Quest for the right Drug
ווסווי VOSEVI (SOFOSBUVIR, VELPATASVIR, VOXILAPREVIR)
תרופה במרשם
תרופה בסל
נרקוטיקה
ציטוטוקסיקה
צורת מתן:
פומי : PER OS
צורת מינון:
טבליות מצופות פילם : FILM COATED TABLETS
עלון לרופא
מינוניםPosology התוויות
Indications תופעות לוואי
Adverse reactions התוויות נגד
Contraindications אינטראקציות
Interactions מינון יתר
Overdose הריון/הנקה
Pregnancy & Lactation אוכלוסיות מיוחדות
Special populations תכונות פרמקולוגיות
Pharmacological properties מידע רוקחי
Pharmaceutical particulars אזהרת שימוש
Special Warning עלון לרופא
Physicians Leaflet
Interactions : אינטראקציות
4.5 Interaction with other medicinal products and other forms of interaction As Vosevi contains sofosbuvir, velpatasvir and voxilaprevir, any interactions that have been identified with these active substances individually may occur with Vosevi. Pharmacokinetic interactions Potential for Vosevi to affect other medicinal products Velpatasvir and voxilaprevir are inhibitors of drug transporters P-gp, breast cancer resistance protein (BCRP), organic anion-transporting polypeptide (OATP) 1B1 and OATP1B3. Co-administration of Vosevi with medicinal products that are substrates of these transporters may increase the exposure of such medicinal products. Medicinal products that are sensitive substrates of these transporters and for which elevated plasma levels are associated with serious events are contraindicated (see Table 2). Dabigatran etexilate (P-gp substrate) and rosuvastatin (OATP1B and BCRP substrate) are contraindicated (see section 4.3 and Table 2). Potential for other medicinal products to affect Vosevi Sofosbuvir, velpatasvir and voxilaprevir are substrates of drug transporters P-gp and BCRP. Velpatasvir and voxilaprevir are substrates of drug transporters OATP1B1 and OATP1B3. In vitro, slow metabolic turnover of velpatasvir primarily by CYP2B6, CYP2C8 and CYP3A4 and of voxilaprevir primarily by CYP3A4 was observed. Medicinal products that may decrease plasma exposure of Vosevi Medicinal products that are strong inducers of P-gp and/or strong inducers of CYP2B6, CYP2C8, or CYP3A4 (e.g. carbamazepine, phenobarbital, phenytoin, rifampicin, rifabutin and St. John’s wort) may decrease plasma concentrations of sofosbuvir, velpatasvir and/or voxilaprevir leading to reduced therapeutic effect of Vosevi. The use of such medicinal products with Vosevi is contraindicated (see section 4.3 and Table 2). Medicinal products that are moderate P-gp inducers and/or moderate CYP inducers (e.g. efavirenz, modafinil, oxcarbazepine or rifapentine) may decrease sofosbuvir, velpatasvir and/or voxilaprevir plasma concentrations leading to reduced therapeutic effect of Vosevi. Co-administration with such medicinal products is not recommended with Vosevi (see section 4.4 and Table 2). Medicinal products that may increase plasma exposure of Vosevi Co-administration with medicinal products that inhibit P-gp or BCRP may increase sofosbuvir, velpatasvir or voxilaprevir plasma concentrations. Medicinal products that inhibit OATP1B, CYP2B6, CYP2C8, or CYP3A4 may increase plasma concentrations of velpatasvir or voxilaprevir. The use of strong inhibitors of OATP1B (e.g. ciclosporin) with Vosevi is not recommended (see section 4.4 and Table 2). Clinically