Fibrates

  • Email
  • Help

The European Medicines Agency has completed a review of the safety and effectiveness of fibrates. The Agency’s Committee for Medicinal Products for Human Use (CHMP) has concluded that the benefits of fibrates continue to outweigh their risks but that they should not be used as ‘first line’ in the treatment of blood lipid (fat) disorders, such as high cholesterol, except in rare cases. This means that newly diagnosed patients with blood lipid disorders should not be treated using these medicines in the first instance, unless they have very high levels of triglycerides (a type of fat). However, fibrates can be used in patients who cannot take statins (another type of medicine used to lower blood lipid levels).

What are fibrates?

Fibrates are a class of medicines that can be used to lower the level of lipids, such as cholesterol and triglycerides, in the blood. Blood lipid disorders are a risk factor of heart disease (such as heart attack and stroke) and fibrates are used to improve lipid levels in patients in whom dietary restrictions and exercise have not been enough.

Fibrates are ‘PPAR agonists’. This means that they activate a type of receptor called the ‘peroxisome proliferator activated receptor’. This receptor can be found in many cells throughout the body, where it is involved in breaking down dietary fat, especially triglycerides and cholesterol. When the receptors are activated, the break down of fats is accelerated, and this helps clear the blood of cholesterol and triglycerides.

Fibrates have been in use since the 1960s. Currently, four fibrates are available in the European Union:

  • bezafibrate. This medicine has been available since 1977. It is marketed mainly under the trade names Bezalip, Cedur, Eulitop and Befizal, as well as generic medicines. It is sold in Austria, Belgium, Cyprus, Finland, France, Germany, Greece, Hungary, Italy, Luxembourg, Malta, the Netherlands, Portugal, Romania, Spain, Sweden and the United Kingdom (UK);
  • ciprofibrate. This medicine has been available since 1995. It is marketed mainly under the trade name Lipanor or Modalim, as well as generic medicines. It is sold in Belgium, Bulgaria, Cyprus, the Czech Republic, Estonia, France, Greece, Hungary, Latvia, Lithuania, Luxembourg, the Netherlands, Poland, Portugal, Romania, Slovakia and the UK;
  • fenofibrate. This medicine has been available since 1975. It is marketed mainly under the trade name Lipanthyl, as well as generic medicines. It is sold in all European Union (EU) Member States except Denmark and the Netherlands, as well as in Iceland and Norway;
  • gemfibrozil. This medicine has been available since 1981. It is marketed mainly under the trade name Lopid, as well as generic medicines. It is sold in Austria, Cyprus, Denmark, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, the Netherlands, Portugal, Slovenia, Slovakia, Spain, Sweden and the UK.

These medicines have all been authorised via national procedures.

Why were fibrates reviewed?

In 2005, the CHMP’s Pharmacovigilance Working Party (PhVWP) noted that there was limited evidence of the long-term benefit of fibrates in reducing cardiovascular risk, compared with the stronger evidence for statins (another type of medicine used for lowering blood cholesterol). As a result, the Working Party undertook a review of the benefits and risks of all fibrate-containing medicines on behalf of the medicines regulatory authorities of the countries where the medicines were marketed. The aim of the review was to establish how fibrates should be used, taking into account their safety, their effectiveness in lowering lipid levels and the availability of other lipid-lowering medicines that were not around when fibrates were first used. Looking at the data, the PhVWP came to the conclusion that there were no new safety issues with fibrates and that fibrate-containing medicines still had a role to play in improving lipid levels, but that they should not be used as first-line treatment.

The conclusions of the PhVWP were transmitted to the companies that market fibrates, so that they could implement the changes recommended by the Working Party. However, a number of them questioned the restriction. Consequently, the UK medicines regulatory agency referred the matter to the CHMP on 20 October 2009, to carry out a full assessment of the benefit-risk balance of fibrates and to issue an opinion on whether the marketing authorisations for fibrate-containing medicines should be maintained or varied across the EU.

Which data has the CHMP reviewed?

The CHMP looked at the information gathered by the PhVWP during its review, as well as the responses provided by the companies to specific questions. The Committee also looked at the latest data from clinical studies including a trial looking at the effect of using fenofibrate as an ‘add-on’ to statins.

What are the conclusions of the CHMP?

The Committee endorsed the conclusions of the PhVWP that fibrates are still a safe option for lowering lipid levels, but that their use as first-line treatment is not justified. Fibrates should be used only when statins are contra-indicated or not tolerated. However, the Committee noted that fibrates are more effective than statins in lowering triglyceride levels and therefore their use as a first-line treatment in patients with severe hypertriglyceridaemia (very high blood levels of triglycerides) is still appropriate.

