natgillin/translations-raw huggingface dataset:
I undergruppen af patienter med genotype 1 og lav virusmængde (< 600. 000 IE/ ml) som bliver HCV- RNA negative ved behandlingsuge 4 og som stadig er HCV- RNA negative ved uge 24, kan behandlingen enten stoppe efter denne 24 ugers behandlingsperiode eller blive videreført i yderligere 24 uger (dvs. en samlet 48 ugers behandlingsperiode).
In the subset of patients with genotype 1 infection and low viral load (< 600,000 IU/ ml) who become HCV-RNA negative at treatment week 4 and remain HCV-RNA negative at week 24, the treatment could either be stopped after this 24 week treatment course or pursued for an additional 24 weeks (i. e. overall 48 weeks treatment duration).
Patienter inficeret med genotype 4 betragtes generelt som sværere at behandle, og begrænsede undersøgelsesresultater (n=66) tyder på, at de er forenelige med en behandlingsperiode som for genotype 1.
In general, patients infected with genotype 4 are considered harder to treat and limited study data (n=66) indicate they are compatible with a duration of treatment as for genotype 1.
5. 1).
The negative predictive value for sustained response in HCV/ HIV co-infected patients treated with Rebetol in combination with peginterferon alfa-2b was 99% (67/ 68; Study 1) (see section 5.1).
3 En positiv forudsigelig værdi på 50% (52/ 104; Undersøgelse 1) blev observeret for HCV/ HIV co - inficerede patienter, der modtog kombinationsbehandling.
A positive predictive value of 50% (52/ 104; Study 1) was observed for HCV/ HIV co-infected patients receiving combination therapy.
Rebetol kapsler i kombination med interferon alfa- 2b:
Rebetol Capsules in combination with interferon alfa-2b:
Under disse kliniske undersøgelser, i hvilke patienter blev behandlet i et år, var det usandsynligt, at patienter, der ikke viste et virologisk respons efter seks måneders behandling (HCV- RNA under laveste detektionsgrænse), fik vedvarende virologisk respons (HCV - RNA under laveste detektionsgrænse seks måneder efter afbrudt behandling). • Genotype 1:
During those clinical trials in which patients were treated for one year, patients who failed to show a virological response after six months of treatment (HCV-RNA below lower limit of detection) were unlikely to become sustained virological responders (HCV-RNA below lower limit of detection six months after withdrawal of treatment). • Genotype 1:
Behandling bør fortsættes i en periode på yderligere seks måneder (svarende til i alt et år) hos patienter, som udviser negativ HCV- RNA efter seks måneders behandling. • Genotyper non- 1:
Treatment should be continued for another six month period (i. e., a total of one year) in patients who exhibit negative HCV-RNA after six months of treatment. • Genotypes Non-1:
Beslutningen om at forlænge behandling til et år hos patienter med negativ HCV- RNA efter seks måneders behandling bør træffes på grundlag af andre prognostiske faktorer (såsom alder > 40 år, mandligt køn, bridging fibrose).
The decision to extend therapy to one year in patients with negative HCV- RNA after six months of treatment should be based on other prognostic factors (e. g., age > 40 years, male gender, bridging fibrosis).
Børn i alderen 3 år eller ældre samt unge:
Children aged three years and older, and adolescents:
(for patienter som vejer < 47 kg eller som ikke er i stand til at synke kapsler, se venligst produktresume for ribavirin 40 mg/ ml oral opløsning).
(for patients who weigh < 47 kg, or are unable to swallow capsules, please refer to the SPC for ribavirin 40 mg/ ml oral solution).
I kliniske undersøgelser udført i denne population, blev ribavirin og interferon alfa- 2b benyttet i doser af henholdsvis 15 mg/ kg/ dag og 3 MIE/ m2 tre gange ugentligt (Tabel 2).
In clinical studies performed in this population ribavirin and interferon alfa-2b were used in doses of 15 mg/ kg/ day and 3 MIU/ m2 three times a week respectively (Table 2).
Rebetol kapsler skal indtages oralt hver dag fordelt på to doser samtidig med et måltid (morgen og aften).
Rebetol capsules are to be administered orally each day in two divided doses with food (morning and evening).
