Cyclophosphamide is indicated for the treatment of: Malignant lymphomas (Stages III and IV of the Ann Arbor staging system), Hodgkin's disease, lymphocytic lymphoma (nodular or diffuse), mixed-cell type lymphoma, histiocytic lymphoma, Burkitt's lymphoma Multiple myeloma Leukemias: chronic lymphocytic leukemia, chronic granulocytic leukemia (it is usually ineffective in acute blastic crisis), acute myelogenousand monocytic leukemia, acute lymphoblastic (stem-cell) leukemia (cyclophosphamide given during remission is effective in prolonging its duration) Mycosis fungoides (advanced disease) Neuroblastoma (disseminated disease) Adenocarcinoma of the ovary Retinoblastoma Carcinoma of the breast Cyclophosphamide, although effective alone in susceptible malignancies, is more frequently used concurrently or sequentially with other antineoplastic drugs. Minimal Change Nephrotic Syndrome in Pediatric Patients: Cyclophosphamide is indicated for the treatment of biopsy proven minimal change nephrotic syndrome in pediatrics patients who failed to adequately respond to or are unable to tolerate adrenocorticosteroid therapy.
Cyclophosphamide is biotransformed principally in the liver to active alkylating metabolites by a mixed function microsomal oxidase system. These metabolites interfere with the growth of susceptible rapidly proliferating malignant cells. The mechanism of action is thought to involve cross-linking of tumor cell DNA. Cyclophosphamide is well absorbed after oral administration with a bioavailability greater than 75%. The unchanged drug has an elimination half-life of 3 to 12 hours. It is eliminated primarily in the form of metabolites, but from 5 to 25% of the dose is excreted in urine as unchanged drug. Several cytotoxic and noncytotoxic metabolites have been identified in urine and in plasma. Concen- trations of metabolites reach a maximum in plasma 2 to 3 hours after an intravenous dose. Plasma protein binding of unchanged drug is low but some metabolites are bound to an extent greater than 60%. It has not been demonstrated that any single metabolite is responsible for either the therapeutic or toxic effects of cyclophosphamide. Although elevated levels of metabolites of cyclophosphamide have been observed in patients with renal failure, increased clinical toxicity in such patients has not been demonstrated.
Intravenous (Adult)- Malignancies: Low dose regimen: 2-6 mg/kg wkly as a single dose; Moderate dose regimen: 10-15 mg/kg wkly as a single dose; High dose regimen: 20-40 mg/kg as a single dose every 10-20 days. Alternatively, 80-300 mg/m2 daily as a single dose, or 300-600 mg/m2 wkly as a single dose, or 600-1,500 mg/m2 as a single dose or Short infusion at 10- to 20-day intervals. Oral (Child)- Nephrotic syndrome: 2 mg/kg daily for 8-12 wk. Max cumulative dose: 168 mg/kg. Max duration: 90 days. Oral (Adult)- Malignancies: Low dose regimen: 2-6 mg/kg wkly in divided dose. Alternatively, 100-300 mg daily in divided doses, or 50-250 mg/m2 daily or 80-300 mg/m2 daily in divided doses.
The rate of metabolism and the leukopenic activity of cyclophosphamide reportedly are increased by chronic administration of high doses of phenobarbital. The physician should be alert for possible combined drug actions, desirable or undesirable, involving cyclophosphamide even though cyclophosphamide has been used successfully concurrently with other drugs, including other cytotoxic drugs. Cyclophosphamide treatment, which causes a marked and persistent inhibition of cholinesterase activity, potentiates the effect of succinylcholine chloride. If a patient has been treated with cyclophosphamide within 10 days of general anesthesia, the anesthesiologist should be alerted.
Patient with bone marrow aplasia, urinary outflow obstruction, UTI, acute infection, drug- or radiation-induced urothelial toxicity. Pregnancy. Patient with DM, severe immunosuppression, acute porphyria, pre-existing CV disease or those at risk for cardiotoxicity. Renal and hepatic impairment. Lactation.
Alopecia, skin and nails hyperpigmentation, nausea and vomiting, mucositis, inappropriate antidiuretic hormone secretion, carbohydrate metabolism disturbances, gonadal suppression, interstitial pulmonary fibrosis.
Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
No specific antidote for cyclophosphamide is known. Overdosage should be managed with supportive measures, including appropriate treatment for any concurrent infection, myelosuppression, or cardiac toxicity should it occur.
Store at a temperature not exceeding 25°C in a dry place. Protect from light and moisture. Do not freeze.
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