Zessly

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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This medicinal product is subject to additional monitoring. This will allow quick identification 
of new safety information. Healthcare professionals are asked to report any suspected adverse 
reactions. See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zessly 100 mg powder for concentrate for solution for infusion. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial contains 100 mg of infliximab. Infliximab is a chimeric human-murine IgG1 monoclonal 
antibody produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology. After 
reconstitution each ml contains 10 mg of infliximab. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder for concentrate for solution for infusion (powder for concentrate). 
 
The powder is a freeze-dried white pellet. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Rheumatoid arthritis 
 
Zessly, in combination with methotrexate, is indicated for the reduction of signs and symptoms as 
well as the improvement in physical function in: 
• adult patients with active disease when the response to disease-modifying antirheumatic 

drugs (DMARDs), including methotrexate, has been inadequate. 
• adult patients with severe, active and progressive disease not previously treated with 

methotrexate or other DMARDs. 
In these patient populations, a reduction in the rate of the progression of joint damage, as measured 
by X-ray, has been demonstrated (see section 5.1). 
 
Adult Crohn’s disease 
 
Zessly is indicated for: 
• treatment of moderately to severely active Crohn’s disease, in adult patients who have not 

responded despite a full and adequate course of therapy with a corticosteroid and/or an 
immunosuppressant; or who are intolerant to or have medical contraindications for such 
therapies. 

• treatment of fistulising, active Crohn’s disease, in adult patients who have not responded 
despite a full and adequate course of therapy with conventional treatment (including 
antibiotics, drainage and immunosuppressive therapy). 

 
Paediatric Crohn’s disease 
 
Zessly is indicated for treatment of severe, active Crohn’s disease, in children and adolescents aged 
6 to 17 years, who have not responded to conventional therapy including a corticosteroid, an 
immunomodulator and primary nutrition therapy; or who are intolerant to or have contraindications 



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for such therapies. Infliximab has been studied only in combination with conventional 
immunosuppressive therapy. 
 
Ulcerative colitis 
 
Zessly is indicated for treatment of moderately to severely active ulcerative colitis in adult patients 
who have had an inadequate response to conventional therapy including corticosteroids and 6-
mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical 
contraindications for such therapies. 
 
Paediatric ulcerative colitis 
 
Zessly is indicated for treatment of severely active ulcerative colitis, in children and adolescents 
aged 6 to 17 years, who have had an inadequate response to conventional therapy including 
corticosteroids and 6-MP or AZA, or who are intolerant to or have medical contraindications for 
such therapies. 
 
Ankylosing spondylitis 
 
Zessly is indicated for treatment of severe, active ankylosing spondylitis, in adult patients who have 
responded inadequately to conventional therapy. 
 
Psoriatic arthritis 
 
Zessly is indicated for treatment of active and progressive psoriatic arthritis in adult patients when 
the response to previous DMARD therapy has been inadequate. 
Zessly should be administered 
• in combination with methotrexate 
• or alone in patients who show intolerance to methotrexate or for whom methotrexate is 

contraindicated 
Infliximab has been shown to improve physical function in patients with psoriatic arthritis, and to 
reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with 
polyarticular symmetrical subtypes of the disease (see section 5.1). 
 
Psoriasis 
 
Zessly is indicated for treatment of moderate to severe plaque psoriasis in adult patients who failed 
to respond to, or who have a contraindication to, or are intolerant to other systemic therapy 
including cyclosporine, methotrexate or PUVA (see section 5.1). 
 
4.2 Posology and method of administration 
 
Zessly treatment is to be initiated and supervised by qualified physicians experienced in the 
diagnosis and treatment of rheumatoid arthritis, inflammatory bowel diseases, ankylosing 
spondylitis, psoriatic arthritis or psoriasis. Zessly should be administered intravenously. Zessly 
infusions should be administered by qualified healthcare professionals trained to detect any 
infusion-related issues. Patients treated with Zessly should be given the package leaflet and the 
patient reminder card. 
 
During Zessly treatment, other concomitant therapies, e.g. corticosteroids and immunosuppressants 
should be optimised. 
 



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Posology 
 
Adults (≥ 18 years) 
 
Rheumatoid arthritis 
 
3 mg/kg given as an intravenous infusion followed by additional 3 mg/kg infusion doses at 2 and 
6 weeks after the first infusion, then every 8 weeks thereafter.  
 
Zessly must be given concomitantly with methotrexate. 
 
Available data suggest that the clinical response is usually achieved within 12 weeks of treatment. 
If a patient has an inadequate response or loses response after this period, consideration may be 
given to increase the dose step-wise by approximately 1.5 mg/kg, up to a maximum of 7.5 mg/kg 
every 8 weeks. Alternatively, administration of 3 mg/kg as often as every 4 weeks may be 
considered. If adequate response is achieved, patients should be continued on the selected dose or 
dose frequency. Continued therapy should be carefully reconsidered in patients who show no 
evidence of therapeutic benefit within the first 12 weeks of treatment or after dose adjustment.  
 
Moderately to severely active Crohn’s disease 
 
5 mg/kg given as an intravenous infusion followed by an additional 5 mg/kg infusion 2 weeks after 
the first infusion. If a patient does not respond after 2 doses, no additional treatment with infliximab 
should be given. Available data do not support further infliximab treatment, in patients not 
responding within 6 weeks of the initial infusion. 
 
In responding patients, the alternative strategies for continued treatment are: 
• Maintenance: Additional infusion of 5 mg/kg at 6 weeks after the initial dose, followed by 

infusions every 8 weeks or 
• Re-administration: Infusion of 5 mg/kg if signs and symptoms of the disease recur (see ‘Re-

administration’ below and section 4.4). 
 
Although comparative data are lacking, limited data in patients who initially responded to 5 mg/kg 
but who lost response indicate that some patients may regain response with dose escalation (see 
section 5.1). Continued therapy should be carefully reconsidered in patients who show no evidence 
of therapeutic benefit after dose adjustment. 
 
Fistulising, active Crohn’s disease 
 
5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusions at 2 and 
6 weeks after the first infusion. If a patient does not respond after 3 doses, no additional treatment 
with infliximab should be given. 
 
In responding patients, the alternative strategies for continued treatment are: 
• Maintenance: Additional infusions of 5 mg/kg every 8 weeks or 
• Re-administration: Infusion of 5 mg/kg if signs and symptoms of the disease recur followed 

by infusions of 5 mg/kg every 8 weeks (see ‘Re-administration’ below and section 4.4). 
 
Although comparative data are lacking, limited data in patients who initially responded to 5 mg/kg 
but who lost response indicate that some patients may regain response with dose escalation (see 
section 5.1). Continued therapy should be carefully reconsidered in patients who show no evidence 
of therapeutic benefit after dose adjustment. 
 
In Crohn’s disease, experience with re-administration if signs and symptoms of disease recur is 
limited and comparative data on the benefit/risk of the alternative strategies for continued treatment 
are lacking. 
 



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Ulcerative colitis 
 
5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 
6 weeks after the first infusion, then every 8 weeks thereafter. 
 
Available data suggest that the clinical response is usually achieved within 14 weeks of treatment, 
i.e. three doses. Continued therapy should be carefully reconsidered in patients who show no 
evidence of therapeutic benefit within this time period. 
 
Ankylosing spondylitis 
 
5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 
6 weeks after the first infusion, then every 6 to 8 weeks. If a patient does not respond by 6 weeks 
(i.e. after 2 doses), no additional treatment with infliximab should be given. 
 
Psoriatic arthritis 
 
5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 
6 weeks after the first infusion, then every 8 weeks thereafter.  
 
Psoriasis 
 
5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 
6 weeks after the first infusion, then every 8 weeks thereafter. If a patient shows no response after 
14 weeks (i.e. after 4 doses), no additional treatment with infliximab should be given. 
 
Re-administration for Crohn’s disease and rheumatoid arthritis 
 
If the signs and symptoms of disease recur, Zessly can be re-administered within 16 weeks 
following the last infusion. In clinical studies, delayed hypersensitivity reactions have been 
uncommon and have occurred after infliximab-free intervals of less than 1 year (see sections 4.4 
and 4.8). The safety and efficacy of re-administration after an infliximab-free interval of more than 
16 weeks has not been established. This applies to both Crohn’s disease patients and rheumatoid 
arthritis patients. 
 
Re-administration for ulcerative colitis 
 
The safety and efficacy of re-administration, other than every 8 weeks, has not been established 
(see sections 4.4 and 4.8). 
 
Re-administration for ankylosing spondylitis 
 
The safety and efficacy of re-administration, other than every 6 to 8 weeks, has not been established 
(see sections 4.4 and 4.8). 
 
Re-administration for psoriatic arthritis 
 
The safety and efficacy of re-administration, other than every 8 weeks, has not been established 
(see sections 4.4 and 4.8). 
 
Re-administration for psoriasis 
 
Limited experience from re-treatment with one single infliximab dose in psoriasis after an interval 
of 20 weeks suggests reduced efficacy and a higher incidence of mild to moderate infusion 
reactions when compared to the initial induction regimen (see section 5.1). 
 



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Limited experience from re-treatment following disease flare by a re-induction regimen suggests a 
higher incidence of infusion reactions, including serious ones, when compared to 8-weekly 
maintenance treatment (see section 4.8). 
 
Re-administration across indications 
 
In case maintenance therapy is interrupted, and there is a need to restart treatment, use of a re-
induction regimen is not recommended (see section 4.8). In this situation, Zessly should be re-
initiated as a single dose followed by the maintenance dose recommendations described above. 
 
Special populations 
 
Elderly  
Specific studies of infliximab in elderly patients have not been conducted. No major age-related 
differences in clearance or volume of distribution were observed in clinical studies. No dose 
adjustment is required (see section 5.2). For more information about the safety of infliximab in 
elderly patients see sections 4.4 and 4.8. 
 
Renal and/or hepatic impairment 
Infliximab has not been studied in these patient populations. No dose recommendations can be 
made (see section 5.2). 
 
Paediatric population 
 
Crohn’s disease (6 to 17 years) 
 
5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 
6 weeks after the first infusion, then every 8 weeks thereafter. Available data do not support further 
infliximab treatment in children and adolescents not responding within the first 10 weeks of 
treatment (see section 5.1). 
 
Some patients may require a shorter dosing interval to maintain clinical benefit, while for others a 
longer dosing interval may be sufficient. Patients who have had their dose interval shortened to less 
than 8 weeks may be at greater risk for adverse reactions. Continued therapy with a shortened 
interval should be carefully considered in those patients who show no evidence of additional 
therapeutic benefit after a change in dosing interval. 
 
The safety and efficacy of infliximab have not been studied in children with Crohn’s disease below 
the age of 6 years. Currently available pharmacokinetic data are described in section 5.2 but no 
recommendation on a posology can be made in children younger than 6 years. 
 
Ulcerative colitis (6 to 17 years) 
 
5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 
6 weeks after the first infusion, then every 8 weeks thereafter. Available data do not support further 
infliximab treatment in paediatric patients not responding within the first 8 weeks of treatment 
(see section 5.1). 
The safety and efficacy of infliximab have not been studied in children with ulcerative colitis below 
the age of 6 years. Currently available pharmacokinetic data are described in section 5.2 but no 
recommendation on a posology can be made in children younger than 6 years. 
 
Psoriasis 
 
The safety and efficacy of infliximab in children and adolescents younger than 18 years for the 
indication of psoriasis have not been established. Currently available data are described in section 
5.2 but no recommendation on a posology can be made. 
 



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Juvenile idiopathic arthritis, psoriatic arthritis and ankylosing spondylitis 
 
The safety and efficacy of infliximab in children and adolescents younger than 18 years for the 
indications of juvenile idiopathic arthritis, psoriatic arthritis and ankylosing spondylitis have not 
been established. Currently available data are described in section 5.2 but no recommendation on a 
posology can be made. 
 
Juvenile rheumatoid arthritis 
 
The safety and efficacy of infliximab in children and adolescents younger than 18 years for the 
indication of juvenile rheumatoid arthritis have not been established. Currently available data are 
described in sections 4.8 and 5.2 but no recommendation on a posology can be made. 
 
Method of administration 
 
Zessly should be administered intravenously over a 2 hour period. All patients administered Zessly 
are to be observed for at least 1-2 hours post-infusion for acute infusion-related reactions. 
Emergency equipment, such as adrenaline, antihistamines, corticosteroids and an artificial airway 
must be available. Patients may be pre-treated with e.g., an antihistamine, hydrocortisone and/or 
paracetamol and infusion rate may be slowed in order to decrease the risk of infusion-related 
reactions especially if infusion-related reactions have occurred previously (see section 4.4). 
 
Shortened infusions across adult indications 
 
In carefully selected adult patients who have tolerated at least 3 initial 2-hour infusions of Zessly 
(induction phase) and are receiving maintenance therapy, consideration may be given to 
administering subsequent infusions over a period of not less than 1 hour. If an infusion reaction 
occurs in association with a shortened infusion, a slower infusion rate may be considered for future 
infusions if treatment is to be continued. Shortened infusions at doses > 6 mg/kg have not been 
studied (see section 4.8).  
 
For preparation and administration instructions, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance, to other murine proteins, or to any of the excipients listed 
in section 6.1. 
 
Patients with tuberculosis or other severe infections such as sepsis, abscesses, and opportunistic 
infections (see section 4.4). 
 
Patients with moderate or severe heart failure (NYHA class III/IV) (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.  
 
Infusion reactions and hypersensitivity 
 
Infliximab has been associated with acute infusion-related reactions, including anaphylactic shock, 
and delayed hypersensitivity reactions (see section 4.8). 
Acute infusion reactions including anaphylactic reactions may develop during (within seconds) or 
within a few hours following infusion. If acute infusion reactions occur, the infusion must be 
interrupted immediately. Emergency equipment, such as adrenaline, antihistamines, corticosteroids 



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and an artificial airway must be available. Patients may be pre-treated with e.g., an antihistamine, 
hydrocortisone and/or paracetamol to prevent mild and transient effects. 
Antibodies to infliximab may develop and have been associated with an increased frequency of 
infusion reactions. A low proportion of the infusion reactions was serious allergic reactions. An 
association between development of antibodies to infliximab and reduced duration of response has 
also been observed. Concomitant administration of immunomodulators has been associated with 
lower incidence of antibodies to infliximab and a reduction in the frequency of infusion reactions. 
The effect of concomitant immunomodulator therapy was more profound in episodically-treated 
patients than in patients given maintenance therapy. Patients who discontinue immunosuppressants 
prior to or during infliximab treatment are at greater risk of developing these antibodies. Antibodies 
to infliximab cannot always be detected in serum samples. If serious reactions occur, symptomatic 
treatment must be given and further Zessly infusions must not be administered (see section 4.8). 
 
In clinical studies, delayed hypersensitivity reactions have been reported. Available data suggest an 
increased risk for delayed hypersensitivity with increasing infliximab-free interval. Patients should 
be advised to seek immediate medical advice if they experience any delayed adverse reaction (see 
section 4.8). If patients are re-treated after a prolonged period, they must be closely monitored for 
signs and symptoms of delayed hypersensitivity. 
 
Infections 
 
Patients must be monitored closely for infections including tuberculosis before, during and after 
treatment with Zessly. Because the elimination of infliximab may take up to six months, monitoring 
should be continued throughout this period. Further treatment with Zessly must not be given if a 
patient develops a serious infection or sepsis. 
 
Caution should be exercised when considering the use of Zessly in patients with chronic infection 
or a history of recurrent infections, including concomitant immunosuppressive therapy. Patients 
should be advised of and avoid exposure to potential risk factors for infection as appropriate. 
 
Tumour necrosis factor alpha (TNFα) mediates inflammation and modulates cellular immune 
responses. Experimental data show that TNFα is essential for the clearing of intracellular infections. 
 
Clinical experience shows that host defence against infection is compromised in some patients 
treated with infliximab. 
 
It should be noted that suppression of TNFα may mask symptoms of infection such as fever. Early 
recognition of atypical clinical presentations of serious infections and of typical clinical 
presentation of rare and unusual infections is critical in order to minimise delays in diagnosis and 
treatment. 
 
Patients taking TNF-blockers are more susceptible to serious infections. 
Tuberculosis, bacterial infections, including sepsis and pneumonia, invasive fungal, viral, and other 
opportunistic infections have been observed in patients treated with infliximab. Some of these 
infections have been fatal; the most frequently reported opportunistic infections with a mortality 
rate of > 5% include pneumocystosis, candidiasis, listeriosis and aspergillosis. 
Patients who develop a new infection while undergoing treatment with Zessly, should be monitored 
closely and undergo a complete diagnostic evaluation. Administration of Zessly should be 
discontinued if a patient develops a new serious infection or sepsis, and appropriate antimicrobial or 
antifungal therapy should be initiated until the infection is controlled. 
 
Tuberculosis 
There have been reports of active tuberculosis in patients receiving infliximab. It should be noted 
that in the majority of these reports tuberculosis was extrapulmonary, presenting as either local or 
disseminated disease. 
 



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Before starting treatment with Zessly, all patients must be evaluated for both active and inactive 
(‘latent’) tuberculosis. This evaluation should include a detailed medical history with personal 
history of tuberculosis or possible previous contact with tuberculosis and previous and/or current 
immunosuppressive therapy. Appropriate screening tests, (e.g. tuberculin skin test, chest X-ray, 
and/or Interferon Gamma Release Assay), should be performed in all patients (local 
recommendations may apply). It is recommended that the conduct of these tests should be recorded 
in the patient’s reminder card. Prescribers are reminded of the risk of false negative tuberculin skin 
test results, especially in patients who are severely ill or immunocompromised. 
 
If active tuberculosis is diagnosed, Zessly therapy must not be initiated (see section 4.3). 
 
If latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should 
be consulted. In all situations described below, the benefit/risk balance of Zessly therapy should be 
very carefully considered. 
 
If inactive (‘latent’) tuberculosis is diagnosed, treatment for latent tuberculosis must be started with 
antituberculosis therapy before the initiation of Zessly, and in accordance with local 
recommendations. 
 
In patients who have several or significant risk factors for tuberculosis and have a negative test for 
latent tuberculosis, antituberculosis therapy should be considered before the initiation of Zessly. 
 
Use of antituberculosis therapy should also be considered before the initiation of Zessly in patients 
with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot 
be confirmed. 
Some cases of active tuberculosis have been reported in patients treated with infliximab during and 
after treatment for latent tuberculosis. 
All patients should be informed to seek medical advice if signs/symptoms suggestive of 
tuberculosis (e.g. persistent cough, wasting/weight loss, low-grade fever) appear during or after 
Zessly treatment. 
 
Invasive fungal infections 
In patients treated with Zessly, an invasive fungal infection such as aspergillosis, candidiasis, 
pneumocystosis, histoplasmosis, coccidioidomycosis or blastomycosis should be suspected if they 
develop a serious systemic illness, and a physician with expertise in the diagnosis and treatment of 
invasive fungal infections should be consulted at an early stage when investigating these patients. 
Invasive fungal infections may present as disseminated rather than localised disease, and antigen 
and antibody testing may be negative in some patients with active infection. Appropriate empiric 
antifungal therapy should be considered while a diagnostic workup is being performed taking into 
account both the risk for severe fungal infection and the risks of antifungal therapy. 
 
For patients who have resided in or travelled to regions where invasive fungal infections such as 
histoplasmosis, coccidioidomycosis, or blastomycosis are endemic, the benefits and risks of Zessly 
treatment should be carefully considered before initiation of Zessly therapy. 
 
Fistulising Crohn’s disease 
Patients with fistulising Crohn’s disease with acute suppurative fistulas must not initiate Zessly 
therapy until a source for possible infection, specifically abscess, has been excluded (see section 
4.3). 
 
Hepatitis B (HBV) reactivation 
 
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including 
infliximab, who are chronic carriers of this virus. Some cases have had fatal outcome. 
 
Patients should be tested for HBV infection before initiating treatment with Zessly. For patients 
who test positive for HBV infection, consultation with a physician with expertise in the treatment of 



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hepatitis B is recommended. Carriers of HBV who require treatment with Zessly should be closely 
monitored for signs and symptoms of active HBV infection throughout therapy and for several 
months following termination of therapy. Adequate data of treating patients who are carriers of 
HBV with antiviral therapy in conjunction with TNF-antagonist therapy to prevent HBV 
reactivation are not available. In patients who develop HBV reactivation, Zessly should be stopped 
and effective antiviral therapy with appropriate supportive treatment should be initiated. 
 
Hepatobiliary events 
 
Cases of jaundice and non-infectious hepatitis, some with features of autoimmune hepatitis, have 
been observed in the post-marketing experience of infliximab. Isolated cases of liver failure 
resulting in liver transplantation or death have occurred. Patients with symptoms or signs of liver 
dysfunction should be evaluated for evidence of liver injury. If jaundice and/or ALT elevations ≥ 5 
times the upper limit of normal develop(s), Zessly should be discontinued, and a thorough 
investigation of the abnormality should be undertaken. 
 
Concurrent administration of TNF-alpha inhibitor and anakinra 
 
Serious infections and neutropenia were seen in clinical studies with concurrent use of anakinra and 
another TNFα-blocking agent, etanercept, with no added clinical benefit compared to etanercept 
alone. Because of the nature of the adverse reactions seen with combination of etanercept and 
anakinra therapy, similar toxicities may also result from the combination of anakinra and other 
TNFα-blocking agents. Therefore, the combination of Zessly and anakinra is not recommended. 
 
Concurrent administration of TNF-alpha inhibitor and abatacept 
 
In clinical studies concurrent administration of TNF-antagonists and abatacept has been associated 
with an increased risk of infections including serious infections compared to TNF-antagonists 
alone, without increased clinical benefit. The combination of Zessly and abatacept is not 
recommended. 
 
Concurrent administration with other biological therapeutics 
 
There is insufficient information regarding the concomitant use of infliximab with other biological 
therapeutics used to treat the same conditions as infliximab. The concomitant use of infliximab with 
these biologics is not recommended because of the possibility of an increased risk of infection, and 
other potential pharmacological interactions. 
 
Switching between biological DMARDs 
 
Care should be taken and patients should continue to be monitored when switching from one 
biologic to another, since overlapping biological activity may further increase the risk for adverse 
reactions, including infection. 
 
Vaccinations 
It is recommended that patients, if possible, be brought up to date with all vaccinations in 
agreement with current vaccination guidelines prior to initiating infliximab therapy. Patients on 
infliximab may receive concurrent vaccinations, except for live vaccines (see sections 4.5 and 4.6). 
 
In a subset of 90 adult patients with rheumatoid arthritis from the study 2 a similar proportion of 
patients in each treatment group (methotrexateplus: placebo [n=17], 3mg/kg [n=27] or 6mg/kg 
infliximab [n=46]) mounted an effective two-fold increase in titers to a polyvalent pneumococcal 
vaccine, indicating that infliximab did not interfere with T-cell independent humoral immune 
responses. However,studies from the published literature in variousindications (e.g. rheumatoid 
arthritis, psoriasis, Crohn’s disease) suggestthat non-live vaccinations received during treatment 
with anti-TNF therapies, including infliximab, may elicit a lower immune response than in patients 
not receiving anti-TNF therapy." 



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Live vaccines/therapeutic infectious agents 
 
In patients receiving anti-TNF therapy, limited data are available on the response to vaccination 
with live vaccines or on the secondary transmission of infection by live vaccines. Use of live 
vaccines can result in clinical infections, including disseminated infections. The concurrent 
administration of live vaccines with Zessly is not recommended. 
 
In infants exposed in utero to infliximab, fatal outcome due to disseminated Bacillus Calmette-
Guérin (BCG) infection has been reported following administration of BCG vaccine after birth. At 
least a six month waiting period following birth is recommended before the administration of live 
vaccines to infants exposed in utero to infliximab (see section 4.6). 
 
Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g., BCG bladder 
instillation for the treatment of cancer) could result in clinical infections, including disseminated 
infections. It is recommended that therapeutic infectious agents not be given concurrently with 
Zessly. 
 
Autoimmune processes 
 
The relative deficiency of TNFα caused by anti-TNF therapy may result in the initiation of an 
autoimmune process. If a patient develops symptoms suggestive of a lupus-like syndrome following 
treatment with Zessly and is positive for antibodies against double-stranded DNA, further treatment 
with Zessly must not be given (see section 4.8). 
 
Neurological events 
 
Use of TNF-blocking agents, including infliximab, has been associated with cases of new onset or 
exacerbation of clinical symptoms and/or radiographic evidence of central nervous system 
demyelinating disorders, including multiple sclerosis, and peripheral demyelinating disorders, 
including Guillain-Barré syndrome. In patients with pre-existing or recent onset of demyelinating 
disorders, the benefits and risks of anti-TNF treatment should be carefully considered before 
initiation of Zessly therapy. Discontinuation of Zessly should be considered if these disorders 
develop. 
 
Malignancies and lymphoproliferative disorders 
 
In the controlled portions of clinical studies of TNF-blocking agents, more cases of malignancies 
including lymphoma have been observed among patients receiving a TNF blocker compared with 
control patients. During clinical studies of infliximab across all approved indications the incidence 
of lymphoma in infliximab-treated patients was higher than expected in the general population, but 
the occurrence of lymphoma was rare. In the post-marketing setting, cases of leukaemia have been 
reported in patients treated with a TNF-antagonist. There is an increased background risk for 
lymphoma and leukaemia in rheumatoid arthritis patients with long-standing, highly active, 
inflammatory disease, which complicates risk estimation. 
 
In an exploratory clinical study evaluating the use of infliximab in patients with moderate to severe 
chronic obstructive pulmonary disease (COPD), more malignancies were reported in infliximab-
treated patients compared with control patients. All patients had a history of heavy smoking. 
Caution should be exercised in considering treatment of patients with increased risk for malignancy 
due to heavy smoking. 
 
With the current knowledge, a risk for the development of lymphomas or other malignancies in 
patients treated with a TNF-blocking agent cannot be excluded (see section 4.8). Caution should be 
exercised when considering TNF-blocking therapy for patients with a history of malignancy or 
when considering continuing treatment in patients who develop a malignancy. 
 



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Caution should also be exercised in patients with psoriasis and a medical history of extensive 
immunosuppressant therapy or prolonged PUVA treatment. 
 
Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 
22 years of age) treated with TNF-blocking agents (initiation of therapy ≤ 18 years of age), 
including infliximab in the post-marketing setting. Approximately half the cases were lymphomas. 
The other cases represented a variety of different malignancies and included rare malignancies 
usually associated with immunosuppression. A risk for the development of malignancies in patients 
treated with TNF-blockers cannot be excluded. 
 
Post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients 
treated with TNF-blocking agents including infliximab. This rare type of T-cell lymphoma has a 
very aggressive disease course and is usually fatal. Almost all patients had received treatment with 
AZA or 6-MP concomitantly with or immediately prior to a TNF-blocker. The vast majority of 
infliximab cases have occurred in patients with Crohn’s disease or ulcerative colitis and most were 
reported in adolescent or young adult males. The potential risk with the combination of AZA or 6-
MP and Zessly should be carefully considered. A risk for the development for hepatosplenic T-cell 
lymphoma in patients treated with infliximab cannot be excluded (see section 4.8). 
 
Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker 
therapy, including infliximab (see section 4.8). Periodic skin examination is recommended, 
particularly for patients with risk factors for skin cancer. 
 
A population-based retrospective cohort study using data from Swedish national health registries 
found an increased incidence of cervical cancer in women with rheumatoid arthritis treated with 
infliximab compared to biologics-naïve patients or the general population, including those over 60 
years of age. Periodic screening should continue in women treated with Zessly, including those 
over 60 years of age. 
 
All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma (for 
example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), or who 
had a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular 
intervals before therapy and throughout their disease course. This evaluation should include 
colonoscopy and biopsies per local recommendations. Current data do not indicate that infliximab 
treatment influences the risk for developing dysplasia or colon cancer . 
 
Since the possibility of increased risk of cancer development in patients with newly diagnosed 
dysplasia treated with infliximab is not established, the risk and benefits of continued therapy to the 
individual patients should be carefully considered by the clinician. 
 
Heart failure 
 
Zessly should be used with caution in patients with mild heart failure (NYHA class I/II). Patients 
should be closely monitored and Zessly must not be continued in patients who develop new or 
worsening symptoms of heart failure (see sections 4.3 and 4.8). 
 
Haematologic reactions 
 
There have been reports of pancytopenia, leukopenia, neutropenia, and thrombocytopenia in 
patients receiving TNF-blockers, including infliximab. All patients should be advised to seek 
immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias 
(e.g. persistent fever, bruising, bleeding, pallor). Discontinuation of Zessly therapy should be 
considered in patients with confirmed significant haematologic abnormalities. 
 



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Others 
 
There is limited safety experience of infliximab treatment in patients who have undergone surgical 
procedures, including arthroplasty. The long half-life of infliximab should be taken into 
consideration if a surgical procedure is planned. A patient who requires surgery while on Zessly 
should be closely monitored for infections, and appropriate actions should be taken. 
 
Failure to respond to treatment for Crohn’s disease may indicate the presence of a fixed fibrotic 
stricture that may require surgical treatment. There is no evidence to suggest that infliximab 
worsens or causes fibrotic strictures. 
 
Special populations 
 
Elderly  
The incidence of serious infections in infliximab-treated patients 65 years and older was greater 
than in those under 65 years of age. Some of those had a fatal outcome. Particular attention 
regarding the risk for infection should be paid when treating the elderly (see section 4.8). 
 
Paediatric population 
 
Infections 
 
In clinical studies, infections have been reported in a higher proportion of paediatric patients 
compared to adult patients (see section 4.8). 
 
Vaccinations 
 
It is recommended that paediatric patients, if possible, be brought up to date with all vaccinations in 
agreement with current vaccination guidelines prior to initiating Zessly therapy. Paediatric patients 
on infliximab may receive concurrent vaccinations, except for live vaccines (see sections 4.5 and 
4.6).  
 
Malignancies and lymphoproliferative disorders 
 
Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 
22 years of age) treated with TNF-blocking agents (initiation of therapy ≤ 18 years of age), 
including infliximab in the post-marketing setting. Approximately half the cases were lymphomas. 
The other cases represented a variety of different malignancies and included rare malignancies 
usually associated with immunosuppression. A risk for the development of malignancies in children 
and adolescents treated with TNF-blockers cannot be excluded. 
 
Post-marketing cases of hepatosplenic T-cell lymphoma have been reported in patients treated with 
TNF-blocking agents including infliximab. This rare type of T-cell lymphoma has a very aggressive 
disease course and is usually fatal. Almost all patients had received treatment with AZA or 6-MP 
concomitantly with or immediately prior to a TNF-blocker. The vast majority of infliximab cases 
have occurred in patients with Crohn’s disease or ulcerative colitis and most were reported in 
adolescent or young adult males. The potential risk with the combination of AZA or 6-MP and 
Zessly should be carefully considered. A risk for the development for hepatosplenic T-cell 
lymphoma in patients treated with infliximab cannot be excluded (see section 4.8). 
 
Sodium Content 
 
Zessly contains less than 1 mmol (23 mg) sodium per dose, that is to say essentially ‘sodium-free’. 
Zessly is however, diluted in sodium chloride 9 mg/ml (0.9%) solution for infusion. This should be 
taken into consideration for patients on a controlled sodium diet (see section 6.6). 
 



14 
 

4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. 
 
In rheumatoid arthritis, psoriatic arthritis and Crohn's disease patients, there are indications that 
concomitant use of methotrexate and other immunomodulators reduces the formation of antibodies 
against infliximab and increases the plasma concentrations of infliximab. However, the results are 
uncertain due to limitations in the methods used for serum analyses of infliximab and antibodies 
against infliximab. 
 
Corticosteroids do not appear to affect the pharmacokinetics of infliximab to a clinically relevant 
extent. 
 
The combination of Zessly with other biological therapeutics used to treat the same conditions as 
Zessly, including anakinra and abatacept, is not recommended (see section 4.4). 
 
It is recommended that live vaccines not be given concurrently with Zessly. It is also recommended 
that live vaccines not be given to infants after in utero exposure to infliximab for at least 6 months 
following birth (see section 4.4). 
 
It is recommended that therapeutic infectious agents not be given concurrently with Zessly (see 
section 4.4). 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
 
Women of childbearing potential should consider the use of adequate contraception to prevent 
pregnancy and continue its use for at least 6 months after the last Zessly treatment. 
 
Pregnancy 
 
The moderate number of prospectively collected pregnancies exposed to infliximab resulting in live 
birth with known outcomes, including approximately 1,100 exposed during the first trimester, does 
not indicate an increase in the rate of malformation in the newborn. 
 
Based on an observational study from Northern Europe, an increased risk (OR, 95% CI; p-value) 
for C-section section (1.50, 1.14-1.96; p = 0.0032), preterm birth (1.48, 1.05-2.09; p = 0.024), small 
for gestational age (2.79, 1.54-5.04; p = 0.0007), and low birth weight (2.03, 1.41-2.94; p = 0.0002)  
was observed in women exposed during pregnancy to infliximab (with or without 
immunomodulators/corticosteroids, 270 pregnancies) as compared to women exposed to 
immunomodulators and/or corticosteroids only (6,460 pregnancies). The potential contribution of 
exposure to infliximab and/or the severity of the underlying disease in these outcomes remains 
unclear.  
 
Due to its inhibition of TNFα, infliximab administered during pregnancy could affect normal 
immune responses in the newborn. In a developmental toxicity study conducted in mice using an 
analogous antibody that selectively inhibits the functional activity of mouse TNFα, there was no 
indication of maternal toxicity, embryotoxicity or teratogenicity (see section 5.3). 
 
The available clinical experience is limited. Infliximab should only be used during pregnancy if 
clearly needed. 
 
Infliximab crosses the placenta and has been detected in the serum of infants up to 6 months 
following birth. After in utero exposure to infliximab, infants may be at increased risk of infection, 
including serious disseminated infection that can become fatal. Administration of live vaccines (e.g. 
BCG vaccine) to infants exposed to infliximab in utero is not recommended for at least 6 months 



15 
 

after birth (see sections 4.4 and 4.5). Cases of agranulocytosis have also been reported (see section 
4.8). 
 
Breast-feeding 
 
It is unknown whether infliximab is excreted in human milk or absorbed systemically after 
ingestion. Because human immunoglobulins are excreted in milk, women must not breast feed for 
at least 6 months after Zessly treatment. 
 
Fertility 
 
There are insufficient preclinical data to draw conclusions on the effects of infliximab on fertility 
and general reproductive function (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Zessly may have a minor influence on the ability to drive and use machines. Dizziness may occur 
following administration of infliximab (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Upper respiratory tract infection was the most common adverse drug reaction (ADR) reported in 
clinical trials, occurring in 25.3% of infliximab-treated patients compared with 16.5% of control 
patients. The most serious ADRs associated with the use of TNF blockers that have been reported 
for infliximab include HBV reactivation, CHF (congestive heart failure), serious infections 
(including sepsis, opportunistic infections and TB), serum sickness (delayed hypersensitivity 
reactions), haematologic reactions, systemic lupus erythematosus/lupus-like syndrome, 
demyelinating disorders, hepatobiliary events, lymphoma, HSTCL, leukaemia, Merkel cell 
carcinoma, melanoma, paediatric malignancy, sarcoidosis/sarcoid-like reaction, intestinal or 
perianal abscess (in Crohn’s disease), and serious infusion reactions (see section 4.4). 
 
