METHOBLASTIN

What it is

METHOBLASTIN is methotrexate sodium available as 2.5 mg and 10 mg tablets.

Approved indications —

Treatment of breast cancer, gestational choriocarcinoma and in patients with chorioadenoma destruens and hydatidiform mole — Palliation of acute and subacute lymphocytic leukaemia, with greatest effect observed in palliation of acute lymphoblastic (stem cell) leukaemias — Treatment of the advanced stages (III and IV, Peters Staging System) of lymphosarcoma, particularly in children and in advanced cases of mycosis fungoides — Symptomatic control of severe, recalcitrant, disabling psoriasis which is not adequately responsive to other forms of therapy, but only when the diagnosis has been established by biopsy and/or after dermatologic consultations — Management of severe, recalcitrant, active rheumatoid arthritis in adults not responding to or intolerant of an adequate trial of NSAIDs and one or more disease modifying drugs

Dosing overview

METHOBLASTIN must only be used once a week in the treatment of psoriasis and rheumatoid arthritis. Dosing varies substantially by indication and patient factors. For choriocarcinoma and similar trophoblastic diseases, the recommended dose is 15–30 mg daily for a five day course, with courses usually repeated three to five times as required with a rest period of one or more weeks between courses. For leukaemia maintenance therapy, methotrexate is administered 2 times weekly in doses of 30 mg/m². For psoriasis, weekly single oral dose schedules are 10–25 mg per week until adequate response is achieved, with a maximum dose of 50 mg per week. For rheumatoid arthritis, the starting dose is a single oral dose of 7.5 mg once weekly, which in non-responsive patients may be increased to 15 mg/week after six weeks, and if necessary gradually increased further to a maximum total weekly dose of 20 mg.

Key safety warnings

METHOBLASTIN must be used only by physicians experienced in antimetabolite chemotherapy, or in the case of non-oncological conditions, by a specialist physician. Patients should be fully informed of the risk of fatal or severe toxic reactions involved with methotrexate administration and should be under constant supervision of the physician. Mistaken daily use instead of the correct weekly dosing regimen may cause serious and sometimes life-threatening or fatal toxicity. Great care should be taken with dispensing to ensure the correct tablet strength of METHOBLASTIN is given to the patient. Diarrhoea and ulcerative stomatitis are frequent toxic effects and require interruption of therapy; otherwise, haemorrhage enteritis and death from intestinal perforation may occur. Gastrointestinal toxicity has been reported with concomitant administration of methotrexate (usually in high doses) along with nonsteroidal anti-inflammatory agents (NSAIDs). Methotrexate may produce marked depression of bone marrow, anaemia, aplastic anaemia, leukopenia, neutropenia, thrombocytopenia and bleeding. Unexpectedly severe (sometimes fatal) marrow suppression and aplastic anaemia have been reported with concomitant administration of methotrexate (usually in high doses) along with NSAIDs. Methotrexate may be hepatotoxic, particularly at high dosage or with prolonged therapy. Liver atrophy, necrosis, cirrhosis, fatty changes and periportal fibrosis have been reported. Since changes may occur without previous signs of gastrointestinal or haematological toxicity, it is imperative that hepatic function 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. Methotrexate-induced lung disease including acute or chronic interstitial pneumonitis and pleural effusion is a potentially dangerous lesion, which may occur acutely at any time during therapy and which has been reported at low doses. It is not always fully reversible and fatalities have been reported. Methotrexate has caused fetal death and/or congenital abnormalities. Therefore, it is not recommended in women of childbearing potential unless there is appropriate medical evidence that the benefits can be expected to outweigh the considered risks.

Contraindications

METHOBLASTIN should not be given to pregnant women, breast-feeding women, patients with severe hepatic impairment, patients with severe renal impairment, patients with alcoholism or alcoholic liver disease, patients who have overt or laboratory evidence of immunodeficiency syndromes, patients with bone marrow depression or pre-existing blood dyscrasias such as bone marrow hypoplasia, leukopenia, thrombocytopenia or anaemia, patients with severe, acute or chronic infections, patients with a known hypersensitivity to methotrexate or to any of the excipients, or psoriasis and rheumatoid arthritis patients with peptic ulcer disease or ulcerative colitis. During methotrexate therapy concurrent vaccinations with live vaccines must not be carried out. The combination of methotrexate with retinoids such as acitretin is contraindicated.

PBS listing

METHOBLASTIN 10 mg tablet is listed on the PBS without restriction at an ex-manufacturer price of A$7.50.

Regulatory history

METHOBLASTIN was first registered on the ARTG in 1991, with methotrexate 10 mg tablets (ARTG 15417) and 2.5 mg tablets (ARTG 15418) listed on 23 September 1991. Updated blister pack formulations were registered on 28 August 2023 (ARTG 410933 for 10 mg and ARTG 410932 for 2.5 mg). In July 2018, the PBAC recommended listing of new pre-filled syringe forms for severe active rheumatoid arthritis and severe psoriasis with authority required (streamlined) restriction. In September 2023, the PBAC recommended inclusion of nurse practitioners as eligible prescribers for rheumatological conditions using low-dose methotrexate.