Pyrimethamine
Other antiprotozoals
Other antiprotozoals
Antifolate that, with sulfadiazine and folinic acid, is the classic treatment for toxoplasmosis; it can suppress the bone marrow.
Quick facts
- Group
- 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.
Mechanism of action
The figure shows pyrimethamine bound to dihydrofolate reductase-thymidylate synthase of Toxoplasma gondii.
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 →
- Toxoplasma retinochoroiditis Ocular toxoplasmosis (retinochoroiditis) →
- Part of sulfadoxine-pyrimethamine and artesunate combinations for malaria prevention and treatment Malaria →
Adverse effects
Common
- Loss of appetite and vomiting (less with meals)
- Glossitis (sore, red tongue), a sign of folate deficiency
- Rash
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
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.
Connections
← Back to the class: 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 (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.