The Food and Drug Administration is 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).
The impurity 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.
Recent testing of these recalled lots of losartan potassium tablets showed NMBA levels higher than the FDA’s interim acceptable intake limits. The FDA’s evaluation suggests that the nitrosamines found in ARBs may be generated when specific chemicals and reaction conditions are present in the manufacturing process of the drug’s API, and may also result from the reuse of materials, such as solvents.
“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.
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, two 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.
