Generic
Pemetrexed
8 brands available in the market
At a glance
Pemetrexed is a folate analog metabolic inhibitor used for the treatment of non-squamous non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma.
Description
Pemetrexed is a folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication. In vitro studies show that Pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase (GARFT), which are folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides.
Indications
- Non-squamous Non-Small Cell Lung Cancer (NSCLC)
- Malignant Pleural Mesothelioma
Therapeutic class
Cytotoxic Chemotherapy
Pharmacological class
Folate Analog Metabolic Inhibitor (Antifolate)
Pharmacology
Pemetrexed is a folate analog that inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). After entry into cells, it is converted to polyglutamate forms that are retained in cells and act as inhibitors of TS and GARFT.
Mechanism of action
Inhibits folate-dependent enzymes to prevent DNA and RNA synthesis, stopping cancer cell growth.
Dosage
Adult Dose (Intravenous):
- NSCLC (with Pembrolizumab and platinum): 500 mg/m² on Day 1 every 21 days for 4 cycles
- NSCLC (with Cisplatin): 500 mg/m² on Day 1 every 21 days for up to 6 cycles
- NSCLC (maintenance): 500 mg/m² on Day 1 every 21 days
- Mesothelioma (with Cisplatin): 500 mg/m² on Day 1 every 21 days
- Requires creatinine clearance ≥45 mL/min
Administration
- Administered as IV infusion over 10 minutes on Day 1
- Cytotoxic drug; follow special handling and disposal procedures
- Do not use calcium-containing solutions for reconstitution
- Store reconstituted product at 2-8°C for up to 24 hours
Missed dose
If you miss a dose, take it as soon as you remember; skip if it's almost time for next dose; do not double the dose.
Side effects
Side Effects:
- Myelosuppression (neutropenia, thrombocytopenia, anemia)
- Renal failure
- Bullous and exfoliative skin toxicity (SJS/TEN)
- Interstitial pneumonitis
- Radiation recall
Precautions & warnings
- Vitamin supplementation (folic acid and vitamin B12) must be initiated before first dose and continued for 21 days after last dose; increased myelosuppression risk without supplementation
- Withhold if creatinine clearance <45 mL/min
- Permanently discontinue for severe bullous/exfoliative skin toxicity
- Permanently discontinue if pneumonitis is confirmed
- Permanently discontinue for radiation recall
Contraindications
- History of severe hypersensitivity reaction to Pemetrexed
Drug interactions
- Ibuprofen (CrCl 45-79 mL/min): Increases Pemetrexed AUC; avoid 2 days before, day of, and 2 days after administration; if unavoidable, monitor frequently for myelosuppression, renal, and GI toxicity
Food interactions
Take with food for better absorption.
Use in pregnancy
Use in Pregnancy: Can cause fetal harm when administered to a pregnant woman; advise women of potential risk to the fetus.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: No information on presence in human milk; due to potential serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for one week after the last dose.
Pediatric use
Safety and effectiveness not established in pediatric patients.
Geriatric use
No overall differences in safety or effectiveness observed between elderly and younger patients.
Renal / hepatic impairment
Renal Impairment: Requires CrCl ≥45 mL/min; withhold if CrCl <45 mL/min; avoid ibuprofen (CrCl 45-79 mL/min).
Hepatic Impairment: Caution in liver disease; dose adjustment may be needed.
Overdose effects
No drugs approved for overdose treatment; in animal studies, leucovorin may mitigate toxicities; not known if dialyzable.
Storage conditions
Store below 30°C in a cool and dry place, away from sunlight; keep out of reach of children.
Chemical structure
Pemetrexed