[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Other antiprotozoals](https://durgical.com/en/pharmacology/classes/other-antiprotozoals/) › Pyrimethamine

# Pyrimethamine

## Other antiprotozoals?

Other antiprotozoals

Antifolate that, with sulfadiazine and folinic acid, is the classic treatment for toxoplasmosis; it can suppress the bone marrow.

Updated Nov 1, 2026

## Quick facts

**Group**
[Other antiprotozoals](https://durgical.com/en/pharmacology/classes/other-antiprotozoals/)

**Target**
Parasite dihydrofolate reductase (bifunctional DHFR-thymidylate synthase of Toxoplasma and Plasmodium)

**Used for**
Toxoplasmosis · Toxoplasma retinochoroiditis

**Key effects**
Loss of appetite and vomiting · Glossitis · Rash

**Monitor**
Complete blood count with platelets · Skin

**ATC**
P01BD01

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

On this page

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

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

- Study Test yourself

- Connections Connections

## Mechanism of action

✂**Parasite dihydrofolate reductase (bifunctional DHFR-thymidylate synthase of Toxoplasma and Plasmodium)**Pyrimethamine

ⓘ The figure shows pyrimethamine bound to dihydrofolate reductase-thymidylate synthase of Toxoplasma gondii.

**Target in 3D:** Parasite dihydrofolate reductase (bifunctional DHFR-thymidylate synthase of Toxoplasma and Plasmodium). PDB structure 7FGW (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/7FGW) · Drag to rotate · pinch to zoom

A diaminopyrimidine folic acid antagonist. It binds the parasite's dihydrofolate reductase much more tightly than the human enzyme and stops dihydrofolate being reduced to tetrahydrofolate, so the parasite cannot make DNA. A sulfonamide (sulfadiazine) blocks the earlier step, dihydropteroate synthase, and the pair acts synergistically. At treatment doses the human enzyme is also affected, which is why folinic acid is added. Resistance comes from mutations in the parasite enzyme.

- Binds parasite dihydrofolate reductase
- No tetrahydrofolate: DNA synthesis stops
- Sulfadiazine blocks the step before: synergy
- Folinic acid protects the patient's marrow

## Indications

- Toxoplasmosis (including in people with HIV and congenital infection), always with a sulfonamide and folinic acid [Toxoplasmosis →](https://durgical.com/en/conditions/toxoplasmosis/)
- Toxoplasma retinochoroiditis [Ocular toxoplasmosis (retinochoroiditis) →](https://durgical.com/en/conditions/ocular-toxoplasmosis/)
- Part of sulfadoxine-pyrimethamine and artesunate combinations for malaria prevention and treatment [Malaria →](https://durgical.com/en/conditions/malaria/)

## Adverse effects

### Common

- Loss of appetite and vomiting (less with meals)
- Glossitis (sore, red tongue), a sign of folate deficiency
- Rash

### Serious (rare, important)

- Folate deficiency: megaloblastic anaemia, leucopenia, thrombocytopenia, pancytopenia
- Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) and anaphylaxis, mainly with the sulfonamide
- Overdose is especially dangerous in children; deaths have occurred after accidental ingestion
- Pulmonary eosinophilia (rare)

## Contraindications

- Hypersensitivity to pyrimethamine
- Documented megaloblastic anaemia from folate deficiency
- Caution: seizure disorders, kidney or liver impairment, possible folate deficiency

## Key interactions

**Sulfonamides, trimethoprim-sulfamethoxazole, proguanil, methotrexate, zidovudine**
Additive bone marrow suppression (antifolate effect)

**Lorazepam**
Mild liver toxicity reported

**Phenytoin and other drugs that lower folate**
Higher risk of folate deficiency

## What is monitored

- Complete blood count with platelets, frequently during high-dose treatment
- Skin: rash means stopping the drug
- Sore throat, pallor, bruising (purpura) or glossitis
- Kidney and liver function

## Administration and safety

- Oral, with meals to reduce anorexia and vomiting.
- Always given with folinic acid (calcium folinate), not folic acid.
- Long courses with regular blood counts; keep tablets away from children.

## Pregnancy and breastfeeding

Teratogenic in animals; used only when the benefit outweighs the risk, with folinic acid. In early pregnancy, toxoplasmosis without fetal infection is usually managed with spiramycin.

## Nursing care

- Before: baseline blood count, kidney and liver function, sulfa allergy and pregnancy status.
- Check that folinic acid is prescribed and given with every course.
- Watch for rash, sore throat, fever, pallor, bleeding or a sore red tongue and report them at once.
- Teaching: stop and seek care for any rash; store tablets out of children's reach (overdose can be fatal).

## Pharmacokinetics

**Absorption**
Oral, slow but complete

**Distribution**
Wide tissue distribution; mostly bound to plasma proteins; enters breast milk

**Elimination**
Slow

**Half-life**
About 96 hours

## Memory aid

«PYRImethamine needs a PAIR and a SHIELD»: the pair is sulfadiazine, the shield is folinic acid (leucovorin).

## Test yourself

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

## Which enzyme does pyrimethamine inhibit?

Dihydrofolate reductase of the parasite, blocking the formation of tetrahydrofolate needed for DNA synthesis.

## Why is folinic acid and not folic acid given with it?

Folinic acid is already reduced, so it bypasses the blocked enzyme in human cells; folic acid would still need dihydrofolate reductase to be activated.

## What is the classic combination for toxoplasmosis?

Pyrimethamine + sulfadiazine + folinic acid (leucovorin).

## Which laboratory test is followed during treatment?

The complete blood count with platelets, because the drug can cause megaloblastic anaemia, leucopenia and thrombocytopenia.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/pyrimethamine/)

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

## Connections

## Related drugs 4

- [Sulfadiazine](https://durgical.com/en/pharmacology/sulfadiazine/)
- [Calcium folinate](https://durgical.com/en/pharmacology/calcium-folinate/)
- [Sulfamethoxazole + trimethoprim (co-trimoxazole)](https://durgical.com/en/pharmacology/sulfamethoxazole-trimethoprim/)
- [Atovaquone](https://durgical.com/en/pharmacology/atovaquone/)

## Related conditions 3

- [Toxoplasmosis](https://durgical.com/en/conditions/toxoplasmosis/)
- [Ocular toxoplasmosis (retinochoroiditis)](https://durgical.com/en/conditions/ocular-toxoplasmosis/)
- [Malaria](https://durgical.com/en/conditions/malaria/)

[← Back to the class: Other antiprotozoals](https://durgical.com/en/pharmacology/classes/other-antiprotozoals/)

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 - PYRIMETHAMINE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2c57a992-619b-40ce-9395-f12ac47a2c67) (DailyMed (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=P01BD) (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.

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