• Procedure started
  • Under evaluation
  • CHMP opinion
  • European Commission final decision

Overview

Outcome of a procedure under Article 107 of Directive 2001/83/EC

The European Medicines Agency has completed a review of the safety and effectiveness of ketoprofen-containing medicines used topically (on the skin). The Agency's Committee for Medicinal Products for Human Use (CHMP) has concluded that the benefits of topical ketoprofen continue to outweigh its risks, but that further measures should be put in place to minimise the risk of adverse skin reactions.

Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID). NSAIDs work by blocking an enzyme called cyclo-oxygenase, which is involved in the production of prostaglandins. Prostaglandins are messengers in the development of inflammation. Blocking their production helps to reduce the signs of inflammation.

Topical formulations of ketoprofen are used to treat the symptoms of pain and inflammation in conditions such as minor trauma (sprains, bruising), tendonitis (inflammation of a tendon), small-joint osteoarthritis (swelling and pain in the small joints), acute low-back pain and phlebitis (inflammation of a vein).

Topical ketoprofen-containing medicines have been available in all Member States except for the Netherlands since 1978. They may be available as creams, gels, solutions, sprays and plasters under various trade names and as generics. They may be obtained with or without a prescription.

Since their marketing authorisation, the French medicines regulatory agency (Afssaps) has reviewed the safety of topical ketoprofen-containing medicines several times because of reports of photoallergy (allergic reactions to a medicine following exposure to sunlight) in patients using these medicines. As a result, measures to reduce harm were implemented in France, such as the inclusion of warnings and precautions in the French product information, a pictogram on the packaging and dissemination of letters to healthcare professionals. In spite of these measures, new cases of photoallergy have been reported, which occurred even in cases of exposure to dim sunlight. In addition, new skin reactions have been reported in people using topical ketoprofen together with products containing octocrylene (a chemical sunscreen found in several cosmetics and care products such as shampoo, skin creams, anti-ageing creams, make-up removers and hair sprays). These reactions occurred even without exposure to sunlight.
In December 2009, after re-assessing these medicines, the French agency considered that their benefit-risk balance was no longer positive and decided to suspend the marketing authorisations of all topical medicines containing ketoprofen in France.

As required by Article 107, the French agency informed the CHMP of its actions so that the Committee could prepare an opinion on whether the marketing authorisations for topical products containing ketoprofen should be maintained, changed, suspended or revoked across the EU.

The CHMP looked into all the available safety data, including data from member states' databases and data provided by the companies marketing topical ketoprofen in the EU. In particular, the Committee considered the responses given by the companies to a list of questions on photosensitivity reactions, including photoallergy, in patients using these medicines.

The CHMP noted that the number of reports of adverse skin reactions including photoallergy is low throughout the EU and that the risk of these side effects could potentially be reduced using appropriate minimisation measures. The Committee also noted that, although alternative topical NSAIDs are available in the EU, ketoprofen is the only topical NSAID authorised for the treatment of acute low-back pain.

The CHMP concluded that the benefits of topical ketoprofen-containing medicines continue to outweigh their risks but recommended the following risk minimisation measures:

  • these medicines should no longer be available over the counter but should only be obtained with a prescription from a doctor;
  • strengthened warnings on sun exposure should be included in the product information, as well as information on adverse skin reactions when topical ketoprofen is used together with octocrylene;
  • the risks of photoallergy with topical ketoprofen and the way to prevent it should be clearly communicated to healthcare professionals and to patients.

Finally, the CHMP agreed to review the effectiveness of these risk minimization measures in three years time.

  • Doctors, pharmacists and patients should be aware of the risk of photoallergy with topical ketoprofen.
  • Doctors should tell their patients how to use topical ketoprofen-containing medicines appropriately.
  • Patients should make sure that the treated areas are protected from sunlight during the whole period of ketoprofen treatment and the two weeks after stopping the treatment. They should also wash their hands carefully after each application of ketoprofen.
  • Patients should discontinue treatment immediately if they develop any skin reaction after application of these medicines, and seek their doctor's advice.
  • Patients who have any questions should speak to their doctor or pharmacist.

