Myleran (Busulfan)

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

• Chronic myelogenous leukemia (CML): helps achieve disease control as part of combination chemotherapy.
• Acute myeloid leukemia (AML): used in conditioning regimens to eradicate malignant cells before stem cell transplantation.
• Hematopoietic stem cell transplantation (HSCT) conditioning: provides myeloablation to prepare the patient for engraftment.

• Busulfan exerts its cytotoxic effect by alkylating nucleophilic sites on DNA. The drug forms intra‑ and interstrand cross‑links that prevent DNA strand separation, thereby inhibiting replication and transcription. This blockade triggers apoptosis in rapidly dividing hematopoietic cells, contributing to myeloablation required for transplant conditioning and to the eradication of leukemic clones. The alkylation is non‑selective, affecting both malignant and normal proliferating cells, which underlies its therapeutic and toxicity profile.

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

Common Side Effects

• Nausea and vomiting: gastrointestinal upset that may require anti‑emetic therapy.
• Oral mucositis: painful inflammation of the mouth lining.
• Skin hyperpigmentation: darkening of the skin, especially on the face and hands.
• Cytopenias: reduced red cells, white cells, and platelets leading to anemia, neutropenia, and thrombocytopenia.
• Fatigue: persistent tiredness affecting daily activities.

Serious or Rare Side Effects

• Pulmonary fibrosis: progressive scarring of lung tissue that can impair breathing.
• Hepatic veno‑occlusive disease: blockage of small hepatic veins causing liver dysfunction.
• Seizures: neurologic events that may need anticonvulsant prophylaxis.
• Severe infections: opportunistic infections due to profound immunosuppression.

When using Busulfan, several precautionary measures should be observed to minimize risks.

• Dose individualization: dosing is calculated based on body surface area and therapeutic drug monitoring.
• Liver function monitoring: assess hepatic enzymes before and during therapy.
• Pulmonary assessment: perform baseline lung function tests and monitor for respiratory symptoms.
• Concomitant medications: avoid drugs that lower seizure threshold without prophylaxis.
• Pregnancy and lactation: contraindicated in pregnancy (Category D) and not recommended while breastfeeding.
• Store at ambient temperature: keep tablets below 25 °C in the original container, protected from moisture and light.

Busulfan can interact with other medicines, potentially altering its efficacy, toxicity, or plasma concentration.

Major Interactions (Avoid)

• Azole antifungals (e.g., fluconazole, itraconazole): markedly increase Busulfan plasma levels.
• Phenytoin and carbamazepine: significantly reduce Busulfan exposure, risking treatment failure.

Moderate Interactions (Monitor Closely)

• Acetaminophen: may modestly raise Busulfan concentrations.
• Other alkylating agents: additive myelosuppression requires careful blood count monitoring.
• Anticonvulsants without prophylaxis: may lower seizure threshold, necessitating dose adjustment.
• Renal impairment: reduced clearance can increase exposure; monitor renal function.