ALIMTA

What it is

ALIMTA is an antifolate antineoplastic agent that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase, which are key folate-dependent enzymes for the de novo biosynthesis of thymidine and purine nucleotides essential for cell replication. ALIMTA is supplied as an aqueous, clear, slightly yellow to green-yellow concentrate for solution for infusion. It is available in three vial sizes: 100 mg in 4 mL, 500 mg in 20 mL, and 1000 mg in 40 mL.

Approved indications

— Malignant pleural mesothelioma in combination with cisplatin. — Initial treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology, in combination with cisplatin. — Locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology after prior platinum-based chemotherapy, as monotherapy.

Dosing overview

When used in combination with cisplatin, the recommended dose of ALIMTA is 500 mg/m² administered as an intravenous infusion over 10 minutes on the first day of each 21-day cycle. As single agent therapy, the recommended dose is also 500 mg/m² administered as an intravenous infusion over 10 minutes on the first day of each 21-day cycle. Pre-treatment with dexamethasone (or equivalent) reduces the incidence and severity of cutaneous reaction, with dexamethasone 4 mg given orally twice daily the day before, the day of, and the day after ALIMTA administration in clinical trials. Patients must take low-dose oral folic acid daily, with at least 5 daily doses during the 7-day period preceding the first dose and continuing during therapy and for 21 days after the last dose, plus one intramuscular injection of vitamin B₁₂ during the week preceding the first dose and every 3 cycles thereafter.

Key safety warnings

ALIMTA can suppress bone marrow function as manifested by anaemia, neutropenia, thrombocytopenia, or pancytopenia, with myelosuppression being the dose-limiting toxicity; patients should be monitored for myelosuppression and ALIMTA should not be given until absolute neutrophil count returns to ≥1500 cells/mm³ and platelet count returns to ≥100,000 cells/mm³. Serious renal events, including acute renal failure, have been reported with pemetrexed alone or in association with other chemotherapeutic agents, with many patients having underlying risk factors such as dehydration or pre-existing hypertension or diabetes. Due to gastrointestinal toxicity of pemetrexed given in combination with cisplatin, severe dehydration has been observed; therefore, patients should receive adequate antiemetic treatment and appropriate hydration prior to and/or after receiving treatment. Serious cardiovascular events, including myocardial infarction and cerebrovascular events, have been uncommonly reported during clinical studies with pemetrexed, usually when given in combination with another cytotoxic agent, with most patients having pre-existing cardiovascular risk factors. Cases of radiation pneumonitis have been reported in patients treated with radiation either prior, during, or subsequent to pemetrexed therapy, and particular attention should be paid to these patients with caution exercised with use of other radiosensitising agents.

Contraindications

ALIMTA is contraindicated in patients who have a history of severe hypersensitivity reaction to pemetrexed or to any excipients in this product.

PBS listing

In March 2016, the PBAC recommended listing pemetrexed 1 g under Section 100 (Efficient Funding of Chemotherapy) for the treatment of locally advanced or metastatic non-small cell lung cancer and mesothelioma, with the same ex-manufacturer price per mg as the currently listed strengths.

Regulatory history

ALIMTA pemetrexed 500 mg powder for injection was first listed on the Australian Register of Therapeutic Goods on 30 June 2004, with the 100 mg vial strength first listed on 8 November 2007.