87 lots of losartan recalled as FDA investigation reveals more impurities in BP drugs

An ongoing FDA investigation of generic angiotensin II receptor blocker (ARB) drugs used to treat hypertension and heart failure found higher-than-acceptable levels of the carcinogen N-Nitroso-N-methyl-4-aminobutyric acid (NMBA) in recent batches of losartan potassium tablets, prompting a voluntary recall of 87 lots, the agency announced March 1.

The FDA first approved generic losartan tablets in the U.S. in 2010, but last November manufacturer Sandoz announced it was recalling one lot of its losartan potassium hydrochlorothiazide tablets after they were found to contain a trace amount of N-nitrosodiethylamine (NDEA), a probable human carcinogen.

It was the third ARB to be recalled after more than 20 countries announced they were recalling valsartan drugs last July and ScieGen Pharmaceuticals issued a recall of irbesartan in November. Valsartan was recalled after testing found evidence of N-nitrosodimethylamine (NDMA), another carcinogen, and irbesartan was recalled for containing NDEA.

“We are deeply concerned about the presence of a third nitrosamine impurity in certain ARB medications, but it’s important to underscore that, based on the FDA’s initial evaluation, the increased risk of cancer to patients with NMBA exposure appears to be the same for NDMA exposure but less than the risk from NDEA exposure,” FDA Commissioner Scott Gottlieb, MD, said in the agency’s statement about losartan. “That said, any presence of such impurities in drug products is not acceptable.”

As with valsartan, the FDA guesses a change in the manufacturing process behind losartan may be responsible for the accidental generation of probable carcinogens. But, while NMBA is the third type of nitrosamine impurity to be detected in an ARB medicine as of late, this is the first recall that’s resulted from the presence of NMBA, a known animal and potential human carcinogen.

The 87 lots of losartan tablets, which include 25 mg, 50 mg and 100 mg doses, were manufactured in India by Hetero Labs and distributed by Camber Pharmaceuticals, according to the FDA. The agency said recent analyses of NDMA and NDEA in recalled valsartan found the actual risk to patients is relatively low, but the FDA plans to continue its investigation into ARB impurities.

“Because of the potential for discovering other nitrosamine impurities, we are conducting an extensive organic chemistry analysis to develop novel testing methods to detect additional nitrosamine impurities, including NMBA,” Gottlieb said. “We’re continuing to share these testing methods with international regulators, industry and the public to help manufacturers and other regulators evaluate these products for any potential nitrosamine impurity. We are making important strides at understanding how these impurities form and we are continuing to examine if nitrosamine impurities may also arise during the manufacture of other ARB drug products.”

As with any drug, the FDA recommends patients currently taking losartan included in the recalled lots continue with their regimen until their physician approves another drug or course of treatment.

Find a full list of losartan products included in the recall here.