busulfan: clinical use

Prescribing considerations

• Restrict initiation and supervision to clinicians experienced in cytotoxic therapy or transplant conditioning.
• Profound myelosuppression is expected in transplant conditioning; ensure infection, transfusion and supportive-care pathways are available.
• Assess previous chemotherapy, radiotherapy or transplantation because these may increase hepatic sinusoidal obstruction risk.
• Review seizure history and provide protocol-appropriate anticonvulsant prophylaxis for high-intensity treatment.
• Discuss gonadotoxicity and fertility preservation before treatment where feasible.
• Avoid live vaccines and review interacting medicines, particularly deferasirox, itraconazole, metronidazole and paracetamol.

Contraindications and cautions

• Hypersensitivity to busulfan or product excipients.
• Previous demonstrated resistance to busulfan for the tablet product.
• Pregnancy for the intravenous transplant-conditioning product.
• The tablet contains lactose and is unsuitable for specified rare hereditary disorders of galactose metabolism or absorption.

Monitoring

• Frequent full blood count with differential and platelets until recovery or stable control.
• Liver tests and clinical features of hepatic sinusoidal obstruction syndrome.
• Renal function during intravenous therapy; use caution in renal impairment.
• Respiratory symptoms and lung function where toxicity is suspected.
• Cardiac function during intravenous conditioning where clinically appropriate.
• Busulfan pharmacokinetic exposure when required by the transplant protocol, particularly with deferasirox.
• Urate status in chronic myeloid leukaemia where tumour-cell breakdown may cause hyperuricaemia.

Clinical pharmacology

Busulfan is a bifunctional alkylating agent. Reactive intermediates alkylate DNA, disrupting replication and producing cytotoxic and myeloablative effects. Oral bioavailability is variable, while the intravenous formulation provides controlled systemic delivery.

Formulation and product differences

• Tablets are swallowed whole and contain lactose; they are licensed for transplant conditioning and selected chronic haematological disorders.
• The infusion is a cytotoxic concentrate containing dimethylacetamide and macrogol. It requires aseptic dilution, central venous administration and specialist handling.
• The infusion must not be given by rapid intravenous injection, bolus or peripheral injection; polycarbonate syringes must not be used.

Solution for infusion

Route: Intravenous

Strengths: 6 mg/mL

Tablet

Route: Oral

Strengths: 2 mg