Busulfan


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Chronic myeloid leukaemia Remission induction: Initial: 0.06 mg/kg/day. Max: 4 mg/day. Continue until WBC count is 15,000-25,000 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/day, as continuous maintenance. Polycythemia vera 4-6 mg/day continued for 4-6 wk. Essential thrombocythemia 2-4 mg/day. Conditioning regimens for bone marrow transplantation 1 mg/kg 6 hrly for 4 days, starting 7 days before transplantation; cyclophosphamide is given for 2 days, starting 24 hr after final dose of busulfan. IV Conditioning regimens for bone marrow transplantation 0.8 mg/kg ideal body wt 6 hrly for 4 days starting 7 days before transplantation; cyclophosphamide is given for 2 days initiated for at least 24 hr after final dose of busulfan.
Dosage Details
Intravenous
Conditioning regimens for bone marrow transplantation
Adult: 0.8 mg/kg ideal body wt 6 hrly for 4 days starting 7 days before transplantation; cyclophosphamide is given for 2 days initiated for at least 24 hr after final dose of busulfan. Doses should be given over 2 hr through a central venous catheter using an infusion pump.
Child: 0-17 yr <9 kg: 1 mg/kg; 9-<16 kg: 1.2 mg/kg; 16-23 kg: 1.1 mg/kg; >23-34 kg: 0.95 mg/kg; >34 kg: 0.8 mg/kg. Doses are given 6 hrly for 4 days followed by cyclophosphamide or melphalan, started at least 24 hr after final dose of busulfan.

Oral
Conditioning regimens for bone marrow transplantation
Adult: 1 mg/kg 6 hrly for 4 days, starting 7 days before transplantation; cyclophosphamide is given for 2 days, starting 24 hr after final dose of busulfan.
Child: <18 yr Up to 37.5 mg/m2 6 hrly for 4 days, starting 7 days before transplantation; cyclophosphamide is given for 2 days, starting 24 hr after final dose of busulfan.

Oral
Polycythemia vera
Adult: 4-6 mg daily continued for 4-6 wk w/ 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.

Oral
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.

Oral
Essential thrombocythemia
Adult: 2-4 mg daily.
Special Patient Group
Obese patients: Base dosage on BSA or adjusted ideal body wt.
Administration
May be taken with or without food. Take w/ chilled liqd, ensure adequate fluid intake.
Reconstitution
Each dose should be diluted in NaCl 0.9% or glucose 5% to a final concentration of approx 0.5 mg/mL.
Contraindications
Patient w/ chronic myelogenous leukemia whose disease was resistant to prior therapy w/ the drug; definitive diagnosis of chronic myelogenous leukemia has not firmly established.
Special Precautions
Discontinue if lung toxicity develops. Severe hepatic or renal impairment. Pregnancy and lactation.
Adverse Reactions
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.
Potentially Fatal: Hepatic veno-occlusive disease, hyperbilirubinaemia; "busulfan lung", manifested by bronchopulmonary dysplasia w/ a diffuse interstitial pulmonary fibrosis, characterised by persistent cough, fever, rales and dyspnoea.
IV/Parenteral/PO: D
MonitoringParameters
Monitor blood counts carefully during therapy. Evaluate transaminases, alkaline phosphatase and bilirubin daily for at least 28 days post transplant.
Overdosage
Symptoms: Myelosuppression, bone marrow depression, pancytopenia. Management: Supportive treatment. Consider haemodialysis.
Drug Interactions
Additive myelosuppression w/ other myelosuppressive agents. Cytotoxic agents may increase risk of pulmonary toxicity. May reduce response to vaccines, possibility of generalised infections w/ live vaccines. Increased risk of adverse effects if given in conjunction w/ or soon after radiotherapy. Decreased clearance when used w/ cyclophosphamide, itraconazole or paracetamol. Combination w/ thioguanine may result in oesophageal varices, hepatotoxicity and portal HTN. Increased clearance by phenytoin.
Action
Description: Busulfan reacts w/ N-7 position of guanosine and interferes w/ DNA replication and RNA transcription by alkylating and cross-linking the DNA strands.
Pharmacokinetics:
Absorption: Rapidly and completely absorbed from the GI tract (oral). Bioavailability: 47-103% (oral). Time to peak plasma concentration: Approx 1 hr (oral); w/in 5 min (IV).
Distribution: Crosses the blood-brain barrier; concentrations in CSF are approx equal to concurrent plasma concentrations. Plasma protein binding: Approx 30% (irreversible), mainly to albumin.
Metabolism: Undergoes extensive hepatic metabolism mainly via conjugation w/ glutathione, either spontaneously or mediated by the enzyme glutathione-S-transferase.
Excretion: Via urine, 25-60% as metabolites; approx 1% as unchanged drug. Plasma elimination half-life: Approx 2-3 hr.
Chemical Structure

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Storage
Tab: Store below 25°C. Inj concentrate: Store between 2-8°C. Do not freeze.
ATC Classification
L01AB01 - busulfan ; Belongs to the class of alkylating agents, alkyl sulfonates. Used in the treatment of cancer.
Disclaimer: This information is independently developed by MIMS based on Busulfan from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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