Plegridy

1  
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 
Plegridy 63 micrograms solution for injection in pre-filled syringe 
Plegridy 94 micrograms solution for injection in pre-filled syringe 
Plegridy 125 micrograms solution for injection in pre-filled syringe 
Plegridy 63 micrograms solution for injection in pre-filled pen 
Plegridy 94 micrograms solution for injection in pre-filled pen 
Plegridy 125 micrograms solution for injection in pre-filled pen 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Plegridy 63 micrograms solution for injection in pre-filled syringe (for subcutaneous use) 
Each pre-filled syringe contains 63 micrograms of peginterferon beta-1a* in 0.5 mL solution for 
injection. 
 
Plegridy 94 micrograms solution for injection in pre-filled syringe (for subcutaneous use) 
Each pre-filled syringe contains 94 micrograms of peginterferon beta-1a* in 0.5 mL solution for 
injection. 
 
Plegridy 125 micrograms solution for injection in pre-filled syringe (for subcutaneous use) 
Each pre-filled syringe contains 125 micrograms of peginterferon beta-1a* in 0.5 mL solution for 
injection. 
 
Plegridy 125 micrograms solution for injection in pre-filled syringe (for intramuscular use) 
Each pre-filled syringe contains 125 micrograms of peginterferon beta-1a* in 0.5 mL solution for 
injection. 
 
Plegridy 63 micrograms solution for injection in pre-filled pen (for subcutaneous use) 
Each pre-filled pen contains 63 micrograms of peginterferon beta-1a* in 0.5 mL solution for injection. 
 
Plegridy 94 micrograms solution for injection in pre-filled pen (for subcutaneous use) 
Each pre-filled pen contains 94 micrograms of peginterferon beta-1a* in 0.5 mL solution for injection. 
 
Plegridy 125 micrograms solution for injection in pre-filled pen (for subcutaneous use)Each pre-filled 
pen contains 125 micrograms of peginterferon beta-1a* in 0.5 mL solution for injection. 
 
The dose indicates the quantity of the interferon beta-1a moiety of peginterferon beta-1a without 
consideration of the PEG moiety attached. 
*The active substance, peginterferon beta-1a, is a covalent conjugate of interferon beta-1a, produced in 
Chinese hamster ovary cells, with 20,000 Dalton (20 kDa) methoxy poly(ethyleneglycol) using an 
O-2-methylpropionaldehyde linker. 
 
The potency of this medicinal product should not be compared to the one of another pegylated or 
non-pegylated protein of the same therapeutic class. For more information see section 5.1. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection). 
 
Clear and colourless solution with pH 4.5-5.1. 
 
 



3 

4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Plegridy is indicated in adult patients for the treatment of relapsing remitting multiple sclerosis (see 
section 5.1). 
 
4.2 Posology and method of administration 
 
Treatment should be initiated under supervision of a physician experienced in the treatment of multiple 
sclerosis. 
 
Plegridy may be administered subcutaneously (SC) using a single-use pre-filled pen or pre-filled 
syringe or intramuscularly (IM) using a single use pre-filled syringe. 
 
Efficacy of peginterferon beta-1a  administered subcutaneously has been demonstrated over placebo. 
Direct comparative data for peginterferon beta-1a  versus non-pegylated interferon beta or data on 
efficacy of peginterferon beta-1a  after switching from a non-pegylated interferon beta are not 
available. This should be considered when switching patients between pegylated and non-pegylated 
interferons (see section 5.1).  
 
Posology 
 
The recommended dose of Plegridy is 125 micrograms injected SC or IM every 2 weeks (14 days). 
 
Treatment initiation  
It is generally recommended that patients start SC or IM treatment with 63 micrograms at dose 1 (on 
day 0), increasing to 94 micrograms at dose 2 (on day 14), reaching the full dose of 125 micrograms 
by dose 3 (on day 28) and continuing with the full dose (125 micrograms) every 2 weeks (14 days) 
thereafter (see Table 1a for SC use or Table 1b for IM use).  
 
Subcutaneous route  
An initiation pack is available containing the first 2 doses (63 micrograms and 94 micrograms).  
 
Table 1a: Titration schedule at initiation via SC route 

Dose Time* Amount (micrograms) Syringe label 
Dose 1  Day 0 63  Orange  
Dose 2  Day 14 94  Blue 
Dose 3  Day 28 125 (full dose)  Grey 

*Dosed every 2 weeks (14 days) 
 
Intramuscular route  
An administration dose pack contains the full 125 microgram dose in 1 pre-filled syringe.   
 
The Plegridy titration clips, designed for use with the pre-filled syringe are intended to limit the dose 
that is administered to 63 micrograms (dose 1 (1/2 dose), yellow titration clip) and 94 micrograms 
(dose 2 (3/4 dose), purple titration clip), for day 0 and day 14 respectively.  Each Plegridy titration clip 
should be used once, and then discarded along with any remaining medicinal product.  Patients should 
use the full dose of 125 micrograms (no clip required) from day 28 onwards (dosing every 14 days).  
 
Table 1b Titration schedule at initiation via IM route 

Dose Time* Amount (micrograms) Titration clip 
Dose 1  Day 0 63  Yellow  
Dose 2  Day 14 94  Purple 
Dose 3  Day 28 125 (full dose)  No clips needed 

*Dosed every 2 weeks (14 days) 
 



4 

Dose titration at the initiation of treatment may help to ameliorate flu-like symptoms that can occur at 
treatment initiation with interferons. Prophylactic and concurrent use of anti-inflammatory, analgesic 
and/or antipyretic treatments may prevent or ameliorate flu-like symptoms sometimes experienced 
during interferon treatment (see section 4.8). 
 
Switching between the SC and IM routes of administration and vice versa has not been studied.  Based 
upon bioequivalence demonstrated between the two routes of administration it is not expected that 
dose titration will be required if switching between SC and IM, or vice versa (see sections 5.1 and 5.2). 
 
If a dose is missed, it should be administered as soon as possible.  
• If 7 days or more to the next planned dose: Patients should administer their missed dose 

immediately. Treatment can then continue with the next scheduled dose as planned. 
• If less than 7 days to the next planned dose: Patients should begin a new 2 week dosing schedule 

starting from when they administer their missed dose. A patient should not administer two doses 
of peginterferon beta-1a within 7 days of each other.  

 
Special populations  
 
Elderly population 
The safety and efficacy of peginterferon beta-1a in patients over the age of 65 have not been 
sufficiently studied due to the limited number of such patients included in clinical trials. 
 
Renal impairment 
No dosage adjustments are necessary in patients with renal impairment based on study data in mild, 
moderate, and severe renal impairment and end stage renal disease (see sections 4.4 and 5.2).   
 
Hepatic impairment 
Peginterferon beta-1a has not been studied in patients with hepatic impairment (see section 4.4). 
 
Paediatric population 
The safety and efficacy of peginterferon beta-1a in children and adolescents aged 0 to 18 years have 
not been established in multiple sclerosis. No data are available.  
 
Method of administration  
  
It is recommended that a healthcare professional trains patients in the proper technique for self—
administering SC injections using the SC pre-filled syringe/pre-filled pen or IM injections using the 
IM pre-filled syringes as appropriate. Patients should be advised to rotate sites for SC or IM injections 
every two weeks. The usual sites for subcutaneous injections include abdomen, arm, and thigh.  The 
usual site for intramuscular injection is the thigh.  
 
Each Plegridy pre-filled pen/syringe for SC is provided with the needle pre-attached.  Plegridy prefilled 
syringe for IM use is supplied as a prefilled syringe with a separate needle for IM use.  
 
Both IM and SC pre-filled syringes and SC pre-filled pens are for single use only and should be discarded 
after use. 
 
 Precautions to be taken before handling or administering the medicinal product 
Once removed from the refrigerator, Plegridy should be allowed to warm to room temperature (up to 
25 °C) for about 30 minutes prior to injection. External heat sources such as hot water must not be 
used to warm the medicinal product 
 
Plegridy pre-filled syringe must not be used if the liquid is coloured, cloudy, or contains floating 
particles. The liquid in the syringe must be clear and colourless. 
 



5 

Plegridy pre-filled pen must not be used unless the green stripes are visible in the pen injection status 
window. Plegridy pre-filled pen must not be used if the liquid is coloured, cloudy, or contains floating 
particles. The liquid in the medicinal product window must be clear and colourless. 
 
4.3 Contraindications 
 
- Hypersensitivity to natural or recombinant interferon beta or peginterferon or to any of the 

excipients listed in section 6.1. 
- Patients with current severe depression and/or suicidal ideation (see sections 4.4 and 4.8). 
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Hepatic injury  
 
Elevated serum hepatic transaminase levels, hepatitis, autoimmune hepatitis and rare cases of severe 
hepatic failure have been reported with interferon beta medicinal products. Elevations in hepatic 
enzymes have been observed with the use of peginterferon beta-1a. Patients should be monitored for 
signs of hepatic injury (see section 4.8). 
 
Depression 
 
Peginterferon beta-1a should be administered with caution to patients with previous depressive 
disorders (see section 4.3). Depression occurs with increased frequency in the multiple sclerosis 
population and in association with interferon use. Patients should be advised to immediately report any 
symptoms of depression and/or suicidal ideation to their prescribing physician. 
 
Patients exhibiting depression should be monitored closely during therapy and treated appropriately. 
Cessation of therapy with peginterferon beta-1a should be considered (see section 4.8). 
 
Hypersensitivity reactions 
 
Serious hypersensitivity reactions including cases of anaphylaxis have been reported as a rare 
complication of treatment with interferon beta, including peginterferon beta-1a. Patients should be 
advised to discontinue treatment with peginterferon beta-1a and seek immediate medical care if they 
experience signs and symptoms of anaphylaxis or severe hypersensitivity. Treatment with 
peginterferon beta-1a should not be restarted (see section 4.8). 
 
Injection site reactions 
 
Injection site reactions, including injection site necrosis, have been reported with the use of 
subcutaneous interferon beta. To minimise the risk of injection site reactions patients should be 
instructed in the use of an aseptic injection technique. The procedure for the self-administration by the 
patient should be reviewed periodically especially if injection site reactions have occurred. If the 
patient experiences any break in the skin, which may be accompanied by swelling or drainage of fluid 
from the injection site, the patient should be advised to speak with their doctor. One patient treated 
with peginterferon beta-1a  in clinical trials experienced an injection site necrosis with SC 
peginterferon beta-1a. Whether to discontinue therapy following a single site of necrosis is dependent 
on the extent of necrosis (see section 4.8). 
 



6 

Decreased peripheral blood counts 
 
Decreased peripheral blood counts in all cell lines, including rare pancytopenia and severe 
thrombocytopenia, have been reported in patients receiving interferon beta. Cytopenias, including rare 
severe neutropenia and thrombocytopenia, have been observed in patients treated with peginterferon 
beta-1a. Patients should be monitored for symptoms or signs of decreased peripheral blood counts (see 
section 4.8). 
 
Renal and urinary disorders  
 
Nephrotic syndrome (class effects) 
Cases of nephrotic syndrome with different underlying nephropathies including collapsing focal 
segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranoproliferative 
glomerulonephritis (MPGN) and membranous glomerulopathy (MGN) have been reported during 
treatment with interferon-beta products. Events were reported at various time points during treatment 
and may occur after several years of treatment with interferon beta. Periodic monitoring of early signs 
or symptoms, e.g. oedema, proteinuria and impaired renal function is recommended, especially in 
patients at higher risk of renal disease. Prompt treatment of nephrotic syndrome is required and 
discontinuation of treatment with peginterferon beta-1a should be considered. 
 
Severe renal impairment 
Caution should be used when administering peginterferon beta-1a  to patients with severe renal 
impairment. 
 
Thrombotic microangiopathy (TMA) (class effects) 
 
Cases of TMA, manifested as thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic 
syndrome (HUS), including fatal cases, have been reported with interferon beta products. Events were 
reported at various time points during treatment and may occur several weeks to several years after 
starting treatment with interferon beta. Early clinical features include thrombocytopenia, new onset 
hypertension, fever, central nervous system symptoms (e.g. confusion, paresis) and impaired renal 
function. Laboratory findings suggestive of TMA include decreased platelet counts, increased serum 
lactate dehydrogenase (LDH) due to haemolysis and schistocytes (erythrocyte fragmentation) on a 
blood film. Therefore if clinical features of TMA are observed, further testing of blood platelet levels, 
serum LDH, blood films and renal function is recommended. If TMA is diagnosed, prompt treatment 
is required (considering plasma exchange) and immediate discontinuation of peginterferon beta-1a is 
recommended. 
 
Laboratory abnormalities 
 
Laboratory abnormalities are associated with the use of interferons. In addition to those laboratory 
tests normally required for monitoring patients with multiple sclerosis, complete blood and differential 
blood cell counts, platelet counts, and blood chemistries, including liver function tests (e.g. aspartate 
aminotransferase (AST), alanine aminotransaminase (ALT)), are recommended prior to initiation and 
at regular intervals following introduction of peginterferon beta-1a therapy and then periodically 
thereafter in the absence of clinical symptoms.  
 
Patients with myelosuppression may require more intensive monitoring of complete blood cell counts, 
with differential and platelet counts. 
 
Hypothyroidism and hyperthyroidism have been observed with the use of interferon beta products. 
Regular thyroid function tests are recommended in patients with a history of thyroid dysfunction or as 
clinically indicated. 
 
Seizure 
 
Peginterferon beta-1a should be administered with caution to patients with a history of seizures, to 



7 

those receiving treatment with anti-epileptics, particularly if their epilepsy is not adequately controlled 
with anti-epileptics (see section 4.8). 
 
Cardiac disease 
 
Worsening of cardiac disease has been reported in patients receiving interferon beta. The incidence of 
cardiovascular events was similar between peginterferon beta-1a (125 micrograms every 2 weeks) and 
placebo treatment groups (7% in each group). No serious cardiovascular events were reported in 
patients who received peginterferon beta-1a in the ADVANCE study.  Nevertheless, patients with pre-
existing- significant cardiac disease, such as congestive heart failure, coronary artery disease or 
arrhythmia should be monitored for worsening of their cardiac condition, particularly during initiation 
of treatment.   
 
Immunogenicity 
 
Patients may develop antibodies to peginterferon beta-1a. Data from patients treated up to 2 years with 
peginterferon beta-1a  administered SC suggests that less than 1% (5/715) developed persistent 
neutralising- antibodies to the interferon beta-1a portion of peginterferon beta-1a. Neutralising 
antibodies have the potential to reduce clinical efficacy. However, the development of antibodies 
against the interferon moiety of peginterferon beta-1a had no discernible impact on safety or clinical 
efficacy, although the analysis was limited by the low immunogenicity incidence. 
 
Three percent of patients (18/681) developed persistent antibodies to the PEG moiety of peginterferon 
beta-1a.  In the clinical study conducted, the development of antibodies against the PEG moiety of 
peginterferon beta-1a had no discernible impact on safety, or clinical efficacy (including annualised 
relapse rate, magnetic resonance imaging (MRI) lesions, and disability progression). 
 
Hepatic impairment 
 
Caution should be used and close monitoring considered when administering peginterferon beta-1a to 
patients with severe hepatic impairment. Patients should be monitored for signs of hepatic injury and 
caution exercised when interferons are used concomitantly with other medicinal products associated 
with hepatic injury (see sections 4.8 and 5.2). 
 
Sodium content 
 
This medicinal product contains less than 1 mmol (23 mg) sodium, that is to say it is essentially 
“sodium-free”. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. The clinical studies indicate that multiple sclerosis 
patients can receive peginterferon beta-1a and corticosteroids during relapses. Interferons have been 
reported to reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and 
animals. Caution should be exercised when peginterferon beta-1a  is administered in combination with 
medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic 
cytochrome P450 system for clearance, e.g. some classes of antiepileptics and antidepressants. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
A large amount of data (more than 1,000 pregnancy outcomes) from registries and post-marketing 
experience indicates no increased risk of major congenital anomalies after pre-conception exposure to 
interferon beta or such exposure during the first trimester of pregnancy. However, the duration of 
exposure during the first trimester is uncertain, because data were collected when interferon beta use 



8 

was contraindicated during pregnancy, and treatment likely interrupted when pregnancy was detected 
and/or confirmed. Experience with exposure during the second and third trimester is very limited.  
 
Based on animal data (see section 5.3), there is a possibly increased risk for spontaneous abortion.  
The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot adequately be 
evaluated based on the currently available data, but the data do not suggest an increased risk so far. 
 
If clinically needed, the use of peginterferon beta-1ay may be considered during pregnancy. 
 
Breast-feeding 
 
It is not known whether peginterferon beta-1a is secreted in human milk. Limited information 
available on the transfer of interferon beta-1a into breast milk, together with the chemical / 
physiological characteristics of interferon beta, suggests that levels of interferon beta-1a excreted in 
human milk are negligible. No harmful effects on the breastfed newborn/infant are anticipated.  
 
Peginterferon beta-1a can be used during breast-feeding.  
 
Fertility 
 
There are no data on the effects of peginterferon beta-1a on human fertility.  In animals, anovulatory 
effects were observed at very high doses (see section 5.3).  No information is available on the effects 
of peginterferon beta-1a on male fertility in animals. 
 
