The European Medicines Agency’s (EMA’s) Pharmacovigilance Risk Assessment Committee (PRAC) has recommended that levamisole-containing medicines be withdrawn from the EU market because their benefits no longer outweigh their risks for the treatment of parasitic worm infections in adults and children.

The recommendation is based on an EU-wide review of spontaneous reports of leukoencephalopathy and central nervous system demyelination following levamisole use, either in its authorized indication or in the context of off-label use, misuse, or accidental exposure. 

The review confirmed that a rare but serious side effect of levamisole is leukoencephalopathy — a debilitating and potentially life-threatening condition if left untreated that is difficult to diagnose, the EMA said.

Information and new data gathered through the continuous safety monitoring of medicines showed that the onset of leukoencephalopathy is unpredictable and can occur after a single dose of levamisole. Symptoms might develop up to several months after treatment. In addition, no measures were identified to mitigate the risk in any specific patient group.

Moreover, “other medicines are authorized in the EU for the treatment of parasitic worm infections,” the EMA added.

Rapid Paralysis 

Levamisole is an anthelminthic used in adults and children to treat infections caused by the parasitic worms Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, Strongyloides stercoralis, and Trichostrongylus colubriformis.

It works primarily by stimulating nicotinic acetylcholine receptors – proteins found on the surface of the worm’s nerve cells. This leads to rapid paralysis of the worm’s muscles, preventing movement and allowing it to be expelled from the infected person’s gut.

Medicines containing levamisole are available as tablets taken orally, generally as a single dose. The EMA said they are authorised in Hungary, Lithuania, Latvia, and Romania under the trade names Decaris and Levamisol Arena.

Leukoencephalopathy Awareness 

Neurologic symptoms in patients with levamisole-associated leukoencephalopathy vary depending on the localisation of the lesions and may include muscular weakness, language impairment, cognitive dysfunction, ataxia, and paresis.

The EMA advised that people who have been treated with medicines containing levamisole should seek medical advice immediately if they develop muscle weakness, difficulty speaking, confusion, or difficulty controlling movements.

A direct healthcare professional communication informing healthcare professionals of the recommendation to withdraw levamisole medicines from the EU market because of the risk of leukoencephalopathy will be made available.

The PRAC recommendations will now be sent to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human, which will adopt a position, the EMA said. 

Rob Hicks is a retired National Health Service doctor. A well-known TV and radio broadcaster, he has written several books and has regularly contributed to national newspapers, magazines, and online publications. He is based in the United Kingdom.