qanastek/EMEA-V3 huggingface dataset:
No pharmacokinetic interactions were noted between Rebetol and peginterferon alfa-2b or interferon alfa-2b in a multiple-dose pharmacokinetic study.
L- ebda interazzjonijiet farmakokinetiċi ma kienu nnotati bejn Rebetol u peginterferon alfa- 2b jew interferon alfa- 2b fi studju dwar il- farmakokinetika b’ dożi multipli.
Antacid:
Antiaċidi:
The bioavailability of ribavirin 600 mg was decreased by co-administration with an antacid containing magnesium aluminium and simethicone; AUCtf decreased 14%.
Il- biodisponibbiltà ta ’ ribavirin 600 mg kienet imnaqqsa meta ngħata flimkien ma ’ antaċidi li kien fihom magnesium aluminium u simethicone; l- AUCtf tnaqqas b’ 14%.
It is possible that the decreased bioavailability in this study was due to delayed transit of ribavirin or modified pH.
Jista ’ jkun li l- biodisponibilità kienet imnaqqsa f' dan l- istudju minħabba l- ittardjar tal- ġarr ta ’ ribavirin jew tal- bdil fil- pH.
This interaction is not considered to be clinically relevant.
Din l- azzjoni reċiproka mhijiex ikkunsidrata li hi klinikament relevanti.
Nucleoside analogs:
Analogi tan- Nuklejosajd:
Pharmacologically, ribavirin increases phosphorylated metabolites of purine nucleosides in vitro.
Farmakoloġikament, ribavirin iżid il- metaboli fosforilati tan - nuklejosajd tal- purina in vitro.
This activity could potentiate the risk of lactic acidosis induced by purine nucleoside analogs (e.g. didanosine or abacavir).
Din l- attività tista ’ twassal għar- riskju akbar ta ’ aċidożi lattika kkaġunata minn analogi tan- nuklejosajd tal- purina (eż. didanosine jew abacavir).
Co-administration of Rebetol and didanosine is not recommended.
L użu fl- istess ħin ta ’ Rebetol u didanosine mhux irrakkomandat.
Reports of mitochondrial toxicity, in particular lactic acidosis and pancreatitis, of which some fatal, have been reported (see section 4.4).
Rapporti ta ’ tossiċità mitokondrijali, l- aktar aċidożi lattika u pankrejatite, ftit minnhom fatali, kienu rrappurtati (ara sezzjoni 4. 4).
The concomitant use of
Kien irrapportat li l- anemija ħraxet minħabba ribavirin meta zidovudine ikun parti mill- kors li jintuża għall- kura ta ’ l- HIV għalkemm il- mekkaniżmu eżatt għad irid jiġi ċċarat.
9 ribavirin with zidovudine is not recommended due to an increased risk of anaemia (see section 4.4).
L- użu ta ’ ribavirin flimkien ma ’ zidovudine mhux irrakkomandat minħabba żieda fir- riskju ta ’ anemija (ara sezzjoni 4. 4).
This would be particularly important in patients with a known history of zidovudine induced anaemia.
Dan ikun importanti b’ mod partikolari f’ pazjenti li fil- passat kellhom anemija minħabba li ħadu zidovudine.
Any potential for interactions may persist for up to two months (five half-lives for ribavirin) after cessation of Rebetol therapy due to the long half-life (see section 5.2).
Kwalunkwe possibbiltà ta ’ interazzjonijiet tista ’ tippersisti sa xaharejn (ħames half- lives għal ribavirin) wara l- waqfien tat- terapija b’ Rebetol minħabba l- half- life twil (ara sezzjoni 5. 2).
The re is no evidence that ribavirin interacts with non-nucleoside reverse transcriptase inhibitors or protease inhibitors.
M’ hemm l- ebda evidenza li ribavirin jagħmel xi interazzjoni ma ’ l- impedituri li mhumiex nuklejosidi tar- reverse transcriptase jew impedituri protease.
The use of Rebetol is contraindicated during pregnancy.
L- użu ta ’ Rebetol huwa kontra- indikat waqt it- tqala.
Preclinical data:
Informazzjoni ta ’ qabel l- użu kliniku:
In animal studies, ribavirin produced reversible effects on spermatogenesis (see section
Fi studji fuq annimali, ribavirin għamel effetti riversibbli fuq l- ispermatoġenesi (ara
5.3).
sezzjoni 5. 3).
- Teratogenicity:
- Teratoġeniċità:
Significant teratogenic and/or embryocidal potential have been demonstrated for
Possibbilta ’ ta ’ effetti teratoġeniċi u/ jew fatali għall- embriju intwerew għal ribavirin
ribavirin in all animal species in which adequate studies have been conducted, occurring at doses as low as one twentieth of the recommended human dose (see section 5.3).
fl- ispeċi ta ’ annimali kollha li fuqhom saru studji xierqa, b’ dożi baxxi sa ’ frazzjoni ekwivalenti għall waħda f’ għoxrin tad- doża rrakkomandata fil- bniedem (ara sezzjoni 5. 3).
- Genotoxicity:
- Effett tossiku fuq il- ġeni:
Ribavirin induces genotoxicity (see section 5.3).
Ribavirin jikkawża effett tossiku fuq il- ġeni (ara sezzjoni 5. 3).
Rebetol must not be used by females who are pregnant (see sections 4.3, 4.4 and 5.3).
Rebetol m’ għandux jintuża minn nisa waqt it- tqala (ara sezzjonijiet 4. 3 u 4. 4 u 5. 3).
Extreme care must be taken to avoid pregnancy in female patients.
Għandha tingħata attenzjoni kbira biex it- tqala tkun evitata f’ pazjenti nisa.
Rebetol therapy must not be initiated until a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy.
It- terapija b’ Rebetol m’ għandhiex tinbeda qabel ma jinkiseb riżultat negattiv ta ’ test tat- tqala preċiż qabel tinbeda t- terapija.
Females of childbearing potential and their partners must each use an effective contraceptive during treatment and for four months after treatment has been concluded; routine monthly pregnancy tests must be performed during this time (see section 4.4).
Nisa li jista ’ jkollhom it- tfal u s- sieħeb tagħhom, għandhom it- tnejn jużaw mezzi kontraċettivi effettivi waqt il- kura u għal erba ’ xhur wara li l- kura tkun spiċċat; testijiet tat- tqala ta ’ rutina kull xahar għandhom isiru matul dan iż- żmien (ara sezzjoni 4. 6).
If pregnancy does occur during treatment or within four months from stopping treatment, the patient must be advised of the significant teratogenic risk of ribavirin to the foetus.