4.7 Effects on ability to drive and use machines 
 
Peginterferon beta-1a has no or negligible influence on the ability to drive and use machines.   
 
4.8 Undesirable effects 
 
Summary of safety profile 
 
The most common adverse drug reactions (ADR) (at a higher incidence than placebo) for 
Peginterferon beta-1a 125 micrograms subcutaneously every 2 weeks were injection site erythema, 
influenza like illness, pyrexia, headache, myalgia, chills, injection site pain, asthenia, injection site 
pruritus, and arthralgia. 
The most commonly reported adverse reaction leading to discontinuation in patients treated with 
peginterferon beta-1a 125 micrograms subcutaneously every 2 weeks was influenza-like illness (<1%). 
 
Tabulated list of adverse reactions via subcutaneous route of administration 
In clinical studies, a total of 1,468 patients received peginterferon beta-1a SC for up to 278 weeks with 
an overall exposure equivalent of 4,217 person -years. 1,285 patients received at least 1 year, 1,124 
patients have received at least 2 years, 947 patients received at least 3 years, and 658 patients received 
at least 4 years of treatment with peginterferon beta-1a. The experience in the randomised, 
uncontrolled phase (year 2) of the ADVANCE study and in the extension study ATTAIN (treatment 
received for up to 4 years) was consistent with the experience in the 1 year placebo-controlled phase of 
the ADVANCE study.  
 
Table 2 summarizes ADRs (incidence above placebo and with a reasonable possibility of causality) 
from 512 patients treated with peginterferon beta-1a 125 micrograms SC every 2 weeks and 
500 patients who received placebo for up to 48 weeks and post-marketing data. 
 
The ADRs are presented as MedDRA preferred terms under the MedDRA System Organ Class. The 
incidence of the adverse reactions below are expressed according to the following categories:  
- Very common (≥1/10) 
- Common (≥1/100 to <1/10) 
- Uncommon (≥1/1,000 to <1/100) 



9 

- Rare (≥1/10,000 to <1/1,000) 
- Very rare (<1/10,000) 
- Not known (cannot be estimated from the available data) 
 
Table 2 Tabulated summary of adverse drug reactions 

MedDRA system organ class Adverse reaction Frequency category 
Blood and lymphatic system 
disorders 

Thrombocytopenia Uncommon 
Thrombotic microangiopathy 
including thrombotic 
thrombocytopenic 
purpura/haemolytic uraemic 
syndrome* 

Rare 

Immune system disorders Angioedema  Uncommon 
Hypersensitivity    
Anaphylaxis1  Not known  

Psychiatric disorders Depression Common 
Nervous system disorders Headache Very common 
 Seizure Uncommon 
Respiratory, thoracic and 
mediastinal disorders 

Pulmonary arterial 
hypertension┼ 

Not known 

Gastrointestinal disorders Nausea Common 
 Vomiting 

Skin and subcutaneous tissue 
disorders 

Alopecia$ Common 
Pruritus 
Urticaria Uncommon 

Musculoskeletal and 
connective tissue disorders 

Myalgia Very common 
 Arthralgia 

Renal and urinary disorders Nephrotic syndrome, 
glomerulosclerosis 

Rare 

General disorders and 
administration site conditions 

Influenza like illness Very common 
 Pyrexia 

Chills 
Injection site erythema 
Injection site pain 
Injection site pruritus 
Asthenia 
Hyperthermia  Common 

 Injection site inflammation 
Pain 
Injection site haematoma 
Injection site swelling 
Injection site oedema 
Injection site rash 
Injection site warmth 
Injection site discolouration 

 Injection site necrosis Rare 
Investigations Alanine aminotransferase 

increased 
Common 

Aspartate aminotransferase 
increased 
Gamma-glutamyltransferase 
increased 
White blood cell count 
decreased 
Haemoglobin decreased  



10 

MedDRA system organ class Adverse reaction Frequency category 
Body temperature increased  

 Platelet count decreased Uncommon 
*Class label for interferon beta products (see section 4.4). 
┼ Class label for interferon products, see below Pulmonary arterial hypertension 
$ Class label for interferon products 
1 Adverse reactions derived only during post marketing experience 
 
Description of selected adverse reactions via subcutaneous route of administration 
 
Flu-like symptoms 
Influenza -like illness was experienced by 47% of patients receiving peginterferon beta-1a 
125 micrograms every 2 weeks and 13% of patients receiving placebo. The incidence of flu-like 
symptoms (e.g. influenza -like illness, chills, hyperpyrexia, musculoskeletal pain, myalgia, pain, 
pyrexia) was highest at the initiation of treatment and generally decreased over the first 6 months. Of 
the patients who reported flu-like symptoms 90% reported them as mild or moderate in severity. None 
were considered serious in nature. Less than 1% of patients who received peginterferon beta-1a  during 
the placebo-controlled phase of the ADVANCE study discontinued treatment due to flu-like 
symptoms. An open -label study in patients switching from interferon beta therapy to peginterferon 
beta-1a evaluated the onset and duration of prophylactically treated flu-like symptoms. In patients 
experiencing flu-like symptoms, the median time to onset was 10 hours (interquartile range, 7 to 
16 hours) after injection, and the median duration was 17 hours (interquartile range, 12 to 22 hours). 
 
Injection site reactions (ISRs) 
ISRs (e.g. injection site erythema, pain, pruritus, or oedema) were reported by 66% of patients who 
received peginterferon beta-1a 125 micrograms every 2 weeks compared to 11% of patients receiving 
placebo. Injection site erythema was the most commonly reported injection site reaction. Of the 
patients who experienced injection site reactions 95% reported them as mild or moderate in severity. 
One patient out of 1,468 patients who received peginterferon beta-1a in clinical studies experienced an 
injection site necrosis which resolved with standard medical treatment. 
 
Hepatic transaminase abnormalities 
The incidence of hepatic transaminase increases was greater in patients receiving peginterferon beta-1a 
compared to placebo. The majority of enzyme elevations were <3 times the upper limit of normal 
(ULN). Elevations of alanine aminotransferase and aspartate aminotransferase (>5 times ULN), were 
reported in 1% and <1% of placebo-treated patients and 2% and <1% of patients treated with 
peginterferon beta-1a respectively. Elevations of serum hepatic transaminases combined with elevated 
bilirubin were observed in two patients who had pre-existing liver test abnormalities prior to receiving 
peginterferon beta-1a in the clinical trials. Both cases resolved following discontinuation of the 
medicinal product.  
 
Haematological disorders 
Decreases in white blood cell (WBC) counts of <3.0 x 109/L were observed in 7% of patients 
receiving peginterferon beta-1a and in 1% receiving placebo. Mean WBC counts remained within 
normal limits in patients treated with peginterferon beta-1a. Decreases in WBC  counts were not 
associated with an increased risk of infections or serious infections. The incidence of potentially 
clinically significant decreases in lymphocyte counts (<0.5 x 109/L) (<1%), neutrophil counts 
(≤1.0 x 109/L) (<1%) and platelet counts (≤100 x 109/L) (≤1%) was similar in peginterferon beta-1a-
treated patients compared to placebo-treated patients. Two serious cases were reported in patients 
treated with peginterferon beta-1a: one patient (<1%) experienced severe thrombocytopenia (platelet 
count <10 x 109/L), another patient (<1%) experienced severe neutropenia (neutrophil count 
<0.5 x 109/L). In both patients, cell counts recovered after discontinuation of peginterferon beta-1a. 
Slight decreases in mean red blood cell (RBC) counts were observed in peginterferon beta-1atreated 
patients. The incidence of potentially clinically significant decreases in RBC counts (<3.3 x 1012/L) 
was similar in peginterferon beta-1a treated patients compared to placebo- treated- patients. 
 



11 

Hypersensitivity reactions 
Hypersensitivity events were reported in 16% of patients treated with peginterferon beta-1a 
125 micrograms every 2 weeks and 14% of patients who received placebo. Less than 1% of 
peginterferon beta-1a  treated patients experienced a serious hypersensitivity event (e.g. angioedema, 
urticaria) and they recovered promptly after treatment with anti-histamines and/or corticosteroids. In 
post marketing experience, serious hypersensitivity events including cases of anaphylaxis (frequency 
not known) have been reported following peginterferon beta-1a administration. 
 
Pulmonary arterial hypertension 
Cases of pulmonary arterial hypertension (PAH) have been reported with interferon beta products. 
Events were reported at various time points including up to several years after starting treatment with 
interferon beta. 
 
Intramuscular route of administration   
An open-label, crossover study enrolled 136 subjects to assess the bioequivalence of single doses of 
125 micrograms of peginterferon beta-1a administered SC and IM injection in healthy volunteers. The 
most commonly reported AEs (with >10% incidence in either arm) across both treatment periods were 
chills (35.6% in IM vs 26.9% in SC ), pain (22.0% in IM vs 14.2% in SC), injection site pain (11.4% 
in IM vs 14.9% in SC), injection site erythema (2.3% in IM vs 25.4% in SC ), and headache (35.6% in 
IM vs 41.0% in SC).  Injection site reactions were reported with a lower frequency in IM (14.4%) 
compared to SC (32.1%).  
 
Abnormal urine protein was reported in 1/130 (0.8%) for the SC arm and 4/131 (3.1%) in the IM 
group without any associated adverse drug reactions.  
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9  Overdose 
 
In case of over-dose, patients may be hospitalized for observation and appropriate supportive treatment 
should be given. 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antineoplastic and immunomodulating agents, immunostimulants, 
interferons, ATC code: L03AB13 
 
Peginterferon beta-1a is an interferon beta-1a conjugated with a single, linear molecule of 20,000 Da 
methoxy poly(ethyleneglycol)-O-2-methylpropionaldehyde (20 kDa 
mPEG-O-2-methylpropionaldehyde) at a degree of substitution of 1 mole of polymer/mole of protein. 
The average molecular mass is approximately 44 kDa of which the protein moiety constitutes 
approximately 23 kDa. 
 
Mechanism of action 
 
A definitive mechanism of action of peginterferon beta-1a in multiple sclerosis (MS) is not known. 
peginterferon beta-1a binds to the type I interferon receptor on the surface of cells and elicits a cascade 
of intracellular events leading to the regulation of interferon-responsive gene expression. Biological 
effects that may be mediated by peginterferon beta-1a include up-regulation of anti-inflammatory 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


12 

cytokines (e.g. IL-4, IL-10, IL-27), down-regulation of pro-inflammatory cytokines (e.g. IL-2, IL-12, 
IFN-γ, TNF-α) and inhibiting the migration of activated T cells across the blood brain barrier; however 
additional mechanisms may be involved. Whether the mechanism of action of peginterferon beta-1a in 
MS is mediated by the same pathway(s) as the biological effects described above is not known because 
the pathophysiology of MS is only partially understood. 
 
Pharmacodynamic effects 
 
Peginterferon beta-1a is interferon beta-1a conjugated to a single, linear 20 kDa methoxy 
poly(ethyleneglycol) molecule at the alpha-amino group of the N-terminal amino acid residue.  
 
Interferons are a family of naturally occurring proteins that are induced by cells in response to 
biological and chemical stimuli, and mediate numerous cellular responses that have been classified as 
antiviral, antiproliferative, and immunomodulatory in nature.  The pharmacological properties of 
peginterferon beta-1a are consistent with those of interferon beta-1a and are believed to be mediated 
by the protein portion of the molecule. 
 
Pharmacodynamic responses were evaluated by measuring the induction of interferon-responsive 
genes including those encoding 2′,5′-oligoadenylate synthetase (2′,5′-OAS), myxovirus resistance 
protein A (MxA), and several chemokines and cytokines, as well as neopterin (D-erythro-1, 2, 3,-
trihydroxypropylpterin), a product of the interferon-inducible enzyme, GTP-cyclohydrolase I. Gene 
induction in healthy human subjects was greater in terms of peak level and exposure (area under the 
effect curve) for peginterferon beta-1a compared to non-pegylated interferon beta-1a (IM) when both 
were given at the same dose by activity (6 MIU). The duration of this response was sustained and 
prolonged for peginterferon beta-1a, with elevations detected up to 15 days compared to 4 days for 
non-pegylated interferon beta-1a. Increased concentrations of neopterin were observed in both healthy 
subjects and multiple sclerosis patients treated with peginterferon beta-1a, with a sustained and 
prolonged elevation over 10 days compared to 5 days observed for non-pegylated interferon beta-1a. 
Neopterin concentrations return to baseline after the two week dosing interval.  
 
Clinical efficacy and safety via subcutaneous route 
 
The efficacy and safety of peginterferon beta-1a was assessed from the placebo controlled- first year of 
a 2 year randomised, double-blind, clinical study in patients with relapsing remitting multiple sclerosis 
(the ADVANCE study). 1512 patients were randomised to and dosed with 125 micrograms 
peginterferon beta-1a injected subcutaneously every 2 (n=512) or 4 (n=500) weeks versus placebo 
(n=500).  
 
The primary endpoint was the annualised relapse rate (ARR) over 1 year. The study design and patient 
demographics are presented in Table .3  
 
No data are available from clinical efficacy/safety studies directly comparing pegylated with 
non-pegylated interferon beta-1a, or from patients switching between non-pegylated and pegylated 
interferon. 
 



13 

Table 3: Study design  
Study design 
Disease history Patients with RRMS, with at least 2 relapses 

within the prior 3 years, and 1 relapse in the 
prior year, with an EDSS score of ≤5.0 

Follow-up 1 year 
Study population 83% treatment-naïve patients 

47% ≥2 relapses in prior year 
38% at least 1 Gd+ lesion at baseline 
92% ≥9 T2  lesions baseline 
16% EDSS ≥4 
17% previously treated 

Baseline characteristics 
Mean age (years) 37 
Mean/Median disease duration (years) 3.6/2.0 
Mean number of relapses within the past 3 years 2.5 
Mean EDSS score at baseline 2.5 

RRMS: relapsing remitting multiple sclerosis 
EDSS: expanded disability status scale 
Gd+: gadolinium-enhancing 
 
Peginterferon beta-1a every 2 weeks significantly reduced the annualized relapse rate (ARR) by 36% 
compared to placebo (p=0.0007) at one year (Table 4) with consistent reductions of the ARR noted in 
subgroups defined by demographic and baseline disease characteristics. peginterferon beta-1a  also 
significantly reduced the risk of relapse by 39% (p=0.0003), the risk of sustained disability progression 
confirmed at 12 weeks by 38% (p=0.0383) and at 24 weeks (post-hoc analysis) by 54% (p=0.0069), 
the number of new or newly enlarging T2 lesions by 67% (p<0.0001), the number of Gd-enhancing 
lesions by 86% (p<0.0001) and the number of new T1 hypointense lesions compared to placebo by 
53% (p<0.0001). A treatment effect was observed as early as 6 months, with peginterferon beta-1a  
125 micrograms every 2 weeks demonstrating a 61% reduction (p<0.0001) in new or newly enlarging 
T2 lesions as compared with placebo. Across relapse and MRI endpoints peginterferon beta-1a  
125 micrograms every two weeks showed a numerically greater treatment effect over the peginterferon 
beta-1a  every four weeks dosing regimen at year 1.  
 
Results over 2 years confirmed that efficacy was maintained beyond the placebo controlled first year 
of the study. Patients exposed to peginterferon beta-1a  every 2 weeks showed statistically significant 
reductions compared to patients exposed to peginterferon beta-1a  every 4 weeks over 2 years in a 
post-hoc analysis for endpoints including ARR (24%, p=0.0209), the risk of relapse (24%, p=0.0212), 
the risk of disability progression with 24 week confirmation (36%, p=0.0459), and MRI endpoints 
(new/enlarging T2 60%, Gd+ 71%, and new T1 hypointense lesions 53%; p<0.0001 for all). In the 
ATTAIN extension study, long-term efficacy with peginterferon beta-1a  was maintained with 
continuous treatment up to 4 years as shown by clinical and MRI measures of MS disease activity. Of 
a total of 1,468 patients, 658 patients continued at least 4 years of treatment with peginterferon 
beta-1a. 
 
Results for this study are shown in Table 4. 
 



