ate tenofovir, in vivo inhibition of OAT1 is unlikely. Inhibition of OAT3 has not been studied in vivo. Dolutegravir may increase plasma concentrations of medicinal products in which excretion is dependent upon OAT3.
Rilpivirine 25 mg once daily is not likely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes.
Rilpivirine inhibits P-gp in vitro (IC50 is 9.2 μM). In a clinical study, rilpivirine did not significantly affect the pharmacokinetics of digoxin. However, it may not be completely excluded that rilpivirine can increase the exposure to other medicinal products transported by P-gp that are more sensitive to intestinal P-gp inhibition, e.g. dabigatran etexilate.
Rilpivirine is an in vitro inhibitor of the transporter MATE-2K with an IC50 of < 2.7 nM. The clinical implications of this finding are currently unknown.
Interaction table
Selected established and theoretical interactions between dolutegravir, rilpivirine and co-administered medicinal products are listed in Table 1.
(increase is indicated as “↑”, decrease as “↓”, no change as “↔”, area under the concentration versus time curve as “AUC”, maximum observed concentration as “Cmax”, concentration at end of dosing interval as “C”).
Table 1: Drug Interactions
Medicinal products by therapeutic areas
Interaction
Geometric mean change (%)
Recommendations concerning co-administration
Antiviral active substances
Tenofovir disoproxil / Dolutegravir1
Tenofovir disoproxil / Rilpivirine1,2
Dolutegravir ↔
AUC ↑ 1%
Cmax ↓ 3%
C ↓ 8%
Tenofovir ↔
Rilpivirine
AUC ↔
Cmin ↔
Cmax ↔
Tenofovir
AUC ↑ 23%
Cmin ↑ 24%
Cmax ↑ 19%
No dose adjustment is required.
Tenofovir alafenamide / Dolutegravir
Tenofovir alafenamide / Rilpivirine1
Dolutegravir ↔
(Not studied)
Rilpivirine ↔
No dose adjustment is required.
Lamivudine/ Dolutegravir
Lamivudine/ Rilpivirine
Dolutegravir ↔
Rilpivirine ↔
(Not studied)
No dose adjustment is required.
Entecavir/ Dolutegravir
Entecavir/ Rilpivirine
Dolutegravir ↔
(Not studied)
Rilpivirine ↔
(Not studied)
No dose adjustment is required.
Boceprevir/ Dolutegravir1
Boceprevir/ Rilpivirine
Dolutegravir ↔
AUC ↑ 7%
Cmax ↑ 5%
C ↑ 8%
Boceprevir ↔
(historical controls).
Rilpivirine ↑
(Not studied, inhibition of CYP3A enzymes).
No dose adjustment is required.
Daclatasvir/ Dolutegravir1
Daclatasvir/ Rilpivirine
Dolutegravir ↔
AUC ↑ 33%
Cmax ↑ 29%
C ↑ 45%
Daclatasvir ↔
Rilpivirine ↔
No dose adjustment is required.
Simeprevir/ Dolutegravir
Simeprevir/ Rilpivirine
Dolutegravir ↔
Rilpivirine ↔
AUC ↔
Cmin ↑ 25%
Cmax ↔
Simeprevir ↔
AUC ↔
Cmin ↔
Cmax ↑ 10%
No dose adjustment is required.
Sofosbuvir / Dolutegravir1
Sofosbuvir / Rilpivirine
Dolutegravir ↔
(Not studied)
Rilpivirine ↔
AUC ↔
Cmin ↔
Cmax ↔
Sofosbuvir ↔
AUC ↔
Cmax ↑ 21%
Sofosbuvir metabolite GS-331007 ↔
AUC ↔
Cmax ↔
No dose adjustment is required.
Ledipasvir/Sofosbuvir / Dolutegravir1
Ledipasvir/S |
