Current Edition

FDA clears 40 impurity-free ARBs to ease antihypertensive shortages

  • As part of efforts to resolve ongoing safety issues and maintain supplies of a key high blood pressure drug, the Food and Drug Administration released a list of 40 angiotensin II receptor blockers, or ARBs, that do not contain any known nitrosamine impurities.
  • The agency will keep the list updated, and expects it to continue to grow as further assessments are carried out.
  • According to the FDA’s investigations, the potential carcinogenic contaminants seem to be created when certain chemicals and reaction conditions combine in manufacturing. Reusing solvents and other materials may also play a part.

Since last July, the FDA has been working to understand why nitrosamines have been appearing in some manufacturer’s active pharmaceutical ingredients for the blood pressure medication valsartan, and for other related ARBs.

The nitrosamine impurities, N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA), are both cancer-causing compounds and appear to be generated in certain manufacturing conditions.

The FDA and the European Medicines Agency launched a probe last year after finding active pharmaceutical ingredient of valsartan made by a Chinese manufacturer to be contaminated with NDMA. The investigation spread to other “sartan” drugs, which treat high blood pressure, and eventually found another possible carcinogen, NDEA, to be present.

Drugs chief Janet Woodcock said the agency has issued nearly 40 recalls since then.

But Woodcock warned that patients should not stop taking medicines and the risks remain small, according to a transcript on the FDA’s website.

“Well, first, don’t stop taking your medicine! The risk of exposure to cancer is so much lower than your risk of a heart-related or other problem if you would stop your medicine,” she said.

The aim of the FDA’s list of ARB medications regarded as free from known nitrosamine impurities is to help healthcare providers as they select treatment options for their patients. The list also includes products that remain under investigation, but for which nitrosamine impurities either have not been detected or are below the interim acceptable intake limits.

The agency continues to monitor and recall lots of valsartan-, losartan- and irbesartan-containing tablets as required to maintain patient safety. However, this can lead to shortages —? valsartan tablets are currently in shortage in the U.S., and other ARBs may be at risk of falling into a similar situation.

Regulators are taking steps to fill in gaps as required, though. As an example, the FDA will allow the temporary distribution of specific lots of losartan that contain impurities above the interim acceptable intake limit, for a short period of time.