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Generic Name: valproic acid

(val proe ik)

valproic acid: Apo-Valproic Acid (CAN), Gen-Valproic

(CAN), Novo-Valproic (CAN), Nu-Valprox (CAN), ratioValproic (CAN)

Capsules: Depakene

is a compound containing equal proportions of valproic

acid and sodium valproate.
Indications
Sole and adjunctive therapy in simple (petit mal) and
complex absence seizures
Depakote ER: Treatment of epilepsy in children > 10
yr; treatment of acute manic or mixed episodes
associated with bipolar disorder, with or without
psychotic features

sodium valproate

Adjunctive therapy with multiple seizure types,

including absence seizures

Syrup:

Depakote ER: Treatment of bipolar mania

Depakene

Depakote, Depacote ER: Prophylaxis of migraine

headaches

valproate acid
Injection: Depacon, Epiject (CAN), divalproex sodium
Tablets, enteric coated: Depakote, Depakote ER,
Depakote Sprinkle, Divalproex, Epival (CAN)

Divalproex, sodium valproate injection: Treatment of

complex partial seizures as monotherapy or with other
antiepileptics

Drug class - Antiepileptic

Unlabeled uses: Adjunct in symptom management of

schizophrenia, treatment of aggressive outbursts in
children with attention-deficit hyperactivity disorder,
organic brain syndrome

Therapeutic actions

Contraindications and cautions

Mechanism of action not understood: antiepileptic

activity may be related to the metabolism of the
inhibitory neurotransmitter, GABA; divalproex sodium

Contraindicated with hypersensitivity to valproic acid,

hepatic disease or significant hepatic impairment.

Pregnancy Category D

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Use cautiously with children < 18 mo; children < 2 yr,
especially with multiple antiepileptics, congenital
metabolic disorders, severe seizures accompanied by
severe mental retardation, organic brain disorders
(higher risk of developing fatal hepatotoxicity);
pregnancy (fetal neural tube defects; do not
discontinue to prevent major seizures; discontinuing
such medication is likely to precipitate status
epilepticus, hypoxia and risk to both mother and
fetus); lactation.

Acute mania or bipolar disorder: Initially, 25 mg/kg/day

PO once daily. Dose should be increased rapidly to
achieve the lowest therapeutic dose. Maximum dose
60 mg/kg/day PO (Depakote ER only).

Available forms

PEDIATRIC PATIENTS > 10 YR 10-15 mg/kg/day PO.

Capsules250 mg; syrup250 mg/5 mL;

PEDIATRIC PATIENTS Use extreme caution. Fatal

hepatotoxicity has occurred. Children < 2 yr are
especially susceptible. Monitor all children carefully.

DR tablets125, 250, 500 mg;

Bipolar mania: 750 mg PO daily in divided doses; do

not exceed 60 mg/kg/day (Divalproex DR tablets only).
Migraine: 250 mg PO bid; up to 1,000 mg/day has
been used (Divalproex DR tablets); 500 mg ER tablet
once a day.

sprinkle capsules125
mg;

Route

Onset

Peak

injection100 mg/mL;

Oral

Varies

14 hr

ER tablets250, 500 mg

IV

Rapid

1 hr

Dosages
ADULTS: Dosage is expressed as valproic acid
equivalents. Initial dose is 1015 mg/kg/day PO,
increasing at 1-wk intervals by 510 mg/kg/day until
seizures are controlled or side effects preclude further
increases. Maximum recommended dosage is 60
mg/kg/day PO. If total dose > 250 mg/day, give in
divided doses.

Pharmacokinetics

Metabolism: Hepatic;
T1/2: 616 hr

Distribution: Crosses placenta; enters breast milk

Excretion: Urine
IV facts
Preparation: Dilute vial in 5% dextrose injection, 0.9%
sodium chloride injection or lactated Ringers injection.
Stable for 24 hr at room temperature. Discard unused
portions.

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Infusion: Administer over 60 min, not more than 20
mg/min. Do not use > 14 days; switch to oral products
as soon as possible.

