natgillin/translations-raw huggingface dataset:
Two NS5B substitutions, L159F and V321A, were detected in post-treatment relapse samples from multiple genotype 3 HCV infected subjects in the Phase 3 clinical studies.
U kliničkim ispitivanjima faze 3 su u uzorcima mnogih ispitanika zaraženih genotipom 3 HCV-a s relapsom nakon liječenja bile otkrivene dvije NS5B supstitucije, L159F i V321A.
Table 21: Outcomes by therapeutic regimen and treatment duration, a comparison across studies in genotype 4, 5 and 6 HCV infection
Tablica 21: Ishodi prema terapijskom režimu i trajanju liječenja, usporedba ispitivanja za infekciju genotipom 4, 5 i 6 HCV-a Populacija bolesnika (broj/naziv ispitivanja)
Treatment-experienced patients with genotype 1, 4, 5 and 6 HCV infection Sovaldi has not been studied in a Phase 3 study in treatment-experienced patients with genotype 1, 4, 5 and 6 HCV infection.
Sovaldi nije ispitan u kliničkom ispitivanju faze 3 u liječenju prethodno liječenih bolesnika s infekcijom HCV-om genotipa 1, 4, 5 i 6.
Table 7: Response rates in study FISSION SOF+RBV
Table 7: Stope odgovora u ispitivanju FISSION SOF+RBV
A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
PROIZVOĐAČ(I) ODGOVORAN(ODGOVORNI) ZA PUŠTANJE SERIJE LIJEKA U
Relative to subjects with normal renal function (eGFR >80 mL/min/1.73 m2), the sofosbuvir AUC0-inf was 61%, 107% and 171% higher in mild, moderate and severe renal impairment, while the GS-331007 AUC0-inf was 55%, 88% and 451% higher, respectively.
U odnosu na ispitanike s normalnom funkcijom bubrega (eGFR > 80 ml/min/1,73 m2), AUC0-inf sofosbuvira bio je 61%, 107% odnosno
Rilpivirine ↔ Cmax 1.05 (0.97, ↔ AUC 1.06 (1.02, ↔ Cmin 0.99 (0.94, 1.04) Sofosbuvir ↑ Cmax 1.21 (0.90, 1.62) ↔ AUC 1.09 (0.94, Cmin (NA)
Rilpivirin ↔ Cmax 1,05 (0,97; ↔ AUC 1,06 (1,02; ↔ Cmin 0,99 (0,94; 1,04) Sofosbuvir ↑ Cmax 1,21 (0,90; 1,62) ↔ AUC 1,09 (0,94; Cmin (NA)
Table 20: Outcomes by therapeutic regimen and treatment duration, a comparison across studies in genotype 3 HCV infection
Tablica 20: Ishodi prema terapijskom režimu i trajanju liječenja, usporedba ispitivanja za infekciju genotipom 3 HCV-a
Table 9: Response rates in study POSITRON SOF+RBV
Tablica 9: Stope odgovora u ispitivanju POSITRON SOF+RBV
The proportion of subjects who permanently discontinued treatment due to adverse reactions was 1.4% for subjects receiving placebo, 0.5% for subjects receiving sofosbuvir + ribavirin for 12 weeks, 0% for subjects receiving sofosbuvir + ribavirin for 16 weeks, 11.1% for subjects receiving peginterferon alfa + ribavirin for 24 weeks and 2.4% for subjects receiving sofosbuvir + peginterferon alfa + ribavirin for 12 weeks.
među ispitanicima koji su primali peginterferon alfa + ribavirin tijekom 24 tjedna i 2,4% među ispitanicima koji su primali sofosbuvir + peginterferon alfa + ribavirin tijekom 12 tjedana.
b. The denominator for relapse is the number of subjects with HCV RNA <LLOQ at their last on-treatment assessment.
b. Nazivnik za relaps je broj ispitanika s HCV RNK < donje granice kvantifikacije na njihovom posljednjem pregledu za vrijeme trajanja terapije.
