The combination of Eviplera and H2-receptor antagonists should be used with particular caution as co-administration may cause significant decreases in rilpivirine plasma concentrations (reduced absorption, increase in gastric pH). Only H2-receptor antagonists that can be dosed once daily should be used. A strict dosing schedule with intake of the H2-receptor antagonists at least 12 hours before or at least 4 hours after Eviplera should be used. The interaction between famotidine and emtricitabine or tenofovir disoproxil has not been studied. Coadministration of famotidine (40 mg single dose taken 12 hours before rilpivirine) and rilpivirine decrease rilpivirine AUC by 9% and had no effect on Cmax. Coadministration of famotidine (40 mg single dose taken 2 hours before rilpivirine) and rilpivirine decreased rilpivirine AUC and Cmax by 76% and 85%. Coadministration of famotidine (40 mg single dose taken 4 hours after rilpivirine) and rilpivirine increased rilpivirine AUC and Cmax by 13% and 21%. [These interaction studies have been performed with a dose higher than the recommended dose for rilpivirine hydrochloride assessing the maximal effect on the co-administered medicinal product. The dosing recommendation is applicable to the recommended dose of rilpivirine of 25 mg once daily.]

Coadministration of RPV with drugs that increase gastric pH may decrease plasma concentrations of RPV and loss of virologic response and possible resistance to RPV or to the class of NNRTIs. Use of RPV with H2-receptor antagonists requires staggered administration. Administer H2-receptor antagonists at least 12 hours before or at least 4 hours after COMPLERA. Famotidine taken 12 hours before rilpivirine or 4 hours after rilpivirine did not affect rilpivirine concentrations. Rilpivirine concentrations decreased when famotidine was taken 2 hours before rilpivirine. Coadministration of famotidine (40 mg single dose) and rilpivirine (150 mg single) was studied in 4 subjects. Famotidine taken 12 hours before rilpivirine decreased rilpivirine Cmax and AUC by 1% and 9%. Famotidine taken 2 hours before rilpivirine decreased rilpivirine Cmax and AUC by 85% and 76% (n=23). Famotidine taken 4 hours after rilpivirine increased rilpivirine Cmax and AUC by 21% and 13%. [The interaction studies have been performed with a dose higher than the recommended dose for RPV (25 mg once daily) assessing the maximal effect on the coadministered drug.]

Coadministration of rilpivirine (150 mg single dose) and famotidine (40 mg single dose) was studied in 24 HIV-negative subjects. When famotidine was administered 2 hours before rilpivirine, the Cmax and AUC of rilpivirine decreased by 85% and 76%, respectively (data from 23 subjects). Coadministration of famotidine 12 hours before rilpivirine decreased rilpivirine Cmax and AUC by 1% and 9% respectively. Coadministration of famotidine 4 hours after rilpivirine increased rilpivirine Cmax and AUC by 21% and 13%, respectively.