natgillin/translations-raw huggingface dataset:
4 undersøgelser (se Dosisjusteringsvejledninger, Tabel 3).
Guidelines were developed in clinical trials for dose modification (see Dosage modification guidelines, Table 3).
En mulig negativ indflydelse af reduktion af ribavirin- dosis på effekt- resultater kunne ikke udelukkes.
The potential negative impact of ribavirin dose reduction on efficacy results could not be ruled out.
Tabel 3
4 Table 3
Vejledning til justering af dosis
Dosage modification guidelines
Reducer kun Ribavirin Reducer kun
Reduce only Ribavirin Reduce only
daglig voksendosis til 600 mg/ dag *,
daily dose adult to
peginterferon alfa- 2b - dosis (voksne) eller
peginterferon alfa-2b
kombinations - behandling,
combination therapy
pædiatrisk dosis til 7, 5 mg/ kg, hvis:
600 mg/ day*, paediatric to 7.5 mg/ kg, if:
interferon alfa- 2b- dosis (voksne og pædiatrisk) til halv dosis, hvis:
(adult) or interferon alfa- 2b dose (adult and paediatric) to one-half dose, if:
hvis:
if:
<
-
8, 5 g/ dl
< 8.5 g/ dl
≥ 2 g/ dl fald i hæmoglobin under en hvilken som
≥ 2 g/ dl decrease in haemoglobin during any 4 week period during treatment (permanent dose reduction)
< 12 g/ dl efter
< 12 g/ dl after 4 weeks of dose reduction
Hæmoglobin hos: patienter med stabil hjertesygdom Børn: ingen data (se pkt.
White blood cells Neutrophils
4. 4)
Platelets
helst
-
4 ugers periode under behandling (permanent dosisreduktion)
Adult < 50 x 109/ l
4 ugers dosisreduktion
Adult < 25 x 109/ l
Hvide blodlegemer Neutrofile Blodplader
Paediatric <
- < 1, 5 x 109/ l - < 0, 75 x 109/ l - Voksne < 50 x 109/ l Børn < 80 x 109/ l
80 x 109/ l
< 1, 0 x 109/ l < 0, 5 x 109/ l Voksne < 25 x 109/ l Børn < 50 x 109/ l
Paediatric < 50 x 109/ l
> 5 mg/ dl
mg/ dl
Voksne > 4 mg/ dl Børn > 5 mg/ dl (i > 4 uger)
Adult > 4 mg/ dl
Kreatinin Alanin aminotransferase / aspartat aminotransferase (ALAT/ ASAT)
Paediatric > 5 mg/ dl (for > 4 weeks) Creatinine
> 2, 0 mg/ dl 2 x baseline og > 10 x ULN **
2 x baseline and > 10 x ULN**
* Indtages fordelt på to doser, morgen og aften. ** Øvre grænse for normalområdet
* Administered in two divided doses, in the morning and in the evening. ** Upper limit of normal
5. 2).
The pharmacokinetics of ribavirin are altered in patients with renal dysfunction due to reduction of apparent clearance in these patients (see section 5.2).
Det anbefales derfor, at nyrefunktionen vurderes hos alle patienter før initiering af Ribavirin.
Therefore, it is recommended that renal function be evaluated in all patients prior to initiation of Ribavirin.
4. 3).
Patients with creatinine clearance < 50 ml/ minute must not be treated with Ribavirin (see section 4.3).
Hvis serumkreatinin stiger til > 2 mg/ dl (Tabel 3), skal Ribavirin og peginterferon alfa- 2b/ interferon alfa - 2b seponeres.
If serum creatinine rises to > 2 mg/ dl (Table 3), Ribavirin and peginterferon alfa- 2b/ interferon alfa-2b must be discontinued.
Ingen dosisjustering af Ribavirin er derfor nødvendig hos patienter med nedsat leverfunktion.
Therefore, no dose adjustment of Ribavirin is required in patients with hepatic impairment.
