Ixifi

/ Pfizer

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. The drug 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.
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. 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.
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. Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit after dose adjustment.
In Crohn’s disease, experience with re-administration if signs and symptoms of disease recur is limited and comparative data on the benefit/risk of the alternative strategies for continued treatment are lacking.
Ulcerative colitis: 5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter.Available data suggest that the clinical response is usually achieved within 14 weeks of treatment, i.e. three doses. Continued
therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit within this time period.
Ankylosing spondylitis: 5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 6 to 8 weeks. If a patient does not respond by 6 weeks (i.e. after 2 doses), no additional treatment with infliximab should be given.
Psoriatic arthritis: 5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter.
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. 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.
Re-administration for ankylosing spondylitis: The safety and efficacy of re-administration, other than every 6 to 8 weeks, has not been established.
Re-administration for psoriatic arthritis: The safety and efficacy of re-administration, other than every 8 weeks, has not been established.
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.
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.
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. In this situation, Ixifi® should be re-initiated as a single dose followed by the maintenance dose recommendations described above.
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.
Renal and/or hepatic impairment: Infliximab has not been studied in these patient populations. No dose recommendations can be made.
Method of administration: Ixifi® should be administered intravenously over a 2 hour period. All patients administered Ixifi® 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.
Shortened infusions across adult indications: In carefully selected adult patients who have tolerated at least 3 initial 2-hour infusions of Ixifi® (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.

Rheumatoid arthritis: 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.
Ankylosing spondylitis: Treatment of severe, active ankylosing spondylitis, in adult patients who have responded inadequately to conventional therapy.
Psoriatic arthritis: Treatment of active and progressive psoriatic arthritis in adult patients when the response to previous DMARD therapy has been inadequate. The drug 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.
Psoriasis: Treatment of moderate to severe plaque psoriasis in adult patients who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or psoralen ultra-violet A (PUVA).
Adult Crohn’s disease: 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).
Ulcerative colitis: 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.

Hypersensitivity to the active substance, to other murine proteins.
Patients with tuberculosis or other severe infections such as sepsis, abscesses, and opportunistic infections.
Patients with moderate or severe heart failure (NYHA class III/IV).

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.
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 infusions must not be administered.
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. 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. Because the elimination of infliximab may take up to six months, monitoring should be continued throughout this period. Further treatment must not be given if a patient develops a serious infection or sepsis.
Caution should be exercised when considering the use of this drug 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 minimize 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 this drug, should be monitored closely and undergo a complete diagnostic evaluation. Administration 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 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, therapy must not be initiated.
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 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 and in accordance with local recommendations.
In patients who have several or significant risk factors for tuberculosis and have a negative test for latent tuberculosis, antituberculosis therapy should be considered before the initiation.
Use of antituberculosis therapy should also be considered before the initiation 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 treatment.
Invasive fungal infections
In patients treated with this drug, 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 localized 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 treatment should be carefully considered before initiation of this therapy.
Fistulising Crohn’s disease
Patients with fistulising Crohn’s disease with acute suppurative fistulas must not initiate therapy until a source for possible infection, specifically abscess, has been excluded.
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. 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 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, this drug 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), treatment should be discontinued, and a thorough investigation of the abnormality should be undertaken.
Concurrent administration of TNF-alpha inhibitor and anakinra
Serious infections and neutropenia were seen in clinical studies with concurrent use of anakinra and another TNFα-blocking agent, etanercept, with no added clinical benefit compared to etanercept alone. Because of the nature of the adverse reactions seen with combination of etanercept and anakinra therapy, similar toxicities may also result from the combination of anakinra and other TNFα-blocking agents. Therefore, the combination with 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 this drug and abatacept is not recommended.
Concurrent administration with other biological therapeutics
There is insufficient information regarding the concomitant use of infliximab with other biological therapeutics used to treat the same conditions as infliximab. The concomitant use of infliximab with these biologics is not recommended because of the possibility of an increased risk of infection, and other potential pharmacological interactions.
Switching between biological DMARDs
Care should be taken and patients should continue to be monitored when switching from one biologic to another, since overlapping biological activity may further increase the risk for adverse reactions, including infection.
Vaccinations
It is recommended that patients, if possible, be brought up to date with all vaccinations in agreement with current vaccination guidelines prior to initiating infliximab therapy. Patients on infliximab may receive concurrent vaccinations, except for live vaccines.
In a subset of 90 adult patients with rheumatoid arthritis from the study 2 a similar proportion of patients in each treatment group (methotrexate plus: placebo [n=17], 3mg/kg [n=27] or 6mg/kg infliximab [n=46]) mounted an effective two-fold increase in titers to a polyvalent pneumococcal vaccine, indicating that infliximab did not interfere with T-cell independent humoral immune responses. However, studies from the published literature in 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 is not recommended.
Infant exposure in utero:
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. Administration of live vaccines to infants exposed to infliximab in utero is not recommended for 6 months after birth. A twelve month waiting period following birth is recommended before the administration of BCG vaccine to infants exposed in utero to infliximab. 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.
Infant exposure via breast milk:
live vaccines can be administered to a breastfed infant when the mother is receiving infliximab as long as infant infliximab serum levels are monitored.
Therapeutic infectious agents:
Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g., BCG bladder instillation for the treatment of cancer) could result in clinical infections, including disseminated infections. It is recommended that therapeutic infectious agents not be given concurrently.
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 and is positive for antibodies against double-stranded DNA, further treatment with this drug must not be given.
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. Discontinuation 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. 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 this drug should be carefully considered. A risk for the development for hepatosplenic T-cell lymphoma in patients treated with infliximab cannot be excluded.
Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy, including infliximab. 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 this drug, 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:
This drug should be used with caution in patients with mild heart failure (NYHA class I/II). Patients should be closely monitored and treatment must not be continued in patients who develop new or worsening symptoms of heart failure.
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 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 this drug 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.
See prescribing information for full details.

Upper respiratory tract infection was the most common adverse drug reaction (ADR) reported in clinical studies, 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 prescribing information for full details.

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 this drug with other biological therapeutics used to treat the same conditions including anakinra and abatacept, is not recommended.
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 6 months following birth, except to BCG vaccine where administration is not recommended for 12 months after 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. A live vaccine can be administered to a breastfed infant while the mother is receiving infliximab as long as infant infliximab serum levels are monitored. It is recommended that therapeutic infectious agents not be given concurrently with this medicinal product.
See prescribing information for full details.

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 for C-section section, preterm birth, small for gestational age, and low birth weight 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.
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 to infants exposed to infliximab in utero is not recommended for 6 months after birth except to BCG vaccine where administration is not recommended for 12 months after 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.
Cases of agranulocytosis have also been reported.
Breast-feeding:
Limited data from published literature indicate infliximab has been detected at low levels in human milk at concentrations up to 5% of the maternal serum level. Infliximab has also been detected in infant serum after exposure to infliximab via breast milk. systemic exposure in a breastfed infant is expected to be low because infliximab is largely degraded in the gastrointestinal tract, live vaccines can be administered to a breastfed infant when the mother is receiving infliximab as long as infant infliximab serum levels are monitored. Infliximab could be considered for use during breast-feeding
Fertility:
There are insufficient preclinical data to draw conclusions on the effects of infliximab on fertility and general reproductive function.
See prescribing information for full details.

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

Storage: Unopened vial in a refrigerator (2°C – 8°C).
Compatibility: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.