Divalproex sodium

A stable coordination compound comprised of sodium valproate and valproic acid used to treat manic episodes associated with bipolar disorder, epilepsy, and migraine headaches.

Brand names: Depakote, Depakote ER, and Depakote Sprinkles.

Dosages expressed as valproic acid equivalents

Tablet, delayed-release (Depakote)

125mg 250mg 500mg Tablet, extended-release (Depakote ER)

250mg 500mg Capsule (Depakote Sprinkles)


Indicated for treatment of manic episodes associated with bipolar disorder

Epilepsy: Complex partial seizures: Indicated as monotherapy and adjunctive therapy for complex partial seizures that occur either in isolation or in association with other types of seizures

Indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures

Adult: 10-15 mg/kg/day orally initially; may increase by 5-10 mg/kg/week to achieve optimal clinical response; not to exceed 60 mg/kg/day

Depakote: If daily dose greater than 250 mg, give as divided dose


10-15 mg/kg/day orally initially; may increase by 5-10 mg/kg/week to achieve optimal clinical response; not to exceed 60 mg/kg/day.

Children under 10 years: Safety and efficacy not established Migraine Prophylaxis

Indicated for prophylaxis of migraine headaches.

There is no evidence of use for acute treatment of migraine.

No adjustment necessary for renal impairment.

With liver impairment lower doses are required.

Low serum albumin levels may cause an increase in unbound drug.

The drug should be swallowed hole, is not chewed or crushed.

Capsules may be opened and sprinkled on spoonful of soft food immediately before administration

Common side effects include:



Weakness/lack of energy





Abdominal pain


Loss of appetite

Vision changes

Flu syndrome



Loss of control of bodily movements

Rapid, involuntary eye movements


Mood swings

Abnormal thinking.

Hair loss

Weight loss/weight changes




Runny or stuffy nose

Stomach upset

Changes in menstrual periods

Enlarged breasts


Unusual or unpleasant taste in mouth

Worsening depression

Suicidal thoughts or behavior

Unusual changes in mood or behavior

Acute or subacute cognitive decline and behavioral change.

Side effects include:

Hair texture and colorchange


Erythema multiforme

Toxic epidermal necrolysis

Stevens-Johnson syndrome

Elevated testosterone level

Nail and nailbed disorders

Weight gain

Absent, or absent viable sperm in semen.

Has no known severe interactions with other drugs.

Serious interactions of divalproex sodium include:





sodium oxybate

sodium phenylacetate


Divalproex sodium has mild-moderate interactions with many different drugs.

Hepatic failure resulting in fatalities has occurred

Children younger than 2 years are at increased risk for fatal hepatotoxicity

Should not be used in women of childbearing age unless the drug is essential to the management of the medical condition.

All non-pregnant women of childbearing potential should use effective birth control if taking this drug.

May cause neural tube defects, and increases risk for lower cognitive test scores compared with those exposed in utero to other antiseizure medications.

Women taking valproate should use effective contraception.

Life-threatening pancreatitis have been reported in children and adults



Liver disease

Urea cycle disorders

Mitochondrial disorders.

Migraine headache prevention in women who are pregnant or plan to become pregnant

Probability of thrombocytopenia increases significantly as total trough valproate plasma concentrations increase.

Hypothermia has been reported.

In utero exposure increases risk for poor cognitive outcomes and anatomical malformations, compared with 3 other common anti-epileptic drugs-carbamazepine, lamotrigine, phenytoin.

May produce false-positive urine ketone test and alter thyroid function tests.

Reversible cerebral and cerebellar atrophy have been reported.

May be associatedwith central nervous system (CNS) depression and impair physical or mental abilities.

Somnolence in the elderly can occur.

Should not be utilized in post-traumatic seizure prophylaxis in patients with acute head trauma as studies show increased mortality.

There is positive evidence of human fetal risk, so the drug should be used during pregnancy for seizures or manic episodes associated with bipolar disorder that are unresponsive to other treatments only in emergencies when no safer drug is available.

Has teratogenic side effects of causing neural tube defects as well as for a cognitive development in children exposed to valproate in utero.

Should not be used for migraine headache prevention as safer alternatives exist.

Children born to women who take the drug during pregnancy have an increased risk for lower cognitive test scores.

Can cause neural tube defects.

Is excreted in breast milk.

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