Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Harvoni

Harvoni 90 mg/400 mg film-coated tablets Harvoni 45 mg/200 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 15–16

HOS-132252 · Präparat HOS-097208

15  Medicinal product by Effects on medicinal Recommendation concerning co-administration therapeutic areas product levels. with Harvoni Mean ratio (90% confidence interval) for AUC, Cmax, Cmina, b Lopinavir boosted with Interaction not studied. When given with lopinavir/ritonavir used in ritonavir + emtricitabine/ Expected: conjunction with tenofovir disoproxil fumarate, tenofovir disoproxil ↑ Lopinavir Harvoni is expected to increase the concentration of fumarate ↑ Ritonavir tenofovir.

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) lopinavir (HOS-086269) tenofovir disoproxil (HOS-108843) fumarate (HOS-108845) tenofovir disoproxil fumarate (HOS-110471) ritonavir (HOS-084521) emtricitabine (HOS-085840)

Wechselwirkungen · Harvoni

Harvoni 90 mg/400 mg film-coated tablets Harvoni 45 mg/200 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 16–17

HOS-132258 · Präparat HOS-097208

16  Medicinal product by Effects on medicinal Recommendation concerning co-administration therapeutic areas product levels. with Harvoni Mean ratio (90% confidence interval) for AUC, Cmax, Cmina, b Elvitegravir/ cobicistat/ Interaction not studied. When given with elvitegravir/ cobicistat/ emtricitabine/ tenofovir Expected: emtricitabine/ tenofovir disoproxil fumarate, disoproxil fumarate ↔ Emtricitabine Harvoni is expected to increase the concentration of (150 mg/ 150 mg/ 200 mg/ ↑ Tenofovir tenofovir. 300 mg once daily)/ ledipasvir (90 mg once Observed: The safety of tenofovir disoproxil fumarate in the daily)c/ sofosbuvir (400 mg Elvitegravir setting of Harvoni and a pharmacokinetic enhancer once daily)c ↔ Cmax 0.88 (0.82, 0.95) (e.g. ritonavir or cobicistat) has not been ↔ AUC 1.02 (0.95, 1.09) established. ↑ Cmin 1.36 (1.23, 1.49) The combination should be used with caution with Cobicistat frequent renal monitoring, if other alternatives are ↔ Cmax 1.25 (1.18, 1.32) not available (see section 4.4). ↑ AUC 1.59 (1.49, 1.70) ↑ Cmin 4.25 (3.47, 5.22)

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) cobicistat (HOS-088111) fumarate (HOS-108845) tenofovir disoproxil fumarate (HOS-110471) ritonavir (HOS-084521) elvitegravir (HOS-088110) emtricitabine (HOS-085840)

Wechselwirkungen · Harvoni

Harvoni 33.75 mg/150 mg coated granules in sachet Harvoni 45 mg/200 mg coated granules in sachet · Abschnitt 4.5 · PDF-Seite 50–51

HOS-132334 · Präparat HOS-097208

50 Medicinal product by Effects on medicinal Recommendation concerning co-administration therapeutic areas product levels. with Harvoni Mean ratio (90% confidence interval) for AUC, Cmax, Cmina, b HIV ANTIVIRAL AGENTS: REVERSE TRANSCRIPTASE INHIBITORS Efavirenz/ emtricitabine/ Efavirenz No dose adjustment of Harvoni or efavirenz/ tenofovir disoproxil ↔ Cmax 0.87 (0.79, 0.97) emtricitabine/ tenofovir disoproxil fumarate is fumarate ↔ AUC 0.90 (0.84, 0.96) required. (600 mg/ 200 mg/ 300 mg/ ↔ Cmin 0.91 (0.83, 0.99) once daily)/ ledipasvir (90 mg once daily)c/ Emtricitabine sofosbuvir (400 mg once ↔ Cmax 1.08 (0.97, 1.21) daily)c, d ↔ AUC 1.05 (0.98, 1.11) ↔ Cmin 1.04 (0.98, 1.11)

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 disoproxil (HOS-108843) fumarate (HOS-108845) efavirenz (HOS-087947) tenofovir disoproxil fumarate (HOS-110471) emtricitabine (HOS-085840)

Wechselwirkungen · Harvoni

Harvoni 33.75 mg/150 mg coated granules in sachet Harvoni 45 mg/200 mg coated granules in sachet · Abschnitt 4.5 · PDF-Seite 51

HOS-132338 · Präparat HOS-097208

GS-331007 ↔ Cmax 0.86 (0.76, 0.96) ↔ AUC 0.90 (0.83, 0.97) ↔ Cmin 1.07 (1.02, 1.13) Emtricitabine/ rilpivirine/ Emtricitabine No dose adjustment of Harvoni or emtricitabine/ tenofovir disoproxil ↔ Cmax 1.02 (0.98, 1.06) rilpivirine/ tenofovir disoproxil fumarate is fumarate ↔ AUC 1.05 (1.02, 1.08) required. (200 mg/ 25 mg/ 300 mg ↔ Cmin 1.06 (0.97, 1.15) once daily)/ ledipasvir (90 mg once daily)c/ Rilpivirine sofosbuvir (400 mg once ↔ Cmax 0.97 (0.88, 1.07) daily)c, d ↔ AUC 1.02 (0.94, 1.11) ↔ Cmin 1.12 (1.03, 1.21)