HCV/HIV co-infected patients - PHOTON-1 (study 123) Sofosbuvir was studied in an open-label clinical study evaluating the safety and efficacy of 12 or 24 weeks of treatment with sofosbuvir and ribavirin in subjects with genotype 1, 2 or 3 chronic hepatitis C co-infected with HIV-1.
Sofosbuvir je bio ispitan u otvorenom kliničkom ispitivanju u kojem se ocjenjivala sigurnost i djelotvornost 12 tjedana ili 24 tjedna liječenja sofosbuvirom i ribavirinom u ispitanika s kroničnim hepatitisom C uzrokovanim genotipom 1, 2 ili 3 i istodobnom infekcijom virusom HIV-1.
No dose adjustment of sofosbuvir or ciclosporin is required when sofosbuvir and ciclosporin are used concomitantly.
Nije potrebna prilagodba doze sofosbuvira ili ciklosporina kad se sofosbuvir i ciklosporin primjenjuju istodobno.
• Carbamazepine, phenobarbital and phenytoin (medicines used to treat epilepsy and prevent seizures).
• gospinu travu (Hypericum perforatum - biljni pripravak koji se primjenjuje za liječenje depresije); • karbamazepin, fenobarbital i fenitoin (lijekovi koji se primjenjuju za liječenje epilepsije i sprječavanje napadaja).
Very common haemoglobin decreased anaemia, neutropenia, lymphocyte count decreased, platelet count decreased
Poremećaji krvi i limfnog sustava: Vrlo često smanjeni hemoglobin anemija, neutropenija, smanjeni broj limfocita, smanjeni broj trombocita
level was 6.4 log10 IU/mL; 21% had cirrhosis; 78% had HCV genotype 3; 65% were prior relapsers.
(raspon: 19 do 44 kg/m 2); 73% imalo je početnu razinu HCV RNK veću od 6 log10 IU/ml; 34% imalo je cirozu; 63% imalo je HCV-genotip 3; 75% je prethodno imalo relaps.
Overall SVR12 Genotype 2 Genotype 3 Outcome for subjects without SVR12 On-treatment virologic failure 0/103 Relapse b
Ishod u ispitanika bez SVR12 Virološki neuspjeh uz liječenje
Emtricitabine ↔ Cmax 0.97 (0.88, ↔ AUC 0.99 (0.94, ↔ Cmin 1.04 (0.98, 1.11) Sofosbuvir ↓ Cmax 0.81 (0.60, 1.10) ↔ AUC 0.94 (0.76, Cmin (NA)
Emtricitabin ↔ Cmax 0,97 (0,88; ↔ AUC 0,99 (0,94; ↔ Cmin 1,04 (0,98; 1,11) Sofosbuvir ↓ Cmax 0,81 (0,60; 1,10) ↔ AUC 0,94 (0,76;
R-methadone ↔ Cmax 0.99 (0.85, ↔ AUC 1.01 (0.85, ↔ Cmin 0.94 (0.77, 1.14) S-methadone ↔ Cmax 0.95 (0.79, ↔ AUC 0.95 (0.77, ↔ Cmin 0.95 (0.74, 1.22) Sofosbuvir ↓ Cmax 0.95c (0.68, 1.33) ↑ AUC 1.30c (1.00, Cmin (NA)
R-metadon ↔ Cmax 0,99 (0,85; ↔ AUC 1,01 (0,85; ↔ Cmin 0,94 (0,77; 1,14) S-metadon ↔ Cmax 0,95 (0,79; ↔ AUC 0,95 (0,77; ↔ Cmin 0,95 (0,74; 1,22) Sofosbuvir ↓ Cmax 0,95c (0,68; 1,33) ↑ AUC 1,30c (1,00;
c. Other includes subjects who did not achieve SVR12 and did not meet virologic failure criteria (e.g., lost to follow-up).
