(Reuters) – Online pharmacy Valisure reported that it found a new cancer-causing impurity in some versions of widely prescribed blood pressure medicine valsartan, but U.S. regulators said on Tuesday that the amount in the drugs was well below levels deemed to be potentially harmful.
Connecticut-based Valisure informed the U.S. Food and Drug Administration in a citizen petition https://www.regulations.gov/document?D=FDA-2019-P-2869-0001 last week that it had found through its own testing an impurity called dimethylformamide (DMF) in some batches of the drug. DMF is classified as a probable human carcinogen by the World Health Organization.
The findings were first reported by Bloomberg earlier on Tuesday.
The FDA said it would review the petition, but “it is important to note that the amounts of DMF being reported are more than 100 times less than those determined by international standards as the level of concern to patients.”
Valisure analyzed valsartan from multiple manufacturers including Novartis AG and several generic manufacturers. Valsartan is the generic name of Novartis’ Diovan.
The amount of DMF found ranged from 8 nanograms per pill to over 100,000 nanograms per pill, the pharmacy said. All were significantly below the current permissible level of 8.8 milligrams per day.
In its petition, the pharmacy called the FDA standard too high and asked regulators to lower the acceptable intake limit for DMF to match that of other probable carcinogens that have been found in valsartan – N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA). DMF is widely used in the production of active ingredients for medicines but is classified by the FDA as a Class 2 solvent, which must be “limited in pharmaceutical products because of its inherent toxicity”.
While the FDA has been investigating the presence of certain impurities in a class of hypertension drugs called angiotensin II receptor blockers (ARBs), including valsartan, this is the first time DMF has been linked to the pills.
It is also the first time a possible impurity has been flagged in Diovan, the branded version of valsartan.
Generic valsartan has been recalled by several companies, including Teva Pharmaceutical Industries Ltd and Mylan NV, after a Chinese bulk manufacturer recalled the product from the U.S. market last July after detecting the presence of NDMA.
Novartis said DMF is not used in its internal manufacturing processes for Diovan.
However, the company “cannot currently fully exclude the possibility that traces of DMF (within applicable limits) may have been present in materials of other drug substances suppliers,” Novartis spokesman Eric Althoff said in an emailed statement.
(Reporting by Manojna Maddipatla in Bengaluru and Michael Erman in New York; editing by Bill Berkrot)