dosage adjustment of Caspofungin in renal failure




Caspofungin.JPG

Caspofungin

CLINICAL USE

  • Invasive aspergillosis in adult patients who are refractory to or intolerant of amphotericin B and/or itraconazole
  • Invasive candidiasis
  • Empirical treatment of systemic fungal infections in patients with neutropenia

    DOSE IN NORMAL RENAL FUNCTION

    70 mg loading dose on day 1 followed by 50 mg daily, thereafterIf patient weighs >80 kg use 70 mg daily

    PHARMACOKINETICS

  • Molecular weight                           :1213.4 (as acetate)
  • %Protein binding                           :97
  • %Excreted unchanged in urine     : 1.4
  • Volume of distribution (L/kg)       :No data
  • half-life – normal/ESRD (hrs)      :12–15 days/Increased but not significantly.

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : Dose as in normal renal function
  • 10 to 20     : Dose as in normal renal function
  • <10           : Dose as in normal renal function

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Not dialysed. Dose as in normal renal function
  • HD                     :Not dialysed. Dose as in normal renal function
  • HDF/high flux   :Unlikely to be dialysed. Dose as in normal renal function
  • CAV/VVHD      :Not dialysed. Dose as in normal renal function

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs
  • Ciclosporin: monitor liver enzymes as transient increases in ALT and AST have been reported with concomitant administration. Avoid co-administration if possible. Increases AUC of caspofungin by 35%
  • Tacrolimus: reduces tacrolimus trough concentration by 26%

    ADMINISTRATION

    Reconstition

    10.5 mL water for injection

    Route

    IV infusion

    Rate of Administration

    Approximately 1 hour

    Comments

  • Caspofungin is unstable in fluids containing glucose; add to 250 mL sodium chloride 0.9% or lactated Ringer’s solution
  • If patient is fluid restricted, doses of 35 or 50 mg may be added to 100 mL infusion fluid

    OTHER INFORMATION

  • In established renal failure the AUC is increased by 30–49% but a change in dosage schedule is not required
  • Plasma concentrations of caspofungin decline in a polyphasic manner. A short α-phase occurs immediately post infusion, followed by a β-phase with a half-life of 9–11 hours. An additional γ-phase also occurs with a half-life of 40–50 hours. Distribution rather than excretion or biotransformation is the dominant mechanism influencing plasma clearance
  • Caspofungin has been used at a dose of 50 mg daily in combination with IV amphotericin B to successfully treat fungal peritonitis