Pyrimethamine
Aminopyrimidine derivative
Also known as: Daraprim · Malocide · Pirimecidan · BW-50-63 · pirimetamina · pyrimethaminum · RP-4753
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Toxoplasmosis | 0.5-1 mg/kg PO once daily for 2 days, then 0.25 mg/kg PO once daily for 2 weeks | PO | once daily | 2 days, then 2 weeks | 🌎 NA |
| Toxoplasmosis | 0.25-0.5 mg/kg once daily for 28 days | PO | once daily | 28 days | 🌎 NA |
| Neospora | 1 mg/kg once daily for 28 days | PO | once daily | 28 days | 🌎 NA |
| Hepatazoon canis | 0.25-0.5 mg/kg once daily for 2-4 weeks | PO | once daily | 2-4 weeks | 🌎 NA |
| Hepatazoon americanum | 0.25 mg/kg PO q24h | PO | q24h | — | 🌎 NA |
| Hepatazoon americanum | 0.25 mg/kg PO q24h for 14 days | PO | q24h | 14 days | 🌎 NA |
| Neosporosis | 1 mg/kg PO daily | PO | daily | — | 🌎 NA |
- Toxoplasmosis: Given with sulfadiazine at 30-50 mg/kg PO divided two to four times a day for 1-2 weeks
- Neospora: Given with trimethoprim sulfa
- Hepatazoon canis: Given with trimethoprim sulfa and clindamycin
- Hepatazoon americanum: Given with Trimethoprim/sulfa (15 mg/kg PO q12h) and clindamycin (10 mg/kg q8h). Once remission attained, decoquinate can maintain.
- Hepatazoon americanum: Given with Trimethoprim/sulfa (15 mg/kg PO q12h for 14 days) and clindamycin (10 mg/kg q8h for 14 days). Once remission attained, decoquinate can maintain.
- Neosporosis: Given with trimethoprim/sulfa (15-30 mg/kg PO twice daily).
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Toxoplasmosis | 0.5-1 mg/kg PO once daily for 2 days, then 0.25 mg/kg PO once daily for 2 weeks | PO | once daily | 2 days, then 2 weeks | 🌎 NA |
| Toxoplasmosis (enteroepithelial cycle) | 2 mg/kg, PO once daily | PO | once daily | — | 🌎 NA |
| Toxoplasmosis (extraintestinal cycle) | 0.5-1 mg/kg PO divided two to three times daily | PO | divided two to three times daily | — | 🌎 NA |
| Protozoal myocarditis | 1 mg/kg PO once daily for 3 days, then decrease dose to 0.5 mg/kg PO once a day | PO | once daily | 3 days, then ongoing | 🌎 NA |
| Toxoplasmosis | 0.5 mg/kg PO per day | PO | per day | 7-10 days | 🌎 NA |
- Toxoplasmosis: Given with sulfadiazine at 30-50 mg/kg PO divided two to four times a day for 1-2 weeks
- Toxoplasmosis (extraintestinal cycle): Combined with sulfonamides (e.g., triple sulfa, sulfadiazine) at 60 mg/kg PO or IM divided two to three times daily
- Protozoal myocarditis: Given with sulfadimethoxine 25 mg/kg PO, IV, or IM once a day
- Toxoplasmosis: Given with sulfadiazine at 30 mg/kg, PO q12h. Do not use continuously for longer than 2 weeks. Supplementation with folic acid 5 mg/day or folinic acid 1 mg/kg/day may alleviate toxicity.
Birds
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Coccidian organisms in raptors (Toxoplasmosis, Atoxoplasmosis, Sarcocystis) | 0.5 mg/kg PO twice daily for 14-28 days | PO | twice daily | 14-28 days | 🌎 NA |
Horses
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Equine protozoal myeloencephalitis | 1 mg/kg PO once a day for 90-120 days (or longer) | PO | once a day | 90-120 days (or longer) | 🌎 NA |
- Equine protozoal myeloencephalitis: Given with a sulfa or potentiated sulfa (sulfadiazine 20 mg/kg PO once or twice a day). Monitor CBC's.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Pyrimethamine is a potent antiprotozoal agent primarily used in veterinary medicine to treat severe protozoal infections such as toxoplasmosis, neosporosis, and Hepatozoon americanum in small animals, as well as Equine Protozoal Myeloencephalitis (EPM) in horses. It is almost always used in combination with sulfonamides to achieve a synergistic blockade of folic acid synthesis.
Clinical Pearl: Because it targets folate metabolism, host bone marrow suppression is a significant risk, particularly in cats. Supplementation with folinic acid (not folic acid, which the protozoa can sometimes utilize) or Baker's yeast is often recommended to mitigate hematologic toxicity.
