- After months of investigation, the Food and Drug Administration has zeroed in on what it believes to be a contributing cause of potential carcinogenic contaminants recently found in a number of generic blood pressure medications, most notably valsartan.
- Impurities in certain angiotensin II receptor blockers, or ARBs, appear to be generated when certain chemicals and reaction conditions are present during the manufacturing process of the drugs' active pharmaceutical ingredient. Reuse of materials such as solvents may also play a role, the FDA said in a Jan. 25 statement.
- One challenge confronting the FDA and other regulators has been detection of the impurity in question, N-nitrosodimethylamine (NDMA), which is hard to detect using standard methods. The FDA has since developed new techniques to identify its presence.
In mid-2018, the FDA and the European Medicines Agency launched a probe after finding active pharmaceutical ingredient of valsartan made by a Chinese manufacturer to be contaminated with the potential carcinogen NDMA. The investigation spread to other "sartan" drugs, which treat high blood pressure, and eventually found another possible carcinogen, NDEA, to be present.
Investigation by the FDA and others remains ongoing. In the meantime, however, the FDA has taken a number of actions to limit the spread of contaminated API, including placing the Zhejiang Huahai Pharmaceutical facility from which impurities were first spotted on import alert. As a result, API and finished drugs from the company cannot enter the U.S.
The FDA is also maintaining lists of valsartan, losartan and irbesartan lots currently under recall. Torrent Pharmaceuticals and Solco Healthcare are two of the most recent drugmakers to put out voluntary recalls for sartan-based products.
Exposure to NMDA and NDEA, which can be found environmentally, above a certain limit carries carcinogenic risk the FDA has deemed unacceptable. Still, the agency believes the risk to any individual patient taking sartan-based drugs to be relatively small.
If 8,000 people took the highest daily valsartan dose found to contain NDMA for four years, FDA scientists estimate, one additional case of cancer above the average rate may occur.
Because of the role these medicines play, the FDA has sought to balance its containment efforts with maintaining access.
"We remind patients taking these medications or any recalled ARB to continue taking their current medicine until their pharmacist provides a replacement or their doctor provides an alternative treatment option," said Woodcock and Gottlieb in a statement.
Not all generics of valsartan, losartan and irbesartan contain NDMA or NDEA, so pharmacists may be able to provide other medications, and physicians may prescribe a different medication to treat hypertension.