n of 140 mg/m² melphalan (BuMel)
initiated for at least 24 hours following the 16th dose of Busilvex. (see section 4.5).
Busilvex is administered as a two-hour infusion every 6 hours over 4 consecutive days for a total of 16 doses prior to cyclophosphamide or melphalan and conventional haematopoietic progenitor cell transplantation (HPCT).
Obese patients
In adults
For obese patients, dosing based on adjusted ideal body weight (AIBW) should be considered.
Ideal body weight (IBW) is calculated as follows:
IBW men (kg) =50 + 0.91x (height in cm-152);
IBW women (kg) = 45 + 0.91x (height in cm-152).
Adjusted ideal body weight (AIBW) is calculated as follows:
AIBW= IBW+0.25x (actual body weight - IBW).
In paediatric population
The medicinal product is not recommended in obese children and adolescents with body mass index Weight (kg)/ (m) ² > 30 kg/m² until further data become available.
Patients with renal impairment
Studies in renally impaired patients have not been conducted, however, as busulfan is moderately excreted in the urine, dose modification is not recommended in these patients.
However, caution is recommended (see sections 4.8 and 5.2).
Patients with hepatic impairment
Busilvex as well as busulfan has not been studied in patients with hepatic impairment.
Caution is recommended, particularly in those patients with severe hepatic impairment (see section 4.4).
Elderly patients
Patients older than 50 years of age (n=23) have been successfully treated with Busilvex without dose-adjustment. However, for the safe use of Busilvex in patients older than 60 years only limited information is available. Same dose (see section 5.2) for elderly as for adults (< 50 years old) should be used.
Method of administration
Precautions to be taken before handling or administering the medicinal product
Busilvex must be diluted prior to administration. A final concentration of approximately 0.5 mg/ml busulfan should be achieved. Busilvex should be administered by intravenous infusion via central venous catheter.
For instructions on dilution of the medicinal product before administration, see section 6.6.
Busilvex should not be given by rapid intravenous, bolus or peripheral injection.
All patients should be pre-medicated with anticonvulsant medicinal products to prevent seizures reported with the use of high dose busulfan.
It is recommended to administer anticonvulsants 12 h prior to Busilvex to 24 h after the last dose of Busilvex.
In adult and paediatric studies, patients received either phenytoin or benzodiazepines as seizure prophylaxis treatment (see sections 4.4 and 4.5).
Antiemetics should be administered prior to the first dose of Busilvex and continued on a fixed schedule according to local practice through its administration.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Pregnancy (see section 4.6).
4.4 Special warnings and precautions for use
The consequence of treatment with Busilvex at the recommended dose and schedule is profound myelosuppression, occurring in all patients. Severe granulocytopenia, thrombocytopenia, anaemia, or any combination thereof may develop. Frequent complete blood counts, including differential white blood cell
Prophylactic or empiric use of anti-infectives (bacterial, fungal, viral) should be considered for the prevention and management of infections dur |
