sodium valproate

CLINICAL USE

All forms of epilepsy

DOSE IN NORMAL RENAL FUNCTION

Oral: 600 mg – 2.5 g daily in divided doses IV: For continuation of existing oral —therapy, IV and oral doses are equivalent, give the same dose. For initiation of new therapy: give —a loading dose of 400–800 mg (up to 10 mg/kg), followed by either a constant infusion or intermittent doses up to a cumulative daily dose of 2.5 g

PHARMACOKINETICS

Molecular weight :166.2

%Protein binding :90–95

%Excreted unchanged in urine : 3–7

Volume of distribution (L/kg) :0.1–0.41

half-life – normal/ESRD (hrs) :6–15/Unchanged

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 : 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

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Antidepressants: antagonise anticonvulsant effect

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

Antimalarials: mefloquine antagonises anticonvulsant effect; increased convulsions with chloroquine and hydroxychloroquine

Antipsychotics: antagonise anticonvulsant effect; increased neutropenia with olanzapine

Ciclosporin: variable ciclosporin blood level response

Ulcer-healing drugs: metabolism inhibited by cimetidine, increased concentration

ADMINISTRATION

Reconstition

Use solvent provided

Route

IV, oral, PR (unlicensed)

Rate of Administration

3–5 minutes bolus, or continuous infusion

Comments

–

OTHER INFORMATION

Increases ketones in urine. May give false positive urine tests for ketones
Sodium valproate serum levels do not correlate with anti-epileptic activity
Monitor serum levels to ensure not greater than 100 micrograms/mL, or if non-compliance is suspected
Suppositories are available on a named patient basis

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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