Inflectra

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 

 

Inflectra 100 mg powder for concentrate for solution for infusion 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

One vial contains 100 mg of infliximab*. After reconstitution each mL contains 10 mg of infliximab.  

 

* Infliximab is a chimeric human-murine IgG1 monoclonal antibody produced in murine hybridoma 

cells by recombinant DNA technology. 

 

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 white. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Rheumatoid arthritis 

 

Inflectra, 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 

 

Inflectra 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 

 

Inflectra 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. Infliximab has been studied only in combination with conventional 

immunosuppressive therapy. 

 



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Ulcerative colitis 

 

Inflectra is indicated for treatment of moderately to severely active ulcerative colitis in adult patients 

who have had an inadequate response to conventional therapy including corticosteroids and 

6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical 

contraindications for such therapies. 

 

Paediatric ulcerative colitis 

 

Inflectra 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 

 

Inflectra is indicated for treatment of severe, active ankylosing spondylitis, in adult patients who have 

responded inadequately to conventional therapy. 

 

Psoriatic arthritis 

 

Inflectra is indicated for treatment of active and progressive psoriatic arthritis in adult patients when 

the response to previous DMARD therapy has been inadequate. 

 

Inflectra should be administered 

• in combination with methotrexate 

• or alone in patients who show intolerance to methotrexate or for whom methotrexate is 
contraindicated. 

 

Infliximab has been shown to improve physical function in patients with psoriatic arthritis, and to 

reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with 

polyarticular symmetrical subtypes of the disease (see section 5.1). 

 

Psoriasis 

 

Inflectra 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 psoralen ultra-violet A (PUVA) (see section 5.1). 

 

4.2 Posology and method of administration 

 

Inflectra 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. Inflectra should be administered intravenously. Inflectra infusions 

should be administered by qualified healthcare professionals trained to detect any infusion-related 

issues. Patients treated with Inflectra should be given the package leaflet and the patient reminder 

card. 

 

During Inflectra 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. 



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Inflectra must be given concomitantly with methotrexate.  

 

Available data suggest that the clinical response is usually achieved within 12 weeks of treatment. If a 

patient has an inadequate response or loses response after this period, consideration may be given to 

increase the dose step-wise by approximately 1.5 mg/kg, up to a maximum of 7.5 mg/kg every 

8 weeks. Alternatively, administration of 3 mg/kg as often as every 4 weeks may be considered. If 

adequate response is achieved, patients should be continued on the selected dose or dose frequency. 

Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic 

benefit within the first 12 weeks of treatment or after dose adjustment. 

 

Moderately to severely active Crohn’s disease 

5 mg/kg given as an intravenous infusion followed by an additional 5 mg/kg infusion 2 weeks after the 

first infusion. If a patient does not respond after 2 doses, no additional treatment with infliximab 

should be given. Available data do not support further infliximab treatment, in patients not responding 

within 6 weeks of the initial infusion. 

 

In responding patients, the alternative strategies for continued treatment are: 

• Maintenance: Additional infusion of 5 mg/kg at 6 weeks after the initial dose, followed by 
infusions every 8 weeks or 

• Re-administration: Infusion of 5 mg/kg if signs and symptoms of the disease recur (see 
‘Re-administration’ below and section 4.4). 

 

Although comparative data are lacking, limited data in patients who initially responded to 5 mg/kg but 

who lost response indicate that some patients may regain response with dose escalation (see 

section 5.1). Continued therapy should be carefully reconsidered in patients who show no evidence of 

therapeutic benefit after dose adjustment. 

 

Fistulising, active Crohn’s disease 

5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusions at 2 and 6 weeks 

after the first infusion. If a patient does not respond after 3 doses, no additional treatment with 

infliximab should be given. 

 

In responding patients, the alternative strategies for continued treatment are: 

• Maintenance: Additional infusions of 5 mg/kg every 8 weeks or 

• Re-administration: Infusion of 5 mg/kg if signs and symptoms of the disease recur followed by 
infusions of 5 mg/kg every 8 weeks (see ‘Re-administration’ below and section 4.4). 

 

Although comparative data are lacking, limited data in patients who initially responded to 5 mg/kg but 

who lost response indicate that some patients may regain response with dose escalation (see 

section 5.1). Continued therapy should be carefully reconsidered in patients who show no evidence of 

therapeutic benefit after dose adjustment. 

 

In Crohn’s disease, experience with re-administration if signs and symptoms of disease recur is limited 

and comparative data on the benefit/risk of the alternative strategies for continued treatment are 

lacking. 

 

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. 

 



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Ankylosing spondylitis 

5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 

6 weeks after the first infusion, then every 6 to 8 weeks. If a patient does not respond by 6 weeks (i.e. 

after 2 doses), no additional treatment with infliximab should be given. 

 

Psoriatic arthritis 

5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 

6 weeks after the first infusion, then every 8 weeks thereafter. 

 

Psoriasis 

5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 

6 weeks after the first infusion, then every 8 weeks thereafter. If a patient shows no response after 

14 weeks (i.e. after 4 doses), no additional treatment with infliximab should be given. 

 

Re-administration for Crohn’s disease and rheumatoid arthritis 

If the signs and symptoms of disease recur, infliximab can be re-administered within 16 weeks 

following the last infusion. In clinical studies, delayed hypersensitivity reactions have been uncommon 

and have occurred after infliximab-free intervals of less than 1 year (see sections 4.4 and 4.8). The 

safety and efficacy of re-administration after an infliximab-free interval of more than 16 weeks has not 

been established. This applies to both Crohn’s disease patients and rheumatoid arthritis patients. 

 

Re-administration for ulcerative colitis 

The safety and efficacy of re-administration, other than every 8 weeks, has not been established (see 

sections 4.4 and 4.8). 

 

Re-administration for ankylosing spondylitis 

The safety and efficacy of re-administration, other than every 6 to 8 weeks, has not been established 

(see sections 4.4 and 4.8). 

 

Re-administration for psoriatic arthritis 

The safety and efficacy of re-administration, other than every 8 weeks, has not been established (see 

sections 4.4 and 4.8). 

 

Re-administration for psoriasis 

Limited experience from re-treatment with one single infliximab dose in psoriasis after an interval of 

20 weeks suggests reduced efficacy and a higher incidence of mild to moderate infusion reactions 

when compared to the initial induction regimen (see section 5.1). 

 

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, infliximab should be 

re-initiated as a single dose followed by the maintenance dose recommendations described above. 

 

Special populations 

 

Elderly  

 

Specific studies of infliximab in elderly patients have not been conducted. No major age-related 

differences in clearance or volume of distribution were observed in clinical studies. No dose 

adjustment is required (see section 5.2). For more information about the safety of infliximab in elderly 

patients (see sections 4.4 and 4.8). 

 



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Renal and/or hepatic impairment 

 

Infliximab has not been studied in these patient populations. No dose recommendations can be made 

(see section 5.2). 

 

Paediatric population 

 

Crohn’s disease (6 to 17 years) 

5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 

6 weeks after the first infusion, then every 8 weeks thereafter. Available data do not support further 

infliximab treatment in children and adolescents not responding within the first 10 weeks of treatment 

(see section 5.1). 

 

Some patients may require a shorter dosing interval to maintain clinical benefit, while for others a 

longer dosing interval may be sufficient. Patients who have had their dose interval shortened to less 

than 8 weeks may be at greater risk for adverse reactions. Continued therapy with a shortened interval 

should be carefully considered in those patients who show no evidence of additional therapeutic 

benefit after a change in dosing interval. 

 

The safety and efficacy of infliximab have not been studied in children with Crohn’s disease below the 

age of 6 years. Currently available pharmacokinetic data are described in section 5.2 but no 

recommendation on a posology can be made in children younger than 6 years. 

 

Ulcerative colitis (6 to 17 years) 

5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 

6 weeks after the first infusion, then every 8 weeks thereafter. Available data do not support further 

infliximab treatment in paediatric patients not responding within the first 8 weeks of treatment (see 

section 5.1). 

 

The safety and efficacy of infliximab have not been studied in children with ulcerative colitis below 

the age of 6 years. Currently available pharmacokinetic data are described in section 5.2 but no 

recommendation on a posology can be made in children younger than 6 years. 

 

Psoriasis 

The safety and efficacy of infliximab in children and adolescents younger than 18 years for the 

indication of psoriasis have not been established. Currently available data are described in section 5.2 

but no recommendation on a posology can be made. 

 

Juvenile idiopathic arthritis, psoriatic arthritis and ankylosing spondylitis 

The safety and efficacy of infliximab in children and adolescents younger than 18 years for the 

indications of juvenile idiopathic arthritis, psoriatic arthritis and ankylosing spondylitis have not been 

established. Currently available data are described in section 5.2 but no recommendation on a 

posology can be made. 

 

Juvenile rheumatoid arthritis 

The safety and efficacy of infliximab in children and adolescents younger than 18 years for the 

indication of juvenile rheumatoid arthritis have not been established. Currently available data are 

described in sections 4.8 and 5.2 but no recommendation on a posology can be made. 

 

Method of administration 

 

Infliximab should be administered intravenously over a 2 hour period. All patients administered 

infliximab 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). 



