natgillin/translations-raw huggingface dataset:
Taking Harvoni with any of these may make Harvoni work less well or make any side effects of the medicines worse.
Uzimanje lijeka Harvoni s bilo kojim od ovih lijekova može oslabiti djelovanje lijeka Harvoni ili pogoršati neke nuspojave ovih lijekova.
Your doctor may give you a different medicine or adjust the dose of the medicine you are taking.
Vam može dati drugi lijek ili prilagoditi dozu lijeka koji uzimate.
The clinical studies enrolled patients with or without cirrhosis, who were treatment-naïve or with prior treatment failure after therapy with PEG-IFN + ribavirin +/- an HCV protease inhibitor.
Klinička ispitivanja uključila su pacijente s cirozom ili bez nje, koji prethodno nisu bili liječeni ili u kojih je prethodno liječenje PEG-IFN + ribavirinom +/- inhibitorom proteaze HCV-a bilo neuspješno.
HCV PRODUCTS Simeprevir (150 mg once daily)/ ledipasvir (30 mg once daily)
LIJEKOVI PROTIV HCV-a Simeprevir (150 mg jedanput na dan)/ ledipasvir (30 mg jedanput na dan)
Patients in the latter treatment arm received placebo (for ledipasvir/sofosbuvir and ribavirin) during the first 12 weeks, followed by active blinded therapy during the subsequent 12 weeks.
Pacijenti u ovoj drugoj terapijskoj skupini primali su placebo (umjesto ledipasvira/sofosbuvira i ribavirina) tijekom prvih 12 tjedana,
Following treatment with ledipasvir/sofosbuvir with ribavirin for 12 weeks in post-liver transplant patients with compensated liver disease (SOLAR-1), none (n = 8) of the patients with baseline NS5A RAVs conferring a ledipasvir fold-change of > 100 relapsed.
Nakon liječenja ledipasvirom/sofosbuvirom s ribavirinom provedenog tijekom 12 tjedana u pacijenata poslije transplantacije jetre s kompenziranom bolešću jetre (SOLAR-1), nijedan (n = 8) od pacijenata s početnim NS5A RAV-ovima koji nose promjenu osjetljivosti na ledipasvir > 100 nije imao relaps.
Other c
Ostalo c
Sofosbuvir is extensively metabolised in the liver to form the pharmacologically active nucleoside analogue triphosphate GS-461203.
Sofosbuvir je nukleotidni predlijek iz kojeg unutarstaničnim metabolizmom nastaje farmakološki djelatan uridinu analogni trifosfat (GS-461203), koji se može ugraditi u
Harvoni has been shown to increase tenofovir exposure, especially when used together with an HIV regimen containing tenofovir disoproxil fumarate and a pharmacokinetic enhancer (ritonavir or cobicistat).
Primjena s određenim antiretrovirusnim režimima liječenja HIV-a Pokazalo se da Harvoni povećava izloženost tenofoviru, osobito kad se primjenjuje zajedno s režimom liječenja HIV-a koji sadrži tenofovirdizoproksilfumarat i farmakokinetički pojačivač (ritonavir ili kobicistat).
IL28CC genotype FibroTest-Determined Metavir score b
Metavir rezultat određen FibroTestom b
AUC and Cmax of ledipasvir were 77% and 58% higher, respectively, in females than males; however, the relationship between gender and ledipasvir exposures was not considered clinically relevant.
AUC i Cmax ledipasvira bile su 77 % odnosno 58 % više u žena nego u muškaraca;
Following 12 weeks of treatment with ledipasvir/sofosbuvir with ribavirin in treatment-experienced patients with compensated cirrhosis (SIRIUS, n = 77), 8/8 patients with baseline NS5A RAVs conferring > 100-fold reduced susceptibility to ledipasvir achieved SVR12.
Nakon 12 tjedana liječenja ledipasvirom/sofosbuvirom s ribavirinom prethodno liječenih pacijenata s kompenziranom cirozom (SIRIUS, n = 77), 8/8 pacijenata s početnim NS5A RAV-ovima koji nose smanjenu osjetljivost na ledipasvir za > 100 puta postiglo je SVR12.
c. Analysis (by deep sequencing) included NS5A resistance-associated polymorphisms that conferred > 2.5-fold change in EC50 (K24G/N/R, M28A/G/T, Q30E/G/H/L/K/R/T, L31I/F/M/V, P32L, S38F, H58D, A92K/T, and Y93C/F/H/N/S for genotype 1a and L31I/F/M/V, P32L, P58D, A92K, and Y93C/H/N/S for genotype 1b HCV infection).
