From the Guidelines
Depakote ER (extended-release divalproex sodium) should be taken at bedtime to minimize side effects like drowsiness, dizziness, and stomach upset that may be more bothersome during daytime activities. The extended-release formulation maintains steady blood levels over 24 hours, so once-daily dosing is effective regardless of timing. However, for some patients who experience morning grogginess with bedtime dosing, morning administration may be preferable. Some key points to consider when taking Depakote ER include:
- Consistency is key: taking Depakote ER at the same time each day to maintain stable blood levels 1
- The medication should be swallowed whole with water and can be taken with food to reduce stomach irritation
- Individual factors like medical condition, other medications, and personal response to the drug may influence the optimal dosing schedule
- There is limited direct evidence on the optimal timing of Depakote ER dosing, but the most recent and highest quality study available does not specifically address this question 1. In clinical practice, the decision on when to take Depakote ER should be based on individual patient factors and healthcare provider guidance, prioritizing minimizing side effects and maintaining stable blood levels.
From the Research
Dosing Schedule for Depakote (Valproate) ER
The optimal dosing schedule for Depakote (Valproate) ER is a topic of discussion among neurologists and epilepsy caregivers.
- The study 2 suggests that twice-daily administration of ER formulations of valproic acid may be more beneficial than once-daily administration, as it minimizes the risk of breakthrough seizures due to sub-therapeutic plasma levels.
- However, the study 3 provides guidance on the optimal time for obtaining a blood sample for valproic acid concentration in relation to the dose, which can be useful in determining the dosing schedule.
- The study 4 compares the bioavailability of divalproex extended release (ER) tablets with conventional divalproex tablets and discusses the pharmacokinetic factors affecting the conversion from conventional divalproex to divalproex ER.
Morning vs Bedtime Dosing
- The study 3 suggests that when taking divalproex-ER once daily in the morning, a blood sample collected 21 to 24 hours later is expected to have a concentration within 3% of the trough value.
- Conversely, for divalproex-ER dosed once-daily in the evening, a blood draw 12 to 15 hours later will give a plasma VPA concentration value that is 18% to 25% higher, on average, than the trough value.
- The study 5 recommends that valproate is given in three to four doses per day, but does not specify whether morning or bedtime dosing is preferred.
Key Considerations
- The timing of the blood sample does matter and impacts the proper interpretation of the VPA concentration 3.
- The dosing flexibility and consistency of plasma concentrations may simplify the management of antiepileptic drug therapy 2.
- The increased compliance observed with fewer dosages per day should be weighed against the impact or forgiveness of omitted dose(s) and the shorter 'forgiveness' period associated with once-daily administration 2.