Tabulated list of adverse reactions 
 
Table 1 lists ADRs based on experience from clinical studies as well as adverse reactions, some 
with fatal outcome, reported from post-marketing experience. Within the organ system classes, 
adverse reactions are listed under headings of frequency using the following categories: very 
common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 
to < 1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data). 
Within each frequency grouping, undesirable effects are presented in order of decreasing 
seriousness. 
 



16 
 

Table 1 
Undesirable effects in clinical studies and from post-marketing experience 

Infections and infestations 
Very common: Viral infection (e.g. influenza, herpes virus infection). 
Common: Bacterial infections (e.g. sepsis, cellulitis, 

abscess). 
Uncommon: Tuberculosis, fungal infections (e.g. candidiasis, 

onychomycosis ). 
Rare: Meningitis, opportunistic infections (such as invasive 

fungal infections [pneumocystosis, histoplasmosis, 
aspergillosis, coccidioidomycosis, cryptococcosis, 
blastomycosis], bacterial infections [atypical 
mycobacterial, listeriosis, salmonellosis], and viral 
infections [cytomegalovirus]), parasitic infections, 
hepatitis B reactivation. 

Not known: Vaccine breakthrough infection (after in utero exposure to 
infliximab)*. 

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

Rare: Lymphoma, non-Hodgkin’s lymphoma, Hodgkin’s 
disease, leukaemia, melanoma, cervical cancer. 

Not known: Hepatosplenic T-cell lymphoma (primarily in adolescents 
and young adult males with Crohn’s disease and ulcerative 
colitis), Merkel cell carcinoma. 

Blood and lymphatic 
system disorders 

Common: Neutropenia, leukopenia, anaemia, 
lymphadenopathy.  

Uncommon: Thrombocytopenia, lymphopenia, lymphocytosis. 
Rare: Agranulocytosis (including infants exposed in 

utero to infliximab), thrombotic thrombocytopenic 
purpura, pancytopenia, haemolytic anaemia, 
idiopathic thrombocytopenic purpura. 

Immune system disorders 
Common: Allergic respiratory symptom. 
Uncommon: Anaphylactic reaction, lupus-like syndrome, serum 

sickness or serum sickness-like reaction. 
Rare: Anaphylactic shock, vasculitis, sarcoid-like reaction. 

Psychiatric disorders 
Common: Depression, insomnia. 
Uncommon: Amnesia, agitation, confusion, somnolence, nervousness. 
Rare: Apathy. 



17 
 

Nervous system disorders 
Very common: Headache. 
Common: Vertigo, dizziness, hypoesthesia, 

paraesthesia.  
Uncommon: Seizure, neuropathy. 
Rare: Transverse myelitis, central nervous system 

demyelinating disorders (multiple sclerosis-like disease 
and optic neuritis), peripheral demyelinating disorders 
(such as Guillain-Barré syndrome, chronic inflammatory 
demyelinating polyneuropathy and multifocal motor 
neuropathy). 

Eye disorders 
Common: Conjunctivitis. 
Uncommon: Keratitis, periorbital oedema, hordeolum. 
Rare: Endophthalmitis. 
Not known: Transient visual loss occurring during or within 2 hours 

of infusion. 

Cardiac disorders 
Common: Tachycardia, palpitation. 
Uncommon: Cardiac failure (new onset or worsening), arrhythmia, 

syncope, bradycardia. 
Rare: Cyanosis, pericardial effusion. 
Not known: Myocardial ischaemia/myocardial infarction. 

Vascular disorders 
Common: Hypotension, hypertension, ecchymosis, hot flush, 

flushing. 
Uncommon: Peripheral ischaemia, thrombophlebitis, haematoma. 
Rare: Circulatory failure, petechia, vasospasm. 

Respiratory, thoracic 
and mediastinal 
disorders 

Very common: Upper respiratory tract infection, sinusitis. 
Common: Lower respiratory tract infection (e.g. bronchitis, 

pneumonia), dyspnoea, epistaxis. 
Uncommon: Pulmonary oedema, bronchospasm, pleurisy, pleural 

effusion. 
Rare: Interstitial lung disease (including rapidly progressive 

disease, lung fibrosis and pneumonitis). 
Gastrointestinal disorders 

Very common: Abdominal pain, nausea. 
Common: Gastrointestinal haemorrhage, diarrhoea, 

dyspepsia, gastroesophageal reflux, constipation. 
Uncommon: Intestinal perforation, intestinal stenosis, 

diverticulitis, pancreatitis, cheilitis. 

Hepatobiliary disorders 
Common: Hepatic function abnormal, transaminases increased. 
Uncommon: Hepatitis, hepatocellular damage, cholecystitis. 
Rare: Autoimmune hepatitis, jaundice. 
Not known: Liver failure. 



18 
 

Skin and subcutaneous 
tissue disorders 

Common: New onset or worsening psoriasis including pustular 
psoriasis (primarily palm & soles), urticaria, rash, pruritus, 
hyperhidrosis, dry skin, fungal dermatitis, eczema, 
alopecia. 

Uncommon: Bullous eruption, seborrhoea, rosacea, skin papilloma, 
hyperkeratosis, abnormal skin pigmentation. 

Rare: Toxic epidermal necrolysis, Stevens-Johnson 
Syndrome, erythema multiforme, furunculosis, linear 
IgA bullous dermatosis (LABD), acute generalised 
exanthematous pustulosis (AGEP), lichenoid 
reactions. 

Not known: Worsening of symptoms of dermatomyositis. 

Musculoskeletal and 
connective tissue disorders 

Common: Arthralgia, myalgia, back pain. 
Renal and urinary disorders 

Common: Urinary tract infection. 
Uncommon: Pyelonephritis. 

Reproductive system and 
breast disorders 

Uncommon: Vaginitis. 
General disorders and 
administration site 
conditions 

Very common: Infusion-related reaction, pain. 
Common: Chest pain, fatigue, fever, injection site reaction, 

chills, oedema. 
Uncommon: Impaired healing. 
Rare: Granulomatous lesion. 

Investigations 
Uncommon: Autoantibody positive. 
Rare: Complement factor abnormal. 

* including bovine tuberculosis (disseminated BCG infection), see section 4.4 
 
Infusion-related reactions 
 
An infusion-related reaction was defined in clinical studies as any adverse event occurring during 
an infusion or within 1 hour after an infusion. In Phase III clinical studies, 18% of infliximab-
treated patients compared with 5% of placebo-treated patients experienced an infusion-related 
reaction. Overall, a higher proportion of patients receiving infliximab monotherapy experienced an 
infusion-related reaction compared to patients receiving infliximab with concomitant 
immunomodulators. Approximately 3% of patients discontinued treatment due to infusion-related 
reactions and all patients recovered with or without medical therapy. Of infliximab-treated patients 
who had an infusion reaction during the induction period, through week 6, 27% experienced an 
infusion reaction during the maintenance period, week 7 through week 54. Of patients who did not 
have an infusion reaction during the induction period, 9% experienced an infusion reaction during 
the maintenance period. 
 
In a clinical study of patients with rheumatoid arthritis, infusions were to be administered over 
2 hours for the first 3 infusions. The duration of subsequent infusions could be shortened to not less 
than 40 minutes in patients who did not experience serious infusion reactions. In this trial, sixty six 
percent of the patients (686 out of 1,040) received at least one shortened infusion of 90 minutes or 



19 
 

less and 44% of the patients (454 out of 1,040) received at least one shortened infusion of 60 
minutes or less. Of the infliximab-treated patients who received at least one shortened infusion, 
infusion-related reactions occurred in 15% of patients and serious infusion reactions occurred in 
0.4% of patients. 
 
In a clinical study of patients with Crohn’s disease, infusion-related reactions occurred in 16.6% 
(27/163) of patients receiving infliximab monotherapy, 5% (9/179) of patients receiving infliximab 
in combination with AZA, and 5.6% (9/161) of patients receiving AZA monotherapy. One serious 
infusion reaction (< 1%) occurred in a patient on infliximab monotherapy. 
 
In post-marketing experience, cases of anaphylactic-like reactions, including laryngeal/pharyngeal 
oedema and severe bronchospasm, and seizure have been associated with infliximab administration 
(see section 4.4). Cases of transient visual loss occurring during or within 2 hours of infliximab 
infusion have been reported. Events (some fatal) of myocardial ischaemia/infarction and arrhythmia 
have also been reported, some in close temporal association with infusion of infliximab. 
 
Infusion reactions following re-administration of infliximab 
 
A clinical study in patients with moderate to severe psoriasis was designed to assess the efficacy 
and safety of long-term maintenance therapy versus re-treatment with an induction regimen of 
infliximab (maximum of four infusions at 0, 2, 6, and 14 weeks) following disease flare. Patients 
did not receive any concomitant immunosuppressant therapy. In the re-treatment arm, 4% (8/219) 
of patients experienced a serious infusion reaction versus < 1% (1/222) on maintenance therapy. 
The majority of serious infusion reactions occurred during the second infusion at week 2. The 
interval between the last maintenance dose and the first re-induction dose ranged from 35-231 days. 
Symptoms included, but were not limited to, dyspnoea, urticaria, facial oedema, and hypotension. 
In all cases, infliximab treatment was discontinued and/or other treatment instituted with complete 
resolution of signs and symptoms. 
 
Delayed hypersensitivity 
 
In clinical studies delayed hypersensitivity reactions have been uncommon and have occurred after 
infliximab-free intervals of less than 1 year. In the psoriasis studies, delayed hypersensitivity 
reactions occurred early in the treatment course. Signs and symptoms included myalgia and/or 
arthralgia with fever and/or rash, with some patients experiencing pruritus, facial, hand or lip 
oedema, dysphagia, urticaria, sore throat and headache. 
 
There are insufficient data on the incidence of delayed hypersensitivity reactions after infliximab-
free intervals of more than 1 year but limited data from clinical studies suggest an increased risk for 
delayed hypersensitivity with increasing infliximab-free interval (see section 4.4). 
 
In a 1-year clinical study with repeated infusions in patients with Crohn's disease, the incidence of 
serum sickness-like reactions was 2.4%. 
 
Immunogenicity 
 
Patients who developed antibodies to infliximab were more likely (approximately 2-3 fold) to 
develop infusion-related reactions. Use of concomitant immunosuppressant agents appeared to 
reduce the frequency of infusion-related reactions. 
In clinical studies using single and multiple infliximab doses ranging from 1 to 20 mg/kg, 
antibodies to infliximab were detected in 14% of patients with any immunosuppressant therapy, and 
in 24% of patients without immunosuppressant therapy. In rheumatoid arthritis patients who 
received the recommended repeated treatment dose regimens with methotrexate, 8% of patients 
developed antibodies to infliximab. In psoriatic arthritis patients who received 5 mg/kg with and 
without methotrexate, antibodies occurred overall in 15% of patients (antibodies occurred in 4% of 
patients receiving methotrexate and in 26% of patients not receiving methotrexate at baseline). In 
Crohn's disease patients who received maintenance treatment, antibodies to infliximab occurred 



20 
 

overall in 3.3% of patients receiving immunosuppressants and in 13.3% of patients not receiving 
immunosuppressants. The antibody incidence was 2-3 fold higher for patients treated episodically. 
Due to methodological limitations, a negative assay did not exclude the presence of antibodies to 
infliximab. Some patients who developed high titres of antibodies to infliximab had evidence of 
reduced efficacy. In psoriasis patients treated with infliximab as a maintenance regimen in the 
absence of concomitant immunomodulators, approximately 28% developed antibodies to infliximab 
(see section 4.4: “Infusion reactions and hypersensitivity”). 
 
Infections 
 
Tuberculosis, bacterial infections, including sepsis and pneumonia, invasive fungal, viral, and other 
opportunistic infections have been observed in patients receiving infliximab. Some of these 
infections have been fatal; the most frequently reported opportunistic infections with a mortality 
rate of > 5% include pneumocystosis, candidiasis, listeriosis and aspergillosis (see section 4.4). 
 
In clinical studies 36% of infliximab-treated patients were treated for infections compared with 
25% of placebo-treated patients. 
 
In rheumatoid arthritis clinical studies, the incidence of serious infections including pneumonia was 
higher in infliximab plus methotrexate-treated patients compared with methotrexate alone 
especially at doses of 6 mg/kg or greater (see section 4.4). 
 
In post-marketing spontaneous reporting, infections are the most common serious adverse reaction. 
Some of the cases have resulted in a fatal outcome. Nearly 50% of reported deaths have been 
associated with infection. Cases of tuberculosis, sometimes fatal, including miliary tuberculosis and 
tuberculosis with extra-pulmonary location have been reported (see section 4.4). 
 
Malignancies and lymphoproliferative disorders 
 
In clinical studies with infliximab in which 5,780 patients were treated, representing 5,494 patient 
years, 5 cases of lymphomas and 26 non-lymphoma malignancies were detected as compared with 
no lymphomas and 1 non-lymphoma malignancy in 1,600 placebo-treated patients representing 941 
patient years. 
 
In long-term safety follow-up of clinical studies with infliximab of up to 5 years, representing 6,234 
patients-years (3,210 patients), 5 cases of lymphoma and 38 cases of non-lymphoma malignancies 
were reported. 
 
Cases of malignancies, including lymphoma, have also been reported in the post-marketing setting 
(see section 4.4). 
 
In an exploratory clinical study involving patients with moderate to severe COPD who were either 
current smokers or ex-smokers, 157 adult patients were treated with infliximab at doses similar to 
those used in rheumatoid arthritis and Crohn’s disease. Nine of these patients developed 
malignancies, including 1 lymphoma. The median duration of follow-up was 0.8 years (incidence 
5.7% [95% CI 2.65%-10.6%]. There was one reported malignancy amongst 77 control patients 
(median duration of follow-up 0.8 years; incidence 1.3% [95% CI 0.03%-7.0%]). The majority of 
the malignancies developed in the lung or head and neck. 
 
A population-based retrospective cohort study found an increased incidence of cervical cancer in 
women with rheumatoid arthritis treated with infliximab compared to biologics-naïve patients or 
the general population, including those over 60 years of age (see section 4.4). 
 
In addition, post-marketing cases of hepatosplenic T-cell lymphoma have been reported in patients 
treated with infliximab with the vast majority of cases occurring in Crohn’s disease and ulcerative 
colitis, and most of whom were adolescent or young adult males (see section 4.4). 
 



21 
 

Heart failure 
 
In a Phase II study aimed at evaluating infliximab in CHF, higher incidence of mortality due to 
worsening of heart failure were seen in patients treated with infliximab, especially those treated 
with the higher dose of 10 mg/kg (i.e. twice the maximum approved dose). In this study 150 
patients with NYHA Class III-IV CHF (left ventricular ejection fraction ≤ 35%) were treated with 3 
infusions of infliximab 5 mg/kg, 10 mg/kg, or placebo over 6 weeks. At 38 weeks, 9 of 101 patients 
treated with infliximab (2 at 5 mg/kg and 7 at 10 mg/kg) died compared to one death among the 49 
patients on placebo. 
There have been post-marketing reports of worsening heart failure, with and without identifiable 
precipitating factors, in patients taking infliximab. There have also been post-marketing reports of 
new onset heart failure, including heart failure in patients without known pre-existing 
cardiovascular disease. Some of these patients have been under 50 years of age. 
 
Hepatobiliary events 
 
In clinical studies, mild or moderate elevations of ALT and AST have been observed in patients 
receiving infliximab without progression to severe hepatic injury. Elevations of ALT ≥ 5 x Upper 
Limit of Normal (ULN) have been observed (see Table 2). Elevations of aminotransferases were 
observed (ALT more common than AST) in a greater proportion of patients receiving infliximab 
than in controls, both when infliximab was given as monotherapy and when it was used in 
combination with other immunosuppressive agents. Most aminotransferase abnormalities were 
transient; however, a small number of patients experienced more prolonged elevations. In general, 
patients who developed ALT and AST elevations were asymptomatic, and the abnormalities 
decreased or resolved with either continuation or discontinuation of infliximab, or modification of 
concomitant therapy. In post-marketing surveillance, cases of jaundice and hepatitis, some with 
features of autoimmune hepatitis, have been reported in patients receiving infliximab (see section 
4.4). 
 



22 
 

Table 2 
Proportion of patients with increased ALT activity in clinical studies 

1 Placebo patients received methotrexate while infliximab patients received both infliximab 
and methotrexate. 

2 Placebo patients in the two Phase III studies in Crohn’s disease, received an initial dose of 
5 mg/kg infliximab at study start and were on placebo in the maintenance phase. Patients 
who were randomised to the placebo maintenance group and then later crossed over to 
infliximab are included in the infliximab group in the ALT analysis. In the Phase IIIb trial in 
Crohn’s disease, placebo patients received AZA 2.5 mg/kg/day as active control in addition 
to placebo infliximab infusions. 

3 Number of patients evaluated for ALT. 
4 Median follow-up is based on patients treated. 
 
Antinuclear antibodies (ANA)/Anti-double-stranded DNA (dsDNA) antibodies 
 
Approximately half of infliximab-treated patients in clinical studies who were ANA negative at 
baseline developed a positive ANA during the study compared with approximately one fifth of 
placebo-treated patients. Anti-dsDNA antibodies were newly detected in approximately 17% of 
infliximab-treated patients compared with 0% of placebo-treated patients. At the last evaluation, 
57% of infliximab-treated patients remained anti-dsDNA positive. Reports of lupus and lupus-like 
syndromes, however, remain uncommon (see section 4.4). 
 
Paediatric population 
 
Juvenile rheumatoid arthritis patients 
 
Infliximab was studied in a clinical study in 120 patients (age range: 4-17 years old) with active 
juvenile rheumatoid arthritis despite methotrexate. Patients received 3 or 6 mg/kg infliximab as a 3-
dose induction regimen (weeks 0, 2, 6 or weeks 14, 16, 20 respectively) followed by maintenance 
therapy every 8 weeks, in combination with methotrexate. 
 

