Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

As Eviplera contains emtricitabine, rilpivirine hydrochloride and tenofovir disoproxil, any interactions that have been identified with these active substances individually may occur with Eviplera.
Interaction studies with these active substances have only been performed in adults.

Rilpivirine is primarily metabolised by CYP3A Medicinal products that induce or inhibit CYP3A may thus affect the clearance of rilpivirine (see section 5.2).

Concomitant use contraindicated

Co-administration of Eviplera and medicinal products that induce CYP3A has been observed to decrease the plasma concentrations of rilpivirine which could potentially lead to loss of therapeutic effect of Eviplera (see section 4.3).

Co-administration of Eviplera with proton pump inhibitors has been observed to decrease the plasma concentrations of rilpivirine (due to an increase in gastric pH) which could potentially lead to loss of therapeutic effect of Eviplera (see section 4.3).

Concomitant use not recommended

Eviplera should not be administered concomitantly with other medicinal products containing emtricitabine, tenofovir disoproxil or tenofovir alafenamide. Eviplera should not be administered concomitantly with rilpivirine hydrochloride unless needed for dose adjustment with rifabutin (see section 4.2).
Due to similarities with emtricitabine, Eviplera should not be administered concomitantly with other cytidine analogues, such as lamivudine (see section 4.4). Eviplera should not be administered concomitantly with adefovir dipivoxil.

Didanosine
The co-administration of Eviplera and didanosine is not recommended (see section 4.4 and Table 1).

Renally eliminated medicinal products
Since emtricitabine and tenofovir are primarily eliminated by the kidneys, co-administration of Eviplera with medicinal products that reduce renal function or compete for active tubular secretion (e.g. cidofovir) may increase serum concentrations of emtricitabine, tenofovir and/or the co-administered medicinal products.

Use of Eviplera should be avoided with concurrent or recent use of a nephrotoxic medicinal product.
Some examples include, but are not limited to, aminoglycosides, amphotericin B, foscarnet, ganciclovir, pentamidine, vancomycin, cidofovir or interleukin-2 (also called aldesleukin).

Other NNRTIs
It is not recommended to co-administer Eviplera with other NNRTIs.

Concomitant use where caution is recommended
Cytochrome P450 enzyme inhibitors
Co-administration of Eviplera with medicinal products that inhibit CYP3A enzyme activity has been observed to increase rilpivirine plasma concentrations.

QT prolonging medicinal products
Eviplera should be used with caution when co-administered with a medicinal product with a known risk of Torsade de Pointes. There is limited information available on the potential for a pharmacodynamic interaction between rilpivirine and medicinal products that prolong the QTc interval of the electrocardiogram. In a study of healthy subjects, supratherapeutic doses of rilpivirine (75 mg once daily and 300 mg once daily) have been shown to prolong the QTc interval of the ECG (see section 5.1).

P-glycoprotein substrates
Rilpivirine inhibits P-glycoprotein (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.

Other interactions

Interactions between Eviplera or its individual component(s) and co-administered medicinal products are listed in Table 1 below (increase is indicated as “↑”, decrease as “↓” and no change as “↔”).



Table 1: Interactions between Eviplera or its individual component(s) and other medicinal products

Medicinal product by therapeutic      Effects on medicinal product         Recommendation concerning areas                               levels.                  co-administration with Eviplera Mean percent change in AUC,
Cmax, Cmin
ANTI-INFECTIVES
Antiretrovirals
Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs/N[t]RTIs) Didanosine/Emtricitabine            Interaction not studied.             Co-administration of Eviplera and Didanosine (400 mg once daily)/     Didanosine:                          didanosine is not recommended Rilpivirine1                        AUC: ↑ 12%                           (see section 4.4).
Cmin: N/A
Cmax: ↔                              Increased systemic exposure to didanosine may increase
Rilpivirine:                         didanosine related adverse
AUC: ↔                               reactions. Rarely, pancreatitis and Cmin: ↔                              lactic acidosis, sometimes fatal, Cmax: ↔                              have been reported.
Didanosine/Tenofovir disoproxil     Co-administration of tenofovir       Co-administration of tenofovir disoproxil and didanosine results in disoproxil and didanosine at a dose a 40-60% increase in systemic        of 400 mg daily has been exposure to didanosine.              associated with a significant decrease in CD4+ cell count,
possibly due to an intracellular interaction increasing phosphorylated (i.e. active) didanosine. A decreased dosage of
250 mg didanosine co-administered with tenofovir disoproxil therapy has been associated with reports of high rates of virological failure within several tested combinations for the treatment of HIV-1 infection.



