dosage adjustment of Daptomycin in renal failure




Daptomycin.JPG

Daptomycin

CLINICAL USE

Antibacterial agent

DOSE IN NORMAL RENAL FUNCTION

4–6 mg/kg once daily for 7 to 14 days depending on indication

PHARMACOKINETICS

  • Molecular weight                           :1620.7
  • %Protein binding                           :90–92
  • %Excreted unchanged in urine     : Approximately 50%
  • Volume of distribution (L/kg)       :0.092–0.104
  • half-life – normal/ESRD (hrs)      :8.1–9/29.41

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

    30–50 Dose as in normal renal function<30 4 mg/kg every 48 hours

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Not dialysed. Dose as in GFR<30 mL/min
  • HD                     :Not dialysed. Dose as in GFR<30 mL/min
  • HDF/high flux   :Dialysed. Dose as in GFR<30 mL/min
  • CAV/VVHD
  • /VVhdFSlightly dialysed. 4–6 mg/kg every 48 hours2

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugsWarfarin: Monitor INR when on daptomycinCiclosporin: increased risk of myopathy – try to avoid concomitant useLipid-regulating drugs: increased risk of myopathy with fibrates and statins – try to avoid concomitant use

    ADMINISTRATION

    Reconstition

    7 mL sodium chloride 0.9% or water for injection to give a solution of 50 mg/mL

    Route

    IV infusion

    Rate of Administration

    Over 30 minutes

    Comments

    Once reconstituted, stable for 12 hours at room temperature and 48 hours refrigeratedAdd to 50 mL sodium chloride 0.9% before administration. Stable for 12 hours at room temperature or 24 hours refrigeratedIncompatible with dextrose solutions Compatible with solutions containing aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin and lidocaine

    OTHER INFORMATION

    May cause renal impairment Vials do not contain any bacteriostatic or fungiostatic agentsCompany advises to administer post dialysisMonitor creatinine phosphokinase levels, muscle pain or weaknessIncreased risk of myopathy in severe renal failure due to increased daptomycin levels15% of dose is removed by 4 hours of haemodialysis and 11% over 48 hours by peritoneal dialysisTherapeutic concentrations of daptomycin are unlikely due to low PD clearance of drug therefore systemic use for peritonitis is unlikely to work