Important information about NDMA impurities in ranitidine products
- The U.S. Food and Drug Administration has requested a manufacturer’s market withdrawal of ranitidine, known commonly by the brand name Zantac. This means ranitidine products will not be available for new or existing prescriptions or over-the-counter (OTC) use in the U.S.
- FDA has found N-nitrosodimethylamine (NDMA) levels in some ranitidine products increase with time and temperature posing a risk to consumers, and therefore the agency has requested the withdrawal of all ranitidine products from the U.S. market.
- Consumers should stop taking any OTC ranitidine they may currently have. Patients taking prescription ranitidine should speak with their health care professional about other treatment options before stopping the medicine. Multiple drugs are approved for the same or similar uses as ranitidine.
- Consumers should dispose of any ranitidine products properly, and not buy more of it including compounded ranitidine.
- To date, FDA’s testing has not found NDMA in products used for similar treatment like famotidine (Pepcid), cimetidine (Tagamet), esomeprazole (Nexium), lansoprazole (Prevacid) or omeprazole (Prilosec).
A. FDA is requesting a market withdrawal of all remaining prescription and OTC ranitidine products on the U.S. market. This means that ranitidine will not be available for use in the U.S. The agency is taking this action because FDA laboratory testing results show that levels of NDMA in ranitidine may increase to unacceptable levels over time. The tests also show NDMA levels increase in some ranitidine products when the drug is exposed to higher than room temperatures. Based on these findings, FDA has determined that many currently marketed ranitidine products could expose consumers to unacceptable health risks. All ranitidine products, including the oral liquid/syrup, will be withdrawn by their manufacturers and will not be available on the U.S. market.
This differs from past actions because this is the first time FDA is requesting market withdrawal of all ranitidine products.
A. If a company can show, through scientific data, that their ranitidine product is stable and the NDMA levels do not increase over time to unsafe levels, FDA may consider allowing that ranitidine product back on the U.S. market.
A. In light of the current COVID-19 pandemic, we recommend 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 these steps, which include ways to safely dispose of these medications at home.
A. Any product in storage and not yet distributed would have to be evaluated following FDA guidance to show it would be safe throughout its shelf-life before the manufacturer can put it back on the market.
A. Yes, all formulations of ranitidine are affected by this action.
A. Yes, compounded ranitidine products are affected by this action. FDA also has safety concerns over the compounding of ranitidine-containing drugs intended for animal use. Animal owners should consult their veterinarian for alternative treatment options.
A. At this time, FDA is not withdrawing approvals of ranitidine new drug applications and abbreviated new drug applications (NDAs/ANDAs for ranitidine).
A. FDA will contact ANDA applicants as needed regarding pending submissions that are affected by this withdrawal. If a company can show, through scientific data, that their ranitidine product is stable and the NDMA levels do not increase over time to unsafe levels, FDA may consider allowing that ranitidine product on the U.S. market.
A. FDA laboratory tests show that temperature and time generally raise the level of NDMA in some ranitidine products above the acceptable daily intake limit of 96 nanograms per day.
A. FDA does not expect nitrosamines to cause harm when ingested at low levels. Nitrosamine impurities may increase the risk of cancer if people are exposed to them at above acceptable levels and over long periods of time, but a person taking a drug that contains nitrosamines at, or below, the acceptable daily intake limits every day for 70 years is not expected to have an increased risk of cancer.
A. FDA does not have scientific evidence to determine how long NDMA has been present in ranitidine products.
A. This is an ongoing investigation and the agency is working to fully determine the root cause. NDMA was present in both the finished drug product samples and the active pharmaceutical ingredients (APIs) that the FDA tested. The FDA’s simulated gastric fluid and simulated intestinal fluid testing results illustrated that NDMA was not formed in the conditions of the stomach or the intestines. However, the FDA’s recent laboratory testing results demonstrate that levels of NDMA in some ranitidine finished drug products increase over time at room temperature. Increased temperatures also resulted in increased levels of NDMA in some ranitidine finished drug product.
A. FDA has ongoing assessment, surveillance, compliance and pharmaceutical quality efforts across every product area, and we will continue to work with drug manufacturers to ensure safe, effective and high-quality drugs for the American public. When we identify new and previously unrecognized risks to safety and quality, we react swiftly to resolve the problem, as we have done in responding to the recent findings of nitrosamine in certain medicines.
Today, we have better testing methods than ever before, and we know what to look for in products’ chemical structures and manufacturing processes that may increase the risk of forming low levels of nitrosamines. Improved technology enables us to detect even trace amounts of impurities in drug products and may be the reason why more products have been found to have low levels of nitrosamines. The agency has strict standards for safety, effectiveness and quality, and our staff makes every effort to help keep the U.S. drug supply as safe as possible. We also work closely with international drug regulatory agencies so that we leverage resources and testing done outside the U.S. which can help inform testing of the U.S. drug supply. As our investigations and testing continue, along with the investigations done by international drug regulatory agencies, we may find low levels of nitrosamines in additional drugs.
A. Drug manufacturers and FDA continually gain new knowledge about drugs, which is why FDA constantly evaluates quality and safety information over time. As testing methods have become more sophisticated and sensitive, FDA and industry can identify and mitigate previously-unknown risks to patients.
Through extensive investigation and information-sharing with international regulatory agencies and private sector laboratories, the agency is now able to scientifically show that time and increased temperature can cause increased levels of NDMA in some ranitidine products that may pose a health risk.
A. There are no approved new animal drugs containing ranitidine. However, veterinarians can prescribe an approved human drug for extra-label (off label) use in animals under certain conditions. If a veterinarian has prescribed extra-label use of an approved human drug containing ranitidine for use in their animal patients, the drug will no longer be available. One common extra-label use of approved human drugs containing ranitidine is for treatment or control of gastric ulcers in horses.
A. Animal owners should consult their veterinarian for alternative treatment options.
A. GastroGard is approved for treatment and prevention of recurrence of gastric ulcers in horses and foals 4 weeks of age and older. UlcerGard is approved for the prevention of gastric ulcers in horses. Animal owners should consult their veterinarian for appropriate treatment options.