Ranitidine-containing medicinal products

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  • Under evaluation
  • CHMP opinion
  • European Commission final decision
Current status:
Opinion provided by Committee for Medicinal Products for Human Use

Overview

EMA confirms recommendation to suspend all ranitidine medicines in the EU

EMA’s human medicines committee (CHMP) has 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 has 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 will continue working with national authorities, EDQM1 the European Commission and international partners to make sure effective measures are taken to prevent the presence of these impurities in medicines.


1The European Directorate for the Quality of Medicines & HealthCare  

Key facts

Approved name
Ranitidine-containing medicinal products
International non-proprietary name (INN) or common name

ranitidine

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
Opinion provided by Committee for Medicinal Products for Human Use
Opinion date
17/09/2020

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:

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