METHOTREXATE

What it is

Methotrexate Accord is a sterile yellow to orange solution for injection. The product is available in two strengths: 1 mL contains 25 mg methotrexate (1 vial of 2 mL solution for injection contains 50 mg methotrexate) or 1 mL contains 100 mg methotrexate (1 vial of 10 mL solution for injection contains 1000 mg methotrexate). Methotrexate must only be used by physicians experienced in anti-metabolite chemotherapy, or in the case of non-oncological conditions, by a specialist physician.

Approved indications

— Breast cancer, gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. — Acute leukaemias, particularly acute lymphoblastic leukaemia, when used in combination with other chemotherapeutic agents for palliative treatment. — Burkitt's lymphoma at advanced stages (III and IV), lymphosarcoma especially in children, and advanced cases of mycosis fungoides. — Epidermoid cancers of the head and neck, osteogenic sarcoma and bronchogenic carcinoma when used in high-dose schedules. — Severe, recalcitrant, disabling psoriasis which is not adequately responsive to other forms of treatment.

Dosing overview

Dosing varies substantially by indication and treatment protocol. For trophoblastic neoplasms, methotrexate is administered intramuscularly in doses of 15 mg to 30 mg daily for a five-day course, with repeat courses given after one or more weeks; three to five courses of therapy are usually employed. For breast carcinoma, methotrexate dosage is 40 mg/m² intravenously on the first and eighth days. For lymphoblastic leukaemia induction, doses of 3.3 mg/m² orally in combination with prednisolone 60 mg/m² daily have been given; when remission is attained, a maintenance dosage of methotrexate 30 mg/m² intramuscularly twice weekly may be given. For psoriasis using a weekly single dose schedule, 10 to 25 mg intramuscularly or intravenously per week is recommended until adequate response is achieved, with weekly dosage not exceeding 50 mg.

Key safety warnings

Deaths have been reported with the use of methotrexate. Methotrexate may produce marked depression of the bone marrow, anaemia, aplastic anaemia, leucopenia, neutropenia, thrombocytopenia and bleeding. Methotrexate may be hepatotoxic particularly at high dosage or with prolonged therapy; liver atrophy, necrosis, cirrhosis, fatty changes and periportal fibrosis have been reported, and hepatic function must be determined prior to initiation of treatment and monitored regularly throughout therapy. Potentially fatal opportunistic infections, especially Pneumocystis jirovecii pneumonia, may occur with methotrexate therapy. Pulmonary toxicity including acute or chronic interstitial pneumonitis and pulmonary fibrosis, which can progress rapidly and is potentially fatal, has been associated with methotrexate therapy and may occur acutely at any time during therapy. Methotrexate has caused foetal death and/or congenital anomalies and is not recommended in women of child bearing potential unless there is appropriate medical evidence that the benefits can be expected to outweigh the considered risks. Diarrhoea and ulcerative stomatitis are frequent toxic effects and require interruption of therapy, otherwise haemorrhagic enteritis and death from intestinal perforation may occur. Mistaken daily use instead of weekly use may cause serious and sometimes life-threatening or fatal toxicity.

Contraindications

Methotrexate is contraindicated in patients with severe renal impairment. In the treatment of psoriasis, methotrexate is contraindicated in pregnant women and in patients with poor nutritional status, bone marrow depression, hepatic disorders or in those with pre-existing blood dyscrasias such as bone marrow hypoplasia, leucopenia, thrombocytopenia or anaemia. Methotrexate is contraindicated in patients with overt or laboratory evidence of immunodeficiency syndrome(s). Methotrexate is contraindicated in patients with active, infectious disease or psoriasis patients with serious infections, and in psoriasis and rheumatoid arthritis patients with peptic ulcer disease or ulcerative colitis. Methotrexate is contraindicated in patients with a known hypersensitivity to it or to any of the excipients.

Regulatory history

Methotrexate Accord 50 mg/2 mL injection vial (ARTG 213736) and Methotrexate Accord 1000 mg/10 mL injection vial (ARTG 213737) were first listed on the ARTG on 2014-10-10.