FDA and EMA tell heart medicine makers to test for 'cancer-causing' impurities

Manufacturers of heartburn medications in both the US and Europe are being told by regulatory agencies to test for potential cancer-causing impurities.

In July 2018, the FDA discovered that certain heart and blood pressure medications, known as Angiotensin II receptor blockers (ARBs), may contain chemicals known as nitrosamines, which when taking for long periods of time, can cause cancer.

More so, last year, the European Medicines Agency (EMA) found that a number of blood pressure medicines known as ‘sartans’ included nitrosamine impurities, leading to product recalls and a new set of manufacturing requirements for those medicines.

Since July 2018, the FDA has recalled almost 40 ARBs from the market and has issued regulatory guidance

Now, the FDA has launched an investigation to understand the cause of nitrosamine impurities in common heartburn medications. The FDA has asked manufacturers of Zantac (ranitidine) and nizatidine to test for N-nitrosodimethylamine (NDMA) impurities – a chemical form of nitrosamine – and send their samples to the FDA.

If manufacturers discover batches contain NDMA above the acceptable daily intake limit (96 nanograms per day or 0.32 parts per million for ranitidine), then they should inform the FDA and not release the batch onto the market.

Whilst the FDA has determined that ranitidine doesn’t form NDMA in typical stomach conditions, the agency still needs to fully assess how ranitidine and nizatidine behave in the human body. The FDA believes there may be a link between the presence of nitrates and the formation of NDMA in the body if ranitidine or nizatidine are present. As such, consumers taking these drugs should consider limiting their intake of processed meats and preservatives such as sodium nitrate, since they contain nitrates.

The EMA in response has outlined a three-step process for manufacturers to follow so they can identify and control nitrosamine and NDMA impurities. The agency is asking companies to complete a risk assessment of products potentially containing or contaminated with NDMA by 26 April 2020.

Manufacturers in Europe should also perform further confirmatory testing on products identified to be at risk of NDMA and report their findings to the EMA as soon as possible.

The EMA has set an initial deadline of 26 September 2022 for manufacturers to complete the task by but may shorten the date if a higher risk to public health is found.