Remicade

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Remicade 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 murine hybridoma 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
Remicade, 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
Remicade 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
Remicade 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 
for such therapies. Remicade has been studied only in combination with conventional 
immunosuppressive therapy.

Ulcerative colitis
Remicade 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 



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6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical 
contraindications for such therapies.

Paediatric ulcerative colitis
Remicade 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
Remicade is indicated for treatment of severe, active ankylosing spondylitis, in adult patients who 
have responded inadequately to conventional therapy.

Psoriatic arthritis
Remicade is indicated for treatment of active and progressive psoriatic arthritis in adult patients when 
the response to previous DMARD therapy has been inadequate.
Remicade should be administered
 in combination with methotrexate
 or alone in patients who show intolerance to methotrexate or for whom methotrexate is 

contraindicated
Remicade 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
Remicade 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 
ciclosporin, methotrexate or PUVA (see section 5.1).

4.2 Posology and method of administration

Remicade 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. Remicade should be administered intravenously. Remicade infusions 
should be administered by qualified healthcare professionals trained to detect any infusion-related 
issues. Patients treated with Remicade should be given the package leaflet and the patient reminder 
card.

During Remicade treatment, other concomitant therapies, e.g., corticosteroids and 
immunosuppressants should be optimised.

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.

Remicade 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.



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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.

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.



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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, Remicade can be re-administered within 16 weeks 
following the last infusion. In clinical studies, delayed hypersensitivity reactions have been 
uncommon and have occurred after Remicade-free intervals of less than 1 year (see sections 4.4 and 
4.8). The safety and efficacy of re-administration after a Remicade-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 Remicade 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).

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, Remicade should be 
re-initiated as a single dose followed by the maintenance dose recommendations described above.

Special populations
Elderly
Specific studies of Remicade 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 Remicade in elderly 
patients (see sections 4.4 and 4.8).

Renal and/or hepatic impairment
Remicade 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).



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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 Remicade 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 Remicade 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 Remicade 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.

Juvenile idiopathic arthritis, psoriatic arthritis and ankylosing spondylitis
The safety and efficacy of Remicade 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 Remicade 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
Remicade should be administered intravenously over a 2 hour period. All patients administered 
Remicade 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 Remicade 
(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.



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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 tradename 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 
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 Remicade 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 Remicade 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 Remicade-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 Remicade. Because the elimination of infliximab may take up to six months, 
monitoring should be continued throughout this period. Further treatment with Remicade must not be 
given if a patient develops a serious infection or sepsis.

Caution should be exercised when considering the use of Remicade 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 (TNF) mediates inflammation and modulates cellular immune 
responses. Experimental data show that TNF is essential for the clearing of intracellular infections. 



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Clinical experience shows that host defence against infection is compromised in some patients treated 
with infliximab.

It should be noted that suppression of TNF 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 Remicade, should be 
monitored closely and undergo a complete diagnostic evaluation. Administration of Remicade 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 Remicade. It should be noted that 
in the majority of these reports tuberculosis was extrapulmonary, presenting as either local or 
disseminated disease.

Before starting treatment with Remicade, 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, Remicade 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 Remicade 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 Remicade, 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 Remicade.

Use of antituberculosis therapy should also be considered before the initiation of Remicade 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 Remicade 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 Remicade 
treatment.

Invasive fungal infections
In patients treated with Remicade, an invasive fungal infection such as aspergillosis, candidiasis, 
pneumocystosis, histoplasmosis, coccidioidomycosis or blastomycosis should be suspected if they 



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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 Remicade 
treatment should be carefully considered before initiation of Remicade therapy.

Fistulising Crohn’s disease
Patients with fistulising Crohn’s disease with acute suppurative fistulas must not initiate Remicade 
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 Remicade. For patients 
who test positive for HBV infection, consultation with a physician with expertise in the treatment of 
hepatitis B is recommended. Carriers of HBV who require treatment with Remicade 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, Remicade 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 Remicade. 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), Remicade 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 TNF-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 
TNF-blocking agents. Therefore, the combination of Remicade 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 Remicade 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.



