Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-119728 · Präparat HOS-095005

Medicinal products that are affected by the use of etravirine

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-119729 · Präparat HOS-095005

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-119730 · Präparat HOS-095005

Known and theoretical interactions with selected antiretrovirals and non-antiretroviral medicinal products are listed in table 2. The table is not all-inclusive.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-119731 · Präparat HOS-095005

Interaction table

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-119732 · Präparat HOS-095005

Interactions between etravirine and co-administered medicinal products are listed in table 2 (increase is indicated as “↑”, decrease as “↓”, no change as “↔”, not done as “ND”, confidence interval as “CI”).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 7

HOS-119733 · Präparat HOS-095005

Table 2: Interactions and dose recommendations with other medicinal products Medicinal products by Effects on drug levels Recommendations therapeutic areas Least Squares Mean Ratio concerning (90% CI; 1.00 = No effect) co-administration 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).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): tenofovir (HOS-088083) stavudine (HOS-088080) tenofovir disoproxil (HOS-108843) lamivudine (HOS-085829) didanosine (HOS-085836) zidovudine (HOS-085837) abacavir (HOS-088077) emtricitabine (HOS-085840)

Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 7–8

HOS-119734 · Präparat HOS-095005

7 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. 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)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): indinavir (HOS-084518) lopinavir (HOS-086269) atazanavir (HOS-086180) protease (HOS-085623) saquinavir (HOS-084522) amprenavir (HOS-086183) rilpivirine (HOS-088090) darunavir (HOS-086181) efavirenz (HOS-087947) nevirapine (HOS-088064) fosamprenavir (HOS-086182) ritonavir (HOS-084521)

Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 8–9

HOS-119735 · Präparat HOS-095005

8  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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): atazanavir (HOS-086180) cobicistat (HOS-088111) darunavir (HOS-086181) ritonavir (HOS-084521) tipranavir (HOS-086184)

Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-119736 · Präparat HOS-095005

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, except etravirine for fosamprenavir/ritonavir AUC ↔ 1.06 (0.99-1.14) which is not recommended Cmin ↔ 1.08 (0.98-1.19) with maraviroc. No dose Cmax ↔ 1.05 (0.95-1.17) adjustment for INTELENCE Maraviroc/darunavir/ maraviroc* is necessary. ritonavir AUC ↑ 3.10 (2.57-3.74) See also section 4.4. 150/600/100 mg twice Cmin ↑ 5.27 (4.51-6.15) 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

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): enfuvirtide (HOS-088107) maraviroc (HOS-086186) darunavir (HOS-086181) fosamprenavir (HOS-086182) ritonavir (HOS-084521)

Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 9–10

HOS-119738 · Präparat HOS-095005

9 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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): lopinavir (HOS-086269) atazanavir (HOS-086180) propafenone (HOS-084530) flecainide (HOS-086203) lidocaine (HOS-108866) mexiletine (HOS-086341) bepridil (HOS-085612) dolutegravir (HOS-089992) quinidine (HOS-085593) digoxin (HOS-086172) azithromycin (HOS-088112) disopyramide (HOS-085595) darunavir (HOS-086181) raltegravir (HOS-086187) ritonavir (HOS-084521) amiodarone (HOS-085596)

Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 10–11

HOS-119739 · Präparat HOS-095005

10  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)

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): phenobarbital (HOS-085617) ketoconazole (HOS-084513) carbamazepine (HOS-085618) voriconazole (HOS-084524) itraconazole (HOS-084516) fluconazole (HOS-087945) clarithromycin (HOS-084517) phenytoin (HOS-084531) warfarin (HOS-085950) posaconazole (HOS-085622)

Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 11–12

HOS-119740 · Präparat HOS-095005

11 ANTIMALARIALS Artemether/ artemether Close monitoring of Lumefantrine AUC ↓ 0.62 (0.48-0.80) antimalarial response is 80/480 mg, 6 doses at 0, Cmin ↓ 0.82 (0.67-1.01) warranted when 8, 24, 36, 48, andCmax ↓ 0.72 (0.55-0.94) 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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): lumefantrine (HOS-114826) artemether (HOS-116383) rifabutin (HOS-086262) diazepam (HOS-085904) dexamethasone (HOS-084535) rifapentine (HOS-116386)

Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 12–13

HOS-119741 · Präparat HOS-095005

12 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. Daclatasvir Not studied. Co-administration of etravirine Co-administration of with daclatasvir may decrease daclatasvir INTELENCE and daclatasvir concentrations. is 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. 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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): elbasvir (HOS-108814) daclatasvir (HOS-119742) lovastatin (HOS-086157) atorvastatin (HOS-086304) simvastatin (HOS-086158) rosuvastatin (HOS-086307) fluvastatin (HOS-086305) hepatitis C virus (HOS-108813) ribavirin (HOS-088127) grazoprevir (HOS-108815) ranitidine (HOS-085660) norethindrone (HOS-088136) pravastatin (HOS-086306)

Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 13–14

HOS-119744 · Präparat HOS-095005

13  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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): paroxetine (HOS-086246) tadalafil (HOS-086316) methadone (HOS-086198) serotonin (HOS-085477) clopidogrel (HOS-087927) tacrolimus (HOS-085202) tenofovir disoproxil fumarate (HOS-110471) sirolimus (HOS-085172) sildenafil (HOS-086162) cyclosporine (HOS-084512) omeprazole (HOS-085912) vardenafil (HOS-086163)

Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 14

HOS-119745 · Präparat HOS-095005

Paediatric population

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Wechselwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.5 · PDF-Seite 14

HOS-119746 · Präparat HOS-095005

Interaction studies have only been performed in adults.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-119747 · Präparat HOS-095005

Summary of the safety profile

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Nebenwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-119748 · Präparat HOS-095005

The most frequent (incidence ≥ 10%) adverse reactions of all intensities reported for etravirine were rash, diarrhoea, nausea and headache. In the Phase III studies, the rates of discontinuation due to any adverse reaction were 7.2% in patients receiving etravirine. The most common adverse reaction leading to discontinuation was rash.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-119749 · Präparat HOS-095005

Tabulated list of adverse reactions

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Nebenwirkungen · Intelence

INTELENCE 25 mg tablets INTELENCE 100 mg tablets INTELENCE 200 mg tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-119750 · Präparat HOS-095005

Adverse reactions reported in patients treated with etravirine are summarised in Table 3. The adverse reactions are listed by system organ class (SOC) and frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000) and very rare (< 1/10,000).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.