FDA notice on sitagliptin contamination
The Food and Drug Administration (FDA) recently reported the detection of a nitrosamine impurity (Nitroso-STG-19, known as NTTP) in samples of sitagliptin. NTTP belongs to the nitrosamine class of compounds, some of which are classified as probable or possible human carcinogens. Prior to the announcement, there were no data directly evaluating the carcinogenic potential of NTTP. Currently the acceptable intake of NTTP is 37 ng per day. Further FDA evaluation determined that exposure to 246.7 ng per day of NTTP presents minimal additional cancer risk when compared to a lifetime exposure to NTTP at the 37 ng per day level. The FDA will determine on a case-by-case basis whether samples with levels between 37-246.7 ng per day should be released for distribution. As such, the FDA is currently allowing the temporary distribution of sitagliptin containing NTTP up to 246.7 ng per day. The FDA recommends that clinicians continue prescribing sitagliptin when clinically appropriate to avoid interruption in patient’s treatment. Nitrosamine contamination detected in metformin resulted in recalls in 2020 and 2022, leading to shortages and leaving patients and providers seeking a comparable alternative.
Sitagliptin, a Dipeptidyl Peptidase 4 (DPP-4) Inhibitor (Januvia; Merck & Co.), is an oral hypoglycemic agent that is used to treat adults with type 2 diabetes mellitus as monotherapy or in combination with metformin (Janumet, Janumet XR) as an adjunct to diet and exercise. Januvia was approved by the FDA in October 2016. It was not stated if contaminated samples came from Merck or a third-party manufacturer.
Prepared on behalf of the PES Drug & Therapeutics committee by Dania Al-Hamad and Kristal Matlock
Last updated 11/08/22