natgillin/translations-raw huggingface dataset:
> 2.5 to ≤ 5.0 x ULN 
> 2,5 do ≤ 5,0 x GGN
1 When considering OLYSIO combination treatment with peginterferon alfa and ribavirin in HCV genotype 1a patients, 
1 Kada se razmatra kombinirano liječenje lijekom OLYSIO s peginterferonom alfa i ribavirinom u bolesnika s HCV
OLYSIO is not recommended in patients with moderate or severe hepatic impairment (Child-Pugh class B or C) (see sections 4.2, 4.8 and 5.2). 
Lijek OLYSIO se ne preporučuje u bolesnika s umjerenim ili teškim oštećenjem jetre (Child-Pugh stadij B ili C) (vidjeti dijelove 4.2, 4.8 i 5.2).
Data from an ongoing, long-term follow-up study (study HPC3002) in patients who did not achieve SVR with a simeprevir-based regimen in a previous phase 2 study showed that in 70% (16/23) of these patients emerging mutations were no longer detected after a median follow-up of 88 weeks (range 47-147 weeks). 
70% (16/23) tih bolesnika, nastale mutacije više nije bilo moguće detektirati nakon medijana praćenja od 88 tjedana (raspon 47-147 tjedana).
> 2.0 to ≤ 5.0 x ULN 13 (4.5%) 
> 2,0 do ≤ 5,0 x GGN 13 (4,5%)
1 In HCV genotype 1a infected patients with cirrhosis, testing for the presence of the Q80K polymorphism may be considered prior to initiation of therapy with OLYSIO in combination with sofosbuvir (see section 4.4). 
1 U bolesnika s infekcijom HCV genotipom 1a s cirozom može se prije početka liječenja s lijekom OLYSIO u kombinaciji sa sofosbuvirom uzeti u obzir ispitivanje prisutnosti Q80K polimorfizma (vidjeti dio 4.4).
2 Treatment-experienced to prior treatment with peginterferon and ribavirin. 
2 Prethodno iskustvo liječenja s peginterferonom i ribavirinom.
ANTICOAGULANTS Warfarin and other vitamin K antagonists warfarin 10 mg: 
varfarin 10 mg:
Chemistry 
FARMACEUTSKI
All grades Grade 3 
Objedinjena ispitivanja faze 3
1 Treatment-experienced to prior treatment with peginterferon and ribavirin. 
1 Prethodno iskustvo liječenja s peginterferonom i ribavirinom.
Plasma Cmax and AUC of simeprevir were similar during co-administration of simeprevir with peginterferon alfa and ribavirin compared with administration of simeprevir alone. 
simeprevira u plazmi bili su slični tijekom istovremene primjene simeprevira s peginterferonom alfa i ribavirinom u usporedbi sa primjenom samo simeprevira.
HCV geno/subtype and presence of Q80K polymorphism in HCV genotype 1a Genotype 1a with Q80K without Q80K 
HCV geno/podtip i prisutnost Q80K polimorfizma u HCV genotipu 1a Genotip 1a s Q80K bez Q80K
Sofosbuvir2 400 mg once daily sofosbuvir AUC 3.16 (2.25-4.44) ↑ sofosbuvir Cmax 1.91 (1.26-2.90) ↑ sofosbuvir Cmin not studied GS-331007 AUC 1.09 (0.87-1.37) ↔ GS-331007 Cmax 0.69 (0.52-0.93) ↓ GS-331007 Cmin not studied simeprevir AUC 0.94 (0.67-1.33) ↔ simeprevir Cmax 0.96 (0.71-1.30) ↔ simeprevir Cmin not studied 
400 mg jedanput na dan sofosbuvir AUC 3,16 (2,25-4,44) ↑ sofosbuvir Cmax 1,91 (1,26-2,90) ↑ sofosbuvir Cmin nije ispitano GS-331007 AUC 1,09 (0,87-1,37) ↔ GS-331007 Cmax 0,69 (0,52-0,93) ↓ GS-331007 Cmin nije ispitano simeprevir AUC 0,94 (0,67-1,33) ↔ simeprevir Cmax 0,96 (0,71-1,30) ↔ simeprevir Cmin nije ispitano
testing for NS3 Q80K polymorphism should be performed before starting treatment (see section 4.4). 
genotipom 1a, prije početka liječenja treba provesti ispitivanje na NS3 Q80K polimorfizam (vidjeti dio 4.4).