Ostalo uključuje ispitanike koji nisu postigli SVR12 i nisu zadovoljili kriterije virološkog neuspjeha
The safety of Sovaldi has not been assessed in patients with severe renal impairment or ESRD (see section 4.4).
Sigurnost Sovaldija nije procijenjena u bolesnika s teškim oštećenjem bubrega ili završnim stadijem bolesti bubrega
GS-331007 ↔ Cmax 1.06 (0.99, ↔ AUC 1.01 (0.97, Cmin (NA)
GS-331007 ↔ Cmax 1,06 (0,99; ↔ AUC 1,01 (0,97; Cmin (ND/NP)
Respiratory, thoracic and mediastinal disorders: Very common dyspnoea, cough
Poremećaji dišnog sustava, prsišta i sredoprsja: Vrlo često dispneja, kašalj
HIV ANTIVIRAL AGENTS: HIV PROTEASE INHIBITORS Darunavir boosted with ritonavirf
HIV ANTIVIRUSNI LIJEKOVI: INHIBITORI PROTEAZE HIV-A
Sofosbuvir was studied in an open-label clinical study evaluating the safety and efficacy of 24 weeks of treatment with sofosbuvir and ribavirin in liver transplant recipients with chronic hepatitis C. Eligible subjects were ≥18 years old and had undergone liver transplantation 6 to 150 months prior to screening.
Sofosbuvir je bio ispitan u otvorenom kliničkom ispitivanju u kojem se ocjenjivala sigurnost i djelotvornost liječenja sofosbuvirom i ribavirinom u trajanju od 24 tjedna u bolesnika s kroničnim hepatitisom C kojima je transplantirana jetra.
No dose adjustment of Sovaldi is required for patients with mild, moderate or severe hepatic impairment (Child-Pugh-Turcotte [CPT] class A, B or C) (see section 5.2).
(Child-Pugh-Turcotte [CPT] stadij A, B ili C) (vidjeti dio 5.2).
0.085 ± 0.034 μM for genotype 3a (n = 106).
0,11 ± 0,029 μM za genotip 1b (n = 29), 0,035 ± 0,018 μM za genotip 2 (n = 15) i 0,085 ± 0,034 μM za genotip 3a (n = 106).
Table 12 presents the subgroup analysis by genotype for cirrhosis and response to prior HCV treatment.
Tablica 12 prikazuje analizu prisutnosti ciroze i odgovora na prethodno liječenje HCV-a u podskupinama prema genotipu.
The efficacy of sofosbuvir was evaluated in five Phase 3 studies in a total of 1,568 subjects with genotypes 1 to 6 chronic hepatitis C. One study was conducted in treatment-naïve subjects with genotype 1, 4, 5 or 6 chronic hepatitis C in combination with peginterferon alfa 2a and ribavirin and the other four studies were conducted in subjects with genotype 2 or 3 chronic hepatitis C in combination with ribavirin including one in treatment-naïve subjects, one in interferon intolerant,
Jedno je ispitivanje bilo provedeno u kombinaciji s peginterferonom alfa 2a i ribavirinom u ispitanika koji prethodno nisu bili liječeni i imali su kronični hepatitis C uzrokovan genotipovima 1, 4, 5 ili 6, dok su ostala četiri ispitivanja bila provedena u kombinaciji s ribavirinom u ispitanika s kroničnim hepatitisom C uzrokovanim genotipovima 2 ili 3 uključujući jedno u ispitanika koji prethodno nisu bili liječeni, jedno u ispitanika koji nisu podnosili interferon, nisu bili pogodni za liječenje interferonom ili nisu dali pristanak za liječenje interferonom, jedno u ispitanika prethodno liječenih režimom na bazi interferona i jedno u svih ispitanika bez obzira na prethodno liječenje ili sposobnost primanja liječenja interferonom.
Sofosbuvir is not a substrate for hepatic uptake transporters, organic anion-transporting polypeptide (OATP) 1B1 or 1B3, and organic cation transporter (OCT) 1.