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Shortened infusions across adult indications 

 

In carefully selected adult patients who have tolerated at least 3 initial 2-hour infusions of infliximab 

(induction phase) and are receiving maintenance therapy, consideration may be given to administering 

subsequent infusions over a period of not less than 1 hour. If an infusion reaction occurs in association 

with a shortened infusion, a slower infusion rate may be considered for future infusions if treatment is 

to be continued. Shortened infusions at doses >6 mg/kg have not been studied (see section 4.8). 

 

For preparation and administration instructions, see section 6.6. 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance, to other murine proteins, or to any of the excipients listed in 

section 6.1. 

 

Patients with tuberculosis or other severe infections such as sepsis, abscesses, and opportunistic 

infections (see section 4.4). 

 

Patients with moderate or severe heart failure (NYHA class III/IV) (see sections 4.4 and 4.8). 

 

4.4 Special warnings and precautions for use 

 

Traceability 

 

In order to improve the traceability of biological medicinal products, the name and the batch number 

of the administered product should be clearly recorded. 

 

Infusion reactions and hypersensitivity 

 

Infliximab has been associated with acute infusion-related reactions, including anaphylactic shock, 

and delayed hypersensitivity reactions (see section 4.8). 

 

Acute infusion reactions including anaphylactic reactions may develop during (within seconds) or 

within a few hours following infusion. If acute infusion reactions occur, the infusion must be 

interrupted immediately. Emergency equipment, such as adrenaline, antihistamines, corticosteroids 

and an artificial airway must be available. Patients may be pre-treated with e.g. an antihistamine, 

hydrocortisone and/or paracetamol to prevent mild and transient effects. 

 

Antibodies to infliximab may develop and have been associated with an increased frequency of 

infusion reactions. A low proportion of the infusion reactions was serious allergic reactions. An 

association between development of antibodies to infliximab and reduced duration of response has 

also been observed. Concomitant administration of immunomodulators has been associated with lower 

incidence of antibodies to infliximab and a reduction in the frequency of infusion reactions. The effect 

of concomitant immunomodulator therapy was more profound in episodically-treated patients than in 

patients given maintenance therapy. Patients who discontinue immunosuppressants prior to or during 

infliximab treatment are at greater risk of developing these antibodies. Antibodies to infliximab cannot 

always be detected in serum samples. If serious reactions occur, symptomatic treatment must be given 

and further infliximab infusions must not be administered (see section 4.8). 

 

In clinical studies, delayed hypersensitivity reactions have been reported. Available data suggest an 

increased risk for delayed hypersensitivity with increasing infliximab-free interval. Patients should be 

advised to seek immediate medical advice if they experience any delayed adverse reaction (see section 

4.8). If patients are re-treated after a prolonged period, they must be closely monitored for signs and 

symptoms of delayed hypersensitivity. 

 



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Infections 

 

Patients must be monitored closely for infections including tuberculosis before, during and after 

treatment with infliximab. Because the elimination of infliximab may take up to six months, 

monitoring should be continued throughout this period. Further treatment with infliximab must not be 

given if a patient develops a serious infection or sepsis. 

 

Caution should be exercised when considering the use of infliximab in patients with chronic infection 

or a history of recurrent infections, including concomitant immunosuppressive therapy. Patients 

should be advised of and avoid exposure to potential risk factors for infection as appropriate. 

 

Tumour necrosis factor alpha (TNFα) mediates inflammation and modulates cellular immune 

responses. Experimental data show that TNFα is essential for the clearing of intracellular infections. 

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

with infliximab. 

 

It should be noted that suppression of TNFα may mask symptoms of infection such as fever. Early 

recognition of atypical clinical presentations of serious infections and of typical clinical presentation 

of rare and unusual infections is critical in order to minimise delays in diagnosis and treatment.  

 

Patients taking TNF-blockers are more susceptible to serious infections. 

 

Tuberculosis, bacterial infections, including sepsis and pneumonia, invasive fungal, viral, and other 

opportunistic infections have been observed in patients treated with infliximab. Some of these 

infections have been fatal; the most frequently reported opportunistic infections with a mortality rate 

of > 5% include pneumocystosis, candidiasis, listeriosis and aspergillosis. 

 

Patients who develop a new infection while undergoing treatment with infliximab, should be 

monitored closely and undergo a complete diagnostic evaluation. Administration of infliximab should 

be discontinued if a patient develops a new serious infection or sepsis, and appropriate antimicrobial 

or antifungal therapy should be initiated until the infection is controlled. 

 

Tuberculosis 

 

There have been reports of active tuberculosis in patients receiving infliximab. It should be noted that 

in the majority of these reports tuberculosis was extrapulmonary, presenting as either local or 

disseminated disease. 

 

Before starting treatment with infliximab, 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, infliximab 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 infliximab 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 infliximab, and in accordance with local 

recommendations. 

 



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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 infliximab.  

 

Use of anti-tuberculosis therapy should also be considered before the initiation of infliximab in 

patients with a past history of latent or active tuberculosis in whom an adequate course of treatment 

cannot be confirmed. 

 

Some cases of active tuberculosis have been reported in patients treated with infliximab during and 

after treatment for latent tuberculosis. 

 

All patients should be informed to seek medical advice if signs/symptoms suggestive of tuberculosis 

(e.g. persistent cough, wasting/weight loss, low-grade fever) appear during or after infliximab 

treatment. 

 

Invasive fungal infections 

 

In patients treated with infliximab, an invasive fungal infection such as aspergillosis, candidiasis, 

pneumocystosis, histoplasmosis, coccidioidomycosis or blastomycosis should be suspected if they 

develop a serious systemic illness, and a physician with expertise in the diagnosis and treatment of 

invasive fungal infections should be consulted at an early stage when investigating these patients.  

 

Invasive fungal infections may present as disseminated rather than localised disease, and antigen and 

antibody testing may be negative in some patients with active infection. Appropriate empiric 

antifungal therapy should be considered while a diagnostic workup is being performed taking into 

account both the risk for severe fungal infection and the risks of antifungal therapy. 

 

For patients who have resided in or travelled to regions where invasive fungal infections such as 

histoplasmosis, coccidioidomycosis, or blastomycosis are endemic, the benefits and risks of infliximab 

treatment should be carefully considered before initiation of infliximab therapy. 

 

Fistulising Crohn’s disease 

 

Patients with fistulising Crohn’s disease with acute suppurative fistulas must not initiate infliximab 

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 infliximab. 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 infliximab 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, infliximab should be stopped and effective 

antiviral therapy with appropriate supportive treatment should be initiated. 

 

Hepatobiliary events 

 

Cases of jaundice and non-infectious hepatitis, some with features of autoimmune hepatitis, have been 

observed in the post-marketing experience of infliximab. Isolated cases of liver failure resulting in 

liver transplantation or death have occurred. Patients with symptoms or signs of liver dysfunction 

should be evaluated for evidence of liver injury. If jaundice and/or ALT elevations ≥ 5 times the upper 

limit of normal develop(s), infliximab should be discontinued, and a thorough investigation of the 

abnormality should be undertaken. 



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Concurrent administration of TNF-alpha inhibitor and anakinra 

 

Serious infections and neutropenia were seen in clinical studies with concurrent use of anakinra and 

another TNFα-blocking agent, etanercept, with no added clinical benefit compared to etanercept alone. 

Because of the nature of the adverse reactions seen with combination of etanercept and anakinra 

therapy, similar toxicities may also result from the combination of anakinra and other TNFα-blocking 

agents. Therefore, the combination of infliximab 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 infliximab and abatacept is not recommended. 

 

Concurrent administration with other biological therapeutics 

 

There is insufficient information regarding the concomitant use of infliximab with other biological 

therapeutics used to treat the same conditions as infliximab. The concomitant use of infliximab with 

these biologics is not recommended because of the possibility of an increased risk of infection, and 

other potential pharmacological interactions. 

 

Switching between biological DMARDs 

 

Care should be taken and patients should continue to be monitored when switching from one biologic 

to another, since overlapping biological activity may further increase the risk for adverse reactions, 

including infection. 

 

Vaccinations 

 

It is recommended that patients, if possible, be brought up to date with all vaccinations in agreement 

with current vaccination guidelines prior to initiating Inflectra 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 

infliximab [n = 46]) mounted an effective two-fold increase in titres to a polyvalent pneumococcal 

vaccine, indicating that infliximab did not interfere with T-cell independent humoral immune 

responses. However, studies from the published literature in various indications (e.g. rheumatoid 

arthritis, psoriasis, Crohn’s disease) suggest that non-live vaccinations received during treatment with 

anti-TNF therapies, including infliximab, may elicit a lower immune response than in patients not 

receiving anti-TNF therapy. 

 

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 infliximab 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 



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infections. It is recommended that therapeutic infectious agents not be given concurrently with 

infliximab. 

 

Autoimmune processes 

 

The relative deficiency of TNFα caused by anti-TNF therapy may result in the initiation of an 

autoimmune process. If a patient develops symptoms suggestive of a lupus-like syndrome following 

treatment with infliximab and is positive for antibodies against double-stranded DNA, further 

treatment with infliximab 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 infliximab therapy. Discontinuation of infliximab should be considered if these disorders develop. 

 

Malignancies and lymphoproliferative disorders 

 

In the controlled portions of clinical studies of TNF-blocking agents, more cases of malignancies 

including lymphoma have been observed among patients receiving a TNF blocker compared with 

control patients. During clinical studies of infliximab across all approved indications the incidence of 

lymphoma in infliximab-treated patients was higher than expected in the general population, but the 

occurrence of lymphoma was rare. In the post-marketing setting, cases of leukaemia have been 

reported in patients treated with a TNF-antagonist. There is an increased background risk for 

lymphoma and leukaemia in rheumatoid arthritis patients with long-standing, highly active, 

inflammatory disease, which complicates risk estimation. 

