Dose Conversion Between Divalproex and Valproic Acid
When converting between divalproex sodium and valproic acid, a 1:1 dose conversion should be used based on valproate content, with an 8-20% higher divalproex extended-release (ER) daily dose required when converting from regular divalproex. 1
Understanding the Formulations
- Valproic acid: The active ingredient in all formulations
- Divalproex sodium: Contains sodium valproate and valproic acid in a 1:1 molar relationship
- Formulation types:
- Regular divalproex (delayed-release/DR): Enteric-coated tablets
- Divalproex ER: Extended-release tablets with lower bioavailability
Conversion Guidelines
Standard Conversion Factors
- Divalproex sodium contains approximately 87% valproate content by weight
- When converting between formulations, consider the following:
Valproic acid to regular divalproex: Use equivalent doses (1:1 conversion)
- Example: 500 mg valproic acid = 500 mg divalproex sodium
Regular divalproex to divalproex ER: Increase dose by 8-20% 1
- Example: 1000 mg divalproex DR = 1080-1200 mg divalproex ER
Timing for conversion:
- When converting from twice-daily divalproex to once-daily divalproex ER, the optimal strategy is immediate conversion 12 hours after the last divalproex dose 2
- Delayed conversion may result in subtherapeutic valproate levels
Pharmacokinetic Considerations
Bioavailability differences: Divalproex ER has approximately 89% bioavailability compared to regular divalproex when administered at equal total daily doses 1
Concentration profiles:
- Divalproex ER provides less fluctuation in valproic acid concentrations
- Achieves higher minimum concentrations and lower maximum concentrations compared to multiple daily divalproex dosing 1
Therapeutic monitoring:
- Divalproex ER predose trough concentration consistently represents the lowest concentration during a dosing interval
- Regular divalproex trough levels are less predictable due to absorption lag time, diurnal variation, and multiple daily dosing 1
Special Considerations
Enzyme induction: Patients on enzyme-inducing medications may require higher doses of all valproate formulations 2, 3
Therapeutic range: The therapeutic range for valproic acid is typically 50-100 mg/L 3
Switching strategies: When converting from regular divalproex to divalproex ER, an immediate conversion strategy (giving divalproex ER 12 hours after the last regular divalproex dose) causes the least perturbation in plasma valproate levels 2
By following these conversion guidelines, clinicians can maintain therapeutic valproate levels while potentially improving patient adherence through simplified dosing regimens.