Dosage Forms. Capsule, Extended Release: 125 mg; Tablet, Extended Release: 125 mg, 250 mg, 500 mg
Common FDA Label Indication, Dosing, and Titration.
1. Absence seizure, simple and complex: 15 mg/kg/d po, may titrate to 60 mg/kg/d
2. Complex partial epileptic seizure: 10-15 mg/kg/d po, may titrate to 60 mg/kg/d
3. Manic bipolar disorder: 25 mg/kg/d po, may titrate to 60 mg/kg/d
4. Migraine prophylaxis: 500 mg po daily for 1 wk, then 1000 mg po daily
Off-Label Uses. None
MOA. Divalproex is comprised of sodium valproate and valproic acid. Valproic acid is a carboxylic acid compound whose anticonvulsant activity might be mediated by an inhibitory neurotransmitter, GABA. Valproic acid might increase GABA levels by inhibiting GABA metabolism or enhancing postsynaptic GABA activity. Valproic acid also limits repetitive neuronal firing through voltage- and usage-dependent sodium channels.
Drug Characteristics: Divalproex
Medication Safety Issues: Divalproex
Drug Interactions: Divalproex
Adverse Reactions: Divalproex
Efficacy Monitoring Parameters. Reduction in number of seizures or control of manic symptoms. Therapeutic range for epilepsy, 50-100 mcg/mL. Therapeutic range for acute mania, 50-125 mcg/mL.
Toxicity Monitoring Parameters. Signs/symptoms of peripheral edema, increased heart rate, pancreatitis (abdominal pain, nausea, vomiting), monitor LFTs, ammonia levels, and CBC; emergence or worsening of depression, suicidal behavior or ideation, or unusual changes in behavior.
Key Patient Counseling Points. Avoid activities requiring mental alertness until drug effects are realized; drug may cause somnolence or dizziness. Take with food to avoid GI irritation. Do not discontinue drug abruptly, as this may precipitate status epilepticus. Avoid alcohol.
Clinical Pearls. Safety and efficacy in children <10 y of age have not been established. To convert from valproic acid to divalproex, initiate divalproex at the same daily dose and schedule; once stabilized, give divalproex bid or tid. Divalproex can produce teratogenic effects, so use with caution in women of childbearing potential. Multiple other dosage forms available as valproic acid.