|VALPROIC ACID (DIVALPROEX SODIUM, SODIUM VALPROATE)
Depacon, Depakene, Depakote, Depakote ER, Depakote Sprinkle, Epival , Zalkote
Classifications: anticonvulsant; gamma-aminobutyric acid (gaba) inhibitor; Therapeutic: anticonvulsant
Pregnancy Category: D
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
Anticonvulsant whose mechanism of action is believed to be related to increased bioavailability of the inhibitory neurotransmitter
gamma-aminobutyric acid (GABA) to brain neurons. It may also suppress repetitive neuronal firing through inhibition of voltage-sensitive
Depresses abnormal neuron discharges in the CNS, thus decreasing seizure activity.
Alone or with other anticonvulsants in management of absence (petit mal) and mixed seizures; mania; migraine headache prophylaxis.
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.
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;
encephalopathy; AIDS; pregnancy (category D); child <2 y; children <18 y for treatment of mania.
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; HIV; hypoalbuminemia; organic brain syndrome.
Route & Dosage
Note: May need to increase dose when converting from immediate release to extended release products Management of Seizures
Adult/Child (≥10 y): PO/IV 1015 mg/kg/d in divided doses when total daily dose >250 mg, increase at 1 wk intervals by 510 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.
Adult: PO 250 mg t.i.d. (max: 60 mg/kg/d)
Dose reduction recommended.
- Give tablets and capsules whole; instruct patient to swallow whole & not to chew. Instruct to swallow sprinkle capsules
whole or sprinkle entire contents on teaspoonful of soft food, and instruct to not chew food.
- Avoid using a carbonated drink as diluent for the syrup because it will release drug from delivery vehicle; free drug painfully
irritates oral and pharyngeal membranes.
- Reduce gastric irritation by administering drug with food because serious GI adverse effects can lead to discontinuation
of therapy. Enteric-coated tablet or syrup formulation is usually well tolerated.
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: 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,
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.
and other cns depressants
potentiate depressant effects; other anticonvulsants
increase or decrease anticonvulsant and barbiturate
levels; haloperidol, loxapine, maprotiline, maoi
, tricyclic antidepressants
can increase CNS depression
or lower seizure threshold; aspirin, dipyridamole, warfarin
increase risk of spontaneous bleeding; clonazepam
may precipitate absence seizures; salicylates
, cimetidine, isoniazid
may increase valproic acid levels and toxicity. Mefloquine
can decrease valproic acid levels; meropenem
may decrease valproic acid levels; cholestyramine
may decrease absorption. Herbal: Ginkgo
may decrease anticonvulsant effectiveness.
Readily from GI tract. Peak:
14 h valproic acid; 35 h divalproex. Therapeutic Range:
50100 mcg/mL. Distribution:
Crosses placenta; distributed into breast milk. Metabolism:
In liver. Elimination:
Primarily in urine; small amount in feces and expired air. Half-Life:
Assessment & Drug Effects
- Monitor for therapeutic effectiveness achieved with serum levels of valproic acid at 50100 mcg/mL.
- Monitor patient alertness especially with multiple drug therapy for seizure control. Evaluate plasma levels of the adjunctive
anticonvulsants periodically as indicators for possible neurologic toxicity.
- Monitor patient carefully during dose adjustments and promptly report presence of adverse effects. Increased dosage is associated
with frequency of adverse effects.
- Lab tests: Perform baseline platelet counts, bleeding time, and serum ammonia, then repeat at least q2mo, especially during
the first 6 mo of therapy.
- Multiple drugs for seizure control increase the risk of hyperammonemia, marked by lethargy, anorexia, asterixis, increased
seizure frequency, and vomiting. Report such symptoms promptly to physician. If they persist with decreased dosage, the
drug will be discontinued.
Patient & Family Education
- Do not discontinue therapy abruptly; such action could result in loss of seizure control. Consult physician before you stop
or alter dosage regimen.
- Note to diabetic patients: Drug may cause a false-positive test for urine ketones. Notify physician if this occurs; a differential
diagnostic blood test may be indicated.
- Notify physician promptly if spontaneous bleeding or bruising occurs (e.g., petechiae, ecchymotic areas, otorrhagia, epistaxis,
- Withhold dose and notify physician for following symptoms: visual disturbances, rash, jaundice, light-colored stools, protracted
vomiting, diarrhea. Fatal liver failure has occurred in patients receiving this drug.
- Avoid alcohol and self-medication with other depressants during therapy.
- Consult physician before using any OTC drugs during anticonvulsant therapy. Combination drugs containing aspirin, sedatives,
and medications for hay fever or other allergies are particularly UNSAFE.
- Do not drive or engage in potentially hazardous activities until response to drug is known.
- Inform doctor or dentist before any kind of surgery that you are taking valproic acid.
- Carry medical identification card at all times. It needs to indicate medical diagnosis, medication(s), physician's name,
address, and telephone number.