Analiza (detaljnim sekvencioniranjem) je uključila polimorfizme NS5A povezane s rezistencijom koji su nosili > 2,5 puta veću promjenu u EC50 (K24G/N/R, M28A/G/T, Q30E/G/H/L/K/R/T, L31I/F/M/V, P32L, S38F, H58D, A92K/T i Y93C/F/H/N/S za infekciju HCV-om genotipa 1a i L31I/F/M/V, P32L, P58D, A92K i Y93C/H/N/S za infekciju HCV-om genotipa 1b).
The safety of ledipasvir/sofosbuvir has not been assessed in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2) or end stage renal disease (ESRD) requiring haemodialysis (see section 5.2).
Sigurnost ledipasvira/sofosbuvira nije procijenjena u pacijenata s teškim oštećenjem bubrega (procjena brzine glomerularne filtracije [eGFR] < 30 ml/min/1,73 m2) ili završnim stadijem bolesti bubrega (ESRD) koji zahtijeva hemodijalizu (vidjeti dio 5.2).
Abacavir/ lamivudine (600 mg/ 300 mg once daily)/ ledipasvir (90 mg once daily)
Abakavir/ lamivudin (600 mg/ 300 mg jedanput na dan)/ ledipasvir (90 mg jedanput na dan)
The majority of the sofosbuvir dose recovered in urine was GS-331007 (78%) while 3.5% was recovered as sofosbuvir.
Veći dio doze sofosbuvira otkrivene u mokraći činio je GS-331007 (78 %), dok je
SIRIUS included patients with compensated cirrhosis who first failed therapy with pegylated interferon (PEG-IFN) + ribavirin, and then failed a regimen consisting of a pegylated interferon + ribavirin + an NS3/4A protease inhibitor.
Prethodno liječeni odrasli pacijenti s cirozom - SIRIUS - genotip 1 Ispitivanje SIRIUS uključilo je pacijente s kompenziranom cirozom u kojih je prvo bila neuspješna terapija pegiliranim interferonom (PEG-IFN) + ribavirinom, a zatim je bio neuspješan režim koji se sastojao od pegiliranog interferona + ribavirina + inhibitora proteaze NS3/4A.
Orange, diamond-shaped, film-coated tablet of dimensions 19 mm x 10 mm, debossed with “GSI” on one side and “7985” on the other side.
Narančasta, filmom obložena tableta u obliku dijamanta, veličine 19 mm x 10 mm, s utisnutim “GSI”
Raltegravir (400 mg twice daily)/ sofosbuvir (400 mg once daily)
Raltegravir (400 mg dvaput na dan)/ sofosbuvir (400 mg jedanput na dan)
d. 3/3 of these patients had cirrhosis.
d. 3/3 pacijenta imalo je cirozu. e. 0/4 pacijenta imalo je cirozu.
The safety of Harvoni has not been assessed in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2) or end stage renal disease (ESRD) requiring haemodialysis.
Sigurnost lijeka Harvoni nije procijenjena u pacijenata s teškim oštećenjem bubrega (procjena brzine glomerularne filtracije [eGFR] < 30 ml/min/1,73 m2) ili završnim stadijem bolesti bubrega (ESRD)
Not interpretable a. Two patients in the LDV/SOF 12-week treatment arm, one patient in the LDV/SOF+RBV 12-week treatment arm, two patients in the LDV/SOF 24-week treatment arm, and two patients in the LDV/SOF+RBV 24-week treatment arm did not have a confirmed genotype 1 subtype.
LDV/SOF + RBV-om, dva pacijenta u terapijskoj skupini liječenoj 24 tjedna LDV/SOF-om i dva pacijenta u terapijskoj skupini liječenoj 24 tjedna LDV/SOF+RBV-om nije bila potvrđena podvrsta genotipa 1.
The group of NS5A RAVs that conferred > 100-fold shift and was observed in patients were the following substitutions in genotype 1a (M28A, Q30H/R/E, L31M/V/I, H58D, Y93H/N/C) or in genotype 1b (Y93H).
