The active pharmaceutical ingredient (API) in Macleods’ losartan potassium hydrochlorothiazide tablets, indicated for the treatment of hypertension, was found to have trace amounts of the possible carcinogen N-nitrosodiethylamine (NDEA) and is being recalled by the Mumbai-based company.
Losartan tablets being recalled by Macleods were manufactured by Hetero Labs, a pharmaceutical company based in Hyderabad, India, which previously faced regulatory issues after NDEA was found in a batch of losartan in September 2018.
Camber Pharmaceutical also recalled losartan tablets manufactured by Hetero Labs, when NMBA impurity was discovered in the API. N-Nitroso N-Methyl 4-aminobutyric acid (NMBA) is also a possible carcinogen and is associated with other nitrosamine impurities that have been found in sartan products, such as NDEA.
NBMA is the latest impurity to be found within sartan products and has opened the ongoing investigations regulatory agencies are running.
While Camber has not received any reports of adverse events, it has issued a recall on 87 lots of its losartan tablets.
Macleods also stated that it has not received any reports of adverse events related to the recalled lot. The tablets were distributed nationwide by the pharmaceutical company’s distributor.
Sartan medications have been facing regulatory investigations regarding possible carcinogenic impurities as NDEA and N-nitrosodimethylamine (NDMA) have been identified in valsartan, losartan, and other sartans produced by other companies.
In July 2018, the European Medicines Agency (EMA) announced the recall of the heart-medication valsartan supplied by the Chinese API manufacturer Zhejiang Huahai Pharmaceuticals. At the time of the recall, the EMA suggested that the impurity could have been introduced into the active substance throughf changes made to the way the ingredient is manufactured.
In February 2019, the European Medicines Agency (EMA) found in its investigation into sartan medicines, including losartan and valsartan, and moved to require companies to review processing procedures and prove products are without impurities.
At the time of the investigation, the EMA stated, “It is now known that these impurities can form during the production of sartans that contain a specific ring structure known as a tetrazole ring under certain conditions and when certain solvents, reagents, and other raw materials are used.”
Impurities that can develop during this process include NDMA, NDEA, NMBA, N-Nitrosoethlisoproplamine (EPINA), and N-Nitrosodiisopropylamine (DIPNA).