TOMUDEX

What it is

TOMUDEX contains raltitrexed. TOMUDEX is a powder for injection presented as a white to cream coloured solid cake practically free from visible particles. Each vial contains 2 mg raltitrexed. Raltitrexed is a folate analogue belonging to the family of anti-metabolites and has potent inhibitory activity against thymidylate synthase. Compared to other anti-metabolites such as fluorouracil or methotrexate, raltitrexed acts as a direct and specific thymidylate synthase inhibitor.

Approved indications

— Palliative treatment of advanced colorectal cancer (distant metastases or unresectable local disease), for use as a single agent

Dosing overview

The dose of TOMUDEX is calculated on the basis of body surface area, with a recommended dose of 3 mg/m² given intravenously as a single short intravenous infusion in 50 to 250 mL of either 0.9% sodium chloride solution or 5% glucose solution. The infusion is recommended to be given over a 15 minute period. In the absence of toxicity, treatment may be repeated every 3 weeks. Dose escalation above 3 mg/m² is not recommended, since higher doses have been associated with an increased incidence of life-threatening or fatal toxicity. For patients with renal impairment, dose modifications are recommended if creatinine clearance is ≤ 65 mL/min, ranging from 75% of the standard dose given 4-weekly for creatinine clearance of 55–65 mL/min, to 50% of the standard dose given 4-weekly for creatinine clearance of 25–54 mL/min. No dosage adjustment is necessary for patients with mild to moderate hepatic impairment.

Key safety warnings

Severe diarrhoea can occur and may be associated with concurrent haematological suppression especially leukopenia. Severe diarrhoea and vomiting, if untreated, may proceed to dehydration, hypovolemia and renal impairment. Leucopenia (neutropenia in particular), anaemia and thrombocytopenia have been reported as possible adverse drug reactions. Severe leucopenia (neutropenia in particular) and thrombocytopenia can occur and may be life-threatening or fatal especially if associated with signs of gastrointestinal toxicity. Elderly patients are more vulnerable to the toxic effects of TOMUDEX. Since renal function tends to decline with age and the plasma clearance of raltitrexed is reduced with renal function impairment, there is a potential for accumulation of raltitrexed in elderly patients. It is recommended that TOMUDEX is only given by or under the supervision of a physician who is experienced in cancer chemotherapy. Patients undergoing therapy should be subject to appropriate supervision so that signs of possible toxic effects or adverse reactions (particularly diarrhoea) may be detected and treated promptly.

Contraindications

TOMUDEX is contraindicated in patients with hypersensitivity to raltitrexed or any of the excipients; in pregnant women, in women who may become pregnant during treatment or women who are breast-feeding; in patients with severe renal impairment (creatinine clearance <25 mL/minute); and with concomitant administration of calcium folinate (folinic acid), folic acid or vitamin preparations containing these agents.

PBS listing

TOMUDEX powder for intravenous infusion 2 mg in single use vial is listed on the PBS with 2 items, unrestricted restriction type, and an ex-manufacturer price of A$260.71.

Regulatory history

TOMUDEX was first listed on the Australian Register of Therapeutic Goods on 15 July 1996. Initial approval was granted on 21 June 2010. In September 2021, the PBAC recommended changes to provide unrestricted benefit listings, including unrestricted listing for use in effective ongoing combination chemotherapy where there is fluorouracil cardiotoxicity.