DEPAKOTE DR (Divalproex sodium DR)

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

• Divalproex sodium is available under the following different brand names: Depakote, Depakote ER, and Depakote Sprinkles.

Dosages of Divalproex Sodium:Dosage Forms and Strengths

Dosages expressed as valproic acid equivalents

Tablet, delayed-release (Depakote)

• 125mg
• 250mg
• 500mg

Tablet, extended-release (Depakote ER)

• 250mg
• 500mg

Capsule (Depakote Sprinkles)

• 125mg

Dosage Considerations – Should be Given as Follows: ManiaIndicated for the treatment of manic episodes associated with bipolar disorder

• Depakote initial dose: 750 mg/day orally in divided doses
• Depakote ER initial dose: 25 mg/kg orally once daily Increase as rapidly as possible to achieve the lowest therapeutic dose that provides desired clinical effect or plasma concentration
• Not to exceed 60 mg/kg/day

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
• Simple and complex absence seizures: Also 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 a daily dose greater than 250 mg, give a divided dose

Pediatric:

• 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 ProphylaxisIndicated for prophylaxis of migraine headaches; there is no evidence of use for acute treatment

• Depakote initial dose: 250 mg orally twice daily for 1 week
• Depakote ER initial dose: 500 mg orally once/day for 1 week
• May increase dose up to 1000 mg/day if needed

Dosage ModificationsConversion to monotherapy: Decrease concomitant anti-epilepsy drug dosage approximately 25% every 2 weeks

Renal impairment

• No adjustment is necessary; protein binding is reduced and may cause measurement of total valproate concentrations to be inaccurate

Hepatic impairment

• Administer lower doses
• Contraindicated in severe impairment

Dosing ConsiderationsMonitor liver function tests (LFT’s)

Conversion from Depakote to Depakote ER:

• Administered Depakote ER once daily using a dose 8-20% higher than the total daily dose of Depakote

Therapeutic range

• Low serum albumin levels may cause an increase in unbound drugs (while total concentration may appear normal)
• Epilepsy: 50-100 mcg/mL total valproate
• Mania: 50-125 mcg/mL total valproate; maximum concentrations generally achieved within 14 days

Administration

• Swallow whole, do not chew or crush
• Capsules may be opened and sprinkled on a spoonful of soft food immediately before administration
• If a dose is skipped, do not double the next dose

Depakote or Depakote Sprinkles:

• If a daily dose greater than 250 mg, give a divided dose

Depakote ER:

• Administer once daily.