Skupinu NS5A RAV-ova koji su nosili povećanje > 100 puta i koji su bili opaženi u pacijenata činile su sljedeće supstitucije u genotipu 1a (M28A, Q30H/R/E, L31M/V/I, H58D, Y93H/N/C) ili u genotipu 1b (Y93H).
In the rat studies, exposure to sofosbuvir could not be determined but exposure margins based on the major human metabolite was approximately 5 times higher than the clinical exposure at 400 mg sofosbuvir.
U ispitivanjima na štakorima, izloženost sofosbuviru nije se mogla odrediti, ali granice izloženosti na temelju glavnog metabolita u ljudi bile su približno
Harvoni + ribavirin for 24 weeks (see sections 4.4 and 5.1).
Harvoni s ribavirinom tijekom 24 tjedna (vidjeti dijelove 4.4 i
Medicinal products that are potent P-glycoprotein (P-gp) inducers in the intestine (rifampicin, rifabutin, St. John's wort [Hypericum perforatum], carbamazepine, phenobarbital and phenytoin).
Lijekovi koji su jaki induktori P-glikoproteina (P-gp) u crijevima (rifampicin, rifabutin, gospina trava
↔ Cmin 1.00 (0.81, 1.23) Ethinyl estradiol ↑ Cmax 1.40 (1.18, 1.66)
↔ Cmin 1,00 (0,81; 1,23) Etinilestradiol ↑ Cmax 1,40 (1,18; 1,66)
NS5A RAVs were seen at relapse in 5/5 patients (for genotype 1a: Q30R/H + L31M/V [n = 1] and Q30R [n = 1]; for genotype 1b: Y93H [n = 3]).
relapsu su u 5/5 pacijenata opaženi NS5A RAV-ovi (za genotip 1a: Q30R/H + L31M/V [n = 1] i Q30R [n = 1]; za genotip 1b: Y93H [n = 3]).
Genotype 4d 0.60 Genotype 5a
Genotip 3a Genotip 4a Genotip 4d Genotip 5a b b
24% (4/17)e a. These 4 non-cirrhotic relapsers all had baseline NS5A resistance-associated polymorphisms.
Ova 4 pacijenta bez ciroze s relapsom imala su početne polimorfizme NS5A povezane s rezistencijom.
Very common side effects (may affect more than 1 in 10 people)
(mogu se javiti u više od 1 na 10 osoba)
Famotidine (40 mg single dose)/ ledipasvir (90 mg single dose)c/ sofosbuvir (400 mg single dose)
Famotidin (jedna doza od 40 mg)/ ledipasvir (jedna doza od 90 mg)c/ sofosbuvir (jedna doza od 400 mg)
Genotype 1b 0.004 Genotype 2a
Genotip 1a Genotip 1b Genotip 2a Genotip 2b b b
Treatment-naïve Patients without cirrhosis Patients with cirrhosis Treatment-experienced
Pacijenti bez ciroze Pacijenti s cirozom
↑ Cmin 1.45 (1.27, 1.64) Emtricitabine ↔ Cmax 0.98 (0.94, 1.02)
↑ Cmin 1,45 (1,27; 1,64) Emtricitabin ↔ Cmax 0,98 (0,94; 1,02)
Male gender
zbog spola.
Harvoni contains sunset yellow FCF aluminium lake (E110)
Harvoni sadrži boju sunset yellow FCF aluminium lake (E110)
Mean ratio (90% confidence interval) for AUC, Cmax, Cmin a, b
Srednja vrijednost omjera (90 % interval pouzdanosti) za AUC,
No clinically relevant pharmacokinetic differences due to gender have been identified for sofosbuvir or GS-331007.
Nisu utvrđene nikakve klinički važne razlike u farmakokinetici sofosbuvira ili GS-331007
ION-4 was an open-label clinical study that evaluated the safety and efficacy of 12 weeks of treatment with ledipasvir/sofosbuvir without ribavirin in HCV treatment-naïve and treatment-experienced patients with genotype 1 or 4 CHC who were co-infected with HIV-1.
Ispitivanje ION-4 bilo je otvoreno kliničko ispitivanje kojim se procijenila sigurnost i djelotvornost liječenja ledipasvirom/sofosbuvirom bez ribavirina tijekom 12 tjedana u pacijenata s CHC-om uzrokovanim HCV-om genotipa 1 ili 4 te istovremeno zaraženih virusom HIV-1, koji prethodno nisu bili liječeni i koji su prethodno bili liječeni.
