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  • Ixifi®
    / Pfizer


    Active Ingredient
    Infliximab 100 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Vial

    1,2,3,5 X 15 ml

    not in the basket chart

    Related information


    Dosage

    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.


    Indications

    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.


    Contra-Indications

    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).


    Special Precautions

    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.
    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.
    Patients taking TNF-blockers are more susceptible to serious infections.
    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. See prescribing information for full details.
    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.
    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.
    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.
    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 infliximab therapy. Patients on infliximab may receive concurrent vaccinations, except for live vaccines.
    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.
    Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g., BCG bladder instillation for the treatment of cancer) could result in clinical infections, including disseminated infections. It is recommended that therapeutic infectious agents not be given concurrently with 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.
    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.
    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.
    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   therapy should be considered in patients with confirmed significant haematologic abnormalities.
    See prescribing information for full details.


    Side Effects

    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 prescribing information for full details.


    Drug interactions

    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.
    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.
    It is recommended that therapeutic infectious agents not be given concurrently with infliximab.
    See prescribing information for full details.


    Pregnancy and Lactation

    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.
    LactationIt is unknown whether infliximab is excreted in human milk or absorbed systemically after ingestion.
    See prescribing information for full details.


    Overdose

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


    Important notes

    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.


    Manufacturer
    PFIZER Manufacturing Belgium NV, Belgium
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