Coadministration is contraindicated. Coadministration of rifampicin and rilpivirine had no effect on rifampicin AUC or Cmax; AUC of 25-desacetyl-rifampicin decreased by 9% but there was no change in Cmax. Rilpivirine AUC, Cmin and Cmax decreased by 80%, 89% and 69% (induction of CYP3A). Interaction not studied with tenofovir alafenamide. Coadministration is likely to cause significant decreases in the plasma concentrations of tenofovir alafenamide (induction of P-gp).

Coadministration may decreased rilpivirine concentrations. Coadministration is contraindicated due to potential for loss of virologic response and development of resistance. Coadministration of rifampin (600 mg once daily) and rilpivirine (150 mg once daily) was studied in 16 subjects. Rilpivirine Cmax, AUC and Cmin decreased by 69%, 80% and 89%, respectively. Rifampin Cmax increased by 2% but AUC decreased by 1%; there was no change in 25-desacetylrifampin Cmax, but AUC decreased by 9%. (This interaction study has been performed with a dose higher than the recommended dose for rilpivirine. The dosing recommendation is applicable to the recommended dose of rilpivirine 25 mg once daily.)

The pharmacokinetics of tenofovir alafenamide and tenofovir diphosphate were determined in healthy volunteers following administration of tenofovir alafenamide alone (25 mg once daily, with emtricitabine) and with rifampicin (600 mg once daily). Rifampicin decreased tenofovir alafenamide AUC and Cmax by 55% and 50%. Plasma tenofovir Cmax, C24 and AUC decreased by 65%, 55% and 54% respectively. Intracellular tenofovir diphosphate (i.e. active entity) concentrations Cmax, C24 and AUC decreased by 38%, 43% and 36%, respectively, but AUC was still 4.21-fold higher than that achieved with standard dose tenofovir-DF alone (300 mg once daily). Rifampicin did not alter emtricitabine pharmacokinetics.

The pharmacokinetics of tenofovir alafenamide and tenofovir diphosphate (TDF-DP) were determined following administration of tenofovir alafenamide alone (25 mg once daily, with bictegravir and emtricitabine) or tenofovir alafenamide (25 mg twice daily, with bictegravir and emtricitabine) and rifampicin (600 mg once daily). Following twice daily administration with rifampicin, the plasma AUC of tenofovir alafenamide and its active intracellular metabolite (TFV-DP) were modestly decreased by ~14% and ~24% when compared to tenofovir alafenamide once daily alone. This modest change is not expected to alter the efficacy of tenofovir alafenamide.