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Busulfan oral

Updated 2 Feb 2023 | Alkylating agents


Busulfan oral formulations

Drugs List

  • busulfan 2mg tablets
  • Therapeutic Indications


    Conditioning prior to haematopoietic progenitor cell transplantation
    Leukaemia - chronic granulocytic
    Management of thrombocythemia
    Treatment of polycythemia vera

    Conditioning treatment prior to haematopoietic progenitor cell transplantation
    Palliative treatment of the chronic phase of chronic granulocytic leukaemia
    Treatment of polycythemia vera, particularly in cases with marked thrombocytosis
    Treatment of selected cases of essential thrombocythaemia
    Treatment of selected cases of myelofibrosis


    Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

    Patients treated with high dose busulfan should be given prophylactic anticonvulsant therapy, preferably with a benzodiazepine rather than phenytoin.

    Busulfan is ineffective once blast transformation has occurred.


    Conditioning prior to haematopoietic progenitor cell transplantation:
    Recommended dose is 1 mg/kg busulfan every 6 hours for 4 days, starting 7 days prior to transplantation.

    60 mg/kg/day cyclophosphamide is usually given for 2 days, commencing 24 hours after final dose of busulfan.

    Drug level monitoring is recommended

    Chronic granulocytic leukaemia :
    Induction treatment:
    The dose is 60 micrograms/kg/day with an initial daily maximum of 4 mg, which may be given as a single dose.

    The dose should be increased only if the response is inadequate after three weeks.

    Interrupt treatment if the leukocyte count has fallen to 15 to 25 x 10 to the power of 9 per litre (typically 12 to 20 weeks). Following which a further fall in leukocyte count may occur over the next 2 weeks.

    Continued treatment at the induction rate after this point or following depression of the platelet count to below 100 x 10 to the power of 9 per litre is associated with a significant risk of prolonged and possibly irreversible bone marrow aplasia.

    Maintenance treatment:
    Further courses are usually given when the leukocyte count has risen to 50 x 10 to the power of 9 per litre, or when symptoms return.

    Continuous treatment may be more practical when the duration of unmaintained remissions is short.

    The usual maintenance dose is 0.5 to 2 mg/day, with the aim of maintaining a leucocyte count of 10 to 15 x 10 to the power of 9 per litre.

    Polycythaemia vera:
    The usual dose is 4 to 6 mg daily, continued for 4 to 6 weeks.

    Further courses are given when a relapse occurs. Alternatively, maintenance therapy may be given using approximately half the induction dose.

    If polycythaemia is controlled primarily by venesection, short courses may be given solely to control the platelet count.

    Essential thrombocythaemia:
    The usual initial dose is 2 to 4 mg daily.

    Interrupt treatment if the total leucocyte count falls below 5 x 10 to the power of 9 per litre or the platelet count falls below 500 x 10 to the power of 9 per litre.

    The usual initial dose is 2 to 4 mg daily.


    (See Dosage; Adult)


    Conditioning prior to haematopoietic progenitor cell transplantation:
    Consult local treatment protocols.
    Administered up to a maximum of 37.5 mg/metre square busulfan every 6 hours for 4 days, starting 7 days prior to transplantation.

    60 mg/kg/day cyclophosphamide is usually given for 2 days, commencing 24 hours after final dose of busulfan.

    Drug level monitoring is recommended

    Chronic granulocytic leukaemia
    The manufacturer advises that busulfan may be used to treat Philadelphia chromosome positive disease. However, the manufacturer notes that the Philadelphia chromosome negative juvenile variant responds poorly.


    As the tablets should not be halved or otherwise divided, should the patient require a daily dose of less than the content of 1 tablet, the dose should be adjusted by introducing one or more busulfan free days.