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 disoproxil (HOS-108843) fumarate (HOS-108845) rilpivirine (HOS-088090) tenofovir disoproxil fumarate (HOS-110471) emtricitabine (HOS-085840)

Wechselwirkungen · Harvoni

Harvoni 33.75 mg/150 mg coated granules in sachet Harvoni 45 mg/200 mg coated granules in sachet · Abschnitt 4.5 · PDF-Seite 52–53

HOS-132349 · Präparat HOS-097208

52 Medicinal product by Effects on medicinal Recommendation concerning co-administration therapeutic areas product levels. with Harvoni Mean ratio (90% confidence interval) for AUC, Cmax, Cmina, b Atazanavir boosted with Atazanavir When given with tenofovir disoproxil fumarate used ritonavir (300 mg/ 100 mg ↔ Cmax 1.07 (0.99, 1.14) in conjunction with atazanavir/ritonavir, Harvoni once daily) + emtricitabine/ ↔ AUC 1.27 (1.18, 1.37) increased the concentration of tenofovir. tenofovir disoproxil ↑ Cmin 1.63 (1.45, 1.84) fumarate (200 mg/ 300 mg The safety of tenofovir disoproxil fumarate in the once daily)/ ledipasvir Ritonavir setting of Harvoni and a pharmacokinetic enhancer (90 mg once daily)c/ ↔ Cmax 0.86 (0.79, 0.93) (e.g. ritonavir or cobicistat) has not been sofosbuvir (400 mg once ↔ AUC 0.97 (0.89, 1.05) established. daily)c, d ↑ Cmin 1.45 (1.27, 1.64) The combination should be used with caution with Dosed simultaneouslyf Emtricitabine frequent renal monitoring, if other alternatives are ↔ Cmax 0.98 (0.94, 1.02) not available (see section 4.4). ↔ AUC 1.00 (0.97, 1.04) ↔ Cmin 1.04 (0.96, 1.12) Atazanavir concentrations are also increased, with a risk for an increase in bilirubin levels/icterus. That Tenofovir risk is even higher if ribavirin is used as part of the ↑ Cmax 1.47 (1.37, 1.58) HCV treatment. ↔ AUC 1.35 (1.29, 1.42) ↑ Cmin 1.47 (1.38, 1.57)

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) atazanavir (HOS-086180) cobicistat (HOS-088111) tenofovir disoproxil (HOS-108843) ribavirin (HOS-088127) fumarate (HOS-108845) tenofovir disoproxil fumarate (HOS-110471) ritonavir (HOS-084521) emtricitabine (HOS-085840)

Wechselwirkungen · Harvoni

Harvoni 33.75 mg/150 mg coated granules in sachet Harvoni 45 mg/200 mg coated granules in sachet · Abschnitt 4.5 · PDF-Seite 53–54

HOS-132354 · Präparat HOS-097208

53 Medicinal product by Effects on medicinal Recommendation concerning co-administration therapeutic areas product levels. with Harvoni Mean ratio (90% confidence interval) for AUC, Cmax, Cmina, b Darunavir boosted with Darunavir When given with darunavir/ritonavir used in ritonavir (800 mg/ 100 mg ↔ Cmax 1.01 (0.96, 1.06) conjunction with tenofovir disoproxil fumarate, once daily) + emtricitabine/ ↔ AUC 1.04 (0.99, 1.08) Harvoni increased the concentration of tenofovir. tenofovir disoproxil ↔ Cmin 1.08 (0.98, 1.20) fumarate (200 mg/ 300 mg The safety of tenofovir disoproxil fumarate in the once daily)/ ledipasvir Ritonavir setting of Harvoni and a pharmacokinetic enhancer (90 mg once daily)c/ ↔ Cmax 1.17 (1.01, 1.35) (e.g. ritonavir or cobicistat) has not been sofosbuvir (400 mg once ↔ AUC 1.25 (1.15, 1.36) established. daily)c, d ↑ Cmin 1.48 (1.34, 1.63) The combination should be used with caution with Dosed simultaneouslyf Emtricitabine frequent renal monitoring, if other alternatives are ↔ Cmax 1.02 (0.96, 1.08) not available (see section 4.4). ↔ AUC 1.04 (1.00, 1.08) ↔ Cmin 1.03 (0.97, 1.10)

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) cobicistat (HOS-088111) tenofovir disoproxil (HOS-108843) fumarate (HOS-108845) darunavir (HOS-086181) tenofovir disoproxil fumarate (HOS-110471) ritonavir (HOS-084521) emtricitabine (HOS-085840)

Wechselwirkungen · Harvoni

Harvoni 33.75 mg/150 mg coated granules in sachet Harvoni 45 mg/200 mg coated granules in sachet · Abschnitt 4.5 · PDF-Seite 54

HOS-132358 · Präparat HOS-097208

GS-331007 ↔ Cmax 1.10 (1.04, 1.16) ↔ AUC 1.20 (1.16, 1.24) ↔ Cmin 1.26 (1.20, 1.32) Lopinavir boosted with Interaction not studied. When given with lopinavir/ritonavir used in ritonavir + emtricitabine/ Expected: conjunction with tenofovir disoproxil fumarate, tenofovir disoproxil ↑ Lopinavir Harvoni is expected to increase the concentration of fumarate ↑ Ritonavir tenofovir.

