Tolperisone

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On 21 June 2012, the European Medicines Agency completed a review of the safety and effectiveness of tolperisone. The Agency’s Committee for Medicinal Products for Human Use (CHMP) concluded that the benefits of tolperisone-containing medicines given orally (by mouth) continue to outweigh their risks, but that their use should be restricted to the treatment of adults with post-stroke spasticity (stiffness). The Committee also recommended that the marketing authorisations for tolperisone-containing medicines given by injection should be revoked throughout the European Union (EU).

After re-examination, the Committee confirmed these recommendations on 18 October 2012.

What is tolperisone?

Tolperisone is a muscle relaxant. Tolperisone-containing medicines have been authorised in several countries in the EU since the 1960s for the treatment of muscle spasms (involuntary contractions) and spasticity caused by different conditions. These include neurological diseases (related to the brain or nerves, such as multiple sclerosis), locomotor diseases (related to the spine and large joints such as the hip), vascular diseases (related to the blood vessels), rehabilitation following surgery, and Little’s disease (also known as cerebral palsy, a rare disease where there is damage to parts of the brain that control movement).

The exact way tolperisone works is not known, but it is thought to act in the brain and spinal cord to reduce the nerve impulses that make the muscles contract and become rigid. By reducing these impulses, tolperisone is believed to reduce muscle contraction, helping to relieve the stiffness.

Medicines containing tolperisone are available as tablets or solution for injection in Bulgaria, Cyprus, the Czech Republic, Germany, Hungary, Latvia, Lithuania, Poland, Romania and Slovakia, under various trade names.

Why were tolperisone-containing medicines reviewed?

As tolperisone-containing medicines have been developed by different companies and have been authorised through national procedures in the EU Member States, they are used to treat different conditions in different countries. In Germany, several indications approved in other countries were not authorised because the German medicines agency considered that tolperisone’s effectiveness had not been proven in those indications. In addition, numerous reports of hypersensitivity (allergic) reactions to tolperisone had been reported post-marketing in Germany. Consequently, the German medicines agency considered that a full assessment of the benefit-risk balance of tolperisone should be carried out in all approved indications. On 15 July 2011, it asked the CHMP to issue an opinion on whether the marketing authorisations for tolperisone-containing products should be maintained, varied, suspended or withdrawn across the EU.

Which data has the CHMP reviewed?

The CHMP reviewed data on the effectiveness of oral and injectable tolperisone in the different indications, including data from published clinical studies and analyses of various studies provided by the companies that market these medicines. The Committee also reviewed the available post-marketing data on spontaneous reports of side effects.

What are the conclusions of the CHMP?

The CHMP noted that most of the studies with oral tolperisone, performed in the 1960s and 1970s, were of a lower standard than that expected today. The available data to support the use of tolperisone-containing medicines in locomotor diseases, vascular diseases, rehabilitation following surgery and Little’s disease are limited and not convincing. Only in the treatment of spasticity caused by neurological diseases was a study considered to be of acceptable quality, showing a moderate improvement of 32% in spasticity with oral tolperisone, compared with a 14% improvement in the placebo (a dummy treatment) group. However, the study only included adults with post-stroke spasticity.

Regarding the safety of tolperisone, the CHMP noted that more than half of the spontaneous reports of side effects with tolperisone were hypersensitivity reactions, while only a small number of hypersensitivity reports had been observed during the clinical trials that supported tolperisone’s marketing authorisation. The Committee therefore recommended that the product information should be updated to reflect this risk and include a warning on the signs of hypersensitivity.

Therefore, based on the evaluation of the currently available data and considering that the risk of hypersensitivity reactions is more significant than previously identified, the CHMP concluded that the benefits of oral tolperisone-containing medicines continue to outweigh its risks only when used in the treatment of post-stroke spasticity in adults. In addition, since extremely limited data are available to support the safety and dosing recommendations of injectable tolperisone, the CHMP concluded that the benefits of this formulation do not outweigh the identified risks, and that the marketing authorisations for tolperisone-containing medicines given by injection should be revoked.

The CHMP confirmed the above conclusions after re-examining its opinion. The full changes made to the information to doctors and patients are under the 'All documents' tab.

What are the recommendations for patients?
  • Patients should be aware that the benefits of oral tolperisone continue to outweigh its risks only for the treatment of post-stroke spasticity in adults.
  • Patients currently using tolperisone for any other indication or using injectable tolperisone should speak to their doctor at their next routine appointment so they can switch to an appropriate alternative treatment.
  • Patients should note that symptoms of hypersensitivity can include flushing, rash, severe itching of the skin (with raised lumps), wheezing, difficulty breathing, difficulty in swallowing, fast heartbeat, low blood pressure and fast decrease in blood pressure. Patients should stop taking tolperisone and inform their doctor if they experience any of these symptoms.
  • Patients who have any questions should speak to their doctor or pharmacist.
What are the recommendations for prescribers?
  • Prescribers are advised that the indication for oral tolperisone has been restricted to the treatment of post-stroke spasticity in adults. Doctors should stop prescribing tolperisone for any other indication.
  • Prescribers are advised that injectable tolperisone should no longer be used in the EU.
  • Patients should be informed of the possibility of hypersensitivity reactions during treatment with tolperisone. If symptoms of hypersensitivity occur, treatment should be stopped immediately.

The European Commission issued a decision on this opinion on 21 January 2013.

Name Language First published Last updated
Questions and answers on the review of tolperisone-containing medicines BG = bălgarski 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines ES = español 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines CS = čeština 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines DA = dansk 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines DE = Deutsch 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines ET = eesti keel 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines EL = elliniká 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines EN = English 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines FR = français 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines IT = italiano 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines LV = latviešu valoda 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines LT = lietuvių kalba 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines HU = magyar 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines MT = Malti 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines NL = Nederlands 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines PL = polski 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines PT = português 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines RO = română 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines SK = slovenčina 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines SL = slovenščina 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines FI = suomi 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines SV = svenska 2012-06-22 2013-04-02

Key facts

Approved nameTolperisone
International non-proprietary name (INN) or common name

Tolperisone

Associated names-
Class-
Reference numberEMEA/H/A-31/1311
TypeArticle 31 referrals

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

StatusEuropean Commission final decision
Opinion date18/10/2012

All documents

Name Language First published Last updated
Questions and answers on the review of tolperisone-containing medicines BG = bălgarski 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines ES = español 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines CS = čeština 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines DA = dansk 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines DE = Deutsch 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines ET = eesti keel 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines EL = elliniká 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines EN = English 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines FR = français 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines IT = italiano 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines LV = latviešu valoda 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines LT = lietuvių kalba 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines HU = magyar 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines MT = Malti 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines NL = Nederlands 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines PL = polski 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines PT = português 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines RO = română 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines SK = slovenčina 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines SL = slovenščina 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines FI = suomi 2012-06-22 2013-04-02
Questions and answers on the review of tolperisone-containing medicines SV = svenska 2012-06-22 2013-04-02
Tolperisone: Product information as approved by the CHMP on 19 October 2012 pending endorsement by the European Commission (English only) 2012-10-19  
Assessment report for tolperisone-containing medicinal products (English only) 2013-04-02  
Tolperisone Article-31 referral - Annex I BG = bălgarski 2013-04-02  
Tolperisone Article-31 referral - Annex I ES = español 2013-04-02  
Tolperisone Article-31 referral - Annex I CS = čeština 2013-04-02  
Tolperisone Article-31 referral - Annex I DA = dansk 2013-04-02  
Tolperisone Article-31 referral - Annex I DE = Deutsch 2013-04-02  
Tolperisone Article-31 referral - Annex I ET = eesti keel 2013-04-02  
Tolperisone Article-31 referral - Annex I EL = elliniká 2013-04-02  
Tolperisone Article-31 referral - Annex I EN = English 2013-04-02  
Tolperisone Article-31 referral - Annex I FR = français 2013-04-02  
Tolperisone Article-31 referral - Annex I IT = italiano 2013-04-02  
Tolperisone Article-31 referral - Annex I LV = latviešu valoda 2013-04-02  
Tolperisone Article-31 referral - Annex I LT = lietuvių kalba 2013-04-02  
Tolperisone Article-31 referral - Annex I HU = magyar 2013-04-02  
Tolperisone Article-31 referral - Annex I MT = Malti 2013-04-02  
Tolperisone Article-31 referral - Annex I NL = Nederlands 2013-04-02  
Tolperisone Article-31 referral - Annex I PL = polski 2013-04-02  
Tolperisone Article-31 referral - Annex I PT = português 2013-04-02  
Tolperisone Article-31 referral - Annex I RO = română 2013-04-02  
Tolperisone Article-31 referral - Annex I SK = slovenčina 2013-04-02  
Tolperisone Article-31 referral - Annex I SL = slovenščina 2013-04-02  
Tolperisone Article-31 referral - Annex I FI = suomi 2013-04-02  
Tolperisone Article-31 referral - Annex I SV = svenska 2013-04-02  