Genotype 1, prior relapsers2, with compensated cirrhosis or without cirrhosis 
Genotip 1, s prethodnim relapsom2, s kompenziranom cirozom ili bez ciroze
tacrolimus AUC 0.83 (0.59-1.16) ↓ tacrolimus Cmax 0.76 (0.65-0.90) ↓ tacrolimus Cmin not studied simeprevir AUC 1.85 (1.18-2.91) ↑6 simeprevir Cmax 1.79 (1.22-2.62) ↑6 simeprevir Cmin not studied6 
takrolimus AUC 0,83 (0,59-1,16) ↓ takrolimus Cmax 0,76 (0,65-0,90) ↓ takrolimus Cmin nije ispitano simeprevir AUC 1,85 (1,18-2,91) ↑6 simeprevir Cmax 1,79 (1,22-2,62) ↑6 simeprevir Cmin nije ispitano6
Patients had compensated liver disease (including cirrhosis), HCV RNA of at least 10,000 IU/ml, and liver histopathology consistent with CHC (if available). 
10 000 IU/ml i histopatologiju jetre u skladu s kroničnim hepatitisom C (ukoliko je dostupna).
ANTIDEPRESSANTS Escitalopram 10 mg once daily escitalopram AUC 1.00 (0.97-1.03) ↔ escitalopram Cmax 1.03 (0.99-1.07) ↔ escitalopram Cmin 1.00 (0.95-1.05) ↔ simeprevir AUC 0.75 (0.68-0.83) ↓ simeprevir Cmax 0.80 (0.71-0.89) ↓ simeprevir Cmin 0.68 (0.59-0.79) ↓ 
Escitalopram 10 mg jedanput na dan escitalopram AUC 1,00 (0,97-1,03) ↔ escitalopram Cmax 1,03 (0,99-1,07) ↔ escitalopram Cmin 1,00 (0,95-1,05) ↔ simeprevir AUC 0,75 (0,68-0,83) ↓ simeprevir Cmax 0,80 (0,71-0,89) ↓ simeprevir Cmin 0,68 (0,59-0,79) ↓
600 mg once daily efavirenz AUC 0.90 (0.85-0.95) ↔ efavirenz Cmax 0.97 (0.89-1.06) ↔ efavirenz Cmin 0.87 (0.81-0.93) ↔ simeprevir AUC 0.29 (0.26-0.33) ↓ simeprevir Cmax 0.49 (0.44-0.54) ↓ simeprevir Cmin 0.09 (0.08-0.12) ↓ 
600 mg jedanput na dan efavirenz AUC 0,90 (0,85-0,95) ↔ efavirenz Cmax 0,97 (0,89-1,06) ↔ efavirenz Cmin 0,87 (0,81-0,93) ↔ simeprevir AUC 0,29 (0,26-0,33) ↓ simeprevir Cmax 0,49 (0,44-0,54) ↓ simeprevir Cmin 0,09 (0,08-0,12) ↓
OLYSIO is not recommended for patients with moderate or severe hepatic impairment (Child-Pugh class B or C) (see sections 4.4 and 5.2). 
Lijek OLYSIO se ne preporučuje za bolesnike s umjerenim ili teškim oštećenjem jetre (Child-Pugh stadij B ili C) (vidjeti dijelove 4.4 i 5.2).
Sustained virologic response (SVR) was the primary endpoint in all studies and was defined as HCV RNA less than the lower limit of quantification (LLOQ) detectable or undetectable 12 weeks (SVR12) or 24 weeks (SVR24) after the planned end of treatment (studies C206, C208, C212, C216, HPC2002, HPC3007 and HPC3011) or after the actual end of treatment (studies HPC2014, HPC3017, HPC3018 and HPC3021) (LLOQ of 25 IU/ml and limit of detection of 15 IU/ml, except in studies HPC2014 and HPC3021 where LLOQ and limit of detection were 15 IU/ml). 