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) lopinavir (HOS-086269) tenofovir disoproxil (HOS-108843) fumarate (HOS-108845) tenofovir disoproxil fumarate (HOS-110471) ritonavir (HOS-084521) emtricitabine (HOS-085840)

Wechselwirkungen · Harvoni

Harvoni 33.75 mg/150 mg coated granules in sachet Harvoni 45 mg/200 mg coated granules in sachet · Abschnitt 4.5 · PDF-Seite 55

HOS-132363 · Präparat HOS-097208

GS-331007 ↔ Cmax 1.09 (0.99, 1.19) ↔ AUC 1.02 (0.97, 1.08) Elvitegravir/ cobicistat/ Interaction not studied. When given with elvitegravir/ cobicistat/ emtricitabine/ tenofovir Expected: emtricitabine/ tenofovir disoproxil fumarate, disoproxil fumarate ↔ Emtricitabine Harvoni is expected to increase the concentration of (150 mg/ 150 mg/ 200 mg/ ↑ Tenofovir tenofovir. 300 mg once daily)/ ledipasvir (90 mg once Observed: The safety of tenofovir disoproxil fumarate in the daily)c/ sofosbuvir (400 mg Elvitegravir setting of Harvoni and a pharmacokinetic enhancer once daily)c ↔ Cmax 0.88 (0.82, 0.95) (e.g. ritonavir or cobicistat) has not been ↔ AUC 1.02 (0.95, 1.09) established. ↑ Cmin 1.36 (1.23, 1.49) The combination should be used with caution with Cobicistat frequent renal monitoring, if other alternatives are ↔ Cmax 1.25 (1.18, 1.32) not available (see section 4.4). ↑ AUC 1.59 (1.49, 1.70) ↑ Cmin 4.25 (3.47, 5.22)

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) cobicistat (HOS-088111) fumarate (HOS-108845) tenofovir disoproxil fumarate (HOS-110471) ritonavir (HOS-084521) elvitegravir (HOS-088110) emtricitabine (HOS-085840)

Wechselwirkungen · Epclusa

Epclusa 400 mg/100 mg film-coated tablets Epclusa 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 10–11

HOS-136144 · Präparat HOS-097846

10 Medicinal product by Effects on medicinal product levels. therapeutic areas/Possible Mean ratio (90% confidence interval)a,b Recommendation concerning Mechanism of Interaction Active Cmax AUC Cminco-administration with Epclusa Rifapentine Interaction not studied. Co-administration of Epclusa with Expected: rifapentine is expected to decrease ↓ Sofosbuvir the concentration of sofosbuvir and ↓ Velpatasvir velpatasvir, leading to reduced (Induction of P-gp and therapeutic effect of Epclusa. CYPs) Co-administration is not recommended (see section 4.4). HIV ANTIVIRAL AGENTS: REVERSE TRANSCRIPTASE INHIBITORS Tenofovir disoproxil Epclusa has been shown to increase tenofovir exposure (P-gp-inhibition). The fumarate increase in tenofovir exposure (AUC and Cmax) was around 40-80% during co- treatment with Epclusa and tenofovir disoproxil fumarate/emtricitabine as part of various HIV regimens.

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) tenofovir disoproxil (HOS-108843) fumarate (HOS-108845) rifapentine (HOS-116386) tenofovir disoproxil fumarate (HOS-110471) emtricitabine (HOS-085840)

Wechselwirkungen · Epclusa

Epclusa 400 mg/100 mg film-coated tablets Epclusa 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 11