Rebetol pædiatrisk dosis baseret på kropsvægt
Rebetol paediatric dose based on body weight
Patientvægt (kg) 47 - 49 50 – 65
Patient weight (kg) 47 - 49 50 - 65
Rebetol dosis 600 mg 800 mg
Daily Rebetol dose 600 mg 800 mg
Antal 200 mg kapsler 3 kapsler a 4 kapsler b
Number of 200 mg capsules 3 capsules a 4 capsules b
1 morgen, 2 aften b:
1 morning, 2 b
2 morgen, 2 aften
2 morning, 2
Behandlingsvarighed hos børn og unge Genotype 1:
Duration of treatment in children and adolescents Genotype 1:
Den anbefalede behandlingsvarighed er 1 år.
The recommended duration of treatment is 1 year.
Patienter, som ikke opnår virologisk respons efter 12 uger, har meget lille sandsynlighed for at blive vedvarende virologiske responders (negativ prædiktiv værdi 96%).
Patients who fail to achieve virological response at 12 weeks are highly unlikely to become sustained virological responders (negative predictive value 96%).
Virologisk respons er defineret som fravær af påviselig HCV- RNA efter 12 ugers behandling.
Virological response is defined as absence of detectable HCV-RNA at Week 12 of treatment.
Behandlingen bør afbrydes hos disse patienter.
Treatment should be discontinued in these patients.
Dosisjustering for alle patienter Hvis der udvikles alvorlige bivirkninger eller unormale laboratorieværdier under behandling med Rebetol og peginterferon alfa- 2b eller interferon alfa- 2b, justeres doserne af hvert lægemiddel efter behov, indtil bivirkningerne aftager.
Dose modification for all patients If severe adverse reactions or laboratory abnormalities develop during therapy with Rebetol and peginterferon alfa-2b or interferon alfa-2b, modify the dosages of each product if appropriate, until the adverse reactions abate.
Da bindingsstyrke kan være af betydning for behandlingens udfald, bør dosis holdes så tæt som muligt til den anbefalede standarddosis.
As adherence might be of importance for outcome of therapy, the dose should be kept as close as possible to the recommended standard dose.
Den potentielle negative virkning af nedsættelse af ribavirin dosis på resultater af virkningsgrad kunne ikke udelukkes.
The potential negative impact of ribavirin dose reduction on efficacy results could not be ruled out.
Dosisjusteringsvejledninger Reducer kun Rebetol Reducer kun
Dosage modification guidelines Reduce only Rebetol Reduce only
Afbryd
Discontinue
Laboratorieværdier
Laboratory Values
daglig voksendosis til
daily dose adult to
peginterferon alfa- 2b
peginterferon alfa-2b
kombinations -
combination therapy
600 mg/ dag *,
600 mg/ day*,
(voksen) eller interferon
(adult) or interferon alfa-
behandling, hvis:
if:
pædiatrisk dosis til 7, 5 mg/ kg, hvis:
paediatric to 7.5 mg/ kg, if:
dosis (voksen og pædiatrisk)
2b dose (adult and paediatric)
til halv dosis, hvis:
to one-half dose, if:
Hæmoglobin Voksne:
Haemoglobin Adult:
Hæmoglobin hos: patienter med tidligere stabil hjertesygdom Pædiatrisk: ikke relevant (se pkt.
in: patients with history of stable cardiac disease Paediatric: not applicable (see section 4.4)
4. 4)
≥ 2 g/ dl 4
≥ 2 g/ dl fald i hæmoglobin under en hvilken som helst 4 ugers periode under behandling (permanent dosisreduktion)
decrease in haemoglobin during any week period during treatment (permanent dose reduction)
12 g/ dl efter ugers dosis - reduktion
< 12 g/ dl after 4 weeks of dose reduction
Hvide blodlegemer Neutrofile
White blood cells Neutrophils
Voksne < 50 x 109/ l
Adult < 50 x 109/ l
Voksne < 25 x 109/ l
Adult < 25 x 109/ l
Pædiatrisk < 80 x 109/ l
Paediatric < 80 x 109/ l
Pædiatrisk
Paediatric
Bilirubin – direkte
Bilirubin – Direct
Voksne > 4 mg/ dl Pædiatrisk > 5 mg/ dl (i > 4 uger)
Adult > 4 mg/ dl
Creatinin Alanin aminotransferase / aspartat aminotransferase (ALT/ AST)
Paediatric > 5 mg/ dl (for > 4 weeks)
- -
Creatinine
> 2, 0 mg/ dl 2 x baseline og > 10 x ULN **
> 2.0 mg/ dl
Indtages fordelt på to doser, morgen og aften. ** Øvre grænse for normalområdet
Alanine
Specielle populationer
- -
5. 2).
