose stools, bedwetting in children, inflammation of the sinuses, bronchitis, eye pain, 
problem with your tear ducts, conjunctivitis (“pink eye”), agitation, sleepiness, sleepwalking, problem with 
behaviour, nervousness, stuffy or runny nose, sneezing, rapid breathing, pale or reddened skin, bruising, 
fingers and toes very sensitive to cold, problem with skin or nails, psoriasis (new or worsened), increased 
sweating, increased need to pass urine, fine shaking movements, decreased sensitivity to touch, arthritis.  
 
Rarely reported side effects (at least 1 in every 10,000 patients, but less than 1 in every 1,000 patients): 
pneumonia 
 
Very rarely reported side effects (less than 1 in every 10,000 patients): 
low blood pressure, puffy face, diabetes, leg cramps, back pain, kidney problems, nerve damage, bleeding 
gums, aplastic anaemia. Pure red cell aplasia, a condition where the body stopped or reduced the production 
of red blood cells, has been reported. This causes severe anaemia, symptoms of which would include unusual 
tiredness and a lack of energy. 
 
Very rarely sarcoidosis, (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin 
lesions and swollen glands) has been reported. Loss of consciousness has occurred very rarely, mostly in 
elderly patients treated at high doses. Cases of stroke (cerebrovascular events) have been reported. Check 
with your doctor immediately if you have any of these symptoms.  
Periodontal (affecting gums) and dental disorders, altered mental status, loss of consciousness, acute 
hypersensitivity reactions including urticaria (hives), angioedema (swelling of the hands, feet, ankles, face, 
lips, mouth, or throat which may cause difficulty in swallowing or breathing), bronchoconstriction and 
anaphylaxis (a severe, whole-body allergic reaction) have been reported, but their frequency is unknown.  
 
Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin 
and the membranes of the ears, brain and spinal cord) has been reported with Viraferon use. 
 
Other side effects not listed above may also occur in some patients. If any of the side effects gets serious, or if you 
notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. 



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5. HOW TO STORE VIRAFERON 
 
Keep out of the reach and sight of children. 
 
Store in a refrigerator (2°C - 8°C).  
Do not freeze.  
For short term travelling, the solution can be kept out of the refrigerator at or below 25°C for a period up to 
seven days before use. Viraferon can be put back in the refrigerator at any time during this seven-day period. 
If the product is not used during the seven-day period, it should be discarded. 
 
Do not use Viraferon after the expiry date which is stated on the package. 
 
Do not use Viraferon if you notice changes in the appearance of Viraferon. 
 
Any unused product must be discarded after withdrawal of the dose. 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose 
of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What Viraferon contains 
 
- The active substance is recombinant interferon alfa-2b, 5 million IU in a single dose vial 
- The other ingredients are disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, 

edetate disodium, sodium chloride, m-cresol, polysorbate 80 and water for injections. 
 
What Viraferon looks like and contents of the pack 
 
Viraferon is presented as a solution for injection 
- The clear and colourless solution is contained in a glass vial with 1 injection syringe, 1 injection 

needle and 1 cleansing swab. Pack of 1, 6 or 12. Vial alone is also available. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: Manufacturer: 
SP Europe SP Labo N.V. 
73, rue de Stalle Industriepark 30 
B-1180 Bruxelles B-2220 Heist-op-den-Berg 
Belgium Belgium 
 
For any information about this medicinal product, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Rue de Stalle/Stallestraat 73 
B-1180 Bruxelles/Brussel/Brüssel 
Tél/Tel: + 32-(0)2 370 92 11 
 

Luxembourg/Luxemburg 
Rue de Stalle 73 
B-1180 Bruxelles/Brüssel 
Belgique/Belgien 
Tél/Tel: + 32-(0)2 370 92 11 
 

България 
ул. "Проф. Милко Бичев" № 7, ет.3 
BG-София 1504  
Тел.: +359 2 944 1073 

Magyarország 
Alkotás u. 53. 
H-1123 Budapest 
Tel.: + 36 1 457-8500 



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Česká republika 
Na Příkopě 25 
CZ-110 00 Praha 1 
Tel: + 420 221771250 
 

Malta 
168 Christopher Street 
MT-VLT02 Valletta 
Tel: + 356-21 23 21 75 
 

Danmark 
Lautrupbjerg 2 
DK-2750 BallerupTlf: + 45-44 39 50 00 
 

Nederland 
Maarssenbroeksedijk 4 
NL-3542 DN Utrecht 
Tel: + 31-(0)800 778 78 78 

Deutschland 
Thomas-Dehler-Straße 27 
D-81737 München  
Tel: + 49-(0)89 627 31-0 
 

Norge 
Pb. 398 
N-1326 Lysaker 
Tlf: + 47 67 16 64 50 
 

Eesti 
Järvevana tee 9 
EE-11314 Tallinn 
Tel: + 372 654 96 86 
 

Österreich 
Badener Strasse 23 
A-2514 Traiskirchen 
Tel: + 43-(0)2252 502-0 
 

Ελλάδα 
Αγίου Δημητρίου 63 
GR-174 55 Άλιμος  
Tηλ: + 30-210 98 97 300 
 

Polska 
Al. Jerozolimskie 195a 
PL-02-222 Warszawa 
Tel.: + 48-(0)22 478 41 50 
 

España 
Km. 36, Ctra. Nacional I 
E-28750 San Agustín de Guadalix – Madrid 
Tel: + 34-91 848 85 00 
 

Portugal 
Rua Agualva dos Açores 16 
P-2735-557 Agualva-Cacém 
Tel: + 351-21 433 93 00 
 

France 
92 rue Baudin  
F-92300 Levallois-Perret 
Tél: + 33-(0)1 41 06 35 00 
 

România 
Şos. Bucureşti-Ploieşti, nr. 17-21,  
Băneasa Center, et. 8, sector 1 
RO-013682 Bucureşti 
Tel. + 40 21 233 35 30 
 



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Ireland 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW 
Tel: + 44-(0)1 707 363 636 
 

Slovenija 
Dunajska 22 
SI-1000 Ljubljana 
Tel. + 386 01 3001070 
 

Ísland 
Hörgatún 2 
IS-210 Garðabær 
Sími: + 354 535 70 00 
 

Slovenská republika 
Strakova 5 
SK-811 01 Bratislava 
Tel: + 421 (2) 5920 2712 
 

Italia 
Via fratelli Cervi snc, 
Centro Direzionale Milano Due 
Palazzo Borromini 
I-20090 Segrate (Milano) 
Tel: + 39-02 21018.1 
 

Suomi/Finland 
PL 3/PB 3 
FIN-02201 Espoo/Esbo 
Puh/Tel: + 358-(0)20-7570 300 
 

Κύπρος 
Οδός Αγίου Νικολάου, 8 
CY-1055 Λευκωσία 
Τηλ: + 357-22 757188 
 

Sverige 
Box 6185 
S-102 33 Stockholm 
Tel: + 46-(0)8 522 21 500 
 

Latvija 
Bauskas 58a -401 
Rīga, LV-1004  
Tel: + 371-7 21 38 25 
 

United Kingdom 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW - UK 
Tel: + 44-(0)1 707 363 636 
 

Lietuva 
Kęstučio g. 65/40 
LT-08124 Vilnius 
Tel. + 370 52 101868 

 

 
 
This leaflet was last approved on 
 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: 
http://www.emea.europa.eu/ 
 



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HOW TO SELF INJECT VIRAFERON 
 
The following instructions explain how to inject Viraferon yourself. Please read the instructions carefully and 
follow them step by step. Your doctor or his/her assistant will instruct you how to self-inject Viraferon. Do 
not attempt to inject yourself unless you are sure you understand the procedure and requirement of self-
injection. 
 
Preparation 
Collect necessary items before you begin: 
- a vial of Viraferon solution for injection; 
- a 1 ml syringe; 
- a needle for the subcutaneous injection (for example 0.4 × 13 mm [27 gauge 0.5 inch]); 
- a cleansing swab. 
Wash your hands carefully. 
 
Measuring the dose of Viraferon 
Remove the cap from the vial. If this is a multidose vial, you will only have to remove the cap when 
preparing the first dose. Clean the rubber stopper on the top of the vial containing the Viraferon solution with 
a cleansing swab. 
Remove the syringe from the wrapping. Do not touch the tip of the syringe. Take the needle and place it 
firmly onto the tip of the syringe. 
Remove the needle guard without touching the needle, and fill the syringe with air by pulling the plunger to 
the level that represents your dose as prescribed by your doctor. 
Hold the Viraferon vial upright without touching the cleaned top of the vial with your hands. 
Insert the needle into the vial containing the Viraferon solution and inject air into the vial. 
Turn the vial and the syringe upside down in one hand. Be sure the tip of needle is in the Viraferon solution. 
Your other hand will be free to move the plunger. Pull back on the plunger slowly to draw the correct dose as 
prescribed by your doctor into the syringe. 
Remove the needle from the vial and check for air bubbles in the syringe. If you see any bubbles, pull the 
plunger slightly back; tap the syringe gently, with the needle pointing up, until the bubbles disappear. Push 
up the plunger slowly back to the correct dose. Replace the needle guard and place the syringe with the 
needle on a flat surface. 
 
Be sure the solution is at room temperature up to 25°C. If the solution is cold, warm the syringe between your 
palms. Examine the solution prior to administration: it should be clear and colourless. Do not use if 
discolouration or particulate matter is present. You are now ready to inject the dose. 
 
Injecting the solution 
Select the injection site. The best sites for injection are tissues with a layer of fat between skin and muscle: 
thigh, outer surface of the upper arm (you may need the assistance of another person to use this site), 
abdomen (except the navel or waistline). If you are exceptionally thin, use only the thigh or outer surface of 
the arm for injection. 
Change your injection site each time. 
 
Cleanse and disinfect the skin where the injection is to be made. Wait for the area to dry. Remove the needle 
guard. With one hand, pinch a fold of loose skin. With your other hand hold the syringe as you would a 
pencil. Insert the needle into the pinched skin at an angle of 45° to 90°. Inject the solution by pushing the 
plunger all the way down gently. Pull the needle straight out of the skin. Press the injection site with a small 
bandage or sterile gauze if necessary for several seconds. Do not massage the injection site. If there is 
bleeding, cover with an adhesive bandage. 
The vial and injection materials intended for single use must be discarded. Dispose of the syringe and needle 
safely in a closed container. For multidose vials, be sure to return the vial to the refrigerator. 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Viraferon, 10 million IU/ml solution for injection 
Interferon alfa-2b 

 
Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Viraferon is and what it is used for 
2. Before you use Viraferon 
3. How to use Viraferon 
4. Possible side effects 
5. How to store Viraferon 
6. Further information 
 
 
1. WHAT VIRAFERON IS AND WHAT IT IS USED FOR 
 
Viraferon (interferon alfa-2b) modifies the response of the body's immune system to help fight infections and 
severe diseases. Viraferon is used in adult patients for the treatment of chronic hepatitis B or C, which are viral 
infections of the liver. 
 
Viraferon is used in combination with ribavirin in children and adolescents 3 years of age and older who have 
previously untreated chronic hepatitis C. 
 
 
2. BEFORE YOU USE VIRAFERON 
 
Do not use Viraferon 
- if you are allergic (hypersensitive) to interferon or any of the other ingredients of Viraferon. 
- if you have severe heart disease. 
- if you have poor kidney or liver function. 
- if you have advanced decompensated (uncontrolled) liver disease. 
- if you have hepatitis and have been treated recently with medications that suppress the immune system 

(other than short-term treatment with cortisone-type medicine). 
- if you have a history of seizures (convulsions). 
- if you have a history of autoimmune disease, or have had an organ transplant and are taking medicine that 

suppresses your immune system (your immune system helps protect you from infection). 
- if you have thyroid disease that is not well controlled. 
Children and adolescents: 
- if you have had serious nervous or mental problems, such as severe depression or thoughts of suicide. 
 
Take special care with Viraferon 
- if you are pregnant or planning to become pregnant (see Pregnancy). 
- if you have had a severe nervous or mental disorder. The use of interferon alfa-2b in children and 

adolescents with existence of or history of severe psychiatric conditions is contraindicated (see “Do not use 
Viraferon”) 

- if you have ever had depression or develop symptoms associated with depression (e.g. feelings of sadness, 
dejection, etc.) while on treatment with Viraferon (see section 4). 



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- if you have psoriasis, it may get worse during treatment with Viraferon. 
- when receiving Viraferon, you may temporarily have a greater risk of getting an infection. Check with 

your doctor if you think you are getting an infection. 
- if you develop symptoms associated with a cold or other respiratory infection, such as fever, cough, or any 

difficulty in breathing, tell your doctor. 
- if you notice unusual bleeding or bruising check with your doctor immediately. 
- if you develop symptoms of a severe allergic reaction (such as difficulty in breathing, wheezing, or hives) 

while on this medication seek medical help immediately. 
- if you are also being treated for HIV, please see Using other medicines. 
- if you have received an organ transplant, either kidney or liver, interferon treatment may increase the risk 

of rejection. Be sure to discuss this with your doctor. 
 
Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving Viraferon 
and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and 
membranes of the mouth during long-term treatment with the combination of Viraferon with ribavirin. You 
should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some 
patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly 
afterwards. 
 
During the one year of treatment, many children did not grow or gain weight as much as expected. However, 
during the 6 months after treatment, this trend was generally reversed, although a few children did not return 
to their previous rate of growth within the first year after completing treatment. 
 
Tell your doctor if you have ever had a heart attack or a heart problem; if you have a history of breathing 
irregularities or pneumonia, problems with blood clotting, liver condition, thyroid problems, diabetes, or high 
or low blood pressure. 
 
Tell your doctor if you have ever been treated for depression or any other psychiatric disorder; confusion; 
unconsciousness; thoughts of suicide or attempted suicide. 
 
Be sure to tell your doctor if you are taking the Chinese herbal medication Shosaikoto. 
 
Using other medicines 
Viraferon will add to the effects of substances that slow down your nervous system, possibly causing 
drowsiness. Therefore, check with your doctor or pharmacist about drinking alcoholic beverages, or taking 
sleeping pills, sedatives or strong pain medications.  
 
Tell your doctor if you are taking theophylline or aminophylline for asthma, and about all other medication 
you are taking, or have taken recently, even those not prescribed, as the dose of some medications may have 
to be adjusted while you are treated with Viraferon. 

 
Patients who also have HIV infection: Lactic acidosis and worsening liver function are side effects associated 
with Highly Active Anti-Retroviral Therapy (HAART), an HIV treatment. If you are receiving HAART, the 
addition of Viraferon and ribavirin may increase your risk of lactic acidosis and of liver failure. Your doctor 
will monitor you for signs and symptoms of these conditions (Please be sure to read the ribavirin Patient 
Leaflet also). Additionally, patients treated with Viraferon and ribavirin combination therapy and zidovudine 
could be at increased risk of developing anaemia (low number of red blood cells). 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. 
 
Using Viraferon with food and drink 
While being treated with Viraferon, your doctor may want you to drink extra fluids to help prevent low blood 
pressure. 
 



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Pregnancy and breast-feeding 
Ask your doctor or pharmacist for advice before taking any medicine. In studies in pregnant animals, 
interferons have sometimes caused miscarriage. The effect on human pregnancy is not known. 
If you are prescribed Viraferon in combination with ribavirin, ribavirin can be very damaging to an unborn 
baby, thus both female and male patients must take special precautions in their sexual activity if there is any 
chance for pregnancy to occur: 
- if you are a girl or a woman of childbearing age, you must have a negative pregnancy test before treatment, 
each month during treatment, and for the 4 months after treatment is stopped. You and your partner must 
each use an effective contraceptive during the time you are taking ribavirin and for 4 months after stopping 
treatment. This can be discussed with your doctor.  
- if you are a man who is taking ribavirin, do not have sex with a pregnant woman unless you use a condom. 
This will lessen the chance for ribavirin to be left in the woman’s body. If your female partner is not pregnant 
now but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 
7 months after treatment has stopped. This can be discussed with your doctor. If you are a male patient, you 
and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 
7 months after stopping treatment. This can be discussed with your doctor. 
 
It is not known whether this product is present in human milk. Therefore, do not breast-feed an infant if you 
are taking Viraferon. In combination therapy with ribavirin, take notice of the respective informing texts of 
ribavirin containing medicinal products. 
 
Driving and using machines 
Do not drive or use machinery if you become drowsy, tired, or confused from this medicine. 
 
 
3. HOW TO USE VIRAFERON 
 
Your doctor has prescribed Viraferon specifically for you and your current condition; do not share this medicine 
with anyone else. 
 
Your doctor has determined the exact dosage for administration of Viraferon according to your individual needs. 
The dosage will vary according to the disease being treated. 
 
If you are injecting Viraferon yourself, please be sure that the dose that has been prescribed for you is clearly 
provided with the package of medicine you receive. Dosages that are to be administered 3 times a week are best 
given every other day. 
 
The usual starting dose for each condition follows; however, individual doses may vary, and the doctor may 
change your dose based on your specific needs: 
 
Chronic hepatitis B: 5 to 10 million IU 3 times a week (every other day) injected subcutaneously (under the skin). 
 
Chronic hepatitis C: Adults - 3 million IU 3 times a week (every other day) injected subcutaneously (under the 
skin) in combination with ribavirin or alone. Children 3 years of age and older and adolescents - 
3 million IU/m2 3 times a week (every other day) injected subcutaneously (under the skin) in combination with 
ribavirin (Please also see ribavirin package leaflet).  
 
Your doctor may prescribe a different dose of Viraferon alone or in combination with other medicines (e.g. 
ribavirin). If you are prescribed Viraferon in combination with another medicine, please refer also to the Package 
Leaflet of the medicine to be used in combination. Your doctor will determine the exact dosage schedule and 
regimen according to your needs. If you have the impression that the effect of Viraferon is too strong or too 
weak, talk to your doctor or pharmacist. 
 
Subcutaneous use: 



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Viraferon is usually intended for subcutaneous use. This means that Viraferon is injected with a short needle into 
the fatty tissue just under the skin. If you are injecting this medicine yourself, you will be instructed how to 
prepare and give the injection. Detailed instructions for subcutaneous administration are provided with this leaflet 
(see HOW TO SELF INJECT VIRAFERON at the end of the leaflet). 
 
One dose of Viraferon is given on each scheduled day. Viraferon is given three times a week, every other day, for 
example on Monday, Wednesday, and Friday. Interferons may cause unusual tiredness; if you are injecting this 
medicine yourself, or giving it to a child, use it at bedtime. 
 
Use Viraferon exactly as prescribed by your doctor. Do not exceed the recommended dosage, and take Viraferon 
for as long as prescribed. 
 
If you use more Viraferon than you should 
Contact your doctor or healthcare professional as soon as possible. 
 
If you forget to take Viraferon 
If you are self-administering treatment, or if you are the caregiver of a child taking Viraferon in combination 
with ribavirin, inject the recommended dose as soon as you remember and continue treatment as usual Do not 
take a double dose to make up for a forgotten dose. If you are scheduled to inject this product every day, and 
you accidentally missed a full day’s dose, continue treatment at the usual dose the following day. Contact 
your doctor or pharmacist if needed. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Viraferon can cause side effects, although not everybody gets them. Although not all of 
these side effects may occur, they may need medical attention if they do. 
 
Some people get depressed when taking Viraferon alone or in combination treatment with ribavirin, and in some 
cases people had suicidal thoughts or aggressive behaviour (sometimes directed against others). Some patients have 
actually committed suicide. Be sure to seek emergency care if you notice that you are becoming depressed or have 
suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend 
to help you stay alert to signs of depression or changes in your behaviour. 
 
Paediatric Use: Children are particularly prone to develop depression when being treated with Viraferon and 
ribavirin. Immediately contact the doctor or seek emergency care if they display any unusual behavioural 
symptoms, feel depressed, or feel they want to harm themselves or others. 
 
If any of the following side effects happen, stop taking Viraferon and tell your doctor immediately or go to 
the casualty department at your nearest hospital: 
• swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in 

swallowing or breathing; hives; fainting. 
These are all very serious side effects. If you have them, you may have had a serious allergic reaction to 
Viraferon. You may need urgent medical attention or hospitalisation. These very serious side effects are very 
rare. 
 
