Effects include bone marrow suppression, hemorrhagic cystitis, premature gonadal failure and infections.
A synthetic antineoplastic drug chemically related to the nitrogen mustards.
Cyclophosphamide is converted in the liver into acrolein and phosphoramide which interfere with cell growth by interfering with the action DNA.
Biotransformed principally in the liver to active alkylating metabolites by a microsomal oxidase system.
Metabolites interfere with the growth of susceptible rapidly proliferating malignant cells by cross-linking of tumor cell DNA.
Well absorbed after oral administration.
Bioavailability greater than 75% and elimination half-life of 3 to 12 hours.
Eliminated mainly in the form of metabolites, but 5%-25% of the dose is excreted in urine as unchanged drug.
Concentrations of metabolites reach a maximum in plasma 2 to 3 hours after an intravenous dose.
Plasma protein binding of the drug is low but some metabolites are bound to an extent greater than 60%.
Second malignancies have developed in some patients and include urinary bladder, myeloproliferative, or lymphoproliferative malignancies.
Can cause fetal harm when administered to a pregnant woman.
Interferes with oogenesis and spermatogenesis and may cause sterility in both sexes.
Associated with amenorrhea with decreased estrogen and increased gonadotropin secretion, and patients generally resume regular menses within a few months after cessation of therapy.
Men may develop oligospermia or azoospermia associated with increased gonadotropin but normal testosterone secretion.
Azoospermia is reversible in some patients.
Hemorrhagic cystitis may develop and rarely can be severe and even fatal.
May cause fibrosis of the urinary bladder which may be severe extensive and may develop with or without accompanying cystitis.
Bladder injury is due to the drug’s metabolites excreted in the urine.
Increasing fluid intake during the time of the drug administration prevents cyctitis by reducing the time metabolites remain in the bladder.
Hemorrhagic cystitis is usually temporary, but can become severe and protracted.
Rarely associated with cardiac dysfunction at recommended doses.
Acute cardiac toxicity, including CHF, may occur with with doses as low as 2.4 g/m2 when administered in high doses as part of a transplant regimen.
Acute cardiac toxicity may be associated with hemorrhagic myocarditis, and secondary hemopericardium.
Rarely, pericarditis has been reported.
No long-term residual cardiac abnormalities occur with acute cardiac toxicity..
May potentiate doxorubicin-induced cardiotoxicity.
Associated with myelosuppression.
Urinalysis should be performed regularly since microscopic hematuria may precede hemorrhagic cystitis.
The chronic administration of high doses of phenobarbital are associated with greater degree of myelosuppression.
Inhibits cholinesterase activity, and potentiates the effect of succinylcholine chloride.
May interfere with normal wound healing.
Metabolites of the drug are excreted in breast milk.
Common side effects include nausea, vomiting, anorexia, abdominal discomfort, diarrhea, alopecia, and myelosuppression.
Interstitial pneumonitis and interstitial pulmonary fibrosis has been reported, rarely, and in patients receiving high doses for a prolonged period of time.
Oral dosage is usually in the range of 1 to 5 mg/kg/day for both initial and maintenance dosing.
Dosage does not need to be modified with renal impairment.
For minimal change Nephrotic Syndrome in children: an oral dose of 2.5 to 3 mg/kg daily for a period of 60 to 90 days is recommended.