Laboratory analysis of varenicline products
FDA continues to investigate the presence of the N-nitroso-varenicline impurity in varenicline. Varenicline is a prescription drug used for smoking cessation. FDA has identified levels of N-nitroso-varenicline above FDA’s acceptable intake limit in some samples of varenicline finished drugs.
FDA is posting its laboratory results in the table below showing N-nitroso-varenicline levels in varenicline products currently available for the U.S. market. Testing of varenicline is still ongoing, and FDA posted its analytical method used in laboratory testing.
For reference, consuming up to the acceptable intake limit, 37 nanograms, of N-nitroso-varenicline per day is considered reasonably safe for humans, based on lifetime exposure. N-nitroso-varenicline may increase the risk of cancer if people are exposed to it above the acceptable intake limit and over a long period of time, but a person taking a drug that contains N-nitroso-varenicline at-or-below the acceptable intake limit every day for 70 years is not expected to have an increased risk of cancer. Agency scientists evaluated the risk of exposure to N-nitroso-varenicline at interim acceptable intake levels up to 185 ng per day (92.5 ppm) and determined that it presents minimal additional cancer risk when compared to a lifetime of exposure to N-nitroso-varenicline at the 37 ng per day (18.5 ppm) level.
|Company (Manufacturer)||Product||Lots Tested||N-nitroso-varenicline level in micrograms/tablet (nanograms/tablet)||N-nitroso-varenicline level in parts per million (ppm)|
|Pfizer||Chantix (varenicline) 1mg||EA6080, EC9841, EC9847, EC9848, EX2099, DR5086||0.15-0.47
|Par Pharmaceuticals||Varenicline 1 mg||31960807, 31960801||0.003
|Apotex||APO-Varenicline Tartrate 1 mg)||TG2183, TG2181, TG2182||0.027-0.044
|Apotex||APO-Varenicline Tartrate 0.5 mg||TG2180, TG2178, TG2179||0.014-0.021
As discussed in the July 16, 2021 CDER Statement update, Apotex is distributing Apo-Varenicline, a Canadian-approved drug product, under FDA's temporary exercise of regulatory flexibility and discretion. Par Pharmaceutical’s varenicline product was approved by FDA on August 11, 2021.