2
Det anbefales således, at nyrefunktionen vurderes hos alle patienter før initiering af Rebetol.
Therefore, it is recommended that renal function be evaluated in all patients prior to initiation of Rebetol.
4. 3).
Patients with creatinine clearance < 50 ml/ minute must not be treated with Rebetol (see section 4.3).
Personer med nedsat nyrefunktion bør monitoreres mere omhyggeligt af hensyn til udviklingen af anæmi.
Subjects with impaired renal function should be more carefully monitored with respect to the development of anaemia.
Hvis serum creatinin stiger til > 2 mg/ dl (Tabel 3), skal Rebetol og peginterferon alfa- 2b/ interferon alfa- 2b seponeres.
If serum creatinine rises to > 2 mg/ dl (Table 3), Rebetol and peginterferon alfa-2b/ interferon alfa-2b must be discontinued.
Anvendelse ved nedsat leverfunktion:
Use in hepatic impairment:
5. 2).
No pharmacokinetic interaction appears between ribavirin and hepatic function (see section 5.2).
Ingen dosisjustering af Rebetol er således nødvendig hos patienter med nedsat leverfunktion.
Therefore, no dose adjustment of Rebetol is required in patients with hepatic impairment.
Der synes ikke at være en significant aldersrelateret effekt på ribavirins farmakokinetik.
There does not appear to be a significant age-related effect on the pharmacokinetics of ribavirin.
5. 2).
However, as in younger patients, renal function must be determined prior to administration of Rebetol (see section 5.2).
Rebetol som kapsler eller oral opløsning kan bruges i kombination med interferon alfa- 2b til børn (3 år eller ældre) og unge.
Rebetol as capsules or oral solution may be used in combination with interferon alfa-2b in children (3 years of age and older) and adolescents.
4. 1).
The selection of formulation is based on individual characteristics of the patient (see section 4.1).
5 eller andre former for interferon (det vil sige foruden alfa- 2b) hos disse patienter er ikke blevet evalueret.
Safety and effectiveness of Rebetol with pegylated or other forms of interferon (i. e. not alfa-2b) in these patients have not been evaluated.
Patienter med samtidig HCV/ HIV infektion:
Patients co-infected with HCV/ HIV:
4. 4).
Patients taking NRTI treatment in association with ribavirin and interferon alfa-2b or peginterferon alfa-2b may be at increased risk of mitochondrial toxicity, lactic 5 acidosis and hepatic decompensation (see section 4.4).
4. 4, 4. 6 og 5. 3).
- Pregnant women (see sections 4.4, 4.6 and 5.3).
Rebetol må ikke initieres, før et negativt resultat fra en
Rebetol must not be initiated until a report of a
graviditetstest er opnået umiddelbart før behandlingsstart.
negative pregnancy test has been obtained immediately prior to initiation of therapy.
- Kvinder, der ammer.
- Women who are breast-feeding.
- Anamnese med tidligere alvorlig hjertesygdom, inklusive ustabil eller ukontrolleret hjertesygdom, i
- A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease,
4. 4).
in the previous six months (see section 4.4).
- Alvorlige svækkende sygdomstilstande inklusive patienter med kronisk nyreinsufficiens,
- Severe, debilitating medical conditions, including patients with chronic renal failure, patients
patienter med creatinin clearance < 50 ml/ minut og/ eller i hæmodialyse.
with creatinine clearance < 50 ml/ minute and/ or on haemodialysis.
- Alvorligt nedsat leverfunktion eller ikke- kompenseret levercirrose.