 

In an exploratory clinical study evaluating the use of infliximab in patients with moderate to severe 

chronic obstructive pulmonary disease (COPD), more malignancies were reported in 

infliximab-treated patients compared with control patients. All patients had a history of heavy 

smoking. Caution should be exercised in considering treatment of patients with increased risk for 

malignancy due to heavy smoking. 

 

With the current knowledge, a risk for the development of lymphomas or other malignancies in 

patients treated with a TNF-blocking agent cannot be excluded (see section 4.8). Caution should be 

exercised when considering TNF-blocking therapy for patients with a history of malignancy or when 

considering continuing treatment in patients who develop a malignancy. 

 

Caution should also be exercised in patients with psoriasis and a medical history of extensive 

immunosuppressant therapy or prolonged PUVA treatment. 

 

Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 

22 years of age) treated with TNF-blocking agents (initiation of therapy ≤ 18 years of age), including 

infliximab in the post-marketing setting. Approximately half the cases were lymphomas. The other 

cases represented a variety of different malignancies and included rare malignancies usually associated 

with immunosuppression. A risk for the development of malignancies in patients treated with 

TNF-blockers cannot be excluded. 

 

Post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients 

treated with TNF-blocking agents including infliximab. This rare type of T-cell lymphoma has a very 

aggressive disease course and is usually fatal. Almost all patients had received treatment with AZA or 

6-MP concomitantly with or immediately prior to a TNF-blocker. The vast majority of infliximab 

cases have occurred in patients with Crohn’s disease or ulcerative colitis and most were reported in 

adolescent or young adult males. The potential risk with the combination of AZA or 6-MP and 



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infliximab should be carefully considered. A risk for the development for hepatosplenic T-cell 

lymphoma in patients treated with infliximab cannot be excluded (see section 4.8). 

 

Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker 

therapy, including infliximab (see section 4.8). Periodic skin examination is recommended, 

particularly for patients with risk factors for skin cancer. 

 

A population-based retrospective cohort study using data from Swedish national health registries 

found an increased incidence of cervical cancer in women with rheumatoid arthritis treated with 

infliximab compared to biologics-naïve patients or the general population, including those over 

60 years of age. Periodic screening should continue in women treated with infliximab, including those 

over 60 years of age. 

 

All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma (for 

example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), or who had a 

prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular intervals 

before therapy and throughout their disease course. This evaluation should include colonoscopy and 

biopsies per local recommendations. Current data do not indicate that infliximab treatment influences 

the risk for developing dysplasia or colon cancer. 

 

Since the possibility of increased risk of cancer development in patients with newly diagnosed 

dysplasia treated with infliximab is not established, the risk and benefits of continued therapy to the 

individual patients should be carefully considered by the clinician.  

 

Heart failure 

 

Infliximab should be used with caution in patients with mild heart failure (NYHA class I/II). Patients 

should be closely monitored and infliximab must not be continued in patients who develop new or 

worsening symptoms of heart failure (see sections 4.3 and 4.8). 

 

Haematologic reactions 

 

There have been reports of pancytopenia, leukopenia, neutropenia, and thrombocytopenia in patients 

receiving TNF-blockers, including infliximab. All patients should be advised to seek immediate 

medical attention if they develop signs and symptoms suggestive of blood dyscrasias (e.g. persistent 

fever, bruising, bleeding, pallor). Discontinuation of infliximab therapy should be considered in 

patients with confirmed significant haematologic abnormalities. 

 

Others 

 

There is limited safety experience of infliximab treatment in patients who have undergone surgical 

procedures, including arthroplasty. The long half-life of infliximab should be taken into consideration 

if a surgical procedure is planned. A patient who requires surgery while on infliximab should be 

closely monitored for infections, and appropriate actions should be taken. 

 

Failure to respond to treatment for Crohn’s disease may indicate the presence of a fixed fibrotic 

stricture that may require surgical treatment. There is no evidence to suggest that infliximab worsens 

or causes fibrotic strictures. 

 

Special populations  

 

Elderly 

 

The incidence of serious infections in infliximab-treated patients 65 years and older was greater than 

in those under 65 years of age. Some of those had a fatal outcome. Particular attention regarding the 

risk for infection should be paid when treating the elderly (see section 4.8). 

 



13 

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 infliximab therapy. Paediatric patients 

on infliximab may receive concurrent vaccinations, except for live vaccines (see sections 4.5 and 4.6). 

 

Malignancies and lymphoproliferative disorders 

Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 

22 years of age) treated with TNF-blocking agents (initiation of therapy ≤ 18 years of age), including 

infliximab in the post-marketing setting. Approximately half the cases were lymphomas. The other 

cases represented a variety of different malignancies and included rare malignancies usually associated 

with immunosuppression. A risk for the development of malignancies in children and adolescents 

treated with TNF-blockers cannot be excluded. 

 

Post-marketing cases of hepatosplenic T-cell lymphoma have been reported in patients treated with 

TNF-blocking agents including infliximab. This rare type of T-cell lymphoma has a very aggressive 

disease course and is usually fatal. Almost all patients had received treatment with AZA or 6-MP 

concomitantly with or immediately prior to a TNF-blocker. The vast majority of infliximab cases have 

occurred in patients with Crohn’s disease or ulcerative colitis and most were reported in adolescent or 

young adult males. The potential risk with the combination of AZA or 6-MP and infliximab should be 

carefully considered. A risk for the development for hepatosplenic T-cell lymphoma in patients treated 

with infliximab cannot be excluded (see section 4.8). 

 

Sodium content 

 

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

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 infliximab with other biological therapeutics used to treat the same conditions as 

infliximab, including anakinra and abatacept, is not recommended (see section 4.4). 

 

It is recommended that live vaccines not be given concurrently with infliximab. 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 infliximab (see 

section 4.4). 

 



14 

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 infliximab treatment. 

 

Pregnancy 

 

The moderate number of prospectively collected pregnancies exposed to infliximab resulting in live 

birth with known outcomes, including approximately 1,100 exposed during the first trimester, does not 

indicate an increase in the rate of malformation in the newborn.  

 

Based on an observational study from Northern Europe, an increased risk (OR, 95% CI; p-value) for 

C-section (1.50, 1.14-1.96; p = 0.0032), preterm birth (1.48, 1.05-2.09; p = 0.024), small for 

gestational age (2.79, 1.54-5.04; p = 0.0007), and low birth weight (2.03, 1.41-2.94; p = 0.0002) was 

observed in women exposed during pregnancy to infliximab (with or without 

immunomodulators/corticosteroids, 270 pregnancies) as compared to women exposed to 

immunomodulators and/or corticosteroids only (6,460 pregnancies). The potential contribution of 

exposure to infliximab and/or the severity of the underlying disease in these outcomes remains 

unclear. 

 

Due to its inhibition of TNFα, infliximab administered during pregnancy could affect normal immune 

responses in the newborn. In a developmental toxicity study conducted in mice using an analogous 

antibody that selectively inhibits the functional activity of mouse TNFα, there was no indication of 

maternal toxicity, embryotoxicity or teratogenicity (see section 5.3). 

 

The available clinical experience is limited. Infliximab should only be used during pregnancy if 

clearly needed. 

 

Infliximab crosses the placenta and has been detected in the serum of infants up to 6 months following 

birth. After in utero exposure to infliximab, infants may be at increased risk of infection, including 

serious disseminated infection that can become fatal. Administration of live vaccines (e.g. BCG 

vaccine) to infants exposed to infliximab in utero is not recommended for at least 6 months 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 infliximab 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 

 

Inflectra may have a minor influence on the ability to drive and use machines. Dizziness may occur 

following administration of infliximab (see section 4.8). 

 



15 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

Upper respiratory tract infection was the most common adverse drug reaction (ADR) reported in 

clinical trials, occurring in 25.3% of infliximab-treated patients compared with 16.5% of control 

patients. The most serious ADRs associated with the use of TNF blockers that have been reported for 

infliximab include HBV reactivation, CHF (congestive heart failure), serious infections (including 

sepsis, opportunistic infections and TB), serum sickness (delayed hypersensitivity reactions), 

haematologic reactions, systemic lupus erythematosus/lupus-like syndrome, demyelinating disorders, 

hepatobiliary events, lymphoma, HSTCL, leukaemia, Merkel cell carcinoma, melanoma, paediatric 

malignancy, sarcoidosis/sarcoid-like reaction, intestinal or perianal abscess (in Crohn’s disease), and 

serious infusion reactions (see section 4.4). 

 

Tabulated list of adverse reactions 

 

Table 1 lists the 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 

Adverse reactions in clinical studies and from post-marketing experience 

Infections and infestations 

Very common: Viral infection (e.g. influenza, herpes virus infection). 

Common: Bacterial infections (e.g. sepsis, cellulitis, abscess).  

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

Rare: Meningitis, opportunistic infections (such as invasive fungal infections 

[pneumocystosis, histoplasmosis, aspergillosis, coccidioidomycosis, 

cryptococcosis, blastomycosis], bacterial infections [atypical 

mycobacterial, listeriosis, salmonellosis], and viral infections 

[cytomegalovirus]), parasitic infections, hepatitis B reactivation. 

Not known: Vaccine breakthrough infection (after in utero exposure to 

infliximab)*. 

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

Rare: Lymphoma, non-Hodgkin’s lymphoma, Hodgkin’s disease, leukaemia, 

melanoma, cervical cancer. 

Not known: Hepatosplenic T-cell lymphoma (primarily in adolescents and young 

adult males with Crohn’s disease and ulcerative colitis), Merkel cell 

carcinoma. 

Blood and lymphatic system disorders 

Common: Neutropenia, leukopenia, anaemia, lymphadenopathy. 

Uncommon: Thrombocytopenia, lymphopenia, lymphocytosis.  

Rare: Agranulocytosis (including infants exposed in utero to infliximab), 

thrombotic thrombocytopenic purpura, pancytopenia, haemolytic 

anaemia, idiopathic thrombocytopenic purpura. 

Immune system disorders 

Common: Allergic respiratory symptom. 

Uncommon: Anaphylactic reaction, lupus-like syndrome, serum sickness or serum 

sickness-like reaction. 

Rare:  Anaphylactic shock, vasculitis, sarcoid-like reaction. 

Psychiatric disorders 

Common: Depression, insomnia. 

Uncommon: Amnesia, agitation, confusion, somnolence, nervousness. 

Rare: Apathy. 



16 

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. 

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. 



17 

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. 

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 infliximab administration 

(see section 4.4).  

Cases of transient visual loss occurring during or within 2 hours of infliximab infusion have been 

reported. Events (some fatal) of myocardial ischaemia/infarction and arrhythmia have 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 infliximab 

 

A clinical study in patients with moderate to severe psoriasis was designed to assess the efficacy and 

safety of long-term maintenance therapy versus re-treatment with an induction regimen of infliximab 



18 

(maximum of four infusions at 0, 2, 6 and 14 weeks) following disease flare. Patients did not receive 

any concomitant immunosuppressant therapy. In the re-treatment arm, 4% (8/219) of patients 

experienced a serious infusion reaction versus < 1% (1/222) on maintenance therapy. The majority of 

serious infusion reactions occurred during the second infusion at week 2. The interval between the last 

maintenance dose and the first re-induction dose ranged from 35-231 days. Symptoms included, but 

were not limited to, dyspnoea, urticaria, facial oedema, and hypotension. In all cases, infliximab 

treatment was discontinued and/or other treatment instituted with complete resolution of signs and 

symptoms. 

 

Delayed hypersensitivity 

 

In clinical studies delayed hypersensitivity reactions have been uncommon and have occurred after 

infliximab-free intervals of less than 1 year. In the psoriasis studies, delayed hypersensitivity reactions 

occurred early in the treatment course. Signs and symptoms included myalgia and/or arthralgia with 

fever and/or rash, with some patients experiencing pruritus, facial, hand or lip oedema, dysphagia, 

urticaria, sore throat and headache. 

 

There are insufficient data on the incidence of delayed hypersensitivity reactions after infliximab-free 

intervals of more than 1 year but limited data from clinical studies suggest an increased risk for 

delayed hypersensitivity with increasing infliximab-free interval (see section 4.4). 

 

In a 1-year clinical study with repeated infusions in patients with Crohn’s disease (ACCENT I study), 

the incidence of serum sickness-like reactions was 2.4%. 

 

Immunogenicity 

 

Patients who developed antibodies to infliximab were more likely (approximately 2-3 fold) to develop 

infusion-related reactions. Use of concomitant immunosuppressant agents appeared to reduce the 

frequency of infusion-related reactions. 

 

In clinical studies using single and multiple infliximab doses ranging from 1 to 20 mg/kg, antibodies 

to infliximab were detected in 14% of patients with any immunosuppressant therapy, and in 24% of 

patients without immunosuppressant therapy. In rheumatoid arthritis patients who received the 

recommended repeated treatment dose regimens with methotrexate, 8% of patients developed 

antibodies to infliximab. In psoriatic arthritis patients who received 5 mg/kg with and without 

methotrexate, antibodies occurred overall in 15% of patients (antibodies occurred in 4% of patients 

receiving methotrexate and in 26% of patients not receiving methotrexate at baseline). In Crohn’s 

disease patients who received maintenance treatment, antibodies to infliximab occurred overall in 

3.3% of patients receiving immunosuppressants and in 13.3% of patients not receiving 

immunosuppressants. The antibody incidence was 2-3 fold higher for patients treated episodically. 

Due to methodological limitations, a negative assay did not exclude the presence of antibodies to 

infliximab. Some patients who developed high titres of antibodies to infliximab had evidence of 

reduced efficacy. In psoriasis patients treated with infliximab as a maintenance regimen in the absence 

of concomitant immunomodulators, approximately 28% developed antibodies to infliximab (see 

section 4.4: “Infusion reactions and hypersensitivity”). 

 

Infections 

 

Tuberculosis, bacterial infections, including sepsis and pneumonia, invasive fungal, viral, and other 

opportunistic infections have been observed in patients receiving infliximab. Some of these infections 

have been fatal; the most frequently reported opportunistic infections with a mortality rate of > 5% 

include pneumocystosis, candidiasis, listeriosis and aspergillosis (see section 4.4). 

 

In clinical studies 36% of infliximab-treated patients were treated for infections compared with 25% of 

placebo-treated patients. 

 



19 

In rheumatoid arthritis clinical studies, the incidence of serious infections including pneumonia was 

higher in infliximab plus methotrexate-treated patients compared with methotrexate alone especially at 

doses of 6 mg/kg or greater (see section 4.4). 

 

In post-marketing spontaneous reporting, infections are the most common serious adverse reaction. 

Some of the cases have resulted in a fatal outcome. Nearly 50% of reported deaths have been 

associated with infection. Cases of tuberculosis, sometimes fatal, including miliary tuberculosis and 

tuberculosis with extra-pulmonary location have been reported (see section 4.4). 

 

Malignancies and lymphoproliferative disorders 

 

In clinical studies with infliximab in which 5,780 patients were treated, representing 5,494 patient 

years, 5 cases of lymphomas and 26 non-lymphoma malignancies were detected as compared with no 

lymphomas and 1 non-lymphoma malignancy in 1,600 placebo-treated patients representing 

941 patient years. 

 

In long-term safety follow-up of clinical studies with infliximab of up to 5 years, representing 

6,234 patients-years (3,210 patients), 5 cases of lymphoma and 38 cases of non-lymphoma 

malignancies were reported. 

 

Cases of malignancies, including lymphoma, have also been reported in the post-marketing setting 

(see section 4.4). 

 

In an exploratory clinical study involving patients with moderate to severe COPD who were either 

current smokers or ex-smokers, 157 adult patients were treated with infliximab at doses similar to 

those used in rheumatoid arthritis and Crohn’s disease. Nine of these patients developed malignancies, 

including 1 lymphoma. The median duration of follow-up was 0.8 years (incidence 5.7% [95% CI 

2.65%-10.6%]. There was one reported malignancy amongst 77 control patients (median duration of 

follow-up 0.8 years; incidence 1.3% [95% CI 0.03%-7.0%]). The majority of the malignancies 

developed in the lung or head and neck. 

 

A population-based retrospective cohort study found an increased incidence of cervical cancer in 

women with rheumatoid arthritis treated with infliximab compared to biologics-naïve patients or the 

general population, including those over 60 years of age (see section 4.4). 

 

In addition, post-marketing cases of hepatosplenic T-cell lymphoma have been reported in patients 

treated with infliximab with the vast majority of cases occurring in Crohn’s disease and ulcerative 

colitis, and most of whom were adolescent or young adult males (see section 4.4). 

 

Heart failure 

 

In a Phase II study aimed at evaluating infliximab in CHF, higher incidence of mortality due to 

worsening of heart failure were seen in patients treated with infliximab, especially those treated with 

the higher dose of 10 mg/kg (i.e. twice the maximum approved dose). In this study 150 patients with 

NYHA Class III-IV CHF (left ventricular ejection fraction ≤ 35%) were treated with 3 infusions of 

infliximab 5 mg/kg, 10 mg/kg, or placebo over 6 weeks. At 38 weeks, 9 of 101 patients treated with 

infliximab (2 at 5 mg/kg and 7 at 10 mg/kg) died compared to one death among the 49 patients on 

placebo. 

 

There have been post-marketing reports of worsening heart failure, with and without identifiable 

precipitating factors, in patients taking infliximab. There have also been post-marketing reports of new 

onset heart failure, including heart failure in patients without known pre-existing cardiovascular 

disease. Some of these patients have been under 50 years of age. 

 



20 

Hepatobiliary events 

 

In clinical studies, mild or moderate elevations of ALT and AST have been observed in patients 

receiving infliximab without progression to severe hepatic injury. Elevations of ALT ≥5 x Upper 

Limit of Normal (ULN) have been observed (see Table 2). Elevations of aminotransferases were 

observed (ALT more common than AST) in a greater proportion of patients receiving infliximab than 

in controls, both when infliximab was given as monotherapy and when it was used in combination 

with other immunosuppressive agents. Most aminotransferase abnormalities were transient; however, 

a small number of patients experienced more prolonged elevations. In general, patients who developed 

ALT and AST elevations were asymptomatic, and the abnormalities decreased or resolved with either 

continuation or discontinuation of infliximab, or modification of concomitant therapy. In 

post-marketing surveillance, cases of jaundice and hepatitis, some with features of autoimmune 

hepatitis, have been reported in patients receiving infliximab (see section 4.4).  

