Interactions : אינטראקציות

4.5    Interaction with other medicinal products and other forms of interaction

Medicinal products that affect etravirine exposure
Etravirine is metabolised by, CYP3A4, CYP2C9 and CYP2C19 followed by glucuronidation of the metabolites by uridine diphosphate glucuronosyl transferase (UDPGT). Medicinal products that induce CYP3A4, CYP2C9, or CYP2C19 may increase the clearance of etravirine resulting in lowered plasma concentrations of etravirine.
Co-administration of etravirine and medicinal products that inhibit CYP3A4, CYP2C9, or CYP2C19 may decrease the clearance of etravirine and may result in increased plasma concentrations of etravirine.

Medicinal products that are affected by the use of etravirine
Etravirine is a weak inducer of CYP3A4. Co-administration of etravirine with medicinal products primarily metabolised by CYP3A4 may result in decreased plasma concentrations of such medicinal products, which could decrease or shorten their therapeutic effects.
Etravirine is a weak inhibitor of CYP2C9 and CYP2C19. Etravirine is also a weak inhibitor of P-glycoprotein. Co-administration with medicinal products primarily metabolised by CYP2C9 or CYP2C19 or transported by P-glycoprotein may result in increased plasma concentrations of such medicinal products, which could increase or prolong their therapeutic effect or alter their adverse events profile.

Known and theoretical interactions with selected antiretrovirals and non-antiretroviral medicinal products are listed in table.1. The table is not all-inclusive.

Interaction table*
Interactions between etravirine and co-administered medicinal products are listed in table.1 (increase is indicated as “↑”, decrease as “↓”, no change as “↔”, not done as “ND”, confidence interval as ““CI.”).


Table 1: Interactions and dose recommendations with other medicinal products Medicinal products by        Effects on drug levels                             Recommendations therapeutic areas            Least Squares                                      concerning Mean Ratio                                         co-administration
(90% CI; 1.00 = No effect)
ANTI-INFECTIVES
Antiretrovirals
NRTIs
Didanosine                  didanosine                                         No significant effect on 400 mg once daily           AUC ↔ 0.99 (0.79-1.25)                             didanosine and etravirine PK
Cmin ND                                            parameters is seen.
Cmax ↔ 0.91 (0.58-1.42)                            INTELENCE and didanosine etravirine                                         can be used without dose AUC ↔ 1.11 (0.99-1.25)                             adjustments.
Cmin ↔ 1.05 (0.93-1.18)
Cmax ↔ 1.16 (1.02-1.32)
Tenofovir disoproxil        tenofovir                                          No significant effect on 245 mg once dailyb          AUC ↔ 1.15 (1.09-1.21)                             tenofovir and etravirine PK
Cmin ↑ 1.19 (1.13-1.26)                            parameters is seen.
Cmax ↑ 1.15 (1.04-1.27)                            INTELENCE and tenofovir etravirine                                         can be used without dose AUC ↓ 0.81 (0.75-0.88)                             adjustments.
Cmin ↓ 0.82 (0.73-0.91)
Cmax ↓ 0.81 (0.75-0.88)
Other NRTIs                 Not studied, but no interaction expected based     INTELENCE can be used on the primary renal elimination route for other with these NRTIs without NRTIs (e.g., abacavir, emtricitabine,              dose adjustment.
lamivudine, stavudine and zidovudine).
NNRTIs
Efavirenz                   Combining two NNRTIs has not been shown to It is not recommended to Nevirapine                  be beneficial. Concomitant use of etravirine       co-administer INTELENCE Rilpivirine                 with efavirenz or nevirapine may cause a           with other NNRTIs.
significant decrease in the plasma concentration of etravirine and loss of therapeutic effect of etravirine.
Concomitant use of etravirine with rilpivirine may cause a decrease in the plasma concentration of rilpivirine and loss of therapeutic effect of rilpivirine.
HIV Protease Inhibitors (PIs) - Unboosted (i.e. without co-administration of low-dose ritonavir) Indinavir                   Concomitant use of etravirine with indinavir       It is not recommended to may cause a significant decrease in the plasma     co-administer INTELENCE concentration of indinavir and loss of             with indinavir.
therapeutic effect of indinavir.
Nelfinavir                  Not studied. etravirine is expected to increase It is not recommended to nelfinavir plasma concentrations.                  co-administer INTELENCE with nelfinavir.