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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 Remicade 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 ASPIRE study a similar proportion 
of patients in each treatment group (methotrexate plus: placebo [n = 17], 3 mg/kg [n = 27] or 6 mg/kg 
Remicade [n = 46]) mounted an effective two-fold increase in titers to a polyvalent pneumococcal 
vaccine, indicating that Remicade did not interfere with T-cell independent humoral immune 
responses. However, studies from the published literature in various indications (e.g. rheumatoid 
arthritis, psoriasis, Crohn’s disease) suggest that non-live vaccinations received during treatment with 
anti-TNF therapies, including Remicade, may elicit a lower immune response than in patients not 
receiving anti-TNF therapy.

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 Remicade 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 
Remicade.

Autoimmune processes
The relative deficiency of TNF 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 Remicade and is positive for antibodies against double-stranded DNA, further 
treatment with Remicade 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 Remicade therapy. Discontinuation of Remicade 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 Remicade across all approved indications the incidence of 
lymphoma in Remicade-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 



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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 Remicade in patients with moderate to severe 
chronic obstructive pulmonary disease (COPD), more malignancies were reported in 
Remicade-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.

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 
Remicade 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 Remicade 
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 
Remicade should be carefully considered. A risk for the development for hepatosplenic T-cell 
lymphoma in patients treated with Remicade cannot be excluded (see section 4.8).

Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker 
therapy, including Remicade (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 Remicade, 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 Remicade is not established, the risk and benefits of continued therapy to the 
individual patients should be carefully considered by the clinician.



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Heart failure
Remicade should be used with caution in patients with mild heart failure (NYHA class I/II). Patients 
should be closely monitored and Remicade 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, leucopenia, neutropenia, and thrombocytopenia in patients 
receiving TNF-blockers, including Remicade. 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 Remicade therapy should be considered in 
patients with confirmed significant haematologic abnormalities.

Others
There is limited safety experience of Remicade 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 Remicade 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 Remicade-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 Remicade 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 
Remicade 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 Remicade 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 Remicade should be 
carefully considered. A risk for the development for hepatosplenic T-cell lymphoma in patients 
treated with Remicade cannot be excluded (see section 4.8).



13

Sodium content
Remicade contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’. 
Remicade 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).

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 Remicade with other biological therapeutics used to treat the same conditions as 
Remicade, including anakinra and abatacept, is not recommended (see section 4.4).

It is recommended that live vaccines not be given concurrently with Remicade. 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 Remicade (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 Remicade treatment.

Pregnancy
The moderate number of prospectively collected pregnancies exposed to infliximab resulting in live 
birth with known outcomes, including approximately 1100 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 (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 TNF, 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 TNF, 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.



14

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 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 Remicade 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

Remicade may have a minor influence on the ability to drive and use machines. Dizziness may occur 
following administration of Remicade (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 
Remicade 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.

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)*.



15

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 or ulcerative colitis), 
Merkel cell carcinoma.

Blood and lymphatic system 
disorders

Common: Neutropenia, leucopenia, 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.
Nervous system disorders

Very common: Headache.
Common: Vertigo, dizziness, hypoaesthesia, 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).

Not known: Cerebrovascular accidents in close temporal association with 
infusion.

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.



16

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.

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

Description of selected adverse drug reactions

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. 



17

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 (ASPIRE), 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 
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 (SONIC), 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 Remicade administration
(see section 4.4).
Cases of transient visual loss occurring during or within 2 hours of Remicade infusion have been 
reported. Events (some fatal) of myocardial ischaemia/infarction and arrhythmia have been reported, 
some in close temporal association with infusion of infliximab; cerebrovascular accidents have also 
been reported in close temporal association with infusion of infliximab.