Anvendelse hos ældre (≥ 65 år):
Use in the elderly (≥ 65 years of age):
5. 2).
However, as in younger patients, renal function must be determined prior to administration of Ribavirin (see section 5.2).
5 Anvendelse hos patienter i alderen under 18 år:
Use in patients under the age of 18 years:
Ribavirin kan bruges i kombination med interferon alfa- 2b til børn (3 år eller ældre) og unge.
Ribavirin may be used in combination with interferon alfa-2b in children (3 years of age and older) and adolescents.
Sikkerhed og effekt af Ribavirin med pegyleret eller andre former for interferon (det vil sige foruden alfa- 2b) hos disse patienter er ikke blevet evalueret.
5 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:
Ribavirin må ikke initieres, før et negativt resultat fra en
Ribavirin must not be initiated until a report of
graviditetstest er opnået umiddelbart før behandlingsstart.
a negative pregnancy test has been obtained immediately prior to initiation of therapy.
- Anamnese med allerede eksisterende alvorlig hjertesygdom, inklusive ustabil eller ukontrolleret
- A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac
4. 4).
disease, in the previous six months (see section 4.4).
patienter med kreatininclearance < 50 ml/ minut og/ eller i hæmodialyse.
with creatinine clearance < 50 ml/ minute and/ or on haemodialysis.
- 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
Alvorlig CNS- påvirkning, særligt depression, selvmordstanker og selvmordsforsøg, er set hos nogle patienter under Ribavirin - 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 Ribavirin 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 Ribavirin i kombination med interferon alfa- 2b, blev selvmordstanker eller - forsøg rapporteret oftere end hos voksne patienter (2, 4% mod 1%) i behandling og i løbet af de 6 måneders opfølgning efter behandling.
Among children and adolescents, treated with Ribavirin 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 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 Ribavirin og peginterferon alfa- 2b eller interferon alfa- 2b afbrydes, og at patienten følges, og psykiatrisk intervention institueres ved behov.
If psychiatric symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with Ribavirin and peginterferon alfa-2b or interferon alfa-2b be discontinued, and the patient followed, with psychiatric intervention as appropriate.
Patienter med eksisterende eller tidligere alvorlige psykiatriske lidelser:
Patients with existence of or history of severe psychiatric conditions:
Hvis behandling med Ribavirin 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 diagnostisk og terapeutisk håndtering af den psykiatriske lidelse er blevet sikret.
If treatment with Ribavirin 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 Ribavirin 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 som monoterapi er ifølge resultater fra kliniske undersøgelser ikke effektivt, og Ribavirin skal ikke anvendes alene.
6 Based on results of clinical trials, the use of ribavirin as monotherapy is not effective and Ribavirin 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 kronisk hepatitis C- undersøgelserne fik foretaget en leverbiopsi før inklusion, men i visse tilfælde (eksempelvis 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.
4. 3).
Ribavirin 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 partners of male patients taking Ribavirin (see sections 4.6 and 5.3).
Et fald i hæmoglobinniveau til < 10 g/ dl blev set hos op til 14% af voksne patienter og hos 7% af børn og unge behandlet med Ribavirin 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 Ribavirin in combination with peginterferon alfa-2b (adults only) or interferon alfa-2b (adults and children or adolescents) in clinical trials.
Selvom ribavirin ikke har nogen direkte kardiovaskulære virkninger, kan anæmi i forbindelse med Ribavirin medføre forringelse af hjertefunktionen eller forværring af symptomerne på koronarsygdom eller begge.
Although ribavirin has no direct cardiovascular effects, anaemia associated with Ribavirin may result in deterioration of cardiac function, or exacerbation of the symptoms of coronary disease, or both.
4. 3).
Thus, Ribavirin must be administered with caution to patients with pre-existing cardiac disease (see section 4.3).
I tilfælde af udvikling af akut overfølsomhedsreaktion (for eksempel urticaria, angioødem, bronkiekonstriktion, anafylaksi), skal Ribavirin øjeblikkeligt seponeres og passende medicinsk behandling initieres.
