Legend: As substrates of metabolizing enzymes, cabotegravir and/or
rilpivirine concentrations can be increased or decreased when
co-administered with drugs that either inhibit or induce those enzymes.
The black line shows a theoretical concentration vs time profile of a
drug given in the absence of an enzyme inhibitor or inducer. It would be
anticipated that concentrations would be maintained above
4xPAIC90 prior to the next dose being given. However, in
the presence of an enzyme inducer (blue line), concentrations would be
expected to fall more rapidly and may fall below the
4xPAIC90 prior to the next scheduled dose. The areas
highlighted in grey represents the window of concentrations where
selection for mutant drug-resistant virus is most at risk as
concentrations may be effective against susceptible strains, but not
resistant strains. The bottom blue area represents where concentrations
are expected to be ineffective, and risk of viral rebound occurs.
Conversely, when given with an enzyme inhibitor (top blue line)
concentrations are expected to persist or perhaps accumulate to higher
concentrations, increasing the risk of toxicities or adverse events,
e.g. QTc prolongation with rilpivirine.