Filenews 23 April 2021
On 11 March 2021, the EMA Safety Committee (PRAC) concluded that the benefits of iphosphamide solutions for infusion continue to outweigh their risks in the treatment of various types of cancer, including various solid tumours and blood cancers such as lymphomas (white blood cell cancer).
The review by the Committee on Pharmacovigilance – Risk Assessment (PRAC) was initiated because two recent studies have shown that the risk of encephalopathy (brain disorders) taking iphosphamide in solution form is higher than taking it in powder form. Encephalopathy caused by iphosphamide is considered a very common, known risk and is generally reversible.
The Committee for Pharmacovigilance – Risk Assessment (PRAC) examined all available data and concluded that the increased risk of iphosphamide encephalopathy administered as a solution could neither be confirmed nor excluded due to data limitations. The PRAC recommended that the existing warning on iphosphamide-induced encephalopathy in the product information should be updated with the latest information on this adverse reaction, including characteristics and risk factors, as well as highlighting the need for close patient monitoring.
Companies trading in iphosphamide in solution form should carry out studies to investigate the stability of medicinal products in order to determine optimal storage conditions.
Information for the public
- Encephalopathy (brain disorders) is a very common, known side effect of iphosphamide and is generally reversible. Two recent studies have shown that the use of iphosphamide solutions may increase the risk of this side effect compared to the use of the powder form. However, an in-depth review of all available data could neither confirm nor exclude this increased risk.
- The package leaflet for these medicines will be updated with the latest information on factors that may increase the risk of encephalopathy and how to identify signs of this side effect.
- Tell your doctor immediately if you experience confusion, drowsiness, unconsciousness, hallucinations, hallucinations (false beliefs), blurred vision, disturbance of perception (difficulty understanding information provided through the senses), problems with movement such as muscle spasms or contractions, restlessness, slow or irregular movement, loss of bladder control and seizures (convulsions).
- Talk to your doctor before you are given the medicine of iphosphamide. if you have previously been treated with another cancer medicine called sisplatin.
- Tell your doctor if you have taken medicines that affect the brain, such as medicines to treat or prevent vomiting and nausea, sleeping pills, opioid painkillers or antiallergic medicines.
- If you have any concerns about your treatment, you should discuss them with your doctor.
Information for health professionals
- Administration of iphosphamide may cause encephalopathy and other neurotoxic effects. These known, very common side effects are generally reversible.
- A review of all available data on iphosphamide-induced encephalopathy has concluded that the increased risk of iphosphamide encephalopathy in solution form could neither be confirmed nor excluded due to limited data.
- Existing warnings in section 4.4 (Special warnings and precautions in use) of the Summary of Product Characteristics will be reviewed to include the following information:
- The iphosphamide-induced toxicity of THE CNS may occur within a few hours of administration until a few days after administration and in most cases is resolved within 48-72 hours of discontinuation of iphosphamide. If toxicity to THE CNS occurs, iphosphamide should be discontinued.
- Patients should be closely monitored for symptoms of encephalopathy, especially if patients are at increased risk of encephalopathy. Symptoms may include confusion, drowsiness, coma, hallucinations, blurred vision, psychotic behavior, extrapyramid symptoms, urinary incontinence and seizures.
- The toxicity to the CNS appears to be dose-dependent. Risk factors for the development of iphosphamide-related encephalopathy include hypoalumaticemia, impaired renal function, low performance status, pelvic disease and previous or co-administered nephrotoxic therapies including sisplatin.
- Due to the possibility of additional effects, medicines acting on the CNS (such as anti-ematetics, sedatives, drugs or antihistamines) should be used with particular caution or, if necessary, discontinued in case of encephalopathy caused by isosphamide..
More about medicines
Iphosphamide is used to treat various cancers, including various solid tumors and lymphomas. It is given through the vein and is available as a ready solution, concentrate for solution and powder for solution for infusion in Germany and France. In most other EU Member States it is only available as powder for infusion solution.
More about the process
The iphosphamide review was initiated at the request of the European Commission, in accordance with Article 31 of Regulation (EC) No 1782/2003. 2001/83.
The review was carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the committee responsible for assessing safety issues for medicinal products for human use, which made a number of recommendations. The PRAC recommendations were sent to the Coordination Group on Mutual Recognition and Decentralised Procedures - Human (CMDh), which adopted its position. CMDh is a body representing EU Member States as well as Iceland, Liechtenstein and Norway. It is responsible for ensuring harmonised safety standards for medicines authorised through national procedures across the EU.
As the CMDh position was adopted by a majority, the CMDh position will now be sent to the European Commission, which will in due course take a legally binding decision at EU level.
Source: eyenews
