Pyrimethamine and Sulfadiazine
5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine; 4-amino-N-pyrimidin-2-ylbenzenesulfonamide
Also known as: ReBalance · Fansidar (related compound) · Pyrimethamine/Sulfadiazine
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
Horses
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Treatment of EPM | 20 mg/kg sulfadiazine with 1 mg/kg pyrimethamine; equivalent to 4 mL of ReBalance suspension per 50 kg (110 lb) body weight | PO | once daily | 90-270 days (based upon clinical response) | 🌎 NA |
| Maintaining clinical remission (for horses that have had two relapses) | pyrimethamine/sulfadiazine | PO | twice weekly (first and fourth day of each week) | Ongoing | 🌎 NA |
- Treatment of EPM: Administer at least 1 hour before feeding with hay or grain. Administer using a suitable oral dosing syringe; insert nozzle through the interdental space and deposit the dose on the back of the tongue.
- Maintaining clinical remission (for horses that have had two relapses): After completing regular therapy for EPM.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Pyrimethamine and sulfadiazine is a synergistic antimicrobial and antiprotozoal combination primarily used in veterinary medicine to treat Equine Protozoal Myeloencephalitis (EPM) caused by Sarcocystis neurona.
- Synergistic Action: By combining a sulfonamide with a diaminopyrimidine, the formulation achieves a sequential blockade of the folate synthesis pathway, which is lethal to susceptible protozoa and bacteria.
- Off-label Uses: While FDA-approved specifically for horses, this combination (or similar folate antagonist combinations) is sometimes utilized off-label in small animal medicine to treat severe protozoal infections such as Toxoplasmosis in cats and Neosporosis in dogs.
- Clinical Considerations: Prolonged therapy (often 3-9 months) is required for EPM. Clinicians must monitor for bone marrow suppression due to systemic folate deficiency.
Mechanism of action
This combination exerts its antiprotozoal and antibacterial effects through a sequential blockade of the folic acid synthesis pathway, which is essential for nucleic acid (DNA/RNA) production in the parasite:
- Sulfadiazine acts as a structural analogue of para-aminobenzoic acid (PABA). It competitively inhibits the enzyme dihydropteroate synthase, blocking the conversion of PABA → dihydrofolic acid (DFA).
- Pyrimethamine specifically targets and inhibits the enzyme dihydrofolate reductase, blocking the conversion of DFA → tetrahydrofolic acid (THFA) (the active form of folate).
Pharmacological Pearl: Pyrimethamine has a much higher affinity for protozoal dihydrofolate reductase compared to bacterial or mammalian forms, making it highly effective against protozoal parasites like Sarcocystis neurona and Toxoplasma gondii.
Safety & warnings
Contraindications
- Hypersensitivity to pyrimethamine or sulfadiazine
- Horses intended for human consumption
Adverse effects
- Bone marrow suppression (anemia, leukopenia, neutropenia, thrombocytopenia)
- Reduced appetite or anorexia
- Loose stools or diarrhea
- Urticaria (hives)
- Treatment crisis (temporary worsening of neurologic signs due to parasite die-off)
- CNS effects (seizures, depression - though often secondary to the underlying EPM)
Precautions
Use with extreme caution in horses with preexisting hematologic abnormalities or those receiving other bone marrow-suppressing drugs.
Pregnancy/Nursing: Pyrimethamine is teratogenic in rats, and fetal abnormalities have been seen in foals. Sulfas cross the placenta and are distributed into milk. Use in pregnant animals only when benefits clearly outweigh risks. Consider using milk replacer for nursing offspring.
Treatment Crisis: Neurologic signs may worsen during the first few days to 5 weeks of treatment due to an inflammatory reaction secondary to dying parasites in the CNS.
Drug interactions
May decrease the bioavailability of sulfonamides if administered concurrently.
Sulfonamides may displace other highly bound drugs, potentially increasing their free (active) plasma concentrations and risk of toxicity.
Reportedly antagonistic towards the activity of pyrimethamine; clinical significance is unclear.
Use with pyrimethamine/sulfa is not recommended in humans as adverse effects may be additive; however, this combination has been used clinically in horses.
Monitoring
- CBC (including platelets): baseline and at least monthly during therapy
- GI adverse effects (appetite, stool consistency)
- Clinical Efficacy: Improvement in neurologic signs
- CSF Western Blot test (monitoring for negative status)
Pharmacokinetics
Half-life
Absorption
Pyrimethamine oral bioavailability is approximately 56% in horses. Sulfadiazine is well absorbed after oral administration.
Distribution
Pyrimethamine CNS levels are approximately 25-50% of those found in plasma. Sulfadiazine enters the CSF; Volume of distribution is approximately 0.58 L/kg.
Metabolism
Hepatic metabolism (specific details not provided in monograph).
Elimination
Renal excretion.
Overdose
Acute overdosage information (>2X) in horses is not well documented. When administered at 2X the labeled dose for 92 days, signs included loose stools, slight increases in ALP, declines in red blood cell parameters (RBC, HCT, Hgb, PCV), and depressed appetite. Treatment should be supportive and symptomatic.
Available products
Formulations
- Oral suspension
Veterinary
- Sulfadiazine (as the sodium salt) 250 mg/mL and Pyrimethamine 12.5 mg/mL Oral Suspension in quart (946.4 mL) bottles (ReBalance Antiprotozoal Oral Suspension)
Human-labeled
- Fansidar (Sulfadoxine & Pyrimethamine) - discontinued in the US market
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store at controlled room temperature (15-30°C / 59-86°F) and protect from freezing.
Client information
Important Administration Instructions
- Shake the bottle well before every use to ensure the medication is properly mixed.
- Fasting is required: Give this medication on an empty stomach, at least 1 hour before feeding your horse hay or grain. Food can prevent the drug from being absorbed properly.
What to Expect
- Treatment Crisis: It is common for your horse's neurologic signs to temporarily worsen during the first few days to weeks of treatment. This is usually caused by inflammation as the parasites die off in the nervous system. Do not stop the medication, but do inform your veterinarian.
- Long-term Therapy: Treatment for EPM is a marathon, not a sprint. Daily treatment is typically required for 3 to 9 months.
When to Call the Vet
Watch closely for signs of drug toxicity, which can affect the bone marrow. Contact your veterinarian immediately if you notice:
- Severe depression or lethargy
- Unexplained bleeding or bruising (e.g., bleeding gums)
- Bloody diarrhea or severe loose stools
- Complete loss of appetite
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.