Medicinal product by therapeutic         Effects on medicinal product         Recommendation concerning areas                                    levels.               co-administration with Eviplera Mean percent change in AUC,
Cmax, Cmin
Protease inhibitors (PIs) - boosted (with co-administration of low-dose ritonavir) Atazanavir/Ritonavir/Emtricitabine Interaction not studied.                Concomitant use of Eviplera with Atazanavir/Ritonavir/Rilpivirine      Interaction not studied.             ritonavir-boosted PIs causes an Atazanavir (300 mg once daily)/       Atazanavir:                          increase in the plasma Ritonavir (100 mg once daily)/        AUC: ↓ 25%                           concentrations of rilpivirine Tenofovir disoproxil (245 mg once Cmax: ↓ 28%                              (inhibition of CYP3A enzymes).
daily)                                Cmin: ↓ 26%
No dose adjustment is required.
Tenofovir:
AUC: ↑ 37%
Cmax: ↑ 34%
Cmin: ↑ 29%
Darunavir/Ritonavir/Emtricitabine     Interaction not studied.
Darunavir (800 mg once daily)/        Darunavir:
Ritonavir (100 mg once daily)/        AUC: ↔
Rilpivirine1                          Cmin: ↓ 11%
Cmax: ↔

Rilpivirine:
AUC: ↑ 130%
Cmin: ↑ 178%
Cmax: ↑ 79%
Darunavir (300 mg once daily)/      Darunavir:
Ritonavir (100 mg once daily)/      AUC: ↔
Tenofovir disoproxil                Cmin: ↔
(245 mg once daily)
Tenofovir:
AUC: ↑ 22%
Cmin: ↑ 37%
Lopinavir/Ritonavir/Emtricitabine   Interaction not studied.
Lopinavir (400 mg twice daily)/     Lopinavir:
Ritonavir (100 mg twice daily)/     AUC: ↔
Rilpivirine1                        Cmin: ↓ 11%
(soft capsule)                      Cmax: ↔

Rilpivirine:
AUC: ↑ 52%
Cmin: ↑ 74%
Cmax: ↑ 29%
Lopinavir (400 mg twice daily)/     Lopinavir/Ritonavir:
Ritonavir (100 mg twice daily)/     AUC: ↔
Tenofovir disoproxil (245 mg once   Cmax: ↔ daily)                              Cmin: ↔
Tenofovir:
AUC: ↑ 32%
Cmax: ↔
Cmin: ↑ 51%
CCR5 antagonists
Maraviroc/Emtricitabine             Interaction not studied.              No clinically relevant drug-drug Maraviroc/Rilpivirine               Interaction not studied.              interaction is expected.
Maraviroc (300 mg twice daily)/     AUC: ↔
Tenofovir disoproxil (245 mg once   Cmax: ↔                               No dose adjustment is required.
daily)                              Tenofovir concentrations not measured, no effect is expected.



Medicinal product by therapeutic        Effects on medicinal product        Recommendation concerning areas                                 levels.                 co-administration with Eviplera Mean percent change in AUC,
Cmax, Cmin
Integrase strand transfer inhibitors
Raltegravir/Emtricitabine            Interaction not studied.              No clinically relevant drug-drug Raltegravir/Rilpivirine              Raltegravir:                          interaction is expected.
AUC: ↑ 9%
Cmin: ↑ 27%                           No dose adjustment is required.
Cmax: ↑ 10%

Rilpivirine:
AUC: ↔
Cmin: ↔
Cmax: ↔
Raltegravir (400 mg twice daily)/     Raltegravir:
Tenofovir disoproxil                  AUC: ↑ 49%
C12h: ↑ 3%
Cmax: ↑ 64%
(mechanism of interaction unknown)

Tenofovir:
AUC: ↓ 10%
C12h: ↓ 13%
Cmax: ↓ 23%
Other antiviral agents
Ledipasvir/Sofosbuvir                 Ledipasvir:                          No dose adjustment is (90 mg/400 mg once daily)/            AUC: ↔                               recommended. The increased Emtricitabine/Rilpivirine/            Cmax: ↔                              exposure of tenofovir could Tenofovir disoproxil                  Cmin: ↔                              potentiate adverse reactions (200 mg/25 mg/245 mg once daily)                                           associated with tenofovir Sofosbuvir:                          disoproxil, including renal
AUC: ↔                               disorders. Renal function should Cmax: ↔                              be closely monitored (see section 4.4).
GS-3310074:
AUC: ↔
Cmax: ↔
Cmin: ↔

