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

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