Leitlinien & Arzneimittelsicherheit

HOS-083948 · has-adverse-reaction-information · PDF-Seite 14

Summary of the safety profile Upper respiratory tract infection was the most common adverse drug reaction (ADR) reported in clinical trials, occurring in 25.3% of infliximab-treated patients compared with 16.5% of control patients. The most serious ADRs associated with the use of TNF blockers that have been reported for Remicade include HBV reactivation, CHF (congestive heart failure), serious infections (including sepsis, opportunistic infections and TB), serum sickness (delayed hypersensitivity reactions), haematologic reactions, systemic lupus erythematosus/lupus-like syndrome, demyelinating disorders, hepatobiliary events, lymphoma, HSTCL, leukaemia, Merkel cell carcinoma, melanoma, paediatric malignancy, sarcoidosis/sarcoid-like reaction, intestinal or perianal abscess (in Crohn’s disease), and serious infusion reactions (see section 4.4). Tabulated list of adverse reactions Table 1 lists ADRs based on experience from clinical studies as well as adverse reactions, some with fatal outcome, reported from post-marketing experience. Within the organ system classes, adverse reactions are listed under headings of frequency using the following categories: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Table 1 Undesirable effects in clinical studies and from post-marketing experience Infections and infestations Very Common: Viral infection (e.g. influenza, herpes virus infection). Common: Bacterial infections (e.g. sepsis, cellulitis, abscess). Uncommon: Tuberculosis, fungal infections (e.g. candidiasis, onychomycosis). Rare: Meningitis, opportunistic infections (such as invasive fungal infections [pneumocystosis, histoplasmosis, aspergillosis, coccidioidomycosis, cryptococcosis, blastomycosis], bacterial infections [atypical mycobacterial, listeriosis, salmonellosis], and viral infections [cytomegalovirus]), parasitic infections, hepatitis B

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HOS-083944 · has-contraindication-information · PDF-Seite 6

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). 6

HOS-083943 · has-indication-information · PDF-Seite 2

Rheumatoid arthritis Remicade, in combination with methotrexate, is indicated for the reduction of signs and symptoms as well as the improvement in physical function in:  adult patients with active disease when the response to disease-modifying antirheumatic drugs (DMARDs), including methotrexate, has been inadequate.  adult patients with severe, active and progressive disease not previously treated with methotrexate or other DMARDs. In these patient populations, a reduction in the rate of the progression of joint damage, as measured by X-ray, has been demonstrated (see section 5.1). Adult Crohn’s disease Remicade is indicated for:  treatment of moderately to severely active Crohn’s disease, in adult patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies.  treatment of fistulising, active Crohn’s disease, in adult patients who have not responded despite a full and adequate course of therapy with conventional treatment (including antibiotics, drainage and immunosuppressive therapy). Paediatric Crohn’s disease Remicade is indicated for treatment of severe, active Crohn’s disease, in children and adolescents aged 6 to 17 years, who have not responded to conventional therapy including a corticosteroid, an immunomodulator and primary nutrition therapy; or who are intolerant to or have contraindications for such therapies. Remicade has been studied only in combination with conventional immunosuppressive therapy. Ulcerative colitis Remicade is indicated for treatment of moderately to severely active ulcerative colitis in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies. 2 Paediatric ulcerative colitis Remicade is indicated for treatment of severely active ulcerative colitis, in children and adolescents aged 6 to 17 years, who have had an inadequate response to conventional therapy including corticosteroids and 6-MP or AZA, or who are intolerant to or have medical contraindications for such therapies. Ankylosing spondylitis Remicade is indicated for treatment of severe, active ankylosing spondylitis, in adult patien

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HOS-083946 · has-interaction-information · PDF-Seite 12

