Review of widely used ranitidine medicines to treat conditions such as heartburn and stomach ulcers due to detection of impurity, N-nitrosodimethylamine (NDMA), a probable human carcinogen!
- 23 сентября 2019
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EMA is to start a review of ranitidine medicines after tests showed that some of these products contained an impurity called N-nitrosodimethylamine (NDMA) at levels which raise concerns according to the principles of the ICH M7 guideline.
The results on a limited sample of products showed that for the majority of both ranitidine APIs and finished products, NDMA was above the acceptable intake established during the referral procedure under Article 31 of Directive 2001/83/EC for sartans with tetrazole ring (considering the maximum daily dose authorized in the EU, and long-term use in 50 kg adult), please refer to the table below.
NDEA, DIPNA, EIPNA
Acceptable Intake [ng/day]
Acceptable Intake [ng/day]
NDMA – N-nitrosodimethylamine
NDEA – N-nitrosodiethylamine,
NMBA – 4-(methyl)(nitroso)amino)butanoic acid
DIPNA – N-nitrosodiisopropylamine
EIPNA – N-nitrosoethylisopropylamine
NDMA is classified as a probable human carcinogen (a substance that could cause cancer) on the basis of animal studies. It is present in some foods and in water supplies but is not expected to cause harm when ingested in very low levels.
The review of ranitidine medicines was initiated on 12 September 2019 at the request of the European Commission, under Article 31 of Directive 2001/83/EC, to evaluate the relevance of the findings, the potential root causes and their impact on the benefit-risk balance of medicinal products containing ranitidine.
Ranitidine belongs to a class of medicines known as H2 (histamine-2) blockers, which work by blocking histamine receptors in the stomach and reducing the production of stomach acid.
It is used to treat and prevent conditions caused by excess acid in the stomach such as heartburn and stomach ulcers. Ranitidine-containing medicines are authorised by national authorities and are available as tablets and injectable formulations.
The LC-MS method for the detection of NDMA in ranitidine drug substance and drug products published by FDA is available here.
This method should be validated by the user if the resulting data are used to support a required quality assessment of the API or drug product, or if the results are used in a regulatory submission.
Patients who have any questions about their current treatment can speak to their doctor or pharmacist. There are several other medicines used for the same conditions as ranitidine that could be used as an alternative.
It should be noted here that ranitidine is an over-the-counter (OTC) and prescription drug.
Sources: EMA, EC, FDA