The FDA has asked drugmakers to pull all prescription and over-the-counter products based on ranitidine off the market immediately, after a review failed to alleviate concerns about a cancer risk.
The move extends voluntary recalls last year by several drugmakers – including Sanofi, Sandoz and the drug’s original developer GlaxoSmithKline – which were implemented after preliminary investigations last summer suggested a carcinogenic impurity was present in a range of ranitidine products.
Now, the US regulator says new evidence from its probe into the nitrosamine contaminant known as N-nitrosodimethylamine (NDMA) shows that the level increases in some ranitidine products over time when stored at room temperature.
That “may result in consumer exposure to unacceptable levels of this impurity,” it said, as it implemented a ban on new and existing prescriptions for the gastrointestinal drug, commonly known as Zantac and used to treat conditions like heartburn.
Low levels of NDMA are ingested in the diet as the substance is found in food and water, but not at levels expected to cause an increase in cancer risk.
“We didn’t observe unacceptable levels of NDMA in many of the samples that we tested,” said Janet Woodcock, who leads the FDA’s Centre for Drug Evaluation and Research (CDER),
“However, since we don’t know how or for how long the product might have been stored, we decided that it should not be available to consumers and patients unless its quality can be assured,” she added.
Testing found that NDMA increased during normal storage conditions, and that there was a bigger rise if samples were exposed to higher temperatures during distribution and handling by patients.
Put simply, “the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA,” according to the FDA.
The FDA has been investigating NDMA and other nitrosamine impurities in blood pressure and heart failure medicines called angiotensin II receptor blockers or ‘sartans’ since last year, and is also looking into levels in diabetes drug metformin.
Meanwhile, in Europe the CHMP has also asked manufacturers of all drugs considered at risk of NDMA impurities to review their products and report the outcome by 1 October this year.
The FDA is advising consumers to stop taking any OTC ranitidine products they may have and dispose of them at home.
They should also consider using other approved OTC products that have similar uses. So far, NDMA hasn’t been found in in famotidine, cimetidine, esomeprazole, lansoprazole or omeprazole, which are all alternative treatments for heartburn.
People prescribed ranitidine should seek medical advice before stopping treatment, it adds.