FDA Updates Investigation into ARB Drug Products

PUBLISHED: Mar 1, 2019
Relevant to: All Healthcare Organizations

The U.S. 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.

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.

Recent FDA analyses of NDMA and NDEA in recalled valsartan found that overall, the risk to individual patients is very low, although this doesn’t diminish the significance of this issue or the FDA’s concerns. The agency continues to evaluate the risks nitrosamines pose to patients. The FDA and drug manufacturers continue to test all ARBs for nitrosamine impurities. If NDEA, NDMA, NMBA, or other nitrosamine impurities are found in products at levels above the interim acceptable intake limits, the FDA will work with companies to swiftly remove affected products from the market.

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.

The FDA reminds patients taking an ARB medication from a recalled lot to 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.

Want to read the full alert and receive alert emails?

Browse Additional Alerts