From the Guidelines
Valproic acid and divalproex are essentially the same medication with different formulations, with divalproex being generally preferred due to better tolerability and once or twice daily dosing options. The main difference between valproic acid and divalproex is the formulation, as divalproex sodium is a stable coordination compound of sodium valproate and valproic acid that dissociates into valproic acid in the gastrointestinal tract 1. Some key points to consider when choosing between valproic acid and divalproex include:
- Divalproex has an enteric coating, which reduces gastrointestinal side effects like nausea, vomiting, and heartburn
- Divalproex is available in an extended-release formulation, allowing for once or twice daily dosing, while valproic acid typically requires multiple daily doses
- Both medications have identical therapeutic effects for seizures, bipolar disorder, and migraine prevention, with typical dosing ranges of 750-2000 mg daily depending on the condition
- Blood level monitoring (therapeutic range 50-125 μg/mL) is recommended for both
- They share the same side effect profile including weight gain, hair loss, tremor, liver toxicity, and teratogenicity, making them contraindicated in pregnancy
- The choice between them usually comes down to tolerability, with divalproex being more expensive but better tolerated by most patients. It's worth noting that the evidence from the study 1 does not directly compare valproic acid and divalproex, but it does provide information on the efficacy and safety of divalproex sodium and sodium valproate in the prevention of migraine headache.
From the FDA Drug Label
Divalproex sodium is a stable co-ordination compound comprised of sodium valproate and valproic acid in a 1:1 molar relationship and formed during the partial neutralization of valproic acid with 0. 5 equivalent of sodium hydroxide. Valproic acid is a carboxylic acid designated as 2-propylpentanoic acid. The main difference between valproic acid and divalproex (valproate) is that divalproex is a stable co-ordination compound composed of sodium valproate and valproic acid in a 1:1 molar relationship, whereas valproic acid is a carboxylic acid designated as 2-propylpentanoic acid 2, 3.
- Key differences:
- Chemical composition: Divalproex is a compound composed of sodium valproate and valproic acid, while valproic acid is a single carboxylic acid.
- Formation: Divalproex is formed through the partial neutralization of valproic acid with sodium hydroxide.
- Molecular structure: Divalproex has a specific structure as a co-ordination compound, whereas valproic acid has a distinct structure as a carboxylic acid.
From the Research
Difference between Valproic Acid and Divalproex (Valproate)
- Valproic acid and divalproex (valproate) are two related but distinct medications, with divalproex being a compound of valproic acid and sodium valproate 4, 5, 6, 7, 8.
- Divalproex sodium extended-release (divalproex-ER) maintains plasma valproic acid (VPA) concentrations for 24 hours when administered once-daily, whereas enteric-coated, delayed-release divalproex sodium requires multiple daily doses to achieve the same effect 4.
- Studies have shown that divalproex sodium is better tolerated than valproic acid, with fewer gastrointestinal side effects, such as nausea, vomiting, and dyspepsia 5, 6.
- However, some studies have found that divalproex may be less effective than valproic acid in certain clinical settings, such as in the treatment of psychiatric disorders 7.
- The conversion from divalproex to divalproex extended release (ER) requires an 8-20% higher daily dose of divalproex ER to achieve equivalent valproic acid concentrations 8.
- Divalproex ER has lower bioavailability than conventional divalproex tablets, but it offers the benefit of once-daily administration and less fluctuation in valproic acid concentrations 8.
Pharmacokinetic Differences
- Divalproex ER has a lower peak valproate concentration compared to valproic acid, which may enhance tolerability but also explain the lower effectiveness 7.
- The absorption lag time, diurnal variation, and multiple doses during a 24-hour interval can affect the predose trough concentration of divalproex, whereas divalproex ER consistently represents the lowest concentration during a dosing interval 8.
Clinical Implications
- The choice between valproic acid and divalproex (valproate) depends on the specific clinical setting and patient needs, with divalproex being a better option for patients who require a more convenient once-daily administration and fewer gastrointestinal side effects 5, 6, 8.
- However, valproic acid may be a better option for patients who require a more effective treatment for certain psychiatric disorders, despite the potential for more gastrointestinal side effects 7.