Busulfan tablets are usually given in courses or administered continuously. The dose must be adjusted for the individual patient under close clinical and haematological control. Should a patient require an average daily dose of less than the content of the available busulfan tablets, this can be achieved by introducing one or more busulfan-free days between treatment days. The tablets should not be divided (see Instructions for Use/Handling under Cautions for Usage).
Obese Patients: Dosing based on body surface area or adjusted ideal body weight should be considered in the obese (see Pharmacology: Pharmacokinetics under Actions).
The relevant literature should be consulted for full details of treatment schedules.
CHRONIC MYELOID LEUKAEMIA: Populations: Induction in Adults: Treatment is usually initiated as soon as the condition is diagnosed. The dose is 0.06 mg/kg/day, with an initial daily maximum of 4 mg, which may be given as a single dose.
There is individual variation in the response to busulfan and in a small proportion of patients, the bone marrow may be extremely sensitive (see Precautions).
The blood count must be monitored at least weekly during the induction phase and it may be helpful to plot counts on semi-log graph paper.
The dose should be increased only if the response is inadequate after three weeks.
Treatment should be continued until the total leukocyte count has fallen to between 15 and 25 x 109/l (typically 12 to 20 weeks). Treatment may then be interrupted, following which a further fall in the leukocyte count may occur over the next two weeks.
Continued treatment at the induction dose after this point or following depression of the platelet count to below 100 x 109/l is associated with a significant risk of prolonged and possibly irreversible bone marrow aplasia.
Maintenance in Adults: Control of the leukaemia may be achieved for long periods without further busulfan treatment; further courses are usually given when the leukocyte count rises to 50 x 109/l, or symptoms return.
Some clinicians prefer to give continuous maintenance therapy. Continuous treatment is more practical when the duration of unmaintained remissions is short.
The aim is to maintain a leukocyte count of 10 to 15 x 109/l and blood counts must be performed at least every four weeks. The usual maintenance dosage is on average 0.5 to 2 mg/day, but individual requirements may be much less. Should a patient require an average daily dose of less than the content of one tablet, the maintenance dose may be adjusted by introducing one or more busulfan-free days between treatment days.
NOTE: lower doses of busulfan should be used if it is administered in conjunction with other cytotoxic agents (see Adverse Reactions and Interactions).
Paediatric Population: Chronic myeloid leukaemia is rare in the paediatric age group.
Busulfan may be used to treat Philadelphia chromosome positive (Ph' positive) disease, but the Ph' negative juvenile variant responds poorly.
POLYCYTHAEMIA VERA: The usual dosage is 4 to 6 mg daily, continued for four to six weeks, with careful monitoring of the blood count, particularly the platelet count.
Further courses are given when relapse occurs; alternatively, maintenance therapy may be given using approximately half the induction dose.
If the polycythaemia is controlled primarily by venesection, short courses of busulfan may be given solely to control the platelet count.
MYELOFIBROSIS: The usual initial dose is 2 to 4 mg daily.
Very careful haematological control is required because of the extreme sensitivity of the bone marrow in this condition.
ESSENTIAL THROMBOCYTHAEMIA: The usual dosage is 2 to 4 mg per day.
Treatment should be interrupted if the total leukocyte count falls below 5 x 109/l or the platelet count below 500 x 109/l.