Metamizole is a very old product. Based on some experience I trust that - at least for Europe - many API suppliers hold CEP prior to nitrosamine Guideline. So no discussion on nitrosamines and especially on NDSRIs. I am pretty curious about any API supply issues may be faced now…
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I’m also quite curious about how this situation will unfold, especially considering the limited number of MTZ suppliers, no more than two. From experience, I believe the major challenge will lie in the final product rather than the API itself.
Pharma. companies in Brazil were expected to complete their nitrosamine risk assessment portfolios by June 2025, as per ANVISA’s guidelines. MTZ is a significant product in the Brazilian market, and with dengue cases on the rise, I assume ANVISA does not foresee a supply shortage. That makes any developments around MTZ particularly interesting.
What intrigues me is the apparent lack of awareness or new information regarding MTZ’s nitrosamine impurity. The MTZ impurity C is accepted at relatively high levels in the final product. If companies are justifying this based on older in vivo studies (as mentioned by @Igor ), and agencies are accepting these justifications without scrutiny, it could set a concerning precedent.
The studies being referenced are not particularly robust. One is essentially a summary from an annual meeting with no raw data, and the other builds on that to present teratogenicity findings—if I’m recalling correctly. There are also a few Ames tests involving NMAA, but the results vary and don’t fully meet regulatory expectations. One article even mentions a recent Ames test conducted by a private company, but the results haven’t been disclosed.
This limited availability of data and reliance on older studies does raise some important questions about the robustness of current risk assessments and how safety is being evaluated.
It’s certainly a topic worth following closely, and I’m interested to see how the conversation and regulatory perspectives evolve over time 
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At least for EU, the available in Vivo studies are not adequate to support or justify non mutagenicity, cause are not in line with current OECD principles.
I agree with you on mixed results of AMES test.
Also limited data on robust read across
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