From the Guidelines
Divalproex and sodium valproate are essentially interchangeable in terms of their therapeutic effects, but they differ in their formulation and absorption profiles, with divalproex offering a potentially more favorable side effect profile due to its delayed-release formulation. Divalproex and sodium valproate are both forms of valproic acid, an anticonvulsant medication used to treat epilepsy, bipolar disorder, and migraines. The key difference between them lies in their chemical structure and formulation: divalproex sodium is a stable coordination compound of sodium valproate and valproic acid in a 1:1 molar ratio, while sodium valproate is simply the sodium salt of valproic acid 1. This structural difference affects how the medications are absorbed in the body, with divalproex available as delayed-release or extended-release formulations that dissolve in the intestines rather than the stomach, potentially causing fewer gastrointestinal side effects.
- Key points to consider when choosing between divalproex and sodium valproate include:
- The desired release profile, with divalproex generally preferred when slower, more controlled release is beneficial
- The potential for gastrointestinal side effects, with divalproex potentially offering a more favorable profile
- The equivalent dosing between the two forms, though specific dosing should always be determined by a healthcare provider Both medications convert to valproic acid in the bloodstream and have the same therapeutic effects, working by increasing levels of the inhibitory neurotransmitter GABA in the brain, as evidenced by their good efficacy for conditions such as migraines 1.
From the FDA Drug Label
Equivalent oral doses of divalproex sodium products and valproic acid capsules deliver equivalent quantities of valproate ion systemically. The difference between divalproex (valproate) and sodium valproate is that they are different formulations that deliver equivalent quantities of valproate ion systemically, with minor clinical importance under steady state conditions achieved in chronic use in the treatment of epilepsy 2.
- The rate of valproate ion absorption may vary with the formulation administered.
- The efficacy of valproate as an anticonvulsant in chronic use is unlikely to be affected by differences in formulation.
From the Research
Difference between Divalproex and Sodium Valproate
- Divalproex is a formulation that contains sodium valproate and valproic acid in a 1:1 molar ratio 3
- Sodium valproate is a component of divalproex, and the active substance absorbed is the valproate ion, regardless of the formulation used 3
- The differences in indications between valproate derivatives, including divalproex and sodium valproate, do not seem justified, and interchangeability between them is possible at identical dosages 3
Pharmacokinetic Characteristics
- Divalproex and sodium valproate have similar pharmacokinetic profiles, with the main difference being the rate of absorption 4
- The absorption characteristics of different oral formulations of valproic acid/divalproex available in the US have been compared, showing marked differences in the rate of absorption 4
- Divalproex sodium has a longer time to maximum concentration (Tmax) compared to valproic acid, likely due to its gastro-resistant galenic form 3
Clinical Implications
- The use of divalproex sodium in the treatment of adults with bipolar disorder has been established, with a broad spectrum of activity in the treatment of bipolar depression, rapid cycling, and other related psychiatric disorders 5
- The combination of risperidone and divalproex sodium is used to treat the manic phase of bipolar disorder, and risperidone does not affect the steady-state pharmacokinetics of divalproex sodium 6