HOS-136146 · Präparat HOS-097846

Patients receiving tenofovir disoproxil fumarate and Epclusa concomitantly should be monitored for adverse reactions associated with tenofovir disoproxil fumarate. Refer to the tenofovir disoproxil fumarate-containing product’s Summary of Product Characteristics for recommendations on renal monitoring (see section 4.4). Efavirenz/ emtricitabine/ Efavirenz ↔ ↔ ↔ Co-administration of Epclusa with tenofovir disoproxil Sofosbuvir ↑ ↔ efavirenz/ emtricitabine/ tenofovir fumarate 1.4 disoproxil fumarate is expected to (600/ 200/ 300 mg once (1.1, decrease the concentration of daily)/ sofosbuvir/ 1.7) velpatasvir. Co-administration of velpatasvir (400/ 100 mg Velpatasvir ↓ ↓ ↓ Epclusa with efavirenz-containing once daily)c, d 0.53 0.47 0.43 regimens is not recommended (see (0.43, (0.39, (0.36, section 4.4). 0.64) 0.57) 0.52) Emtricitabine/ rilpivirine/ Rilpivirine ↔ ↔ ↔ No dose adjustment of Epclusa or tenofovir disoproxil Sofosbuvir ↔ ↔ emtricitabine/ rilpivirine/ tenofovir fumarate Velpatasvir ↔ ↔ ↔ disoproxil fumarate is required. (200/ 25/ 300 mg once daily)/ sofosbuvir/ velpatasvir (400/ 100 mg once daily)c, d HIV ANTIVIRAL AGENTS: HIV PROTEASE INHIBITORS Atazanavir boosted with Atazanavir ↔ ↔ ↑ No dose adjustment of Epclusa, ritonavir (300/ 100 mg once 1.4 atazanavir (ritonavir boosted) or daily) + emtricitabine/ (1.2, emtricitabine/ tenofovir disoproxil tenofovir disoproxil 1.6) fumarate is required. fumarate (200/ 300 mg once Ritonavir ↔ ↑ daily)/ sofosbuvir/ 1.3 velpatasvir (400/ 100 mg (1.5, once daily)c, d 1.4) Sofosbuvir ↔ ↔

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) atazanavir (HOS-086180) protease (HOS-085623) tenofovir disoproxil (HOS-108843) fumarate (HOS-108845) rilpivirine (HOS-088090) efavirenz (HOS-087947) tenofovir disoproxil fumarate (HOS-110471) ritonavir (HOS-084521) emtricitabine (HOS-085840)

Wechselwirkungen · Epclusa

Epclusa 400 mg/100 mg film-coated tablets Epclusa 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 11

HOS-136147 · Präparat HOS-097846

Velpatasvir ↑ ↑ ↑ 1.6 2.4 4.0 (1.4, (2.2, (3.6, 1.7) 2.6) 4.5) Darunavir boosted with Darunavir ↔ ↔ ↔ No dose adjustment of Epclusa, ritonavir (800/ 100 mg once Ritonavir ↔ ↔ ↔ darunavir (ritonavir boosted) or daily) + emtricitabine/ Sofosbuvir ↓ ↓ emtricitabine/ tenofovir disoproxil tenofovir disoproxil 0.62 0.72 fumarate is required. fumarate (200/ 300 mg once (0.54, (0.66, daily)/ sofosbuvir/ 0.71) 0.80) velpatasvir (400/ 100 mg Velpatasvir ↓ ↔ ↔ once daily)c, d 0.76 (0.65, 0.89)

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 disoproxil (HOS-108843) fumarate (HOS-108845) darunavir (HOS-086181) ritonavir (HOS-084521) emtricitabine (HOS-085840)

Wechselwirkungen · Epclusa

Epclusa 400 mg/100 mg film-coated tablets Epclusa 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 11–12

HOS-136148 · Präparat HOS-097846

11 Medicinal product by Effects on medicinal product levels. therapeutic areas/Possible Mean ratio (90% confidence interval)a,b Recommendation concerning Mechanism of Interaction Active Cmax AUC Cmin co-administration with Epclusa Lopinavir boosted with Lopinavir ↔ ↔ ↔ No dose adjustment of Epclusa, ritonavir (4x200 mg/ 50 mg Ritonavir ↔ ↔ ↔ lopinavir (ritonavir boosted) or once daily) + emtricitabine/ Sofosbuvir ↓ ↓ emtricitabine/ tenofovir disoproxil tenofovir disoproxil 0.59 0.7 fumarate is required. fumarate (200/ 300 mg once (0.49 (0.6, daily)/ sofosbuvir/ 0.71) 0.8) velpatasvir (400/ 100 mg Velpatasvir ↓ ↔ ↑ once daily)c, d 0.70 1.6 (0.59, (1.4, 0.83) 1.9) HIV ANTIVIRAL AGENTS: INTEGRASE INHIBITORS Raltegravir (400 mg twice Raltegravir ↔ ↔ ↓ No dose adjustment of Epclusa, daily)g + emtricitabine/ 0.79 raltegravir or emtricitabine/ tenofovir disoproxil (0.42, tenofovir disoproxil fumarate is fumarate (200/ 300 mg once 1.5) required. daily)/ sofosbuvir/ Sofosbuvir ↔ ↔ velpatasvir (400/ 100 mg Velpatasvir ↔ ↔ ↔ once daily)c, d Elvitegravir/ cobicistat/ Elvitegravir ↔ ↔ ↔ No dose adjustment of Epclusa or emtricitabine/ tenofovir Cobicistat ↔ ↔ ↑ elvitegravir/ cobicistat/ alafenamide fumarate 2.0 emtricitabine/ tenofovir (150/ 150/ 200/ 10 mg once (1.7, alafenamide fumarate is required. daily)/ sofosbuvir/ 2.5) velpatasvir (400/ 100 mg Tenofovir ↔ ↔ once daily)c, d alafenamide Sofosbuvir ↔ ↑ 1.4 (1.2, 1.5) Velpatasvir ↑ ↑ ↑ 1.3 1.5 1.6 (1.2, (1.4, (1.4, 1.5) 1.7) 1.8) Elvitegravir/ cobicistat/ Elvitegravir ↔ ↔ ↔ No dose adjustment of Epclusa or emtricitabine/ tenofovir Cobicistat ↔ ↔ ↑ elvitegravir/ cobicistat/ disoproxil fumarate 1.7 emtricitabine/ tenofovir disoproxil (150/ 150/ 200/ 300 mg (1.5, fumarate is required. once daily)/ sofosbuvir/ 1.9) velpatasvir (400/ 100 mg Sofosbuvir ↔ ↔ once daily)c, d Velpatasvir ↔ ↔ ↑ 1.4 (1.2, 1.5) Dolutegravir (50 mg once Dolutegravir ↔ ↔ ↔ No dose adjustment of Epclusa or daily)/ sofosbuvir/ Sofosbuvir ↔ ↔ dolutegravir is required. velpatasvir (400/ 100 mg once daily) Velpatasvir ↔ ↔ ↔

