Hi, everyone
I am an analyst.
Because of Inderal-LA (Propranolol Hydrochloride) capsules Pfizer recalls, I will study the nitroso-Propranolol in my drug product.
The API vender provide me the report explaining the potency of DNA damaging were similar between NDMA and NO-Propranolol and the acceptance intake should be similar to NDMA, 96 ng/ day.
Do it be correct?
Hi,
the carcinogenic potency of all the beta-blockers is still under discussion.
In Europe. Very recently EMA aknowlegded that:
All the β-blockers have a secondary amine that can undergo nitrosylation under suitable conditions to give the N-nitrosamine derivative.
• Besides carvedilol and nebivolol, all the other β-blockers have bulky (isopropyl, isopropyl with further substitution, or tert-butyl) groups at the α-position to the secondary amine.
• Carvedilol and nebivolol have CH2 groups at both α-positions, however the substituents on both sides of the amino group are large/bulky groups that render considerable steric hindrance.
• It is very likely that these factors reduce the carcinogenic potency of any related Nnitrosamine however it is recognised that further investigation is needed to completely understand this
I remember that the position of each autority (EMA, TGA, U.S.FDA, KFDA, etc) may be different and each authority may accept the proposed limit or ask a tighter limit.
kind regards
The latest EMA Nitrosamine Implementation Oversight Group meeting discussed beta blockers specifically. The industry presentation slides are a must read for anyone working with Propranolol.
Unlike other NDSRIs, an experimental study is available for N-Nitrosopropranolol reported in 1983 by Ilene H. Raisfeld-Danse and Jack Chen from the State University of New York at Stony Brook, New York. As per the published literature, N-Nitrosoproranolol (NNP) is unlikely to be a carcinogen. Therefore, in my opinion, comparing NNP with NDMA is absurd.