Bioequivalence and Bioavailability Forum

Dear BE Proff:
As per SBOA-
Age was a predictive covariate on CLNR/F (non-renal) clearance in the AF PPK analysis. Based on the PPK analysis, a 50 year old subject would have a 13.4% decrease while an 80 year old subject would have a 15.7% increase in steady state exposures relative to the typical 65 year old subject. Given the modest differences in exposure described above between the young and elderly subjects there is no basis for dosage adjustment.

The effect of gender was evaluated in a prospectively-designed trial that indicated there was no clinically meaningful difference in apixaban PK between males and females (CV185022).

The lower exposure in the high weight group (≥ 120 kg) did not result in loss of efficacy compared to warfarin. Further, a lower dose of 2.5 mg BID is proposed for low weight (≤ 60 kg) patients who were at higher risk for bleeding (defined previously) to over come increased bleeding risk. Given the favorable safety and tolerability profile in the Phase 3 studies, no dosage adjustment is proposed on the basis of body weight alone.

Regards,
Divyen Shah