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) lopinavir (HOS-086269) cobicistat (HOS-088111) dolutegravir (HOS-089992) tenofovir disoproxil (HOS-108843) fumarate (HOS-108845) tenofovir disoproxil fumarate (HOS-110471) raltegravir (HOS-086187) ritonavir (HOS-084521) elvitegravir (HOS-088110) emtricitabine (HOS-085840)

Wechselwirkungen · Epclusa

Epclusa 200 mg/50 mg coated granules in sachet Epclusa 150 mg/37.5 mg coated granules in sachet · Abschnitt 4.5 · PDF-Seite 42

HOS-136192 · Präparat HOS-097846

(Induction of P-gp and Observed: ↓ ↓ CYPs) Sofosbuvir 0.64 0.76 (0.53, (0.63, 0.77) 0.91) Rifapentine Interaction not studied. Co-administration of Epclusa with Expected: rifapentine is expected to decrease ↓ Sofosbuvir the concentration of sofosbuvir and ↓ Velpatasvir velpatasvir, leading to reduced (Induction of P-gp and therapeutic effect of Epclusa. CYPs) Co-administration is not recommended (see section 4.4). HIV ANTIVIRAL AGENTS: REVERSE TRANSCRIPTASE INHIBITORS Tenofovir disoproxil Epclusa has been shown to increase tenofovir exposure (P-gp-inhibition). The fumarate increase in tenofovir exposure (AUC and Cmax) was around 40-80% during co- treatment with Epclusa and tenofovir disoproxil fumarate/emtricitabine as part of various HIV regimens.

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) tenofovir disoproxil (HOS-108843) fumarate (HOS-108845) rifapentine (HOS-116386) tenofovir disoproxil fumarate (HOS-110471) emtricitabine (HOS-085840)

Wechselwirkungen · Epclusa

Epclusa 200 mg/50 mg coated granules in sachet Epclusa 150 mg/37.5 mg coated granules in sachet · Abschnitt 4.5 · PDF-Seite 42

HOS-136193 · Präparat HOS-097846

Patients receiving tenofovir disoproxil fumarate and Epclusa concomitantly should be monitored for adverse reactions associated with tenofovir disoproxil fumarate. Refer to the tenofovir disoproxil fumarate-containing product’s Summary of Product Characteristics for recommendations on renal monitoring (see section 4.4). Efavirenz/ emtricitabine/ Efavirenz ↔ ↔ ↔ Co-administration of Epclusa with tenofovir disoproxil Sofosbuvir ↑ ↔ efavirenz/ emtricitabine/ tenofovir fumarate 1.4 disoproxil fumarate is expected to (600/ 200/ 300 mg once (1.1, decrease the concentration of daily)/ sofosbuvir/ 1.7) velpatasvir. Co-administration of velpatasvir (400/ 100 mg Velpatasvir ↓ ↓ ↓ Epclusa with efavirenz-containing once daily)c, d 0.53 0.47 0.43 regimens is not recommended (see (0.43, (0.39, (0.36, section 4.4). 0.64) 0.57) 0.52)

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) tenofovir disoproxil (HOS-108843) fumarate (HOS-108845) efavirenz (HOS-087947) tenofovir disoproxil fumarate (HOS-110471) emtricitabine (HOS-085840)

Wechselwirkungen · Epclusa

Epclusa 200 mg/50 mg coated granules in sachet Epclusa 150 mg/37.5 mg coated granules in sachet · Abschnitt 4.5 · PDF-Seite 42–43

