In light of ongoing investigations by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) over the detection of nitrosamine impurities in ranitidine, an over-the-counter (OTC) and prescription drug used to decrease the amount of acid in the stomach, several pharmaceutical companies (GlaxoSmithKline, Novartis, and Apotex) have issued voluntary recalls of ranitidine products and several retailers (Walmart, CVS Pharmacy) have suspended sales of ranitidine products as outlined below. These actions are being taken due to the actual or potential detection (depending on the product) of N-nitrosodimethylamine (NDMA), a probable human carcinogen.

Apotex is voluntarily, on a precautionary basis, recalling ranitidine tablets 75 mg and 150 mg (all pack sizes and formats) to the retail level nationwide in the US due to possible NDMA impurities. The affected ranitidine hydrochloride tablets were distributed nationwide in the US to warehousing chains. To date (as of September 27, 2019), Apotex says it has not received any reports of adverse events related to use of the product.

Sandoz, the generics arm of Novartis, is voluntarily recalling all quantities and lots within expiry of ranitidine hydrochloride capsules in the US to the consumer level because of confirmed contamination NDMA above levels established by the FDA in batches of Sandoz’ ranitidine hydrochloride capsules. To date (as of September 23, 2019), Sandoz says it has not received any reports of adverse events related to use of the product as part of this recall.

In a filing with the Bombay Stock Exchange, GlaxoSmithKline (GSK) reported on September 25, 2019 that it had been contacted by regulatory authorities regarding the detection of NDMA in ranitidine products. “Based on the information received and correspondence with regulatory authorities, GSK made the decision to suspend the release, distribution and supply of all dose forms of ranitidine hydrochloride products to all markets, including India, as a precautionary action pending the outcome of ongoing tests and investigations,” said the company in its statement. 

Subsequently, Saraca Laboratories was notified by the European Directorate for the Quality of Medicines & HealthCare (EDQM) that its certificate of suitability for ranitidine hydrochloride had been suspended. GSK manufactures ranitidine hydrochloride IP Tablets 150 mg and 300 mg (Zinetac) using API from Saraca Laboratories and another supplier, SMS Lifesciences India, for supply to the Indian market.

Based on the information provided and as a precautionary action, GSK made the decision to initiate a voluntary recall (pharmacy/retail level recall) of Zinetac tablets 150 mg and 300 mg products manufactured in India using APIs sourced from Saraca Laboratories. In its filing announced on September 25, 2019, GSK reported that its product manufactured using APIs from SMS Lifesciences India will not be recalled at this point in time. GSK said, however, in its filing that all such products will remain on hold and they will not be released to the market while the company awaits test results.

GSK says it is continuing with investigations into the potential source of the NDMA. These investigations include continued engagement with its API suppliers.

Walmart, the US-based retailer, announced this week (October 2, 2019) that it is suspending the sale of all OTC ranitidine products in stores, clubs and online, including Zantac, Equate, and Member’s Mark brands. The company said it is taking this action after closely monitoring the recent product alert from the FDA that ranitidine products may contain a low level of NDMA.

CVS Pharmacy, a US-based pharmacy chain, announced on September 28, 2019 that it had suspended the sale of all Zantac brand and CVS Health brand ranitidine products until further notice. The company said that this action is being taken “out of an abundance of caution” due to the recent product alert from the FDA that ranitidine products may contain a low level of NDMA.

The recalls come as both the FDA and EMA continue their investigations and provide related information on testing protocols for the detection of nitrosamine impurities in ranitidine (see story).

Source: Apotex and FDA and FDA; Sandoz and FDA; GlaxoSmithKline; Walmart; CVS