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  • Metoject 50 mg/ml S.C
    / Tzamal

    Active Ingredient
    Methotrexate 50 mg/ml

    Status in Israel

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Pre-filled Syringe (solution for injection)

    1 x 7.5 mg

    not in the basket chart 41377 13742

    Pre-filled Syringe (solution for injection)

    1 x 10 mg

    not in the basket chart 41378 13743

    Pre-filled Syringe (solution for injection)

    1 x 12.5 mg

    not in the basket chart 41379 13744

    Pre-filled Syringe (solution for injection)

    1 x 15 mg

    not in the basket chart 41380 13745

    Pre-filled Syringe (solution for injection)

    1 x 17.5 mg

    not in the basket chart 41381 13746

    Pre-filled Syringe (solution for injection)

    1 x 20 mg

    not in the basket chart 41382 13747

    Pre-filled Syringe (solution for injection)

    1 x 22.5 mg

    not in the basket chart 41383 13748

    Pre-filled Syringe (solution for injection)

    1 x 25 mg

    not in the basket chart 41384 137429

    Pre-filled Syringe (solution for injection)

    1 x 27 mg

    not in the basket chart 41385 13750

    Pre-filled Syringe (solution for injection)

    1 x 30mg

    not in the basket chart 41386 13751


    Dosage in adult patients with rheumatoid arthritis: The recommended initial dose is 7.5 mg of methotrexate once weekly, administered subcutaneously. Depending on the
    individual activity of the disease and tolerability by the patient, the initial dose may be increased gradually by 2.5 mg per week. A weekly dose of 25 mg should in general not be exceeded.
    However, doses exceeding 20 mg/week are associated with significant increase in toxicity, especially bone marrow suppression. Response to treatment can be expected after approximately 4 – 8 weeks. Upon achieving the therapeutically desired result, the dose should be reduced gradually to the lowest possible effective maintenance dose.
    Dosage in children and adolescents below 16 years with polyarthritic forms of juvenile idiopathic arthritis: The recommended dose is 10-15 mg/m² body surface area (BSA)/
    once weekly administered subcutaneously. In therapy-refractory, cases the weekly dosage may be increased up to 20mg/m2 body surface area/once weekly. However, an increased monitoring
    frequency is indicated if the dose is increased.  Patients with JIA should always be referred to a rheumatologyspecialist in the treatment of children/adolescents.
    Use in children < 3 years of age is not recommended as insufficient data on efficacy and safety is available for this population.
    Dosage in patients with psoriasis vulgaris and psoriatic arthritis: It is recommended that a test dose of 5 – 10 mg should be administered subcutaneously, one week prior to therapy to
    detect idiosyncratic adverse reactions. The recommended initial dose is 7.5 mg of methotrexate once weekly, administered subcutaneously. The dose is to be increased gradually but should not, in general, exceed a weekly dose of 25 mg of methotrexate. Doses exceeding 20 mg per week can be associated with significant increase in toxicity, especially bone marrow suppression. Response to treatment can generally be expected after approximately 2 – 6 weeks. Upon achieving the therapeutically desired result, the dose should be reduced gradually to the lowest possible effective maintenance dose. The dose should be increased as necessary but should in general not exceed the maximum recommended weekly dose of 25 mg. In a few exceptional cases a higher dose might be clinically justified, but should not exceed a maximum weekly dose of 30 mg of methotrexate as toxicity will markedly increase.
    Dosage in patients with Crohn’s Disease:  Induction treatment: 25 mg/week administered subcutaneously. Response to treatment can be expected after approximately 8 to 12 weeks.
    Maintenance treatment: 15 mg/week administered subcutaneously. There is not sufficient experience in the paediatric population to recommend Metoject 50 mg/ml for the treatment of Crohn’s Disease in this population.
    Patients with renal impairment: Metoject should be used with caution in patients with impaired renal function. The dose should be adjusted as follows: Creatinine clearance (ml/min) Dose
    > 50 100% 20 – 50 50% < 20 Metoject must not be used.
    Patients with hepatic impairment: Methotrexate should be administered with great caution, if at all, to patients with significant current or previous liver disease, especially if due to alcohol. If bilirubin is > 5 mg/dl (85.5 μmol/l), methotrexate is contraindicated.
    Use in elderly patients: Dose reduction should be considered in elderly patients due to reduced liver and kidney function as well as lower folate reserves which occur with increased age.
    Use in patients with a third distribution space (pleural effusions, ascites): As the half-life of methotrexate can be prolonged to 4 times the normal length in patients who possess a third distribution space dose reduction or, in some cases, discontinuation of methotrexate administration may be required.
    Duration and method of administration: The medicinal is for single use only. Metoject solution for injection should be given subcutaneously. The overall duration of the treatment is decided by the physician.
    Note: If changing the oral application to parenteral administration a reduction of the dose may be required due to the variable bioavailability of methotrexate after oral administration. Folic acid supplementation may be considered according to current treatment guidelines.
    For full details see prescribing information.


