qanastek/EMEA-V3 huggingface dataset:
Limited safety data (N = 25) are available in co-infected patients with CD4+ cell counts < 200/ µl (see section 4.4).
Hemm tagħrif limitat (N = 25) dwar is- sigurtà f’ pazjenti li jkollhom infezzjoni fl- istess ħin b’ għadd ta ’ ċelluli CD4+ < 200/ µl (ara sezzjoni 4. 4).
Please refer to the respective Summary of Product Characteristics of the antiretroviral medicinal products that are to be taken concurrently with HCV therapy for awareness and management of toxicities specific for each product and the potential for overlapping toxicities with Ribavirin in combination with peginterferon alfa-2b.
14 tossiċitajiet speċifiċi għal kull prodott u l- potenzjal ta ’ tossiċitajiet f’ daqqa b’ Ribavirin f’ kombinazzjoni ma ’ peginterferon alfa- 2b.
In clinical trials of 118 children or adolescents 3 to 16 years of age, 6% discontinued therapy due to adverse events.
Fi provi kliniċi fuq 118- il tifel u tifla jew adoloxxent bejn l- etajiet ta ’ 3 snin sa 16- il sena, 6% waqqfu t- terapija minħabba reazzjonijiet avversi.
In general, the adverse event profile in the limited paediatric population studied was similar to that observed in adults, although there is a paediatric-specific concern regarding growth inhibition, as decrease in height (mean percentile decrease of growth velocity of 9%) and weight (mean percentile decrease of 13%) percentile were observed during treatment (see section 4.4).
B’ mod ġenerali, il- profil ta ’ effetti avversi fil- popolazzjoni pedjatrika limitata li kienet studjata kien simili għal dak osservat fl- adulti, għalkemm l- impediment ta ’ żvilupp huwa ta ’ tħassib speċifiku għall- popolazzjoni pedjatrika, peress li tnaqqis perċentwali fit- tul (tnaqqis perċentwali medju tar- rata tat- tkabbir ta ’ 9%) u fil- piż (tnaqqis perċentwali medju ta ’ 13%) kienu osservati waqt it- trattament (ara sezzjoni 4. 4).
Furthermore, suicidal ideation or attempts were reported more frequently compared to adult patients (2.4% vs 1%) during treatment and during the 6 month follow-up after treatment.
Barra minn hekk, ħsibijiet jew tentattivi ta ’ suwiċidju kienu rapportati b’ mod aktar ta ’ spiss meta mqabbla mal- popolazzjoni adulta (2. 4% vs 1%) waqt it- trattament u fis- 6 xhur wara t- trattament.
In addition, injection site disorders, fever,
Bħal fil- każ ta ’ pazjenti adulti, tfal u adoloxxenti kellhom ukoll effetti psikjatriċi avversi oħra (eż., dipressjoni, burdati emozzjonali, u ngħas) (ara sezzjoni 4. 4).
14 anorexia, vomiting, and emotional lability occurred more frequently in children and adolescents compared to adult patients.
Barra minn hekk, disturbi mnejn ingħatat l- injezzjoni, deni, anoreksja, remettar, u burdati emozzjonali b’ mod aktar frekwenti fit- tfal u l- adoloxxenti meta mqabbla mal - pazjenti adulti.
Dose modifications were required in 30% of patients, most commonly for anaemia and neutropaenia.
30% tal- pazjenti kellhom bżonn tibdil fid- doża, l- aktar minħabba anemija u newtropenja.
Reported adverse reactions listed in Table 5 are based on experience from paediatric clinical trials.
Reazzjonijiet mhux mixtieqa elenkati rapportati fi provi kliniċi pedjatriċi, u li ma ġewx irrapportati qabel b’ inċidenza ta ’ ≥ 1% f’ adulti huma murija f’ Tabella 5a.
Within the organ system classes, adverse reactions are listed under headings of frequency using the following categories: very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10).
L- effetti kollha rrapportati b’ inċidenza ta ’ ≥ 10% fi provi pedjatriċi li kienu rrapportati qabel fl- adulti (Tabella 5) m’ humiex ripetuti fit - tabella pedjatrika.
ribavirin with interferon alfa-2b injection in paediatric patients
Tabella 5 Effetti mhux mixtieqa fi provi kliniċi pedjatriċi (≥ 1% ta ’ pazjenti trattati b’ Ribavirin + injezzjoni ta ’ interferon alfa- 2b)
System Organ Class
Klassifika tas- Sistema tal- Organi
Viral infection, pharyngitis Fungal infection, bacterial infection, pulmonary infection, otitis media, tooth abscess, herpes simplex, urinary tract infection, vaginitis, gastroenteritis
Infezzjoni virali, farinġite Infezzjoni tal- fungu, infezzjoni batterika, infezzjoni pulmonari, otitis media, tnawwir ta ’ snien, herpes simplex, infezzjoni tal- passaġġ awrinarju, vaginite, gastroenterite
Neoplasms benign, malignant and unspecified (including cysts and polyps) Common:
Neoplażmi beninni, malinni u mhux speċifikati (li jinkludu ċisti u polipi) Komuni:
Anaemia, neutropenia Thrombocytopenia, lymphadenopathy
Anemija, newtropenija Thromboċitopenija, limfadenopatija
Psychiatric disorders
Disturbi psikjareiċi
Anorexia Hypertriglyceridemia, hyperuricemia, increased appetite
Anoreksja Ipertrigliċeridemja, iperurikemija, żieda fl- aptit
Depression, insomnia, emotional lability Suicidal ideation, aggressive reaction, confusion, behaviour disorder, agitation, somnambulism, anxiety, nervousness, sleep disorder, abnormal dreaming, apathy
Dipressjoni, nuqqas ta ’ rqad, burdati emozzjonali Ħsibijiet suwiċidali, reazzjoni aggressiva, konfużjoni, disturbi ta ’ mġieba, agitazzjoni, ħmar il- lejl, ansjetà, nervożità, disturbi fl- irqad, ħolm mhux normali, apatija
Headache, dizziness Hyperkinesia, tremor, dysphonia, paresthaesia, hypoaesthesia, hyperaesthesia, concentration impaired, somnolence
Uġigħ ta ’ ras, sturdament Iperkinesja, disfonja, tregħid, paresteżija, iperestesija, ipoestesija, tiddgħajjef il- konċentrazzjoni, ngħas
Conjunctivitis, eye pain, abnormal vision, lacrimal gland disorder
15
Raynaud’ s disease, flushing, pallor
Il- marda ta ’ Raynaud, fwawar, sfurija
Dyspnoea, tachypnea, epistaxis, coughing, nasal congestion, nasal irritation, rhinorrhea, sneezing
Dispnea, takipnea, epistassi, sogħla, konġestjoni nasali, irritazzjoni nasali, rinorrea, għatis
Diarrhoea, vomiting, nausea, abdominal pain Mouth ulceration, stomatitis ulcerative, stomatitis, right upper quadrant pain, dyspepsia, glossitis, gastroesophogeal reflux, rectal disorder, gastrointestinal disorder, constipation, loose stools, toothache, tooth disorder
Dijarea, remettar, tqalligħ, uġigħ addominali Ulċeri fil- ħalq, stomatite ulcerativa, stomatite, uġigħ fil- kwadrant lemini ta ’ fuq, dispepsja, glossite, rifluss gastroesofogeali, disturbi fir- rektum, disturbi gastrointestinali, stitikezza, ippurhar merħi, uġigħ fis- snien, disturbi fis- snien
Very common:
Disturbi fil- ġilda u fit- tessut ta ’ taħt il- ġilda Komuni ħafna:
Alopecia, rash Photosensitivity reaction, maculopapular rash, eczema, acne, skin disorder, nail disorder, skin discolouration, pruritus, dry skin, erythema, bruise, sweating increased
Alopeċja, raxx Reazzjoni ta ’ fotosensittività, raxx makulopapulari, ekżema, akni, disturbi tal- ġilda, disturbi tad- dwiefer, tibdil fil- kulur tal- ġilda, ħakk, ġilda xotta, eritema, tbenġil, żieda fl- għaraq
Renal and urinary disorders
Disturbi fil- kliewi u fis- sistema awrinarja
Arthralgia, myalgia, musculoskeletal pain
Artralġja, uġigħ fil- muskoli, uġigħ muskoluskeletriku
Reproductive system and breast disorders
Disturbi fis- sistema riproduttiva u tas- sider
Enuresis, micturition disorder, urinary incontinence
Enuresi, disturbi biex tgħaddi l- awrina, inkontinenza fl - awrina
Female: amenorrhea, menorrhagia, menstrual disorder, vaginal disorder, Male: testicular pain
Nisa: amenorrea, menorraġja, disturbi menstruwali, disturbi vaġinali Irġiel: uġigħ testikulari
General disorders and administration site Very common:
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Komuni ħafna:
conditions Injection site inflammation, injection site reaction, fatigue, rigors, fever, influenza-like symptoms, malaise, irritability
Infjammazzjoni fis- sit tal- injezzjoni, reazzjoni fi- sit tal - injezzjoni, għeja, tertir, deni, sintomi bħal tal- influwenza, tħossok ma tiflaħx, irritabilità
Chest pain, asthenia, oedema, injection site pain
Uġigħ fis- sider, astenja, edema, uġigħ fis- sit tal- injezzjoni
Growth rate decrease (height and/ or weight decrease for age)
Tnaqqis fir- rata tat- tkabbir (tnaqqis fit- tul u/ jew piż għall- età),
Skin laceration
Qtugħ tal- ġilda
In clinical trials with Ribavirin used in combination with peginterferon alfa-2b or interferon alfa-2b, the maximum overdose reported was a total dose of 10 g of Ribavirin (50 x 200 mg capsules) and 39 MIU of interferon alfa-2b (13 subcutaneous injections of 3 MIU each) taken in one day by a patient in an attempt at suicide.
