The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has concluded that the benefits of ifosfamide solutions for infusion continue to outweigh their risks in the treatment of different types of cancers, including various solid tumours and blood cancers such as lymphomas (cancer of white blood cells).
The PRAC review was started because two recent studies suggested that the risk of encephalopathy (brain disorders) with ifosfamide supplied in solution forms is higher than with the powder form. Ifosfamide-induced encephalopathy is a very common, known risk and is generally reversible.
After reviewing all the available data, the PRAC concluded that the increased risk of encephalopathy with ifosfamide solution cannot be confirmed or excluded due to the limited data. Regarding the warning for ifosfamide-induced encephalopathy in the package leaflet, the PRAC recommended updating the package leaflet with the most recent information on this side effect, including its characteristics and risk factors, as well as highlighting the need to closely monitor patients.
Companies that market ifosfamide supplied as a solution will be required to carry out studies investigating the stability of the medicines in order to establish the optimal storage conditions.
Information for patients
Encephalopathy (brain disorders) is a very common, known side effect of ifosfamide and is generally reversible. Two recent studies have suggested that the use of ifosfamide solutions may increase the risk of this side effect compared with use of the powder form However, a thorough review of all the available data has shown that this higher risk can
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 recognise the signs of this side effect.
Contact your doctor immediately if you experience symptoms such as confusion, sleepiness, unconsciousness, hallucinations, delusions, blurred vision, perception disorder (difficulty understanding information perceived by the senses), problems with movement such as muscle spasms or contractions, restlessness, slow or irregular movements, loss of bladder control and seizures (fits).
If you have previously been treated with another cancer drug (cisplatin), contact your doctor before administering ifosfamide. Inform your doctor if you have been taking any medicines that affect the brain, such as sleeping pills, opioid painkillers, allergy medicines or medicines for treating or preventing nausea and vomiting.
If you have any concerns about your treatment, do not hesitate to discuss them with your doctor.
Information for healthcare professionals
Administration of ifosfamide can cause encephalopathy and other neurotoxic effects. These known, very common side effects are generally reversible.
A review of all available data on ifosfamide-induced encephalopathy has shown that the increased risk of encephalopathy with ifosfamide solution cannot be confirmed or ruled out due to limited data.
The existing warnings in section 4.4 (Special warnings and precautions for use) of the summary of product characteristics will be revised to include the following information: CNS toxicity due to ifosfamide may appear within hours to a few days after initial administration and disappears in most cases within 48 to 72 hours after ifosfamide discontinuation. In case of CNS toxicity, ifosfamide treatment should be discontinued.
Patients should be closely monitored for symptoms of encephalopathy, especially in patients with increased risk of encephalopathy. Symptoms may include confusion, somnolence, coma, hallucination, blurred vision, psychotic behaviour, extrapyramidal disorder, urinary incontinence and seizures.
CNS toxicity appears to be dose-dependent. Risk factors for the development of ifosfamide-induced encephalopathy include hypoalbuminaemia, renal insufficiency, poor performance status, pelvic disease and previous or concomitant nephrotoxic treatments such as cisplatin.
Due to possible additive effects, drugs affecting the CNS (such as antiemetics, sedatives, narcotics or antihistamines) should be used with particular caution or, if possible, discontinued in ifosfamide-induced encephalopathy.
More about the medicine
Ifosfamide is used to treat several cancers, including various solid tumors and lymphomas. It is administered intravenously and has been authorised in Germany and France as ready-to-use solution, a concentrate for solution and powder for solution for injection. In most other EU Member States it is only available as a powder for solution for injection.
The following ifosfamide-based medicinal product is authorised and available on the market in Belgium: Holoxan.
More information is available on the EMA website.