natgillin/translations-raw huggingface dataset:
Within each group, patients were randomized in a 1:1 ratio to receive ledipasvir/sofosbuvir + ribavirin for 12 or 24 weeks.
Unutar svake skupine, bolesnici su bili randomizirani u omjeru 1:1 za primjenu ledipasvira/sofosbuvira u kombinaciji s ribavirinom tijekom 12 ili 24 tjedna.
Reduced susceptibility to sofosbuvir was associated with the primary NS5B substitution S282T in all replicon genotypes examined.
Smanjena osjetljivost na sofosbuvir bila je povezana s primarnom S282T supstitucijom u NS5B u svim ispitanim genotipovima replikona.
Genotype 2b 16-530b
16-530b
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.
Bolesnici u ovoj drugoj terapijskoj skupini primali su placebo (umjesto ledipasvira/sofosbuvira i ribavirina) tijekom prvih 12 tjedana, nakon čega je tijekom sljedećih 12 tjedana uslijedila terapija djelatnim tvarima na zaslijepljeni način.
Afterwards, close monitoring and potential dose adjustment of ciclosporin may be required.
Međutim, kasnije je opravdano pažljivo praćenje i eventualna prilagodba doze ciklosporina.
Race and gender
Rasa i spol
Harvoni can be used in these patients with no dose adjustment when no other relevant treatment options are available (see section 4.4, 4.8, 5.1 and 5.2).
U tih se bolesnika Harvoni može primjenjivati bez prilagodbe doze kada nisu dostupne nikakve druge odgovarajuće mogućnosti liječenja (vidjeti dijelove 4.4, 4.8, 5.1 i 5.2).
In non-cirrhotic patients relapses only occurred in the presence of baseline NS5A RAVs, and during therapy with ledipasvir/sofosbuvir without ribavirin.
Bolesnici bez ciroze imali su relaps samo u prisutnosti početnih NS5A RAV i tijekom terapije ledipasvirom/sofosbuvirom bez ribavirina.
For genotype 3 infection, ledipasvir/sofosbuvir was given with or without ribavirin, also for 12 weeks (Table 19).
Za infekciju genotipom 3, ledipasvir/sofosbuvir davao se s ribavirinom ili bez njega također 12 tjedana (tablica 19).
The median terminal half-life of ledipasvir in healthy volunteers following administration of ledipasvir/sofosbuvir in the fasted state was 47 hours.
Medijan terminalnog poluvijeka ledipasvira nakon primjene ledipasvira/sofosbuvira natašte u zdravih dobrovoljaca iznosio je 47 sati.
NARCOTIC ANALGESICS Methadone
OPIOIDNI ANALGETICI
The pharmacokinetics of sofosbuvir were studied in HCV negative patients with mild (eGFR ≥ 50 and < 80 mL/min/1.73 m2), moderate (eGFR ≥ 30 and < 50 mL/min/1.73 m2), severe renal impairment (eGFR < 30 mL/min/1.73 m2) and patients with ESRD requiring haemodialysis following a single 400 mg dose of sofosbuvir,relative to patients with normal renal function (eGFR > 80 mL/min/1.73 m2).
Farmakokinetika sofosbuvira bila je ispitana u HCV-negativnih bolesnika s blagim (eGFR ≥ 50 i < 80 ml/min/1,73 m2), umjerenim (eGFR ≥ 30 i < 50 ml/min/1,73 m2), teškim oštećenjem bubrega (eGFR < 30 ml/min/1,73 m2) i bolesnika sa završnim stadijem bolesti bubrega koji su trebali hemodijalizu, nakon jedne doze od 400 mg sofosbuvira u odnosu na bolesnike s normalnom funkcijom bubrega (eGFR > 80 ml/min/1,73 m2).
Based on the population pharmacokinetic analysis in HCV-infected patients, geometric mean steady-state AUC0-24 for ledipasvir (n = 2,113), sofosbuvir (n = 1,542), and GS-331007 (n = 2,113) were 7,290, 1,320 and 12,000 ng•h/mL, respectively.
