natgillin/translations-raw huggingface dataset:
• Hepatic laboratory testing including direct bilirubin levels should be performed at baseline, during the first 4 weeks of starting treatment and as clinically indicated thereafter.
• na začetku, v prvih 4 tednih po začetku zdravljenja in pozneje kot je klinično indicirano je treba opraviti jetrne laboratorijske teste, vključno z ravnjo direktnega bilirubina, • zdravljenje je treba prekiniti pri bolnikih, pri katerih so se pojavili znaki dekompenzacije jeter.
Medicinal products transported by Pgp in the intestine While dasabuvir is an in vitro inhibitor of P-gp, no significant change was observed in the exposure of the P-gp substrate, digoxin, when administered with dasabuvir with ombitasvir/paritaprevir/ritonavir.
Dasabuvir sicer in vitro zavira P-gp, vendar niso ugotovili pomembne spremembe izpostavljenosti substratu P-gp digoksinu, če je bil uporabljen skupaj z dasabuvirjem in kombinacijo ombitasvir/paritaprevir/ritonavir.
Tablet core
Jedro tablete:
Following a 400 mg 14C-dasabuvir dose, approximately 94% of the radioactivity was recovered in faeces with limited radioactivity (approximately 2%) in urine.
94 % radioaktivnosti pojavilo v blatu in le malo radioaktivnosti (približno 2 %) v urinu.
Phase 3 global multicentre trials conducted with dasabuvir and ombitasvir/paritaprevir/ritonavir with or without ribavirin (RBV).
Preglednica 6: Globalna multicentrična preskušanja 3. faze z dasabuvirjem in ombitasvir/paritaprevir/ritonavir, z ribavirinom (RBV) ali brez njega.
Dasabuvir with ombitasvir/paritaprevir/ritonavir is expected to increase the exposure to rosuvastatin more than 3-fold.
Pričakovati je, da dasabuvir skupaj s kombinacijo ombitasvir/paritaprevir/ritonavir zveča izpostavljenost rosuvastatinu za več kot 3-krat.
Ritonavir dose in ombitasvir/paritaprevir/ ritonavir will provide atazanavir pharmacokinetic enhancement.
Odmerek ritonavirja v kombinaciji ombitasvir/paritap revir/ritonavir zagotavlja farmakokinetično okrepitev atazanavirja.
The physician in charge of the diabetic care of the patient should be informed when direct acting antiviral therapy is initiated.
O začetku zdravljenja z neposredno delujočim protivirusnim zdravilom je treba obvestiti zdravnika, odgovornega za zdravljenje sladkorne bolezni pri zadevnem bolniku.
You may need closer monitoring of your blood glucose levels and/or adjustment of your diabetes medicines after starting Exviera.
Po začetku jemanja zdravila Exviera morda potrebujete skrbno spremljanje ravni sladkorja v krvi in/ali prilagoditev zdravila za zdravljenje sladkorne bolezni.
Treated subjects (N = 233) had a median age of 49 years (range: 26 to 69); 10% were Black; 12% had compensated cirrhosis; 66% were treatment-naïve; 32% had failed prior treatment with pegIFN/RBV; 2% had failed prior treatment with sofosbuvir.
Mediana starosti zdravljenih preiskovalcev (N= 233) je bila 49 let (razpon: od 26 do 69); 10 % je bilo črncev, 12 % jih je imelo kompenzirano cirozo; 66 % jih še ni bilo zdravljenih; 32 % jih je doživelo neuspeh predhodnega zdravljenja s pegIFN/RBV, 2 % jih je doživelo neuspeh predhodnega zdravljenja s sofosbuvirjem.
The highest documented single dose of dasabuvir administered to healthy volunteers was 2 g. No study drug-related adverse reactions or clinically significant laboratory abnormalities were observed.
Največji dokumentirani enkratni odmerek dasabuvirja, uporabljen pri zdravih prostovoljcih, je bil 2 g.
Subjects with liver transplant and GT4 infection were dosed with ombitasvir/paritaprevir/ritonavir with RBV (noncirrhotic for 12 weeks [n=2] and cirrhotic for 24 weeks [n=1].
Preiskovanci s presajenimi jetri in GT4 okužbo so prejemali ombitasvir/paritaprevir/ritonavir z RBV (brez ciroze 12 tednov [n=2] in s cirozo 24 tednov [n=1]).
Subjects with HCV GT4 received ombitasvir/paritaprevir/ritonavir with ribavirin for 12 or 24 Weeks.
Preiskovanci s HCV GT4 so prejemali ombitasvir/paritaprevir/ritonavir z ribavirinom 12 ali 24 tednov.
Dasabuvir administered with ombitasvir/paritaprevir/ritonavir did not affect the exposures of the CYP2C9 substrate warfarin.
Zdravila, ki se presnovijo s CYP2C9 Dasabuvir, uporabljen s kombinacijo ombitasvir/paritaprevir/ritonavir, ni vplival na izpostavljenost substratu CYP2C9 varfarinu.
CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.
dezipramin, metoprolol in dekstrometorfan) ni pričakovati, da bi bila potrebna prilagoditev odmerka.
Contents of the pack and other information
Shranjevanje zdravila Exviera Vsebina pakiranja in dodatne informacije
The majority of adverse reactions presented in Table 3 were of grade 1 severity in dasabuvir- and ombitasvir/paritaprevir/ritonavir-containing regimens.
Večina neželenih učinkov, predstavljenih v preglednici 3, je bila v shemah z dasabuvirjem in kombinacijo ombitasvir/paritaprevir/ritonavir 1. stopnje glede na resnost.
*Note: Follow the genotype 1a dosing recommendations in patients with an unknown genotype 1 subtype or with mixed genotype 1 infection.
24 tednov (glejte poglavje 5.1) *Opomba: Pri bolnikih z neznano podvrsto genotipa 1 ali z mešano okužbo z genotipom 1 upoštevajte priporočila za odmerjanje pri genotipu 1a.
PEARL-IV - genotype 1a, treatment-naïve, without cirrhosis
PEARL-IV - genotip 1a, še nezdravljeni, brez ciroze
In a pooled analysis of clinical trials with dasabuvir and ombitasvir/paritaprevir/ritonavir with and without ribavirin, 1% of subjects experienced serum ALT levels greater than 5 times the upper limit of normal (ULN) after starting treatment.
V kumulativni analizi kliničnih preskušanj dasabuvirja s kombinacijo ombitasvir/paritaprevir/ritonavir z ribavirinom ali brez njega se je po začetku zdravljenja zvišanje ALT v serumu nad 5-kratno zgornjo normalno mejo (ZNM) pojavilo pri 1 % preiskovancev.
The impact of prior dasabuvir, ombitasvir, or paritaprevir treatment experience on the efficacy of other NS5A inhibitors, NS3/4A protease inhibitors, or NS5B inhibitors has not been studied.
ombitasvirjem ali paritaprevirjem na učinkovitost drugih zaviralcev NS5A, zaviralcev proteaz NS3/4A
Medicinal products metabolised by glucuronidation Dasabuvir is an inhibitor of UGT1A1 in vivo.
Dasabuvir zavira UGT1A1 in vivo.
Co-administration of dasabuvir and ombitasvir/paritaprevir/ritonavir with systemic tacrolimus, sirolimus or everolimus increases the concentrations of the immunosuppressant due to CYP3A inhibition by ritonavir (see section 4.5).
Uporaba s takrolimusom, sirolimusom in everolimusom Sočasna uporaba dasabuvirja in kombinacije obmitasvir/paritaprevir/ritonavir s sistemsko delujočimi takrolimusom, sirolimusom ali everolimusom poveča koncentracije imunosupresiva zaradi CYP3A
randomised, global multicentre, open-label
randomizirano, globalno, multicentrično, odprto
In Part 2, subjects with HCV GT1 received dasabuvir and ombitasvir/paritaprevir/ritonavir with or without ribavirin for 12 or 24 weeks.
V delu 2 so preiskovanci s HCV GT1 prejemali dasabuvir in ombitasvir/paritaprevir/ritonavir z ali brez ribavirina 12 ali 24 tednov.
Mechanism: CYP3A4/CY P2C8 induction by rifampicin.
Indukcija CYP3A4/CYP2C 8 z rifampicinom.
Tacrolimus or sirolimus whole blood concentrations should be monitored upon initiation and throughout co-administration with dasabuvir and ombitasvir/paritaprevir/ritonavir and the dose and/or dosing frequency should be adjusted as needed.
Koncentracije takrolimusa ali sirolimusa v polni krvi je potrebno spremljati na začetku in vseskozi med sočasno uporabo z dasabuvirjem in kombinacijo ombitasvir/paritaprevir/ritonavir, odmerek in/ali pogostnost odmerjanja je potrebno ustrezno prilagoditi.
Medicinal products transported by the OATP family Refer to the ombitasvir/paritaprevir/ritonavir Summary of Product Characteristics for details on OATP1B1, OATP1B3 and OATP2B1 substrates (see also Table 2).
Za podrobnosti o substratih OATP1B1, OATP1B3 in OATP2B1 glejte povzetek glavnih značilnosti zdravila za ombitasvir/paritaprevir/ritonavir (glejte tudi preglednico 2).
In Part 1b, all subjects received dasabuvir and ombitasvir/paritaprevir/ritonavir with ribavirin for 12 weeks.
V delu 1b so vsi preiskovanci prejemali dasabuvir in ombitasvir/paritaprevir/ritonavir z ribavirinom 12 tednov.
In subjects with all three favourable baseline laboratory values (AFP < 20 ng/mL, platelets ≥ 90 x 109/L, and albumin ≥ 35 g/L), relapse rates were similar in subjects treated for 12 or 24 weeks.
trombocite ≥ 90 x 109/l in albumin ≥ 35 g/l), so bili deleži recidiva podobni pri tistih, ki so bili zdravljeni 12 tednov, in pri tistih, ki so bili zdravljeni 24 tednov.
AUC Ctrough
AUC Ctrough Klinične opombe
Mechanism: CYP2C19 induction by ritonavir.
Mehanizem: Indukcija CYP2C19 z ritonavirjem.
Clinical monitoring and dose adjustment may be needed for other CYP1A2 substrates (e.g. ciprofloxacin, cyclobenzaprine, theophylline and caffeine).
CYP1A2 (npr. ciprofloksacin, ciklobenzaprin, teofilin in kofein).
↔ S
V
Design:
Oblika:
A majority (86.8%) had baseline HCV RNA levels of at least 800,000 IU/mL and a majority (84.2%) had genotype 1a infection; 15.8% had portal fibrosis (F2) and 5.3% had bridging fibrosis (F3); and 94.7% were naïve to prior HCV treatment.
800.000 i.e./ml in večina (84,2 %) je bila okužena z genotipom 1a; 15,8 % jih je imelo portalno fibrozo (F2) in 5,3 % jih je imelo fibrozo z mostiči (F3); 94,7 % jih predhodno še ni bilo zdravljenih za HCV.
400 mg twice daily
400 mg dvakrat na dan
Symptoms include: o Feel sick (nauseous), are sick (vomit) or lose your appetite o Notice yellowing of your skin or eyes o Your urine is darker than normal o Confusion o Notice swelling of your stomach area
• opazna porumenelost kože ali oči • vaš urin je temnejši od običajnega
Prior pegIFN/RBV relapser
Predhodno recidiv ob pegIFN/RBV
Peg-IFN + RBV, n (%) Baseline albumin, median g/L < 35, n (%)
Starost, mediana leta (razpon) Moški spol, n (%) Predhodno zdravljenje za HCV: nezdravljeni, n (%) Peg-IFN + RBV, n (%) Izhodiščni albumin, median g/L < 35, n (%)
Exviera 250 mg film-coated tablets dasabuvir
Exviera 250 mg filmsko obložene tablete dasabuvir
In a phase 2, multicentre, open-label, single arm study, 38 treatment-naïve or pegIFN/RBV treatment experienced, non-cirrhotic subjects with genotype 1 infection who were on stable doses of methadone (N=19) or buprenorphine with or without naloxone (N=19) received 12 weeks of dasabuvir in combination with ombitasvir/paritaprevir/ritonavir and ribavirin.
bolnikov, že zdravljenih s pegIFN/RBV, brez ciroze in okuženih z genotipom 1, ki so dobivali stabilne odmerke metadona (N = 19) ali buprenorfina, z naloksonom ali brez njega, (N = 19) 12 tednov prejemalo dasabuvir v kombinaciji z ombitasvirjem/paritaprevirjem/ritonavirjem in ribavirinom.
Methadone ↔ ombitasvir/paritaprevir and dasabuvir (based on the cross-study comparison)
NP ↔ ombitasvir /paritaprevir in dasabuvir (na podlagi primerjave med študijami)
• If you have any further questions, ask your doctor or pharmacist.
- Če imate dodatna vprašanja, se posvetujte z zdravnikom ali farmacevtom.
Tacrolimus whole blood concentrations should be monitored upon initiation and throughout coadministration with dasabuvir and ombitasvir/paritaprevir/ ritonavir and the dose and/or dosing frequency should be adjusted as needed.
Koncentracije takrolimusa v polni krvi je potrebno spremljati na začetku in vseskozi med sočasno uporabo z dasabuvirjem in kombinacijo ombitasvir/paritapre vir/ritonavir, odmerek in/ali pogostnost odmerjanja je potrebno ustrezno prilagoditi.
Ethinyloestradiol containing oral contraceptives are contraindicated (see section 4.3).
Peroralni kontraceptivi, ki vsebujejo etinilestradiol, so kontraindicirani (glejte poglavje
5 mg once daily
5 mg enkrat na dan
PARTICULARS TO APPEAR ON THE OUTER PACKAGING Outer carton of multipack containing 56 (4 packs of 14) film-coated tablets - including blue box
Zunanja škatla (večkratno pakiranje) vsebuje 56 (4 škatle po 14) filmsko obloženih tabletvključuje modro okence
The activity of dasabuvir was reduced by 5- and 11-fold by C316N and S556G, respectively; 46-fold by M414T or Y448H; and 1569-fold by the C316Y substitutions in the genotype 1b replicon.
Aktivnost dasabuvirja se je s substitucijo C316N v replikonu genotipa 1b zmanjšala za 5-krat, s S556G za 11-krat, z M414T ali Y448H za 46-krat in s C316Y za 1569-krat.
Geometric mean Cmax, AUC of multiple doses of dasabuvir 250 mg twice daily and ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg once daily with food in healthy volunteers
Preglednica 18: Geometrična sredina Cmax in AUC večkratnih odmerkov dasabuvirja 250 mg dvakrat na dan in kombinacijo ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg enkrat na dan s hrano pri zdravih prostovoljcih.
Selected treatment emergent laboratory abnormalities
Preglednica 4: Izbrane laboratorijske nepravilnosti, ki so se pojavile med zdravljenjem
In genotype 1a, substitutions C316Y, M414T, Y448H, A553T, G554S, S556G/R, and Y561H in HCV NS5B reduced susceptibility to dasabuvir.
Pri genotipu 1a so substitucije C316Y, M414T, Y448H, A553T, G554S, S556G/R in Y561H v genu
Medicines you must not take with Exviera Medicine or active substance
Zdravila, ki jih ne smete jemati z zdravili Exviera
• Anaemia (low number of red blood cells).
Pogosti: pojavijo se lahko pri največ 1 od 10 bolnikov • anemija (majhno število rdečih krvnih celic)
GARNET - Genotype 1b, Treatment-Naïve without cirrhosis.
GARNET - genotip 1b, še nezdravljeni, brez ciroze
Mechanism: Increase in paritaprevir exposures may be due to inhibition of
Večja izpostavljenost paritaprevirju je lahko posledica zavrtja
Exviera is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults (see sections 4.2, 4.4 and 5.1).
(CHC - chronic hepatitis C) pri odraslih (glejte poglavja 4.2, 4.4 in 5.1).
In the genotype 1a replicon, the activity of dasabuvir was reduced 21- to 32-fold by the M414T, S556G or Y561H substitutions; 152- to 261-fold by the A553T, G554S or S556R substitutions; and 1472- and 975-fold by the C316Y and Y448H substitutions, respectively.
S556G ali Y561H zmanjšale aktivnost dasabuvirja za 21- do 32-krat, substitucije A553T, G554S ali S556R za 152- do 261-krat in substituciji C316Y in Y448H za 1472- in 975-krat.