14 

Table 4: Clinical and MRI results 
 Placebo 

 
 

Peginterferon 
beta-1a  

125 micrograms 
every 2 weeks 

Peginterferon 
beta-1a  

125 micrograms 
every 4 weeks 

Clinical endpoints  
N 500 512 500 
Annualised relapse rate 0.397 0.256 0.288 

Rate ratio 
95% CI 
P-value 

 0.64 
0.50 – 0.83 
p=0.0007 

0.72 
0.56 – 0.93 
p=0.0114 

Proportion of subjects relapsed 0.291 0.187 0.222 
HR 
95% CI 
P-value 

 0.61  
0.47 – 0.80  
p=0.0003 

0.74 
0.57 – 0.95 
p=0.020 

Proportion with 12-week confirmed 
disability progression*  

0.105 0.068 
 

0.068 

HR 
95% CI 
P-value 

 0.62 
0.40 – 0.97 
p=0.0383 

0.62 
0.40 – 0.97 
p=0.0380 

Proportion with 24-week confirmed 
disability progression*  

0.084 0.040 
 

0.058 
 

HR 
95% CI 
P-value 

 0.46  
(0.26 – 0.81) 
p=0.0069 

0.67 
(0.41 – 1.10) 
p=0.1116 

MRI endpoints  
N 476 457 462 

 
Mean [Median] no. of new or newly 
enlarging T2 hyperintense lesions 
(range) 

13.3 [6.0] 
(0 – 148) 

4.1 [1.0]  
(0 – 69) 

9.2 [3.0] 
(0 – 113) 

Lesion mean ratio (95% CI) 
P-value 

 0.33 (0.27, 0.40) 
p≤0.0001 

0.72 (0.60, 0.87) 
p=0.0008 

Mean [Median] no. of Gd-enhancing 
lesions (range) 

1.4^ [0.0]  
(0 – 39) 

0.2 [0.0]  
(0 – 13) 

0.9 [0.0] 
(0 – 41) 

% reduction vs placebo 
P-value 

 86 
p<0.0001 

36 
p=0.0738 

Mean [Median] no. of new T1 
hypointense lesions (range) 

3.8 [1.0]  
(0 – 56) 

1.8 [0.0]  
(0 – 39) 

3.1 [1.0] 
(0 – 61) 

% reduction vs placebo 
P-value 

 53 
p<0.0001 

18 
0.0815 

HR: hazard ratio 
CI: confidence interval 
* Sustained disability progression was defined as at least a 1 point increase from baseline EDSS ≥ 1 or 
1.5 point increase for patients with baseline EDSS of 0, sustained for 12/24 weeks. 
^n=477 
 
Patients who failed previous MS treatment were not included in the study. 
 
Subgroups of patients with higher disease activity were defined by relapse and MRI criteria as reported 
below, with the following efficacy results: 
 



15 

- For patients with ≥1 relapse in the previous year and ≥9 T2 lesions or ≥1 Gd+ lesion (n=1,401), 
the annual relapse rate at 1 year was 0.39 for placebo, 0.29 for peginterferon beta-1a  every 
4 weeks and 0.25 for peginterferon beta-1a  every 2 weeks.  
Results in this subgroup were consistent with those in the overall population. 
 

- For patients with ≥2 relapses in the previous year and at least 1 Gd+ lesion (n=273), the annual 
relapse rate at 1 year was 0.47 for placebo, 0.35 for peginterferon beta-1a  every 4 weeks, and 
0.33 for peginterferon beta-1a  every 2 weeks.   
Results in this subgroup were numerically consistent with those in the overall population but not 
statistically significant. 
 

IM and SC bioequivalence study  
An -open-label, crossover study enrolled 136 subjects to assess the bioequivalence of single doses of 
125 micrograms of Plegridy administered SC and IM injection in healthy volunteers.   
 
The serum concentration of neopterin, a marker of interferon beta activity, following administration of 
125 micrograms peginterferon beta-1a  IM and SC was measured for pharmacodynamic (PD) 
analysis.   
 
The serum neopterin concentration versus time profiles following single doses of 125 micrograms 
peginterferon beta-1a  SC or 125 micrograms peginterferon beta-1a  IM were similar, with maximal 
concentrations (Epeak) reached at a median ETmax of 40.1 hours and 44.0 hours, respectively.  Geometric 
mean neopterin levels increased from baseline to maximum concentration similarly between the 
2 injection routes, with the increase from 8.0 to 22.6  nmol/L for SC, and from 8.1 to 23.2 nmol/L for 
IM. The overall systemic exposure to neopterin (EAUC0 336h and EAUC0-504h) were also similar 
between the 2 routes of administration.  
 
Since bioequivalence was demonstrated between the IM and SC routes of administration, it is expected 
that IM and SC peginterferon beta-1a will have a similar efficacy profile. 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Plegridy in one or more subsets of the paediatric population in treatment of multiple sclerosis (see 
section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
The serum half-life of peginterferon beta-1a is prolonged compared with non-pegylated interferon 
beta-1a. Serum concentration of peginterferon beta-1a was dose-proportional in the range of 63 to 
188 micrograms as observed in a single dose and a multiple dose study in healthy subjects. 
Pharmacokinetics observed in multiple sclerosis patients were consistent with those seen in healthy 
subjects. 
 
Absorption 
 
Following subcutaneous administration of peginterferon beta-1a in multiple sclerosis patients, the peak 
concentration was reached between 1 to 1.5 days post-dose.  The observed Cmax (mean±SE) was 
280 ± 79 pg/mL following repeat dosing of 125 micrograms every two weeks.  
  
Subcutaneous peginterferon beta-1a resulted in approximately 4-, 9-, and 13-fold higher exposure 
(AUC168h) values and approximately 2-, 3.5- and 5-fold higher Cmax, following single doses of 
63 (6 MIU), 125 (12 MIU), and 188 (18 MIU) micrograms respectively, compared to intramuscular 
administration of 30 (6 MIU) micrograms non-pegylated beta-1a.  
 



16 

Distribution 
 
Following repeat dosing of 125 micrograms doses every two weeks by subcutaneous administration, 
the volume of distribution uncorrected for bioavailability (mean±SE) was 481 ± 105 L. 
 
Biotransformation and elimination 
 
Urinary (renal) clearance is postulated to be a major excretory pathway for peginterferon beta-1a. The 
process of covalently conjugating a PEG moiety to a protein can alter the in vivo properties of the 
unmodified protein, including decreased renal clearance and decreased proteolysis thus extending the 
circulating half-life. Accordingly, the half-life (t1/2) of peginterferon beta-1a is approximately 2-fold 
longer than non-pegylated interferon beta-1a in healthy volunteers.  In multiple sclerosis patients, the 
t1/2 (mean±SE) of peginterferon beta-1a was 78 ± 15 hours at steady state. The mean steady state 
clearance of peginterferon beta-1a was 4.1 ± 0.4 L/hr. 
 
Special populations 
 
Elderly patients 
Clinical experience in patients aged above 65 years is limited. However, results from a population 
pharmacokinetic analysis (in patients up to 65 years) suggest that age does not impact peginterferon 
beta-1a clearance.   
 
Renal impairment 
A single-dose study in healthy subjects and subjects with various degrees of renal impairment (mild, 
moderate, and severe renal impairment as well as subjects with end state renal disease) showed a 
fractional increase in AUC (13-62%) and Cmax (42-71%) in subjects with mild (estimated glomerular 
filtration rate 50 to ≤80 mL/min/1.73m2), moderate (estimated glomerular filtration rate 30 to 
<50 mL/min/1.73m2), and severe (estimated glomerular filtration rate <30 mL/min/1.73m2) renal 
impairment, compared to subjects with normal renal function (estimated glomerular filtration rate 
>80 mL/min/1.73m2).  Subjects with end stage renal disease requiring 2-3 times haemodialysis weekly 
showed similar AUC and Cmax as compared to subjects with normal renal function. Each 
haemodialysis reduced peginterferon beta-1a concentration by approximately 24%, suggesting that 
haemodialysis partially removes peginterferon beta-1a from systemic circulation.  
 
Hepatic function  
The pharmacokinetics of peginterferon beta-1a has not been evaluated in patients with hepatic 
insufficiency.   
 
Gender 
No gender effect on the pharmacokinetics of peginterferon beta-1a was found in a population 
pharmacokinetic analysis. 
 
Race 
Race had no effect on the pharmacokinetics of peginterferon beta-1a in a population pharmacokinetic 
analysis. 
 
IM and SC bioequivalence study  
The pharmacokinetic (PK)  profiles following single doses of 125 micrograms peginterferon beta-1a  
IM and 125 micrograms peginterferon beta-1a  SC in healthy volunteers were similar, with maximal 
concentrations reached at 40.0 hours post-dose (for both SC and IM), and t1/2 values of 97.1 hours and 
79.1 hours, respectively.  Statistical analysis of Cmax and AUC∞ further demonstrated bioequivalence 
between 125 micrograms peginterferon beta-1a IM and SC. The geometric mean ratio (90% 
confidence interval) of IM versus SC for Cmax was 1.08 (0.98 to 1.20) and 1.09 (1.02 to 1.16) for 
AUC∞. These values fall within the designated 0.80 to 1.25 equivalence range.  
 



17 

5.3 Preclinical safety data 
 
Toxicity 
 
Following repeated subcutaneous administration of peginterferon beta-1a in rhesus monkeys at doses 
up to 400-fold (based on exposure, AUC) the recommended therapeutic dose; no effects other than the 
known mild pharmacological responses by rhesus monkeys to interferon beta-1a were observed after 
the first and second weekly dose.  Repeated dose toxicology studies were limited to 5 weeks as 
exposure was greatly diminished from 3 weeks onwards, due to the formation of anti-drug antibodies 
by rhesus monkeys to human interferon beta-1a. Therefore, the long-term safety of chronic 
administration of peginterferon beta-1a  to patients cannot be assessed on the basis of these studies. 
 
Mutagenesis 
 
Peginterferon beta-1a was not mutagenic when tested in an in vitro bacterial reverse mutation (Ames) 
test and was not clastogenic in an in vitro assay in human lymphocytes. 
 
Carcinogenesis 
 
Peginterferon beta-1a has not been tested for carcinogenicity in animals. Based on the known 
pharmacology of interferon beta-1a and clinical experience with interferon beta, the potential for 
carcinogenicity is expected to be low. 
 
Reproductive toxicity 
 
Peginterferon beta-1a has not been tested for reproductive toxicity in pregnant animals. Fertility and 
developmental studies in rhesus monkeys have been carried out with non-pegylated interferon beta-1a. 
At very high doses, anovulatory and abortifacient effects were observed in animals. No information is 
available on the potential effects of peginterferon beta-1a on male fertility. Upon repeated dosing with 
peginterferon beta-1a of sexually mature female monkeys, effects on menstrual cycle length and 
progesterone levels were observed. Reversibility of the effects on menstrual cycle length was 
demonstrated. The validity of extrapolating these non-clinical data to humans is unknown.  
 
Data from studies with other interferon beta compounds did not show teratogenic potential. The 
available information on the effects of interferon beta-1a in the peri- and postnatal periods is limited. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium acetate trihydrate 
Acetic acid, glacial 
Arginine hydrochloride  
Polysorbate 20  
Water for injections 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
Plegridy for SC or IM administration can be stored at room temperature (up to 25 °C) for up to 30 days 
as long as it is stored away from light. If Plegridy is at room temperature for a total of 30 days, it 



18 

should be used or discarded. If it is not clear if Plegridy has been stored at room temperature 30 days 
or more, it should be discarded. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2 °C to 8 °C). 
Do not freeze. 
Store in the original package in order to protect from light. 
 
See section 6.3 for additional information on storage at room temperature. 
 
6.5 Nature and contents of container  
 
Pre-filled syringe / pre-filled pen (subcutaneous)  
1 mL pre-filled syringe made of glass (Type I) with a bromobutyl rubber stopper and thermoplastic 
and polypropylene rigid needle shield, containing 0.5 mL of solution. A 29 gauge, 0.5 inch staked 
needle is pre-affixed to the syringe. 
 
A pre-filled syringe of Plegridy is contained within a single-use, disposable, spring-powered pen 
injector called Plegridy Pen. The syringe inside the pen is a 1 mL pre-filled syringe made of glass 
(Type I) with a bromobutyl rubber stopper and thermoplastic and polypropylene rigid needle shield, 
containing 0.5 mL of solution.  A 29 gauge, 0.5 inch staked needle is pre-affixed to the syringe. 
 
Pack sizes 
The Plegridy initiation pack contains 1x 63 micrograms pre-filled syringe (orange labelled syringe, 1st 
dose) and 1x 94 micrograms pre-filled syringe (blue labelled syringe, 2nd dose) in sealed plastic trays. 
 
The Plegridy Pen initiation pack contains 1x 63 micrograms pre-filled pen (orange labelled pen, 1st 
dose) and 1x 94 micrograms pre-filled pen (blue labelled pen, 2nd dose) in a protective plastic tray. 
 
Box of two or six 125 microgram pre-filled syringes (grey labelled syringes) in sealed plastic trays.  
 
Box of two 125 microgram pre-filled pens (grey labelled pens) in a protective plastic tray. 
 
Multipacks containing 6 (3 packs of 2) 125 microgram pre-filled pens (grey labelled pens). The pack 
contains 3 inner cartons. Each inner carton contains 2 pens in a protective plastic tray. 
 
Not all pack sizes may be marketed. 
 
Pre-filled syringe (intramuscular)  
1 mL pre-filled Luer-Lok syringe made of glass (Type I) with a bromobutyl rubber stopper containing 
0.5 mL of solution and supplied with a 23 gauge, 1.25 inch needle. A single pre-filled syringe contains 
0.5 mL of solution of Plegridy containing 125 micrograms of peginterferon beta-1a.  
 
Box of two or six 125 microgram pre-filled syringes in sealed plastic trays.  
 
Not all pack sizes may be marketed. 
 
 
6.6 Special precautions for disposal and other handling 
 
Plegridy prefilled syringes (for IM and SC administration) and pen (for SC administration) are for 
single-use only.  
 
Before use check the dosage form to be used. It should not have any cracks or damage and the 



19 

solution should be clear, colourless and not have any particles in it.   
 
Once removed from the refrigerator, the Plegridy pre-filled syringe or pen to be used should be 
allowed to warm to room temperature (15°C to 30°C) for about 30 minutes.   
 
Do not use external heat sources such as hot water to warm the Plegridy pre-filled syringe or pen 
Titration of Plegridy doses for patients initiating treatment is described in section 4.2.   
 
Pre-filled syringe / pre-filled pen (subcutaneous) 
Patients initiating treatment with Plegridy via SC administration should use initiation packs.   
 
Pre-filled syringe (intramuscular)  
Patients initiating treatment with Plegridy via IM administration should use Plegridy Titration clips 
which may be attached to the syringe to limit the dose. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Biogen Netherlands B.V. 
Prins Mauritslaan 13 
1171 LP Badhoevedorp 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/934/001 
EU/1/14/934/002 
EU/1/14/934/003 
EU/1/14/934/004 
EU/1/14/934/005 
EU/1/14/934/006 
EU/1/14/934/007 
EU/1/14/934/008 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
Date of first authorisation: 18 July 2014 
Date of latest renewal: 25 March 2019 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
  



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 
SUBSTANCE(S) AND MANUFACTURER(S) RESPONSIBLE 
FOR BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 



21 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer(s) of the biological active substance(s) 
 
Biogen Inc. 
250 Binney Street 
Cambridge, MA 02142 
USA 
 
Biogen Inc. 
5000 Davis Drive 
Research Triangle Park, NC 27709-4627 
USA 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Biogen (Denmark) Manufacturing ApS 
Biogen Allé 1 
DK-3400 Hillerød 
Denmark 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 
and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 
• Risk Management Plan (RMP) 

 
The Marketing Authorisation Holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
Marketing Authorisation and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
  



22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



24 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
Pre-Filled Syringe Initiation Pack 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Plegridy 63 micrograms solution for injection in pre-filled syringe 
Plegridy 94 micrograms solution for injection in pre-filled syringe 
peginterferon beta-1a 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 pre-filled syringe contains 63 micrograms of peginterferon beta-1a in 0.5 mL. 
1 pre-filled syringe contains 94 micrograms of peginterferon beta-1a in 0.5 mL. 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium acetate trihydrate, acetic acid glacial, arginine hydrochloride, polysorbate 20, water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
Initiation Pack 
1 pre-filled syringe of 63 micrograms  
1 pre-filled syringe of 94 micrograms 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use  
Read the package leaflet before use.  
For single use only. 
 
Table on the inner lid 
Injection Record 
Day 0 (63 micrograms) 
Day 14 (94 micrograms) 
Date  
Injection Site 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 



25 

 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
If a refrigerator is not available, syringes can be left at room temperature (up to 25°C) for up to 
30 days.  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
Do not freeze. 
Store in the original package in order to protect from light. 
 
 
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 
 
Biogen Netherlands B.V. 
Prins Mauritslaan 13 
1171 LP Badhoevedorp 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/934/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Plegridy 63 
Plegridy 94 
 



26 

 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



27 

 MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
Pre-Filled Syringe Double Lid Initiation Pack 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Plegridy 63 micrograms solution for injection in pre-filled syringe 
Plegridy 94 micrograms solution for injection in pre-filled syringe 
peginterferon beta-1a 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Biogen Netherlands B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Initiation Pack 
 
Subcutaneous use  
 
Read the package leaflet before use.  
Store in a refrigerator. 
Do not freeze. 
Store in the original package in order to protect from light. 
  



28 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Pre-Filled Syringe Label Initiation Pack 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Plegridy 63 mcg injection 
Plegridy 94 mcg injection 
peginterferon beta-1a 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
0.5 mL 
 
 
6. OTHER 
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
Pre-Filled Syringe 125 mcg 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Plegridy 125 micrograms solution for injection in pre-filled syringe 
peginterferon beta-1a 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 125 micrograms of peginterferon beta-1a in 0.5 mL. 
 
 
3. LIST OF EXCIPIENTS 
 



29 

Sodium acetate trihydrate, acetic acid glacial, arginine hydrochloride, polysorbate 20, water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
2 pre-filled syringes  
6 pre-filled syringes  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use  
Read the package leaflet before use.  
For single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
If a refrigerator is not available, syringes can be left at room temperature (up to 25°C) for up to 
30 days.  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
Do not freeze. 
Store in the original package in order to protect from light. 
 
