Cyclophosphamide
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Contents |
Introduction
- Tradename: Cytoxan.
Indications
- Hodgkin's & non-Hodgkin's lymphoma
- leukemias
- breast cancer
- ovarian cancer
- multiple myeloma
- head & neck cancer
- bladder cancer
- gastric cancer
- hepatocellular carcinoma
- lung cancer
- osteogenic sarcoma
- soft tissue sarcoma
- immunosuppression
-
- hematologic complications
- renal complications
- CNS complications
Dosage
- 500-1500 mg/m2 every 3-4 weeks ( cancer chemotherapy)
- 400 mg/m2 for 4 days every 4-6 weeks
- Tabs: 50 mg.
Pharmacokinetics
- completely abdorbed from GI tract
- metabolized in the liver by cyt P450s CYP2B6 & CYP3A4 to active metabolite
- metabolites (85-90%) & parent compound (< 30%) eliminated in the urine
- elimination 1/2life is 3-12 hours
- elimination by dialysis 20-50%
- elimination via liver
- elimination via kidney
- 1/2life = 3-12 hours
- elimination by hemodialysis = +
Monitor
- complete blood count ( CBC) with differential
- maintain WBC > 3000, neutrophils > 1500/ mm3
- chemistry profile
- urinalysis & urine cytology
- cystoscopy if hematuria
- monitor with immunosuppressive agents
Adverse-effects
-
- generally occurs 3 weeks after therapy
- hair will regrow, perhaps with different color or texture
- cardiac toxicity
- nausea/vomiting more frequent with larger doses
- anorexia, diarrhea, stomatitis, mucositis, jaundice
-
- symptoms of UTI
- hematuria
- negative urine cultures
- gonadal suppression ( ovarian failure)
- bone marrow suppression
- leukopenia (more common than b or c)
- anemia
- thrombocytopenia
- onset: 7 days; nadir: 10-14 days; recovery: 21 days
- increased risk of lymphoma & other hematologic malignancies
- from increased ADH & water intoxication
- decreased water clearance
- predisposing factors
- pre-exisiting renal disease
- rapid rate of infusion
- other (< 1%)
- hypoglycemia, stomatitis, hemorrhagic colitis, darkening of skin & fingernails, hypokalemia, hyperuricemia, nasal stuffiness (large IV doses)
- hypoglycemia, stomatitis, hemorrhagic colitis, darkening of skin & fingernails, hypokalemia, hyperuricemia, nasal stuffiness (large IV doses)
Drug-interactions
- cyclophosphamide may decrease digoxin levels
- cyclophosphamide may potentiate effect of warfarin
- thiazide diuretics may increase the duration of leukopenia
- cardiotoxic drugs: doxirubicin
- drugs that effects cyt P450
Mechanism-of-action
- alkylating agent Mechanism of drug resistance:
- increased drug inactivation via activation of aldehyde dehydrogenase
More General Terms
- immunosuppressive agent
- antineoplastic agent (chemotherapeutic agent)
- disease-modifying antirheumatic agent (DMARD)
- alkylating agent
Additional Terms
- aldehyde dehydrogenase
- cytochrome P450 2B6 (cytochrome P450 2B1, phenobarbital-inducible, CYP2B6)
- cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
Internet Database
References
- The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 792
- Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 856-57
- Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- Kaiser Permanente Northern California Regional Drug Formulary, 1998
- Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 529, 533
- Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