Održani virološki odgovor (engl. sustained virologic response, SVR) bio je primarna mjera ishoda u svim ispitivanjima i bio je definiran kao HCV RNA manja od donje granice kvantifikacije (engl. lower limit of quantification, LLOQ) detektabilne ili nedetektabilne 12 tjedana (SVR12) ili 24 tjedna (SVR24) nakon planiranog završetka liječenja (ispitivanja C206, C208, C212, C216, HPC2002,
Erythromycin 500 mg three times a day erythromycin AUC 1.90 (1.53-2.36) ↑ erythromycin Cmax 1.59 (1.23-2.05) ↑ erythromycin Cmin 3.08 (2.54-3.73) ↑ simeprevir AUC 7.47 (6.41-8.70) ↑ simeprevir Cmax 4.53 (3.91-5.25) ↑ simeprevir Cmin 12.74 (10.19-15.93) ↑ 
Eritromicin 500 mg tri puta na dan eritromicin AUC 1,90 (1,53-2,36) ↑ eritromicin Cmax 1,59 (1,23-2,05) ↑ eritromicin Cmin 3,08 (2,54-3,73) ↑ simeprevir AUC 7,47 (6,41-8,70) ↑ simeprevir Cmax 4,53 (3,91-5,25) ↑ simeprevir Cmin 12,74 (10,19-15,93) ↑
Ledipasvir 30 mg once daily ledipasvir AUC 1.92 (1.77-2.07) ↑ ledipasvir Cmax 1.81 (1.69-2.94) ↑ ledipasvir Cmin not studied simeprevir AUC 2.69 (2.44-2.96) ↑ simeprevir Cmax 2.61 (2.34-2.86) ↑ simeprevir Cmin not studied 
Ledipasvir 30 mg jedanput na dan ledipasvir AUC 1,92 (1,77-2,07) ↑ ledipasvir Cmax 1,81 (1,69-2,94) ↑ ledipasvir Cmin nije ispitano simeprevir AUC 2,69 (2,44-2,96) ↑ simeprevir Cmax 2,61 (2,34-2,86) ↑ simeprevir Cmin nije ispitano
> 2.50 to ≤ 5.00 x ULN 
> 2,50 do ≤ 5,00 x GGN
Common: may affect up to 1 in 10 people: - increased ‘bilirubin' levels in your blood (bilirubin is a pigment made by the liver)* - being sensitive to sunlight (photosensitivity) - constipation. 
Često: mogu se javiti u do 1 na 10 osoba: - povišene razine “bilirubina“ u Vašoj krvi (bilirubin je pigment kojeg stvara jetra)* - osjetljivost na sunčevu svjetlost (fotoosjetljivost) - zatvor. * U kliničkom ispitivanju na bolesnicima azijatskog porijekla iz Kine i Južne Koreje, prijavljene su povišene razine “bilirubina“ u krvi u više od 1 na 10 ljudi (vrlo često).
(OATP1B1 transporter and/or CYP3A4 enzyme inhibition) 
(inhibicija prijenosnika OATP1B1 i/ili enzima CYP3A4)
NAME OF THE MEDICINAL PRODUCT OLYSIO 150 mg capsules simeprevir 
NAZIV LIJEKA OLYSIO 150 mg kapsule simeprevir
0.035 mg once daily/ 1 mg once daily ethinylestradiol AUC 1.12 (1.05-1.20) ↔ ethinylestradiol Cmax 1.18 (1.09-1.27) ↑ ethinylestradiol Cmin 1.00 (0.89-1.13) ↔ norethindrone AUC 1.15 (1.08-1.22) ↔ norethindrone Cmax 1.06 (0.99-1.14) ↔ norethindrone Cmin 1.24 (1.13-1.35) ↑ 
1 mg jedanput na dan etinilestradiol AUC 1,12 (1,05-1,20) ↔ etinilestradiol Cmax 1,18 (1,09-1,27) ↑ etinilestradiol Cmin 1,00 (0,89-1,13) ↔ noretindron AUC 1,15 (1,08-1,22) ↔ noretindron Cmax 1,06 (0,99-1,14) ↔ noretindron Cmin 1,24 (1,13-1,35) ↑
> 1.5 to ≤ 2.5 x ULN 
> 1,5 do ≤ 2,5 x GGN