 

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 
inflixim

ab 
placebo 

inflixim

ab 
placebo 

inflixim

ab 
placebo 

inflixim

ab 

Rheumatoid 

arthritis1 
375 1,087 58.1 58.3 3.2% 3.9% 0.8% 0.9% 

Crohn’s 

disease2 
324 1,034 53.7 54.0 2.2% 4.9% 0.0% 1.5% 

Paediatric 

Crohn’s 

disease 

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

Ulcerative 

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

Paediatric 

Ulcerative 

colitis 

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

Ankylosing 

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

Psoriatic 

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

Plaque 

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

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). 

 



21 

Paediatric population 

 

Juvenile rheumatoid arthritis patients 

 

Infliximab was studied in a clinical study in 120 patients (age range: 4-17 years old) with active 

juvenile rheumatoid arthritis despite methotrexate. Patients received 3 or 6 mg/kg infliximab as a 

3-dose induction regimen (weeks 0, 2, 6 or weeks 14, 16, 20, respectively) followed by maintenance 

therapy every 8 weeks, in combination with methotrexate. 

 

Infusion reactions 

Infusion reactions occurred in 35% of patients with juvenile rheumatoid arthritis receiving 3 mg/kg 

compared with 17.5% of patients receiving 6 mg/kg. In the 3 mg/kg infliximab group, 4 out of 

60 patients had a serious infusion reaction and 3 patients reported a possible anaphylactic reaction (2 

of which were among the serious infusion reactions). In the 6 mg/kg group, 2 out of 57 patients had a 

serious infusion reaction, one of whom had a possible anaphylactic reaction (see section 4.4). 

 

Immunogenicity 

Antibodies to infliximab developed in 38% of patients receiving 3 mg/kg compared with 12% of 

patients receiving 6 mg/kg. The antibody titres were notably higher for the 3 mg/kg compared to the 

6 mg/kg group. 

 

Infections 

Infections occurred in 68% (41/60) of children receiving 3 mg/kg over 52 weeks, 65% (37/57) of 

children receiving infliximab 6 mg/kg over 38 weeks and 47% (28/60) of children receiving placebo 

over 14 weeks (see section 4.4). 

 

Paediatric Crohn’s disease patients 

 

The following adverse reactions were reported more commonly in paediatric Crohn’s disease patients 

in the REACH study (see section 5.1) than in adult Crohn’s disease patients: anaemia (10.7%), blood 

in stool (9.7%), leukopenia (8.7%), flushing (8.7%), viral infection (7.8%), neutropenia (6.8%), 

bacterial infection (5.8%), and respiratory tract allergic reaction (5.8%). In addition, bone fracture 

(6.8%) was reported, however, a causal association has not been established. Other special 

considerations are discussed below. 

 

Infusion-related reactions 

In 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. 

 

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, 



22 

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). 

 

Other special populations 

 

Elderly 

 

In rheumatoid arthritis clinical studies, the incidence of serious infections was greater in infliximab 

plus methotrexate-treated patients 65 years and older (11.3%) than in those under 65 years of age 

(4.6%). In patients treated with methotrexate alone, the incidence of serious infections was 5.2% in 

patients 65 years and older compared to 2.7% in patients under 65 (see section 4.4). 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 

 

No case of overdose has been reported. Single doses up to 20 mg/kg have been administered without 

toxic effects. 

 



23 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: immunosuppressants, tumour necrosis factor alpha (TNFα) inhibitors, 

ATC code: L04AB02. 

 

Inflectra is a biosimilar medicinal product. Detailed information is available on the website of the 

European Medicines Agency http://www.ema.europa.eu. 

 

Mechanism of action 

 

Infliximab is a chimeric human-murine monoclonal antibody that binds with high affinity to both 

soluble and transmembrane forms of TNFα but not to lymphotoxin α (TNFβ). 

 

Pharmacodynamic effects 

 

Infliximab inhibits the functional activity of TNFα in a wide variety of in vitro bioassays. Infliximab 

prevented disease in transgenic mice that develop polyarthritis as a result of constitutive expression of 

human TNFα and when administered after disease onset, it allowed eroded joints to heal. In vivo, 

infliximab rapidly forms stable complexes with human TNFα, a process that parallels the loss of TNFα 

bioactivity.  

 

Elevated concentrations of TNFα have been found in the joints of rheumatoid arthritis patients and 

correlate with elevated disease activity. In rheumatoid arthritis, treatment with infliximab reduced 

infiltration of inflammatory cells into inflamed areas of the joint as well as expression of molecules 

mediating cellular adhesion, chemoattraction and tissue degradation. After infliximab treatment, 

patients exhibited decreased levels of serum interleukin 6 (IL-6) and C-reactive protein (CRP), and 

increased haemoglobin levels in rheumatoid arthritis patients with reduced haemoglobin levels, 

compared with baseline. Peripheral blood lymphocytes further showed no significant decrease in 

number or in proliferative responses to in vitro mitogenic stimulation when compared with untreated 

patients’ cells. In psoriasis patients, treatment with infliximab resulted in decreases in epidermal 

inflammation and normalisation of keratinocyte differentiation in psoriatic plaques. In psoriatic 

arthritis, short term treatment with infliximab reduced the number of T-cells and blood vessels in the 

synovium and psoriatic skin. 

 

Histological evaluation of colonic biopsies, obtained before and 4 weeks after administration of 

infliximab, revealed a substantial reduction in detectable TNFα. Infliximab treatment of Crohn’s 

disease patients was also associated with a substantial reduction of the commonly elevated serum 

inflammatory marker, CRP. Total peripheral white blood cell counts were minimally affected in 

infliximab-treated patients, although changes in lymphocytes, monocytes and neutrophils reflected 

shifts towards normal ranges. Peripheral blood mononuclear cells (PBMC) from infliximab-treated 

patients showed undiminished proliferative responsiveness to stimuli compared with untreated 

patients, and no substantial changes in cytokine production by stimulated PBMC were observed 

following treatment with infliximab. Analysis of lamina propria mononuclear cells obtained by biopsy 

of the intestinal mucosa showed that infliximab treatment caused a reduction in the number of cells 

capable of expressing TNFα and 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. 

 



24 

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 anti-inflammatory drugs (NSAIDs) was permitted. 

 

The primary endpoints were the reduction of signs and symptoms as assessed by the American 

College of Rheumatology criteria (ACR20 for 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 

  Infliximabb 

 Controla 
3 mg/kg 

q 8 wks 

3 mg/kg 

q 4 wks 

10 mg/kg 

q 8 wks 

10 mg/kg 

q 4 wks 

All 

infliximabb 

Patients with ACR20 

response/Patients 

evaluated (%) 

15/88 

(17%) 

36/86 

(42%) 

41/86 

(48%) 

51/87 

(59%) 

48/81 

(59%) 

176/340 

(52%) 

Total scored (van der Heijde-modified Sharp score) 

Change from baseline 

(Mean ± SDc) 

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

Median 

(Interquartile range) 

4.0 

(0.5,9.7) 

0.5 

(-1.5,3.0) 

0.1 

(-2.5,3.0) 

0.5 

(-1.5,2.0) 

-0.5 

(-3.0,1.5) 

0.0 

(-1.8,2.0) 



25 

  Infliximabb 

 Controla 
3 mg/kg 

q 8 wks 

3 mg/kg 

q 4 wks 

10 mg/kg 

q 8 wks 

10 mg/kg 

q 4 wks 

All 

infliximabb 

Patients with no 

deterioration/patients 

evaluated (%)c 

13/64 

(20%) 

34/71 

(48%) 

35/71 

(49%) 

37/77 

(48%) 

44/66 

(67%) 

150/285 

(53%) 

HAQ change from 

baseline over timee 

(patients evaluated) 

87 86 85 87 81 339 

Mean ± SDc 0.2 ± 0.3 0.4 ± 0.3 0.5 ± 0.4 0.5 ± 0.5 0.4 ± 0.4 0.4 ± 0.4 
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, multicentre, 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. 



26 

 

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 

 



27 

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) 

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%). 



28 

 

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. 

 

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. 



29 

 

Beginning at week 22, patients who initially responded to treatment and subsequently lost their 

response were eligible to cross over to active re-treatment every 8 weeks at a dose of infliximab 

5 mg/kg higher than the dose to which they were originally randomised. Among patients in the 

infliximab 5 mg/kg group who crossed over because of loss of fistula response after week 22, 

57% (12/21) responded to re-treatment with infliximab 10 mg/kg every 8 weeks. 

 

There was no significant difference between placebo and infliximab for the proportion of patients with 

sustained closure of all fistulas through week 54, for symptoms such as proctalgia, abscesses and 

urinary tract infection or for number of newly developed fistulas during treatment. 

 

Maintenance therapy with infliximab every 8 weeks significantly reduced disease-related 

hospitalisations and surgeries compared with placebo. Furthermore, a reduction in corticosteroid use 

and improvements in quality of life were observed. 

 

Adult ulcerative colitis 

 

The safety and efficacy of infliximab were assessed in two (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 

infliximab, or 10 mg/kg infliximab 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 infliximab 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). 

