Ranitidine-containing medicinal products

  • Procedure started
  • Under evaluation
  • CHMP opinion
  • European Commission final decision
Current status:
European Commission final decision

Overview

EMA confirms recommendation to suspend all ranitidine medicines in the EU

On 17 September 2020, EMA’s human medicines committee (CHMP) confirmed its recommendation to suspend all ranitidine medicines in the EU due to the presence of low levels of an impurity called N-nitrosodimethylamine (NDMA). This follows a re-examination of CHMP’s April 2020 opinion, which was requested by one of the companies marketing ranitidine medicines.

NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on animal studies. It is present in some foods and water supplies and is not expected to cause harm when ingested at very low levels.

Available safety data do not show that ranitidine increases the risk of cancer, and any possible risk is likely to be very low. However, NDMA has been found in several ranitidine medicines above levels considered acceptable, and there are unresolved questions about the source of this impurity.

There is some evidence that NDMA may form from the degradation of ranitidine itself with increasing levels seen over its shelf life. It is not clear if NDMA can also be formed from ranitidine inside the body. Some studies suggest that it can, while others do not. Given the uncertainties, the CHMP has recommended in April 2020 a precautionary suspension of these medicines in the EU.

Ranitidine medicines are used for reducing stomach acid in patients with conditions such as heartburn and stomach ulcers. Alternatives are available and patients should contact their healthcare professionals for advice about which medicine to take.

Following the re-examination, the CHMP maintained the conditions for lifting the suspension of the medicines, including requirements for companies to provide more data on the possible formation of NDMA from ranitidine inside the body. The formation of NDMA in the body is expected to be very low following a single low dose of ranitidine given by injection or infusion (drip). Therefore, the CHMP slightly amended the conditions for lifting the suspension for those ranitidine medicines that are given by injection or infusion as a single, low dose.

Many ranitidine medicines have not been available in the EU for several months. This is because national authorities have recalled them as a precaution while the EMA review was ongoing.

Since 2018 NDMA and similar compounds known as nitrosamines have been detected in several medicines. EU regulators have acted to identify possible sources of the impurities and set strict requirements for manufacturers.

EMA is continuing to work with national authorities, EDQM,1 the European Commission and international partners to make sure effective measures are taken to prevent the presence of these impurities in medicines. 

1 The European Directorate for the Quality of Medicines & HealthCare

Key facts

About this medicine
Approved name
Ranitidine-containing medicinal products
International non-proprietary name (INN) or common name
ranitidine
About this procedure
Reference number
EMEA/H/A-31/1491
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
Key dates and outcomes
CHMP opinion date
17/09/2020
EC decision date
24/11/2020

All documents

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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