PARTNERS WITH
Cyclophosphamide
Non-platinum based Alkylating Agents
MECHANISM OF ACTION
Cyclophosphamide is an alkylating agent that prevents cell division by cross-linking DNA strands and decreasing DNA synthesis. It is a cell cycle phase nonspecific agent. Cyclophosphamide also possesses potent immunosuppressive activity. Cyclophosphamide is a prodrug that must be metabolized to active metabolites in the liver.
Elimination
Urine (10 to 20% as unchanged drug); feces (4%)
MECHANISM OF KIDNEY INJURY
ATN (Acute tubular necrosis)
CLINICAL KIDNEY SYNDROME
AKI, Cardiac arrhythmia, bladder cancer, azoospermia, ulcerative cystitis, hemorrhagic cystitis, infertility, oligospermia, ovarian failure, ureteral disease, toxic nephrosis
CARDIOVASCULAR ADVERSE EFFECTS
Arrhythmias, CHF, myocarditis/ pericarditis (hemorrhagic)
LYTE ABNORMALITIES
Metabolic acidosis (HAGMA, NAGMA), Elevated BUN, Hyponatremia
RISK FACTORS
urinary flow obstruction is a contraindication, Higher and cumulative doses ( used in bone marrow transplant, rheumatological diseases) are associated with risk for hemorrhagic cystitis. active urinary tract infections, volume depletion, old patient's
MITIGATION STRATEGIES
Dose adjustment needed for level of kidney function. Also administration differs in different renal replacement therapy modalities. - Hemorrhagic cystitis, discontinue cyclophosphamide treatment. To minimize bladder toxicity, increase normal fluid intake during and for 1 to 2 days after cyclophosphamide dose. Most adult patients will require a fluid intake of at least 2 L/day. High-dose regimens should be accompanied by vigorous hydration with or without mesna therapy. Morning administration may be preferred to ensure adequate hydration throughout the day.
SUGGESTIONS
Discontinue offending drug, Volume expansion, Dose adjustment (details in notes section below), CrCl ≥10 mL/minute: No dosage adjustment required. CrCl <10 mL/minute: Administer 75% of normal dose. Hemodialysis: Moderately dialyzable (20% to 50%); administer 50% of normal dose; administer after hemodialysis. Continuous ambulatory peritoneal dialysis (CAPD): Administer 75% of normal dose. Continuous renal replacement therapy (CRRT): Administer 100% of normal dose.
NOTES/COMMENTS
eGFR 30-59 ml/min , full to 75% of dose
eGFR < 15 ml/min, full dose if curative, can also consider 50% of dose
PHARMACOKINETICS
Molecular Weight
261
Volume of Distribution
30-50L
Plasma Protein Binding
Metabolism
microsomal hyrodxylation
Bioavailability
Half-life elimination
3-12Hrs
Time to peak
Excretion
Renal, 10-20%
Dialyzable?
Moderately dialyzable (20% to 50% removal based on limited data with low-flux dialyzers). on dialysis days, administer after hemodialysis, allowing at least 12 hours before the next hemodialysis session.
REF:
PATHOLOGY SLIDES:
ENTRY UPDATES:
Kartik Kalra
United States
Sep 25, 2022