   HIV PIs - Boosted with low-dose ritonavir
Atazanavir/ritonavir       atazanavir                INTELENCE and
300/100 mg once daily      AUC ↓ 0.86 (0.79-0.93)    atazanavir/ritonavir can be Cmin ↓ 0.62 (0.55-0.71)   used without dose
Cmax ↔ 0.97 (0.89-1.05)   adjustment.
etravirine
AUC ↑ 1.30 (1.18-1.44)
Cmin ↑ 1.26 (1.12-1.42)
Cmax ↑ 1.30 (1.17-1.44)
Darunavir/ritonavir        darunavir                 INTELENCE and
600/100 mg twice daily     AUC ↔ 1.15 (1.05-1.26)    darunavir/ritonavir can be Cmin ↔ 1.02 (0.90-1.17)   used without dose
Cmax ↔ 1.11 (1.01-1.22)   adjustments (see also etravirine                section 5.1).
AUC ↓ 0.63 (0.54-0.73)
Cmin ↓ 0.51 (0.44-0.61)
Cmax ↓ 0.68 (0.57-0.82)
Fosamprenavir/ritonavir    amprenavir                Amprenavir/ritonavir and 700/100 mg twice daily     AUC ↑ 1.69 (1.53-1.86)    fosamprenavir/ritonavir may Cmin ↑ 1.77 (1.39-2.25)   require dose reduction when
Cmax ↑ 1.62 (1.47-1.79)   co-administered with etravirine                INTELENCE. Using the oral
AUC ↔a                    solution may be considered
Cmin ↔a                   for dose reduction.
Cmax ↔a
Lopinavir/ritonavir        lopinavir                 INTELENCE and
(tablet)                   AUC ↔ 0.87 (0.83-0.92)    lopinavir/ritonavir can be 400/100 mg twice daily     Cmin ↓ 0.80 (0.73-0.88)   used without dose
Cmax ↔ 0.89 (0.82-0.96)   adjustments.
etravirine
AUC ↓ 0.65 (0.59-0.71)
Cmin ↓ 0.55 (0.49-0.62)
Cmax ↓ 0.70 (0.64-0.78)
Saquinavir/ritonavir       saquinavir                INTELENCE and
1,000/100 mg twice daily AUC ↔ 0.95 (0.64-1.42)      saquinavir/ritonavir can be Cmin ↓ 0.80 (0.46-1.38)   used without dose
Cmax ↔ 1.00 (0.70-1.42)   adjustments.
etravirine
AUC ↓ 0.67 (0.56-0.80)
Cmin ↓ 0.71 (0.58-0.87)
Cmax ↓ 0.63 (0.53-0.75)
Tipranavir/ritonavir       tipranavir                It is not recommended to 500/200 mg twice daily     AUC ↑ 1.18 (1.03-1.36)    co-administer
Cmin ↑ 1.24 (0.96-1.59)   tipranavir/ritonavir and
Cmax ↑ 1.14 (1.02-1.27)   INTELENCE (see etravirine                section 4.4).
AUC ↓ 0.24 (0.18-0.33)
Cmin ↓ 0.18 (0.13-0.25)
Cmax ↓ 0.29 (0.22-0.40)
HIV PIs – Boosted with cobicistat


Atazanavir/cobicistat       Not studied. Co-administration of etravirine     Co-administration of Darunavir/cobicistat        with atazanavir/cobicistat or                    INTELENCE with darunavir/cobicistat may decrease plasma         atazanavir/cobicistat or concentrations of the PI and/or cobicistat,      darunavir/cobicistat is not which may result in loss of therapeutic effect   recommended.
and development of resistance.
CCR5 Antagonists
Maraviroc                   maraviroc                                        The recommended dose for 300 mg twice daily          AUC ↓ 0.47 (0.38-0.58)                           maraviroc when combined Cmin ↓ 0.61 (0.53-0.71)                          with INTELENCE and a PI Cmax ↓ 0.40 (0.28-0.57)                          is 150 mg twice daily,.
etravirine                                       except for
AUC ↔ 1.06 (0.99-1.14)                           fosamprenavir/ritonavir Cmin ↔ 1.08 (0.98-1.19)                          which is not recommended Cmax ↔ 1.05 (0.95-1.17)                          with maraviroc. No dose Maraviroc/darunavir/        maraviroc*                                       adjustment for INTELENCE ritonavir                   AUC ↑ 3.10 (2.57-3.74)                           is necessary.
150/600/100 mg twice        Cmin ↑ 5.27 (4.51-6.15)                          See also section 4.4.
daily                       Cmax ↑ 1.77 (1.20-2.60)
* compared to maraviroc 150 mg twice daily.
Fusion Inhibitors
Enfuvirtide                 etravirine*                                      No interaction is expected for 90 mg twice daily           AUC ↔a                                           either INTELENCE or C0h ↔a                                           enfuvirtide when
Enfuvirtide concentrations not studied and no    co-administered.
effect is expected.
* based on population pharmacokinetic analyses
Integrase Strand Transfer Inhibitors
Dolutegravir                dolutegravir                                     Etravirine significantly 50 mg once daily            AUC ↓ 0.29 (0.26-0.34)                           reduced plasma Cmin ↓ 0.12 (0.09-0.16)                          concentrations of
Cmax ↓ 0.48 (0.43-0.54)                          dolutegravir. The effect of etravirine                                       etravirine on dolutegravir AUC ↔a                                           plasma concentrations was Cmin ↔a                                          mitigated by
Cmax ↔a                                          co-administration of darunavir/ritonavir or
Dolutegravir +              dolutegravir                                     lopinavir/ritonavir, and is darunavir/ritonavir         AUC↓ 0.75 (0.69-0.81)                            expected to be mitigated by 50 mg once daily +          Cmin ↓ 0.63 (0.52-0.77)                          atazanavir/ritonavir.
600/100 mg twice daily      Cmax ↓ 0.88 (0.78-1.00) etravirine                                       INTELENCE should only be AUC ↔a                                           used with dolutegravir when Cmin ↔a                                          co-administered with Cmax ↔a                                          atazanavir/ritonavir, darunavir/ritonavir, or
Dolutegravir +              dolutegravir                                     lopinavir/ritonavir. This Lopinavir/ritonavir         AUC↔ 1.11(1.02-1.20)                             combination can be used 50 mg once daily +          Cmin ↑ 1.28 (1.13-1.45)                          without dose adjustment.
400/100 mg twice daily      Cmax ↔ 1.07 (1.02-1.13) etravirine
AUC ↔a
Cmin ↔a
Cmax ↔a


Raltegravir             raltegravir                                       INTELENCE and raltegravir 400 mg twice daily      AUC ↓ 0.90 (0.68-1.18)                            can be used without dose
Cmin ↓ 0.66 (0.34-1.26)                           adjustments.
Cmax ↓ 0.89 (0.68-1.15) etravirine
AUC ↔ 1.10 (1.03-1.16)
Cmin ↔ 1.17 (1.10-1.26)
Cmax ↔ 1.04 (0.97-1.12)
ANTIARRHYTHMICS
Digoxin                 digoxin                                           INTELENCE and digoxin 0.5 mg single dose      AUC ↑ 1.18 (0.90-1.56)                            can be used without dose Cmin ND                                           adjustments. It is
Cmax ↑ 1.19 (0.96-1.49)                           recommended that digoxin levels be monitored when digoxin is combined with
INTELENCE.
Amiodarone              Not studied. INTELENCE is expected to             Caution is warranted and Bepridil                decrease plasma concentrations of these           therapeutic concentration Disopyramide            antiarrhythmics.                                  monitoring, if available, is Flecainide                                                                recommended for Lidocaine (systemic)                                                      antiarrhythmics when Mexiletine                                                                co-administered with Propafenone                                                               INTELENCE.
Quinidine
ANTIBIOTICS
Azithromycin            Not studied. Based on the biliary elimination     INTELENCE and pathway of azithromycin, no drug interactions     azithromycin can be used are expected between azithromycin and             without dose adjustments.
INTELENCE.
Clarithromycin          clarithromycin                                    Clarithromycin exposure was 500 mg twice daily      AUC ↓ 0.61 (0.53-0.69)                            decreased by etravirine; Cmin ↓ 0.47 (0.38-0.57)                           however, concentrations of Cmax ↓ 0.66 (0.57-0.77)                           the active metabolite, 14-OH-clarithromycin                              14-OH-clarithromycin, were AUC ↑ 1.21 (1.05-1.39)                            increased. Because Cmin ↔ 1.05 (0.90-1.22)                           14-OH-clarithromycin has Cmax ↑ 1.33 (1.13-1.56)                           reduced activity against etravirine                                        Mycobacterium avium AUC ↑ 1.42 (1.34-1.50)                            complex (MAC), overall Cmin ↑ 1.46 (1.36-1.58)                           activity against this pathogen Cmax ↑ 1.46 (1.38-1.56)                           may be altered; therefore alternatives to clarithromycin should be considered for the treatment of MAC.
ANTICOAGULANTS
Warfarin                Not studied. Etravirine is expected to increase   It is recommended that the plasma concentrations of warfarin.                international normalised ratio (INR) be monitored when warfarin is combined with
INTELENCE.
ANTICONVULSANTS
Carbamazepine           Not studied. Carbazamepine, phenobarbital and     Combination not Phenobarbital           phenytoin are expected to decrease plasma         recommended.
Phenytoin               concentrations of etravirine.


