Busulfan

Busulfan is indicated for Chronic myeloid leukemia, 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.

Polycythemia vera:

• Adult: 4-6 mg daily continued for 4-6 wk with blood count monitoring, particularly platelet. Further courses may be given if relapse occurs; alternatively, a maintenance therapy approx half the induction dose may be given.

Chronic myeloid leukaemia:

• Adult: Remission induction: Initially, 0.06 mg/kg daily. Max: 4 mg daily. May increase dose if response is inadequate after 3 wk. Continue until WBC count falls to 15,000-25,000 cells/mm³ (usually 12-20 wk); may stop earlier if platelet count is <100,000 cells/mm³. Maintenance: If WBC count rises to 50,000 cells/mm³ or symptoms return: Resume induction dose; if remission is <3 mth: 0.5-2 mg daily, given as continuous maintenance.
• Child: Same as adult dose.

Essential thrombocythemia:

• Adult: 2-4 mg daily.

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.

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.

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.

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

Cytotoxic Chemotherapy

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