Regulatory Focus™ > News Articles > 2019 > 3 > To Prevent Losartan Shortages, FDA Allows Higher Impurity Levels

To Prevent Losartan Shortages, FDA Allows Higher Impurity Levels

Posted 21 March 2019 | By Zachary Brennan 

To Prevent Losartan Shortages, FDA Allows Higher Impurity Levels

To ensure patient access to the blood pressure medicine losartan, the US Food and Drug Administration (FDA) said late Wednesday that it will not object to certain manufacturers temporarily distributing losartan with one impurity above the interim acceptable intake limit until that impurity can be eliminated.

For such companies, losartan “containing 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” will be allowed “until the impurity can be eliminated,” FDA said.

The agency also said it expects companies will be able to manufacture losartan without nitrosamine impurities and replenish the US supply in about six months.

Earlier this month, NMBA was detected in tablets using active pharmaceutical ingredients (APIs) made by Hetero Labs. Another Indian drugmaker, Torrent Pharmaceuticals, also expanded its recall of losartan products to include an additional 114 lots, as they were made using APIs from Hetero that contained NMBA.

That recall was part of a series of recalls tied to the discovery of nitrosamine impurities in angiotensin II receptor blocker (ARB) drugs in the last year.
Previously, N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) impurities prompted recalls of ARB drugs containing APIs manufactured by HeteroMylan Pharmaceuticals and Zhejiang Huahai Pharmaceuticals.

But for NMBA, FDA scientists have now evaluated the risk of exposure to levels up to 9.82 ppm and “determined that it presents no meaningful difference in cancer risk over a six-month time period when compared to a lifetime of exposure to NMBA at 0.96 ppm.” And while companies look to gain approval for manufacturing processes that produce nitrosamine-free losartan for patients, FDA said that distributing losartan containing NMBA up to 9.82 ppm will help maintain an adequate supply.

“Manufacturers should contact FDA’s Drug Shortages Staff when their 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,” FDA added.

In a related note, FDA also said medications containing only amlodipine or hydrochlorothiazide (HCTZ) are not being recalled. “Manufacturers are recalling medications containing amlodipine in combination with valsartan or losartan, and medications containing hydrochlorothiazide HCTZ in combination with valsartan or losartan,” the agency said.

FDA updates on angiotensin II receptor blocker (ARB) recalls including valsartan, losartan and irbesartan

Regulatory Focus newsletters

All the biggest regulatory news and happenings.