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• 2H-1,3,2-Oxazaphosphorin-2-amine, N,N-bis(2-chloroethyl)tetrahydro-, 2-oxide, (+-)-
• 2H-1,3,2-Oxazaphosphorine, 2-(bis(2-chloroethyl)amino)tetrahydro-, 2-oxide
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ACUTE EXPOSURE INFORMATION
- USES: Cyclophosphamide is used orally and intravenously as an antineoplastic agent for many types of malignancies (ie, lymphomas, leukemias, multiple myeloma, mycosis fungoides, pediatric CNS tumors, ovarian and breast cancer) and as an antirheumatic drug for a variety of conditions, including systemic lupus erythematosus and juvenile rheumatoid arthritis.
- PHARMACOLOGY: Cyclophosphamide is an alkylating agent that prevents cell division by cross-linking DNA strands and thus decreasing DNA synthesis. It is a prodrug that is metabolized in the liver and has active metabolites.
- TOXICOLOGY: After overdose, the effects of decreased DNA synthesis and cell death are noticed primarily in organ systems with rapidly dividing cells (bone marrow, gastrointestinal tract).
- EPIDEMIOLOGY: Acute cyclophosphamide poisoning is rare. The incidence of cyclophosphamide toxicity during therapeutic use varies depending on the dosage and the length of duration of therapy and sequential or concurrent use of other cytotoxic drugs, and some toxic effects (ie, cystitis) are far more common than pneumonitis or pulmonary fibrosis.
- WITH THERAPEUTIC USE
- COMMON: The most common effects observed include alopecia, which usually starts 3 weeks after therapy, effects on fertility (ie, irreversible sterility, amenorrhea), gastrointestinal effects (ie, nausea, vomiting, diarrhea, anorexia, mucositis, stomatitis), a potentially fatal acute hemorrhagic cystitis (in up to 40% of patients), and myelosuppression. Less common effects in patients include facial flushing, headache, skin rashes, SIADH, and renal tubular necrosis.
- RARE: Rare but life-threatening side effects include cardiac effects (ie, congestive heart failure, cardiac necrosis, and hemorrhagic myocarditis), pulmonary effects (ie, interstitial pneumonitis and pulmonary fibrosis), anaphylactic reactions, hepatotoxicity, electrolyte imbalances, renal injury, secondary malignancy, and toxic epidermal necrolysis.
- Cyclophosphamide is teratogenic (FDA pregnancy category D) and long-term use is associated with an increased risk of a variety of malignancies.
- WITH POISONING/EXPOSURE
- Overdose reports are limited. Severe left ventricular dysfunction, pleural and pericardial effusion, and myelosuppression have been reported. An extension of adverse effects (ie, alopecia, nausea, vomiting, diarrhea, stomatitis, hemorrhagic cystitis) should be expected.
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