Review ranitidine medicines following detection of NDMA

Action at EU level

At the request of the European Commission, EMA is to start a review of ranitidine medicines after tests showed that some of these products contained an impurity called N-nitrosodimethylamine (NDMA).

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.

EMA is evaluating the data to assess whether patients using ranitidine are at any risk from NDMA and will provide information about this as soon as it is available.

Ranitidine medicines are used widely to reduce the production of stomach acid in patients with conditions such as heartburn and stomach ulcers. They are available over-the-counter and on prescription.

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.

In 2018, NDMA and similar compounds known as nitrosamines were found in a number of blood pressure medicines known as ‘sartans’, leading to some recalls and to an EU review, which set strict new manufacturing requirements for these medicines.

EMA is currently working on guidance for avoiding nitrosamines in other classes of medicines. EMA will continue to cooperate with national authorities, EDQM and international partners to protect patients and ensure that effective measures are taken to prevent these impurities from being present in medicines.

Update September 26, 2019:

Based on initial results for nitrosamine impurity in ranitidine medicines in Europe, the CEP (Certificate of Suitability of Monographs of the European Pharmacopoeia concerning the active substance) of "SARACA LABORATORIES LIMITED IN 502 319 Gaddapotharam Village" ("Saraca"), R1-CEP 2004-057-Rev 07, was suspended by the EDQM (European Directorate for the Quality of Medicines) on September 19, 2019.

Update October 24, 2019:

Based on further results for nitrosamine impurity in ranitidine medicines in Europe, the CEPs (Certificate of Suitability of Monographs of the European Pharmacopoeia concerning the active substance) of "Union Quimico Farmaceutica, S.A. (Uquifa S.A.) ES 08008 Barcelona" ("Uquifa"), R1-CEP 1996-102-Rev 04 and "DR. REDDY'S LABORATORIES LIMITED IN 500 034 Hyderabad" ("Dr. Reddy's"), R1-CEP 2000-342-Rev 05 und R1-CEP 2002-075-Rev 05 were suspendeded by the EDQM (European Directorate for the Quality of Medicines) on October 11, 2019.

Update November 20, 2019:

Based on further results for nitrosamine impurity in ranitidine medicines in Europe, the CEPs (Certificate of Suitability of Monographs of the European Pharmacopoeia concerning the active substance) of "ORCHEV PHARMA PRIVATE LIMITED IN 360 002 Rajkot" („Orchev“), R1-CEP 2007-320-Rev 02 and "SOLARA ACTIVE PHARMA SCIENCES LIMITED IN 600 032 Chennai" ("Solara"), R1-CEP 2001-228-Rev 08 were suspendeded by the EDQM (European Directorate for the Quality of Medicines) on November 4 and 12, 2019. 

More about the medicine

Ranitidine belongs to a class of medicines known as H2 (histsamine-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.

More about the procedure

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.

The review will be carried out by the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which will adopt an opinion. The CHMP opinion will then be forwarded to the European Commission, which will issue a final legally binding decision applicable in all EU Member States.

Austria's situation

Update September 26, 2019:

NDMA is classified as a probable human carcinogen (a substance that could cause cancer) and the CEP Ranitidine hydrochloride by „Saraca“ was suspended. Therefore medicinal products and batches containing active substance from the manufacturer "Saraca" are recalled to pharmacy level as a precautionary measure.

Update October 24, 2019:

NDMA is classified as a probable human carcinogen (a substance that could cause cancer) and the CEPs Ranitidine hydrochloride by „Uquifa“ and „Dr. Reddy’s“ were suspended. Therefore medicinal products and batches containing active substance from the manufacturers „Uquifa“ or „Dr. Reddy’s“ are recalled to pharmacy level as a precautionary measure.

Update November 20, 2019:

NDMA is classified as a probable human carcinogen (a substance that could cause cancer) and the CEPs Ranitidine hydrochloride by „Orchev“ and „Solara“ were suspended. Therefore medicinal products and batches containing active substance from the manufacturers „Orchev“ or „Solara“ are recalled to pharmacy level as a precautionary measure.

Appropriate investigations have been initiated to identify possible further affected ranitidine medicine on the Austrian market. According to these results and benefit-risk assessment BASG has initiated measures by recalling affected batches.

Following medicinal products affected by nitrosamine impurity are recalled to pharmacy level as a precautionary measure in Austria (as of November 20, 2019):

1. Ulsal 150 mg - Filmtabletten
2. Ulsal 150 mg Brausetabletten
3. Ulsal 300 mg Brausetabletten
4. Ulsal 300 mg - Filmtabletten
5. Ulsal 50 mg/2 ml - Ampullen

Following medicinal products have already been recalled:

6. Ranitidin Stada 150 mg Filmtabletten

7. Ranitidin Stada 300 mg Filmtabletten

8. Ulsal 300 mg lösliche Tabletten

9. Ranitidin Accord 150 mg Filmtabletten

10. Ranitidin Accord 300 mg Filmtabletten

11. Zantac 150 mg - Brausetabletten

12. Zantac 300 mg - Brausetabletten

13. Ranitidin "ratiopharm" 150 mg - Filmtabletten

14. Ranitidin "ratiopharm" 300 mg - Filmtabletten

15. Ranitidin 1A Pharma 300 mg – Filmtabletten

16. Ranic Hexal 150 mg – Filmtabletten

17. Ranic Hexal 300 mg – Filmtabletten

Information of affected batch numbers and recalls please see "Market Surveillance". Please find enclosed all recalled batches as of November 20, 2019.

BASG has not received adverse reactions in connection with this issue.

BASG recommendations

Recommendations for healthcare professionals:

Please evaluate the use of an alternative medicinal product. In Austria there are no medicinal products containing ranitidine available at the moment.

Recommendations for patients:

There is no acute risk to public health. From today's perspective, there is no acute need to discard an opened package. If you have any further questions or feel insecure, please contact your physician. Your physician may prescribe an appropriate alternative if necessary.

Further information

EMA press releases (September 13, 2019):

EMA to review ranitidine medicines following detection of NDMA
EMA to provide guidance on avoiding nitrosamines in human medicines

Recalls by 1A Pharma GmbH, Hexal Pharma GmbH, Accord Healthcare B.V., GlaxoSmithKline Pharma GmbH, Teva B.V., STADA Arzneimittel GmbH and Gebro Pharma GmbH

Inquiries:

Dr. Christoph Baumgärtel, Tel.: +43 50555 - 36004

E-Mail:

Press inquiries:

Risk communication department, Tel.: +43 50555 - 25000

E-Mail:

Further inquiry note

am-qualitaetsmangel@basg.gv.at