From the Guidelines
Divalproex (valproate) is primarily used to treat seizure disorders, bipolar disorder, and prevent migraine headaches, with a standard dosage for migraine prevention of 500-1000 mg daily, as recommended by studies such as 1 and 1.
Typical Use and Dosage
For epilepsy, the typical adult dosage starts at 10-15 mg/kg/day, divided into 2-3 doses, gradually increasing to a maximum of 60 mg/kg/day as needed. For bipolar disorder, treatment usually begins with 750 mg daily in divided doses, with a typical maintenance range of 1000-2000 mg daily.
Mechanism of Action and Side Effects
Divalproex works by increasing levels of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the brain, which helps stabilize electrical activity and mood. Common side effects include nausea, drowsiness, dizziness, and weight gain.
Monitoring and Administration
Regular liver function tests, complete blood counts, and drug levels are necessary during treatment. Patients should take divalproex with food to minimize gastrointestinal upset, and the medication should never be stopped abruptly as this may trigger seizures or mood destabilization, as noted in studies like 1 and 1.
Key Considerations
- Blood level monitoring is essential, with therapeutic ranges typically between 50-125 μg/mL, though this varies by indication.
- Adverse events with divalproex sodium and sodium valproate are not uncommon and include weight gain, hair loss, tremor, and teratogenic potential, such as neural tube defects, as discussed in 1 and 1.
- The choice of divalproex should be based on the individual patient's condition, medical history, and response to treatment, considering the findings from 1, 1, and 1.
From the FDA Drug Label
DOSAGE AND ADMINISTRATION Valproic acid is administered orally. Valproic acid is indicated as monotherapy and adjunctive therapy in complex partial seizures in adults and pediatric patients down to the age of 10 years, and in simple and complex absence seizures. Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. The recommended initial dose is 15 mg/kg/day, increasing at one week intervals by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases. The maximum recommended dosage is 60 mg/kg/day.
The typical use of Divalproex (valproate) is as monotherapy and adjunctive therapy in:
- Complex partial seizures in adults and pediatric patients down to the age of 10 years
- Simple and complex absence seizures The typical dosage is:
- Initial dose: 10 to 15 mg/kg/day for complex partial seizures and 15 mg/kg/day for simple and complex absence seizures
- Dose increase: 5 to 10 mg/kg/week to achieve optimal clinical response
- Maximum recommended dosage: 60 mg/kg/day
- Therapeutic valproate serum concentrations: 50 to 100 μg/mL 2
From the Research
Typical Use of Divalproex
- Divalproex (valproate) is approved by the Food and Drug Administration for bipolar disorder, epilepsy, and migraine prophylaxis 3.
- It is used to treat manic episodes associated with bipolar disorder, epilepsy, and to prevent migraine headaches 4, 5.
- Divalproex is also used to treat bipolar depression, rapid cycling, psychotic symptoms, impulsive aggression, and post-traumatic stress disorder 5.
Dosage of Divalproex
- Divalproex extended release (DVP ER) is given once daily, which can improve compliance and reduce adverse events 3.
- The dosage of divalproex can be adjusted based on the patient's response and tolerance to the medication 5.
- Higher serum levels of valproate, particularly above 110 microg/ml, are associated with more reports of weight gain, sedation, and reductions in platelet count 6.
Administration and Formulations
- Divalproex is available in delayed release and extended release formulations 3.
- The extended release formulation is designed to provide once-daily administration with improved therapy 4.
- Controlled release hydrophilic matrix formulations of divalproex sodium have been designed and evaluated via in vitro and in vivo studies 4.