EMA Recommends Withdrawal of Levamisole Medicines from EU Market Due to Serious Brain Side Effects
Key Insights
The European Medicines Agency's safety committee (PRAC (search)) has recommended withdrawing all levamisole-containing medicines from the EU market following an EU-wide safety review.
The review confirmed that levamisole can cause leukoencephalopathy (search), a rare but serious side effect that damages the brain's white matter and can be debilitating or life-threatening.
Symptoms of leukoencephalopathy (search) can occur after a single dose and may develop within one day to several months after treatment, with no identified measures to reduce the risk.
The European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC (search)) has recommended the complete withdrawal of levamisole-containing medicines from the European Union market, citing an unacceptable risk-benefit profile due to serious brain-related side effects. The decision follows a comprehensive EU-wide safety review that concluded the benefits of these antiparasitic medicines no longer outweigh their risks.
Serious Brain Complications Identified
The review confirmed that leukoencephalopathy (search) is a rare but serious side effect of levamisole that damages the white matter of the brain. This white matter consists of nerve fibers covered by myelin, a protective layer essential for efficient communication between different brain regions. The condition can be debilitating and life-threatening, particularly if left untreated, and presents significant diagnostic challenges.
According to the PRAC (search) assessment, leukoencephalopathy (search) can occur after a single dose of levamisole, with symptoms potentially developing within one day to several months after treatment. The unpredictable onset and severity of this condition contributed significantly to the regulatory decision.
Clinical Manifestations and Risk Factors
In patients with levamisole-associated leukoencephalopathy (search), neurologic symptoms vary depending on the location of brain lesions and may include muscular weakness, language impairment, cognitive dysfunction, ataxia, and paresis. The review found no measures to reduce the risk of developing leukoencephalopathy, nor could it identify any patient groups at higher or lower risk.
Healthcare professionals are advised that patients who have been treated with levamisole-containing medicines should seek immediate medical attention if they develop muscle weakness, difficulty speaking, confusion, or difficulty controlling movements.
Regulatory Decision Based on Comprehensive Evidence
The PRAC (search) recommendation stems from a thorough assessment of new safety data gathered through continuous monitoring of EU-authorized medicines. The review included reports of serious leukoencephalopathy (search) cases and central nervous system demyelination following levamisole use, whether for authorized indications or off-label use, misuse, or accidental exposure.
The committee also reviewed published scientific literature and incorporated input from independent expert panels in infectious diseases and neurology, as well as guidance from the World Health Organization.
Current Market Status and Alternatives
Levamisole medicines are currently authorized in Hungary, Lithuania, Latvia, and Romania under the trade names Decaris and Levamisol Arena. These oral tablet formulations are typically administered as single doses for treating infections caused by parasitic worms including Ascaris lumbricoides (search), Necator americanus (search), Ancylostoma duodenale (search), Strongyloides stercoralis (search), and Trichostrongylus colubriformis (search).
The drug works by stimulating nicotinic acetylcholine receptors (search) on worm nerve cells, leading to rapid muscle paralysis and expulsion from the infected person's gut. However, the PRAC (search) noted that other anthelminthic treatments remain authorized and available in the EU for treating parasitic worm infections (search).
Implementation and Next Steps
The review was initiated at the request of Romania's national medicines agency (NAMMDR) under Article 31 of Directive 2001/83/EC. The PRAC (search) recommendations will now be forwarded to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which represents EU Member States plus Iceland, Liechtenstein, and Norway, for final adoption.
A direct healthcare professional communication (DHPC) will be distributed to relevant healthcare professionals and published on the EMA website to ensure widespread awareness of the withdrawal recommendation and associated safety concerns.