Health Canada has released the results of its testing of sartan drugs in Canada. Health Canada tested samples of certain sartan drugs (valsartan, candesartan, irbesartan, losartan, and olmesartan), which represent numerous products, as part of its ongoing collaborative work to address impurities found in some sartan drugs in Canada and internationally.
Several valsartan products have been recalled in Canada since this summer, after the impurities N‑nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) were found in the active pharmaceutical ingredient. Both NDEA and NDMA are classified as probable human carcinogens, which means that long-term exposure could increase the risk of cancer. Health Canada has previously communicated cancer risk estimates for NDMA based on the levels detected in certain recalled valsartan products.
Health Canada tested 48 samples representing 43 different products and did not identify any new safety concerns. Of the 48 samples, six valsartan samples representing four products were found to contain levels of impurities that were, on average, higher than what is considered to be reasonably safe. All four of the products have already been recalled from the Canadian market.
While Health Canada’s assessment initially focused on valsartan, the Department expanded its scope in consideration that NDMA and NDEA impurities could potentially be present in certain other sartans. The five sartan drugs Health Canada is focused on (valsartan, candesartan, irbesartan, losartan, and olmesartan) all share a similar chemical structure. Based on information to date, sartans that do not have this chemical structure are not thought to be at risk for the formation of NDMA, NDEA or other similar impurities.
Health Canada continues to hold manufacturers responsible for the safety and effectiveness of drugs sold on the Canadian market.
The Department has requested and assessed information from companies and—based on its own analysis and information shared by international regulatory partners—believes that the impurities found in certain sartans may be linked to certain manufacturing processes and practices.
Health Canada has asked companies marketing the five sartans in Canada to test their products for the NDMA and NDEA impurities. The testing applies to product currently available in Canada and to any new inventory before its release. To support this initiative, Health Canada is also publishing a laboratory test method to provide an option for regulators and industry to detect NDMA and NDEA impurities. Health Canada will continue to assess new developments to determine whether additional testing is necessary.
Health Canada actions taken to date include:
- Requesting that companies recall products found to contain NDMA and NDEA that exceeded acceptable levels, and monitoring the effectiveness of those recalls;
- Requesting and assessing information from companies on the manufacturing processes for the five sartan drugs to identify potential causes of the impurities and mitigation measures;
- Stopping the import of active pharmaceutical ingredients—and requiring the testing of inventory that had already been imported—from the Chuannan site of Zhejiang Huahai Pharmaceuticals in China, because of general concerns with their manufacturing practices and procedures;
- Testing samples of the five sartans for NDMA and NDEA impurities; and
- Requesting companies to test the five sartans for the NDMA and NDEA impurities.
Please refer to the following website in Health Canada for details:
http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/../68620a-eng.php
In Hong Kong, there are 252 registered pharmaceutical products containing valsartan (83 products), candesartan (19 products), irbesartan (64 products), losartan (69 products) and olmesartan (17 products). All products are prescription-only medicines.
Regarding impurities in valsartan, a public announcement was issued on 6 Jul 2018, and letters to inform local healthcare professionals were issued by the Department of Health (DH) on 6 Jul 2018, 9 Jul 2018, 25 Jul 2018 and 3 Aug 2018. Related news for the detection of impurities in sartan-containing products was also previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since 6 Jul 2018, with the latest update posted on 19 Dec 2018.
In brief, there are four manufacturers, namely Zhejiang Huahai, Zhejiang Tianyu and Zhuhai Rundu in China and Hetero Labs Limited in India, reported to have detection of trace amounts of NDMA in the valsartan Active Pharmaceutical Ingredient (API) by various overseas drug regulatory authorities. The DH contacted the certificate holders of all registered valsartan products to follow up on the local impact regarding valsartan API produced by the above mentioned manufacturers.
For API produced by Zhejiang Huahai, there are 5 affected products (HK-61786, HK-61787, HK-61784, HK-61785 and HK-60794) marketed in Hong Kong. The DH instructed the certificate holders to recall all the products from the market as a precautionary measure on 6 Jul 2018, and the DH noted that all the recalls have been completed.
For API produced by Zhejiang Tianyu, amongst the registered pharmaceutical products containing valsartan, there is only one product namely Retoni Tablets 80mg (HK-65604) registered by Swiss Pharmaceutical Co Limited (Swiss Pharmaceutical) which has used API produced by Zhejiang Tianyu and is available in the local market. As confirmed with Swiss Pharmaceutical, the API was tested by the Taiwan Food and Drug Administration (TFDA) and the company has not received any notice from the TFDA for NDMA contamination. The DH collected samples of Retoni tablets for analysis and no NDMA was detected.
For API produced by Zhuhai Rundu and Hetero Labs Limited, the certificate holders confirmed that the valsartan products available in local market are not manufactured using API produced by Zhuhai Rundu or Hetero Labs Limited.
Regarding the announcements issued by various overseas drug regulatory authorities on the detection of the second impurity of NDEA in the valsartan API produced by Zhejiang Huahai, there should be no local impact as all valsartan products manufactured using API produced by Zhejiang Huahai have been recalled from the market.
Regarding the announcements issued by various overseas drug regulatory authorities on the detection of NDEA in the valsartan API produced by Mylan Laboratories Limited in India, the certificate holders confirmed that the valsartan products available in local market are not manufactured using API produced by this company.
Regarding the European Medicines Agency’s (EMA) and the US Food and Drug Administration’s (FDA) announcement on the detection of NDEA in the losartan API produced by Hetero Labs Limited, the FDA’s announcement on NDEA in the losartan API produced by Zhejiang Huahai, and the announcements issued by EMA, FDA and TFDA on NDEA in the irbesartan API produced by Aurobindo Pharma in India, the DH has contacted the certificate holders of all registered candesartan, irbesartan, losartan and olmesartan products and will continue to follow up on the impact of NDEA impurities on the products available in the local market. On 20 Dec 2018, the DH endorsed Actavis Hong Kong Limited to recall one batch (batch number: 058818) of Irbesartan HCT Actavis Tablets 150/12.5mg (HK-63378) from the market as a precautionary measure because an impurity was detected in one of the raw materials of this batch of product, a public announcement was issued on 20 Dec 2018. The DH will closely monitor the recall.
So far, the DH has received 16 cases of adverse drug reaction related to valsartan, candesartan, irbesartan, losartan and olmesartan. None of them is concluded to be related to the presence of NDMA and/or NDEA. The DH will keep vigilant on any further updates on the matter issued by overseas regulatory authorities.
Patients who are taking the above products should not stop taking the medicines, but should seek advice from their healthcare professionals as soon as possible for proper arrangement.
Ends/Friday, December 21, 2018
Issued at HKT 17:30
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