 
Indication 

Number of patients
3
 Median follow-up 

(wks)4 
 

≥ 3 x ULN 
 

≥ 5 x ULN 

placebo infliximab placebo infliximab placebo infliximab placebo infliximab 
Rheumatoid 
arthritis

1
 

375 1,087 58.1 58.3 3.2% 3.9% 0.8% 0.9% 

Crohn’s 
disease

2
 

324 1,034 53.7 54.0 2.2% 4.9% 0.0% 1.5% 

Paediatric 
Crohn’s 
disease 

N/A 139 N/A 53.0 N/A 4.4% N/A 1.5% 

Ulcerative 
colitis 

242 482 30.1 30.8 1.2% 2.5% 0.4% 0.6% 

Paediatric 
Ulcerative 
colitis 

N/A 60 N/A 49.4 N/A 6.7% N/A 1.7% 

Ankylosing 
spondylitis 

76 275 24.1 101.9 0.0% 9.5% 0.0% 3.6% 

Psoriatic 
arthritis 

98 191 18.1 39.1 0.0% 6.8% 0.0% 2.1% 

Plaque 
psoriasis 

281 1,175 16.1 50.1 0.4% 7.7% 0.0% 3.4% 



23 
 

Infusion reactions 
Infusion reactions occurred in 35% of patients with juvenile rheumatoid arthritis receiving 3 mg/kg 
compared with 17.5% of patients receiving 6 mg/kg. In the 3 mg/kg Infliximab group, 4 out of 60 
patients had a serious infusion reaction and 3 patients reported a possible anaphylactic reaction (2 
of which were among the serious infusion reactions). In the 6 mg/kg group, 2 out of 57 patients had 
a serious infusion reaction, one of whom had a possible anaphylactic reaction (see section 4.4). 
 
Immunogenicity 
Antibodies to infliximab developed in 38% of patients receiving 3 mg/kg compared with 12% of 
patients receiving 6 mg/kg. The antibody titres were notably higher for the 3 mg/kg compared to the 
6 mg/kg group. 
 
Infections 
Infections occurred in 68% (41/60) of children receiving 3 mg/kg over 52 weeks, 65% (37/57) of 
children receiving infliximab 6 mg/kg over 38 weeks and 47% (28/60) of children receiving 
placebo over 14 weeks (see section 4.4). 
 
Paediatric Crohn’s disease patients 
 
The following adverse reactions were reported more commonly in paediatric Crohn’s disease 
patients (see section 5.1) than in adult Crohn’s disease patients: anaemia (10.7%), blood in stool 
(9.7%), leukopenia (8.7%), flushing (8.7%), viral infection (7.8%), neutropenia (6.8%),  bacterial 
infection (5.8%), and respiratory tract allergic reaction (5.8%). In addition, bone fracture (6.8%) 
was reported, however, a causal association has not been established. Other special considerations 
are discussed below. 
 
Infusion-related reactions 
In the paediatric Crohn’s disease study, 17.5% of randomised patients experienced 1 or more 
infusion reactions. There were no serious infusion reactions, and 2 subjects in the paediatric 
Crohn’s disease study had non-serious anaphylactic reactions. 
 
Immunogenicity 
Antibodies to infliximab were detected in 3 (2.9%) paediatric patients. 
 
Infections 
In the paediatric Crohn’s disease study, infections were reported in 56.3% of randomised subjects 
treated with infliximab. Infections were reported more frequently for subjects who received q8 
week as opposed to q12 week infusions (73.6% and 38.0%, respectively), while serious infections 
were reported for 3 subjects in the q8 week and 4 subjects in the q12 week maintenance treatment 
group. The most commonly reported infections were upper respiratory tract infection and 
pharyngitis, and the most commonly reported serious infection was abscess. Three cases of 
pneumonia (1 serious) and 2 cases of herpes zoster (both non-serious) were reported. 
 
Paediatric ulcerative colitis patients 
 
Overall, the adverse reactions reported in the paediatric ulcerative colitis trial and adult ulcerative 
colitis studies were generally consistent. In the paediatric ulcerative colitis trial, the most common 
adverse reactions were upper respiratory tract infection, pharyngitis, abdominal pain, fever, and 
headache. The most common adverse event was worsening of ulcerative colitis, the incidence of 
which was higher in patients on the q12 week vs. the q8 week dosing regimen. 
 
Infusion-related reactions 
Overall, 8 (13.3%) of 60 treated patients experienced one or more infusion reactions, with 4 of 22 
(18.2%) in the q8 week and 3 of 23 (13.0%) in the q12 week treatment maintenance group. No 
serious infusion reactions were reported. All infusion reactions were mild or moderate in intensity. 
 



24 
 

Immunogenicity 
Antibodies to infliximab were detected in 4 (7.7%) patients through week 54. 
 
Infections 
Infections were reported in 31 (51.7%) of 60 treated patients in the paediatric ulcerative colitis trial 
and 22 (36.7%) required oral or parenteral antimicrobial treatment. The proportion of patients with 
infections in the paediatric ulcerative colitis trial was similar to that in the paediatric Crohn’s 
disease study but higher than the proportion in the adults’ ulcerative colitis studies. The overall 
incidence of infections in the paediatric ulcerative colitis trial was 13/22 (59%) in the every 8 week 
maintenance treatment group and 14/23 (60.9%) in the every 12 week maintenance treatment 
group. Upper respiratory tract infection (7/60 [12%]) and pharyngitis (5/60 [8%]) were the most 
frequently reported respiratory system infections. Serious infections were reported in 12% (7/60) of 
all treated patients. 
 
In this study, there were more patients in the 12 to 17 year age group than in the 6 to 11 year age 
group (45/60 [75.0%]) vs.15/60 [25.0%]). While the numbers of patients in each subgroup are too 
small to make any definitive conclusions about the effect of age on safety events, there were higher 
proportions of patients with serious adverse events and discontinuation due to adverse events in the 
younger age group than in the older age group. While the proportion of patients with infections was 
also higher in the younger age group, for serious infections, the proportions were similar in the two 
age groups. Overall proportions of adverse events and infusion reactions were similar between the 6 
to 11 and 12 to 17 year age groups. 
 
Post-marketing experience 
 
Post-marketing spontaneous serious adverse reactions with infliximab in the paediatric population 
have included malignancies including hepatosplenic T-cell lymphomas, transient hepatic enzyme 
abnormalities, lupus-like syndromes, and positive auto-antibodies (see sections 4.4 and 4.8). 
 
Additional information on special populations 
 
Elderly  
In rheumatoid arthritis clinical studies, the incidence of serious infections was greater in infliximab 
plus methotrexate-treated patients 65 years and older (11.3%) than in those under 65 years of age 
(4.6%). In patients treated with methotrexate alone, the incidence of serious infections was 5.2% in 
patients 65 years and older compared to 2.7% in patients under 65 (see section 4.4). 
 
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 
 
No case of overdose has been reported. Single doses up to 20 mg/kg have been administered 
without toxic effects. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunosuppressants, tumour necrosis factor alpha (TNFα) inhibitors, 
ATC code: L04AB02. 
 



25 
 

Zessly is a biosimilar medicinal product. Detailed information is available on the website of the 
European Medicines Agency http://www.ema.europa.eu. 
 
Mechanism of action 
 
Infliximab is a chimeric human-murine monoclonal antibody that binds with high affinity to both 
soluble and transmembrane forms of TNFα but not to lymphotoxin α (TNFß). 
 
Pharmacodynamic effects 
 
Infliximab inhibits the functional activity of TNFα in a wide variety of in vitro bioassays. 
Infliximab prevented disease in transgenic mice that develop polyarthritis as a result of constitutive 
expression of human TNFα and when administered after disease onset, it allowed eroded joints to 
heal. In vivo, infliximab rapidly forms stable complexes with human TNFα, a process that parallels 
the loss of TNFα bioactivity. 
 
Elevated concentrations of TNFα have been found in the joints of rheumatoid arthritis patients and 
correlate with elevated disease activity. In rheumatoid arthritis, treatment with infliximab reduced 
infiltration of inflammatory cells into inflamed areas of the joint as well as expression of molecules 
mediating cellular adhesion, chemoattraction and tissue degradation. After infliximab treatment, 
patients exhibited decreased levels of serum interleukin 6 (IL-6) and C-reactive protein (CRP), and 
increased haemoglobin levels in rheumatoid arthritis patients with reduced haemoglobin levels, 
compared with baseline. Peripheral blood lymphocytes further showed no significant decrease in 
number or in proliferative responses to in vitro mitogenic stimulation when compared with 
untreated patients’ cells. In psoriasis patients, treatment with infliximab resulted in decreases in 
epidermal inflammation and normalisation of keratinocyte differentiation in psoriatic plaques. In 
psoriatic arthritis, short-term treatment with infliximab reduced the number of T-cells and blood 
vessels in the synovium and psoriatic skin. 
 
Histological evaluation of colonic biopsies, obtained before and 4 weeks after administration of 
infliximab, revealed a substantial reduction in detectable TNFα. Infliximab treatment of Crohn’s 
disease patients was also associated with a substantial reduction of the commonly elevated serum 
inflammatory marker, CRP. Total peripheral white blood cell counts were minimally affected in 
infliximab-treated patients, although changes in lymphocytes, monocytes and neutrophils reflected 
shifts towards normal ranges. Peripheral blood mononuclear cells (PBMC) from infliximab-treated 
patients showed undiminished proliferative responsiveness to stimuli compared with untreated 
patients, and no substantial changes in cytokine production by stimulated PBMC were observed 
following treatment with infliximab. Analysis of lamina propria mononuclear cells obtained by 
biopsy of the intestinal mucosa showed that infliximab treatment caused a reduction in the number 
of cells capable of expressing TNFα and interferonγ. Additional histological studies provided 
evidence that treatment with infliximab reduces the infiltration of inflammatory cells into affected 
areas of the intestine and the presence of inflammation markers at these sites. Endoscopic studies of 
intestinal mucosa have shown evidence of mucosal healing in infliximab-treated patients. 
 
Clinical efficacy and safety 
 
Adult rheumatoid arthritis 
 
The efficacy of infliximab was assessed in two multicentre, randomised, double-blind, pivotal 
clinical studies. In both studies concurrent use of stable doses of folic acid, oral corticosteroids 
(≤ 10 mg/day) and/or non-steroidal anti-inflammatory drugs (NSAIDs) was permitted. 
The primary endpoints were the reduction of signs and symptoms as assessed by the American 
College of Rheumatology criteria (ACR20 for study 1 (described below), landmark ACR-N for 
study 2 (described below)), the prevention of structural joint damage, and the improvement in 
physical function. A reduction in signs and symptoms was defined to be at least a 20% 
improvement (ACR20) in both tender and swollen joint counts, and in 3 of the following 5 criteria: 
(1) evaluator’s global assessment, (2) patient’s global assessment, (3) functional/disability measure, 



26 
 

(4) visual analogue pain scale and (5) erythrocyte sedimentation rate or C-reactive protein. ACR-N 
uses the same criteria as the ACR20, calculated by taking the lowest percent improvement in 
swollen joint count, tender joint count, and the median of the remaining 5 components of the ACR 
response. Structural joint damage (erosions and joint space narrowing) in both hands and feet was 
measured by the change from baseline in the total van der Heijde-modified Sharp score (0-440). 
The Health Assessment Questionnaire (HAQ; scale 0-3) was used to measure patients’ average 
change from baseline scores over time, in physical function. 
 
Study 1 evaluated responses at 30, 54 and 102 weeks in a placebo-controlled study of 428 patients 
with active rheumatoid arthritis despite treatment with methotrexate. Approximately 50% of 
patients were in functional Class III. Patients received placebo, 3 mg/kg or 10 mg/kg infliximab at 
weeks 0, 2 and 6, and then every 4 or 8 weeks thereafter. All patients were on stable methotrexate 
doses (median 15 mg/wk) for 6 months prior to enrolment and were to remain on stable doses 
throughout the study. 
 
Results from week 54 (ACR20, total van der Heijde-modified Sharp score and HAQ) are shown in 
Table 3. Higher degrees of clinical response (ACR50 and ACR70) were observed in all infliximab 
groups at 30 and 54 weeks compared with methotrexate alone. 
 
A reduction in the rate of the progression of structural joint damage (erosions and joint space 
narrowing) was observed in all infliximab groups at 54 weeks (Table 3). 
 
The effects observed at 54 weeks were maintained through 102 weeks. Due to a number of 
treatment withdrawals, the magnitude of the effect difference between infliximab and the 
methotrexate alone group cannot be defined. 
 

Table 3 
Effects on ACR20, Structural Joint Damage and Physical Function at week 54, study 1 

a control = All patients had active RA despite treatment with stable methotrexate doses for 6 
months prior to enrolment and were to remain on stable doses throughout the study. 
Concurrent use of stable doses of oral corticosteroids (≤ 10 mg/day) and/or NSAIDs was 
permitted, and folate supplementation was given. 

 infliximabb 
 Controla 3 mg/kg 

q 8 wks 
3 mg/kg 
q 4 wks 

10 mg/kg q 
8 wks 

10 mg/kg 
q 4 wks 

All 
infliximabb 

Patients with ACR20 
response/ 
Patients evaluated (%) 

15/88 
(17%) 

36/86 
(42%) 

41/86 
(48%) 

51/87 
(59%) 

48/81 
(59%) 

176/340 
(52%) 

 
Total scored (van der 
Heijde-modified Sharp 
score) 

      

Change from baseline 
(Mean ± SDc) 

7.0 ± 10.3 1.3 ± 6.0 1.6 ± 8.5 0.2 ± 3.6 -0.7 ± 3.8 0.6 ± 5.9 

Median 
(Interquartile range) 
 

4.0 
(0.5,9.7) 

0.5 
(-1.5,3.0) 

0.1 
(-2.5,3.0) 

0.5 
(-1.5,2.0) 

-0.5 
(-3.0,1.5) 

0.0 
(-1.8,2.0) 

Patients with no 
deterioration/patients 
evaluated (%)c 

13/64 
(20%) 

34/71 
(48%) 

35/71 
(49%) 

37/77 
(48%) 

44/66 
(67%) 

150/285 
(53%) 

 
HAQ change from 
baseline over timee 
(patients evaluated) 

87 86 85 87 81 339 

Mean ± SDc 0.2 ± 0.3 0.4 ± 0.3 0.5 ± 0.4 0.5 ± 0.5 0.4 ± 0.4 0.4 ± 0.4 



27 
 

b all infliximab doses given in combination with methotrexate and folate with some on 
corticosteroids and/or NSAIDs 

c p < 0.001, for each infliximab treatment group vs. control 
d greater values indicate more joint damage. 
e HAQ = Health Assessment Questionnaire; greater values indicate less disability. 
 
Study 2 evaluated responses at 54 weeks in 1,004 methotrexate naive patients with early (≤ 3 years 
disease duration, median 0.6 years) active rheumatoid arthritis (median swollen and tender joint 
count of 19 and 31, respectively). All patients received methotrexate (optimised to 20 mg/wk by 
week 8) and either placebo, 3 mg/kg or 6 mg/kg infliximab at weeks 0, 2, and 6 and every 8 weeks 
thereafter. Results from week 54 are shown in Table 4. 
 
After 54 weeks of treatment, both doses of infliximab + methotrexate resulted in statistically 
significantly greater improvement in signs and symptoms compared to methotrexate alone as 
measured by the proportion of patients achieving ACR20, 50 and 70 responses. 
 
In study 2, more than 90% of patients had at least two evaluable X-rays. Reduction in the rate of 
progression of structural damage was observed at weeks 30 and 54 in the infliximab + methotrexate 
groups compared to methotrexate alone. 
 

Table 4 
Effects on ACRn, Structural Joint Damage and Physical Function at week 54, study 2 

 infliximab + MTX 
 Placebo + MTX 3 mg/kg 6 mg/kg Combined 
Subjects randomised 282 359 363 722 
Percentage ACR improvement     
Mean ± SDa 24.8 ± 59.7 37.3 ± 52.8 42.0 ± 47.3 39.6 ± 50.1 
Change from baseline in total van der 
Heijde-modified Sharp scoreb 

    

Mean ± SDa 3.70 ± 9.61 0.42 ± 5.82 0.51 ± 5.55 0.46 ± 5.68 
Median 0.43 0.00 0.00 0.00 
Improvement from baseline in HAQ 
averaged over time from week 30 to 
week 54c 

    

Mean ± SDd 0.68 ± 0.63 0.80 ± 0.65 0.88 ± 0.65 0.84 ± 0.65 
a p < 0.001, for each infliximab treatment group vs. control. 
b greater values indicate more joint damage. 
c HAQ = Health Assessment Questionnaire; greater values indicate less disability. 
d p = 0.030 and < 0.001 for the 3 mg/kg and 6 mg/kg treatment groups respectively vs. placebo 

+ MTX. 
 
Data to support dose titration in rheumatoid arthritis come from study 1, study 2 and study 3. 
Study 3 was a randomised, multicenter, double-blind, 3-arm, parallel-group safety study. In one of 
the study arms (group 2, n = 329), patients with an inadequate response were allowed to dose titrate 
with 1.5 mg/kg increments from 3 up to 9 mg/kg. The majority (67%) of these patients did not 
require any dose titration. Of the patients who required a dose titration, 80% achieved clinical 
response and the majority (64%) of these required only one adjustment of 1.5 mg/kg. 
 
Adult Crohn’s disease 
 
Induction treatment in moderately to severely active Crohn’s disease 
 
The efficacy of a single dose treatment with infliximab was assessed in 108 patients with active 
Crohn’s disease (Crohn’s Disease Activity Index (CDAI) ≥ 220 ≤ 400) in a randomised, double-
blinded, placebo-controlled, dose-response study. Of these 108 patients, 27 were treated with the 
recommended dosage of infliximab 5 mg/kg. All patients had experienced an inadequate response 



28 
 

to prior conventional therapies. Concurrent use of stable doses of conventional therapies was 
permitted, and 92% of patients continued to receive these therapies. 
 
The primary endpoint was the proportion of patients who experienced a clinical response, defined 
as a decrease in CDAI by ≥ 70 points from baseline at the 4-week evaluation and without an 
increase in the use of medicinal products or surgery for Crohn’s disease. Patients who responded at 
week 4 were followed to week 12. Secondary endpoints included the proportion of patients in 
clinical remission at week 4 (CDAI < 150) and clinical response over time. 
 
At week 4, following administration of a single dose, 22/27 (81%) of infliximab-treated patients 
receiving a 5 mg/kg dose achieved a clinical response vs. 4/25 (16%) of the placebo-treated patients 
(p < 0.001). Also at week 4, 13/27 (48%) of infliximab-treated patients achieved a clinical 
remission (CDAI < 150) vs. 1/25 (4%) of placebo-treated patients. A response was observed within 
2 weeks, with a maximum response at 4 weeks. At the last observation at 12 weeks, 13/27 (48%) of 
infliximab-treated patients were still responding. 
 
Maintenance treatment in moderately to severely active Crohn’s disease in adults 
 
The efficacy of repeated infusions with infliximab was studied in a 1-year clinical study (study 4). 
A total of 573 patients with moderately to severely active Crohn’s disease (CDAI ≥ 220 ≤ 400) 
received a single infusion of 5 mg/kg at week 0. 178 of the 580 enrolled patients (30.7%) were 
defined as having severe disease (CDAI score > 300 and concomitant corticosteroid and/or 
immunosuppressants) corresponding to the population defined in the indication (see section 4.1). At 
week 2, all patients were assessed for clinical response and randomised to one of 3 treatment 
groups; a placebo maintenance group, 5 mg/kg maintenance group and 10 mg/kg maintenance 
group. All 3 groups received repeated infusions at week 2, 6 and every 8 weeks thereafter. 
 
Of the 573 patients randomised, 335 (58%) achieved clinical response by week 2. These patients 
were classified as week-2 responders and were included in the primary analysis (see Table 5). 
Among patients classified as non-responders at week 2, 32% (26/81) in the placebo maintenance 
group and 42% (68/163) in the infliximab group achieved clinical response by week 6. There was 
no difference between groups in the number of late responders thereafter. 
 
The co-primary endpoints were the proportion of patients in clinical remission (CDAI < 150) at 
week 30 and time to loss of response through week 54. Corticosteroid tapering was permitted after 
week 6. 
 



29 
 

Table 5 
Effects on response and remission rate in patients with moderately to severely active Crohn’s 

disease, data from study 4 (week-2 responders) 
 Study  4 (week-2 responders) 

% of Patients 
 Placebo 

Maintenance 
(n = 110) 

infliximab 
Maintenance 

5 mg/kg 
(n = 113) 
(p value) 

infliximab 
Maintenance 

10 mg/kg 
(n = 112) 
(p value) 

Median time to loss of 
response through week 54 

19 weeks 38 weeks 
(0.002) 

 

> 54 weeks (< 0.001) 
 

Week 30 
Clinical Responsea 

27.3 51.3 
(< 0.001) 

59.1 
(< 0.001) 

 
Clinical Remission 20.9 38.9 

(0.003) 
45.5 

(< 0.001) 
 

Steroid-Free Remission 10.7 (6/56) 31.0 (18/58) 
(0.008) 

 

36.8 (21/57) 
(0.001) 

Week 54 
Clinical Responsea 

15.5 38.1 
(< 0.001) 

47.7 
(< 0.001) 

Clinical Remission 13.6 28.3 
(0.007) 

38.4 
(< 0.001) 

Sustained Steroid-Free 
Remissionb 

5.7 (3/53) 17.9 (10/56) 
(0.075) 

28.6 (16/56) 
(0.002) 

a Reduction in CDAI ≥ 25% and ≥ 70 points. 
b CDAI < 150 at both week 30 and 54 and not receiving corticosteroids in the 3 months prior 

to week 54 among patients who were receiving corticosteroids at baseline. 
 
Beginning at week 14, patients who had responded to treatment, but subsequently lost their clinical 
benefit, were allowed to cross over to a dose of infliximab 5 mg/kg higher than the dose to which 
they were originally randomised. Eighty nine percent (50/56) of patients who lost clinical response 
on infliximab 5 mg/kg maintenance therapy after week 14 responded to treatment with infliximab 
10 mg/kg. 
 
Improvements in quality of life measures, a reduction in disease-related hospitalisations and 
corticosteroid use were seen in the infliximab maintenance groups compared with the placebo 
maintenance group at weeks 30 and 54. 
 
Infliximab with or without AZA was assessed in a randomised, double-blind, active comparator 
study of 508 adult patients with moderate to severe Crohn’s disease (CDAI ≥ 220 ≤ 450) who were 
naive to biologics and immunosuppressants and had a median disease duration of 2.3 years. At 
baseline 27.4% of patients were receiving systemic corticosteroids, 14.2% of patients were 
receiving budesonide, and 54.3% of patients were receiving 5-ASA compounds. Patients were 
randomised to receive AZA monotherapy, infliximab monotherapy, or infliximab plus AZA 
combination therapy. Infliximab was administered at a dose of 5 mg/kg at weeks 0, 2, 6, and then 
every 8 weeks. AZA was given at a dose of 2.5 mg/kg daily.  
 
The primary endpoint of the study was corticosteroid-free clinical remission at week 26, defined as 
patients in clinical remission (CDAI of < 150) who, for at least 3 weeks, had not taken oral 
systemic corticosteroids (prednisone or equivalent) or budesonide at a dose > 6 mg/day. For results 
see Table 6. The proportions of patients with mucosal healing at week 26 were significantly greater 
in the infliximab plus AZA combination (43.9%, p < 0.001) and infliximab monotherapy groups 
(30.1%, p = 0.023) compared to the AZA monotherapy group (16.5%). 



30 
 

 
Table 6 

Percent of patients with Crohn’s disease achieving corticosteroid-free clinical remission at 
week 26 

 AZA Monotherapy infliximab 
Monotherapy 

infliximab + AZA 
Combination Therapy 

Week 26    
All randomised patients 30.0% (51/170) 44.4% (75/169)  

(p = 0.006)* 
56.8% (96/169) 
 (p < 0.001)* 

* P-values represent each infliximab treatment group vs. AZA monotherapy. 
 
Similar trends in the achievement of corticosteroid-free clinical remission were observed at week 
50. Furthermore, improved quality of life as measured by IBDQ was observed with infliximab. 
 
Induction treatment in fistulising active Crohn’s disease 
 
The efficacy was assessed in a randomised, double-blinded, placebo-controlled study in 94 patients 
with fistulising Crohn’s disease who had fistulas that were of at least 3 months’ duration. Thirty one 
of these patients were treated with infliximab 5 mg/kg. Approximately 93% of the patients had 
previously received antibiotic or immunosuppressive therapy. 
 
Concurrent use of stable doses of conventional therapies was permitted, and 83% of patients 
continued to receive at least one of these therapies. Patients received three doses of either placebo 
or infliximab at weeks 0, 2, and 6. Patients were followed up to 26 weeks. The primary endpoint 
was the proportion of patients who experienced a clinical response, defined as ≥ 50% reduction 
from baseline in the number of fistulae draining upon gentle compression on at least two 
consecutive visits (4 weeks apart), without an increase in the use of medicinal products or surgery 
for Crohn’s disease. 
 
Sixty eight percent (21/31) of infliximab-treated patients receiving a 5 mg/kg dose regimen 
achieved a clinical response vs. 26% (8/31) placebo-treated patients (p = 0.002). The median time 
to onset of response in the infliximab-treated group was 2 weeks. The median duration of response 
was 12 weeks. Additionally, closure of all fistulae was achieved in 55% of infliximab-treated 
patients compared with 13% of placebo-treated patients (p = 0.001). 
 
Maintenance treatment in fistulising active Crohn’s disease 
 
The efficacy of repeated infusions with infliximab in patients with fistulising Crohn’s disease was 
studied in a 1-year clinical study (clinical Study 5). A total of 306 patients received 3 doses of 
infliximab 5 mg/kg at week 0, 2, and 6. At baseline, 87% of the patients had perianal fistulae, 14% 
had abdominal fistulae, 9% had rectovaginal fistulae. The median CDAI score was 180. At week 
14, 282 patients were assessed for clinical response and randomised to receive either placebo or 
5 mg/kg infliximab every 8 weeks through week 46. 
 
Week-14 responders (195/282) were analysed for the primary endpoint, which was time from 
randomisation to loss of response (see Table 7). Corticosteroid tapering was permitted after week 6. 
 



31 
 

Table 7 
Effects on response rate in patients with fistulising Crohn’s disease, data from study 5 (week-

14 responders) 
                            Study 5 (week-14 responders) 
 Placebo 

Maintenance 
(n = 99) 

infliximab 
Maintenance 

(5 mg/kg) 
(n = 96) 

p-value 

Median time to loss of response 
through week 54 

14 weeks > 40 weeks < 0.001 

Week 54    
Fistula Response (%) a 23.5 46.2 0.001 
Complete fistula response (%) b 19.4 36.3 0.009 
a A ≥ 50% reduction from baseline in the number of draining fistulas over a period of ≥ 4 weeks. 
b  Absence of any draining fistulas. 
 
Beginning at week 22, patients who initially responded to treatment and subsequently lost their 
response were eligible to cross over to active re-treatment every 8 weeks at a dose of infliximab 
5 mg/kg higher than the dose to which they were originally randomised. Among patients in the 
infliximab 5 mg/kg group who crossed over because of loss of fistula response after week 22, 57% 
(12/21) responded to re-treatment with infliximab 10 mg/kg every 8 weeks. 
 
There was no significant difference between placebo and infliximab for the proportion of patients 
with sustained closure of all fistulas through week 54, for symptoms such as proctalgia, abscesses 
and urinary tract infection or for number of newly developed fistulas during treatment. 
 
Maintenance therapy with infliximab every 8 weeks significantly reduced disease-related 
hospitalisations and surgeries compared with placebo. Furthermore, a reduction in corticosteroid 
use and improvements in quality of life were observed. 
 
Adult ulcerative colitis 
 
The safety and efficacy of infliximab were assessed in two (studies 6 and 7) randomised, double-
blind, placebo-controlled clinical studies in adult patients with moderately to severely active 
ulcerative colitis (Mayo score 6 to 12; Endoscopy subscore ≥ 2) with an inadequate response to 
conventional therapies [oral corticosteroids, aminosalicylates and/or immunomodulators (6-MP, 
AZA)]. Concomitant stable doses of oral aminosalicylates, corticosteroids, and/or 
immunomodulatory agents were permitted. In both studies, patients were randomised to receive 
either placebo, 5 mg/kg infliximab, or 10 mg/kg infliximab at weeks 0, 2, 6, 14, and 22, and in 
study 6 at weeks 30, 38, and 46. Corticosteroid taper was permitted after week 8. 
 



32 
 

Table 8 
Effects on clinical response in adult patients with moderately to severely active ulcerative 

colitis, clinical remission and mucosal healing at weeks 8 and 30. Combined data from studies 
6 & 7 

  infliximab 
 Placebo 5 mg/kg 10 mg/kg Combined 
Subjects randomised 244 242 242 484 
Percentage of subjects in clinical response and in sustained clinical response 
Clinical response at week 8a 33.2% 66.9% 65.3% 66.1% 
Clinical response at week 30a 27.9% 49.6% 55.4% 52.5% 
Sustained response  
(clinical response at both week 
8 and week 30)a 

19.3% 45.0% 49.6% 47.3% 

Percentage of subjects in clinical remission and sustained remission 
Clinical remission at week 8a 10.2% 36.4% 29.8% 33.1% 
Clinical remission at week 30a 13.1% 29.8% 36.4% 33.1% 
Sustained remission 
(in remission at both week 8 
and week 30)a 

5.3% 19.0% 24.4% 21.7% 

Percentage of subjects with mucosal healing 
Mucosal healing at week 8a 32.4% 61.2% 60.3% 60.7% 
Mucosal healing at week 30a 27.5% 48.3% 52.9% 50.6% 
a p < 0.001, for each infliximab treatment group vs. placebo.  
 
The efficacy of infliximab through week 54 was assessed in study 6. At 54 weeks, 44.9% of 
patients in the combined infliximab treatment group were in clinical response compared to 19.8% in 
the placebo treatment group (p < 0.001). Clinical remission and mucosal healing occurred in a 
greater proportion of patients in the combined infliximab treatment group compared to the placebo 
treatment group at week 54 (34.6% vs. 16.5%, p < 0.001 and 46.1% vs. 18.2%, p < 0.001, 
respectively). The proportions of patients in sustained response and sustained remission at week 54 
were greater in the combined infliximab treatment group than in the placebo treatment group 
(37.9% vs. 14.0%, p < 0.001; and 20.2% vs. 6.6%, p < 0.001, respectively). 
 
A greater proportion of patients in the combined infliximab treatment group were able to 
discontinue corticosteroids while remaining in clinical remission compared to the placebo treatment 
group at both week 30 (22.3% vs. 7.2%, p < 0.001, pooled study 6 & study 7 data) and week 54 
(21.0% vs. 8.9%, p = 0.022, study 6 data). 
 
The pooled data analysis from study 6 and study 7 and their extensions, analysed from baseline 
through 54 weeks, demonstrated a reduction of ulcerative colitis-related hospitalisations and 
surgical procedures with infliximab treatment. The number of ulcerative colitis-related 
hospitalisations was significantly lower in the 5 and 10 mg/kg infliximab treatment groups than in 
the placebo group (mean number of hospitalisations per 100 subject-years: 21 and 19 vs. 40 in the 
placebo group; p = 0.019 and p = 0.007, respectively). The number of ulcerative colitis-related 
surgical procedures was also lower in the 5 and 10 mg/kg infliximab treatment groups than in the 
placebo group (mean number of surgical procedures per 100 subject-years: 22 and 19 vs. 34; 
p = 0.145 and p = 0.022, respectively). 
 
The proportion of subjects who underwent colectomy at any time within 54 weeks following the 
first infusion of study agent were collected and pooled from study 6 and study 7 and their 
extensions. Fewer subjects underwent colectomy in the 5 mg/kg infliximab group (28/242 or 11.6% 
[N.S.]) and the 10 mg/kg infliximab group (18/242 or 7.4% [p = 0.011]) than in the placebo group 
(36/244; 14.8%). 
 
The reduction in incidence of colectomy was also examined in another randomised, double-blind 
study in hospitalised patients (n = 45) with moderately to severely active ulcerative colitis who 
failed to respond to intravenous corticosteroids and who were therefore at higher risk for 



33 
 

colectomy. Significantly fewer colectomies occurred within 3 months of study infusion in patients 
who received a single dose of 5 mg/kg infliximab compared to patients who received placebo 
(29.2% vs. 66.7% respectively, p = 0.017). 
 
In  study 6 and study 7, infliximab improved quality of life, confirmed by statistically significant 
improvement in both a disease specific measure, IBDQ, and by improvement in the generic 36-item 
short form survey SF-36. 
 
Adult ankylosing spondylitis 
 
Efficacy and safety of infliximab were assessed in two multicenter, double-blind, placebo-
controlled studies 8 and 9 in patients with active ankylosing spondylitis (Bath Ankylosing 
Spondylitis Disease Activity Index [BASDAI] score ≥ 4 and spinal pain ≥ 4 on a scale of 1-10). 
 
In the first study, (study 8), which had a 3 month double-blind phase, 70 patients received either 
5 mg/kg infliximab or placebo at weeks 0, 2, 6 (35 patients in each group). At week 12, placebo 
patients were switched to infliximab 5 mg/kg every 6 weeks up to week 54. After the first year of 
the study, 53 patients continued into an open-label extension to week 102. 
 
In the second clinical study, (study 9), 279 patients were randomised to receive either placebo 
(Group 1, n = 78) or 5 mg/kg infliximab (Group 2, n = 201) at 0, 2, and 6 weeks and every 6 weeks 
to week 24. Thereafter, all subjects continued on infliximab every 6 weeks to week 96. Group 1 
received 5 mg/kg infliximab. In group 2, starting with the week 36 infusion, patients who had a 
BASDAI ≥ 3 at 2 consecutive visits, received 7.5 mg/kg infliximab every 6 weeks thereafter 
through week 96. 
 
In the second clinical study (study 9), improvement in signs and symptoms was observed as early as 
week 2. At week 24, the number of ASAS 20 responders was 15/78 (19%) in the placebo group, 
and 123/201 (61%) in the 5 mg/kg infliximab group (p < 0.001). There were 95 subjects from group 
2 who continued on 5 mg/kg every 6 weeks. At 102 weeks there were 80 subjects still on infliximab 
treatment and among those, 71 (89%) were ASAS 20 responders. 
 
In the first study, (study 8), improvement in signs and symptoms was also observed as early as 
week 2. At week 12, the number of BASDAI 50 responders were 3/35 (9%) in the placebo group, 
and 20/35 (57%) in the 5 mg/kg group (p < 0.01). There were 53 subjects who continued on 
5 mg/kg every 6 weeks. At 102 weeks there were 49 subjects still on infliximab treatment and 
among those, 30 (61%) were BASDAI 50 responders. 
 
In both studies, physical function and quality of life as measured by the BASFI and the physical 
component score of the SF-36 were also improved significantly. 
 
