ing the neutropenic period. Platelet and red blood cell support, as well as the use of growth factors such as granulocyte colony stimulating agent (G-CSF), should be employed as medically indicated.
In adults, absolute neutrophil counts < 0.5x109/l at a median of 4 days post transplant occurred in 100% of patients and recovered at median day 10 and 13 days following autologous and allogeneic transplant respectively (median neutropenic period of 6 and 9 days respectively). Thrombocytopenia (< 25x109/l or requiring platelet transfusion) occurred at a median of 5-6 days in 98% of patients. Anaemia (haemoglobin< 8.0 g/dl) occurred in 69% of patients.
In paediatric population, absolute neutrophil counts < 0.5x109/l at a median of 3 days post transplant occurred in 100% of patients and lasted 5 and 18.5 days in autologous and allogeneic transplant respectively. In children, thrombocytopenia (< 25x109/l or requiring platelet transfusion) occurred in 100% of patients. Anaemia (haemoglobin< 8.0 g/dl) occurred in 100% of patients.
In children < 9 kg, a therapeutic drug monitoring may be justified on a case by case basis, in particular in extremely young children and neonates (see section 5.2).
The Fanconi anaemia cells have hypersensitivity to cross-linking agents. There is limited clinical experience of the use of busulfan as a component of a conditioning regimen prior to HSCT in children with Fanconi's anaemia. Therefore Busilvex should be used with caution in this type of patients.
Hepatic impairment
Busilvex as well as busulfan has not been studied in patients with hepatic impairment. Since busulfan is mainly metabolized through the liver, caution should be observed when Busilvex is used in patients with pre-existing impairment of liver function, especially in those with severe hepatic impairment. It is recommended when treating these patients that serum transaminase, alkaline phosphatase, and bilirubin should be monitored regularly 28 days following transplant for early detection of hepatotoxicity.
Hepatic veno-occlusive disease is a major complication that can occur during treatment with Busilvex. Patients who have received prior radiation therapy, greater than or equal to three cycles of chemotherapy, or prior progenitor cell transplant may be at an increased risk (see section 4.8).
Caution should be exercised when using paracetamol prior to (less than 72 hours) or concurrently with Busilvex due to a possible decrease in the metabolism of busulfan (See section 4.5).
As documented in clinical studies, no treated patients experienced cardiac tamponade or other specific cardiac toxicities related to Busilvex. However cardiac function should be monitored regularly in patients receiving Busilvex (see section 4.8).
Occurrence of acute respiratory distress syndrome with subsequent respiratory failure associated with interstitial pulmonary fibrosis was reported in Busilvex studies in one patient who died, although, no clear aetiology was identified. In addition, busulfan might induce pulmonary toxicity that may be additive to the effects produced by other cytotoxic agents. Therefore, attention should be paid to this pulmonary issue in patients with prior history of mediastinal or pulmonary radiation (see section 4.8).
Periodic monitoring of renal function should be considered during therapy with Busilvex (see section 4.8).
Seizures have been reported with high dose busulfan treatment. Special caution should be ex |
