Yes

Anticonvulsant, Miscellaneous

Monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures (Depacon™, Depakote®)

Sole and adjunctive therapy of simple and complex absence seizures (Depacon™, Depakene®, Depakote®)

Adjunctively in patients with multiple seizure types that include absence seizures (Depacon™, Depakene®)

Mania (Depakote®)

Migraine (Deapakote®)

Unlabeled use: Behavior disorders in patients with Alzheimer's disease

D

Clinical effects on the fetus: Crosses the placenta. Neural tube, cardiac, facial (characteristic pattern of dysmorphic facial features), skeletal, multiple other defects reported. Epilepsy itself, number of medications, genetic factors, or a combination of these probably influence the teratogenicity of anticonvulsant therapy. Risk of neural tube defects with use during first 30 days of pregnancy warrants discontinuation prior to pregnancy and through this period of possible.

Breast-feeding/lactation: Crosses into breast milk. American Academy of Pediatrics considers compatible with breast-feeding.

Hypersensitivity to valproic acid or derivatives or any component; hepatic dysfunction

Hepatic failure resulting in fatalities has occurred in patients; children <2 years of age are at considerable risk; other risk factors include organic brain disease, mental retardation with severe seizure disorders, congenital metabolic disorders, and patients on multiple anticonvulsants. Hepatotoxicity has been reported after 3 days to 6 months of therapy. Monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause severe thrombocytopenia, inhibition of platelet aggregation and bleeding; tremors may indicate overdosage; use with caution in patients receiving other anticonvulsants.

Hyperammonemia may occur, even in the absence of overt liver function abnormalities. Asymptomatic elevations require continued surveillance; symptomatic elevations should prompt modification or discontinuation of valproate therapy. CNS depression may occur with valproate use. Patients must be cautioned about performing tasks which require mental alertness (operating machinery or driving). Effects with other sedative drugs or ethanol may be potentiated.

>10%:

Central nervous system: Somnolence, dizziness, headache

Gastrointestinal: Nausea, vomiting, diarrhea

Neuromuscular & skeletal: Weakness

Ocular: Diplopia, blurred vision

1% to 10%:

Cardiovascular: Peripheral edema

Central nervous system: Ataxia, emotional lability, abnormal thinking, amnesia, insomnia, nervousness

Dermatologic: Rash, alopecia

Endocrine & metabolic: Change in menstrual cycle

Gastrointestinal: Abdominal pain, anorexia, dyspepsia, increased appetite, constipation, weight gain or loss

Hematologic: Thrombocytopenia

Neuromuscular & skeletal: Tremor

Ocular: Nystagmus

Otic: Tinnitus

Respiratory: Flu syndrome, rhinitis

<1%: Erythema multiforme, hyperammonemia, pancreatitis, prolongation of bleeding time, transient increased liver enzymes, liver failure

Symptoms of overdose include coma, deep sleep, motor restlessness, visual hallucinations

Supportive treatment is necessary; naloxone has been used to reverse CNS depressant effects, but may block action of other anticonvulsants

CYP2C19 enzyme substrate; CYP2C9 and 2D6 enzyme inhibitor, CYP3A3/4 enzyme inhibitor (weak)

Valproic acid may displace clozapine from protein binding site resulting in decreased clozapine serum concentrations

Carbamazepine, lamotrigine, and phenytoin may induce the metabolism of valproic acid; monitor

Valproic acid may increase, decrease, or have no effect on carbamazepine and phenytoin levels

Valproic acid may increase serum concentrations of carbamazepine - epoxide (active metabolite); monitor

Cholestyramine may bind VPA in GI tract; monitor

Clarithromycin, erythromycin, troleandomycin, felbamate, and isoniazid may inhibit the metabolism of VPA; monitor

VPA inhibits the metabolism of lamotrigine; monitor

VPA appears to inhibit the metabolism of nimodipine and phenobarbital; monitor

Injection is physically compatible and chemically stable in D₅W, NS, and LR for at least 24 hours when stored in glass or PVC; store vials at room temperature 15°C to 30°C (59°F to 86°F)

Causes increased availability of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, to brain neurons or may enhance the action of GABA or mimic its action at postsynaptic receptor sites

Protein binding: 80% to 90% (dose dependent)

Metabolism: Extensively in the liver

Half-life (increased in neonates and patients with liver disease): Children: 4-14 hours; Adults: 8-17 hours

Time to peak serum concentration: Within 1-4 hours; 3-5 hours after divalproex (enteric coated)

Elimination: 2% to 3% excreted unchanged in urine

Children and Adults:

Children receiving more than 1 anticonvulsant (ie, polytherapy) may require doses up to 100 mg/kg/day in 3-4 divided doses

I.V.: Administer as a 60 minute infusion ( less than or equal to 20 mg/min) with the same frequency as oral products; switch patient to oral products as soon as possible

Rectal: Dilute syrup 1:1 with water for use as a retention enema; loading dose: 17-20 mg/kg one time; maintenance: 10-15 mg/kg/dose every 8 hours

Not dialyzable (0% to 5%)

Dosing adjustment/comments in hepatic impairment: Reduce dose

Alcohol: Additive CNS depression, avoid or limit alcohol

Food:

Valproic acid may cause GI upset; take with large amount of water or food to decrease GI upset. May need to split doses to avoid GI upset.

Food may delay but does not affect the extent of absorption

Coated particles of divalproex sodium may be mixed with semisolid food (eg, applesauce or pudding) in patients having difficulty swallowing; particles should be swallowed and not chewed

Valproate sodium oral solution will generate valproic acid in carbonated beverages and may cause mouth and throat irritation; do not mix valproate sodium oral solution with carbonated beverages

Milk: No effect on absorption; may take with milk

Sodium: SIADH and water intoxication; monitor fluid status. May need to restrict fluid.

Liver enzymes, CBC with platelets

Therapeutic: 50-100 mg/mL (SI: 350-690 mmol/L); Toxic: >200 mg/mL (SI: >1390 mmol/L). Seizure control may improve at levels >100 mg/mL (SI: 690 mmol/L), but toxicity may occur at levels of 100-150 mg/mL (SI: 690-1040 mmol/L).

False-positive result for urine ketones

No information available to require special precautions

No effects or complications reported

When used to treat generalized seizures, patient instructions are determined by patient's condition and ability to understand.

Pregnancy precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures.

Do not crush enteric coated drug product or capsules

Capsule, sprinkle, as divalproex sodium (Depakote® Sprinkle®): 125 mg

Capsule, as valproic acid (Depakene®): 250 mg

Injection, as sodium valproate (Depacon™): 100 mg/mL (5 mL)

Syrup, as sodium valproate (Depakene®): 250 mg/5 mL (5 mL, 50 mL, 480 mL)

Tablet, delayed release, as divalproex sodium (Depakote®): 125 mg, 250 mg, 500 mg

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