Emtricitabine:
AUC: ↔
Cmax: ↔
Cmin: ↔

Rilpivirine:
AUC: ↔
Cmax: ↔
Cmin: ↔
Tenofovir:
AUC: ↑ 40%
Cmax: ↔
Cmin: ↑ 91%



Medicinal product by therapeutic        Effects on medicinal product    Recommendation concerning areas                                 levels.             co-administration with Eviplera Mean percent change in AUC,
Cmax, Cmin
Sofosbuvir/Velpatasvir                Sofosbuvir:                      No dose adjustment is (400 mg/100 mg once daily)/           AUC: ↔                           recommended. The increased Emtricitabine/Rilpivirine/Tenofovir   Cmax: ↔                          exposure of tenofovir could disoproxil                                                             potentiate adverse reactions (200 mg/25 mg/245 mg once daily)      GS-3310074:                      associated with tenofovir AUC: ↔                           disoproxil, including renal
Cmax: ↔                          disorders. Renal function should
Cmin: ↔                          be closely monitored (see section 4.4).
Velpatasvir:
AUC: ↔
Cmax: ↔
Cmin: ↔

Emtricitabine:
AUC: ↔
Cmax: ↔
Cmin: ↔

Rilpivirine:
AUC: ↔
Cmax: ↔
Cmin: ↔
Tenofovir:
AUC: ↑ 40%
Cmax: ↑ 44%
Cmin: ↑ 84%



Medicinal product by therapeutic      Effects on medicinal product    Recommendation concerning areas                                 levels.           co-administration with Eviplera Mean percent change in AUC,
Cmax, Cmin
Sofosbuvir/Velpatasvir/            Interaction not studied with      No dose adjustment is Voxilaprevir (400 mg/100 mg/       Eviplera.                         recommended. The increased 100 mg + 100 mg once daily)5/                                        exposure of tenofovir could Rilpivirine/Emtricitabine          Expected:                         potentiate adverse reactions (25 mg/200 mg once daily)6         Sofosbuvir:                       associated with tenofovir AUC: ↔                            disoproxil, including renal
Cmax: ↔                           disorders. Renal function should be closely monitored (see
GS-3310074:                       section 4.4).
AUC: ↔
Cmax: ↔
Cmin: ↔

Velpatasvir:
AUC: ↔
Cmax: ↔
Cmin: ↔

Voxilaprevir
AUC: ↔
Cmax: ↔
Cmin: ↔
Rilpivirine:
AUC: ↔
Cmin: ↔
Cmax: ↔

Emtricitabine:
AUC: ↔
Cmax: ↔
Cmin: ↔

Tenofovir:
AUC: ↑
Cmax: ↑
Cmin: ↑
Sofosbuvir/Emtricitabine           Interaction not studied.          No dose adjustment is required.
Sofosbuvir (400 mg once daily)/    Sofosbuvir:
Rilpivirine (25 mg once daily)     AUC: ↔
Cmax: ↑ 21%
GS-3310074:
AUC: ↔
Cmax: ↔

Rilpivirine:
AUC: ↔
Cmax: ↔
Cmin: ↔
Sofosbuvir/Tenofovir disoproxil    Interaction not studied.
Ribavirin/Tenofovir disoproxil     Ribavirin:                        No dose adjustment is required.
AUC: ↔
Cmax: ↔
Cmin: N/A



Medicinal product by therapeutic      Effects on medicinal product    Recommendation concerning areas                               levels.             co-administration with Eviplera Mean percent change in AUC,
Cmax, Cmin
Herpesvirus antiviral agents
Famciclovir/Emtricitabine           Famciclovir:                     No dose adjustment is required.
AUC: ↔
Cmax: ↔
Cmin: N/A

Emtricitabine:
AUC: ↔
Cmax: ↔
Cmin: N/A
Antifungals
Ketoconazole/Emtricitabine          Interaction not studied.         Concomitant use of Eviplera with Ketoconazole (400 mg once daily)/   Ketoconazole:                    azole antifungal agents may cause Rilpivirine1                        AUC: ↓ 24%                       an increase in the plasma Cmin: ↓ 66%                      concentrations of rilpivirine
Cmax: ↔                          (inhibition of CYP3A enzymes).