Jekk it- tqala sseħħ waqt il- kura, jew sa erba ’ xhur wara li l- kura tkun twaqqfet, il- pazjenta għandha tkun infurmata bir- riskju teratoġeniku sinifikanti ta ’ ribavirin għall- fetu.
Male patients and their female partners:
Pazjenti irġiel u nisa sieħba tagħhom:
Extreme care must be taken to avoid pregnancy in partners of male patients taking Rebetol (see sections 4.3, 4.4 and 5.3).
Għandha tingħata attenzjoni kbira biex it- tqala tkun evitata fis - sieħba ta ’ pazjenti irġiel li jkunu qed jieħdu Rebetol (ara sezzjonijiet 4. 3, 4. 4 u 5. 3).
Ribavirin accumulates intracellularly and is cleared from the body very slowly.
Ribavirin jakkumula fiċ- ċelluli u jitneħħa mill- ġisem bil- mod ħafna.
It is unknown whether the ribavirin that is contained in sperm will exert its potential teratogenic or genotoxic effects on the human embryo/foetus.
Mhux magħruf jekk dak ir- ribavirin li jinsab fl- isperma jeżerċitax l- effetti teratoġeniċi jew dawk tossiċi fuq il- ġeni fuq l- embriju/ fetu tal- bniedem.
Although data on approximately 300 prospectively followed pregnancies with paternal exposure to ribavirin have not shown an increased risk of malformation compared to the general population, nor any specific pattern of malformation, male patients and their female partners of childbearing age must be counseled to each use an effective contraceptive during treatment with Rebetol and for seven months after treatment Men whose partners are pregnant must be instructed to use a condom to minimise delivery of ribavirin to the partner.
Għalkemm tagħrif minn madwar 300 tqala b’ missirijiet li ġew esposti għal ribavirin li kienu segwiti b’ mod
It is not known whether ribavirin is excreted in human milk.
Mhuwiex magħruf jekk ribavirin joħroġx mal- ħalib tal- omm.
Because of the potential for adverse reactions in nursing infants, nursing must be discontinued prior to initiation of treatment.
Minħabba l- potenzjal ta ’ reazzjonijiet avversi fit- trabi li jkunu qed jerdgħu, it- treddigħ għandu jitwaqqaf qabel tinbeda l- kura.
Rebetol has no or negligible influence on the ability to drive and use machines; however, peginterferon alfa-2b or interferon alfa-2b used in combination may have an effect.
Rebetol m’ għandu l- ebda effett, jew ftit li xejn għandu effett fuq il- ħila biex issuq u tħaddem magni; madankollu, peginterferon alfa- 2b jew interferon alfa- 2b użati b’ mod kombinat għandu mnejn ikollhom effett.
Thus, patients who develop fatigue, somnolence, or confusion during treatment must be cautioned to avoid driving or operating machinery.
Għalhekk, pazjenti li jiżviluppaw għeja kbira, ħedla, jew konfużjoni waqt il- kura għandhom ikunu avżati biex jevitaw li jsuqu jew li jħaddmu l- magni.
10 The safety of Rebetol capsules is evaluated from data from three clinical trials in patients with no previous exposure to interferon (interferon-naïve patients): two trials studied Rebetol in combination with interferon alfa-2b, one trial studied Rebetol in combination with peginterferon alfa-2b.
Is- sigurtà ta ’ Rebetol hija evalwata minn informazzjoni minn tliet studji kliniċi f’ pazjenti li ma kellhom l- ebda esponiment għal interferon qabel (pazjenti naïve b’ interferon): żewġ provi studjaw Rebetol flimkien ma ’ interferon alfa- 2b, fi prova waħda sar studju b’ Rebetol flimkien ma ’ peginterferon alfa- 2b.
Patients who are treated with interferon alfa-2b and ribavirin after previous relapse from interferon therapy or who are treated for a shorter period are likely to have an improved safety profile than that described below.
Il- pazjenti kkurati b’ interferon alfa- 2b u ribavirin wara li rkadew minn terapija b’ interferon jew li huma kkurati għal perijodu iqsar x’ aktarx li jkollhom profil ta ’ sigurtà itjeb minn dak li huwa deskritt hawn taħt.
The adverse reactions listed in Table 4 are based on experience from clinical trials in adult naïve patients treated for 1 year and post-marketing use.
Ir- reazzjonijiet avversi elenkati f’ Tabella 4 huma bbażati fuq esperjenza minn provi kliniċi f’ pazjenti adulti naive ikkurati għal sena u użu ta ’ wara t- tqegħid fis- suq.
A certain number of adverse reactions, generally attributed to interferon therapy but that have been reported in the context of hepatitis C therapy (in combination with ribavirin) are also listed for reference in Table 4.
Ċertu numru ta ’ reazzjonijiet avversi, ġeneralment marbuta ma ’ terapija b’ interferon iżda li kienu rrappurtati fil- kuntest tat- terapija b’ epatite C (flimkien ma ’ ribavirin) huma ukoll murija f’ Tabella 4.
Also, refer to peginterferon alfa-2b and interferon alfa-2b SPCs for adverse reactions that may be attributable to interferon monotherapy.
Minbarra hekk, irreferi għall- SPC’ s ta ’ peginterferon alfa- 2b u interferon alfa- 2b għar- reazzjonijiet avversi li jistgħu jiġu attribwiti għal monoterapija b’ interferon.
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); uncommon (≥1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known.
Fost il- klassijiet tas- sistema ta ’ l- organi, l- effetti avversi huma mniżżla skond il- frekwenza permezz tal- kategoriji li ġejjin: komuni ħafna (≥1/ 10); komuni (≥1/ 100 sa < 1/ 10); mhux komuni (≥1/ 1, 000 sa < 1/ 100); rari (≥ 1/ 10, 000 sa < 1/ 1, 000); rari ħafna (< 1/ 10, 000); mhux magħruf.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa huma mniżżla skond kemm huma serji, l- ewwel l- aktar serji.
Adverse reactions reported during clinical trials or following the marketing use of Rebetol with pegylated interferon alfa-2b or interferon alfa-2b injection
Reazzjonijiet avversi rrapurtati waqt provi kliniċi jew wara l- użu ta ’ wara t- tqegħid fis - suq ta ’ Rebetol ma ’ interferon alfa- 2b pegilat jew injezzjoni ta ’ interferon alfa- 2b.
