CHEXATE

What it is

CHEXATE 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 advanced stages (III and IV, Peters Staging System) of lymphosarcoma, particularly in children and advanced cases of mycosis fungoides. — Symptomatic control of severe, recalcitrant, disabling psoriasis which is not adequately responsive to other forms of therapy, when the diagnosis has been established by biopsy and/or after dermatologic consultation. — 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

For antineoplastic chemotherapy, oral administration in tablet form is often preferred since absorption is rapid and effective serum levels are obtained. For psoriasis, the recommended starting dose is a weekly single oral dose of 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. In non-responsive patients, dosage may be increased to 15 mg per week after six weeks, and if necessary, gradually increased further to a maximum total weekly dose of 20 mg.

Key safety warnings

CHEXATE must be used only by physicians experienced in antimetabolite chemotherapy, or in the case of non-oncological conditions, by a specialist physician. Both the physician and the pharmacist should emphasise to the patient the importance of the weekly dosing regimen: mistaken daily use may cause serious and sometimes life-threatening or fatal toxicity. Diarrhoea and ulcerative stomatitis are frequent toxic effects and require interruption of therapy; otherwise, haemorrhage enteritis and death from intestinal perforation may occur. Methotrexate may produce marked depression of bone marrow, anaemia, aplastic anaemia, leukopenia, neutropenia, thrombocytopenia and bleeding. Methotrexate may be hepatotoxic, particularly at high dosage or with prolonged therapy, with liver atrophy, necrosis, cirrhosis, fatty changes and periportal fibrosis 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. 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. Pulmonary symptoms (especially a dry, non-productive cough) may require interruption of treatment and careful investigation. Potentially fatal opportunistic infections, especially *Pneumocystis jirovecii* pneumonia, may occur with methotrexate therapy.

Contraindications

CHEXATE 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, and 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

The 2.5 mg tablet is listed on the PBS as one unrestricted item with an ex-manufacturer price of A$5.42. The 10 mg tablet has two PBS items with restricted and unrestricted status, with an ex-manufacturer price of A$37.50.

Regulatory history

CHEXATE methotrexate (as sodium) 2.5 mg and 10 mg tablets were first registered on the ARTG on 14 November 2022.