Check with your doctor immediately if any of the following side effects occur: 
• chest pain or persistent and severe cough; irregular or rapid heartbeat; shortness of breath, confusion, 

difficulty remaining alert, numbness or tingling sensation or pain in hands or feet; seizure 
(convulsions); trouble sleeping, thinking or concentrating; altered mental state; suicidal thoughts, 
suicide attempt, changed behaviour or aggressive behaviour (sometimes directed against others), 
hallucinations; severe stomach pain; black or tar like stools; blood in stool or urine, severe 
nosebleed; waxy pallor, high sugar level in blood, fever or chills beginning after a few weeks of 



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treatment, lower back or side pain, difficult urination, problems with your eyes or your eyesight or 
hearing, loss of hearing, severe or painful reddening or sores on your skin or mucous membrane. 

These may signal serious side effects that may need urgent medical attention. Your doctor will test your 
blood to ensure that your white blood cell (cells that fight infection) and red blood cell (cells that carry iron 
and oxygen) counts, platelets (blood clotting cells) and other laboratory values are at acceptable levels. 
 
At the beginning of treatment with Viraferon, you may experience a flu-like reaction, with fever, fatigue, 
headache, muscle ache, joint pain and chills/rigors. Your doctor may recommend that you take paracetamol if 
you develop these symptoms. 
 
Other side effects that may occur include: 
 
Very commonly reported side effects (at least 1 in every 10 patients):  
pain, swelling and redness or skin damage at site of injection, hair loss, dizziness, changes in appetite, 
stomach or abdominal pains, diarrhoea, nausea (feeling sick), viral infection, depression, emotional lability, 
insomnia, anxiety, sore throat and painful swallowing, fatigue, chills/rigors, fever, flu-like reaction, feeling 
of general discomfort, headaches, weight loss, vomiting, irritability, weakness, mood swings, coughing 
(sometimes severe), shortness of breath, itching, dry skin, rash, sudden and severe muscle pain, joint pain, 
musculoskeletal pain, changes in laboratory blood values including decreased white blood cell count. Some 
children have had a decrease in their rate of growth (height and weight). 
 
Commonly reported side effects (at least 1 in every 100 patients, but less than 1 in every 10 patients): 
thirst, dehydration, high blood pressure, migraines, swollen glands, flushing, menstrual problems, 
decreased sexual drive, vaginal problem, breast pain, pain in testicle, problems with thyroid gland, red 
gums, dry mouth, red or sore mouth or tongue, tooth ache or tooth disorder, herpes simplex (fever blisters), 
taste change, upset stomach, dyspepsia (heartburn), constipation, enlargement of liver (liver problems, 
sometimes severe), loose stools, bedwetting in children, inflammation of the sinuses, bronchitis, eye pain, 
problem with your tear ducts, conjunctivitis (“pink eye”), agitation, sleepiness, sleepwalking, problem with 
behaviour, nervousness, stuffy or runny nose, sneezing, rapid breathing, pale or reddened skin, bruising, 
fingers and toes very sensitive to cold, problem with skin or nails, psoriasis (new or worsened), increased 
sweating, increased need to pass urine, fine shaking movements, decreased sensitivity to touch, arthritis.  
 
Rarely reported side effects (at least 1 in every 10,000 patients, but less than 1 in every 1,000 patients): 
pneumonia 
 
Very rarely reported side effects (less than 1 in every 10,000 patients): 
low blood pressure, puffy face, diabetes, leg cramps, back pain, kidney problems, nerve damage, bleeding 
gums, aplastic anaemia. Pure red cell aplasia, a condition where the body stopped or reduced the production 
of red blood cells, has been reported. This causes severe anaemia, symptoms of which would include unusual 
tiredness and a lack of energy. 
 
Very rarely sarcoidosis, (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin 
lesions and swollen glands) has been reported. Loss of consciousness has occurred very rarely, mostly in 
elderly patients treated at high doses. Cases of stroke (cerebrovascular events) have been reported. Check 
with your doctor immediately if you have any of these symptoms.  
Periodontal (affecting gums) and dental disorders, altered mental status, loss of consciousness, acute 
hypersensitivity reactions including urticaria (hives), angioedema (swelling of the hands, feet, ankles, face, 
lips, mouth, or throat which may cause difficulty in swallowing or breathing), bronchoconstriction and 
anaphylaxis (a severe, whole-body allergic reaction) have been reported, but their frequency is unknown.  
 
Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin 
and the membranes of the ears, brain and spinal cord) has been reported with Viraferon use. 
 
Other side effects not listed above may also occur in some patients. If any of the side effects gets serious, or if you 
notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. 



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5. HOW TO STORE VIRAFERON 
 
Keep out of the reach and sight of children. 
 
Store in a refrigerator (2°C - 8°C).  
Do not freeze.  
For short term travelling, the solution can be kept out of the refrigerator at or below 25°C for a period up to 
seven days before use. Viraferon can be put back in the refrigerator at any time during this seven-day period. 
If the product is not used during the seven-day period, it should be discarded. 
 
Do not use Viraferon after the expiry date which is stated on the package. 
 
Do not use Viraferon if you notice changes in the appearance of Viraferon 
 
Any unused product must be discarded after withdrawal of the dose. 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose 
of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What Viraferon contains 
 
- The active substance is recombinant interferon alfa-2b, 10 million IU in a single dose vial 
- The other ingredients are disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, 

edetate disodium, sodium chloride, m-cresol, polysorbate 80 and water for injections. 
 
What Viraferon looks like and contents of the pack 
 
Viraferon is presented as a solution for injection 
- The clear and colourless solution is contained in a glass with 1 injection syringe, 1 injection needle and 

1 cleansing swab. Pack of 1, 6 or 12. Vial alone is also available. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: Manufacturer: 
SP Europe SP Labo N.V. 
73, rue de Stalle Industriepark 30 
B-1180 Bruxelles B-2220 Heist-op-den-Berg 
Belgium Belgium 
 
For any information about this medicinal product, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Rue de Stalle/Stallestraat 73 
B-1180 Bruxelles/Brussel/Brüssel 
Tél/Tel: + 32-(0)2 370 92 11 
 

Luxembourg/Luxemburg 
Rue de Stalle 73 
B-1180 Bruxelles/Brüssel 
Belgique/Belgien 
Tél/Tel: + 32-(0)2 370 92 11 
 

България 
ул. "Проф. Милко Бичев" № 7, ет.3 
BG-София 1504  
Тел.: +359 2 944 1073 

Magyarország 
Alkotás u. 53. 
H-1123 Budapest 
Tel.: + 36 1 457-8500 



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Česká republika 
Na Příkopě 25 
CZ-110 00 Praha 1 
Tel: + 420 221771250 
 

Malta 
168 Christopher Street 
MT-VLT02 Valletta 
Tel: + 356-21 23 21 75 
 

Danmark 
Lautrupbjerg 2 
DK-2750 Ballerup 
Tlf: + 45-44 39 50 00 
 

Nederland 
Maarssenbroeksedijk 4 
NL-3542 DN Utrecht 
Tel: + 31-(0)800 778 78 78 

Deutschland 
Thomas-Dehler-Straße 27 
D-81737 München  
Tel: + 49-(0)89 627 31-0 
 

Norge 
Pb. 398 
N-1326 Lysaker 
Tlf: + 47 67 16 64 50 
 

Eesti 
Järvevana tee 9 
EE-11314 Tallinn 
Tel: + 372 654 96 86 
 

Österreich 
Badener Strasse 23 
A-2514 Traiskirchen 
Tel: + 43-(0)2252 502-0 
 

Ελλάδα 
Αγίου Δημητρίου 63 
GR-174 55 Άλιμος  
Tηλ: + 30-210 98 97 300 
 

Polska 
Al. Jerozolimskie 195a 
PL-02-222 Warszawa 
Tel.: + 48-(0)22 478 41 50 
 

España 
Km. 36, Ctra. Nacional I 
E-28750 San Agustín de Guadalix – Madrid 
Tel: + 34-91 848 85 00 
 

Portugal 
Rua Agualva dos Açores 16 
P-2735-557 Agualva-Cacém 
Tel: + 351-21 433 93 00 
 

France 
92 rue Baudin  
F-92300 Levallois-Perret 
Tél: + 33-(0)1 41 06 35 00 
 

România 
Şos. Bucureşti-Ploieşti, nr. 17-21,  
Băneasa Center, et. 8, sector 1 
RO-013682 Bucureşti 
Tel. + 40 21 233 35 30 



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Ireland 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW 
Tel: + 44-(0)1 707 363 636 
 

Slovenija 
Dunajska 22 
SI-1000 Ljubljana 
Tel. + 386 01 3001070 
 

Ísland 
Hörgatún 2 
IS-210 Garðabær 
Sími: + 354 535 70 00 
 

Slovenská republika 
Strakova 5 
SK-811 01 Bratislava 
Tel: + 421 (2) 5920 2712 
 

Italia 
Via fratelli Cervi snc, 
Centro Direzionale Milano Due 
Palazzo Borromini 
I-20090 Segrate (Milano) 
Tel: + 39-02 21018.1 
 

Suomi/Finland 
PL 3/PB 3 
FIN-02201 Espoo/Esbo 
Puh/Tel: + 358-(0)20-7570 300 
 

Κύπρος 
Οδός Αγίου Νικολάου, 8 
CY-1055 Λευκωσία 
Τηλ: + 357-22 757188 
 

Sverige 
Box 6185 
S-102 33 Stockholm 
Tel: + 46-(0)8 522 21 500 
 

Latvija 
Bauskas 58a -401 
Rīga, LV-1004  
Tel: + 371-7 21 38 25 
 

United Kingdom 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW - UK 
Tel: + 44-(0)1 707 363 636 
 

Lietuva 
Kęstučio g. 65/40 
LT-08124 Vilnius 
Tel. + 370 52 101868 

 

 
 
This leaflet was last approved on 
 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: 
http://www.emea.europa.eu/ 
 



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HOW TO SELF INJECT VIRAFERON 
 
The following instructions explain how to inject Viraferon yourself. Please read the instructions carefully and 
follow them step by step. Your doctor or his/her assistant will instruct you how to self-inject Viraferon. Do 
not attempt to inject yourself unless you are sure you understand the procedure and requirement of self-
injection. 
 
Preparation 
Collect necessary items before you begin: 
- a vial of Viraferon solution for injection; 
- a 2 ml syringe; 
- a needle for the subcutaneous injection (for example 0.4 × 13 mm [27 gauge 0.5 inch]); 
- a cleansing swab. 
Wash your hands carefully. 
 
Measuring the dose of Viraferon 
Remove the cap from the vial. If this is a multidose vial, you will only have to remove the cap when 
preparing the first dose. Clean the rubber stopper on the top of the vial containing the Viraferon solution with 
a cleansing swab. 
Remove the syringe from the wrapping. Do not touch the tip of the syringe. Take the needle and place it 
firmly onto the tip of the syringe. 
Remove the needle guard without touching the needle, and fill the syringe with air by pulling the plunger to 
the level that represents your dose as prescribed by your doctor. 
Hold the Viraferon vial upright without touching the cleaned top of the vial with your hands. 
Insert the needle into the vial containing the Viraferon solution and inject air into the vial. 
Turn the vial and the syringe upside down in one hand. Be sure the tip of needle is in the Viraferon solution. 
Your other hand will be free to move the plunger. Pull back on the plunger slowly to draw the correct dose as 
prescribed by your doctor into the syringe. 
Remove the needle from the vial and check for air bubbles in the syringe. If you see any bubbles, pull the 
plunger slightly back; tap the syringe gently, with the needle pointing up, until the bubbles disappear. Push 
up the plunger slowly back to the correct dose. Replace the needle guard and place the syringe with the 
needle on a flat surface. 
 
Be sure the solution is at room temperature up to 25°C. If the solution is cold, warm the syringe between your 
palms. Examine the solution prior to administration: it should be clear and colourless. Do not use if 
discolouration or particulate matter is present. You are now ready to inject the dose. 
 
Injecting the solution 
Select the injection site. The best sites for injection are tissues with a layer of fat between skin and muscle: 
thigh, outer surface of the upper arm (you may need the assistance of another person to use this site), 
abdomen (except the navel or waistline). If you are exceptionally thin, use only the thigh or outer surface of 
the arm for injection. 
Change your injection site each time. 
 
Cleanse and disinfect the skin where the injection is to be made. Wait for the area to dry. Remove the needle 
guard. With one hand, pinch a fold of loose skin. With your other hand hold the syringe as you would a 
pencil. Insert the needle into the pinched skin at an angle of 45° to 90°. Inject the solution by pushing the 
plunger all the way down gently. Pull the needle straight out of the skin. Press the injection site with a small 
bandage or sterile gauze if necessary for several seconds. Do not massage the injection site. If there is 
bleeding, cover with an adhesive bandage. 
The vial and injection materials intended for single use must be discarded. Dispose of the syringe and needle 
safely in a closed container. For multidose vials, be sure to return the vial to the refrigerator. 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Viraferon, 18 million IU/3 ml solution for injection 
Interferon alfa-2b 

 
Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Viraferon is and what it is used for 
2. Before you use Viraferon 
3. How to use Viraferon 
4. Possible side effects 
5. How to store Viraferon 
6. Further information 
 
 
1. WHAT VIRAFERON IS AND WHAT IT IS USED FOR 
 
Viraferon (interferon alfa-2b) modifies the response of the body's immune system to help fight infections and 
severe diseases. Viraferon is used in adult patients for the treatment of chronic hepatitis B or C, which are viral 
infections of the liver. 
 
Viraferon is used in combination with ribavirin in children and adolescents 3 years of age and older who have 
previously untreated chronic hepatitis C. 
 
 
2. BEFORE YOU USE VIRAFERON 
 
Do not use Viraferon 
- if you are allergic (hypersensitive) to interferon or any of the other ingredients of Viraferon. 
- if you have severe heart disease. 
- if you have poor kidney or liver function. 
- if you have advanced decompensated (uncontrolled) liver disease. 
- if you have hepatitis and have been treated recently with medications that suppress the immune system 

(other than short-term treatment with cortisone-type medicine). 
- if you have a history of seizures (convulsions). 
- if you have a history of autoimmune disease, or have had an organ transplant and are taking medicine that 

suppresses your immune system (your immune system helps protect you from infection). 
- if you have thyroid disease that is not well controlled. 
Children and adolescents: 
- if you have had serious nervous or mental problems, such as severe depression or thoughts of suicide. 
 
Take special care with Viraferon 
- if you are pregnant or planning to become pregnant (see Pregnancy). 
- if you have had a severe nervous or mental disorder. The use of interferon alfa-2b in children and 

adolescents with existence of or history of severe psychiatric conditions is contraindicated (see “Do not use 
Viraferon”) 

- if you have ever had depression or develop symptoms associated with depression (e.g. feelings of sadness, 
dejection, etc.) while on treatment with Viraferon (see section 4). 



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- if you have psoriasis, it may get worse during treatment with Viraferon. 
- when receiving Viraferon, you may temporarily have a greater risk of getting an infection. Check with 

your doctor if you think you are getting an infection. 
- if you develop symptoms associated with a cold or other respiratory infection, such as fever, cough, or any 

difficulty in breathing, tell your doctor. 
- if you notice unusual bleeding or bruising check with your doctor immediately. 
- if you develop symptoms of a severe allergic reaction (such as difficulty in breathing, wheezing, or hives) 

while on this medication seek medical help immediately. 
- if you are also being treated for HIV, please see Using other medicines. 
- if you have received an organ transplant, either kidney or liver, interferon treatment may increase the risk 

of rejection. Be sure to discuss this with your doctor. 
 
Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving Viraferon 
and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and 
membranes of the mouth during long-term treatment with the combination of Viraferon with ribavirin. You 
should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some 
patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly 
afterwards. 
 
During the one year of treatment, many children did not grow or gain weight as much as expected. However, 
during the 6 months after treatment, this trend was generally reversed, although a few children did not return 
to their previous rate of growth within the first year after completing treatment. 
 
Tell your doctor if you have ever had a heart attack or a heart problem; if you have a history of breathing 
irregularities or pneumonia, problems with blood clotting, liver condition, thyroid problems, diabetes, or high 
or low blood pressure. 
 
Tell your doctor if you have ever been treated for depression or any other psychiatric disorder; confusion; 
unconsciousness; thoughts of suicide or attempted suicide. 
 
Be sure to tell your doctor if you are taking the Chinese herbal medication Shosaikoto. 
 
Using other medicines 
Viraferon will add to the effects of substances that slow down your nervous system, possibly causing 
drowsiness. Therefore, check with your doctor or pharmacist about drinking alcoholic beverages, or taking 
sleeping pills, sedatives or strong pain medications.  
 
Tell your doctor if you are taking theophylline or aminophylline for asthma, and about all other medication 
you are taking, or have taken recently, even those not prescribed, as the dose of some medications may have 
to be adjusted while you are treated with Viraferon. 

 
Patients who also have HIV infection: Lactic acidosis and worsening liver function are side effects associated 
with Highly Active Anti-Retroviral Therapy (HAART), an HIV treatment. If you are receiving HAART, the 
addition of Viraferon and ribavirin may increase your risk of lactic acidosis and of liver failure. Your doctor 
will monitor you for signs and symptoms of these conditions (Please be sure to read the ribavirin Patient 
Leaflet also). Additionally, patients treated with Viraferon and ribavirin combination therapy and zidovudine 
could be at increased risk of developing anaemia (low number of red blood cells). 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. 
 
Using Viraferon with food and drink 
While being treated with Viraferon, your doctor may want you to drink extra fluids to help prevent low blood 
pressure. 
 



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Pregnancy and breast-feeding 
Ask your doctor or pharmacist for advice before taking any medicine. In studies in pregnant animals, 
interferons have sometimes caused miscarriage. The effect on human pregnancy is not known. 
If you are prescribed Viraferon in combination with ribavirin, ribavirin can be very damaging to an unborn 
baby, thus both female and male patients must take special precautions in their sexual activity if there is any 
chance for pregnancy to occur: 
- if you are a girl or a woman of childbearing age, you must have a negative pregnancy test before treatment, 
each month during treatment, and for the 4 months after treatment is stopped. You and your partner must 
each use an effective contraceptive during the time you are taking ribavirin and for 4 months after stopping 
treatment. This can be discussed with your doctor.  
- if you are a man who is taking ribavirin, do not have sex with a pregnant woman unless you use a condom. 
This will lessen the chance for ribavirin to be left in the woman’s body. If your female partner is not pregnant 
now but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 
7 months after treatment has stopped. This can be discussed with your doctor. If you are a male patient, you 
and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 
7 months after stopping treatment. This can be discussed with your doctor. 
 
It is not known whether this product is present in human milk. Therefore, do not breast-feed an infant if you 
are taking Viraferon. In combination therapy with ribavirin, take notice of the respective informing texts of 
ribavirin containing medicinal products. 
 
Driving and using machines 
Do not drive or use machinery if you become drowsy, tired, or confused from this medicine. 
 
 
3. HOW TO USE VIRAFERON 
 
Your doctor has prescribed Viraferon specifically for you and your current condition; do not share this medicine 
with anyone else. 
 
Your doctor has determined the exact dosage for administration of Viraferon according to your individual needs. 
The dosage will vary according to the disease being treated. 
 
If you are injecting Viraferon yourself, please be sure that the dose that has been prescribed for you is clearly 
provided with the package of medicine you receive. Dosages that are to be administered 3 times a week are best 
given every other day. 
 
The usual starting dose for each condition follows; however, individual doses may vary, and the doctor may 
change your dose based on your specific needs: 
 
Chronic hepatitis B: 5 to 10 million IU 3 times a week (every other day) injected subcutaneously (under the skin). 
 
Chronic hepatitis C: Adults - 3 million IU 3 times a week (every other day) injected subcutaneously (under the 
skin) in combination with ribavirin or alone. Children 3 years of age and older and adolescents - 
3 million IU/m2 3 times a week (every other day) injected subcutaneously (under the skin) in combination with 
ribavirin (Please also see ribavirin package leaflet).  
 
