In July and August Pfizer voluntarily recalled a total of 16 lots of its smoking-cessation drug, Chantix (varenicline), due to unacceptably high levels of the carcinogen N-nitroso-varenicline, and the Food and Drug Administration (FDA) has taken steps to address the shortage.
The company still hasn’t publicly announced any resolution timeline for its shortage, and a company representative was not available for interviews on the matter. However, in the interim, the US Food and Drug Administration (FDA) has relaxed regulations and turned to drug companies Apotex and Par Pharmaceuticals to help fill the gap.
Currently, the FDA tells patients that the benefit of using recalled Chantix before a replacement is available still outweighs the risks posed by an increased level of N-nitroso-varenicline.
FDA flexes regulations, expedites
As of Jul 16, the FDA has increased its intake limit from 37 nanograms (ng) of N-nitroso-varenicline per day to 185, which the agency says “presents minimal additional cancer risk when compared to a lifetime of exposure to N-nitroso-varenicline at the 37 ng per day level.”
This regulation change has cleared the way for the Canadian-approved product APO-Varenicline Tartrate, made by Apotex, to be sold in the United States. An FDA lab report published Aug 23 found N-nitroso-varenicline levels of 27 to 44 ng per 1-milligram (mg) tablet. Lots of Chantix, on the other hand, had 150 to 470 ng per 1-mg tablet.
According to Apotex Corp, the FDA had reached out regarding the possibility of importing the product and has granted both an approved abbreviated new drug application (ANDA) and an emergency authorization for importation that expires Sep 30.
“Apotex was able to meet the needs of US patients without impacting product supply to Canadian patients,” Jordan Berman, MBA, Apotex vice president of global corporate affairs, business transformation, and strategy, told CIDRAP News. “We accomplished this by modifying our production schedule and increasing the production of this important product to ensure continuity of care.”
The FDA also worked with Par Pharmaceutical on its ANDA for a generic version of the drug, achieving approval Aug 11, “well ahead” of schedule, according to Fierce Pharma. The company launch timeline is still unknown, but the product had favorable results in the FDA lab report, with 3 ng of N-nitroso-varenicline per 1 mg tablet across two tested lots.
Pfizer’s patent for Chantix had expired in May 2020, 14 years after the drug came onto the market. As of Aug 24, the FDA database lists tentative ANDA approvals for Apotex, Teva Pharmaceuticals, Mylan, and Watson Labs, all ranging from May 3, 2013 (Mylan) to Jun 2, 2020 (Apotex).
A tentative approval means that the application meets the key requirements but a marketing requirement is missing, such as a patent or exclusivity issue. Even when this conflict is resolved, final approval is not granted automatically.