From the Guidelines
Divalproex sodium is available in both extended-release (ER) and delayed-release (DR) formulations, with the DR formulation being enteric coated. The DR formulation has an enteric coating that prevents dissolution in the stomach, releasing the medication in the small intestine to reduce gastrointestinal irritation. Some key points to consider when prescribing divalproex sodium include:
- The DR formulation is typically dosed 2-3 times daily to maintain therapeutic levels.
- The ER formulation uses a different technology that allows for gradual release of the medication over 24 hours, enabling once-daily dosing, which improves adherence.
- When converting from DR to ER, the total daily dose remains the same, but the ER dose is given once daily.
- For example, if a patient takes 500 mg DR twice daily (1000 mg total), they would take 1000 mg ER once daily.
- The therapeutic range for both formulations is 50-125 mcg/mL, although this information is not directly provided by the study 1. The ER formulation may cause fewer gastrointestinal side effects and has less peak-to-trough fluctuation in blood levels, which can improve patient outcomes in terms of morbidity, mortality, and quality of life. Both formulations are used to treat seizures, bipolar disorder, and migraines, but the ER formulation's once-daily dosing makes it preferable for many patients to improve medication adherence, as evidenced by guidelines on the management and prevention of migraines 1.
From the Research
Divalproex ER vs DR Formulations
- Divalproex ER (extended-release) and DR (delayed-release) are two different formulations of divalproex sodium, with distinct pharmacokinetic properties 2, 3, 4, 5, 6.
- The DR formulation is enteric-coated, which affects its absorption and bioavailability 2, 3, 5, 6.
Bioavailability and Dosing
- The bioavailability of divalproex ER is lower than that of the DR formulation, but can be equivalent with 8-20% higher daily doses 3, 5, 6.
- Divalproex ER can be administered once-daily, while the DR formulation requires multiple daily doses to maintain therapeutic plasma concentrations 2, 3, 5, 6.
- The peak-to-trough fluctuation in plasma concentrations is lower for divalproex ER compared to the DR formulation, resulting in more stable valproic acid levels 2, 3, 5, 6.
Clinical Implications
- Divalproex ER is associated with improved tolerability, reduced side effects, and better seizure control compared to the DR formulation 4.
- Patients can be converted from the DR formulation to divalproex ER with a 8-20% higher daily dose, resulting in equivalent exposure and improved pharmacokinetic profiles 3, 5, 6.
- The ER formulation is suitable for once-daily dosing, while the DR formulation should not be dosed once-daily at high total daily doses due to the risk of clinical toxicity 2.