In April 2020, the FDA requested the removal of all prescription and over-the-counter (OTC) ranitidine drugs from the market immediately. The request was part of an ongoing investigation of a contaminant known as N-Nitrosodimethylamine (NDMA) in ranitidine medications (commonly known by the brand name Zantac). The agency has determined that the impurity in some ranitidine products increases over time and when stored at higher than room temperatures and may result in consumer exposure to unacceptable levels of this impurity. As a result of this immediate market withdrawal request, ranitidine products will not be available for new or existing prescriptions or OTC use in the U.S.
In a little over a year, the popular drug Chantix has come under scrutiny for a very similar situation. Chantix manufacturer Pfizer is pausing distribution of its anti-smoking treatment, Chantix, after finding elevated levels of cancer-causing agents called nitrosamines in the pills.
The drug maker is recalling 12 lots of the anti-smoking drug.
Pfizer said the impacted lots of Chantix contained levels of nitrosamines that were unacceptable. The FDA has in the past reached out to companies whose drugs had N-nitrosodimethylamine (NDMA) over accepted levels.Chantix was approved by the FDA in May 2006 as a prescription medication which helps adults aged 18 and over quit smoking and is used for 12 to 24 weeks.
In the case of Zantac, it wasn’t until a third party laboratory found high levels of N-Nitrosodimethylamine (NDMA), that the FDA continued its investigation. They found that impurity (NDMA) in some ranitidine products increases over time and when stored at higher than room temperatures and may result in consumer exposure to unacceptable levels of this impurity.
Further testing of ranitidine found that storage of the drug for prolonged periods of time or at higher than room temperatures significantly increased the levels of NDMA. Also, according to the FDA, “The testing also showed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA. These conditions may raise the level of NDMA in the ranitidine product above the acceptable daily intake limit.”
Initially approved in 1983, Zantac has been one of the most popular drugs on the market worldwide. Glaxo aggressively marketed the safety of the drug, which resulted in $1 billion total Zantac sales in December of 1986. Since that time various pharmaceutical companies have acquired the marketing rights to Zantac including: Glaxo, Warner-Lambert, Pfizer, Boehringer, and finally Sanofi in 2017.
In spite of Zantac’s popularity and the emergence of generic equivalents, the pharmaceutical companies marketing the antacid drug knew about the drug’s dangers, especially its link to cancer.
A 2011 scientific study found that, out of eight pharmaceuticals that were observed, “ranitidine showed the strongest potential to form N-nitrosodimethylamine (NDMA)” when present in drinking water during chloramine disinfection, and that “ranitidine gave a much higher yield of NDMA in the present study than reported in [previous] literature.
In 2016, a peer reviewed study in the scientific journal Carcinogenesis found an alarming 400 fold increase in the quantity of NDMA in urine excreted by the patient during a 24 hour period after ingestion of the drug.
We are in the early stages of the Chantix investigation, so it is difficult to say if that drug will experience the same difficulties and associated medical issues as Zantac.