- Severe hepatic dysfunction or decompensated cirrhosis of the liver.
- Hæmoglobinopatier (for eksempel thalassemia, seglcelleanæmi).
- Haemoglobinopathies (e. g., thalassemia, sickle-cell anaemia).
- Initiering af peginterferon alfa- 2b er kontraindiceret i HCV/ HIV patienter med cirrhose og en
- Initiation of peginterferon alfa-2b is contraindicated in HCV/ HIV patients with cirrhosis and a
Child- Pugh score ≥ 6.
Child-Pugh score ≥ 6.
- Eksisterende eller tidligere alvorlig psykiatrisk lidelse, især alvorlig depression, selvmordstanker
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal
eller selvmordsforsøg.
ideation, or suicide attempt.
På grund af samtidig indgift af peginterferon alfa- 2b eller interferon alfa- 2b:
Because of co-administration with peginterferon alfa-2b or interferon alfa-2b:
- Autoimmun hepatitis eller tidligere autoimmun sygdom.
- Autoimmune hepatitis; or history of autoimmune disease.
Alvorlig CNS- påvirkning, særlig depression, selvmordstanker og selvmordsforsøg, er set hos nogle patienter under Rebetol kombinationsbehandling med peginterferon alfa- 2b eller interferon alfa- 2b, og selv efter behandlingsophør især under 6- måneders opfølgningsperioden.
Severe CNS effects, particularly depression, suicidal ideation and attempted suicide have been observed in some patients during Rebetol combination therapy with peginterferon alfa-2b or interferon alfa-2b, and even after treatment discontinuation mainly during the 6-month follow-up period.
Blandt børn og unge, behandlet med Rebetol i kombination med interferon alfa- 2b, blev selvmordstanker eller - forsøg rapporteret oftere end hos voksne patienter (2, 4% mod 1%) under behandling og under den 6- måneders opfølgning efter behandling.
Among children and adolescents, treated with Rebetol in combination with interferon alfa-2b, suicidal ideation or attempts were reported more frequently compared to adult patients (2.4% versus 1%) during treatment and during the 6-month follow-up after treatment.
Andre CNS virkninger inklusive aggressiv opførsel (sommetider rettet mod andre), forvirring og ændret mental tilstand er blevet set med alfa interferoner.
Other CNS effects including aggressive behaviour (sometimes directed against others), confusion and alterations of mental status have been observed with alpha interferons.
Hvis psykiatriske symptomer vedvarer eller forværres, eller selvmordstanker identificeres, anbefales det, at behandling med Rebetol og peginterferon alfa- 2b eller interferon alfa- 2b afbrydes, og at patienten følges med passende psykiatrisk intervention.
If psychiatric symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with Rebetol and peginterferon alfa-2b or interferon alfa-2b be discontinued, and the patient followed, with psychiatric intervention as appropriate.
Hvis behandling med Rebetol i kombination med peginterferon alfa- 2b eller interferon alfa- 2b vurderes nødvendig hos voksne patienter med eksisterende eller tidligere alvorlige psykiatriske lidelser, bør denne kun initieres efter en passende individualiseret diagnosticering og terapeutisk håndtering af den psykiatriske lidelse er blevet sikret.
If treatment with Rebetol in combination with peginterferon alfa-2b or interferon alfa-2b is judged necessary in adult patients with existence or history of severe psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and therapeutic management of the psychiatric condition.
4. 3).
The use of Rebetol and interferon alfa-2b in children and adolescents with existence of or history of severe psychiatric conditions is contraindicated (see section 4.3).
6 Anvendelse af ribavirin i monoterapi er ifølge resultater fra kliniske undersøgelser ikke effektivt, og Rebetol skal ikke anvendes alene.
Based on results of clinical trials, the use of ribavirin as monotherapy is not effective and Rebetol must not be used alone.
Sikkerhed og effekt af denne kombination er udelukkende vist for ribavirin kapsler sammen med peginterferon alfa- 2b eller interferon alfa- 2b injektionsvæske, opløsning.
The safety and efficacy of this combination have been established only using ribavirin capsules together with peginterferon alfa-2b or interferon alfa-2b solution for injection.
