Table 3.
Interim limit criteria of nitrosamines in pharmaceuticals.
|
Drug |
Maximum daily dose (mg/day) | Acceptable intake NDMA and NMBA (ng/day)Π |
Acceptable intake NDMA and NMBA (ppm)≠ |
Acceptable intake NDEA, DIPNA, and EIPNA (ng/day)Π | Acceptable intake NDEA (ppm) ≠ | Acceptable intake MNP (ng/day) | Acceptable intake MNP (ppm) |
|---|---|---|---|---|---|---|---|
| Valsartan | 320 | 96 | 0.3 | 26.5 | 0.083 | – | – |
| Losartan | 100(US) 150(EMA) |
96 96 |
0.96* 0.64** |
26.5 26.5 |
0.27* 0.177** |
– - |
– - |
| Irbesartan | 300 | 96 | 0.32 | 26.5 | 0.088 | – | – |
| Azilsartan | 80 | 96 | 1.2 | 26.5 | 0.33 | – | – |
| Olmesartan | 40 | 96 | 2.4 | 26.5 | 0.66 | – | – |
| Eprosartan | 800 | 96 | 0.12 | 26.5 | 0.033 | – | – |
| Candesartan | 32 | 96 | 3.0 | 26.5 | 0.83 | – | – |
| Telmisartan | 80 | 96 | 1.2 | 26.5 | 0.33 | – | – |
| Metformin | 3000 | 96 | 0.032 | – | – | – | – |
| Rifampin | 600 | – | – | – | – | 96 | 0.16 |
If multiple nitrosamines are present in pharmaceuticals, the sum of nitrosamines must be lower than 26.5 ng/day (based on the AI of the most toxic nitrosamine (US-FDA).
Π
The acceptable intake defines the daily exposure to a compound such as NDMA, NDEA, NMBA, DIPNA, and EIPNA that raises the cancer risk to approximately 1:100,000 after 70 years of exposure; ≠ These values are based on the maximum daily dose given on the drug label; * US FDA limit criteria; **EMA limit criteria.