If an acute hypersensitivity reaction (e. g., urticaria, angioedema, bronchoconstriction, anaphylaxis) develops, Ribavirin must be discontinued immediately and appropriate medical therapy instituted.
Ved kombinationsbehandling med alfa- interferoner er der i sjældne tilfælde set retinopati herunder blødninger i nethinden, ekssudater, papilødem, opticus neuropati og synstab grundet nethindearterie - eller - veneobstruktion.
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.
Patienter med allerede eksisterende øjensygdomme (f. eks. diabetisk eller hypertensiv retinopati) bør få foretaget regelmæssige øjenundersøgelser, 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
Vækst og udvikling:
7 Growth and Development:
Under et 1- årigt behandlingsforløb var der et fald i hastigheden for lineær vækst (gennemsnitligt percentilfald på 9%) og et fald i hastigheden for vægtøgning (gennemsnitligt
During a 1-year course of therapy there was a decrease in the rate of linear growth (mean percentile decrease of 9%) and a decrease in the rate of weight gain (mean percentile decrease of 13%).
Disse tendenser blev generelt vendt under 6 måneders opfølgning efter behandling.
A general reversal of these trends was noted during the 6 months follow-up post treatment.
Baseret på foreløbige data fra en langsigtet opfølgningsundersøgelse, havde 12 (14%) af 84 børn dog en > 15 procent nedgang i hastigheden af lineær vækst, af hvilke 5 (6%) børn havde en > 30 procent nedgang på trods af, at behandlingen havde været afbrudt i mere end et år.
However, based on interim data from a long-term follow-up study, 12 (14%) of 84 children had a > 15 percentile decrease in rate of linear growth, of whom 5 (6%) children had a > 30 percentile decrease despite being off treatment for more than 1 year.
Risiko/ benefit af den kombinerede anvendelse af Ribavirin og interferon alfa- 2b bør derfor vurderes hos små børn før initiering af behandling.
Therefore, the risk/ benefit of the combined use of Ribavirin 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 Ribavirin i kombination med interferon alfa- 2b.
Physicians are advised to monitor the growth of children taking Ribavirin in combination with interferon alfa-2b.
Thyreoidea- monitorering:
Thyroid Monitoring:
Omtrent 12% af børn behandlet med Ribavirin og interferon alfa- 2b udviklede en stigning af TSH.
Approximately 12% of children treated with Ribavirin 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 inden for 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 Ribavirin og interferon alfa- 2b har været observeret.
Thyroid dysfunction during treatment with Ribavirin and interferon alfa-2b has been observed.
Samtidig infektion med HCV/ hiv:
HCV/ HIV Co-infection:
Der bør udvises forsigtighed hos hiv- positive personer, som samtidig er inficeret med HCV, 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.
- frarådes samtidig indgift af Ribavirin og didanosin på grund af risiko for mitokondrietoksicitet
- co-administration of Ribavirin and didanosine is not recommended due to the risk of
- bør samtidig indgift af Ribavirin og stavudin undgås for at begrænse risiko for overlappende
- co-administration of Ribavirin and stavudine should be avoided to limit the risk of overlapping
Hepatisk dekompensering hos HCV/ hiv- co- inficerede patienter med fremskreden cirrose:
Hepatic decompensation in HCV/ HIV co-infected patients with advanced cirrhosis:
Patienter med samtidig HCV/ hiv- infektion og fremskreden cirrose, som modtager HAART - behandling, kan have en øget risiko for nedsat leverfunktion og død.
Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic decompensation and death.
Tillæg af behandling med alfa - interferoner alene eller i kombination med ribavirin kan øge risikoen hos denne patientundergruppe.
Adding treatment with alfa interferons alone or in combination with ribavirin may increase the risk in this patient subset.
Andre baseline- faktorer hos co- inficerede patienter, som kan associeres med en højere risiko for hepatisk dekompensering, omfatter behandling med didanosin og forhøjede bilirubinserum - koncentrationer.
