What is the recommended treatment and dosage of Toltazuril (generic name) for equine protozoal myeloencephalitis (EPM) in horses?

Toltrazuril Treatment for Equine Protozoal Myeloencephalitis (EPM)

The recommended treatment dosage for toltrazuril in horses with EPM is 5-7.5 mg/kg orally once daily for 28 days, with 7.5 mg/kg showing the highest cerebrospinal fluid (CSF) concentrations and likely better clinical outcomes. 1

Pharmacokinetics and Dosing

Toltrazuril demonstrates favorable pharmacokinetic properties for treating EPM:

• Absorption: Rapidly absorbed after oral administration with peak serum concentrations at approximately 18 hours 1
• CSF Penetration: Dose-dependent penetration into CSF, which is critical for treating this neurological condition 1
• Elimination: Prolonged elimination half-life of approximately 61.4 hours 1
• Metabolism: Primarily metabolized to toltrazuril sulfone, which becomes the predominant metabolite after multiple days of treatment 1

Dosing Recommendations Based on Evidence:

• Dose range: 5-7.5 mg/kg orally once daily 1
• Duration: 28 days (based on similar studies with ponazuril, a metabolite of toltrazuril) 2, 3
• Administration: With food to enhance absorption

Efficacy and Clinical Outcomes

Research demonstrates that toltrazuril and its derivatives are effective against S. neurona, the causative organism of EPM:

• At 5-7.5 mg/kg daily dosing, toltrazuril achieves CSF concentrations that reach effective in vitro levels against S. neurona 1
• Higher dosing (7.5 mg/kg) results in greater CSF concentrations (mean 0.386 mg/L after 10 days) compared to lower doses 1
• Similar compounds (ponazuril) showed 62% clinical success rate in treating naturally occurring EPM 3
• Prophylactic administration can reduce clinical signs and delay seroconversion in challenged horses 4

Safety Profile

Toltrazuril demonstrates a favorable safety profile at therapeutic doses:

• A toxicity study using 50 mg/kg (5-10× the therapeutic dose) for 10 days showed only mild clinical abnormalities 5
• Observed mild effects at high doses included:
  • Mild anorexia and weight loss
  • Transient increases in bilirubin and serum protein
  • Mild increases in hematocrit, hemoglobin, and albumin 5
  • No significant microscopic tissue changes were noted on post-mortem examination

Monitoring During Treatment

• Clinical assessment: Regular neurological examinations to track improvement
• Laboratory monitoring: Consider baseline and periodic CBC and chemistry panels, particularly if using higher doses
• Duration of therapy: Complete the full 28-day course even if clinical signs improve earlier

Comparison to Alternative Treatments

Ponazuril (a metabolite of toltrazuril) has been more extensively studied for EPM:

• Administered at 5 mg/kg daily for 28 days 2, 3
• Achieves CSF concentrations of approximately 0.162 mg/L after 7 days 2
• Shows 62% clinical success rate in naturally occurring EPM 3

Practical Considerations

• Administration: Oral paste or suspension formulations are typically used
• Storage: Store at room temperature, protected from light
• Compounding: May need to be compounded for equine use in some regions
• Cost: Treatment course may be expensive; consider this factor when discussing options with horse owners

Potential Pitfalls and Caveats

• Diagnosis confirmation: Ensure proper diagnosis of EPM before initiating treatment
• Concurrent treatments: Limited data on drug interactions with toltrazuril in horses
• Extra-label use: In many regions, toltrazuril use for EPM may be extra-label; follow appropriate regulations
• Treatment failures: Some horses may not respond adequately and may require alternative or additional therapies

While toltrazuril shows promise in treating EPM, clinical judgment should guide treatment decisions based on individual case severity, drug availability, and regulatory considerations.