 
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 
 
Biogen Netherlands B.V. 
Prins Mauritslaan 13 
1171 LP Badhoevedorp 
The Netherlands 
 



30 

 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/934/003 
EU/1/14/934/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Plegridy 125 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



31 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
Pre-Filled Syringe Double Lid 125 mcg  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Plegridy 125 micrograms solution for injection in pre-filled syringe 
peginterferon beta-1a 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Biogen Netherlands B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Subcutaneous use  
 
Read the package leaflet before use.  
Store in a refrigerator. 
Do not freeze. 
Store in the original package in order to protect from light. 
 
  



32 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Pre-Filled Syringe Label 125 mcg 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Plegridy 125 mcg injection 
peginterferon beta-1a 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
0.5 mL  
 
 
6. OTHER 
  



33 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
Pre-Filled Pen Initiation Pack 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Plegridy 63 micrograms solution for injection in pre-filled pen 
Plegridy 94 micrograms solution for injection in pre-filled pen 
peginterferon beta-1a 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 pre-filled pen contains 63 micrograms of peginterferon beta-1a in 0.5 mL. 
1 pre-filled pen contains 94 micrograms of peginterferon beta-1a in 0.5 mL. 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium acetate trihydrate, acetic acid glacial, arginine hydrochloride, polysorbate 20, water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
Initiation Pack 
1 pre-filled pen of 63 micrograms  
1 pre-filled pen of 94 micrograms 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use  
Read the package leaflet before use.  
For single use only. 
 
Table on the inner lid 
Injection Record 
Day 0 (63 micrograms) 
Day 14 (94 micrograms) 
Date  
Injection Site 
 
open here 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 



34 

 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
If a refrigerator is not available, pens can be left at room temperature (up to 25°C) for up to 30 days.  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
Do not freeze. 
Store in the original package in order to protect from light. 
 
 
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 
 
Biogen Netherlands B.V. 
Prins Mauritslaan 13 
1171 LP Badhoevedorp 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/934/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Plegridy 63 
Plegridy 94 
 



35 

 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



36 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Pre-Filled Pen Label Initiation pack 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Plegridy 63 mcg injection  
Plegridy 94  mcg injection  
peginterferon beta-1a 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
0.5 mL 
 
 
6. OTHER 
 



37 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
Pre-Filled Pen 125 mcg 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Plegridy 125 micrograms solution for injection in pre-filled pen 
peginterferon beta-1a 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled pen contains 125 micrograms of peginterferon beta-1a in 0.5 mL. 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium acetate trihydrate, acetic acid glacial, arginine hydrochloride, polysorbate 20, water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
2 pre-filled pens 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use  
Read the package leaflet before use.  
For single use only. 
 
open here 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
If a refrigerator is not available, pens can be left at room temperature (up to 25°C) for up to 30 days.  
 



38 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
Do not freeze. 
Store in the original package in order to protect from light. 
 
 
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 
 
Biogen Netherlands B.V. 
Prins Mauritslaan 13 
1171 LP Badhoevedorp 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/934/005 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Plegridy 125 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



39 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
MULTIPACK OUTER CARTON 
 
Pre-filled pen 125 mcg Multipack (with bluebox)  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Plegridy 125 micrograms solution for injection in pre-filled pen 
peginterferon beta-1a 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled pen contains 125 micrograms of peginterferon beta-1a in 0.5 mL. 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium acetate trihydrate, acetic acid glacial, arginine hydrochloride, polysorbate 20, water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
 Multipack: 6 (3 packs of 2) pre-filled pens of 125 micrograms. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use  
Read the package leaflet before use.  
For single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
If a refrigerator is not available, pens can be left at room temperature (up to 25°C) for up to 30 days.  
 
 



40 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
Do not freeze. 
Store in the original package in order to protect from light. 
 
 
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 
 
Biogen Netherlands B.V. 
Prins Mauritslaan 13 
1171 LP Badhoevedorp 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/934/006 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Plegridy 125 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



41 

PARTICULARS TO APPEAR ON THE INTERMEDIATE PACKAGING 
 
MULTIPACK INNER CARTON 
 
Pre-Filled Pen 125 mcg Multipack (without bluebox) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Plegridy 125 micrograms solution for injection in pre-filled pen 
peginterferon beta-1a 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled pen contains 125 micrograms of peginterferon beta-1a in 0.5 mL. 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium acetate trihydrate, acetic acid glacial, arginine hydrochloride, polysorbate 20, water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
2 pre-filled pens. Component of a multipack, cannot be sold separately.  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use  
Read the package leaflet before use.  
For single use only. 
 
open here 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
If a refrigerator is not available, pens can be left at room temperature (up to 25°C) for up to 30 days.  
 



42 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
Do not freeze. 
Store in the original package in order to protect from light. 
 
 
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 
 
Biogen Netherlands B.V. 
Prins Mauritslaan 13 
1171 LP Badhoevedorp 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/934/006 
 
 
13. BATCH NUMBER 

 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Plegridy 125 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 



43 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Pre-Filled Pen Label 125 mcg 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Plegridy 125 mcg injection  
peginterferon beta-1a 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
0.5 mL  
 
 
6. OTHER 
 
 
  



44 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
Pre-Filled Syringe 125 mcg for intramuscular use 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Plegridy 125 micrograms solution for injection in pre-filled syringe 
peginterferon beta-1a 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each  pre-filled syringe contains 125 micrograms of peginterferon beta-1a in 0.5 mL. 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium acetate trihydrate, acetic acid glacial, arginine hydrochloride, polysorbate 20, water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
2 pre-filled syringes  
6 pre-filled syringes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use.  
Intramuscular use  
For single use only. 
If using Plegridy for the first time the dose may need to be increased gradually.   
 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
If a refrigerator is not available, syringes can be left at room temperature (up to 25 °C) for up to 
30 days.  



45 

 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator.  
Do not freeze. 
Store in the original package in order to protect from light. 
 
 
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 
 
Biogen Netherlands B.V. 
Prins Mauritslaan 13 
1171 LP Badhoevedorp 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/934/007 
EU/1/14/934/008 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Plegridy 125 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



46 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
Pre-Filled Syringe Double Lid 125 mcg for intramuscular injection 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Plegridy 125 micrograms solution for injection in pre-filled syringe 
peginterferon beta-1a 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Biogen Netherlands B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Intramuscular use  
 
Read the package leaflet before use.  
Store in a refrigerator. 
Do not freeze. 
Store in the original package in order to protect from light. 
 



47 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Pre-Filled Syringe Label 125 mcg for intramuscular injection 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Plegridy 125 mcg injection 
peginterferon beta-1a 
IM 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
0.5 mL  
 
 
6. OTHER 



48 

   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
  



49 

 
Package leaflet: Information for the user 

 
Plegridy 63 micrograms solution for injection in pre-filled syringe 
Plegridy 94 micrograms solution for injection in pre-filled syringe 

Plegridy 125 micrograms solution for injection in pre-filled syringe 
peginterferon beta-1a 

 
Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Plegridy is and what it is used for  
2. What you need to know before you use Plegridy  
3. How to use Plegridy  
4. Possible side effects  
5. How to store Plegridy  
6. Contents of the pack and other information 
7.  Instructions for injecting Plegridy pre-filled syringe  
 
 
1. What Plegridy is and what it is used for 
 
What Plegridy is 
The active substance in Plegridy is peginterferon beta-1a. Peginterferon beta-1a is a modified 
long-acting form of interferon. Interferons are natural substances made in the body to help protect 
from infections and diseases.  
 
What Plegridy is used for 
This medicine is used to treat relapsing-remitting multiple sclerosis (MS) in adults aged 18 or 
over.  
MS is a long term illness that affects the central nervous system (CNS), including the brain and spinal 
cord, in which the body’s immune system (its natural defences) damages the protective layer (myelin) 
that surrounds the nerves in the brain and spinal cord. This disrupts the messages between the brain 
and other parts of the body, causing the symptoms of MS. Patients with relapsing-remitting MS have 
periods when the disease is not active (remission) in between flare-ups of symptoms (relapses). 
 
Everyone has their own set of MS symptoms. These can include: 
- Feeling off-balance or light headed, walking problems, stiffness and muscle spasms, tiredness, 

numbness in the face, arms or legs 
- Acute or chronic pain, bladder and bowel problems, sexual problems and problems with vision 
- Difficulty thinking and concentrating, depression. 
 
How Plegridy works 
Plegridy seems to work by stopping the body’s immune system from damaging your brain and 
spinal cord. This can help to reduce the number of relapses that you have and slow down the disabling 
effects of MS. Treatment with Plegridy can help to prevent you from getting worse, although it will 
not cure MS. 
 
 



50 

2. What you need to know before you use Plegridy 
 
Do not use Plegridy  
- If you are allergic to peginterferon beta-1a, interferon beta-1a or any of the ingredients of this 

medicine (listed in section 6). See section 4 for the symptoms of an allergic reaction. 
- If you have severe depression or think about committing suicide. 
 
Warnings and precautions  
Talk to your doctor if you have ever had: 
- Depression or problems affecting your mood 
- Thoughts about committing suicide 

- Your doctor may still prescribe Plegridy for you, but it’s important to let your doctor know 
if you have had depression or any similar problems affecting your mood in the past. 

 
Talk to your doctor, pharmacist or nurse before injecting Plegridy if you have any of the 
conditions listed below. They may get worse while using Plegridy:  
- Serious liver or kidney problems 
- Irritation at an injection site, which can lead to skin and tissue damage (injection site 

necrosis). When you are ready to inject, carefully follow the instructions in section 7 
“Instructions for injecting Plegridy pre-filled syringe”, at the end of this leaflet. This is to reduce 
the risk of injection site reactions. 

- Epilepsy or other seizure disorders, not controlled by medicine 
- Heart problems, which can cause symptoms such as chest pain (angina), particularly after any 

activity; swollen ankles, shortness of breath (congestive heart failure); or an irregular heartbeat 
(arrhythmia). 

- Thyroid problems 
- A low number of white blood cells or platelets, which can cause an increased risk of infection, 

or bleeding 
 

Other things to consider when using Plegridy 
- You will need blood tests to determine your numbers of blood cells, blood chemistry and your 

levels of liver enzymes. These will be performed before you start using Plegridy, regularly after 
treatment with Plegridy has been initiated and then periodically during treatment, even if you 
have no particular symptoms. These blood tests will be in addition to the tests which are 
normally done to monitor your MS. 

- The functioning of your thyroid gland will be checked regularly or whenever thought necessary 
by your doctor. 

- Blood clots in the small blood vessels may occur during your treatment. These blood clots could 
affect your kidneys. This might happen several weeks to several years after starting Plegridy. 
Your doctor may want to check your blood pressure, blood (platelet count) and the function of 
your kidneys. 

 
If you accidentally prick yourself or someone else with the needle in Plegridy, the area affected should 
be washed immediately with soap and water and a doctor or nurse should be contacted as soon as 
possible. 
 
Children and adolescents 
Plegridy is not to be used in children and adolescents below 18 years old. The safety and effectiveness 
of Plegridy in this age group are not known. 
 



51 

Other medicines and Plegridy 
Plegridy should be used carefully with medicines that are broken down in the body by a group of 
proteins called “cytochrome P450” (e.g. some medicines used for epilepsy or depression). 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines, especially those used to treat epilepsy or depression. This includes any medicines obtained 
without a prescription. 
 
Sometimes you will need to remind other healthcare professionals that you are being treated with 
Plegridy. For example, if you are prescribed other medicines, or if you have a blood test. Plegridy may 
affect the other medicines or the test result. 
 
Pregnancy and breast-feeding  
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or 
pharmacist for advice before taking this medicine.  

No harmful effects on the breastfed newborn/infant are anticipated. Plegridy can be used during breast-
feeding. 

 
Driving and using machines  
Plegridy has no or negligible influence on the ability to drive and use machines. 
 
Plegridy contains sodium  
This medicine contains less than 1 mmol sodium (23 mg), that is to say it is essentially “sodium-free”. 
 
 
3. How to use Plegridy 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure. 
 
The usual dose 
One injection of Plegridy 125 micrograms every 14 days (every two weeks). Try to use Plegridy at the 
same time on the same day, every time you inject. 
 
Starting Plegridy 
If you are new to Plegridy, your doctor may advise you to gradually increase your dose so that you can 
adjust to the effects of Plegridy before taking the full dose. You will be provided with an Initiation 
Pack containing your first 2 injections: one orange syringe with Plegridy 63 micrograms (for day 0) 
and one blue syringe with Plegridy 94 micrograms (for day 14). 
 
After that you will be provided with a maintenance pack containing grey syringes with Plegridy 
125 micrograms (for day 28 and then every two weeks). 
 
Read the instructions in section 7 “Instructions for injecting Plegridy pre-filled syringe” at the end of 
this leaflet before you start using Plegridy. 
Use the record table printed on the inside of the lid of the Initiation Pack to keep a track of your 
injection dates. 
 
Injecting yourself 
Plegridy is to be injected under the skin (subcutaneous injection). Alternate the sites you use for 
injections. Do not use the same injection site for consecutive injections. 
  



52 

 
You can inject Plegridy yourself without the help of your doctor, if you have been trained how to do 
this.  
- Read and follow the advice given in the instructions in section 7 “Instructions for injecting 

Plegridy pre-filled syringe” before you start.  
- If you have trouble handling the syringe, ask your doctor or nurse who may be able to help. 
 
How long to use Plegridy 
Your doctor will tell you how long you need to keep using Plegridy. It is important to continue using 
Plegridy regularly. Do not make changes unless your doctor tells you. 
 
If you use more Plegridy than you should 
You must only inject Plegridy once every 2 weeks.  
- If you have used more than one injection of Plegridy in a 7-day period, contact your doctor or 

nurse straight away. 
 
If you forget to use Plegridy 
You need to inject Plegridy once every 2 weeks. This regular schedule helps to deliver the treatment as 
evenly as possible.  
 
If you do miss your usual day, inject as soon as you can and carry on as usual. However, do not inject 
more than once in a 7-day period. Do not use two injections to make up for a missed injection.  
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects 
- Liver problems 
(common - may affect up to 1 in 10 people) 
If you get any of these symptoms:  
- Yellowing of your skin or the whites of your eyes 
- Itching all over 
- Feeling sick, being sick (nausea and vomiting) 
- Easy bruising of the skin 

- Contact a doctor immediately. They may be signs of a possible liver problem. 
 
- Depression 
(common - may affect up to 1 in 10 people) 
If you: 
- Feel unusually sad, anxious or worthless or 
- Have thoughts about suicide 

- Contact a doctor immediately. 
 
- Serious allergic reaction 
(uncommon - may affect up to 1 in 100 people) 
If you get any of these: 
- Difficulty breathing 
- Swelling around the face (lips, tongue or throat) 
- Skin rashes or redness 

- Contact a doctor immediately. 



53 

 
- Seizures 
(uncommon - may affect up to 1 in 100 people) 
If you have a seizure or a fit  

- Contact a doctor immediately. 
 
- Injection site damage 
(rare - may affect up to 1 in 1,000 people) 
If you get any of these symptoms:  
- Any break in the skin together with swelling, inflammation or fluid leaking around the injection 

site 
- Contact a doctor for advice. 

 
- Kidney problems including scarring that may reduce your kidney function  
(rare - may affect up to 1 in 1,000 people) 
If you get some or all of these symptoms: 
- Foamy urine 
- Fatigue 
- Swelling, particularly in the ankles and eyelids, and weight gain. 

- Contact a doctor as they may be signs of a possible kidney problem.  
 

- Blood problems  
(rare - may affect up to 1 in 1,000 people) 
The following may occur: Blood clots in the small blood vessels that can affect your kidneys 
(thrombotic thrombocytopenic purpura or haemolytic uremic syndrome). Symptoms may include 
increased bruising, bleeding, fever, extreme weakness, headache, dizziness or light-headedness.  Your 
doctor may find changes in your blood and the function of your kidneys. 
 
If you get some or all of these symptoms: 
- Increased bruising or bleeding 
- Extreme weakness 
- Headache, dizziness or light-headedness 

- Contact a doctor immediately. 
 
Other side effects 
Very common side effects  
(may affect more than 1 in 10 people) 
- Flu-like symptoms.  These symptoms are not really flu, see below. You can’t pass it on to 

anyone else. 
- Headache  
- Muscle pain (myalgia) 
- Pain in your joints, arms, legs or neck (arthralgia) 
- Chills 
- Fever 
- Feeling weak and tired (asthenia) 
- Redness, itching or pain around the place you have injected 

- If any of these effects trouble you, contact a doctor. 
 
Flu-like symptoms 
Flu-like symptoms are more common when you first start using Plegridy. They gradually get less as 
you keep using your injections. See below for simple ways to manage these flu-like symptoms if you 
get them. 
  



54 

 
Three simple ways to help reduce the impact of flu-like symptoms: 
1. Consider the timing of your Plegridy injection. The start and end of flu-like symptoms are 

different for every patient. On average, flu-like symptoms begin approximately 10 hours after 
injection and last between 12 and 24 hours. 

2. Take paracetamol or ibuprofen half an hour before your Plegridy injection and continue to take 
paracetamol or ibuprofen for the duration of your flu-like symptoms. Speak to your doctor or 
pharmacist about how much to take and how long to take it. 

3. If you have a fever, drink plenty of water to keep you hydrated. 
 
Common side effects 
(may affect up to 1 in 10 people) 
- Feeling or being sick (nausea or vomiting) 
- Hair loss (alopecia) 
- Itchy skin (pruritus)  
- Increase in body temperature 
- Changes around the place you have injected such as swelling, inflammation, bruising, warmth, 

rash or colour change 
- Changes in your blood which might cause tiredness or reduced ability to fight infection 
- Increases in liver enzymes in the blood (will show up in blood tests) 

- If any of these effects trouble you, contact a doctor. 
 
Uncommon side effects 
(may affect up to 1 in 100 people) 
- Hives  
- Changes in your blood which might cause unexplained bruising or bleeding. 

- If any of these effects trouble you, contact a doctor. 
 
 Frequency not known  
(frequency cannot be estimated from the available data) 
- Pulmonary arterial hypertension: A disease of severe narrowing of the blood vessels in the lungs 

resulting in high blood pressure in the blood vessels that carry blood from the heart to the lungs. 
Pulmonary arterial hypertension has been seen at various time points during treatment, including 
several years after starting treatment with interferon beta-products. 

 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
In order to improve the traceability of this medicine, your doctor or pharmacist should record the name 
and the lot number of the product you have been given in your patient file. You may also wish to make 
a note of these details in case you are asked for this information in the future. 
 
 
5. How to store Plegridy 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and the label after “EXP”. 
The expiry date refers to the last day of that month. 
 
- Store in the original package in order to protect from light. Only open the pack when you need a 

new syringe.  
 

- Store in a refrigerator (fridge) 2º -8 ºC.  

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


55 

- Do not freeze. Throw away any Plegridy that is accidentally frozen.  
 

- Plegridy can be kept outside a fridge at room temperature (up to 25 °C) for up to 30  days but it 
must be kept away from light.  

- Packs can be taken out of the fridge and then put back in a fridge more than once if you 
need to. 

- Make sure the time the syringes spend out of a fridge is no more than 30 days in total.   
- Throw away any syringe that is kept out of the fridge for more than 30 days.   
- If you are unsure of the number of days you have kept a syringe out of the fridge, throw 

the syringe away.   
 
- Do not use this medicine if you notice any of the following: 

- If the syringe is broken. 
- If the solution is coloured, cloudy or you can see particles floating in it. 

 
- Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how 

to throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Plegridy contains  
The active ingredient is peginterferon beta-1a. 
 
Each 63 microgram pre-filled syringe contains 63 micrograms of peginterferon beta-1a in 0.5 mL 
solution for injection. 
Each 94 microgram pre-filled syringe contains 94 micrograms of peginterferon beta-1a in 0.5 mL 
solution for injection. 
Each 125 microgram pre-filled syringe contains 125 micrograms of peginterferon beta-1a in 0.5 mL 
solution for injection. 
 
The other ingredients are: Sodium acetate trihydrate, acetic acid glacial, arginine hydrochloride, 
polysorbate 20 and water for injections (see Section 2 “Plegridy contains sodium”). 
 
What Plegridy looks like and contents of the pack 
Plegridy is a clear and colourless solution for injection in a glass pre-filled syringe with an attached 
needle. 
 
Pack sizes: 
- The Plegridy Initiation Pack contains one orange pre-filled syringe of 63 micrograms and one blue 
pre-filled syringe of 94 micrograms.  
- The 125 micrograms grey syringes are provided in a pack containing either two or six pre-filled 
syringes. 
 
Not all pack sizes may be marketed.  
 
Marketing Authorisation Holder 
Biogen Netherlands B.V. 
Prins Mauritslaan 13 
1171 LP Badhoevedorp 
The Netherlands 
 
Manufacturer 
Biogen (Denmark) Manufacturing ApS 
Biogen Allé 1 
DK-3400 Hillerød 
Denmark 



56 

 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien 
Biogen Belgium NV/SA 
 +32 2 2191218 
 

Lietuva 
Biogen Lithuania UAB 
 +370 5 259 6176 
 

България 
ТП ЕВОФАРМА 
 +359 2 962 12 00 
 

Luxembourg/Luxemburg 
Biogen Belgium NV/SA 
 +32 2 2191218 
 

Česká republika 
Biogen (Czech Republic) s.r.o. 
 +420 255 706 200 

Magyarország 
Biogen Hungary Kft. 
 +36 1 899 9883 

Danmark 
Biogen Denmark A/S 
 +45 77 41 57 57 
 

Malta 
Pharma. MT Ltd.. 
 +356 21337008 

Deutschland 
Biogen GmbH 
 +49 (0) 89 99 6170 
 

Nederland 
Biogen Netherlands B.V. 
 +31 20 542 2000 
 

Eesti 
Biogen Estonia OÜ 
 +372 618 9551 
 

Norge 
Biogen Norway AS 
 +47 23 40 01 00 

Ελλάδα 
Genesis Pharma SA 
 +30 210 8771500 
 

Österreich 
Biogen Austria GmbH 
 +43 1 484 46 13 

España 
Biogen Spain S.L. 
 +34 91 310 7110 
 

Polska 
Biogen Poland Sp. z o.o. 
 +48 22 351 51 00 
 

France 
Biogen France SAS 
 +33 (0)1 41 37 9595 
 

Portugal 
Biogen Portugal  
Sociedade Farmacêutica, Unipessoal Lda. 
 +351 21 318 8450 
 

Hrvatska 
Biogen Pharma d.o.o. 
 +385 1 775 73 22 
 

România 
Johnson & Johnson Romania S.R.L.  
 +40 21 207 18 00 

Ireland 
Biogen Idec (Ireland) Ltd. 
 +353 (0)1 463 7799 
 

Slovenija 
Biogen Pharma d.o.o. 
 +386 1 511 02 90 

Ísland 
Icepharma hf 
 +354 540 8000 

Slovenská republika 
Biogen Slovakia s.r.o. 
 +421 2 323 34008 
 



57 

Italia 
Biogen Italia s.r.l. 
 +39 02 584 9901 

Suomi/Finland 
Biogen Finland Oy 
 +358 207 401 200 
 

Κύπρος 
Genesis Pharma Cyprus Ltd 
 +357 22 76 57 40 
 
 

Sverige 
Biogen Sweden AB 
 +46 8 594 113 60 

Latvija 
Biogen Latvia SIA 
 +371 68 688 158 
 

United Kingdom 
Biogen Idec Limited 
 +44 (0) 1628 50 1000 
 

 
This leaflet was last revised in <{MM/YYYY}> <{month YYYY}>. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
 
 
7. Instructions for injecting Plegridy pre-filled syringe 
BEFORE YOU START 
How to inject Plegridy 
 
Read the instructions for use before you start using Plegridy and each time you get a refill of your 
prescription. There may be new information. This information does not take the place of talking to 
your doctor or nurse about your medical condition or your treatment.  
 
Note:  
• Before you use the Plegridy pre-filled syringe for the first time, your doctor or nurse should 

show you or your carer how to prepare and inject the Plegridy pre-filled syringe. 
• Plegridy pre-filled syringe is for injecting the medicine under the skin only (subcutaneous)  
• Each Plegridy pre-filled syringe can be used once only.  
 Do not share your Plegridy pre-filled syringe with anyone else to avoid giving an infection to 

them or getting an infection from them. 
 Do not use more than one pre-filled syringe every 14 days (every 2 weeks). 
 Do not use your syringe if it has been dropped or is visibly damaged. 

 
Dosage schedule 
The Initiation Pack contains your first two injections to gradually adjust your dose. Choose the correct 
syringe from a pack. 
 

When Which dose Which pack 
Day 0 
(63 micrograms) 

First injection: 
63 micrograms, choose 

orange syringe 

 

 

Day 14 
(94 micrograms) 

Second injection: 
94 micrograms, choose 

blue syringe 
Day 28 and then 
every two weeks 
after that 
(125 micrograms) 

Full dose injection: 
125 micrograms, choose 

grey syringe 

 
 
 

 



58 

 Do not use more than one pre-filled syringe per 14-day period (every 2 weeks). 
 

Supplies needed for your Plegridy injection  
Plegridy pre-filled syringe (see Figure A)  
Before Use – Parts of your Plegridy pre-filled syringe (Figure A) 
 

 
 

Additional supplies which are not included in the pack (See Figure B):  
• Alcohol wipe 
• Gauze pad  
• Adhesive bandage 

 
Ask your doctor, pharmacist, or nurse for instructions on throwing away used syringes. 
 

 
 
Preparing for your injection 
Step 1: Remove your pre-filled syringe from the fridge 
• Remove one Plegridy pack out of the fridge and select the appropriate pre-filled syringe from 

the pack. 
• Close the pack and put pack back in the fridge after removing one pre-filled syringe.  
• Let the Plegridy pre-filled syringe warm to room temperature for at least 30 minutes.  

  Do not use external heat sources such as hot water to warm the Plegridy pre-filled syringe.  
 

Step 2: Collect your supplies and wash your hands  
• Find a well-lit, clean, flat surface to work on, like a table. Collect all the supplies you will need 

to give yourself or to receive an injection.  
• Wash your hands with soap and water.  



59 

 

Step 3: Check the Plegridy pre-filled syringe 
 

 
• Check the expiry date on the Plegridy 

pre-filled syringe (See Figure C).  
 Do not use Plegridy pre-filled 

syringe past the expiry date.  
 
• Check that your Plegridy medicine is 

clear and colourless (See Figure D).  
 Do not use the Plegridy pre-filled 

syringe if the liquid is coloured, 
cloudy, or has floating particles in 
it.  

o You might see air bubbles in the 
Plegridy medicine. This is normal 
and does not need to be expelled 
before your injection.  

 
 

 

 
Giving your injection 

Step 4: Choose and clean your injection site  
• Plegridy pre-filled syringe is for 

subcutaneous injection (injection into 
skin).  

 
• Plegridy pre-filled syringe should be 

injected into the abdomen, thigh, or the 
back of the upper arm. (See Figure E).  

 Do not inject directly into your belly 
button.  

 
 Do not inject into an area of the body 

where the skin is irritated, tender, 
red, bruised, tattooed, infected, or 
scarred.  

 
• Choose an injection site and wipe the 

skin with an alcohol wipe.  
 
• Let the injection site dry before injecting 

the dose.  
 

 Do not touch or blow this area again 
before giving the injection.  

 

 

 



60 

Step 5: Firmly remove the needle cover 
• Using one hand, hold the syringe by the 

glass barrel. With your other hand, firmly 
grasp needle cover and pull it straight off 
the needle (See Figure F). 

 
 Use caution when removing the 

needle cover to avoid getting a 
needle stick injury.  
 

 Do not touch the needle.  
 

 Caution - Do not recap the Plegridy 
pre-filled syringe. You could get a 
needle injury. 
 

 

 

 
Step 6:  Gently pinch the injection site 
• Gently pinch the skin around the cleaned 

injection site using thumb and forefinger 
to create a slight bulge (See Figure G). 

 

 

Step 7: Inject medicine  
• Hold the Plegridy pre-filled syringe at a 

90° angle to the injection site. Quickly 
insert the needle straight into the skin 
fold until the needle is fully under the 
skin. (See Figure H).  

 
• After the needle is in, let go of your skin.  
 

 Do not pull back on the plunger. 
 

 



61 

• Slowly push the plunger all the way 
down until syringe is empty (See Figure 
I). 

 Do not take your Plegridy pre-filled 
syringe out of the injection site until 
you have pushed the plunger all the 
way down. 

 
• Keep the needle inserted in for 5 seconds 

(see Figure J). 

 
 

Step 8: Remove the pre-filled syringe from your injection site 
• Pull the needle straight out (See Figure 

K). 
 Caution - Do not recap the Plegridy 

pre-filled syringe. You could get a 
needle injury. 

 Do not reuse the Plegridy pre-filled 
syringe. 

 
 
 
After your injection  
Step 9: Disposing of the used Plegridy pre-filled syringe  
• Check with your doctor, pharmacist or nurse about the right way to throw away the used 

syringe.  
 
Step 10: Care for your injection site  
• If needed, apply a gauze pad or adhesive bandage to the injection site.  
 
Step 11: Check your injection site 
• After 2 hours, check the injection site for redness, swelling, or tenderness. 
• If you have a skin reaction and it does not clear up in a few days, contact your doctor or nurse. 
 



62 

Record date and location 
• Record the date and location of each injection. 
• For the first injections, you can use the record table printed on the inside of the lid of the 

Initiation Pack. 
 

General warnings  
 Do not reuse your Plegridy pre-filled syringe.  
 Do not share your Plegridy pre-filled syringe.  

• Keep Plegridy pre-filled syringe and all medicines out of reach of children. 
 

Storage  
• Recommended storage is controlled refrigeration 2°C to 8°C in the closed original carton to 

protect from light.  
• If needed, Plegridy may be stored in the closed original carton without refrigeration up to 25°C 

for up to 30 days.  
• Plegridy can be removed from and returned to, a refrigerator if necessary. The total 

combined time out of refrigeration at a temperature up to 25°C, should not exceed 
30 days.  

 Do not freeze or expose to high temperatures. 
 
 



63 

Package leaflet: Information for the user 
 

Plegridy 63 micrograms solution for injection in pre-filled pen 
Plegridy 94 micrograms solution for injection in pre-filled pen 
Plegridy 125 micrograms solution for injection in pre-filled pen 

peginterferon beta-1a 
 
Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Plegridy is and what it is used for  
2. What you need to know before you use Plegridy  
3. How to use Plegridy  
4. Possible side effects  
5. How to store Plegridy  
6. Contents of the pack and other information 
7.  Instructions for injecting Plegridy pre-filled pen  
 
 
1. What Plegridy is and what it is used for 
 
What Plegridy is 
The active substance in Plegridy is peginterferon beta-1a. Peginterferon beta-1a is a modified 
long-acting form of interferon. Interferons are natural substances made in the body to help protect 
from infections and diseases.  
 
What Plegridy is used for 
This medicine is used to treat relapsing-remitting multiple sclerosis (MS) in adults aged 18 or 
over.  
MS is a long term illness that affects the central nervous system (CNS), including the brain and spinal 
cord, in which the body’s immune system (its natural defences) damages the protective layer (myelin) 
that surrounds the nerves in the brain and spinal cord. This disrupts the messages between the brain 
and other parts of the body, causing the symptoms of MS. Patients with relapsing-remitting MS have 
periods when the disease is not active (remission) in between flare-ups of symptoms (relapses). 
 
Everyone has their own set of MS symptoms. These can include: 
- Feeling off-balance or light headed, walking problems, stiffness and muscle spasms, tiredness, 

numbness in the face, arms or legs 
- Acute or chronic pain, bladder and bowel problems, sexual problems and problems with vision 
- Difficulty thinking and concentrating, depression. 
 
How Plegridy works 
Plegridy seems to work by stopping the body’s immune system from damaging your brain and 
spinal cord. This can help to reduce the number of relapses that you have and slow down the disabling 
effects of MS. Treatment with Plegridy can help to prevent you from getting worse, although it will 
not cure MS. 
 
 



64 

2. What you need to know before you use Plegridy 
 
Do not use Plegridy  
- If you are allergic to peginterferon beta-1a, interferon beta-1a or any of the ingredients of this 

medicine (listed in section 6). See section 4 for the symptoms of an allergic reaction. 
- If you have severe depression or think about committing suicide. 
 
Warnings and precautions  
Talk to your doctor if you have ever had: 
- Depression or problems affecting your mood 
- Thoughts about committing suicide 

- Your doctor may still prescribe Plegridy for you, but it’s important to let your doctor know 
if you have had depression or any similar problems affecting your mood in the past. 

 
Talk to your doctor, pharmacist or nurse before injecting Plegridy if you have any of the 
conditions listed below. They may get worse while using Plegridy:  
- Serious liver or kidney problems 
- Irritation at an injection site, which can lead to skin and tissue damage (injection site 

necrosis). When you are ready to inject, carefully follow the instructions in section 7 
“Instructions for injecting Plegridy pre-filled pen”, at the end of this leaflet. This is to reduce the 
risk of injection site reactions. 

- Epilepsy or other seizure disorders, not controlled by medicine 
- Heart problems, which can cause symptoms such as chest pain (angina), particularly after any 

activity; swollen ankles, shortness of breath (congestive heart failure); or an irregular heartbeat 
(arrhythmia). 

- Thyroid problems 
- A low number of white blood cells or platelets, which can cause an increased risk of infection, 

or bleeding 
 

Other things to consider when using Plegridy 
- You will need blood tests to determine your numbers of blood cells, blood chemistry and your 

levels of liver enzymes. These will be performed before you start using Plegridy, regularly after 
treatment with Plegridy has been initiated and then periodically during treatment, even if you 
have no particular symptoms. These blood tests will be in addition to the tests which are 
normally done to monitor your MS. 

- The functioning of your thyroid gland will be checked regularly or whenever thought necessary 
by your doctor for other reasons. 