Fluconazole2                        Rilpivirine:                     At a dose of 25 mg of rilpivirine, Itraconazole2                       AUC: ↑ 49%                       no dose adjustment is required.
Posaconazole2                       Cmin: ↑ 76%
Voriconazole2                       Cmax: ↑ 30%
Ketoconazole/Tenofovir disoproxil   Interaction not studied.
Antimycobacterials
Rifabutin/Emtricitabine             Interaction not studied.         Co-administration is likely to Rifabutin (300 mg once daily)/      Rifabutin:                       cause significant decreases in Rilpivirine3                        AUC: ↔                           rilpivirine plasma concentrations Cmin: ↔                          (induction of CYP3A enzymes).
Cmax: ↔                          When Eviplera is co-administered with rifabutin, an additional 25 mg
25-O-desacetyl-rifabutin:        tablet of rilpivirine per day is
AUC: ↔                           recommended to be taken
Cmin: ↔                          concomitantly with Eviplera, for
Cmax: ↔                          the duration of the rifabutin co- administration.
Rifabutin (300 mg once daily)/      Rilpivirine:
Rilpivirine (25 mg once daily)      AUC: ↓ 42%
Cmin: ↓ 48%
Cmax: ↓ 31%

Rifabutin (300 mg once daily)/      Rilpivirine:
Rilpivirine (50 mg once daily)      AUC: ↑ 16%*
Cmin: ↔*
Cmax: ↑ 43%*
*compared to 25 mg once daily rilpivirine alone
Rifabutin/Tenofovir disoproxil      Interaction not studied.



Medicinal product by therapeutic       Effects on medicinal product     Recommendation concerning areas                                  levels.            co-administration with Eviplera Mean percent change in AUC,
Cmax, Cmin
Rifampicin/Emtricitabine            Interaction not studied.           Eviplera must not be used in Rifampicin (600 mg once daily)/     Rifampicin:                        combination with rifampicin as Rilpivirine1                        AUC: ↔                             co-administration is likely to cause Cmin: N/A                          significant decreases in rilpivirine Cmax: ↔                            plasma concentrations (induction of CYP3A enzymes). This may
25-desacetyl-rifampicin:           result in loss of therapeutic effect AUC: ↓ 9%                          of Eviplera (see section 4.3).
Cmin: N/A
Cmax: ↔

Rilpivirine:
AUC: ↓ 80%
Cmin: ↓ 89%
Cmax: ↓ 69%
Rifampicin (600 mg once daily)/     Rifampicin:
Tenofovir disoproxil (245 mg once   AUC: ↔ daily)                              Cmax: ↔

Tenofovir:
AUC: ↔
Cmax: ↔
Rifapentine2                        Interaction not studied with any   Eviplera must not be used in components of Eviplera.            combination with rifapentine as co-administration is likely to cause significant decreases in rilpivirine plasma concentrations (induction of CYP3A enzymes). This may result in loss of therapeutic effect of Eviplera (see section 4.3).
Macrolide antibiotics
Clarithromycin                      Interaction not studied with any   The combination of Eviplera with Erythromycin                        components of Eviplera.            these macrolide antibiotics may cause an increase in the plasma concentrations of rilpivirine
(inhibition of CYP3A enzymes).

Where possible, alternatives such as azithromycin should be considered.
ANTICONVULSANTS
Carbamazepine                       Interaction not studied with any   Eviplera must not be used in Oxcarbazepine                       components of Eviplera.            combination with these Phenobarbital                                                          anticonvulsants as Phenytoin                                                              co-administration may cause significant decreases in rilpivirine plasma concentrations (induction of CYP3A enzymes). This may result in loss of therapeutic effect of Eviplera (see section 4.3).



Medicinal product by therapeutic        Effects on medicinal product         Recommendation concerning areas                                 levels.                  co-administration with Eviplera Mean percent change in AUC,
Cmax, Cmin
GLUCOCORTICOIDS
Dexamethasone (systemic, except       Interaction not studied with any      Eviplera should not be used in for single dose use)                  components of Eviplera.               combination with systemic dexamethasone (except as a single dose) as co-administration may cause significant dose dependent decreases in rilpivirine plasma concentrations (induction of
CYP3A enzymes). This may result in loss of therapeutic effect of Eviplera (see section 4.3).