Alle patienter i undersøgelserne ved kronisk hepatitis C fik foretaget en leverbiopsi før inklusion, men i visse tilfælde (eksempelvis ved patienter med genotype 2 og 3) kan behandling være mulig uden histologisk bekræftelse.
All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i. e. patients with genotype 2 and 3), treatment may be possible without histological confirmation.
Gældende behandlingsvejledninger bør tages i betragtning med hensyn til, om en leverbiopsi er nødvendig før start af behandling.
6 Current treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing treatment.
Teratogen risiko:
Teratogenic risk:
4. 3).
Rebetol must not be used by women who are pregnant (see section 4.3).
4. 6 og 5. 3).
Extreme care must be taken to avoid pregnancy in female patients (see sections 4.6 and 5.3).
Mandlige patienter og deres kvindelige partnere:
Male patients and their female partners:
4. 6 og 5. 3).
Extreme care must be taken to avoid pregnancy in partners of male patients taking Rebetol (see sections 4.6 and 5.3).
Hæmolyse:
Haemolysis:
Et fald i hæmoglobin niveau til < 10 g/ dl blev set hos op til 14% voksne patienter og hos 7% af børn og unge behandlet med Rebetol i kombination med peginterferon alfa- 2b (kun voksne) eller interferon alfa- 2b (voksne, børn eller unge) i kliniske undersøgelser.
A decrease in haemoglobin levels to < 10 g/ dl was observed in up to 14% of adult patients and 7% of children and adolescents treated with Rebetol in combination with peginterferon alfa-2b (adults only) or interferon alfa-2b (adults and children or adolescents) in clinical trials.
Selv om ribavirin ikke har nogen direkte kardiovaskulære virkninger, kan anæmi i forbindelse med Rebetol medføre forringelse af hjertefunktionen eller forværring af symptomerne på koronarsygdom eller begge.
Although ribavirin has no direct cardiovascular effects, anaemia associated with Rebetol may result in deterioration of cardiac function, or exacerbation of the symptoms of coronary disease, or both.
Rebetol skal således anvendes med forsigtighed til patienter med forud eksisterende hjertesygdom (se pkt.
Thus, Rebetol must be administered with caution to patients with pre-existing cardiac disease (see section 4.3).
4. 2).
Cardiac status must be assessed before start of therapy and monitored clinically during therapy; if any deterioration occurs, therapy must be stopped (see section 4.2).
Kardiovaskulært:
Cardiovascular:
Voksne patienter med tidligere hjertesvigt, myokardieinfarkt og/ eller tidligere eller eksisterende arytmisygdomme skal følges tæt.
Adult patients with a history of congestive heart failure, myocardial infarction and/ or previous or current arrhythmic disorders must be closely monitored.
Det anbefales, at de patienter, som har haft hjerteabnormaliteter, skal have taget elektrokardiogram før og under behandlingsforløbet.
It is recommended that those patients who have pre-existing cardiac abnormalities have electrocardiograms taken prior to and during the course of treatment.
Der er ingen resultater for børn eller unge med tidligere hjertesygdomme i anamnesen.
There are no data in children or adolescents with a history of cardiac disease.
I tilfælde af udvikling af akut overfølsomhedsreaktion (for eksempel urticaria, angioødem, bronkiekonstriktion, anafylaksi), skal Rebetol øjeblikkeligt seponeres og passende medicinsk behandling initieres.
If an acute hypersensitivity reaction (e. g., urticaria, angioedema, bronchoconstriction, anaphylaxis) develops, Rebetol must be discontinued immediately and appropriate medical therapy instituted.
Okulære ændringer:
Ocular changes:
Ribavirin anvendes i kombinationsbehandling med alfa- interferoner.
Ribavirin is used in combination therapy with alpha interferons.
Der er i sjældne tilfælde set retinopati herunder blødninger i nethinden, ekssudater, papilødem, optisk neuropati og synstab grundet nethinde arterie - eller veneobstruktion i kombinationsbehandling med alfa- interferoner.
Retinopathy including retinal haemorrhages, cotton wool spots, papilloedema, optic neuropathy and retinal artery or vein obstruction which may result in loss of vision have been reported in rare instances with combination therapy with alpha interferons.
Alle patienter bør ved baseline få foretaget en undersøgelse af øjet.
All patients should have a baseline eye examination.
Patienter med allerede eksisterende øjensygdomme (f. eks. diabetisk eller hypertensiv retinopati) bør få foretaget regelmæssige undersøgelser af øjet, hvis de er i kombinationsbehandling med alfa- interferoner.
Patients with preexisting ophthalmologic disorders (e. g., diabetic or hypertensive retinopathy) should receive periodic ophthalmologic exams during combination therapy with alpha interferons.
Kombinationsbehandling med alfa - interferoner skal ophøre hos patienter, der udvikler ny eller forværring af øjensygdom.
Combination therapy with alpha interferons should be discontinued in patients who develop new or worsening ophthalmologic disorders.
Enhver patient, der udvikler betydelig leverfunktionsabnormalitet under behandling, skal følges nøje.
Any patient developing significant liver function abnormalities during treatment must be monitored closely.
Afbryd behandling hos patienter, der udvikler forlængede koagulationsmarkører, hvilket kan være tegn på leversvigt.
Discontinue treatment in patients who develop prolongation of coagulation markers which might indicate liver decompensation.
5. 3).
In addition, preclinical juvenile toxicity results have demonstrated a minor, dose-related decrease in overall growth in neonatal rats dosed with ribavirin (see section 5.3).
Risiko/ benefit af den kombinerede anvendelse af Rebetol og interferon alfa- 2b bør derfor vurderes hos små børn før initiering af behandling.
Therefore, the risk/ benefit of the combined use of Rebetol and interferon alfa-2b should be assessed in young children prior to the initiation of therapy.
Det anbefales, at læger monitorerer væksten af børn, der tager Rebetol i kombination med interferon alfa- 2b.
Physicians are advised to monitor the growth of children taking Rebetol in combination with interferon alfa-2b.
Thyreoidea monitorering:
7 Thyroid Monitoring:
Omtrent 12% af børn behandlet med Rebetol og interferon alfa- 2b udviklede en forøgning af TSH.
Approximately 12% of children treated with Rebetol and interferon alfa-2b developed increase in TSH.
Inden initiering af interferon alfa- 2b behandling, skal TSH niveauet evalueres og mulige thyreoideaabnormaliteter detekteret på dette tidspunkt, skal behandles med konventionel behandling.
Prior to initiation of interferon alfa-2b therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be treated with conventional therapy.
Interferon alfa- 2b behandling kan initieres, hvis TSH niveauet kan fastholdes indenfor normalområdet ved medicinsk behandling.
Interferon alfa-2b therapy may be initiated if TSH levels can be maintained in the normal range by medication.
Thyreoideadysfunktion under behandling med Rebetol og interferon alfa- 2b har været observeret.
Thyroid dysfunction during treatment with Rebetol and interferon alfa-2b has been observed.
Hvis thyreoideaabnormaliteter detekteres, bør patientens thyreoideastatus evalueres og behandles klinisk passende.
If thyroid abnormalities are detected, the patient ’ s thyroid status should be evaluated and treated as clinically appropriate.
Samtidig infektion med HCV/ HIV:
HCV/ HIV Co-infection:
Der bør udvises forsigtighed hos HIV- positive personer, som samtidig er inficeret med HVC, og som får behandling med nukleosid revers transcriptase- hæmmer (NRTI) (især ddI og d4T) og kombineret interferon alfa- 2b/ ribavirin behandling.
Caution should be taken in HIV-positive subjects co-infected with HCV who receive nucleoside reverse transcriptase inhibitor (NRTI) treatment (especially ddI and d4T) and associated interferon alfa-2b/ ribavirin treatment.
Hos den HIV- positive population, som får et NRTI regimen, bør lægen nøje følge markører for mitokondrietoksicitet og mælkesyreacidose, når ribavirin indgives.
In the HIV-positive population receiving an NRTI regimen, physicians should carefully monitor markers of mitochondrial toxicity and lactic acidosis when ribavirin is administered.
Især anbefales:
In particular: