In July, thousands of batches of valsartan were recalled after a possible carcinogen – a substance that could cause cancer – was discovered. Since then, the number of valsartan products being recalled and has grown, while products containing two other ‘sartans’ used to treat high blood pressure – losartan (losartan potassium hctz) and irbesartan – have also been recalled by the FDA.
This article was first published on 30 November 2018.
Article last updated: 08 March 2019
The investigation into the contamination of angiotensin II receptor blockers (ARBs), such as valsartan, losartan, and irbesartan, is ongoing. We will continue updating this page as new information is released by the Food and Drug Administration (FDA) and European Medicines Agency (EMA).
Important: If you are currently taking valsartan, losartan, irbesartan, or any other ARB, please continue taking it as prescribed unless told otherwise by your doctor or pharmacist.
Scroll down to see our timeline of events and key announcements made by the FDA and EMA
Lists of Blood Pressure Drugs Being Recalled
Currently, batches of valsartan, irbesartan, and losartan are being recalled. To find out which specific lots are subject to the recall, follow these links:
- List of valsartan products under recall
- List of irbesartan products under recall
- List of losartan products under recall
These lists strictly apply to the US market. You can find recall information for other countries by following these links:
For other countries, head to the website of the national regulatory body.
Why Are ARBs Such as Valsartan Being Recalled?
The first recall of valsartan was issued in July, after a substance called N-nitrosodimethylamine (NDMA) was found in valsartan produced by Chinese firm, Zhejiang Huahai Pharmaceuticals (Huahai).
NDMA is listed as a probable carcinogen by the World Health Organization (WHO). There is “conclusive evidence that NDMA is a potent carcinogen in experimental animals when ingested through drinking water,” according to the organization.
The valsartan manufactured by Huahai is used as the active pharmaceutical ingredient (API) in medications produced around the world designed to treat high blood pressure (hypertension).
Huahai voluntarily informed the EMA of the contamination, leading to recalls in 23 countries.
In the US, the FDA soon followed suit and issued a recall for products from Teva Pharmaceuticals, Solco Healthcare, and Major Pharmaceuticals that contained valsartan sourced from Huahai.
For more information about the initial recall, read the post we published at the time:
What Has Happened Since the First Valsartan Recall?
Since then, valsartan produced by Huahai has been placed on the FDA’s Import Alert, which prevents valsartan produced in the company’s Chuannan factory from legally entering the US.
The FDA and EMA also discovered traces of N-Nitrosodiethylamine (NDEA) in valsartan produced by Huahai which, like NDMA, is listed as a probable carcinogen.
The FDA says the chemicals are “formed from a specific sequence of manufacturing steps and chemical reactions.”
NDMA was discovered in valsartan produced by another manufacturer, Hetero Labs, in September. Products made by Camber Pharmaceuticals using valsartan sourced from the Indian company were subsequently recalled.
At the end of October, the first non-valsartan product was added to the recall: irbesartan. Irbesartan produced by Indian company, Aurobindo Pharma Limited, and used by ScieGen Pharmaceuticals in products labeled as Westminster Pharmaceuticals and GSMS Inc., was found to contain traces of NDEA.
In November, a third ARB was recalled: losartan. Only one lot was recalled – Losartan Potassium Hydrochlorothiazide Tablets by Sandoz Inc. The losartan API, produced by the first company embroiled in the recall – Zhejiang Huahai Pharmaceuticals – was also found to contain NDEA.
NDEA was then found in valsartan produced by another company, Mylan Pharmaceuticals. The US-based company used valsartan produced in India by its manufacturing division, Mylan Laboratories Limited. Teva, one of the three companies to recall valsartan sourced from Huahai in the first place, subsequently issued a recall of valsartan product that used Mylan-produced APIs.
What About in Europe?
Given that the EMA and FDA are working closely, events have shaped up similarly in Europe. Soon after the initial recall was made, regulators found NDMA in valsartan produced by another Chinese firm, Zhejiang Tianyu Pharmaceutical. The FDA confirmed the contaminated valsartan was not supplied to the US market.
Both Tianya and Huahai have been banned from supplying valsartan to the EU market. Aurobindo and Mylan have been banned from supplying irbesartan and valsartan respectively.
Regarding losartan, the EMA found low traces of NDEA in losartan produced by Hetero Labs, but no further action has yet been taken.
The EMA and FDA’s investigation into the manufacturing of ingredients used in ARB medications is ongoing. We will continue to update this page as announcements are made. Below you can find a timeline of events, as well as links to the relevant announcements.
Up-to-Date Timeline of Products Being Recalled and Other Important Information (FDA & EMA)
We regularly update this article to ensure it is kept up-to-date.
Key FDA Announcements Regarding the Valsartan Recall
- 13 July 2018 – The first recall of valsartan products is issued by the FDA after NDMA was found in valsartan API produced by Zhejiang Huahai Pharmaceuticals. FDA Announcement.
- 08 August 2018 – Camber Pharmaceuticals recalls valsartan products with valsartan API produced by Hetero Labs, after NDMA was found. FDA Announcement.
- 28 September 2018 – FDA places Zhejiang Huahai Pharmaceuticals on import alert
- 26 October 2018 – Aurobindo Pharma issue a recall 22 batches of irbesartan, supplied to ScieGen Pharmaceuticals for the US market, after NDEA was found. FDA Announcement.
- 30 October 2018 – ScieGen issue a recall themselves for products using irbesartan API produced by Aurobindo. The products produced by ScieGen were labeled as Westminster Pharmaceuticals and Golden State Medical Supply, Inc [GSMS]. FDA Announcement.
