Valproic acid
Synonym :
Sodium Valproate
Mechanism :
The mechanisms by which valproate exerts its therapeutic effects have not been established. It has been suggested that its activity in epilepsy is related to increased brain concentrations of gamma-aminobutyric acid (GABA).
Indication :
- Generalized tonic-clonic seizures
- Generalized absence seizures
- Generalized atonic seizures
- Generalized myoclonic seizures
- Photosensitive epilepsy
- Mania
- Choreoathetosis
- Infantile spasms
Contraindications :
Contraindicated in patients with known hypersensitivity to the drug, in patients with known urea cycle disorders, in active liver disease and family history of liver dysfunction, and in porphyria.
Dosing :
Oral: Start with 10-15 mg/kg/day in 2 divided doses and maintain at 30-60 mg/kg/day. Even doses of 30-40 mg/kg/day have been used in infantile spasms. Max dose: 60 mg/kg/day.
Status Epilepticus:
Loading dose: 20 mg/kg IV, then 10 mg/kg/dose every 12 hours.
Adverse Effect :
Drowsiness, nausea, diarrhea, tremor, thrombocytopenia, weight gain, rarely weight loss, hair loss (usually transient within first 6 months). The risk of hepatotoxicity with sodium valproate appears to be greatest in children <3 years of age with severe epilepsy, other neurological problems and/or receiving at least one other antiepileptic.
Interaction :
Ethosuximide: Synergy in absence (typical and atypical) and myoclonic seizures
Lamotrigine: Synergistic in absence (typical and atypical), tonic-clonic and myoclonic seizures.
Phenytoin: May increase free phenytoin levels.
Antidepressants, Antipsychotics, Chloroquine and Mefloquine: Anti-convulsant effect may be antagonized.
Carbamazepine: Often lowers plasma concentration of sodium valproate.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in normal renal function |
| HD | Not dialysed. Dose as in normal renal function |
| HDF/High flux | Dialysed. Dose as in normal renal function |
| CAV/VVHD | Unknown dialysability. Dose as in normal renal function |
Hepatic Dose :
Use is not recommended in hepatic impairment as clearance of the drug is reduced and in severe hepatic impairment, the use of this drug is contraindicated. Drug clearance may be decreased by 50% in cirrhosis.