Your doctor may prescribe a different dose of Viraferon alone or in combination with other medicines (e.g. 
ribavirin). If you are prescribed Viraferon in combination with another medicine, please refer also to the Package 
Leaflet of the medicine to be used in combination. Your doctor will determine the exact dosage schedule and 
regimen according to your needs. If you have the impression that the effect of Viraferon is too strong or too 
weak, talk to your doctor or pharmacist. 
 
Subcutaneous use: 



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Viraferon is usually intended for subcutaneous use. This means that Viraferon is injected with a short needle into 
the fatty tissue just under the skin. If you are injecting this medicine yourself, you will be instructed how to 
prepare and give the injection. Detailed instructions for subcutaneous administration are provided with this leaflet 
(see HOW TO SELF INJECT VIRAFERON at the end of the leaflet). 
 
One dose of Viraferon is given on each scheduled day. Viraferon is given three times a week, every other day, for 
example on Monday, Wednesday, and Friday. Interferons may cause unusual tiredness; if you are injecting this 
medicine yourself, or giving it to a child, use it at bedtime. 
 
Use Viraferon exactly as prescribed by your doctor. Do not exceed the recommended dosage, and take Viraferon 
for as long as prescribed. 
 
If you use more Viraferon than you should 
Contact your doctor or healthcare professional as soon as possible. 
 
If you forget to take Viraferon 
If you are self-administering treatment, or if you are the caregiver of a child taking Viraferon in combination 
with ribavirin, inject the recommended dose as soon as you remember and continue treatment as usual. Do 
not take a double dose to make up for a forgotten dose. If you are scheduled to inject this product every day, 
and you accidentally missed a full day’s dose, continue treatment at the usual dose the following day. Contact 
your doctor or pharmacist if needed. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Viraferon can cause side effects, although not everybody gets them. Although not all of 
these side effects may occur, they may need medical attention if they do. 
 
Some people get depressed when taking Viraferon alone or in combination treatment with ribavirin, and in some 
cases people had suicidal thoughts or aggressive behaviour (sometimes directed against others). Some patients have 
actually committed suicide. Be sure to seek emergency care if you notice that you are becoming depressed or have 
suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend 
to help you stay alert to signs of depression or changes in your behaviour. 
 
Paediatric Use: Children are particularly prone to develop depression when being treated with Viraferon and 
ribavirin. Immediately contact the doctor or seek emergency care if they display any unusual behavioural 
symptoms, feel depressed, or feel they want to harm themselves or others. 
 
If any of the following side effects happen, stop taking Viraferon and tell your doctor immediately or go to 
the casualty department at your nearest hospital: 
• swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in 

swallowing or breathing; hives; fainting. 
These are all very serious side effects. If you have them, you may have had a serious allergic reaction to 
Viraferon. You may need urgent medical attention or hospitalisation. These very serious side effects are very 
rare. 
 
Check with your doctor immediately if any of the following side effects occur: 
• chest pain or persistent and severe cough; irregular or rapid heartbeat; shortness of breath, confusion, 

difficulty remaining alert, numbness or tingling sensation or pain in hands or feet; seizure 
(convulsions); trouble sleeping, thinking or concentrating; altered mental state; suicidal thoughts, 
suicide attempt, changed behaviour or aggressive behaviour (sometimes directed against others), 
hallucinations; severe stomach pain; black or tar like stools; blood in stool or urine, severe 
nosebleed; waxy pallor, high sugar level in blood, fever or chills beginning after a few weeks of 



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treatment, lower back or side pain, difficult urination, problems with your eyes or your eyesight or 
hearing, loss of hearing, severe or painful reddening or sores on your skin or mucous membrane. 

These may signal serious side effects that may need urgent medical attention. Your doctor will test your 
blood to ensure that your white blood cell (cells that fight infection) and red blood cell (cells that carry iron 
and oxygen) counts, platelets (blood clotting cells) and other laboratory values are at acceptable levels. 
 
At the beginning of treatment with Viraferon, you may experience a flu-like reaction, with fever, fatigue, 
headache, muscle ache, joint pain and chills/rigors. Your doctor may recommend that you take paracetamol if 
you develop these symptoms. 
 
Other side effects that may occur include: 
 
Very commonly reported side effects (at least 1 in every 10 patients):  
pain, swelling and redness or skin damage at site of injection, hair loss, dizziness, changes in appetite, 
stomach or abdominal pains, diarrhoea, nausea (feeling sick), viral infection, depression, emotional lability, 
insomnia, anxiety, sore throat and painful swallowing, fatigue, chills/rigors, fever, flu-like reaction, feeling 
of general discomfort, headaches, weight loss, vomiting, irritability, weakness, mood swings, coughing 
(sometimes severe), shortness of breath, itching, dry skin, rash, sudden and severe muscle pain, joint pain, 
musculoskeletal pain, changes in laboratory blood values including decreased white blood cell count. Some 
children have had a decrease in their rate of growth (height and weight). 
 
Commonly reported side effects (at least 1 in every 100 patients, but less than 1 in every 10 patients): 
thirst, dehydration, high blood pressure, migraines, swollen glands, flushing, menstrual problems, 
decreased sexual drive, vaginal problem, breast pain, pain in testicle, problems with thyroid gland, red 
gums, dry mouth, red or sore mouth or tongue, tooth ache or tooth disorder, herpes simplex (fever blisters), 
taste change, upset stomach, dyspepsia (heartburn), constipation, enlargement of liver (liver problems, 
sometimes severe), loose stools, bedwetting in children, inflammation of the sinuses, bronchitis, eye pain, 
problem with your tear ducts, conjunctivitis (“pink eye”), agitation, sleepiness, sleepwalking, problem with 
behaviour, nervousness, stuffy or runny nose, sneezing, rapid breathing, pale or reddened skin, bruising, 
fingers and toes very sensitive to cold, problem with skin or nails, psoriasis (new or worsened), increased 
sweating, increased need to pass urine, fine shaking movements, decreased sensitivity to touch, arthritis.  
 
Rarely reported side effects (at least 1 in every 10,000 patients, but less than 1 in every 1,000 patients): 
pneumonia 
 
Very rarely reported side effects (less than 1 in every 10,000 patients): 
low blood pressure, puffy face, diabetes, leg cramps, back pain, kidney problems, nerve damage, bleeding 
gums, aplastic anaemia. Pure red cell aplasia, a condition where the body stopped or reduced the production 
of red blood cells, has been reported. This causes severe anaemia, symptoms of which would include unusual 
tiredness and a lack of energy. 
 
Very rarely sarcoidosis, (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin 
lesions and swollen glands) has been reported. Loss of consciousness has occurred very rarely, mostly in 
elderly patients treated at high doses. Cases of stroke (cerebrovascular events) have been reported. Check 
with your doctor immediately if you have any of these symptoms.  
Periodontal (affecting gums) and dental disorders, altered mental status, loss of consciousness, acute 
hypersensitivity reactions including urticaria (hives), angioedema (swelling of the hands, feet, ankles, face, 
lips, mouth, or throat which may cause difficulty in swallowing or breathing), bronchoconstriction and 
anaphylaxis (a severe, whole-body allergic reaction) have been reported, but their frequency is unknown.  
 
Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin 
and the membranes of the ears, brain and spinal cord) has been reported with Viraferon use. 
 
Other side effects not listed above may also occur in some patients. If any of the side effects gets serious, or if you 
notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. 



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5. HOW TO STORE VIRAFERON 
 
Keep out of the reach and sight of children. 
 
Store in a refrigerator (2°C - 8°C).  
Do not freeze.  
For short term travelling, the solution can be kept out of the refrigerator at or below 25°C for a period up to 
seven days before use. Viraferon can be put back in the refrigerator at any time during this seven-day period. 
If the product is not used during the seven-day period, it should be discarded. 
 
Once opened, the product may be stored for a maximum of 28 days at 2ºC – 8ºC. 
 
Do not use Viraferon after the expiry date which is stated on the package. 
 
Do not use Viraferon if you notice changes in the appearance of Viraferon. 
 
 
6. FURTHER INFORMATION 
 
What Viraferon contains 
 
- The active substance is recombinant interferon alfa-2b, 18 million IU in a multiple dose vial 
- The other ingredients are disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, 

edetate disodium, sodium chloride, m-cresol, polysorbate 80 and water for injections. 
- One ml of solution contains 6 million IU of interferon alfa-2b 
 
What Viraferon looks like and contents of the pack 
 
Viraferon is presented as a solution for injection 
The clear and colourless solution is contained in a glass vial. 
 
Viraferon is available in four different pack sizes: 
- Pack of 1 vial 
- Pack of 1 vial, 6 injection syringes, 6 injection needles and 12 cleansing swabs 
- Pack of 2 vials 
- Pack of 12 vials 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: Manufacturer: 
SP Europe SP Labo N.V. 
73, rue de Stalle Industriepark 30 
B-1180 Bruxelles B-2220 Heist-op-den-Berg 
Belgium Belgium 
 
For any information about this medicinal product, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Rue de Stalle/Stallestraat 73 
B-1180 Bruxelles/Brussel/Brüssel 
Tél/Tel: + 32-(0)2 370 92 11 
 

Luxembourg/Luxemburg 
Rue de Stalle 73 
B-1180 Bruxelles/Brüssel 
Belgique/Belgien 
Tél/Tel: + 32-(0)2 370 92 11 
 



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България 
ул. "Проф. Милко Бичев" № 7, ет.3 
BG-София 1504  
Тел.: +359 2 944 1073 

Magyarország 
Alkotás u. 53. 
H-1123 Budapest 
Tel.: + 36 1 457-8500 
 

Česká republika 
Na Příkopě 25 
CZ-110 00 Praha 1 
Tel: + 420 221771250 
 

Malta 
168 Christopher Street 
MT-VLT02 Valletta 
Tel: + 356-21 23 21 75 
 

Danmark 
Lautrupbjerg 2 
DK-2750 Ballerup 
Tlf: + 45-44 39 50 00 

Nederland 
Maarssenbroeksedijk 4 
NL-3542 DN Utrecht 
Tel: + 31-(0)800 778 78 78 

Deutschland 
Thomas-Dehler-Straße 27 
D-81737 München  
Tel: + 49-(0)89 627 31-0 
 

Norge 
Pb. 398 
N-1326 Lysaker 
Tlf: + 47 67 16 64 50 
 

Eesti 
Järvevana tee 9 
EE-11314 Tallinn 
Tel: + 372 654 96 86 
 

Österreich 
Badener Strasse 23 
A-2514 Traiskirchen 
Tel: + 43-(0)2252 502-0 
 

Ελλάδα 
Αγίου Δημητρίου 63 
GR-174 55 Άλιμος  
Tηλ: + 30-210 98 97 300 
 

Polska 
Al. Jerozolimskie 195a 
PL-02-222 Warszawa 
Tel.: + 48-(0)22 478 41 50 
 

España 
Km. 36, Ctra. Nacional I 
E-28750 San Agustín de Guadalix – Madrid 
Tel: + 34-91 848 85 00 
 

Portugal 
Rua Agualva dos Açores 16 
P-2735-557 Agualva-Cacém 
Tel: + 351-21 433 93 00 
 

France 
92 rue Baudin  
F-92300 Levallois-Perret 
Tél: + 33-(0)1 41 06 35 00 
 

România 
Şos. Bucureşti-Ploieşti, nr. 17-21,  
Băneasa Center, et.8, sector 1 
RO-013682 Bucureşti 
Tel. + 40 21 233 35 30 
 

Ireland 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW 
Tel: + 44-(0)1 707 363 636 

Slovenija 
Dunajska 22 
SI-1000 Ljubljana 
Tel. + 386 01 3001070 
 

Ísland 
Hörgatún 2 
IS-210 Garðabær 
Sími: + 354 535 70 00 
 

Slovenská republika 
Strakova 5 
SK-811 01 Bratislava 
Tel: + 421 (2) 5920 2712 
 

Italia 
Via fratelli Cervi snc, 
Centro Direzionale Milano Due 
Palazzo Borromini 
I-20090 Segrate (Milano) 

Suomi/Finland 
PL 3/PB 3 
FIN-02201 Espoo/Esbo 
Puh/Tel: + 358-(0)20-7570 300 
 



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Tel: + 39-02 21018.1 
 
Κύπρος 
Οδός Αγίου Νικολάου, 8 
CY-1055 Λευκωσία 
Τηλ: + 357-22 757188 
 

Sverige 
Box 6185 
S-102 33 Stockholm 
Tel: + 46-(0)8 522 21 500 
 

Latvija 
Bauskas 58a -401 
Rīga, LV-1004  
Tel: + 371-7 21 38 25 
 

United Kingdom 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW - UK 
Tel: + 44-(0)1 707 363 636 
 

Lietuva 
Kęstučio g. 65/40 
LT-08124 Vilnius 
Tel. + 370 52 101868 

 

 
 
This leaflet was last approved on 
 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: 
http://www.emea.europa.eu/ 
 



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HOW TO SELF INJECT VIRAFERON 
 
The following instructions explain how to inject Viraferon yourself. Please read the instructions carefully and 
follow them step by step. Your doctor or his/her assistant will instruct you how to self-inject Viraferon. Do 
not attempt to inject yourself unless you are sure you understand the procedure and requirement of self-
injection. 
 
Preparation 
Collect necessary items before you begin: 
- a vial of Viraferon solution for injection; 
- a 1 ml syringe; 
- a needle for the subcutaneous injection (for example 0.4 × 13 mm [27 gauge 0.5 inch]); 
- a cleansing swab. 
Wash your hands carefully. 
 
Measuring the dose of Viraferon 
Remove the cap from the vial. If this is a multidose vial, you will only have to remove the cap when 
preparing the first dose. Clean the rubber stopper on the top of the vial containing the Viraferon solution with 
a cleansing swab. 
Remove the syringe from the wrapping. Do not touch the tip of the syringe. Take the needle and place it 
firmly onto the tip of the syringe. 
Remove the needle guard without touching the needle, and fill the syringe with air by pulling the plunger to 
the level that represents your dose as prescribed by your doctor. 
Hold the Viraferon vial upright without touching the cleaned top of the vial with your hands. 
Insert the needle into the vial containing the Viraferon solution and inject air into the vial. 
Turn the vial and the syringe upside down in one hand. Be sure the tip of needle is in the Viraferon solution. 
Your other hand will be free to move the plunger. Pull back on the plunger slowly to draw the correct dose as 
prescribed by your doctor into the syringe. 
Remove the needle from the vial and check for air bubbles in the syringe. If you see any bubbles, pull the 
plunger slightly back; tap the syringe gently, with the needle pointing up, until the bubbles disappear. Push 
up the plunger slowly back to the correct dose.  
 
Volume to be withdrawn according to the dose: 
 

Volume (ml) Corresponding dose (million IU) using 
Viraferon 18 million IU/3 ml solution for 

injection 

0.25 

0.1 

0.5 

1 

1.5 

2 

2.5 

3 

1.5 

0.6 

3 

6 

9 

12 

15 

18 

 



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Replace the needle guard and place the syringe with the needle on a flat surface. 
 
Be sure the solution is at room temperature up to 25°C. If the solution is cold, warm the syringe between your 
palms. Examine the solution prior to administration: it should be clear and colourless. Do not use if 
discolouration or particulate matter is present. You are now ready to inject the dose. 
 
Injecting the solution 
Select the injection site. The best sites for injection are tissues with a layer of fat between skin and muscle: 
thigh, outer surface of the upper arm (you may need the assistance of another person to use this site), 
abdomen (except the navel or waistline). If you are exceptionally thin, use only the thigh or outer surface of 
the arm for injection. 
Change your injection site each time. 
 
Cleanse and disinfect the skin where the injection is to be made. Wait for the area to dry. Remove the needle 
guard. With one hand, pinch a fold of loose skin. With your other hand hold the syringe as you would a 
pencil. Insert the needle into the pinched skin at an angle of 45° to 90°. Inject the solution by pushing the 
plunger all the way down gently. Pull the needle straight out of the skin. Press the injection site with a small 
bandage or sterile gauze if necessary for several seconds. Do not massage the injection site. If there is 
bleeding, cover with an adhesive bandage. 
The vial and injection materials intended for single use must be discarded. Dispose of the syringe and needle 
safely in a closed container. For multidose vials, be sure to return the vial to the refrigerator. 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Viraferon, 25 million IU/2.5 ml solution for injection 
Interferon alfa-2b 

 
Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Viraferon is and what it is used for 
2. Before you use Viraferon 
3. How to use Viraferon 
4. Possible side effects 
5. How to store Viraferon 
6. Further information 
 
 
1. WHAT VIRAFERON IS AND WHAT IT IS USED FOR 
 
Viraferon (interferon alfa-2b) modifies the response of the body's immune system to help fight infections and 
severe diseases. Viraferon is used in adult patients for the treatment of chronic hepatitis B or C, which are viral 
infections of the liver. 
 
Viraferon is used in combination with ribavirin in children and adolescents 3 years of age and older who have 
previously untreated chronic hepatitis C. 
 
 
2. BEFORE YOU USE VIRAFERON 
 
Do not use Viraferon 
- if you are allergic (hypersensitive) to interferon or any of the other ingredients of Viraferon. 
- if you have severe heart disease. 
- if you have poor kidney or liver function. 
- if you have advanced decompensated (uncontrolled) liver disease. 
- if you have hepatitis and have been treated recently with medications that suppress the immune system 

(other than short-term treatment with cortisone-type medicine). 
- if you have a history of seizures (convulsions). 
- if you have a history of autoimmune disease, or have had an organ transplant and are taking medicine that 

suppresses your immune system (your immune system helps protect you from infection). 
- if you have thyroid disease that is not well controlled. 
Children and adolescents: 
- if you have had serious nervous or mental problems, such as severe depression or thoughts of suicide. 
 
Take special care with Viraferon 
- if you are pregnant or planning to become pregnant (see Pregnancy). 
- if you have had a severe nervous or mental disorder. The use of interferon alfa-2b in children and 

adolescents with existence of or history of severe psychiatric conditions is contraindicated (see “Do not use 
Viraferon”) 

- if you have ever had depression or develop symptoms associated with depression (e.g. feelings of sadness, 
dejection, etc.) while on treatment with Viraferon (see section 4). 



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- if you have psoriasis, it may get worse during treatment with Viraferon. 
- when receiving Viraferon, you may temporarily have a greater risk of getting an infection. Check with 

your doctor if you think you are getting an infection. 
- if you develop symptoms associated with a cold or other respiratory infection, such as fever, cough, or any 

difficulty in breathing, tell your doctor. 
- if you notice unusual bleeding or bruising check with your doctor immediately. 
- if you develop symptoms of a severe allergic reaction (such as difficulty in breathing, wheezing, or hives) 

while on this medication seek medical help immediately. 
- if you are also being treated for HIV, please see Using other medicines. 
- if you have received an organ transplant, either kidney or liver, interferon treatment may increase the risk 

of rejection. Be sure to discuss this with your doctor. 
 
Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving Viraferon 
and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and 
membranes of the mouth during long-term treatment with the combination of Viraferon with ribavirin. You 
should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some 
patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly 
afterwards. 
 
During the one year of treatment, many children did not grow or gain weight as much as expected. However, 
during the 6 months after treatment, this trend was generally reversed, although a few children did not return 
to their previous rate of growth within the first year after completing treatment. 
 
Tell your doctor if you have ever had a heart attack or a heart problem; if you have a history of breathing 
irregularities or pneumonia, problems with blood clotting, liver condition, thyroid problems, diabetes, or high 
or low blood pressure. 
 
Tell your doctor if you have ever been treated for depression or any other psychiatric disorder; confusion; 
unconsciousness; thoughts of suicide or attempted suicide. 
 
Be sure to tell your doctor if you are taking the Chinese herbal medication Shosaikoto. 
 
Using other medicines 
Viraferon will add to the effects of substances that slow down your nervous system, possibly causing 
drowsiness. Therefore, check with your doctor or pharmacist about drinking alcoholic beverages, or taking 
sleeping pills, sedatives or strong pain medications.  
 
Tell your doctor if you are taking theophylline or aminophylline for asthma, and about all other medication 
you are taking, or have taken recently, even those not prescribed, as the dose of some medications may have 
to be adjusted while you are treated with Viraferon. 

