Table 1.

Interactions between rilpivirine and other drugs

Coadministered drug	Participants	Duration	Dose		PK Rilpivirine			PK Coadministered drug			Comments
			Rilpivirine	Coadministered drug	Cmax	AUC24h	Cmin	Cmax	AUC24h	Cmin
Rifabutin18	18 HIV-negative volunteers	11 days	150 mg qd	300 mg qd	35%	46%	49%	NC	NC	NC	Reduced rilpivirine exposure due to CYP3A4 induction by rifabutin
Rifampicin22	16 HIV-negative volunteers	7 days	150 mg qd	600 mg qd	69%	80%	89%	NC	NC	NC	Reduced rilpivirine exposure due to CYP3A4 induction by rifampicin
Darunavir/ritonavir24	16 HIV-negative volunteers	Session 1 – RIL 11 days Session 2 – DVR/r 22 days, RIL 11 days	150 mg qd	800 mg/100 mg qd	↑79%	↑130%	↑178%	10%	11%	11%	Increased rilpivirine exposure due to CYP3A4 inhibition; the increase is not clinically relevant and no dose modification is recommended
Tenofovir33	15 healthy volunteers	Session 1 – RIL 8 days Session 2 – TDF 16 days, RIL 8 days	150 mg qd	300 mg qd	3%	↑2%	NC	↑21%	↑24%	↑24%	Increase in TDF exposure is not clinically relevant and no dose modification is recommended
Atorvastatin26	16 HIV-negative volunteers	Session 1 – Atorvastatin 4 days Session 2 – RIL 14 days, atorvastatin 4 days	150 mg qd	40 mg qd	NC	NC	NC	↑35%	↑21% (total HMG-CoA reductase activity)	NC	No dosage adjustment needed
Ketoconazole34	16 healthy subjects	11 days	150 mg qd	400 mg qd	↑30%	↑49%	↑76%	15%	24%	66%	Increased RIL exposure due to CYP3A4 inhibition by ketoconazole
Famotidine35	24 HIV-negative subjects	Famotidine administered 2 hours before, 12 hours before and 4 hours after rilpivirine	150 mg qd	40 mg qd	85% (2 hours before)	AUC∞ 76% (2 hours before)	?	NC	NC	NC	Acid suppressing agent such as famotidine reduce bioavailability of RIL and therefore should be adequately space apart when given together
Sildenafil28	16 HIV-negative male volunteers	12 days RIL 75 mg qd and 50 mg sildenafil on day 12	75 mg qd	50 mg one dose	NC	NC	NC	NC	NC	NC	No dosage adjustment needed
Ethinylestradiol and norethindrone27	18 HIV-negative female volunteers	3 oral contraceptive cycles	25 mg qd	Ethinylestradiol 35 μg and norethindrone 1 mg	NC	NC	NC	EST: ↑17% NE: NC	EST: NC NE: NC	EST: NC NE: NC	No dosage adjustment needed
Methadone25	13 HIV-negative volunteers		25 mg qd	60–100 mg dose individualized	NC	NC	NC	R-methadone: 14% S-methadone: 13%	R-methadone: 16% S-methadone: 16%	R-methadone: 24% S-methadone: 21%	Clinical monitoring for methadone withdrawal symptoms is recommended

Abbreviations: AUC_24h, area under the curve over 24 hours; AUC_∞, area under the curve zero to infinity; C_max, maximum concentration; C_min, minimum concentration; DRV, darunavir; EST, ethinylestradiol; NE, norethindrone; NC, no change; P, pharmacokinetics; qd, once daily; RIL, rilpivirine; TDF, tenofovir.