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cyclophosphamide drug interactions

What are the drug-drug interactions of cyclophosphamide? and what are the mechanisms of interaction?
by anne chua, 01/17/2007

Cyclophosphamide (Cytoxan)
(sye-kloh- FOS-fah-myd)
Pregnancy Category: D Cytoxan Cytoxan Lyophilized Neosar Procytox (Abbreviation: CYC) (Rx)

Classification: Antineoplastic, alkylating agent

See Also: See also Antineoplastic Agents and Alkylating Agents .

Action/Kinetics: Metabolized in the liver to both active antineoplastic alkylating agents and inactive metabolites. The active metabolites alkylate nucleic acids, thus interfering with the growth of neoplastic and normal tissues. The cytotoxic action is due to cross-linking of strands of DNA and RNA and inhibition of protein synthesis. Also possesses immunosuppressive activity. t 1/2: 3-12 hr, but remnants of drug and/or metabolites detectable in serum after 72 hr; in children, the t 1/2 averages 4.1 hr. Metabolites are excreted through the urine with up to 25% of cyclophosphamide excreted unchanged. Cyclophosphamide is also excreted in milk.

Uses: Often used in combination with other antineoplastic drugs. Malignancies: Malignant lymphomas (Stages III and IV, Ann Arbor Staging System), Hodgkin's disease, lymphocytic lymphoma (nodular or diffuse), mixed-cell-type lymphoma, histiocytic lymphoma, Burkitt's lymphoma, multiple myeloma, neuroblastoma (disseminated), adenocarcinoma of the ovary, retinoblastoma, carcinoma of the breast. Leukemias: Chronic lymphocytic and granulocytic leukemia, acute myelogenous and monocytic leukemia, acute lymphoblastic leukemia in children. Other: Mycosis fungoides, nephrotic syndrome in children. Investigational: Rheumatic diseases including rheumatoid arthritis and lupus erythematosus, Wegemer's granulomatosis, multiple sclerosis, polyarteritis nodosa, polymyositis (use with corticosteroids), severe neuropsychiatric lupus erythematosus.

Contraindications: Lactation. Severe bone marrow depression.

Special Concerns: Use with caution in clients with thrombocytopenia, leukopenia, previous radiation therapy, bone marrow infiltration of tumor cells, previous therapy causing cytotoxicity, and impaired liver and kidney function. May interfere with wound healing.

Additional Side Effects: Acute hemorrhagic cystitis. Bone marrow depression appears frequently during days 9-14 of therapy. Alopecia occurs more frequently than with other drugs. Secondary neoplasia (especially of urinary bladder), pulmonary fibrosis, cardiotoxicity darkening of skin or fingernails. Interference with oogenesis and spermatogenesis.

Laboratory Test Alterations: Uric acid in blood and urine; false + Pap test; serum pseudocholinesterase. Suppression of certain skin tests.

Overdose Management: Treatment: General supportive measures. Dialysis.

Drug Interactions: Allopurinol / Chance of bone marrow toxicity Anticoagulants / Anticoagulant effects Chloramphenicol / Metabolism of cyclophosphamide to active metabolites pharmacologic effect Digoxin / Serum digoxin levels Doxorubicin / Cardiotoxicity Insulin / Hypoglycemia Phenobarbital / Rate of metabolism of cyclophosphamide in liver Quinolone antibiotics / Antimicrobial effect of quinolones Succinylcholine / Neuromuscular blockade R/T cholinesterase activity Thiazide diuretics / Chance of leukopenia

How Supplied: Powder for injection: 100 mg, 200 mg, 500 mg, 1 g, 2 g; Tablet: 25 mg, 50 mg

?IV Malignancies.
Initial, with no hematologic deficiency: 40-50 mg/kg in divided doses over 2-5 days. Alternative therapy: 10-15 mg/kg q 7-10 days or 3-5 mg/kg twice weekly.
?Tablets Malignancies.
Initial and maintenance: 1-5 mg/kg depending on client tolerance. Attempt to maintain leukocyte count at 3,000-4,000/mm 3. Adjust dosage for kidney or liver disease.
Nephrotic syndrome in children.
2.5-3 mg/kg/day for 60-90 days.

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