Valisure, an online pharmacy, in a filing to FDA last week said it discovered the carcinogen dimethylformamide (DMF) in the common heart drug valsartan—marking the fourth carcinogen found in the drug.
FDA in July 2018 announced a voluntary recall of several drugs used to treat heart failure and high blood pressure because they tested positive for the organic chemicals N-Nitrosodimethylamine and N-Nitrosodiethylamine, which are impurities the International Agency for Research on Cancer has classified as a probable human carcinogen.
FDA said the carcinogens were chemical byproducts of processing the drugs' active ingredients, which include irbesartan, losartan, and valsartan. FDA said individuals who have taken drugs with those ingredients might have been exposed to trace amounts of the impurities over the past four years because of a change in how companies synthesized the ingredients. The agency said the chemicals would not have been detected during routine inspections because scientists would have had to have known the chemicals would be created by the new manufacturing process, and regulators and drugmakers had just discovered that information.
FDA at the time estimated that one million to two million people might have taken medications containing the impurities, and recommended that physicians and pharmacists give patients alternative treatments.
Pharmacy identities DMF in valsartan still on the market
In a filing submitted to FDA last week Valisure said it has discovered the carcinogen DMF in valsartan, which commonly is combined with other medications into a single pill and has several generic varieties.
According to CNN, DMF is a solvent used in chemical manufacturing and pharmaceutical production. DMF is used to break down the initial raw materials within a drug, but the substance is supposed to mostly disappear by the time the pill is sold.
The World Health Organization in 2018 classified DMF as a probable carcinogen, and CDC has said DMF can cause cancer, liver damage, and other health issues.
Valisure said it found DMF in valsartan made by five of the six drugmakers it tested, including Novartis, which makes a brand-name version of valsartan called Diovan. According to Bloomberg, some of the drugs that showed traces of DMF were included on FDA's list of recommended alternatives following the July 2018 voluntary recall.
According to Eric Althoff, a spokesperson for Novartis, the drugmaker does not use DMF in making Diovan, however it "cannot currently fully exclude the possibility that traces of DMF (within acceptable limits) may have been present in materials" provided to suppliers.
FDA says patients should continue taking medications
Jeremy Kahn, a spokesperson for FDA, said the agency will review the claims, but added that "the amounts of DMF being reported are more than 100 items less than those determined by international standards as the level of concern to patients." According to Kahn, international standards dictate that drugs can contain the equivalent of 8.8 million nanograms of daily exposure to DMF.
FDA said patients should continue taking their blood pressure medications and should consult their physicians about other treatments.
"The risk associated with abruptly discontinuing the use of these important medicines far outweighs the low risk that our scientists estimate to be associated with continuing the medicine until the patient's doctor or pharmacist provides a safe replacement or a different treatment option," Kahn said (Edney, Bloomberg, 6/18; Christensen, CNN, 6/18; Lovelace, CNBC, 6/18; Gibson, CBS News, 6/18).
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