The recall of -sartans (part 1)

The past few months witnessed the recall of several medicines (notably in the US) as these contained amounts of nitrosamines (specifically, N-Nitrosodimethylamine (NDMA), N-Nitroso-N-methyl-4-aminobutyric acid (NMBA), N-Nitrosodiethylamine (NDEA)), all suspected of being carcinogens according to International Agency for Research on Cancer (IARC). These nitrosamines were detected in certain angiotensin II receptor blockers (ARBs; prescribed for multiple conditions such as hypertension and heart failure) having the "-sartan" active ingredient, viz., irbesartan, losartan, and valsartan. The contamination had occurred during the production processes (the first was seen in products from Zhejiang Huahai Pharmaceutical Co. Ltd) (this will be elaborated in my post next week). The presence of the nitrosamines led to the recall of the -sartans and patients resorted to replacements... until last week.

Last Thursday, the US Food and Drug Administration (FDA), via FDA Commissioner Scott Gottlieb and Janet Woodcock (Center for Drug Evaluation and Research), identified 40 generics that are free of nitrosamines and, thus, safe for ingestion. At the same time, they also urged patients to take the impure batches of losartan. Their reasoning is as follows:
1. The recall of impure medicines led to the shortage of pure medicines as the manufacturers struggled to keep up with the demand
2. For a patient having no access to the pure medicines and not taking any medicine for their condition, the risk from other health complications (such as stroke or heart failures) cannot be ignored
3. The impure batches of losartan have negligible amounts of nitrosamines that may not increase the risk for cancer if taken for a short time

Therefore, in their opinion, it is in the best interests of patients to take the impure losartans until the shortage is resolved in approximately six months. The pros (regulating blood pressure and decreasing the probabilities of heart failures or strokes) outweigh the cons (cancer risk).

FDA's list of pure generics and their recommendation to take impure losartan are not without flaws. Regarding the list, the onus is in on the doctors and pharmacies to ensure that the prescribed (and dispensed) medicine is one of those. At the same time, it would be in the best interests of the patients (or their families) to check the prescription against the list. Regarding the temporary use of impure losartan, whilst this would make sense given the cons, what would be the outcome in vulnerable patients? Furthermore, what would be the outcome if the patient has been taking impure -sartans for several years? For a patient recently prescribed -sartans, the carcinogenic risk might be low; this would not hold for someone having taken the impure -sartans for years. These are arguments that both doctors and the FDA ought to consider.

Nonetheless, for any patients taking a -sartan based medicine, the first port of call ought to be their doctor and asking for a replacement. And, regardless of what the doctor prescribes and what the pharmacy delivers, it is imperative to check against FDA's acceptable list of nitrosamine-free ARBs.

Sources:

FDA's list: https://www.fda.gov/Drugs/DrugSafety/ucm634620.htm

https://www.fda.gov/Safety/Recalls/ucm625492.htm

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm635251.htm

https://www.drugs.com/drug-interactions/losartan.html

https://www.webmd.com/hypertension-high-blood-pressure/news/20190405/fda-issues-list-of-safe-blood-pressure-meds

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