CLINICAL USE

Schizophrenia and other psychoses Anxiety Severe nausea and vomiting

DOSE IN NORMAL RENAL FUNCTION

Schizophrenia: initially 5 mg twice daily, increased by 5 mg after 1 week, then at intervals of 3 days according to response Anxiolytic and anti-emetic: 2–4 mg daily in divided doses; maximum 6 mg

PHARMACOKINETICS

  • Molecular weight                           : 407.5
  • %Protein binding                           : >99
  • %Excreted unchanged in urine     : <1
  • Volume of distribution (L/kg)       : 160
  • half-life – normal/ESRD (hrs)      : 22/–

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : Dose as in normal renal function. Start with low dose
  • 10 to 20     : Dose as in normal renal function. Start with low dose
  • <10           : Dose as in normal renal function. Start with low dose

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                : Not dialysed. Dose as in GFR <10 mL/min
  • HD                     : Not dialysed. Dose as in GFR <10 mL/min
  • HDF/high flux   : Unknown dialysability. Dose as in GFR <10 mL/min
  • CAV/VVHD      : Unlikely to be dialysed. Dose as in GFR 10 to 20 mL/min

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs

  • Anaesthetics: enhanced hypotensive effect
  • Analgesics: increased risk of convulsions with tramadol; enhanced hypotensive and sedative effects with opioids
  • Anti-arrhythmics: increased risk of ventricular arrhythmias with anti- arrhythmics that prolong the QT interval, e.g. procainamide, disopyramide and amiodarone – avoid concomitant use with amiodarone
  • Antibacterials: increased risk of ventricular arrhythmias with moxifloxacin – avoid concomitant use
  • Antidepressants: increased level of tricyclics; possibly increased risk of antimuscarinic side effects
  • Anti-epileptics: antagonism (convulsive threshold lowered)
  • Antimalarials: avoid concomitant use with artemether/lumefantrine
  • Antipsychotics: increased risk of ventricular arrhythmias with pimozide – avoid concomitant use
  • Antivirals: concentration possibly increased with ritonavir Anxiolytics and hypnotics: increased sedative effects
  • Beta-blockers: enhanced hypotensive effect; increased risk of ventricular arrhythmias with sotalol
  • Diuretics: enhanced hypotensive effect
  • Lithium: increased risk of extrapyramidal side effects and possibly neurotoxicity
  • Pentamidine: increased risk of ventricular arrhythmias
  • Sibutramine: increased risk of CNS toxicity – avoid concomitant use

    ADMINISTRATION

    Reconstition

    –

    Route

    Oral

    Rate of Administration

    –

    Comments

    –

    OTHER INFORMATION

    Reduce starting dose in elderly or frail patients by at least half .

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