From the FDA Drug Label
In adult patients and pediatric patients 10 years of age or older with epilepsy previously receiving divalproex sodium delayed-release tablets, divalproex sodium extended-release tablets should be administered once-daily using a dose 8 to 20% higher than the total daily dose of divalproex sodium delayed-release tablets Plasma valproate C min concentrations for divalproex sodium extended-release tablets on average are equivalent to divalproex sodium delayed-release tablets, but may vary across patients after conversion
The main difference between divalproex ER and divalproex DR is the dosing frequency, with divalproex ER administered once-daily and divalproex DR administered more frequently.
- When converting from divalproex DR to divalproex ER, the dose should be increased by 8 to 20% and administered once-daily.
- Plasma valproate concentrations may vary across patients after conversion, so monitoring is recommended to ensure therapeutic levels are achieved 1.
From the Research
Divalproex extended-release (ER) is the preferred formulation over delayed-release (DR) due to its improved tolerability, reduced side effects, and enhanced patient preference, as evidenced by a study published in 2004 2.
Key Differences Between Divalproex ER and DR
- Divalproex ER is taken once daily, typically at bedtime, providing steady drug levels over 24 hours, which improves adherence and may reduce side effects.
- Divalproex DR (also called Depakote) is usually taken twice daily with meals because food enhances absorption.
- When converting from DR to ER formulation, the total daily dose remains the same, but is given as a single dose.
- ER formulations may cause fewer gastrointestinal side effects and have less peak-to-trough fluctuation in drug levels.
Considerations for Choosing Between ER and DR Formulations
- Patient preference: ER formulations may be preferred by patients due to the convenience of once-daily dosing.
- Adherence concerns: ER formulations may improve adherence due to the simplicity of the dosing regimen.
- Side effect profiles: ER formulations may have a more favorable side effect profile, with reduced gastrointestinal side effects and less peak-to-trough fluctuation in drug levels.
- Insurance coverage: The choice between ER and DR formulations may also depend on insurance coverage and cost considerations.
Evidence Supporting the Use of Divalproex ER
- A study published in 2009 found that once-daily dosing is appropriate for extended-release divalproex, but not for enteric-coated, delayed-release divalproex 3.
- Another study published in 2004 found that divalproex ER is associated with superior tolerability and improved seizure control compared to divalproex DR 2.
- A study published in 2003 found that switching psychiatric patients from a delayed-release to an extended-release formulation of divalproex sodium is safe and effective 4.