Heart-burn for pharma firms: After Valsartan, FDA red-flags Ranitidine for cancer-causing impurity

PT Jyothi Datta Mumbai | Updated on September 17, 2019 Published on September 17, 2019

All eyes on DCGI to see if it echoes the alert, since over 180 variants sell in India

First, the alarm was sounded for the presence of a “probable” cancer-causing substance in Valsartan, used to treat blood pressure and heart failure. And now, a similar concern has been expressed by the United States Food and Drug Administration (USFDA) on heart-burn drug Ranitidine.

Over the weekend, the USFDA said that “some Ranitidine medicines, including some products commonly known as the brand-name drug Zantac, contain a nitrosamine impurity called N-nitrosodimethylamine (NDMA) at low levels.” NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on results from laboratory tests, the regulatory authority said. And while the agency was working with international regulators and industry to determine the source of this impurity in Ranitidine, it did not stop people from taking the medicine and advised them to talk to their doctors if they wished to discontinue it.

In India, Ranitidine has multiple producers, as did Valsartan. And the spotlight is on the Drug Controller General of India (DCGI) to see how it advises doctors prescribing these medicines.

“The impurity is minimal, but the DCGI needs to get it checked and get pharmaceutical companies to submit data on these drugs,” said Ravi Wankhedkar, former President of the Indian Medical Association. There has been no advisory to doctors yet from the drug regulator’s office, he told BusinessLine, adding that the situation was similar with Valsartan. Doctors continue to to prescribe both drugs, he added.

The size of the Ranatidine market is pegged at ₹730 crore a year (including combinations of the drug), with over 180 generic versions in the market, according to data from AIOCD-AWACS. A host of companies including Cadila Pharma, GlaxoSmithKline, JB Chemicals and Zydus Cadila sell versions of the drug. Interestingly, Sanofi, which sells Zantac globally, does not sell it in India.

The USFDA’s red-flag on Valsartan, too, saw several drug regulators issue cautionary directives.

In India, the Valsartan market was pegged at ₹263 crore a year, with over 50 manufacturers, including Novartis, Cipla, Lupin and Torrent, making generic versions and combinations.

Carcinogen alert

NDMA is an environmental contaminant found in water and foods. In the case of Valsartan, the impurity trail seemed to trace back to the active pharmaceutical ingredient sourced largely from China and India. Companies including Hetero and Aurobindo recalled their products.

The FDA action on Ranitidine came about following an investigation of NDMA and other nitrosamine impurities in blood pressure and heart failure medicines called Angiotensin II Receptor Blockers (ARBs) since last year. In the case of ARBs, the FDA has recommended recalls as it discovered unacceptable levels of nitrosamines.

The FDA is evaluating whether the low levels of NDMA in Ranitidine pose a risk to patients. “Patients should be able to trust that their medicines are as safe as they can be and that the benefits of taking them outweigh any risk to their health. Although NDMA may cause harm in large amounts, the levels the FDA is finding in Ranitidine from preliminary tests barely exceed amounts you might expect to find in common foods,” it said.

Published on September 17, 2019
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