U.S. flag An official website of the United States government
  1. Home
  2. Drugs
  3. Drug Safety and Availability
  4. Information about Nitrosamine Impurities in Medications
  1. Drug Safety and Availability

Information about Nitrosamine Impurities in Medications

Losartan Valsartan and other ARBs

Metformin

Ranitidine (Zantac)

Rifampin/Rifapentine


FDA issues guidance,“Control of N-Nitrosamine Impurities in Human Drugs”

Update [2/24/2021] To ensure the safety of the U.S. drug supply, the guidance recommends that manufacturers should conclude the risk assessment of approved or marketed products, the first of three steps manufacturers should follow to mitigate nitrosamine impurities in their products, within 6 months of publication of the guidance. Through today’s revision to the guidance, FDA extends the recommended timeframe for completion of risk assessments to March 31, 2021. Manufacturers do not need to submit risk assessment documents to the agency, but they should retain these documents so that they are available if requested.

[9/1/2020] FDA is announcing the availability of a guidance for industry, entitled “Control of N-Nitrosamine Impurities in Human Drugs.” This guidance recommends steps manufacturers of active pharmaceutical ingredients and drug products should take to detect and prevent objectionable levels of nitrosamine impurities in pharmaceutical products. The guidance also describes conditions that may introduce nitrosamine impurities.

  • FDA has been investigating the presence of impurities, called nitrosamines, in some types of medications.
  • Nitrosamines are common in water and foods, including cured and grilled meats, dairy products and vegetables. Everyone is exposed to some level of nitrosamines.
  • FDA, in collaboration with regulatory counterparts around the world, has set internationally-recognized acceptable daily intake limits for nitrosamines. If drugs contain levels of nitrosamines above the acceptable daily intake limits, FDA recommends these drugs be recalled by the manufacturer as appropriate.
  • Nitrosamine impurities may increase the risk of cancer if people are exposed to them 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. 
  • Patients taking prescription medications with potential nitrosamine impurities should not stop taking their medications. Patients should talk to their health care professionals about concerns and other treatment options.
  • Consumers taking over-the-counter medications with potential nitrosamine impurities may consider using other OTC products approved for their condition.
  • Find information about medications that have been recalled due to potential nitrosamine impurities on the FDA recalls webpage.
  • The agency is working to determine the source of these impurities and will keep the public informed.
  • Health care professionals should continue to prescribe medications when clinically appropriate even though they may have low levels of nitrosamine impurities.
  • Health care professionals can educate patients about alternative treatment options to medications with potential nitrosamine impurities if available and clinically appropriate.
  • Find information about medications that have been recalled due to potential nitrosamine impurities on the FDA recalls webpage.
  • If a medication has been recalled, pharmacists may be able to dispense the same medication from a manufacturing lot that has not been recalled. Prescribers may also determine whether there is an alternative treatment option for patients.
  • FDA will continue to investigate the presence of nitrosamine impurities in drugs and will communicate new information as it becomes available.
  • Manufacturers are responsible for understanding their processes, which includes preventing the presence of unacceptable impurities. Manufacturers are also responsible for developing and using suitable methods to detect and limit unacceptable impurities, including any new impurities that may arise when they make changes to their manufacturing processes. 
  • FDA has published testing methods that can be used by industry to detect nitrosamine impurities.
  • FDA, in collaboration with regulatory counterparts around the world, has set internationally-recognized acceptable daily intake limits for nitrosamines. If drugs contain levels of nitrosamines above the acceptable daily intake limits, FDA recommends these drugs be recalled by the manufacturer as appropriate or not be released for distribution to the market.
  • The agency is working with industry to determine the source of these impurities, but there are multiple reasons why nitrosamines can be present in medicines.

 

More information

 

 

Back to Top