Adult psoriatic arthritis 
 
Efficacy and safety were assessed in two multicenter, double-blind, placebo-controlled studies in 
patients with active psoriatic arthritis (studies 10 and 11). 
 
In the first clinical study, (study 10), efficacy and safety of infliximab were studied in 104 patients 
with active polyarticular psoriatic arthritis. During the 16-week double-blind phase, patients 
received either 5 mg/kg infliximab or placebo at weeks 0, 2, 6, and 14 (52 patients in each group). 
Starting at week 16, placebo patients were switched to infliximab and all patients subsequently 
received 5 mg/kg infliximab every 8 weeks up to week 46. After the first year of the study, 
78 patients continued into an open-label extension to week 98. 
 
In the second clinical study, (study 11), efficacy and safety of infliximab were studied in 200 
patients with active psoriatic arthritis (≥ 5 swollen joints and ≥ 5 tender joints). Forty six percent of 
patients continued on stable doses of methotrexate (≤ 25 mg/week). During the 24-week double-
blind phase, patients received either 5 mg/kg infliximab or placebo at weeks 0, 2, 6, 14, and 22 



34 
 

(100 patients in each group). At week 16, 47 placebo patients with < 10% improvement from 
baseline in both swollen and tender joint counts were switched to infliximab induction (early 
escape). At week 24, all placebo-treated patients crossed over to infliximab induction. Dosing 
continued for all patients through week 46. 
 
Key efficacy results for study 10 and study 11 in patients with active psoriatic arthritis are shown in 
Table 9 below: 
 

Table 9 
Effects on ACR and PASI in patients with active psoriatic arthritis, data from study 10 and 

study 11 
  Study  10  Study 11* 

 Placebo 
(week 16) 

infliximab 
(week 16) 

infliximab 
(week 98) 

Placebo 
(week 24) 

infliximab 
(week 24) 

infliximab 
(week 54) 

Patients randomised 52 52 N/Aa 100 100 100 
ACR response 
(% of patients) 

      

N 52 52 78 100 100 100 
ACR 20 response* 5 (10%) 34 (65%) 48 (62%) 16 (16%) 54 (54%) 53 (53%) 
ACR 50 response* 0 (0%) 24 (46%) 35 (45%) 4 (4%) 41 (41%) 33 (33%) 
ACR 70 response* 0 (0%) 15 (29%) 27 (35%) 2 (2%) 27 (27%) 20 (20%) 
PASI response 
(% of patients)b 

      

N    87 83 82 
PASI 75 response**    1 (1%) 50 (60%) 40 (48.8%) 

* ITT-analysis where subjects with missing data were included as non-responders. 
a Week 98 data for study 10 includes combined placebo crossover and infliximab patients who 

entered the open-label extension. 
b Based on patients with PASI ≥ 2.5 at baseline for study 10, and patients with ≥ 3% BSA 

psoriasis skin involvement at baseline in study 11. 
** PASI 75 response for study 10 not included due to low N; p < 0.001 for infliximab vs. placebo 

at week 24 for study 11. 
 
In study 10 and study 11 in patients with active psoriatic arthritis, clinical responses were observed 
as early as week 2 and were maintained through week 98 and week 54 respectively. Efficacy has 
been demonstrated with or without concomitant use of methotrexate. Decreases in parameters of 
peripheral activity characteristic of psoriatic arthritis (such as number of swollen joints, number of 
painful/tender joints, dactylitis and presence of enthesopathy) were seen in the infliximab-treated 
patients. 
 
Radiographic changes were assessed in study 11. Radiographs of hands and feet were collected at 
baseline, weeks 24 and 54. Infliximab treatment reduced the rate of progression of peripheral joint 
damage compared with placebo treatment at the week 24 primary endpoint as measured by change 
from baseline in total modified vdH-S score (mean ± SD score was 0.82 ± 2.62 in the placebo group 
compared with -0.70 ± 2.53 in the infliximab group; p < 0.001). In the infliximab group, the mean 
change in total modified vdH-S score remained below 0 at the week 54 timepoint. 
 
Infliximab-treated patients demonstrated significant improvement in physical function as assessed 
by HAQ. Significant improvements in health-related quality of life were also demonstrated as 
measured by the physical and mental component summary scores of the SF-36 in study 11. 
 
Adult psoriasis 
 
The efficacy of infliximab was assessed in two multicenter, randomised, double-blind studies 12 
and 13. Patients in both studies had plaque psoriasis (Body Surface Area [BSA] ≥ 10% and 



35 
 

Psoriasis Area and Severity Index [PASI] score ≥ 12). The primary endpoint in both studies was the 
percent of patients who achieved ≥ 75% improvement in PASI from baseline at week 10. 
 
Study 12 evaluated the efficacy of infliximab induction therapy in 249 patients with plaque 
psoriasis that had previously received PUVA or systemic therapy. Patients received either 3 or 5 
mg/kg infliximab or placebo infusions at weeks 0, 2 and 6. Patients with a PGA score ≥ 3 were 
eligible to receive an additional infusion of the same treatment at week 26. 
 
In study 12 in patients with plaque psoriasis, the proportion of patients achieving PASI 75 at week 
10 was 71.7% in the 3 mg/kg infliximab group, 87.9% in the 5 mg/kg infliximab group, and 5.9% 
in the placebo group (p < 0.001). By week 26, twenty weeks after the last induction dose, 30% of 
patients in the 5 mg/kg group and 13.8% of patients in the 3 mg/kg group were PASI 75 responders. 
Between weeks 6 and 26, symptoms of psoriasis gradually returned with a median time to disease 
relapse of > 20 weeks. No rebound was observed.  
 
Study 13 evaluated the efficacy of infliximab induction and maintenance therapy in 378 patients 
with plaque psoriasis. Patients received 5 mg/kg infliximab- or placebo-infusions at weeks 0, 2, and 
6 followed by maintenance therapy every 8 weeks through week 22 in the placebo group and 
through week 46 in the infliximab group. At week 24, the placebo group crossed over to infliximab 
induction therapy (5 mg/kg) followed by infliximab maintenance therapy (5 mg/kg). Nail psoriasis 
was assessed using the Nail Psoriasis Severity Index (NAPSI). Prior therapy with PUVA, 
methotrexate, cyclosporin, or acitretin had been received by 71.4% of patients, although they were 
not necessarily therapy resistant. Key results are presented in Table 10. In infliximab treated 
subjects, significant PASI 50 responses were apparent at the first visit (week 2) and PASI 75 
responses by the second visit (week 6). Efficacy was similar in the subgroup of patients that were 
exposed to previous systemic therapies compared to the overall study population. 
 



36 
 

Table 10 
Summary of PASI response, PGA response and percent of patients with all nails cleared at weeks 10, 

24, and 50. Study 13 
 Placebo → infliximab 

5 mg/kg 
(at week 24) 

infliximab 
5 mg/kg 

Week 10 
N 77 301 

≥ 90% improvement 1 (1.3%) 172 (57.1%)a 
≥ 75% improvement 2 (2.6%) 242 (80.4%)a 
≥ 50% improvement 6 (7.8%) 274 (91.0%) 
PGA of cleared (0) or minimal (1) 3 (3.9%) 242 (82.9%)ab 
PGA of cleared (0), minimal (1), or mild (2) 14 (18.2%) 275 (94.2%)ab 

Week 24 
N 77 276 

≥ 90% improvement 1 (1.3%) 161 (58.3%)a 
≥ 75% improvement 3 (3.9%) 227 (82.2%)a 
≥ 50% improvement 5 (6.5%) 248 (89.9%) 
PGA of cleared (0) or minimal (1) 2 (2.6%) 203 (73.6%)a 
PGA of cleared (0), minimal (1), or mild (2) 15 (19.5%) 246 (89.1%)a 

Week 50 
N 68 281 

≥ 90% improvement 34 (50.0%) 127 (45.2%) 
≥ 75% improvement 52 (76.5%) 170 (60.5%) 
≥ 50% improvement 61 (89.7%) 193 (68.7%) 
PGA of cleared (0) or minimal (1) 46 (67.6%) 149 (53.0%) 
PGA of cleared (0), minimal (1), or mild (2) 59 (86.8%) 189 (67.3%) 
All nails cleared c 
Week 10 1/65 (1.5%) 16/235 (6.8%) 
Week 24 3/65 (4.6%) 58/223 (26.0%)a 
Week 50 27/64 (42.2%) 92/226 (40.7%) 

 
a p < 0.001, for each infliximab treatment group vs. control. 
b n = 292. 
c Analysis was based on subjects with nail psoriasis at baseline (81.8% of subjects). Mean 

baseline NAPSI scores were 4.6 and 4.3 in infliximab and placebo group. 
 
Significant improvements from baseline were demonstrated in DLQI (p < 0.001) and the physical 
and mental component scores of the SF 36 (p < 0.001 for each component comparison). 
 
Paediatric population 
 
Paediatric Crohn’s disease (6 to 17 years) 
 
In the paediatric Crohn’s disease study 14, 112 patients (6 to 17 years, median age 13.0 years) with 
moderate to severe, active Crohn’s disease (median paediatric CDAI of 40) and an inadequate 
response to conventional therapies were to receive 5 mg/kg infliximab at weeks 0, 2, and 6. All 
patients were required to be on a stable dose of 6-MP, AZA or MTX (35% were also receiving 
corticosteroids at baseline). Patients assessed by the investigator to be in clinical response at week 
10 were randomised and received 5 mg/kg infliximab at either q8 weeks or q12 weeks as a 
maintenance treatment regimen. If response was lost during maintenance treatment, crossing over to 
a higher dose (10 mg/kg) and/or shorter dosing interval (q8 weeks) was allowed. Thirty two (32) 
evaluable paediatric patients crossed over (9 subjects in the q8 weeks and 23 subjects in the q12 
weeks maintenance groups). Twenty four of these patients (75.0%) regained clinical response after 
crossing over. 
 



37 
 

The proportion of subjects in clinical response at week 10 was 88.4% (99/112). The proportion of 
subjects achieving clinical remission at week 10 was 58.9% (66/112). 
 
At week 30, the proportion of subjects in clinical remission was higher in the q8 week (59.6%, 
31/52) than the q12 week maintenance treatment group (35.3%, 18/51; p = 0.013). At week 54, the 
figures were 55.8% (29/52) and 23.5% (12/51) in the q8 weeks and q12 weeks maintenance groups, 
respectively (p < 0.001). Data about fistulas were derived from PCDAI scores. Of the 22 subjects 
that had fistulas at baseline, 63.6% (14/22), 59.1% (13/22) and 68.2% (15/22) were in complete 
fistula response at week 10, 30, and 54, respectively, in the combined q8 weeks and q12 weeks 
maintenance groups. 
 
In addition, statistically and clinically significant improvements in quality of life and height, as well 
as a significant reduction in corticosteroid use, were observed versus baseline. 
 
Paediatric ulcerative colitis (6 to 17 years) 
The safety and efficacy of infliximab were assessed in a multicenter, randomised, open-label, 
parallel-group clinical study 15 in 60 paediatric patients aged 6 through 17 years (median age 14.5 
years) with moderately to severely active ulcerative colitis (Mayo score of 6 to 12; endoscopic 
subscore ≥ 2) with an inadequate response to conventional therapies. At baseline 53% of patients 
were receiving immunomodulator therapy (6-MP, AZA and/or MTX) and 62% of patients were 
receiving corticosteroids. Discontinuation of immunomodulators and corticosteroid taper were 
permitted after week 0. 
 
All patients received an induction regimen of 5 mg/kg infliximab at weeks 0, 2, and 6. Patients who 
did not respond to infliximab at week 8 (n = 15) received no further medicinal product and returned 
for safety follow-up. At week 8, 45 patients were randomised and received 5 mg/kg infliximab at 
either q8 weeks or q12 weeks as a maintenance treatment regimen. 
 
The proportion of patients in clinical response at week 8 was 73.3% (44/60). Clinical response at 
week 8 was similar between those with or without concomitant immunomodulator use at baseline. 
Clinical remission at week 8 was 33.3% (17/51) as measured by the Paediatric Ulcerative Colitis 
Activity Index (PUCAI) score. 
 
At week 54, the proportion of patients in clinical remission as measured by the PUCAI score was 
38% (8/21) in the q8 week maintenance group and 18% (4/22) in the q12 week maintenance 
treatment group. For patients receiving corticosteroids at baseline, the proportion of patients in 
remission and not receiving corticosteroids at week 54 was 38.5% (5/13) for the q8 week and 0% 
(0/13) for the q12 week maintenance treatment group. 
 
In this study, there were more patients in the 12 to 17 year age group than in the 6 to 11 year age 
group (45/60 vs.15/60). While the numbers of patients in each subgroup are too small to draw 
definitive conclusions about the effect of age, there was a higher number of patients in the younger 
age group who stepped up in dose or discontinued treatment due to inadequate efficacy. 
 
Other paediatric indications 
The European Medicines Agency has waived the obligation to submit the results of studies with  
the reference medicinal product containing infliximab in all subsets of the paediatric population in 
rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, psoriasis 
and Crohn's disease (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Single intravenous infusions of 1, 3, 5, 10 or 20 mg/kg of infliximab yielded dose proportional 
increases in the maximum serum concentration (Cmax) and area under the concentration-time curve 
(AUC). The volume of distribution at steady state (median Vd of 3.0 to 4.1 litres) was not dependent 
on the administered dose and indicated that infliximab is predominantly distributed within the 
vascular compartment. No time-dependency of the Pharmacokinetics was observed. The 



38 
 

elimination pathways for infliximab have not been characterised. Unchanged infliximab was not 
detected in urine. No major age- or weight-related differences in clearance or volume of distribution 
were observed in rheumatoid arthritis patients. The pharmacokinetics of infliximab in elderly 
patients has not been studied. Studies have not been performed in patients with liver or renal 
disease. 
 
At single doses of 3, 5, or 10 mg/kg, the median Cmax values were 77, 118, and 277 micrograms/ml, 
respectively. The median terminal half-life at these doses ranged from 8 to 9.5 days. In most 
patients, infliximab could be detected in the serum for at least 8 weeks after the recommended 
single dose of 5 mg/kg for Crohn’s disease and the rheumatoid arthritis maintenance dose of 
3 mg/kg every 8 weeks. 
 
Repeated administration of infliximab (5 mg/kg at 0, 2, and 6 weeks in fistulising Crohn´’s disease, 
3 or 10 mg/kg every 4 or 8 weeks in rheumatoid arthritis) resulted in a slight accumulation of 
infliximab in serum after the second dose. No further clinically relevant accumulation was 
observed. In most fistulising Crohn’s disease patients, infliximab was detected in serum for 
12 weeks (range 4-28 weeks) after administration of the regimen. 
 
Paediatric population 
Population pharmacokinetic analysis based on data obtained from patients with ulcerative colitis 
(N = 60), Crohn’s disease (N = 112), juvenile rheumatoid arthritis (N = 117) and Kawasaki disease 
(N = 16) with an overall age range from 2 months to 17 years indicated that exposure to infliximab 
was dependent on body weight in a non-linear way. Following administration of 5 mg/kg infliximab 
every 8 weeks, the predicted median steady-state infliximab exposure (area under concentration-
time curve at steady state, AUCss) in paediatric patients aged 6 years to 17 years was 
approximately 20% lower than the predicted median steady-state drug exposure in adults. The 
median AUCss in paediatric patients aged 2 years to less than 6 years was predicted to be 
approximately 40% lower than that in adults, although the number of patients supporting this 
estimate is limited. 
 
5.3 Preclinical safety data 
 
Infliximab does not cross react with TNFα from species other than human and chimpanzee. 
Therefore, conventional preclinical safety data with infliximab are limited. In a developmental 
toxicity study conducted in mice using an analogous antibody that selectively inhibits the functional 
activity of mouse TNFα, there was no indication of maternal toxicity, embryotoxicity or 
teratogenicity. In a fertility and general reproductive function study, the number of pregnant mice 
was reduced following administration of the same analogous antibody. It is not known whether this 
finding was due to effects on the males and/or the females. In a 6-month repeated dose toxicity 
study in mice, using the same analogous antibody against mouse TNFα, crystalline deposits were 
observed on the lens capsule of some of the treated male mice. No specific ophthalmologic 
examinations have been performed in patients to investigate the relevance of this finding for 
humans. 
Long-term studies have not been performed to evaluate the carcinogenic potential of infliximab. 
Studies in mice deficient in TNFα demonstrated no increase in tumours when challenged with 
known tumour initiators and/or promoters. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Disodium succinate hexahydrate 
Succinic acid 
Sucrose  
Polysorbate 80  
 



39 
 

6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other 
medicinal products. 
 
6.3 Shelf life 
 
Before reconstitution: 
 
4 years at 2°C – 8°C. 
 
Zessly may be stored at temperatures up to a maximum of 30°C for a single period of up to 
6 months, but not exceeding the original expiry date. The new expiry date must be written on the 
carton. Upon removal from refrigerated storage, Zessly must not be returned to refrigerated storage. 
 
After reconstitution: 
 
Chemical and physical in use stability of the reconstituted solution has been demonstrated for 
24 hours at 2 °C – 30 °C. From a microbiological point of view, the product should be used as soon 
as possible but within 3 hours of reconstitution and dilution. If not used immediately, in use storage 
times and conditions prior to use are the responsibility of the user and should not be longer than 24 
hours at 2°C – 8°C. 
 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C). 
 
For storage conditions up to 30°C before reconstitution of the medicinal product, see section 6.3.  
 
For storage conditions after reconstitution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Type 1 glass vial with rubber stopper and aluminium crimp protected by a plastic cap. 
 
Zessly is available in packs containing 1, 2, 3, 4 or 5 vials.  
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
1. Calculate the dose and the number of Zessly vials needed. Each Zessly vial contains 100 mg 

infliximab. Calculate the total volume of reconstituted Zessly solution required. 
 
2. Under aseptic conditions, reconstitute each Zessly vial with 10 ml of water for injections, 

using a syringe equipped with a 21-gauge (0.8 mm) or smaller needle. Remove flip-top from 
the vial and wipe the top with a 70% alcohol swab. Insert the syringe needle into the vial 
through the centre of the rubber stopper and direct the stream of water for injections to the 
glass wall of the vial. Gently swirl the solution by rotating the vial to dissolve the lyophilised 
powder. Avoid prolonged or vigorous agitation. DO NOT SHAKE. Foaming of the solution 
on reconstitution is not unusual. Allow the reconstituted solution to stand for 5 minutes. 
Check that the solution is colourless to light brown and opalescent. The solution may develop 
a few fine translucent particles, as infliximab is a protein. Do not use if opaque particles, 
discolouration, or other foreign particles are present. 

 



40 
 

3. Dilute the total volume of the reconstituted Zessly solution dose to 250 ml with sodium 
chloride 9 mg/ml (0.9%) solution for infusion. Do not dilute the reconstituted Zessly solution 
with any other diluent. The dilution can be accomplished by withdrawing a volume of the 
sodium chloride 9 mg/ml (0.9%) solution for infusion from the 250-ml glass bottle or 
infusion bag equal to the volume of reconstituted Zessly. Slowly add the total volume of 
reconstituted Zessly solution to the 250-ml infusion bottle or bag. Gently mix. 

 
4. Administer the infusion solution over a period of not less than the infusion time 

recommended (see section 4.2). Use only an infusion set with an in-line, sterile, non-
pyrogenic, low protein-binding filter (pore size 1.2 micrometre or less). Since no preservative 
is present, it is recommended that the administration of the solution for infusion is to be 
started as soon as possible and within 3 hours of reconstitution and dilution. When 
reconstitution and dilution are performed under aseptic conditions, Zessly infusion solution 
can be used within 24 hours if stored at 2°C – 8°C. Do not store any unused portion of the 
infusion solution for reuse. 

 
5. No physical biochemical compatibility studies have been conducted to evaluate the co-

administration of Zessly with other agents. Do not infuse Zessly concomitantly in the same 
intravenous line with other agents. 

 
6. Visually inspect Zessly for particulate matter or discolouration prior to administration. Do 

not use if visibly opaque particles, discolouration or foreign particles are observed. 
 
7. Any unused medicinal product or waste material should be disposed of in accordance with 

local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sandoz GmbH 
Biochemiestr. 10 
6250 Kundl 
Austria 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1280/001 
EU/1/18/1280/002 
EU/1/18/1280/003 
EU/1/18/1280/004 
EU/1/18/1280/005 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 18 May 2018 
 
 
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 
 



41 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 

 



42 
 

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) 
 
Boehringer Ingelheim Pharma GmbH & Co. KG 
Birkendorfer Strasse 65 
88397 Biberach an der Riss 
GERMANY 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Sandoz GmbH 
Biochemiestr. 10 
6336 Langkampfen 
AUSTRIA 
 
 
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 (PSUR) 
 
The requirements for submission of PSUR 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.  

 
• Additional risk minimisation measures  
 
The educational programme consists of a patient reminder card to be held by the patient. The card is 
aimed at both serving as a reminder to record the dates and outcomes of specific tests and to 
facilitate the patient sharing of special information with healthcare professionals(s) (HCPs) treating 
the patient about on-going treatment with the product. 



43 
 

 
The patient reminder card shall contain the following key messages: 
 

• A reminder to patients to show the patient reminder card to all treating HCPs, including in 
conditions of emergency, and a message for HCPs that the patient is using Zessly 

 
• A statement that the brand name and batch number should be recorded 

 
• Provision to record the type, date, and result of TB screenings 

 
• That treatment with Zessly may increase the risks of serious infections/sepsis, opportunistic 

infections, tuberculosis, hepatitis B reactivation, and BCG breakthrough in infants with in 
utero exposure to infliximab, and when to seek attention from a HCP 

 
• Contact details of the prescriber 



44 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



45 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



46 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zessly 100 mg powder for concentrate for solution for infusion 
infliximab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains  100 mg of infliximab. 
After reconstitution each ml contains 10 mg of infliximab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Disodium succinate hexahydrate, succinic acid, sucrose, polysorbate 80. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion 
1 vial 100 mg 
2 vials 100 mg 
3 vials 100 mg 
4 vials 100 mg 
5 vials 100 mg 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Intravenous use.  
Dilute before use. 
 
 
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 
EXP, if not refrigerated    
 
 
9. SPECIAL STORAGE CONDITIONS 



47 
 

 
Store in a refrigerator. 
Can be stored at  temperatures  up to 30°C for a single period up to 6 months, but not exceeding the 
original expiry date. 
 
 
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 
 
Sandoz GmbH 
Biochemiestr. 10 
6250 Kundl 
Austria 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1280/001 1 vial 100 mg 
EU/1/18/1280/002 2 vials 100 mg 
EU/1/18/1280/003 3 vials 100 mg 
EU/1/18/1280/004 4 vials 100 mg 
EU/1/18/1280/005 5 vials 100 mg 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted.  
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC  
SN  
NN  



48 
 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING 
UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Zessly 100 mg powder for concentrate 
infliximab 
IV use only 
 
 
2. METHOD OF ADMINISTRATION 
 
Intravenous use after reconstitution and dilution. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
100 mg 
 
 
6. OTHER 



49 
 

Zessly 

infliximab 

PATIENT REMINDER CARD 

Name patient:  
Name doctor: 
Telephone number doctor: 
 

This patient  reminder card contains important 
safety information that you need to be aware of 
before and during treatment with Zessly. 

Show this card to any doctor involved in your 
treatment. 

Please read the Zessly ‘Package Leaflet’ 
carefully before you start using this medicine. 

Date of Zessly therapy initiation: 

Current administrations: 

It is important that you and your doctor record 
the brand name and batch number of your 
medicine. 

Ask your doctor to record the type and date of 
last screening(s) for tuberculosis (TB) below:  

Test:   Test: 

Date:   Date: 

Result:    Result: 

Please make sure you also have a list of all other 
medicines that you are using with you at any 
visit to a healthcare professional. 

List of allergies: 

 

 

List of other medicines: 
 

INFECTIONS 

Before treatment with Zessly 

• Tell your doctor if you have an infection even if it 
is a very minor one 

• It is very important that you tell your doctor if 
you have ever had TB, or if you have been in 
close contact with someone who has had TB. 
Your doctor will test you to see if you have TB. 
Ask your doctor to record the type and date of 
your last screening(s) for TB on the card 

• Tell your doctor if you have hepatitis B or if you 
know or suspect you are a carrier of the hepatitis 
B virus. 

During treatment with Zessly 

• Tell your doctor straight away if you have 
signs of an infection. Signs include a fever, 
feeling tired, (persistent) cough, shortness of 
breath, weight loss, night sweats, diarrhoea, 
wounds, dental problems, burning when 
urinating or ‘flu-like’ signs. 

PREGNANCY AND VACCINATIONS 

• In case you have received Zessly while you were 
pregnant, it is important that you inform your 
baby’s doctor about it before your baby receives 
any vaccine. Your baby should not receive a ‘live 
vaccine’, such as BCG (used to prevent 
tuberculosis) within 6 months after birth. 

Keep this card with you for 4 months after your dose 
of Zessly, or in case of pregnancy for at least 6 
months after the birth of your baby. Side effects may 
occur a long time after your last dose. 



50 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



51 
 

Package leaflet: Information for the user 
 

Zessly 100 mg powder for concentrate for solution for infusion 
infliximab 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
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. 
• Your doctor will also give you a patient reminder card, which contains important safety 

information you need to be aware of before and during your treatment with Zessly. 
• If you have any further questions, ask your doctor. 
• 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. This includes any possible side effects not 

listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Zessly is and what it is used for 
2. What you need to know before you use Zessly 
3. How Zessly will be given 
4. Possible side effects 
5. How to store Zessly 
6. Contents of the pack and other information 
 
 
1. What Zessly is and what it is used for 
 
Zessly contains the active substance infliximab. Infliximab is a monoclonal antibody - a type of 
protein that attaches to a specific target in the body called TNF (tumour necrosis factor) alpha. 
 
Zessly belongs to a group of medicines called ‘TNF blockers’. It is used in adults for the following 
inflammatory diseases: 
• Rheumatoid arthritis 
• Psoriatic arthritis 
• Ankylosing spondylitis (Bechterew’s disease) 
• Psoriasis. 
 
Zessly is also used in adults and children 6 years of age or older for: 
• Crohn’s disease 
• Ulcerative colitis. 
 
Zessly works by selectively attaching to TNF alpha and blocking its action. TNF alpha is involved 
in inflammatory processes of the body so blocking it can reduce the inflammation in your body. 
 
Rheumatoid arthritis 
Rheumatoid arthritis is an inflammatory disease of the joints. If you have active rheumatoid arthritis 
you will first be given other medicines. If these medicines do not work well enough, you will be 
given Zessly which you will take in combinationwith another medicine called methotrexate to: 
• Reduce the signs and symptoms of your disease 
• Slow down the damage in your joints 
• Improve your physical function. 
 



52 
 

Psoriatic arthritis 
Psoriatic arthritis is an inflammatory disease of the joints, usually accompanied by psoriasis. If you 
have active psoriatic arthritis you will first be given other medicines. If these medicines do not 
work well enough, you will be given Zessly to: 
• Reduce the signs and symptoms of your disease 
• Slow down the damage in your joints 
• Improve your physical function. 
 
Ankylosing spondylitis (Bechterew’s disease) 
Ankylosing spondylitis is an inflammatory disease of the spine. If you have ankylosing spondylitis 
you will first be given other medicines. If these medicines do not work well enough, you will be 
given Zessly to: 
• Reduce the signs and symptoms of your disease 
• Improve your physical function. 
 
Psoriasis 
Psoriasis is an inflammatory disease of the skin. If you have moderate to severe plaque psoriasis, 
you will first be given other medicines or treatments, such as phototherapy. If these medicines or 
treatments do not work well enough, you will be given Zessly to reduce the signs and symptoms of 
your disease. 
 
Ulcerative colitis 
Ulcerative colitis is an inflammatory disease of the bowel. If you have ulcerative colitis you will 
first be given other medicines. If these medicines do not work well enough, you will be given 
Zessly to treat your disease. 
 
Crohn’s disease 
Crohn’s disease is an inflammatory disease of the bowel. If you have Crohn’s disease you will first 
be given other medicines. If these medicines do not work well enough, you will be given Zessly to: 
• treat active Crohn’s disease 
• reduce the number of abnormal openings (fistulae) between your bowel and your skin that 

have not been controlled by other medicines or surgery. 
 
 
2. What you need to know before you use Zessly 
 
You should not be given Zessly if: 
• You are allergic to infliximab or to any of the other ingredients of this medicine (listed in 

section 6). 
• You are allergic (hypersensitive) to proteins that come from mice. 
• You have tuberculosis (TB) or another serious infection such as pneumonia or sepsis.  
• You have heart failure that is moderate or severe. 
 
Do not use Zessly if any of the above applies to you. If you are not sure, talk to your doctor before 
you are given Zessly. 
 
Warnings and precautions 
Talk to your doctor before or during treatment with Zessly if you have: 
 
Had treatment with any medicine containing infliximab before 
• Tell your doctor if you have had treatment with medicines containing infliximab in the past 

and are now starting Zessly treatment again. 
• If you have had a break in your treatment with infliximab of more than 16 weeks, there is a 

higher risk for allergic reactions when you start the treatment again. 
 



53 
 

Infections 
• Tell your doctor before you are given Zessly if you have an infection, even if it is a very 

minor one. 
• Tell your doctor before you are given Zessly if you have ever lived in or travelled to an area 

where infections called histoplasmosis, coccidioidomycosis, or blastomycosis are common. 
These infections are caused by specific types of fungi that can affect the lungs or other parts 
of your body. 

• You may get infections more easily when you are being treated with Zessly. If you are 65 or 
older, you have a greater risk. 

• These infections may be serious and include tuberculosis, infections caused by viruses, fungi, 
bacteria or other organisms in the environment and sepsis that may be life-threatening. 

Tell your doctor straight away if you get signs of infection during treatment with Zessly. Signs 
include fever, cough, flu-like signs, feeling unwell, red or hot skin, wounds or dental problems. 
Your doctor may recommend temporarily stopping Zessly. 
 
Tuberculosis (TB) 
• It is very important that you tell your doctor if you have ever had TB or if you have been in 

close contact with someone who has had or has TB. 
• Your doctor will test you to see if you have TB. Cases of TB have been reported in patients 

treated with infliximab, even in patients who have already been treated with medicines for 
TB. Your doctor will record these tests on your patient reminder card. 

• If your doctor feels that you are at risk for TB, you may be treated with medicines for TB 
before you are given Zessly. 

Tell your doctor straight away if you get signs of TB during treatment with Zessly. Signs include 
persistent cough, weight loss, feeling tired, fever, night sweats. 
 
Hepatitis B virus  
• Tell your doctor before you are given Zessly if you are a carrier of hepatitis B or have ever 

had it. 
• Tell your doctor if you think you might be at risk of contracting hepatitis B. 
• Your doctor should test you for hepatitis B virus. 
• Treatment with TNF blockers such as Zessly may result in reactivation of hepatitis B virus in 

patients who carry this virus, which can be life-threatening in some cases. 
 
Heart problems 
• Tell your doctor if you have any heart problems, such as mild heart failure. 
• Your doctor will want to closely monitor your heart. 
Tell your doctor straight away if you get new or worsening signs of heart failure during treatment 
with Zessly. Signs include shortness of breath or swelling of your feet. 
 
Cancer and lymphoma 
• Tell your doctor before you are given Zessly if you have or have ever had lymphoma (a type 

of blood cancer) or any other cancer. 
• Patients with severe rheumatoid arthritis, who have had the disease for a long time, may be at 

higher risk of developing lymphoma. 
• Children and adults taking Zessly may have an increased risk of developing lymphoma or 

another cancer. 
• Some patients who have received TNF-blockers, including infliximab, have developed a rare 

type of cancer called hepatosplenic T-cell lymphoma. Of these patients, most were teenage 
boys or young men and most had either Crohn’s disease or ulcerative colitis. This type of 
cancer has usually resulted in death. Almost all patients had also received medicines 
containing azathioprine or 6-mercaptopurine in addition to TNF-blockers. 

• Some patients treated with infliximab have developed certain kinds of skin cancer. If there 
are any changes in your skin or growths on the skin during or after therapy, tell your doctor. 

• Some women being treated for rheumatoid arthritis with infliximab have developed cervical 
cancer. For women taking Zessly including those over 60 years of age, your doctor may 
recommend regular screening for cervical cancer. 



54 
 

 
Lung disease or heavy smoking 
• Tell your doctor before you are given Zessly if you have a lung disease called chronic 

obstructive pulmonary disease (COPD) or if you are a heavy smoker. 
• Patients with COPD and patients who are heavy smokers may have a higher risk of 

developing cancer with Zessly treatment. 
 
Nervous system disease 
• Tell your doctor if you have or have ever had a problem that affects your nervous system 

before you are given Zessly. This includes multiple sclerosis, Guillain-Barré syndrome, if 
you have fits or have been diagnosed with ‘optic neuritis’. 

Tell your doctor straight away if you get symptoms of a nerve disease during treatment with Zessly. 
Signs include changes in your vision, weakness in your arms or legs, numbness or tingling in any 
part of your body. 
 
Abnormal skin openings 
• Tell your doctor if you have any abnormal skin openings (fistulae) before you are given 

Zessly. 
 
Vaccinations 
• Talk to your doctor if you recently have had or are due to have a vaccine. 
• You should receive recommended vaccinations before starting Zessly treatment. You may 

receive some vaccines during treatment with Zessly but you should not receive live    
vaccines (vaccines that contain a living but weakened infectious agent) while using Zessly 
because they may cause infections. 

• If you received Zessly while you were pregnant, your baby may also be at higher risk for 
getting an infection with live vaccines for up to six months after birth. It is important that you 
tell your baby's doctors and other healthcare professionals about your Zessly use so they can 
decide when your baby should receive any vaccine, including live vaccines such as BCG 
(used to prevent tuberculosis). For more information see section on Pregnancy and breast-
feeding. 

 
Therapeutic infectious agents 
• Talk to you doctor if you have recently received or are scheduled to receive treatment with a 

therapeutic infectious agent (such as BCG instillation used for the treatment of cancer). 
 
Operations or dental procedures 
• Tell your doctor if you are going to have any operations or dental procedures. 
• Tell your surgeon or dentist that you are having treatment with Zessly by showing them your 

patient reminder card. 
 
Liver problems 
• Some patients receiving treatment with medicines containing infliximab have developed 

serious liver problems. 
Tell your doctor straight away if you get symptoms of liver problems during treatment with Zessly. 
Signs include yellowing of the skin and eyes, dark-brown coloured urine, pain or swelling in the 
upper right side of the stomach area, joint pain, skin rashes, or fever. 
 
Low blood counts 
• In some patients receiving treatment with medicines containing infliximab, the body may not 

make enough of the blood cells that help fight infections or help stop bleeding. 
Tell your doctor straight away if you get symptoms of low blood counts during treatment with 
Zessly. Signs include persistent fever, bleeding or bruising more easily, small red or purple spots 
caused by bleeding under the skin, or looking pale. 
 



55 
 

Immune system disorder 
• Some patients receiving treatment with medicines containing infliximab have developed 

symptoms of an immune system disorder called lupus. 
Tell your doctor straight away if you develop symptoms of lupus during treatment with Zessly. 
Signs include joint pain or a rash on cheeks or arms that is sensitive to the sun. 
 
