Drug Safety Alerts

Ranitidine (Zantac) Products FDA Withdrawal Request

4/1/2020

On April 1, 2020, the United States Food and Drug Administration (FDA) announced that it is requesting manufacturers withdraw all prescription and over-the-counter (OTC) ranitidine drugs from the market immediately. This is the latest step in an ongoing investigation of a contaminant known as N-Nitrosodimethylamine (NDMA) in ranitidine medications (commonly known by the brand name Zantac). The agency has determined that the impurity in some ranitidine products increases over time and when stored at higher than room temperatures and may result in consumer exposure to unacceptable levels of this impurity. As a result of this immediate market withdrawal request, ranitidine products will not be available for new or existing prescriptions or OTC use in the U.S.

The FDA has advised that in the summer of 2019, it became aware of independent laboratory testing that found NDMA, a probable human carcinogen, in ranitidine. Low levels of NDMA are commonly ingested in the diet, for example NDMA is present in foods and in water. According to the FDA, these low levels would not be expected to lead to an increase in the risk of cancer, but sustained higher levels of exposure may increase the risk of cancer in humans. The FDA advised that it conducted thorough laboratory tests and found NDMA in ranitidine at low levels. The FDA further advised that at that time, it did not have enough scientific evidence to recommend whether individuals should continue or stop taking ranitidine medicines, and continued its investigation and warned the public in September 2019 of the potential risks and to consider alternative OTC and prescription treatments.

In this announcement, the FDA reported that new FDA testing and evaluation prompted by information from third-party laboratories confirmed that NDMA levels increase in ranitidine even under normal storage conditions, and NDMA has been found to increase significantly in samples stored at higher temperatures, including temperatures the product may be exposed to during distribution and handling by consumers. According to the FDA, the testing also showed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA, and these conditions may raise the level of NDMA in the ranitidine product above the acceptable daily intake limit.

The FDA is sending letters to all manufacturers of ranitidine requesting they withdraw their products from the market. The FDA is also advising consumers taking OTC ranitidine to stop taking any tablets or liquid they currently have, dispose of them properly and not buy more; for those who wish to continue treating their condition, they should consider using other approved OTC products. Patients taking prescription ranitidine should speak with their health care professional about other treatment options before stopping the medicine, as there are multiple drugs approved for the same or similar uses as ranitidine that do not carry the same risks from NDMA. The FDA reports that to date, its testing has not found NDMA in famotidine (Pepcid), cimetidine (Tagamet), esomeprazole (Nexium), lansoprazole (Prevacid) or omeprazole (Prilosec).

In light of the current COVID-19 pandemic, the FDA recommends patients and consumers not take their medicines to a drug take-back location but follow the specific disposal instructions in the medication guide or package insert or follow the agency’s recommended steps, which include ways to safely dispose of these medications at home.

The FDA encourages health care professionals and patients to report adverse reactions or quality problems with any human drugs to the agency’s MedWatch Adverse Event Reporting program.

CVS Caremark Response:

In response to the action taken by the FDA, CVS Caremark Mail Service Pharmacies will no longer be filling prescriptions for these products.

For more information regarding this issue, health care providers may contact the FDA consumer inquiry at 1‑888‑INFO‑FDA (1‑888‑463‑6332) or visit https://www.fda.gov.