Concerns over a cancer-causing impurity in a drug used to treat blood pressure and heart failure have prompted India’s drug regulator to take serious action. “Imports of drugs that contain Valsartan as their active ingredient have been stopped temporarily,” Dr Eswara Reddy, Drugs Controller General of India told THE WEEK. The decision to stop the imports came after the United States Food and Drug Administration issued an alert over the presence of an impurity in drugs that contain Valsartan as an active pharmaceutical ingredient. Valsartan is an angiotensin-II-receptor antagonist used to treat hypertension (high blood pressure), heart attack and heart failure. It is available on its own or in combination with other active substances.
“The US Food and Drug Administration is alerting health care professionals and patients of a voluntary recall of several drug products containing the active ingredient Valsartan, used to treat high blood pressure and heart failure. This recall is due to an impurity, N-nitrosodimethylamine (NDMA), which was found in the recalled products,” it said in a statement issued last month. On August 2, the US FDA expanded its list of recalled drugs too. Several US-based pharmaceutical companies have recalled their products that contain the ingredient Valsartan, where the ingredient was supplied to them by the Chinese company Zhejiang Huahai Pharmaceuticals. The European Medicines Agency is also reviewing drugs containing the impurity. Globally, at least 22 countries have recalled the drug owing to the cancer-causing impurity.
NDMA is classified as a probable human carcinogen, a substance that could cause cancer, based on results from laboratory tests. The presence of NDMA was unexpected and is thought to be related to changes in the way the active substance was manufactured, the statement said. The FDA’s review is ongoing and has included investigating the levels of NDMA in the recalled products, assessing the possible effect on patients who have been taking them and what measures can be taken to reduce or eliminate the impurity from future batches produced by the company.
In India, the DCGI said that a show cause notice had been issued to the Indian agent of the Chinese company, who failed to inform the drug regulator of action taken on the issue. “We have also written to our zonal office in Mumbai to probe the issue further," Reddy added.
“When used in combination with Sacubitril, Valsartan is a very good drug for patients of heart failure. In these patients, it has shown significant reduction in mortality, and is among a new class of drugs to treat the disease. We will not be prescribing it until the impurity is removed. For patients of hypertension, however, there are several other drugs, so Valsartan, by itself, wouldn't be missed much,” said Dr Shuvanan Ray, head of department of cardiology, Fortis Hospital, Anandapur, Kolkata.
In India, the drug is sold in combination with other ingredients by several companies including Novartis, and the Ahmedabad-based Torrent Pharmaceuticals. A spokesperson of Novartis told THE WEEK that the affected products are not marketed in India. “Novartis initiated the recall of defined specific batches of Sandoz Valsartan and Sandoz Valsartan HCT Film coated tablets because of a confirmed impurity above the typically established limit. This is in line with our commitment to meeting the highest quality standards for all of our marketed products and in agreement with the local health authorities. The impurity was identified as N-Nitrosodimethylamine (NDMA). No other Sandoz or Novartis products have been affected by this recall and both Sandoz Valsartan and Sandoz Valsartan HCT Film coated tablets are not marketed in India. All other Novartis products containing Valsartan, including Vymada, use a different API source, manufactured within Novartis, with a different way of producing it, where in the relevant synthesis process this specific impurity is not formed,” the spokesperson said.
Torrent Pharmaceuticals India, that markets the anti-hypertensive drug under the brand name Valzaar, refused to comment on the issue. Valzaar has been recalled in other countries.