Busulfan

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.

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, 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

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.