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.