Cyclophosphamide.JPG

Cyclophosphamide

CLINICAL USE

Alkylating agent:Immunosuppression of autoimmune diseases including rheumatoid arthritisTreatment of malignant disease

DOSE IN NORMAL RENAL FUNCTION

Autoimmune disease: Oral: 1–2.5 mg/kg/day —IV: Usually 0.5–1 g/m —2 or 10–15 mg/kg repeated at intervals, e.g. monthly (pulse therapy)Malignant disease: Oral: 50–250 mg/m —2 daily or according to local protocol

PHARMACOKINETICS

  • Molecular weight                           :279.1
  • %Protein binding                           :Parent drug 0–10: alkylating metabolites >60
  • %Excreted unchanged in urine     : 5–25
  • Volume of distribution (L/kg)       :0.78
  • half-life – normal/ESRD (hrs)      :3–12/10

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : Dose as in normal renal function
  • 10 to 20     : 75–100% of normal dose depending on clinical indication and local protocol
  • <10           : 50–100% of normal dose depending on clinical indication and local protocol

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Dialysed. Dose as in GFR
  • <10           : mL/min. Following dose, do not perform
  • CAPD                : exchange for 12 hours
  • HD                     :Dialysed. Dose as in GFR
  • <10           : mL/min. Dose at minimum of 12 hours before
  • HD                     : session
  • HDF/high flux   :Dialysed. Dose as in GFR
  • <10           : mL/min. Dose at minimum of 12 hours before HDF session
  • CAV/VVHD      :Dialysed. Dose as in GFR=10–20 mL/min

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugsAntipsychotics: avoid concomitant use with clozapine, increased risk of agranulocytosisCytotoxics: increased toxicity with high- dose cyclophosphamide and pentostatin – avoid concomitant use

    ADMINISTRATION

    Reconstition

    Add 5 mL water for injection to each 100 mg (sodium chloride 0.9% for Endoxana)

    Route

    Oral, IV

    Rate of Administration

    Directly into vein over 2–3 minutes, OR directly into tubing of fast running IV infusion with patient supine

    Comments

    IV route occasionally used for pulse therapy. Can be administered as an IV infusionInjection can be administered orally down an NG tube

    OTHER INFORMATION

    Prodrug – converted by hepatic microsomal enzymes to alkylating metabolites (great inter-patient variability in metabolism). Excretion primarily renal. Reduce IV dose to 75% of oral dose, bioavailability is 75%Cyclophosphamide and its alkylating metabolites can be eliminated by dialysisPatients receiving chronic indefinite therapy may be at increased risk of developing urothelial carcinomaIf patient is anuric and on dialysis, neither cyclophosphamide or its metabolites, nor Mesna should appear in the urinary tract. The use of Mesna may therefore be unnecessary, although this would be a clinical decisionIf the patient is still passing urine, Mesna should be given to prevent urothelial toxicity