cyclophosphamide (sye-kloe-fos-fa-mide) Cytoxan, Procytox

 Indications

Alone or with other modalities in the management of:

Hodgkin’s disease, Malignant lymphomas, Multiple myeloma,

Leukemias, Mycosis fungoides, Neuroblastoma,

Ovarian carcinoma, Breast carcinoma, and a variety of

other tumors. Minimal change nephrotic syndrome in

children. Unlabeled Use: Severe active rheumatoid

arthritis or granulomatosis with polyangiitis.

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.

Pharmacokinetics

Absorption: Inactive parent drug is well absorbed

from the GI tract. Converted to active drug by the liver.

Distribution: Widely distributed. Limited penetration

of the blood-brain barrier. Crosses the placenta;

enters breast milk.

Metabolism and 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

Contraindications/Precautions

Contraindicated in: Hypersensitivity; OB, Lactation:

Pregnancy or lactation.

Use Cautiously in: Active infections; Bone marrow

depression; Other chronic debilitating illnesses; OB:

Patients with childbearing potential.

Adverse Reactions/Side Effects

Resp: PULMONARY FIBROSIS. CV: MYOCARDIAL FIBROSIS,

hypotension. GI: anorexia, nausea, vomiting. GU:

HEMORRHAGIC CYSTITIS, hematuria. Derm: alopecia.

Endo: gonadal suppression, syndrome of inappropriate

antidiuretic hormone (SIADH). Hemat: LEUKOPENIA,

thrombocytopenia, anemia.Metab: hyperuricemia.

Misc: secondary neoplasms.

Interactions

Drug-Drug: Phenobarbital or rifampin mayq

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). Maypserum digoxin

levels. Additive bone marrow depression with other antineoplastics

or radiation therapy. May potentiate

the effects of warfarin. Maypantibody response to

live-virus vaccines andqrisk of adverse reactions.

Prolongs the effects of cocaine.

Route/Dosage

Many regimens are used.

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 q 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 q 3–4 wk.

Availability (generic available)

Capsules: 25 mg, 50 mg. Lyophilized powder for

injection: 500 mg/vial, 1 g/vial, 2 g/vial.