cyclophosphamide

cyclophosphamide /cy·clo·phos·pha·mide/ (-fos´fah-mīd) a cytotoxic alkylating agent of the nitrogen mustard group; used as an antineoplastic, as an immunosuppressant to prevent transplant rejection, and to treat some diseases characterized by abnormal immune function.

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cy·clo·phos·pha·mide (skl-fsf-md)

n.

A highly toxic, immunosuppressive, antineoplastic drug, used in the treatment of Hodgkin's disease, lymphoma, and certain other forms of cancer, such as leukemia and breast cancer.

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cyclophosphamide

[-fos′fəmīd]

an alkylating agent.

indications It is prescribed in the treatment of neoplasms and as an immunosuppressant in organ transplantation.

contraindications It is teratogenic in animals. It is not used during pregnancy. Adequate methods of contraception should be considered for both males and females who are using it. It is used neither in patients with known hypersensitivity to the drug nor in patients with severely depressed bone marrow function. It is used with caution with impaired renal or hepatic function or with various blood disorders.

adverse effects Among the more serious adverse reactions are anorexia, vomiting, alopecia, leukopenia, cardiotoxicity, thrombocytopenia, and potentially serious hemorrhagic cystitis.

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cyclophosphamide (sīklōfos´fmīd´),

n brand names: Cytoxan, Neosar, Procytox;
drug class: antineoplastic alkylating agent;
action: alkylates DNA, RNA; inhibits enzymes that allow synthesis of amino acids in proteins;
uses: Hodgkin's disease; lymphomas; leukemia; cancer of female reproductive tract, lung, prostate; multiple myeloma; neuroblastoma; retinoblastoma; Ewing's sarcoma.

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cyclophosphamide

a neoplastic suppressant used in the treatment of lymphomas and leukemias.

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immunosuppressants

Drugs that prevent or reduce the immune response. They are used in the treatment of a variety of severe inflammations such as uveitis, scleritis, keratoconjunctivitis sicca, Behçet's syndrome, sympathetic ophthalmia, and to prevent corneal graft rejection. They include the corticosteroids (e.g. prednisolone), ciclosporin (cyclosporine), tacrolimus, and cytotoxic agents (e.g. azathioprine, chlorambucil, cyclophosphamide, methotrexate). It must be noted that immunosuppressants render the patient more susceptible to infection because immunity is reduced.

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cyclophosphamide Warning - Hazardous drug!

Cytoxan, Endoxana (UK), Procytox (CA)

Pharmacologic class: Alkylating agent, nitrogen mustard

Therapeutic class: Antineoplastic

Pregnancy risk category D

Action

Unclear. Thought to prevent cell division by cross-linking DNA strands, thereby interfering with growth of susceptible cancer cells.

Availability

Powder for injection: 100 mg, 200 mg, 500 mg, 1 g, 2 g

Tablets: 25 mg, 50 mg

⊘Indications and dosages

➣ Hodgkin's disease; malignant lymphoma; multiple myeloma; leukemia; advanced mycosis fungoides; neuroblastoma; ovarian cancer; breast cancer; and certain other tumors

Adults: Initially, 40 to 50 mg/kg I.V. in divided doses over 2 to 5 days, or 10 to 15 mg/kg I.V. q 10 days, or 3 to 5 mg/kg I.V. twice weekly.

Children: Initially, 2 to 8 mg/kg or 60 to 250 mg/m² P.O. or I.V. daily in divided doses for 6 or more days. Maintenance dosage is 2 to 5 mg/kg or 50 to 150 mg/m² P.O. twice weekly.

➣ Biopsy-proven nephrotic syndrome in children

Children: 2.5 to 3 mg/kg/day P.O. for 60 to 90 days

Off-label uses

• Severe rheumatologic conditions
• Selected cases of severe progressive rheumatoid arthritis and systemic lupus erythematosus

Contraindications

• Hypersensitivity to drug
• Severe bone marrow depression
• Breastfeeding

Precautions

Use cautiously in:
• renal or hepatic impairment, adrenalectomy, mild to moderate bone marrow depression, other chronic debilitating illnesses
• females of childbearing age
• pregnant patients.