Sofosbuvir nije supstrat jetrenih prijenosnika za unos tvari, polipeptida za prijenos organskih aniona (OATP) 1B1 ili 1B3 i prijenosnika organskih kationa (OCT) 1. Iako je podložan aktivnoj tubularnoj sekreciji, GS-331007 nije supstrat bubrežnih prijenosnika uključujući prijenosnik organskih aniona
Sovaldi is contraindicated with rifabutin, a potent intestinal P-gp inducer (see section 4.3).
Sovaldi je kontraindiciran s rifabutinom, jakim induktorom intestinalnog P-gp-a (vidjeti dio 4.3).
4.5 Interaction with other medicinal products and other forms of interaction
4.5 Interakcije s drugim lijekovima i drugi oblici interakcija Sofosbuvir je nukleotidni predlijek.
Sovaldi is contraindicated with rifampicin, a potent intestinal P-gp inducer (see section 4.3).
Sovaldi je kontraindiciran s rifampicinom, jakim induktorom intestinalnog P-gp-a (vidjeti dio 4.3).
Treatment-experienced (VALENCE)
Odrasli koji prethodno nisu i oni koji jesu bili liječeni - VALENCE (ispitivanje 133)
Table 14 presents the subgroup analysis by genotype for cirrhosis and exposure to prior HCV treatment.
Tablica 14 prikazuje analizu prisutnosti ciroze i prethodne izloženosti liječenju HCV-a u podskupinama prema genotipu.
Emtricitabinef (200 mg once daily)d
(200 mg jedanput na dan)d
GS-331007 ↓ Cmax 0.73c (0.65, 0.83) ↔ AUC 1.04c (0.89, Cmin (NA)
Cmin (ND/NP) GS-331007 ↓ Cmax 0,73c (0,65; 0,83) ↔ AUC 1,04c (0,89; Cmin (ND/NP)
Genotype 1bc No cirrhosisc Cirrhosisc n = number of subjects with SVR12 response; N = total number of subjects per group.
S cirozom 93% (13/14) n = broj ispitanika s odgovorom SVR12; N = ukupni broj ispitanika u skupini.
Darunavir ↔ Cmax 0.97 (0.94, ↔ AUC 0.97 (0.94, ↔ Cmin 0.86 (0.78, 0.96) Sofosbuvir ↑ Cmax 1.45 (1.10, 1.92) ↑ AUC 1.34 (1.12, 1.59) Cmin (NA)
Darunavir ↔ Cmax 0,97 (0,94; ↔ AUC 0,97 (0,94; ↔ Cmin 0,86 (0,78; 0,96) Sofosbuvir ↑ Cmax 1,45 (1,10; 1,92) ↑ AUC 1,34 (1,12; 1,59) Cmin (ND/NP) GS-331007 ↔ Cmax 0,97 (0,90; ↔ AUC 1,24 (1,18; Cmin (ND/NP)
Table 2: Ribavirin dose modification guideline for co-administration with Sovaldi Laboratory values
Tablica 2: Smjernica za prilagodbu doze ribavirina kod istodobne primjene sa Sovaldijem Laboratorijske vrijednosti Sniziti dozu ribavirina na 600 mg/dan ako:
NAME OF THE MEDICINAL PRODUCT Sovaldi 400 mg film-coated tablets sofosbuvir
Uputa o lijeku: Informacija za korisnika Sovaldi 400 mg filmom obložene tablete sofosbuvir
Sofosbuvir ↓ Cmax 0.23 (0.19, 0.29) ↓ AUC 0.28 (0.24, 0.32) Cmin (NA)
Sofosbuvir ↓ Cmax 0,23 (0,19; 0,29)
Treated subjects (n = 278) had a median age of 54 years (range: 21 to 75); 54% of the subjects were male; 91% were White; 5% were Black; 11% were Hispanic or Latino; mean body mass index was 28 kg/m2 (range: 18 to 53 kg/m2); 70% had baseline HCV RNA levels greater than 6 log10 IU/mL;
Medijan dobi liječenih ispitanika (n = 278) bio je 54 godine (raspon: 21 do 75); 54% ispitanika bili su muškarci; 91% bili su bijelci, 5% bili su crnci; 11% bili su hispano- ili latino-porijekla; srednja vrijednost indeksa tjelesne mase bila je 28 kg/m2 (raspon: 18 to 53 kg/m2); 70% imalo je početne razine HCV RNK veće od 6 log10 IU/ml; 16% imalo je cirozu; 49% imalo je HCV-genotip 3.
