Generic Name

Busulfan

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Classification

FDA Approved Indications

• Chronic myelogenous leukemia (CML) in chronic phase; used as part of bone marrow conditioning regimens before stem cell transplantation

Mechanism of Action

Busulfan works by alkylating DNA, leading to cross-linking of DNA strands, which prevents cell replication and causes cell death, primarily affecting rapidly dividing cells like cancer cells.

Dosage and Administration

Adult: The dosing varies based on regimen and condition; typically, an oral dose of 4-6 mg daily in divided doses for several days, or intravenous dosing as per protocol; close monitoring is required.

Pediatric: Dosing determined by body surface area or weight, with careful monitoring; consult oncology protocols.

Geriatric: Use with caution; consider decreased organ function and comorbidities affecting drug metabolism and clearance.

Renal Impairment: Adjust dose as needed; dose adjustment guidelines are limited, so close monitoring of toxicity is essential.

Hepatic Impairment: No specific adjustments established; use caution, considering hepatic function.

Pharmacokinetics

Absorption: Oral bioavailability varies; intravenous administration provides predictable plasma levels.

Distribution: Widely distributed across tissues, crosses the blood-brain barrier.

Metabolism: Metabolized hepatically; exact pathways are not fully understood.

Excretion: Primarily excreted in urine.

Half Life: Approximate elimination half-life is about 2-3 hours, but effective half-life during therapy depends on infusion duration and regimen.

Contraindications

• Hypersensitivity to busulfan or other alkylating agents

Precautions

• Use with caution in patients with existing bone marrow suppression, hepatic impairment, or renal impairment; risk of severe myelosuppression, pulmonary toxicity, and secondary malignancies; pregnancy category D—risk to fetus; effective contraception required for males and females during therapy.

Adverse Reactions - Common

• Myelosuppression (Very common)
• Nausea and vomiting (Common)
• Stomatitis (Common)
• Alopecia (Common)

Adverse Reactions - Serious

• Seizures (Rare)
• Pulmonary fibrosis or toxicity (Rare)
• Secondary malignancies (e.g., leukemia) (Rare)

Drug-Drug Interactions

• Other myelosuppressive agents
• CYP450 enzyme inducers or inhibitors may alter metabolism

Drug-Food Interactions

• Avoid alcohol and grapefruit juice, which can affect liver enzymes

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Report signs of infection, bleeding, or unusual bleeding gums.
• Follow precautions to prevent infections.
• Use effective contraception during and for some months after therapy.
• Avoid alcohol and hepatotoxic drugs.

Special Considerations

Black Box Warnings:

• Severe myelosuppression leading to infection, hemorrhage, and potentially fatal implementing.
• Secondary malignancies, especially leukemia.
• Potential for pulmonary toxicity.

Genetic Factors: Genetic polymorphisms in glutathione S-transferases (GSTs) may influence drug metabolism and toxicity.

Lab Test Interference: May cause changes in liver function tests, blood counts.

Overdose Management

Signs/Symptoms: Severe myelosuppression, nausea, vomiting, seizures, pulmonary symptoms.

Treatment: Supportive care, including hematopoietic growth factors, anticonvulsants for seizures, and broad-spectrum antibiotics for infections; no specific antidote.

Storage and Handling

Storage: Store at room temperature, protected from moisture and light.

Stability: Stable under proper storage conditions for the duration specified in the package insert.