Fi studji kliniċi b’ Ribavirin li intuża flimkien ma ’ peginterferon alfa- 2b jew interferon alfa- 2b, id- doża eċċessiva massima rrappurtata kienet doża totali ta ’ 10 g ta ’ Ribavirin (50 kapsula x 200 mg) u 39 MIU ta ’ interferon alfa- 2b (13 injezzjonijiet taħt il- ġilda ta ’ 3 MIU each) meħuda f’ ġurnata waħda minn pazjent f’ tentattiv ta ’ suwiċidju.
The patient was observed for two days in the emergency room, during which time no adverse event from the overdose was noted.
Il- pazjent kien osservat għal jumejn fil- kamra tal- emerġenza, u matul dak iż- żmien l- ebda reazzjoni avversa mid- doża eċċessiva ma kien innutat.
Direct acting antivirals, nucleosides and nucleotides (excl. reverse transcriptase inhibitors), ATC code:
Antivirali li jaġixxu direttament, nukleosidi u nukleotidi (li jeskludu. reverse transcriptase inhibitors), Kodiċi ATC:
Ribavirin is a synthetic nucleoside analogue which has shown in vitro activity against some RNA and DNA viruses.
16 Ribavirin huwa analogu sintetiku ta ’ nucleosajd li wera attività in vitro kontra xi RNA u DNA tal- virusis.
The mechanism by which ribavirin in combination with peginterferon alfa-2b or interferon alfa-2b exerts its effects against HCV is unknown.
Il- mekkaniżmu li bih Ribavirin flimkien ma ’ peginterferon alfa- 2b jew interferon alfa- 2b jeżerċita l- effetti tiegħu kontra HCV mhux magħruf.
Oral formulations of Ribavirin monotherapy have been investigated as therapy for chronic hepatitis C in several clinical trials.
Formulazzjonijiet orali tal- monoterapija ta ’ Ribavirin kienu mistħarrġa bħala terapija għal epatite Ċ kronika f’ diversi provi kliniċi.
Results of these investigations showed that Ribavirin monotherapy had no effect on eliminating hepatitis virus (HCV-RNA) or improving hepatic histology after six to 12 months of therapy and six months of follow-up.
Ir- riżultati ta ’ dan l- istħarriġ wera li l- monoterapija b’ Ribavirin ma kellha l- ebda effett fuq l- eliminazzjoni tal- virus tal- epatite (HCV- RNA) jew fit- titjib tal- istoloġija epatika wara sitta sa 12- il xahar ta ’ terapija u sitt xhur ta ’ follow- up.
Ribavirin clinical trials in adults The use of Ribavirin in combination treatment with peginterferon alfa-2b or interferon alfa-2b was evaluated in a number of clinical trials.
L- użu ta ’ Ribavirin fit- trattament ta ’ kombinazzjoni ma ’ peginterferon alfa- 2b jew interferon alfa- 2b kien evalwat f’ għadd ta ’ studji kliniċi.
Eligible patients for these trials had chronic hepatitis C confirmed by a positive HCV-RNA polymerase chain reaction assay (PCR) (> 30 IU/ ml), a liver biopsy consistent with a histological diagnosis of chronic hepatitis with no other cause for the chronic hepatitis, and abnormal serum ALT.
Pazjenti eliġibbli għal dawn l- istudji kellhom epatite kronika Ċ ikkonfermata mill- assaġġ pożittiv permezz tal - polymerase chain reaction (PCR) (> 30 IU/ ml) għal HCV- RNA, bijopsija tal- fwied konsistenti ma dijanjosi istoloġika ta ’ epatite kronika mingħajr l- ebda kawża oħra għall- epatite kronika u kwantitajiet anormali ta ’ ALT fis- serum.
Naïve patients Three trials examined the use of interferon in naïve patients, two with Ribavirin + interferon alfa-2b (C95-132 and I95-143) and one with Ribavirin + peginterferon alfa-2b (C/ I98-580).
Pazjenti inkonsapevoli Tliet provi eżaminaw l- użu ta ’ interferon f’ pazjenti inkonsapevoli, tnejn b’ Ribavirin + interferon alfa - 2b (C95- 132 u I95- 143) u wieħed b’ Ribavirin + peginterferon alfa- 2b (C/ I98- 580).
The sustained response at the end of
Fil- każijiet kollha, it- trattament kien għal sena b’ follow- up ta ’ sitt xhur.
16 follow-up was significantly increased by the addition of Ribavirin to interferon alfa-2b (41% vs 16%, p < 0.001).
Ir- rispons sostnut fit- tmiem il- follow- up żdied b’ mod sinifikanti fiż- żieda ta ’ Ribavirin ma ’ interferon alfa- 2b (41% vs 16%, p < 0. 001).
In clinical trials C95-132 and I95-143, Ribavirin + interferon alfa-2b combination therapy proved to be significantly more effective than interferon alfa-2b monotherapy (a doubling in sustained response).
Fil- provi kliniċi C95- 132 u I95- 143, it- terapija bil- kombinazzjoni Ribavirin + interferon alfa- 2b intweriet li kienet aktar effettiva mill- monoterapija b’ interferon alfa- 2b (irdoppjar fir- rispons sostnut).
Combination therapy also decreased the relapse rate.
It- terapija kombinata naqqset ukoll ir- rata tan- numru ta ’ pazjenti li rkadew.
This was true for all HCV genotypes, particularly Genotype 1, in which the relapse rate was reduced by 30% compared with interferon alfa-2b monotherapy.
Dan kien jgħodd għall- ġenotipi kollha ta ’ HCV, b’ mod partikulari Ġenotip 1, li fih ir- rata ta ’ pazjenti li rkadew naqqset bi 30% meta mqabbla mal- monoterapija ta ’ interferon alfa- 2b.
