Therapeutic Goods Administration (TGA) announces that it is investigating the potential contamination of ‘sartan’ blood pressure medicines. These medicines have names that end in ‘sartan’, including valsartan, irbesartan, candesartan, losartan and olmesartan.
Internationally, a number of these medicines have been identified as having unacceptable levels of impurities - specifically N-nitroso compounds. The issue was first identified in Jul 2018 in valsartan-containing medicines that were manufactured using an active pharmaceutical ingredient (API) sourced from a Chinese API manufacturer. These products were recalled in some overseas countries, but TGA investigations found that no valsartan products being supplied in Australia used API from this manufacturer. Later, it was identified that other sartan APIs from the Chinese API manufacturer, and also sartan APIs sourced from other manufacturers, were also affected. Some products supplied in Australia used APIs from these sources. As of 30 Jan 2019, four products supplied in Australia have been recalled as a result of this safety concern.
N-nitroso compounds are commonly found in low levels in a variety of foods, particularly smoked and cured meats, as well as in some drinking water and in air pollution. Long-term exposure, over years, can increase an individual’s risk of developing cancer. The additional risk posed by N-nitroso compounds in sartan medicines, at the concentrations identified to date, is considered to be very low. However, such contamination is considered unacceptable for a medicine. The actual health risks depend on dose and will vary from person to person.
Patients who take ‘sartan’ medicines - even if they are affected by this safety issue - should not stop their treatment without first consulting a doctor or pharmacist. As the risks are associated with long term exposure, there is no immediate health risk. Consumers should be aware that not all ‘sartan’ medications are affected. It is also important to note that even when there is a problem with a product, not all batches may be affected. Suddenly stopping blood pressure medicines can pose a greater and more immediate risk to health than potential contamination with N-nitroso compounds.
The TGA is working with international regulators and medicine sponsors to investigate and resolve this issue. The TGA is also undertaking testing of Australian ‘sartan’ medications to determine if any further batches are affected. The effect of this issue on medicine shortages is also being closely monitored. The TGA will publish updated information as it becomes available. In the meantime, if consumers have any questions or concerns about this issue, they should speak to their health professional. Information for health professionals is provided in the individual recall notices for affected products.
Please refer to the following website in TGA for details:
http://www.tga.gov.au/alert/sartan-blood-pressure-medicines
Currently in Hong Kong, there are 250 registered pharmaceutical products containing valsartan (83 products), candesartan (19 products), irbesartan (62 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 16 Feb 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, 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 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/Tuesday, Feb 26, 2019
Issued at HKT 17:00
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