   ANTIFUNGALS
Fluconazole                fluconazole                                        INTELENCE and 200 mg once in the         AUC ↔ 0.94 (0.88-1.01)                             fluconazole can be used morning                    Cmin ↔ 0.91 (0.84-0.98)                            without dose adjustments.
Cmax ↔ 0.92 (0.85-1.00) etravirine
AUC ↑ 1.86 (1.73-2.00)
Cmin ↑ 2.09 (1.90-2.31)
Cmax ↑ 1.75 (1.60-1.91)
Itraconazole               Not studied. Posaconazole, a potent inhibitor of   INTELENCE and these Ketoconazole               CYP3A4, may increase plasma concentrations         antifungals can be used Posaconazole               of etravirine. Itraconazole and ketoconazole are   without dose adjustments.
potent inhibitors as well as substrates of
CYP3A4. Concomitant systemic use of itraconazole or ketoconazole and etravirine may increase plasma concentrations of etravirine.
Simultaneously, plasma concentrations of itraconazole or ketoconazole may be decreased by Etravirine.
Voriconazole               voriconazole                                       INTELENCE and 200 mg twice daily         AUC ↑ 1.14 (0.88-1.47)                             voriconazole can be used
Cmin ↑ 1.23 (0.87-1.75)                            without dose adjustments.
Cmax ↓ 0.95 (0.75-1.21) etravirine
AUC ↑ 1.36 (1.25-1.47)
Cmin ↑ 1.52 (1.41-1.64)
Cmax ↑ 1.26 (1.16-1.38)
ANTIMALARIALS
Artemether/      artemether                                                   Close monitoring of Lumefantrine     AUC ↓ 0.62 (0.48-0.80)                                       antimalarial response is Cmin ↓ 0.82 (0.67-1.01)
80/480 mg, 6 doses at 0,                                                      warranted when Cmax ↓ 0.72 (0.55-0.94)
8, 24, 36, 48, and                                                            co-administering 60 hours         dihydroartemisinin                                           INTELENCE and AUC ↓ 0.85 (0.75-0.97)                                       artemether/lumefantrine as a Cmin ↓ 0.83 (0.71-0.97)                                      significant decrease in Cmax ↓ 0.84 (0.71-0.99)                                      exposure of artemether and lumefantrine                                                 its active metabolite, AUC ↓ 0.87 (0.77-0.98)                                       dihydroartemisinin, may Cmin ↔ 0.97 (0.83-1.15)                                      result in decreased Cmax ↔ 1.07 (0.94-1.23)                                      antimalarial efficacy. No etravirine                                                   dose adjustment is needed for AUC ↔ 1.10 (1.06-1.15)                                       INTELENCE.
Cmin ↔ 1.08 (1.04-1.14)
Cmax ↔ 1.11 (1.06-1.17)
ANTIMYCOBACTERIALS
Rifampicin       Not studied. Rifampicin and rifapentine are                  Combination not Rifapentine      expected to decrease plasma concentrations of                recommended.
etravirine.
INTELENCE should be used in combination with a boosted PI. Rifampicin is contraindicated in combination with boosted PIs.


