Rilpivirine should not be co-administered with rifampicin as significant decreases in rilpivirine plasma concentrations may occur (due to CYP3A enzyme induction), which may result in loss of therapeutic effect of rilpivirine. Coadministration of rifampicin (600 mg once daily) and a higher than the recommended dose of rilpivirine had no effect on AUC or Cmax of rifampicin.  The AUC of 25-O-desacetyl rifampicin decreased by 9%, but Cmax was unchanged. Rilpivirine AUC, Cmin and Cmax decreased by 80%, 89% and 69%, respectively, due to induction of CYP3A enzymes. Rilpivirine must not be used in combination with rifampicin as co-administration is likely to result in loss of therapeutic effect of rilpivirine.

 

Coadministration is contraindicated due to the potential for significant decreases in rilpivirine plasma concentrations due to CYP3A enzyme induction, which may result in loss of virologic response. Coadministration of rilpivirine (150 mg once daily) and rifampicin (600 mg once daily) was studied in 16 subjects. Rilpivirine Cmax, AUC and Cmin decreased by 69%, 80% and 89%, respectively. Rifampicin Cmax increased by 2% and AUC decreased by 1%. There was no change in Cmax of 25-desacetylrifampicin, but AUC decreased by 9%.

Coadministration of rilpivirine (150 mg once daily) and rifampicin (600 mg once daily) was studied in 16 HIV-negative subjects. Rilpivirine Cmax, AUC and Cmin decreased by 69%, 80% and 89%, respectively. Rifampicin Cmax increased by 2% and AUC decreased by 1%. There was no change in Cmax of 25-desacetyl-rifampicin, but AUC decreased by 9%.
van Heeswijk R, et al. The effects of CYP3A4 modulation on the pharmacokinetics of TMC278, an investigational non-nucleoside reverse transcriptase inhibitor. 7th International Workshop on Clinical Pharmacology of HIV Therapy, Lisbon, April 2006, abstract 74.