System Organ Class and infestations
Sistema tal- klassifika tal- organi
Very common:
Infezzjonijiet u infestazzjonijiet Komuni ħafna:
Viral infection, pharyngitis Fungal infection, otitis media, herpes simplex, urinary tract infection
Infezzjonijiet virali, farinġite Infezzjoni bil- fungu, otitis media, herpes simplex, infezzjoni fil- passaġġ ta ’ l- awrina
Pneumonia*
Pnewmonja *
Common:
Neoplażmi beninni, malinni u dawk mhux speċifikati (inklużi ċisti u polipi) Komuni:
Neoplasm unspecified
Neoplażmi mhux speċifikati
Anaemia, neutropenia Thrombocytopenia, lymphadenopathy, lymphopenia Aplastic anaemia* Pure red cell aplasia, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura
11 idjopatika, purpura tromboċitopenika trombotika
Endocrine disorders
Disturbi fis- sistema tal- endokrini
Sarcoidosis* Vogt-Koyanagi-Harada syndrome, systemic lupus erythematosus, rheumatoid arthritis (new or aggravated), vasculitis, acute hypersensitivity reactions including urticaria, angioedema, bronchoconstriction, anaphylaxis
Sarkojdożi * Sindrome ta ’ Vogt- Koyanagi- Harada, lupus erythematosus sistemiku, arthrite rewmatika (toħroġ mill- ġdid jew taggrava), vaskulite, reazzjonijiet ta ’ sensittività eċċessiva inkluża urtikarja, anġjo- edema, bronkokostrizzjoni, anafilassi
Hypothyroidism, hyperthyroidism Diabetes
Ipotajrojdiżmu, ipertajrojdiżmu Dijabete
Hyperglycaemia, hyperuricaemia, hypocalcaemia, dehydration, increased appetite, thirst
Anoressija Ipergliċemija, iperuriċemija, ipokalċemija, deidrazzjoni, żieda fl- aptit, għatx
Hypertriglyceridemia*
Ipertrigliċeridimja *
Depression, insomnia, anxiety, emotional lability Suicidal ideation, psychosis, aggressive behaviour, confusion, agitation, nervousness, sleep disorder, abnormal dreaming, abnormal crying, apathy, decreased libido
Dipressjoni, insomnja, ansjetà, burdati emozzjonali Ħsibijiet ta ’ suwiċidju, psikożi, imġieba aggressiva, konfużjoni, aġitazzjoni, nervosità, disturbi ta ’ l- irqad, ħolm anormali, biki anormali, apatija, tnaqqis fil- libido
Suicide* Mental status change
Attentati ta ’ suwiċidju Alluċinazzjoni Suwiċidju * Bidla fl- istat mentali
Headache, dizziness, dry mouth, concentration impaired Ataxia, tremor, paresthaesia, dysphonia, taste loss, hypoaesthesia, hyperaesthesia, somnolence, migraine, hypertonia, dysgeusia
Ataksja, tregħid, paraesteżija, disfonija, telf tat- togħma, ipoesteżija, iperesteżija, ngħas, emigranja, ipertonija, diffikulta` biex tibla ’
Seizure (convulsion)*, peripheral neuropathy* Cerebrovascular haemorrhage*, cerebrovascular ischaemia*, encephalopathy*, polyneuropathy*
Aċċessjoni (konvulżjoni) *, newropatija periferali * Emorraġija ċerebrovaskulari *, iskemija ċerebrovaskulari *, enċefalopatija *, polinewropatija *
Facial palsy, neuropathies (including mononeuropathies)
Paraliżi tal- wiċċ, newropatiji (inklużi mononwropatiji)
Blurred vision, conjunctivitis, eye pain, abnormal vision, lacrimal gland disorder
Vista imċajpra, konġunktivite, uġigħ fl- għajnejn, vista anormali, disturbi fil- glandola tad- dmugħ
Retinal haemorrhages*, retinopathies (including macular oedema)*, retinal artery obstruction*, retinal vein obstruction*, optic neuritis*, papilloedema*, loss of visual acuity or visual field*, cotton wool spots*
Emorraġiji tar- retina *, retinopatiji (inkluża edema makulari) *, imblukkar ta ’ l- arterja tar- retina *, imblukkar tal - vina tar- retina *, newrite ottika *, papillo- edema *, telf ta ’ l - akutezza tal- vista jew tal- medda viżiva *, dbabar bħal tajjar *
Ear and labyrinth disorders
Disturbi fil- widnejn u fis- sistema labirintika Komuni:
Vertigo, hearing impairment/loss, tinnitus, earache
Vertigo, smigħ jiddgħajjef/ jintilef, tinnitus, uġigħ fil - widnejn
Palpitation, tachycardia Cardiomyopathy*, arrhythmia* Myocardial infarction*, cardiac ischaemia*
Palpitazzjonijiet, takikardija Kardjomijopatija *, arritmija * Infart mijokardijaku *, iskemija kardijaka *
Vascular disorders Common:
Komuni:
Respiratory, thoracic and mediastinal disorders
Pressjoni baxxa, pressjoni għolja, sinkope, fwawar Iskemija periferika *
Hypotension, hypertension, syncope, flushing Peripheral ischaemia*
Disturbi respiratorji, toraċiċi u medjastinali Komuni ħafna:
Very common:
Dispneja, sogħla
Dyspnoea, coughing Sinusitis, bronchitis, epistaxis, rhinitis, respiratory disorder, nasal congestion, rhinorrhea, nonproductive cough
Sinużite, bronkite, epistassi, flissjoni, disturb respiratorju, konġestjoni nażali, rajnorreja, sogħla fil- vojt
Pulmonary infiltrates*, pneumonitis*, interstitial pneumonitis*
Disturbi gastro- intestinali
Gastro-intestinal disorders
Infiltrati pulmonari *, pnewmonite *, pnewmonite fl - interstizzju *
Diarrhoea, vomiting, nausea, abdominal pain Ulcerative stomatitis, stomatitis, colitis, upper right quadrant pain, dyspepsia, gastroesophogeal reflux*, glossitis, gingival bleeding, gingivitis, loose stools, constipation, flatulence
Dijarea, rimettar, dardir, uġigħ ta ’ żaqq Stomatite ulċerattiva, stomatite, kolite, uġigħ ta ’ żaqq fil - kwadrant ta ’ fuq fin- naħa tal- lemin, dispepsja, ittella ’ mill - istonku *, glossite, fsada fil- ħanek, ġinġivite, ippurgar maħlul, stitikezza, gass fl- istonku
Not Known:
Mhux magħruf:
Pancreatitis* Ischaemic colitus*, ulcerative colitus* Periodontal disorder, dental disorder
Pankrejatite * Kolite iskemika *, kolite ulċerattiva * Disturbi paradentali, disturbi fis- snien
Hepatomegaly, jaundice, hyperbilirubinemia* Hepatotoxicity (including fatalities)*
Fwied kbir, suffejra, iperbilirubinimja * Epatotossiċità (inklużi imwiet) *
Alopecia, pruritus, skin dry, rash Psoriasis, aggravated psoriasis, eczema, photosensitivity reaction, maculopapular rash, erythematous rash, dermatitis, acne, furunculosis*, erythema, skin disorder, bruise, sweating increased, abnormal hair texture, nail disorder* 12
Alopeċja, ħakk, ġilda xotta, raxx Psorajiżi, psorajiżi taggrava, ekżema, reazzjoni ta ’ fotosensittività, raxx makulopapulari, raxx ħamrani, dermatite, akne, furunkulożi *, eritema, disturbi tal- ġilda, tbenġil, żieda fl- għaraq, għamla tax- xagħar anormali, disturbi fid- dwiefer *
Stevens Johnson syndrome*, toxic epidermal necrolysis*, erythema multiforme*
Disturbi muskolu- skeltrali u tal- connective tissue
Musculoskeletal and connective tissue disorders
Sindrome ta ’ Stevens Johnson *, nekroliżi tossika tal- ġilda *, erythema multiforme *
Arthralgia, myalgia, musculoskeletal pain Arthritis Rhabdomyolysis*, myositis*
Artralġja, mijalġja, uġigħ muskolu- skeletrali Artrite Rabdomajoliżi *, myożite *
Renal and urinary disorders Common:
Komuni:
Micturition frequency, polyuria Renal failure*, renal insufficiency* Nephrotic syndrome*
Disturbi fis- sistema riproduttiva u fis- sider
Reproductive system and breast disorders
Frekwenza ta ’ l- awrina, awrina tiżdied Indeboliment tal- kliewi *, insuffiċjenza tal- kliewi * Sindrome nefrotika *
Female: amenorrhea, menorrhagia, menstrual disorder, dysmenorrhea, breast pain, ovarian disorder, vaginal disorder.
