Pemetrexed

Antimetabolites
Antimetabolites
High alert
An error with this medicine can cause serious harm: double checks and protocols are used.

A multi-target antifolate for non-squamous lung cancer and mesothelioma. Folic acid and vitamin B12 are given beforehand to reduce its toxicity.

Updated Nov 1, 2026

Quick facts

Group: Antimetabolites
Target: Thymidylate synthase (also DHFR and GARFT)
Used for: Non-squamous non-small cell lung cancer
Key effects: Fatigue · Myelosuppression · Mouth sores
Monitor: Complete blood count before each dose
ATC: L01BA04

No doses: the clinician sets them by the current guideline.

Mechanism of action

Thymidylate synthase (also DHFR and GARFT)Pemetrexed

The crystal shows pemetrexed (ligand LYA, its research code LY231514) in human thymidylate synthase together with the substrate dUMP.

Target in 3D: Thymidylate synthase (also DHFR and GARFT). PDB structure 1JU6 (RCSB PDB, public domain). View the structure at RCSB PDB

Pemetrexed enters cells through the reduced folate carrier and folate receptors and is converted to polyglutamates, which are retained and more potent. It inhibits several folate-dependent enzymes: mainly thymidylate synthase, but also dihydrofolate reductase and glycinamide ribonucleotide formyltransferase (GARFT) of purine synthesis. Both thymidine and purine production stop, and DNA synthesis fails.

Pemetrexed enters through folate carriers and is polyglutamated
It inhibits thymidylate synthase
It also blocks DHFR and GARFT (purine synthesis)
No thymidine or purines: DNA synthesis stops

Indications

Non-squamous non-small cell lung cancer: first-line with platinum (and immunotherapy), and maintenance. Lung cancer →
Malignant pleural mesothelioma, with cisplatin. Malignant pleural mesothelioma →

Adverse effects

Common

Fatigue, nausea, loss of appetite
Myelosuppression
Mouth sores, rash

Contraindications

History of severe hypersensitivity to pemetrexed

Key interactions

Ibuprofen: Raises pemetrexed exposure, especially with reduced kidney function; avoided in the days around each dose.

What is monitored

Complete blood count before each dose
Creatinine clearance before each dose
Skin and breathing symptoms

Administration and safety

Folic acid starts before the first dose and continues throughout; vitamin B12 is injected before the first dose and repeated during treatment.
A corticosteroid (dexamethasone) is given around each dose to reduce skin reactions.
Hazardous drug: chemotherapy handling precautions.

Pregnancy and breastfeeding

Can cause fetal harm; effective contraception is advised for women and men.

Nursing care

Confirm folic acid adherence and the date of the last vitamin B12 injection before every dose.
Ask about over-the-counter ibuprofen and other pain relievers.
Check creatinine and counts; report rash, mouth sores or breathlessness.
Teaching: effective contraception during treatment.

Pharmacokinetics

Absorption: Intravenous infusion.
Metabolism: Little metabolism; polyglutamated inside cells.
Elimination: Mostly unchanged in the urine: kidney function decides whether it can be given.

Test yourself

Think of the answer, then tap the question to see it.

Which vitamins are given before and during pemetrexed, and why?

Folic acid and vitamin B12: they reduce severe myelosuppression and gastrointestinal toxicity.

Which enzyme is the main target of pemetrexed?

Thymidylate synthase (also DHFR and GARFT).

Why is ibuprofen avoided around pemetrexed doses?

It raises pemetrexed exposure, increasing toxicity, especially when kidney function is reduced.

Add to my cards (3)

Connections

← Back to the class: Antimetabolites

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - PEMETREXED injection, powder, for solution (DailyMed (U.S. National Library of Medicine), 2026); Pemetrexed Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); RCSB PDB - 1JU6: Human Thymidylate Synthase Complex with dUMP and LY231514, A Pyrrolo(2,3-d)pyrimidine-based Antifolate (RCSB Protein Data Bank, 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.