Rifamycins with rilpivirine
Pharmacokinetic interaction studies between oral rilpivirine and
rifampicin and rifabutin have reported a decrease in rilpivirine
exposure . Coadministration of rifampicin 600 mg with oral rilpivirine
150 mg daily reduced the AUC24h, Cmaxand Cmin of oral rilpivirine by 80%, 69% and 89%,
respectively. There is no in-human data on the interaction with LAI
rilpivirine, but PBPK modelling predicted a 39% decrease in AUC of LAI
rilpivirine in the presence of rifampicin. Increasing the dosing
frequency of LAI rilpivirine was unable to compensate for the
interaction . The significant reduction in exposure to rilpivirine poses
a risk of subtherapeutic concentrations, therefore, coadministration of
oral and LAI rilpivirine with rifampicin is contraindicated .
In another study, coadministration of oral rilpivirine 150 mg once daily
together with rifabutin 300 mg daily was found to reduce the
AUC24h, Cmax, and Cminof oral rilpivirine by 46%, 35%, and 49% respectively . Similarly,
PBPK modelling predicted rifabutin to decrease the AUC and
Cmin of monthly LAI rilpivirine 600 mg by 18% and 19%
respectively. With bimonthly administration of LAI rilpivirine 900 mg,
the decrease in AUC and Cmin was 20% and 21%
respectively . The reduction in rilpivirine exposure resulted in a
prediction of only 20% of individuals achieving the minimum effective
concentration (>50 ng/ml) with monthly dosing and none of
the individuals on the bimonthly dose achieved concentrations above this
limit. Just as the interaction of oral rilpivirine with modest CYP
inducers can be overcome by increasing the dose of oral rilpivirine to
50 mg daily, simulations of dose adjustment by addition of oral
rilpivirine 25 mg daily to the monthly injection of rilpivirine was
shown to overcome the interaction with rifabutin. Rifabutin is however
not widely available in TB endemic areas and thus the utility of this
approach is limited. Also, co-administration of moderate inducers with
LAI cabotegravir and rilpivirine is not currently recommended where
alternatives exist.