 
Patients who also have HIV infection: Lactic acidosis and worsening liver function are side effects associated 
with Highly Active Anti-Retroviral Therapy (HAART), an HIV treatment. If you are receiving HAART, the 
addition of Viraferon and ribavirin may increase your risk of lactic acidosis and of liver failure. Your doctor 
will monitor you for signs and symptoms of these conditions (Please be sure to read the ribavirin Patient 
Leaflet also). Additionally, patients treated with Viraferon and ribavirin combination therapy and zidovudine 
could be at increased risk of developing anaemia (low number of red blood cells). 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. 
 
Using Viraferon with food and drink 
While being treated with Viraferon, your doctor may want you to drink extra fluids to help prevent low blood 
pressure. 
 



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Pregnancy and breast-feeding 
Ask your doctor or pharmacist for advice before taking any medicine. In studies in pregnant animals, 
interferons have sometimes caused miscarriage. The effect on human pregnancy is not known. 
If you are prescribed Viraferon in combination with ribavirin, ribavirin can be very damaging to an unborn 
baby, thus both female and male patients must take special precautions in their sexual activity if there is any 
chance for pregnancy to occur: 
- if you are a girl or a woman of childbearing age, you must have a negative pregnancy test before treatment, 
each month during treatment, and for the 4 months after treatment is stopped. You and your partner must 
each use an effective contraceptive during the time you are taking ribavirin and for 4 months after stopping 
treatment. This can be discussed with your doctor.  
- if you are a man who is taking ribavirin, do not have sex with a pregnant woman unless you use a condom. 
This will lessen the chance for ribavirin to be left in the woman’s body. If your female partner is not pregnant 
now but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 
7 months after treatment has stopped. This can be discussed with your doctor. If you are a male patient, you 
and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 
7 months after stopping treatment. This can be discussed with your doctor. 
 
It is not known whether this product is present in human milk. Therefore, do not breast-feed an infant if you 
are taking Viraferon. In combination therapy with ribavirin, take notice of the respective informing texts of 
ribavirin containing medicinal products. 
 
Driving and using machines 
Do not drive or use machinery if you become drowsy, tired, or confused from this medicine. 
 
 
3. HOW TO USE VIRAFERON 
 
Your doctor has prescribed Viraferon specifically for you and your current condition; do not share this medicine 
with anyone else. 
 
Your doctor has determined the exact dosage for administration of Viraferon according to your individual needs. 
The dosage will vary according to the disease being treated. 
 
If you are injecting Viraferon yourself, please be sure that the dose that has been prescribed for you is clearly 
provided with the package of medicine you receive. Dosages that are to be administered 3 times a week are best 
given every other day. 
 
The usual starting dose for each condition follows; however, individual doses may vary, and the doctor may 
change your dose based on your specific needs: 
 
Chronic hepatitis B: 5 to 10 million IU 3 times a week (every other day) injected subcutaneously (under the skin). 
 
Chronic hepatitis C: Adults - 3 million IU 3 times a week (every other day) injected subcutaneously (under the 
skin) in combination with ribavirin or alone. Children 3 years of age and older and adolescents - 
3 million IU/m2 3 times a week (every other day) injected subcutaneously (under the skin) in combination with 
ribavirin (Please also see ribavirin package leaflet).  
 
Your doctor may prescribe a different dose of Viraferon alone or in combination with other medicines (e.g. 
ribavirin). If you are prescribed Viraferon in combination with another medicine, please refer also to the Package 
Leaflet of the medicine to be used in combination. Your doctor will determine the exact dosage schedule and 
regimen according to your needs. If you have the impression that the effect of Viraferon is too strong or too 
weak, talk to your doctor or pharmacist. 
 
Subcutaneous use: 



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Viraferon is usually intended for subcutaneous use. This means that Viraferon is injected with a short needle into 
the fatty tissue just under the skin. If you are injecting this medicine yourself, you will be instructed how to 
prepare and give the injection. Detailed instructions for subcutaneous administration are provided with this leaflet 
(see HOW TO SELF INJECT VIRAFERON at the end of the leaflet). 
 
One dose of Viraferon is given on each scheduled day. Viraferon is given three times a week, every other day, for 
example on Monday, Wednesday, and Friday. Interferons may cause unusual tiredness; if you are injecting this 
medicine yourself, or giving it to a child, use it at bedtime. 
 
Use Viraferon exactly as prescribed by your doctor. Do not exceed the recommended dosage, and take Viraferon 
for as long as prescribed. 
 
If you use more Viraferon than you should 
Contact your doctor or healthcare professional as soon as possible. 
 
If you forget to take Viraferon 
If you are self-administering treatment, or if you are the caregiver of a child taking Viraferon in combination 
with ribavirin, inject the recommended dose as soon as you remember and continue treatment as usual. Do 
not take a double dose to make up for a forgotten dose. If you are scheduled to inject this product every day, 
and you accidentally missed a full day’s dose, continue treatment at the usual dose the following day. Contact 
your doctor or pharmacist if needed. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Viraferon can cause side effects, although not everybody gets them. Although not all of 
these side effects may occur, they may need medical attention if they do. 
 
Some people get depressed when taking Viraferon alone or in combination treatment with ribavirin, and in some 
cases people had suicidal thoughts or aggressive behaviour (sometimes directed against others). Some patients have 
actually committed suicide. Be sure to seek emergency care if you notice that you are becoming depressed or have 
suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend 
to help you stay alert to signs of depression or changes in your behaviour. 
 
Paediatric Use: Children are particularly prone to develop depression when being treated with Viraferon and 
ribavirin. Immediately contact the doctor or seek emergency care if they display any unusual behavioural 
symptoms, feel depressed, or feel they want to harm themselves or others. 
 
If any of the following side effects happen, stop taking Viraferon and tell your doctor immediately or go to 
the casualty department at your nearest hospital: 
• swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in 

swallowing or breathing; hives; fainting. 
These are all very serious side effects. If you have them, you may have had a serious allergic reaction to 
Viraferon. You may need urgent medical attention or hospitalisation. These very serious side effects are very 
rare. 
 
Check with your doctor immediately if any of the following side effects occur: 
• chest pain or persistent and severe cough; irregular or rapid heartbeat; shortness of breath, confusion, 

difficulty remaining alert, numbness or tingling sensation or pain in hands or feet; seizure 
(convulsions); trouble sleeping, thinking or concentrating; altered mental state; suicidal thoughts, 
suicide attempt, changed behaviour or aggressive behaviour (sometimes directed against others), 
hallucinations; severe stomach pain; black or tar like stools; blood in stool or urine, severe 
nosebleed; waxy pallor, high sugar level in blood, fever or chills beginning after a few weeks of 



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treatment, lower back or side pain, difficult urination, problems with your eyes or your eyesight or 
hearing, loss of hearing, severe or painful reddening or sores on your skin or mucous membrane. 

These may signal serious side effects that may need urgent medical attention. Your doctor will test your 
blood to ensure that your white blood cell (cells that fight infection) and red blood cell (cells that carry iron 
and oxygen) counts, platelets (blood clotting cells) and other laboratory values are at acceptable levels. 
 
At the beginning of treatment with Viraferon, you may experience a flu-like reaction, with fever, fatigue, 
headache, muscle ache, joint pain and chills/rigors. Your doctor may recommend that you take paracetamol if 
you develop these symptoms. 
 
Other side effects that may occur include: 
 
Very commonly reported side effects (at least 1 in every 10 patients):  
pain, swelling and redness or skin damage at site of injection, hair loss, dizziness, changes in appetite, 
stomach or abdominal pains, diarrhoea, nausea (feeling sick), viral infection, depression, emotional lability, 
insomnia, anxiety, sore throat and painful swallowing, fatigue, chills/rigors, fever, flu-like reaction, feeling 
of general discomfort, headaches, weight loss, vomiting, irritability, weakness, mood swings, coughing 
(sometimes severe), shortness of breath, itching, dry skin, rash, sudden and severe muscle pain, joint pain, 
musculoskeletal pain, changes in laboratory blood values including decreased white blood cell count. Some 
children have had a decrease in their rate of growth (height and weight). 
 
Commonly reported side effects (at least 1 in every 100 patients, but less than 1 in every 10 patients): 
thirst, dehydration, high blood pressure, migraines, swollen glands, flushing, menstrual problems, 
decreased sexual drive, vaginal problem, breast pain, pain in testicle, problems with thyroid gland, red 
gums, dry mouth, red or sore mouth or tongue, tooth ache or tooth disorder, herpes simplex (fever blisters), 
taste change, upset stomach, dyspepsia (heartburn), constipation, enlargement of liver (liver problems, 
sometimes severe), loose stools, bedwetting in children, inflammation of the sinuses, bronchitis, eye pain, 
problem with your tear ducts, conjunctivitis (“pink eye”), agitation, sleepiness, sleepwalking, problem with 
behaviour, nervousness, stuffy or runny nose, sneezing, rapid breathing, pale or reddened skin, bruising, 
fingers and toes very sensitive to cold, problem with skin or nails, psoriasis (new or worsened), increased 
sweating, increased need to pass urine, fine shaking movements, decreased sensitivity to touch, arthritis.  
 
Rarely reported side effects (at least 1 in every 10,000 patients, but less than 1 in every 1,000 patients): 
pneumonia 
 
Very rarely reported side effects (less than 1 in every 10,000 patients): 
low blood pressure, puffy face, diabetes, leg cramps, back pain, kidney problems, nerve damage, bleeding 
gums, aplastic anaemia. Pure red cell aplasia, a condition where the body stopped or reduced the production 
of red blood cells, has been reported. This causes severe anaemia, symptoms of which would include unusual 
tiredness and a lack of energy. 
 
Very rarely sarcoidosis, (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin 
lesions and swollen glands) has been reported. Loss of consciousness has occurred very rarely, mostly in 
elderly patients treated at high doses. Cases of stroke (cerebrovascular events) have been reported. Check 
with your doctor immediately if you have any of these symptoms.  
Periodontal (affecting gums) and dental disorders, altered mental status, loss of consciousness, acute 
hypersensitivity reactions including urticaria (hives), angioedema (swelling of the hands, feet, ankles, face, 
lips, mouth, or throat which may cause difficulty in swallowing or breathing), bronchoconstriction and 
anaphylaxis (a severe, whole-body allergic reaction) have been reported, but their frequency is unknown.  
 
Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin 
and the membranes of the ears, brain and spinal cord) has been reported with Viraferon use. 
 
Other side effects not listed above may also occur in some patients. If any of the side effects gets serious, or if you 
notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. 



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5. HOW TO STORE VIRAFERON 
 
Keep out of the reach and sight of children. 
 
Store in a refrigerator (2°C - 8°C).  
Do not freeze.  
For short term travelling, the solution can be kept out of the refrigerator at or below 25°C for a period up to 
seven days before use. Viraferon can be put back in the refrigerator at any time during this seven-day period. 
If the product is not used during the seven-day period, it should be discarded. 
 
Once opened, the product may be stored for a maximum of 28 days at 2ºC – 8ºC. 
 
Do not use Viraferon after the expiry date which is stated on the package. 
 
Do not use Viraferon if you notice changes in the appearance of Viraferon. 
 
 
6. FURTHER INFORMATION 
 
What Viraferon contains 
 
- The active substance is recombinant interferon alfa-2b, 25 million IU in a multiple dose vial 
- The other ingredients are disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, 

edetate disodium, sodium chloride, m-cresol, polysorbate 80 and water for injections. 
- One ml of solution contains 10 million IU of interferon alfa-2b 
 
What Viraferon looks like and contents of the pack 
 
Viraferon is presented as a solution for injection 
The clear and colourless solution is contained in a glass vial. 
 
Viraferon is available in four different pack sizes: 
- Pack of 1 vial 
- Pack of 1 vial, 6 injection syringes, 6 injection needles and 12 cleansing swabs 
- Pack of 2 vials 
- Pack of 12 vials 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: Manufacturer: 
SP Europe SP Labo N.V. 
73, rue de Stalle Industriepark 30 
B-1180 Bruxelles B-2220 Heist-op-den-Berg 
Belgium Belgium 
 
For any information about this medicinal product, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Rue de Stalle/Stallestraat 73 
B-1180 Bruxelles/Brussel/Brüssel 
Tél/Tel: + 32-(0)2 370 92 11 
 

Luxembourg/Luxemburg 
Rue de Stalle 73 
B-1180 Bruxelles/Brüssel 
Belgique/Belgien 
Tél/Tel: + 32-(0)2 370 92 11 
 



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България 
ул. "Проф. Милко Бичев" № 7, ет.3 
BG-София 1504  
Тел.: +359 2 944 1073 

Magyarország 
Alkotás u. 53. 
H-1123 Budapest 
Tel.: + 36 1 457-8500 
 

Česká republika 
Na Příkopě 25 
CZ-110 00 Praha 1 
Tel: + 420 221771250 
 

Malta 
168 Christopher Street 
MT-VLT02 Valletta 
Tel: + 356-21 23 21 75 
 

Danmark 
Lautrupbjerg 2 
DK-2750 Ballerup 
Tlf: + 45-44 39 50 00 
 

Nederland 
Maarssenbroeksedijk 4 
NL-3542 DN Utrecht 
Tel: + 31-(0)800 778 78 78 

Deutschland 
Thomas-Dehler-Straße 27 
D-81737 München  
Tel: + 49-(0)89 627 31-0 

Norge 
Pb. 398 
N-1326 Lysaker 
Tlf: + 47 67 16 64 50 

Eesti 
Järvevana tee 9 
EE-11314 Tallinn 
Tel: + 372 654 96 86 
 

Österreich 
Badener Strasse 23 
A-2514 Traiskirchen 
Tel: + 43-(0)2252 502-0 
 

Ελλάδα 
Αγίου Δημητρίου 63 
GR-174 55 Άλιμος  
Tηλ: + 30-210 98 97 300 

Polska 
Al. Jerozolimskie 195a 
PL-02-222 Warszawa 
Tel.: + 48-(0)22 478 41 50 
 

España 
Km. 36, Ctra. Nacional I 
E-28750 San Agustín de Guadalix – Madrid 
Tel: + 34-91 848 85 00 
 

Portugal 
Rua Agualva dos Açores 16 
P-2735-557 Agualva-Cacém 
Tel: + 351-21 433 93 00 
 

France 
92 rue Baudin  
F-92300 Levallois-Perret 
Tél: + 33-(0)1 41 06 35 00 
 

România 
Şos. Bucureşti-Ploieşti, nr. 17-21,  
Băneasa Center, et. 8, sector 1 
RO-013682 Bucureşti 
Tel. + 40 21 233 35 30 

Ireland 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW 
Tel: + 44-(0)1 707 363 636 

Slovenija 
Dunajska 22 
SI-1000 Ljubljana 
Tel. + 386 01 3001070 
 

Ísland 
Hörgatún 2 
IS-210 Garðabær 
Sími: + 354 535 70 00 
 

Slovenská republika 
Strakova 5 
SK-811 01 Bratislava 
Tel: + 421 (2) 5920 2712 
 

Italia 
Via fratelli Cervi snc, 
Centro Direzionale Milano Due 
Palazzo Borromini 
I-20090 Segrate (Milano) 
Tel: + 39-02 21018.1 

Suomi/Finland 
PL 3/PB 3 
FIN-02201 Espoo/Esbo 
Puh/Tel: + 358-(0)20-7570 300 
 



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Κύπρος 
Οδός Αγίου Νικολάου, 8 
CY-1055 Λευκωσία 
Τηλ: + 357-22 757188 
 

Sverige 
Box 6185 
S-102 33 Stockholm 
Tel: + 46-(0)8 522 21 500 
 

Latvija 
Bauskas 58a -401 
Rīga, LV-1004  
Tel: + 371-7 21 38 25 

United Kingdom 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW - UK 
Tel: + 44-(0)1 707 363 636 
 

Lietuva 
Kęstučio g. 65/40 
LT-08124 Vilnius 
Tel. + 370 52 101868 

 

 
 
This leaflet was last approved on 
 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: 
http://www.emea.europa.eu/ 
 



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HOW TO SELF INJECT VIRAFERON 
 
The following instructions explain how to inject Viraferon yourself. Please read the instructions carefully and 
follow them step by step. Your doctor or his/her assistant will instruct you how to self-inject Viraferon. Do 
not attempt to inject yourself unless you are sure you understand the procedure and requirement of self-
injection. 
 
Preparation 
Collect necessary items before you begin: 
- a vial of Viraferon solution for injection; 
- a 1 ml syringe; 
- a needle for the subcutaneous injection (for example 0.4 × 13 mm [27 gauge 0.5 inch]); 
- a cleansing swab. 
Wash your hands carefully. 
 
Measuring the dose of Viraferon 
Remove the cap from the vial. If this is a multidose vial, you will only have to remove the cap when 
preparing the first dose. Clean the rubber stopper on the top of the vial containing the Viraferon solution with 
a cleansing swab. 
Remove the syringe from the wrapping. Do not touch the tip of the syringe. Take the needle and place it 
firmly onto the tip of the syringe. 
Remove the needle guard without touching the needle, and fill the syringe with air by pulling the plunger to 
the level that represents your dose as prescribed by your doctor. 
Hold the Viraferon vial upright without touching the cleaned top of the vial with your hands. 
Insert the needle into the vial containing the Viraferon solution and inject air into the vial. 
Turn the vial and the syringe upside down in one hand. Be sure the tip of needle is in the Viraferon solution. 
Your other hand will be free to move the plunger. Pull back on the plunger slowly to draw the correct dose as 
prescribed by your doctor into the syringe. 
Remove the needle from the vial and check for air bubbles in the syringe. If you see any bubbles, pull the 
plunger slightly back; tap the syringe gently, with the needle pointing up, until the bubbles disappear. Push 
up the plunger slowly back to the correct dose.  
 
Volume to be withdrawn according to the dose: 
 

Volume (ml) Corresponding dose (million IU) using Viraferon 
25 million IU/2.5 ml solution for injection 

0.25 

0.1 

0.5 

1 

1.5 

2 

2.5 

2.5 

1 

5 

10 

15 

20 

25 

 
Replace the needle guard and place the syringe with the needle on a flat surface. 
 
Be sure the solution is at room temperature up to 25°C. If the solution is cold, warm the syringe between your 



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palms. Examine the solution prior to administration: it should be clear and colourless. Do not use if 
discolouration or particulate matter is present. You are now ready to inject the dose. 
 
Injecting the solution 
Select the injection site. The best sites for injection are tissues with a layer of fat between skin and muscle: 
thigh, outer surface of the upper arm (you may need the assistance of another person to use this site), 
abdomen (except the navel or waistline). If you are exceptionally thin, use only the thigh or outer surface of 
the arm for injection. 
Change your injection site each time. 
 
Cleanse and disinfect the skin where the injection is to be made. Wait for the area to dry. Remove the needle 
guard. With one hand, pinch a fold of loose skin. With your other hand hold the syringe as you would a 
pencil. Insert the needle into the pinched skin at an angle of 45° to 90°. Inject the solution by pushing the 
plunger all the way down gently. Pull the needle straight out of the skin. Press the injection site with a small 
bandage or sterile gauze if necessary for several seconds. Do not massage the injection site. If there is 
bleeding, cover with an adhesive bandage. 
The vial and injection materials intended for single use must be discarded. Dispose of the syringe and needle 
safely in a closed container. For multidose vials, be sure to return the vial to the refrigerator. 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Viraferon, 18 million IU solution for injection, multidose pen 
Interferon alfa-2b 

 
Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Viraferon is and what it is used for 
2. Before you use Viraferon 
3. How to use Viraferon 
4. Possible side effects 
5. How to store Viraferon 
6. Further information 
 
 
1. WHAT VIRAFERON IS AND WHAT IT IS USED FOR 
 
Viraferon (interferon alfa-2b) modifies the response of the body's immune system to help fight infections and 
severe diseases. Viraferon is used in adult patients for the treatment of chronic hepatitis B or C, which are viral 
infections of the liver. 
 
Viraferon is used in combination with ribavirin in children and adolescents 3 years of age and older who have 
previously untreated chronic hepatitis C. 
 