Rilpivirine 25 mg once daily rilpivirine AUC 1.12 (1.05-1.19) ↔ rilpivirine Cmax 1.04 (0.95-1.13) ↔ rilpivirine Cmin 1.25 (1.16-1.35) ↑ simeprevir AUC 1.06 (0.94-1.19) ↔ simeprevir Cmax 1.10 (0.97-1.26) ↑ simeprevir Cmin 0.96 (0.83-1.11) ↔ 
Rilpivirin 25 mg jedanput na dan rilpivirin AUC 1,12 (1,05-1,19) ↔ rilpivirin Cmax 1,04 (0,95-1,13) ↔ rilpivirin Cmin 1,25 (1,16-1,35) ↑ simeprevir AUC 1,06 (0,94-1,19) ↔ simeprevir Cmax 1,10 (0,97-1,26) ↑ simeprevir Cmin 0,96 (0,83-1,11) ↔
400 mg twice a day raltegravir AUC 1.08 (0.85-1.38) ↑ raltegravir Cmax 1.03 (0.78-1.36) ↔ raltegravir Cmin 1.14 (0.97-1.36) ↑ simeprevir AUC 0.89 (0.81-0.98) ↔ simeprevir Cmax 0.93 (0.85-1.02) ↔ simeprevir Cmin 0.86 (0.75-0.98) ↓ 
400 mg dva puta na dan raltegravir AUC 1,08 (0,85-1,38) ↑ raltegravir Cmax 1,03 (0,78-1,36) ↔ raltegravir Cmin 1,14 (0,97-1,36) ↑ simeprevir AUC 0,89 (0,81-0,98) ↔ simeprevir Cmax 0,93 (0,85-1,02) ↔ simeprevir Cmin 0,86 (0,75-0,98) ↓
patients, with compensated cirrhosis or without cirrhosis treatment-naïve patients or prior relapsers: 12 weeks SMV + peg-IFN-alfa + RBV, followed by 12 or 36 weeks peg-IFN-alfa + RBV3; prior non-responder patients (partial and null responders): 12 weeks SMV + peg-IFN-alfa + RBV, followed by 36 weeks peg-IFN-alfa + RBV 
36 tjedana peg-IFN-alfa + RBV3; bolesnici koji prethodno nisu odgovorili na liječenje (s djelomičnim odgovorom ili bez odgovora): 12 tjedana SMV + peg-IFN-alfa + RBV, nakon čega je slijedilo 36 tjedana peg-IFN-alfa + RBV
24 weeks OLYSIO + sofosbuvir or 12 weeks OLYSIO + sofosbuvir + ribavirin2 
+ sofosbuvir + ribavirin2 12 tjedana OLYSIO
(OATP1B1/3 transporter and/or CYP3A4 enzyme inhibition) 
(inhibicija prijenosnika OATP1B1/3 i/ili enzima CYP3A4)
OLYSIO is not recommended in patients with moderate or severe hepatic impairment (Child-Pugh class B or C) (see sections 4.2 and 4.4). 
Lijek OLYSIO se ne preporučuje u bolesnika s umjerenim ili teškim oštećenjem jetre (Child-Pugh stadij B ili C) (vidjeti dijelove 4.2 i 4.4).
Rifampicin1 600 mg once daily rifampicin AUC 1.00 (0.93-1.08) ↔ rifampicin Cmax 0.92 (0.80-1.07) ↔ rifampicin Cmin not studied 25-desacetyl-rifampicin AUC 1.24 (1.13-1.36) ↑ 25-desacetyl-rifampicin Cmax 1.08 (0.98-1.19) ↔ 25-desacetyl-rifampicin Cmin not studied simeprevir AUC 0.52 (0.41-0.67) ↓ simeprevir Cmax 1.31 (1.03-1.66) ↑ simeprevir Cmin 0.08 (0.06-0.11) ↓ 
600 mg jedanput na dan rifampicin AUC 1,00 (0,93-1,08) ↔ rifampicin Cmax 0,92 (0,80-1,07) ↔ rifampicin Cmin nije ispitano 25-dezacetil-rifampicin AUC 1,24 (1,13-1,36) ↑ 25-dezacetil-rifampicin Cmax 1,08 (0,98-1,19) ↔ 25-dezacetil-rifampicin Cmin nije ispitano simeprevir AUC 0,52 (0,41-0,67) ↓ simeprevir Cmax 1,31 (1,03-1,66) ↑ simeprevir Cmin 0,08 (0,06-0,11) ↓
