Health Canada is advising Canadians that multiple lots of losartan-containing drugs are being voluntarily recalled by Teva Canada, Apotex Inc., Pharmascience Inc., and Pro Doc Limitée because of the potential for a nitrosamine impurity, N-nitroso-N-methyl-4-aminobutyric acid (NMBA). NMBA is potentially a human carcinogen, which means that long-term exposure could increase the potential risk of cancer.
Teva Canada is voluntarily recalling two lots of combination losartan/hydrochlorothiazide (HCTZ) tablets after testing of one lot identified levels of NMBA above what is considered reasonably safe if the drug were taken over a lifetime. Apotex Inc., Pharmascience Inc., and Pro Doc Limitée are voluntarily recalling multiple lots of losartan-containing products as a precaution. For details of the affected products, please refer to the website in Health Canada.
The losartan active pharmaceutical ingredient (API) in all of the recalled products is manufactured by Hetero Labs Ltd. Unit 1, in India. These recalls represent all lots of drugs distributed in Canada that contain losartan API manufactured at Hetero Labs Ltd. Unit 1.
Please refer to the following website in Health Canada for details:
http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/../69272a-eng.php
In Hong Kong, the following pharmaceutical products are registered by Hind Wing Co Ltd (Hind Wing):
- Apo-Losartan Tablets 50mg (HK-61932), which is currently a registered product. As confirmed with Hing Wing, one affected batch (NK1253) has been imported into Hong Kong.
- Apo-Losartan Tablets 100mg (HK-61933), which is currently a registered product. Three affected batches (NG2092, NH5932 and NL1460) have been imported.
- Apo-Losartan/HCTZ Tablets 100mg/25mg (HK-62634), which was previously registered but the registration has expired. One affected batch (NZ8845) has been imported.
- Apo-Losartan/HCTZ Tablets 50mg/12.5mg (HK-62635), which was previously registered but the registration has expired. Two affected batches (NZ8848 and NL1441) have been imported.
All products are prescription-only medicines. Hind Wing has initiated recall of the affected batches and the Department of Health (DH) will closely monitor the recall.
The other products recalled in Canada are not registered pharmaceutical products in Hong Kong.
Currently in Hong Kong, there are 248 registered pharmaceutical products containing valsartan (83 products), candesartan (19 products), irbesartan (62 products), losartan (67 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 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 8 Mar 2019.
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 N-nitrosodimethylamine (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 N-nitrosodiethylamine (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 announcements issued by various overseas drug regulatory authorities on the detection of NDEA in the losartan API produced by Hetero Labs Limited, Zhejiang Huahai and IPCA in India, and the announcements on NDEA in the irbesartan API produced by Aurobindo Pharma in India and Zhejiang Huahai, 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 noted that the recall has been completed.
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 impurities such as NDMA, NDEA and/or N-nitroso-N-methyl-4-aminobutyric acid (NMBA). The DH will keep vigilant on any safety updates on detection of impurities in sartan-containing products 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/Monday, Mar 11, 2019
Issued at HKT 17:00
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