Tolperisone Article-31 referral - Annex II BG = bălgarski 2013-04-02  
Tolperisone Article-31 referral - Annex II ES = español 2013-04-02  
Tolperisone Article-31 referral - Annex II CS = čeština 2013-04-02  
Tolperisone Article-31 referral - Annex II DA = dansk 2013-04-02  
Tolperisone Article-31 referral - Annex II DE = Deutsch 2013-04-02  
Tolperisone Article-31 referral - Annex II ET = eesti keel 2013-04-02  
Tolperisone Article-31 referral - Annex II EL = elliniká 2013-04-02  
Tolperisone Article-31 referral - Annex II EN = English 2013-04-02  
Tolperisone Article-31 referral - Annex II FR = français 2013-04-02  
Tolperisone Article-31 referral - Annex II IT = italiano 2013-04-02  
Tolperisone Article-31 referral - Annex II LV = latviešu valoda 2013-04-02  
Tolperisone Article-31 referral - Annex II LT = lietuvių kalba 2013-04-02  
Tolperisone Article-31 referral - Annex II HU = magyar 2013-04-02  
Tolperisone Article-31 referral - Annex II MT = Malti 2013-04-02  
Tolperisone Article-31 referral - Annex II NL = Nederlands 2013-04-02  
Tolperisone Article-31 referral - Annex II PL = polski 2013-04-02  
Tolperisone Article-31 referral - Annex II PT = português 2013-04-02  
Tolperisone Article-31 referral - Annex II RO = română 2013-04-02  
Tolperisone Article-31 referral - Annex II SK = slovenčina 2013-04-02  
Tolperisone Article-31 referral - Annex II SL = slovenščina 2013-04-02  
Tolperisone Article-31 referral - Annex II FI = suomi 2013-04-02  
Tolperisone Article-31 referral - Annex II SV = svenska 2013-04-02  
Tolperisone Article-31 referral - Annex III BG = bălgarski 2013-04-02  
Tolperisone Article-31 referral - Annex III ES = español 2013-04-02  
Tolperisone Article-31 referral - Annex III CS = čeština 2013-04-02  
Tolperisone Article-31 referral - Annex III DA = dansk 2013-04-02  
Tolperisone Article-31 referral - Annex III DE = Deutsch 2013-04-02  
Tolperisone Article-31 referral - Annex III ET = eesti keel 2013-04-02  
Tolperisone Article-31 referral - Annex III EL = elliniká 2013-04-02  
Tolperisone Article-31 referral - Annex III EN = English 2013-04-02  
Tolperisone Article-31 referral - Annex III FR = français 2013-04-02  
Tolperisone Article-31 referral - Annex III IT = italiano 2013-04-02  
Tolperisone Article-31 referral - Annex III LV = latviešu valoda 2013-04-02  
Tolperisone Article-31 referral - Annex III LT = lietuvių kalba 2013-04-02  
Tolperisone Article-31 referral - Annex III HU = magyar 2013-04-02  
Tolperisone Article-31 referral - Annex III MT = Malti 2013-04-02  
Tolperisone Article-31 referral - Annex III NL = Nederlands 2013-04-02  
Tolperisone Article-31 referral - Annex III PL = polski 2013-04-02  
Tolperisone Article-31 referral - Annex III PT = português 2013-04-02  
Tolperisone Article-31 referral - Annex III RO = română 2013-04-02  
Tolperisone Article-31 referral - Annex III SK = slovenčina 2013-04-02  
Tolperisone Article-31 referral - Annex III SL = slovenščina 2013-04-02  
Tolperisone Article-31 referral - Annex III FI = suomi 2013-04-02  
Tolperisone Article-31 referral - Annex III SV = svenska 2013-04-02  
Tolperisone Article-31 referral - Annex IV BG = bălgarski 2013-04-02  
Tolperisone Article-31 referral - Annex IV ES = español 2013-04-02  
Tolperisone Article-31 referral - Annex IV CS = čeština 2013-04-02  
Tolperisone Article-31 referral - Annex IV DA = dansk 2013-04-02  
Tolperisone Article-31 referral - Annex IV DE = Deutsch 2013-04-02  
Tolperisone Article-31 referral - Annex IV ET = eesti keel 2013-04-02  
Tolperisone Article-31 referral - Annex IV EL = elliniká 2013-04-02  
Tolperisone Article-31 referral - Annex IV EN = English 2013-04-02  
Tolperisone Article-31 referral - Annex IV FR = français 2013-04-02  
Tolperisone Article-31 referral - Annex IV IT = italiano 2013-04-02  
Tolperisone Article-31 referral - Annex IV LV = latviešu valoda 2013-04-02  
Tolperisone Article-31 referral - Annex IV LT = lietuvių kalba 2013-04-02  
Tolperisone Article-31 referral - Annex IV HU = magyar 2013-04-02  
Tolperisone Article-31 referral - Annex IV MT = Malti 2013-04-02  
Tolperisone Article-31 referral - Annex IV NL = Nederlands 2013-04-02  
Tolperisone Article-31 referral - Annex IV PL = polski 2013-04-02  
Tolperisone Article-31 referral - Annex IV PT = português 2013-04-02  
Tolperisone Article-31 referral - Annex IV RO = română 2013-04-02  
Tolperisone Article-31 referral - Annex IV SK = slovenčina 2013-04-02  
Tolperisone Article-31 referral - Annex IV SL = slovenščina 2013-04-02  
Tolperisone Article-31 referral - Annex IV FI = suomi 2013-04-02  
Tolperisone Article-31 referral - Annex IV SV = svenska 2013-04-02  

Document description

  • Questions and answers (Q&A) - easy-to-understand summary of key issues and Committee conclusions
  • Summary of Opinion - contains the CHMP opinion of the referred medicine(s)
  • List of the medicines affected by the referral (Annex I)
  • Scientific conclusions of the Committee (Annex II)

The following two documents are sometimes available:

  • Changes to the summary of product characteristics, labeling or package leaflet (also known as Annex III) - available when changes have been recommended by the Committee
  • Conditions of the marketing authorisation (also known as Annex IV) - available when the Committee recommends measures to be taken for the marketing authorisation(s) such as safety measures or extra studies

Current status:
European Commission final decision

More information on tolperisone