Mechanism of action
Pyrimethamine is a folic acid antagonist. It competitively inhibits the enzyme dihydrofolate reductase (DHFR) → blocks the reduction of dihydrofolic acid to tetrahydrofolic acid (the active form of folate) → depletes folate reserves essential for purine and pyrimidine synthesis → halts protozoal DNA and RNA synthesis.
When combined with sulfonamides (which inhibit dihydropteroate synthase earlier in the pathway), it produces a synergistic, sequential blockade of the folate synthesis pathway.
Safety & warnings
Contraindications
- Known hypersensitivity to pyrimethamine
- Preexisting hematologic disorders (use with extreme caution)
- Pregnancy (potentially teratogenic, weigh risks vs. benefits)
- Pregnancy (teratogenic)
- Pre-existing bone marrow suppression
Adverse effects
- Small animals: Anorexia, malaise, vomiting, depression
- Small animals: Bone marrow depression (anemia, thrombocytopenia, leukopenia)
- Cats: Highly susceptible to adverse reactions (noted 4-6 days after starting combination therapy)
- Horses: Leukopenias, thrombocytopenia, and anemias
- Bone marrow suppression (anemia, leukopenia, thrombocytopenia)
- Lethargy
Precautions
Hematologic Toxicity: Hematologic effects can develop rapidly. Frequent monitoring is recommended, particularly if therapy persists longer than 2 weeks. Oral administration of folinic acid, folic acid, or Brewer's yeast has been suggested to alleviate adverse effects.
Feline Sensitivity: Some clinicians recommend avoiding its use in cats entirely because of its adverse effect profile.
Pregnancy: Pyrimethamine is teratogenic in rats and fetal abnormalities have been seen in foals. FDA Category C. Weigh risks against benefits. Excreted in maternal milk; consider using milk replacer.
Drug interactions
Reportedly antagonistic towards the activity of pyrimethamine; clinical significance is unclear.
Synergistic with pyrimethamine in activity against toxoplasmosis and malaria.
Use with pyrimethamine/sulfa is not recommended in humans as adverse effects may be additive, however, this combination has been used clinically in horses.
May increase folate deficiency
May increase folate deficiency
Monitoring
- CBC with platelet count (frequent monitoring recommended)
- Clinical efficacy
- Signs of abnormal bleeding or lassitude
- Complete Blood Count (CBC) every 1-2 weeks
- Appetite and body weight
- Signs of bleeding, bruising, or lethargy
Pharmacokinetics
Half-life
Absorption
No pharmacokinetic data located for veterinary species. In humans, well absorbed from the gut after oral administration.
Distribution
Distributed primarily to the kidneys, liver, spleen, and lungs. Crosses the blood-brain barrier. Volume of distribution is about 3 L/kg. 80% bound to plasma proteins. Enters milk in levels greater than serum.
Metabolism
Unknown how or where the drug is metabolized, but metabolites are found in the urine.
Elimination
Excreted in the urine.
Overdose
Reports of acute overdosage in animals were not located. In humans, signs include vomiting, nausea, anorexia, CNS stimulation (including seizures), and hematologic effects.
Treatment recommendations:
- Standard procedures to empty the gut or prevent absorption.
- Parenteral barbiturates for seizures.
- Folinic acid for hematologic effects.
- Long-term monitoring (at least 1 month) of renal and hematopoietic systems.
Available products
Formulations
- Tablets: 25 mg
- 25 mg tablet
Human-labeled
- Pyrimethamine Tablets: 25 mg; Daraprim® (GlaxoSmithKline); (Rx)
- Daraprim 25 mg tablets
Regulatory status
Often used under the cascade from human medicine.
Listed as a Pharmacy (P) medicine in the provided monograph.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store tablets in tight, light-resistant containers. Tablets may be crushed to make oral suspensions. If cherry syrup, corn syrup, or sucrose-containing liquids are used, store the suspension at room temperature and discard after 7 days (sugars adversely affect stability).
Client information
Important: This medication is used to treat serious parasitic infections and requires careful monitoring.
- Give exactly as directed: It is often given with other antibiotics (like sulfa drugs) for maximum effect. Do not skip doses.
- Watch for side effects: Contact your veterinarian immediately if your pet becomes lethargic, stops eating, vomits, or shows signs of unusual bleeding or bruising (such as pale gums or red spots on the skin).
- Dosing challenges in cats: The commercial tablets are 25 mg, which makes accurate dosing for cats very difficult. The tablets also taste bad to cats. Your veterinarian will likely recommend a specially compounded liquid or capsule to ensure accurate and easier dosing.
- Pregnancy warning: Do not handle this medication if you are pregnant, and do not use it in pregnant pets unless explicitly directed by your veterinarian.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.