Busilvex

busulfan

This is a summary of the European public assessment report (EPAR). It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the studies performed, to reach its recommendations on how to use the medicine.

If you need more information about your medical condition or your treatment, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist. If you want more information on the basis of the CHMP recommendations, read the scientific discussion (also part of the EPAR).

What is Busilvex?

Busilvex is a concentrate to be made up into a solution for infusion (drip into a vein). It contains the active substance busulfan.

What is Busilvex used for?

Busilvex is used in adults and children as a ‘conditioning’ (preparative) treatment before transplantation of haematopoietic progenitor cells (the cells that make blood cells). This type of transplant is used in patients who need to replace their blood-making cells, because they have a blood disorder (such as a rare type of anaemia) or a cancer of the blood. Busilvex treatment is followed by treatment with another medicine (cyclophosphamide in adults, and cyclophosphamide or melphalan in children).

Because of the number of patients in the European Union (EU) that undergo this type of conditioning and transplant is low, busulfan was designated as an ‘orphan medicine’ (a medicine used in rare diseases) on 29 December 2000.

The medicine can only be obtained with a prescription.

How is Busilvex used?

Busilvex should be used by a doctor who has experience in treatments given before transplantation. The recommended dose of Busilvex in adults is 0.8 mg per kilogram body weight. In children up to 17 years of age, the recommended dose of Busilvex is based on the weight of the child and varies between 0.8 and 1.2 mg/kg. Busilvex is given as a central intravenous infusion (drip into a central vein in the chest). Each infusion lasts for two hours and it is given to the patient every six hours on four consecutive days before treatment with cyclophosphamide or melphalan and the transplant. Before receiving Busilvex, patients are given anticonvulsive medicines (to prevent seizures) and anti-emetic medicines (to prevent vomiting).

How does Busilvex work?

The active substance in Busilvex, busulfan, belongs to a group of medicines called ‘alkylating agents’. These substances are ‘cytotoxic’. This means that they kill cells, especially cells that develop rapidly, such as cancer or progenitor (or ‘stem’) cells (cells that make other types of cell). Busulfan is used before transplantation to destroy abnormal cells and the patient’s existing haematopoietic progenitor cells. This is called ‘myeloablation’. Cyclophosphamide or melphalan is then used to suppress the immune system, so that the body’s natural defences are decreased. This helps the transplanted cells to ‘engraft’ (when they start to grow and produce normal blood cells).

How has Busilvex been studied?

The effects of Busilvex were first tested in experimental models before being studied in humans. The applicant also presented data from the scientific literature.

Busilvex has been studied in patients, mainly with blood cancer, who needed transplantation of haematopoietic progenitor cells. There were two main studies involving 103 adults and one involving 55 children. The main measures of effectiveness were the number of patients with myeloablation (with reduced counts of white blood cells and platelets) and ‘engraftment’ (the time for the white blood cells to return to higher levels).

What benefit has Busilvex shown during the studies?

All adults and children achieved myeloablation. On average, engraftment was reached in 10 days in adults and 11 days in children with ‘autotransplantation’ (when the patient receives their own cells, harvested and stored before the transplant). Engraftment was obtained in 13 days in adults and 21 days in children with ‘allotransplantation’ (when the patient receives cells from a donor).

What is the risk associated with Busilvex?

Apart from the decrease in blood cell counts, which is the intended effect of the medicine, the most serious side effects of Busilvex are infection, liver disorders including blocking of a liver vein, graft-versus-host disease (when the transplanted cells attack the body) and respiratory (lung) disorders. For the full list of all side effects reported with Busilvex, see the package leaflet.

Busilvex should not be used in people who may be hypersensitive (allergic) to busulfan or any of the other ingredients. It must not be used in women who are pregnant. Breast-feeding should be stopped when treatment with Busilvex is started. Busilvex can affect fertility in both sexes. Because of this, female patients should not become pregnant during treatment and for up to six months afterwards, and male patients are advised not to father a child during and for up to six months after treatment with Busilvex.

Caution is needed when Busilvex is used at the same time as other medicines, such as itraconazole (used to treat some infections), ketobemidone (used to treat pain) and paracetamol. See the package leaflet for full details.

Why has Busilvex been approved?

The Committee for Medicinal Products for Human Use (CHMP) concluded that the effectiveness of Busilvex had been shown, and that it provides an alternative to busulfan tablets, which have disadvantages such as the large number of tablets that need to be taken. The Committee decided that Busilvex’s benefits are greater than its risks as conditioning treatment prior to haematopoietic progenitor cell transplantation. The Committee recommended that Busilvex be given marketing authorisation.

Other information about Busilvex

The European Commission granted a marketing authorisation valid throughout the EU for Busilvex to Pierre Fabre Médicament on 9 July 2003. The marketing authorisation was renewed on 9 July 2008.

This EPAR was last updated on 22/08/2012 .

More detail is available in the summary of product characteristics

Product details

Publication details

Product information

20/07/2012  Busilvex -EMEA/H/C/000472 -II/0014

Contents

• Annex I - Summary of product characteristics
• Annex IIA - Manufacturing-authorisation holder responsible for batch release
• Annex IIB - Conditions of the marketing authorisation
• Annex IIIA - Labelling
• Annex IIIB - Package leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.

Pharmacotherapeutic group

Antineoplastic agents

Therapeutic indication

Busilvex followed by cyclophosphamide (BuCy2) is indicated as conditioning treatment prior to conventional haematopoietic progenitor cell transplantation (HPCT) in adult patients when the combination is considered the best available option.

Busilvex followed by cyclophosphamide (BuCy4) or melphalan (BuMel) is indicated as conditioning treatment prior to conventional haematopoietic progenitor cell transplantation in paediatric patients.

Changes since initial authorisation of medicine

Initial marketing-authorisation documents