Mara: amenorreja, menorraġja, disturbi mestruwali, dismenorreja, uġigħ fis- sider, disturbi fl- ovarji, disturb vaġinali.
Male: impotence, prostatitis Sexual dysfunction (not specified)*
Raġel: impotenza, prostatite Disfunzjoni sesswali (mhux speċifikata) *
Injection site inflammation, injection site reaction, fatigue, rigors, fever, flu-like symptoms, asthenia, irritability
Infjammazzjoni tas- sit mnejn tingħata l- injezzjoni, reazzjoni tas- sit ta ’ l- injezzjoni, għeja, tertir ta ’ bard, deni, sintomi bħal ta ’ l- influwenza, astenija, irritabilità
Chest pain, peripheral oedema, malaise, injection site pain, face oedema*
Uġigħ tas- sider, edema periferali, tħossok ma tiflaħx, uġigħ fis- sit ta ’ l- injezzjoni, edema fil- wiċċ *
Injection site necrosis
Nekrożi tas- sit ta ’ l- injezzjoni
Weight decrease Cardiac murmur, urine abnormal
Tnaqqis tal- piż Ħsejjes fil- qalb, awrina anormali
* Since ribavirin is always prescribed with an alpha interferon product, and the listed adverse drug reactions included reflecting post-marketing experience do not allow precise quantification of frequency, the frequency reported above is from clinical trials using ribavirin in combination with interferon alfa-2b (pegylated or nonpegylated).
* Minħabba li ribavirin dejjem jiġi ordnat ma ’ prodott alfa interferon, u r- reazzjonijiet avversi tal- mediċina elenkati li kienu inklużi kienu jirriflettu esperjenza ta ’ wara t- tqegħid fis- suq li ma tippermettix li tiġi kwantifikata b’ mod preċiż il- frekwenza,
A reduction in haemoglobin concentrations by > 4 g/dl was observed in 30% of patients treated with Rebetol and peginterferon alfa-2b and 37% of patients treated with Rebetol + interferon alfa-2b.
Tnaqqis fil- konċentrazzjonijiet ta ’ l- emoglobina b ’ > 4 g/ dl kien osservat fi 30% tal- pazjenti kkurati b’ Rebetol u peginterferon alfa- 2b u f’ 37% tal- pazjenti kkurati b’ Rebetol + interferon alfa- 2b.
Haemoglobin levels dropped below 10 g/dl in up to 14% of adult patients and 7% of children and adolescents treated with Rebetol in combination with either peginterferon alfa-2b (adults only) or interferon alfa-2b.
Il- livelli ta ’ l- emoglobina niżlu għal inqas minn 10 g/ dl f’ 14% tal- pazjenti adulti u 7% ta ’ tfal u adolexxenti kkurati b’ Rebetol flimkien ma ’ peginterferon alfa- 2b (adulti biss) jew ma ’ interferon alfa- 2b.
Most cases of anaemia, neutropaenia, and thrombocytopaenia were mild (WHO grades 1 or 2).
Il- biċċa l- kbira tal- każijiet ta ’ anemija, newtropenja, u tromboċitopenija kienu ħfief (gradi tal- WHO ta ’ 1 jew 2).
There were some cases of more severe neutropenia in patients treated with Rebetol in combination with peginterferon alfa-2b (WHO grade 3:
Kien hemm xi każijiet ta ’ newtropenja aktar severa f’ pazjenti kkurati b’ Rebetol flimkien ma ’ peginterferon alfa- 2b (grad tal- WHO 3:
39 of 186 [21%]; and WHO grade 4:
39 minn 186 [21%]; u grad 4 tal- WHO:
13 of 186 [7%]); WHO grade 3 leukopenia was also reported in 7% of this treatment group.
Lewkopinja ta ’ grad 3 tal- WHO kien ukoll rappurtat f’ 7% ta ’ dan il- grupp ta ’ kura.
An increase in uric acid and indirect bilirubin values associated with haemolysis was observed in some patients treated with Rebetol used in combination with peginterferon alfa-2b or interferon alfa-2b in clinical trials, but values returned to baseline levels by four weeks after the end of therapy.
Żieda fil- uric acid u valuri indiretti ta ’ bilirubin assoċjati ma ’ ħemoliżi kienet osservata f’ xi pazjenti kurati b’ Rebetol użat flimkien ma ’ peginterferon alfa- 2b jew interferon alfa- 2b fi provi kliniċi, iżda il - valuri marru lura għal dawk tal- livelli fil- linja bażi wara erba ’ ġimgħat minn meta ntemmet it- terapija.
Among those patients with elevated uric acid levels, very few patients treated with the combination developed clinical gout, none of which required treatment modification or discontinuation from the clinical trials.
