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Pharmacologic class: Alkylating agent
Therapeutic class: Antineoplastic
Pregnancy risk category D
FDA Box Warning
• Drug causes profound myelosuppression at recommended dosage. Give under supervision of physician experienced in allogeneic hematopoietic stem cell transplantation, cancer chemotherapy, and management of severe pancytopenia, in facility with adequate diagnostic and treatment resources.
Unclear. Thought to interfere with bacterial cell-wall synthesis by cross-linking strands of DNA and disrupting RNA transcription, which causes cell to rupture and die. Exhibits minimal immunosuppressant activity.
Injection: 6 mg/ml in 10-ml ampules
Tablets: 2 mg
Indications and dosages
➣ Chronic myelogenous leukemia
Adults: 4 to 8 mg P.O. daily until white blood cell (WBC) count decreases to 15,000/mm3; then discontinue drug until WBC count rises to 50,000/mm3, and then resume as needed.
Children: 0.06 to 0.12 mg/kg/day P.O. or 1.8 to 4.6 mg/m2/day P.O. Adjust dosage to maintain WBC count at approximately 20,000/mm3. Drug should be withheld when WBC count decreases to approximately 15,000/mm3.
➣ Allogenic hematopoietic stem cell transplantation
Adults: 0.8 mg/kg I.V. q 6 hours for 4 days. Starting 6 hours after 16th dose of busulfan injection, give cyclophosphamide 60 mg/kg/day I.V. over 1 hour for 2 days.
• Adjunctive therapy in ovarian cancer
• Bone marrow transplantation
• Hypersensitivity to drug
• Patients not definitively diagnosed with chronic myelogenous leukemia
• Pregnancy or breastfeeding
Use cautiously in:
• active infections, decreased bone marrow reserve, chronic debilitating disease, depressed neutrophil and platelet counts, seizure disorders, obesity
• patients receiving concurrent myelosuppressive or radiation therapy
• females of childbearing age.
• Give oral doses on empty stomach.
• When administering I.V., withdraw dose from ampule using 5-micron filter needle. Remove filter needle and use new needle to add busulfan to diluent.
• Dilute for injection using dextrose 5% in water or normal saline solution.
• Infuse I.V. dose over 2 hours, using an infusion pump.
• Flush I.V. catheter before and after each infusion with 5 ml D5W or normal saline solution.
☞ Be aware that drug is highly toxic and has a narrow therapeutic index.
• Maintain vigorous hydration to reduce risk of renal toxicity.
• Handle patient gently to avoid bruising.
CNS: anxiety, confusion, depression, dizziness, headache, insomnia, weakness, encephalopathy, seizures, cerebral hemorrhage, coma
CV: chest pain, hypotension, hypertension, tachycardia, ECG changes, heart block, left-sided heart failure, thrombosis, pericardial effusion, ventricular extrasystole, atrial fibrillation, arrhythmias, cardiac tamponade, cardiomegaly
EENT: cataracts, ear disorders, epistaxis, pharyngitis
GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, abdominal enlargement, pancreatitis, hematemesis, dry mouth, stomatitis, anorexia
GU: dysuria, hematuria, sterility, gyne-comastia, oliguria
Hematologic: febrile neutropenia, thrombotic microangiopathy, profound myelosuppression
Hepatic: hepatitis, hepatomegaly
Metabolic: hypokalemia, hypomagnesemia, hypophosphatemia, hyperuricemia, hyperglycemia
Musculoskeletal: arthralgia, myalgia, back pain
Respiratory: hyperventilation, dyspnea, pulmonary fibrosis
Skin: pruritus, rash, acne, alopecia, erythema nodosum, exfoliative dermatitis, hyperpigmentation
Other: allergic reactions, chills, fever, injection site infection or inflammation; severe bacterial, viral, fungal infections; sepsis; tumor lysis syndrome
Drug-drug. Anticoagulants, aspirin, nonsteroidal anti-inflammatory drugs: increased risk of bleeding
Live-virus vaccines: decreased antibody response to vaccine, increased risk of adverse reactions
Myelosuppressants: additive bone marrow depression
Nephrotoxic and ototoxic drugs (such as aminoglycosides, loop diuretics): additive nephrotoxicity and ototoxicity
Thioguanine: increased risk of hepatotoxicity
Drug-diagnostic tests. Alkaline phosphatase, aspartate aminotransferase, bilirubin, nitrogenous compounds (urea): increased levels
Hemoglobin, WBCs: decreased values
• Monitor patient closely for adequate hydration.
• Check for signs and symptoms of local or systemic infections.
• Assess for bleeding and excessive bruising.
• Evaluate oral hygiene regularly.
• Monitor CBC and WBC and platelet counts daily if patient is receiving I.V. busulfan.
• Monitor renal and hepatic function.
☞ Know that diffuse pulmonary fibrosis ("busulfan lung") is a rare but potentially life-threatening complication, with symptom onset as late as 10 years after therapy.
• Inform patient that drug doesn't cure leukemia but may induce remission.
• Advise patient to drink plenty of fluids to avoid dehydration.
☞ Instruct patient to immediately report inability to eat or drink. Prescriber may add another drug to improve appetite.
• Inform patient that he's at increased risk for infection. Advise him to avoid contact with people with known infections and to avoid public transportation, if possible.
• Tell patient he's at increased risk for bleeding and bruising.
• Advise patient to avoid activities that can cause injury and to use soft toothbrush and electric razor to avoid gum and skin injury.
• Inform patient that he'll undergo frequent blood testing to monitor drug effects.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.
busulfanAn alkyl sulphonate, the sole antineoplastic activity of which is myelosuppression. At low doses, it suppresses granulocytopoiesis; at higher doses, it evokes pancytopenia. Bulsulfan was the standard therapy for chronic myeloid leukaemia (CML) until imatinib was developed for oncological therapy.
Marrow suppression, pulmonary fibrosis, seizures, hepatic veno-occlusive disease, wasting syndrome, thrombocytopaenia.