 
2. BEFORE YOU USE VIRAFERON 
 
Do not use Viraferon 
- if you are allergic (hypersensitive) to interferon or any of the other ingredients of Viraferon. 
- if you have severe heart disease. 
- if you have poor kidney or liver function. 
- if you have advanced decompensated (uncontrolled) liver disease. 
- if you have hepatitis and have been treated recently with medications that suppress the immune system 

(other than short-term treatment with cortisone-type medicine). 
- if you have a history of seizures (convulsions). 
- if you have a history of autoimmune disease, or have had an organ transplant and are taking medicine that 

suppresses your immune system (your immune system helps protect you from infection). 
- if you have thyroid disease that is not well controlled. 
Children and adolescents: 
- if you have had serious nervous or mental problems, such as severe depression or thoughts of suicide. 
 
Take special care with Viraferon 
- if you are pregnant or planning to become pregnant (see Pregnancy). 
- if you have had a severe nervous or mental disorder. The use of interferon alfa-2b in children and 

adolescents with existence of or history of severe psychiatric conditions is contraindicated (see “Do not use 
Viraferon”) 

- if you have ever had depression or develop symptoms associated with depression (e.g. feelings of sadness, 
dejection, etc.) while on treatment with Viraferon (see section 4). 



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- if you have psoriasis, it may get worse during treatment with Viraferon. 
- when receiving Viraferon, you may temporarily have a greater risk of getting an infection. Check with 

your doctor if you think you are getting an infection. 
- if you develop symptoms associated with a cold or other respiratory infection, such as fever, cough, or any 

difficulty in breathing, tell your doctor. 
- if you notice unusual bleeding or bruising check with your doctor immediately. 
- if you develop symptoms of a severe allergic reaction (such as difficulty in breathing, wheezing, or hives) 

while on this medication seek medical help immediately. 
- if you are also being treated for HIV, please see Using other medicines. 
- if you have received an organ transplant, either kidney or liver, interferon treatment may increase the risk 

of rejection. Be sure to discuss this with your doctor. 
 
Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving Viraferon 
and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and 
membranes of the mouth during long-term treatment with the combination of Viraferon with ribavirin. You 
should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some 
patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly 
afterwards. 
 
During the one year of treatment, many children did not grow or gain weight as much as expected. However, 
during the 6 months after treatment, this trend was generally reversed, although a few children did not return 
to their previous rate of growth within the first year after completing treatment. 
 
Tell your doctor if you have ever had a heart attack or a heart problem; if you have a history of breathing 
irregularities or pneumonia, problems with blood clotting, liver condition, thyroid problems, diabetes, or high 
or low blood pressure. 
 
Tell your doctor if you have ever been treated for depression or any other psychiatric disorder; confusion; 
unconsciousness; thoughts of suicide or attempted suicide. 
 
Be sure to tell your doctor if you are taking the Chinese herbal medication Shosaikoto. 
 
Using other medicines 
Viraferon will add to the effects of substances that slow down your nervous system, possibly causing 
drowsiness. Therefore, check with your doctor or pharmacist about drinking alcoholic beverages, or taking 
sleeping pills, sedatives or strong pain medications.  
 
Tell your doctor if you are taking theophylline or aminophylline for asthma, and about all other medication 
you are taking, or have taken recently, even those not prescribed, as the dose of some medications may have 
to be adjusted while you are treated with Viraferon. 

 
Patients who also have HIV infection: Lactic acidosis and worsening liver function are side effects associated 
with Highly Active Anti-Retroviral Therapy (HAART), an HIV treatment. If you are receiving HAART, the 
addition of Viraferon and ribavirin may increase your risk of lactic acidosis and of liver failure. Your doctor 
will monitor you for signs and symptoms of these conditions (Please be sure to read the ribavirin Patient 
Leaflet also). Additionally, patients treated with Viraferon and ribavirin combination therapy and zidovudine 
could be at increased risk of developing anaemia (low number of red blood cells). 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. 
 
Using Viraferon with food and drink 
While being treated with Viraferon, your doctor may want you to drink extra fluids to help prevent low blood 
pressure. 
 



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Pregnancy and breast-feeding 
Ask your doctor or pharmacist for advice before taking any medicine. In studies in pregnant animals, 
interferons have sometimes caused miscarriage. The effect on human pregnancy is not known. 
If you are prescribed Viraferon in combination with ribavirin, ribavirin can be very damaging to an unborn 
baby, thus both female and male patients must take special precautions in their sexual activity if there is any 
chance for pregnancy to occur: 
- if you are a girl or a woman of childbearing age, you must have a negative pregnancy test before treatment, 
each month during treatment, and for the 4 months after treatment is stopped. You and your partner must 
each use an effective contraceptive during the time you are taking ribavirin and for 4 months after stopping 
treatment. This can be discussed with your doctor.  
- if you are a man who is taking ribavirin, do not have sex with a pregnant woman unless you use a condom. 
This will lessen the chance for ribavirin to be left in the woman’s body. If your female partner is not pregnant 
now but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 
7 months after treatment has stopped. This can be discussed with your doctor. If you are a male patient, you 
and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 
7 months after stopping treatment. This can be discussed with your doctor. 
 
It is not known whether this product is present in human milk. Therefore, do not breast-feed an infant if you 
are taking Viraferon. In combination therapy with ribavirin, take notice of the respective informing texts of 
ribavirin containing medicinal products. 
 
Driving and using machines 
Do not drive or use machinery if you become drowsy, tired, or confused from this medicine. 
 
 
3. HOW TO USE VIRAFERON 
 
Your doctor has prescribed Viraferon specifically for you and your current condition; do not share this medicine 
with anyone else. 
 
Your doctor has determined the exact dosage for administration of Viraferon according to your individual needs. 
The dosage will vary according to the disease being treated. 
 
If you are injecting Viraferon yourself, please be sure that the dose that has been prescribed for you is clearly 
provided with the package of medicine you receive. Dosages that are to be administered 3 times a week are best 
given every other day. 
 
The usual starting dose for each condition follows; however, individual doses may vary, and the doctor may 
change your dose based on your specific needs: 
 
Chronic hepatitis B: 5 to 10 million IU 3 times a week (every other day) injected subcutaneously (under the skin). 
 
Chronic hepatitis C: Adults - 3 million IU 3 times a week (every other day) injected subcutaneously (under the 
skin) in combination with ribavirin or alone. Children 3 years of age and older and adolescents - 
3 million IU/m2 3 times a week (every other day) injected subcutaneously (under the skin) in combination with 
ribavirin (Please also see ribavirin package leaflet).  
 
Your doctor may prescribe a different dose of Viraferon alone or in combination with other medicines (e.g. 
ribavirin). If you are prescribed Viraferon in combination with another medicine, please refer also to the Package 
Leaflet of the medicine to be used in combination. Your doctor will determine the exact dosage schedule and 
regimen according to your needs. If you have the impression that the effect of Viraferon is too strong or too 
weak, talk to your doctor or pharmacist. 
 
Subcutaneous use: 



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Viraferon is usually intended for subcutaneous use. This means that Viraferon is injected with a short needle into 
the fatty tissue just under the skin. If you are injecting this medicine yourself, you will be instructed how to 
prepare and give the injection. Detailed instructions for subcutaneous administration are provided with this leaflet 
(see HOW TO SELF INJECT VIRAFERON at the end of the leaflet). 
 
One dose of Viraferon is given on each scheduled day. Viraferon is given three times a week, every other day, for 
example on Monday, Wednesday, and Friday. Interferons may cause unusual tiredness; if you are injecting this 
medicine yourself, or giving it to a child, use it at bedtime. 
 
Use Viraferon exactly as prescribed by your doctor. Do not exceed the recommended dosage, and take Viraferon 
for as long as prescribed. 
 
If you use more Viraferon than you should 
Contact your doctor or healthcare professional as soon as possible. 
 
If you forget to take Viraferon 
If you are self-administering treatment, or if you are the caregiver of a child taking Viraferon in combination 
with ribavirin, inject the recommended dose as soon as you remember and continue treatment as usual Do not 
take a double dose to make up for a forgotten dose. If you are scheduled to inject this product every day, and 
you accidentally missed a full day’s dose, continue treatment at the usual dose the following day. Contact 
your doctor or pharmacist if needed. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Viraferon can cause side effects, although not everybody gets them. Although not all of 
these side effects may occur, they may need medical attention if they do. 
 
Some people get depressed when taking Viraferon alone or in combination treatment with ribavirin, and in some 
cases people had suicidal thoughts or aggressive behaviour (sometimes directed against others). Some patients have 
actually committed suicide. Be sure to seek emergency care if you notice that you are becoming depressed or have 
suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend 
to help you stay alert to signs of depression or changes in your behaviour. 
 
Paediatric Use: Children are particularly prone to develop depression when being treated with Viraferon and 
ribavirin. Immediately contact the doctor or seek emergency care if they display any unusual behavioural 
symptoms, feel depressed, or feel they want to harm themselves or others. 
 
If any of the following side effects happen, stop taking Viraferon and tell your doctor immediately or go to 
the casualty department at your nearest hospital: 
• swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in 

swallowing or breathing; hives; fainting. 
These are all very serious side effects. If you have them, you may have had a serious allergic reaction to 
Viraferon. You may need urgent medical attention or hospitalisation. These very serious side effects are very 
rare. 
 
Check with your doctor immediately if any of the following side effects occur: 
• chest pain or persistent and severe cough; irregular or rapid heartbeat; shortness of breath, confusion, 

difficulty remaining alert, numbness or tingling sensation or pain in hands or feet; seizure 
(convulsions); trouble sleeping, thinking or concentrating; altered mental state; suicidal thoughts, 
suicide attempt, changed behaviour or aggressive behaviour (sometimes directed against others), 
hallucinations; severe stomach pain; black or tar like stools; blood in stool or urine, severe 
nosebleed; waxy pallor, high sugar level in blood, fever or chills beginning after a few weeks of 



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treatment, lower back or side pain, difficult urination, problems with your eyes or your eyesight or 
hearing, loss of hearing, severe or painful reddening or sores on your skin or mucous membrane. 

These may signal serious side effects that may need urgent medical attention. Your doctor will test your 
blood to ensure that your white blood cell (cells that fight infection) and red blood cell (cells that carry iron 
and oxygen) counts, platelets (blood clotting cells) and other laboratory values are at acceptable levels. 
 
At the beginning of treatment with Viraferon, you may experience a flu-like reaction, with fever, fatigue, 
headache, muscle ache, joint pain and chills/rigors. Your doctor may recommend that you take paracetamol if 
you develop these symptoms. 
 
Other side effects that may occur include: 
 
Very commonly reported side effects (at least 1 in every 10 patients):  
pain, swelling and redness or skin damage at site of injection, hair loss, dizziness, changes in appetite, 
stomach or abdominal pains, diarrhoea, nausea (feeling sick), viral infection, depression, emotional lability, 
insomnia, anxiety, sore throat and painful swallowing, fatigue, chills/rigors, fever, flu-like reaction, feeling 
of general discomfort, headaches, weight loss, vomiting, irritability, weakness, mood swings, coughing 
(sometimes severe), shortness of breath, itching, dry skin, rash, sudden and severe muscle pain, joint pain, 
musculoskeletal pain, changes in laboratory blood values including decreased white blood cell count. Some 
children have had a decrease in their rate of growth (height and weight). 
 
Commonly reported side effects (at least 1 in every 100 patients, but less than 1 in every 10 patients): 
thirst, dehydration, high blood pressure, migraines, swollen glands, flushing, menstrual problems, 
decreased sexual drive, vaginal problem, breast pain, pain in testicle, problems with thyroid gland, red 
gums, dry mouth, red or sore mouth or tongue, tooth ache or tooth disorder, herpes simplex (fever blisters), 
taste change, upset stomach, dyspepsia (heartburn), constipation, enlargement of liver (liver problems, 
sometimes severe), loose stools, bedwetting in children, inflammation of the sinuses, bronchitis, eye pain, 
problem with your tear ducts, conjunctivitis (“pink eye”), agitation, sleepiness, sleepwalking, problem with 
behaviour, nervousness, stuffy or runny nose, sneezing, rapid breathing, pale or reddened skin, bruising, 
fingers and toes very sensitive to cold, problem with skin or nails, psoriasis (new or worsened), increased 
sweating, increased need to pass urine, fine shaking movements, decreased sensitivity to touch, arthritis.  
 
Rarely reported side effects (at least 1 in every 10,000 patients, but less than 1 in every 1,000 patients): 
pneumonia 
 
Very rarely reported side effects (less than 1 in every 10,000 patients): 
low blood pressure, puffy face, diabetes, leg cramps, back pain, kidney problems, nerve damage, bleeding 
gums, aplastic anaemia. Pure red cell aplasia, a condition where the body stopped or reduced the production 
of red blood cells, has been reported. This causes severe anaemia, symptoms of which would include unusual 
tiredness and a lack of energy. 
 
Very rarely sarcoidosis, (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin 
lesions and swollen glands) has been reported. Loss of consciousness has occurred very rarely, mostly in 
elderly patients treated at high doses. Cases of stroke (cerebrovascular events) have been reported. Check 
with your doctor immediately if you have any of these symptoms.  
Periodontal (affecting gums) and dental disorders, altered mental status, loss of consciousness, acute 
hypersensitivity reactions including urticaria (hives), angioedema (swelling of the hands, feet, ankles, face, 
lips, mouth, or throat which may cause difficulty in swallowing or breathing), bronchoconstriction and 
anaphylaxis (a severe, whole-body allergic reaction) have been reported, but their frequency is unknown.  
 
Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin 
and the membranes of the ears, brain and spinal cord) has been reported with Viraferon use. 
 
Other side effects not listed above may also occur in some patients. If any of the side effects gets serious, or if you 
notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. 



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5. HOW TO STORE VIRAFERON 
 
Keep out of the reach and sight of children. 
 
Store in a refrigerator (2°C - 8°C).  
Do not freeze.  
Each pen is intended for a maximum four-week use period and must then be discarded. A maximum of 
48 hours (two days) of exposure to 25°C is permitted over the four-week period to cover accidental delays in 
returning the pen to the refrigerator. 
 
Depending upon your dose, you may have extra needles and swabs left in the pack. Please discard these 
appropriately and safely. 
 
Do not use Viraferon after the expiry date which is stated on the package. 
 
Do not use Viraferon if you notice changes in the appearance of Viraferon. 
 
 
6. FURTHER INFORMATION 
 
What Viraferon contains 
 
- The active substance is recombinant interferon alfa-2b, 18 million IU/pen 
- The other ingredients are disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, 

edetate disodium, sodium chloride, m-cresol, polysorbate 80 and water for injections. 
 
What Viraferon looks like and contents of the pack 
 
Viraferon is presented as a solution for injection 
The clear and colourless solution is contained in a glass cartridge. 
The pen is designed to deliver its contents of 18 million IU in doses ranging from 1.5 to 6 million IU. The 
pen will deliver a maximum of 12 doses of 1.5 million IU over a period not to exceed 4 weeks. 
 
Viraferon is available in three different pack sizes: 
Viraferon, 18 million IU/pen, solution for injection: 
- Pack of 1 pen, 12 injection needles and 12 cleansing swabs 
- Pack of 2 pens, 24 injection needles and 24 cleansing swabs 
- Pack of 8 pens, 96 injection needles and 96 cleansing swabs 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: Manufacturer: 
SP Europe SP Labo N.V. 
73, rue de Stalle Industriepark 30 
B-1180 Bruxelles B-2220 Heist-op-den-Berg 
Belgium Belgium 
 
For any information about this medicinal product, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Rue de Stalle/Stallestraat 73 
B-1180 Bruxelles/Brussel/Brüssel 
Tél/Tel: + 32-(0)2 370 92 11 

Luxembourg/Luxemburg 
Rue de Stalle 73 
B-1180 Bruxelles/Brüssel 
Belgique/Belgien 



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 Tél/Tel: + 32-(0)2 370 92 11 
 

България 
ул. "Проф. Милко Бичев" № 7, ет.3 
BG-София 1504  
Тел.: +359 2 944 1073 

Magyarország 
Alkotás u. 53. 
H-1123 Budapest 
Tel.: + 36 1 457-8500 

Česká republika 
Na Příkopě 25 
CZ-110 00 Praha 1 
Tel: + 420 221771250 
 

Malta 
168 Christopher Street 
MT-VLT02 Valletta 
Tel: + 356-21 23 21 75 
 

Danmark 
Lautrupbjerg 2 
DK-2750 Ballerup 
Tlf: + 45-44 39 50 00 

Nederland 
Maarssenbroeksedijk 4 
NL-3542 DN Utrecht 
Tel: + 31-(0)800 778 78 78 

Deutschland 
Thomas-Dehler-Straße 27 
D-81737 München  
Tel: + 49-(0)89 627 31-0 
 

Norge 
Pb. 398 
N-1326 Lysaker 
Tlf: + 47 67 16 64 50 
 

Eesti 
Järvevana tee 9 
EE-11314 Tallinn 
Tel: + 372 654 96 86 
 

Österreich 
Badener Strasse 23 
A-2514 Traiskirchen 
Tel: + 43-(0)2252 502-0 
 

Ελλάδα 
Αγίου Δημητρίου 63 
GR-174 55 Άλιμος  
Tηλ: + 30-210 98 97 300 
 

Polska 
Al. Jerozolimskie 195a 
PL-02-222 Warszawa 
Tel.: + 48-(0)22 478 41 50 
 

España 
Km. 36, Ctra. Nacional I 
E-28750 San Agustín de Guadalix – Madrid 
Tel: + 34-91 848 85 00 
 

Portugal 
Rua Agualva dos Açores 16 
P-2735-557 Agualva-Cacém 
Tel: + 351-21 433 93 00 
 



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France 
92 rue Baudin  
F-92300 Levallois-Perret 
Tél: + 33-(0)1 41 06 35 00 
 

România 
Şos. Bucureşti-Ploieşti, nr. 17-21,  
Băneasa Center, et. 8, sector 1 
RO-013682 Bucureşti 
Tel. + 40 21 233 35 30 

Ireland 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW 
Tel: + 44-(0)1 707 363 636 
 

Slovenija 
Dunajska 22 
SI-1000 Ljubljana 
Tel. + 386 01 3001070 
 

Ísland 
Hörgatún 2 
IS-210 Garðabær 
Sími: + 354 535 70 00 
 

Slovenská republika 
Strakova 5 
SK-811 01 Bratislava 
Tel: + 421 (2) 5920 2712 
 

Italia 
Via fratelli Cervi snc, 
Centro Direzionale Milano Due 
Palazzo Borromini 
I-20090 Segrate (Milano) 
Tel: + 39-02 21018.1 
 

Suomi/Finland 
PL 3/PB 3 
FIN-02201 Espoo/Esbo 
Puh/Tel: + 358-(0)20-7570 300 
 

Κύπρος 
Οδός Αγίου Νικολάου, 8 
CY-1055 Λευκωσία 
Τηλ: + 357-22 757188 

Sverige 
Box 6185 
S-102 33 Stockholm 
Tel: + 46-(0)8 522 21 500 

Latvija 
Bauskas 58a -401 
Rīga, LV-1004  
Tel: + 371-7 21 38 25 

United Kingdom 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW - UK 
Tel: + 44-(0)1 707 363 636 
 

Lietuva 
Kęstučio g. 65/40 
LT-08124 Vilnius 
Tel. + 370 52 101868 

 

 
 
This leaflet was last approved on 
 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: 
http://www.emea.europa.eu/ 
 



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HOW TO SELF INJECT VIRAFERON 
 
The following instructions explain how to inject Viraferon yourself. Please read the instructions carefully and 
follow them step by step. Your doctor or his/her assistant will instruct you how to self-inject Viraferon. Do 
not attempt to inject yourself unless you are sure you understand the procedure and requirement of self-
injection. 
 
Preparation 
Collect necessary items before you begin: 
- the Viraferon multidose pen; 
- a needle for subcutaneous injection (provided in the packaging); 
- a cleansing swab. 
Wash your hands carefully. Use the injection needles provided in the packaging only for Viraferon. Use a new 
injection needle for each dose. Be sure the solution is at room temperature at the time of injection. 
 
Diagrams A and B show you all the different parts of the pen and the injection needle. The most important 
parts to note are as follows: 
 
- The push button scale tells you what dose has been set. 
- The colour coding strip brown and the push button are at the bottom of the pen as it is held cap up. 
- The pen can only be fully capped when the triangle on the cap scale is aligned with the dosage 

indicator on the barrel. 
 