 



30 

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, ACT 1 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 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 multicentre, 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 



31 

102 weeks there were 49 subjects still on infliximab treatment and among those, 30 (61%) were 

BASDAI 50 responders. 

 

In both studies, physical function and quality of life as measured by the BASFI and the physical 

component score of the SF-36 were also improved significantly. 

 

Adult psoriatic arthritis 

 

Efficacy and safety were assessed in two multicentre, 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. 



32 

 

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 

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 multicentre, 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. 

 



33 

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 

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 



34 

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 multicentre, 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 for 

safety follow-up. At week 8, 45 patients were randomised and received 5 mg/kg infliximab at either 

q8 weeks or q12 weeks as a maintenance treatment regimen. 

 

The proportion of patients in clinical response at week 8 was 73.3% (44/60). Clinical response at week 

8 was similar between those with or without concomitant immunomodulator use at baseline. Clinical 

remission at week 8 was 33.3% (17/51) as measured by the Paediatric Ulcerative Colitis Activity 

Index (PUCAI) score. 

 

At week 54, the proportion of patients in clinical remission as measured by the PUCAI score was 38% 

(8/21) in the q8 week maintenance group and 18% (4/22) in the q12 week maintenance treatment 

group. For patients receiving corticosteroids at baseline, the proportion of patients in remission and not 

receiving corticosteroids at week 54 was 38.5% (5/13) for the q8 week and 0% (0/13) for the 

q12 week maintenance treatment group. 

 

In this study, there were more patients in the 12 to 17 year age group than in the 6 to 11 year age group 

(45/60 vs.15/60). While the numbers of patients in each subgroup are too small to draw definitive 

conclusions about the effect of age, there was a higher number of patients in the younger age group 

who stepped up in dose or discontinued treatment due to inadequate efficacy. 

 

Other paediatric indications 

 

The European Medicines Agency has waived the obligation to submit the results of studies with the 

reference medicinal product containing infliximab in all subsets of the paediatric population in 

rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, psoriasis 

and Crohn’s disease (see section 4.2 for information on paediatric use). 

 

5.2 Pharmacokinetic properties 

 

Single intravenous infusions of 1, 3, 5, 10 or 20 mg/kg of infliximab yielded dose proportional 

increases in the maximum serum concentration (Cmax) and area under the concentration-time curve 

(AUC). The volume of distribution at steady state (median Vd of 3.0 to 4.1 litres) was not dependent 

on the administered dose and indicated that infliximab is predominantly distributed within the vascular 

compartment. No time-dependency of the Pharmacokinetics was observed. The 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 



35 

arthritis patients. The pharmacokinetics of infliximab in elderly patients has not been studied. Studies 

have not been performed in patients with liver or renal disease. 

 

At single doses of 3, 5, or 10 mg/kg, the median Cmax values were 77, 118 and 277 micrograms/mL, 

respectively. The median terminal half-life at these doses ranged from 8 to 9.5 days. In most patients, 

infliximab could be detected in the serum for at least 8 weeks after the recommended single dose of 

5 mg/kg for Crohn’s disease and the rheumatoid arthritis maintenance dose of 3 mg/kg every 8 weeks. 

 

Repeated administration of infliximab (5 mg/kg at 0, 2 and 6 weeks in fistulising Crohn’s disease, 3 or 

10 mg/kg every 4 or 8 weeks in rheumatoid arthritis) resulted in a slight accumulation of infliximab in 

serum after the second dose. No further clinically relevant accumulation was observed. In most 

fistulising Crohn’s disease patients, infliximab was detected in serum for 12 weeks (range 4-28 weeks) 

after administration of the regimen. 

 

Paediatric population 

 

Population pharmacokinetic analysis based on data obtained from patients with ulcerative colitis 

(N=60), Crohn’s disease (N=112), juvenile rheumatoid arthritis (N=117) and Kawasaki disease 

(N=16) with an overall age range from 2 months to 17 years indicated that exposure to infliximab was 

dependent on body weight in a non-linear way. Following administration of 5 mg/kg infliximab every 

8 weeks, the predicted median steady-state infliximab exposure (area under concentration-time curve 

at steady state, AUCss) in paediatric patients aged 6 years to 17 years was approximately 20% lower 

than the predicted median steady-state medicinal product exposure in adults. The median AUCss in 

paediatric patients aged 2 years to less than 6 years was predicted to be approximately 40% lower than 

that in adults, although the number of patients supporting this estimate is limited. 

 

5.3 Preclinical safety data 

 

Infliximab does not cross react with TNFα from species other than human and 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 TNFα, there was no indication of maternal toxicity, embryotoxicity or teratogenicity. In a 

fertility and general reproductive function study, the number of pregnant mice was reduced following 

administration of the same analogous antibody. It is not known whether this finding was due to effects 

on the males and/or the females. In a 6-month repeated dose toxicity study in mice, using the same 

analogous antibody against mouse TNFα, crystalline deposits were observed on the lens capsule of 

some of the treated male mice. No specific ophthalmologic examinations have been performed in 

patients to investigate the relevance of this finding for humans. 

 

Long-term studies have not been performed to evaluate the carcinogenic potential of infliximab. 

Studies in mice deficient in TNFα demonstrated no increase in tumours when challenged with known 

tumour initiators and/or promoters. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Sucrose 

Polysorbate 80 

Sodium dihydrogen phosphate monohydrate 

Disodium phosphate dihydrate  

 

6.2 Incompatibilities 

 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 

products. 



36 

 

6.3 Shelf life 

 

Before reconstitution 

 

5 years at 2 °C – 8 °C. 

 

Inflectra 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, Inflectra 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 - 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 – 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). 

 

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 a (butyl) rubber stopper and an aluminium seal with a flip-off button. 

 

Pack sizes of 1, 2, 3, 4, 5 vials. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 

 

1. The dose and the number of Inflectra vials have to be calculated. Each Inflectra vial contains 

100 mg infliximab. The required total volume of reconstituted Inflectra solution has to be 

calculated. 

 

2. Under aseptic conditions, each Inflectra vial should be reconstituted with 10 mL of water for 

injections, using a syringe equipped with a 21-gauge (0.8 mm) or smaller needle. The flip-top 

from the vial has to be removed and the top has to be wiped with a 70% alcohol swab. The 

syringe needle should be inserted into the vial through the centre of the rubber stopper and the 

stream of water for injections directed to the glass wall of the vial. The solution has to be gently 

swirled by rotating the vial to dissolve the powder. Prolonged or vigorous agitation must be 

avoided. THE VIAL MUST NOT BE SHAKEN. Foaming of the solution on reconstitution may 

occur. The reconstituted solution should stand for 5 minutes. The solution should be colourless 

to light yellow and opalescent. The solution may develop a few fine translucent particles, as 

infliximab is a protein. The solution must not be used if opaque particles, discolouration, or 

other foreign particles are present. 

 

3. The required volume of the reconstituted Inflectra solution should be diluted to 250 mL with 

sodium chloride 9 mg/mL (0.9%) solution for infusion. Do not dilute the reconstituted Inflectra 

solution with any other diluent. The dilution can be accomplished by withdrawing a volume of 



37 

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 Inflectra. The required volume of reconstituted 

Inflectra solution should slowly be added to the 250-mL infusion bottle or bag and gently be 

mixed. 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 Inflectra in 

the infusion bag only.  

 

4. The infusion solution has to be administered over a period of not less than the infusion time 

recommended (see section 4.2). Only an infusion set with an in-line, sterile, non-pyrogenic, low 

protein-binding filter (pore size 1.2 micrometre or less) should be used. 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). Any unused 

portion of the infusion solution should not be stored for reuse. 

 

5. Inflectra should be visually inspected for particulate matter or discolouration prior to 

administration. If visibly opaque particles, discolouration or foreign particles are observed it 

should not be used. 

 

6. Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/854/001 

EU/1/13/854/002 

EU/1/13/854/003 

EU/1/13/854/004 

EU/1/13/854/005 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 10 September 2013 

Date of latest renewal: 21 June 2018 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

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



38 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE 

SUBSTANCE AND MANUFACTURER 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 

 



39 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturers of the biological active substance 

 

CELLTRION Inc. 

23 Academy-ro, 

Yeonsu-gu, Incheon, 22014 

Republic of Korea 

 

CELLTRION Inc. (Plant II, CLT2) 

20 Academy –ro 51 beon-gil,  

Yeonsu-gu, Incheon, 22014 

Republic of Korea 

 

Name and address of the manufacturer responsible for batch release 

 

Hospira Zagreb d.o.o. 

Prudnička cesta 60 

10291 Prigorje Brdovečko 

Croatia 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

• Periodic safety update reports (PSURs) 
 

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 

reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 

subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

• Risk management plan (RMP) 
 

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 

activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 

marketing authorisation and any agreed subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency;  

• Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 



40 

• 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 (HCPs) treating the patient 

about on-going treatment with the product. 

 

The patient reminder card shall contain the following key messages: 

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

• 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 Inflectra 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 



41 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

 



42 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 



43 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Inflectra 100 mg powder for concentrate for solution for infusion 

infliximab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One vial contains 100 mg of infliximab.  

After reconstitution one mL contains 10 mg of infliximab. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: sucrose, polysorbate 80, sodium dihydrogen phosphate monohydrate, disodium phosphate 

dihydrate 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for concentrate for solution for infusion. 