Infusion reactions following re-administration of Remicade
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 Remicade 
(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, dyspnea, urticaria, facial oedema, and hypotension. In all cases, Remicade 
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 
Remicade-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 Remicade-free 
intervals of more than 1 year but limited data from clinical studies suggest an increased risk for 
delayed hypersensitivity with increasing Remicade-free interval (see section 4.4).

In a 1-year clinical study with repeated infusions in patients with Crohn's disease (ACCENT I study), 
the incidence of serum sickness-like reactions was 2.4%.



18

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 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 Remicade. 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 Remicade 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 



19

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 Remicade 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).

Heart failure
In a Phase II study aimed at evaluating Remicade in CHF, higher incidence of mortality due to 
worsening of heart failure were seen in patients treated with Remicade, 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 
Remicade 5 mg/kg, 10 mg/kg, or placebo over 6 weeks. At 38 weeks, 9 of 101 patients treated with 
Remicade (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 Remicade. 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 Remicade 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 Remicade than 
in controls, both when Remicade 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 Remicade, 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 Remicade (see section 4.4).

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

Indication Number of patients3 Median follow-up 
(wks)4

≥ 3 x ULN ≥ 5 x ULN

placebo infliximab placebo infliximab placebo infliximab placebo infliximab
Rheumatoid 
arthritis1

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

Crohn’s 
disease2

324 1034 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%



20

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%

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

2
Placebo patients in the 2 Phase III studies in Crohn’s disease, ACCENT I and ACCENT II, 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, SONIC, 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
Remicade 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.

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 Remicade 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 
in the REACH study (see section 5.1) than in adult Crohn’s disease patients: anaemia (10.7%), blood 
in stool (9.7%), leucopenia (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 REACH, 17.5% of randomised patients experienced 1 or more infusion reactions. There were no 
serious infusion reactions, and 2 subjects in REACH had non-serious anaphylactic reactions.



21

Immunogenicity
Antibodies to infliximab were detected in 3 (2.9%) paediatric patients.

Infections
In the REACH 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 (C0168T72) and adult 
ulcerative colitis (ACT 1 and ACT 2) studies were generally consistent. In C0168T72, 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.

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 C0168T72 and 22 (36.7%) required 
oral or parenteral antimicrobial treatment. The proportion of patients with infections in C0168T72 
was similar to that in the paediatric Crohn’s disease study (REACH) but higher than the proportion in 
the adults ulcerative colitis studies (ACT 1 and ACT 2). The overall incidence of infections in 
C0168T72 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 



22

(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 (TNF) inhibitors, 
ATC code: L04AB02.

Mechanism of action
Infliximab is a chimeric human-murine monoclonal antibody that binds with high affinity to both 
soluble and transmembrane forms of TNF but not to lymphotoxin  (TNFß).

Pharmacodynamic effects
Infliximab inhibits the functional activity of TNF 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 TNF and when administered after disease onset, it allowed eroded joints to heal. In vivo, 
infliximab rapidly forms stable complexes with human TNF, a process that parallels the loss of TNF
bioactivity.

Elevated concentrations of TNF 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 Remicade 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 TNF. 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 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


23

of the intestinal mucosa showed that infliximab treatment caused a reduction in the number of cells 
capable of expressing TNF and interferon. 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: ATTRACT and ASPIRE. In both studies concurrent use of stable doses of folic acid, oral 
corticosteroids (≤ 10 mg/day) and/or non-steroidal antiinflammatory 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 ATTRACT, landmark ACR-N for ASPIRE), 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, (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.

The ATTRACT study 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, ATTRACT

infliximab
b

Control
a

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 

infliximab
b

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 score
d

(van der 
Heijde-modified Sharp score)
Change from baseline (Mean ±

SD
c
)

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)



24

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 ± SD
c 0.2 ± 0.3 0.4 ± 0.3 0.5 ± 0.4 0.5 ± 0.5 0.4 ± 0.4 0.4 ± 0.4

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.