Na temelju analize populacijske farmakokinetike u bolesnika zaraženih HCV-om, geometrijska srednja vrijednost AUC0-24 u stanju dinamičke ravnoteže za ledipasvir (n = 2113), sofosbuvir (n = 1542) i GS-331007 (n = 2113) iznosila je 7290, 1320 odnosno 12 000 ng•h/ml.
Among the patients who had decompensated cirrhosis (pre- or post-transplant), 64% and 36% were CPT class B and C at screening, respectively, 24% had a baseline Model for End Stage Liver Disease (MELD) score greater than 15.
Među bolesnicima koji su imali dekompenziranu cirozu (prije ili poslije transplantacije), 64 % imalo je pri probiru CPT stadij B, a 36 % CPT stadij C, 24 % imalo je početni rezultat na modelu za izračun završnog stadija bolesti jetre (engl.
Co-administration will significantly decrease ledipasvir and sofosbuvir plasma concentrations and could result in loss of efficacy of Harvoni (see section 4.5).
Istodobna primjena značajno će smanjiti koncentracije ledipasvira i sofosbuvira u plazmi i tako može dovesti do gubitka djelotvornosti lijeka Harvoni (vidjeti dio 4.5).
A conservative 24 weeks of therapy is advised in all treatment-experienced genotype 3 patients and those treatment-naïve genotype 3 patients with cirrhosis (see section 4.2).
Konzervativna 24-tjedna terapija savjetuje se u svih prethodno liječenih bolesnika s genotipom 3 i bolesnika s genotipom 3 i cirozom koji prethodno nisu bili liječeni (vidjeti dio 4.2).
Population pharmacokinetic analysis in HCV-infected patients showed that within the age range (18 to 80 years) analysed, age did not have a clinically relevant effect on the exposure to ledipasvir, sofosbuvir or GS-331007.
Analiza populacijske farmakokinetike u bolesnika zaraženih HCV-om pokazala je da unutar analiziranog raspona dobi (18 do 80 godina), dob nije imala klinički važan učinak na izloženost ledipasviru, sofosbuviru ili GS-331007.
Demographics and baseline characteristics were balanced across the treatment groups.
Demografske i početne značajke bile su slične u svim terapijskim skupinama.
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 bolesnika u kojih je liječenje ledipasvirom/sofosbuvirom bilo neuspješno vidi se selekcija mutacija za rezistenciju na inhibitor NS5A koje znatno smanjuju osjetljivost na ledipasvir (vidjeti dio 5.1).
• If you are sick (vomit) less than 5 hours after taking Harvoni, take another tablet.
• Ako povratite u razdoblju kraćem od 5 sati nakon uzimanja lijeka Harvoni, uzmite drugu tabletu.
The clinical data to support the use of Harvoni in adults infected with HCV genotype 3 are limited (see section 5.1).
Klinički podaci koji podupiru primjenu lijeka Harvoni u odraslih zaraženih HCV-om genotipa 3 su ograničeni (vidjeti dio 5.1).
GS-331007 is not a substrate for renal transporters including organic anion transporter (OAT) 1 or OAT3, or OCT2.
GS-331007 nije supstrat bubrežnih prijenosnika koji uključuju prijenosnik organskih aniona (OAT)1, OAT3 ili OCT2.
0.59-1.00 = F3-F4.
0,32-0,58 = F2; 0,59-1,00 = F3-F4.
Co-administration of Harvoni with rosuvastatin may significantly increase the concentration of rosuvastatin (several fold-increase in AUC) which is associated with increased risk of myopathy, including rhabdomyolysis.
Istodobna primjena lijeka Harvoni s rosuvastatinom može značajno povećati koncentraciju rosuvastatina (AUC povećana nekoliko puta), što je povezano s povećanim rizikom od miopatije, uključujući rabdomiolizu.
