Levamisole-containing medicinal products - referral

Current status

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Overview

EMA recommends withdrawal of marketing authorisations for levamisole medicines.

Leukoencephalopathy confirmed as a serious side effect of levamisole.

Background

EMA’s safety committee (PRAC) recommended that medicines containing levamisole be withdrawn from the EU market. This follows an EU-wide review which concluded that the benefits of these medicines no longer outweigh their risks for the treatment of parasitic worm infections in adults and children.

The review confirmed that leukoencephalopathy is a rare but serious side effect of levamisole. Leukoencephalopathy damages the white matter of the brain, which is made of nerve fibres covered by myelin, a protective layer that allows efficient communication between different parts of the brain. This condition can be debilitating and life-threatening, particularly if left untreated, and its diagnosis is complex.

The information reviewed by PRAC showed that leukoencephalopathy can occur after a single dose of levamisole and that symptoms may develop up to several months after treatment. The review did not identify any measures to reduce the risk or any group of people who may be at higher or lower risk. In addition, other medicines are authorised in the EU for the treatment of parasitic worm infections. Given that levamisole medicines are used to treat mild parasitic worm infections, and that levamisole-induced leukoencephalopathy is a serious condition with an unpredictable onset, PRAC concluded that the benefits of levamisole medicines no longer outweigh the risks and recommended that their marketing authorisations be withdrawn in the EU.

The PRAC recommendation is based on the assessment of new data gathered through the continuous safety monitoring of medicines authorised in the EU. These included reports of serious cases of leukoencephalopathy and demyelination of the central nervous system (loss of myelin in the brain and spinal cord) following use of levamisole, as well as a review of the published scientific literature. The PRAC also considered input from a panel of independent experts in infectious diseases and neurologists, and from the World Health Organization.

EMA continuously monitors the safety of medicines authorised in the EU. When new evidence shows that a medicine’s risks may outweigh its benefits, the Agency acts to protect public health. The recommendation to withdraw medicines containing levamisole reflects EMA’s commitment to ensuring that medicines available in the EU meet robust standards of safety, effectiveness and quality.

More about the medicine

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

Levamisole works mainly by stimulating nicotinic acetylcholine receptors, which are 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 gut of the infected person.

Medicines for human use containing levamisole are available as tablets to be taken by mouth, generally as a single dose. They are authorised in Hungary, Lithuania, Latvia and Romania under the trade names Decaris and Levamisol Arena.

More about the procedure

The review of medicines containing levamisole was initiated at the request of the Romanian medicines agency (NAMMDR), under Article 31 of Directive 2001/83/EC.

The review has been carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which made a set of recommendations. The PRAC recommendations will now be sent to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position. The 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 via national procedures across the EU.

Levamisole-containing medicinal products Article-31 referral - EMA recommends withdrawal of marketing authorisations for levamisole medicines

Adopted Reference Number: EMA/31681/2026

Key facts

About this medicine

• Approved name:
  Levamisole-containing medicinal products
• International non-proprietary name (INN) or common name:
  levamisole
• Associated names:
  • Decaris
  • Levamisol Arena
• Class:
  Anthelmintic products

About this procedure

• Current status:
  Recommendation provided by Pharmacovigilance Risk Assessment Committee
• Reference number:
  EMA/REF/0000293746
• Type:
  Article 31 referrals

  This type of referral is triggered when the interest of the Union is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.

• Authorisation model:
  Nationally authorised product(s)
• Decision making model:
  PRAC-CMDh

Key dates and outcomes

• Procedure start date:
  04/09/2025
• PRAC recommendation date:
  12/02/2026

All documents

Procedure started

Levamisole-containing medicinal products Article-31 referral - Notification

Levamisole-containing medicinal products Article-31 referral - PRAC list of questions

Reference Number: EMADOC-1700519818-2392926

Levamisole-containing medicinal products Article-31 referral - Annex I

Reference Number: EMADOC-1700519818-2418899

Under evaluation

Levamisole-containing medicinal products Article-31 referral - Timetable for the procedure

Reference Number: EMADOC-1700519818-2392927 Rev. 2

Levamisole-containing medicinal products Article-31 referral - PRAC starts safety review of levamisole, a medicine used to treat parasitic worm infections

Reference Number: EMA/281577/2025

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Levamisole-containing medicinal products Article-31 referral - EMA recommends withdrawal of marketing authorisations for levamisole medicines

Adopted Reference Number: EMA/31681/2026

Description of documents published

Please note that some of the listed documents apply only to certain procedures.

• Overview - lay-language summary of the stage of the procedure
• Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
• Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
• List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
• Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
• List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
• List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
• Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
• Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
• Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
• Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
• Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
• Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
• Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
• Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

Note that older documents may have different titles.