How to store Sovaldi
Moguće nuspojave Kako čuvati Sovaldi
The pharmacokinetic properties of sofosbuvir and the predominant circulating metabolite GS-331007 have been evaluated in healthy adult subjects and in subjects with chronic hepatitis C. Following oral administration, sofosbuvir was absorbed quickly and the peak plasma concentration was observed ~0.5-2 hour post-dose, regardless of dose level.
Farmakokinetička svojstva sofosbuvira i glavnog cirkulirajućeg metabolita GS-331007 ocijenjena su u zdravih odraslih ispitanika i u ispitanika s kroničnim hepatitisom C.
Treated subjects (n = 499) had a median age of 50 years (range: 19 to 77); 66% of the subjects were male; 87% were White; 3% were Black; 14% were Hispanic or Latino; mean body mass index was 28 kg/m2 (range: 17 to 52 kg/m2); 57% had baseline HCV RNA levels greater than 6 log10 IU/mL;
Medijan dobi liječenih ispitanika (n = 499) bio je 50 godina (raspon: 19 do 77); 66% ispitanika bili su muškarci; 87% bili su bijelci, 3% bili su crnci; 14% bili su hispano- ili latino-porijekla; srednja vrijednost indeksa tjelesne mase bila je 28 kg/m2 (raspon: 17 do 52 kg/m2); 57% je imalo početnu razinu HCV RNK veću od 6 log10 IU/ml; 20% imalo je cirozu; 72% imalo je HCV genotip 3.
Table 6: SVR12 rates for selected subgroups in NEUTRINO SOF+PEG+RBV
Stope odgovora za odabrane podskupine prikazane su u tablici 6. Table 6: Stope SVR12 za odabrane podskupine u ispitivanju NEUTRINO SOF+PEG+RBV
Raltegravir ↓ Cmax 0.57 (0.44, 0.75) ↓ AUC 0.73 (0.59, 0.91) ↔ Cmin 0.95 (0.81, 1.12) Sofosbuvir ↔ Cmax 0.87 (0.71, ↔ AUC 0.95 (0.82, Cmin (NA)
Raltegravir ↓ Cmax 0,57 (0,44; 0,75) ↓ AUC 0,73 (0,59; 0,91) ↔ Cmin 0,95 (0,81; 1,12) Sofosbuvir ↔ Cmax 0,87 (0,71; ↔ AUC 0,95 (0,82; Cmin (ND/NP) GS-331007 ↔ Cmax 1,09 (0,99; ↔ AUC 1,03 (0,97; Cmin (ND/NP)
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Table 18: Outcomes by therapeutic regimen and treatment duration, a comparison across studies in genotype 1 HCV infection
Tablica 18: Ishodi prema terapijskom režimu i trajanju liječenja, usporedba ispitivanja za infekciju genotipom 1 HCV-a Populacija bolesnika (broj/naziv ispitivanja)
FISSION was a randomised, open-label, active-controlled study that evaluated 12 weeks of treatment with sofosbuvir and ribavirin compared to 24 weeks of treatment with peginterferon alfa 2a and ribavirin in treatment-naïve subjects with genotype 2 or 3 HCV infection.