Fost dawk il- pazjenti b’ livelli ta ’ uric acid għoji, kien hemm numru żgħir ħafna ta ’ pazjenti li kienu kkurati bil- kombinazzjoni żviluppaw gotta, u ħadd minnhom ma kellu bżonn tibdil fil- kura jew twaqqif mill- provi kliniċi.
For HCV/HIV co-infected patients receiving Rebetol in combination with peginterferon alfa-2b, other undesirable effects (that were not reported in mono-infected patients) which have been reported in the studies with a frequency > 5% were: oral candidiasis (14%), lipodystrophy acquired (13%), CD4 lymphocytes decreased (8%), appetite decreased (8%), gamma-glutamyltransferase increased (9%),
Pazjenti infettati fl- istess ħin b’ HCV/ HIV Għall- pazjenti nfettati fl- istess ħin b’ HCV/ HIV li qed jirċievu Rebetol f’ kombinazzjoni ma ’ peginterferon alfa- 2b, effetti oħra mhux mixtieqa (li ma kienux irrappurtati f’ pazjenti b’ infezzjoni waħda) li kienu rrappurtati fl- istudji b’ frekwenza ta ’ > 5% kienu: kandidijażi orali (14%), lipodistrofija akkwiżita (13%), tnaqqis fil- limfoċiti CD4 (8%), tnaqqis fl- aptit (8%), żieda tal - gamma- glutamyltransferase (9%), uġigħ fid- dahar (5%), żieda ta ’ l- amylase fid- demm (6%), żieda tal- lactic acid fid- demm (5%), epatite ċitolitika (6%), żieda tal- lipase (6%) u uġigħ fir- riġel (6%).
Mitochondrial toxicity:
Tossiċità mitokondrijali:
Mitochondrial toxicity and lactic acidosis have been reported in HIV-positive patients receiving NRTI regimen and associated-ribavirin for co-HCV infection (see section 4.4).
Tossiċità mitokondrijali u aċidożi lattika kienu rrappurtati f’ pazjenti pożittivi għall- HIV li kienu qed jirċievu kors ta ’ NRTI flimkien ma’ ribavarin għall- infezzjoni fl- istess ħin b’ HCV (ara sezzjoni 4. 4).
Laboratory values for HCV/HIV co-infected patients:
Valuri tal- laboratorju għall- pazjenti nfettati fl- istess ħin b’ HCV/ HIV:
Although haematological toxicities of neutropenia, thrombocytopenia and anaemia occurred more frequently in HCV/HIV co-infected patients, the majority could be managed by dose modification and rarely required premature discontinuation of treatment (see section 4.4).
Għalkemm tossiċitajiet ħematoloġiċi ta ’ newtropenja, tromboċitopenja u anemija seħħew b’ mod aktar frekwenti f’ pazjenti li kellhom fl- istess ħin infezzjoni b’ HCV/ HIV, il- parti l- kbira setgħu ikunu maniġġjati b’ tibdil fid- doża u rari kellhom bżonn iwaqqfu l- kura aktar kmieni (ara sezzjoni 4. 4).
Haematological abnormalities were more frequently reported in patients receiving Rebetol in combination with peginterferon alfa-2b when compared to patients receiving Rebetol in combination with interferon alfa-2b.
Anormalitajiet ħematoloġiċi kienu rrappurtati b’ mod aktar frekwenti f’ pazjenti li kienu qed jirċievu Rebetol f’ kombinazzjoni ma ’ peginterferon alfa- 2b meta mqabbla ma ’ pazjenti li kienu qed jirċievu Rebetol f’ kombinazzjoni ma ’ interferon alfa- 2b.
In Study 1 (see section 5.1), decrease in absolute neutrophil count levels below 500 cells/mm3 was observed in 4% (8/194) of patients and decrease in platelets below 50,000/mm3 was observed in 4% (8/194) of patients receiving Rebetol in combination with peginterferon alfa-2b.
Fi studju 1 (ara sezzjoni 5. 1) tnaqqis fl- għadd assolut tan- newtrofili taħt il- 500 ċellula/ mm3 dehru f’ 4% (8/ 194) tal- pazjenti u tnaqqis fl- għadd tal- plejtlits għal taħt 50, 000/ mm3 deher f’ 4% (8/ 194) tal- pazjenti li kienu qed jirċievu Rebetol f’ kombinazzjoni ma ’ peginterferon alfa- 2b.
Anaemia (haemoglobin < 9.4 g/dl) was reported in 12% (23/194) of patients treated with Rebetol in combination with peginterferon alfa-2b.
Anemija (ħemoglobina < 9. 4 g/ dl) kienet irrappurtata fi 12% (23/ 194) tal - pazjenti kkurati b’ Rebetol f’ kombinazzjoni ma ’ peginterferon alfa- 2b.
Treatment with Rebetol in combination with peginterferon alfa-2b was associated with decreases in absolute CD4+ cell counts within the first 4 weeks without a reduction in CD4+ cell percentage.
Kura b’ Rebetol f’ kombinazzjoni ma ’ peginterferon alfa- 2b kienet assoċjata ma ’ tnaqqis fl- għadd assolut ta ’ ċelluli CD4+ fl- ewwel 4 ġimgħat mingħajr tnaqqis fil- perċentwali taċ- ċelluli CD4+.
The decrease in CD4+ cell counts was reversible upon dose reduction or cessation of therapy.
It - tnaqqis fl- għadd ta ’ ċelluli CD4+ kien riversibbli bi tnaqqis tad- doża jew twaqqif tat- terapija.
The use of Rebetol in combination with peginterferon alfa-2b had no observable negative impact on the control of HIV viraemia during therapy or follow-up.
L- użu ta ’ Rebetol f’ kombinazzjoni ma ’ peginterferon alfa- 2b ma deherx li kellu impatt negattiv fuq il - kontroll ta ’ virimja bl- HIV waqt it- terapija jew fiż- żmien ta ’ follow up.
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 Rebetol in combination with peginterferon alfa-2b.
Jekk jogħġbok irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott tal- prodotti mediċinali antiretrovirali li jkollhom jittieħdu fl- istes ħin ma ’ terapija HCV għall- għarfien u maniġġjar tat - tossiċitajiet speċifiċi għal kull prodott u l- potenzjal li jista ’ jkun hemm tossiċitajiet f’ daqqa b ’ Rebetol f’ kombinazzjoni ma ’ peginterferon alfa- 2b.
Children and adolescents:
14 Tfal u adolexxenti:
In clinical trials of 118 children or adolescents 3 to 16 years of age, 6% discontinued therapy due to adverse events.
