Divalproex Sodium

Anti-epileptic · Carboxylic acid derivative

Indications

Syp/Tab: All forms of epilepsy. Migraine prophylaxis. Inj: For patients temporarily unable to take oral valproate.

Dosage

Adults: ORAL: Complex Partial Seizures: Initial: 10-15 mg/kg/day. Titrate: Increase by 5-10 mg/kg/wk. Max: 60 mg/kg/day. Absence Seizures: Initial: 15 mg/kg/day. Titrate: Increase by 5-10 mg/kg/wk. Max: 60 mg/kg/day. Bipolar Disorder: Manic Episodes: Initial: 750 mg in divided doses. Titrate: Increase rapidly to clinical effect. Max: 60 mg/kg/day. Migraine prophylaxis: Starting dose 250 mg twice daily, some patients may benefit from upto 1000 mg/day. Adults: INJECTION: Initiation of valproate treatment by IV administration. Initially 10 mg/kg (usually 400-800 mg) by IV injection (over 3-5 mins) followed by IV infusion or IV injection (over 3-5 mins) in 2-4 divided doses or by continuous IV infusion up to max 2.5 gm daily; usual range 1-2 gm daily(20-30 mg/kg daily). Children: All forms of epilepsy: ORAL: Neonate, initially 20 mg/kg once daily; usual maintenance dose 10 mg/kg twice…

Administration

IV: Following dilution to final concentration, administer over 60 min at a rate of <20 mg/min. Alternatively, single doses upto 15 mg/kg have been administered as a rapid infusion over 5-10 min (1.5-3 mg/kg/min). Reconstitution: Injection should be diluted in 50 mL of a compatible diluent. Compatibility: Physically compatible and chemically stable in D5W, NS and LR for at least 24 hours when stored in glass or PVC. See manufacturer direction. Stability: Store vial at room temperature 15°C-30°C.

Adverse Effects

GI upset, weight gain, hair loss, angioedema, thrombocytopenia, agranulocytosis, bone-marrow failure, rash, pancreatitis, liver injury, tremor, extrapyramidal disorder, stupor, somnolence, convulsions, memory impairment, headache, nystagmus, confusion, aggression, agitation, disturbed attention, hyponatraemia, anaemia, alopecia, dysmenorrhoea, haemorrhage, deafness, hepatic failure, hyperammonaemia.

Risk Factor (Pregnancy/Lactation)

Pregnancy: Positive evidence of risk: Use only when no safer alternative exists for a serious problem. Lactation: Contraindicated or not recommended. Contraindications: Active liver disease, history of hepatic disease, porphyria. Pancreatitis, POLG-related disorders. Precautions: Women of child bearing age. Perform LFTs, blood tests prior to therapy. Renal impairment, SLE, diabetes. Warn patients of risk of wt gain. Monitor patients for suicidal thoughts or behaviour.

Interactions

Barbiturates, MAOIs, anticonvulsants and thymoleptics e.g. imipramine, salicylates, antipsychotics, antidepressants, benzodiazepines, carbamazepine, lamotrigine, phenobarbital, primidone, phenytoin, zidovudine, felbamate, mefloquine, coumarin anticoagulants, cimetidine, erythromycin, colestyramine, carbapenem antibiotics, St John's wort.

Advice to Patient

Take with meals. Do not crush or chew capsule or enteric coated tablet, swallow whole. Delayed-release sprinkle capsules may be opened and contents mixed with food for easier swallowing. Contact prescriber if there is change in menstrual pattern, vomiting, constipation, unrelieved diarrhoea, skin rash, stomach cramps, constant stomach pain, facial swelling, malaise, weakness, unusual bruising or bleeding, blood in urine/stool/vomitus, increased sleepiness, restlessness, yellowing of skin or eyes. Avoid alcohol during therapy. Take sufficient amount of fluids (2-3 litres per day) to maintain hydration, unless restricted by the prescriber. If you have diabetes, check blood glucose level regularly.

Pharmacokinetics

Metabolism: Extensively hepatic. Bioavailability: Depakote ER: Approx. 90% relative to IV dose and approx. 89% relative to delayed release formulation. In paediatric patients 10-17 yrs of age, once-daily administration of Depakote-ER produced valproate plasma concentration-time profiles similar to adults. Half-life elimination: (Increased in neonates, elderly, and patients with liver impairment): Newborns (exposed to VPA in utero): 30-60 hrs. Neonates first wk of life: 40-45 hrs. Neonates <10 days: 10-67 hrs. Children >2 mths: 7-13 hrs. Children and Adolescents 2-14 yrs: 9 hrs. Adults: 9-19 hrs. Time to peak, serum: Oral: Depakote tab and sprinkle caps: Approx. 4 hrs; Depakote ER: 4-17 hrs; Stavzor: 2 hrs; Epival: 4 hrs. Rectal (off-label route): 1-3 hrs. Excretion: Urine (30%-50% as glucuronide conjugate, <3% as unchanged drug); children >10 yrs of age have pharmacokinetic parameters…

Brands with this active ingredient

Compiled by Healify Pharmacy from published drug references. How we compile it →

Always consult a pharmacist or doctor.