Alternatives should be considered,
particularly for long-term use.
PROTON PUMP INHIBITORS
Omeprazole/Emtricitabine              Interaction not studied.              Eviplera must not be used in Omeprazole (20 mg once daily)/        Omeprazole:                           combination with proton pump Rilpivirine1                          AUC: ↓ 14%                            inhibitors as co-administration is Cmin: N/A                             likely to cause significant
Cmax: ↓ 14%                           decreases in rilpivirine plasma concentrations (reduced
Rilpivirine:                          absorption, increase in gastric pH).
Lansoprazole2                         AUC: ↓ 40%                            This may result in loss of Rabeprazole2                          Cmin: ↓ 33%                           therapeutic effect of Eviplera (see Pantoprazole2                         Cmax: ↓ 40%                           section 4.3).
Esomeprazole2
Omeprazole/Tenofovir disoproxil       Interaction not studied.
H2-RECEPTOR ANTAGONISTS
Famotidine/Emtricitabine              Interaction not studied.              The combination of Eviplera and Famotidine (40 mg single dose         Rilpivirine:                          H2-receptor antagonists should be taken 12 hours before rilpivirine)/   AUC: ↓ 9%                             used with particular caution as Rilpivirine1                          Cmin: N/A                             co-administration may cause Cmax: ↔                               significant decreases in rilpivirine Cimetidine2                                                                 plasma concentrations (reduced Nizatidine2                                                                 absorption, increase in gastric pH).
Ranitidine2                                                                 Only H2-receptor antagonists that Famotidine (40 mg single dose         Rilpivirine:                          can be dosed once daily should be taken 2 hours before rilpivirine)/    AUC: ↓ 76%                            used. A strict dosing schedule Rilpivirine1                          Cmin: N/A                             with intake of the H2-receptor Cmax: ↓ 85%                           antagonists at least 12 hours before Famotidine (40 mg single dose         Rilpivirine:                          or at least 4 hours after Eviplera taken 4 hours after rilpivirine)/     AUC: ↑ 13%                            should be used.
Rilpivirine1                          Cmin: N/A
Cmax: ↑ 21%
Famotidine/Tenofovir disoproxil       Interaction not studied.
ANTACIDS
Antacids (e.g. aluminium or           Interaction not studied with any of   The combination of Eviplera and magnesium hydroxide, calcium          the components of Eviplera.           antacids should be used with carbonate)                                                                  caution as co-administration may cause significant decreases in rilpivirine plasma concentrations
(reduced absorption, gastric pH increase). Antacids should only be administered either at least 2 hours before or at least 4 hours after
Eviplera.


Medicinal product by therapeutic      Effects on medicinal product    Recommendation concerning areas                               levels.             co-administration with Eviplera Mean percent change in AUC,
Cmax, Cmin
NARCOTIC ANALGESICS
Methadone/Emtricitabine             Interaction not studied.         No dose adjustments are required Methadone (60-100 mg once daily,    R(-) methadone:                  when initiating co-administration individualised dose)/Rilpivirine    AUC: ↓ 16%                       of methadone with Eviplera.
Cmin: ↓ 22%                      However, clinical monitoring is
Cmax: ↓ 14%                      recommended as methadone maintenance therapy may need to
Rilpivirine:                     be adjusted in some patients.
AUC: ↔*
Cmin: ↔*
Cmax: ↔*
*based on historic controls
Methadone/Tenofovir disoproxil      Methadone:
AUC: ↔
Cmin: ↔
Cmax: ↔

Tenofovir:
AUC: ↔
Cmin: ↔
Cmax: ↔
ANALGESICS
Paracetamol/Emtricitabine           Interaction not studied.         No dose adjustment is required.
Paracetamol (500 mg single dose)/   Paracetamol:
Rilpivirine1                        AUC: ↔
Cmin: N/A
Cmax: ↔

Rilpivirine:
AUC: ↔
Cmin: ↑ 26%
Cmax: ↔
Paracetamol/Tenofovir disoproxil    Interaction not studied.
ORAL CONTRACEPTIVES
Ethinylestradiol/Norethindrone/     Interaction not studied.         No dose adjustment is required.
Emtricitabine
Ethinylestradiol (0.035 mg once     Ethinylestradiol: daily)/Rilpivirine                  AUC: ↔
Cmin: ↔
Norethindrone (1 mg once daily)/    Cmax: ↑ 17%
Rilpivirine
Norethindrone:
AUC: ↔
Cmin: ↔
Cmax: ↔
Rilpivirine:
AUC: ↔*
Cmin: ↔*
Cmax: ↔*
*based on historic controls
Ethinylestradiol/Norethindrone/     Ethinylestradiol:
Tenofovir disoproxil                AUC: ↔
Cmax: ↔

