Since the United States stopped using ranitidine, the European Union also announced a complete stop. According to the EMA document issued by the European drug administration, the EMA human drug committee (CHMP) recommended that all ranitidine drugs in the EU be discontinued because of the low level of NDMA impurities. According to animal studies, NDMA is classified as a possible human carcinogen (a substance that may cause cancer). It exists in some food and water supplies and will not cause harm if ingested at very low levels.
The existing safety data do not show that ranitidine increases the risk of cancer, and all possible risks are very low. However, NDMA has been found to exceed the acceptable level in several ranitidine drugs, and the source of this impurity is unknown. The document shows that many ranitidine drugs have not been listed in the EU for several months because the US National Department has recalled them as a preventive measure during the EMA review.
EMA also proposed the conditions for canceling the suspension of ranitidine, including requiring the company to submit more data. Since 2018, NDMA and similar compounds have been detected in a large number of drugs. EU regulators have taken measures to find possible sources of these impurities and set strict new requirements for manufacturers.
The NDMA storm escalated again – 30 days after the FDA asked all ranitidine products to be withdrawn from the market, the EU also asked for a complete ban on the use of ranitidine.
In the announcement, the FDA requires manufacturers to immediately withdraw all prescriptions and OTC ranitidine drugs from the market – this is the latest measure taken after the continuous investigation of the pollutant nitrosamine impurity (NDMA) in ranitidine drugs. The reason is that FDA has determined that if some ranitidine products are stored above room temperature, the impurities in them will increase with storage time and lead to consumers’ exposure to unacceptable impurity levels.
Since the FDA requires a comprehensive and immediate recall, there will be no new or old prescription or over-the-counter ranitidine products in the U.S. market.
According to incomplete statistics, many pharmaceutical companies such as Novartis, GSK, Sanofi, TIVA and Dr. Reddy have recalled ranitidine.
Many local drug administrations have taken action. A week ago, the official website of the FDA was updated, and the well-known generic drug company amneal voluntarily recalled nizatidine. The statement shows that since the potential level of N-nitrosodimethylamine (NDMA) impurity is higher than the level set by FDA, 15mg / ml nizatidine oral solution is voluntarily recalled nationwide.
According to biomedical media reports, the popular antacid nizatidine has been controversial since ranitidine was called nationwide last year for fear of similar NDMA pollution. In fact, drug regulatory authorities in the United States, Canada, South Korea, India and Italy have expressed their views on NDMA impurities.
In December 2019, the Chinese Pharmacopoeia Committee issued a public notice to revise the drug standards related to ranitidine and planned to add NDMA impurity control. In 2019, FDA found that ranitidine products contained NDMA impurities through a laboratory test. However, because the NDMA content in ranitidine drugs was low, the agency chose to continue the investigation.
In October of the same year, South Korean regulators said that after the US FDA announced on September 13 that a low amount of NDMA impurities were detected in ranitidine drugs, MFDs had found that the NDMA content in seven ranitidine raw materials exceeded the standard.
In the same month, Sanofi voluntarily recalled its ranitidine products from pharmacies in the United States and Canada, and withdrew the drug from several pharmacy retailer platforms including CVs, Walgreens and Rite Aid. In addition, GlaxoSmithKline and Novartis also recalled or stopped the production of ranitidine tablets. In addition, it is reported that at the request of Health Canada, companies selling ranitidine products in Canada have stopped any further distribution until evidence is provided that their NDMA content does not exceed an acceptable level.
Looking forward, the NDMA storm has appeared as early as 2018. In 2018, the long-term use of valsartan may lead to an increase in cancer risk, which led to the recall of various marketed valsartan drugs in 22 countries and regions around the world.
Ranitidine involves a number of enterprises. Statistics show that ranitidine has been on the market for 40 years and occupies the position of “blockbuster” in the world: as early as 1986, ranitidine became the drug with the largest sales performance in the world, the first blockbuster with sales of more than US $1 billion, and the first drug with cumulative sales of us $50 billion in the history of pharmacy.
According to public information, ranitidine was first developed by Allen & hanburys Co., Ltd., where John Bradshaw is located. The company is a subsidiary of GlaxoSmithKline. Ranitidine was first listed in the UK in October 1981. The original research company is GlaxoSmithKline. Ranitidine is a potent histamine H2 receptor antagonist, which can effectively inhibit the gastric acid secretion caused by histamine, pentagastrin and carbamoylcholine, and reduce the gastric acid and gastric enzyme activities.
It is found on the official website of the State Food and drug administration that there are 579 approval numbers with “ranitidine” as the keyword, which is enough to prove that many enterprises are involved. Since the United States stopped using ranitidine, the EU has also completely banned it. Alopah will continue to pay attention to the direction of relevant drugs.