Divalproex

# Divalproex ## Overview Divalproex is a stable coordination compound of valproic acid and sodium valproate. It dissociates to valproic acid in the GI tract. Exact mechanism unknown; increases brain GABA, modulates voltage-gated sodium channels. ## Primary Indications - Bipolar disorder (acute mania, maintenance) - Seizure disorders (complex partial, absence, generalized tonic-clonic) - Migraine prophylaxis ## Adult Dosing - **Bipolar (mania):** Start 750–1000 mg/day PO divided BID-TID; titrate up to target 60 mg/kg/day. Max 60 mg/kg/day or 3000 mg/day. - **Epilepsy:** Start 10–15 mg/kg/day PO divided; increase by 5–10 mg/kg/week. Max 60 mg/kg/day. - **Migraine prophylaxis:** Start 250 mg PO BID; typical 500–1000 mg/day in divided doses. Max 1500 mg/day. ## Pediatric Dosing - **Epilepsy (≥10 years):** Start 10–15 mg/kg/day; increase by 5–10 mg/kg/week. Max 60 mg/kg/day. - **Bipolar (children, off-label):** Weight-based; start 15–20 mg/kg/day; target 20–30 mg/kg/day. Consult local protocol. - **Migraine (adolescents):** Not first-line; limited data. ## Dose Adjustments - **Hepatic impairment:** Avoid in severe disease; reduce dose in mild-moderate (unclear evidence). - **Renal impairment:** Caution with high doses due to protein binding displacement; unclear specific reduction. - **Elderly:** Start lower, titrate slowly (e.g., 250 mg BID). Reduce dose if toxicity. ## Contraindications - Hypersensitivity to valproate - Active liver disease or significant hepatic dysfunction - Urea cycle disorders - Known mitochondrial polymerase gamma (POLG) mutation (risk of fatal liver failure) ## Adverse Effects - **Common:** Nausea, vomiting, sedation, tremor, weight gain, alopecia. - **Serious:** Hepatotoxicity (esp. <2 years old, polytherapy), pancreatitis, thrombocytopenia, hyperammonemic encephalopathy, teratogenicity (neural tube defects). - **Black box:** Hepatotoxicity, pancreatitis, fetal risk. ## Key Drug Interactions - **Lamotrigine:** Valproate doubles lamotrigine half-life; reduce lamotrigine dose by 50%. - **Phenytoin/carbamazepine:** Valproate may increase phenytoin free fraction; decreases carbamazepine metabolism. - **Aspirin/NSAIDs:** Increase valproate free fraction; risk of toxicity. - **Antipsychotics, antidepressants:** Additive sedation. ## Monitoring - Baseline: LFTs, CBC, ammonia (if urea cycle disorder suspected). - During therapy: LFTs, CBC every 3–6 months; valproate trough levels (therapeutic 50–125 µg/mL for epilepsy; wider for bipolar). - Watch ammonia levels if encephalopathic symptoms. ## Clinical Pearls - **Extended release (ER)** can be given once daily with food; not interchangeable mg-for-mg with delayed release (DR) due to different absorption. - **Titrate dose** slowly to minimize GI upset. - **Depakote Sprinkle** capsules can be swallowed whole or opened onto soft food—do not crush or chew. - **Discontinue abruptly** only with caution due to withdrawal seizures (epilepsy). - **Pregnancy:** Avoid if possible; supplement with high-dose folate if used. --- *This information is for educational use only. Always verify current prescribing information, dosing protocols, and patient-specific factors before initiating or adjusting therapy.*