Switching from Depakote XL 2000mg Nightly to 1000mg BID
You can safely switch the patient directly today by giving 1000mg of regular Depakote (divalproex) this morning and 1000mg tonight, maintaining the same total daily dose of 2000mg. 1, 2
Rationale for Direct Conversion
Bioequivalence at equal total daily doses: When converting from Depakote XL (extended-release) to regular divalproex at the same total daily dose, the formulations provide comparable drug exposure, making direct conversion appropriate 2
No dose adjustment needed: Since you're maintaining the same 2000mg total daily dose, simply split it into 1000mg twice daily 1
Immediate implementation: The patient took their last XL dose last night, so start the BID regimen this morning with 1000mg, then 1000mg approximately 12 hours later 1
Pharmacokinetic Considerations
Extended-release has lower bioavailability: Depakote XL has approximately 89% bioavailability compared to regular divalproex, but this difference is only clinically significant when converting from regular divalproex to XL (requiring 8-20% dose increase) 2
Converting back requires no adjustment: When switching from XL back to regular divalproex, the same total daily dose is appropriate because regular divalproex has higher bioavailability 2
Concentration fluctuation differences: Regular divalproex BID will have greater peak-to-trough fluctuation (~46%) compared to XL, but this is well-tolerated and does not cause breakthrough seizures 1
Practical Implementation Today
Morning dose: Give 1000mg regular divalproex this morning (approximately 12 hours after last XL dose)
Evening dose: Give 1000mg regular divalproex tonight, approximately 12 hours after morning dose 1
Timing flexibility: The 12-hour interval doesn't need to be exact; a window of ±2 hours is acceptable for clinical practice 1
Monitoring Recommendations
Therapeutic drug monitoring: Check valproic acid trough level (just before morning dose) in 3-5 days after conversion to ensure levels remain therapeutic (typically 50-100 mg/L for seizure control, 50-125 mg/L for bipolar disorder) 3, 2
Clinical observation: Monitor for breakthrough symptoms (seizures, mood instability) over the next week, though this is unlikely with equal total daily dosing 1
Peak levels occur at 4 hours: With regular divalproex, peak concentrations occur approximately 4 hours post-dose, with extended plateaus thereafter 1
Common Pitfalls to Avoid
Don't increase the dose: A common error is thinking you need to increase the total daily dose when converting from XL to regular formulation—this is incorrect and could lead to toxicity 2
Don't wait to start: There's no need to taper or overlap formulations; direct substitution is safe 1, 2
Don't check levels too early: Steady-state with BID dosing takes 2-3 days; checking levels before this may be misleading 2