busulfan

busulfan /bu·sul·fan/ (bu-sul´fan) an antineoplastic used in treating chronic granulocytic leukemia, polycythemia vera, myeloid metaplasia, and myeloproliferative syndrome; also used in lieu of whole body irradiation in bone marrow transplantation.

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bu·sul·fan (by-slfn)

n.

An alkylating agent that is used as an antineoplastic drug in the treatment of chronic myelocytic leukemia.

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busulfan

[bo̅o̅sul′fən]

an alkylating agent.

indication It is prescribed in the treatment of chronic myelocytic leukemia.

contraindications Radiation therapy, depressed neutrophil or platelet counts, concurrent administration of neoplastic medication, or known hypersensitivity to this drug prohibits its use.

adverse reactions Among the more serious adverse reactions are alveolar hyperplasia (busulfan lung), depression of the bone marrow, and severe nausea and diarrhea. Amenorrhea commonly occurs.

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busulfan (byōōsul´fn),

n brand name: Myleran;
drug class: antineoplastic;
action: changes essential cellular ions to covalent bonding with resultant alkylation, which interferes with biologic function of deoxyribonucleic acid;
uses: treatment of chronic myelocytic leukemia.

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busulfan

an alkylating antineoplastic agent used in the treatment of chronic granulocytic leukemia.

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busulfan Warning - Hazardous drug!

Busilvex (UK), Busulfex, Myleran

Pharmacologic class: Alkylating agent

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Boxed 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.

Action

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.

Availability

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.

Off-label uses

• Adjunctive therapy in ovarian cancer
• Bone marrow transplantation

Contraindications

• Hypersensitivity to drug
• Patients not definitively diagnosed with chronic myelogenous leukemia
• Pregnancy or breastfeeding

Precautions

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.

Administration

• 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.

Route	Onset	Peak	Duration
P.O.	1-2 wk	Wks	Up to 1 mo
I.V.	Unknown	Unknown	13 days

Adverse reactions

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, gynecomastia, oliguria

Hematologic: 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

Interactions

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

Patient monitoring

• 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.

Patient teaching

• 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.

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busulfan

BU, Myleran^® Oncology An alkyl sulfonate, the sole antineoplastic activity of which is myelosuppression; at low doses, it suppresses granulocytopoiesis; at higher doses, evokes pancytopenia Indications CML Toxicity Confined to BM Response rate 85–90%