Adverse effects
CNS: Sedation, tremor (may be dose-related),
emotional upset, depression, psychosis, aggression,
hyperactivity, behavioral deterioration, weakness

Complex interactions with phenytoin; breakthrough

seizures have occurred with the combination of
valproic acid and phenytoin
Increased serum levels and toxicity with salicylates,
cimetidine, chlorpromazine, erythromycin, felbamate
Decreased effects with carbamazepine, rifampin,
lamotrigine
Decreased serum levels with charcoal

Dermatologic: Transient increases in hair loss, rash,

petechiae

Increased sedation with alcohol, other CNS

depressants

GI: Nausea, vomiting, indigestion, diarrhea, abdominal

cramps, constipation, anorexia with weight loss,
increased appetite with weight gain, life-threatening
pancreatitis, hepatic failure

Drug-lab test
test

GU: Irregular menses, secondary amenorrhea

Hematologic: Slight elevations in AST, ALT, LDH;
increases in serum bilirubin, abnormal changes in
other LFTs, altered bleeding time; thrombocytopenia;
bruising; hematoma formation; frank hemorrhage;
relative lymphocytosis; hypofibrinogenemia;
leukopenia, eosinophilia, anemia, bone marrow
suppression

Interactions
Drug-drug
Increased serum phenobarbital,
primidone, ethosuximide, diazepam, zidovudine levels

False interpretation of urine ketone

Assessment
History: Hypersensitivity to valproic acid; hepatic
impairment; pregnancy, lactation
Physical: Weight; skin color, lesions; orientation, affect,
reflexes; bowel sounds, normal output; CBC and
differential, bleeding time tests, LFTs, serum ammonia
level, exocrine pancreatic function tests, EEG
Interventions
Give drug with food if GI upset occurs; substitution of
the enteric-coated formulation also may be of benefit;
have patient swallow SR tablet whole; do not cut,
crush, or chew.

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WARNING: Reduce dosage, discontinue, or substitute
other antiepileptics gradually; abrupt discontinuation
of all antiepileptics may precipitate absence seizures.
BLACK BOX WARNING: Arrange for frequent LFTs;
discontinue drug immediately with significant hepatic
impairment, suspected or apparent significant hepatic
impairment; continue LFTs to determine if hepatic
impairment progresses in spite of drug discontinuation.
WARNING: Arrange for patient to have platelet counts,
bleeding time determination before therapy,
periodically during therapy, and prior to surgery.
Monitor patient carefully for clotting defects (bruising,
blood-tinged toothbrush). Discontinue if there is
evidence of hemorrhage, bruising, or disorder
ofhemostasis.
Monitor ammonia levels, and discontinue if there is
clinically significant elevation in level.
Monitor serum levels of valproic acid and other
antiepileptic drugs given concomitantly, especially
during the first few weeks of therapy. Adjust dosage on
the basis of these data and clinical response.
BLACK BOX WARNING: Arrange for counseling for
women of childbearing age who wish to become
pregnant; drug may be teratogenic.
BLACK BOX WARNING: Discontinue drug at any sign of
pancreatitis.

WARNING: Evaluate for therapeutic serum levels

usually 50100 mcg/mL.
Teaching points
Take this drug exactly as prescribed. Do not chew
tablets or capsules before swallowing them. Swallow
them whole to prevent local irritation of mouth and
throat. Sprinkle tablets may be opened and sprinkled
on applesauce or pudding.
Do not discontinue this drug abruptly or change
dosage, except on the advice of your health care
provider.
Avoid alcohol and sleep-inducing and over-the-counter
drugs. These could cause dangerous effects.
Have frequent checkups, including blood tests, to
monitor your drug response. Keep all appointments for
checkups.
Use contraceptive techniques at all times. If you want
to become pregnant, consult your health care provider.
Wear a medical ID tag to alert emergency medical
personnel that you have epilepsy and are taking
antiepileptic medication.
If you have diabetes, this drug may interfere with urine
tests for ketones.
You may experience these side effects: Drowsiness
(avoid driving or performing other tasks requiring

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alertness; take at bedtime); GI upset (take with food or
milk, eat frequent small meals; if problem persists,
substitute enteric-coated drug); transient increase in
hair loss.

Report bruising, pink stain on the toothbrush,

yellowing of the skin or eyes, pale feces, rash,
pregnancy; abdominal pain with nausea, vomiting,
anorexia.