EMA Safety Committee Initiates Review of Levamisole Following Fatal Leukoencephalopathy Case
Key Insights
The European Medicines Agency (search)'s safety committee has launched a comprehensive review of levamisole-containing medicines following reports of serious leukoencephalopathy (search) cases, including one death.
Leukoencephalopathy (search) is a potentially life-threatening condition that damages brain white matter and can cause confusion, weakness, movement difficulties, and impaired speech or vision.
The review will assess whether marketing authorizations for levamisole medicines should be maintained, modified, suspended, or withdrawn across the EU based on the benefit-risk balance.
The European Medicines Agency (search)'s Pharmacovigilance Risk Assessment Committee (PRAC (search)) has initiated a comprehensive safety review of medicines containing levamisole, following serious concerns about the risk of leukoencephalopathy (search), a potentially fatal brain condition. The review was triggered by new safety data, including reported cases of serious leukoencephalopathy following levamisole use, one of which resulted in death.
Critical Safety Concerns Emerge
Leukoencephalopathy (search) is a potentially serious condition that damages the white matter of the brain, which consists of nerve fibers covered by a protective layer called myelin that enables efficient communication between different brain regions. The condition can be life-threatening and debilitating, particularly when left undiagnosed or untreated, leading to a range of neurological symptoms including confusion, weakness or impaired muscle function, difficulties with movement coordination, and impaired or lost speech or vision.
While leukoencephalopathy (search) has already been identified as a potential risk with levamisole, with product information including the general term encephalopathy (search), the new data has prompted a more thorough investigation. The review follows continuous safety monitoring of medicines authorized in the EU, which revealed additional serious cases and supporting data published in medical literature.
Comprehensive Review Scope
PRAC (search) will examine all available evidence regarding the risk of leukoencephalopathy (search) with levamisole-containing medicines, including any risk minimization measures already in place. The committee will also address demyelination (search) in the central nervous system, which involves the loss of myelin in the brain and spinal cord and represents a form of leukoencephalopathy, as some reported cases describe this specific safety concern.
The committee will assess the impact of leukoencephalopathy (search) and demyelination (search) risks on the benefit-risk balance of these medicines and issue recommendations on whether their marketing authorizations should be maintained, varied, suspended, or withdrawn across the EU.
Current Market Status and Mechanism
Levamisole is an anthelmintic medicine used in adults and children to treat infections caused by specific parasitic worms, including Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, Strongyloides stercoralis, and Trichostrongylus colubriformis. The drug works primarily by stimulating nicotinic acetylcholine receptors (search), proteins found on the surface of the worm's nerve cells, leading to rapid paralysis of the worm's muscles and preventing movement, allowing the parasite to be expelled from the infected person's gut.
Medicines containing levamisole are available as oral tablets, generally administered in a single dose, and are currently authorized in Hungary, Lithuania, Latvia, and Romania under the trade names Decaris (search) and Levamisol Arena (search).
Regulatory Process
The review was initiated at the request of the Romanian medicines agency (search) (NAMMDR) under Article 31 of Directive 2001/83/EC. Following PRAC (search)'s evaluation, recommendations will be sent to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which represents EU Member States as well as Iceland, Liechtenstein, and Norway.
If the CMDh position is adopted by consensus, PRAC (search) recommendations will be directly implemented in all Member States where the medicines are authorized. If adopted by majority vote, the position will be forwarded to the European Commission for a final legally-binding decision applicable across all EU Member States.