Other baseline factors in co-infected patients that may be associated with a higher risk of hepatic decompensation include treatment with didanosine and elevated bilirubin serum concentrations.
Patienter som udvikler hepatisk inkompensation, bør have deres antihepatiske behandling seponeret øjeblikkeligt, og ARV - behandlingen skal revurderes.
Patients progressing to hepatic decompensation should have their anti-hepatitis treatment immediately discontinued and the ARV treatment reassessed.
Hæmatologiske unormaliteter hos patienter med samtidig HCV/ hiv- infektion:
Haematological abnormalities in HCV/ HIV co-infected patients:
Patienter, der samtidig er inficeret med HCV/ hiv og som modtager peginterferon alfa- 2b/ ribavirin behandling og HAART, kan have øget risiko for at udvikle hæmatologiske unormaliteter (som neutropeni, trombocytopeni og anæmi) sammenlignet med HCV- monoinficerede patienter.
HCV/ HIV co-infected patients receiving peginterferon alfa-2b/ ribavirin treatment and HAART may be at increased risk to develop haematological abnormalities (as neutropenia, thrombocytopenia and anaemia) compared to HCV mono-infected patients.
Selvom hovedparten af dem kunne afhjælpes med en reduktion i dosis, bør tæt monitorering af hæmatologiske parametre foretages i denne population af patienter (se pkt.
Although, the majority of them could be managed by dose reduction, close monitoring of haematological parameters should be undertaken in this population of patients (see section 4.2 and below “ Laboratory tests” and section 4.8).
4. 2 og under ” Laboratorieanalyser ” og pkt.
Patients treated with ribavirin and zidovudine are at increased risk of developing anaemia; therefore, the concomitant use of ribavirin with zidovudine is not recommended (see section 4.5).
4. 8).
8 Patients with low CD4 counts:
8 Hos patienter, der er co- inficeret med HCV/ hiv, er begrænsede effekt - og sikkerhedsdata (N = 25) tilgængelige i patienter med CD4- tællinger mindre end 200 celler/ µl.
In patients co-infected with HCV/ HIV, limited efficacy and safety data (N = 25) are available in subjects with CD4 counts less than 200 cells/ µl.
For de antiretrovirale lægemidler, der skal tages samtidig med HCV- behandling, henvises der til disses respektive produktresuméer for kendskab og håndtering af toksiciteter, der er specifikke for det enkelte produkt samt potentialet for overlappende toksiciteter med Ribavirin og peginterferon alfa- 2b.
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 and peginterferon alfa-2b.
Dentale og parodontale lidelser, som kan føre til tab af tænder, er blevet rapporteret hos patienter, der fik Ribavirin og peginterferon alfa- 2b - eller interferon alfa- 2b - kombinationsbehandling.
Dental and periodontal disorders, which may lead to loss of teeth, have been reported in patients receiving Ribavirin and peginterferon alfa-2b or interferon alfa-2b combination therapy.
Herudover kan mundtørhed have en skadelig virkning på tænder og mundslimhinder under langtidsbehandling med kombinationen af Ribavirin og peginterferon alfa- 2b eller interferon alfa- 2b.
In addition, dry mouth could have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with the combination of Ribavirin and peginterferon alfa-2b or interferon alfa-2b.
Acceptable baselineværdier, der kan betragtes som en vejledning før initiering af Ribavirin- behandling:
Acceptable baseline values that may be considered as a guideline prior to initiation of Ribavirin therapy:
Voksne: ≥12 g/ dl (kvinder); ≥13 g/ dl (mænd) Pædiatrisk: ≥11 g/ dl (kvinder); ≥12 g/ dl (mænd)
Adult: ≥ 12 g/ dl (females); ≥ 13 g/ dl (males) Paediatric: ≥ 11 g/ dl (females); ≥ 12 g/ dl (males)
Blodplader Neutrofiltal
Platelets Neutrophil Count
≥100. 000/ mm3 ≥1. 500/ mm3
≥ 100,000/ mm3 ≥ 1,500/ mm3
skal udføres efter 2 og 4 ugers behandling og herefter regelmæssigt efter
Laboratory evaluations are to be conducted at weeks 2 and 4 of therapy, and periodically thereafter as clinically appropriate.
Kvindelige patienter skal have en rutine- graviditetstest udført hver måned under behandling og i fire måneder derefter.
Female patients must have a routine pregnancy test performed monthly during treatment and for four months thereafter.
Kvindelige partnere til mandlige patienter skal have en rutine - graviditetstest udført hver måned under behandling og i syv måneder derefter (se pkt.
Female partners of male patients must have a routine pregnancy test performed monthly during treatment and for seven months thereafter (see section 4.6).
Derfor skal muligheden for udvikling af gigt følges nøje hos prædisponerede patienter.
Uric acid may increase with Ribavirin due to haemolysis; therefore, the potential for development of gout must be carefully monitored in pre-disposed patients.
Resultater af in vitro- undersøgelser med både humane og rotte- levermikrosompræparater viste ingen cytokrom P450- enzymmedieret metabolisme af ribavirin.
Results of in vitro studies using both human and rat liver microsome preparations indicated no cytochrome P450 enzyme mediated metabolism of ribavirin.
Ribavirin hæmmer ikke cytokrom P450 - enzymer.
Ribavirin does not inhibit cytochrome P450 enzymes.
Der er således minimal mulighed for P450- enzymbaserede interaktioner.
Therefore, there is a minimal potential for P450 enzyme-based interactions.
Ingen interaktionsundersøgelser er udført med Ribavirin og andre lægemidler med undtagelse af peginterferon alfa- 2b, interferon alfa- 2b og antacida.
No interaction studies have been conducted with Ribavirin and other medicinal products, except for peginterferon alfa-2b, interferon alfa-2b and antacids.
Der sås ingen farmakokinetiske interaktioner mellem Ribavirin og peginterferon alfa- 2b eller interferon alfa- 2b i en flerdosis- farmakokinetisk undersøgelse.
No pharmacokinetic interactions were noted between Ribavirin and peginterferon alfa-2b or interferon alfa-2b in a multiple-dose pharmacokinetic study.
Biotilgængeligheden af ribavirin 600 mg blev reduceret ved samtidig indtagelse af et antacidum indeholdende magnesium, aluminium og simeticon; AUCtf faldt 14%.
The bioavailability of ribavirin 600 mg was decreased by co-administration with an antacid containing magnesium aluminium and simethicone; AUCtf decreased 14%.
9 purinnukleosid- analoger (såsom didanosin eller abacavir).
Use of nucleoside analogs, alone or in combination with other nucleosides, has resulted in lactic acidosis.
Samtidig indgivelse af Ribavirin og didanosin anbefales ikke.
Pharmacologically, ribavirin increases phosphorylated metabolites of purine nucleosides in vitro.
Dette vil være særligt vigtigt for patienter, der har zidovudininduceret anæmi i anamnesen.
This would be particularly important in patients with a known history of zizovudine induced anaemia.
5. 2).
Any potential for interactions may persist for up to two months (five half-lives for ribavirin) after cessation of Ribavirin therapy due to the long half-life (see section 5.2).
Der er ingen tegn på, at ribavirin har interaktion med ikke- nukleosid reverse transcriptase- hæmmere eller proteasehæmmere.
There is no evidence that ribavirin interacts with non-nucleoside reverse transcriptase inhibitors or protease inhibitors.
Anvendelsen af Ribavirin er kontraindiceret under graviditet.
The use of Ribavirin is contraindicated during pregnancy.
Betydeligt teratogent og/ eller embryocidt potentiale er vist for ribavirin i alle
Significant teratogenic and/ or embryocidal potential have been demonstrated for
4. 3, 4. 4 og 5. 3).
Ribavirin must not be used by females who are pregnant (see sections 4.3, 4.4 and 5.3).