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Busulfan

2mg
Cytotoxic Chemotherapy
0.00 (0)


Action Period: ...

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.


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Generic Indications

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Drug Indications

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


Dosage Administration

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.

Contraindication

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.


Side Effect

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.


Precaution Warning

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






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Busulfan

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