• outer cartons containing 3 bottles of 28 (84) film-coated tablets.
• kutije koje sadrže 1 bocu s 28 filmom obloženih tableta • kutije koje sadrže 3 boce s 28 (84) filmom obloženih tableta.
All patients were treatment-naïve to HCV therapy without cirrhosis, 26% (13/50) of patients were HIV antiretroviral naïve and 74% (37/50) of patients were receiving concomitant HIV antiretroviral therapy.
Ni jedan pacijent nije bio prethodno liječen terapijom protiv HCV-a i ni jedan nije imao cirozu; 26 % (13/50) pacijenata prethodno nije bilo liječeno antiretrovirusnim lijekovima protiv
c. Patients with missing cirrhosis status were excluded from this subgroup analysis.
c. Pacijenti bez podatka o statusu ciroze bili su isključeni iz analize ove podskupine.
Table 9: Demographics and baseline characteristics in study ION-1 Patient disposition
Tablica 9: Demografske i početne značajke u ispitivanju ION-1
Table 8: Relapse rates by baseline characteristics in the ION-3 study, virological failure population* LDV/SOF
Tablica 8: Stope relapsa prema početnim značajkama u ispitivanju ION-3, populacija s virološkim neuspjehom*
Proton pump inhibitors Omeprazole (20 mg once daily)/ ledipasvir (90 mg single dose)c/ sofosbuvir (400 mg single dose)
Inhibitori protonske pumpe Omeprazol (20 mg jedanput na dan)/ ledipasvir (jedna doza od 90 mg)c/ sofosbuvir (jedna doza od 400 mg)
Darunavir boosted with ritonavir (800 mg/ 100 mg once daily)/ sofosbuvir (400 mg once daily)
Darunavir pojačan ritonavirom (800 mg/ 100 mg jedanput na dan)/ sofosbuvir (400 mg jedanput na dan)
The sofosbuvir resistance-associated substitution S282T was not detected in the baseline NS5B sequence of any patient in Phase 3 studies by population or deep sequencing.
Supstitucija S282T povezana s rezistencijom na sofosbuvir nije bila otkrivena populacijskim ili detaljnim sekvencioniranjem u početnoj NS5B sekvenci ni u jednog pacijenta u ispitivanjima faze 3,
and L31M substitution in genotype 1a conferred high levels of reduced susceptibility to ledipasvir (fold-change in EC50 ranging from 544-fold to 1,677-fold).
Ciljana mutageneza u vidu supstitucije Y93H u oba genotipa 1a i 1b, kao i Q30R i L31M supstitucija u genotipu 1a, dovela je do jako smanjene osjetljivosti na ledipasvir (promjena u EC50 u rasponu od 544 do 1677 puta).
The proportion of patients who permanently discontinued treatment due to adverse events was 0%, < 1% and 1% for patients receiving ledipasvir/sofosbuvir for 8, 12 and 24 weeks, respectively; and < 1%, 0%, and 2% for patients receiving ledipasvir/sofosbuvir + ribavirin combination therapy for 8, 12 and 24 weeks, respectively.
odnosno 1 % kod pacijenata koji su primali ledipasvir/sofosbuvir tijekom 8, 12 odnosno 24 tjedna; te < 1 %, 0 %, odnosno 2 % kod pacijenata koji su primali kombiniranu terapiju ledipasvirom/sofosbuvirom
In non-cirrhotic patients relapses only occurred in the presence of baseline NS5A RAVs, and during therapy with ledipasvir/sofosbuvir without ribavirin.
NS5A RAV i tijekom terapije ledipasvirom/sofosbuvirom bez ribavirina.
Table 13: Relapse rates for selected subgroups in study ION-2 LDV/SOF
Tablica 13: Stope relapsa u odabranim podskupinama u ispitivanju ION-2 LDV/SOF
NS5A RAVs were seen at the time of relapse in 11/13 patients (for genotype 1a: Q30R alone [n = 2], Y93C [n = 1], Y93H/C [n = 2], Q30R + H58D [n = 1], M28T + Q30H [n = 1]; for genotype 1b: Y93H [n = 3], Y93H/C [n = 1]).
