Ketoconazole-containing medicines

Current status:
European Commission final decision

Overview

On 25 July 2013, the European Medicines Agency's Committee on Medicinal Products for Human Use (CHMP) recommended that the marketing authorisations of oral ketoconazole-containing medicines should be suspended throughout the European Union (EU). The CHMP concluded that the risk of liver injury is greater than the benefits in treating fungal infections.

Patients currently taking oral ketoconazole for fungal infections should make a non-urgent appointment with their doctor to discuss suitable alternative treatments. Doctors should no longer prescribe oral ketoconazole and should review patients' treatment options.

The EU-wide review of oral ketoconazole was triggered by the suspension of the medicine in France. The French medicine agency, the National Agency for the Safety of Medicine and Health Products (ANSM), concluded that the benefit-risk balance of oral ketoconazole was negative because of a high level of liver injury associated with the medicine and in view of the currently available alternative treatments, which are deemed to be safer. European legislation requires that there is a coordinated European approach when a Member State takes regulatory action in relation to a medicine that is authorised in more than one country.

Having assessed the available data on the risks with oral ketoconazole, the CHMP concluded that, although liver injury such as hepatitis is a known side effect of antifungal medicines, the incidence and the seriousness of liver injury with oral ketoconazole were higher than with other antifungals. The CHMP was concerned that reports of liver injury occurred early after starting treatment with recommended doses, and it was not possible to identify measures to adequately reduce this risk. The Committee also concluded that the clinical benefit of oral ketoconazole is uncertain as data on its effectiveness are limited and do not meet current standards, and alternative treatments are available.

Taking into account the increased rate of liver injury and the availability of alternative antifungal treatments, the CHMP concluded that the benefits did not outweigh the risks. Topical formulations of ketoconazole (such as creams, ointments and shampoos) can continue to be used as the amount of ketoconazole absorbed throughout the body is very low with these formulations.

The CHMP opinion was sent to the European Commission, which endorsed it and adopted a final legally binding decision valid throughout the EU on 11 October 2013.

The European Medicines Agency is aware that ketoconazole is used off-label for treating patients with Cushing's syndrome. In order to ensure that these patients will not be left without treatment, national competent authorities may make these medicines available under controlled conditions.

Key facts

Approved name
Ketoconazole-containing medicines
International non-proprietary name (INN) or common name
ketoconazole
Associated names
  • Nizoral
  • Fungoral
Class
Antifungal
Reference number
EMEA/H/A-31/1314
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.

Status
European Commission final decision
Opinion date
25/07/2013
EC decision date
11/10/2013

All documents

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 havebeen recommended by the Committee
  • Conditions of the marketing authorisation (also known as Annex IV) - available when the Committee recommends measures to be takenfor the marketing authorisation(s) such as safety measures or extra studies

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