2 Viral relapse rates are calculated with a denominator of patients with undetectable HCV RNA at actual EOT. 
2 Stope virološkog relapsa izračunate su s nazivnikom koji predstavlja broj bolesnika s nedetektabilnom HCV RNK pri stvarnom kraju liječenja.
Daclatasvir 60 mg once daily daclatasvir AUC 1.96 (1.84-2.10) ↑ daclatasvir Cmax 1.50 (1.39-1.62) ↑ daclatasvir Cmin 2.68 (2.42-2.98) ↑ simeprevir AUC 1.44 (1.32-1.56) ↑ simeprevir Cmax 1.39 (1.27-1.52) ↑ simeprevir Cmin 1.49 (1.33-1.67) ↑ 
60 mg jedanput na dan daklatasvir AUC 1,96 (1,84-2,10) ↑ daklatasvir Cmax 1,50 (1,39-1,62) ↑ daklatasvir Cmin 2,68 (2,42-2,98) ↑ simeprevir AUC 1,44 (1,32-1,56) ↑ simeprevir Cmax 1,39 (1,27-1,52) ↑ simeprevir Cmin 1,49 (1,33-1,67) ↑
Triazolam (oral) 
Triazolam (peroralno) Nije ispitano.
Antimycobacterials Bedaquiline 
Lijekovi za liječenje infekcija mikobakterijama
Table 14: Treatment outcome in HCV genotype 1 infected patients without cirrhosis receiving 12 weeks simeprevir + sofosbuvir, with or without ribavirin (study HPC2002) Treatment outcome simeprevir + sofosbuvir N = 21 % (n/N) 
Tablica 14: Ishod liječenja u bolesnika inficiranih HCV genotipom 1 bez ciroze koji su primali 12 tjedana simeprevir + sofosbuvir, s ili bez ribavirina (ispitivanje HPC2002)
Budesonide Fluticasone Methylprednisolone Prednisone 
Budezonid Flutikazon Metilprednizolon Prednizon
(intestinal CYP3A4 enzyme and P-gp transporter inhibition) 
(inhibicija intestinalnog enzima CYP3A4 i P-gp prijenosnika)
Table 23 shows the response rates in HCV genotype 4 infected patients. 
U tablici 23 prikazane su stope odgovora u bolesnika inficiranih HCV genotipom
Baseline HCV RNA levels > 800,000 IU/ml 
BMI ≥ 30 kg/m2 Medijan razina početnih HCV RNA (log10 IU/ml)
Genotype 4, treatment-naïve or treatment-experienced2, with compensated cirrhosis or without cirrhosis 
Genotip 4, prethodno neliječeni ili prethodno liječeni 2, s kompenziranom cirozom ili bez ciroze
Genotype 1, treatment-naïve or treatment-experienced2, without cirrhosis 
Genotip 1, prethodno neliječeni ili prethodno liječeni2, bez ciroze
24 weeks3 
24 tjedna OLYSIO
Efficacy in treatment-experienced patients with HCV genotype 1 infection In study HPC3007 (PROMISE), patients who relapsed after prior IFN-based therapy received simeprevir (150 mg once daily) + peginterferon alfa-2a + ribavirin for 12 weeks, followed by 12 or 36 additional weeks of peginterferon alfa-2a + ribavirin (see tables 17 and 18). 
Djelotvornost u bolesnika s infekcijom HCV genotipom 1 koji su prethodno bili liječeni U ispitivanju HPC3007 (PROMISE), bolesnici koji su doživjeli relaps nakon prethodne terapije temeljene na IFN primali su simeprevir (150 mg jedanput dnevno) + peginterferon alfa-2a + ribavirin tijekom 12 tjedana, nakon čega je slijedilo 12 ili 36 dodatna tjedna peginterferona alfa-2a + ribavirina (vidjeti tablice 17 i 18).