Rifabutin                With an associated boosted PI:                    The combination of 300 mg once daily        No interaction study has been performed. Based    INTELENCE with a boosted on historical data, a decrease in etravirine      PI and rifabutin should be exposure may be expected whereas an increase      used with caution due to the in rifabutin exposure and especially in           risk of decrease in etravirine 25-O-desacetyl-rifabutin may be expected.         exposure and the risk of increase in rifabutin and
With no associated boosted PI (out of the         25-O-desacetyl-rifabutin recommended indication for etravirine):           exposures.
rifabutin                                         Close monitoring for AUC ↓ 0.83 (0.75-0.94)                            virologic response and for Cmin ↓ 0.76 (0.66-0.87)                           rifabutin related adverse Cmax ↓ 0.90 (0.78-1.03)                           reactions is recommended.
25-O-desacetyl-rifabutin                          Please refer to the product AUC ↓ 0.83 (0.74-0.92)                            information of the associated Cmin ↓ 0.78 (0.70-0.87)                           boosted PI for the dose Cmax ↓ 0.85 (0.72-1.00)                           adjustment of rifabutin to be etravirine                                        used.
AUC ↓ 0.63 (0.54-0.74)
Cmin ↓ 0.65 (0.56-0.74)
Cmax ↓ 0.63 (0.53-0.74)
BENZODIAZEPINES
Diazepam                 Not studied. Etravirine is expected to increase   Alternatives to diazepam plasma concentrations of diazepam.                should be considered.
CORTICOSTEROIDS
Dexamethasone            Not studied. Dexamethasone is expected to         Systemic dexamethasone (systemic)               decrease plasma concentrations of etravirine      should be used with caution or alternatives should be considered, particularly for chronic use.
OESTROGEN-BASED CONTRACEPTIVES
Ethinylestradiol    ethinylestradiol                                       The combination of 0.035 mg once daily AUC ↑ 1.22 (1.13-1.31)                                 oestrogen- and/or Norethindrone       Cmin ↔ 1.09 (1.01-1.18)                                progesterone-based 1 mg once daily     Cmax ↑ 1.33 (1.21-1.46)                                contraceptives and norethindrone                                          INTELENCE can be used AUC ↔ 0.95 (0.90-0.99)                                 without dose adjustment.
Cmin ↓ 0.78 (0.68-0.90)
Cmax ↔ 1.05 (0.98-1.12) etravirine
AUC ↔a
Cmin ↔a
Cmax ↔a
HEPATITIS C VIRUS (HCV) DIRECT-ACTING ANTIVIRALS
Ribavirin           Not studied, but no interaction expected based         The combination of on the renal elimination pathway of ribavirin.         INTELENCE and ribavirin can be used without dose adjustments.


Boceprevir                boceprevir                                        The clinical significance of 800 mg 3 times daily +    AUC ↑ 1.10 (0.94-1.28)                            the reductions in etravirine etravirine 200 mg every   Cmax ↑ 1.10 (0.94-1.29)                           pharmacokinetic parameters 12 hours                  Cmin ↓ 0.88 (0.66-1.17)                           and boceprevir Cmin in the etravirine                                        setting of the combination AUC ↓ 0.77 (0.66-0.91)                            therapy with HIV
Cmax ↓ 0.76 (0.68-0.85)                           antiretroviral medicines Cmin ↓ 0.71 (0.54-0.95)                           which also affect the pharmacokinetics of etravirine and/or boceprevir has not been directly assessed. Increased clinical and laboratory monitoring for
HIV and HCV suppression is recommended.
Daclatasvir               Not studied. Co-administration of etravirine      Co-administration of with daclatasvir may decrease daclatasvir         Intelence and daclatasvir is concentrations.                                   not recommended.
Elbasvir/grazoprevir      Not studied. Co-administration of etravirine      Co-administration is with elbasvir/grazoprevir may decrease elbasvir   contraindicated (see and grazoprevir concentrations, leading to        section 4.3).
reduced therapeutic effect of elbasvir/grazoprevir.
Simeprevir                Not studied. Concomitant use of etravirine with   Co-administration of simeprevir may decrease plasma concentrations     Intelence and simeprevir is of simeprevir.                                    not recommended.

HERBAL PRODUCTS
St John's wort    Not studied. St John’s wort is expected to                Combination not (Hypericum perforatum) decrease the plasma concentrations of                     recommended.
etravirine.
HMG CO-A REDUCTASE INHIBITORS
Atorvastatin      atorvastatin                                              The combination of 40 mg once daily  AUC ↓ 0.63 (0.58-0.68)                                    INTELENCE and
Cmin ND                                                   atorvastatin can be given Cmax ↑ 1.04 (0.84-1.30)                                   without any dose 2-OH-atorvastatin                                         adjustments, however, the AUC ↑ 1.27 (1.19-1.36)                                    dose of atorvastatin may Cmin ND                                                   need to be altered based on Cmax ↑ 1.76 (1.60-1.94)                                   clinical response.
etravirine
AUC ↔ 1.02 (0.97-1.07)
Cmin ↔ 1.10 (1.02-1.19)
Cmax ↔ 0.97 (0.93-1.02)
Fluvastatin       Not studied. No interaction between pravastatin           Dose adjustments for these Lovastatin        and etravirine is expected.                               HMG Co-A reductase Pravastatin       Lovastatin, rosuvastatin and simvastatin are              inhibitors may be necessary.
Rosuvastatin      CYP3A4 substrates and co-administration with
Simvastatin       etravirine may result in lower plasma concentrations of the HMG Co-A reductase inhibitor. Fluvastatin, and rosuvastatin are metabolised by CYP2C9 and co-administration with etravirine may result in higher plasma concentrations of the HMG Co-A reductase inhibitor.

