FDA Eases Limits on NMBA in Losartan to Prevent Shortage
March 20, 2019 – Amid concerns of a drug shortage, the U.S. FDA will allow certain manufacturers to temporarily distribute losartan products that contain N-Nitroso-N-methyl-4-aminobutyric acid (NMBA) above the interim acceptable limit of 0.96 parts per million (ppm) and below 9.82 ppm.
NMBA is the third nitrosamine identified as an impurity in angiotensin II receptor blockers (ARBs), or “sartan” drugs, in the past year. It is considered a probable human carcinogen, meaning it may cause cancer. The other two nitrosamines identified as ARB impurities, N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) are also considered probable human carcinogens. Although no immediate threat to patients has been identified, the FDA has established interim limits on the presence of NMBA, NDMA, and NDEA in these drugs.
The nitrosamine impurities have led to a series of recalls of losartan-, irbesartan-, and valsartan-containing products since mid-2018. The FDA has been working with manufacturers to address the manufacturing processes believed to be the source of the impurities. However, the extent of the recalls has led to drug shortages (valsartan) and created the possibility for more. In an effort to ensure patient access, the FDA is allowing the distribution of losartan products with an NMBA content of less than 9.82ppm until the impurity issue is resolved. The agency estimates the losartan supply will be replenished and clear of NMBA in approximately six months.