“May all be happy, may all be healed, may all be at peace and may no one ever suffer."
Busulfan is an alkylating agent that contains 2 labile methanesulfonate groups attached to opposite ends of a 4-carbon alkyl chain. Once busulfan is hydrolyzed, the methanesulfonate groups are released and carbonium ions are produced. These carbonium ions alkylate DNA, which results in the interference of DNA replication and RNA transcription, ultimately leading to the disruption of nucleic acid function. Specifically, its mechanism of action through alkylation produces guanine-adenine intrastrand crosslinks. This occurs through an SN2 reaction in which the relatively nucleophilic guanine N7 attacks the carbon adjacent to the mesylate leaving group. This kind of damage cannot be repaired by cellular machinery and thus the cell undergoes apoptosis.
Busulfan is indicated for Chronic myeloid leukaemia, Polycythemia vera, Essential thrombocythemia, Conditioning regimens for bone marrow transplantation, Conditioning regimens for bone marrow transplantation
Polycythemia vera:
Chronic myeloid leukaemia:
Essential thrombocythemia:
Patient with chronic myelogenous leukemia whose disease was resistant to prior therapy with the drug; definitive diagnosis of chronic myelogenous leukemia has not firmly established.
Bone marrow depression, manifested as leucopenia, thrombocytopenia and anaemia; hyperpigmentation, GI disturbances, impaired fertility and gonadal function. Rarely, dry skin, gynaecomastia, cataract formation, at high doses, CNS effects including convulsions.
Overdose Effects
Symptoms: Myelosuppression, bone marrow depression, pancytopenia.
Management: Supportive treatment. Consider haemodialysis.
Discontinue if lung toxicity develops. Severe hepatic or renal impairment. Pregnancy and lactation.
Pregnancy & Lactation
Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk