CLINICAL USE


Opiate analgesia

DOSE IN NORMAL RENAL FUNCTION

IV: 25–50 mg every 4 hoursOral: 50–150 mg every 4 hoursS/C, IM: 25–100 mg every 4 hours

PHARMACOKINETICS

  • Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :283.8
  • %Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :60–80
  • %Excreted unchanged in urine &nbsp &nbsp : 5

  • Volume of distribution (L/kg) &nbsp &nbsp &nbsp :4.17

  • half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :3–6/7–32

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50 &nbsp &nbsp : Dose as in normal renal function
  • 10 to 20 &nbsp &nbsp : Use small doses – increase dosing interval to 6 hours and decrease dose by 25%
  • <10 &nbsp &nbsp &nbsp &nbsp &nbsp : Avoid if possible. If not, use small doses: increase dosing interval to 8 hours and decrease dose by 50%

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Unknown dialysability. Dose as in GFR <10 mL/min

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

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs
  • Anti-arrhythmics: delayed absorption of mexiletine
  • Antidepressants: possible CNS excitation or depression with MAOIs and moclobemide – avoid concomitant use; possibly increased serotonergic effects with duloxetine; increased sedative effects with tricyclics
  • Antipsychotics: enhanced sedative and hypotensive effect
  • Antivirals: concentration reduced by ritonavir but concentration of toxic pethidine metabolite increased – avoid concomitant use
  • Dopaminergics: risk of CNS toxicity with rasagiline – avoid concomitant use; hyperpyrexia and CNS toxicity reported with selegiline – avoid concomitant useSodium oxybate: enhanced effect of sodium oxybate – avoid concomitant use

    ADMINISTRATION

    Reconstition

    –

    Route

    IV, oral, SC, IM

    Rate of Administration

    IV: Bolus 3–4 minutes

    Comments

    –

    OTHER INFORMATION

    Risk of CNS and respiratory depression or convulsions, particularly in ERF patients receiving regular doses, due to accumulation of active metabolite, norpethidine. Norpethidine levels can be measured
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