Myleran

Busulfan is indicated for Chronic myeloid leukaemia, Polycythemia vera, Essential thrombocythemia, Conditioning regimens for bone marrow transplantation, Conditioning regimens for bone marrow transplantation

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.

Additive myelosuppression with other myelosuppressive agents. Cytotoxic agents may increase risk of pulmonary toxicity. May reduce response to vaccines, possibility of generalised infections with live vaccines. Increased risk of adverse effects if given in conjunction with or soon after radiotherapy. Decreased clearance when used wit cyclophosphamide, itraconazole or paracetamol. Combination with thioguanine may result in oesophageal varices, hepatotoxicity and portal HTN. Increased clearance by phenytoin.

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.

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

Discontinue if lung toxicity develops. Severe hepatic or renal impairment. Pregnancy and lactation.

Cytotoxic Chemotherapy

Symptoms: Myelosuppression, bone marrow depression, pancytopenia.
Management: Supportive treatment. Consider haemodialysis.

Tab: Store below 25°C.
Inj concentrate: Store between 2-8°C.
Do not freeze.