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 &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp : 144.2
  • %Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp : 85–94
  • %Excreted unchanged in urine &nbsp &nbsp : <3

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

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

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50 &nbsp &nbsp : Dose as in normal renal function
  • 10 to 20 &nbsp &nbsp : Dose as in normal renal function
  • <10 &nbsp &nbsp &nbsp &nbsp &nbsp : Start with a low dose, adjust according to response

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

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

  • HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp : Dialysed. Dose as in GFR
  • <10 &nbsp &nbsp &nbsp &nbsp &nbsp : mL/ min
  • HDF/high flux &nbsp : Dialysed. Dose as in GFR
  • <10 &nbsp &nbsp &nbsp &nbsp &nbsp : mL/ min
  • CAV/VVHD &nbsp &nbsp &nbsp: 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

    ADMINISTRATION

    Reconstition

    –

    Route

    Oral

    Rate of Administration

    –

    Comments

    –

    OTHER INFORMATION

    May cause carnitine deficiency Dialysis removes about 20% of dose .
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