Fi provi kliniċi b’ 118 tifel u tifla jew adolexxenti ta ’ età minn 3 sa 16- il sena, 6% waqqfu t- terapija minħabba effetti 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 ’ l- effetti avversi fil- popolazzjoni pedjatrika limitata li kienet studjata kien simili għal dak li ġie osservat fl- adulti, għalkemm l- inibizzjoni ta ’ żvilupp hija ta ’ tħassib speċifiku għall- popolazzjoni pedjatrika, peress li tnaqqis fit- tul (tnaqqis medju perċentwali tar- rata ta ’ tkabbir b’ 9%) u piż (tnaqqis medju perċentwali ta ’ 13%) perċentwali kienu osservati waqt il- kura (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.
Minbarra hekk, każijiet ta ’ fissazzjoni ta ’ suwiċidju jew attentati ta ’ suwiċidju kienu rrappurtati b’ mod aktar frekwenti meta mqabbla mal- pazjenti adulti (2. 4% vs 1%) waqt il- kura u fis- 6 xhur ta ’ wara l- kura.
As in adult patients, children and adolescents also experienced other psychiatric adverse events (e.g., depression, emotional lability, and somnolence) (see section 4.4).
Bħalma ġralhom il- pazjenti adulti, it- tfal u l - adolexxenti kellhom ukoll effetti psikjatriċi oħra (eż dipressjoni, burdati emozzjonali u tħeddil) (ara sezzjoni 4. 4).
In addition, injection site disorders, fever, anorexia, vomiting, and emotional lability occurred more frequently in children and adolescents compared to adult patients.
Kien hemm ukoll reazzjonijiet mnejn ingħatat l- injezzjoni, deni, anoressja, rimettar u burdati emozzjonali b’ mod aktar frekwenti fit- tfal u fl- adolexxenti 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 newtropenija.
Reported adverse reactions listed in Table 5 are based on experience from paediatric clinical trials.
Reazzjonijiet avversi elenkati f’ Tabella 5 huma ibbażati fuq esperjenza minn provi kliniċi pedjatriċi.
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).
Fost il- klassijiet tas- sistemi ta ’ organi, reazzjonijiet avversi huma elenkati taħt it- titli ta ’ frekwenza permezz tal- kategoriji li ġejjin: komuni ħafna (≥1/ 10); komuni (≥1/ 100 sa < 1/ 10).
Adverse reactions very commonly and commonly reported during clinical trials of Rebetol with interferon alfa-2b injection in paediatric patients
Reazzjonijiet avversi irrappurtati b’ mod komuni ħafna jew komuni waqt provi kliniċi b’ Rebetol ma ’ injezzjoni ta ’ interferon alfa- 2b f’ pazjenti pedjatriċi.
System Organ Class
Klassi tas- Sistema ta ’ l- Organi
Viral infection, pharyngitis Fungal infection, bacterial infection, pulmonary infection,
Infezzjoni virali, farinġite Infezzjoni tal- fungu, infezzjoni tal- batteri, infezzjoni pulmonari, otitis media, snien jitħaffru, herpes simplex, infezzjoni fil- passaġġ ta’ l- awrina, vaġinite, gastroenterite
otitis media, tooth abscess, herpes simplex, urinary tract infection, vaginitis, gastroenteritis Neoplasms benign, malignant and unspecified (including cysts and polyps) Common:
Neoplażmi beninni, malinni u dawk mhux speċifikati (inklużi ċesti u polipi) Komuni:
Neoplasm unspecified
Neoplasmi mhux speċifikati
Anaemia, neutropenia Thrombocytopenia, lymphadenopathy
Anemija, newtropenija Tromboċitopenja, limfadenopatija
Hypothyroidism Hyperthyroidism, virilism
Ipotajrojdiżmu Ipertajrojdiżmu, viriliżmu
Anorexia Hypertriglyceridemia, hyperuricemia, increased appetite
Anoressija Ipertrigliċeridemija, iperuriċemija, żieda fl- aptit
Depression, insomnia, emotional lability Suicidal ideation, aggressive reaction, confusion, behaviour disorder, agitation, somnambulism, anxiety, nervousness, sleep disorder, abnormal dreaming, apathy
Dipressjoni, insomnja, burdati emozzjonali Ħsibijiet dwar suwiċidju, reazzjoni aggressiva, konfużjoni, disturbi fl- imġieba, aġitazzjoni, sonnambuliżmu, ansjetà, nervi, disturbi ta ’ l- irqad, ħolm anormali, apatija
Headache, dizziness Hyperkinesia, tremor, dysphonia, paresthaesia, hypoaesthesia, hyperaesthesia, concentration impaired, somnolence
Uġigħ ta ’ ras, sturdament Iperkinesja, tregħid, disfonja, paraesteżija, ipoesteżija, tiddgħajjef il- konċenrazzjoni, ngħas
Conjunctivitis, eye pain, abnormal vision, lacrimal gland disorder
Konġuntivite, uġigħ fl- għajnejn, vista anormali, disturbi fil - glandola tad- dmugħ
Raynaud’s disease, flushing, pallor
Marda ta ’ Raynaud’ s, fwawar, issir pallidu
Gastro-intestinal disorders
Qtugħ
Dyspnoea, tachypnea, epistaxis, coughing, nasal congestion, nasal irritation, rhinorrhea, sneezing
ta ’ nifs, nifs imgħaġġel, epistassi, sogħla, konġestjoni
Very common:
nasali, irritazzjoni nasali, rajnorreja, għatis Disturbi gastro- intestinali Komuni ħafna:
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, rimettar, dardir, uġigħ addominali Ulċera fil- ħalq, stomatite b’ ulċera, stomatite, uġigħ fil - kwadrant ta ’ fuq tal- lemin, dispepsja, glossite, ittella ’ mill - istonku, disturbi fir- rektum, disturbi gastro- intestinali, stitikezza, ippurgar maħlul, uġigħ tas- snien, disturbi fis - snien
Very common:
Disturbi fil- ġilda u fit- tessuti 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, akne, disturbi tal- ġilda, disturbi fid- dwiefer, il- ġilda titlef il - kulur, ħakk, ġilda xotta, erytema, tbenġil, żieda fl- għaraq
Musculoskeletal and connective tissue disorders Very common:
Disturbi muskolu- skeltrali u tal- connective tissue Komuni ħafna:
Arthralgia, myalgia, musculoskeletal pain
Artralġja, mijalġja, uġigħ muskolu- skeletrali
Enuresis, micturition disorder, urinary incontinence
Enureżi, disturbi biex tgħaddi l- awrina, inkontinenza ta ’ l - awrina
Female: amenorrhea, menorrhagia, menstrual disorder, vaginal disorder, Male: testicular pain
Raġel: uġigħ fit- testikoli
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 tas- sit mnejn tingħata l- injezzjoni, reazzjoni tas- sit ta ’ l- injezzjoni, għeja, tertir, deni, sintomi bħal ta ’ l - influwenza, tħossok ma tiflaħx, irritabilità
Chest pain, asthenia, oedema, injection site pain 15
Uġigħ tas- sider, astenja, edema, uġigħ fis- sit ta ’ l- injezzjoni
Growth rate decrease (height and/or weight decrease for age)
Tnaqqis fir- rata tat- tkabbir (tnaqqis fit- tul u/ jew piż għall - età)
Injury, poisoning and procedural complications
Korriment, avvelenament u komplikazzjonijiet ta ’ Komuni:
Skin laceration
xi proċedura Laċerazzjoni tal- ġilda
In clinical trials with Rebetol used in combination with peginterferon alfa-2b or interferon alfa-2b, the maximum overdose reported was a total dose of 10 g of Rebetol (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’ Rebetol użat flimkien ma ’ peginterferon alfa- 2b jew interferon alfa- 2b, id- doża eċċessiva massima rrappurtata kienet doża totali ta ’ 10 g ta ’ Rebetol (50 kapsula ta ’ 200 mg) u 39 MIU ta ’ interferon alfa- 2b (13 injezzjonijiet taħt il- ġilda ta ’ 3 MIU kull waħda) 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 ta ’ l- emerġenza, u matul dak iż- żmien l- ebda avveniment avvers mid- doża eċċessiva ma kien innutat.