The European Commission issued a decision on this opinion on 29 November 2010.

Questions and answers on the review of the marketing authorisations for topical formulations of ketoprofen

български (BG) (160.31 KB - PDF)
español (ES) (79.93 KB - PDF)
čeština (CS) (88.61 KB - PDF)
dansk (DA) (81.22 KB - PDF)
Deutsch (DE) (143.19 KB - PDF)
eesti keel (ET) (80.85 KB - PDF)
ελληνικά (EL) (161.54 KB - PDF)
français (FR) (142.89 KB - PDF)
italiano (IT) (141.81 KB - PDF)
latviešu valoda (LV) (161.96 KB - PDF)
lietuvių kalba (LT) (148.64 KB - PDF)
magyar (HU) (83.77 KB - PDF)
Malti (MT) (159.18 KB - PDF)
Nederlands (NL) (81.78 KB - PDF)
polski (PL) (146.91 KB - PDF)
português (PT) (140.41 KB - PDF)
română (RO) (86.33 KB - PDF)
slovenčina (SK) (145.88 KB - PDF)
slovenščina (SL) (83.35 KB - PDF)
Suomi (FI) (141.32 KB - PDF)
svenska (SV) (140.61 KB - PDF)

Key facts

About this medicine

Approved name
Ketoprofen topical
International non-proprietary name (INN) or common name
ketoprofen
Associated names
  • Fastum
  • Ketum
  • Orudis

About this procedure

Current status
European Commission final decision
Reference number
EMEA/H/A-107/001259
Type
Article 107 procedures (prior to July 2012)

This type of procedure was triggered when a Member State varied, suspended or revoked the marketing authorisation for a medicine in its territory because of a safety issue. This procedure has been replaced by Article 107i.

Key dates and outcomes

CHMP opinion date
22/07/2010
EC decision date
29/11/2010

All documents

Assessment report for KETOPROFEN containing medicinal products (topical formulations)

Ketoprofen - Article 107 referral - Annex I

български (BG) (118.03 KB - PDF)
español (ES) (121.15 KB - PDF)
čeština (CS) (118.05 KB - PDF)
dansk (DA) (126.25 KB - PDF)
Deutsch (DE) (118.59 KB - PDF)
eesti keel (ET) (114.9 KB - PDF)
ελληνικά (EL) (127.25 KB - PDF)
français (FR) (117.56 KB - PDF)
íslenska (IS) (204.51 KB - PDF)
italiano (IT) (120.98 KB - PDF)
latviešu valoda (LV) (119.2 KB - PDF)
lietuvių kalba (LT) (118.86 KB - PDF)
magyar (HU) (122.98 KB - PDF)
Malti (MT) (123.76 KB - PDF)
Nederlands (NL) (119.23 KB - PDF)
norsk (NO) (170.49 KB - PDF)
polski (PL) (121.24 KB - PDF)
português (PT) (118.98 KB - PDF)
română (RO) (117.61 KB - PDF)
slovenčina (SK) (118.96 KB - PDF)
slovenščina (SL) (116.54 KB - PDF)
Suomi (FI) (112.14 KB - PDF)
svenska (SV) (101.59 KB - PDF)

Ketoprofen - Article 107 referral - Annex II

български (BG) (116.07 KB - PDF)
español (ES) (103.91 KB - PDF)
čeština (CS) (104.33 KB - PDF)
dansk (DA) (102.53 KB - PDF)
Deutsch (DE) (106.64 KB - PDF)
eesti keel (ET) (95.46 KB - PDF)
ελληνικά (EL) (118.66 KB - PDF)
français (FR) (101.71 KB - PDF)
italiano (IT) (103.24 KB - PDF)
latviešu valoda (LV) (100.77 KB - PDF)
lietuvių kalba (LT) (106.13 KB - PDF)
magyar (HU) (108.71 KB - PDF)
Malti (MT) (103.9 KB - PDF)
Nederlands (NL) (103.39 KB - PDF)
polski (PL) (108.03 KB - PDF)
português (PT) (104.5 KB - PDF)
română (RO) (100.53 KB - PDF)
slovenčina (SK) (109.25 KB - PDF)
slovenščina (SL) (99.81 KB - PDF)
Suomi (FI) (97.87 KB - PDF)
svenska (SV) (102.72 KB - PDF)

