Sir,Ranitidine is an H2 blocker popularly available as an over-the-counter (OTC) and prescription drug in India, with 1.3 billion population. In April 2020, the Food and Drug Administration (FDA) recalled all ranitidine products (injectable and oral) after the revelation of low-level N-nitrosodimethylamine (NDMA) presence.[1] N-Nitrosamines have marked as human carcinogens, associated with cancers of stomach, esophagus, nasopharynx, and bladder.[2] This drug evolution started with Glaxo holdings described in the flowchart until April 2020 [Figure 1]. The most popular OTC version of ranitidine, well-known as Zantac, used for relieving and preventing heartburn for decades. The prescription version is permitted to treat gastroesophageal reflux disease (GERD), gastric ulcers, and duodenal ulcers and prevent stress ulcers.[3] It inhibits both gastric acid secretion and basal gastric secretion, induced by secretagogues such as histamine and pentagastrin.
Figure 1
Inception and evolution of ranitidine from its first approval till date
Inception and evolution of ranitidine from its first approval till dateNew testing confirmed that a combination of heat and time might be the culprit for NDMA contamination. The longer the exposure, the higher the contamination level.[1] The drug is banned based on risk versus benefit ratio evaluated after postmarketing surveillance and adverse drug reaction (ADR) reporting system. The question now arises: Why the delay in reporting of contamination by the carcinogen NDMA? Was it a result of the crippled pharmacovigilance protocol? How do we strengthen the system to curb further damage?The Indian public is infamous for their tendency toward self-medication, stereotypically not supervised by physicians. Therefore, they miss the critical step of getting warned about ADR reporting, which implicates their lack of awareness and attitude toward safety issues associated with any medications. In the same line, the general population is unaware of the severe side effects of ranitidine, even after the intervention done by the FDA. Although each country has its procedure to ban the availability of the drug, the Indian market tends to continue selling until the stock persists due to authorized lack of supervision. Considering countries' concern with the use, availability, and distribution of the banned drug, it is an utmost challenge to make the masses aware of the same, especially in India's rural pockets.Consensus data reveal that GERD affects >10% of the Indian population attributable to dietary habits such as a plethora of spices and nonvegetarian food.[4] Antacids, histamine H2 receptor blockers (H2RAs), and proton pump inhibitors (PPI) are frequently used drugs for relieving symptoms. Popular heartburn drug, Zantac (ranitidine) is imposed to be withdrawn from the market, so the next alternatives will be cimetidine, famotidine, pantoprazole, rabeprazole, esomeprazole, lansoprazole, omeprazole, etc., for OTC antacid drugs. Cimetidine and famotidine had already encountered an issue with the shortage of raw materials in Canada and other countries. Whereas the PPI class of drugs directly blocks the stomach's acid secretion, which may increase the risk of gastric infection or diminish the absorption of magnesium and vitamin B12. However, the statement advised, “Before switching to another agent, review if patients still require treatment or could be stepped down to an antacid or alginate.”[5]Hence, finally, is this recall an awakening for us to support the ban of OTC drugs, which has been under the line of fire for safeguarding the Indian community since decades?
Figure 1