Myleran (Busulfan)

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

• Chronic myeloid leukemia: reduces leukemic cell proliferation and helps achieve disease control.
• Bone marrow transplantation conditioning: eradicates residual hematopoietic cells to facilitate donor stem‑cell engraftment.
• Acute myeloid leukemia (pre‑transplant): contributes to remission induction when incorporated into conditioning regimens.

• Busulfan alkylates DNA by forming covalent bonds with nucleophilic sites, creating interstrand cross‑links that block DNA replication and transcription. The resulting inhibition of DNA synthesis triggers apoptosis, particularly in rapidly dividing hematopoietic and malignant cells, providing its antineoplastic effect.

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

Common Side Effects

• Nausea: mild to moderate gastrointestinal upset.
• Oral mucositis: inflammation and ulceration of the mouth lining.
• Skin hyperpigmentation: darkening of the skin, especially on the face and hands.
• Low blood counts (myelosuppression): decreased neutrophils, platelets, or red cells.

Serious or Rare Side Effects

• Pulmonary fibrosis: progressive scarring of lung tissue.
• Hepatic veno‑occlusive disease: obstruction of small hepatic veins causing liver dysfunction.
• Seizures: rare neurologic events, especially at high plasma concentrations.

Before initiating therapy, several safety measures should be observed.

• Baseline blood counts: monitor CBC before and during treatment.
• Liver function: assess hepatic enzymes and bilirubin prior to therapy.
• Pulmonary assessment: perform baseline lung function tests and watch for respiratory symptoms.
• Drug interactions: avoid concurrent strong CYP2B6 inducers or inhibitors without dose adjustment.
• Pregnancy and lactation: contraindicated unless benefits outweigh risks; discuss with a specialist.
• Store at ambient temperature below 25°C: keep capsules in original container, protect from moisture and light.

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

Major Interactions (Avoid)

• Strong CYP2B6 inducers (e.g., rifampicin, carbamazepine): may reduce busulfan exposure.
• Strong CYP2B6 inhibitors (e.g., clozapine, itraconazole): may increase toxicity risk.
• Concomitant thiotepa or cyclophosphamide: additive myelosuppression.

Moderate Interactions (Monitor Closely)

• Anticonvulsants (e.g., phenytoin, phenobarbital): may alter plasma levels.
• Azole antifungals (e.g., fluconazole): may increase busulfan concentrations.
• Radiation therapy: may enhance pulmonary toxicity.