Ranitidine Banned again after being Removed from the U.S. Market: Will a Chain Reaction be in China?

The Committee for Medicinal Products for Human Use (CHMP) under the EMA has recommended the suspension of all ranitidine drugs in the EU on Apr. 30.

This is another notification issued by a foreign organization on the suspension of ranitidine following the U.S. FDA’s requirement on Apr. 1 that pharmaceutical enterprises shall immediately remove all ranitidine drugs from the market.

Ranitidine has many indications overseas, including the gastrointestinal tract and esophagitis treatment, etc.

Source: Medicine Helper APP

Wherein, the quadruple therapy used overseas for Helicobacter pylori infection of the gastrointestinal tract includes ranitidine, metronidazole, basic bismuth subsalicylate, and tetracycline hydrochloride, unlike that in China.

The method used in China is selecting the antimicrobial agents (such as amoxicillin, tetracycline, and furazolidone) that are known to have low drug resistance rates in combination with bismuth (i.e., bismuth-containing quadruple therapy) and increasing the dose of metronidazole. From this aspect alone, for patients with Helicobacter pylori infection of the same number in China and overseas, the demand for ranitidine overseas will be far higher than that in China. Furthermore, there is also a certain number of off-label uses.

Uses outside the FDA Package Insert (Adults)

Source:  Medicine Helper APP

The  reason for the suspension given by the CHMP is the same as that of the FDA: the  potential carcinogenicity of the impurity NDMA in ranitidine. The valsartan  event caused due to NMDA aroused wide concern last year, and API enterprises  including Huahai Pharmaceutical, etc. were affected.

According  to queries on the website of the National Medical Products Administration of  China (NMPA), ranitidine, an important gastrointestinal drug, has 579  formulations in China, including injection, tablet, effervescent tablet and  capsule dosage forms.

And  there are 16 related API enterprises in China.

Source:  NMPA website

Based  on previous experience, there is a pattern that many pharmaceutical products are  banned first abroad and then in China. For example, Analgin was officially  banned by the U.S. FDA and removed from the U.S. market in 1977, and the  clinical applications of many dosage forms were halted. Thereafter, about 30  countries including Japan, Australia, and Iran, etc. have explicitly banned or  restricted the use of Analgin in succession, and China announced the  cancellation of Analgin injection and other Analgin varieties on Mar. 17,  2020.

Whether  ranitidine will also go on such a path is unknown, however, there is something  different: NDMA is an impurity instead of a substance necessarily present in  ranitidine. Whether the impurity can be eliminated by optimizing the process is  a problem for enterprises. However, the removal of this impurity is very  difficult from the current view, otherwise, foreign enterprises would not have  easily agreed to the banning requirement.

And,  as old pharmaceutical bio based products, ranitidine’s “dividend period” should also be  approaching the end. It is possible that related enterprises will take the  initiative to remove ranitidine products from the market considering the decline  in profits and the risks. Furthermore, the comparison between any pharmaceutical  product’s therapeutic effects and risks is related to whether it is  irreplaceable. The removal of ranitidine suggests that other drugs can  substitute it, such as omeprazole. If there were no other substitutes,  ranitidine would not have been banned even if it had carcinogenic risks. A chain  reaction may be caused in China within a period. Therefore, related enterprises  should be prepared now, to avoid the sudden cancellation similar to that of  Analgin.

References:

• Fifth  Chinese National Consensus Report on the Management of Helicobacter pylori  Infection

• Medicine Helper APP

• NMPA website

  https://www.ema.europa.eu/en/news/suspension-ranitidine-medicines-eu

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