Posology : מינונים

4.2 Posology and method of administration

General
The bioavailability of oral Busulfan shows large intra-individual variations ranging from 47% to 103% (mean 80%) in adults and from 22% to 120% (mean 68%) in children (see section 5.2).

There are other formulations available which may be more suitable for paediatric patients.

Myleran 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 Myleran tablets, this can be achieved by introducing one or more busulfan free days between treatment days. The tablets should not be divided (see section 6.6).

Obese patients

Dosing based on body surface area or adjusted ideal body weight should be considered in the obese (see section 5.2).
The relevant literature should be consulted for full details of treatment schedules.


Chronic granulocytic leukaemia (also called chronic myeloid leukaemia): 
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 Myleran and in a small proportion of patients the bone marrow may be extremely sensitive (see section 4.4).

The blood count must be monitored at least weekly during the induction phase and it may be helpful to plot counts on semilog graph paper.

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

Treatment should be continued until the total leucocyte count has fallen to between 15 and 25 x 109 per litre (typically 12 to 20 weeks). Treatment may then be interrupted, following which a further fall in the leucocyte 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 10 9 per litre 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 Myleran treatment; further courses are usually given when the leucocyte count rises to 50 x 109 per litre, 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 leucocyte count of 10 to 15 x 109 per litre and blood counts must be performed at least every 4 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 Myleran free days between treatment days.

NOTE: Lower doses of Busulphan should be used if it is administered in conjunction with other cytotoxic agents (see section 4.5 and 4.8).

Paediatric population

Chronic granulocytic leukaemia is very rare in the paediatric age group. Myleran may be used to treat Philadelphia chromosome positive (Ph' positive) disease, but the Ph' negative juvenile variant responds poorly.