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.

The ASPIRE study 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 ASPIRE, 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, ASPIRE

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 ATTRACT, ASPIRE and the START 
study. START 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.



25

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 
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 (ACCENT I).
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.

Table 5
Effects on response and remission rate, data from ACCENT I (week-2 responders)

ACCENT I (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)



26

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 
(SONIC) 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%).

Table 6
Percent of patients achieving corticosteroid-free clinical remission at week 26, SONIC

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.



27

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 fistulae 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 (ACCENT II). 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.

Table 7
Effects on response rate, data from ACCENT II (week-14 responders)

ACCENT II (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.



28

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 Remicade were assessed in two (ACT 1 and ACT 2) 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 
Remicade, or 10 mg/kg Remicade at weeks 0, 2, 6, 14 and 22, and in ACT 1 at weeks 30, 38 and 46. 
Corticosteroid taper was permitted after week 8.

Table 8
Effects on clinical response, clinical remission and mucosal healing at weeks 8 and 30.

Combined data from ACT 1 & 2
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 Remicade through week 54 was assessed in the ACT 1 study.
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 ACT 1 & ACT 2 data) and week 54 (21.0% vs. 8.9%, 
p = 0.022, ACT1 data).

The pooled data analysis from the ACT 1 and ACT 2 studies 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 



29

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 the ACT 1 and ACT 2 studies 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 (C0168Y06) 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 
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 ACT 1 and ACT 2, 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 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 (P01522), 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 (ASSERT), 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 ASSERT, 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 P01522, 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.



30

Adult psoriatic arthritis
Efficacy and safety were assessed in two multicenter, double-blind, placebo-controlled studies in 
patients with active psoriatic arthritis.

In the first clinical study (IMPACT), 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 (IMPACT 2), 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 
(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 IMPACT and IMPACT 2 are shown in Table 9 below:

Table 9
Effects on ACR and PASI in IMPACT and IMPACT 2

IMPACT IMPACT 2*
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 IMPACT includes combined placebo crossover and infliximab patients who entered the open-label 
extension.

b
Based on patients with PASI ≥ 2.5 at baseline for IMPACT, and patients with ≥ 3% BSA psoriasis skin involvement at 
baseline in IMPACT 2.

** PASI 75 response for IMPACT not included due to low N; p < 0.001 for infliximab vs. placebo at week 24 for 
IMPACT 2.

In IMPACT and IMPACT 2, 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 IMPACT 2. 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 



31

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 IMPACT 2.

Adult psoriasis
The efficacy of infliximab was assessed in two multicenter, randomised, double-blind studies: SPIRIT 
and EXPRESS. Patients in both studies had plaque psoriasis (Body Surface Area [BSA] ≥ 10% and 
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.

SPIRIT 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 SPIRIT, 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.
EXPRESS 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, ciclosporin, 
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.

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

weeks 10, 24 and 50. EXPRESS
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



32

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 clearedc

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 REACH study, 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.
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 (C0168T72) 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 



33

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 
Remicade 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 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 Remicade 
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 



34

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 TNF from species other than human and chimpanzees. 
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 TNF, 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 TNF, 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 TNF demonstrated no increase in tumours when challenged with known 
tumour initiators and/or promoters.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sucrose
Polysorbate 80
Monobasic sodium phosphate
Dibasic sodium phosphate

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:
3 years at 2 °C – 8 °C.

Remicade may be stored at temperatures up to a maximum of 25 °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, Remicade must not be returned to refrigerated 
storage.

After reconstitution and dilution:
Chemical and physical in use stability of the diluted solution has been demonstrated for up to 28 days 
at 2 °C to 8 °C and for an additional 24 hours at 25 °C after removal from refrigeration. From a 
microbiological point of view, the infusion solution should be administered immediately, in use 
storage times and conditions prior to use are the responsibility of the user and would normally not be 
longer than 24 hours at 2 °C to 8 °C, unless reconstitution/dilution has been taken place in controlled 
and validated aseptic conditions.

