CYCLOPHOSPHAMIDE

(sye-kloe-foss'fa-mide)

Cytoxan, Neosar, Procytox

Classifications: antineoplastic; alkylating agent;
Therapeutic: antineoplastic
Pregnancy Category: C

Availability

25 mg, 50 mg tablets; 100 mg, 200 mg, 500 mg, 1 g, 2 g vials

Action

Cell-cycle-nonspecific alkylating agent chemically related to the nitrogen mustards. Action mechanism thought to be the result of cross-linkage of DNA strands, thereby blocking synthesis of DNA, RNA, and protein.

Therapeutic Effect

Has pronounced immunosuppressive activity and therapeutic effects that are usually accompanied by some evidence of toxicity.

Uses

As single agent or in combination with other chemotherapeutic agents in treatment of malignant lymphoma, multiple myeloma, leukemias, mycosis fungoides (advanced disease), neuroblastoma, adenocarcinoma of ovary, carcinoma of breast, or malignant neoplasms of lung.

Unlabeled Uses

To prevent rejection in homotransplantation; to treat severe rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Wegener's granulomatosis, nephrotic syndrome.

Contraindications

Men and women in childbearing years; serious infections (including chickenpox, herpes zoster); live virus vaccines; myelosuppression; dehydration; pregnancy (category C), lactation.

Cautious Use

History of radiation or cytotoxic drug therapy; hepatic and renal impairment, elderly; recent history of steroid therapy; bone marrow infiltration with tumor cells; history of urate calculi and gout; patients with leukopenia, thrombocytopenia.

Route & Dosage

Neoplasm
Adult: PO Initial 1–5 mg/kg/d; Maintenance 1–5 mg/kg q7–10d. IV Initial 40–50 mg/kg in divided doses over 2–5 d up to 100 mg/kg; Maintenance 10– 15 mg/kg q7–10d or 3–5 mg twice weekly.
Child: PO Initial 2–8 mg/kg or 60–250 mg/m²; Maintenance 2–5 mg/kg or 50–150 mg/m² twice weekly. IV Initial 2–8 mg/kg or 60–250 mg/m².

Renal Impairment
Cl_cr <10 mL/min: give 50% of dose; administer post-dialysis, give supplemental dose of 35%

Administration

Oral

Administer PO drug on empty stomach. If nausea and vomiting are severe, however, it may be taken with food. An antiemetic medication may be prescribed to be given before the drug.
Store cyclophosphamide PO solution in refrigerator at 2°–8° C (36°–46° F), and use within 14 d.

Intravenous

PREPARE: Direct: Add 5 mL bacteriostatic water for injection (paraben-preserved only) to each 100 mg and shake gently to dissolve. Intermittent: May be further diluted with 100–250 mL D5W, NS, D5/NS, RL, or other compatible solution.

ADMINISTER: Direct/Intermittent: Give each 100 mg or fraction thereof over 10–15 min.

INCOMPATIBILITIES Y-site: Amphotericin B cholesteryl complex, lansoprazole.

Store at temperature between 2° and 30° C (36° and 86° F) unless otherwise recommended by the manufacturer.

Adverse Effects (≥1%)

Body as a Whole: Transient dizziness, fatigue, facial flushing, diaphoresis, drug fever, anaphylaxis, secondary neoplasia. GI: Nausea, vomiting, mucositis, anorexia, hepatotoxicity, diarrhea. Hematologic: Leukopenia, neutropenia, acute myeloid leukemia, anemia, thrombophlebitis, interference with normal healing. Metabolic: Severe hyperkalemia, SIADH, hyponatremia, weight gain (but without edema) or weight loss, hyperuricemia. Respiratory: Pulmonary emboli and edema, pneumonitis, interstitial pulmonary fibrosis. Skin: Alopecia (reversible), transverse ridging of nails, pigmentation of nail beds and skin (reversible), nonspecific dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome. Urogenital: Sterile hemorrhagic and nonhemorrhagic cystitis, bladder fibrosis, nephrotoxicity.

