VALPROIC ACID (DIVALPROEX SODIUM, SODIUM VALPROATE)
(val-proe'ic)
Depacon, Depakene, Depakote, Depakote ER, Depakote Sprinkle, Epival , Zalkote
Classifications: central nervous system (cns) agent; anticonvulsant; gaba inhibitor
Pregnancy Category: D

Availability

250 mg capsules; 125 mg sprinkle capsules; 125 mg, 250 mg, 500 mg delayed-release tablets; 500 mg sustained-release tablets; 250 mg/5 mL syrup; 100 mg/mL injection

Actions

Anticonvulsant unrelated chemically to other drugs used to treat seizure disorders. Mechanism of action unknown; may be related to increased bioavailability of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) to brain neurons. Inhibits secondary phase of platelet aggregation.

Therapeutic Effects

Depresses abnormal neuron discharges in the CNS, thus decreasing seizure activity.

Uses

Alone or with other anticonvulsants in management of absence (petit mal) and mixed seizures; mania; migraine headache prophylaxis.

Unlabeled Uses

Status epilepticus refractory to IV diazepam, petit mal variant seizures, febrile seizures in children, other types of seizures including psychomotor (temporal lobe), myoclonic, akinetic and tonic-clonic seizures, photosensitivity seizures, and those refractory to other anticonvulsants.

Contraindications

Hypersensitivity to valproate sodium; thrombocytopenia, patient with bleeding disorders or liver dysfunction or disease; cirrhosis, pancreatitis; congenital metabolic disorders, those with severe seizures, or on multiple anticonvulsant drugs; AIDS; pregnancy (category D), lactation; child <2 y; children <18 y for treatment of mania.

Cautious Use

History of kidney disease, renal impairment or failure; adjunctive treatment with other anticonvulsants; congenital metabolic disorders, those with severe epilepsy, use as sole anticonvulsant drug; hypoalbuminemia; organic brain syndrome; children <2 y especially in first 6 mo of therapy.

Route & Dosage

Note: May need to increase dose when converting from immediate release to extended-release products

Management of Seizures, Mania
Adult/Child: PO/IV 15 mg/kg/d in divided doses when total daily dose >250 mg, increase at 1 wk intervals by 5–10 mg/kg/d until seizures are controlled or adverse effects develop (max: 60 mg/kg/d)

Migraine Headache Prophylaxis
Adult: PO 250 mg b.i.d. (max: 1000 mg/d) or Depakote ER 500 mg q.d. x 1 wk, may increase to 1000 mg q.d.

Mania
Adult: PO 250 mg t.i.d. (max: 60 mg/kg/d)

Administration

Oral
Intravenous

PREPARE: IV Infusion: Dilute each dose in 50 mL or more of D5W, NS, or RL.  

ADMINISTER: IV Infusion: Give a single dose over at least 60 min (20 mg/min). Avoid rapid infusion.  

INCOMPATIBILITIES Solution/additive: No compatibility data available. Should avoid mixing with other drugs.

Adverse Effects (1%)

CNS: Breakthrough seizures, sedation, drowsiness, dizziness, increased alertness, hallucinations, emotional upset, aggression; deep coma, death (with overdose). GI: Nausea, vomiting, indigestion (transient), hypersalivation, anorexia with weight loss, increased appetite with weight gain, abdominal cramps, diarrhea, constipation, liver failure, pancreatitis. Hematologic: Prolonged bleeding time, leukopenia, lymphocytosis, thrombocytopenia, hypofibrinogenemia, bone marrow depression, anemia. Skin: Skin rash, photosensitivity, transient hair loss, curliness or waviness of hair. Endocrine: Irregular menses, secondary amenorrhea. Metabolic: Hyperammonemia (usually asymptomatic) hyperammonemic encephalopathy in patients with urea cycle disorders. Respiratory: Pulmonary edema (with overdose).

Diagnostic Test Interference

Valproic acid produces false-positive results for urine ketones, elevated AST, ALT, LDH, and serum alkaline phosphatase, prolonged bleeding time, altered thyroid function tests.

Interactions

Drug: Alcohol and other cns depressants potentiate depressant effects; other anticonvulsants, barbiturates increase or decrease anticonvulsant and barbiturate levels; haloperidol, loxapine, maprotiline, maois, phenothiazines, thioxanthenes, tricyclic antidepressants can increase CNS depression or lower seizure threshold; aspirin, dipyridamole, warfarin increase risk of spontaneous bleeding and decrease clotting; clonazepam may precipitate absence seizures; salicylates, cimetidine may increase valproic acid levels and toxicity. Mefloquine can decrease valproic acid levels; isoniazid may increase valproic acid levels and hepatotoxicity; meropenem may decrease valproic acid levels; cholestyramine may decrease absorption. Herbal: Ginkgo may decrease anticonvulsant effectiveness.

Pharmacokinetics

Absorption: Readily absorbed from GI tract. Peak: 1–4 h valproic acid; 3–5 h divalproex. Therapeutic Range: 50–100 g/mL. Distribution: Crosses placenta; distributed into breast milk. Metabolism: Metabolized in liver. Elimination: Excreted primarily in urine; small amount excreted in feces and expired air. Half-Life: 5–20 h.

Nursing Implications

Assessment & Drug Effects

Patient & Family Education


Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug