Pyrimethamine and Sulfadiazine
**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.
Mecanismo: 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: 1. **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)**. 2. **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*.
Dosificación por especie
- 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) · 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) · pyrimethamine/sulfadiazine · PO · twice weekly (first and fourth day of each week) · Ongoing · After completing regular therapy for EPM.
Las dosis son una referencia clínica para médicos veterinarios. Confirme siempre con la información vigente del producto y el paciente individual.
Vías de administración
Contraindicaciones
- Hypersensitivity to pyrimethamine or sulfadiazine
- Horses intended for human consumption
Efectos adversos
- 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)
Interacciones farmacológicas
- Antacids · May decrease the bioavailability of sulfonamides if administered concurrently.
- Highly protein-bound drugs (e.g., methotrexate, phenylbutazone, thiazide diuretics, salicylates, probenecid, phenytoin, warfarin) · Sulfonamides may displace other highly bound drugs, potentially increasing their free (active) plasma concentrations and risk of toxicity.
- p-Aminobenzoic acid (PABA) · Reportedly antagonistic towards the activity of pyrimethamine; clinical significance is unclear.
- Trimethoprim · Use with pyrimethamine/sulfa is not recommended in humans as adverse effects may be additive; however, this combination has been used clinically in horses.
Monitoreo
- 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)
Sobredosis
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.
La referencia de fármacos de VetSheet está destinada a médicos veterinarios como apoyo a la decisión clínica; no sustituye el juicio profesional ni la información vigente del fabricante.