busulfan
Busulfex, Myleran

Available forms
Available by prescription only
Injection for I.V. infusion: 6 mg/ml
Tablets (scored): 2 mg

Indications and dosages
  Dosages and indications may vary. Check package insert for recommended protocol.
 Chronic myelogenous leukemia. Adults: For remission induction, usual dose is 4 to 8 mg P.O. daily; however dose may range from 1 to 12 mg P.O. daily (0.06 mg/kg or 1.8 mg/m²). For maintenance therapy, 1 to 3 mg P.O. daily.
Children: 0.06 mg/kg or 1.8 mg/m² P.O. daily. Dose should be adjusted to maintain WBC count of about 20,000/mm³.
 Myelofibrosis ◇. Adults: Initially, 2 to 4 mg P.O. daily, followed by the same dose two to three times weekly.
 Allogenic hematopoietic stem cell transplantation ◇. Adults: 0.8 mg/kg of ideal body weight or actual body weight (whichever is lower) I.V. q 6 hr for 4 consecutive days for a total of 16 doses. Give phenytoin for seizure prophylaxis.

Pharmacodynamics
Antineoplastic action: Busulfan is an alkylating agent that exerts its cytotoxic activity by interfering with DNA replication and RNA transcription, causing a disruption of nucleic acid function.

Pharmacokinetics
Absorption: Well absorbed from the GI tract.
Distribution: Distribution into the brain and CSF is unknown.
Metabolism: Metabolized in the liver.
Excretion: Cleared rapidly from plasma. Drug and its metabolites are excreted in urine.

Contraindications and precautions
Contraindicated in patients whose chronic myelogenous leukemia has shown previous resistance to drug. Also contraindicated in patients with chronic lymphocytic leukemia or acute leukemia and in those in blastic crisis of chronic myelogenous leukemia.
  Use cautiously in patients recently given other myelosuppressants or radiation treatment; in those with depressed neutrophil or platelet counts, head trauma, or seizures; and in patients taking other drugs that reduce the seizure threshold.

Interactions
Drug-drug. Acetaminophen, cyclophosphamide, phenytoin, thioguanine: Increase busulfan clearance. Use together cautiously.
Itraconazole: Decreases busulfan clearance. Avoid use together if possible.

Adverse reactions
CNS: weakness, fatigue.
EENT: cataracts.
GI: cheilosis, dry mouth, anorexia.
Hematologic: leukopenia (WBC count decreasing after about 10 days and continuing to decrease for 2 weeks after stopping drug), thrombocytopenia, anemia, severe pancytopenia.
Metabolic: profound hyperuricemia caused by increased cell lysis.
Respiratory: irreversible pulmonary fibrosis (commonly called busulfan lung).
Skin: alopecia, transient hyperpigmentation, rash, urticaria, anhidrosis, jaundice.
Other: gynecomastia, Addison-like wasting syndrome.

Effects on lab test results
• May increase uric acid levels.
• May decrease hemoglobin and RBC, WBC, and platelet counts.

Overdose and treatment
Signs and symptoms of overdose include hematologic problems, such as leukopenia and thrombocytopenia.
 Treatment is supportive and includes transfusion of blood components and antibiotics for infections that may develop.

Special considerations
• Drug-induced cellular dysplasia may interfere with interpretation of cytologic studies.
• Avoid all I.M. injections when platelet count is below 100,000/mm³.
• Patient response (increased appetite, sense of well-being, decreased total leukocyte count, reduction in size of spleen) usually begins 1 to 2 weeks after starting drug.
• Observe patient for signs or symptoms of infection, such as fever and sore throat.
• Monitor uric acid, CBC, and kidney function.
• Monitor serum alkaline phosphatase, bilirubin, and serum aminotransferase levels for possible hepatotoxicity.
• Monitor leukocyte count; manufacturer recommends stopping busulfan when leukocyte count is 15,000/mm³ or less.
 ALERT Pulmonary fibrosis may be delayed for 4 to 6 months.
• Minimize hyperuricemia by adequate hydration, alkalinization of urine, and administration of allopurinol.
Pregnant patients
• Busulfan may cause fetal harm (malformations, bone marrow depression, growth retardation, and death). Also, drug may impair fertility. Avoid use in pregnant women.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. However, potential for mutagenicity, carcinogenicity, and serious adverse reactions in the infant should be taken into consideration when patient decides whether to breast-feed.

Patient education
• Advise patient to use caution when taking aspirin-containing products and to promptly report signs and symptoms of bleeding.
• Tell patient to take drug at the same time each day.
• Emphasize importance of continuing to take drug despite nausea and vomiting.
• Persistent cough and progressive dyspnea with alveolar exudate may result from drug toxicity, not pneumonia. Instruct patient to report symptoms so dosage adjustments can be made.
• Review the signs and symptoms of infection, and tell patient to report them promptly if they occur.
• Advise patient to use contraception during therapy.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use