Busulphan

Indications

Busulphan is used for: Chronic myeloid leukaemia, Bone marrow transplantation, Polycythemia vera, Essential thrombocythemia,

Adult Dose

Oral Palliative treatment of chronic myeloid leukemia Adult: 60 mcg/kg daily. Maintenance: 0.5-2 mg daily. Max: 4 mg daily. Polycythemia vera Adult: 4-6 mg daily continued for 4-6 wk with blood counts monitoring. Essential thrombocythemia Adult: 2-4 mg daily. Conditioning regimens for bone marrow transplantation Adult: 3.5-4 mg/kg daily in divided doses for 4 days up to a total dose of 14-16 mg/kg. Usually used with cyclophosphamide for ablation of recipient's bone marrow.

Child Dose

Renal Dose

Administration

May be taken with or without food. Take w/ chilled liqd, ensure adequate fluid intake.

Contra Indications

Pregnancy and lactation. Hypersensitivity.

Precautions

Prior treatment with other myelosuppressive drugs, patients predisposed to seizures. May cause secondary malignancies (tumors, acute leukaemias, ovarian failure). Previous irradiation/therapy. Monitor blood counts carefully during therapy. Discontinue if lung toxicity develops.

Pregnancy-Lactation

Interactions

Decreased clearance when used with cyclophosphamide and itraconazole. Increased clearance by phenytoin. May reduce response to vaccines, possibility of generalized infections with live vaccines. Combination with thioguanine results in oesophageal varices and abdominal liver function tests. Potentially Fatal: Cytotoxic agents may increase risk of pulmonary toxicity.

Adverse Effects

Side effects of Busulphan : GI symptoms, anorexia, wt loss, weakness, hyperpigmentation, amenorrhoea, cataracts, cough or hoarseness, impaired fertility and gonadal function, dry skin, liver damage, gynaecomastia. Potentially Fatal: Bone marrow depression manifesting as thrombocytopaenia, leucopaenia, anaemia. Interstitial pulmonary fibrosis (known as "busulfan lung" on prolonged treatment).

Mechanism of Action

Busulfan reacts with N-7 position of guanosine and interferes with DNA replication and RNA transcription by alkylating and cross-linking the DNA strands.