Outcome for patients without SVR12 On-treatment failure2 
Ishod za bolesnike bez SVR12
GLUCOCORTICOIDS Dexamethasone (systemic) 
Deksametazon (sistemski)
Refer to table 3 for treatment stopping rules based on HCV RNA levels at weeks 4, 12 and 24 for patients receiving treatment with OLYSIO, peginterferon alfa and ribavirin. 
Pogledajte tablicu 3 za pravila prekida liječenja temeljena na razinama HCV RNK u 4., 12. i 24.
(OATP1B1/3 transporter inhibition) 
(inhibicija OATP1B1/3 prijenosnika)
Genotype 1, treatment-naïve or treatment-experienced2, with compensated cirrhosis 
Genotip 1, prethodno neliječeni ili prethodno liječeni 2, s kompenziranom cirozom
Ranitidine 
Bedakilin
HCV geno/subtype and presence of baseline Q80K polymorphism in HCV genotype 1a HCV genotype 1a with Q80K 
HCV geno/podtip i prisutnost početnog Q80K polimorfizma u HCV genotipu 1a
NAME OF THE MEDICINAL PRODUCT OLYSIO 150 mg hard capsules simeprevir 
NAZIV LIJEKA OLYSIO 150 mg tvrde kapsule simeprevir
Table 22: Treatment outcome in HCV genotype 1 infected patients with HIV-1 co-infection 
Tablica 22: Ishod liječenja u bolesnika inficiranih HCV genotipom 1 i koinfekcijom HIV-om-1 (ispitivanje C212)
300 mg once daily tenofovir AUC 1.18 (1.13-1.24) ↔ tenofovir Cmax 1.19 (1.10-1.30) ↑ tenofovir Cmin 1.24 (1.15-1.33) ↑ simeprevir AUC 0.86 (0.76-0.98) ↓ simeprevir Cmax 0.85 (0.73-0.99) ↓ simeprevir Cmin 0.93 (0.78-1.11) ↓ 
Tenofovir dizoproksil fumarat 300 mg jedanput na dan tenofovir AUC 1,18 (1,13-1,24) ↔ tenofovir Cmax 1,19 (1,10-1,30) ↑ tenofovir Cmin 1,24 (1,15-1,33) ↑ simeprevir AUC 0,86 (0,76-0,98) ↓ simeprevir Cmax 0,85 (0,73-0,99) ↓ simeprevir Cmin 0,93 (0,78-1,11) ↓
Simeprevir in combination with peginterferon alfa and ribavirin: During the first 12 weeks treatment with simeprevir, dyspnoea was reported in 11.8% of simeprevir-treated patients, compared to 7.6% in placebo-treated patients (all grades; pooled phase 3). 
Dispneja Simeprevir u kombinaciji s peginterferonom alfa i ribavirinom: Tijekom prvih 12 tjedana liječenja simeprevirom, dispneja je bila prijavljena u 11,8% bolesnika liječenih simeprevirom, u usporedbi sa 7,6% bolesnika liječenih placebom (svi stupnjevi; objedinjeno za fazu 3).
Eighty-nine percent (54/61) of the simeprevir-treated treatment-naïve patients and prior relapsers without cirrhosis were eligible for 24 weeks of treatment; in these patients the SVR12 rate was 87%. 
Osamdeset i devet posto (54/61) bolesnika bez ciroze liječenih simeprevirom, koji prethodno nisu bili liječeni ili su prethodno doživjeli relaps bilo je pogodno za 24 tjedna liječenja; u tih bolesnika stopa
sofosbuvir N = 286 n (%) 
12 tjedana simeprevir + sofosbuvir N = 286 n (%)
It is not recommended to co-administer OLYSIO with these anticonvulsants as co-administration may result in loss of therapeutic effect of OLYSIO. 
Ne preporučuje se istovremeno primjenjivati lijek OLYSIO s ovim antikonvulzivima jer istovremena primjena može dovesti do gubitka terapijskog učinka lijeka
NARCOTIC ANALGESICS Methadone7 
Metadon7
Short term monotherapy data of simeprevir from studies C201 (genotype 1) and C202 (genotype 2, 3, 4, 5 and 6) in patients receiving 200 mg once daily simeprevir for 7 days is presented in table 9. 