    
 

 
 Diagram A Diagram B 

Cap 

Cap 
scale 

Rubber 
membrane 

Dosage 
indicator 

Push 
button 
scale 

Needle 

Reservoir 

Pen barrel 

Colour 
coding 

Push 
button 



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Measuring the dose of Viraferon 
Take the pen out of the refrigerator about one-half hour before administering the dose so that the solution in 
the pen is at room temperature when it is injected. 
 
When you are ready to give your injection prepare your pen as follows: 
 
Check that Viraferon, solution for injection, is clear and colourless in appearance prior to use. If it does not 
have a clear uniform appearance or if it contains any particles, do not use. 
 
Pull off the cap of the pen and disinfect the rubber membrane (see Diagram C) with one cleansing swab. 

 
 

Diagram C 
 
Remove the protective tab from the injection needle. Note that the rear portion of the injection needle is 
revealed once the protective tab is removed (see Diagram D). 
 

 
 

Diagram D 
 
Gently push the injection needle onto the pen as shown in Diagram E. (Notice that the rear portion of the 
injection needle will pierce through the rubber membrane that you disinfected previously). Now screw the 
injection needle onto the pen securely by turning it in a clockwise direction (see Diagram F). 
 

 

 

 
 
 Diagram E Diagram F 
 



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First, pull off the outer injection needle cap (Diagram G). Then, pull off the inner injection needle cap 
carefully, bearing in mind that the injection needle will now be exposed (Diagram H). Keep the outer 
injection needle cap for later use. 
 
 

 

 

 

 
 
 Diagram G Diagram H 
 
The pen is now ready to use. Since a small amount of air may collect in the injection needle and reservoir 
during storage, the next step is to remove any air bubbles. This is called performing the Air-Shot. 
 
Hold the Viraferon, solution for injection, multidose pen with the injection needle point upwards. 
 
Tap the reservoir with your finger so that any air bubbles rise to the top of the reservoir, just below the 
injection needle (Diagram I). 

 
 

Diagram I 
 
Hold the pen by the barrel and turn the reservoir in the direction as indicated by the arrow in Diagram J 
(clockwise) until you feel it click. 
 

 
 

Diagram J 
 



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Keeping the pen pointing upwards, press the push button up fully and see if a drop of Viraferon, solution for 
injection, appears at the injection needle tip (Notice the drop at the tip of injection needle in Diagram K 
below). 
 

 
 

Diagram K 
 
If no drop appears, use a different pen, and return the faulty pen to your provider. 
 
Note: some air may remain in the pen, but this is not important as you have removed the air from the 
injection needle and the dose will be accurate. 
 
Replace the Viraferon, solution for injection, multidose pen cap with the ‘triangle’ opposite the dosage 
indicator as seen in Diagram L. 
 

 
 

Diagram L 
 
The pen is now ready to set the dose. For the next step hold the pen in the middle of the barrel. This will 
allow the push button to move freely, ensuring that the correct dose is set. 
 
To set the required dose, hold the pen horizontally by the barrel with one hand. With the other hand, turn the 
cap in a clockwise direction indicated by the arrow in Diagram M. You will observe the push button rising, 
indicating the dose set. To set the correct dose, turn the cap as many times as indicated as follows: 



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Number of “turns” and “clicks” Corresponding doses (million IU) using 
Viraferon, solution for injection, 
multidose pen 18 million IU/pen 

 

1 full turn (5 clicks) 

6 clicks 

7 clicks 

8 clicks 

9 clicks 

2 full turns (10 clicks) 

11 clicks 

12 clicks 

13 clicks 

14 clicks 

3 full turns (15 clicks) 

16 clicks 

17 clicks 

18 clicks 

19 clicks 

4 full turns (20 clicks)* 

1.5 

1.8 

2.1 

2.4 

2.7 

3 

3.3 

3.6 

3.9 

4.2 

4.5 

4.8 

5.1 

5.4 

5.7 

6 

 

 
 

Diagram M 
 

*4 full turns correspond to the maximum dose to be administered in one injection. The pen is designed to deliver its contents of 
18 million IU in doses ranging from 1.5 to 6 million IU. The pen will deliver a maximum of 12 doses of 1.5 million IU over a period 
not to exceed 4 weeks. 
 



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The push button scale will show you the dose set (see Diagram N below). For doses corresponding to full 
turns, the scale should line up with the correct dose marking. For doses corresponding to clicks intermediate 
between full turns, the scale should line up between the two appropriate full-turn dose markings. At that point 
check that you have the correct dose. 
 
 

 
 

Diagram N 
 
After each complete turn make sure that the triangle is opposite the dosage indicator (see Diagram O). If you 
have set a wrong dose, simply turn the cap back (anti-clockwise) as far as you can until the push button is 
fully home and start again. Once the correct dose is set you are ready to give the injection. 

 
Diagram O 

Injecting the solution 
Select the injection site. The best sites for injection are tissues with a layer of fat between skin and muscle: 
thigh, outer surface of the upper arm (you may need the assistance of another person to use this site), 
abdomen (except the navel or waistline). If you are exceptionally thin, use only the thigh or outer surface of 
the arm for injection. Change your injection site each time. 
 
Cleanse and disinfect the skin where the injection is to be made. Wait for the area to dry. 
With one hand, pinch a fold of loose skin. With your other hand, pick up the pen and hold it as you would a 
pencil. Insert the needle into the pinched skin at an angle of approximately 45°. 
 



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Then press the push button down fully (see Diagram P). 
 

 
Diagram P 

 
Keeping the push button down, leave the injection needle in place for a few seconds to allow the Viraferon, 
solution for injection, to distribute under the skin, then remove. 
 
Carefully replace the outer injection needle cap (See Diagram Q). 
 

 
Diagram Q 

 
Completely unscrew the injection needle assembly using an anti-clockwise turning motion as shown in 
Diagram R. Then carefully lift it off the pen and discard the capped injection needle (see Diagram S). 
 
 

 

 
 Diagram R Diagram S 



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Replace the pen cap with the triangle once again opposite the dosage indicator as shown in Diagram T. Then 
return the pen to the refrigerator. 
 

 
 

Diagram T 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Viraferon, 30 million IU solution for injection, multidose pen 
Interferon alfa-2b 

 
Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Viraferon is and what it is used for 
2. Before you use Viraferon 
3. How to use Viraferon 
4. Possible side effects 
5. How to store Viraferon 
6. Further information 
 
 
1. WHAT VIRAFERON IS AND WHAT IT IS USED FOR 
 
Viraferon (interferon alfa-2b) modifies the response of the body's immune system to help fight infections and 
severe diseases. Viraferon is used in adult patients for the treatment of chronic hepatitis B or C, which are viral 
infections of the liver. 
 
Viraferon is used in combination with ribavirin in children and adolescents 3 years of age and older who have 
previously untreated chronic hepatitis C. 
 
 
2. BEFORE YOU USE VIRAFERON 
 
Do not use Viraferon 
- if you are allergic (hypersensitive) to interferon or any of the other ingredients of Viraferon. 
- if you have severe heart disease. 
- if you have poor kidney or liver function. 
- if you have advanced decompensated (uncontrolled) liver disease. 
- if you have hepatitis and have been treated recently with medications that suppress the immune system 

(other than short-term treatment with cortisone-type medicine). 
- if you have a history of seizures (convulsions). 
- if you have a history of autoimmune disease, or have had an organ transplant and are taking medicine that 

suppresses your immune system (your immune system helps protect you from infection). 
- if you have thyroid disease that is not well controlled. 
Children and adolescents: 
- if you have had serious nervous or mental problems, such as severe depression or thoughts of suicide. 
 
Take special care with Viraferon 
- if you are pregnant or planning to become pregnant (see Pregnancy). 
- if you have had a severe nervous or mental disorder. The use of interferon alfa-2b in children and 

adolescents with existence of or history of severe psychiatric conditions is contraindicated (see “Do not use 
Viraferon”) 

- if you have ever had depression or develop symptoms associated with depression (e.g. feelings of sadness, 
dejection, etc.) while on treatment with Viraferon (see section 4). 



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- if you have psoriasis, it may get worse during treatment with Viraferon. 
- when receiving Viraferon, you may temporarily have a greater risk of getting an infection. Check with 

your doctor if you think you are getting an infection. 
- if you develop symptoms associated with a cold or other respiratory infection, such as fever, cough, or any 

difficulty in breathing, tell your doctor. 
- if you notice unusual bleeding or bruising check with your doctor immediately. 
- if you develop symptoms of a severe allergic reaction (such as difficulty in breathing, wheezing, or hives) 

while on this medication seek medical help immediately. 
- if you are also being treated for HIV, please see Using other medicines. 
- if you have received an organ transplant, either kidney or liver, interferon treatment may increase the risk 

of rejection. Be sure to discuss this with your doctor. 
 
Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving Viraferon 
and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and 
membranes of the mouth during long-term treatment with the combination of Viraferon with ribavirin. You 
should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some 
patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly 
afterwards. 
 
During the one year of treatment, many children did not grow or gain weight as much as expected. However, 
during the 6 months after treatment, this trend was generally reversed, although a few children did not return 
to their previous rate of growth within the first year after completing treatment. 
 
Tell your doctor if you have ever had a heart attack or a heart problem; if you have a history of breathing 
irregularities or pneumonia, problems with blood clotting, liver condition, thyroid problems, diabetes, or high 
or low blood pressure. 
 
Tell your doctor if you have ever been treated for depression or any other psychiatric disorder; confusion; 
unconsciousness; thoughts of suicide or attempted suicide. 
 
Be sure to tell your doctor if you are taking the Chinese herbal medication Shosaikoto. 
 
Using other medicines 
Viraferon will add to the effects of substances that slow down your nervous system, possibly causing 
drowsiness. Therefore, check with your doctor or pharmacist about drinking alcoholic beverages, or taking 
sleeping pills, sedatives or strong pain medications.  
 
Tell your doctor if you are taking theophylline or aminophylline for asthma, and about all other medication 
you are taking, or have taken recently, even those not prescribed, as the dose of some medications may have 
to be adjusted while you are treated with Viraferon. 

 
Patients who also have HIV infection: Lactic acidosis and worsening liver function are side effects associated 
with Highly Active Anti-Retroviral Therapy (HAART), an HIV treatment. If you are receiving HAART, the 
addition of Viraferon and ribavirin may increase your risk of lactic acidosis and of liver failure. Your doctor 
will monitor you for signs and symptoms of these conditions (Please be sure to read the ribavirin Patient 
Leaflet also). Additionally, patients treated with Viraferon and ribavirin combination therapy and zidovudine 
could be at increased risk of developing anaemia (low number of red blood cells). 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. 
 
Using Viraferon with food and drink 
While being treated with Viraferon, your doctor may want you to drink extra fluids to help prevent low blood 
pressure. 
 



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Pregnancy and breast-feeding 
Ask your doctor or pharmacist for advice before taking any medicine. In studies in pregnant animals, 
interferons have sometimes caused miscarriage. The effect on human pregnancy is not known. 
If you are prescribed Viraferon in combination with ribavirin, ribavirin can be very damaging to an unborn 
baby, thus both female and male patients must take special precautions in their sexual activity if there is any 
chance for pregnancy to occur: 
- if you are a girl or a woman of childbearing age, you must have a negative pregnancy test before treatment, 
each month during treatment, and for the 4 months after treatment is stopped. You and your partner must 
each use an effective contraceptive during the time you are taking ribavirin and for 4 months after stopping 
treatment. This can be discussed with your doctor.  
- if you are a man who is taking ribavirin, do not have sex with a pregnant woman unless you use a condom. 
This will lessen the chance for ribavirin to be left in the woman’s body. If your female partner is not pregnant 
now but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 
7 months after treatment has stopped. This can be discussed with your doctor. If you are a male patient, you 
and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 
7 months after stopping treatment. This can be discussed with your doctor. 
 
It is not known whether this product is present in human milk. Therefore, do not breast-feed an infant if you 
are taking Viraferon. In combination therapy with ribavirin, take notice of the respective informing texts of 
ribavirin containing medicinal products. 
 
Driving and using machines 
Do not drive or use machinery if you become drowsy, tired, or confused from this medicine. 
 
 
3. HOW TO USE VIRAFERON 
 
Your doctor has prescribed Viraferon specifically for you and your current condition; do not share this medicine 
with anyone else. 
 
Your doctor has determined the exact dosage for administration of Viraferon according to your individual needs. 
The dosage will vary according to the disease being treated. 
 
If you are injecting Viraferon yourself, please be sure that the dose that has been prescribed for you is clearly 
provided with the package of medicine you receive. Dosages that are to be administered 3 times a week are best 
given every other day. 
 
The usual starting dose for each condition follows; however, individual doses may vary, and the doctor may 
change your dose based on your specific needs: 
 
Chronic hepatitis B: 5 to 10 million IU 3 times a week (every other day) injected subcutaneously (under the skin). 
 
Chronic hepatitis C: Adults - 3 million IU 3 times a week (every other day) injected subcutaneously (under the 
skin) in combination with ribavirin or alone. Children 3 years of age and older and adolescents - 
3 million IU/m2 3 times a week (every other day) injected subcutaneously (under the skin) in combination with 
ribavirin (Please also see ribavirin package leaflet).  
 
Your doctor may prescribe a different dose of Viraferon alone or in combination with other medicines (e.g. 
ribavirin). If you are prescribed Viraferon in combination with another medicine, please refer also to the Package 
Leaflet of the medicine to be used in combination. Your doctor will determine the exact dosage schedule and 
regimen according to your needs. If you have the impression that the effect of Viraferon is too strong or too 
weak, talk to your doctor or pharmacist. 
 
Subcutaneous use: 



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Viraferon is usually intended for subcutaneous use. This means that Viraferon is injected with a short needle into 
the fatty tissue just under the skin. If you are injecting this medicine yourself, you will be instructed how to 
prepare and give the injection. Detailed instructions for subcutaneous administration are provided with this leaflet 
(see HOW TO SELF INJECT VIRAFERON at the end of the leaflet). 
 
One dose of Viraferon is given on each scheduled day. Viraferon is given three times a week, every other day, for 
example on Monday, Wednesday, and Friday. Interferons may cause unusual tiredness; if you are injecting this 
medicine yourself, or giving it to a child, use it at bedtime. 
 
Use Viraferon exactly as prescribed by your doctor. Do not exceed the recommended dosage, and take Viraferon 
for as long as prescribed. 
 
If you use more Viraferon than you should 
Contact your doctor or healthcare professional as soon as possible. 
 
If you forget to take Viraferon 
If you are self-administering treatment, or if you are the caregiver of a child taking Viraferon in combination 
with ribavirin, inject the recommended dose as soon as you remember and continue treatment as usual. Do 
not take a double dose to make up for a forgotten dose. If you are scheduled to inject this product every day, 
and you accidentally missed a full day’s dose, continue treatment at the usual dose the following day. Contact 
your doctor or pharmacist if needed. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Viraferon can cause side effects, although not everybody gets them. Although not all of 
these side effects may occur, they may need medical attention if they do. 
 
Some people get depressed when taking Viraferon alone or in combination treatment with ribavirin, and in some 
cases people had suicidal thoughts or aggressive behaviour (sometimes directed against others). Some patients have 
actually committed suicide. Be sure to seek emergency care if you notice that you are becoming depressed or have 
suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend 
to help you stay alert to signs of depression or changes in your behaviour. 
 
Paediatric Use: Children are particularly prone to develop depression when being treated with Viraferon and 
ribavirin. Immediately contact the doctor or seek emergency care if they display any unusual behavioural 
symptoms, feel depressed, or feel they want to harm themselves or others. 
 
If any of the following side effects happen, stop taking Viraferon and tell your doctor immediately or go to 
the casualty department at your nearest hospital: 
• swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in 

swallowing or breathing; hives; fainting. 
These are all very serious side effects. If you have them, you may have had a serious allergic reaction to 
Viraferon. You may need urgent medical attention or hospitalisation. These very serious side effects are very 
rare. 
 
Check with your doctor immediately if any of the following side effects occur: 
• chest pain or persistent and severe cough; irregular or rapid heartbeat; shortness of breath, confusion, 

difficulty remaining alert, numbness or tingling sensation or pain in hands or feet; seizure 
(convulsions); trouble sleeping, thinking or concentrating; altered mental state; suicidal thoughts, 
suicide attempt, changed behaviour or aggressive behaviour (sometimes directed against others), 
hallucinations; severe stomach pain; black or tar like stools; blood in stool or urine, severe 
nosebleed; waxy pallor, high sugar level in blood, fever or chills beginning after a few weeks of 



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treatment, lower back or side pain, difficult urination, problems with your eyes or your eyesight or 
hearing, loss of hearing, severe or painful reddening or sores on your skin or mucous membrane. 

These may signal serious side effects that may need urgent medical attention. Your doctor will test your 
blood to ensure that your white blood cell (cells that fight infection) and red blood cell (cells that carry iron 
and oxygen) counts, platelets (blood clotting cells) and other laboratory values are at acceptable levels. 
 
At the beginning of treatment with Viraferon, you may experience a flu-like reaction, with fever, fatigue, 
headache, muscle ache, joint pain and chills/rigors. Your doctor may recommend that you take paracetamol if 
you develop these symptoms. 
 
Other side effects that may occur include: 
 
Very commonly reported side effects (at least 1 in every 10 patients):  
pain, swelling and redness or skin damage at site of injection, hair loss, dizziness, changes in appetite, 
stomach or abdominal pains, diarrhoea, nausea (feeling sick), viral infection, depression, emotional lability, 
insomnia, anxiety, sore throat and painful swallowing, fatigue, chills/rigors, fever, flu-like reaction, feeling 
of general discomfort, headaches, weight loss, vomiting, irritability, weakness, mood swings, coughing 
(sometimes severe), shortness of breath, itching, dry skin, rash, sudden and severe muscle pain, joint pain, 
musculoskeletal pain, changes in laboratory blood values including decreased white blood cell count. Some 
children have had a decrease in their rate of growth (height and weight). 
 
Commonly reported side effects (at least 1 in every 100 patients, but less than 1 in every 10 patients): 
thirst, dehydration, high blood pressure, migraines, swollen glands, flushing, menstrual problems, 
decreased sexual drive, vaginal problem, breast pain, pain in testicle, problems with thyroid gland, red 
gums, dry mouth, red or sore mouth or tongue, tooth ache or tooth disorder, herpes simplex (fever blisters), 
taste change, upset stomach, dyspepsia (heartburn), constipation, enlargement of liver (liver problems, 
sometimes severe), loose stools, bedwetting in children, inflammation of the sinuses, bronchitis, eye pain, 
problem with your tear ducts, conjunctivitis (“pink eye”), agitation, sleepiness, sleepwalking, problem with 
behaviour, nervousness, stuffy or runny nose, sneezing, rapid breathing, pale or reddened skin, bruising, 
fingers and toes very sensitive to cold, problem with skin or nails, psoriasis (new or worsened), increased 
sweating, increased need to pass urine, fine shaking movements, decreased sensitivity to touch, arthritis.  
 
Rarely reported side effects (at least 1 in every 10,000 patients, but less than 1 in every 1,000 patients): 
pneumonia 
 
Very rarely reported side effects (less than 1 in every 10,000 patients): 
low blood pressure, puffy face, diabetes, leg cramps, back pain, kidney problems, nerve damage, bleeding 
gums, aplastic anaemia. Pure red cell aplasia, a condition where the body stopped or reduced the production 
of red blood cells, has been reported. This causes severe anaemia, symptoms of which would include unusual 
tiredness and a lack of energy. 
 
Very rarely sarcoidosis, (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin 
lesions and swollen glands) has been reported. Loss of consciousness has occurred very rarely, mostly in 
elderly patients treated at high doses. Cases of stroke (cerebrovascular events) have been reported. Check 
with your doctor immediately if you have any of these symptoms.  
Periodontal (affecting gums) and dental disorders, altered mental status, loss of consciousness, acute 
hypersensitivity reactions including urticaria (hives), angioedema (swelling of the hands, feet, ankles, face, 
lips, mouth, or throat which may cause difficulty in swallowing or breathing), bronchoconstriction and 
anaphylaxis (a severe, whole-body allergic reaction) have been reported, but their frequency is unknown.  
 
Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin 
and the membranes of the ears, brain and spinal cord) has been reported with Viraferon use. 
 
Other side effects not listed above may also occur in some patients. If any of the side effects gets serious, or if you 
notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. 



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5. HOW TO STORE VIRAFERON 
 
Keep out of the reach and sight of children. 
 
Store in a refrigerator (2°C - 8°C).  
Do not freeze.  
Each pen is intended for a maximum four-week use period and must then be discarded. A maximum of 
48 hours (two days) of exposure to 25°C is permitted over the four-week period to cover accidental delays in 
returning the pen to the refrigerator. 
 
Depending upon your dose, you may have extra needles and swabs left in the pack. Please discard these 
appropriately and safely. 
 
Do not use Viraferon after the expiry date which is stated on the package. 
 
Do not use Viraferon if you notice changes in the appearance of Viraferon. 
 
 
6. FURTHER INFORMATION 
 
What Viraferon contains 
 
- The active substance is recombinant interferon alfa-2b, 30 million IU/pen 
- The other ingredients are disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, 

edetate disodium, sodium chloride, m-cresol, polysorbate 80 and water for injections. 
 
What Viraferon looks like and contents of the pack 
 
Viraferon is presented as a solution for injection 
The clear and colourless solution is contained in a glass cartridge. 
The pen is designed to deliver its contents of 30 million IU in doses ranging from 2.5 to 10 million IU. The 
pen will deliver a maximum of 12 doses of 2.5 million IU over a period not to exceed 4 weeks. 
 
Viraferon is available in three different pack sizes: 
Viraferon, 30 million IU/pen, solution for injection: 
- Pack of 1 pen, 12 injection needles and 12 cleansing swabs 
- Pack of 2 pens, 24 injection needles and 24 cleansing swabs 
- Pack of 8 pens, 96 injection needles and 96 cleansing swabs 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: Manufacturer: 
SP Europe SP Labo N.V. 
73, rue de Stalle Industriepark 30 
B-1180 Bruxelles B-2220 Heist-op-den-Berg 
Belgium Belgium 
 
For any information about this medicinal product, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Rue de Stalle/Stallestraat 73 
B-1180 Bruxelles/Brussel/Brüssel 
Tél/Tel: + 32-(0)2 370 92 11 

Luxembourg/Luxemburg 
Rue de Stalle 73 
B-1180 Bruxelles/Brüssel 
Belgique/Belgien 



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 Tél/Tel: + 32-(0)2 370 92 11 
 

България 
ул. "Проф. Милко Бичев" № 7, ет.3 
BG-София 1504  
Тел.: +359 2 944 1073 

Magyarország 
Alkotás u. 53. 
H-1123 Budapest 
Tel.: + 36 1 457-8500 

Česká republika 
Na Příkopě 25 
CZ-110 00 Praha 1 
Tel: + 420 221771250 
 

Malta 
168 Christopher Street 
MT-VLT02 Valletta 
Tel: + 356-21 23 21 75 
 

Danmark 
Lautrupbjerg 2 
DK-2750 Ballerup 
Tlf: + 45-44 39 50 00 

Nederland 
Maarssenbroeksedijk 4 
NL-3542 DN Utrecht 
Tel: + 31-(0)800 778 78 78 

Deutschland 
Thomas-Dehler-Straße 27 
D-81737 München  
Tel: + 49-(0)89 627 31-0 
 

Norge 
Pb. 398 
N-1326 Lysaker 
Tlf: + 47 67 16 64 50 
 

Eesti 
Järvevana tee 9 
EE-11314 Tallinn 
Tel: + 372 654 96 86 
 

Österreich 
Badener Strasse 23 
A-2514 Traiskirchen 
Tel: + 43-(0)2252 502-0 
 

Ελλάδα 
Αγίου Δημητρίου 63 
GR-174 55 Άλιμος  
Tηλ: + 30-210 98 97 300 
 

Polska 
Al. Jerozolimskie 195a 
PL-02-222 Warszawa 
Tel.: + 48-(0)22 478 41 50 
 

España 
Km. 36, Ctra. Nacional I 
E-28750 San Agustín de Guadalix – Madrid 
Tel: + 34-91 848 85 00 
 

Portugal 
Rua Agualva dos Açores 16 
P-2735-557 Agualva-Cacém 
Tel: + 351-21 433 93 00 
 



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France 
92 rue Baudin  
F-92300 Levallois-Perret 
Tél: + 33-(0)1 41 06 35 00 
 

România 
Şos. Bucureşti-Ploieşti, nr. 17-21,  
Băneasa Center, et. 8, sector 1 
RO-013682 Bucureşti 
Tel. + 40 21 233 35 30 
 

Ireland 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW 
Tel: + 44-(0)1 707 363 636 

Slovenija 
Dunajska 22 
SI-1000 Ljubljana 
Tel. + 386 01 3001070 
 

Ísland 
Hörgatún 2 
IS-210 Garðabær 
Sími: + 354 535 70 00 

Slovenská republika 
Strakova 5 
SK-811 01 Bratislava 
Tel: + 421 (2) 5920 2712 
 

Italia 
Via fratelli Cervi snc, 
Centro Direzionale Milano Due 
Palazzo Borromini 
I-20090 Segrate (Milano) 
Tel: + 39-02 21018.1 
 

Suomi/Finland 
PL 3/PB 3 
FIN-02201 Espoo/Esbo 
Puh/Tel: + 358-(0)20-7570 300 
 

Κύπρος 
Οδός Αγίου Νικολάου, 8 
CY-1055 Λευκωσία 
Τηλ: + 357-22 757188 
 

Sverige 
Box 6185 
S-102 33 Stockholm 
Tel: + 46-(0)8 522 21 500 
 

Latvija 
Bauskas 58a -401 
Rīga, LV-1004  
Tel: + 371-7 21 38 25 
 

United Kingdom 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW - UK 
Tel: + 44-(0)1 707 363 636 
 

Lietuva 
Kęstučio g. 65/40 
LT-08124 Vilnius 
Tel. + 370 52 101868 

 

 
 
This leaflet was last approved on 
 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: 
http://www.emea.europa.eu/ 
 



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HOW TO SELF INJECT VIRAFERON 
 
The following instructions explain how to inject Viraferon yourself. Please read the instructions carefully and 
follow them step by step. Your doctor or his/her assistant will instruct you how to self-inject Viraferon. Do 
not attempt to inject yourself unless you are sure you understand the procedure and requirement of self-
injection. 
 
Preparation 
Collect necessary items before you begin: 
- the Viraferon multidose pen; 
- a needle for subcutaneous injection (provided in the packaging); 
- a cleansing swab. 
Wash your hands carefully. Use the injection needles provided in the packaging only for Viraferon. Use a new 
injection needle for each dose. Be sure the solution is at room temperature at the time of injection. 
 
Diagrams A and B show you all the different parts of the pen and the injection needle. The most important 
parts to note are as follows: 
 
- The push button scale tells you what dose has been set. 
- The colour coding strip blue and the push button are at the bottom of the pen as it is held cap up. 
- The pen can only be fully capped when the triangle on the cap scale is aligned with the dosage 

indicator on the barrel. 
 

    
 

 
 Diagram A Diagram B 

Cap 

Cap 
scale 

Rubber 
membrane 

Dosage 
indicator 

Push 
button 
scale 

Needle 

Reservoir 

Pen barrel 

Colour 
coding 

Push 
button 



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Measuring the dose of Viraferon 
Take the pen out of the refrigerator about one-half hour before administering the dose so that the solution in 
the pen is at room temperature when it is injected. 
 
When you are ready to give your injection prepare your pen as follows: 
 
Check that Viraferon, solution for injection, is clear and colourless in appearance prior to use. If it does not 
have a clear uniform appearance or if it contains any particles, do not use. 
 
Pull off the cap of the pen and disinfect the rubber membrane (see Diagram C) with one cleansing swab. 

 
 

Diagram C 
 
Remove the protective tab from the injection needle. Note that the rear portion of the injection needle is 
revealed once the protective tab is removed (see Diagram D). 
 

 
 

Diagram D 
 
Gently push the injection needle onto the pen as shown in Diagram E. (Notice that the rear portion of the 
injection needle will pierce through the rubber membrane that you disinfected previously). Now screw the 
injection needle onto the pen securely by turning it in a clockwise direction (see Diagram F). 
 

 

 

 
 
 Diagram E Diagram F 
 



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First, pull off the outer injection needle cap (Diagram G). Then, pull off the inner injection needle cap 
carefully, bearing in mind that the injection needle will now be exposed (Diagram H). Keep the outer 
injection needle cap for later use. 
 
 

 

 

 

 
 
 Diagram G Diagram H 
 
The pen is now ready to use. Since a small amount of air may collect in the injection needle and reservoir 
during storage, the next step is to remove any air bubbles. This is called performing the Air-Shot. 
 
Hold the Viraferon, solution for injection, multidose pen with the injection needle point upwards. 
 
Tap the reservoir with your finger so that any air bubbles rise to the top of the reservoir, just below the 
injection needle (Diagram I). 

 
 

Diagram I 
 
Hold the pen by the barrel and turn the reservoir in the direction as indicated by the arrow in Diagram J 
(clockwise) until you feel it click. 
 

 
 

Diagram J 
 



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Keeping the pen pointing upwards, press the push button up fully and see if a drop of Viraferon, solution for 
injection, appears at the injection needle tip (Notice the drop at the tip of injection needle in Diagram K 
below). 
 

 
 

Diagram K 
 
If no drop appears, use a different pen, and return the faulty pen to your provider. 
 
Note: some air may remain in the pen, but this is not important as you have removed the air from the 
injection needle and the dose will be accurate. 
 
Replace the Viraferon, solution for injection, multidose pen cap with the ‘triangle’ opposite the dosage 
indicator as seen in Diagram L. 
 

 
 

Diagram L 
 
The pen is now ready to set the dose. For the next step hold the pen in the middle of the barrel. This will 
allow the push button to move freely, ensuring that the correct dose is set. 
 



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To set the required dose, hold the pen horizontally by the barrel with one hand. With the other hand, turn the 
cap in a clockwise direction indicated by the arrow in Diagram M. You will observe the push button rising, 
indicating the dose set. To set the correct dose, turn the cap as many times as indicated as follows: 
 

Number of “turns” and 
“clicks” 

Corresponding doses (million IU) using 
Viraferon, solution for injection, multidose 

pen 30 million IU/pen: 

 

1 full turn (5 clicks) 

6 clicks 

7 clicks 

8 clicks 

9 clicks 

2 full turns (10 clicks) 

11 clicks 

12 clicks 

13 clicks 

14 clicks 

3 full turns (15 clicks) 

16 clicks 

17 clicks 

18 clicks 

19 clicks 

4 full turns (20 clicks)* 

2.5 

3 

3.5 

4 

4.5 

5 

5.5 

6 

6.5 

7 

7.5 

8 

8.5 

9 

9.5 

10 

 

 
 

Diagram M 
 

* 4 full turns correspond to the maximum dose to be administered in one injection. The pen is designed to deliver its contents of 
30 million IU in doses ranging from 2.5 to 10 million IU. The pen will deliver a maximum of 12 doses of 2.5 million IUover a period 
not to exceed 4 weeks. 
 



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The push button scale will show you the dose set (see Diagram N below). For doses corresponding to full 
turns, the scale should line up with the correct dose marking. For doses corresponding to clicks intermediate 
between full turns, the scale should line up between the two appropriate full-turn dose markings. At that point 
check that you have the correct dose. 
 
 

 
 

Diagram N 
 
After each complete turn make sure that the triangle is opposite the dosage indicator (see Diagram O). If you 
have set a wrong dose, simply turn the cap back (anti-clockwise) as far as you can until the push button is 
fully home and start again. Once the correct dose is set you are ready to give the injection. 

 
Diagram O 

Injecting the solution 
Select the injection site. The best sites for injection are tissues with a layer of fat between skin and muscle: 
thigh, outer surface of the upper arm (you may need the assistance of another person to use this site), 
abdomen (except the navel or waistline). If you are exceptionally thin, use only the thigh or outer surface of 
the arm for injection. Change your injection site each time. 
 
Cleanse and disinfect the skin where the injection is to be made. Wait for the area to dry. 
With one hand, pinch a fold of loose skin. With your other hand, pick up the pen and hold it as you would a 
pencil. Insert the needle into the pinched skin at an angle of approximately 45°. 
 



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Then press the push button down fully (see Diagram P). 
 

 
Diagram P 

 
Keeping the push button down, leave the injection needle in place for a few seconds to allow the Viraferon, 
solution for injection, to distribute under the skin, then remove. 
 
Carefully replace the outer injection needle cap (See Diagram Q). 
 

 
Diagram Q 

 
Completely unscrew the injection needle assembly using an anti-clockwise turning motion as shown in 
Diagram R. Then carefully lift it off the pen and discard the capped injection needle (see Diagram S). 
 
 

 

 
 Diagram R Diagram S 



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Replace the pen cap with the triangle once again opposite the dosage indicator as shown in Diagram T. Then 
return the pen to the refrigerator. 

 
Diagram T 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Viraferon, 60 million IU solution for injection, multidose pen 
Interferon alfa-2b 

 
Read all of this leaflet carefully before you start using this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Viraferon is and what it is used for 
2. Before you use Viraferon 
3. How to use Viraferon 
4. Possible side effects 
5. How to store Viraferon 
6. Further information 
 
 
1. WHAT VIRAFERON IS AND WHAT IT IS USED FOR 
 
Viraferon (interferon alfa-2b) modifies the response of the body's immune system to help fight infections and 
severe diseases. Viraferon is used in adult patients for the treatment of chronic hepatitis B or C, which are viral 
infections of the liver. 
 
Viraferon is used in combination with ribavirin in children and adolescents 3 years of age and older who have 
previously untreated chronic hepatitis C. 
 
 
2. BEFORE YOU USE VIRAFERON 
 
Do not use Viraferon 
- if you are allergic (hypersensitive) to interferon or any of the other ingredients of Viraferon. 
- if you have severe heart disease. 
- if you have poor kidney or liver function. 
- if you have advanced decompensated (uncontrolled) liver disease. 
- if you have hepatitis and have been treated recently with medications that suppress the immune system 

(other than short-term treatment with cortisone-type medicine). 
- if you have a history of seizures (convulsions). 
- if you have a history of autoimmune disease, or have had an organ transplant and are taking medicine that 

suppresses your immune system (your immune system helps protect you from infection). 
- if you have thyroid disease that is not well controlled. 
Children and adolescents: 
- if you have had serious nervous or mental problems, such as severe depression or thoughts of suicide. 
 
Take special care with Viraferon 
- if you are pregnant or planning to become pregnant (see Pregnancy). 
- if you have had a severe nervous or mental disorder. The use of interferon alfa-2b in children and 

adolescents with existence of or history of severe psychiatric conditions is contraindicated (see “Do not use 
Viraferon”) 

- if you have ever had depression or develop symptoms associated with depression (e.g. feelings of sadness, 
dejection, etc.) while on treatment with Viraferon (see section 4). 



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- if you have psoriasis, it may get worse during treatment with Viraferon. 
- when receiving Viraferon, you may temporarily have a greater risk of getting an infection. Check with 

your doctor if you think you are getting an infection. 
- if you develop symptoms associated with a cold or other respiratory infection, such as fever, cough, or any 

difficulty in breathing, tell your doctor. 
- if you notice unusual bleeding or bruising check with your doctor immediately. 
- if you develop symptoms of a severe allergic reaction (such as difficulty in breathing, wheezing, or hives) 

while on this medication seek medical help immediately. 
- if you are also being treated for HIV, please see Using other medicines. 
- if you have received an organ transplant, either kidney or liver, interferon treatment may increase the risk 

of rejection. Be sure to discuss this with your doctor. 
 
Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving Viraferon 
and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and 
membranes of the mouth during long-term treatment with the combination of Viraferon with ribavirin. You 
should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some 
patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly 
afterwards. 
 
During the one year of treatment, many children did not grow or gain weight as much as expected. However, 
during the 6 months after treatment, this trend was generally reversed, although a few children did not return 
to their previous rate of growth within the first year after completing treatment. 
 
Tell your doctor if you have ever had a heart attack or a heart problem; if you have a history of breathing 
irregularities or pneumonia, problems with blood clotting, liver condition, thyroid problems, diabetes, or high 
or low blood pressure. 
 
Tell your doctor if you have ever been treated for depression or any other psychiatric disorder; confusion; 
unconsciousness; thoughts of suicide or attempted suicide. 
 
Be sure to tell your doctor if you are taking the Chinese herbal medication Shosaikoto. 
 
Using other medicines 
Viraferon will add to the effects of substances that slow down your nervous system, possibly causing 
drowsiness. Therefore, check with your doctor or pharmacist about drinking alcoholic beverages, or taking 
sleeping pills, sedatives or strong pain medications.  
 
Tell your doctor if you are taking theophylline or aminophylline for asthma, and about all other medication 
you are taking, or have taken recently, even those not prescribed, as the dose of some medications may have 
to be adjusted while you are treated with Viraferon. 

 
Patients who also have HIV infection: Lactic acidosis and worsening liver function are side effects associated 
with Highly Active Anti-Retroviral Therapy (HAART), an HIV treatment. If you are receiving HAART, the 
addition of Viraferon and ribavirin may increase your risk of lactic acidosis and of liver failure. Your doctor 
will monitor you for signs and symptoms of these conditions (Please be sure to read the ribavirin Patient 
Leaflet also). Additionally, patients treated with Viraferon and ribavirin combination therapy and zidovudine 
could be at increased risk of developing anaemia (low number of red blood cells). 
 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. 
 
Using Viraferon with food and drink 
While being treated with Viraferon, your doctor may want you to drink extra fluids to help prevent low blood 
pressure. 
 



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Pregnancy and breast-feeding 
Ask your doctor or pharmacist for advice before taking any medicine. In studies in pregnant animals, 
interferons have sometimes caused miscarriage. The effect on human pregnancy is not known. 
If you are prescribed Viraferon in combination with ribavirin, ribavirin can be very damaging to an unborn 
baby, thus both female and male patients must take special precautions in their sexual activity if there is any 
chance for pregnancy to occur: 
- if you are a girl or a woman of childbearing age, you must have a negative pregnancy test before treatment, 
each month during treatment, and for the 4 months after treatment is stopped. You and your partner must 
each use an effective contraceptive during the time you are taking ribavirin and for 4 months after stopping 
treatment. This can be discussed with your doctor.  
- if you are a man who is taking ribavirin, do not have sex with a pregnant woman unless you use a condom. 
This will lessen the chance for ribavirin to be left in the woman’s body. If your female partner is not pregnant 
now but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 
7 months after treatment has stopped. This can be discussed with your doctor. If you are a male patient, you 
and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 
7 months after stopping treatment. This can be discussed with your doctor. 
 
It is not known whether this product is present in human milk. Therefore, do not breast-feed an infant if you 
are taking Viraferon. In combination therapy with ribavirin, take notice of the respective informing texts of 
ribavirin containing medicinal products. 
 
Driving and using machines 
Do not drive or use machinery if you become drowsy, tired, or confused from this medicine. 
 
 
3. HOW TO USE VIRAFERON 
 
Your doctor has prescribed Viraferon specifically for you and your current condition; do not share this medicine 
with anyone else. 
 
Your doctor has determined the exact dosage for administration of Viraferon according to your individual needs. 
The dosage will vary according to the disease being treated. 
 
If you are injecting Viraferon yourself, please be sure that the dose that has been prescribed for you is clearly 
provided with the package of medicine you receive. Dosages that are to be administered 3 times a week are best 
given every other day. 
 
The usual starting dose for each condition follows; however, individual doses may vary, and the doctor may 
change your dose based on your specific needs: 
 
Chronic hepatitis B: 5 to 10 million IU 3 times a week (every other day) injected subcutaneously (under the skin). 
 
Chronic hepatitis C: Adults - 3 million IU 3 times a week (every other day) injected subcutaneously (under the 
skin) in combination with ribavirin or alone. Children 3 years of age and older and adolescents - 
3 million IU/m2 3 times a week (every other day) injected subcutaneously (under the skin) in combination with 
ribavirin (Please also see ribavirin package leaflet).  
 