In HCV-infected patients with severe renal impairment treated with ledipasvir/sofosbuvir for 12 weeks (n = 18), the pharmacokinetics of ledipasvir, sofosbuvir, and GS-331007 were consistent with that observed in HCV negative patients with severe renal impairment.
U bolesnika zaraženih HCV-om s teškim oštećenjem bubrega koji su liječeni ledipasvirom/sofosbuvirom tijekom 12 tjedana (n=18), farmakokinetika ledipasvira, sofosbuvira i GS-331007 bila je u skladu s onom opaženom u HCV-negativnih bolesnika s teškim oštećenjem bubrega.
Medicinal products that increase gastric pH are expected to decrease concentration of ledipasvir.
Očekuje se da će lijekovi koji povećavaju želučani pH smanjiti koncentraciju ledipasvira.
Decreases in haemoglobin to < 10 g/dL and < 8.5 g/dL during treatment were experienced by 39% and 13% of patients treated with ledipasvir/sofosbuvir with ribavirin, respectively.
Tijekom liječenja, hemoglobin se snizio na < 10 g/dl u 39 % odnosno na < 8,5 g/dl u 13 % bolesnika liječenih ledipasvirom/sofosbuvirom s ribavirinom.
Among patients with a baseline HCV RNA < 6 million IU/mL, the SVR was 97% (119/123) with 8-week treatment of ledipasvir/sofosbuvir and 96% (126/131) with 12-week treatment of ledipasvir/sofosbuvir.
Među bolesnicima s početnim HCV RNK < 6 milijuna IU/ml, SVR je bio 97 % (119/123) uz osmotjedno liječenje ledipasvirom/sofosbuvirom i 96 % (126/131) uz 12-tjedno liječenje ledipasvirom/sofosbuvirom.
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.
Ispitivanje SIRIUS uključilo je bolesnike 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.
After a single 90 mg dose of [14C]-ledipasvir in healthy subjects, the blood to plasma ratio of [14C]-radioactivity ranged between 0.51 and 0.66.
Nakon jedne doze od 90 mg [14C]-ledipasvira u zdravih ispitanika, omjer [14C]-radioaktivnosti u krvi u odnosu na plazmu kretao se u rasponu između 0,51 i 0,66.
Ledipasvir solubility decreases as pH increases.
Topljivost ledipasvira smanjuje se s povećanjem pH.
After a single 400 mg dose of [14C]-sofosbuvir in healthy subjects, the blood to plasma ratio of [14C]-radioactivity was approximately 0.7.
Nakon jedne doze od 400 mg [14C]-sofosbuvira u zdravih ispitanika, omjer [14C]-radioaktivnosti u krvi u odnosu na plazmu bio je približno 0,7.
Table 2: Guidance for ribavirin dosing when administered with Harvoni to patients with decompensated cirrhosis
Tablica 2: Smjernice za doziranje ribavirina kada se primjenjuje s lijekom Harvoni bolesnicima s dekompenziranom cirozom
Afterwards, close monitoring and potential dose adjustment of tacrolimus may be required.
Međutim, kasnije je opravdano pažljivo praćenje i eventualna prilagodba doze takrolimusa.
Women of childbearing potential / contraception in males and females When Harvoni is used in combination with ribavirin, extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients.
Kad se Harvoni primjenjuje u kombinaciji s ribavirinom, potreban je krajnji oprez kako bi se izbjegla trudnoća u bolesnica i partnerica muških bolesnika.
Harvoni 90 mg/400 mg film-coated tablets ledipasvir/sofosbuvir
Harvoni 90 mg/400 mg filmom obložene tablete ledipasvir/sofosbuvir
Steady-state Cmax for ledipasvir, sofosbuvir and GS-331007 were 323, 618 and 707 ng/mL, respectively.
Cmax u stanju dinamičke ravnoteže za ledipasvir, sofosbuvir i GS-331007 iznosila je 323, 618 odnosno 707 ng/ml.
