Coadministration of rilpivirine (150 mg once daily) and darunavir/ritonavir increased rilpivirine AUC, Cmin and Cmax by 130%, 178% and 79%, respectively. There was no change in darunavir AUC or Cmax, but Cmin decreased by 11%. Boosted darunavir and rilpivirine can be used without dose adjustments.

No dosage adjustments are recommended when darunavir/ritonavir is co-administered with rilpivirine. Coadministration of rilpivirine (150 mg once daily) and darunavir/ritonavir (800/100 mg once daily) was studied in 14-15 subjects. Darunavir Cmax, AUC and Cmin decreased by 10%, 11% and 11%, respectively. Rilpivirine Cmax, AUC and Cmin increased by 79%, 130% and 178%, respectively

Concomitant use of rilpivirine with ritonavir-boosted PIs causes an increase in the plasma concentrations of rilpivirine, but no dose adjustment is required.  Coadministration of darunavir/ritonavir (800/100 mg once daily) and a higher than the recommended dose of rilpivirine had no effect on darunavir AUC or Cmax, but decreased Cmin by 11%.  Rilpivirine AUC, Cmin and Cmax increased by 130%, 178% and 79%, respectively, due to inhibition of CYP3A enzymes.

Concomitant use of rilpivirine with darunavir/ritonavir may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). No dose adjustment is required when rilpivirine is co-administered with darunavir/ritonavir.  Coadministration of rilpivirine (150 mg once daily) and darunavir/ritonavir (800/100 mg once daily) was studied in 14 subjects.  Rilpivirine Cmax increased by 79% and AUC and Cmin increased by 2.3- and 2.78-fold, respectively. Darunavir Cmax, AUC and Cmin decreased by 10%, 11% and 11%, respectively.

Coadministration of rilpivirine (25 mg, once daily) and darunavir/ritonavir (800/100 mg, once daily) was studied in a parallel trial (RPV alone n=15, RPV+DRV/r n=14) in HIV positive adolescent patients aged 12-23 years old. Rilpivirine AUC, Cmax and C24 increased by ~183%, ~179% and ~229, respectively. No changes in darunavir/ritonavir pharmacokinetics were detected. Four patients in this study had a rilpivirine Cmax concentration associated with increased risk of QTc prolongation in clinical trials. Currently the manufacturer does not recommend a dosage adjustment when rilpivirine and darunavir/ritonavir are used in combination. The authors suggest more closely monitoring QTc might be considered in patients prescribed this combination, especially if they are prescribed multiple medications with QTc prolonging effects. Of note, this study reported a sex-difference, with females having a higher rilpivirine AUC and C24 than males when coadministered darunavir/ritonavir.

Coadministration of rilpivirine (150 mg once daily) and darunavir/ritonavir (800/100 mg once daily) was studied in 14 HIV-negative subjects.  Rilpivirine Cmax increased by 79% and AUC and Cmin increased by 2.3- and 2.78-fold, respectively. Darunavir Cmax, AUC and Cmin decreased by 10%, 11% and 11%, respectively.