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Indications

REMS

Divalproex sodium only:

Contraind./Precautions

Contraindicated in:

Use Cautiously in:

Adv. Reactions/Side Effects

CV: peripheral edema.

Derm: alopecia, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), rash.

EENT: visual disturbances.

GI: abdominal pain, anorexia, diarrhea, indigestion, nausea, vomiting, constipation, HEPATOTOXICITY, PANCREATITIS.

Hemat: thrombocytopenia, leukopenia.

Metab: appetite, HYPERAMMONEMIA, weight gain.

Neuro: agitation, dizziness, headache, insomnia, sedation, tremor, ataxia, confusion, depression, HYPOTHERMIA, SUICIDAL THOUGHTS.

Interactions

Drug-Drug:

Availability

Valproic Acid

(Generic available)

Valproate Sodium

(Generic available)

Divalproex Sodium

(Generic available)

Route/Dosage

see Calculator

Regular-release and delayed-release formulations usually given in 2–4 divided doses daily; extended-release formulation (Depakote ER) usually given once daily

Seizure Disorders

Bipolar Disorder

Migraine Prevention

US Brand Names

divalproex sodium: Depakote, Depakote ER, Depakote Sprinkle

valproate sodium: Depacon

valproic acid: Depakene

Action

Therapeutic Effects:

Classifications

Therapeutic Classification: anticonvulsants, vascular headache suppressants

Pharmacokinetics

Absorption: Well absorbed following oral administration; divalproex is enteric-coated, and absorption is delayed. Extended-release form produces lower blood levels. IV administration results in complete bioavailability.

Distribution: Rapidly distributed into plasma and extracellular water. Cross blood-brain barrier.

Protein Binding: 80–90% ( in neonates, elderly, renal impairment, or chronic hepatic impairment).

Metabolism/Excretion: Mostly metabolized by the liver; minimal amounts excreted unchanged in urine.

Half-life: Adults: 9–16 hr.

Canadian Brand Names

divalproex sodium: Epival

Time/Action Profile

(onset = anticonvulsant effect; peak = blood levels)

ROUTEONSETPEAKDURATION
PO — liquid2–4 days15–120 min6–24 hr
PO — capsules2–4 days1–4 hr6–24 hr
PO — delayed-release products2–4 days3–5 hr12–24 hr
PO — extended-release products2–4 days7–14 hr24 hr
IV2–4 daysend of infusion6–24 hr

Patient/Family Teaching

Pronunciation

divalproex sodium: dye-val-PROE-ex SOE-dee-um

valproate sodium: val-PROE-ate SOE-dee-um

valproic acid: val-PROE-ik AS-id