NS5A RAV-ovi su u vrijeme relapsa bili opaženi u 11/13 pacijenata (za genotip 1a: samo Q30R [n = 2], Y93C [n = 1], Y93H/C [n = 2], Q30R + H58D [n = 1], M28T + Q30H [n = 1]; za genotip 1b: Y93H [n = 3], Y93H/C [n = 1]).
Baseline NS5A RAVs were overrepresented in patients who experienced relapse in the Phase 3 studies (see “Clinical efficacy and safety”).
Početni NS5A RAV bili su više zastupljeni u pacijenata koji su u ispitivanjima faze 3 imali relaps
ION-3 evaluated 8 weeks of treatment with ledipasvir/sofosbuvir with or without ribavirin and 12 weeks of treatment with ledipasvir/sofosbuvir in treatment-naïve non-cirrhotic patients with genotype 1 CHC.
U ispitivanju ION-3 procjenjivalo se 8 tjedana liječenja ledipasvirom/sofosbuvirom s ribavirinom ili bez njega te 12 tjedana liječenja ledipasvirom/sofosbuvirom pacijenata s CHC-om uzrokovanim genotipom 1, bez ciroze, koji prethodno nisu bili liječeni.
NS5A transient replicons
NS5A prolazni replikoni Medijan (raspon)
- Harvoni (without ribavirin) for 12 weeks (in patients without cirrhosis) or 24 weeks (in patients with cirrhosis) may be considered for patients who are ineligible for or intolerant to ribavirin.
U pacijenata koji nisu pogodni za liječenje ribavirinom ili ga ne podnose može se razmotriti primjena lijeka Harvoni (bez ribavirina) tijekom 12 tjedana (u pacijenata bez ciroze) ili 24 tjedna (u pacijenata s cirozom).
Recommendation concerning co-administration with Harvoni
Preporuka za istovremenu primjenu s lijekom Harvoni
Abacavir ↔ Cmax 0.92 (0.87, 0.97)
Abakavir ↔ Cmax 0,92 (0,87; 0,97)
↑ Cmin 1.36 (1.23, 1.49) Cobicistat ↔ Cmax 1.25 (1.18, 1.32)
↑ Cmin 1,36 (1,23; 1,49) Kobicistat ↔ Cmax 1,25 (1,18; 1,32)
Emtricitabine ↔ Cmax 1.08 (0.97, 1.21)
Emtricitabin ↔ Cmax 1,08 (0,97; 1,21)
Refer to tenofovir disoproxil fumarate, emtricitabine/tenofovir disoproxil fumarate, or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate Summary of Product Characteristics for recommendations on renal monitoring.
Pročitajte Sažetke opisa svojstava lijeka za tenofovirdizoproksilfumarat, emtricitabin/tenofovirdizoproksilfumarat ili elvitegravir/kobicistat/emtricitabin/tenofovirdizoproksilfumarat zbog preporuka o nadziranju funkcije bubrega.
Table 6: Demographics and baseline characteristics in study ION-3 Patient disposition
Tablica 6: Demografske i početne značajke u ispitivanju ION-3
c/ sofosbuvir (400 mg once daily)c
c/ sofosbuvir (400 mg jedanput na dan)c
In vitro potential for ledipasvir/sofosbuvir to affect other medicinal products At concentrations achieved in the clinic, ledipasvir is not an inhibitor of hepatic transporters including the OATP 1B1 or 1B3, BSEP, OCT1, OCT2, OAT1, OAT3, multidrug and toxic compound extrusion (MATE) 1 transporter, multidrug resistance protein (MRP) 2 or MRP4.
uključujući OATP 1B1 ili 1B3, BSEP, OCT1, OCT2, OAT1, OAT3, prijenosnika za izbacivanje mnogih lijekova i toksičnih spojeva (MATE) 1, proteina odgovornog za rezistenciju na mnoge lijekove (MRP) 2 ili MRP4.
d. Patients with missing cirrhosis status were excluded from this subgroup analysis.
d. Pacijenti bez podatka o statusu ciroze bili su isključeni iz analize ove podskupine.
Emtricitabine ↔ Cmax 1.02 (0.98, 1.06)
Emtricitabin ↔ Cmax 1,02 (0,98; 1,06)
Previously treated adults with or without cirrhosis - ION-2 (study 0109) - Genotype 1 ION-2 was a randomised, open-label study that evaluated 12 and 24 weeks of treatment with ledipasvir/sofosbuvir with or without ribavirin (randomised 1:1:1:1) in genotype 1 HCV-infected patients with or without cirrhosis who failed prior therapy with an interferon-based regimen, including regimens containing an HCV protease inhibitor.
