Sanofi Recalls Three Hypertension Drugs in the UK and South Korea Due to Azide Impurity Concerns

Compiled & Translated by | Tom Li

According to a recent report by the *Korea Biomedical Review*, following a series of safety-related recalls of "sartan" drugs overseas, Sanofi is withdrawing three hypertension medications (Aprovel, CoAprovel, and Rovelito) from the South Korean market. All three drugs contain irbesartan, and regulatory authorities in multiple countries have detected that the medications may be contaminated with "azide" impurities. Additionally, the UK Medicines and Healthcare products Regulatory Agency (MHRA) announced this Monday the recall of certain batches of Sanofi's Aprovel and CoAprovel, as well as irbesartan film-coated tablets manufactured by Zentiva.

As early as late April, the detection of azide impurities in certain sartan medications raised concerns among regulatory authorities. These drugs are primarily used to treat hypertension and prevent heart attacks and strokes. In recall notices issued in May for medications such as irbesartan, losartan, and valsartan, Health Canada identified the azide impurities contaminating the products as mutagens, or chemicals capable of inducing changes in cellular DNA. The Canadian regulatory agency stated at the time that these mutations could increase the risk of cancer in patients taking the drugs.

《Korean Biomedical Review》 noted that Sanofi’s recall of contaminated sartan drugs in South Korea is a precautionary measure. Citing a Sanofi Korea official, the publication reported that the company is “addressing the presence of azide impurities in products manufactured after January of this year,” but “has not yet determined whether azide impurities are present in finished drug products produced prior to January 2021.” The official explained that because azide testing requires considerable time, Sanofi decided to proactively recall this batch of irbesartan. In the first half of this year, three irbesartan products generated combined revenue of 16.9 billion won ($14.7 million) in South Korea. Sanofi has agreed to cooperate with South Korea’s Ministry of Food and Drug Safety, which is currently investigating allegations that the medications contain carcinogenic impurities.

In late May this year, Health Canada advised the public that multiple pharmaceutical manufacturers are recalling large quantities of irbesartan, losartan, and valsartan drug products after test results indicated that azide impurities exceeded acceptable limits. The initial recall involved nine companies, including Teva, Sandoz, and Sun Pharma. In mid-June, Sanofi Canada added 12 lots of prescription irbesartan tablets marketed under the Avalide and Avapro brand names to the recall list.

Notably, this is not the first time sartan-class drugs have been recalled due to impurity issues. In 2018, the U.S. Food and Drug Administration (FDA) discovered that two carcinogenic nitrosamines, NDMA and NDEA, could be formed under certain manufacturing conditions for sartan drugs. In July 2018, following the detection of N-nitrosodimethylamine (NDMA) impurities in valsartan active pharmaceutical ingredients (API), the European Medicines Agency (EMA) recalled all medicinal products containing valsartan API from Zhejiang Huahai Pharmaceutical across EU member states. Subsequently, regulatory authorities in the United States, Japan, and China also initiated recalls. The FDA stated that following the global recall of sartan drugs in 2018, the U.S. valsartan supply faced shortages in early 2019.

Additionally, the common diabetes medication metformin has also been subject to a series of recalls over the past two years. Following the detection of the carcinogenic nitrosamine NDMA in samples, the FDA in May 2020 directed five pharmaceutical companies—Apotex, Actavis, Amneal, Lupin, and Marksans—to recall extended-release metformin products. Over the subsequent months, several other pharmaceutical manufacturers also added their products to the recall list.

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