Dosing Divalproex ER Twice Daily
Divalproex ER (extended-release) should be administered once daily, not twice daily, as it is specifically designed for once-daily dosing to maintain therapeutic plasma valproic acid levels over 24 hours. 1
Pharmacokinetic Considerations
- Divalproex ER was specifically developed as a once-daily formulation to improve patient compliance and reduce side effects compared to the standard twice-daily delayed release (DR) formulation 2
- Once-daily dosing of divalproex ER maintains plasma valproic acid concentrations within therapeutic range for 24 hours, making twice-daily dosing unnecessary 1
- Divalproex ER produces 42-48% lower peak-to-trough fluctuations compared to the immediate-release formulation, supporting its once-daily dosing schedule 3
Clinical Implications of Inappropriate Twice-Daily Dosing
- Administering divalproex ER twice daily may lead to:
Proper Conversion from Twice-Daily to Once-Daily Dosing
- When converting from twice-daily immediate-release divalproex to once-daily divalproex ER, the optimal strategy is immediate conversion 12 hours after the last twice-daily dose 4
- The total daily dose of divalproex ER should be increased by 14-20% compared to the immediate-release formulation to maintain equivalent drug exposure (AUC) 3
- For example, a patient taking 875 mg of immediate-release divalproex should be converted to 1000 mg of divalproex ER once daily 3
Monitoring Recommendations
- Monitor valproic acid levels after conversion to ensure therapeutic concentrations are maintained 4
- Target therapeutic range for valproic acid is typically 50-100 mg/L 4
- Patients on enzyme-inducing medications may require higher doses of divalproex ER to maintain therapeutic levels 4
Specific Dosing Guidelines for Mood Stabilization
- For mood stabilization in psychiatric conditions, the recommended initial dosage of divalproex sodium is 125 mg twice daily with titration to a therapeutic blood level (40-90 mcg/mL) 5
- However, this recommendation refers to the immediate-release formulation, not the extended-release version 5
Important Considerations and Precautions
- Divalproex ER is the appropriate formulation for once-daily administration, especially when large total daily doses are required 1
- The immediate-release formulation should not be dosed once daily at high total daily doses due to risk of toxicity 1
- Monitor liver enzyme levels regularly in patients taking divalproex for any indication 5
- Also monitor platelets, prothrombin time, and partial thromboplastin time as clinically indicated 5
Conclusion
Based on pharmacokinetic studies and clinical evidence, divalproex ER should be administered once daily rather than twice daily. Twice-daily dosing of the extended-release formulation is not recommended and may lead to unnecessary fluctuations in drug levels and increased risk of adverse effects.