Lab urges FDA to suspend ranitidine sales due to degradation risk
Regulators targeted Zantac and other ranitidine and nizatidine medicines last year, after receiving reports of batches being contaminated with nitrosamines, the carcinogenic impurity that previously triggered the recalls of sartan products. In December 2019, the US Food and Drug Administration (FDA) asked manufacturers to test all lots for N-nitrosodimethylamine (NDMA) before releasing them.
Since then, companies including Glenmark and Mylan have voluntarily recalled ranitidine and nizatidine medicines over concerns they may contain unacceptable levels of NDMA. However, the FDA is yet to force manufacturers to take all ranitidine and nizatidine medicines off the market.
Emery thinks that needs to change. The contract research laboratory organization made its case for tougher action against ranitidine medicines in a citizen petition that set out data it has generated on the products.
Responding to evidence that ranitidine may be heat unstable, Emery put the active ingredient and the Zantac Cool Mint brand through stability studies. Ranitidine kept at 70°C breached the safe limit for NDMA in less than one week, raising concerns that products that appear safe when they leave a manufacturing plant may be contaminated with potentially dangerous levels of the carcinogen when taken by consumers.
Levels of NDMA in Zantac Cool Mint kept at 70°C and ranitidine stored at 25°C remained below the limit over the course of the 14-day study. However, Emery thinks the nature of the ranitidine supply chain mean those data only offer limited reassurance.
Emery wrote, “Significantly elevated temperatures can occur within closed vehicles during transportation and during storage of the drug, because there is no requirement for ranitidine to be cold chained. The drug is very likely exposed to elevated temperatures during shipment and commercial storage as well as post-purchase storage by consumers.”
Those fears led Emery to ask the US FDA to recall and suspend the sale of all ranitidine medicines and warn consumers about the heat instability risk.
Pulling all ranitidine medicines from the market would ensure consumer safety while the FDA and manufacturers work to revise regulations and processes in light of the concerns about the instability of ranitidine.
When ranitidine returns to the market, Emery thinks it should be a prescription-only medicine that is shipped in temperature-controlled vehicles. Given the potential for NDMA to accumulate after a batch is released, Emery wants dispensing pharmacies to test for levels of the impurity.