The Committee also noted that there were new data for fenofibrate that supported a change to the PhVWP recommendations, based on the results of the add-on study. As a result, the Committee also allowed the use of fenofibrate together with a statin in some circumstances for patients at risk when using a statin on its own was not enough to completely control blood lipid levels.

Based on the evaluation of the currently available data and the scientific discussion within the Committee, the CHMP concluded that the benefits of fibrates continue to outweigh their risks within these restrictions. The Committee recommended specific changes to the information to doctors and patients for all four fibrates.

What are the recommendations for patients?
  • Patients who are currently taking fibrates to lower their blood lipid levels should continue to do so. There are no new safety concerns with the medicines.
  • However, patients taking a fibrate-containing medicine should arrange to see their doctor to check that the medicine is the most appropriate option to lower their blood lipid levels.
  • Patients who have any questions should speak to their doctor or pharmacist.
What are the recommendations for prescribers?
  • Doctors are reminded that fibrates should not be used as first-line treatment in patients with high lipid levels, except in specific groups:
    • patients with severe hypertriglyceridaemia;
    • patients for whom statins are contra-indicated or who cannot tolerate them.
  • They should review the treatment of patients who are receiving fibrates to help control their lipid levels to ensure that the patient is receiving the most appropriate treatment.

The European Commission issued a decision on 28 February 2011.

Name Language First published Last updated
Questions and answers on the review of medicines containing fibrates BG = bălgarski 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates ES = español 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates CS = čeština 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates DA = dansk 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates DE = Deutsch 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates ET = eesti keel 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates EL = elliniká 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates EN = English 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates FR = français 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates IT = italiano 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates LV = latviešu valoda 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates LT = lietuvių kalba 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates HU = magyar 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates MT = Malti 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates NL = Nederlands 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates PL = polski 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates PT = português 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates RO = română 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates SK = slovenčina 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates SL = slovenščina 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates FI = suomi 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates SV = svenska 2010-10-22 2013-04-03

Key facts

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

bezafibrate, ciprofibrate, fenofibrate, gemfibrozil

Associated namesBezalip, Lipanor, Lipanthyl, Lopid
Classfibrates
Reference numberEMEA/H/A-31/001238
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 date21/10/2010

All documents

Name Language First published Last updated
Questions and answers on the review of medicines containing fibrates BG = bălgarski 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates ES = español 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates CS = čeština 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates DA = dansk 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates DE = Deutsch 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates ET = eesti keel 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates EL = elliniká 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates EN = English 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates FR = français 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates IT = italiano 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates LV = latviešu valoda 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates LT = lietuvių kalba 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates HU = magyar 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates MT = Malti 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates NL = Nederlands 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates PL = polski 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates PT = português 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates RO = română 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates SK = slovenčina 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates SL = slovenščina 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates FI = suomi 2010-10-22 2013-04-03
Questions and answers on the review of medicines containing fibrates SV = svenska 2010-10-22 2013-04-03
Fibrates (bezafibrate, ciprofibrate, fenofibrate and gemfibrozil) - Article-31 referral - changes to product information (English only) 2010-10-22  
Assessment report for fenofibrate-, bezafibrate-, ciprofibrate- and gemfibrozil-containing medicinal products (English only) 2013-04-03  
Fibrates Article-31 referral - Annex I BG = bălgarski 2013-04-03  
Fibrates Article-31 referral - Annex I ES = español 2013-04-03  
Fibrates Article-31 referral - Annex I CS = čeština 2013-04-03  
Fibrates Article-31 referral - Annex I DA = dansk 2013-04-03  
Fibrates Article-31 referral - Annex I DE = Deutsch 2013-04-03  
Fibrates Article-31 referral - Annex I ET = eesti keel 2013-04-03  
Fibrates Article-31 referral - Annex I EL = elliniká 2013-04-03  
Fibrates Article-31 referral - Annex I EN = English 2013-04-03  
Fibrates Article-31 referral - Annex I FR = français 2013-04-03  
Fibrates Article-31 referral - Annex I IT = italiano 2013-04-03  
Fibrates Article-31 referral - Annex I LV = latviešu valoda 2013-04-03  
Fibrates Article-31 referral - Annex I LT = lietuvių kalba 2013-04-03  
Fibrates Article-31 referral - Annex I HU = magyar 2013-04-03  
Fibrates Article-31 referral - Annex I MT = Malti 2013-04-03  
Fibrates Article-31 referral - Annex I NL = Nederlands 2013-04-03  
Fibrates Article-31 referral - Annex I PL = polski 2013-04-03  
Fibrates Article-31 referral - Annex I PT = português 2013-04-03  
Fibrates Article-31 referral - Annex I RO = română 2013-04-03  
Fibrates Article-31 referral - Annex I SK = slovenčina 2013-04-03  
Fibrates Article-31 referral - Annex I SL = slovenščina 2013-04-03  
Fibrates Article-31 referral - Annex I FI = suomi 2013-04-03  
Fibrates Article-31 referral - Annex I SV = svenska 2013-04-03  
Fibrates Article-31 referral - Annex II BG = bălgarski 2013-04-03  
Fibrates Article-31 referral - Annex II ES = español 2013-04-03  
Fibrates Article-31 referral - Annex II CS = čeština 2013-04-03  
Fibrates Article-31 referral - Annex II DA = dansk 2013-04-03  
Fibrates Article-31 referral - Annex II DE = Deutsch 2013-04-03  
Fibrates Article-31 referral - Annex II ET = eesti keel 2013-04-03  
Fibrates Article-31 referral - Annex II EL = elliniká 2013-04-03  
Fibrates Article-31 referral - Annex II EN = English 2013-04-03  
Fibrates Article-31 referral - Annex II FR = français 2013-04-03  
Fibrates Article-31 referral - Annex II IT = italiano 2013-04-03  
Fibrates Article-31 referral - Annex II LV = latviešu valoda 2013-04-03  
Fibrates Article-31 referral - Annex II LT = lietuvių kalba 2013-04-03  
Fibrates Article-31 referral - Annex II HU = magyar 2013-04-03  
Fibrates Article-31 referral - Annex II MT = Malti 2013-04-03  
Fibrates Article-31 referral - Annex II NL = Nederlands 2013-04-03  
Fibrates Article-31 referral - Annex II PL = polski 2013-04-03  
Fibrates Article-31 referral - Annex II PT = português 2013-04-03  
Fibrates Article-31 referral - Annex II RO = română 2013-04-03  
Fibrates Article-31 referral - Annex II SK = slovenčina 2013-04-03  
Fibrates Article-31 referral - Annex II SL = slovenščina 2013-04-03  
Fibrates Article-31 referral - Annex II FI = suomi 2013-04-03  
Fibrates Article-31 referral - Annex II SV = svenska 2013-04-03  
Fibrates Article-31 referral - Annex III BG = bălgarski 2013-04-03  
Fibrates Article-31 referral - Annex III ES = español 2013-04-03  
Fibrates Article-31 referral - Annex III CS = čeština 2013-04-03  
Fibrates Article-31 referral - Annex III DA = dansk 2013-04-03  
Fibrates Article-31 referral - Annex III DE = Deutsch 2013-04-03  
Fibrates Article-31 referral - Annex III ET = eesti keel 2013-04-03  
Fibrates Article-31 referral - Annex III EL = elliniká 2013-04-03  
Fibrates Article-31 referral - Annex III EN = English 2013-04-03  
Fibrates Article-31 referral - Annex III FR = français 2013-04-03  
Fibrates Article-31 referral - Annex III IT = italiano 2013-04-03  
Fibrates Article-31 referral - Annex III LV = latviešu valoda 2013-04-03  
Fibrates Article-31 referral - Annex III LT = lietuvių kalba 2013-04-03  
Fibrates Article-31 referral - Annex III HU = magyar 2013-04-03  
Fibrates Article-31 referral - Annex III MT = Malti 2013-04-03  
Fibrates Article-31 referral - Annex III NL = Nederlands 2013-04-03  
Fibrates Article-31 referral - Annex III PL = polski 2013-04-03  
Fibrates Article-31 referral - Annex III PT = português 2013-04-03  
Fibrates Article-31 referral - Annex III RO = română 2013-04-03  
Fibrates Article-31 referral - Annex III SK = slovenčina 2013-04-03  
Fibrates Article-31 referral - Annex III SL = slovenščina 2013-04-03  
Fibrates Article-31 referral - Annex III FI = suomi 2013-04-03  
Fibrates Article-31 referral - Annex III SV = svenska 2013-04-03  

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