On April 3, 2020, The European Medicines Agency (EMA)—the European equivalent of the U.S. Food and Drug Administration (FDA)—recommended the suspension of all ranitidine (Zantac) medicines due to the presence of N-nitrosodimethylamine (NDMA), a cancer-causing agent.
The FDA had made a similar move on April 1, 2020, just two days earlier. Independent tests showed that the levels of NDMA could increase in ranitidine medications over time and with exposure to high temperatures, so the FDA requested the recall of all ranitidine medications from the U.S. market.
At the request of a ranitidine manufacturer, the EMA recently re-examined its position. On September 18, 2020, it released a letter confirming the recommendation that all ranitidine medications remain suspended in the European Union (EU).
Can NDMA Form in the Body After Ingestion of Ranitidine?
In its initial recommendation, the EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended the suspension of ranitidine (Zantac) medicines because investigators had found unsafe levels of NDMA in several of the products. It also reported “unresolved questions about the source of the impurities.”
Those unresolved questions included concerns about how the NDMA ended up in the drugs in the first place. The EMA acknowledged the research showing NDMA could form from the degradation of ranitidine even under normal storage conditions. But might the impurity also form within the human body?
Valisure, the online pharmacy that first detected NDMA, argued that the ranitidine molecule itself was unstable, and could form NDMA during human digestion. The FDA, however, was unable to confirm that finding in its own studies.
“It is not clear whether NDMA can also be formed from ranitidine inside the body,” the EMA stated. “Some studies suggest that it can while others do not. Given the uncertainties, the CHMP has recommended a precautionary suspension of these medicines in the EU.”
At the time, the EMA recommended conditions for lifting the suspension of ranitidine medications and pledged to continue working with national authorities to address the problem of NDMA and other impurities in prescription drugs.
EMA Confirms Suspension of All Ranitidine Medications
After the initial suspension, one of the companies marketing ranitidine asked the CHMP to re-examine its conclusions. On September 18, 2020, following this re-examination, the CHMP confirmed its recommendation:
“EMA’s human medicines committee (CHMP) has confirmed its recommendation to suspend all ranitidine medicines in the EU due to the presence of low levels of an impurity called N-nitrosodimethylamine (NDMA),” the letter reads.
The CHMP also maintained the conditions for lifting the suspension, including requirements for companies to provide more data on the possible formation of NDMA from ranitidine inside the body. The organization did slightly amend those conditions for ranitidine medicines given by injection or infusion, as the formation of NDMA with these one-time single doses is expected to be very low.
In the meantime, the EMA advised patients to talk to their doctors about alternative medicines for reducing stomach acid.
In the U.S., the FDA has recalled all forms of ranitidine from the market after determining the drug presented more risks than benefits to the general population.