    Rheumatoid Arthritis: Methotrexate can be used in the treatment of selected adults with severe rheumatoid arthritis, only when the diagnosis has been well established according to rheumatological standards, with inadequate response to other forms of antirheumatic therapy, including full dose NSAIDs and usually a trial of at least one or more disease-modifying antirheumatic drugs. Juvenile Idiopathic Arthritis: Treatment of Polyarthritic forms of severe, active juvenile idiopathic arthritis in patients 3 years of age and above when the response to non-steroidal anti-inflammatory drugs (NSAIDs) has been inadequate Psoriasis in adult patients: because of the high risk attending its use, Methotrexate is indicated only in the symptomatic control of severe recalcitrant, disabling psoriasis which is not adequately responsive to other forms of therapy, and only when the diagnosis has been established, as by biopsy and/or after dermatological consultation.


    Metoject is contraindicated in the case of hypersensitivity to methotrexate or to any of the excipients, liver insufficiency, alcohol abuse, severe renal insufficiency (creatinine clearance less than 20 ml/min. pre-existing blood dyscrasias, such as bone marrow, hypoplasia, leukopenia, thrombocytopenia, or significant anaemia, serious, acute or chronic infections such as tuberculosis, HIV or other immunodeficiency syndromes,ulcers of the oral cavity and known active gastrointestinal ulcer disease,pregnancy, breast-feeding,concurrent vaccination with live vaccines.

