Myleran (Busulfan)

Busulfan is an alkylating antineoplastic agent used in specific hematologic malignancies and transplant protocols.

• Chronic myeloid leukemia (CML): reduces leukemic cell proliferation and improves survival when combined with other agents.
• Bone marrow transplantation conditioning: eradicates residual disease and creates immunosuppression to facilitate engraftment.
• Acute myeloid leukemia (AML) conditioning: incorporated into high‑dose regimens to achieve myeloablation before stem cell rescue.

• Busulfan exerts its cytotoxic effect by alkylating DNA at the N7 position of guanine residues, forming intra‑ and interstrand cross‑links that block DNA replication and transcription. This damage triggers cell‑cycle arrest and apoptosis in rapidly dividing hematopoietic cells. The drug is primarily metabolized by hepatic glutathione S‑transferase, and its activity is dose‑dependent, often requiring therapeutic drug monitoring.

Busulfan may cause a range of adverse reactions, varying from mild to severe.

Common Side Effects

• Nausea and vomiting: gastrointestinal upset occurring early in treatment.
• Oral mucositis: inflammation and ulceration of the mouth lining.
• Skin hyperpigmentation: diffuse darkening, especially on sun‑exposed areas.
• Bone marrow suppression: decreased blood cell counts leading to fatigue and infection risk.

Serious or Rare Side Effects

• Pulmonary fibrosis: progressive scarring of lung tissue, potentially life‑threatening.
• Hepatic veno‑occlusive disease: obstruction of small hepatic veins causing liver dysfunction.
• Seizures: central nervous system events, particularly at high plasma concentrations.

When prescribing Busulfan, clinicians should observe several safety measures to minimize risks.

• Therapeutic drug monitoring: adjust dose based on plasma levels to avoid toxicity.
• Hepatic function assessment: evaluate liver enzymes before and during therapy.
• Concomitant anticonvulsant use: consider prophylactic antiepileptic medication in high‑risk patients.
• Avoid in patients with severe pulmonary disease: risk of exacerbating lung injury.
• Store at ambient temperature: keep tablets in original container, protect from moisture and heat.

Busulfan interacts with several agents that can alter its plasma concentration or increase toxicity.

Major Interactions (Avoid)

• Azathioprine: combined use markedly increases myelosuppression.
• Chloramphenicol: inhibits hepatic metabolism, raising Busulfan levels.
• Phenytoin: induces metabolism, potentially reducing efficacy.

Moderate Interactions (Monitor Closely)

• Acetaminophen: may compete for glutathione pathways, modestly affecting clearance.
• Rifampin: enzyme induction can lower Busulfan exposure.
• Concomitant radiation therapy: additive bone marrow toxicity.