VALPROATE/DIVALPROEX

Indications & Dose:

Simple, complex (petit mal) absence, mixed, tonic-clonic (grand mal) seizures, mania in bipolar disorders in adults (divalproex sodium), prophylaxis of adult migraine (divalproex sodium)

• BY MOUTH

Adult

Epilepsy •  PO for monotherapy 5-15 mg/kg/ day divided in 1-3 doses, may increase by 5-10 mg/kg/ day qwk; for polytherapy, initial dose 14-30 mg/ kg/ day, if dose exceeds 250 mg qd, divide into 2 or more doses, max 60 mg/kg/day; IV same as PO; administer as 60 min infusion at a rate not exceeding 20 mg/min

Mania: (Divalproex sodium) • PO 750 mg/day in divided doses; increase until desired effect or plasma concentration at trough of 50- 1 25 ug/ml; max 60 mg/kg/day Migraine:

• PO 250 mg bid; dose may be increased up to 1000 mg/d if necessary

Children

• PO same as adult; children receiving polytherapy may require doses up to 100 mg/kg/day in 3-4 divided doses

• RECT dilute syr 1:1 with water; give loading dose 17-20 mg/kg once as retention enema; maintenance 10-l5 mg/kg/day q8h 

Contraindications:

Hepatic disease. 

Side Effects:

Cautions:

Precautions:

Renal disease, Addison’s disease, blood dyscrasias; children <2 yr, patients with organic brain disease, and patients on multiple anticonvulsants (polytherapy) at increased risk of hepatotoxicity

Interaction:

Drugs

Carbamazepine, phenytoin: Increase, decrease, or no effect on carbamazepine and phenytoin concentrations

Cholestyramine,colestipol: Reduced absorption of valpruic acid

Clorithromycin, erythromycin. troleandomycin: Increased valproic acid concentrations

Clonazepam: Absence seizure reported with concurrent use

Clozapine: Reduced serum clozapine concentrations

Felbamate: Increased valproic acid concentrations

Isoniazid: Increased valproic acid concentrations

Lamotrigine: Increased plasma lamotrigine concentrations; decreased valproic acid concentrations

Nimodipine: Increased nimodipine area under the plasma concentration time curve

Phenobarbital, primidone: Increased phenobarbital levels

Salicylates: Increased valproate levels

Zidovudine: Increased zidovudine levels

Warnings:

Adverse Effects:

Lactations:

Teratogenic; increased risk of neural tube defects (1%-2% when used between day 17-30 after fertilization); compatible with breast feeding 

Special Precautions:

Counselling:

Side Effects Or Adverse Reactions:

CNS: Ataxia, behavioral changes, coma, depression, diplopia, dizziness, drowsiness, encephalopathy, hallucinations, headache, incoordination, nystagmus, paresthesia,. sedation, tremors

GI: Anorexia, constipation, cramps, diarrhea, heartburn, hepatic failure, nausea, pancreatitis, stomatitis, vomiting

GU: Amenorrhea, breast enlargement, enuresis, galactorrhea, irregular menses

HEME: Anew, hypoftbrittogenemia, leukopenia, lymphocytosis, thrombocytopenia

METAB: Abnormal thyroid function tests, carnitine deficiency, hyperammonemia, hyperglycemia, hyponatremia, syndrome of inappropriate antidiuretic hormone release

SKIN: Alopecia, erythema multiform, pruritus, rash, Steven-Johnson syndrome 

Patient And Carer Advice: