Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Epclusa

Epclusa 400 mg/100 mg film-coated tablets Epclusa 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-136135 · Präparat HOS-097846

Famotidine dosed 12 hours Velpatasvir ↔ ↔ prior to Epclusad

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): famotidine (HOS-112087)

Wechselwirkungen · Epclusa

Epclusa 400 mg/100 mg film-coated tablets Epclusa 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-136136 · Präparat HOS-097846

(Increase in gastric pH) Proton pump inhibitors Omeprazole Sofosbuvir ↓ ↓ Co-administration with proton (20 mg once daily)/ 0.66 0.71 pump inhibitors is not sofosbuvir/ velpatasvir (0.55, (0.60, recommended. If it is considered (400/ 100 mg single dose 0.78) 0.83) necessary to co-administer, then fasted)c Epclusa should be administered with food and taken 4 hours before Omeprazole dosed Velpatasvir ↓ ↓ proton pump inhibitor at max simultaneously with 0.63 0.64 doses comparable to omeprazole Epclusad (0.50, (0.52, 20 mg. 0.78) 0.79) Lansoprazolee Rabeprazolee Pantoprazolee Esomeprazolee

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): omeprazole (HOS-085912)

Wechselwirkungen · Epclusa

Epclusa 400 mg/100 mg film-coated tablets Epclusa 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-136137 · Präparat HOS-097846

(Increase in gastric pH) Omeprazole Sofosbuvir ↓ ↔ (20 mg once daily)/ 0.79 sofosbuvir/ velpatasvir (0.68, (400/ 100 mg single dose 0.92) fed)c

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): omeprazole (HOS-085912)

Wechselwirkungen · Epclusa

Epclusa 400 mg/100 mg film-coated tablets Epclusa 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-136138 · Präparat HOS-097846

Omeprazole dosed 4 hours Velpatasvir ↓ ↓ after Epclusad 0.67 0.74 (0.58, (0.63, (Increase in gastric pH) 0.78) 0.86)

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): omeprazole (HOS-085912)

Wechselwirkungen · Epclusa

Epclusa 400 mg/100 mg film-coated tablets Epclusa 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8–9

HOS-136139 · Präparat HOS-097846

8 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 ANTIARRHYTHMICS Amiodarone Effect on amiodarone, velpatasvir, and Co-administration of amiodarone sofosbuvir concentrations unknown. with a sofosbuvir containing regimen may result in serious symptomatic bradycardia. Use only if no other alternative is available. Close monitoring is recommended if this medicinal product is administered with Epclusa (see sections 4.4 and 4.8). Digoxin Interaction only studied with velpatasvir. Co-administration of Epclusa with Expected: digoxin may increase the ↔ Sofosbuvir concentration of digoxin. Caution Digoxin (0.25 mg single Effect on velpatasvir exposure not studied is warranted and therapeutic dose)f/ velpatasvir (100 mg Expected: concentration monitoring of single dose) ↔ Velpatasvir digoxin is recommended when co-administered with Epclusa. (Inhibition of P-gp) Observed: Digoxin ↑ ↑ 1.9 1.3 (1.7, (1.1, 2.1) 1.6) ANTICOAGULANTS Dabigatran etexilate Interaction not studied. Clinical monitoring, looking for Expected: signs of bleeding and anaemia, is ↑ Dabigatran recommended when dabigatran ↔ Sofosbuvir etexilate is co-administered with ↔ Velpatasvir Epclusa. A coagulation test helps (Inhibition of P-gp) to identify patients with an increased bleeding risk due to increased dabigatran exposure. Vitamin K antagonists Interaction not studied Close monitoring of INR is recommended with all vitamin K antagonists. This is due to liver function changes during treatment with Epclusa. ANTICONVULSANTS Phenytoin Interaction not studied. Epclusa is contraindicated with Phenobarbital Expected: phenobarbital and phenytoin (see ↓ Sofosbuvir section 4.3). (Induction of P-gp and ↓ Velpatasvir CYPs) Carbamazepine Interaction not studied. Epclusa is contraindicated with Expected: carbamazepine (see section 4.3). ↓ 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): phenobarbital (HOS-085617) carbamazepine (HOS-085618) vitamin K (HOS-091176) digoxin (HOS-086172) dabigatran (HOS-112096) amiodarone (HOS-085596) dabigatran etexilate (HOS-086233) phenytoin (HOS-084531)

Wechselwirkungen · Epclusa

Epclusa 400 mg/100 mg film-coated tablets Epclusa 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-136140 · Präparat HOS-097846

(Induction of P-gp and Observed: ↓0.52 ↓ 0.52 CYPs) Sofosbuvir (0.43, (0.46, 0.62) 0.59)

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

Wechselwirkungen · Epclusa

Epclusa 400 mg/100 mg film-coated tablets Epclusa 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-136141 · Präparat HOS-097846

Oxcarbazepine Interaction not studied. Co-administration of Epclusa with Expected: oxcarbazepine is expected to ↓ Sofosbuvir decrease the concentration of (Induction of P-gp and ↓ Velpatasvir sofosbuvir and velpatasvir, leading CYPs) to reduced therapeutic effect of Epclusa. Co-administration is not recommended (see section 4.4).