12 tjedana liječenja sofosbuvirom i ribavirinom u usporedbi s 24 tjedna liječenja peginterferonom alfa 2a i ribavirinom ispitanika koji prethodno nisu bili liječeni i imali su infekciju genotipovima 2 ili
Efavirenz ↔ Cmax 0.95 (0.85, ↔ AUC 0.96 (0.91, ↔ Cmin 0.96 (0.93, 0.98) Sofosbuvir ↓ Cmax 0.81 (0.60, 1.10) ↔ AUC 0.94 (0.76, Cmin (NA)
Efavirenz ↔ Cmax 0,95 (0,85; ↔ AUC 0,96 (0,91; ↔ Cmin 0,96 (0,93; 0,98) Sofosbuvir ↓ Cmax 0,81 (0,60; 1,10) ↔ AUC 0,94 (0,76; Cmin (ND/NP) GS-331007 ↓ Cmax 0,77 (0,70; 0,84) ↔ AUC 0,84 (0,76; Cmin (ND/NP)
• shortness of breath or worsening of any shortness of breath you already have Tell your doctor or your pharmacist if you notice any of the above side effects during therapy.
Obavijestite svog liječnika ili ljekarnika ako opazite neku od gore navedenih nuspojava tijekom liječenja.
After a single 400 mg oral dose of [14C]-sofosbuvir, sofosbuvir and GS-331007 accounted for approximately 4% and >90% of drug-related material (sum of molecular weight-adjusted AUC of sofosbuvir and its metabolites) systemic exposure, respectively.
4% odnosno > 90% sistemske izloženosti tvarima povezanima s lijekom (zbroj molekularnoj težini prilagođenog AUC sofosbuvira i njegovih metabolita).
Table 19: Outcomes by therapeutic regimen and treatment duration, a comparison across studies in genotype 2 HCV infection
Tablica 19: Ishodi prema terapijskom režimu i trajanju liječenja, usporedba ispitivanja za infekciju genotipom 2 HCV-a Populacija bolesnika (broj/naziv ispitivanja)
The difference in the overall SVR12 rates between sofosbuvir + ribavirin and peginterferon alfa + ribavirin treatment groups was 0.3% (95% confidence interval: -7.5% to 8.0%) and the study met the predefined non-inferiority criterion.
(95% interval pouzdanosti: -7,5% do 8,0%) i ispitivanje je zadovoljilo unaprijed određeni kriterij neinferiornosti.
HIV ANTIVIRAL AGENTS: REVERSE TRANSCRIPTASE INHIBITORS Efavirenzf (600 mg once daily)d
HIV ANTIVIRUSNI LIJEKOVI: INHIBITORI REVERZNE TRANSKRIPTAZE Efavirenzf
Table 16: SVR12 rates for selected subgroups by genotype in study PHOTON-1 HCV genotype 2
Tablica 16 prikazuje analizu prisutnosti ciroze u podskupinama prema genotipu Tablica 16: Stope SVR12 za odabrane podskupine prema genotipu u ispitivanju PHOTON-1
(800/100 mg once daily)
(300 mg jedanput na dan)d
IMMUNOSUPPRESSANTS Ciclosporine
IMUNOSUPRESIVI
Cirrhosis No Yes a. The efficacy analysis includes 3 subjects with recombinant genotype 2/1 HCV infection.
Analiza djelotvornosti uključuje 3 ispitanika s infekcijom rekombinantnim genotipom 2/1 HCV-a
Medicinal products that are potent P-gp inducers in the intestine (rifampicin, rifabutin, St. John's wort, carbamazepine, phenobarbital and phenytoin) may significantly decrease sofosbuvir plasma concentration leading to reduced therapeutic effect of Sovaldi and thus are contraindicated with Sovaldi (see section 4.3).
fenobarbital i fenitoin) mogu značajno smanjiti koncentracije sofosbuvira u plazmi i tako dovesti do smanjenog terapijskog učinka Sovaldija te su stoga kontraindicirani sa Sovaldijem (vidjeti dio 4.3).
Sovaldi is always taken with other medicines.
Sovaldi se uvijek uzima s drugim lijekovima jer sam neće djelovati.
Clinical studies in subjects with genotype 1, 4, 5 and 6 chronic hepatitis C Treatment-naïve subjects - NEUTRINO (study 110) NEUTRINO was an open-label, single-arm study that evaluated 12 weeks of treatment with sofosbuvir in combination with peginterferon alfa 2a and ribavirin in treatment-naïve subjects with genotype 1, 4, 5 or 6 HCV infection.
NEUTRINO je bilo otvoreno ispitivanje na jednoj skupini u kojem se ocijenilo 12 tjedana liječenja sofosbuvirom u kombinaciji s peginterferonom alfa 2a i ribavirinom u ispitanika koji prethodno nisu bili liječeni, a koji su imali infekciju genotipovima 1, 4, 5 ili 6 HCV-a.
No dose adjustment of sofosbuvir or tacrolimus is required when sofosbuvir and tacrolimus are used concomitantly.
Nije potrebna prilagodba doze sofosbuvira ili takrolimusa kad se sofosbuvir i takrolimus primjenjuju istodobno.
Duration of viral suppression prior to transplantation was the most predictive factor for pTVR in those who were HCV RNA <LLOQ at the time of transplantation.
Stope virološkog odgovora u 41 ispitanika s transplantiranom jetrom i HCV RNK < donje granice kvantifikacije opisane su u tablici 17. Trajanje virološke supresije prije transplantacije bilo je najjači prediktivni čimbenik za pTVR u onih koji su imali HCV RNK < donje granice kvantifikacije u vrijeme transplantacije.
Treated subjects (n = 201) had a median age of 56 years (range: 24 to 70); 70% of the subjects were male; 87% were White; 3% were Black; 9% were Hispanic or Latino; mean body mass index was 29 kg/m2 (range: 19 to 44 kg/m2); 73% had baseline HCV RNA levels greater than 6 log10 IU/mL;
Medijan dobi liječenih ispitanika (n = 201) bio je 56 godina (raspon: 24 do 70); 70% ispitanika bili su muškarci; 87% bili su bijelci; 3% bili su crnci; 9% bili su hispano- ili latino-porijekla; srednja vrijednost indeksa tjelesne mase bila je 29 kg/m2
b. Consideration should be given to potentially extending the duration of therapy beyond 12 weeks and up to 24 weeks; especially for those subgroups who have one or more factors historically associated with lower response rates to interferon-based therapies (e.g. advanced fibrosis/cirrhosis, high baseline viral concentrations, black race, IL28B non CC genotype, prior null response to peginterferon alfa and ribavirin therapy).
Potrebno je razmotriti mogućnost produljenja trajanja terapije na više od 12 tjedana do najviše 24 tjedna, osobito u podskupina s jednim ili više čimbenika koji se otprije povezuju s nižim stopama odgovora na terapiju na bazi interferona (npr. uznapredovala fibroza/ciroza,
Treated subjects (n = 419) had a median age of 51 years (range: 19 to 74); 60% of the subjects were male; median body mass index was 25 kg/m2 (range: 17 to 44 kg/m2); the mean baseline HCV RNA
Medijan dobi liječenih ispitanika (n = 419) bio je 51 godina (raspon: 19 do 74); 60% ispitanika bili su muškarci; medijan indeksa tjelesne mase iznosio je 25 kg/m2 (raspon: 17 do 44 kg/m2); srednja vrijednost početne razine HCV RNK bila je 6,4 log10 IU/ml; 21% imalo je cirozu; 78% imalo je HCVgenotip 3; 65% je prethodno imalo relaps.
Common arthralgia, back pain, muscle spasms, myalgia back pain, muscle spasms
mialgija bol u leđima, mišićni grčevi
EXP
Emtricitabin f
• chest pain, feeling weak
• bol u leđima, mišićni grčevi • bol u prsnom košu, osjećaj slabosti
and up to every 4 weeks until the appropriate weight-based dose was reached (1,000 mg daily in subjects <75 kg, 1,200 mg daily in subjects ≥75 kg).
