cyclophosphamide

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.

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

Route/Dosage ⬆ ⬇

PO (Adults ): Induction and maintenance: 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.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Interferes with DNA replication and RNA transcription, ultimately disrupting protein synthesis (cell-cycle phase-nonspecific).

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.
Also has immunosuppressant action in smaller doses.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics, Immunosuppressant agents

Pharmacologic Classification: alkylating agents

Pharmacokinetics ⬆ ⬇

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.

Canadian Brand Names ⬆ ⬇

Time/Action Profile ⬆ ⬇

(effects on blood counts)

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

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 ↓ 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 >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 women of reproductive potential to 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 men with female partners of reproductive potential to wear condoms during and for ≥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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Indications ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