Busulfan
Busulfan (Myleran)
Busulfan
(byou- SUL-fan)
Pregnancy Category: D Busulfex Myleran (Rx)

Classification: Antineoplastic, alkylating agent

See Also: See also Antineoplastic Agents and Alkylating Agents .

Action/Kinetics: Is cell cycle-phase nonspecific; acts predominately against cells of the granulocytic type by alkylating cellular thiol groups. Cross-linking of nucleoproteins occurs. May cause severe bone marrow depression. Leukocyte count drops during the second or third week; thus, weekly laboratory tests are mandatory. Resistance may develop; thought to be due to the altered transport into the cell and/or increased intracellular inactivation. Rapidly absorbed from the GI tract; appears in serum 0.5-2 hr after PO administration. t 1/2: 2.5 hr. Extensively metabolized and excreted in the urine. Clearance is more rapid in children than in adults.
Increased appetite and sense of well-being may occur a few days after therapy is started. Sometimes administered with allopurinol to prevent symptoms of clinical gout.

Uses: Injection: With cyclophosphamide as a conditioning treatment prior to allogeneic hematopoeitic progenitor cell transplantation for chronic myelongenous leukemia. Tablets: Palliative treatment of chronic myelogenous leukemia (granulocytic, myelocytic, myeloid). Less effective in individuals with chronic myelogenous leukemia who lack the Philadelphia (Ph ¹) chromosome. Not effective in individuals where the disease is in the ``blastic'' phase.

Contraindications: Use of tablets unless a diagnosis of chronic myelogenous leukemia has been adequately established. Lactation.

Special Concerns: Safety and efficacy have not been established in children.

Side Effects: Hematologic: Pancytopenia, severe bone marrow hypoplasia, anemia, leukopenia, thrombocytopenia. GI: N&V;, stomatitis, anorexia, diarrhea, abdominal pain, dyspepsia, constipation, dry mouth, rectal disorder, rectal discomfort, abdominal enlargement, jaundice, hepatomegaly, hepatotoxicity hematemesis, pancreatitis. CNS: Insomnia, anxiety, dizziness, depression, confusion, lethargy, hallucinations, delirium, encephalopathy, agitation, seizures, somnolence, cerebral hemorrhage/coma. Respiratory: Bronchopulmonary dysplasia with interstitial pulmonary fibrosis. Rhinitis, lung disorder, cough, epistaxis, dyspnea, pharyngitis, hiccup, asthma, avelolar hemorrhage, hemoptysis, pleural effusion, sinusitis, atelectasis, hypoxia. CV: Tachycardia, hypertension, thrombosis, vasodilation, hypotension, arrhythmia, cardiomegaly, atrial fibrillation, abnormal ECG, heart block, left-sided heart failure, pericardial effusion, ventricular extrasystoles, endocardial fibrosis. Cardiac tamponade in children with thalessemia. Opthalmologic: Cataracts after prolonged use. Dermatologic: Hyperpigmentation, especially in clients with a dark complexion. Rash, pruritus, alopecia, vesicular rash, vesiculo-bullous rash, maculopapular rash, acne, exfoliative dermatitis, erythema nodosum. Metabolic: Syndrome resembling adrenal insufficiency, including symptoms of weakness, severe fatigue, weight loss, anorexia, N&V;, and melanoderma (especially after prolonged use). Also, hyperuricemia and hyperuricosuria in clients with chronic myelogenous leukemia. GU: Oliguria, hematuria, dysuria, hemorrhagic cystitis. Miscellaneous: Cellular dysplasia in various organs, including lymph nodes, pancreas, thyroid, adrenal glands, bone marrow, and liver. Also, cataracts after prolonged use, fever, edema, headache, asthenia, infection, chills, pain, allergic reaction, chest pain, back pain, myalgia, inflammation at injection site, arthralgia, pneumonia, ear disorder.

Laboratory Test Alterations: Uric acid in blood and urine.

Overdose Management: Symptoms: Bone marrow toxicity, CNS stimulation with convulsions and death on the first day. Treatment: If ingestion is recent, gastric lavage or induction of vomiting followed by activated charcoal. Hematologic status must be monitored.

Drug Interactions: Acetaminophen / Busulfan clearance Cyclophosphamide / Cardiac tamponade in clients with thalessemia (rare), but possibly fatal Itraconazole / Busulfan clearance Phenytoin / Busulfan clearance Thioguanine / Risk of esophageal varices with abnormal LFTs

How Supplied: Injection: 6 mg/mL; Tablet: 2 mg

Dosage
?Tablets Chronic myelocytic leukemia.
Adults or children, remission, induction, usual dose: 4-8 mg/day (about 60 mcg/kg or 1.8 mg/m ² per day) until leukocyte count falls below 15,000/mm ³; then, withdraw the drug. Maintenance, when leukocyte reaches about 50,000/mcL: Resume treatment with induction dosage. When remission is less than 3 months, consider 1-3 mg/day that may keep client under control and prevent rapid relapse.
?Injection With cyclophosphamide prior to allogeneic hematopoeitic progenitor cell transplantation.
Adults: 0.8 mg/kg of ideal body weight or actual body weight (whichever is lower) of busulfan q 6 hr for 4 days (i.e., total of 16 doses). For obese or severely obese clients, calculate the dose of busulfan based on adjusted ideal body weight. For cylcophosphamide, 60 mg/kg given on each of 2 days as a 1-hr infusion beginning on BMT day minus 3, 6 hr following the 16th busulfan dose.