   H2-RECEPTOR ANTAGONISTS
Ranitidine         etravirine                                               INTELENCE can be 150 mg twice daily AUC ↓ 0.86 (0.76-0.97)                                   co-administered with Cmin ND                                                  H2-receptor antagonists Cmax ↓ 0.94 (0.75-1.17)                                  without dose adjustments.
IMMUNOSUPPRESSANTS
Cyclosporin        Not studied. Etravirine is expected to decrease          Co-administration with Sirolimus          plasma concentrations of cyclosporine,                   systemic Tacrolimus         sirolimus and tacrolimus.                                immunosuppressants should be done with caution because plasma concentrations of cyclosporin, sirolimus and tacrolimus may be affected when co-administered with
INTELENCE.
NARCOTIC ANALGESICS
Methadone               R(-) methadone                                      No changes in methadone individual dose ranging AUC ↔ 1.06 (0.99-1.13)                              dosage were required based from 60 mg to 130 mg    Cmin ↔ 1.10 (1.02-1.19)                             on clinical status during or once daily              Cmax ↔ 1.02 (0.96-1.09)                             after the period of S(+) methadone                                      INTELENCE
AUC ↔ 0.89 (0.82-0.96)                              co-administration.
Cmin ↔ 0.89 (0.81-0.98)
Cmax ↔ 0.89 (0.83-0.97) etravirine
AUC ↔a
Cmin ↔a
Cmax ↔a
PHOSPHODIESTERASE, TYPE 5 (PDE-5) INHIBITORS
Sildenafil 50 mg single sildenafil                                          Concomitant use of PDE-5 dose                    AUC ↓ 0.43 (0.36-0.51)                              inhibitors with INTELENCE Tadalafil               Cmin ND                                             may require dose adjustment Vardenafil              Cmax ↓ 0.55 (0.40-0.75)                             of the PDE-5 inhibitor to N-desmethyl-sildenafil                              attain the desired clinical AUC ↓ 0.59 (0.52-0.68)                              effect.
Cmin ND
Cmax ↓ 0.75 (0.59-0.96)
PLATELET AGGREGGATION INHIBITORS
Clopidogrel             In vitro data show that etravirine has inhibitory   As a precaution it is properties on CYP2C19. It is therefore possible     recommended that that etravirine may inhibit the metabolism of       concomitant use of etravirine clopidogrel to its active metabolite by such        and clopidogrel should be inhibition of CYP2C19 in vivo. The clinical         discouraged.
relevance of this interaction has not been demonstrated.
PROTON PUMP INHIBITORS
Omeprazole              etravirine                                          INTELENCE can be 40 mg once daily        AUC ↑ 1.41 (1.22-1.62)                              co-administered with proton
Cmin ND                                             pump inhibitors without dose Cmax ↑ 1.17 (0.96-1.43)                             adjustments.


   SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS)
Paroxetine        paroxetine                                                              INTELENCE can be 20 mg once daily  AUC ↔ 1.03 (0.90-1.18)                                                  co-administered with
Cmin ↓ 0.87 (0.75-1.02)                                                 paroxetine without dose Cmax ↔ 1.06 (0.95-1.20)                                                 adjustments.
etravirine
AUC ↔ 1.01 (0.93-1.10)
Cmin ↔ 1.07 (0.98-1.17)
Cmax ↔ 1.05 (0.96-1.15) a
Comparison based on historic control.
b  Study was conducted with tenofovir disoproxil fumarate 300 mg once daily Note: In drug-drug interaction studies, different formulations and/or doses of etravirine were used which led to similar exposures and, therefore, interactions relevant for one formulation are relevant for the other.


Paediatric population
Interaction studies have only been performed in adults.