Diagnostic Test Interference

Cyclophosphamide suppresses positive reactions to Candida, mumps, trichophytons, and tuberculin PPD skin tests. Papanicolaou (PAP) smear may be falsely positive.

Interactions

Drug: Succinylcholine, prolonged neuromuscular blocking activity; doxorubicin may increase cardiac toxicity.

Pharmacokinetics

Absorption: Readily from GI tract. Peak: 1 h PO. Distribution: Widely distributed, including brain, breast milk; crosses placenta. Metabolism: In liver by CYP3A4. Elimination: In urine as active metabolites and unchanged drug. Half-Life: 4–6 h.

Nursing Implications

Assessment & Drug Effects

Lab tests: Total and differential leukocyte count, platelet count, and Hct are determined initially and at least 2 times per week during maintenance period. Baseline and periodic determinations of liver and kidney function and serum electrolytes also should be made. Microscopic urine examinations are recommended after large IV doses.
Thrombocytopenia is rare, but if it occurs (count of 100,000/mm³ or lower), assess for signs of unexplained bleeding or easy bruising. If platelet count indicates thrombocytopenia (≤100,000/mm³), drug will be discontinued.
Marked leukopenia is the most serious side effect. It can be fatal. Nadir may occur in 2–8 d after first dose but may be as late as 1 mo after a series of several daily doses. Leukopenia usually reverses 7–10 d after therapy is discontinued.
During severe leukopenic period, protect patient from infection and trauma and from visitors and medical personnel who have colds or other infections.
Report onset of unexplained chills, sore throat, tachycardia. Monitor temperature carefully and report an elevation immediately. The development of fever in a neutropenic patient (granulocyte count <1000) is a medical emergency because sepsis can develop quickly in these patients.
Observe and report character of wound drainage. During period of neutropenia, purulent drainage may become serosanguineous because there are not enough WBC to create pus. Because of suppressed immune mechanisms, wound healing may be prolonged or incomplete.
Monitor I&O ratio and patterns: Since the drug is a chemical irritant, PO and IV fluid intake is generally increased to help prevent renal irritation and hemorrhagic cystitis. Have patient void frequently, especially after each dose and just before retiring to bed.
Watch for symptoms of water intoxication or dilutional hyponatremia; patients are usually well hydrated as part of the therapy.
Promptly report hematuria or dysuria. Drug schedule is usually interrupted and fluids are forced.
Record body weight at least twice weekly (basis for dose determination). Alert physician to sudden change or slow, steady weight gain or loss over a period of time that appears inconsistent with caloric intake.
Diarrhea may signal onset of hyperkalemia, particularly if accompanied by colicky pain, nausea, bradycardia, and skeletal muscle weakness. These symptoms warrant prompt reporting to physician.
Monitor for hyperuricemia, which occurs commonly during early treatment period in patients with leukemias or lymphoma. Report edema of lower legs and feet; joint, flank, or stomach pain.
Protect patient from potential sources of infection. Cyclophosphamide makes the patient particularly susceptible to varicella-zoster infections (chickenpox, herpes zoster).
Report any sign of overgrowth with opportunistic organisms, especially in patient receiving corticosteroids or who has recently been on steroid therapy.
Report fever, dyspnea, and nonproductive cough. Pulmonary toxicity is not common, but the already debilitated patient is particularly susceptible.

Patient & Family Education

Adhere to dosage regimen and do not omit, increase, decrease, or delay doses. If for any reason drug cannot be taken, notify physician.
Alopecia occurs in about 33% of patients on cyclophosphamide therapy. Hair loss may be noted 3 wk after therapy begins; regrowth (often differs in texture and color) usually starts 5–6 wk after drug is withdrawn and may occur while on maintenance doses.
Use adequate means of contraception during and for at least 4 mo after termination of drug treatment. Breast-feeding should be discontinued before cyclophosphamide therapy is initiated.
Amenorrhea may last up to 1 y after cessation of therapy in 10–30% of women.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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