    Precautions and Warnings

    Concurrent radiotherapy
    History of progenitor cell transplantation
    History of radiotherapy
    Fanconi's anaemia
    Hepatic impairment
    History of seizures
    Renal impairment

    Administration of live vaccines is not recommended
    Consider use of anti-infective prophylaxis during neutropenic phase
    Correct hyperuricaemia before treatment
    Correct hyperuricosuria before treatment
    Give pre-treatment counselling and consideration of sperm cryopreservation
    Maintain adequate hydration of patient prior / during treatment
    Treatment to be prescribed under the supervision of a specialist
    Consult local policy on the safe use of oral anti-cancer drugs
    Staff: Not to be handled by pregnant staff
    Monitor haematological parameters regularly throughout treatment
    Monitor hepatic function
    Consider hepatic veno-occlusive disease if hepatic impairment occurs
    Consider treatment with blood growth factors if severe cytopenias develop
    Consider treatments to prevent hyperuricaemia
    Monitor for signs of hepatotoxicity post transplant
    Potentially leukaemogenic
    Potentially mutagenic and carcinogenic
    Discontinue if pulmonary toxicity occurs
    Consider prophylactic anti-convulsant with high dose therapy
    In obese patients dosing should be based on ideal weight
    Advise patient not to take paracetamol during treatment
    Male & female: May cause infertility
    Male & female: Contraception required during & for 6 months after treatment

    Hepatic veno-occlusive disease can occur during busulfan therapy. Patients who have received prior radiation therapy (three cycles of chemotherapy or more), or prior progenitor cell transplantation may be at an increased risk. A reduced incidence of hepatic veno-occlusive disease and other regimen-related toxicities have been observed in patients treated with high dose busulfan and cyclophosphamide, when the first dose of cyclophosphamide has been delayed for more than 24 hours after the last dose of busulfan.

    Due to the carcinogenic potential of busulfan, careful consideration should be given to the use of busulfan for the treatment of polycythaemia and essential thrombocythaemia. The use of busulfan for these indications should be avoided in younger or asymptomatic patients. Where busulfan treatment is considered necessary, courses should be kept as short as possible.

    Busulfan is considered to be unsafe in patients with porphyria because it has been shown to be porphyrogenic in animals.

    Blood count monitoring
    Regular monitoring is advised, specific recommendations vary by condition.

    Chronic granulocytic leukaemia:
    Induction: Monitored at least weekly.
    Maintenance: Monitor at least every 4 weeks.

    Polycythemia vera: Monitor carefully particularly platelet counts.

    Myelofibrosis: Monitor carefully due to the extreme sensitivity of the bone marrow.

    Pregnancy and Lactation


    Contraindicated in pregnancy.

    There are no adequate studies of busulfan in pregnant women, however, in pre-clinical studies busulfan has caused malformations. A few cases of congenital abnormalities have been reported with low-dose oral busulfan, although not necessarily attributable to the active substance, and third trimester exposure may be associated with impaired intrauterine growth.

    Animal studies have shown busulfan has the potential for teratogenic effects whilst exposure during the later stages of pregnancy has resulted in impairment of fertility in the offspring.

    The effect of concurrent therapies must also be considered.

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( ) or if this is unavailable at the backup site ( ).


    Busulfan is contraindicated in breastfeeding.

    It is not known whether busulfan or its metabolites are excreted in human breast milk. However, due to the potential for serious toxicity in the nursing infant it is recommended that breastfeeding is discontinued during treatment.

    The effect of concurrent therapies must also be considered.

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at

    Side Effects

    Acute leukaemia
    Aplastic anaemia
    Cardiac tamponade
    Cholestatic jaundice
    Corneal thinning
    Dry mucous membranes
    Dry skin
    Dystrophic calcification
    Epithelial dysplasia
    Erythema multiforme
    Erythema nodosum
    Exacerbation of myasthenia gravis
    Haemorrhagic cystitis
    Hepatic fibrosis
    Hepatic veno-occlusive disease
    Hepatocellular atrophy
    Hepatocellular necrosis
    Hyperpigmentation of skin
    Interstitial pneumonitis
    Lens changes
    Liver function disturbances
    Menopausal-like symptoms
    Mouth ulcers
    Ovarian failure
    Pulmonary fibrosis
    Pulmonary ossification
    Sjogren's syndrome
    Testicular atrophy
    Weight loss


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: August 2013

    Reference Sources

    British National Formulary, 65th Edition (2013) Pharmaceutical Press, London.

    BNF for Children (2013-2014) Pharmaceutical Press, London.

    Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

    Summary of Product Characteristics: Busulfan tablets 2mg. Aspen Pharma Trading. Revised January 2013

    N.A.P.O.S. The Drug Database for Acute Porphyria
    Available at:
    Last accessed: August 13, 2013

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