Direct acting antivirals, nucleosides and nucleotides (excl. reverse transcriptase inhibitors), ATC code:
Antivirali li jaġixxu direttament, nuklejosidi u nuklejotidi (ħlief l - impedituri reverse transciptase), Kodiċi ATC:
Ribavirin (Rebetol) is a synthetic nucleoside analogue which has shown in vitro activity against some RNA and DNA viruses.
Ribavirin (Rebetol) huwa analogu sintetiku tan- nuklejosajd li wera attività in vitro kontra xi vajrusis ta ’ l- RNA u d- DNA.
The mechanism by which Rebetol in combination with peginterferon alfa-2b or interferon alfa-2b exerts its effects against HCV is unknown.
Il- mekkaniżmu li bih Rebetol flimkien ma ’ peginterferon alfa- 2b jew interferon alfa- 2b jeżerċita l- effetti tiegħu kontra HCV mhuwiex magħruf.
Oral formulations of Rebetol monotherapy have been investigated as therapy for chronic hepatitis C in several clinical trials.
Formulazzjonijiet orali tal- monoterapija ta ’ Rebetol kienu investigati bħala terapija f’ epatite C kronika f’ diversi provi kliniċi.
Results of these investigations showed that Rebetol 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 ’ dawn l - investigazzjoniet urew li l- monoterapija ta ’ Rebetol ma kellha l- ebda effett fuq l- eliminazzjoni tal- vajrus
Rebetol clinical trials in adults The use of Rebetol in combination treatment with peginterferon alfa-2b or interferon alfa-2b was evaluated in a number of clinical trials.
Studji kliniċi b’ Rebetol fl- adulti L- użu ta ’ Rebetol fil- kura flimkien ma ’ peginterferon alfa- 2b jew interferon alfa- 2b kien evalwat f’ numru 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 C ikkonfermata mil - PCR (> 30 IU/ ml) test pożittiv tal- 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 Rebetol + interferon alfa-2b (C95-132 and I95-143) and one with Rebetol + peginterferon alfa-2b (C/I98-580).
Pazjenti naive Tliet studji eżaminaw l- użu ta ’ interferon f’ pazjenti naive, tnejn b’ Rebetol + interferon alfa- 2b (C95 - 132 u I95- 143) u wieħed b’ Rebetol + peginterferon alfa- 2b (C/ I98- 580).
In all cases the treatment was for one year with a follow-up of six months.
Fil- każijiet kollha, il- kura kienet għal sena b’ follow up ta ’ sitt xhur.
The sustained response at the end of follow-up was significantly increased by the addition of Rebetol to interferon alfa-2b (41% vs 16%, p < 0.001).
Ir- rispons sostnut fit- tmiem tal- follow- up żdied b’ mod sinifikanti biż- żieda ta ’ Rebetol ma ’ interferon alfa- 2b (41% vs 16%, p < 0. 001).
In clinical trials C95-132 and I95-143, Rebetol + interferon alfa-2b combination therapy proved to be significantly more effective than interferon alfa-2b monotherapy (a doubling in sustained response).
Fi studji kliniċi C95- 132 u I95- 143, it- terapija mħallta ta ’ Rebetol + interferon alfa- 2b intweriet li kienet aktar effettiva b’ mod sinifikanti mill- monoterapija ta ’ interferon alfa- 2b (irduppjar fir- rispons sostnut).
Combination therapy also decreased the relapse rate.
It- terapija mħallta 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 ’ l- HCV, b’ mod partikolari għall- 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: • Rebetol (800 mg/day) + peginterferon alfa-2b (1.5 micrograms/kg/week) (n = 511). • Rebetol (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). • Rebetol (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 pazjenti naïve kienu kkurati għal sena b’ wieħed minn dawn il - korsijiet imħallta li ġejjin: • Rebetol (800 mg/ jum) + peginterferon alfa- 2b (1. 5 mikrogrammi/ kg/ ġimgħa) (n = 511). • Rebetol (1, 000/ 1, 200 mg/ jum) + peginterferon alfa- 2b (1. 5 mikrogrammi/ kg/ ġimgħa għal xahar segwiti minn 0. 5 mikrogrammi/ kg/ ġimgħa għal 11- il xahar) (n = 514). • Rebetol (1, 000/ 1, 200 mg/ jum) + interferon alfa- 2b (3 MIU tlett darbiet fil- ġimgħa) (n = 505).
16 In this trial, the combination of Rebetol and peginterferon alfa-2b (1.5 micrograms/kg/week) was significantly more effective than the combination of Rebetol and interferon alfa-2b, particularly in patients infected with Genotype 1.
F’ din il- prova, it- taħlita ta ’ Rebetol u peginterferon alfa- 2b (1. 5 mikrogrammi/ kg/ ġimgħa) kienet aktar effettiva b’ mod sinifikanti mit- taħlita ta ’ Rebetol 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 tal - kura.
HCV genotype and baseline virus load are prognostic factors which are known to affect response rates.