Children and adolescents 
The information above also applies to children and adolescents. In addition: 
• Some children and teenage patients who have received TNF-blockers such as infliximab have 

developed cancers, including unusual types, which sometimes resulted in death. 
• More children taking infliximab developed infections as compared to adults. 
• Children should receive recommended vaccinations before starting Zessly treatment. 

Children may receive some vaccines during treatment with Zessly but should not receive live 
vaccines while using Zessly. 

 
If you are not sure if any of the above apply to you, talk to your doctor before you are given Zessly. 
 
Other medicines and Zessly 
Patients who have inflammatory diseases already take medicines to treat their problem. These 
medicines may cause side effects. Your doctor will advise you what other medicines you must keep 
using while you are having Zessly. 
 
Tell your doctor if you are using or have recently used any other medicines, including any other 
medicines to treat Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, 
psoriatic arthritis or psoriasis or medicines obtained without a prescription, such as vitamins and 
herbal medicines. 
 
In particular, tell your doctor if you are using any of the following medicines: 
• Medicines that affect your immune system. 
• Kineret (anakinra). Zessly and Kineret should not be used together. 
• Orencia (abatacept). Zessly and Orencia should not be used together. 
 
While using Zessly you should not receive live vaccines. If you were using Zessly during 
pregnancy, tell your baby’s doctor and other health care professionals caring for your baby about 
your Zessly use before the baby receives any vaccines. 
 
If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before using 
Zessly. 
 
Pregnancy, breast-feeding, and fertility 
• If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a 

baby, ask your doctor for advice before taking this medicine. Zessly should only be used 
during pregnancy if your doctor feels it is necessary for you. 

• You should avoid getting pregnant when you are being treated with Zessly and for 6 months 
after you stop being treated with it. Discuss the use of contraception during this time with 
your doctor. 

• Do not breast-feed when you are being treated with Zessly or for 6 months after your last 
treatment with Zessly. 

• If you received Zessly during your pregnancy, your baby may have a higher risk for getting 
an infection. 

• It is important that you tell your baby’s doctors and other health care professionals about 
your Zessly use before your baby is given any vaccine. If you received Zessly while 
pregnant, giving BCG vaccine (used to prevent tuberculosis) to your baby within 6 months 
after birth may result in infection with serious complications, including death. Live vaccines 
such as BCG should not be given to your baby within 6 months after birth. For more 
information see section on vaccination. 



56 
 

• Severely decreased numbers of white blood cells have been reported in infants born to 
women treated with infliximab during pregnancy. If your baby has continual fevers or 
infections, contact your baby’s doctor immediately. 

 
Driving and using machines 
Zessly is not likely to affect your ability to drive or use tools or machines. If you feel tired, dizzy or 
unwell after having Zessly, do not drive or use any tools or machines. 
 
Zessly contains Sodium 
Zessly contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’. 
However, before Zessly is given to you, it is mixed with a solution that contains sodium. Talk to 
your doctor if you are on a low salt diet. 
 
 
3. How to use Zessly 
 
Rheumatoid arthritis 
The usual dose is 3 mg for every kg of body weight. 
 
Psoriatic arthritis, ankylosing spondylitis (Bechterew’s disease), psoriasis, ulcerative colitis 
and Crohn's disease 
The usual dose is 5 mg for every kg of body weight. 
 
How Zessly is given 
• Zessly will be given to you by your doctor or nurse. 
• Your doctor or nurse will prepare the medicine for infusion. 
• The medicine will be given as an infusion (drip) over a 2 hours into one of your veins, 

usually in your arm. After the third treatment, your doctor may decide to give your dose of  
Zessly over 1 hour. 

• You will be monitored while you are given Zessly and also for 1 to 2 hours afterwards. 
 
How much Zessly is given 
• The doctor will decide your dose and how often you will be given Zessly. This will depend 

on your disease, weight and how well you respond to Zessly. 
• The table below shows how often you will usually have this medicine after your first dose. 
 

2nd dose 2 weeks after your 1st treatment 
3rd dose 6 weeks after your 1st treatment 
Further doses Every 6 to 8 weeks depending on your disease 

 
Use in children and adolescents 
Zessly should only be used in children if they are being treated for Crohn’s disease or ulcerative 
colitis. These children must be 6 years of age or older. 
 
If you are given too much Zessly 
As this medicine is being given by your doctor or nurse, it is unlikely that you will be given too 
much. There are no known side effects of having too much of Zessly. 
 
If you forget or miss your Zessly infusion 
If you forget or miss an appointment to receive Zessly, make another appointment as soon as 
possible. 
 
If you have any further questions on the use of this medicine, ask your doctor. 
 
 



57 
 

4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Most 
side effects are mild to moderate. However some patients may experience serious side effects and 
may require treatment. Side effects may also occur after your treatment with Zessly has stopped. 
 
Tell your doctor straight away if you notice any of the following: 
• Signs of an allergic reaction such as swelling of your face, lips, mouth or throat, which may 

cause difficulty in swallowing or breathing, skin rash, hives, swelling of the hands, feet or 
ankles. Some of these reactions may be serious or life-threatening. An allergic reaction could 
happen within 2 hours of your injection or later. More signs of allergic side effects that may 
happen up to 12 days after your injection include pain in the muscles, fever, joint or jaw 
pain, sore throat or headache. 

• Signs of a heart problem such as chest discomfort or pain, arm pain, stomach pain, 
shortness of breath, anxiety, light-headedness, dizziness, fainting, sweating, nausea (feeling 
seek), vomiting, fluttering or pounding in your chest, a fast or a slow heartbeat, and swelling 
of your feet. 

• Signs of infection (including TB) such as fever, feeling tired, cough which may be 
persistent, shortness of breath, flu-like symptoms, weight loss, night sweats, diarrhoea, 
wounds, collection of pus in the gut or around the anus (abscess), dental problems or burning 
sensation when urinating. 

• Possible signs of cancer including but not limited to swelling of lymph nodes, weight loss, 
fever, unusual skin nodules, changes in moles or skin colouring, or unusual vaginal bleeding. 

• Signs of a lung problem such as coughing, breathing difficulties or tightness in the chest. 
• Signs of a nervous system problem (including eye problems) such as fits, tingling or 

numbness in any part of your body, weakness in arms or legs, changes in eyesight such as 
double vision or other eye problems. 

• Signs of a liver problem (including hepatitis B infection when you have had hepatitis B in 
the past) such as yellowing of the skin or eyes, dark-brown coloured urine pain or swelling in 
the upper right side of the stomach area, joint pain, skin rashes, or fever. 

• Signs of an immune system disorder such as joint pain or a rash on cheeks or arms that is 
sensitive to the sun (lupus) or cough, shortness of breath, fever or skin rash (sarcoidosis).. 

• Signs of low blood counts such as persistent fever, bleeding or bruising more easily, small 
red or purple spots caused by bleeding under the skin, or looking pale. 

• Signs of serious skin problems such as reddish-target-like spots or circular patches often 
with central blisters on the trunk, large areas of peeling and shedding (exfoliating) skin, 
ulcers of mouth, throat, nose, genitals and eyes or small pus-filled bumps that can spread 
over the body. These skin reactions can be accompanied by fever. 

 
Tell your doctor straight away if you notice any of the above. 
 
The following side effects have been observed with medicines containing infliximab: 
 
Very common (may affect more than 1 in 10 people) 
• Stomach pain, feeling sick 
• Viral infections such as herpes or flu 
• Upper respiratory infections such as sinusitis 
• Headache 
• Side effect due to an infusion 
• Pain. 
 
Common (may affect up to 1 in 10 people) 
• Changes in how your liver works, increase in liver enzymes (shown in blood tests) 
• Lung or chest infections such as bronchitis or pneumonia 
• Difficult or painful breathing, chest pain 
• Bleeding in the stomach or intestines, diarrhoea, indigestion, heartburn, constipation 
• Nettle-type rash (hives), itchy rash or dry skin 



58 
 

• Balance problems or feeling dizzy 
• Fever, increased sweating 
• Circulation problems such as low or high blood pressure, 
• Bruising, hot flush or nosebleed, warm, red skin (flushing) 
• Feeling tired or weak 
• Bacterial infections such as blood poisoning, abscess or infection of the skin (cellulitis) 
• Infection of the skin due to a fungus 
• Blood problems such as anaemia or low white blood cell count 
• Swollen lymph nodes 
• Depression, problems sleeping 
• Eye problems, including red eyes and infections 
• Fast heart beat (tachycardia) or palpitations 
• Pain in the joints, muscles or back 
• Urinary tract infection 
• Psoriasis, skin problems such as eczema and hair loss 
• Reactions at the injection site such as pain, swelling, redness or itching 
• Chills, a build up of fluid under the skin causing swelling 
• Feeling numb or having a tingling feeling 
 
Uncommon (may affect up to 1 in 100 people) 
• Shortage of blood supply, swelling of a vein 
• Collection of blood outside the blood vessels (haematoma) or bruising 
• Skin problems such as blistering, warts, abnormal skin colouration or pigmentation, or 

swollen lips, or thickening of the skin, or red, scaly, and flaky skin 
• Severe allergic reactions (e.g. anaphylaxis), an immune system disorder called lupus, allergic 

reactions to foreign proteins 
• Wounds taking longer to heal 
• Swelling of the liver (hepatitis) or gall bladder, liver damage 
• Feeling forgetful, irritable, confused, nervous 
• Eye problems including blurred or reduced vision, puffy eyes or sties 
• New or worsening heart failure, slow heart rate 
• Fainting 
• Convulsions, nerve problems 
• A hole in the bowel or blockage of the intestine, stomach pain or cramps 
• Swelling of your pancreas (pancreatitis) 
• Fungal infections such as yeast infection or fungal infection of the nails 
• Lung problems (such as oedema) 
• Fluid around the lungs (pleural effusion) 
• Narrowed airway in the lungs, causing difficulty breathing 
• Inflamed lining of the lung, causing sharp chest pains that feel worse with breathing 

(pleurisy) 
• Tuberculosis 
• Kidney infections 
• Low platelet count, too many white blood cells 
• Infections of the vagina 
• Blood test result showing ‘antibodies’ against your own body. 
 
Rare (may affect up to 1 in 1,000 people) 
• A type of blood cancer (lymphoma) 
• Your blood not supplying enough oxygen to your body, circulation problems such as 

narrowing of a blood vessel 
• Inflammation of the lining of the brain (meningitis) 
• Infections due to a weakened immune system 
• Hepatitis B infection when you have had hepatitis B in the past 
• Inflamed liver caused by a problem with the immune system (autoimmune hepatitis) 
• Liver problem that causes yellowing of the skin or eyes (jaundice) 
• Abnormal tissue swelling or growth 



59 
 

• Severe allergic reaction that may cause loss of consciousness and could be life-threatening 
(anaphylactic shock) 

• Swelling of small blood vessels (vasculitis) 
• Immune disorders that could affect the lungs, skin and lymph nodes (such as sarcoidosis). 
• Collections of immune cells resulting from an inflammatory response (granulomatous 

lesions) 
• Lack of interest or emotion 
• Serious skin problems such as toxic epidermal necrolysis, Stevens-Johnson Syndrome and 

acute generalised exanthematous pustulosis  
• Other skin problems such as erythema multiforme, lichenoid reactions (itchy reddish-purple 

skin rash and/or threadlike white-grey lines on mucous membranes), blisters and peeling 
skin, or boils (furunculosis) 

• Serious nervous system disorders such as transverse myelitis, multiple sclerosis-like disease, 
optic neuritis and Guillain-Barré syndrome 

• Inflammation in the eye that may cause changes in the vision, including blindness 
• Fluid in the lining of the heart (pericardial effusion) 
• Serious lung problems (such as interstitial lung disease) 
• Melanoma (a type of skin cancer) 
• Cervical cancer 
• Low blood counts, including a severely decreased number of white blood cells 
• Small red or purple spots caused by bleeding under the skin 
• Abnormal values of a blood protein called ‘complement factor’ which is part of the immune 

system. 
 
Not known (frequency cannot be estimated from the available data) 
• Cancer in children and adults 
• A rare blood cancer affecting mostly teenage boys or young men (hepatosplenic T-cell 

lymphoma) 
• Liver failure 
• Merkel cell carcinoma (a type of skin cancer) 
• Worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle 

weakness) 
• Heart attack 
• Temporary loss of sight during or within 2 hours of infusion 
• Infection due to a live vaccine because of a weakened immune system. 
 
Additional side effects in children and adolescents 
 
Children who took infliximab for Crohn’s disease showed some differences in side effects 
compared with adults who took infliximab for Crohn's disease. The side effects that happened more 
in children were: low red blood cells (anaemia), blood in stool, low overall levels of white blood 
cells (leukopenia), redness or blushing (flushing), viral infections, low levels of white blood cells 
that fight infection (neutropenia), bone fracture, bacterial infection and allergic reactions of the 
breathing tract. 
 
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. 
 
 
5. How to store Zessly 
 
Zessly will generally be stored by the health professionals. The storage details should you need 
them are as follows: 
• Keep this medicine out of the sight and reach of children. 



60 
 

• Do not use this medicine after the expiry date which is stated on the label and the carton after 
“EXP”. The expiry date refers to the last day of that month. 

• Store in a refrigerator (2°C – 8°C). 
• This medicine can also be stored in the original carton outside of refrigerated storage up to a 

maximum of 30°C for a single period of up to six months, but not beyond the original expiry 
date. In this situation, do not return to the refrigerated storage again. Write the new expiry 
date on the carton including day/month/year. Discard this medicine if not used by the new 
expiry date or the expiry date printed on the carton, whichever is earlier. 

• It is recommended that when Zessly is prepared for infusion, it is used as soon as possible 
(within 3 hours). However, if the solution is prepared in germ-free conditions, it can be 
stored in a refrigerator at 2°C – 8°C for 24 hours. 

• Do not use this medicine if it is discoloured or if there are particles present. 
 
 
6. Contents of the pack and other information 
 
What Zessly contains 
• The active substance is infliximab. Each vial contains 100 mg of infliximab. After 

preparation each ml contains 10 mg of infliximab. 
• The other ingredients are disodium succinate hexahydrate, succinic acid, sucrose, 

polysorbate 80. 
 
What Zessly looks like and contents of the pack 
Zessly is supplied as a glass vial containing a powder for concentrate for solution for infusion 
(powder for concentrate). The powder is white. 
Zessly is available in packs containing 1, 2, 3, 4, or 5 vials. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
 
Sandoz GmbH 
Biochemiestr. 10 
6250 Kundl 
Austria 
 
 
Manufacturer 
 
Sandoz GmbH 
Biochemiestr. 10 
6336 Langkampfen 
Austria 
 
 
This leaflet was last revised in {MM/YYYY}. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  



61 
 

------------------------------------------------------------------------------------------------------------------------ 
 
The following information is intended for healthcare professionals only: 
 
Patients treated with infliximab should be given the patient reminder card. 
 
Instructions for use and handling – storage conditions 
 
Store at 2°C – 8°C. 
 
Zessly may be stored at temperatures up to a maximum of 30°C for a single period of up to 
6 months, but not exceeding the original expiry date. The new expiry date must be written on the 
carton. Upon removal from refrigerated storage, Zessly must not be returned to refrigerated storage. 
 
Instructions for use and handling – reconstitution, dilution and administration 
 
In order to improve the traceability of biological medicinal products, the tradename and batch 
number of the administered medicinal product should be clearly recorded. 
 
 
1. Calculate the dose and the number of Zessly vials needed. Each Zessly vial contains 100 mg 

infliximab. Calculate the total volume of reconstituted Zessly solution required. 
 
2. Under aseptic conditions, reconstitute each Zessly vial with 10 ml of water for injections, 

using a syringe equipped with a 21-gauge (0.8 mm) or smaller needle. Remove flip-top from 
the vial and wipe the top with a 70% alcohol swab. Insert the syringe needle into the vial 
through the centre of the rubber stopper and direct the stream of water for injections to the 
glass wall of the vial. Gently swirl the solution by rotating the vial to dissolve the lyophilised 
powder. Avoid prolonged or vigorous agitation. DO NOT SHAKE. Foaming of the solution 
on reconstitution is not unusual. Allow the reconstituted solution to stand for 5 minutes. 
Check that the solution is colourless to light brown and opalescent. The solution may develop 
a few fine translucent particles, as infliximab is a protein. Do not use if opaque particles, 
discolouration, or other foreign particles are present. 

 
3. Dilute the total volume of the reconstituted Zessly solution dose to 250 ml with sodium 

chloride 9 mg/ml (0.9%) solution for infusion. Do not dilute the reconstituted Zessly solution 
with any other diluent. The dilution can be accomplished by withdrawing a volume of the 
sodium chloride 9 mg/ml (0.9%) solution for infusion from the 250-ml glass bottle or 
infusion bag equal to the volume of reconstituted Zessly. Slowly add the total volume of 
reconstituted Zessly solution to the 250-ml infusion bottle or bag. Gently mix. 

 
4. Administer the infusion solution over a period of not less than the infusion time 

recommended. 
Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter 
(pore size 1.2 micrometre or less). Since no preservative is present, it is recommended that 
the administration of the solution for infusion is to be started as soon as possible and within 3 
hours of reconstitution and dilution. When reconstitution and dilution are performed under 
aseptic conditions, Zessly infusion solution can be used within 24 hours if stored at 2°C –
 8°C. Do not store any unused portion of the infusion solution for reuse. 

 
5. No physical biochemical compatibility studies have been conducted to evaluate the co-

administration of Zessly with other agents. Do not infuse Zessly concomitantly in the same 
intravenous line with other agents. 

 
6. Visually inspect Zessly for particulate matter or discolouration prior to administration. Do 

not use if visibly opaque particles, discolouration or foreign particles are observed. 
 



62 
 

7. Any unused product or waste material should be disposed of in accordance with local 
requirements. 


	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