CLINICAL USE

Antibacterial agent

DOSE IN NORMAL RENAL FUNCTION

IV: 1–4 g daily in 3–4 divided doses (as imipenem)IM, mild-moderate infections: 500–750 mg every 12 hours

PHARMACOKINETICS

  • Molecular weight                           :Imipenem: 317.4; cilastatin: 380.4
  • %Protein binding                           :Imipenem: 20; cilastatin: 40
  • %Excreted unchanged in urine     : Imipenem: 20–70; cilastatin: 75
  • Volume of distribution (L/kg)       :Imipenem: 0.23; cilastatin: 0.22
  • half-life – normal/ESRD (hrs)      :Imipenem: 1/4; cilastatin: 1/12

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

    31–70 500 mg every 6–8 hours21–30 500 mg every 8–12 hours<20 250–500 mg (or 3.5 mg/kg whichever is lower) every 12 hours

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Dialysed. Dose as in GFR<20 mL/min
  • HD                     :Dialysed. Dose as in GFR<20 mL/min
  • HDF/high flux   :Dialysed. Dose as in GFR<20 mL/minCAV/VVhDialysed. 250 mg every 6 hours or 500 mg every 8 hours1CVVhd/HDFDialysed. 250 mg every 6 hours or 500 mg every 6–8 hours1

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs

  • Ciclosporin: variable reports of increase/ no change in ciclosporin levels, and of neurotoxicityConvulsions reported with concomitant administration of ganciclovir

    ADMINISTRATION

    Reconstition

    250 mg with 50 mL, 500 mg with 100 mL sodium chloride 0.9% (in some units 500 mg with 50 mL)IM: 2 mL lidocaine 1%

    Route

    IM, IV peripherally or centrally (500 mg/50 mL – given centrally)

    Rate of Administration

    250 or 500 mg dose over 20–30 minutes 1 g over 40–60 minutes

    Comments

    OTHER INFORMATION

    Risk of adverse neurological effects, e.g. convulsions. Extreme caution required in patients with history of CNS diseaseCilastatin can accumulate in patients with impaired renal functionSodium content 1.72 mmol/500 mg vial Imipenem is administered with cilastatin to prevent metabolism of imipenem within the kidneyNon-renal clearance in acute renal failure is less than in chronic renal failurePatients with GFR<5 mL/min should not receive drug unless HD is started within 48 hours. Metabolised to inactive, nephrotoxic metabolites

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