In clinical trial C/ I98-580, 1,530 naïve patients were treated for one year with one of the following combination regimens: • Ribavirin (800 mg/ day) + peginterferon alfa-2b (1.5 micrograms/ kg/ week) (n = 511). • Ribavirin (1,000/ 1,200 mg/ day) + peginterferon alfa-2b (1.5 micrograms/ kg/ week for one month followed by 0.5 microgram/ kg/ week for 11 months) (n = 514). • Ribavirin (1,000/ 1,200 mg/ day) + interferon alfa-2b (3 MIU three times a week) (n = 505).
Fil- prova klinika C/ I98- 580, 1, 530 pazjent inkonsapevoli kien ittrattat għal sena waħda b’ wieħed minn dawn il- programmi ta ’ kombinazzjoni li ġejjin: • Ribavirin (800 mg/ jum) + peginterferon alfa- 2b (1. mikrogrammi/ kg/ ġimgħa) (n = 511). • Ribavirin (1, 000/ 1, mg/ jum) + peginterferon alfa- 2b (1. 5 mikrogrammi/ kg/ ġimgħa għal xahar segwita b’ 0. 5 mikrogrammi/ kg/ ġimgħa għal 11- il xahar) (n = 514). • Ribavirin (1, 000/ 1, 200 mg/ jum) + interferon alfa- 2b (3 MIU tliet darbiet fil- ġimgħa) (n = 505).
In this trial, the combination of Ribavirin and peginterferon alfa-2b (1.5 micrograms/ kg/ week) was significantly more effective than the combination of Ribavirin and interferon alfa-2b, particularly in patients infected with Genotype 1.
F’ din il- prova, il- kombinazzjoni ta ’ Ribavirin ma ’ peginterferon alfa- 2b (1. 5 mikrogrammi/ kg/ ġimgħa) kienet aktar effettiva b’ mod sinifikanti mill- kombinazzjoni ta ’ Ribavirin u interferon alfa- 2b, b’ mod partikolari f’ pazjenti infettati bil- Ġenotip 1.
Sustained response was assessed by the response rate six months after the cessation of treatment.
Rispons sostnut kien stmat mir- rata ta ’ rispons sitt xhur wara l- waqfien mit- trattament.
HCV genotype and baseline virus load are prognostic factors which are known to affect response rates.
Il- ġenotip tal- HCV u l- valuri bażi tal- viral load huma fatturi ta ’ tbassir li huma magħrufa li jaffettwaw ir- rati ta ’ rispons.
However, response rates in this trial were shown to be dependent also on the dose of Ribavirin administered in combination with peginterferon alfa-2b or interferon alfa-2b.
Madankollu, ir- rati ta ’ rispons f’ din il- prova kienu murija li kienu dipendenti wkoll fuq id- doża ta ’ Ribavirin mogħtija flimkien ma ’ peginterferon alfa- 2b jew interferon alfa- 2b.
In those patients that received > 10.6 mg/ kg Ribavirin (800 mg dose in typical 75 kg patient), regardless of genotype or viral load, response rates were significantly higher than in those patients that received ≤ 10.6 mg/ kg Ribavirin (Table 6), while response rates in patients that received > 13.2 mg/ kg Ribavirin were even higher.
F’ dawk il- pazjenti li rċevew > 10. 6 mg/ kg Ribavirin (doża ta ’ 800 mg f’ pazjent tipiku ta ’ 75 kg), hu x’ inhu l- ġenotip jew il- viral load, ir- rati ta ’ rispons kienu ogħla b’ mod sinifikanti f’ dawk il- pazjenti li rċevew ≤ 10. 6 mg/ kg Ribavirin (Tabella 6), filwaqt li r- rati ta ’ rispons f’ pazjenti li rċevew > 13. 2 mg/ kg Ribavirin kienu filfatt ogħla.
Sustained response rates with Ribavirin + peginterferon alfa-2b (by Ribavirin dose [mg/ kg], genotype and viral load)
Rati ta ’ rispons sostnut b’ Ribavirin + peginterferon alfa- 2b (skont id- doża ta ’ Ribavirin [mg/ kg], il- ġenotip u l- viral load)
Ribavirin dose (mg/ kg)
Doża ta ’ P 1. 5/ R P 0. 5/ R Ribavirin (mg/ kg)
All Genotypes All
Il- Ġenotipi kollha
≤ 10.6 > 10.6
Kollha ≤ 10. 6 > 10. 6
Genotype 1 Genotype 1 ≤ 600,000
Ġenotip 1
≤ >
Kollha ≤ 10. 6 > 10. 6
IU/ ml Genotype 1 > 600,000
Ġenotip 1 ≤ 600, 000 IU/ ml
IU/ ml Genotype 2/ 3
Ġenotip 2/ 3
≤ > ≤ >
Kollha ≤ 10. 6 > 10. 6
Ribavirin (800 mg) + peginterferon alfa-2b (1.5 micrograms/ kg) Ribavirin (1,000/ 1,200 mg) + peginterferon alfa-2b (1.5 to 0.5 microgram/ kg) Ribavirin (1,000/ 1,200 mg) + interferon alfa-2b (3 MIU)
Ribavirin (800 mg) + peginterferon alfa- 2b (1. 5 mikrogrammi/ kg) Ribavirin (1, 000/ 1, 200 mg) + peginterferon alfa- 2b (1. 5 sa 0. 5 mikrogrammi/ kg) Ribavirin (1, 000/ 1, 200 mg) + interferon alfa- 2b (3 MIU)
In a separate trial, 224 patients with genotype 2 or 3 received peginterferon alfa-2b, 1.5 microgram/ kg subcutaneously, once weekly, in combination with ribavirin 800 mg – 1,400 mg p. o. for 6 months
Fi prova separata, 224 pazjent b’ ġenotip 2 jew 3 rċevew peginterferon alfa- 2b, 1. 5 mikrogrammi/ kg taħt il- ġilda, darba fil- ġimgħa, flimkien ma ’ ribavirin 800 mg – 1, 400 mg p. o. għal 6 xhur (bażat skont il- piż tal- ġisem, bi tliet pazjenti biss jiżnu aktar minn > 105 kg, li rċevew id- doża ta ’ 1, 400 mg) (Tabella 7).
Twenty-four% had bridging fibrosis or cirrhosis (Knodell 3/ 4).
Erbgħa u għoxrin% kellhom fibrożi li tibbriġġja jew ċirrosi (Knodell 3/ 4).
Virologic Response at End of Treatment, Sustained Virologic Response and Relapse by HCV Genotype and Viral Load* Ribavirin 800-1,400 mg/ day Plus peginterferon alfa-2b 1.5 µg/ kg Once Weekly
Rispons Viroloġiku fl- Aħħar tat- Trattament, Rispons Viroloġiku Sostnut u dawk li Rkadew b’ Ġenotip HCV u Viral Load * Ribavirin 800- 1, 400 mg/ jum ma ’ peginterferon alfa- 2b 1. 5 µg/ kg Darba fil- Ġimgħa
End of Treatment Response
Rispons fi Tmiem it- Trattament
Relapse
Rkadar
All Subjects
L- Individwi Kollha
HCV 2 ≤ 600,000 IU/ ml
HCV 2 ≤ 600, 000 IU/ ml
> 600,000 IU/ mL
> 600, 000 IU/ mL
HCV 3 ≤ 600,000 IU/ ml
HCV 3 ≤ 600, 000 IU/ ml
* Any subject with an undetectable HCV-RNA level at the Follow-Up Week 12 visit and missing data at the Follow-Up Week 24 visit was considered a sustained responder.
* Kull individwu li kellu livelli ta ’ HCV- RNA li ma setgħux jitkejlu fiż- żjara ta ’ 12- il Ġimgħa ta ’ Follow- Up u tagħrif nieqes miż- żjara tal- 24 Ġimgħa kien meqjus bħala risponditur sostnut.
Any subject with missing data in and after the Follow-Up Week 12 window was considered to be a non-responder at Week 24 of follow-up.