HOS-136194 · Präparat HOS-097846

42 Medicinal product by Effects on medicinal product levels. therapeutic areas/Possible Mean ratio (90% confidence interval)a,b Recommendation concerning Mechanism of Interaction Active Cmax AUC Cmin co-administration with Epclusa Emtricitabine/ rilpivirine/ Rilpivirine ↔ ↔ ↔ No dose adjustment of Epclusa or tenofovir disoproxil Sofosbuvir ↔ ↔ emtricitabine/ rilpivirine/ tenofovir fumarate Velpatasvir ↔ ↔ ↔ disoproxil fumarate is required. (200/ 25/ 300 mg once daily)/ sofosbuvir/ velpatasvir (400/ 100 mg once daily)c, d HIV ANTIVIRAL AGENTS: HIV PROTEASE INHIBITORS Atazanavir boosted with Atazanavir ↔ ↔ ↑ No dose adjustment of Epclusa, ritonavir (300/ 100 mg once 1.4 atazanavir (ritonavir boosted) or daily) + emtricitabine/ (1.2, emtricitabine/ tenofovir disoproxil tenofovir disoproxil 1.6) fumarate is required. fumarate (200/ 300 mg once Ritonavir ↔ ↑ daily)/ sofosbuvir/ 1.3 velpatasvir (400/ 100 mg (1.5, once daily)c, d 1.4) Sofosbuvir ↔ ↔

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) atazanavir (HOS-086180) protease (HOS-085623) tenofovir disoproxil (HOS-108843) fumarate (HOS-108845) rilpivirine (HOS-088090) ritonavir (HOS-084521) emtricitabine (HOS-085840)

Wechselwirkungen · Epclusa

Epclusa 200 mg/50 mg coated granules in sachet Epclusa 150 mg/37.5 mg coated granules in sachet · Abschnitt 4.5 · PDF-Seite 43

HOS-136195 · Präparat HOS-097846

Velpatasvir ↑ ↑ ↑ 1.6 2.4 4.0 (1.4, (2.2, (3.6, 1.7) 2.6) 4.5) Darunavir boosted with Darunavir ↔ ↔ ↔ No dose adjustment of Epclusa, ritonavir (800/ 100 mg once Ritonavir ↔ ↔ ↔ darunavir (ritonavir boosted) or daily) + emtricitabine/ Sofosbuvir ↓ ↓ emtricitabine/ tenofovir disoproxil tenofovir disoproxil 0.62 0.72 fumarate is required. fumarate (200/ 300 mg once (0.54, (0.66, daily)/ sofosbuvir/ 0.71) 0.80) velpatasvir (400/ 100 mg Velpatasvir ↓ ↔ ↔ once daily)c, d 0.76 (0.65, 0.89) Lopinavir boosted with Lopinavir ↔ ↔ ↔ No dose adjustment of Epclusa, ritonavir (4x200 mg/ 50 mg Ritonavir ↔ ↔ ↔ lopinavir (ritonavir boosted) or once daily) + emtricitabine/ Sofosbuvir ↓ ↓ emtricitabine/ tenofovir disoproxil tenofovir disoproxil 0.59 0.7 fumarate is required. fumarate (200/ 300 mg once (0.49 (0.6, daily)/ sofosbuvir/ 0.71) 0.8) velpatasvir (400/ 100 mg Velpatasvir ↓ ↔ ↑ once daily)c, d 0.70 1.6 (0.59, (1.4, 0.83) 1.9) HIV ANTIVIRAL AGENTS: INTEGRASE INHIBITORS Raltegravir (400 mg twice Raltegravir ↔ ↔ ↓ No dose adjustment of Epclusa, daily)g + emtricitabine/ 0.79 raltegravir or emtricitabine/ tenofovir disoproxil (0.42, tenofovir disoproxil fumarate is fumarate (200/ 300 mg once 1.5) required. daily)/ sofosbuvir/ Sofosbuvir ↔ ↔ velpatasvir (400/ 100 mg Velpatasvir ↔ ↔ ↔ once daily)c, d

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) tenofovir disoproxil (HOS-108843) fumarate (HOS-108845) darunavir (HOS-086181) tenofovir disoproxil fumarate (HOS-110471) raltegravir (HOS-086187) ritonavir (HOS-084521) emtricitabine (HOS-085840)

Wechselwirkungen · Epclusa

Epclusa 200 mg/50 mg coated granules in sachet Epclusa 150 mg/37.5 mg coated granules in sachet · Abschnitt 4.5 · PDF-Seite 43–44

