Bioequivalence and Bioavailability Forum

Dear VG

❝ As per the Orange book there are two RLD listed one is for 10 mg and the other is for 20 mg.

May be the two RLD given by FDA due to the different clinical indication for each strength.
“10 mg for: “Prophylaxis of DVT Following Hip or Knee Replacement Surgery”
“15 mg and 20 mg for: Reduction in Risk of Stroke in Nonvalvular Atrial Fibrillation, Treatment of DVT Treatment of PE”

❝ Is there a possibility to have a waiver on the 10 mg strength.

SBOA state that

“Rivaroxaban plasma concentrations increased dose-proportionally after administration of the solution (5 and 10 mg) and this was also observed for the tablets up to a dose of 15mg (Figure 16). With higher tablet doses, dose-dependent but less than dose proportional increases in Cmax and AUC were observed (Page no 22)

Though the USFDA reference product label does not mention anything much on the dose proportionality, the Australian Public Assessment Report for Rivaroxaban concluded that there is a dose proportionality between rivaroxaban 10 mg, 15 mg and 20 mg under fed condition.

So we have to demonstrate BE on 10 mg too under fasting condition only, means fasting and fed study for 20 mg and only fasting for 10 mg strength

Regards

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Edit: Standard quotes restored. [Helmut]