- 08 November 2018 – Sandoz Inc. issue a recall of one lot of losartan potassium hydrochlorothiazide (hctz), using losartan API manufactured by Zhejiang Huahai Pharmaceutical, after NDEA was found. FDA Announcement.
- 20 November 2018 – Mylan Pharmaceuticals recalls products containing valsartan API manufactured by the company’s production division, Mylan Laboratories Limited, after NDEA was found. FDA Announcement.
- 27 November 2018 – Teva Pharmaceuticals issues a recall of valsartan products containing valsartan API produced by Mylan. FDA Announcement.
- 06 December 2018 - Mylan Pharmaceuticals expands its nationwide recall of valsartan. The additional 104 lots being recalled include 26 lots of Amlodipine and Valsartan Tablets, 51 lots of Valsartan Tablets, and 27 lots of Valsartan and Hydrochlorothiazide (HCTZ) Tablets. FDA Announcement
- 11 December 2018 – The FDA publicly releases a scathing warning letter it issued to Zhejiang Huahai Pharmaceuticals in late November. The letter criticizes Huahai for not fully considering the implications of changes to the production process of Valsartan in 2011, which included the use if a solvent (the name of which is redacted to protect trade secrets) believed to be linked to the presence of NDMA. The FDA also writes that Huahai failed to investigate customer complaints sufficiently and reissued returned lots of Valsartan to the US market. FDA Announcement
- 19 December 2018 – The FDA publishes interim acceptable intake levels of impurities discovered in valsartan, irbesartan, and losartan-containing products. The FDA states that products above these limits should be subject to a voluntary manufacturer recall. The agency also publishes methods for manufacturers to detect impurities. FDA Announcement
- 20 December 2018 to 03 January 2019 – Torrent Pharmaceuticals recalls two lots of losartan potassium, which is subsequently expanded to 10 lots. Aurobindo Pharma recalls two lots of valsartan tablets, 26 lots of amlodipine and valsartan combination tablets, and 52 lots of valsartan and hydrochlorothiazide (HCTZ) combination tablets. All recalls are due to the presence of NDEA. FDA Announcements:
- Torrent Pharmaceuticals’ losartan recall
- Aurobindo Pharma’s recall of valsartan-containing products
- Expansion of Torrent Pharmaceuticals’ losartan recall
- 18 January 2019 to 25 January 2019 – Solco Healthcare recalls seven lots of irbesartan-containing products, Torrent Pharmaceuticals’ expands its losartan recall to include an additional six lots (16 in total), and Macleods Pharmaceuticals recalls one lot of losartan potassium/hydrochlorothiazide. All recalls are due to the presence of NDEA.
- Solco Healthcare’s recall of irbesartan-containing products
- Expansion of Torrent Pharmaceuticals’ losartan recall
- Macleods Pharmaceuticals’ recall of losartan potassium/hydrochlorothiazide
- 28 February 2019 – The FDA publishes interim acceptable intake levels of a third impurity, N-Nitroso-N-methyl-4-aminobutyric acid (NMBA). The levels are the same as for NDMA. FDA Announcement
Camber Pharmaceuticals, Inc. recalls 87 lots of products containing losartan manufactured by Hetero Labs Limited due to the presence of NMDA. FDA Announcement
- 01 March 2019 – Aurobindo Pharma expands its recall of products containing valsartan to include an additional 38 lots, due to the presence of NDEA. Torrent Pharmaceuticals further expands its voluntary recall to include 114 additional lots of losartan potassium and losartan potassium/hydrochlorothiazide combination tablets, due the presence of NMBA. The FDA also releases a press release regarding the discovery of the third impurity, NMBA.
- Aurobindo Pharma expands valsartan recall
- Torrent Pharmaceuticals expands recall of losartan
- FDA press release regarding the presence of a third impurity, NMBA
Key EMA Announcements Regarding the Valsartan Recall
- 07 July 2018 – The first recall of valsartan products is issued by the EMA after NDMA was found in valsartan API produced by Zhejiang Huahai Pharmaceuticals. EMA Announcement.
- 20 August 2018 – A second Chinese manufacturer, Zhejiang Tianyu, is banned from supplying valsartan to the EU market after NDMA is detected. Huahai had already had its authorization to supply valsartan revoked. EMA Announcement
- 13 September 2018 – A second substance considered a probable carcinogen, NDEA, is detected in valsartan produced by Huahai. EMA Announcement.
- 21 September 2018 – The EMA expands the scope of its review to include other sartans, after small amounts of NDEA is detected in losartan produced by Indian company Hetero Labs. EMA Announcement.
- 28 September 2018 – An inspection by EU authorities and the EDQM finds that “Zhejiang Huahai did not comply with good manufacturing practice (GMP) in the manufacture of valsartan at the Chuannan site” and issues a statement of non-compliance for the manufacture of valsartan. EMA Announcement.
- 15 October 2018 – Huahai is put under increased supervision by EU authorities. Aurobindo Pharma is banned from supplying irbesartan to the EU after low levels of NDEA is detected in irbesartan API manufactured by the Indian company. EMA Announcement.
- 19 November 2018 – NDEA is detected in batches of valsartan produced by Indian company Mylan Laboratories Limited. Mylan is banned from supplying valsartan to the EU market and a recall is issued. EMA Announcement.
- 01 February 2019 – The EMA announces temporary limits for the amount of NDEA and NDMA that can be found in sartan medicines. After a two year transition period, companies will have to demonstrate that their sartan products have no quantifiable levels of these impurities before they can be used in the EU. EMA Announcement.
Take a look at some of the other posts on the MyTherapy blog:
