What is NDMA and why was it a concern in ranitidine?
N-Nitrosodimethylamine (NDMA)
NDMA is classified as a probable human carcinogen, meaning it could cause cancer. It's a common environmental contaminant found in some foods, beverages, and water. While low levels are generally safe, prolonged exposure to higher levels may increase cancer risk. The FDA set an acceptable daily intake limit of 96 nanograms for NDMA in medications. Some tests later showed ranitidine products exceeded this limit.
NDMA's link to ranitidine
The ranitidine molecule is unstable and can break down to form NDMA. Tests by independent labs and the FDA showed that NDMA levels in some ranitidine products increased over time and with exposure to higher temperatures, potentially reaching unsafe levels by the time of use.
The timeline and regulatory action against ranitidine
Initial NDMA discovery
The issue with ranitidine began in 2019 when high levels of NDMA were detected by the online pharmacy Valisure. This discovery prompted an FDA investigation.
FDA's response and recalls
In September 2019, the FDA warned the public about potential NDMA in ranitidine, leading some manufacturers to voluntarily recall their products. As the FDA gathered more data, particularly on NDMA levels increasing over time and with heat, a broader action was deemed necessary.
Total market withdrawal
Due to the safety concerns that NDMA levels increased over time and when stored at higher temperatures, the FDA requested in April 2020 that all ranitidine products be removed from the U.S. market. This action applied to all ranitidine forms, and international regulators took similar steps. More information is available on the FDA's Press Announcement.
Safe alternatives for heartburn and acid reflux
Many safe and effective alternatives are available for those who previously used ranitidine. The FDA confirmed these alternatives did not contain NDMA.
Comparison of alternatives to ranitidine
| Medication (Brand Name) | Class of Drug | How it works | NDMA Contamination Found? | Availability |
|---|---|---|---|---|
| Famotidine (Pepcid) | H2 Blocker | Decreases stomach acid production | No | Prescription & Over-the-Counter |
| Cimetidine (Tagamet) | H2 Blocker | Decreases stomach acid production | No | Prescription & Over-the-Counter |
| Omeprazole (Prilosec) | Proton Pump Inhibitor (PPI) | Nearly shuts down stomach acid production | No | Prescription & Over-the-Counter |
| Esomeprazole (Nexium) | Proton Pump Inhibitor (PPI) | Nearly shuts down stomach acid production | No | Prescription & Over-the-Counter |
| Lansoprazole (Prevacid) | Proton Pump Inhibitor (PPI) | Nearly shuts down stomach acid production | No | Prescription & Over-the-Counter |
Navigating the recall: What to do and what happened next
Recommendations for consumers and patients
The FDA advised OTC users to stop taking ranitidine and dispose of it, suggesting alternative products like famotidine or cimetidine. Prescription users were told to consult their doctor before stopping medication to find alternatives.
Legal ramifications
Thousands of lawsuits were filed against ranitidine manufacturers by plaintiffs claiming cancer resulted from taking the drug. A federal judge dismissed a large group of these cases in 2022, citing insufficient evidence linking ranitidine to cancer, but state-level cases and appeals are ongoing.
Broader context of NDMA contamination
The ranitidine issue followed similar recalls of certain blood pressure medications (ARBs) due to NDMA contamination. These events led to new FDA guidelines for drugmakers to limit nitrosamine impurities.
Conclusion
The market withdrawal of ranitidine, including Zantac, was caused by the drug's degradation into unsafe levels of the probable carcinogen NDMA, which increased over time and with heat. This led the FDA to conclude the drug's safety could not be guaranteed, resulting in the April 2020 recall. The event underscores regulatory efforts to protect public health and has shifted patients to safe alternatives for heartburn and acid reflux. While legal disputes continue regarding long-term health impacts, ranitidine is no longer available in the U.S..
