Alimta
Non-squamous non-small cell lung cancer — initial treatment in combination with cisplatin (locally advanced or metastatic); maintenance treatment after 4 cycles of non-pemetrexed platinum-based chemotherapy; single agent after prior chemotherapy; Malignant pleural mesothelioma — in combination with cisplatin (unresectable or non-surgical candidates).
500 mg/m² IV over 10 minutes on Day 1 of each 21-day cycle
Supplementation required: Folic acid 400-1000 mcg PO daily starting 7 days before first dose, continued throughout and 21 days after last dose; Vitamin B12 1000 mcg IM within 1-3 weeks before first dose, then every 3 cycles
Pre-medication: Dexamethasone 4 mg PO BID day before, day of, and day after to reduce skin reactions
Renal: D/C if CrCl <45 mL/min
Injection: 100 mg, 500 mg lyophilized powder for reconstitution
CrCl <45 mL/min.
- Myelosuppression: Dose-limiting. Grade 3-4 neutropenia (15%), anemia (5%), thrombocytopenia (4%). Folic acid and B12 supplementation significantly reduce toxicity.
- Renal Toxicity: Can cause renal failure. Monitor CrCl before each dose. Avoid NSAIDs in patients with CrCl 45-79 for 2 days before, day of, and 2 days after.
- Bullous/Exfoliative Dermatitis: Fatal cases reported. Pre-medicate with corticosteroids.
- ILD/Pneumonitis: Interrupt and evaluate for new respiratory symptoms.
Nausea (31%), fatigue (25%), anorexia (22%), vomiting (16%), neutropenia (15%), stomatitis (15%), constipation (11%), rash (10%), diarrhea (13%), pharyngitis (9%)
Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.
Pemetrexed is a multi-targeted antifolate that inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT) — all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Inhibition of these enzymes leads to depletion of nucleotide precursors required for DNA and RNA synthesis, causing cell death. It is polyglutamated intracellularly by folylpolyglutamate synthetase, which increases its intracellular retention and potency.
Half-life: 3.5 hours. Protein binding: ~81%. Not significantly metabolized. Primarily excreted unchanged in urine (70-90% within 24 hours). Clearance: 91.8 mL/min. Vd: 16.1 L. Clearance correlated with CrCl.
Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.
- JMEI — Pemetrexed vs. docetaxel in 2L advanced NSCLC. Phase III, n=571.