cyclophosphamide

Absorption: Inactive parent drug is well absorbed from the GI tract. IV administration results in complete bioavailability.

Distribution: Widely distributed. Limited penetration of the blood-brain barrier.

Metabolism/Excretion: Converted to active drug by the liver; 30% eliminated unchanged by the kidneys.

Half-Life: 4–6.5 hr.

Time/Action Profile ⬆ ⬇

(effects on blood counts)

ROUTE	ONSET	PEAK	DURATION
PO, IV	7 days	7–15 days	21 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Active infections;
Bone marrow depression;
Other chronic debilitating illnesses;
Rep: Women of reproductive potential.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, MYOCARDIAL FIBROSIS

Derm: alopecia

Endo: gonadal suppression, syndrome of inappropriate antidiuretic hormone (SIADH)

GI: anorexia, nausea, vomiting

GU: hematuria, ↓fertility, HEMORRHAGIC CYSTITIS

Hemat: thrombocytopenia, anemia, LEUKOPENIA

Metab: hyperuricemia

Resp: PULMONARY FIBROSIS

Misc: SECONDARY MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

Phenobarbital or rifampin may ↑ toxicity of cyclophosphamide.
Concurrent allopurinol or thiazide diuretics may exaggerate bone marrow depression.
May prolong neuromuscular blockade from succinylcholine.
Cardiotoxicity may be additive with other cardiotoxic agents (e.g., cytarabine, daunorubicin, doxorubicin).
May ↓ digoxin levels and effectiveness.
Additive bone marrow depression with other antineoplastics or radiation therapy.
May potentiate the effects of warfarin.
May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.
Prolongs the effects of cocaine.

Route/Dosage ⬆ ⬇

PO (Adults ): 1–5 mg/kg/day.
PO (Children ): Induction: 2–8 mg/kg/day (60–250 mg/m²/day) in divided doses for 6 days or longer. Maintenance: 2–5 mg/kg (50–150 mg/m²/day) twice weekly.
IV (Adults ): 40–50 mg/kg in divided doses over 2–5 days or 10–15 mg/kg every 7–10 days or 3–5 mg/kg twice weekly or 1.5–3 mg/kg/day. Other regimens may use larger doses.
IV (Children ): Induction: 2–8 mg/kg/day (60–250 mg/m²/day) in divided doses for 6 days or longer. Total dose for 7 days may be given as a single weekly dose. Maintenance: 10–15 mg/kg every 7–10 days or 30 mg/kg every 3–4 wk.

Availability ⬆ ⬇

(Generic available)

Capsules: 25 mg; 50 mg
Tablets: 25 mg; 50 mg
Lyophilized powder for injection: 200 mg/vial; 500 mg/vial; 1 g/vial; 2 g/vial
Solution for injection: 100 mg/mL; 200 mg/mL; 500 mg/mL

Assessment ⬆ ⬇

Monitor BP, pulse, respiratory rate, and temperature frequently during administration. Report significant changes.
Monitor urinary output frequently during therapy. To reduce the risk of hemorrhagic cystitis and to promote excretion of uric acid, fluid intake should be at least 3000 mL/day for adults and 1000–2000 mL/day for children. May be administered with mesna. Alkalinization of the urine may be used to help prevent uric acid nephropathy.
Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
Assess nausea, vomiting, and appetite. Weigh weekly. Antiemetics may be given 30 min before administration of medication to minimize GI effects. Anorexia and weight loss can be minimized by feeding frequent light meals.
Assess cardiac and respiratory status for dyspnea, rales/crackles, cough, weight gain, edema. Pulmonary toxicity may occur after prolonged therapy. Cardiotoxicity may occur early in therapy and is characterized by symptoms of HF.

Lab Test Considerations:

Monitor CBC with differential and platelet count before and periodically during therapy. The nadir of leukopenia occurs in 7–12 days (recovery in 17–21 days). Leukocytes should be maintained at 2500–4000/mm³. May also cause thrombocytopenia (nadir 10–15 days) and rarely causes anemia.
- Monitor BUN, serum creatinine, and uric acid before and frequently during therapy to detect nephrotoxicity.
- Monitor ALT, AST, LDH, and serum bilirubin before and frequently during therapy to detect hepatotoxicity.
- Urinalysis should be evaluated before initiating therapy and frequently during therapy to detect hematuria or change in specific gravity indicative of SIADH.
- May suppress positive reactions to skin tests for
  Candida
  , mumps,
  Trichophyton
  , and tuberculin purified-protein derivative. May also produce false-positive results in Papanicolaou smears.

Implementation ⬆ ⬇

Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings.
Do not confuse cyclophosphamide with cyclosporine or cycloserine.
Administer antiemetics before dosing with cyclophosphamide.
PO: Administer in the morning. DNC: Swallow tablets whole; do not crush, break, or chew.

IV Administration:

Provide adequate fluids (PO or IV) during or immediately after IV administration to force diuresis and reduce the risk of urinary tract toxicity.
IV: Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. If powder or solution comes in contact with skin or mucosa, wash thoroughly with soap and water. Discard equipment in specially designated containers.
Diluent: Withdraw prescribed dose of cyclophosphamide from vial with a syringe and dilute with 0.9% NaCl. Do not dilute with sterile water for injection; results in a hypotonic solution not suitable for IV push. Solution is clear, colorless to slight yellow; do not administer solutions that are cloudy, discolored, or contain particulate matter.Concentration: 20 mg/mL.
Rate: Inject very slowly. Monitor IV site; may be an irritant.
Intermittent Infusion: Diluent: Withdraw prescribed dose of cyclophosphamide from vial and dilute to a concentration of 2 mg per mL with 0.9% NaCl, 0.45% NaCl, D5W, D5/0.45% NaCl. Swirl gently to dissolve. Solutions diluted with 0.9% NaCl or 0.45% NaCl may be stored at room temperature for 24 hr or if refrigerated for 6 days. Solutions diluted with D5W or D5/0.45% NaCl are stable up to 24 hr at room temperature or 36 hr if refrigerated.Concentration: 2 mg/mL.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take dose in early morning. Emphasize need for adequate fluid intake for 72 hr after therapy. Patient should void frequently to decrease bladder irritation from metabolites excreted by the kidneys. Report hematuria immediately. If a dose is missed, contact health care professional. Advise caregivers to use gloves when handling capsules. If capsule opens, wash hands thoroughly.
Instruct patient to notify health care professional promptly if fever; sore throat; signs of infection; lower back or side pain; difficult or painful urination; sores in the mouth or on the lips; yellow discoloration of skin or eyes; bleeding gums; bruising; petechiae; blood in urine, stool, or emesis; unusual swelling of ankles or legs; joint pain; shortness of breath; cough; palpitations; weight gain of more than 5 lb in 24 hr; dizziness; loss of consciousness; or confusion occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Patient should also be cautioned not to drink alcoholic beverages or to take products containing aspirin or NSAIDs; may precipitate GI hemorrhage.
Discuss with patient the possibility of hair loss. Explore methods of coping. May also cause darkening of skin and fingernails.
Instruct patient not to receive any vaccinations without advice of health care professional.
Rep: May cause fetal harm. Advise females of reproductive potential use highly effective contraceptive measures for up to 1 yr after last dose and to avoid breastfeeding during and for 1–6 wk after last dose. Advise males with female partners of reproductive potential to wear condoms during and for at least 4 mo after last dose of therapy. Advise patient or notify health care professional if pregnancy is planned or suspected. Patients treated for rheumatic and musculoskeletal diseases should consider discontinuing cyclophosphamide 3–6 mo prior to conception to allow for disease monitoring and potential change to another immunosuppressant. Discontinue cyclophosphamide 12 wk before attempting conception in patients with rheumatic and musculoskeletal diseases who are planning to father a child. Inform patient that this medication may cause sterility and menstrual irregularities or cessation of menses.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