Amid an ongoing series of tainted sartan drug recalls, the US Food and Drug Administration (FDA) announced Wednesday that it will not object to temporary distribution of losartan that contains the impurity N-Nitroso-N-methyl-4-aminobutyric acid (NMBA) above the interim acceptable intake limit of 0.96 parts per million (ppm) and below 9.82 ppm until it can be eliminated.
The goal is to ensure continued access, the FDA said. The agency expects many companies will be able to make losartan without nitrosamine impurities and replenish the US supply in about 6 months.
Scientists at FDA evaluated the risk of exposure to NMBA at levels up to 9.82 ppm and found that it presents “no meaningful difference” in cancer risk over 6 months compared to a lifetime of exposure to NMBA at 0.96 ppm, the agency said in a statement.
“Distributing losartan containing NMBA up to 9.82 ppm will help maintain adequate losartan supply while companies obtain approval for manufacturing processes that produce nitrosamine-free losartan for patients,” the FDA said.
The FDA said manufacturers should contact FDA’s Drug Shortages Staff when manufacturers’ testing of losartan shows levels of NMBA that exceed the interim acceptable intake limit of 0.96 ppm. FDA will determine on a case-by-case basis whether lots containing NMBA greater than 0.96 ppm should be released for distribution.
NMBA is one of three nitrosamine impurities detected in angiotensin II receptor blockers valsartan, losartan, and irbesartan, as well as some combination drugs that contain these medications, since the summer of 2018. The FDA maintains an updated list of recalled sartan products on its website.
Earlier this month, the FDA approved a new generic of valsartan (Diovan) made by Alkem Laboratories.
“We know that the ongoing recalls to prevent certain lots of valsartan that contain unacceptable limits of impurities from reaching patients has resulted in a shortage of these important medicines. So to address the public health consequences of these shortages, we’ve prioritized the review of generic applications for these valsartan products,” FDA Commissioner Scott Gottlieb, MD, said in a news release.
The FDA said it is working with companies and international regulators to ensure products entering the US market do not contain nitrosamine impurities.