Kull individwu li kellu tagħrif nieqes fi u wara l- perijodu ta ’ 12- il Ġimgħa ta ’ Follow- Up kien meqjus li ma wriex rispons fl- 24 Ġimgħa ta ’ follow- up.
14%, for dose modification 18% vs.
Is- 6 xhur ta ’ trattament ta ’ din il- prova kienu tollerati aħjar mill- prova ewlenija bil- kombinazzjoni; għal twaqqif 5% vs.%, għal tibdil fid- doża 18% vs.
In a non-comparative trial, 235 patients with genotype 1 and low viral load (< 600,000 IU/ ml) received peginterferon alfa-2b, 1.5 microgram/ kg subcutaneously, once weekly, in combination with weight adjusted Ribavirin.
Fi prova mhix komparattiva, 235 pazjent b’ ġenotip 1 u viral load baxx (< 600, 000 IU/ ml) irċevew peginterferon alfa- 2b, 1. 5 mikrogramm/ kg taħt il- ġilda, darba fil- ġimgħa, flimkien ma ’ Ribavirin aġġustat skont il- piż.
The overall sustained response rate after a 24-week treatment duration was 50%.
Ir- rata globali tar- rispons sostnut wara trattament fuq 24 ġimgħa kienet ta ’ 50%.
Forty-one percent of subjects (97/ 235) had nondetectable plasma HCV-RNA levels at Week 4 and Week 24 of therapy.
Wieħed u erbgħin fil- mija ta ’ individwi (97/ 235) kellhom livelli ta ’ HCV- RNA fil- plażma li ma setgħux jiġu mkejla mar- 4 Ġimgħa u mal- 24 Ġimgħa ta ’ terapija.
In this subgroup, there was a 92% (89/ 97) sustained virological response rate.
F’ dan is- sottogrupp, kien hemm 92% (89/ 97) li kellhom rata ta ’ rispons viroloġiku sostnut.
The high sustained response rate in this subgroup of patients was identified in an interim analysis (n=49) and prospectively confirmed (n=48).
18 pazjenti ġiet identifikata f’ analiżi li saret waqt li kien għaddej l- istudju (n=49) u kkonfermata b’ mod prospettiv (n=48).
Limited historical data indicate that treatment for 48 weeks might be associated with a higher sustained response rate (11/ 11) and with a lower risk of relapse (0/ 11 as compared to 7/ 96 following 24 weeks of treatment).
Tagħrif storiku limitat jindika li t- trattament għal 48 ġimgħa jista ’ jkun marbut ma ’ rata ogħla ta ’ rispons sostnut (11/ 11) u ma ’ rata aktar baxxa b’ riskju li jirkadu (0/ 11 meta mqabbel ma ’ 7/ 96 fl- 24 ġimgħa ta ’ trattament).
Predictability of sustained virological response in naïve patients Virological response by week 12, defined as a 2-log viral load decrease or undetectable levels of HCV RNA has been shown to be predictive for sustained response (Table 8).
Tbassir għar- rispons viroloġiku sostnut f’ pazjenti inkonsapevoli Ir- rispons viroloġiku sostnut mat- 12- il ġimgħa, mfisser bħala tnaqqis ta ’ 2- log tal- viral load jew livelli li ma jitkejlux ta ’ HCV RNA intweriet li jistgħu jintużaw biex jitbassar ir- rispons sostnut (Tabella 8).
Table 8 Predictability of sustained response by viral response at week 12 and genotype* Treatment Ribavirin (> 10.6mg/ kg) 1
Tabella 8 Tbassir għar- rispons sostnut mir- rispons viroloġiku mat- 12- il ġimgħa u l- ġenotip * Trattament
Genotype
Ġenotip
Viral response at week 12
Ribavirin (> 10. 6mg/ kg) 1 +peginterferon alfa- 2b
Yes 75% (82/ 110)
mat- 12- il ġimgħa Iva 75% (82/ 110)
18 +peginterferon alfa-2b 1.5 48-week treatment
1. 5 Trattament ta ’ 48 ġimgħa
No 25% (28/ 110)
Le 25% (28/ 110)
Ribavirin 800-1400 mg
Ribavirin 800- 1400 mg +peginterferon alfa- 2b
2 and 3
2u3
Yes 99%
Iva 99% (213/ 215)
1.5 24-week treatment
1. 5 Trattament ta ’ 24 ġimgħa
No 1% (2/ 215)
Le 1% (2/ 215)
*reflects patients with 12 week data available
tagħrif ta ’ 12- il
HCV/ HIV Co-infected patients Two trials have been conducted in patients co-infected with HIV and HCV.
Pazjenti infettati fl- istess ħin b’ HCV/ HIV Saru żewġ provi f’ pazjenti infettati fl- istess ħin b’ HIV u HCV.
The response to treatment in both of these trials is presented in Table 9.
Ir- rispons għal trattament f’ dawn iż- żewġ provi jidher f’ Tabella 9.
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 412 previously untreated adult patients with chronic hepatitis C who were co-infected with HIV.
Studju 1 (RIBAVIC; P01017) kien studju multiċentriku u każwali li fih ħadu sehem 412- il pazjent arwolat li ma kinux ġew ittrattati qabel għal epatite Ċ u li kellhom ukoll infezzjoni b’ HIV.
Patients were randomized to receive either Ribavirin (800 mg/ day) plus peginterferon alfa-2b (1.5 µg/ kg/ week) or Ribavirin (800 mg/ day) plus interferon alfa-2b (3 MIU TIW) for 48 weeks with a follow-up period of 6 months.
Il- pazjenti ngħataw b’ mod każwali jew Ribavirin (800 mg/ jum) flimkien ma ’ peginterferon alfa- 2b (1. 5 µg/ kg/ ġimgħa) jew Ribavirin (800 mg/ jum) flimkien ma ’ interferon alfa- 2b (3 MIU TIW) għal 48 ġimgħa b’ perijodu ta ’ follow- up għal 6 xhur.
Study 2 (P02080) was a randomized, single centre study that enrolled 95 previously untreated adult patients with chronic hepatitis C who were co- infected with HIV.
L- istudju 2 (P02080) kien studju każwali b’ ċentru wieħed li fih ġew arwolati 95 pazjent adult b’ epatite Ċ kronika li ma kienux trattati qabel u li kellhom l- HIV fl- istess ħin.
Patients were randomized to receive either Ribavirin (800-1,200 mg/ day based on weight) plus peginterferon alfa-2b (100 or 150 µg/ week based on weight) or Ribavirin (800- 1,200 mg/ day based on weight) plus interferon alfa-2b (3 MIU TIW).
Il- pazjenti ntgħażlu b’ mod każwali biex jew jirċievu Ribavirin (800- 1, 200 mg/ jum skont il- piż) flimkien ma ’ peginterferon alfa- 2b (100 jew 150 µg/ ġimgħa skont il- piż) jew Ribavirin (8001, 200 mg/ jum skont il- piż) flimkien ma ’ interferon alfa- 2b (3 MIU TIW).
The duration of therapy was 48 weeks with a follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load < 800,000 IU/ ml (Amplicor) who were treated for 24 weeks with a 6 month follow-up period.
It- tul tat- terapija kien 48 ġimgħa b’ perijodu ta ’ follow up ta ’ 6 xhur ħlief għal pazjenti infettati b’ ġenotipi 2 jew 3 u viral load < 800, 000 IU/ ml (Amplicor) li kienu trattati għal 24 ġimgħa b’ perijodu ta ’ follow up ta ’ 6 xhur.
Table 9 Sustained virological response based on genotype after Ribavirin in combination with peginterferon alfa-2b in HCV/ HIV co-infected patients
Tabella 9 Rispons viroloġiku sostnut skont il- ġenotip wara Ribavirin ingata flimkien ma ’ peginterferon alfa- 2b f’ pazjenti infettati fl- istess ħin b’ HCV/ HIV
Study 11
Studju 11 Ribavirin
Study 22
Studju 22
Ribavirin (800 mg/ day)
Ribavirin (800 -
Ribavirin (800 mg/ day) +
(800 mg/ jum)
(800- 1,200 mg/ day)
1, 200 mg/ jum
Ribavirin (800- 1,200 mg/ day) d
Ribavirin (800 -
Interferon alfa-
1, 200 mg/ jum) d
d+
) d+
peginterferon alfa-2b (1.5
alfa- 2b (1. 5
2b (3 MIU TIW)
2b (3 MIU
alfa-2b (3 MIU TIW)
TIW)
valueb
µg / kg /
µg / kg/ week)
TIW)
p valuea
or 150c
or 150c µg/ week)
Value ġimgħa) µg/ ġimgħa) pa Kollha
All Genotype 1, 4
19 Ġenotip 1, 4
0.047 0.006
0. 006
0.017 0.007
0. 007
Ribavirin dosing was 800 mg for patients< 60 kg, 1,000 mg for patients 60- 75 kg, and 1,200 mg for patients > 75 kg.
MIU = miljun unità internazzjonali; TIW = tliet darbiet fil- ġimgħa. a: valur p ibbażat fuq it- test Cochran- Mantel Haenszel Chi kwadru. b: valur p ibbażat fuq it- test chi- square. c: individwi < 75 kg ħadu 100 µg/ ġimgħa peginterferon alfa- 2b u individwi ≥ 75 kg irċevew 150 µg/ ġimgħa peginterferon alfa- 2b. d: dożaġġ ta ’ Ribavirin kien 800 mg għal pazjenti < 60 kg, 1, 000 mg għal pazjenti 60- 75 kg, u 1, 200 mg għal pazjenti > 75 kg.
Histological response Liver biopsies were obtained before and after treatment in Study 1 and were available for 210 of the 412 subjects (51%).
Rispons ħistoloġiku Bijopsiji tal- fwied ittieħdu qabel u wara t- trattament fi Studju 1 u kienu disponibbli għal 210 mill- 412 - il individwu (51%).
19 Ribavirin in combination with peginterferon alfa-2b.
Kemm- il punteġġ Metavir u l- grad Ishak naqsu fost l- individwi ttrattati b’ Ribavirin f’ kombinazzjoni ma ’ peginterferon alfa- 2b.
This decline was significant among responders (- 0.3 for Metavir and -1.2 for Ishak) and stable (-0.1 for Metavir and -0.2 for Ishak) among non- responders.
Dan it- tnaqqis kien sinifikanti fost dawk li wrew rispons (- 0. 3 għal Metavir u - 1. 2 għal Ishak) u stabbli (- 0. 1 għal Metavir u - 0. 2 for Ishak) fost dawk li ma kellhomx rispons.
There was no improvement in terms of fibrosis observed in this study.
Ma deherx titjib mil- lat ta ’ fibrosi f’ dan l- istadju.
Steatosis was significantly improved in patients infected with HCV Genotype 3.
L- isteatosi tjiebet b’ mod sinifikanti f’ pazjenti infettati b’ HCV ta ’ Ġenotip 3.
Previous treatment failure patients Retreatment of prior treatment failures (relapse and nonresponder patients) with peginterferon alfa-2b in combination with Ribavirin In a non-comparative trial, 2,293 patients with moderate to severe fibrosis who failed previous treatment with combination alpha interferon/ ribavirin were retreated with peginterferon alfa 2b, 1.5 microgram/ kg subcutaneously, once weekly, in combination with weight adjusted Ribavirin.
Pazjenti bla rispons għal kura li ngħatat qabel Trattament mill- ġdid ta ’ pazjenti li kienu fallew mit- trattament li ngħata qabel (pazjenti li rkadew u li ma kellhomx rispons għall- kura) b ’ peginterferon alfa- 2b flimkien ma ’ Ribavirin Fi prova mhix komparattiva, 1, 336 pazjent b’ fibrożi minn moderata għal severa li t- trattament li ngħatalhom falla meta ngħata flimkien ma ’ alpha interferon/ ribavirin kienu trattati mill- ġdid b’ peginterferon alfa 2b, 1. 5 mikrogramma/ kg mogħtija taħt il- ġilda, darba fil- ġimgħa, flimkien ma ’ ribavirin aġġustat skont id- doża.
Failure to prior therapy was defined as relapse or non-response (HCV-RNA positive at the end of a minimum of 12 weeks of treatment).
Falliment għal terapija li tkun ingħatat qabel kien definit bħala irkadar jew nuqqas ta ’ rispons (HCV- RNA pożittivi fi tmiem ta ’ mill- inqas 12- il ġimgħa ta ’ trattament).
Patients who were HCV-RNA negative at Treatment Week 12 continued treatment for 48 weeks and were followed for 24 weeks post-treatment.
Pazjenti li kienu HCV- RNA negattivi fit- 12- il Ġimgħa ta ’ Trattament għal 48 ġimgħa u kienu segwiti għal 24 ġimgħa wara t- trattament.
Sustained Virologic Response (SVR) is defined as undetectable HCV-RNA at 24 weeks post-treatment (Table 10).
Ir- rispons għat- trattament kien imfisser bħala li ma jitkejjilx għal HCV RNA wara 24 ġimgħa wara t- trattament (Tabella 10).
Table 10 Rates of Response to retreatment in prior treatment failures
Tabella 10 Rati ta ’ Rispons għal trattament mill- ġdid fejn fallew ta ’ qabel
Patients with undetectable HCV– RNA at treatment Week 12 and SVR upon retreatement Overall
Patients b’ HCV- RNA li ma srtgħax jitkejjel fil- Ġimgħa ta ’ Trattament u SVR mat- trattament mill- ġdid Populazzjoni
interferon alpha/ ribavirin
interferon alfa 2b/ Ribavirin
peginterferon alpha/ ribavirin
peginterferon alpha/ ribavirin
Population*
Globali *
Response Week 12% (n/ N)
Ġimgħa 12 ta ’ Rispons 12% (n/ N)
Response SVR% (n/ N) Week 12% 99% CI (n/ N)
Ġimgħa ta ’ SVR% (n/ N) Rispons12% 99% CI (n/ N)
Overall Prior Response
Globali Rispons Qabel
38.6 (549/ 1,423) 59.4 (326/ 549) 54.0,64.8
38. 6 (549/ 1, 423) 59. 4 (326/ 549) 54. 0, 64. 8
31.5 (272/ 863) 50.4 (137/ 272) 42.6, 58.2
31. 5 (272/ 863) 50. 4 (137/ 272) 42. 6, 58. 2
21.7 (497/ 2,293) 19.5, 23.9
21. 7 (497/ 2, 293) 19. 5, 23. 9
67.7 (203/ 300) 59.6 (121/ 203)
67. 7 (203/ 300)
58.1 (200/ 344) 52.5 (105/ 200) 37.7
59. 6 (121/ 203) 50. 7, 68. 5
(243/ 645)
58. 1 (200/ 344)
43.4, 61.6
52. 5 (105/ 200) 43. 4, 61. 6
32.8, 42.6
37. 7 (243/ 645) 32. 8, 42. 6
Genotype 1/ 4
Ġenotip 1/ 4
59.7 (129/ 216)
59. 7 (129/ 216)
51.2 (66/ 129) 39.8, 62.5
51. 2 (66/ 129) 39. 8, 62. 5
48.6 (122/ 251)
48. 6 (122/ 251)
44.3 (54/ 122) 32.7, 55.8
44. 3 (54/ 122) 32. 7, 55. 8
28.6 (134/ 468) 23.3, 34.0
28. 6 (134/ 468) 23. 3, 34. 0
Genotype 2/ 3
Ġenotip 2/ 3
88.9 (72/ 81)
88. 9 (72/ 81)
73.6 (53/ 72) (60.2, 87.0)
73. 6 (53/ 72) (60. 2, 87. 0)
83.7 (77/ 92)
83. 7 (77/ 92)
64.9 (50/ 77) 50.9, 78.9
64. 9 (50/ 77) 50. 9, 78. 9
61.3 (106/ 173) 51.7, 70.8
61. 3 (106/ 173) 51. 7, 70. 8
28.6 (258/ 903)
28. 6 (258/ 903)
57.0 (147/ 258) 49.0, 64.9
57. 0 (147/ 258) 49. 0, 64. 9
12.4 (59/ 476)
12. 4 (59/ 476)
44.1 (26/ 59) 27.4, 60.7
44. 1 (26/ 59) 27. 4, 60. 7
13.6 (188/ 1,385) 11.2, 15.9
13. 6 (188/ 1, 385) 11. 2, 15. 9
23.0 (182/ 790)
23. 0 (182/ 790)
51.6 (94/ 182) 42.1, 61.2
51. 6 (94/ 182) 42. 1, 61. 2
9.9 (44/ 446)
9. 9 (44/ 446)
38.6 (17/ 44) 19.7, 57.5
38. 6 (17/ 44) 19. 7, 57. 5
9.9 (123/ 1,242) 7.7, 12.1
9. 9 (123/ 1, 242) 7. 7, 12. 1
Genotype 2/ 3 Genotype
Ġenotip 2/ 3
70.3 (52/ 74) 56.6, 84.0
70. 3 (52/ 74) 56. 6, 84. 0
53.6 (15/ 28)
53. 6 (15/ 28)
30.2 (343/ 1,135)
30. 2 (343/ 1, 135)
51.3 (176/ 343) 44.4, 58.3
51. 3 (176/ 343) 44. 4, 58. 3
23.0 (162/ 704)
23. 0 (162/ 704)
42.6 (69/ 162) 32.6, 52.6
42. 6 (69/ 162) 32. 6, 52. 6
14.6 (270/ 1,846) 12.5, 16.7
14. 6 (270/ 1, 846) 12. 5, 16. 7
77.1 (185/ 240)
77. 1 (185/ 240)
73.0 (135/ 185) 64.6, 81.4
73. 0 (135/ 185) 64. 6, 81. 4
75.6 (96/ 127) 63.5 (61/ 96) 50.9, 76.2
75. 6 (96/ 127) 63. 5 (61/ 96) 50. 9, 76. 2
55.3 (203/ 367) 48.6, 62.0
55. 3 (203/ 367) 48. 6, 62. 0
42.5 (17/ 40)
42. 5 (17/ 40)
70.6 (12/ 17) 42.1, 99.1
70. 6 (12/ 17) 42. 1, 99. 1
44.4 (12/ 27) 50.0 (6/ 12) 12.8, 87.2
44. 4 (12/ 27) 50. 0 (6/ 12) 12. 8, 87. 2
28.4 (19/ 67) 14.2, 42.5
28. 4 (19/ 67) 14. 2, 42. 5
METAVIR Fibrosis score
Punteġġ Fibrosi
46.0 (193/ 420)
46. 0 (193/ 420)
66.8 (129/ 193) 20
66. 8 (129/ 193) 58. 1, 75. 6
33.6 (78/ 232)
33. 6 (78/ 232)
57.7 (45/ 78)
57. 7 (45/ 78) 43. 3, 72. 1
29.2 (191/ 653)
29. 2 (191/ 653) 24. 7, 33. 8
38.0 (163/ 429)
38. 0 (163/ 429)
62.6 (102/ 163) 52.8, 72.3
62. 6 (102/ 163) 52. 8, 72. 3
32.4 (78/ 241)
32. 4 (78/ 241)
51.3 (40/ 78) 36.7, 65.9
51. 3 (40/ 78) 36. 7, 65. 9
21.9 (147/ 672) 17.8, 26.0
21. 9 (147/ 672) 17. 8, 26. 0
33.6 (192/ 572)
33. 6 (192/ 572)
49.5 (95/ 192) 40.2, 58.8
49. 5 (95/ 192) 40. 2, 58. 8
29.7 (116/ 390)
29. 7 (116/ 390)
44.8 (52/ 116) 32.9, 56.7
44. 8 (52/ 116) 32. 9, 56. 7
16.5 (159/ 966) 13.4, 19.5
16. 5 (159/ 966) 13. 4, 19. 5
Baseline Viral Load HVL (> 600,000 IU/ ml)
Linja bażi tat - tagħbija virali HVL (> 600, 000 IU/ ml)
32.4 (280/ 864)
32. 4 (280/ 864)
56.1 (157/ 280) 48.4, 63.7
56. 1 (157/ 280) 48. 4, 63. 7
LVL (≤ 600,000 IU/ ml)
LVL (≤600, 000 IU/ ml)
48.3 (269/ 557)
48. 3 (269/ 557)
62.8 (169/ 269) 55.2, 70.4
62. 8 (169/ 269) 55. 2, 70. 4
41.0 (118/ 288)
41. 0 (118/ 288)
61.0 (72/ 118) 49.5, 72.6
61. 0 (72/ 118) 49. 5, 72. 6
30.2 (256/ 848) 26.1, 34.2
30. 2 (256/ 848) 26. 1, 34. 2
Non-responder defined as serum/ plasma HCV-RNA positive at the end of a minimum of 12 weeks of treatment.
Non- responder - ma wrewx rispons definit peress li HCV- RNA fis- serum/ plażma fi tmiem it- 12- il ġimgħa ta ’ trattament.
Plasma HCV-RNA is measured with a research-based quantitative polymerase chain reaction assay by a central laboratory *Intent to treat population includes 7 patients for whom at least 12 weeks of prior therapy could not be confirmed.
HCV RNA fil- plażma jitkejjel b’ assaġġ b’ polymerase chain reaction kwantitattiv ibbażat fuq riċerka minn laboraorju ċentrali. * Popolazzjoni bl- intenzjoni li tiġi ttrattata tinkludi 7 pazjenti li għalihom mill- inqas 12- il ġimgħa ta ’ terapija minn qabel ma setgħetx tkun konfermata.
Overall, approximately 36% (821/ 2,286) of patients had undetectable plasma HCV-RNA levels at Week 12 of therapy measured using a research-based test (limit of detection 125 IU/ ml).
B’ mod globali, madwar 37% tal- pazjenti kellhom livelli ta ’ HCV- RNA fil- plażma li ma setgħux jitkejlu mat- 12- il Ġimgħa ta ’ terapija imkejjla permezz ta ’ test ibbażat fuq riċerka (limitu li seta ’ jitkejjel 125 IU/ ml).
In this subgroup, there was a 56% (463/ 823) sustained virological response rate.
F’ dan is- sottogrupp, kien hemm rata ta ’ rispons viroloġiku sostnut ta ’ 57% (282/ 499).
For patients with prior failure on therapy with nonpegylated interferon or pegylated interferon and negative at Week 12, the sustained response rates were 59% and 50%, respectively.
Għal pazjenti li t- terapija ta ’ qabel ma rnexxitx fuqhom b’ interferon mhux pegilat jew interfeon pegilat u negattivi f’ Ġimgħa 12, ir- rati ta ’ rispons sostnut kienu 59% u 47%, rispettivament.
In those patients the SVR was 12%.
F’ pazjenti b ’ > 2 log tat- tnaqqis virali iżda b’ ammont ta ’ virus li jista ’ jiġi mkejjel ma ’ Ġimgħa 12, l - SVR stmat kien globalment madwar 6%.
Nonresponders to prior therapy with pegylated interferon alpha/ ribavirin were less likely to achieve a Week ` 12 response to retreatment than nonresponders to nonpegylated interferon alpha/ ribavirin (12.4% vs.
Dawk li fuqhom it- terapija li ngħatat qabel ma ħadmitx b’ interferon pegilat/ ribavirin kellhom anqas ċans li jiksbu rispons minn dawk li fuqhom it- terapija li ngħatat qabel ma ħadmitx b’ interferon mhux pegilat/ ribavirin (4% vs.
Retreatment of relapse patients with Ribavirin and interferon alfa-2b combination treatment Two trials examined the use of Ribavirin and interferon alfa-2b combination treatment in relapse patients (C95-144 and I95-145); 345 chronic hepatitis patients who had relapsed after previous interferon treatment were treated for six months with a six month follow-up.
Trattament mill- ġdid ta ’ pazjenti li rkadew b’ trattament kkombinat b’ Ribavirin u interferon alfa- 2b Żewġ studji li eżaminaw l- użu kkombinat ta ’ Ribavirin u interferon alfa- 2b f’ pazjenti li jirkadu (C95 - 144 u I95- 145); 345 pazjent b’ epatite kronika li kienu diġà rkadew b’ trattament ta ’ interferon li ngħata qabel, kienu ttrattati għal sitt xhur ta ’ follow- up.
Combination therapy with Ribavirin and interferon alfa-2b resulted in a sustained virological response that was ten-fold higher than that with interferon alfa-2b alone (49% vs 5%, p < 0.0001).
Terapija ta ’ kombinazzjoni b’ Ribavirin u interferon alfa- 2b irriżultat f’ rispons viroloġiku sostnut li kien għaxar darbiet ogħla minn dak b’ interferon alfa- 2b waħdu (49% vs 5%, p < 0. 0001).
This benefit was maintained irrespective of standard predictors of response to interferon alfa-2b such as virus level, HCV genotype and histological staging.
Dan il- benefiċċju baqa ’ jinżamm irrispettivament minn fatturi standard li jbassru r- rispons għal interferon alfa- 2b bħal livell tal- virus, ġenotip ta ’ HCV u l- istadji ħistoloġiċi.
Long-term efficacy data Two large long-term follow-up studies enrolled 1,071 patients and 567 patients after treatment in prior studies with nonpegylated interferon alfa-2b (with or without ribavirin) and pegylated interferon alfa- 2b (with or without ribavirin), respectively.
21 Tagħrif dwar l- effikaċja fit- tul Żewġ studji kbar ta ’ follow- up fuq perijodu fit- tul li għalihom ġew arwolati 1, 071 pazjent u 567 pazjent wara trattament fi studji minn qabel b’ interferon alfa- 2b mhux pegilat (bi jew mingħajr ribavirin) u interferon alfa- 2b pegilat (bi jew mingħajr ribavirin), rispettivament.
The purpose of the studies was to evaluate the durability ofsustained virologic response (SVR) and assess the impact of continued viral negativity on clinicaloutcomes.
L- għan tal- istudji kien sabiex jiġi evalwat kemm idum ir- rispons viroloġiku sostnut (SVR) u sabiex jiġi stmat l- impatt ta ’ negattività virali kontinwa fuq ir- riżultati kliniċi.
At least 5 years of long-term follow-up was completed after treatment in 462 patients and 327 patients, respectively.
Mill- anqas 5 snin ta ’ follow- up fit- tul intemm wara kura fuq 462 pazjent u 327 pazjent, rispettivament.
12 out of 492 sustained responders and only 3 out of 366 sustainedresponders relapsed, respectively, in the studies.
12 minn 492 li sostnew ir- rispons u 3 biss minn 366 pazjent li sostnew r- rispons irkadew, rispettivament, fl- istudji.
The Kaplan-Meier estimate for continued sustained response over 5 years is 97% (95% CI:
L- istima Kaplan- Meier għal rispons sostnut fuq tul ta ’ 5 snin hija 97% (95% CI:
95-99%) for patients receiving nonpegylated interferon alfa-2b (with or without ribavirin), and is 99% (95% CI:
95- 99%) għal pazjenti li kienu qed jirċievu interferon alfa- 2b mhux pegilat (bi jew mingħajr ribavirin), u hija 99% (95% CI:
98-100%) for patients receiving pegylated interferon alfa-2b (with or without ribavirin).
98- 100%) għal pazjenti li kienu qed jirċievu interferon alfa- 2b pegilat (bi jew mingħajr ribavirin).
SVR after treatment of chronic HCV with interferon alfa-2b (pegylated and nonpegylated, with or without ribavirin) results in long-term clearance of the virus providing resolution of the hepatic infection and clinical'cure 'from chronic HCV.
SVR wara kura b’ HCV kroniku b’ interferon alfa- 2b (pegilat u mhux pegilat, bi jew mingħajr ribavirin) wassal għal tneħħija fuq terminu ta ’ żmien twil tal- virus b’ hekk tgħaddi l- infezzjoni epatika ‘ b’ kura ’ klinika minn HCV kronika.
However, this does not preclude the occurrence of hepatic events in patients with cirrhosis (including hepatocarcinoma).
Madankollu, dan ma jeliminax il- possibilità li jseħħu każijiet epatiċi f’ pazjenti b’ ċirrożi (li jinkludi epatokarċinoma).
21 Ribavirin clinical trials in children and adolescents:
Provi kliniċi b’ Ribavirin fi tfal u adoloxxenti:
Children and adolescents 3 to 16 years of age with compensated chronic hepatitis C and detectable HCV-RNA (assessed by a central laboratory using a research-based RT-PCR assay) were enrolled in two multicentre trials and received Ribavirin 15 mg/ kg per day plus interferon alfa-2b 3 MIU/ m 3
Tfal u adoloxxenti minn 3 sa 16- il sena b’ epatite Ċ kronika kumpensata u HCV- RNA li setgħu jitkejlu (imkejjel minn laboratorju ċentrali bl- użu ta ’ assaġġ permezz tal- RT- PCR li jintuża għar- riċerka) kienu arwolati f’ żewġ provi multiċentrali u rċevew Ribavirin 15 mg/ kg kuljum flimkien ma ’ interferon 2 alfa- 2b 3 MIU/ m 3 darbiet fil- ġimgħa għal sena 1 segwit b’ 6 xhur follow- up wara t- trattament.
A total of 118 patients were enrolled:
Kienu arwolati total ta ’ 118- il pazjent:
57% male, 80% Caucasian, and 78% genotype 1, 64% ≤ 12 years of age.
57% irġiel, 80% Kawkasi, u 78% ġenotip 1, 64% ≤ 12- il sena.
The population enrolled mainly consisted in children with mild to moderate hepatitis C.
Il- popolazzjoni arwolata kienet tikkonsisti prinċipalment minn tfal b’ epatite Ċ ħafifa għal moderata.
Sustained virological response rates in children and adolescents were similar to those in adults.
Rati ta ’ rispons viroloġiku sostnut fi tfal u adoloxxenti kienu simili għal dawk tal- adulti.
Due to the lack of data in children with severe progression of the disease, and the potential for undesirable effects, the benefit/ risk of the combination of ribavirin and interferon alfa-2b needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8).
Minħabba nuqqas ta ’ tagħrif fi tfal b’ avvanz sever tal- marda, u l- possibilità ta ’ effetti mhux mixtieqa, il- benefiċċju/ riskju tal- kombinazzjoni ta ’ ribavirin u interferon alfa- 2b f’ din il- popolazzjoni għandu jiġi kkonsidrat b’ attenzjoni (ara sezzjonijiet 4. 1, 4. 4 u 4. 8).
Study results are summarized in Table 11.
Ġabra fil- qosor ta ’ dawn ir- riżultati qed jidhru f’ Tabella 11.
Virological response in previously untreated children and adolescents Ribavirin 15 mg/ kg/ day + interferon alfa-2b 3 MIU/ m2 3 times a week
Rispons viroloġiku fi tfal u adoloxxenti li ma kienux kurati qabel Ribavirin 15 mg/ kg/ jum + interferon alfa- 2b 3 MIU/ m2 3 darbiet fil- ġimgħa
Genotype 2/ 3/ 4 (n=26)
Ġenotip 2/ 3/ 4 (n=26)
* Number (%) of patients
* Għadd (%) ta ’ pazjenti
Defined as HCV-RNA below limit of detection using a research based RT-PCR assay at end of treatment and during follow-up period
Mfisser bħala HCV- RNA taħt il- limitu li jista ’ jitkejjel b’ assaġġ bażat fuq RT- PCR fi tmiem it- trattament u fil- perijodu ta ’ follow- up
Ribavirin is absorbed rapidly following oral administration of a single dose (mean Tmax= 1.5 hours), followed by rapid distribution and prolonged elimination phases (single dose half-lives of absorption, distribution and elimination are 0.05, 3.73 and 79 hours, respectively).
Ribavirin huwa assorbit malajr wara li jingħata mill- ħalq b’ doża waħda (il- medja Tmax= 1. 5 sigħat), segwit minn distribuzzjoni mgħaġġla u fażijiet ta ’ eliminazzjoni mtawwla (half- lives ta ’ assorbiment b’ dożi waħidhom, distribuzzjoni u eliminazzjoni huma 0. 05, 3. 73 u 79 siegħa, rispettivament).
Absorption is extensive with approximately 10% of a radiolabelled dose excreted in the faeces.
L- assorbiment hu estensiv b’ madwar 10% ta ’ doża radjutikkettata eliminata mal- ippurgar.
However, absolute bioavailability is approximately 45 %-65%, which appears to be due to first pass metabolism.
Madankollu, ir- rata assoluta ta ’ bijodisponibilità hi madwar 45% - 65%, li tidher li hi minħabba l- metaboliżmu tal- ewwel passaġġ.
There is a linear relationship between dose and AUCtf following single doses of 200-1,200 mg ribavirin.
Hemm relazzjoni lineari bejn id- doża u l- AUCtf wara dożi
Volume of distribution is approximately 5,000 l.
Il- volum ta ’ distribuzzjoni huwa ta ’ madwar 5, 000 l.
Ribavirin does not bind to plasma proteins.
Ribavirin ma jintrabatx mal- proteini tal- plażma.
Ribavirin has been shown to produce high inter- and intra-subject pharmacokinetic variability following single oral doses (intrasubject variability of approximately 30% for both AUC and Cmax), which may be due to extensive first pass metabolism and transfer within and beyond the blood compartment.
Ribavirin intwera li jipproduċi varjabilità farmakokinetika għolja bejn u fl- individwi wara dożi waħidhom mill- ħalq (b’ varjabilità ta ’ bejn l- individwi ta ’ madwar 30% kemm għal AUC u għal Cmax), li għandha mnejn tkun minħabba l- metaboliżmu estensiv tal- ewwel passaġġ u t- trasferiment ġo u ’ l barra mill- komportament tad- demm.
Ribavirin transport in non-plasma compartments has been most extensively studied in red cells, and has been identified to be primarily via an es-type equilibrative nucleoside transporter.
It- trasport ta ’ ribavirin f’ kompartamenti mhux tal- plażma kien studjat bl- aktar mod estensiv fiċ- ċelluli ħomor, u kien identifikat li jseħħ prinċipalment permezz ta ’ trasportatur ekwilibrattiv tan- nukleosajd tat- tip es.
This type of transporter is present on virtually all cell types and may account for the high volume of distribution of ribavirin.
Dan it- tip ta ’ trasportatur hu preżenti kważi fit- tipi kollha ta ’ ċelluli u jista ’ jkun il- kawża tal- volum għoli tad- distribuzzjoni ta ’ ribavirin.
The ratio of whole blood: plasma ribavirin concentrations is approximately 60:1; the excess of ribavirin in whole blood exists as ribavirin nucleotides sequestered in erythrocytes.
Il- proporzjon ta ’ demm sħiħ: konċentrazzjonijiet ta ’ ribavirin hu madwar 60: 1; ribavirin żejjed fid- demm sħiħ jeżisti bħala nukleotidi ta ’ ribavirin li jinsabu f’ eritroċiti.
1) a reversible phosphorylation pathway; 2) a degradative pathway involving deribosylation and amide hydrolysis to yield a triazole carboxyacid metabolite.
1) passaġġ riversibbli ta ’ fosforilazzjoni; 2) degradazzjoni li tinvolvi t- tneħħija ta ’ ribose (deribosylation) u idrolisi ta ’ amidi li tipproduċi metabolit ta ’ triazole carboxyacid.
Both ribavirin and its triazole carboxamide and triazole carboxylic acid metabolites are also excreted renally.
Kemm ribavirin u l- metaboliti tiegħu triazole carboxamide u triazole carboxylic acid jiġu eliminati permezz tal- kliewi.
22 Upon multiple dosing, ribavirin accumulates extensively in plasma with a six-fold ratio of multiple- dose to single-dose AUC12hr.
Wara dożaġġ multiplu, ribavirin jakkumula b’ mod estensiv fil- plażma bi proporzjon ta ’ sitt darbiet għal kull doża ta ’ AUC12hr.
Following oral dosing with 600 mg BID, steady-state was reached by approximately four weeks, with mean steady state plasma concentrations approximately 2,200 ng/ ml.
Wara d- dożaġġ mill- ħalq ta ’ 600 mg BID, stat ta ’ ekwilibriju ntlaħaq f’ madwar erba ’ ġimgħat, b’ medja tal- konċentrazzjonijiet tal- plażma fi stat fiss ta ’ madwar 2, 200 ng/ ml.
Upon discontinuation of dosing the half-life was approximately 298 hours, which probably reflects slow elimination from non-plasma compartments.
Wara l- waqfien tad- dożaġġ, il- half life kienet ta ’ madwar 298 siegħa, li probabilment tirrifletti l- eliminazzjoni bil- mod mill- kompartament mhux tal- plażma.
Food effect:
L- effett tal- ikel:
The bioavailability of a single oral dose of ribavirin was increased by co-administration of a high fat meal (AUCtf and Cmax both increased by 70%).
Il- bijodisponibilità ta ’ doża waħda mill- ħalq ta ’ ribavirin żdiedet meta ngħata flimkien ma ’ ikla b’ ħafna xaħam (AUCtf u Cmax it- tnejn żdiedu b’ 70%).
It is possible that the increased bioavailability in this study was due to delayed transit of ribavirin or modified pH.
Jista ’ jkun li ż- żieda fil - bijodisponibilità f’ dan l- istudju kienet minħabba dewmien fil- ġarr ta ’ ribavirin jew bidla tal- pH.
The clinical relevance of results from this single dose study is unknown.
Ir - rilevanza klinika tar- riżultati minn dan l- istudju ta ’ doża waħda mhix magħrufa.
In the pivotal clinical efficacy trial, patients were instructed to take ribavirin with food to achieve the maximal plasma concentration of ribavirin.
Fi prova ewlenija dwar l- effikaċja klinika, il- pazjenti ngħataw struzzjonijiet biex jieħdu ribavirin mal- ikel sabiex tintlaħaq il- konċentrazzjoni massima ta ’ ribavirin fil- plażma.
Single-dose ribavirin pharmacokinetics were altered (increased AUCtf and Cmax) in patients with renal dysfunction compared with control subjects (creatinine clearance > 90 ml/ minute).
Il- farmakokinetiċi ta ’ doża waħda ta ’ ribavirin kienu mibdula (żieda fl- AUCtf u Cmax) fpazjenti li l- kliewi tagħhom ma kinux qed jaħdmu sew meta mqabbla ma ’ individwi bħala kontrolli (tneħħija ta ’ kreatinina > 90 ml/ minuta).
This appears to be due to reduction of apparent clearance in these patients.
Dan jidher li kien kien minħabba t- tnaqqis fit- tneħħija apparenti f’ dawn il- pazjenti.