FDA: New Nitrosamine Impurity Detected in Certain Losartan Lots

Officials with the US Food and Drug Administration (FDA) are updating the public on the agency’s ongoing investigation surrounding the recent voluntary recalls of multiple generic angiotensin II receptor blocker (ARB) drug products used to treat high blood pressure and heart failure. Hetero Labs Ltd. in India has announced a recall of 87 lots of losartan potassium tablets (25 mg, 50 mg and 100 mg).

The recalled losartan potassium tablets made by Hetero Labs and distributed by Camber Pharmaceuticals contain the impurity, N-Nitroso-N-methyl-4-aminobutyric acid (NMBA), which is a known animal and potential human carcinogen. This is the first ARB recall resulting from the presence of NMBA, which is the third type of nitrosamine impurity detected in ARB medicines.

Hetero Labs identified NMBA in lots of losartan potassium during recent testing. NMBA has not been found in previously recalled ARB products; however, the FDA is continuing its investigation. Previously, 2 other nitrosamine impurities, NDMA and NDEA, were found in drug products containing the active pharmaceutical ingredients valsartan, losartan, and irbesartan and those products containing nitrosamines above the interim acceptable limits were recalled.

The FDA will continue to update the list of products included in the recall as more information becomes available from ongoing testing. If patients take an ARB drug product, they should check the list periodically, as information may change.

“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. That said, any presence of such impurities in drug products is not acceptable. Over the past few months, the FDA has conducted a major investigation and has worked with drug companies to address the presence of impurities in these products,” FDA Commissioner Scott Gottlieb, MD said in a statement. “Our ongoing effort has determined that the impurities may be generated by specific chemical reactions in the manufacturing process of the drug’s active pharmaceutical ingredients. FDA scientists have developed novel and sophisticated testing methods specifically designed to detect and measure N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) impurities in ARB medicines. 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. 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. The FDA is committed to implementing measures to prevent the formation of these impurities during drug manufacturing processes in the future.”

FDA officials noted in the statement that patients taking an ARB medication from a recalled lot should continue taking their medicine until their doctor or pharmacist provides a replacement or a different treatment option. Any patient taking an ARB from a recalled lot who has not yet spoken to their pharmacist or doctor should do so promptly. Not all ARBs contain nitrosamine impurities.