(genotip 2, 3, 4, 5 i 6) u bolesnika koji uzimaju 200 mg simeprevira jedanput na dan tijekom 7 dana prikazani su u tablici 9.
Felodipine 
Felodipin
LIST OF EXCIPIENTS Contains lactose monohydrate 
Sadrži laktozu hidrat
Recommendation for co-administration 
Preporuke za istovremenu primjenu
Tacrolimus 2 mg patient individualised dose4 
Takrolimus 2 mg
Mild increases in simeprevir concentrations may occur due to mild inhibition of OATP1B1 by sildenafil. 
Moguća su blaga povišenja koncentracija PDE-5 inhibitora u plazmi. (inhibicija intestinalnog enzima CYP3A4) Mogu se javiti blaga povišenja koncentracija simeprevira zbog blage inhibicije OATP1B1 sildenafilom.
Table 19 shows the response rates in HCV genotype 1 infected treatment-naïve patients. 
Tablica 19 pokazuje stope odgovora u bolesnika inficiranih HCV genotipom 1 koji prethodno nisu bili liječeni.
2 Viral relapse rates are calculated with a denominator of patients with undetectable HCV RNA at actual EOT and with at least one follow-up HCV RNA assessment. 
2 Stope virološkog relapsa izračunavaju se s nazivnikom koji predstavlja broj bolesnika s nedetektabilnom HCV RNK pri stvarnom kraju liječenja i s barem jednim praćenjem s procjenom HCV RNK.
The recommended co-administered medicinal product(s) and treatment duration for OLYSIO combination therapy are provided in tables 1 and 2. 
Preporučeni istovremeno primijenjeni lijek(ovi) i trajanje liječenja u kombiniranom liječenju s lijekom
In HCV genotype 1a infected patients with cirrhosis, testing for the presence of the NS3 Q80K polymorphism may be considered prior to initiation of therapy with OLYSIO in combination with sofosbuvir (see section 5.1). 
Prije početka liječenja lijekom OLYSIO u kombinaciji sa sofosbuvirom u bolesnika s infekcijom HCV genotipa 1a s cirozom može se uzeti u obzir ispitivanje na prisutnost NS3 Q80K polimorfizma (vidjeti dio 5.1).
Prior non-responder patients (including partial and null responders) with or without cirrhosis, with or without HIV co-infection 
s ili bez ciroze, s ili bez koinfekcije HIV-om
STATEMENT OF ACTIVE SUBSTANCE(S) Each hard capsule contains simeprevir sodium equivalent to 150 mg simeprevir. 
Jedna tvrda kapsula sadrži simeprevirnatrij što odgovara 150 mg simeprevira.
Fertility 
Terfenadin
90% confidence interval of the geometric mean ratio being within (↔), below (↓) or above (↑) the 0.80 - 1.25 range. 
Smjer strjelice (↑ = povišenje, ↓ = sniženje, ↔ = bez promjene) za svaki farmakokinetički parametar temelji se na intervalu pouzdanosti od 90% omjera geometrijske srednje vrijednosti koji je unutar (↔), ispod (↓) ili iznad (↑) raspona od 0,80
Prior relapsers 
Bolesnici s prethodnim relapsom
WHO toxicity range1 
Raspon toksičnosti prema
SOC 
Osip
Genotype 1, treatment-naïve or treatment-experienced4, HCV/HIV-1 co-infected patients, with compensated cirrhosis or without cirrhosis treatment-naïve patients or prior relapsers without cirrhosis: 12 weeks SMV + peg-IFN-alfa + RBV, followed by 12 or 36 weeks peg-IFN-alfa + RBV prior non-responder patients (partial and null responders) without cirrhosis and all treatment-naïve and treatment-experienced patients with cirrhosis: 12 weeks SMV + peg-IFN-alfa + RBV, followed by 36 weeks peg-IFN-alfa + RBV 
Genotip 1, prethodno neliječeni ili prethodno liječeni4, HCV/HIV-1 koinficirani bolesnici, s kompenziranom cirozom ili bez ciroze prethodno neliječeni bolesnici ili bolesnici s prethodnim relapsom bez ciroze: 12 tjedana SMV +
Genotype 1, treatment-naïve or null responders3, with compensated cirrhosis or without cirrhosis 
Genotip 1, prethodno neliječeni ili koji nisu odgovorili na liječenje3, s kompenziranom cirozom ili bez ciroze
(intestinal CYP3A4 enzyme inhibition) 
(inibicija intestinalnog enzima CYP3A4)
Treatment with OLYSIO must be initiated in combination with peginterferon alfa + ribavirin and administered for 12 weeks and then followed by an additional 36 weeks of peginterferon alfa and + ribavirin. 