Administration

• Verify that patient isn't pregnant before administering.
• Follow facility procedures for safe handling, administration, and disposal of chemotherapeutic drugs.
• Administer tablets on empty stomach. If drug causes severe GI upset, give with food.
• Don't cut or crush tablets.
• Know that dosage may need to be decreased if drug is given with other antineoplastics.
• Dilute each 100 mg of powder with 5 ml of sterile water for injection, to yield 20 mg/ml. Further dilute with compatible fluid, such as 5% dextrose injection, 5% dextrose and normal saline solution for injection, 5% dextrose and Ringer's injection, lactated Ringer's injection, or half-normal saline solution for injection.
• For I.V. injection, give each 100 mg over at least 1 minute. When giving dosages above 500 mg diluted in 100 to 250 ml of compatible solution, administer over 20 to 60 minutes.
• Use solution prepared with bacteriostatic water for injection within 24 hours if stored at room temperature or within 6 days if refrigerated.
• To minimize bladder toxicity, increase patient's fluid intake during therapy and for 1 to 2 days afterward. Most adults require fluid intake of at least 2 L/day.

Route	Onset	Peak	Duration
P.O., I.V.	7 days	7-15 days	21 days

Adverse reactions

CV: cardiotoxicity

GI: nausea, vomiting, diarrhea, abdominal pain or discomfort, stomatitis, oral mucosal ulcers, anorexia, hemorrhagic colitis

GU: urinary bladder fibrosis, hematuria, amenorrhea, decreased sperm count, sterility, acute hemorrhagic cystitis, renal tubular necrosis, hemorrhagic ureteral inflammation

Hematologic: anemia, leukopenia, thrombocytopenia, bone marrow depression, neutropenia

Hepatic: jaundice

Metabolic: hyperuricemia

Respiratory: interstitial pulmonary fibrosis

Skin: nail and pigmentation changes, alopecia

Other: poor wound healing, infections, allergic reactions including anaphylaxis, secondary cancer

Interactions

Drug-drug. Allopurinol, thiazide diuretics: increased risk of leukopenia

Digoxin: decreased digoxin blood level

Cardiotoxic drugs (such as cytarabine, daunorubicin, doxorubicin): additive cardiotoxicity

Chloramphenicol: prolonged cyclophosphamide half-life

Phenobarbital: increased risk of cyclophosphamide toxicity

Quinolones: decreased antimicrobial effect

Succinylcholine: prolonged neuromuscular blockade

Warfarin: increased anticoagulant effect

Drug-diagnostic tests. Hemoglobin, platelets, pseudocholinesterase, red blood cells (RBCs), white blood cells: decreased values

Uric acid: increased level

Patient monitoring

• Assess infusion site for signs of extravasation.
• Monitor hematologic profile to determine degree of hematopoietic suppression. Be aware that leukopenia is an expected drug effect and is used to help determine dosage.
• Monitor urine regularly for RBCs, which may precede hemorrhagic cystitis.

Patient teaching

• Tell patient to take tablets on empty stomach. However, if GI upset occurs, instruct him to take them with food.
☞ Advise patient to promptly report unusual bleeding or bruising, fever, chills, sore throat, cough, shortness of breath, seizures, lack of menstrual flow, unusual lumps or masses, flank or stomach pain, joint pain, mouth or lip sores, or yellowing of skin or eyes.
• Instruct patient to drink 2 to 3 L of fluids daily (unless prescriber has told him to restrict fluids).
• Tell patient that drug may cause hair loss, but that hair usually grows back after treatment ends.
• Advise female patient to use barrier contraception during therapy and for 1 month afterward.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

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cyclophosphamide

Cytoxan^®, Neosar^® Oncology An alkylating chemotherapeutic used for lymphomas, CAs, and for immunosuppression in nephrotic syndrome Adverse effects BM suppression, cystitis, alopecia, N&V Contraindications Hypersensitivity, marked thrombocytopenia, leukopenia, hemorrhagic cystitis, lung toxicity related to previous therapy with an alkylating agent