HOS-136196 · Präparat HOS-097846

43 Medicinal product by Effects on medicinal product levels. therapeutic areas/Possible Mean ratio (90% confidence interval)a,b Recommendation concerning Mechanism of Interaction Active Cmax AUC Cmin co-administration with Epclusa Elvitegravir/ cobicistat/ Elvitegravir ↔ ↔ ↔ No dose adjustment of Epclusa or emtricitabine/ tenofovir Cobicistat ↔ ↔ ↑ elvitegravir/ cobicistat/ alafenamide fumarate 2.0 emtricitabine/ tenofovir (150/ 150/ 200/ 10 mg once (1.7, alafenamide fumarate is required. daily)/ sofosbuvir/ 2.5) velpatasvir (400/ 100 mg Tenofovir ↔ ↔ once daily)c, d alafenamide Sofosbuvir ↔ ↑ 1.4 (1.2, 1.5) Velpatasvir ↑ ↑ ↑ 1.3 1.5 1.6 (1.2, (1.4, (1.4, 1.5) 1.7) 1.8) Elvitegravir/ cobicistat/ Elvitegravir ↔ ↔ ↔ No dose adjustment of Epclusa or emtricitabine/ tenofovir Cobicistat ↔ ↔ ↑ elvitegravir/ cobicistat/ disoproxil fumarate 1.7 emtricitabine/ tenofovir disoproxil (150/ 150/ 200/ 300 mg (1.5, fumarate is required. once daily)/ sofosbuvir/ 1.9) velpatasvir (400/ 100 mg Sofosbuvir ↔ ↔ once daily)c, d Velpatasvir ↔ ↔ ↑ 1.4 (1.2, 1.5) Dolutegravir (50 mg once Dolutegravir ↔ ↔ ↔ No dose adjustment of Epclusa or daily)/ sofosbuvir/ Sofosbuvir ↔ ↔ dolutegravir is required. velpatasvir (400/ 100 mg once daily) Velpatasvir ↔ ↔ ↔

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) cobicistat (HOS-088111) dolutegravir (HOS-089992) tenofovir disoproxil (HOS-108843) fumarate (HOS-108845) elvitegravir (HOS-088110) emtricitabine (HOS-085840)

Wechselwirkungen · Maviret

Maviret 100 mg/40 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 6–8

HOS-139037 · Präparat HOS-098268

6 ANTIMYCOBACTERIALS Rifampicin ↑ glecaprevir 6.52 8.55 Co-administration 600 mg single (5.06, 8.41) (7.01, -- is contraindicated dose 10.4) (see section 4.3). ↔ ↔ ↔ -- (Inhibition of pibrentasvir OATP1B1/3) Rifampicin ↓ glecaprevir 0.14 0.12 -- 600 mg once (0.11, 0.19) (0.09, dailya 0.15) ↓ pibrentasvir 0.17 0.13 -- (Induction of P- (0.14, 0.20) (0.11, gp/BCRP/CYP3A 0.15) ) ETHINYL-OESTRADIOL-CONTAINING PRODUCTS Ethinyloestradiol ↑ EE 1.31 1.28 1.38 Co-administration (EE)/Norgestimate (1.24, 1.38) (1.23, (1.25, 1.52) of Maviret with 35 µg/250 µg once 1.32) ethinyloestradiol- daily ↑ ↔ 1.44 1.45 containing norelgestromi (1.34, (1.33, 1.58) products is n 1.54) contraindicated ↑ norgestrel 1.54 1.63 1.75 due to the risk of (1.34, 1.76) (1.50, (1.62, 1.89) ALT elevations 1.76) (see section 4.3). EE/Levonorgestrel ↑ EE 1.30 1.40 1.56 No dose 20 µg/100 µg once (1.18, 1.44) (1.33, (1.41, 1.72) adjustment is daily 1.48) required with ↑ norgestrel 1.37 1.68 1.77 levonorgestrel, (1.23, 1.52) (1.57, (1.58, 1.98) norethidrone or 1.80) norgestimate as contraceptive progestagen. HERBAL PRODUCTS St. John’s wort Not studied. Co-administration (Hypericum Expected: ↓ glecaprevir and ↓ pibrentasvir may lead to perforatum) reduced therapeutic effect (Induction of P- of Maviret and is gp/CYP3A) contraindicated (see section 4.3). HIV-ANTIVIRAL AGENTS Atazanavir + ↑ glecaprevir ≥4.06 ≥6.53 ≥14.3 Co-administration ritonavir (3.15, 5.23) (5.24, (9.85, 20.7) with atazanavir is 300/100 mg once 8.14) contraindicated dailyb ↑ pibrentasvir ≥1.29 ≥1.64 ≥2.29 due to the risk of (1.15, 1.45) (1.48, (1.95, 2.68) ALT elevations 1.82) (see section 4.3). Darunavir + ↑ glecaprevir 3.09 4.97 8.24 Co-administration ritonavir (2.26, 4.20) (3.62, (4.40, 15.4) with darunavir is 800/100 mg once 6.84) not daily ↔ ↔ ↔ 1.66 recommended. pibrentasvir (1.25, 2.21) Efavirenz/emtricit ↑ tenofovir ↔ 1.29 1.38 Co-administration abine/tenofovir (1.23, (1.31, 1.46) with efavirenz disoproxil 1.35) may lead to fumarate The effect of efavirenz/emtricitabine/tenofovir disoproxil reduced fumarate on glecaprevir and pibrentasvir was not directly therapeutic effect 7 600/200/300 mg quantified within this study, but glecaprevir and of Maviret and is once daily pibrentasvir exposures were significantly lower than not historical controls. recommended. No clinically significant interactions are expected with tenofovir disoproxil fumarate. Elvitegravir/cobici ↔ tenofovir ↔ ↔ ↔ No dose stat/emtricitabine/ ↑ glecaprevir 2.50 3.05 4.58 adjustment is tenofovir (2.08, 3.00) (2.55, (3.15, 6.65) required. alafenamide 3.64) ↑ pibrentasvir ↔ 1.57 1.89 (P-gp, BCRP, and (1.39, (1.63, 2.19) OATP inhibition 1.76) by cobicistat, OATP inhibition by elvitegravir) Lopinavir/ritonavi ↑ glecaprevir 2.55 4.38 Co-administration 18.6 r 400/100 mg (1.84, 3.52) (3.02, is not (10.4, 33.5) twice daily 6.36) recommended. ↑ pibrentasvir 1.40 2.46 5.24 (1.17, 1.67) (2.07, (4.18, 6.58) 2.92) Raltegravir ↑ raltegravir 1.34 1.47 2.64 No dose 400 mg twice (0.89, 1.98) (1.15, (1.42, 4.91) adjustment is daily 1.87) required.