12 tjedana nakon čega slijedi dodatnih 36 tjedana peginterferona alfa i + ribavirina.
Buprenorphine Naloxone 
Buprenorfin Nalokson
Pooled phase 3 studies simeprevir + peginterferon alfa + ribavirin N = 152 n (%) 
simeprevir + peginterferon alfa + ribavirin N = 152 n (%)
Treatment with OLYSIO must be initiated in combination with peginterferon alfa + ribavirin and administered for 12 weeks and then followed by an additional 12 weeks of peginterferon alfa + ribavirin. 
Liječenje lijekom OLYSIO mora se započeti u kombinaciji s peginterferonom alfa + ribavirinom i primijeniti tijekom
Outcome for patients without SVR12 On-treatment failure Viral relapse1 
Ishod za bolesnike bez SVR12 Neuspjeh tijekom liječenja1
Median baseline HCV RNA levels (log10 IU/ml) Presence of cirrhosis no cirrhosis with cirrhosis Prior treatment history treatment-naïve treatment-experienced1 IL28B genotype CC non-CC HCV geno/subtype and presence of baseline Q80K polymorphism in HCV genotype 1a HCV genotype 1a with Q80K HCV genotype 1b 
IL28B genotip CC ne-CC HCV geno/subtip i prisutnost početnog Q80K polimorfizma u HCV genotipu 1a HCV genotip 1a s Q80K HCV genotipe 1b
Significant decrease in plasma concentrations of simeprevir are expected. 
Očekuju se značajna sniženja koncentracije simeprevira u plazmi. (indukcija enzima CYP3A4)
4 Viral relapse rates are calculated with a denominator of patients with undetectable HCV RNA at EOT and with at least one follow-up HCV RNA assessment. 
4 Stope virološkog relapsa izračunate su s nazivnikom koji predstavlja broj bolesnika s nedetektabilnom HCV RNA na završetku liječenja i s najmanje jednom procjenom HCV RNA tijekom praćenja.
1 Viral relapse rates are calculated with a denominator of patients with undetectable HCV RNA at EOT and with at least one follow-up HCV RNA assessment. 
1 Stope virološkog relapa izračunate su s nazivnikom koji predstavlja broj bolesnika s nedetektabilnom HCV RNA na završetku liječenja i s najmanje jednom procjenom HCV RNA tijekom praćenja.
Grade 2 ‘blood bilirubin increased' was reported in one patient (0.3%) receiving 12 weeks of treatment. 
‘Povišen bilirubin u krvi' 2. stupnja bio je prijavljen u jednog bolesnika
Treatment with OLYSIO must be initiated in combination with peginterferon alfa + ribavirin and administered for 12 weeks and then followed by an additional 36 weeks of peginterferon alfa + ribavirin. 
12 tjedana nakon čega slijedi dodatnih 36 tjedana peginterferona alfa + ribavirina.
Significant increases in plasma concentrations of simeprevir are expected. 
Očekuju se značajna povišenja koncentracije simeprevira u plazmi. (blaga do umjerena inhibicija enzima CYP3A4)
Nisoldipine 
Nizoldipin
2 Viral relapse rates are calculated with a denominator of patients with undetectable HCV RNA at EOT and with at least one follow-up HCV RNA assessment. 
2 Stope virološkog relapsa izračunate su s nazivnikom koji predstavlja broj bolesnika s nedetektabilnom HCV RNA na završetku liječenja i s najmanje jednom procjenom HCV RNA praćenja.