Tenofovir:
AUC: ↔
Cmax: ↔
Medicinal product by therapeutic     Effects on medicinal product         Recommendation concerning areas                               levels.                 co-administration with Eviplera Mean percent change in AUC,
Cmax, Cmin
Norgestimate/Ethinylestradiol/     Norgestimate:                         No dose adjustment is required.
Tenofovir disoproxil               AUC: ↔
Cmax: ↔
Cmin: N/A

Ethinylestradiol:
AUC: ↔
Cmax: ↔
Cmin: ↔
ANTIARRHYTHMICS
Digoxin/Emtricitabine              Interaction not studied.              No dose adjustment is required.
Digoxin/Rilpivirine                Digoxin:
AUC: ↔
Cmin: N/A
Cmax: ↔
Digoxin/Tenofovir disoproxil       Interaction not studied.
ANTICOAGULANTS
Dabigatran etexilate               Interaction not studied with any of   A risk for increases in dabigatran the components of Eviplera.           plasma concentrations cannot be excluded (inhibition of intestinal
P-gp.

The combination of Eviplera and dabigatran etexilate should be used with caution.
IMMUNOSUPPRESSANTS
Tacrolimus/Tenofovir disoproxil/   Tacrolimus:                           No dose adjustment is required.
Emtricitabine                      AUC: ↔
Cmax: ↔
Cmin: N/A

Emtricitabine:
AUC: ↔
Cmax: ↔
Cmin: N/A
Tenofovir:
AUC: ↔
Cmax: ↔
Cmin: N/A
ANTIDIABETICS
Metformin/Emtricitabine            Interaction not studied.              No dose adjustment is required.
Metformin (850 mg single dose)/    Metformin:
Rilpivirine                        AUC: ↔
Cmin: N/A
Cmax: ↔
Metformin/Tenofovir disoproxil     Interaction not studied.
HERBAL PRODUCTS
St. John’s wort                    Interaction not studied with any of   Eviplera must not be used in (Hypericum perforatum)             the components of Eviplera.           combination with products containing St. John’s wort as co- administration may cause significant decreases in rilpivirine plasma concentrations. This may result in loss of therapeutic effect of Eviplera (see section 4.3).


Medicinal product by therapeutic    Effects on medicinal product                     Recommendation concerning areas                               levels.                            co-administration with Eviplera Mean percent change in AUC,
Cmax, Cmin
HMG CO-A REDUCTASE INHIBITORS
Atorvastatin/Emtricitabine       Interaction not studied.                          No dose adjustment is required.
Atorvastatin (40 mg once daily)/ Atorvastatin:
Rilpivirine1                     AUC: ↔
Cmin: ↓ 15%
Cmax: ↑ 35%

Rilpivirine:
AUC: ↔
Cmin: ↔
Cmax: ↓ 9%
Atorvastatin/Tenofovir disoproxil Interaction not studied.
PHOSPHODIESTERASE TYPE 5 (PDE-5) INHIBITORS
Sildenafil/Emtricitabine          Interaction not studied.                         No dose adjustment is required.
Sildenafil (50 mg single dose)/   Sildenafil:
Rilpivirine1                      AUC: ↔
Cmin: N/A
Cmax: ↔

Rilpivirine:
AUC: ↔
Vardenafil2                              Cmin: ↔
Tadalafil2                               Cmax: ↔
Sildenafil/Tenofovir disoproxil          Interaction not studied.
N/A = not applicable
1 This interaction study has 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.
2 These are medicinal products within class where similar interactions could be predicted.
3 This interaction study has been performed with a dose higher than the recommended dose for rilpivirine hydrochloride assessing the maximal effect on the co-administered medicinal product.
4 The predominant circulating metabolite of sofosbuvir.
5 Study conducted with additional voxilaprevir 100 mg to achieve voxilaprevir exposures expected in hepatitis C virus (HCV) infected patients.
6 Study conducted with emtricitabine/rilpivirine/tenofovir alafenamide fixed-dose combination tablet.