ION-2 bilo je randomizirano, otvoreno ispitivanje kojim se procijenilo 12 i 24 tjedna liječenja ledipasvirom/sofosbuvirom s ribavirinom ili bez njega u pacijenata (randomiziranih u omjeru 1:1:1:1) s cirozom ili bez nje zaraženih genotipom 1 HCV-a u kojih je prethodna terapija režimom na temelju interferona bila neuspješna, uključujući režime koji su sadržavali inhibitor proteaze HCV-a.
ORAL CONTRACEPTIVES Norgestimate/ ethinyl estradiol (norgestimate 0.180 mg/ 0.215 mg/ 0.25 mg/ ethinyl estradiol 0.025 mg)/ ledipasvir (90 mg once daily)
Norgestimat/etinilestradiol (norgestimat 0,180 mg/ 0,215 mg/ 0,25 mg/ etinilestradiol 0,025 mg)/ ledipasvir (90 mg jedanput na dan)
Elvitegravir/ cobicistat/ emtricitabine/ tenofovir disoproxil fumarate (150 mg/ 150 mg/ 200 mg/ 300 mg once daily)/ ledipasvir (90 mg once daily)
Elvitegravir/ kobicistat/ emtricitabin/ tenofovirdizoproksilfumarat (150 mg/ 150 mg/ 200 mg/ 300 mg jedanput na dan)/ ledipasvir (90 mg jedanput na dan)
c/ sofosbuvir (400 mg once daily)
c/ sofosbuvir (400 mg jedanput na dan)
Lamivudine ↔ Cmax 0.93 (0.87, 1.00)
Lamivudin ↔ Cmax 0,93 (0,87; 1,00)
Relapse a
Relapsa Ostalob
↔ Cmin 1.06 (0.97, 1.15) Rilpivirine ↔ Cmax 0.97 (0.88, 1.07)
↔ Cmin 1,06 (0,97; 1,15) Rilpivirin ↔ Cmax 0,97 (0,88; 1,07)
LIST OF EXCIPIENTS Contains lactose and sunset yellow FCF aluminium lake (E110).
Sadrži laktozu i boju sunset yellow FCF aluminium lake (E110).
Harvoni is contraindicated with carbamazepine, phenobarbital and phenytoin, potent intestinal P-gp inducers (see section 4.3).
Harvoni je kontraindiciran s karbamazepinom, fenobarbitalom i fenitoinom, jakim induktorima intestinalnog P-gp-a (vidjeti dio 4.3).
Darunavir boosted with ritonavir (800 mg/ 100 mg once daily)/ ledipasvir (90 mg once daily)d
Darunavir pojačan ritonavirom (800 mg/ 100 mg jedanput na dan)/ ledipasvir (90 mg jedanput na dan)d
Both sofosbuvir and ledipasvir were fully active against substitutions associated with resistance to other classes of direct-acting antivirals with different mechanisms of actions, such as NS5B non-nucleoside inhibitors and NS3 protease inhibitors.
I sofosbuvir i ledipasvir su bili potpuno djelatni protiv supstitucija povezanih s rezistencijom na druge antivirusne lijekove izravnog djelovanja i različitim mehanizmom djelovanja,
Ciclosporin ↔ Cmax 1.06 (0.94, 1.18)
Ciklosporin ↔ Cmax 1,06 (0,94; 1,18)
It may harm them,
Pacijente koji primaju
b. Patients with missing cirrhosis status were excluded from this subgroup analysis.
Pacijenti bez podatka o statusu ciroze bili su isključeni iz analize ove podskupine.
Relative to patients 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 pacijente s normalnom funkcijom bubrega (eGFR > 80 ml/min/1,73 m2), AUC0-inf sofosbuvira bila je 61 %, 107 % odnosno
Genotype 6e
Genotip 6e b a.
Tacrolimus ↓ Cmax 0.73 (0.59, 0.90)
Takrolimus ↓ Cmax 0,73 (0,59; 0,90)
The pharmacokinetics of ledipasvir were studied with a single dose of 90 mg ledipasvir in HCV negative patients with severe hepatic impairment (CPT class C).
Farmakokinetika ledipasvira bila je ispitana u HCV-negativnih pacijenata s teškim oštećenjem jetre (CPT stadij C) nakon jedne doze od 90 mg ledipasvira.
Emtricitabine/ rilpivirine/ tenofovir disoproxil fumarate (200 mg/ 25 mg/ 300 mg once daily)/ ledipasvir (90 mg once daily)c/ sofosbuvir (400 mg once daily)c, d
Emtricitabin/ rilpivirin/ tenofovirdizoproksilfumarat (200 mg/ 25 mg/ 300 mg jedanput na dan)/ ledipasvir (90 mg jedanput na dan)c/ sofosbuvir (400 mg jedanput na dan)
Treatment of patients with prior exposure to HCV direct-acting antivirals In patients who fail treatment with ledipasvir/sofosbuvir, selection of NS5A resistance mutations that substantially reduce the susceptibility to ledipasvir is seen in the majority of cases (see section 5.1).
U većini slučajeva, u pacijenata u kojih je liječenje ledipasvirom/sofosbuvirom bilo neuspješno vidi se selekcija mutacija za rezistenciju na inhibitor NS5A koje znatno smanjuju osjetljivost na ledipasvir
Table 10: Response rates in study ION-1 LDV/SOF
Tablica 10: Stope odgovora u ispitivanju ION-1 LDV/SOF
Table 7: Response rates in study ION-3 LDV/SOF
Tablica 7: Stope odgovora u ispitivanju ION-3 LDV/SOF
Outcome for patients without SVR On-treatment virologic failure
Ishod u pacijenata bez SVR
- Harvoni + ribavirin for 12 weeks or Harvoni (without ribavirin) for 24 weeks should be considered for previously treated patients with uncertain subsequent retreatment options (see section 4.4).
U prethodno liječenih pacijenata u kojih daljnja mogućnost ponovnog liječenja nije sigurna treba razmotriti primjenu lijeka Harvoni s ribavirinom tijekom 12 tjedana ili lijeka Harvoni (bez ribavirina) tijekom 24 tjedna (vidjeti dio 4.4).
NAME OF THE MEDICINAL PRODUCT Harvoni 90 mg/400 mg film-coated tablets ledipasvir/sofosbuvir
Uputa o lijeku: Informacija za korisnika Harvoni 90 mg/400 mg filmom obložene tablete ledipasvir/sofosbuvir
No Yes a. One patient was excluded from the LDV/SOF 12-week treatment arm and one patient was excluded from the LDV/SOF+RBV 24-week treatment arm as both patients were infected with genotype 4 CHC.
Jedan je pacijent bio isključen iz terapijske skupine liječene 12 tjedana LDV/SOF-om i jedan je pacijent bio isključen iz terapijske skupine liječene 24 tjedna LDV/SOF+RBV jer su imali CHC uzrokovan genotipom 4. b. Nazivnik za relaps je broj pacijenata s HCV RNK < LLOQ na njihovom posljednjem pregledu za vrijeme trajanja terapije.
Co-administration of Harvoni with rifapentine is expected to decrease the concentration of ledipasvir and sofosbuvir, leading to reduced therapeutic effect of Harvoni.
Harvoni s rifapentinom smanjiti koncentraciju ledipasvira i sofosbuvira i tako dovesti do smanjenog terapijskog učinka lijeka Harvoni.
No dose adjustment of Harvoni or ciclosporin is required.
Nije potrebna prilagodba doze lijeka Harvoni ili ciklosporina.
Tacrolimus (5 mg single dose)/ sofosbuvir (400 mg single dose)
Takrolimus (jedna doza od 5 mg)/ sofosbuvir (jedna doza od 400 mg)h
The NS5A substitution Y93C emerged in the HCV of 1 patient (genotype 4), while NS5A RAVs present at baseline were observed at the time of failure in all patients.
NS5A supstitucija Y93C pojavila se u HCV-u kod 1 pacijenta
Treatment-experienced patients had failed prior treatment with PEG-IFN + ribavirin ± an HCV protease inhibitor or sofosbuvir +
U pacijenata koji su prethodno bili liječeni, prethodno liječenje PEG-IFN + ribavirinom ± inhibitorom proteaze HCV-a ili sofosbuvirom + ribavirinom ± PEG-IFN bilo je neuspješno.
Genotype 1a a
Genotip 1aa