TREXJECT

What it is

TREXJECT is a sterile, clear, yellow-brown solution of methotrexate sodium in water for injections, practically free from visible particles. It is presented as a solution for subcutaneous injection in pre-filled syringes. The available strengths are 7.5 mg, 10 mg, 12.5 mg, 15 mg, 17.5 mg, 20 mg, 22.5 mg and 25 mg per pre-filled syringe.

Approved indications

— Symptomatic control of severe, recalcitrant, disabling psoriasis in adults which is not adequately responsive to other forms of treatment. — 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 TREXJECT is injected once weekly. Dosing differs by indication.

For rheumatoid arthritis: A weekly dose of 7.5 to 25 mg is recommended, depending on response and tolerability, with an initial dose of 7.5 mg once weekly administered subcutaneously. The initial dose may be increased gradually by 2.5 mg per week, and a weekly dose of 25 mg should not be exceeded. Response to treatment can be expected after approximately 4–8 weeks. For psoriasis: A weekly dose of 7.5 to 25 mg is recommended, depending on response and tolerability. The initial dose is 7.5 mg once weekly administered subcutaneously, and the dose should be increased gradually but not exceed a weekly dose of 25 mg. Response to treatment can generally be expected after approximately 2–6 weeks.

Key safety warnings

Methotrexate must only be prescribed by physicians experienced in anti-metabolic therapy and the treatment of severe rheumatoid arthritis or psoriasis, and patients should be fully informed of the risk of fatal or severe toxic reactions and be under constant supervision of the physician. Methotrexate may produce depression of the bone marrow, anaemia, aplastic anaemia, leukopenia, neutropenia, thrombocytopenia and bleeding. At high or prolonged doses, methotrexate may be hepatotoxic with liver atrophy, necrosis, cirrhosis, fatty changes and periportal fibrosis reported. Since changes may occur without previous signs of gastro-intestinal or haematological toxicity, 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. Diarrhoea and ulcerative stomatitis are frequent toxic effects and require interruption of therapy, otherwise haemorrhagic enteritis and death from intestinal perforation may occur. 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 and has been reported at low doses. Methotrexate has caused foetal death and/or congenital anomalies and should not be used in pregnant women or in those who might become pregnant. 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.

Contraindications

Methotrexate is contraindicated in patients with hypersensitivity to methotrexate or to any of the excipients, alcoholism or hepatic disorders including alcoholic liver disease or other chronic liver disease, severe renal impairment (creatinine clearance less than 30 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 with overt or laboratory evidence of other immunodeficiency syndromes, patients with peptic ulcer disease or ulcerative colitis and ulcers of the oral cavity, pregnancy and breast-feeding, poor nutritional status, and concurrent vaccination with live vaccines. An increased risk of hepatitis has been reported to result from combined use of methotrexate and retinoids like acitretin, and therefore the combination of methotrexate and such medicinal products is also contraindicated.

PBS listing

TREXJECT is listed on the PBS in five strengths: 7.5 mg, 10 mg, 15 mg, 20 mg and 25 mg pre-filled syringes. Each strength has streamlined restriction with an ex-manufacturer price of A$18.00.

Regulatory history

TREXJECT was first registered on the ARTG on 25 August 2015 with eight strength variants (7.5 mg, 10 mg, 12.5 mg, 15 mg, 17.5 mg, 20 mg, 22.5 mg and 25 mg). In December 2022, the PBAC recommended a change to expand the PBS listing to include utilisation of subcutaneous methotrexate for juvenile idiopathic arthritis.