Treatment outcome dasabuvir and ombitasvir/paritaprevir/ritonavir with RBV for 12 weeks n/N % 95% CI
Izid zdravljenja dasabuvir in ombitasvir/paritaprevir/ritonavir z RBV 12 tednov n/N % 95 % IZ
Mechanism: possibly due to UGT1A1 inhibition by paritaprevir, ombitasvir and dasabuvir.
Morda zavrtje UGT1A1 s paritaprevirjem, ombitasvirjem in dasabuvirjem.
Mechanism: OATP1B inhibition by paritaprevir.
Zavrtje OATP1B s paritaprevirjem.
Table 2 provides the Least Squares Means Ratio (90% Confidence Interval) effect on concentration of dasabuvir and ombitasvir/paritaprevir/ritonavir and concomitant medicinal products.
Preglednica 2 prikazuje vpliv na koncentracije dasabuvirja in kombinacije ombitasvir/paritaprevir/ritonavir ter sočasno uporabljanih zdravil z razmerjem povprečij po metodi najmanjših kvadratov (90 % interval zaupanja).
Very common
Zelo pogosti pruritus
CONTRACEPTIVES ethinyloestra diol/ norgestimate 0.035/0.25 m g once daily
0,035/0,25 mg enkrat na dan
9% had advanced fibrosis (F3) and 98.2% had HCV genotype 1b infection (one subject each had genotype 1a, 1d, and 6 infection).
RNA vsaj 6.000.000 i.e./ml; 9 % jih je imelo napredujočo fibrozo (F3) in 98,2 % jih je imelo okužbo s HCV genotipa 1b (en preiskovanec je imel okužbo genotipa 1a, eden genotipa 1d in eden genotipa 6).
Table 2.
(preglednica 2).
In Part 1a, all subjects received dasabuvir and ombitasvir/paritaprevir/ritonavir with ribavirin for 12 or 24 weeks.
V delu 1a so vsi preiskovanci prejemali dasabuvir in ombitasvir/paritaprevir/ritonavir z ribavirinom 12 ali 24 tednov.
Treatment-naïve and peginterferon+ribavirin-experienced, with compensated cirrhosis
Še nezdravljeni in že zdravljeni s peginteferonom+ribavirinom, s kompenzirano cirozo
400 mg once daily
400 mg enkrat na dan
Alprazolam 0.5 mg single dose
Alprazolam Posamezen odmerek 0,5 mg
Pharmacokinetics of the combination of ombitasvir 25 mg, paritaprevir 150 mg, and ritonavir 100 mg, with dasabuvir 400 mg were evaluated in subjects with mild (CrCl: 60 to 89 ml/min), moderate (CrCl: 30 to 59 ml/min) and severe (CrCl: 15 to 29 ml/min) renal impairment, relative to subjects with normal renal function.
400 mg dasabuvirja) so ocenili pri preiskovancih z blago (očistek kreatinina od 60 do 89 ml/min), zmerno (očistek kreatinina od 30 do 59 ml/min) in hudo (očistek kreatinina od 15 do 29 ml/min)
Treated subjects (N = 22) had a median age of 54 years (range: 34 to 68); 41% were Black; 14% had compensated cirrhosis; 86% were HCV treatment-naïve; 14% had failed prior treatment with pegIFN/RBV; 68% had HCV genotype 1a infection.
Mediana starosti zdravljenih preiskovancev (N = 22) je bila 54 let(razpon: od 34 do 68); 41 % je bilo črncev; 14 % jih je imelo kompenzirano cirozo; 86 % jih še ni bilo zdravljenih; 14 % jih je doživelo neuspeh predhodnega zdravljenja s pegIFN/RBV; 68 % jih je imelo okužbo HCV genotipa 1a.
Treated subjects (N = 63) had a median age of 51 years (range: 31 to 69); 24% were Black; 19% had compensated cirrhosis; 67% were treatment-naïve; 33% had failed prior treatment with pegIFN/RBV; 89% had HCV genotype 1a infection.
Mediana starost zdravljenih preiskovancev (N = 63) je bila 51 let (razpon: od 31 do 69); 24 % je bilo črncev, 19 % jih je imelo kompenzirano cirozo, 67 % jih še ni bilo zdravljenih, 33 % jih je doživelo neuspeh predhodnega zdravljenja pegIFN/RBV, 89 % jih je imelo okužbo s HCV genotipa 1a.
Pharmacodynamic interactions
Farmakodinamično medsebojno delovanje
SVR12 for genotype 1-infected peginterferon+ribavirin-experienced subjects in SAPPHIRE-II
Preglednica 11: SVR12 pri preiskovancih, ki so bili že zdravljeni s peginterferonom+ribavirinom, okuženih z genotipom 1, v preskušanju SAPPHIRE-II
No dose adjustment of dasabuvir is warranted in elderly patients (see section 5.2).
Starejši bolniki Starejšim bolnikom odmerkov dasabuvirja ni treba prilagoditi (glejte poglavje 5.2).
Co-administration of dasabuvir with ombitasvir/paritaprevir/ritonavir combines three direct-acting antiviral medicinal products with distinct mechanisms of action and non-overlapping resistance profiles to target HCV at multiple steps in the viral lifecycle.
Sočasna uporaba dasabuvirja s kombinacijo ombitasvir/paritaprevir/ritonavir združuje tri direktno delujoča protivirusna zdravila z različnimi mehanizmi delovanja.
Hepatic decompensation and hepatic failure, including liver transplantation or fatal outcomes, have been reported post-marketing in patients treated with dasabuvir with ombitasvir/paritaprevir/ritonavir with and without ribavirin.
Tveganje za dekompenzacijo jeter in okvaro jeter pri bolnikih s cirozo Pri bolnikih, ki so jih zdravili z dasabuvirjem z ombitasvirjem/paritaprevirjem/ritonavirjem z ali brez ribavarina so po prihodu zdravila na trg poročali o dekompenzaciji jeter in okvari jeter, vključno s presaditvijo jeter ali smrtnimi izidi.
40 mg once daily
40 mg enkrat na dan
Side effects when taking Exviera and ombitasvir/paritaprevir/ritonavir with ribavirin:
Neželeni učinki pri jemanju zdravila Exviera in kombinacije ombitasvir/paritaprevir/ritonavir z ribavirinom:
Expected: ↓ S-mephenytoin
↓ s-mefenitoin
GT1-infected subjects with or without cirrhosis with severe renal impairment or end-stage renal disease (ESRD)
Preiskovanci, okuženi z genotipom GT1, z ali brez ciroze s hudo okvaro ledvic ali končno ledvično odpovedjo
Immune system disorders Frequency unknown
Bolezni imunskega sistema Neznana pogostnost anafilaktične reakcije anafilaktične reakcije
SVR12 for genotype 1b-infected peginterferon+ribavirin-experienced subjects in PEARL II
Preglednica 12: SVR12 pri preiskovancih, ki so bili že zdravljeni s peginterferonom+ribavirinom, okuženih z genotipom 1b, v preskušanju PEARL II
Tacrolimus 2 mg was dosed alone and 2 mg was administered with dasabuvir + ombitasvir/paritaprevir/ritonavir.
Takrolimus 2 mg je bil uporabljen sam in 2 mg skupaj z dasabuvirjem + kombinacijo ombitasvir/paritaprevir/ritonavir.
SAPPHIRE-I - genotype 1, treatment-naïve, without cirrhosis
SAPPHIRE-I - genotip 1, še nezdravljeni, brez ciroze Oblika:
Carisoprodol
↓ karisoprodol
Coadministration with enzyme inducers may lead to an increased risk of adverse reactions and ALT elevations (see Table 2).
Sočasna uporaba z induktorji encimov lahko zveča tveganje za neželene učinke in zvišanje ALT
NARCOTIC ANALGESICS Paracetamol (given as fixed dose hydrocodone /paracetamol dasabu vir +
Paracetamol (kot fiksni odmerek kombinacije hidrokodon/parac etamol)
Endpoint dasabuvir and ombitasvir/paritaprevir/ritonavir with or without ribavirin for 12 or 24 Weeks N = 200a
Opazovani dogodek dasabuvir in ombitasvir/paritaprevir/ritonavir z ali brez ribavirina, 12 ali 24 tednov N = 200a
Clinical monitoring and dose adjustment maybe needed for smephenytoin.
Morda bo potrebno klinično spremljanje in prilagoditev odmerka za druge substrate
GIVE N WITH
UPORAB LJENO Z
50 mg once daily
50 mg enkrat na dan
In all eight trials, the dasabuvir dose was 250 mg twice daily and the ombitasvir/paritaprevir/ritonavir dose was 25 mg/150 mg/100 mg once daily.
V vseh osmih preskušanjih je bil odmerek dasabuvirja 250 mg dvakrat na dan in odmerek kombinacije ombitasvir/paritaprevir/ritonavir 25/150/100 mg enkrat na dan. Preiskovanci, ki so dobivali ribavirin,
L31F/V or Y93H in combination with L28M, L31F/V or P58S in genotype 1b; and NS5B variants Y448H in genotype 1a, and M414T and Y448H in genotype 1b.
varianta gena NS3A156T v genotipu 1a ter R155Q in D168H v genotipu 1b; varianta gena NS5A Y93C/H v genotipu 1a in L31F/V ali Y93H v kombinaciji z L28M, L31F/V ali P58S v genotipu 1b; in Y448H NS5B v genotipu 1a in M414T in Y448H v genotipu 1b.
Enzalutamid e
PRILOGA I
Dasabuvir does not inhibit organic anion transporter (OAT1) in vivo and is not expected to inhibit organic cation transporters (OCT2), organic anion transporters (OAT3), or multidrug and toxin extrusion proteins (MATE1 and MATE2K) at clinically relevant concentrations; therefore, dasabuvir does not affect medicinal product transport by these proteins.
(OCT2 - organic cation transporters), prenašalce organskih anionov (OAT3) ali ekstruzijskih beljakovin več zdravil in toksinov (MATE1 in MATE2K - multidrug and toxin extrusion proteins).
Treated subjects (N=419) had a median age of 50 years (range: 19 to 70); 45.8% were male; 4.8% were Black; 9.3% had a history of depression or bipolar disorder; 73.3% had baseline HCV RNA of at least 800,000 IU/mL; 20.3% had portal fibrosis (F2) and 10.0% had bridging fibrosis (F3).
Zdravljeni preiskovanci (N = 419) so bili mediano stari 50 let (razpon: od 19 do 70); 45,8 % je bilo moških; 4,8 % je bilo črncev; 9,3 % jih je imelo v anamnezi depresijo ali bipolarno motnjo; 73,3 % jih je imelo izhodiščno koncentracijo HCV RNA vsaj 800.000 i. e./ml; 20,3 % jih je imelo portalno fibrozo (F2) in 10,0 % jih je imelo fibrozo z mostiči (F3).
PEARL-III - genotype 1b, treatment-naïve, without cirrhosis Design:
PEARL-III - genotip 1b, še nezdravljeni, brez ciroze Oblika:
PEARL-II - genotype 1b, pegIFN+RBV-experienced, without cirrhosis Design:
PEARL-II - genotip 1b, že zdravljeni s pegIFN + RBV, brez ciroze
Of the 2,510 HCV genotype 1 infected subjects who were treated with regimens containing dasabuvir, ombitasvir and paritaprevir with or without ribavirin (for 8, 12 or 24 weeks) in Phase 2b and 3 clinical trials, a total of 74 subjects (3%) experienced virologic failure (primarily post-treatment relapse).
pojavila pri skupno 74 od 2.510 preiskovancev (3 %), okuženih s HCV genotipa 1 in zdravljenih s shemami, ki so vsebovale dasabuvir, ombitasvir in paritaprevir z ribavirinom ali brez njega (v obdobju 8, 12 ali 24 tednov).
TURQUOISE-III: treatment-naïve or pegIFN + RBV-experienced with compensated cirrhosis
TURQUOISE-III - še nezdravljeni ali že zdravljeni s pegIFN + RBV, s kompenzirano cirozo Oblika:
S-warfarin dasabuvir ombitasvir paritaprevir
S-varfarin dasabuvir ombitasvir
Mechanism: CYP3A4 induction by phenytoin.
Mehanizem: Indukcija CYP3A4 s fenitoinom.
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS BLISTER FOIL
PODATKI, KI MORAJO BITI NAJMANJ NAVEDENI NA PRETISNEM OMOTU ALI DVOJNEM TRAKU