Il- ġenotip ta ’ l- HCV u l- valuri tal- linja bażi tal- viral load huma fatturi ta ’ tbassir li huma magħrufa li jaffettaw ir- rati tar- rispons.
However, response rates in this trial were shown to be dependent also on the dose of Rebetol 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 ’ Rebetol mogħtija flimkien ma ’ peginterferon alfa- 2b jew interferon alfa- 2b.
In those patients that received > 10.6 mg/kg Rebetol (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 Rebetol (Table 6), while response rates in patients that received > 13.2 mg/kg Rebetol were even higher.
F’ dawk il- pazjenti li rċevew > 10. 6 mg/ kg Rebetol (doża ta ’ 800 mg f’ pazjent tipiku ta ’ 75 kg), mingħajr ma jingħata każ tal- ġenotip jew tal- viral load, ir- rati ta ’ rispons kienu ogħla b’ mod sinifikanti milli f’ dawk il- pazjenti li rċevew ≤ 10. 6 mg/ kg ta ’ Rebetol (Tabella 6), filwaqt li r- rati ta ’ rispons f’ pazjenti li rċevew > 13. 2 mg/ kg ta ’ Rebetol kienu aktar għolja.
Table 6
Tabella 6:
Sustained response rates with Rebetol + peginterferon alfa-2b (by Rebetol dose [mg/kg], genotype and viral load)
Rati ta ’ rispons sostnut b’ Rebetol + peginterferon alfa- 2b (skond id- doża ta ’ Rebetol [mg/ kg], ġenotip u viral load)
HCV Genotype
Ġenotip HCV
Rebetol dose (mg/kg)
Doża ta ’ Rebetol (mg/ kg)
P 1.5/R
P 0. 5/ R
P 0.5/R
Il- Ġenotipi
I/R
Kollha
All Genotypes Genotype 1 Genotype 1
Kollha ≤ 10. 6 > 10. 6
All 10.6 10.6 All 10.6 10.6 All
Kollha ≤ 10. 6 > 10. 6
≤ 600,000 IU/ml Genotype 1
Ġenotip 1:
≤ >
45% 33%
10.6 10.6 All
> 10. 6 Kollha ≤ 10. 6
74% 71% 30%
71% 30%
25% 52% 27%
52% 27%
33% 45% 29%
45% 29%
> 600,000 IU/ml Genotype 2/3
> 600, 000 IU/ ml
10.6 10.6 All 10.6 10.6
> 10. 6
P1.5/R P0.5/R I/R
P1. 5/ R P0. 5/ R I/ R
Rebetol (800 mg) + peginterferon alfa-2b (1.5 micrograms/kg) Rebetol (1,000/1,200 mg) + peginterferon alfa-2b (1.5 to 0.5 microgram/kg) Rebetol (1,000/1,200 mg) + interferon alfa-2b (3 MIU)
Rebetol (800 mg /) + peginterferon alfa- 2b (1. 5 mikrogrammi/ kg) Rebetol (1, 000/ 1, 200 mg) + peginterferon alfa- 2b (1. 5 sa 0. 5 mikrogrammi/ kg) Rebetol (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 (based on body weight, only three patients weighing > 105 kg, received the 1,400 mg dose) (Table 7).
Fi prova separata, 224 pazjent b’ ġenotip 2 jew 3 irċevew peginterferon alfa- 2b, 1. 5 mikrogramma/ kg minn taħt il- ġilda, darba fil- ġimgħa, flimkien ma ’ ribavirin bejn 800 mg u 1, 400 mg p. o. għal 6 xhur (bażat fuq il- piż tal- ġisem, kien hemm tlett pazjenti biss li kienu jiżnu > 105 kg, irċevew id- doża ta ’ 1, 400 mg) (Tabella 7).
Twenty-four% had bridging fibrosis or cirrhosis (Knodell 3/4).
Erbgħa u għoxrin% kellhom bridging fibrosis jew ċirrożi (Knodell 3/ 4).
Virologic Response at End of Treatment, Sustained Virologic Response and Relapse by HCV Genotype and Viral Load* Rebetol 800-1,400 mg/day Plus peginterferon alfa-2b 1.5 μg/kg Once Weekly
Rispons Viroloġiku fl- Aħħar tal- Kura, Rispons Viroloġiku Sostnut u dawk li Rkadew b ’ Ġenotip HCV u Viral Load Rebetol 800- 1, 400 mg/ jum Ma ’ peginterferon alfa- 2b 1. 5 μg/ kg Darna fil- Ġimgħa
of Treatment Response
Rispons fl- Aħħar tal - kura
Relapse
Rata ta ’ kemm
All Subjects
irkadew
94
Individwi kollha
* 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.
* Kwalunkwe individwu li kellu livelli ta ’ HCV- RNA li ma setgħux jitkejjlu fiż- żjara tat- 12- il Ġimgħa ta ’ Follow- Up u dejta nieqsa miż- żjara ta ’ l- 24- Ġimgħa ta ’ Follow- up 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.
Kwalunkwe individwu li kellu dejta nieqsa fil - u wara il- perijodu ta ’ 12- il Ġimgħa ta ’ Follow- Up kien meqjus bħala li ma weriex rispons fl- 24 Ġimgħa follow- up.
49%.
Is- sitt xhur ta ’ kura ta ’ din il- prova kienu tollerati aħjar mill- prova pivitali bit- taħlita, għat- twaqqif 5% vs 14%, għal tibdil fid- doża 18% vs 49%.
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 Rebetol.
Fi prova mhux komparattiva, 235 pazjent b’ ġenotip 1 u viral load baxx (< 600, 000 IU/ ml) irċevew peginterferon alfa- 2b, 1. 5 mikrogrammi taħt il- ġilda, darba kuljum, flimkien ma ’ Rebetol aġġustat skond il- piż.
The overall sustained response rate after a 24-week treatment duration was 50%.
Ir- rata globali tar- rispons sostnut wara kura ta ’ 24- ġimgħa kienet 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 ’ l- individwi (97/ 235) kellhom livelli ta ’ HCV- RNA li ma setgħux jitkejjlu mar- 4 Ġimgħa u ma ’ l- 24 Ġimgħa tat- terapija.
In this subgroup, there was a 92% (89/97) sustained virological response rate.
F’ dan is- sottogrupp, kien hemm rata ta ’ 92% (89/ 97) li kellhom 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).
Ir- rata għolja li nkisbet f’ dan is- sottogrupp ta ’ pazjenti ġiet identifikata f’ analiżi li saret waqt li kien għaddej l- istudju (n=49) u kkonfermata b’ mod prospettiv (n=48).