EMA Starts Review of Ifosfamide to Examine Whether There is a Higher Risk of Encephalopathy

Studies suggest that the risk of encephalopathy is higher with the solution than with the powder form
18 Mar 2020
Anticancer agents & Biologic therapy

On 13 March 2020, the European Medicines Agency’s (EMA’s) Pharmacovigilance Risk Assessment Committee (PRAC) announced that it has started a review of medicines containing ifosfamide to examine whether there is a higher risk of encephalopathy with ifosfamide available as a ready-made solution or concentrate for solution than with the powder form.

Ifosfamide is used to treat different types of cancers, including various solid tumours and haematological malignancies. The medicine is given into a vein and is available as a ready-made solution and a concentrate for solution in France and Germany, as well as a powder for solution for infusion. In most other EU Member States, it is only available as powder.

The risk of encephalopathy is already known and reflected in the product information for these medicines.

In 2016, an investigation in France suggested an incidence of encephalopathy 3 to 4-fold higher with the ready-made solution than with the powder. Analyses carried out at the time concluded that the risk may be linked to the degradation of the active substance and impurities developing over time in the solution. As a result, the solution’s shelf-life was reduced in France.

However, two recent studies(1,2) suggested that the risk of encephalopathy with the solution remains higher than the risk with the powder and a more thorough review was considered needed.

The PRAC will now assess the available data on this risk and recommend whether the marketing authorisations for these products should be maintained, varied, suspended or revoked. 

Citations:

  1. Hillaire-Buys D, Mousset M, Allouchery M, et al. Liquid formulation of ifosfamide increased risk of encephalopathy: A case-control study in a pediatric population. Therapies; Published online 28 October 2019. pii: S0040-5957(19)30153-2. doi: 10.1016/j.therap.2019.08.001.  
  2. Chambord J, Henny F, Salleron J, et al. Ifosfamide-induced encephalopathy: Brand-name (HOLOXAN®) vs generic formulation (IFOSFAMIDE EG®). J Clin Pharm Ther 2019; 44(3):372–380.

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