1 vial 

2 vials 

3 vials 

4 vials 

5 vials 

 

 

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 

 

 



44 

8. EXPIRY DATE 

 

EXP 

EXP, if not refrigerated _________________________ 

 

 

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 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/854/001 1 vial 

EU/1/13/854/002 2 vials 

EU/1/13/854/003 3 vials 

EU/1/13/854/004 4 vials 

EU/1/13/854/005 5 vials 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 



45 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC  

SN  

NN  



46 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL  

 

 

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

 

Inflectra 100 mg powder for concentrate for solution for infusion 

infliximab 

IV 

 

 

2. METHOD OF ADMINISTRATION 

 

For intravenous use after reconstitution and dilution. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

100 mg 

 

 

6. OTHER 

 

 



47 

 

Inflectra 

100 mg powder for concentrate for solution 

for infusion 

 

infliximab 

 

Patient Reminder Card 

 

Show this card to any doctor involved in your 

treatment. 

 

This patient reminder card contains important 

safety information that you need to be aware of 

before and during treatment with Inflectra. 

 

Name patient: 

Name doctor: 

Telephone number doctor: 

 

When starting a new card, please keep this card 

as a reference for 4 months after your last dose of 

Inflectra. 

 

Please read the Inflectra ‘Package Leaflet’ 

carefully before you start using this medicine. 

 

Date of Inflectra therapy initiation: 

 

 

 

Current administrations: 

 

It is important that you and your doctor record 

the brand name and batch number of your 

medicine. 

 

Brand name: 

Batch number: 

 

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 Inflectra 

• 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 tuberculosis 

(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 Inflectra 

• Tell your doctor straight away if you have 
signs of an infection. Signs include a fever, 

feeling tired, (persistent) cough, shortness 

of breath, weight loss, night sweats, 

diarrhoea, wounds, dental problems, 

burning when urinating or ‘flu-like’ signs. 

 

Pregnancy and Vaccinations 

 

• In case you have received Inflectra 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 

last dose of Inflectra, 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. 

 

 

 



48 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



49 

Package leaflet: Information for the user 

 

Inflectra 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 Inflectra. 

• When starting a new card, keep this card as a reference for 4 months after your last dose of 
Inflectra. 

• 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 Inflectra is and what it is used for 

2. What you need to know before you use Inflectra 

3. How Inflectra will be given 

4. Possible side effects 

5. How to store Inflectra 

6. Contents of the pack and other information 

 

 

1. What Inflectra is and what it is used for 

 

Inflectra contains the active substance infliximab, which is of human and mouse origin. Infliximab is a 

monoclonal antibody - a type of protein that attaches to a specific target in the body called TNF 

(tumour necrosis factor) alpha. 

 

Inflectra 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. 
 

Inflectra is also used in adults and children 6 years of age or older for: 

• Crohn’s disease 

• Ulcerative colitis. 
 

Inflectra works by selectively attaching to TNF alpha (tumour necrosis factor 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 

Inflectra which you will take 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. 



50 

 

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 Inflectra 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 

Inflectra 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 Inflectra 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 Inflectra 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 Inflectra 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 Inflectra 

 

You must not be given Inflectra if: 

• you are allergic to infliximab or any of the other ingredients of this medicine (listed in section 6), 

• you are allergic to proteins that come from mice, 

• you have tuberculosis (TB) or another serious infection such as pneumonia or sepsis(serious 
bacterial infection of the blood), 

• you have heart failure that is moderate or severe. 
 

Do not use Inflectra if any of the above applies to you. If you are not sure, talk to your doctor before 

you are given Inflectra. 

 

Warnings and precautions  

Talk to your doctor before or during treatment with Inflectra if you have: 

 

Had treatment with any medicine containing infliximab before 

 

• Tell your doctor if you have had treatment with medicines containing infliximab in the past and 
are now starting Inflectra treatment again. 

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



51 

 

Infections 

 

• Tell your doctor before you are given Inflectra if you have an infection, even if it is a very 
minor one. 

• Tell your doctor before you are given Inflectra 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 Inflectra. If you are 
65 years of age 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 Inflectra. Signs 
include fever, cough, flu-like signs, feeling unwell, red or hot skin, wounds or dental problems. 

Your doctor may recommend temporarily stopping Inflectra. 

 

Tuberculosis (TB) 

 

• It is very important that you tell your doctor if you have ever had TB or if you have been in 
close contact with someone who has had or has TB. 

• Your doctor will test you to see if you have TB. Cases of TB have been reported in patients 
treated with infliximab, even in patients who have already been treated with medicines for TB. 

Your doctor will record these tests on your patient reminder card. 

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

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

 

Hepatitis B virus 

 

• Tell your doctor before you are given Inflectra 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 Inflectra may result in reactivation of hepatitis B virus in 
patients who carry this virus, which can be life-threatening in some cases. 

• If you experience reactivation of hepatitis B, your doctor may need to stop your treatment and 
may give you medicines such as effective antiviral therapy with supportive treatment. 

 

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 Inflectra. Signs include shortness of breath or swelling of your feet. 

 

Cancer and lymphoma 

 

• Tell your doctor before you are given Inflectra 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 Inflectra may have an increased risk of developing lymphoma or 
another cancer. 



52 

• Some patients who have received TNF-blockers, including infliximab have developed a rare 
type of cancer called hepatosplenic T-cell lymphoma. Of these patients, most were teenage boys 

or young men and most had either Crohn’s disease or ulcerative colitis. This type of cancer has 

usually resulted in death. Almost all patients had also received medicines containing 

azathioprine or mercaptopurine in addition to TNF-blockers. 

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

• Some women being treated for rheumatoid arthritis with infliximab have developed cervical 
cancer. For women taking Inflectra 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 Inflectra 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 Inflectra treatment. 

 

Nervous system disease 

 

• Tell your doctor before you are given Inflectra if you have or have ever had a problem that 
affects your nervous system. This includes multiple sclerosis, Guillain-Barré syndrome, if you 

have fits or have been diagnosed with ‘optic neuritis’. 

• Tell your doctor straight away if you get symptoms of a nerve disease during treatment with 
Inflectra. 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 
Inflectra. 

 

Vaccinations 

 

• Talk to your doctor if you recently have had or are due to have a vaccine. 

• You should receive recommended vaccinations before starting Inflectra treatment. You may 
receive some vaccines during treatment with Inflectra but you should not receive live vaccines 

(vaccines that contain a living but weakened infectious agent) while using Inflectra because they 

may cause infections. 

• If you received Inflectra 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 Inflectra 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 your 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 Inflectra by showing them your 
patient reminder card. 

 



53 

 

Liver problems 

 

• Some patients receiving infliximab have developed serious liver problems. 

• Tell your doctor straight away if you get symptoms of liver problems during treatment with 
Inflectra. Signs include yellowing of the skin and eyes, dark-brown coloured urine, pain or 

swelling in the upper right side of the stomach area, joint pain, skin rashes, or fever. 

 

Low blood counts 

 

• In some patients receiving infliximab, the body may not make enough of the blood cells that 
help fight infections or help stop bleeding. 

• Tell your doctor straight away if you get symptoms of low blood counts during treatment with 
Inflectra. 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 infliximab have developed symptoms of an immune system disorder 
called lupus. 

• Tell your doctor straight away if you develop symptoms of lupus during treatment with 
Inflectra. Signs include joint pain or a rash on cheeks or arms that is sensitive to the sun. 

 

Children and adolescents 

The information above also applies to children and adolescents. In addition: 

 

• Some children and teenage patients who have received TNF-blockers such as infliximab have 
developed cancers, including unusual types, which sometimes resulted in death. 

• More children taking infliximab developed infections as compared to adults. 

• Children should receive recommended vaccinations before starting Inflectra treatment. Children 
may receive some vaccines during treatment with Inflectra but should not receive live vaccines 

while using Inflectra. 

 

Inflectra should only be used in children if they are being treated for Crohn’s disease or ulcerative 

colitis. These children must be 6 years of age or older. 

 

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

 

Other medicines and Inflectra 

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 Inflectra. 

 

Tell your doctor if you are using, have recently used or might use 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 (which contains anakinra). Inflectra and Kineret should not be used together. 

• Orencia (which contains abatacept). Inflectra and Orencia should not be used together. 
 

While using Inflectra you should not receive live vaccines. If you were using Inflectra during 

pregnancy, tell your baby’s doctor and other healthcare professionals caring for your baby about your 

Inflectra use before the baby receives any vaccines. 



54 

 

If you are not sure if any of the above applies to you, talk to your doctor or pharmacist before using 

Inflectra. 

 

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

doctor. 

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

• If you received Inflectra 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 
Inflectra use before your baby is given any vaccine. If you received Inflectra 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 infliximab during pregnancy. If your baby has continual fevers or infections, 

contact your baby’s doctor immediately. 

 

Driving and using machines 

Inflectra is not likely to affect your ability to drive or use tools or machines. If you feel tired, dizzy, or 

unwell after having Inflectra, do not drive or use any tools or machines. 

 

Inflectra contains sodium 

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

before Inflectra 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 Inflectra will be given 

 

How much Inflectra is given 

• The doctor will decide your dose and how often you will be given Inflectra. This will depend on 
your disease, weight and how well you respond to Inflectra. 

• 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  

 

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 Inflectra is given 

• Inflectra will be given to you by your doctor or nurse, in a hospital or clinic. 

• Your doctor or nurse will prepare the medicine for infusion. 



