【藥品性質提示】 根據 2019 AGS Beers Criteria，本藥品為【潛在不適當用藥 (PIM)】，不建議用於有骨折風險之老年人(除非用於癲癇、調節情緒)。

治療癲癇、雙極症、預防偏頭痛
Bipolar disorder: Treatment of manic episodes (delayed release) or acute manic or mixed episodes with or without psychotic features (extended release) associated with bipolar disorder, as monotherapy or in combination with atypical antipsychotics.
Partial onset and generalized onset seizures: Monotherapy and adjunctive therapy in the treatment of patients with focal onset seizures with impairment of consciousness or awareness (complex partial) and generalized onset nonmotor seizures (absence), and as adjunctive therapy for multiple seizure types. May be used off-label as monotherapy for other seizure types.
Migraine prophylaxis: Prophylaxis of migraine headaches.

Anticonvulsants
Valproate sodium is an antiepileptic agent with unknown therapeutic mechanism of action, although, it is believed to exert its effect by increasing the concentrations of gamma-aminobutyric acid (GABA) in the brain.

Distribution
1. Vd: 11 L/1.73 m²
2. Protein binding: approximately 10% unbound at 40 mcg/mL and 18.5% unbound at 130 mcg/mL, concentration dependent
Metabolism
Hepatic; glucuronosyltransferase; over 40% by mitochondrial beta-oxidation, glucuronidation
Excretion
1. Renal: 30% to 50% as glucuronide conjugate, less than 3% unchanged
2. Dialyzable: yes (hemodialysis), about 20%
Elimination Half Life
1. 16 h +/- 3 h
2. Children (greater than 2 mo): 7 h to 13 h
3. Neonates (less than 10 days): 10 h to 67 h
4. Liver impairment: increased from 12 h to 18 h

1. Pregnant women, women who plan to become pregnant, or women of childbearing potential for the treatment of epilepsy or bipolar disorder unless essential for the management of her condition
2. Hypersensitivity to valproic acid, divalproex, derivatives, or any component of the formulation
3. Hepatic disease or significant impairment
4. Urea cycle disorders

Valproate crosses the placenta.

Valproate is present in breast milk

Nausea, vomiting, GI irritation, drowsiness, ataxia, transient alopecia, liver dysfunction

Bipolar disorder: Initial 500 to 750 mg/day, increase by 250 to 500 mg every 1 to 3 days to reach desired clinical effect and therapeutic serum concentration, Maximum recommended dosage: 60 mg/kg/day
Partial onset and generalized onset seizures: Initial monotherapy or adjunctive therapy 10 to 15 mg/kg/day, increase by 5-10 mg/kg/day at weekly intervals until optimal clinical response and/or therapeutic levels are achieved, maximum recommended dose: 60 mg/kg/day
Migraine prophylaxis: Initial 500 mg QD or BID; increase dose gradually based on response and tolerability in increments of 250 mg/day at intervals >3 days up to 1 g/day.

Seizures disorders: (Not recommended for ages <6 years)
1. Initial: 10-15mg/kg/day in 1 to 3 divided doses, increased by 5-10mg/kg daily at one week intervals until seizures are controlled
2. Maintenance: 30 to 60 mg/kg/day in 2 to 3 divided doses
Migraine prophylaxis: (Limited data available, for Children ≥12 years and Adolescents)
Initial 500 mg once daily for 15 days, may increase to 1,000 mg once dailiy; dose should be individualized

1. CrCl ≥10 mL/minute: No dosage adjustment necessary.
2. CrCl <10 mL/minute: No specific dosage adjustment necessary; however, free valproate clearance may be reduced up to ~30%.
3. Hemodialysis: No specific dosage adjustment necessary; At therapeutic concentrations, dialysis decreases valproic acid concentrations by 20%

1. Mild to moderate impairment: Not recommended for use in hepatic disease; clearance is decreased with liver impairment.
2. Severe impairment: Use is contraindicated.