- Blood clots in the small blood vessels may occur during your treatment. These blood clots could 
affect your kidneys. This might happen several weeks to several years after starting Plegridy. 
Your doctor may want to check your blood pressure, blood (platelet count) and the function of 
your kidneys. 

 
If you accidentally prick yourself or someone else with the needle in Plegridy, the area affected should 
be washed immediately with soap and water and a doctor or nurse should be contacted as soon as 
possible. 
 
Children and adolescents 
Plegridy is not to be used in children and adolescents below 18 years old. The safety and effectiveness 
of Plegridy in this age group are not known. 
 



65 

Other medicines and Plegridy 
Plegridy should be used carefully with medicines that are broken down in the body by a group of 
proteins called “cytochrome P450” (e.g. some medicines used for epilepsy or depression). 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines, especially those used to treat epilepsy or depression. This includes any medicines obtained 
without a prescription. 
 
Sometimes you will need to remind other healthcare professionals that you are being treated with 
Plegridy. For example, if you are prescribed other medicines, or if you have a blood test. Plegridy may 
affect the other medicines or the test result. 
 
Pregnancy and breast-feeding  
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or 
pharmacist for advice before taking this medicine.  
 
No harmful effects on the breastfed newborn/infant are anticipated. Plegridy can be used during breast-
feeding. 

 
Driving and using machines  
Plegridy has no or negligible influence on the ability to drive and use machines. 
 
Plegridy contains sodium  
This medicine contains less than 1 mmol sodium (23 mg), that is to say it is essentially “sodium-free”. 
 
 
3. How to use Plegridy 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure. 
 
The usual dose 
One injection of Plegridy 125 micrograms every 14 days (every two weeks). Try to use Plegridy at the 
same time on the same day, every time you inject. 
 
Starting Plegridy 
If you are new to Plegridy, your doctor may advise you to gradually increase your dose so that you can 
adjust to the effects of Plegridy before taking the full dose. You will be provided with an Initiation 
Pack containing your first 2 injections: one orange pen with Plegridy 63 micrograms (for day 0) and 
one blue pen with Plegridy 94 micrograms (for day 14). 
 
After that you will be provided with a maintenance pack containing grey pens with Plegridy 
125 micrograms (for day 28 and then every two weeks). 
 
Read the instructions in section 7 “Instructions for injecting Plegridy pre-filled pen” at the end of this 
leaflet before you start using Plegridy. 
Use the record table printed on the inside of the lid of the Initiation Pack to keep a track of your 
injection dates. 
 
Injecting yourself 
Plegridy is to be injected under the skin (subcutaneous injection). Alternate the sites you use for 
injections. Do not use the same injection site for consecutive injections. 
You can inject Plegridy yourself without the help of your doctor, if you have been trained how to do 
this.  
  



66 

 
- Read and follow the advice given in the instructions in section 7 “Instructions for injecting 

Plegridy pre-filled pen” before you start.  
- If you have trouble handling the pen, ask your doctor or nurse who may be able to help. 
 
How long to use Plegridy 
Your doctor will tell you how long you need to keep using Plegridy. It is important to continue using 
Plegridy regularly. Do not make changes unless your doctor tells you. 
 
If you use more Plegridy than you should 
You must only inject Plegridy once every 2 weeks.  
- If you have used more than one injection of Plegridy in a 7-day period, contact your doctor or 

nurse straight away. 
 
If you forget to use Plegridy 
You need to inject Plegridy once every 2 weeks. This regular schedule helps to deliver the treatment as 
evenly as possible.  
 
If you do miss your usual day, inject as soon as you can and carry on as usual. However, do not inject 
more than once in a 7-day period. Do not use two injections to make up for a missed injection.  
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects 
- Liver problems 
(common - may affect up to 1 in 10 people) 
If you get any of these symptoms:  
- Yellowing of your skin or the whites of your eyes  
- Itching all over 
- Feeling sick, being sick (nausea and vomiting) 
- Easy bruising of the skin 

- Contact a doctor immediately. They may be signs of a possible liver problem. 
 
- Depression 
(common - may affect up to 1 in 10 people) 
If you: 
- Feel unusually sad, anxious or worthless or 
- Have thoughts about suicide 

- Contact a doctor immediately. 
 
- Serious allergic reaction 
(uncommon - may affect up to 1 in 100 people) 
If you get any of these: 
- Difficulty breathing 
- Swelling around the face (lips, tongue or throat) 
- Skin rashes or redness 

- Contact a doctor immediately. 
 
- Seizures 
(uncommon - may affect up to 1 in 100 people) 
If you have a seizure or a fit  

- Contact a doctor immediately. 



67 

 
- Injection site damage 
(rare - may affect up to 1 in 1,000 people) 
If you get any of these symptoms:  
- Any break in the skin together with swelling, inflammation or fluid leaking around the injection 

site 
- Contact a doctor for advice. 

 
- Kidney problems including scarring that may reduce your kidney function  
(rare - may affect up to 1 in 1,000 people) 
If you get some or all of these symptoms: 
- Foamy urine 
- Fatigue 
- Swelling, particularly in the ankles and eyelids, and weight gain. 

- Contact a doctor as they may be signs of a possible kidney problem.  
 

- Blood problems  
(rare - may affect up to 1 in 1,000 people) 
The following may occur: Blood clots in the small blood vessels that can affect your kidneys 
(thrombotic thrombocytopenic purpura or haemolytic uremic syndrome). Symptoms may include 
increased bruising, bleeding, fever, extreme weakness, headache, dizziness or light-headedness.  Your 
doctor may find changes in your blood and the function of your kidneys. 
 
If you get some or all of these symptoms: 
- Increased bruising or bleeding 
- Extreme weakness 
- Headache, dizziness or light-headedness 

- Contact a doctor immediately. 
 
Other side effects 
Very common side effects  
(may affect more than 1 in 10 people) 
- Flu-like symptoms.  These symptoms are not really flu, see below. You can’t pass it on to 

anyone else. 
- Headache  
- Muscle pain (myalgia) 
- Pain in your joints, arms, legs or neck (arthralgia) 
- Chills 
- Fever 
- Feeling weak and tired (asthenia) 
- Redness, itching or pain around the place you have injected 

- If any of these effects trouble you, contact a doctor. 
 
Flu-like symptoms 
Flu-like symptoms are more common when you first start using Plegridy. They gradually get less as 
you keep using your injections. See below for simple ways to manage these flu-like symptoms if you 
get them. 
 
Three simple ways to help reduce the impact of flu-like symptoms: 
1. Consider the timing of your Plegridy injection. The start and end of flu-like symptoms are 

different for every patient. On average, flu-like symptoms begin approximately 10 hours after 
injection and last between 12 and 24 hours. 

2. Take paracetamol or ibuprofen half an hour before your Plegridy injection and continue to take 
paracetamol or ibuprofen for the duration of your flu-like symptoms. Speak to your doctor or 
pharmacist about how much to take and how long to take it.  

3. If you have a fever, drink plenty of water to keep you hydrated. 
 



68 

Common side effects 
(may affect up to 1 in 10 people) 
- Feeling or being sick (nausea or vomiting) 
- Hair loss (alopecia) 
- Itchy skin (pruritus)  
- Increase in body temperature 
- Changes around the place you have injected such as swelling, inflammation, bruising, warmth, 

rash or colour change 
- Changes in your blood which might cause tiredness or reduced ability to fight infection 
- Increases in liver enzymes in the blood (will show up in blood tests) 

- If any of these effects trouble you, talk to your doctor. 
 
Uncommon side effects 
(may affect up to 1 in 100 people) 
- Hives  
- Changes in your blood which might cause unexplained bruising or bleeding. 

- If any of these effects trouble you, talk to your doctor. 
 
 Frequency not known 
(frequency cannot be estimated from the available data) 
- Pulmonary arterial hypertension: A disease of severe narrowing of the blood vessels in the lungs 

resulting in high blood pressure in the blood vessels that carry blood from the heart to the lungs. 
Pulmonary arterial hypertension has been seen at various time points during treatment, including 
several years after starting treatment with interferon beta-products. 

 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
In order to improve the traceability of this medicine, your doctor or pharmacist should record the name 
and the lot number of the product you have been given in your patient file. You may also wish to make 
a note of these details in case you are asked for this information in the future. 
 
 
5. How to store Plegridy 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and the label after “EXP”. 
The expiry date refers to the last day of that month. 
 
- Store in the original package in order to protect from light. Only open the pack when you need a 

new pen.  
 

- Store in a refrigerator (fridge), 2º-8ºC.  
- Do not freeze. Throw away any Plegridy that is accidentally frozen.  

 
- Plegridy can be kept outside a fridge at room temperature (up to 25°C) for up to 30 days but it 

must be kept away from light.  
- Packs can be taken out of the fridge and then put back in a fridge more than once if you 

need to. 
- Make sure the time the pens spend out of a fridge is no more than 30 days in total.   
- Throw away any pen that is kept out of the fridge for more than 30 days.   

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


69 

- If you are unsure of the number of days you have kept a pen out of the fridge, throw the 
pen away.   

 
- Do not use this medicine if you notice any of the following: 

- If the pen is broken. 
- If the solution is coloured, cloudy or you can see particles floating in it. 

 
- Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how 

to throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Plegridy contains  
The active ingredient is peginterferon beta-1a. 
 
Each 63 microgram pre-filled pen contains 63 micrograms of peginterferon beta-1a in 0.5 mL solution 
for injection. 
Each 94 microgram pre-filled pen contains 94 micrograms of peginterferon beta-1a in 0.5 mL solution 
for injection. 
Each 125 microgram pre-filled pen contains 125 micrograms of peginterferon beta-1a in 0.5 mL 
solution for injection. 
 
The other ingredients are: Sodium acetate trihydrate, acetic acid glacial, arginine hydrochloride, 
polysorbate 20 and water for injections (see Section 2 “Plegridy contains Sodium”). 
 
What Plegridy looks like and contents of the pack 
Plegridy is a clear and colourless solution for injection in a glass pre-filled pen with an attached 
needle. 
 
Pack sizes: 
- The Plegridy Initiation Pack contains one orange pre-filled pen of 63 micrograms and one blue 
pre-filled pen of 94 micrograms.  
- The 125 micrograms grey pens are provided in a pack containing either two or six pre-filled pens. 
 
Not all pack sizes may be marketed.  
 
Marketing Authorisation Holder 
Biogen Netherlands B.V. 
Prins Mauritslaan 13 
1171 LP Badhoevedorp 
The Netherlands 
 
Manufacturer 
Biogen (Denmark) Manufacturing ApS 
Biogen Allé 1 
DK-3400 Hillerød 
Denmark 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien 
Biogen Belgium NV/SA 
 +32 2 2191218 
 

Lietuva 
Biogen Lithuania UAB 
 +370 5 259 6176 
 



70 

България 
ТП ЕВОФАРМА 
 +359 2 962 12 00 
 

Luxembourg/Luxemburg 
Biogen Belgium NV/SA 
 +32 2 2191218 
 

Česká republika 
Biogen (Czech Republic) s.r.o. 
 +420 255 706 200 

Magyarország 
Biogen Hungary Kft. 
 +36 1 899 9883 

Danmark 
Biogen Denmark A/S 
 +45 77 41 57 57 
 

Malta 
Pharma. MT Ltd.. 
 +356 21337008 

Deutschland 
Biogen GmbH 
 +49 (0) 89 99 6170 
 

Nederland 
Biogen Netherlands B.V. 
 +31 20 542 2000 
 

Eesti 
Biogen Estonia OÜ 
 +372 618 9551 
 

Norge 
Biogen Norway AS 
 +47 23 40 01 00 

Ελλάδα 
Genesis Pharma SA 
 +30 210 8771500 
 

Österreich 
Biogen Austria GmbH 
 +43 1 484 46 13 

España 
Biogen Spain S.L. 
 +34 91 310 7110 
 

Polska 
Biogen Poland Sp. z o.o. 
 +48 22 351 51 00 
 

France 
Biogen France SAS 
 +33 (0)1 41 37 9595 
 

Portugal 
Biogen Portugal  
Sociedade Farmacêutica, Unipessoal Lda. 
 +351 21 318 8450 
 

Hrvatska 
Biogen Pharma d.o.o. 
 +385 1 775 73 22 
 

România 
Johnson & Johnson Romania S.R.L.  
 +40 21 207 18 00 

Ireland 
Biogen Idec (Ireland) Ltd. 
 +353 (0)1 463 7799 
 

Slovenija 
Biogen Pharma d.o.o. 
 +386 1 511 02 90 

Ísland 
Icepharma hf 
 +354 540 8000 

Slovenská republika 
Biogen Slovakia s.r.o. 
 +421 2 323 34008 
 

Italia 
Biogen Italia s.r.l. 
 +39 02 584 9901 

Suomi/Finland 
Biogen Finland Oy 
 +358 207 401 200 
 

Κύπρος 
Genesis Pharma Cyprus Ltd 
 +357 22 76 57 40 
 

Sverige 
Biogen Sweden AB 
 +46 8 594 113 60 



71 

Latvija 
Biogen Latvia SIA 
 +371 68 688 158 
 

United Kingdom 
Biogen Idec Limited 
 +44 (0) 1628 50 1000 
 

 
This leaflet was last revised in <{MM/YYYY}> <{month YYYY}>. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
 
 
7. Instructions for injecting Plegridy pre-filled pen 
 

 Caution! Do not remove the cap until you are ready to inject. 
 
How to Inject Plegridy 
Read the instructions for use before you start using Plegridy and each time you get a refill of your 
prescription. There may be new information. This information does not take the place of talking to 
your doctor or nurse about your medical condition or your treatment. 
 
Note: 
• Before you use the pen for the first time, your doctor or nurse should show you or your carer 

how to prepare and inject the pen. 
• The pen is for use under the skin only (subcutaneous). 
• Each pen can be used once only.  

 Do not share the pen with anyone else to avoid giving an infection to them or getting an 
infection from them. 

 Do not use more than 1 pen every 14 days (every 2 weeks). 
 Do not use the pen if it has been dropped or is visibly damaged. 

 
Dosage schedule 
The Initiation Pack contains your first two injections to gradually adjust your dose. Choose the correct 
pen from a pack. 
 

When Which dose Which pack 
Day 0 
(63 micrograms) 

First injection: 
63 micrograms, choose 

orange pen 

 
 

 

Day 14 
(94 micrograms) 

Second injection: 
94 micrograms, choose 

blue pen 

Day 28 and then 
every two weeks 
after that 
(125 micrograms) 

Full dose injection: 
125 micrograms, choose 

grey pen 

 
 
 

    
 Do not use more than one pen per 14-day period (every 2 weeks). 

 
Supplies needed for your Plegridy Pen injection: 
• 1 Plegridy Pen (see Figure A) 



72 

Before use – Parts of Plegridy Pen (Figure A) 

 
 

 Caution! Do not remove the cap until you are ready to inject. If you remove the cap, do not re-
cap the pen. Re-capping could cause the pen to lock. 

 
Additional supplies which are not included in the pack (see Figure B): 

 
 
Preparing for your injection 
 
Step 1: Remove your pen from the fridge. 
 
a. Remove your Plegridy pack from the fridge and select the appropriate pen (dosage) from the 

pack. 
b. Close the pack and put back in the fridge after removing one pen. 
c. Let the pen warm to room temperature for at least 30 minutes.  

 Do not use external heat sources, such as hot water, to warm your pen.   
 

Step 2: Collect your supplies and wash your hands. 
 
a. Find a well-lit, clean, flat surface to work on like a table. Collect all the supplies you will need 

to give yourself, or receive, an injection. 
b. Wash your hands with soap and water. 
 

 

 
 
  



73 

Step 3: Check your Plegridy pen (see Figure C) 

 
a. Check the injection status window. You 

should see green stripes. 
 

b. Check the expiry date. 
 

c. Check the medicine window and make 
sure the Plegridy medicine is clear and 
colourless. 

 Do not use the pen if: 
• You do not see the green stripes 

in the injection status window. 
• It is expired. 
• The liquid is coloured, cloudy or 

contains floating particles. 
 
Note:  You might see air bubbles in the 
medicine window. This is normal and will not 
affect your dose. 

 
 Do not use the pen if it has been dropped 

or is visibly damaged.  
 

 
Step 4:  Choose and clean your injection site  
a. Choose an injection site in your thigh, 

abdomen, or the back of your upper arm (see 
highlighted areas in Figure D). 
• If some areas are too difficult for you to 

reach, ask a carer who has been trained to 
help you. 

 Do not inject into an area of your body 
where the skin is irritated, red, bruised, 
tattooed, infected, or scarred. 

 Do not inject directly into your belly 
button. 
 

b. Wipe your skin with an alcohol wipe. 
 Note: Do not touch or blow on this area 

again before giving your injection. 
 

c. Let your injection site dry on its own before 
injecting your dose. 

 

 



74 

Giving your injection 
Step 5:  Remove the Plegridy pen cap  
a. Pull the pen cap straight off and set it aside (see 

Figure E). Your pen is now ready to inject. 
 

 Warning! Do not touch, clean, or manipulate 
the needle cover. You could get a needle 
injury or the pen may lock. 

 Caution! Do not re-cap your pen. This could 
lock the pen 

 

 
Step 6: Give the injection 
a. Hold the pen over your injection site. Make 

sure you can see the green stripes in the 
injection status window (see Figure F). 
• You should hold the pen over your 

injection site at 90o angle. 
 

