Drug Guide
Divalproex Sodium
Classification
Therapeutic: Anticonvulsant, Mood Stabilizer
Pharmacological: Prodrug of Valproic Acid, histone deacetylase inhibitor
FDA Approved Indications
- Treatment of epilepsy (partial, generalized, and absence seizures)
- Manic episodes associated with bipolar disorder
- Prophylaxis of migraine headaches
Mechanism of Action
Divalproex Sodium increases gamma-aminobutyric acid (GABA) levels in the brain by inhibiting GABA transaminase and promoting GABA synthesis, leading to stabilization of neuronal activity.
Dosage and Administration
Adult: Initial dose typically 250 mg 2-3 times daily, titrated up to maintenance dose of 750-2000 mg/day in divided doses.
Pediatric: Starting dose varies based on age and weight; typically 15 mg/kg/day divided in 2-3 doses, titrated gradually.
Geriatric: Use with caution; start at lower doses due to increased risk of side effects.
Renal Impairment: Adjust dose as needed; monitor renal function.
Hepatic Impairment: Use with caution; monitor liver function closely.
Pharmacokinetics
Absorption: Well absorbed orally, food may delay absorption.
Distribution: Widely distributed in body tissues with approximately 90% plasma protein binding.
Metabolism: Primarily hepatic via glucuronidation and beta-oxidation; minimal CYP450 involvement.
Excretion: Renally excreted as metabolites; less than 10% excreted unchanged.
Half Life: Approximately 9-16 hours.
Contraindications
- Hypersensitivity to divalproex or valproic acid
- Liver disease
- Urea cycle disorders
Precautions
- History of pancreatitis
- Blood dyscrasias
- Pregnancy Risks (see special considerations)
- Monitor liver function and blood counts regularly
Adverse Reactions - Common
- nausea (common)
- drowsiness (common)
- tremor (common)
- weight gain (common)
Adverse Reactions - Serious
- hepatotoxicity (rare)
- pancreatitis (rare)
- thrombocytopenia (rare)
- Neural Tube Defects in pregnancy (rare (see pregnancy considerations))
Drug-Drug Interactions
- CNS depressants (additive sedation)
- Carbapenem antibiotics (risk of decreased levels)
- Other hepatotoxic drugs
Drug-Food Interactions
N/ADrug-Herb Interactions
N/ANursing Implications
Assessment: Monitor liver function tests, CBC, serum drug levels, and neurological status.
Diagnoses:
- Risk for injury related to sedation or tremors
- Risk for hepatotoxicity
Implementation: Administer with food to minimize GI upset. Titrate dose gradually.
Evaluation: Assess seizure control, mood stabilization, and adverse effects regularly.
Patient/Family Teaching
- Take medication exactly as prescribed.
- Report signs of liver dysfunction (jaundice, abdominal pain), pancreatitis (abdominal pain, nausea), or unusual bleeding.
- Avoid alcohol and CNS depressants.
- Consult provider before pregnancy; discuss risks.
Special Considerations
Black Box Warnings:
- Hepatotoxicity, especially in children under 2 years old
- Impaired cognitive development and neural tube defects in pregnancy
Genetic Factors: Genetic variations may affect drug metabolism and toxicity.
Lab Test Interference: May interfere with certain blood tests; interpret labs accordingly.
Overdose Management
Signs/Symptoms: Somnolence, CV depression, hyperactivity, blurred vision, nystagmus, coma.
Treatment: Supportive care; activated charcoal if ingestion is recent; hemodialysis in severe cases; monitor vital signs and neurological status.
Storage and Handling
Storage: Store at room temperature, 15-30°C, away from moisture, heat, and light.
Stability: Stability varies; refer to manufacturer specifications.