The EMA has started a review of medicinal products containing ifosfamide to check whether there is a higher risk of encephalopathy when ifosfamide is used as a ready-to-use solution or a concentrate for solution than in the form of a powder for solution for injection.
Ifosfamide is used to treat various types of cancer, including various solid tumors and blood cancers such as lymphomas. The risk of encephalopathy is already known and is reflected in the information on the product for these medicinal products.
The product is intended for intravenous administration. In France and Germany it is available as a ready-to-use solution and a concentrate for solution, as well as a powder for solution for injection. In most other EU member states it is available only as a powder for solution for injection.
In 2016, an investigation was conducted in France indicating that the incidence of encephalopathy is 3 – 4 times higher with the use of the ready-made solution than with the powder for solution for injection. Based on the results of the analysis conducted at that time, it was concluded that the risk may be associated with the degradation of the active substance and with impurities that develop over time in the solution. As a result, the shelf life of the medicinal product in France was shortened. However, the results of the two latest studies 1 2 suggested that the risk of encephalopathy with the use of medicinal products containing ifosfamide as a solution remains higher than with the powder for solution for injection, therefore a more thorough review is needed.
EMA will now evaluate the available data on the risk of encephalopathy with ifosfamide ready-to-use solution or concentrate for solution and will provide recommendations on whether the authorization for sale of these products should be maintained, varied, suspended, or revoked.
1Hillaire-Buys D, Mousset M, Allouchery M et al. Liquid formulation of ifosfamide increases the risk of encephalopathy: a case-control study in the pediatric population. Therapies [Internet]. 2019
2Chambord J, Henny F, Salleron J et al. Encephalopathy caused by ifosfamide: trademark (HOLOXAN®) versus generic form (IFOSFAMIDE EG®). J Clin Pharm Ther. 2019; 44: 372–380
The review of medicinal products containing ifosfamide was initiated at the request of France in accordance with Article 31 of Directive 2001/83 / EC.
The review is being carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), which is responsible for assessing safety issues of medicinal products for human use and for providing recommendations. Since medicinal products containing ifosfamide are authorized at the national level, the PRAC recommendations will be forwarded to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will make the decision. The CMDh is a body representing the EU Member States as well as Iceland, Liechtenstein, and Norway.
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