 Warning! Do not rest the pen on the 
injection site until you are ready to inject. 
This may cause the pen to accidently lock. 
 

 

 

  

 
 

b. Firmly press and hold down the pen on your 
injection site. You will hear the clicking sounds 
start. This tells you that the injection is 
happening (see Figure G). 
 

 

 
c. Continue to hold the pen firmly down on your 

injection site until the clicking sounds have 
stopped (see Figure H). 
 

 Do not lift your pen off your injection site 
until the clicking sounds stop and you see 
green ticks in the injection status window. 

 Warning! If you do not hear clicking 
sounds or you do not see green ticks in 
the injection status window after 
attempting to inject, the pen may have 
locked and you may not have received your 
injection. You should then contact your 
doctor, nurse or pharmacist. 

 
 

 
 

 



75 

Step 7: Remove the Plegridy pen from your injection site  
a. After the clicking sound has stopped, lift the 

pen from your injection site. The needle cover 
will extend to cover the needle and will lock 
(see Figure I). 
• If you see blood at your injection site, wipe 

it off with the gauze pad and apply an 
adhesive bandage or plaster 

 

 

 
 

Step 8: Check to make sure you received your full dose of Plegridy (see Figure J) 
a. Check the injection status window. You 

should see green ticks. 
b. Check the medicine window. You should 

see a yellow plunger.  

 
 

 
 
After the injection 
After Use – Parts of your Plegridy pen (see Figure K): 

 
 
Note: After the pen has been removed from the injection site, the needle cover will lock to protect 
against needle injury. Do not re-cap the pen. 



76 

 
Step 9: Dispose of used Plegridy pen 
• Check with your doctor, pharmacist or nurse about the right way to throw away the used pen. 

 Do not re-cap the pen. 
 
Step 10: Care for your injection site 
• If needed, apply a gauze pad or adhesive bandage or plaster to the injection site. 
 
Step 11: Check injection site 
• After 2 hours, check the injection site for redness, swelling, or tenderness. 
• If you have a skin reaction and it does not clear up in a few days, contact your doctor or nurse. 
 
Record date and location 
• Record the date and location of each injection. 
• For the Initiation Pack injections, you can use the record table printed on the inside of the lid of 

the Initiation Pack. 
 
General warnings 

 Do not reuse your Plegridy pen. 
 Do not share your Plegridy pen. 
• Keep Plegridy pen and all medicines out of reach of children. 

Storage 
• Recommended storage is controlled refrigeration 2°C to 8°C in the closed original carton to 

protect from light.  
• If needed, Plegridy may be stored in the closed original carton without refrigeration up to 25°C 

for up to 30 days. 
• Plegridy can be removed from and returned to the refrigerator if necessary. The total 

combined time out of refrigeration at a temperature up to 25°C, should not exceed 
30 days.  

 Do not freeze or expose to high temperatures. 
 
 



77 

Package leaflet: Information for the user 
 

Plegridy 125 micrograms solution for injection in pre-filled syringe 
peginterferon beta-1a 

 
Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Plegridy is and what it is used for  
2. What you need to know before you use Plegridy  
3. How to use Plegridy  
4. Possible side effects  
5. How to store Plegridy  
6. Contents of the pack and other information 
7.  Instructions for injecting Plegridy pre-filled syringe  
 
 
1. What Plegridy is and what it is used for 
 
What Plegridy is 
The active substance in Plegridy is peginterferon beta-1a. Peginterferon beta-1a is a modified 
long-acting form of interferon. Interferons are natural substances made in the body to help protect 
from infections and diseases.  
 
What Plegridy is used for 
This medicine is used to treat relapsing-remitting multiple sclerosis (MS) in adults aged 18 years or 
over.  
 
MS is a long term illness that affects the central nervous system (CNS), including the brain and spinal 
cord, in which the body’s immune system (its natural defences) damages the protective layer (myelin) 
that surrounds the nerves in the brain and spinal cord. This disrupts the messages between the brain 
and other parts of the body, causing the symptoms of MS. Patients with relapsing-remitting MS have 
periods when the disease is not active (remission) in between flare-ups of symptoms (relapses). 
 
Everyone has their own set of MS symptoms. These can include: 
- Feeling off-balance or light headed, walking problems, stiffness and muscle spasms, tiredness, 

numbness in the face, arms or legs 
- Acute or chronic pain, bladder and bowel problems, sexual problems and problems with vision 
- Difficulty thinking and concentrating, depression. 
 
How Plegridy works 
Plegridy seems to work by stopping the body’s immune system from damaging your brain and 
spinal cord. This can help to reduce the number of relapses that you have and slow down the disabling 
effects of MS. Treatment with Plegridy can help to prevent you from getting worse, although it will 
not cure MS. 
 
 
2. What you need to know before you use Plegridy 
 



78 

Do not use Plegridy  
- If you are allergic to peginterferon beta-1a, interferon beta-1a or any of the ingredients of this 

medicine (listed in section 6). See section 4 for the symptoms of an allergic reaction. 
- If you have severe depression or think about committing suicide. 
 
Warnings and precautions  
Talk to your doctor if you have ever had: 
- Depression or problems affecting your mood 
- Thoughts about committing suicide 

- Your doctor may still prescribe Plegridy for you, but it’s important to let your doctor know 
if you have had depression or any similar problems affecting your mood in the past. 

 
Talk to your doctor, pharmacist or nurse before injecting Plegridy if you have any of the 
conditions listed below. They may get worse while using Plegridy:  
- Serious liver or kidney problems 
- Irritation at an injection site, which can lead to skin and tissue damage (injection site 

necrosis). When you are ready to inject, carefully follow the instructions in section 7 
“Instructions for injecting Plegridy pre-filled syringe”, at the end of this leaflet. This is to reduce 
the risk of injection site reactions. 

- Epilepsy or other seizure disorders, not controlled by medicine 
- Heart problems, which can cause symptoms such as chest pain (angina), particularly after any 

activity; swollen ankles, shortness of breath (congestive heart failure); or an irregular heartbeat 
(arrhythmia). 

- Thyroid problems 
- A low number of white blood cells or platelets, which can cause an increased risk of infection, 

or bleeding 
 

Other things to consider when using Plegridy 
- You will need blood tests to determine your numbers of blood cells, blood chemistry and your 

levels of liver enzymes. These will be performed before you start using Plegridy, regularly after 
treatment with Plegridy has been initiated and then periodically during treatment, even if you 
have no particular symptoms. These blood tests will be in addition to the tests which are 
normally done to monitor your MS. 

- The functioning of your thyroid gland will be checked regularly or whenever thought necessary 
by your doctor. 

- Blood clots in the small blood vessels may occur during your treatment. These blood clots could 
affect your kidneys. This might happen several weeks to several years after starting Plegridy. 
Your doctor may want to check your blood pressure, blood (platelet count) and the function of 
your kidneys. 

 
If you accidentally prick yourself or someone else with the needle in Plegridy, the area affected should 
be washed immediately with soap and water and a doctor or nurse should be contacted as soon as 
possible. 
 
Children and adolescents 
Plegridy is not to be used in children and adolescents below 18 years old. The safety and effectiveness 
of Plegridy in this age group are not known. 
 
Other medicines and Plegridy 
Plegridy should be used carefully with medicines that are broken down in the body by a group of 
proteins called “cytochrome P450” (e.g. some medicines used for epilepsy or depression). 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines, especially those used to treat epilepsy or depression. This includes any medicines obtained 
without a prescription. 
 



79 

Sometimes you will need to remind other healthcare professionals that you are being treated with 
Plegridy. For example, if you are prescribed other medicines, or if you have a blood test. Plegridy may 
affect the other medicines or the test result. 
 
Pregnancy and breast-feeding  
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or 
pharmacist for advice before taking this medicine.  

No harmful effects on the breastfed newborn/infant are anticipated. Plegridy can be used during breast-
feeding. 

Driving and using machines  
Plegridy has no or negligible influence on the ability to drive and use machines. 
 
Plegridy contains sodium  
This medicine contains less than 1 mmol sodium (23 mg), that is to say it is essentially “sodium-free”. 
 
3. How to use Plegridy 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure. 
 
The usual dose 
One injection of Plegridy 125 micrograms every 14 days (every two weeks). Try to use Plegridy at the 
same time on the same day, every time you inject. 
 
Starting Plegridy for intramuscular use 
If you are new to Plegridy, your doctor may advise you to gradually increase your dose during the 
first month of treatment. This means that your body can adjust to the effects of Plegridy before getting 
the full dose. 
 
The full dose from the Plegridy intramuscular pre-filled syringe is 125 micrograms. Plegridy Titration 
Clips can be attached to the syringe so that you can gradually increase your dose:  
 
Dose 1 on day 0:  
 1/2 dose (63 micrograms) with YELLOW titration clip 
 
Dose 2 on day 14:  
 3/4 dose (94 micrograms) with PURPLE titration clip 
 
Dose 3 on day 28 and then every 2 weeks:  
 full dose (125 micrograms) – NO titration clip needed 
 
Plegridy supplied in this pack is meant for injection into your thigh muscle.   
 
Read the instructions in section 7 “Instructions for injecting Plegridy pre-filled syringe” at the end of 
this leaflet before you start using Plegridy. 
 
Check with your doctor nurse or pharmacist if you are unsure how you should inject your medicine. 
 
Intramuscular is abbreviated as IM on the syringe label.   
 
Injecting yourself 
Plegridy is to be injected into the thigh muscle (intramuscular injection). Alternate the sites you use 
for injections. Do not use the same injection site for consecutive injections. 
 



80 

You can inject Plegridy yourself without the help of your doctor, if you have been trained how to do 
this.  
- Read and follow the advice given in the instructions in section 7 “Instructions for injecting 

Plegridy pre-filled syringe” before you start.  
- If you have trouble handling the syringe, ask your doctor or nurse who may be able to help. 
 
How long to use Plegridy 
Your doctor will tell you how long you need to keep using Plegridy. It is important to continue using 
Plegridy regularly. Do not make changes unless your doctor tells you. 
 
If you use more Plegridy than you should 
You must only inject Plegridy once every 2 weeks.  
- If you have used more than one injection of Plegridy in a 7-day period, contact your doctor or 

nurse straight away. 
 
If you forget to use Plegridy 
You need to inject Plegridy once every 2 weeks. This regular schedule helps to deliver the treatment as 
evenly as possible.  
 
If you do miss your usual day, inject as soon as you can and carry on as usual. However, do not inject 
more than once in a 7-day period. Do not use two injections to make up for a missed injection.  
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects 
- Liver problems 
(common - may affect up to 1 in 10 people) 
If you get any of these symptoms:  
- Yellowing of your skin or the whites of your eyes 
- Itching all over 
- Feeling sick, being sick (nausea and vomiting) 
- Easy bruising of the skin 

- Contact a doctor immediately. They may be signs of a possible liver problem. 
 
- Depression 
(common - may affect up to 1 in 10 people) 
If you: 
- Feel unusually sad, anxious or worthless or 
- Have thoughts about suicide 

- Contact a doctor immediately. 
 
- Serious allergic reaction 
(uncommon - may affect up to 1 in 100 people) 
If you get any of these: 
- Difficulty breathing 
- Swelling around the face (lips, tongue or throat) 
- Skin rashes or redness 

- Contact a doctor immediately. 



81 

 
- Seizures 
(uncommon - may affect up to 1 in 100 people) 
If you have a seizure or a fit  

- Contact a doctor immediately. 
 
- Injection site damage 
(rare - may affect up to 1 in 1,000 people) 
If you get any of these symptoms:  
- Any break in the skin together with swelling, inflammation or fluid leaking around the injection 

site 
- Contact a doctor for advice. 

 
- Kidney problems including scarring that may reduce your kidney function  
(rare - may affect up to 1 in 1,000 people) 
If you get some or all of these symptoms: 
- Foamy urine 
- Fatigue 
- Swelling, particularly in the ankles and eyelids, and weight gain. 

- Contact a doctor as they may be signs of a possible kidney problem.  
 

- Blood problems  
(rare - may affect up to 1 in 1,000 people) 
The following may occur: Blood clots in the small blood vessels that can affect your kidneys 
(thrombotic thrombocytopenic purpura or haemolytic uremic syndrome). Symptoms may include 
increased bruising, bleeding, fever, extreme weakness, headache, dizziness or light-headedness.  Your 
doctor may find changes in your blood and the function of your kidneys. 
 
If you get some or all of these symptoms: 
- Increased bruising or bleeding 
- Extreme weakness 
- Headache, dizziness or light-headedness 

- Contact a doctor immediately. 
 
Other side effects 
Very common side effects  
(may affect more than 1 in 10 people) 
- Flu-like symptoms.  These symptoms are not really flu, see below. You can’t pass it on to 

anyone else. 
- Headache  
- Muscle pain (myalgia) 
- Pain in your joints, arms, legs or neck (arthralgia) 
- Chills 
- Fever 
- Feeling weak and tired (asthenia) 
- Redness, itching or pain around the place you have injected 

- If any of these effects trouble you, contact a doctor. 
 
Flu-like symptoms 
Flu-like symptoms are more common when you first start using Plegridy. They gradually get less as 
you keep using your injections. See below for simple ways to manage these flu-like symptoms if you 
get them. 
 
Three simple ways to help reduce the impact of flu-like symptoms: 
1. Consider the timing of your Plegridy injection. The start and end of flu-like symptoms are 

different for every patient. On average, flu-like symptoms begin approximately 10 hours after 
injection and last between 12 and 24 hours. 



82 

2. Take paracetamol or ibuprofen half an hour before your Plegridy injection and continue to take 
paracetamol or ibuprofen for the duration of your flu-like symptoms. Speak to your doctor or 
pharmacist about how much to take and how long to take it. 

3. If you have a fever, drink plenty of water to keep you hydrated. 
 
Common side effects 
(may affect up to 1 in 10 people) 
- Feeling or being sick (nausea or vomiting) 
- Hair loss (alopecia) 
- Itchy skin (pruritus)  
- Increase in body temperature 
- Changes around the place you have injected such as swelling, inflammation, bruising, warmth, 

rash or colour change 
- Changes in your blood which might cause tiredness or reduced ability to fight infection 
- Increases in liver enzymes in the blood (will show up in blood tests) 

- If any of these effects trouble you, contact a doctor. 
 
Uncommon side effects 
(may affect up to 1 in 100 people) 
- Hives  
- Changes in your blood which might cause unexplained bruising or bleeding. 

- If any of these effects trouble you, contact a doctor. 
 
 Frequency not known  
(frequency cannot be estimated from the available data) 
- Pulmonary arterial hypertension: A disease of severe narrowing of the blood vessels in the lungs 

resulting in high blood pressure in the blood vessels that carry blood from the heart to the lungs. 
Pulmonary arterial hypertension has been seen at various time points during treatment, including 
several years after starting treatment with interferon beta-products. 

 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
In order to improve the traceability of this medicine, your doctor or pharmacist should record the name 
and the lot number of the product you have been given in your patient file. You may also wish to make 
a note of these details in case you are asked for this information in the future. 
 
 
5. How to store Plegridy 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and the label after “EXP”. 
The expiry date refers to the last day of that month. 
 
- Store in the original package in order to protect from light. Only open the pack when you need a 

new syringe.  
 

- Store in a refrigerator (fridge) 2 º-8 ºC.  
- Do not freeze. Throw away any Plegridy that is accidentally frozen.  

 
- Plegridy can be kept outside a fridge at room temperature (up to 25 °C) for up to 30 days but it 

must be kept away from light.  

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


83 

- Packs can be taken out of the fridge and then put back in a fridge more than once if you 
need to. 

- Make sure the time the syringes spend out of a fridge is no more than 30 days in total.   
- Throw away any syringe that is kept out of the fridge for more than 30 days.   
- If you are unsure of the number of days you have kept a syringe out of the fridge, throw 

the syringe away.   
 
- Do not use this medicine if you notice any of the following: 

- If the syringe is broken. 
- If the solution is coloured, cloudy or you can see particles floating in it. 

 
- Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how 

to throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Plegridy contains  
The active ingredient is peginterferon beta-1a. 
 
Each 125 microgram pre-filled syringe contains 125 micrograms of peginterferon beta-1a in 0.5 mL 
solution for injection. 
 
The other ingredients are: Sodium acetate trihydrate, acetic acid glacial, arginine hydrochloride, 
polysorbate 20 and water for injections (see Section 2 “Plegridy contains sodium”). 
 
What Plegridy looks like and contents of the pack 
Plegridy is a clear and colourless solution for injection in a glass pre-filled syringe supplied with a 
needle.  
 
Pack sizes: 
- The syringes are provided in a pack containing either two or six pre-filled syringes with 23 gauge, 
1.25 inch long sterile needles. 
 
Not all pack sizes may be marketed.  
 
