Conclusion
This study demonstrated an increased risk of bleeding in Asian patients
taking simvastatin concomitantly with rivaroxaban, suggesting potential
clinically relevant pharmacokinetic and pharmacodynamic interactions
between the two drugs. Current European guideline suggests no notable
anticipated effects of atorvastatin on the area-under-the-curve of
rivaroxaban, and does not recommend a need for dose adjustment of the
DOAC [8], while simvastatin was not mentioned. We suggest that the
drug-drug interactions between rivaroxaban and simvastatin should be
further investigated using physiologically-based pharmacokinetic
modeling. The mechanistic explanation of the interaction could hold
important clues towards concomitant use of drugs of similar disposition
profile, particularly when DOAC effects or plasma concentrations are not
routinely measured nor readily accessible.