Adult:
Given as valproate semisodium: Initially, 250 mg bid. Max: 1000 mg daily. Elderly: Initiate at lower dose and increase slowly.
Oral
TREATMENT OF ACUTE MANIC EPISODES
Adult:
Given as valproate semisodium: Initially, 750 mg daily in divided doses, increase as fast as possible to achieve optimal response or desired range of trough plasma concentrations between 50-125 mcg/ml.
Max Dosage: 60 mg/kg daily.
Oral
COMPLEX PARTIAL SEIZURES
Adult:
Oral
COMPLEX PARTIAL SEIZURES
Adult:
As monotherapy, conversion to monotherapy or adjunctive therapy: Given as valproic acid or valproate semisodium, initially 10-15 mg/kg/day in 2-4 divided doses, increased by 5-10 mg/kg/wk. Max: 30mg/kg/day. Given as sodium valproate, 600 mg daily in 2 divided doses, increased by 200 mg every 3 days. Usual range: 1-2 g daily (20 - 30 mg/kg daily). Max: 2.5 g daily.
Oral
SIMPLE AND COMPLEX ABSENCE SEIZURES
Adult:
As monotherapy, conversion to monotherapy or adjunctive therapy: Given as valproic acid or valproate semisodium, initially 15 mg/kg/day in 2-4 divided doses, increased by 5-10 mg/kg/wk. Max: 30 mg/kg/day.
Oral
SIMPLE AND COMPLEX ABSENCE SEIZURES
Child:
As monotherapy, conversion to monotherapy or adjunctive therapy: Given as sodium valproate: >20kg: 400 mg/day in 2 divided doses, increased gradually until control achieved. Usual range: 20-30 mg/kg/day. Max: 35mg/kg/day. <20kg: 20mg/kg daily in 2 divided doses, increased to 40mg/kg daily with serum valproic acid monitoring in severe cases. Monitor clinical chemistry and haematological parameters if > 40mg/kg daily. Given as valproic acid or valproate semisodium ≥10 yr: Initially 15 mg/kg/day in 2-4 divided doses, increased by 5-10 mg/kg/wk. Max: 30mg/kg/day.
Elderly: Initiate at lower dose and increase slowly.
Oral
TREATMENT OF BIPOLAR DISORDERS
Adult:
As valpromide: 900-1800 mg daily in 2 divided doses. Usual dose: 1200 mg daily. Initiate at required dose or dosage may be increased every 2-3 days to reach optimal dose in 2 wk with simultaneous and progressive dose reduction of concurrent psychotropic drugs.
Intravenous
COMPLEX PARTIAL SEIZURES
Adult:
Given as sodium valproate: Initially 400-800 mg daily increasing by 150-300 mg every 3 days until control is achieved. Usual dose: 20-30 mg/kg/day. Daily doses to be given in 3-4 divided doses. Each dose to be given as slow IV Inj over 3-5 minutes or by infusion in 0.9% saline or 5% dextrose over 60 minutes (Max rate: 20 mg/minute). Max: 2.5 g daily.
Intravenous
COMPLEX PARTIAL SEIZURES
Child:
Given as sodium valproate: Initially 300mg/day increased until control is achieved. Usual range: 20-30 mg/kg/day. Max: 40 mg/kg/day with plasma valproic acid levels monitoring.
Elderly: Initiate at lower dose and increase slowly.
Intravenous
SIMPLE AND COMPLEX ABSENCE SEIZURES
Adult:
Given as sodium valproate: Initially 400-800 mg daily increasing by 150-300 mg every 3 days until control is achieved. Usual dose: 20-30 mg/kg/day. Daily doses to be given in 3-4 divided doses. Each dose to be given as slow IV Inj over 3-5 minutes or by infusion in 0.9% saline or 5% dextrose over 60 minutes (Max rate: 20 mg/minute). Max: 2.5 g daily.
Oral
SIMPLE AND COMPLEX ABSENCE SEIZURES
Child:
Given as sodium valproate: Initially 300mg/day increased until control is achieved. Usual range: 20-30 mg/kg/day. Max: 40 mg/kg/day with plasma valproic acid levels monitoring.
Elderly: Initiate at lower dose and increase slowly.
Administration
Should be taken with food.
Precautions
Increased risk of hepatotoxicity in children <2 yr, congenital metabolic disorders, organic brain disease or severe seizure disorders. HIV or cytomegalovirus (CMV) infection; renal impairment; SLE; lactation. Monitor LFT before and during the 1st 6 mth of therapy. Monitor blood cell count (including platelet count), bleeding time and coagulation tests before the start of therapy or before surgery, and in cases of spontaneous bruising or bleeding. Watch out for signs of pancreatitis (e.g. abdominal pain, nausea, vomiting and anorexia), blood and liver toxicity and seek prompt medical advice. Decrease dose or discontinue in patients with excessive somnolence, decreased food or fluid intake. Gradual withdrawal or transition to and from another type of antiepileptic therapy. Suspect hyperammonemic encephalopathy and measure ammonia levels in patients who develop unexplained lethargy, vomiting or changes in mental status. Decrease GI side effects by taking with meals, starting with low dose or taking the enteric coated formulations.
Potentially Life-threatening
Adverse Drug Reactions
Fatal hepatotoxicity esp in children <2 yr, multi-organ hypersensitivty reactions, pancreatitis, blood dyscrasias.
Interactions
Increased risk of convulsions with mefloquine. Increased risk of carnitine deficiency with pivmecillinam and pivampicillin. Increased risk of toxicity with bupropion.
Increased risk of hepatotoxicity and carbamazepine toxicity with a decrease in valproic acid levels with concurrent carbamazepine. Decreased valproic acid and increased ethosuximide serum levels with ethosuximide. Decreased valproic acid levels with carbapenems, rifampicin, phenytoin, phenobarbital (or primidone) and antineoplastic drug regimens. Increased valproic acid levels with felbamate and aspirin. Increased risk of hepatotoxicity with olanzepine. Concurrent use increased phenobarbital, nimodipine, nifedipine, lamotrigine, zidovudine, amitriptyline, nortriptyline and benzodiazepines levels. Concurrent use decreased tigabine and clozapine levels. Increased risk of absence status with clonazepam. Increased risk of hyperammonemia with topiramate. Increased free valproic acid concentrations with highly protein bound drugs.
