Pemetrexed — Drug Monograph

Brand names: Alimta

Drug class: Antimetabolite

Mechanism of Action

Multi-targeted folate antagonist. Polyglutamated intracellularly to active forms that inhibit thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT) — disrupting both thymidine and purine synthesis simultaneously.

FDA Indications

• Non-squamous NSCLC — locally advanced or metastatic (first-line with cisplatin; single agent maintenance; second-line monotherapy)
• Malignant pleural mesothelioma — first-line with cisplatin

Common Side Effects

• Fatigue
• Nausea, vomiting (low-moderate risk)
• Mucositis (reduced by vitamin supplementation)
• Rash/desquamation (reduced by dexamethasone premedication)
• Myelosuppression
• Anorexia

Clinical Pearl

Pemetrexed is active only in non-squamous NSCLC (adenocarcinoma, large cell) — it has NO efficacy in squamous cell carcinoma (high TS expression). This histology-specific activity makes squamous vs. non-squamous distinction mandatory before prescribing. NSAIDs are a critical drug interaction to communicate to all providers.

Related Therapies & Mechanisms

• Gemcitabine (Gemzar) — Antimetabolite · NSCLC
• Bevacizumab (Avastin) — NSCLC
• Carboplatin (Paraplatin) — NSCLC
• Cisplatin (Platinol) — NSCLC