    Special Precautions

    Patients must be clearly informed that the therapy has to be applicated once a week, not every day. Patients undergoing therapy should be subject to appropriate supervision so that signs of possible toxic effects or adverse reactions may be detected and evaluated with minimal delay. Therefore methotrexate should be only administered by, or under the supervision of physicians whose knowledge and experience includes the use of antimetabolite therapy. Because of the possibility of severe or even fatal toxic reactions, the patient should be fully informed by the physician of the risks involved and the recommended safety measures. Use in children < 3 years of age is not recommended as insufficient data on efficacy and safety are available for this population. Recommended examinations and safety measures Before beginning or reinstituting methotrexate therapy after a rest period: Complete blood count with differential blood count and platelets, liver enzymes, bilirubin, serum albumin, chest x-ray and renal function tests. If clinically indicated, exclude tuberculosis and hepatitis. During therapy (at least once a month during the first six months and every three months thereafter): An increased monitoring frequency should be considered also when the dose is increased.
    1. Examination of the mouth and throat for mucosal changes.
    2. Complete blood count with differential blood count and platelets. Haemopoietic suppression caused by methotrexate may occur abruptly and with apparently safe dosages. Any profound drop in white-cell or platelet counts indicates immediate withdrawal of the medicdbinal product and appropriate supportive therapy. Patients should be advised to report all signs and symptoms suggestive of infection. Patients taking simultaneous administration of haematotoxic medicdbinal products (e.g. leflunomide) should be monitored closely with blood count and platelets.
    3. Liver function tests: Particular attention should be given to the appearance of liver toxicity. Treatment should not be instituted or should be discontinued if any abnormality of liver function tests, or liver biopsy, is present or develops during therapy. Such abnormalities should return to normal within two weeks after which treatment may be recommenced at the discretion of the physician. There is no evidence to support use of a liver biopsy to monitor hepatic toxicity in rheumatological indications. For psoriasis patients the need of a liver biopsy prior to and during therapy is controversial. Further research is needed to establish whether serial liver chemistry tests or propeptide of type III collagen can detect hepatotoxicity sufficiently. The evaluation should be performed case by case and differentiate between patients with no risk factors and patients with risk factors such as excessive prior alcohol consumption, persistent elevation of liver enzymes, history of liver disease, family history of inheritable liver disease, diabetes mellitus, obesity, and history of significant exposure to hepatotoxic drugs or chemicals and prolonged methotrexate treatment or cumulative doses of 1.5 g or more. Check of liver-related enzymes in serum: Temporary increases in transaminases to twice or three times of the upper limit of normal have been reported by patients at a frequency of 13 20%. In the case of a constant increase in liver-related enzymes, a reduction of the dose or discontinuation of therapy should be taken into consideration. Due to its potentially toxic effect on the liver, additional hepatotoxic medicdbinal products should not be taken during treatment with methotrexate unless clearly necessary and the consumption of alcohol should be avoided or greatly reduced.
    For full detail see prescribing information.

    Side Effects

    The most relevant undesirable effects are suppression of the haematopoietic system and gastrointestinal disorders. Gastrointestinal disorders: Stomatitis, dyspepsia, nausea, loss of appetite, oral ulcers, diarrhoea. Skin and subcutaneous tissue disorders: Exanthema, erythema, pruritus. Nervous system disorders: Headache, tiredness, drowsiness. Eye disorders. Hepatobiliary disorders: Elevated transaminases. Cardiac disorders: Pericarditis, pericardial effusion, pericardial tamponade. Vascular disorders Hypotension, thromboembolic events Respiratory, thoracic and mediastinal disorders: Common: Pneumonia, interstitial alveolitis/pneumonitis often associated with eosinophilia. Symptoms indicating potentially severe lung injury (interstitial pneumonitis) are: dry, not productive cough, short of breath and fever.Blood and lymphatic system disorders: Leukopenia, anaemia, thrombopenia Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, osteoporosis. Neoplasms benign, malignant and unspecified.

    Drug interactions

    Alcohol, hepatotoxic medicdbinal products, haematotoxic medicdbinal products The probability of methotrexate exhibiting a hepatotoxic effect is increased by regular alcohol consumption and when other hepatotoxic medicdbinal products are taken at the same time. Patients taking other hepatotoxic medicdbinal products concomitantly (e.g. leflunomide) should be monitored with special care. The same should be taken into account with the simultaneous administration of haematotoxic medicdbinal products (e.g. leflunomide, azathioprine, retinoids, sulfasalazine). The incidence of pancytopenia and hepatotoxicity can be increased when leflunomide is combined with methotrexate. Combined treatment with methotrexate and retinoids like acitretin or etretinate increases the risk of hepatotoxicity. Oral antibiotics Oral antibiotics like tetracyclines, chloramphenicol, and nonabsorbable broad-spectrum antibiotics can interfere with the enterohepatic circulation, by inhibition of the intestinal flora or suppression of the bacterial metabolism. Antibiotics Antibiotics, like penicillines, glycopeptides, sulfonamides, ciprofloxacin and cefalotin can, in individual cases, reduce the renal clearance of methotrexate, so that increased serum concentrations of methotrexate with simultaneous haematological and gastro-intestinal toxicity may occur. medicdbinal products with high plasma protein binding.
    For full detail see prescribing information

    medac GmbH