Marketing Authorisation Holder 
Biogen Netherlands B.V. 
Prins Mauritslaan 13 
1171 LP Badhoevedorp 
The Netherlands 
 
Manufacturer 
Biogen (Denmark) Manufacturing ApS 
Biogen Allé 1 
DK-3400 Hillerød 
Denmark 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien 
Biogen Belgium NV/SA 
 +32 2 2191218 
 

Lietuva 
Biogen Lithuania UAB 
 +370 5 259 6176 
 
 



84 

България 
ТП ЕВОФАРМА 
 +359 2 962 12 00 
 

Luxembourg/Luxemburg 
Biogen Belgium NV/SA 
 +32 2 2191218 
 

Česká republika 
Biogen (Czech Republic) s.r.o. 
 +420 255 706 200 

Magyarország 
Biogen Hungary Kft. 
 +36 1 899 9883 

Danmark 
Biogen Denmark A/S 
 +45 77 41 57 57 
 

Malta 
Pharma. MT Ltd.. 
 +356 21337008 

Deutschland 
Biogen GmbH 
 +49 (0) 89 99 6170 
 

Nederland 
Biogen Netherlands B.V. 
 +31 20 542 2000 
 

Eesti 
Biogen Estonia OÜ 
 +372 618 9551 
 

Norge 
Biogen Norway AS 
 +47 23 40 01 00 

Ελλάδα 
Genesis Pharma SA 
 +30 210 8771500 
 

Österreich 
Biogen Austria GmbH 
 +43 1 484 46 13 

España 
Biogen Spain S.L. 
 +34 91 310 7110 
 

Polska 
Biogen Poland Sp. z o.o. 
 +48 22 351 51 00 
 

France 
Biogen France SAS 
 +33 (0)1 41 37 9595 
 

Portugal 
Biogen Portugal  
Sociedade Farmacêutica, Unipessoal Lda. 
 +351 21 318 8450 
 

Hrvatska 
Biogen Pharma d.o.o. 
 +385 1 775 73 22 
 

România 
Johnson & Johnson Romania S.R.L.  
 +40 21 207 18 00 

Ireland 
Biogen Idec (Ireland) Ltd. 
 +353 (0)1 463 7799 
 

Slovenija 
Biogen Pharma d.o.o. 
 +386 1 511 02 90 

Ísland 
Icepharma hf 
 +354 540 8000 

Slovenská republika 
Biogen Slovakia s.r.o. 
 +421 2 323 34008 
 

Italia 
 
 +39 02 584 9901 

Suomi/Finland 
Biogen Finland Oy 
 +358 207 401 200 
 

Κύπρος 
Genesis Pharma Cyprus Ltd 
 +357 22 76 57 40 
 
 

Sverige 
Biogen Sweden AB 
 +46 8 594 113 60 



85 

Latvija 
Biogen Latvia SIA 
 +371 68 688 158 
 

United Kingdom 
Biogen Idec Limited 
 +44 (0) 1628 50 1000 
 

 
This leaflet was last revised in <{MM/YYYY}> <{month YYYY}>. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
 
 
7. Instructions for injecting Plegridy pre-filled syringe  
How to inject Plegridy 
 

Read the instructions for use before you start using Plegridy pre-filled syringe. There may be new 
information. This information does not take the place of talking to your healthcare provider about your 
medical condition or your treatment.   
 
Supplies you will need for the Plegridy injection: 

• 1 Plegridy Administration Dose Pack that contains: 

• 1 Plegridy pre-filled syringe 

• 23 gauge, 1.25 inch long sterile needle 

• a puncture resistant container for disposal of used syringes and needles 

• Additional supplies which are not included in the pack:  
• Alcohol wipe 

• Gauze pad  

• Adhesive bandage 

 
If you are new to Plegridy your dose may be titrated over 2 injections  by using the syringe with 
the Plegridy titration kit. 
 
o Dose 1: 
 ½ dose (yellow titration clip) (not supplied as part of the pack) 
 
o Dose 2:  
 ¾ dose (purple titration clip) (not supplied as part of the pack) 
 
o Dose 3:  
 a full dose (no clip required) 
 
• The   Plegridy titration clips are for single use only with the Plegridy pre-filled syringe. Do not re-use 
the syringe or titration clips. 
 
• You must prepare the Plegridy pre-filled syringe and needle before you put it into the Plegridy 
titration clip 
 
Preparing the dose of Plegridy: 



86 

• Find a well-lit, clean, flat work surface like a table and collect all the supplies you will need to 
give yourself or receive an injection. 

• Take 1 Plegridy pre-filled syringe out of the refrigerator about 30 minutes before you plan on 
injecting the Plegridy dose to allow it to reach room temperature. Do not use external heat sources 
such as hot water to warm the Plegridy pre-filled syringe.  

• Check the expiration date printed on syringe label, lid and outer carton.  Do not use Plegridy pre-
filled syringe past the expiration date. 

• Wash your hands with soap and water.   
 
Preparing the Plegridy injection: 

Step 1: Check the syringe (See Figure A):    

• The syringe should not have any cracks 
or damage. 

• Check that the cap is intact and has not 
been removed.   

• Plegridy should look clear, colorless, 
and should not have any particles in it.     

• Do not use the Plegridy pre-filled syringe 
if: 

• the syringe is cracked or damaged 

• the solution is cloudy, colored, or has 
lumps or particles in it  

• the cap has been removed or is not 
tightly attached  

 

Do not use that syringe if you see any of the 
above.  Get a new syringe.   

 

Figure A 

Step 2: With 1 hand, hold the  syringe right 
under the cap and with the cap pointing up (See 
Figure B).   

• Make sure you are holding the syringe by 
the ridged part, directly under the cap.   

 

 

 

Figure B 



87 

Step 3: With the other hand, grasp the cap and 
bend it at a 90º angle until the cap snaps off 
(See Figure C). 

 

 

 

 

 

 

 

 

 

 

 

This will expose the syringe glass tip (See 
Figure D). 

 

 

Figure C 

 

 

Figure D 
Step 4: Open the single use sterile needle 
package and take out the covered needle. Hold 
the syringe with the glass syringe tip pointing 
up. Press the needle on the  syringe glass tip 
(See Figure E).  

   

 

 

 

 

Figure E 



88 

Step 5: Gently turn the needle forward 
(clockwise) until it is tight and firmly attached 
(See Figure F).  

• If the needle is not firmly attached, the 
syringe may leak and you may not get your 
full dose of Plegridy.  

• Do not  remove the plastic cover from the 
needle.  

 

 

Figure F 

 
Giving the Plegridy injection: 

• Your healthcare provider should show you or a caregiver how to prepare and inject the dose of 
Plegridy before a syringe is used for the first time.  Your healthcare provider or nurse should 
watch you inject the dose of Plegridy the first time the syringe is used. 

• Inject your Plegridy exactly as your healthcare provider has shown you.  

• Plegridy is injected into the muscle (intramuscularly).  

• Plegridy should be injected into the thigh (See Figure G). 

• Change (rotate) your injection sites for each dose.  Do not use the same injection site for each 
injection.   

• Do not inject into an area of the body where the skin is irritated, reddened, bruised, infected or 
scarred in any way. 

Step 6: Choose either your left or right thigh 
and wipe the skin with an alcohol wipe (See 
Figure G).  Let the injection site dry before 
injecting the dose. 

• Do not touch, blow or wipe this area again 
before giving the injection. 

              
      Figure G                     

 

Step 7: Pull the protective cover straight off 
the needle (See Figure H).  Do not twist the 
cover off. 

 

Figure H 



89 

Step 8: With 1 hand, stretch the skin out 
around the injection site.  With the other hand, 
hold the syringe like a pencil.  Use a quick 
dart-like motion and insert the needle at a 90 o 
degree angle, through the skin and into the 
muscle (See Figure I).  Once the needle is in, 
let go of the skin.  

Figure I 

Step 9: Slowly push the plunger down until the 
syringe is empty (See Figure J).   

 

 

 

  

Figure J 
Step 10: Pull the needle out of the skin (See 
Figure K). Press down on the injection site 
with the gauze pad for a few seconds or rub 
gently in a circular motion. 

• If you see blood after you press the 
injection site for a few seconds, wipe it off 
with gauze pad  

• and apply an adhesive bandage. 
 

Figure K 

 
After the Plegridy injection:      

• Do not recap the needle.  Recapping the needle can lead to a needle stick injury. 

• Throw away the used syringes and needles in a sharps container or some type of hard plastic or 
metal container with a screw cap such as a detergent bottle or coffee can.  Check with your 
healthcare provider about the right way to throw away the container.  There may be local or state 
laws about how to throw away used syringes and needles.  Do not throw away used syringes and 
needles in household trash or recycling bins. 

• Plegridy may commonly cause redness, pain, or swelling of your skin at the injection site. 

• Call your healthcare provider right away if your injection site becomes swollen and painful or the 
area looks infected and does not heal within a few days. 

 
General information about the safe and effective use of Plegridy  

• Always use a new syringe and needle for each injection.  Do not re-use your Plegridy syringe or 
needles. 

• Do not share your syringe or needles.  

 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
	C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT  
	A. LABELLING
	B. PACKAGE LEAFLET

<<
  /ASCII85EncodePages false
  /AllowPSXObjects true
  /AllowTransparency false
  /AlwaysEmbed [
    true
  ]
  /AntiAliasColorImages false
  /AntiAliasGrayImages false
  /AntiAliasMonoImages false
  /AutoFilterColorImages true
  /AutoFilterGrayImages true
  /AutoPositionEPSFiles true
  /AutoRotatePages /All
  /Binding /Left
  /CalCMYKProfile (Japan Color 2001 Coated)
  /CalGrayProfile (Gray Gamma 2.2)
  /CalRGBProfile (Adobe RGB \0501998\051)
  /CannotEmbedFontPolicy /Warning
  /CheckCompliance [
    /None
  ]
  /ColorACSImageDict <<
    /HSamples [
      2
      1
      1
      2
    ]
    /QFactor 0.76000
    /VSamples [
      2
      1
      1
      2
    ]
  >>
  /ColorConversionStrategy /sRGB
  /ColorImageAutoFilterStrategy /JPEG
  /ColorImageDepth -1
  /ColorImageDict <<
    /HSamples [
      2
      1
      1
      2
    ]
    /QFactor 0.76000
    /VSamples [
      2
      1
      1
      2
    ]
  >>
  /ColorImageDownsampleThreshold 1.50000
  /ColorImageDownsampleType /Bicubic
  /ColorImageFilter /DCTEncode
  /ColorImageMinDownsampleDepth 1
  /ColorImageMinResolution 150
  /ColorImageMinResolutionPolicy /OK
  /ColorImageResolution 150
  /ColorSettingsFile ()
  /CompatibilityLevel 1.5
  /CompressObjects /Tags
  /CompressPages true
  /ConvertImagesToIndexed true
  /CreateJDFFile false
  /CreateJobTicket false
  /CropColorImages false
  /CropGrayImages false
  /CropMonoImages false
  /DSCReportingLevel 0
  /DefaultRenderingIntent /Default
  /Description <<
    /ENU ([Based on '150dpi-RGB'] Use these settings to create Adobe PDF documents suitable for reliable viewing and printing of business documents.  Created PDF documents can be opened with Acrobat and Adobe Reader 6.0 and later.)
  >>
  /DetectBlends true
  /DetectCurves 0.10000
  /DoThumbnails false
  /DownsampleColorImages true
  /DownsampleGrayImages true
  /DownsampleMonoImages true
  /EmbedAllFonts true
  /EmbedJobOptions true
  /EmbedOpenType false
  /EmitDSCWarnings false
  /EncodeColorImages true
  /EncodeGrayImages true
  /EncodeMonoImages true
  /EndPage -1
  /GrayACSImageDict <<
    /HSamples [
      2
      1
      1
      2
    ]
    /QFactor 0.76000
    /VSamples [
      2
      1
      1
      2
    ]
  >>
  /GrayImageAutoFilterStrategy /JPEG
  /GrayImageDepth -1
  /GrayImageDict <<
    /HSamples [
      2
      1
      1
      2
    ]
    /QFactor 0.76000
    /VSamples [
      2
      1
      1
      2
    ]
  >>
  /GrayImageDownsampleThreshold 1.50000
  /GrayImageDownsampleType /Bicubic
  /GrayImageFilter /DCTEncode
  /GrayImageMinDownsampleDepth 2
  /GrayImageMinResolution 150
  /GrayImageMinResolutionPolicy /OK
  /GrayImageResolution 150
  /ImageMemory 1048576
  /JPEG2000ColorACSImageDict <<
    /Quality 15
    /TileHeight 256
    /TileWidth 256
  >>
  /JPEG2000ColorImageDict <<
    /Quality 15
    /TileHeight 256
    /TileWidth 256
  >>
  /JPEG2000GrayACSImageDict <<
    /Quality 15
    /TileHeight 256
    /TileWidth 256
  >>
  /JPEG2000GrayImageDict <<
    /Quality 15
    /TileHeight 256
    /TileWidth 256
  >>
  /LockDistillerParams false
  /MaxSubsetPct 100
  /MonoImageDepth -1
  /MonoImageDict <<
    /K -1
  >>
  /MonoImageDownsampleThreshold 1.50000
  /MonoImageDownsampleType /Bicubic
  /MonoImageFilter /CCITTFaxEncode
  /MonoImageMinResolution 1200
  /MonoImageMinResolutionPolicy /OK
  /MonoImageResolution 1200
  /Namespace [
    (Adobe)
    (Common)
    (1.0)
  ]
  /NeverEmbed [
    true
  ]
  /OPM 1
  /Optimize true
  /OtherNamespaces [
    <<
      /AsReaderSpreads false
      /CropImagesToFrames true
      /ErrorControl /WarnAndContinue
      /FlattenerIgnoreSpreadOverrides false
      /IncludeGuidesGrids false
      /IncludeNonPrinting false
      /IncludeSlug false
      /Namespace [
        (Adobe)
        (InDesign)
        (4.0)
      ]
      /OmitPlacedBitmaps false
      /OmitPlacedEPS false
      /OmitPlacedPDF false
      /SimulateOverprint /Legacy
    >>
    <<
      /AllowImageBreaks true
      /AllowTableBreaks true
      /ExpandPage false
      /HonorBaseURL true
      /HonorRolloverEffect false
      /IgnoreHTMLPageBreaks false
      /IncludeHeaderFooter false
      /MarginOffset [
        0
        0
        0
        0
      ]
      /MetadataAuthor ()
      /MetadataKeywords ()
      /MetadataSubject ()
      /MetadataTitle ()
      /MetricPageSize [
        0
        0
      ]
      /MetricUnit /inch
      /MobileCompatible 0
      /Namespace [
        (Adobe)
        (GoLive)
        (8.0)
      ]
      /OpenZoomToHTMLFontSize false
      /PageOrientation /Portrait
      /RemoveBackground false
      /ShrinkContent true
      /TreatColorsAs /MainMonitorColors
      /UseEmbeddedProfiles false
      /UseHTMLTitleAsMetadata true
    >>
    <<
      /AddBleedMarks false
      /AddColorBars false
      /AddCropMarks false
      /AddPageInfo false
      /AddRegMarks false
      /BleedOffset [
        0
        0
        0
        0
      ]
      /ConvertColors /ConvertToRGB
      /DestinationProfileName (Japan Color 2001 Coated)
      /DestinationProfileSelector /UseName
      /Downsample16BitImages true
      /FlattenerPreset <<
        /PresetSelector /MediumResolution
      >>
      /FormElements true
      /GenerateStructure false
      /IncludeBookmarks true
      /IncludeHyperlinks true
      /IncludeInteractive false
      /IncludeLayers false
      /IncludeProfiles true
      /MarksOffset 6
      /MarksWeight 0.25000
      /MultimediaHandling /UseObjectSettings
      /Namespace [
        (Adobe)
        (CreativeSuite)
        (2.0)
      ]
      /PDFXOutputIntentProfileSelector /UseName
      /PageMarksFile /RomanDefault
      /PreserveEditing true
      /UntaggedCMYKHandling /UseDocumentProfile
      /UntaggedRGBHandling /UseDocumentProfile
      /UseDocumentBleed false
    >>
  ]
  /PDFX1aCheck false
  /PDFX3Check false
  /PDFXBleedBoxToTrimBoxOffset [
    0
    0
    0
    0
  ]
  /PDFXCompliantPDFOnly false
  /PDFXNoTrimBoxError true
  /PDFXOutputCondition ()
  /PDFXOutputConditionIdentifier (JC200103)
  /PDFXOutputIntentProfile (Japan Color 2001 Coated)
  /PDFXRegistryName (http://www.color.org)
  /PDFXSetBleedBoxToMediaBox true
  /PDFXTrapped /False
  /PDFXTrimBoxToMediaBoxOffset [
    0
    0
    0
    0
  ]
  /ParseDSCComments true
  /ParseDSCCommentsForDocInfo true
  /ParseICCProfilesInComments true
  /PassThroughJPEGImages true
  /PreserveCopyPage true
  /PreserveDICMYKValues true
  /PreserveEPSInfo false
  /PreserveFlatness false
  /PreserveHalftoneInfo false
  /PreserveOPIComments false
  /PreserveOverprintSettings true
  /StartPage 1
  /SubsetFonts true
  /TransferFunctionInfo /Apply
  /UCRandBGInfo /Remove
  /UsePrologue false
  /sRGBProfile (sRGB IEC61966-2.1)
>> setdistillerparams
<<
  /HWResolution [600 600]
  /PageSize [612.000 792.000]
>> setpagedevice