6.4 Special precautions for storage

Store in a refrigerator (2 °C - 8 °C).



35

For storage conditions up to 25 °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.

Remicade is available in packs of 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 Remicade vials needed. Each Remicade vial contains 
100 mg infliximab. Calculate the total volume of reconstituted Remicade solution required.

2. Under aseptic conditions, reconstitute each Remicade 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 yellow 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 Remicade solution dose to 250 ml with sodium 
chloride 9 mg/ml (0.9%) solution for infusion. Do not dilute the reconstituted Remicade 
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 Remicade. Slowly add the total volume of 
reconstituted Remicade solution to the 250-ml infusion bottle or bag. Gently mix. For volumes 
greater than 250 ml, either use a larger infusion bag (e.g. 500 ml, 1000 ml) or use multiple 
250 ml infusion bags to ensure that the concentration of the infusion solution does not exceed 
4 mg/ml. If stored refrigerated after reconstitution and dilution, the infusion solution must be 
allowed to equilibrate at room temperature to 25 °C for 3 hours prior to Step 4 (infusion). 
Storage beyond 24 hours at 2 °C - 8 °C applies to preparation of Remicade in the infusion bag 
only.

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. If not used immediately, in use 
storage times and conditions prior to use are the responsibility of the user and would normally 
not be longer than 24 hours at 2 °C to 8 °C, unless reconstitution/dilution has been taken place 
in controlled and validated aseptic conditions, (see section 6.3 above). 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 Remicade with other agents. Do not infuse Remicade concomitantly in the 
same intravenous line with other agents.



36

6. Visually inspect Remicade 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

Janssen Biologics B.V.
Einsteinweg 101
2333 CB Leiden
The Netherlands

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/99/116/001
EU/1/99/116/002
EU/1/99/116/003
EU/1/99/116/004
EU/1/99/116/005

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 13 August 1999.
Date of latest renewal: 2 July 2009.

10. DATE OF REVISION OF THE TEXT

Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu

http://www.ema.europa.eu/


37

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



38

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

Names and addresses of the manufacturer(s) of the biological active substance(s)

Janssen Biologics B.V., Einsteinweg 101, 2333 CB Leiden, The Netherlands

Janssen Biotech Inc., 200 Great Valley Parkway Malvern, Pennsylvania 19355-1307, United States of 
America

Name and address of the manufacturer(s) responsible for batch release

Janssen Biologics B.V., Einsteinweg 101, 2333 CB Leiden, The Netherlands

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

The requirements for submission of periodic safety update reports 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 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.

The patient reminder card shall contain the following key messages:



39

 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 Remicade

 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 Remicade 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



40

ANNEX III

LABELLING AND PACKAGE LEAFLET



41

A. LABELLING



42

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON

1. NAME OF THE MEDICINAL PRODUCT

Remicade 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 one ml contains 10 mg of infliximab.

3. LIST OF EXCIPIENTS

Excipients: sucrose, polysorbate 80, monobasic sodium phosphate and dibasic sodium phosphate.

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.
Reconstitute and 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 ___________________



43

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator.
Can be stored at room temperature (up to 25 °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

Janssen Biologics B.V.
Einsteinweg 101
2333 CB Leiden
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/99/116/001 1 vial 100 mg
EU/1/99/116/002 2 vials 100 mg
EU/1/99/116/003 3 vials 100 mg
EU/1/99/116/004 4 vials 100 mg
EU/1/99/116/005 5 vials 100 mg

13. BATCH NUMBER

Batch

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.



44

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC:
SN:
NN:



45

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

VIAL LABEL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Remicade 100 mg powder for concentrate
infliximab
IV

2. METHOD OF ADMINISTRATION

For intravenous use after reconstitution and dilution.

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Batch

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

100 mg

6. OTHER



46

Remicade
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 Remicade.

