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

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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