55 

• 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 Inflectra over 

1 hour. 

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

Use in children and adolescents 

In children (6 years of age or older) treated for Crohn’s disease or ulcerative colitis, the recommended 

dose is the same as for adults. 

 

If you are given too much Inflectra 

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 Inflectra. 

 

If you forget or miss your Inflectra infusion 

If you forget or miss an appointment to receive Inflectra, 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 Inflectra 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). 



56 

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

• Signs of serious skin problems such as reddish-target-like spots or circular patches often with 
central blisters on the trunk, large areas of peeling and shedding (exfoliating) skin, ulcers of 

mouth, throat, nose, genitals and eyes or small pus-filled bumps that can spread over the body. 

These skin reactions can be accompanied by fever. 

 

Tell your doctor straight away if you notice any of the above. 

 

The following side effects have been observed with Inflectra: 

 

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 



57 

• New or worsening heart failure, slow heart rate 

• Fainting 

• Convulsions, nerve problems 

• A hole in the bowel or blockage of the intestine, stomach pain or cramps 

• Swelling of your pancreas (pancreatitis) 

• Fungal infections such as yeast infection or fungal infection of the nails 

• Lung problems (such as oedema) 

• Fluid around the lungs (pleural effusion) 

• Narrowed airway in the lungs, causing difficulty breathing 

• Inflamed lining of the lung, causing sharp chest pains that feel worse with breathing (pleurisy) 

• Tuberculosis 

• Kidney infections 

• Low platelet count, too many white blood cells 

• Infections of the vagina  

• Blood test result showing ‘antibodies’ against your own body. 
 

Rare: may affect up to 1 in 1,000 people 

• A type of blood cancer (lymphoma) 

• Your blood not supplying enough oxygen to your body, circulation problems such as narrowing 
of a blood vessel 

• Inflammation of the lining of the brain (meningitis) 

• Infections due to a weakened immune system 

• Hepatitis B infection when you have had hepatitis B in the past  

• Inflamed liver caused by a problem with the immune system (autoimmune hepatitis)  

• Liver problem that causes yellowing of the skin or eyes (jaundice) 

• Abnormal tissue swelling or growth 

• 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, 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 

• Lichenoid reactions (itchy reddish-purple skin rash and/or threadlike white-grey lines on 
mucous membranes) 

• 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) 



58 

• 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 

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

Additional side effects in children and adolescents 

Children who took infliximab for Crohn’s disease showed some differences in side effects compared 

with adults who took infliximab for Crohn’s disease. The side effects that happened more in children 

were: low red blood cells (anaemia), blood in stool, low overall levels of white blood cells 

(leukopenia), redness or blushing (flushing), viral infections, low levels of white blood cells that fight 

infection (neutropenia), bone fracture, bacterial infection and allergic reactions of the breathing tract. 

 

Reporting of side effects 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine.  

 

 

5. How to store Inflectra 

 

Inflectra will generally be stored by the health professionals at the hospital or clinic. 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 Inflectra is prepared for infusion, it is used as soon as possible 
(within 3 hours). However, if the solution is prepared in germ-free conditions, it can be stored in 

a refrigerator at 2 °C – 8 °C 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 Inflectra 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, sodium dihydrogen phosphate monohydrate 
and disodium phosphate dihydrate. 

 

What Inflectra looks like and contents of the pack 

Inflectra is supplied as a glass vial containing a powder for concentrate for solution for infusion. The 

powder is white. 

Inflectra is produced in packs of 1, 2, 3, 4, or 5 vials. Not all pack sizes may be marketed 

 



59 

 

Marketing Authorisation Holder 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

Manufacturer 

Hospira Zagreb d.o.o. 

Prudnička cesta 60 

10291 Prigorje Brdovečko 

Croatia 

 

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

Authorisation holder: 

 

België/Belgique/Belgien 

Pfizer SA/NV 

Tél/Tel: +32 2 554 62 11 

Lietuva 

Pfizer Luxembourg SARL filialas Lietuvoje 

Tel. + 370 52 51 4000 

 

България 

Пфайзер Люксембург САРЛ, Клон 

България 

Тел.: +359 2 970 4333 

Luxembourg/Luxemburg 

Pfizer SA/NV 

Tél/Tel: +32 2 554 62 11 

 

Česká republika 

Pfizer, spol. s r.o. 

Tel: +420-283-004-111 

Magyarország 

Pfizer Kft. 

Tel.: + 36 1 488 37 00 

 

Danmark 

Pfizer ApS 

Tlf: + 45 44 20 11 00 

Malta 

Drugsales Ltd 

Tel: + 356 21 419 070/1/2 

 

Deutschland 

Pfizer Pharma PFE GmbH 

Tel: + 49 (0)800 8535555 

Nederland 

Pfizer bv 

Tel: +31 (0)10 406 43 01 

 

Eesti 

Pfizer Luxembourg SARL Eesti filiaal 

Tel: +372 666 7500 

Norge 

Pfizer AS 

Tlf: +47 67 52 61 00 

 

Ελλάδα 

Aenorasis S.A. 

Τηλ: + 30 210 6136332 

Österreich 

Pfizer Corporation Austria Ges.m.b.H. 

Tel: +43 (0)1 521 15-0 

 

España 

Pfizer, S.L. 

Tel: +34 91 490 99 00 

Polska 

Pfizer Polska Sp. z o.o. 

Tel.: +48 22 335 61 00 

 

France 

Pfizer 

Tél: + 33 (0)1 58 07 34 40 

Portugal 

Laboratórios Pfizer, Lda. 

Tel: +351 21 423 55 00 

 

Hrvatska 

Pfizer Croatia d.o.o. 

Tel: +385 1 3908 777 

România 

Pfizer România S.R.L. 

Tel: +40 (0)21 207 28 00 

 



60 

Ireland 

Pfizer Healthcare Ireland 

Tel: 1800 633 363 (toll free) 

+44 (0) 1304 616161 

Slovenija 

Pfizer Luxembourg SARL 

Pfizer, podružnica za svetovanje s področja 

farmacevtske dejavnosti, Ljubljana 

Tel.: + 386 (0)1 52 11 400 

 

Ísland 

Icepharma hf. 

Sími: +354 540 8000 

Slovenská republika 

Pfizer Luxembourg SARL, organizačná zložka 

Tel: +421–2–3355 5500 

 

Italia 

Pfizer S.r.l. 

Tel: +39 06 33 18 21 

Suomi/Finland 

Pfizer PFE Finland Oy 

Puh/Tel: +358 (0)9 430 040 

 

Κύπρος 

Pfizer ΕΛΛΑΣ Α.Ε. (Cyprus Branch) 

Τηλ: +357 22 817690 

Sverige 

Pfizer AB 

Tel: +46 (0)8 550 520 00 

 

Latvija 

Pfizer Luxembourg SARL filiāle Latvijā 

Tel.: + 371 670 35 775 

United Kingdom 

Hospira UK Limited 

Tel: + 44 (0) 1628 515500 

 

 

 

This leaflet was last revised in {MM/YYYY}. 

 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

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



61 

-------------------------------------------------------------------------------------------------------------- 

 

The following information is intended for healthcare professionals only:  

 

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

 

Instructions for use and handling - storage conditions 

  

Store at 2 °C – 8 °C. 

  

Inflectra 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, Inflectra 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. The dose and the number of Inflectra vials have to be calculated. Each Inflectra vial contains 

100 mg infliximab. The required total volume of reconstituted Inflectra solution has to be 

calculated. 

 

2. Under aseptic conditions, each Inflectra vial should be reconstituted with 10 mL of water for 

injections, using a syringe equipped with a 21-gauge (0.8 mm) or smaller needle. The flip-top 

from the vial has to be removed and the top has to be wiped with a 70% alcohol swab. The 

syringe needle should be inserted into the vial through the centre of the rubber stopper and the 

stream of water for injections directed to the glass wall of the vial. The solution has to be gently 

swirled by rotating the vial to dissolve the powder. Prolonged or vigorous agitation must be 

avoided. THE VIAL MUST NOT BE SHAKEN. Foaming of the solution on reconstitution may 

occur. The reconstituted solution should stand for 5 minutes. The solution should be colourless 

to light yellow and opalescent. The solution may develop a few fine translucent particles, as 

infliximab is a protein. The solution must not be used if opaque particles, discolouration, or 

other foreign particles are present. 

 

3. The required volume of the reconstituted Inflectra solution should be diluted to 250 mL with 

sodium chloride 9 mg/mL (0.9%) solution for infusion. Do not dilute the reconstituted Inflectra 

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 Inflectra. The required volume of reconstituted 

Inflectra solution should slowly be added to the 250-mL infusion bottle or bag and gently be 

mixed. 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 Inflectra in 

the infusion bag only. 

 

4. The infusion solution has to be administered over a period of not less than the infusion time 

recommended (see section 3). Only an infusion set with an in-line, sterile, non-pyrogenic, low 

protein-binding filter (pore size 1.2 micrometre or less) should be used. 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. Any unused portion of the infusion 

solution should not be stored for reuse. 



62 

 

5. Inflectra should be visually inspected for particulate matter or discolouration prior to 

administration. If visibly opaque particles, discolouration or foreign particles are observed it 

should not be used. 

 

6. Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 


	Summary Of Product Characteristics
	A. Manufacturers Of The Biological Active Substance And Manufacturer 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