On April 5, the agency posted a list of about 40 blood pressure and heart medicines where nitrosamine, which has been linked to cancer, is “not present.”
The issue came to light in July 2018 when the FDA said it recalled several medicines with valsartan after impurities were found. Those medications were manufactured by a drugmaker in China.
Since then, the FDA has “been working to thoroughly understand how this issue arose, how we could address and mitigate exposure to this unnecessary risk to patients, and what we could do to prevent these types of impurities from reoccurring in future medications,” according to a press release on April 4.
The health agency’s statement added that the presence of nitrosamines is “not acceptable” in drug products.
“We’re also continuing to work with manufacturers to swiftly remove medications from the market if they contain a nitrosamine impurity at levels higher than the interim acceptable intake limits. Removing the affected medications from the market has led to shortages, and since then we’ve been working to mitigate and prevent shortages as often as possible,” the agency also said.
Common nitrosamines include N,N-dimethylnitrosamine (NDMA), N,N-diethylnitrosamine (NDEA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
A list of the 40 “safe” medications can be accessed via the FDA’s website.
For drugs marked “not present,” it means the FDA “has completed the comprehensive assessment noted above.”
Meanwhile, “TBD” means that “one or more parts of our assessment remain incomplete and the product remains acceptable for distribution and for patient use,” according to the release.
For the lots with “TBD,” “the product did have impurity levels above interim acceptable limits, however they have already been removed from the market,” adding that the agency is “prioritizing the assessments by those of highest patient need and in response to credible information about nitrosamine contamination.”
For a list of losartan recalls, the FDA’s website has details (pdf).
For a list of valsartan recalls until March 1, the FDA’s website has details (pdf).
For a list of irbesartan recalls until March 1, the FDA’s website has details (pdf).
FDA Warning on Shortage
The FDA issued a warning in January about a blood pressure drug shortage caused by frequent recalls.
“Valsartan products are in shortage, and we know that other types of products may fall into shortage soon,” FDA Commissioner Dr. Scott Gottlieb and FDA director of drug evaluation and research Dr. Janet Woodcock said in the joint statement.
In July, the FDA carried out lab tests on valsartan-containing medications manufactured by a company in China, and the agency discovered the presence of NDMA and NDEA. According to the Environmental Protection Agency, NDMA is found in rocket fuel, lubricants, and other additives.
“These two substances are known environmental contaminants and found in water and foods, including meats, dairy products, and vegetables. But their presence in drug products is not acceptable,” the FDA statement said at the time.
The issue surfaced in the summer of 2018 after the FDA was informed that an active ingredient manufactured by Zhejiang Huahai Pharmaceutical Co. Ltd. in Linhai, China, had NDMA inside.
“We also issued them a warning letter outlining several manufacturing violations, including impurity control, change control, and cross-contamination from one manufacturing process line to another,” the FDA statement last month said.
After an investigation into Zhejiang’s manufacturing process, the FDA discovered a change that likely led to the cancer-causing chemicals being introduced. The impurity was also not detected by global health agencies, including the FDA, for some time until last