significant medicinal product interactions with Vosevi mediated by P-gp, BCRP and CYP inhibitors are not expected. Vosevi may be co-administered with P-gp, BCRP and CYP inhibitors. Pharmacodynamic interactions Patients treated with vitamin K antagonists As liver function may change during treatment with Vosevi, close monitoring of International Normalised Ratio (INR) values is recommended. Impact of DAA therapy on medicinal products metabolized by the liver The pharmacokinetics of medicinal products that are metabolized by the liver (e.g. immunosuppressive agents such as calcineurin inhibitors) may be impacted by changes in liver function during DAA therapy, related to clearance of HCV. Patients treated with ethinylestradiol-containing medicinal products Concomitant use with ethinylestradiol-containing medicinal products may increase the risk of alanine aminotransferase (ALT) elevations and is contraindicated (see section 4.3 and Table 2). Interactions between Vosevi and other medicinal products Table 2 provides a listing of established or potentially clinically significant medicinal product interactions (where 90% confidence interval [CI] of the geometric least-squares mean [GLSM] ratio were within “↔”, extended above “↑”, or extended below “↓” the predetermined interaction boundaries). The medicinal product interactions described are based on studies conducted with either sofosbuvir/velpatasvir/voxilaprevir, its components (sofosbuvir, velpatasvir, and/or voxilaprevir), or are predicted medicinal product interactions that may occur with Vosevi. The table is not all-inclusive. Table 2: Interactions between Vosevi and other medicinal products Medicinal product by Effects on medicinal product levels. therapeutic Mean ratio (90% confidence interval)a,b areas/Possible mechanism Recommendation concerning of interaction Active Cmax AUC Cmin co-administration with Vosevi ACID REDUCING AGENTS Antacids e.g. Aluminium or Interaction not studied. It is recommended to separate magnesium hydroxide; Expected: antacid and Vosevi calcium carbonate ↔ Sofosbuvir administration by 4 hours. ↓ Velpatasvir (Increase in gastric pH ↔ Voxilaprevir decreases velpatasvir solubility) H2-receptor antagonists Famotidine Observed: H2-receptor antagonists may be (40 mg single dose) + Sofosbuvir ↔ ↔ administered simultaneously sofosbuvir/velpatasvir/ with or staggered from Vosevi at voxilaprevir a dose that does not exceed doses (400/100/100 mg single comparable with famotidine dose)c Velpatasvir ↔ ↔ 40 mg twice daily. Famotidine dosed simultaneously with Vosevi Voxilaprevir ↔ ↔ Cimetidined Nizatidined Medicinal product by Effects on medicinal product levels. therapeutic Mean ratio (90% confidence interval)a,b areas/Possible mechanism Recommendation concerning of interaction Active Cmax AUC Cmin co-administration with Vosevi Ranitidined (Increase in gastric pH decreases velpatasvir solubility) Famotidine Observed: (40 mg single dose) + Sofosbuvir ↔ ↔ sofosbuvir/velpatasvir/ voxilaprevir (400/100/ 100 mg single dose)c Velpatasvir ↔ ↔ Famotidine dosed 12 hours prior to Vosevi (Increase in gastric pH Voxilaprevir ↔ ↔ decreases velpatasvir solubility) Proton pump inhibitors Omeprazole Observed: Proton pump inhibitors may be (20 mg once daily) + Sofosbuvir ↓ ↓ administered with Vosevi at a sofosbuvir/velpatasvir/ 0.77 0.73 dose that does not exceed doses voxilaprevir (400/100/ (0.65, (0.67, comparable with omeprazole 100 mg single dose)c 0.91) 0.79) 20 mg. Velpatasvir ↓ ↓ Omeprazole dosed 2 hours 0.43 0.46 prior to Vosevi (0.38, (0.41, 0.49) 0.52) Lansoprazoled Rabeprazoled Pantoprazoled Voxilaprevir ↓ ↔ Esomeprazoled 0.76 (0.69, (Increase in gastric pH 0.85) decreases velpatasvir solubility) Omeprazole Observed: (20 mg once daily) + Sofosbuvir ↔ ↔ sofosbuvir/velpatasvir/ voxilaprevir (400/100/ 100 mg single dose)c Velpatasvir ↓ ↓ Omeprazole dosed 4 hours 0.49 0.49 after Vosevi (0.43, (0.43, 0.55) 0.55) (Increase in gastric pH Voxilaprevir ↔ ↔ decreases velpatasvir solubility) Medicinal product by Effects on medicinal product levels. therapeutic Mean ratio (90% confidence interval)a,b areas/Possible mechanism Recommendation concerning of interaction Active Cmax AUC Cmin co-administration with Vosevi ANTIARRHYTHMICS Amiodarone Effect on amiodarone, voxilaprevir, velpatasvir, Coadministration of amiodarone and 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 Vosevi (see sections 4.4 and 4.8). Digoxin Interaction only studied with velpatasvir. Co-administration of Vosevi Expected: with digoxin may increase the ↔ Sofosbuvir concentration of digoxin. ↔ Voxilaprevir Caution is warranted and Digoxin (0.25 mg single Effect on velpatasvir exposure not studied therapeutic concentration dose)e + velpatasvir Expected: monitoring of digoxin is (100 mg single dose) ↔ Velpatasvir recommended. (Inhibition of P-gp) Observed: Digoxin ↑ ↑ 1.88 1.34 (1.71, (1.13, 2.08) 1.60) ANTICOAGULANTS Dabigatran etexilate Effect on sofosbuvir, velpatasvir and Vosevi is contraindicated with (75 mg single dose) + voxilaprevir concentrations not studied dabigatran etexilate (see sofosbuvir/velpatasvir/ Expected: section 4.3). voxilaprevir (400/100/ ↔ Sofosbuvir 100 mg single dose) + ↔ Velpatasvir voxilaprevir (100 mg ↔ Voxilaprevir single dose)f Observed: Dabigatran ↑ ↑ (Inhibition of P-gp) 2.87 2.61 (2.61, (2.41, 3.15) 2.82) Edoxaban Interaction not studied. Co-administration of Vosevi Expected: with edoxaban is not (Inhibition of OATP1B1) ↑ Edoxaban (active metabolite) recommended. Should direct Xa ↔ Sofosbuvir inhibitor use be deemed ↔ Velpatasvir necessary, apixaban or ↔ Voxilaprevir rivaroxaban may be considered. Vitamin K antagonists Interaction not studied. Close monitoring of INR is recommended when Vosevi is (Liver function changes co-administered with all vitamin during treatment with K antagonists. Vosevi). ANTICONVULSANTS Phenytoin Interaction not studied. Vosevi is contraindicated with Phenobarbital Expected: phenobarbital and phenytoin (see ↓ Sofosbuvir section 4.3). ↓ Velpatasvir Medicinal product by Effects on medicinal product levels. therapeutic Mean ratio (90% confidence interval)a,b areas/Possible mechanism Recommendation concerning of interaction Active Cmax AUC Cmin co-administration with Vosevi ↓ Voxilaprevir (Induction of P-gp and CYPs) Carbamazepine Interaction not studied. Vosevi is contraindicated with Expected: carbamazepine (see section 4.3). (Induction of P-gp and ↓ Velpatasvir CYPs) ↓ Voxilaprevir Observed: Sofosbuvir ↓ ↓ 0.52 0.52 (0.43, (0.46 0.62) , 0.59) Medicinal product by Effects on medicinal product levels. therapeutic Mean ratio (90% confidence interval)a,b areas/Possible mechanism Recommendation concerning of interaction Active Cmax AUC Cmin co-administration with Vosevi ANTIFUNGALS Ketoconazole Interaction only studied with velpatasvir No dose adjustment of Vosevi or Expected: ketoconazole is required. (Inhibition of P-gp and ↔ Sofosbuvir CYP3A) ↑ Voxilaprevir Ketoconazole (200 mg Effect on ketoconazole exposure not studied. twice daily) + velpatasvir Expected: (100 mg single dose)f ↔ Ketoconazole Observed: Itraconazoled Velpatasvir ↑ ↑ Posaconazoled 1.29 1.71 Isavuconazoled (1.02, (1.35, 1.64) 2.18) (Inhibition of P-gp and CYP3A) Voriconazole Interaction only studied with voxilaprevir. No dose adjustment of Vosevi or Expected: voriconazole is required. (Inhibition of CYP3A) ↔ Sofosbuvir ↑ Velpatasvir Voriconazole (200 mg Observed: twice daily) + voxilaprevir Voxilaprevir ↔ ↑ (100 mg single dose)f 1.84 (1.66, 2.03) ANTIMYCOBACTERIALS Rifampicin (single dose) Interaction only studied with velpatasvir and Vosevi is contraindicated with voxilaprevir. rifampicin (see section 4.3). (Inhibition of OATP1B) Expected: ↔ Rifampicin ↔ Sofosbuvir Rifampicin (600 mg single Observed: dose) + velpatasvir Velpatasvir ↑ ↑ (100 mg single dose)f 1.28 1.46 (1.05, (1.17, 1.56) 1.83) Rifampicin (600 mg single Voxilaprevir ↑ ↑ dose) + voxilaprevir 11.10 7.91 (100 mg single dose)f (8.23, (6.20, 14.98) 10.09) Rifampicin (multiple dose) Effect on rifampicin exposure not studied. (Induction of P-gp and Expected: CYPs) ↔ Rifampicin Rifampicin (600 mg once Observed: daily) + sofosbuvir Sofosbuvir ↓ ↓ (400 mg single dose)f 0.23 0.28 (0.19, (0.24, 0.29) 0.32) Medicinal product by Effects on medicinal product levels. therapeutic Mean ratio (90% confidence interval)a,b areas/Possible mechanism Recommendation concerning of interaction Active Cmax AUC Cmin co-administration with Vosevi Rifampicin (600 mg once Velpatasvir ↓ ↓ daily) + velpatasvir 0.29 0.18 (100 mg single dose)f (0.23, (0.15, 0.37) 0.22) Rifampicin (600 mg once Voxilaprevir ↔ ↓ daily) + voxilaprevir 0.27 (100 mg single dose)f (0.23, 0.31) Rifabutin Interaction not studied. Vosevi is contraindicated with Expected: rifabutin (see section 4.3). ↓ Velpatasvir ↓ Voxilaprevir (Induction of P-gp and Observed: ↓ ↓ CYPs) Sofosbuvir 0.64 0.76 (0.53 (0.63, , 0.91) 0.77) Rifapentine Interaction not studied. Co-administration of Vosevi Expected: with rifapentine is not (Induction of P-gp and ↓ Sofosbuvir recommended (see section 4.4). CYPs) ↓ Velpatasvir ↓ Voxilaprevir HIV ANTIVIRAL AGENTS: REVERSE TRANSCRIPTASE INHIBITORS Tenofovir disoproxil Vosevi has been shown to increase tenofovir exposure (P-gp inhibition). There was fumarate an increase in tenofovir exposure (AUC and Cmax) of around 40% during co- treatment with Vosevi and darunavir + ritonavir + tenofovir disoproxil (Inhibition of P-gp) fumarate/emtricitabine. Patients receiving tenofovir disoproxil fumarate and Vosevi 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/ Interaction only studied with Co-administration of Vosevi tenofovir disoproxil sofosbuvir/velpatasvir with fumarate (600/200/300 mg Expected: efavirenz/emtricitabine/tenofovir once daily)g + sofosbuvir/ ↓ Voxilaprevir disoproxil fumarate is not velpatasvir (400/100 mg Observed: recommended (see section 4.4). once daily)f, h Efavirenz ↔ ↔ ↔ Sofosbuvir ↑ ↔ (Induction of CYPs) 1.38 (1.14, 1.67) Velpatasvir ↓ ↓ ↓ 0.53 0.47 0.43 (0.43, (0.39, (0.36, 0.64) 0.57) 0.52) Medicinal product by Effects on medicinal product levels. therapeutic Mean ratio (90% confidence interval)a,b areas/Possible mechanism Recommendation concerning of interaction Active Cmax AUC Cmin co-administration with Vosevi Emtricitabine/rilpivirine/ Observed: No dose adjustment of Vosevi or tenofovir alafenamide Rilpivirine ↔ ↔ ↔ emtricitabine/rilpivirine/tenofovi (200/25/25 mg once daily)i Sofosbuvir ↔ ↔ r alafenamide is required. + sofosbuvir/velpatasvir/ Velpatasvir ↔ ↔ ↔ voxilaprevir (400/100/ Voxilaprevir ↔ ↔ ↔ 100 mg once daily) + voxilaprevir (100 mg once daily)f HIV ANTIVIRAL AGENTS: HIV PROTEASE INHIBITORS Atazanavir boosted with Effect on atazanavir and ritonavir exposure not Co-administration of Vosevi ritonavir (300 + 100 mg studied. with atazanavir is expected to single dose) + sofosbuvir/ increase the concentration of voxilaprevir. Co-administration velpatasvir/voxilaprevir Expected: of Vosevi with atazanavir- (400/100/100 mg single ↔ Atazanavir containing regimens is not dose)f ↔ Ritonavir recommended. Observed: (Inhibition of OATP1B, Sofosbuvir ↑ ↑ P-gp and CYP3A) 1.29 1.40 (1.09, (1.25, 1.52) 1.57) Velpatasvir ↑ ↑ 1.29 1.93 (1.07, (1.58, 1.56) 2.36) Voxilaprevir ↑ ↑ 4.42 4.31 (3.65, (3.76, 5.35) 4.93) Darunavir boosted with Observed: No dose adjustment of Vosevi, ritonavir (800 + 100 mg Darunavir ↔ ↔ ↓ darunavir (ritonavir boosted) or once daily) + emtricitabine/ 0.66 emtricitabine/tenofovir tenofovir disoproxil (0.58, disoproxil fumarate is required. fumarate (200/300 mg once 0.74) daily)j + sofosbuvir/ Ritonavir ↑ ↑ ↔ velpatasvir/voxilaprevir 1.60 1.45 (400/100/100 mg once (1.47, (1.35, daily) + voxilaprevir 1.75) 1.57) (100 mg once daily)f Sofosbuvir ↓ ↔ 0.70 (Inhibition of OATP1B, (0.62, P-gp, and CYP3A) 0.78) Velpatasvir ↔ ↔ ↔ Voxilaprevir ↑ ↑ ↑ 1.72 2.43 4.00 (1.51, (2.15, (3.44, 1.97) 2.75) 4.65) Medicinal product by Effects on medicinal product levels. therapeutic Mean ratio (90% confidence interval)a,b areas/Possible mechanism Recommendation concerning of interaction Active Cmax AUC Cmin co-administration with Vosevi Lopinavir Interaction not studied. Co-administration of Vosevi Expected: with lopinavir-containing (Inhibition of OATP1B) ↔ Lopinavir regimens is not recommended. ↔ Sofosbuvir ↔ Velpatasvir ↑ Voxilaprevir HIV ANTIVIRAL AGENTS: INTEGRASE INHIBITORS Raltegravir (400 mg twice Interaction only studied with No dose adjustment of Vosevi, daily)k + emtricitabine/ sofosbuvir/velpatasvir raltegravir or tenofovir disoproxil Expected: emtricitabine/tenofovir disoproxil fumarate is required. fumarate (200/300 mg once ↔ Voxilaprevir daily)j + sofosbuvir/ Observed: velpatasvir (400/100 mg Raltegravir ↔ ↔ ↓ once daily)f, h 0.79 (0.42, 1.48) Sofosbuvir ↔ ↔ Velpatasvir ↔ ↔ ↔ Elvitegravir/cobicistat/ Observed: No dose adjustment of Vosevi or emtricitabine/tenofovir Elvitegravir ↔ ↔ ↑ elvitegravir/cobicistat/ alafenamide fumarate 1.32 emtricitabine/tenofovir (150/150/200/10 