From the Guidelines
Valproic acid and divalproex are not the same, as divalproex is a delayed-release formulation that combines sodium valproate and valproic acid, offering improved tolerability and convenience compared to immediate-release valproic acid. The primary difference between valproic acid and divalproex lies in their formulation and dosing requirements. Divalproex is a delayed-release formulation, which allows for less frequent dosing, typically twice daily, compared to immediate-release valproic acid, which often requires three or four daily doses 1. This delayed-release nature of divalproex results in fewer gastrointestinal side effects, making it better tolerated by many patients. Some key points to consider when choosing between valproic acid and divalproex include:
- Efficacy: Both medications have similar efficacy for treating seizures, bipolar disorder, and migraines.
- Dosing: Divalproex can be divided into fewer administrations, typically twice daily, while valproic acid often requires three or four daily doses.
- Side effects: Divalproex has a better side effect profile, with fewer gastrointestinal side effects, making it a preferred choice in clinical practice.
- Therapeutic drug monitoring: Both medications require monitoring with target serum levels of 50-100 μg/mL for most indications.
- Patient factors: The choice between valproic acid and divalproex should consider individual patient factors, including tolerance, compliance ability, and cost considerations. As noted in a study published in the American Family Physician, evidence for efficacy is good for divalproex sodium and sodium valproate, particularly in patients with prolonged or atypical migraine aura 1.
From the FDA Drug Label
Equivalent oral doses of divalproex sodium products and valproic acid capsules deliver equivalent quantities of valproate ion systemically. Valproic acid dissociates to the valproate ion in the gastrointestinal tract.
The main difference between valproic acid and divalproex is the formulation:
- Valproic acid is administered orally as a capsule.
- Divalproex is a delayed-release formulation of sodium valproate and valproic acid. In terms of efficacy, both formulations deliver equivalent quantities of valproate ion systemically, suggesting similar efficacy in the treatment of epilepsy. For dosage, the recommended initial dose and maximum recommended dosage are the same for both valproic acid and divalproex sodium products, as indicated in the drug labels 2 and 2.
From the Research
Valproic Acid vs Divalproex: Efficacy and Dosage
- Valproic acid and divalproex are two formulations of valproic acid derivatives, with divalproex being a delayed-release formulation of sodium valproate and valproic acid 3.
- Studies have shown that divalproex and valproic acid have similar efficacy in treating epilepsy and mood disorders, with no significant differences in efficacy found in eight studies 4.
- However, divalproex has been found to have a longer Tmax (time to reach maximum concentration) due to its gastro-resistant galenic form, which may affect its absorption characteristics 4.
- In terms of dosage, divalproex and valproic acid are considered to be interchangeable, with similar dosages used in clinical practice 4, 5.
- A study found that patients treated with divalproex sodium had lower rates of gastrointestinal side effects compared to those treated with valproic acid, but there were no differences in efficacy between the two drugs 5.
- Another study found that valproic acid was administered at higher doses than divalproex sodium, but there were no differences in efficacy or discontinuation rates due to side effects 6.
Side Effects and Tolerability
- Divalproex has been found to be better tolerated than valproic acid, with lower rates of gastrointestinal side effects such as nausea, vomiting, and dyspepsia 5, 6.
- However, the difference in side effects between divalproex and valproic acid may not be clinically significant, as there were no differences in discontinuation rates or use of medications to treat gastrointestinal side effects 6.
Clinical Implications
- The choice between divalproex and valproic acid may depend on individual patient factors, such as tolerance to side effects and dosage requirements 4, 5.
- Clinicians should be aware of the potential differences in absorption characteristics and side effects between divalproex and valproic acid, and adjust treatment accordingly 3, 4.