Divalproex Sodium information from DrugsUpdate
P - Contraindicated in pregnancy
L - Caution when used during lactation
Divalproex sodium consists of a compound of sodium valproate and valproic acid in a 1:1 molar relationship in an enteric coated form. It is used in the UK, Canada, and U.S. for the treatment of the manic episodes of bipolar disorder. In rare cases, it is also used as a treatment for major depressive disorder, and increasingly taken long-term for prevention of both manic and depressive phases of bipolar disorder, especially the rapid-cycling variant. It is also used in the US for the treatment of epilepsy, chronic pain associated with neuropathy, and migraine headaches. Its chemical name is sodium hydrogen bis(2-propylpentanoate). The extended release formulation allows for a single daily dose.
In the UK semisodium valproate has been sold for a few years as the proprietary drug Depakote and marketed for psychiatric conditions only. It is about five times the price of sodium valproate, which has been marketed for around 30 years as Epilim by the same company for epilepsy and is also available from other manufacturers as a generic product.
Pharmacodynamics
Pharmacokinetics
Divalproex sodium dissociates to the valproate ion in the GI tract. It is thought to work by increasing brain concentrations of GABA which may also play an important role in the prevention of migraine attacks.
Distribution: Plasma protein binding ranges from 10-18.5%.
Metabolism: Almost entirely by liver.
Divalproex Sodium Indications / Divalproex Sodium Uses
Information Not Available
Divalproex Sodium Adverse Reactions / Divalproex Sodium Side Effects
Behavioural/mood changes; hyperammonaemia; pancreatitis, thrombocytopenia. Abdominal cramps, anorexia, diarrhoea, hair loss, indigestion, nausea and vomiting; tremor; unusual weight loss or gain.
Potentially Fatal: Hepatic failure, pancreatitis.
Precautions
Information Not Available
Special Precautions
Children <2 yr; congenital metabolic disorders; organic brain disease or severe seizure disorders; HIV infection; renal impairment; lactation. Monitor liver function before and during the 1st 6 mth of therapy. Monitor platelet function, signs of pancreatitis and SLE. Gradual withdrawal of valproate. May impair ability to drive or operate machinery. Increased risk of hyperammonaemic encephalopathy in patients with urea cycle disorders.
Other Drug Interactions
Felbamate increases valproate levels. Phenytoin, phenobarbitone and carbamazepine lower valproate levels. Increased risk of hepatotoxity with hepatotoxic drugs.
Potentially Fatal: Potentiates action of CNS depressants (barbiturates, primidone) and alcohol.
Other Interactions
Food Interaction: Food may delay the extent of absorption. Divalproex may cause GI upset; take with large amount of water of food to decrease GI upset.
Dosage
Oral
Primary generalised seizures
Adult: Initially, 10-15 mg/kg/day in 2-4 divided doses, if necessary, increase at 5-10 mg/kg/wk. Max: 60 mg/kg/day.
Child: ≥10 yr: Initially, 10-15 mg/kg/day in 2-4 divided doses, if necessary, increase at 5-10 mg/kg/wk. Max: 60 mg/kg/day.
Oral
Partial seizures
Adult: Initially, 10-15 mg/kg/day in 2-4 divided doses, if necessary, increase at 5-10 mg/kg/wk. Max: 60 mg/kg/day.
Child: ≥10 yr: Initially, 10-15 mg/kg/day in 2-4 divided doses, if necessary, increase at 5-10 mg/kg/wk. Max: 60 mg/kg/day.
Oral
Acute manic episodes of bipolar disorder
Adult: Initially, 25 mg/kg once daily, may increase rapidly to achieve optimal response at the lowest therapeutic dose. Max: 60 mg/kg/day.
Oral
Migraine prophylaxis
Adult: 500 mg once daily for 1 wk, may increase to 1000 mg once daily.
Food(before/after)
Should be taken with food
List of Contraindications
Divalproex Sodium and Pregnancy
Contraindicated in pregnancy
Divalproex Sodium and Lactation
Caution when used during lactation
Divalproex Sodium and Children
Information Not Available
Divalproex Sodium and Geriatic
Information Not Available
Divalproex Sodium and Other Contraindications
Hepatic disease or severe hepatic impairment; porphyria. Pregnancy.
Storage
Oral: Store at 15-30°C.
Lab interference
Oral: Store at 15-30°C.
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