Ketoprofen - Article 107 referral - Annex III

български (BG) (92.16 KB - PDF)
español (ES) (84.48 KB - PDF)
čeština (CS) (82.59 KB - PDF)
dansk (DA) (83.36 KB - PDF)
Deutsch (DE) (85.31 KB - PDF)
eesti keel (ET) (74.67 KB - PDF)
ελληνικά (EL) (93.72 KB - PDF)
français (FR) (81.5 KB - PDF)
íslenska (IS) (70.7 KB - PDF)
italiano (IT) (82.34 KB - PDF)
latviešu valoda (LV) (81.33 KB - PDF)
lietuvių kalba (LT) (83.75 KB - PDF)
magyar (HU) (81.46 KB - PDF)
Malti (MT) (83.44 KB - PDF)
Nederlands (NL) (83.23 KB - PDF)
norsk (NO) (54.62 KB - PDF)
polski (PL) (84.9 KB - PDF)
português (PT) (81.66 KB - PDF)
română (RO) (87.02 KB - PDF)
slovenčina (SK) (81.58 KB - PDF)
slovenščina (SL) (82.17 KB - PDF)
Suomi (FI) (76.03 KB - PDF)
svenska (SV) (80.27 KB - PDF)

Ketoprofen - Article 107 referral - Annex IV

български (BG) (83.17 KB - PDF)
español (ES) (71.16 KB - PDF)
čeština (CS) (72.16 KB - PDF)
dansk (DA) (72.72 KB - PDF)
Deutsch (DE) (73.75 KB - PDF)
eesti keel (ET) (67.96 KB - PDF)
ελληνικά (EL) (83.15 KB - PDF)
français (FR) (70.04 KB - PDF)
italiano (IT) (71.73 KB - PDF)
latviešu valoda (LV) (72.58 KB - PDF)
lietuvių kalba (LT) (73.72 KB - PDF)
magyar (HU) (72.95 KB - PDF)
Malti (MT) (73.29 KB - PDF)
Nederlands (NL) (60.87 KB - PDF)
polski (PL) (73.2 KB - PDF)
português (PT) (49.46 KB - PDF)
română (RO) (71.27 KB - PDF)
slovenčina (SK) (75.01 KB - PDF)
slovenščina (SL) (70.32 KB - PDF)
Suomi (FI) (67.28 KB - PDF)
svenska (SV) (73.78 KB - PDF)

Questions and answers on the review of the marketing authorisations for topical formulations of ketoprofen

български (BG) (160.31 KB - PDF)
español (ES) (79.93 KB - PDF)
čeština (CS) (88.61 KB - PDF)
dansk (DA) (81.22 KB - PDF)
Deutsch (DE) (143.19 KB - PDF)
eesti keel (ET) (80.85 KB - PDF)
ελληνικά (EL) (161.54 KB - PDF)
français (FR) (142.89 KB - PDF)
italiano (IT) (141.81 KB - PDF)
latviešu valoda (LV) (161.96 KB - PDF)
lietuvių kalba (LT) (148.64 KB - PDF)
magyar (HU) (83.77 KB - PDF)
Malti (MT) (159.18 KB - PDF)
Nederlands (NL) (81.78 KB - PDF)
polski (PL) (146.91 KB - PDF)
português (PT) (140.41 KB - PDF)
română (RO) (86.33 KB - PDF)
slovenčina (SK) (145.88 KB - PDF)
slovenščina (SL) (83.35 KB - PDF)
Suomi (FI) (141.32 KB - PDF)
svenska (SV) (140.61 KB - PDF)

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.

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