MYLERAN Film-coated tablet Ref.[10880] Active ingredients: Busulfan

Busulfan is administered orally. The usual adult dose range for remission induction is 4 to 8 mg, total dose, daily. Dosing on a weight basis is the same for both pediatric patients and adults, approximately 60 mcg/kg of body weight or 1.8 mg/m² of body surface, daily. Since the rate of fall of the leukocyte count is dose related, daily doses exceeding 4 mg per day should be reserved for patients with the most compelling symptoms; the greater the total daily dose, the greater is the possibility of inducing bone marrow aplasia.

A decrease in the leukocyte count is not usually seen during the first 10 to 15 days of treatment; the leukocyte count may actually increase during this period and it should not be interpreted as resistance to the drug, nor should the dose be increased. Since the leukocyte count may continue to fall for more than 1 month after discontinuing the drug, it is important that busulfan be discontinued prior to the total leukocyte count falling into the normal range. When the total leukocyte count has declined to approximately 15,000/mcL, the drug should be withheld.

With a constant dose of busulfan, the total leukocyte count declines exponentially; a weekly plot of the leukocyte count on semi-logarithmic graph paper aids in predicting the time when therapy should be discontinued. With the recommended dose of busulfan, a normal leukocyte count is usually achieved in 12 to 20 weeks.

During remission, the patient is examined at monthly intervals and treatment resumed with the induction dosage when the total leukocyte count reaches approximately 50,000/mcL. When remission is shorter than 3 months, maintenance therapy of 1 to 3 mg daily may be advisable in order to keep the hematological status under control and prevent rapid relapse.

Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. ^1-8

There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

There is no known antidote to busulfan. The principal toxic effects are bone marrow depression and pancytopenia. The hematologic status should be closely monitored and vigorous supportive measures instituted if necessary. Induction of vomiting or gastric lavage followed by administration of charcoal would be indicated if ingestion were recent. Dialysis may be considered in the management of overdose as there is 1 report of successful dialysis of busulfan (see CLINICAL PHARMACOLOGY).

Gastrointestinal toxicity with mucositis, nausea, vomiting, and diarrhea has been observed when MYLERAN was used in association with bone marrow transplantation.

Oral LD₅₀ single doses in mice are 120 mg/kg. Two distinct types of toxic response are seen at median lethal doses given intraperitoneally. Within a matter of hours there are signs of stimulation of the central nervous system with convulsions and death on the first day. Mice are more sensitive to this effect than are rats. With doses at the LD₅₀ there is also delayed death due to damage to the bone marrow. At 3 times the LD₅₀, atrophy of the mucosa of the large intestine is found after a week, whereas that of the small intestine is little affected. After doses in the order of 10 times those used therapeutically were added to the diet of rats, irreversible cataracts were produced after several weeks. Small doses had no such effect.

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) (see USP Controlled Room Temperature).