Your doctor may prescribe a different dose of Viraferon alone or in combination with other medicines (e.g. 
ribavirin). If you are prescribed Viraferon in combination with another medicine, please refer also to the Package 
Leaflet of the medicine to be used in combination. Your doctor will determine the exact dosage schedule and 
regimen according to your needs. If you have the impression that the effect of Viraferon is too strong or too 
weak, talk to your doctor or pharmacist. 
 
Subcutaneous use: 



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Viraferon is usually intended for subcutaneous use. This means that Viraferon is injected with a short needle into 
the fatty tissue just under the skin. If you are injecting this medicine yourself, you will be instructed how to 
prepare and give the injection. Detailed instructions for subcutaneous administration are provided with this leaflet 
(see HOW TO SELF INJECT VIRAFERON at the end of the leaflet). 
 
One dose of Viraferon is given on each scheduled day. Viraferon is given three times a week, every other day, for 
example on Monday, Wednesday, and Friday. Interferons may cause unusual tiredness; if you are injecting this 
medicine yourself, or giving it to a child, use it at bedtime. 
 
Use Viraferon exactly as prescribed by your doctor. Do not exceed the recommended dosage, and take Viraferon 
for as long as prescribed. 
 
If you use more Viraferon than you should 
Contact your doctor or healthcare professional as soon as possible. 
 
If you forget to take Viraferon 
If you are self-administering treatment, or if you are the caregiver of a child taking Viraferon in combination 
with ribavirin, inject the recommended dose as soon as you remember and continue treatment as usual. Do 
not take a double dose to make up for a forgotten dose. If you are scheduled to inject this product every day, 
and you accidentally missed a full day’s dose, continue treatment at the usual dose the following day. Contact 
your doctor or pharmacist if needed. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Viraferon can cause side effects, although not everybody gets them. Although not all of 
these side effects may occur, they may need medical attention if they do. 
 
Some people get depressed when taking Viraferon alone or in combination treatment with ribavirin, and in some 
cases people had suicidal thoughts or aggressive behaviour (sometimes directed against others). Some patients have 
actually committed suicide. Be sure to seek emergency care if you notice that you are becoming depressed or have 
suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend 
to help you stay alert to signs of depression or changes in your behaviour. 
 
Paediatric Use: Children are particularly prone to develop depression when being treated with Viraferon and 
ribavirin. Immediately contact the doctor or seek emergency care if they display any unusual behavioural 
symptoms, feel depressed, or feel they want to harm themselves or others. 
 
If any of the following side effects happen, stop taking Viraferon and tell your doctor immediately or go to 
the casualty department at your nearest hospital: 
• swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in 

swallowing or breathing; hives; fainting. 
These are all very serious side effects. If you have them, you may have had a serious allergic reaction to 
Viraferon. You may need urgent medical attention or hospitalisation. These very serious side effects are very 
rare. 
 
Check with your doctor immediately if any of the following side effects occur: 
• chest pain or persistent and severe cough; irregular or rapid heartbeat; shortness of breath, confusion, 

difficulty remaining alert, numbness or tingling sensation or pain in hands or feet; seizure 
(convulsions); trouble sleeping, thinking or concentrating; altered mental state; suicidal thoughts, 
suicide attempt, changed behaviour or aggressive behaviour (sometimes directed against others), 
hallucinations; severe stomach pain; black or tar like stools; blood in stool or urine, severe 
nosebleed; waxy pallor, high sugar level in blood, fever or chills beginning after a few weeks of 



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treatment, lower back or side pain, difficult urination, problems with your eyes or your eyesight or 
hearing, loss of hearing, severe or painful reddening or sores on your skin or mucous membrane. 

These may signal serious side effects that may need urgent medical attention. Your doctor will test your 
blood to ensure that your white blood cell (cells that fight infection) and red blood cell (cells that carry iron 
and oxygen) counts, platelets (blood clotting cells) and other laboratory values are at acceptable levels. 
 
At the beginning of treatment with Viraferon, you may experience a flu-like reaction, with fever, fatigue, 
headache, muscle ache, joint pain and chills/rigors. Your doctor may recommend that you take paracetamol if 
you develop these symptoms. 
 
Other side effects that may occur include: 
 
Very commonly reported side effects (at least 1 in every 10 patients):  
pain, swelling and redness or skin damage at site of injection, hair loss, dizziness, changes in appetite, 
stomach or abdominal pains, diarrhoea, nausea (feeling sick), viral infection, depression, emotional lability, 
insomnia, anxiety, sore throat and painful swallowing, fatigue, chills/rigors, fever, flu-like reaction, feeling 
of general discomfort, headaches, weight loss, vomiting, irritability, weakness, mood swings, coughing 
(sometimes severe), shortness of breath, itching, dry skin, rash, sudden and severe muscle pain, joint pain, 
musculoskeletal pain, changes in laboratory blood values including decreased white blood cell count. Some 
children have had a decrease in their rate of growth (height and weight). 
 
Commonly reported side effects (at least 1 in every 100 patients, but less than 1 in every 10 patients): 
thirst, dehydration, high blood pressure, migraines, swollen glands, flushing, menstrual problems, 
decreased sexual drive, vaginal problem, breast pain, pain in testicle, problems with thyroid gland, red 
gums, dry mouth, red or sore mouth or tongue, tooth ache or tooth disorder, herpes simplex (fever blisters), 
taste change, upset stomach, dyspepsia (heartburn), constipation, enlargement of liver (liver problems, 
sometimes severe), loose stools, bedwetting in children, inflammation of the sinuses, bronchitis, eye pain, 
problem with your tear ducts, conjunctivitis (“pink eye”), agitation, sleepiness, sleepwalking, problem with 
behaviour, nervousness, stuffy or runny nose, sneezing, rapid breathing, pale or reddened skin, bruising, 
fingers and toes very sensitive to cold, problem with skin or nails, psoriasis (new or worsened), increased 
sweating, increased need to pass urine, fine shaking movements, decreased sensitivity to touch, arthritis.  
 
Rarely reported side effects (at least 1 in every 10,000 patients, but less than 1 in every 1,000 patients): 
pneumonia 
 
Very rarely reported side effects (less than 1 in every 10,000 patients): 
low blood pressure, puffy face, diabetes, leg cramps, back pain, kidney problems, nerve damage, bleeding 
gums, aplastic anaemia. Pure red cell aplasia, a condition where the body stopped or reduced the production 
of red blood cells, has been reported. This causes severe anaemia, symptoms of which would include unusual 
tiredness and a lack of energy. 
 
Very rarely sarcoidosis, (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin 
lesions and swollen glands) has been reported. Loss of consciousness has occurred very rarely, mostly in 
elderly patients treated at high doses. Cases of stroke (cerebrovascular events) have been reported. Check 
with your doctor immediately if you have any of these symptoms.  
Periodontal (affecting gums) and dental disorders, altered mental status, loss of consciousness, acute 
hypersensitivity reactions including urticaria (hives), angioedema (swelling of the hands, feet, ankles, face, 
lips, mouth, or throat which may cause difficulty in swallowing or breathing), bronchoconstriction and 
anaphylaxis (a severe, whole-body allergic reaction) have been reported, but their frequency is unknown.  
 
Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin 
and the membranes of the ears, brain and spinal cord) has been reported with Viraferon use. 
 
Other side effects not listed above may also occur in some patients. If any of the side effects gets serious, or if you 
notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. 



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5. HOW TO STORE VIRAFERON 
 
Keep out of the reach and sight of children. 
 
Store in a refrigerator (2°C - 8°C).  
Do not freeze.  
Each pen is intended for a maximum four-week use period and must then be discarded. A maximum of 
48 hours (two days) of exposure to 25°C is permitted over the four-week period to cover accidental delays in 
returning the pen to the refrigerator. 
 
Depending upon your dose, you may have extra needles and swabs left in the pack. Please discard these 
appropriately and safely. 
 
Do not use Viraferon after the expiry date which is stated on the package. 
 
Do not use Viraferon if you notice changes in the appearance of Viraferon. 
 
 
6. FURTHER INFORMATION 
 
What Viraferon contains 
 
- The active substance is recombinant interferon alfa-2b, 60 million IU/pen 
- The other ingredients are disodium phosphate anhydrous, Sodium dihydrogen phosphate monohydrate, 

edetate disodium, sodium chloride, m-cresol, polysorbate 80 and water for injections. 
 
What Viraferon looks like and contents of the pack 
 
Viraferon is presented as a solution for injection 
The clear and colourless solution is contained in a glass cartridge. 
The pen is designed to deliver its contents of 60 million IU in doses ranging from 5 to 20 million IU. The pen 
will deliver a maximum of 12 doses of 5 million IU over a period not to exceed 4 weeks. 
 
Viraferon is available in three different pack sizes: 
Viraferon, 60 million IU/pen, solution for injection: 
- Pack of 1 pen, 12 injection needles and 12 cleansing swabs 
- Pack of 2 pens, 24 injection needles and 24 cleansing swabs 
- Pack of 8 pens, 96 injection needles and 96 cleansing swabs 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: Manufacturer: 
SP Europe SP Labo N.V. 
73, rue de Stalle Industriepark 30 
B-1180 Bruxelles B-2220 Heist-op-den-Berg 
Belgium Belgium 
 
For any information about this medicinal product, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Rue de Stalle/Stallestraat 73 
B-1180 Bruxelles/Brussel/Brüssel 
Tél/Tel: + 32-(0)2 370 92 11 

Luxembourg/Luxemburg 
Rue de Stalle 73 
B-1180 Bruxelles/Brüssel 
Belgique/Belgien 



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 Tél/Tel: + 32-(0)2 370 92 11 
 

България 
ул. "Проф. Милко Бичев" № 7, ет.3 
BG-София 1504  
Тел.: +359 2 944 1073 

Magyarország 
Alkotás u. 53. 
H-1123 Budapest 
Tel.: + 36 1 457-8500 

Česká republika 
Na Příkopě 25 
CZ-110 00 Praha 1 
Tel: + 420 221771250 
 

Malta 
168 Christopher Street 
MT-VLT02 Valletta 
Tel: + 356-21 23 21 75 
 

Danmark 
Lautrupbjerg 2 
DK-2750 Ballerup 
Tlf: + 45-44 39 50 00 

Nederland 
Maarssenbroeksedijk 4 
NL-3542 DN Utrecht 
Tel: + 31-(0)800 778 78 78 

Deutschland 
Thomas-Dehler-Straße 27 
D-81737 München  
Tel: + 49-(0)89 627 31-0 
 

Norge 
Pb. 398 
N-1326 Lysaker 
Tlf: + 47 67 16 64 50 
 

Eesti 
Järvevana tee 9 
EE-11314 Tallinn 
Tel: + 372 654 96 86 

Österreich 
Badener Strasse 23 
A-2514 Traiskirchen 
Tel: + 43-(0)2252 502-0 

Ελλάδα 
Αγίου Δημητρίου 63 
GR-174 55 Άλιμος  
Tηλ: + 30-210 98 97 300 
 

Polska 
Al. Jerozolimskie 195a 
PL-02-222 Warszawa 
Tel.: + 48-(0)22 478 41 50 
 

España 
Km. 36, Ctra. Nacional I 
E-28750 San Agustín de Guadalix – Madrid 
Tel: + 34-91 848 85 00 
 

Portugal 
Rua Agualva dos Açores 16 
P-2735-557 Agualva-Cacém 
Tel: + 351-21 433 93 00 
 

France 
92 rue Baudin  
F-92300 Levallois-Perret 
Tél: + 33-(0)1 41 06 35 00 
 

România 
Şos. Bucureşti-Ploieşti, nr. 17-21,  
Băneasa Center, et.8, sector 1 
RO-013682 Bucureşti 
Tel. + 40 21 233 35 30 

Ireland 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW 
Tel: + 44-(0)1 707 363 636 

Slovenija 
Dunajska 22 
SI-1000 Ljubljana 
Tel. + 386 01 3001070 
 

Ísland 
Hörgatún 2 
IS-210 Garðabær 
Sími: + 354 535 70 00 
 

Slovenská republika 
Strakova 5 
SK-811 01 Bratislava 
Tel: + 421 (2) 5920 2712 
 

Italia 
Via fratelli Cervi snc, 
Centro Direzionale Milano Due 
Palazzo Borromini 
I-20090 Segrate (Milano) 
Tel: + 39-02 21018.1 

Suomi/Finland 
PL 3/PB 3 
FIN-02201 Espoo/Esbo 
Puh/Tel: + 358-(0)20-7570 300 
 



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Κύπρος 
Οδός Αγίου Νικολάου, 8 
CY-1055 Λευκωσία 
Τηλ: + 357-22 757188 
 

Sverige 
Box 6185 
S-102 33 Stockholm 
Tel: + 46-(0)8 522 21 500 
 

Latvija 
Bauskas 58a -401 
Rīga, LV-1004  
Tel: + 371-7 21 38 25 

United Kingdom 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW - UK 
Tel: + 44-(0)1 707 363 636 
 

Lietuva 
Kęstučio g. 65/40 
LT-08124 Vilnius 
Tel. + 370 52 101868 

 

 
 
This leaflet was last approved on 
 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: 
http://www.emea.europa.eu/ 
 



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HOW TO SELF INJECT VIRAFERON 
 
The following instructions explain how to inject Viraferon yourself. Please read the instructions carefully and 
follow them step by step. Your doctor or his/her assistant will instruct you how to self-inject Viraferon. Do 
not attempt to inject yourself unless you are sure you understand the procedure and requirement of self-
injection. 
 
Preparation 
Collect necessary items before you begin: 
- the Viraferon multidose pen; 
- a needle for subcutaneous injection (provided in the packaging); 
- a cleansing swab. 
Wash your hands carefully. Use the injection needles provided in the packaging only for Viraferon. Use a new 
injection needle for each dose. Be sure the solution is at room temperature at the time of injection. 
 
Diagrams A and B show you all the different parts of the pen and the injection needle. The most important 
parts to note are as follows: 
 
- The push button scale tells you what dose has been set. 
- The colour coding strip pink and the push button are at the bottom of the pen as it is held cap up. 
- The pen can only be fully capped when the triangle on the cap scale is aligned with the dosage 

indicator on the barrel. 
 

    
 

 
 Diagram A Diagram B 

Cap 

Cap 
scale 

Rubber 
membrane 

Dosage 
indicator 

Push 
button 
scale 

Needle 

Reservoir 

Pen barrel 

Colour 
coding 

Push 
button 



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Measuring the dose of Viraferon 
Take the pen out of the refrigerator about one-half hour before administering the dose so that the solution in 
the pen is at room temperature when it is injected. 
 
When you are ready to give your injection prepare your pen as follows: 
 
Check that Viraferon, solution for injection, is clear and colourless in appearance prior to use. If it does not 
have a clear uniform appearance or if it contains any particles, do not use. 
 
Pull off the cap of the pen and disinfect the rubber membrane (see Diagram C) with one cleansing swab. 

 
 

Diagram C 
 
Remove the protective tab from the injection needle. Note that the rear portion of the injection needle is 
revealed once the protective tab is removed (see Diagram D). 
 

 
 

Diagram D 
 
Gently push the injection needle onto the pen as shown in Diagram E. (Notice that the rear portion of the 
injection needle will pierce through the rubber membrane that you disinfected previously). Now screw the 
injection needle onto the pen securely by turning it in a clockwise direction (see Diagram F). 
 

 

 

 
 
 Diagram E Diagram F 
 



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First, pull off the outer injection needle cap (Diagram G). Then, pull off the inner injection needle cap 
carefully, bearing in mind that the injection needle will now be exposed (Diagram H). Keep the outer 
injection needle cap for later use. 
 
 

 

 

 

 
 
 Diagram G Diagram H 
 
The pen is now ready to use. Since a small amount of air may collect in the injection needle and reservoir 
during storage, the next step is to remove any air bubbles. This is called performing the Air-Shot. 
 
Hold the Viraferon, solution for injection, multidose pen with the injection needle point upwards. 
 
Tap the reservoir with your finger so that any air bubbles rise to the top of the reservoir, just below the 
injection needle (Diagram I). 

 
 

Diagram I 
 
Hold the pen by the barrel and turn the reservoir in the direction as indicated by the arrow in Diagram J 
(clockwise) until you feel it click. 
 

 
 

Diagram J 
 



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Keeping the pen pointing upwards, press the push button up fully and see if a drop of Viraferon, solution for 
injection, appears at the injection needle tip (Notice the drop at the tip of injection needle in Diagram K 
below). 
 

 
 

Diagram K 
 
If no drop appears, use a different pen, and return the faulty pen to your provider. 
 
Note: some air may remain in the pen, but this is not important as you have removed the air from the 
injection needle and the dose will be accurate. 
 
Replace the Viraferon, solution for injection, multidose pen cap with the ‘triangle’ opposite the dosage 
indicator as seen in Diagram L. 
 

 
 

Diagram L 
 
The pen is now ready to set the dose. For the next step hold the pen in the middle of the barrel. This will 
allow the push button to move freely, ensuring that the correct dose is set. 
 



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To set the required dose, hold the pen horizontally by the barrel with one hand. With the other hand, turn the 
cap in a clockwise direction indicated by the arrow in Diagram M. You will observe the push button rising, 
indicating the dose set. To set the correct dose, turn the cap as many times as indicated as follows: 
 

Number of “turns” and 
“clicks” 

Corresponding doses (million IU) using 
Viraferon, solution for injection, multidose pen 

60 million IU/pen: 

 

1  full turn (5 clicks) 

6 clicks 

7 clicks 

8 clicks 

9 clicks 

2 full turns (10 clicks) 

11 clicks 

12 clicks 

13 clicks 

14 clicks 

3 full turns (15 clicks) 

16 clicks 

17 clicks 

18 clicks 

19 clicks 

4 full turns (20 clicks)* 

5 

6 

7 

8 

9 

10 

11 

12 

13 

14 

15 

16 

17 

18 

19 

20 

 

 
 
 

Diagram M 

*4  full turns correspond to the maximum dose to be administered in one injection. The pen is designed to deliver its contents of 
60 million IU in doses ranging from 5 to 20 million IU. The pen will deliver a maximum of 12 doses of 5 million IU over a period not 
to exceed 4 weeks. 
 



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The push button scale will show you the dose set (see Diagram N below). For doses corresponding to full 
turns, the scale should line up with the correct dose marking. For doses corresponding to clicks intermediate 
between full turns, the scale should line up between the two appropriate full-turn dose markings. At that point 
check that you have the correct dose. 
 

 
Diagram N 

 
After each complete turn make sure that the triangle is opposite the dosage indicator (see Diagram O). If you 
have set a wrong dose, simply turn the cap back (anti-clockwise) as far as you can until the push button is 
fully home and start again. Once the correct dose is set you are ready to give the injection. 

 
Diagram O 

Injecting the solution 
Select the injection site. The best sites for injection are tissues with a layer of fat between skin and muscle: 
thigh, outer surface of the upper arm (you may need the assistance of another person to use this site), 
abdomen (except the navel or waistline). If you are exceptionally thin, use only the thigh or outer surface of 
the arm for injection. Change your injection site each time. 
 
Cleanse and disinfect the skin where the injection is to be made. Wait for the area to dry. 
With one hand, pinch a fold of loose skin. With your other hand, pick up the pen and hold it as you would a 
pencil. Insert the needle into the pinched skin at an angle of approximately 45°. 
 
Then press the push button down fully (see Diagram P). 

 
Diagram P 

 



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Keeping the push button down, leave the injection needle in place for a few seconds to allow the Viraferon, 
solution for injection, to distribute under the skin, then remove. 
 
Carefully replace the outer injection needle cap (See Diagram Q). 
 

 
Diagram Q 

 
Completely unscrew the injection needle assembly using an anti-clockwise turning motion as shown in 
Diagram R. Then carefully lift it off the pen and discard the capped injection needle (see Diagram S). 
 
 

 

 
 
 
 Diagram R Diagram S 
 



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Replace the pen cap with the triangle once again opposite the dosage indicator as shown in Diagram T. Then 
return the pen to the refrigerator. 
 

 
 

Diagram T 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE ANDMANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OF THE MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET