Valproic acid

CLINICAL USE

Treatment of manic episodes associated with bipolar disorder

DOSE IN NORMAL RENAL FUNCTION

1–2 g daily in 2–3 divided doses

PHARMACOKINETICS

Molecular weight : 144.2

%Protein binding : 85–94

%Excreted unchanged in urine : <3

Volume of distribution (L/kg) : 0.1–0.4

half-life – normal/ESRD (hrs) : 14/Increased

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : Dose as in normal renal function

<10 : Start with a low dose, adjust according to response

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD : Not dialysed. Dose as in GFR <10 mL/min

HD : Dialysed. Dose as in GFR

<10 : mL/ min

HDF/high flux : Dialysed. Dose as in GFR

<10 : mL/ min

CAV/VVHD : Dialysed. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Anticoagulants: may increase anticoagulant effect of coumarins

Anti-epileptics: concentration reduced by carbamazepine, phenytoin and primidone; concentration of active carbamazepine metabolite increased; concentration of lamotrigine, primidone, active metabolite of primidone, and possibly ethosuximide increased; sometimes reduces concentration of active metabolite of oxcarbazepine; alters phenytoin concentration; phenytoin and primidone reduce valproate concentration

Antipsychotics: increased risk of neutropenia with olanzapine

Antivirals: may increase zidovudine levels and resulting toxicity

Ciclosporin: variable ciclosporin blood level response Cimetidine: valproate metabolism inhibited