busulfan, Busulfex, Myleran

 Indications

PO: Treatment of chronic myelogenous leukemia

(CML) and bone marrow disorders. IV: With cyclophosphamide

as a conditioning regimen before allogenic

hematopoietic progenitor cell transplantation for

CML.

Action

Disrupts nucleic acid function and protein synthesis

(cell-cycle phase–nonspecific). Therapeutic Effects:

Death of rapidly growing cells, especially malignant

ones.

Pharmacokinetics

Absorption: Rapidly absorbed from the GI tract.

Distribution: Unknown.

Metabolism and Excretion: Extensively metabolized

by the liver.

Half-life: 2.5 hr.

TIME/ACTION PROFILE (effects on blood

counts)

ROUTE ONSET PEAK DURATION

PO 1–2 wk weeks up to 1 mo†

IV unknown unknown 13 days‡

†Complete recovery may take up to 20 mo.

‡After administration of last dose.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Failure to respond

to previous courses; OB, Lactation: Potential for

serious side effects in fetus or infant.

Use Cautiously in: Active infections;pbone marrow

reserve; Obese patients (base dose on ideal body

weight); Other chronic debilitating diseases; Patients

with childbearing potential; Geri: Begin therapy at

lower end of dose range due toqfrequency of impaired

cardiac, hepatic, or renal function.

Adverse Reactions/Side Effects

Incidence and severity of adverse reactions and side effects

are increased with IV use.

CNS: IV—SEIZURES, CEREBRAL HEMORRHAGE/COMA,

anxiety, confusion, depression, dizziness, headache,

encephalopathy, mental status changes, weakness.

EENT: PO—cataracts; IV, epistaxis, pharyngitis, ear

disorders. CV: hepatic veno-oclusive disease (qallogenic

transplantation). Resp: PO—PULMONARY FIBROSIS;

IV, alveolar hemorrhage, asthma, atelectasis,

cough, hemoptysis, hypoxia, pleural effusion, pneumonia,

rhinitis, sinusitis. CV: PO—CARDIAC TAMPONADE

(WITH HIGH-DOSE CYCLOPHOSPHAMIDE); IV, chest pain,

hypotension, tachycardia, thrombosis, arrhythmias,

atrial fibrillation, cardiomegaly, ECG changes, edema,

heart block, heart failure, hypertension, pericardial effusion,

ventricular extrasystoles. GI: PO—drug-induced

hepatitis, nausea, vomiting; IV, abdominal enlargement,

anorexia, constipation, diarrhea, dry mouth,

hematemesis, nausea, rectal discomfort, vomiting, abdominal

pain, dyspepsia, hepatomegaly, pancreatitis,

stomatitis. GU: oliguria, dysuria, hematuria. Derm:

PO—itching, rashes, acne, alopecia, erythema nodosum,

exfoliative dermatitis, hyperpigmentation.

Endo: PO—sterility, gynecomastia. F and E: hypokalemia,

hypomagnesemia, hypophosphatemia. Hemat:

BONE MARROW DEPRESSION. Local: inflammation/pain at

injection site.Metab: PO and IV—hyperuricemia; IV,

hyperglycemia. MS: arthralgia, myalgia, back pain.

Misc: allergic reactions, chills, fever, infection.

Interactions

Drug-Drug: Concurrent or previous (within 72 hr)

use of acetaminophen maypelimination andqtoxicity.

Concurrent use with high-dose cyclophosphamide

in patients with thalassemia may result in cardiac

tamponade. Concurrent use with itraconazole or

phenytoinpblood level effectiveness. Long-term continuous

therapy with thioguanine mayqrisk of hepatic

toxicity.qbone marrow suppression with other

antineoplastics or radiation therapy. Maypthe antibody

response to andqrisk of adverse reactions from

live-virus vaccines.

Route/Dosage

Many other regimens are used. See current protocols

for up-to-date dosage.

PO (Adults): Induction—1.8 mg/m2/day or 60 mcg

(0.06 mg)/kg/day until WBCs 15,000/mm3. Usual

dose is 4–8 mg/day (range 1–12 mg/day). Maintenance—

1–3 mg/day.

PO (Children): 0.06–0.12 mg/kg/day or 1.8–4.6

mg/m2/day initially. Titrate dose to maintain WBC of approximately

20,000/mm3.

IV (Adults): 0.8 mg/kg q 6 hr (dose based on ideal

body weight or actual weight, whichever is less; in

obese patients, dosage should be based on adjusted

ideal body weight) for 4 days (total of 16 doses); given

in combination with cyclophosphamide.

Availability (generic available)

Tablets: 2 mg. Solution for injection: 6 mg/mL.