Show this card to any doctor involved in your 
treatment.

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

Date of Remicade 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 Remicade
 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 Remicade
 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, diarrhea, 
wounds, dental problems, burning when 
urinating or ‘flu-like’ signs.

Pregnancy and Vaccinations

 In case you have received Remicade 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 Remicade, 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.



47

B. PACKAGE LEAFLET



48

Package leaflet: Information for the user

Remicade 100 mg powder for concentrate for solution for infusion
infliximab

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 Remicade.
 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 Remicade is and what it is used for
2. What you need to know before you use Remicade
3. How Remicade will be given
4. Possible side effects
5. How to store Remicade
6. Contents of the pack and other information

1. What Remicade is and what it is used for

Remicade 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.

Remicade 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.

Remicade is also used in adults and children 6 years of age or older for:
 Crohn’s disease
 Ulcerative colitis.

Remicade 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 
Remicade which you will take in combination with another medicine called methotrexate to:
 Reduce the signs and symptoms of your disease
 Slow down the damage in your joints
 Improve your physical function.



49

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 Remicade 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 
Remicade 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 Remicade 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 Remicade 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 Remicade 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 Remicade

You should not be given Remicade if:
 You are allergic to infliximab or to any of the other ingredients in Remicade (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 Remicade if any of the above applies to you. If you are not sure, talk to your doctor before 
you are given Remicade.

Warnings and precautions
Talk to your doctor before or during treatment with Remicade if you have:

Had treatment with Remicade before
 Tell your doctor if you have had treatment with Remicade in the past and are now 

starting Remicade treatment again.
If you have had a break in your Remicade treatment of more than 16 weeks, there is a higher 
risk for allergic reactions when you start the treatment again.



50

Infections
 Tell your doctor before you are given Remicade if you have an infection even if it is a 

very minor one.
 Tell your doctor before you are given Remicade 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 Remicade. 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 Remicade. 
Signs include fever, cough, flu-like signs, feeling unwell, red or hot skin, wounds or dental 
problems. Your doctor may recommend temporarily stopping Remicade.

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 Remicade, 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 Remicade.

Tell your doctor straight away if you get signs of TB during treatment with Remicade. Signs 
include persistent cough, weight loss, feeling tired, fever, night sweats.

Hepatitis B virus
 Tell your doctor before you are given Remicade 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 Remicade 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 Remicade. Signs include shortness of breath or swelling of your feet.

Cancer and lymphoma
 Tell your doctor before you are given Remicade 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 Remicade may have an increased risk of developing 

lymphoma or another cancer.
 Some patients who have received TNF-blockers, including Remicade 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.



51

 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 Remicade have developed 
cervical cancer. For women taking Remicade including those over 60 years of age, your 
doctor may recommend regular screening for cervical cancer.

Lung disease or heavy smoking
 Tell your doctor before you are given Remicade 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 Remicade 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 Remicade. This includes multiple sclerosis, Guillain-Barre 
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 
Remicade. 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 

Remicade.

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

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

 If you received Remicade 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 Remicade 
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 Remicade by showing 

them your patient reminder card.

Liver problems
 Some patients receiving Remicade have developed serious liver problems.
Tell your doctor straight away if you get symptoms of liver problems during treatment with 
Remicade. 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.



52

Low blood counts
 In some patients receiving Remicade, 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 
Remicade. Signs include persistent fever, bleeding or bruising more easily, small red or purple spots 
caused by bleeding under the skin, or looking pale.

Immune system disorder
 Some patients receiving Remicade have developed symptoms of an immune system 

disorder called lupus.
Tell your doctor straight away if you develop symptoms of lupus during treatment with 
Remicade. 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 Remicade 

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

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

If you are not sure if any of the above apply to you, talk to your doctor before you are given 
Remicade.

Other medicines and Remicade
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 Remicade.

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). Remicade and Kineret should not be used together.
 Orencia (abatacept). Remicade and Orencia should not be used together.

While using Remicade you should not receive live vaccines. If you were using Remicade during 
pregnancy, tell your baby’s doctor and other healthcare professionals caring for your baby about your 
Remicade 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 
Remicade.

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. Remicade 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 Remicade and for 6 months 
after you stop being treated with it. Discuss the use of contraception during this time with your 
doctor.



53

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

 If you received Remicade 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 healthcare professionals about your 
Remicade use before your baby is given any vaccine. If you received Remicade 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.

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

Driving and using machines
Remicade is not likely to affect your ability to drive or use tools or machines. If you feel tired, dizzy,
or unwell after having Remicade, do not drive or use any tools or machines.

Remicade contains sodium
Remicade contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’. 
However, before Remicade 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 Remicade will be given

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 Remicade is given
 Remicade 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 2 hours) into one of your veins, usually 

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

 You will be monitored while you are given Remicade and also for 1 to 2 hours afterwards.

How much Remicade is given
 The doctor will decide your dose and how often you will be given Remicade. This will depend 

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

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

Use in children and adolescents
Remicade 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.



54

If you are given too much Remicade
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 Remicade.

If you forget or miss your Remicade infusion
If you forget or miss an appointment to receive Remicade, make another appointment as soon as 
possible.

If you have any further questions on the use of this medicine, ask your doctor.

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 Remicade 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, lightheadedness, dizziness, fainting, sweating, nausea (feeling sick), 
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 signs of a stroke 

(sudden numbness or weakness of your face, arm or leg, especially on one side of your body; 
sudden confusion, trouble speaking or understanding; trouble seeing in one or both eyes, 
trouble walking, dizziness, loss of balance or coordination or a severe headache), fits, 
tingling/numbness in any part of your body, or 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.



55

The following side effects have been observed with Remicade:

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
 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)



56

 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
 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
 Stroke
 Temporary loss of sight during or within 2 hours of infusion



57

 Infection due to a live vaccine because of a weakened immune system.

Additional side effects in children and adolescents
Children who took Remicade for Crohn’s disease showed some differences in side effects compared 
with adults who took Remicade 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
(leucopenia), 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 Remicade

Remicade 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.
 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 25 °C for a single period of up to six months, but not beyond the original expiry 
date. In this situation, do not return to 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 Remicade 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 to 8 °C up to 28 days and for an additional 24 hours at 25 °C after 
removal from the refrigerator.

 Do not use this medicine if it is discoloured or if there are particles present.

6. Contents of the pack and other information

What Remicade 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 sucrose, polysorbate 80, monobasic sodium phosphate and dibasic 

sodium phosphate.

What Remicade looks like and contents of the pack
Remicade is supplied as a glass vial containing a powder for concentrate for solution for infusion. The 
powder is a freeze-dried white pellet.
Remicade is produced in packs of 1, 2, 3, 4 or 5 vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Janssen Biologics B.V.
Einsteinweg 101
2333 CB Leiden
The Netherlands

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


58

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

België/Belgique/Belgien
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Lietuva
UAB Merck Sharp & Dohme
Tel. + 370 5 278 02 47
msd_lietuva@merck.com

България
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
info-msdbg@merck.com

Luxembourg/Luxemburg
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Česká republika
Merck Sharp & Dohme s.r.o.
Tel: +420 233 010 111
dpoc_czechslovak@merck.com

Magyarország
MSD Pharma Hungary Kft.
Tel.: +36 1 888 5300
hungary_msd@merck.com

Danmark
MSD Danmark ApS
Tlf: + 45 4482 4000
dkmail@merck.com

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
malta_info@merck.com

Deutschland
MSD SHARP & DOHME GMBH
Tel: 0800 673 673 673 (+49 (0) 89 4561 2612)
e-mail@msd.de

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000
(+31 23 5153153)
medicalinfo.nl@merck.com