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): oxcarbazepine (HOS-110224)

Wechselwirkungen · Epclusa

Epclusa 400 mg/100 mg film-coated tablets Epclusa 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9–10

HOS-136142 · Präparat HOS-097846

9 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 ANTIFUNGALS Ketoconazole Interaction only studied with velpatasvir No dose adjustment of Epclusa or Expected: ketoconazole is required. ↔ Sofosbuvir Ketoconazole (200 mg Effect on ketoconazole exposure not twice daily)/ velpatasvir studied. (100 mg single dose)d Expected: ↔ Ketoconazole Observed: Velpatasvir ↑ ↑ (Inhibition of P-gp and 1.3 1.7 CYPs) (1.0, (1.4, 1.6) 2.2) Itraconazolee Voriconazolee Posaconazolee Isavuconazolee ANTIMYCOBACTERIALS Rifampicin (600 mg once Effect on rifampicin exposure not studied. Epclusa is contraindicated with daily)/ sofosbuvir (400 mg rifampicin (see section 4.3). single dose)d Expected: ↔ Rifampicin Observed: (Induction of P-gp and Sofosbuvir ↓ ↓ CYPs) 0.23 0.28 (0.19, (0.24, 0.29) 0.32) Rifampicin (600 mg once Effect on rifampicin exposure not studied. daily)/ velpatasvir (100 mg single dose) Expected: ↔ Rifampicin Observed: Velpatasvir ↓ ↓ 0.29 0.18 (Induction of P-gp and (0.23, (0.15, CYPs) 0.37) 0.22) Rifabutin Interaction not studied. Epclusa is contraindicated with Expected: rifabutin (see section 4.3). ↓ 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): ketoconazole (HOS-084513) rifabutin (HOS-086262)

Wechselwirkungen · Epclusa

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

HOS-136143 · Präparat HOS-097846

(Induction of P-gp and Observed: ↓ ↓ CYPs) Sofosbuvir 0.64 0.76 (0.53, (0.63, 0.77) 0.91)

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

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

HOS-136149 · Präparat HOS-097846

HERBAL SUPPLEMENTS St. John’s wort Interaction not studied. Epclusa is contraindicated with Expected: St. John’s wort (see section 4.3). ↓ Sofosbuvir ↓ Velpatasvir (Induction of P-gp and CYPs)

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

Wechselwirkungen · Epclusa

Epclusa 400 mg/100 mg film-coated tablets Epclusa 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12–13

HOS-136150 · Präparat HOS-097846

12 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 HMG-CoA REDUCTASE INHIBITORS Atorvastatin (40 mg single Observed: ↑ ↑ No dose adjustment of Epclusa or dose) + sofosbuvir / Atorvastatin 1.7 1.5 atorvastatin is required. velpatasvir (400/ 100 mg (1.5, (1.5, once daily)d 1.9) 1.6) Rosuvastatin Interaction only studied with velpatasvir Co-administration of Epclusa with Expected: rosuvastatin increases the ↔ Sofosbuvir concentration of rosuvastatin, Rosuvastatin (10 mg single Observed: which is associated with increased dose)/ velpatasvir (100 mg Rosuvastatin ↑ ↑ risk of myopathy, including once daily)d 2.6 2.7 rhabdomyolysis. Rosuvastatin, at a (2.3, (2.5, dose that does not exceed 10 mg, 2.9) 2.9) may be administered with Epclusa. Effect on velpatasvir exposure not studied (Inhibition of OATP1B and Expected: BCRP) ↔ Velpatasvir Pravastatin Interaction only studied with velpatasvir No dose adjustment of Epclusa or Expected: pravastatin is required. ↔ Sofosbuvir Pravastatin (40 mg single Observed: dose)/ velpatasvir (100 mg Pravastatin ↑ ↑ once daily)d 1.3 1.4 (1.1, (1.2, 1.5) 1.5) (Inhibition of OATP1B) Effect on velpatasvir exposure not studied Expected: ↔ Velpatasvir Other statins Expected: Interactions cannot be excluded ↑ Statins with other HMG-CoA reductase inhibitors. When co-administered with Epclusa, careful monitoring for statin adverse reactions should be undertaken and a reduced dose of statins should be considered if required. NARCOTIC ANALGESICS Methadone R-methadone ↔ ↔ ↔ No dose adjustment of Epclusa or (Methadone maintenance methadone is required. therapy [30 to 130 mg S-methadone ↔ ↔ ↔ daily])/ sofosbuvir (400 mg once daily)d Sofosbuvir ↔ ↑ 1.3 (1.0, 1.7) Methadone Interaction only studied with sofosbuvir Expected: ↔ 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): methadone (HOS-086198) atorvastatin (HOS-086304) rosuvastatin (HOS-086307) pravastatin (HOS-086306)

