ISP (Chile) announced the voluntary market withdrawal of Atomoxetine DP (40mg & 80mg) due presence of Nitroso-Atomoxetine

[Naiffer_Host]

This week ANAMDED (National Regulatory Agency from Chile) announced the voluntary recall of all Atomoxetine DP due presence of NDSRIs

Announcement:

Scan24-02-2023-153625.pdf

Smiles: CC1=C(C=CC=C1)O[C@H](CCNC)C2=CC=CC=C2

Smiles: CC1=CC=CC=C1O[C@@H](C2=CC=CC=C2)CCN(N=O)C

[hgajjar]

We can use NNK as point of departure for structure-activity-relationship (SAR) /read-across approach same as Nitroso Duloxetine and Nitroso Fluoxetine

[Naiffer_Host]

Are you suggesting 4-(Methylnitrosoamino)-1-(3-pyridinyl)-1-butanone as surrogate?
SMILES: C1=CN=CC(=C1)C(CCCN(N=O)C)=O

Lhasa Carcinogenicity database: Gold TD50 = 99.9 ng/day ?

[hgajjar]

Yes. EMA has published limit 100 ng/day for both Nitroso Duloxetine and Nitroso Fluoxetine based on NNK.

[Hanimi]

as per the current FDA NDSRI guidance recommendation, N-Nitro Atomoxetine falls under Category-1 with 26.5 ng/day.
Can somebody confirm this assessment?

[Yosukemino]

Hi, @Hanimi.

FDA updated atomoxetine from 26.5ng/day to 100ng/day. Please check the following post.

Updated FDA list of published limits

Hi, guys I want to inform you of the update of the FDA list. In the rev.2, N-nitroso-ciprofloxacin was transferred from the read-across list to the CPCA list. And N-nitroso-atomoxetine was transferred from the CPCA list to the read-across list. 2 N-nitroso-ciprofloxacin Added to Table 1 12/1/2023 2 N-nitroso-ciprofloxacin Deleted from Table 2 12/1/2023 2 N-nitroso-atomoxetine Deleted from Table 1 12/1/2023 2 N-nitroso-atomoxetine Added to Table 2 12/1/2023 N-nitroso-ciprofloxaci…