Ledipasvir was fully active against the sofosbuvir resistance-associated substitution S282T in NS5B while all ledipasvir resistance-associated substitutions in NS5A were fully susceptible to sofosbuvir.
Ledipasvir je bio potpuno djelatan protiv supstitucije S282T u NS5B povezane s rezistencijom na sofosbuvir, dok su sve supstitucije u NS5A povezane s rezistencijom na ledipasvir bile potpuno osjetljive na sofosbuvir.
Antiviral activity
Antivirusno djelovanje
NS5B RAVs: The NS5B substitution S282T emerged in the HCV of 1/17 genotype 3-failures, and in the HCV of 1/3, 1/1 and 1/1 of genotype 4-, 5- and 6-failures, respectively.
NS5B RAV-ovi: NS5B supstitucija S282T pojavila se u HCV-u kod 1/17 neuspjeha kod genotipa 3 te u HCV-u kod 1/3 neuspjeha kod genotipa 4, 1/1 neuspjeha kod genotipa 5 i 1/1 neuspjeha kod genotipa 6.
Patient
Bolesnik
Harvoni + ribavirinA for 12 weeks (see section 5.1).
Harvoni s ribavirinomA tijekom 12 tjedana (vidjeti dio 5.1).
Of the 7 patients who failed to achieve SVR12, 3 relapsed, all had decompensated cirrhosis and were treated with ledipasvir/sofosbuvir + ribavirin for 12 weeks.
Od 7 bolesnika koji nisu uspjeli postići SVR12, 3 su imala relaps, svi su imali dekompenziranu cirozu i bili su liječeni kombinacijom ledipasvir/sofosbuvir + ribavirin 12 tjedana.
(may affect up to 1 in 10 people) • rash
(mogu se javiti u do 1 na 10 osoba)
HCV-Infected Subjects
Ispitanici s infekcijom HCV-om
No liver or heart findings were observed in chronic toxicity studies at exposures 5 times (rat) and 16 times (dog) higher than the clinical exposure.
U ispitivanjima kronične toksičnosti nisu opaženi nikakvi nalazi na jetri ili srcu pri izloženostima koje su 5 puta (štakor) i 16 puta (pas) veće od kliničke izloženosti.
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of ledipasvir, sofosbuvir or Harvoni in pregnant women.
Nema podataka ili su podaci o primjeni ledipasvira, sofosbuvira ili lijeka Harvoni u trudnica ograničeni (manje od 300 trudnoća).
• oxcarbazepine (a medicine used to treat epilepsy and prevent seizures);
• okskarbazepin (lijek koji se primjenjuje za liječenje epilepsije i sprječavanje napadaja);
The 8-week treatment of ledipasvir/sofosbuvir without ribavirin was non-inferior to the 8-week treatment of ledipasvir/sofosbuvir with ribavirin (treatment difference 0.9%; 95% confidence interval: -3.9% to 5.7%) and the 12-week treatment of ledipasvir/sofosbuvir (treatment difference -2.3%; 97.5% confidence interval: -7.2% to 3.6%).
Osmotjedno liječenje ledipasvirom/sofosbuvirom bez ribavirina nije bilo lošije od osmotjednog liječenja ledipasvirom/sofosbuvirom s ribavirinom (terapijska razlika 0,9 %; 95 % interval pouzdanosti: -3,9 % do 5,7 %) i 12-tjednog liječenja ledipasvirom/sofosbuvirom (terapijska razlika -2,3 %; 97,5 % interval pouzdanosti: -7,2 % do 3,6 %).
Sofosbuvir is a pan-genotypic inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication.
Sofosbuvir je pan-genotipski inhibitor HCV NS5B RNK-ovisne RNK polimeraze, koja je neophodna za umnažanje virusa.
No dose adjustment of Harvoni or abacavir/ lamivudine is required.
Nije potrebna prilagodba doze lijeka Harvoni ili abakavira/ lamivudina.