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) lopinavir (HOS-086269) atazanavir (HOS-086180) norgestimate (HOS-110544) levonorgestrel (HOS-089677) cobicistat (HOS-088111) tenofovir disoproxil (HOS-108843) lead (HOS-085592) fumarate (HOS-108845) darunavir (HOS-086181) efavirenz (HOS-087947) raltegravir (HOS-086187) ritonavir (HOS-084521) elvitegravir (HOS-088110) emtricitabine (HOS-085840) norgestrel (HOS-090613)

Wechselwirkungen · Maviret

Maviret 50 mg/20 mg coated granules in sachet · Abschnitt 4.5 · PDF-Seite 33–34

HOS-139091 · Präparat HOS-098268

33 HERBAL PRODUCTS St. John’s wort Not studied. Co-administration (Hypericum Expected: ↓ glecaprevir and ↓ pibrentasvir may lead to reduced perforatum) therapeutic effect of Maviret and is (Induction of P- contraindicated (see gp/CYP3A) section 4.3). HIV-ANTIVIRAL AGENTS Atazanavir + ↑ ≥4.06 ≥6.53 ≥14.3 Co-administration ritonavir glecaprevir (3.15, 5.23) (5.24, 8.14) (9.85, 20.7) with atazanavir is 300/100 mg once ↑ ≥1.29 ≥1.64 ≥2.29 contraindicated due b daily pibrentasvir (1.15, 1.45) (1.48, 1.82) (1.95, 2.68) to the risk of ALT elevations (see section 4.3). Darunavir + ↑ 3.09 4.97 8.24 Co-administration ritonavir glecaprevir (2.26, 4.20) (3.62, 6.84) (4.40, 15.4) with darunavir is not 800/100 mg once ↔ ↔ ↔ 1.66 recommended. daily pibrentasvir (1.25, 2.21) Efavirenz/emtricita ↑ tenofovir ↔ 1.29 1.38 Co-administration bine/tenofovir (1.23, 1.35) (1.31, 1.46) with efavirenz may disoproxil fumarate The effect of efavirenz/emtricitabine/tenofovir disoproxil lead to reduced 600/200/300 mg fumarate on glecaprevir and pibrentasvir was not directly therapeutic effect of once daily quantified within this study, but glecaprevir and Maviret and is not pibrentasvir exposures were significantly lower than recommended. No historical controls. clinically significant interactions are expected with tenofovir disoproxil fumarate. Elvitegravir/cobicis ↔ tenofovir ↔ ↔ ↔ No dose adjustment tat/emtricitabine/ ↑ 2.50 3.05 4.58 is required. tenofovir glecaprevir (2.08, 3.00) (2.55, 3.64) (3.15, 6.65) alafenamide ↑ ↔ 1.57 1.89 pibrentasvir (1.39, 1.76) (1.63, 2.19) (P-gp, BCRP, and OATP inhibition by cobicistat, OATP inhibition by elvitegravir) Lopinavir/ritonavir ↑ 2.55 4.38 18.6 Co-administration is 400/100 mg twice glecaprevir (1.84, 3.52) (3.02, 6.36) (10.4, 33.5) not recommended. daily ↑ 1.40 2.46 5.24 pibrentasvir (1.17, 1.67) (2.07, 2.92) (4.18, 6.58) Raltegravir ↑ raltegravir 1.34 1.47 2.64 No dose adjustment 400 mg twice daily (0.89, 1.98) (1.15, 1.87) (1.42, 4.91) is required.

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) lopinavir (HOS-086269) atazanavir (HOS-086180) cobicistat (HOS-088111) tenofovir disoproxil (HOS-108843) lead (HOS-085592) fumarate (HOS-108845) darunavir (HOS-086181) efavirenz (HOS-087947) raltegravir (HOS-086187) ritonavir (HOS-084521) elvitegravir (HOS-088110) emtricitabine (HOS-085840)

Gegenanzeigen · Biktarvy

Biktarvy 30 mg/120 mg/15 mg film-coated tablets Biktarvy 50 mg/200 mg/25 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 3

HOS-139264 · Präparat HOS-098314

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

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