No interaction studies have been performed. 12 In rheumatoid arthritis, psoriatic arthritis and Crohn's disease patients, there are indications that concomitant use of methotrexate and other immunomodulators reduces the formation of antibodies against infliximab and increases the plasma concentrations of infliximab. However, the results are uncertain due to limitations in the methods used for serum analyses of infliximab and antibodies against infliximab. Corticosteroids do not appear to affect the pharmacokinetics of infliximab to a clinically relevant extent. The combination of Remicade with other biological therapeutics used to treat the same conditions as Remicade, including anakinra and abatacept, is not recommended (see section 4.4). It is recommended that live vaccines not be given concurrently with Remicade. It is also recommended that live vaccines not be given to infants after in utero exposure to infliximab for 12 months following birth. If infant infliximab serum levels are undetectable or infliximab administration was limited to the first trimester of pregnancy, administration of a live vaccine might be considered at an earlier timepoint if there is a clear clinical benefit for the individual infant (see section 4.4). Administration of a live vaccine to a breastfed infant while the mother is receiving infliximab is not recommended unless infant infliximab serum levels are undetectable (see sections 4.4 and 4.6). It is recommended that therapeutic infectious agents not be given concurrently with Remicade (see section 4.4).

HOS-083947 · has-pregnancy-information · PDF-Seite 13

Women of childbearing potential Women of childbearing potential should consider the use of adequate contraception to prevent pregnancy and continue its use for at least 6 months after the last Remicade treatment. Pregnancy The moderate number of prospectively collected pregnancies exposed to infliximab resulting in live birth with known outcomes, including approximately 1100 exposed during the first trimester, does not indicate an increase in the rate of malformation in the newborn. Based on an observational study from Northern Europe, an increased risk (OR, 95% CI; p-value) for C-section (1.50, 1.14-1.96; p = 0.0032), preterm birth (1.48, 1.05-2.09; p = 0.024), small for gestational age (2.79, 1.54-5.04; p = 0.0007), and low birth weight (2.03, 1.41-2.94; p = 0.0002) was observed in women exposed during pregnancy to infliximab (with or without immunomodulators/corticosteroids, 270 pregnancies) as compared to women exposed to immunomodulators and/or corticosteroids only (6,460 pregnancies). The potential contribution of exposure to infliximab and/or the severity of the underlying disease in these outcomes remains unclear. Due to its inhibition of 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 12 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 12 months after 13 birth (see sections 4.4 and 4.5). If infant infliximab serum levels are undetectable or infliximab administration was limited to the first trimester of pregnancy, administration of a live vaccine might be considered at an earlier timepoint if there is a clear clinical benefit for the individual infant. Cases of agranulocytosis have also been reported (see section 4.8). Breast-feeding Limited data from published literatu

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HOS-083945 · has-warning-information · PDF-Seite 7

Traceability In order to improve the traceability of biological medicinal products, the tradename and the batch number of the administered product should be clearly recorded. Infusion reactions and hypersensitivity Infliximab has been associated with acute infusion-related reactions, including anaphylactic shock, and delayed hypersensitivity reactions (see section 4.8). Acute infusion reactions including anaphylactic reactions may develop during (within seconds) or within a few hours following infusion. If acute infusion reactions occur, the infusion must be interrupted immediately. Emergency equipment, such as adrenaline, antihistamines, corticosteroids and an artificial airway must be available. Patients may be pre-treated with e.g., an antihistamine, hydrocortisone and/or paracetamol to prevent mild and transient effects. Antibodies to infliximab may develop and have been associated with an increased frequency of infusion reactions. A low proportion of the infusion reactions was serious allergic reactions. An association between development of antibodies to infliximab and reduced duration of response has also been observed. Concomitant administration of immunomodulators has been associated with lower incidence of antibodies to infliximab and a reduction in the frequency of infusion reactions. The effect of concomitant immunomodulator therapy was more profound in episodically-treated patients than in patients given maintenance therapy. Patients who discontinue immunosuppressants prior to or during Remicade treatment are at greater risk of developing these antibodies. Antibodies to infliximab cannot always be detected in serum samples. If serious reactions occur, symptomatic treatment must be given and further Remicade infusions must not be administered (see section 4.8). In clinical studies, delayed hypersensitivity reactions have been reported. Available data suggest an increased risk for delayed hypersensitivity with increasing Remicade-free interval. Patients should be advised to seek immediate medical advice if they experience any delayed adverse reaction (see section 4.8). If patients are re-treated after a prolonged period, they must be closely monitored for signs and symptoms of delayed hypersensitivity. Infections Patients must be monitored closely for infections including tuberculosis before, during and after treatment with Remicade. Because the elimination of infliximab may take up to six months, monitoring should be continued throughout th

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