Could you please clarify the appropriate daily dose to be considered for nitrosamine risk assessment when the maximum weekly dose is 600 mg?
Should the daily dose be calculated by dividing the weekly dose by 7 days, resulting in a daily dose of approximately 85.7 mg/day, or is there a different approach recommended according to current nitrosamine guidance?
Hi Sreedhar,
There is no specific Nitrosamine guidance available for calculating the MDD or determining the dosage.
The MDD depends on the dosing regimen. If a 600 mg dose is administered as a single dose, followed by a one-week interval before the next dose, the MDD should be considered as 600 mg.
However, if the total 600 mg dose is administered in divided doses over a one-week period, the MDD should be calculated based on the specific dosing regimen.
For further details on the applicable MDD values, you can refer to the relevant SmPC or drug label.
Exactly, you need to understand the dosing regime. If it is a weekly single dose of 600 mg/day, what you may consider is that the total duration of treatment would be shorter, since you would only have 52 dosing days per calendar year. This can be used in the estimation of the total duration of treatment, and have an impact on the interim limit if requried
Calculated the MDD based on relevant PIL or SmPC or drug label. Then do the NI-RA.
Dosing 600 mg single dose/week & 600 mg (daily dose of approximately 85.7 mg/day) - Both are different approach & body response & its clearance (ADME) & difference in the amount of impurities based on the dosing regimen. Hence higher mg in a single dose will be having the higher risk, compare then dividing into 7 days & calculating its 1/7th part. In both case the amount of impurities going in the body and the further ADME Rate is different