The potential risks and benefits associated with co-administration of Harvoni with the fixed-dose combination tablet containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or tenofovir disoproxil fumarate given in conjunction with a boosted HIV protease inhibitor (e.g. atazanavir or darunavir) should be considered, particularly in patients at increased risk of renal dysfunction.
Potrebno je uzeti u obzir moguće rizike i koristi povezane s istovremenom primjenom lijeka Harvoni i tablete s fiksnom kombinacijom doza elvitegravira/kobicistata/emtricitabina/tenofovirdizoproksilfumarata ili tenofovirdizoproksilfumarata koji se daje zajedno s pojačanim inhibitorom proteaze HIV-a (npr. atazanavirom ili darunavirom), osobito u bolesnika s povećanim rizikom od poremećaja funkcije bubrega.
In study 1118, 44 patients with genotype 1 infection, including 12 cirrhotic patients, who had previously failed treatment with sofosbuvir + ribavirin + PEG-IFN or with sofosbuvir + ribavirin were treated with ledipasvir/sofosbuvir + ribavirin for 12 weeks; the SVR was 100% (44/44).
U ispitivanju 1118, 44 bolesnika s infekcijom genotipom 1, uključujući 12 bolesnika s cirozom, u kojih je prethodno liječenje sofosbuvirom s ribavirinom i PEG-IFN-om ili sofosbuvirom s ribavirinom bilo neuspješno bila su liječena ledipasvirom/sofosbuvirom s ribavirinom tijekom 12 tjedana; SVR je iznosio 100 % (44/44).
When ribavirin is added to Harvoni, refer also to the Summary of Product Characteristics of ribavirin.
Kad se ribavirin dodaje lijeku Harvoni, pročitajte također sažetak opisa svojstava lijeka za ribavirin.
Following a single 400 mg oral dose of [14C]-sofosbuvir, mean total recovery of the dose was greater than 92%, consisting of approximately 80%, 14%, and 2.5% recovered in urine, faeces, and expired air, respectively.
Nakon jedne peroralne doze od 400 mg [14C]-sofosbuvira, srednja vrijednost ukupno otkrivene doze bila je veća od 92 % i sastojala se od približno 80 % one otkrivene u mokraći, 14 % u stolici i 2,5 % u izdahnutom zraku.
BOTTLE AND CARTON LABELLING
NALJEPNICA BOCE I KUTIJA
The metabolic activation pathway involves sequential hydrolysis of the carboxyl ester moiety catalysed by human cathepsin A or carboxylesterase 1 and phosphoramidate cleavage by histidine triad nucleotide-binding protein 1 followed by phosphorylation by the pyrimidine nucleotide biosynthesis pathway.
A ili karboksilesteraza 1 i cijepanje fosforamidata histidinskim trijadnim proteinom 1 koji veže nukleotide (engl. histidine triad nucleotide-binding protein 1) za kojom slijedi fosforilacija putem biosinteze pirimidinskih nukleotida.
Demographics and baseline characteristics were balanced across treatment-naïve and treatment-experienced patients.
Demografske i početne značajke bile su slične i u prethodno neliječenih i prethodno liječenih bolesnika.
The safety of tenofovir disoproxil fumarate in the setting of Harvoni and a pharmacokinetic enhancer has not been established.
Sigurnost tenofovirdizoproksilfumarata kad se primjenjuje uz Harvoni i farmakokinetički pojačivač nije ustanovljena.
- Harvoni for 8 weeks may be considered in previously untreated genotype 1-infected patients (see section 5.1, ION-3 study).
- U bolesnika zaraženih genotipom 1 koji prethodno nisu bili liječeni može se razmotriti primjena lijeka Harvoni tijekom 8 tjedana (vidjeti dio 5.1 u ispitivanju ION-3).
Among post-transplant patients with compensated liver disease or patients with decompensated liver disease either pre- or post-transplant (SOLAR-1 and SOLAR-2 studies), relapse was associated with the detection of one or more of the following NS5A RAVs: K24R, M28T, Q30R/H/K, L31V, H58D and Y93H/C in 12/14 genotype 1a patients, and L31M, Y93H/N in 6/6 genotype 1b patients.
Među bolesnicima s kompenziranom bolešću jetre poslije transplantacije ili onima s dekompenziranom bolešću jetre prije ili poslije transplantacije (ispitivanja SOLAR-1 i SOLAR-2), relaps je bio povezan s otkrivanjem jednog ili više sljedećih NS5A RAV-ova: K24R, M28T, Q30R/H/K, L31V, H58D i Y93H/C u 12/14 bolesnika s genotipom 1a, te L31M, Y93H/N u 6/6 bolesnika s genotipom 1b.
In clinical studies, fatigue and headache were more common in patients treated with ledipasvir/sofosbuvir compared to placebo.
U kliničkim su ispitivanjima, umor i glavobolja bili su češći u bolesnika liječenih ledipasvirom/sofosbuvirom nego placebom.
Of the 8 genotype 1b patients who qualified for resistance testing, 7/8 (88%) harboured one or more NS5A RAVs at positions L31 and Y93 at failure, while 1/8 patients had no NS5A RAVs at failure.
Od 8 bolesnika s genotipom 1b koji su zadovoljili mjerila za provjeru rezistencije, 7/8 (88 %) nosilo je jednu ili više NS5A RAV na položajima L31 i Y93 u vrijeme virološkog neuspjeha, dok 1/8 bolesnika nije imao NS5A RAV u vrijeme virološkog neuspjeha.
Refer to the Summary of Product Characteristics for ribavirin for additional information.
Pročitajte sažetak opisa svojstava lijeka za ribavirin zbog dodatnih informacija.
The safety of tenofovir disoproxil fumarate in the setting of Harvoni and a pharmacokinetic enhancer (e.g. ritonavir or cobicistat) has not been established.
Sigurnost tenofovirdizoproksilfumarata kad se primjenjuje uz Harvoni i farmakokinetički pojačivač (npr. ritonavir ili kobicistat) nije ustanovljena.
Cardiac arrhythmias
Oštećenje bubrega
In a pooled analysis of patients who received ledipasvir/sofosbuvir in Phase 3 studies (ION-3, ION-1 and ION-2), 37 patients (29 with genotype 1a and 8 with genotype 1b) qualified for resistance analysis due to virologic failure or early study drug discontinuation and having HCV RNA > 1,000 IU/mL.
U analizi objedinjenih podataka bolesnika koji su primali ledipasvir/sofosbuvir u ispitivanjima faze 3 (ION-3, ION-1 i ION-2), 37 bolesnika (29 s genotipom 1a i 8 s genotipom 1b) zadovoljilo je mjerila za analizu rezistencije zbog virološkog neuspjeha ili ranog prekida primjene lijeka tijekom ispitivanja i imalo je HCV RNK > 1000 IU/ml.
HCV protease inhibitor + PEG-IFN+RBV
Inhibitor proteaze HCV-a + PEG-IFN+RBV
Patients receiving Harvoni concomitantly with elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or with tenofovir disoproxil fumarate and a boosted HIV protease inhibitor should be monitored for tenofovirassociated adverse reactions.
Bolesnike koji primaju Harvoni istovremeno s elvitegravir/kobicistat/emtricitabin/tenofovirdizoproksilfumaratom ili tenofovirdizoproksilfumaratom i pojačanim inhibitorom proteaze HIV-a treba nadzirati zbog nuspojava povezanih s tenofovirom.
Renal impairment No dose adjustment of Harvoni is required for patients with mild or moderate renal impairment.
Nije potrebna prilagodba doze lijeka Harvoni u bolesnika s blagim ili umjerenim oštećenjem bubrega.
In vitro resistance selection and cross-resistance studies indicate ledipasvir targets NS5A as its mode of action.
In vitro ispitivanja selekcije rezistencije i ukrižene rezistencije pokazuju da je ledipasvir po načinu djelovanja usmjeren na NS5A.
Randomisation was stratified by the presence or absence of cirrhosis, HCV genotype (1a versus 1b) and response to prior HCV therapy (relapse/breakthrough versus non-response).
Randomizacija je bila stratificirana prema prisutnosti ili odsutnosti ciroze, genotipu HCV-a (1a naspram 1b) i odgovoru na prethodnu terapiju HCV-a (relaps/proboj naspram bez odgovora).
The safety and efficacy of Harvoni in adolescents aged 12 to < 18 years is based on data from a Phase 2, open-label clinical study (Study 1116) that enrolled 100 patients with genotype 1 HCV infection who were treated with ledipasvir/sofosbuvir for 12 weeks.
Sigurnost i djelotvornost lijeka Harvoni u adolescenata u dobi od 12 do < 18 godina temelje se na podacima iz otvorenog kliničkog ispitivanja faze 2 (ispitivanje 1116), u koje je bilo uključeno 100 bolesnika s infekcijom HCV-a genotipa 1 liječenih ledipasvirom/sofosbuvirom 12 tjedana.
The following adverse drug reactions have been identified with Harvoni (Table 6).
Sljedeće nuspojave utvrđene su za Harvoni (tablica 6).
The sofosbuvir resistance-associated substitution S282T in NS5B was not detected in any virologic failure isolate from the Phase 3 studies.
Supstitucija S282T povezana s rezistencijom na sofosbuvir u NS5B nije bila otkrivena ni u jednom izolatu kod virološkog neuspjeha u ispitivanjima faze 3.
The safety and efficacy of Harvoni in paediatric patients aged < 12 years have not been established.
Pedijatrijska populacija u dobi mlađoj od 12 godina Sigurnost i djelotvornost lijeka Harvoni u pedijatrijskih bolesnika u dobi mlađoj od 12 godina nisu još ustanovljene.
No target organs of toxicity were identified in rat and dog studies with ledipasvir at AUC exposures approximately 7 times the human exposure at the recommended clinical dose.
U ispitivanjima na štakorima i psima nisu utvrđeni ciljni organi toksičnosti ledipasvira pri AUC izloženostima približno 7 puta većim od izloženosti ljudi pri preporučenoj kliničkoj dozi.
The efficacy of ledipasvir [LDV]/sofosbuvir [SOF] was evaluated in three open-label Phase 3 studies with data available for a total of 1,950 patients with genotype 1 CHC.
Djelotvornost lijeka ledipasvir [LDV]/sofosbuvir [SOF] bila je procijenjena u tri otvorena ispitivanja faze 3 s podacima dostupnima za ukupno 1950 bolesnika s CHC-om uzrokovanim genotipom
73m2)
min/ 1,73 m2)
In female rats, the mean number of corpora lutea and implantation sites were slightly reduced at maternal exposures 6-fold the exposure in humans at the recommended clinical dose.
U ženki štakora, srednja vrijednost broja žutih tijela i mjesta implantacije bili su nešto sniženi pri izloženostima majke 6 puta većim od izloženosti ljudi pri preporučenoj kliničkoj dozi.
Among post-transplant patients with compensated liver disease (SOLAR-1 and SOLAR-2 studies), no relapse occurred in patients with baseline NS5A RAVs (n = 23) following 12 weeks of treatment with ledipasvir/sofosbuvir + ribavirin.
Među bolesnicima s kompenziranom bolešću jetre poslije transplantacije (ispitivanja SOLAR-1 i SOLAR-2) nije bilo relapsa u bolesnika s početnim NS5A RAV-ovima (n = 23) nakon 12 tjedana liječenja kombinacijom ledipasvir/sofosbuvir + ribavirin.
CPT Class C cirrhosis pre-transplant CPT Class B or C cirrhosis posttransplant
Ciroza CPT stadija B ili C poslije transplantacije