[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Antimetabolites](https://durgical.com/en/pharmacology/classes/antimetabolites/) › Pemetrexed

# 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](https://durgical.com/en/pharmacology/classes/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.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Clinical What the labels mean

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## 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](https://www.rcsb.org/structure/1JU6) · Drag to rotate · pinch to zoom

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 →](https://durgical.com/en/conditions/lung-cancer/)
- Malignant pleural mesothelioma, with cisplatin. [Malignant pleural mesothelioma →](https://durgical.com/en/conditions/malignant-pleural-mesothelioma/)

## Adverse effects

### Common

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

### Serious (rare, important)

- Severe myelosuppression when folic acid and vitamin B12 are not given
- Renal failure, sometimes fatal
- Bullous and exfoliative skin reactions
- Interstitial pneumonitis; radiation recall

## 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.

## Memory aid

«PEMetrexed needs its PEMs»: Pre-treatment with folic acid and B12, steroids for the skin, and check the kidneys (and ibuprofen).

## 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)](https://durgical.app/estudiar/?add=/en/pharmacology/pemetrexed/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## What the labels mean

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

## Connections

## Related drugs 5

- [Methotrexate](https://durgical.com/en/pharmacology/methotrexate/)
- [Folic acid](https://durgical.com/en/pharmacology/folic-acid/)
- [Cyanocobalamin](https://durgical.com/en/pharmacology/cyanocobalamin/)
- [Dexamethasone](https://durgical.com/en/pharmacology/dexamethasone/)
- [Cisplatin](https://durgical.com/en/pharmacology/cisplatin/)

## Related conditions 2

- [Lung cancer](https://durgical.com/en/conditions/lung-cancer/)
- [Malignant pleural mesothelioma](https://durgical.com/en/conditions/malignant-pleural-mesothelioma/)

[← Back to the class: Antimetabolites](https://durgical.com/en/pharmacology/classes/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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bd0ada98-3237-4465-8ba2-3a12c33116fb) (DailyMed (U.S. National Library of Medicine), 2026); [Pemetrexed Injection: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a607043.html) (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](https://www.rcsb.org/structure/1JU6) (RCSB Protein Data Bank, 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L01BA04) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/pemetrexed/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/pemetrexed/