Ako su se u ispitanika razine hemoglobina održale na ≥ 12 g/dl, doza ribavirina bila je povišena u 2. i 4. tjednu te nakon toga svaka 4 tjedna sve dok nije postignuta odgovarajuća doza prema tjelesnoj težini (1000 mg na dan u ispitanika tjelesne težine < 75 kg, a 1200 mg na dan u ispitanika tjelesne težine ≥ 75 kg).
Overall No cirrhosis Cirrhosis
Ukupno Bez ciroze
SOF+RBV 12 weeks (n = 73)
SOF+RBV 12 tjedana (n = 68)
Cirrhosisa
• omaglica
Cirrhosis No Yes Response to prior HCV treatment Relapser Nonresponder 70% (7/10)
Bez odgovora 70% (7/10)
Overall No cirrhosis Cirrhosis TN = treatment-naïve; TE = treatment-experienced.
TN = prethodno nisu liječeni; TE = prethodno liječeni.
Sovaldi is contraindicated with St. John's wort, a potent intestinal P-gp inducer (see section 4.3).
Sovaldi je kontraindiciran s gospinom travom, jakim induktorom intestinalnog P-gp (vidjeti dio 4.3).
Treated subjects (n = 327) had a median age of 54 years (range: 19 to 70); 64% of the subjects were male; 79% were White; 17% were Black; 14% were Hispanic or Latino; mean body mass index was 29 kg/m2 (range: 18 to 56 kg/m2); 78% had baseline HCV RNA greater than 6 log10 IU/mL; 17% had cirrhosis; 89% had HCV genotype 1 and 11% had HCV genotype 4, 5 or 6.
Medijan dobi liječenih ispitanika (n = 327) bio je 54 godine (raspon: 19 do 70); 64% ispitanika bili su muškarci; 79% bili su bijelci, 17% bili su crnci; 14% bili su hispano ili latino-porijekla; srednja vrijednost indeksa tjelesne mase iznosila je 29 kg/m2 (raspon: 18 do 56 kg/m2); 78% imalo je početni
Based on population pharmacokinetic analysis in subjects with genotypes 1 to 6 HCV infection (n = 986), steady-state AUC0-24 for sofosbuvir and GS-331007 was 1,010 ng•h/mL and 7,200 ng•h/mL, respectively.
infekcije (n = 986), AUC0-24 za sofosbuvir u stanju dinamičke ravnoteže bio je 1010 ng•h/ml, a za
Genotype 1 treatment-naïve SOF+RBV 24 weeks (n = 114)
Genotip 3 SOF+RBV 12 tjedana (n = 11)
ANTIMYCOBACTERIALS Rifampicinf
Tenofovir dizoproksil fumaratf
GS-331007 ↔ Cmax 1.23 (1.14,
GS-331007 7200 ng•h/ml.
--1 Rabies virus, strain SPBN GASGAS, live - 106.8 to 108.1 FFU* per 1.7 ml dose * Focus forming units
Virus bjesnoće, soj SPBN GASGAS, živo: - 106.8 FFU* - 108.1 FFU* po 1,7 ml doze * Focus Forming Units - jedinice formiranja fokusa
Packaging Content
Put primjene Pakovanje Sastav
Withdrawal period
Suspenzija:
• The Committee considered the (Co-)Rapporteur's assessment report;
• Povjerenstvo je razmotrilo izvješće procjene (su)izvjestitelja;
• The Committee considered the referral under Article 29(4) of Directive 2001/83/EC where Germany raised objections as a potential serious risk to public health;
• Povjerenstvo je razmatralo postupak upućivanja prema članku 29. stavku 4. Direktive 2001/83/EZ u kojem je Njemačka postavila primjedbe u smislu potencijalno ozbiljnog rizika za javno zdravlje;
In addition, the applicant refers to relevant clinical guidelines.
Osim toga, podnositelj upućuje na relevantne kliničke smjernice.