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Pemetrexed

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IDDRUG-PEMETREXED
TypeDrug
Aliases
AlimtaLY231514MTAПеметрексед
Statusreviewed 2026-04-27 | pending_clinical_signoff
DiseasesDIS-MESOTHELIOMA DIS-NSCLC
SourcesSRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025

Drug Facts

ClassMulti-targeted antifolate antimetabolite
MechanismPyrrolopyrimidine antifolate that, after intracellular polyglutamation by folylpolyglutamate synthetase, simultaneously inhibits multiple folate-dependent enzymes critical for thymidine and purine biosynthesis: thymidylate synthase (TS — primary target), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). The combined inhibition disrupts both thymidylate and purine de-novo synthesis, halting DNA / RNA production and producing S-phase-specific cytotoxicity. Activity is histology-restricted: highly active in non-squamous NSCLC and malignant pleural mesothelioma (MPM); minimal-to-no activity in squamous NSCLC due to higher baseline TS expression in squamous histology. Mandatory folic acid (vitamin B9) and vitamin B12 supplementation reduce hematologic and mucosal toxicity by ~50% without compromising efficacy (Niyikiza 2002, Vogelzang EMPHACIS). Backbo...
Typical dosingStandard: 500 mg/m² IV over 10 minutes every 21 days. Combinations: + cisplatin 75 mg/m² IV Day 1 (mesothelioma EMPHACIS, NSCLC AVAPERL); + carboplatin AUC 5-6 IV Day 1 (NSCLC alternative); + pembrolizumab 200 mg IV q3w (KEYNOTE-189). Maintenance after induction: 500 mg/m² q3w continuing until progression. CRITICAL pre-medication regimen to mitigate hematologic and mucosal toxicity: folic acid 350-1000 mcg PO daily starting ≥7 days before first pemetrexed dose, continuing throughout treatment and 3 weeks post; vitamin B12 1000 mcg IM ≥7 days before first dose then every 9 weeks throughout treatment; dexamethasone 4 mg PO BID Days 0, 1, 2 of each cycle (rash prophylaxis). Renal adjustment: a...
Ukraine registeredTrue
NSZU reimbursedTrue
Ukraine last verified2026-04-27

Notes

Standard backbone for non-squamous NSCLC (KEYNOTE-189: carbo + pem + pembro vs carbo + pem placebo, OS HR 0.49 in PD-L1-all- comers — practice-defining 1L for non-squamous EGFR/ALK-WT NSCLC) and for malignant pleural mesothelioma (EMPHACIS cis + pem mOS 12.1 vs 9.3 mo — historical 1L until CheckMate-743 added nivo+ipi as combo option). NOT active in squamous NSCLC — histology- specific selection is critical. Mandatory pre-medication: folic acid 350-1000 mcg PO daily (start ≥7 days pre-cycle 1), B12 1000 mcg IM (start ≥7 days pre-cycle 1, then q9 wk), dexamethasone 4 mg PO BID Days 0, 1, 2 of each cycle for rash prophylaxis. Renal function is the dominant gating factor — avoid in CrCl <45. Counsel patients to hold OTC NSAIDs / aspirin around each cycle in renal insufficiency. Monitor CBC weekly through nadir, CMP each cycle, CT chest at any new respiratory symptom (ILD suspicion). UA: generic available; НСЗУ-reimbursed for indicated uses.

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