mg once (1.17, alafenamide fumarate is required. daily)l + 1.49) sofosbuvir/velpatasvir/ Cobicistat ↔ ↑ ↑ voxilaprevir (400/100/ 1.50 3.50 100 mg once daily) + (1.44, (3.01, voxilaprevir (100 mg once 1.58) 4.07) daily)f Tenofovir ↓ ↔ 0.79 (Inhibition of OATP1B, (0.68, P-gp/BCRP and CYP3A) 0.92) Sofosbuvir ↑ ↔ 1.27 (1.09, 1.48) Velpatasvir ↔ ↔ ↑ 1.46 (1.30, 1.64) Voxilaprevir ↑ ↑ ↑ 1.92 2.71 4.50 (1.63, (2.30, (3.68, 2.26) 3.19) 5.50) Dolutegravir (50 mg once Interaction only studied with No dose adjustment of Vosevi or daily) + sofosbuvir/ sofosbuvir/velpatasvir dolutegravir is required. velpatasvir (400/100 mg Expected: once daily)h ↔ Voxilaprevir Observed: Dolutegravir ↔ ↔ ↔ Medicinal product by Effects on medicinal product levels. therapeutic Mean ratio (90% confidence interval)a,b areas/Possible mechanism Recommendation concerning of interaction Active Cmax AUC Cmin co-administration with Vosevi Sofosbuvir ↔ ↔ Velpatasvir ↔ ↔ ↔ HERBAL SUPPLEMENTS St. John’s wort Interaction not studied. Vosevi is contraindicated with Expected: St. John’s wort (see section 4.3). (Induction of P-gp and ↓ Sofosbuvir CYPs) ↓ Velpatasvir ↓ Voxilaprevir HMG-CoA REDUCTASE INHIBITORS Atorvastatin Interaction only studied with sofosbuvir/ Atorvastatin may be velpatasvir. administered with Vosevi at a Expected: dose that does not exceed ↔ Voxilaprevir atorvastatin 20 mg. Atorvastatin (40 mg single Observed: ↑ ↑ dose) + sofosbuvir/ atorvastatin 1.7 1.5 velpatasvir (400/100 mg (1.5, (1.5, once daily) f 1.9) 1.6) Rosuvastatin Effect on sofosbuvir, velpatasvir and Vosevi is contraindicated with voxilaprevir not studied. rosuvastatin (see section 4.3). Expected: ↔ Sofosbuvir ↔ Velpatasvir ↔ Voxilaprevir Rosuvastatin (10 mg single Observed: dose) + sofosbuvir/ Rosuvastatin ↑ ↑ velpatasvir/voxilaprevir 18.9 7.4 (400/100/100 mg once (16.2, (6.7, daily) + voxilaprevir 22.0) 8.2) (100 mg once daily)f (Inhibition of OATP1B and BCRP) Pravastatin Effect on sofosbuvir, velpatasvir and Pravastatin may be administered voxilaprevir not studied. with Vosevi at a dose that does Expected: not exceed pravastatin 40 mg. ↔ Sofosbuvir ↔ Velpatasvir ↔ Voxilaprevir Pravastatin (40 mg single Observed: dose) + sofosbuvir/ Pravastatin ↑ ↑ velpatasvir/voxilaprevir 1.89 2.16 (400/100/100 mg once (1.53, (1.79, daily) + voxilaprevir 2.34) 2.60) (100 mg once daily)f (Inhibition of OATP1B) Other statins Effect on fluvastatin, lovastatin, pitavastatin and Interactions cannot be excluded simvastatin not studied. with other HMG-CoA reductase (Inhibition of OATP1B) inhibitors. Co-administration Medicinal product by Effects on medicinal product levels. therapeutic Mean ratio (90% confidence interval)a,b areas/Possible mechanism Recommendation concerning of interaction Active Cmax AUC Cmin co-administration with Vosevi with Vosevi is not recommended. NARCOTIC ANALGESICS Methadone Interaction only studied with sofosbuvir No dose adjustment of Vosevi or Expected: methadone is required. ↔ Velpatasvir ↔ Voxilaprevir Methadone Observed: (Methadone maintenance R-methadone ↔ ↔ ↔ therapy [30 to 130 mg S-methadone ↔ ↔ ↔ daily]) + sofosbuvir Sofosbuvir ↔ ↑ (400 mg once daily)f 1.30 (1.00, 1.69) IMMUNOSUPPRESSANTS Ciclosporin Observed: Co-administration of Vosevi (600 mg single dose)f + Ciclosporin ↔ ↔ with ciclosporin is not sofosbuvir (400 mg single Sofosbuvir ↑ ↑ recommended (see section 4.4). dose)e 2.54 4.53 (1.87, (3.26, (Inhibition of OATP1B or 3.45) 6.30) P-gp or BCRP) Ciclosporin Ciclosporin ↔ ↓ (600 mg single dose)e + 0.88 velpatasvir (100 mg single (0.78, dose)f 1.0) Velpatasvir ↑ ↑ 1.56 2.03 (1.22, (1.51, 2.01) 2.71) Ciclosporin Ciclosporin ↔ ↔ (600 mg single dose)e + Voxilaprevir ↑ ↑ voxilaprevir (100 mg 19.0 9.4 single dose) f (14.1, (7.4, 25.6) 12.0) Tacrolimus Effect on velpatasvir or voxilaprevir exposure No dose adjustment of Vosevi or not studied. tacrolimus is required at Expected: initiation of co-administration. ↔ Velpatasvir Afterwards, close monitoring and ↔ Voxilaprevir potential dose adjustment of Tacrolimus (5 mg single Observed: tacrolimus may be required. dose)e + sofosbuvir Tacrolimus ↓ ↑ (400 mg single dose)f 0.73 1.09 (0.59, (0.84, 0.90) 1.40) Sofosbuvir ↓ ↑ 0.97 1.13 (0.65, (0.81, 1.43) 1.57) Medicinal product by Effects on medicinal product levels. therapeutic Mean ratio (90% confidence interval)a,b areas/Possible mechanism Recommendation concerning of interaction Active Cmax AUC Cmin co-administration with Vosevi HORMONAL CONTRACEPTIVES Oral norgestimate/ethinyl Observed: Vosevi is contraindicated with estradiol (norgestimate Norelgestromin ↔ ↔ ↔ ethinylestradiol-containing 0.180 mg/0.215 mg/0.25 m medicinal products (see g/ethinyl estradiol section 4.3). Alternative 0.025 mg) + methods of contraception (e.g. sofosbuvir/velpatasvir/ progestin only contraception or Norgestrel ↔ ↔ ↔ voxilaprevir (400/100/ non-hormonal methods) should Ethinyl estradiol ↔ ↔ ↔ 100 mg once daily) + be considered. voxilaprevir (100 mg once daily)f STIMULANTS Modafinil Interaction not studied. Co-administration of Vosevi Expected: with modafinil is not (Induction of P-gp and ↔ Modafinil recommended (see section 4.4). CYPs) ↓ Sofosbuvir ↓ Velpatasvir ↓ Voxilaprevir 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. Lack of pharmacokinetics interaction lower bound 70%. d. These are medicinal products within class where similar interactions could be predicted. e. Bioequivalence/Equivalence boundary 80-125%. f. Lack of pharmacokinetics interaction bounds 70-143%. g. Administered as efavirenz, emtricitabine and tenofovir DF fixed-dose combination. h. Administered as sofosbuvir, velpatasvir fixed-dose combination. i. Administered as emtricitabine, rilpivirine, and tenofovir alafenamide fixed-dose combination. j. Administered as emtricitabine, tenofovir disoproxil fumarate fixed-dose combination. k. Lack of pharmacokinetics interaction bounds 50-200%. l. Administered as elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide fixed-dose combination.
פרטי מסגרת הכללה בסל
א. התרופה תינתן לטיפול בהפטיטיס C כרונית גנוטיפ 1 או 2 או 3 או 4:1. בחולים שטרם קיבלו טיפול למחלתם 2. בחולים שכשלו בטיפול קודם להפטיטיס C כרונית בתרופה ממשפחת ה-DAAs (direct acting antivirals). ב. הטיפול בתרופה ייעשה על פי מרשם של רופא מומחה המטפל במחלות כבד.
שימוש לפי פנקס קופ''ח כללית 1994
לא צוין
תאריך הכללה מקורי בסל
11/01/2018
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תרופה מוגבלת לרישום ע'י רופא מומחה או הגבלה אחרת
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