Wechselwirkungen · Epclusa

Epclusa 400 mg/100 mg film-coated tablets Epclusa 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 13–14

HOS-136151 · Präparat HOS-097846

13 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 IMMUNOSUPPRESSANTS Ciclosporin Ciclosporin ↔ ↔ No dose adjustment of Epclusa or (600 mg single dose)/ ciclosporin is required at initiation sofosbuvir (400 mg single Sofosbuvir ↑ ↑ of co-administration. Afterwards, dose)f 2.5 4.5 close monitoring and potential (1.9, (3.3, dose adjustment of ciclosporin may 3.5) 6.3) be required. Ciclosporin Ciclosporin ↔ ↓ (600 mg single dose)f/ 0.88 velpatasvir (100 mg single (0.78, dose)d 1.0) Velpatasvir ↑ ↑ 1.6 2.0 (1.2, (1.5, 2.0) 2.7) Tacrolimus Tacrolimus ↓ ↑ No dose adjustment of Epclusa or (5 mg single dose)f/ 0.73 1.1 tacrolimus is required at initiation sofosbuvir (400 mg single (0.59, (0.84, of co-administration. Afterwards, dose)d 0.90) 1.4) close monitoring and potential Sofosbuvir ↓ ↑ dose adjustment of tacrolimus may 0.97 1.1 be required. (0.65, (0.81, 1.4) 1.6) Tacrolimus Effect on velpatasvir exposure not studied. Expected: ↔ Velpatasvir ORAL CONTRACEPTIVES Norgestimate/ ethinyl Norel- ↔ ↔ ↔ No dose adjustment of oral estradiol (norgestimate gestromin contraceptives is required. 0.180 mg/ 0.215 mg/ 0.25 mg/ ethinyl estradiol 0.025 mg)/ sofosbuvir (400 mg once daily)d Norgestrel ↔ ↑ ↑ 1.2 1.2 (0.98, (1.0, 1.5) 1.5) Ethinyl ↔ ↔ ↔ estradiol Norgestimate/ ethinyl Norel- ↔ ↔ ↔ estradiol (norgestimate gestromin 0.180 mg/ 0.215 mg/ Norgestrel ↔ ↔ ↔ 0.25 mg/ ethinyl estradiol 0.025 mg)/ velpatasvir Ethinyl ↑ ↔ ↓ (100 mg once daily)d estradiol 1.4 0.83 (1.2, (0.65, 1.7) 1.1) a Mean ratio (90% CI) of co-administered drug pharmacokinetics of study medicinal products alone or in combination. No effect = 1.00. b All interaction studies conducted in healthy volunteers. c Administered as Epclusa. d Lack of pharmacokinetics interaction bounds 70-143%. e These are medicinal products within class where similar interactions could be predicted. f Bioequivalence/Equivalence boundary 80-125%. g Lack of pharmacokinetics interaction bounds 50-200%.

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): norgestimate (HOS-110544) estradiol (HOS-090751) ethinyl estradiol (HOS-088135) tacrolimus (HOS-085202) norgestrel (HOS-090613)

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 38

HOS-136168 · Präparat HOS-097846

As Epclusa contains sofosbuvir and velpatasvir, any interactions that have been identified with these active substances individually may occur with Epclusa.

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

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 38

HOS-136169 · Präparat HOS-097846

Potential for Epclusa to affect other medicinal products

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

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 38

HOS-136170 · Präparat HOS-097846

Velpatasvir is an inhibitor of drug transporter P-gp, breast cancer resistance protein (BCRP), organic anion-transporting polypeptide (OATP) 1B1 and OATP1B3. Co-administration of Epclusa with medicinal products that are substrates of these transporters may increase the exposure of such medicinal products. See Table 4 for examples of interactions with sensitive substrates of P-gp (digoxin), BCRP (rosuvastatin), and OATP (pravastatin).

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): rosuvastatin (HOS-086307) digoxin (HOS-086172) pravastatin (HOS-086306)

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 38

HOS-136171 · Präparat HOS-097846

Potential for other medicinal products to affect Epclusa

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