Eesti
Merck Sharp & Dohme OÜ
Tel.: +372 6144 200
msdeesti@merck.com

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
msdnorge@msd.no

Ελλάδα
MSD Α.Φ.Β.Ε.Ε.
Τηλ: +30 210 98 97 300
dpoc_greece@merck.com

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
msd-medizin@merck.com

España
Merck Sharp & Dohme de España, S.A.
Tel: +34 91 321 06 00
msd_info@merck.com

Polska
MSD Polska Sp. z o.o.
Tel: +48 22 549 51 00
msdpolska@merck.com

France
MSD France
Tél: + 33 (0) 1 80 46 40 40

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
inform_pt@merck.com

Hrvatska
Merck Sharp & Dohme d.o.o.
Tel: + 385 1 6611 333
croatia_info@merck.com

România
Merck Sharp & Dohme Romania S.R.L.
Tel: +40 21 529 29 00
msdromania@merck.com



59

Ireland
Merck Sharp & Dohme Ireland (Human Health) 
Limited
Tel: +353 (0)1 2998700
medinfo_ireland@merck.com

Slovenija
Merck Sharp & Dohme, inovativna zdravila
d.o.o.
Tel: +386 1 5204 201
msd.slovenia@merck.com

Ísland
Vistor hf.
Sími: + 354 535 7000

Slovenská republika
Merck Sharp & Dohme, s. r. o.
Tel: +421 2 58282010
dpoc_czechslovak@merck.com

Italia
MSD Italia S.r.l.
Tel: +39 06 361911
medicalinformation.it@merck.com

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0)9 804 650
info@msd.fi

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ.: 800 00 673 (+357 22866700)
cyprus_info@merck.com

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 77 5700488
medicinskinfo@merck.com

Latvija
SIA Merck Sharp & Dohme Latvija
Tel: + 371 67364224
msd_lv@merck.com

United Kingdom
Merck Sharp & Dohme Limited
Tel: +44 (0) 1992 467272
medicalinformationuk@merck.com

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.

http://www.ema.europa.eu/


60

The following information is intended for healthcare professionals only:

Patients treated with Remicade should be given the patient reminder card.

Instructions for use and handling – storage conditions

Store at 2 °C - 8 °C.

Remicade may be stored at temperatures up to a maximum of 25 °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, Remicade 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 Remicade vials needed. Each Remicade vial contains 
100 mg infliximab. Calculate the total volume of reconstituted Remicade solution required.

2. Under aseptic conditions, reconstitute each Remicade 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 yellow 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 Remicade solution dose to 250 ml with sodium 
chloride 9 mg/ml (0.9%) solution for infusion. Do not dilute the reconstituted Remicade 
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 Remicade. Slowly add the total volume of 
reconstituted Remicade solution to the 250-ml infusion bottle or bag. Gently mix. For volumes 
greater than 250 ml, either use a larger infusion bag (e.g. 500 ml, 1000 ml) or use multiple 
250 ml infusion bags to ensure that the concentration of the infusion solution does not exceed 
4 mg/ml. If stored refrigerated after reconstitution and dilution, the infusion solution must be 
allowed to equilibrate at room temperature to 25 °C for 3 hours prior to Step 4 (infusion). 
Storage beyond 24 hours at 2 °C - 8 °C applies to preparation of Remicade in the infusion bag 
only.

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. If not used immediately, in use storage times and conditions prior 
to use are the responsibility of the user and would normally not be longer than 24 hours at 
2 °C - 8 °C, unless reconstitution/dilution has been taken place in controlled and validated 
aseptic conditions. Do not store any unused portion of the infusion solution for reuse.



61

5. No physical biochemical compatibility studies have been conducted to evaluate the 
co-administration of Remicade with other agents. Do not infuse Remicade concomitantly in the 
same intravenous line with other agents.

6. Visually inspect Remicade for particulate matter or discolouration prior to administration. Do 
not use if visibly opaque particles, discolouration or foreign particles are observed.

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