Production-related contamination with N-nitrosodiethylamine (NDEA) in the active ingredient valsartan from the manufacturer "Mylan Laboratory Limited".

Safety warnings | messages in brief | 23/11/2018

"Valsartan/HCT ratiopharm 80 mg/12.5 mg Film-Coated Tablets" and "Valsartan/HCT ratiopharm 160 mg/25 mg Film-Coated Tablets" (active ingredient: valsartan) have been approved for the treatment of hypertension since August 16, 2013.

In the course of further sartan reviews (a specific class of blood pressure medication), an impurity with N-nitrosodiethylamine (NDEA) was detected in the valsartan active ingredient from the manufacturer "Mylan Laboratory Limited" in Hyderabad, India. NDEA and its related compound N-nitrosodimethylamine (NDMA) are classified as probable human carcinogens by the WHO International Agency for Research on Cancer and the EU.

As a result, the European Directorate for the Quality of Medicines (EDQM) has lifted the existing CEP (= Certificate of Suitability for Quality Control in the Manufacture of an Active Substance) of the active substance manufacturer "Mylan Laboratory Limited" in order to prevent the further use of the active substance valsartan manufactured there in the EU.

Therefore, an EU-wide recall and investigations concerning the extent of contamination of the affected proprietary medicinal products have been initiated.

An initial scientific assessment of the hazard potential is currently taking place at the European level. However, since such contamination cannot be tolerated on the basis of the precautionary principle, a recall of all potentially affected medicinal specialties is being carried out. Further investigations are currently underway throughout Europe and are being coordinated by the European Medicines Agency (EMA) and agreed jointly with the member states. The aim of the procedure is to take harmonized measures throughout Europe to protect patients.

Patients taking valsartan-containing medicinal products should never discontinue the medicinal products without consulting their attending physician, as the health risk of discontinuation is many times higher than the potential risk of contamination. According to current knowledge, there is no acute patient risk.

Measures at EU level Due to the identification of the impurity and the resulting withdrawal of the CEP by the EDQM and the publication of the EMA(https://www.ema.europa.eu/en/news/valsartan-mylan-laboratories-india-can-no-longer-be-used-eu-medicines-due-ndea-impurity), the marketing authorization holders have withdrawn the affected batches from the market.

Situation in Austria In Austria, the following proprietary medicinal products are affected:

Valsartan/HCT ratiopharm 80 mg/12.5 mg film-coated tablets.
Valsartan/HCT ratiopharm 160 mg/25 mg Film-Coated Tablets

Not all batches contain the active ingredient of the manufacturer "Mylan Laboratory Limited", which is why only the affected batches are being recalled for these two medicinal specialties.

The batches with active ingredient of the alternatively used manufacturer "Jubilant Generics Limited" in India are not affected by this contamination and therefore not subject of the current recall.

The marketing authorization holder "Teva B.V." is recalling the following batches from the market at pharmacy level in close coordination with the Federal Office for Safety in Health Care:

Name of the medicinal product	Registration number	Batch numbers	Marketing Authorization Holder
Valsartan/HCT ratiopharm 80 mg/ 12.5 mg Film-coated tablets	1-27777	0001586 0002626 0003214 0004745 0006204 6P601162 6P606334	Teva B.V.
Valsartan/HCT ratiopharm 160 mg/ 25 mg film-coated tablets	1-27778	0000355 0000356 0001612 0003613 6P606289 6P606320	Teva B.V.

Name of the medicinal product

Registration number

Batch

numbers

Marketing Authorization Holder

Valsartan/HCT ratiopharm 80 mg/ 12.5 mg Film-coated tablets

1-27777

0001586

0002626

0003214

0004745

0006204

6P601162

6P606334

Teva B.V.

Valsartan/HCT ratiopharm 160 mg/ 25 mg film-coated tablets

1-27778

0000355

0000356

0001612

0003613

6P606289

6P606320

Teva B.V.

BASG has not received any adverse event reports from Austria.

Recommendations of the BASG

Recommendations for Patients: Patients taking valsartan-containing proprietary medicinal products should never discontinue the proprietary medicinal products without consulting their treating physician, as the health risk of discontinuation is many times higher than the potential risk from contamination. According to current knowledge, there is no acute patient risk.

Further information: