Evaluating the Risk of Nitrosamines: Zantac's 4-Year-Old Recall Is Still Affecting Industry.

The pharmaceutical industry has yet to discover how nitrosamines occur in its drugs and how to mitigate the risk of that happening.

If you had bacon for breakfast, you may have ingested some nitrosamines, the organic compounds that were also found in Sanofi's Zantac and spurred a recall of the blockbuster heartburn treatment four years ago. The recall created an opportunity for legal action by patients who had been taking the drug, and the first court case is set to begin in February 2023 in California.

Consequently, the industry has been challenged with how to discover how nitrosamines occur in its drugs and how to mitigate the risk of that happening. The FDA has issued guidance on allowable amounts in drugs, and physician and patients look to find alternative treatment, if necessary. All three stakeholders are trying to assess the risk of getting cancer from the nitrosamines, and recent studies have shown the risk to be relatively low. According to the FDA, nitrosamines are common in water and foods, including cured and grilled meats, dairy products and vegetables. Everyone is exposed to some level of nitrosamines.

Zantac Trial Impact

In the case of Zantac, more than 3,100 plaintiffs have filed suits against Sanofi, claiming that the company didn't warn of the potential danger of nitrosamines in the drug. According to a recent Bloomberg report, the company is at risk of losing a ton of money; trial judgments against Sanofi could reach $45 billion. Sanofi has repeatedly denied any liability and analysts have stated they are doubtful the plaintiff's case has merit.

"Since 2019, the medical, scientific, and regulatory communities have extensively evaluated the safety of Zantac’s active ingredient ranitidine, and the data shows there is no evidence of consumer harm from real-world use of Zantac," Sanofi said in a recent press release.

In the Bloomberg report, George Gray, professor at George Washington University who specializes in health-related risk analysis, says, “It really is hard to say just how big the risk of these medications might be especially given the benefit they might confer on people.”

Sanofi's statement helped correct its stock price, which fell on the news of the lawsuit.

Both FDA and the European Medicines Agency evaluated the available data and found no evidence that Zantac causes cancer. 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," the FDA states.

Since the recalls and FDA's tightened regulation, the industry is still struggling with how to identify all the causes that create nitrosamine in medications and to prevent it from happening.

Where and when the impurities may occur is a complicated problem caused by numerable factors, ranging from something as straightforward as material used in blister packs to chemical interactions that occur before, during and after the drug making process.

Impact on physicians and patients

The FDA has offered guidance to physicians and patients, recommending physicians continue to prescribe medications when clinically appropriate and educate patients about alternative treatment options. Both pharmacists and prescribers may be able to dispense the same medication from a manufacturing lot that has not been recalled. Patients can find medications that have been recalled due to potential nitrosamine impurities on the FDA recalls webpage.