Sartan drugs have been recalled on a large scale due to potential carcinogens!

Health Canada reminds patients that the recall of some products may affect the supply of medicines.
Patients should be treated according to the doctor's advice.
Unless the doctor recommends stopping the medicine, the patient should continue to take the medicine
.

According to the Korean Biomedical Review, Sanofi is currently recalling some batches of three antihypertensive drugs (Aprovel, CoAprovel and Rovelito tablets) sold in the Korean market because these three contain sartans.
The ingredients of the drug may contain azide-based impurities, which is a potential carcinogen
.

Sanofi said that because drug regulatory agencies in other countries raised the issue of azide-based impurities in drugs and recalled related products, the recall in South Korea is to prevent any safety issues
.

Azide compounds are commonly used chemical raw materials in the pharmaceutical industry
.

01 Many national drug regulatory agencies require recalls

On April 29, the European Council for the Quality and Health of Medicines (EDQM) issued an announcement stating that the azide impurity in sartan-like active substances (API) was found to be mutagenic in a recent investigation, so the relevant CEP holders were contacted The person (the API manufacturer or its agent) orders it to treat the drugs involved in accordance with the requirements to ensure that the azide impurity content in the drugs is below the toxicity concern threshold
.

EDQM also stated that if it is tested that the content of azide impurity in sartan drugs currently on the market is higher than the toxicity concern threshold, it may take measures such as stopping sales of these API manufacturers or agents
.

Immediately afterwards, Health Canada issued a notice to Canadian citizens in May of this year.
During the testing process, it was found that the azide impurities in some batches of irbesartan, losartan and valsartan medicines exceeded the acceptable range.
Some manufacturers are required to recall their products
.

Health Canada also stated that not all of these companies’ irbesartan, losartan and valsartan are affected by this problem, but the recall of some products may affect the supply of medicines, and patients should follow the doctor’s advice.
Treatment
.

Canada is currently testing the impurity content of the recalled drugs and monitoring the effectiveness of the recall
.

In response to the requirements of Health Canada, Sanofi Canada has recalled 12 batches of prescription irbesartan tablets
.

In addition, the British Medicines and Health Products Regulatory Agency also announced on Monday that it requested the recall of certain batches of Sanofi’s Aprovel, CoAprovel and film-coated irbesartan tablets produced by Zentiva
.

In addition to the recall of certain batches of drugs by the European Council for Quality and Health Care of Medicines, Health Canada, and the United Kingdom Medicines and Health Products Regulatory Agency, the US Department of Commerce has also paid attention to the issue of azido-based impurities
.

It is also based on the requirements of these national drug quality regulatory agencies that Sanofi has also recalled some batches of Aprovel, CoAprovel and Rovelito tablet products in South Korea
.
Sanofi stated that it is dealing with the problem of azide-based impurities in products produced after January 2021.
It has not yet determined whether there are azide-based impurities in products produced before January 2021.
The specific test results are still unclear.
It will take a while to come out
.
According to UBIST data, the sales of these three products in South Korea in the first half of the year were 16.
9 billion won (14.
7 million U.
S.
dollars)
.
The recall may affect the sales of these three products in the second half of the year
.

Currently, the Korean Ministry of Food and Drug Safety is investigating the matter
.
The Ministry of Health of South Korea stated that there will be no major safety issues in the recall of these three products
.
An official from the South Korean Ministry of Health said: "If there is a safety issue, we will take additional measures
.
But the latest situation is not the case, so we do not recommend that patients change their medicines without doctor's advice
.
"

02 Sartan drugs recalled more than once

This recall is not the first time that sartan drugs have appeared
.

In January 2019, the French National Agency for the Safety of Medicines and Health Products issued an announcement requesting the nationwide recall of irbesartan antihypertensive drugs because such drugs contain possible N-nitrosodimethylamine (NDMA) and N- Nitrosodiethylamine (NDEA) two possible carcinogenic impurities, and the content is higher than the acceptable range
.
In 2018, the French medical research institute detected NDMA and NDEA impurities in valsartan, and immediately requested 11 related pharmaceutical companies to recall the drug
.
In the same year, the U.
S.
Food and Drug Administration (FDA) also discovered that these two impurities exist in sartan drugs in some cases
.
In July 2018, the European Medicines Agency (EMA) recalled all medicines containing Huahai Pharmaceutical's valsartan raw materials in EU member states due to the detection of NDMA impurities in valsartan raw materials, followed by the United States, Japan and domestic regulatory authorities Recalls have also been initiated one after another
.

In addition to the original manufacturer Sanofi, domestic manufacturers of sartan drugs, there are also many companies that carry out generic drugs.
Hisun, Huahai, Zhengda Tianqing, Dongyang Pharmaceutical, Xinlitai, etc.
all have such products, and Sartan products are included in the "4+7" volume procurement and the subsequent second, third, and fourth batches of national centralized procurement
.

In Medicare drug directory, Valsartan belongs to Group A health insurance; about 16 remaining drugs are losartan health insurance B
.

Whether the sartan drugs marketed in China may contain potentially carcinogenic azide-based impurities and carry out follow-up recalls, no corresponding measures have been observed
.

In October 2020, the State Food and Drug Administration issued the "Measures for the Administration of Drug Recalls (Draft for Comment)" (hereinafter referred to as the "Measures")
.
The Measures pointed out that for drugs that have quality problems or other safety hazards due to research and development, production, sales, storage and transportation, labeling, etc.
, the drug marketing authorization holder must withdraw the drug that has been marketed with defects in accordance with the prescribed procedures, and Take corresponding measures to control and eliminate defects
.
The State Food and Drug Administration is responsible for guiding the supervision and management of drug recalls nationwide in this process
.

The Measures clarify that “the holders of drug marketing licenses are obliged to recall defective drugs, and they should establish and improve a drug recall system, collect relevant information on drug safety, investigate and evaluate potentially defective drugs, and recall defective drugs in a timely manner
.
"

It also stipulates that “if drug recalls are only implemented outside of China and do not involve domestic drug varieties and batches, the enterprise legal person in China designated by the drug marketing authorization holder shall report the relevant information to the location within 5 working days of the start of the overseas recall.
Provinces, autonomous regions, and municipalities directly under the Central Government for drug supervision and administration
.
"

Regarding the potential safety risks of foreign sartan-containing drugs, what impact will it have on similar drugs in China? According to industry insiders, under normal circumstances, if the drugs have known or potential safety issues, the regulatory authorities may Let medical institutions take corresponding measures to suspend the use of these products, and then dispose of these products after investigation
.
For companies, after the establishment of the MAH system, if the company's pharmacovigilance system and drug traceability system are in place, they will actively investigate and carry out corresponding work on products that do exist or have potential safety issues
.

The following is the list of recalls announced by Health Canada: