natgillin/translations-raw huggingface dataset:
Hiv- HCV- co- infektion Den anbefalede dosering af Pegasys, alene eller i kombination med 800 mg ribavirin, er 180 mikrogram subkutant én gang ugentlig i 48 uger, uanset genotype.
HIV-HCV co-infection The recommended dosage for Pegasys, alone or in combination with 800 milligrams of ribavirin, is 180 micrograms once weekly subcutaneously for 48 weeks, regardless of genotype.
Sikkerhed og effekt af kombinationsbehandling med ribavirindoser over 800 mg daglig undersøges på nuværende tidspunkt.
The safety and efficacy of combination therapy with ribavirin doses greater than 800 milligrams daily is currently being studied.
En behandlingsvarighed under 48 uger er ikke tilstrækkeligt undersøgt.
A duration of therapy less that 48 weeks has not been adequately studied.
Forudsigelighed af respons og non- respons – behandlingsnaive patienter Tidligt virologisk respons ved uge 2, defineret som et 2 log viralt fald eller ikke detekterbare koncentrationer af HCV- RNA har vist sig at være prædiktivt for vedvarende respons (se tabel 2 og 6).
Predictability of response and non-response – treatment-naïve patients Early virological response by week 12, defined as a 2 log viral load decrease or undetectable levels of HCV RNA has been shown to be predictive for sustained response (see Tables 2 and 6).
4 Tabel 2:
4 Table 2:
Prædiktiv værdi ved uge 12 for det virologiske respons under kombinationsbehandling med Pegasys efter den anbefalede dosis Genotype
Predictive Value of Week 12 Virological Response at the Recommended Dosing Regimen while on Pegasys Combination Therapy Genotype
Negativ Intet
Positive
Positiv
response
ved -
No
Intet respons ved uge 12
by
varende respons
week 12
Prædiktiv værdi
sustained response
ved uge 12
Predictive by week Value 12
Genotype 1 (N= 569)
Genotype 1 (N= 569)
58% (271/ 467)
58% (271/ 467)
87%
87%
(N=96)
(N=96)
(3/ 3)
(3/ 3) 93
Den negativ prædiktive værdi for vedvarende respons hos patienter behandlet med Pegasys monoterapi var 98%.
The negative predictive value for sustained response in patients treated with Pegasys in monotherapy was 98%.
Der er set en tilsvarende negativ prædiktiv værdi hos hiv- HCV- co- inficerede patienter i behandling med henholdsvis Pegasys monoterapi eller i kombination med ribavirin (100% (130/ 130) eller 98% (83/ 85).
A similar negative predictive value has been observed in HIV-HCV co-infected patients treated with Pegasys monotherapy or in combination with ribavirin (100% (130/ 130) or 98% (83/ 85), respectively).
Der blev set positive prædiktive værdier på 45% (50/ 110) og 70% (59/ 84) hos hhv. genotype 1 og genotype 2/ 3 hiv- HCV- co- inficerede patienter i kombinationsbehandling.
Positive predictive values of 45% (50/ 110) and 70% (59/ 84) were observed for genotype 1 and genotype 2/ 3 HIV-HCV co-infected patients receiving combination therapy.
Forudsigelighed af respons og non- respons – behandlingserfarne patienter Viral suppression ved uge 12 (ikke- detekterbar HCV- RNA defineret som < 50 IE/ ml) har vist sig at være prædiktiv for vedvarende virologisk respons hos ikke- responderende patienter genbehandlet i 48 eller 72 uger.
Predictability of response and non-response – treatment-experienced patients In non-responder patients re-treated for 48 or 72 weeks, viral suppression at week 12 (undetectable HCV RNA defined as < 50 IU/ mL) has been shown to be predictive for sustained virological response.
Sandsynligheden for ikke at opnå et vedvarende virologisk respons med 48 eller 72 ugers behandling, hvis viral suppression ikke var opnået ved uge 12, var henholdsvis 96% (363/ 380) og 96% (324/ 339).
The probabilities of not achieving a sustained virological response with 48 or 72 weeks of treatment if viral suppression was not achieved at week 12 were 96% (363 of 380) and 96% (324 of 339), respectively.
Sandsynligheden for at opnå et vedvarende virologisk respons med 48 eller 72 ugers behandling, hvis viral suppression var opnået ved uge 12, var henholdsvis 35% (20/ 57) og 57% (57/ 100).
The probabilities of achieving a sustained virological response with 48 or 72 weeks of treatment if viral suppression was achieved at week 12 were 35% (20 of 57) and 57% (57 of 100), respectively.
Justering af dosis på grund af bivirkninger
Dose adjustment for adverse reactions
Generelt Når dosisjustering er påkrævet på grund af moderate til svære bivirkninger (kliniske og/ eller laboratoriemæssige) er en initial dosisreduktion til 135 mikrogram almindeligvis tilstrækkelig.
General Where dose adjustment is required for moderate to severe adverse reactions (clinical and/ or laboratory) initial dose reduction to 135 micrograms is generally adequate.
I nogle tilfælde er det dog nødvendigt at nedsætte dosis til 90 eller 45 mikrogram.
However, in some cases, dose reduction to 90 micrograms or 45 micrograms is necessary.
4. 4 og 4. 8).
Dose increases to or towards the original dose may be considered when the adverse reaction abates (see sections 4.4 and 4.8).
Hæmatologiske bivirkninger (se også tabel 3) Det anbefales at nedsætte dosis, hvis neutrofillocyttallet er < 750/ mm3.
Haematological (see also Table 3) Dose reduction is recommended if the neutrophil count is < 750/ mm3.
Hos patienter med et absolut neutrofillocyttal (ANC) < 500 / mm3 skal behandlingen afbrydes, indtil det absolutte neutrofillocyttal er > 1000 / mm3.
For patients with Absolute Neutrophil Count (ANC )< 500/mm3 treatment should be suspended until ANC values return to > 1000/mm3.
Behandlingen bør da genoptages med 90 mikrogram Pegasys, og neutrofillocyttallet skal kontrolleres.
Therapy should initially be re-instituted at 90 micrograms Pegasys and the neutrophil count monitored.
Det anbefales at nedsætte dosis til 90 mikrogram, hvis trombocyttallet er < 50. 000/ mm3.
Dose reduction to 90 micrograms is recommended if the platelet count is < 50,000/ mm3.
Det anbefales at stoppe behandlingen, hvis trombocyttallet falder til < 25. 000/ mm3.
Cessation of therapy is recommended when platelet count decreases to levels < 25,000/ mm3.
Hvis et af følgende indtræffer skal ribavirindosis reduceres til 600 mg/ dag (200 mg om morgenen og 400 mg om aftenen):
Specific recommendations for management of treatment-emergent anaemia are as follows: ribavirin should be reduced to 600 milligrams/ day (200 milligrams in the morning and 400 milligrams in the evening) if either of the following apply:
(1) hæmoglobin falder til < 10 g/ dl og ≥8, 5 g/ dl hos en patient uden signifikant kardiovaskulær sygdom eller (2) hæmoglobin falder med ≥2 g/ dl under en 4 - ugers behandling hos en patient med stabil kardiovaskulær sygdom.
(1) a patient without significant cardiovascular disease experiences a fall in haemoglobin to < 10 g/ dl and ≥ 8.5 g/ dl, or (2) a patient with stable cardiovascular disease experiences a fall in haemoglobin by ≥ 2 g/ dl during any 4 weeks of treatment.
Ribavirin skal seponeres, hvis et af følgende indtræffer:
Ribavirin should be discontinued if either of the following apply:
(1) hæmoglobin falder til < 8, 5 g/ dl hos en patient uden signifikant kardiovaskulær sygdom eller (2) hæmoglobin holder sig på < 12 g/ dl hos en patient med stabil kardiovaskulær sygdom til trods for, at dosis har været reduceret i 4 uger.
(1) A patient without significant cardiovascular disease experiences a fall in haemoglobin confirmed to < 8.5 g/ dl; (2) A patient with stable cardiovascular disease maintains a haemoglobin value < 12 g/ dl despite 4 weeks on a reduced dose.
Hvis abnormaliteten reverterer, kan behandlingen med ribavirin genoptages med en dosis på 600 mg daglig, og dosis kan yderligere øges til 800 mg daglig iht. et lægeligt skøn.
If the abnormality is reversed, ribavirin may be restarted at 600 milligrams daily, and further increased to 800 milligrams daily at the discretion of the treating physician.
5 Tabel 3:
5 Table 3:
Dosisjustering for bivirkninger (se endvidere teksten ovenfor for yderligere vejledning)
Dose Adjustment for Adverse Reaction (For further guidance see also text above)
Reducer
Reduce
Stop Reducer St
Withhold Reduce Withhold
Stop Reducer Stop
Withhold Reduce Withhold
behandlingen
Discontinue
til 600 mg
Ribavirin Ribavirin to 600 mg
med ribavirin
to
135/ 90/ 45 μg
Pegasys Pegasys 135/ 90/ 45
behandlingen
Combination
Absolut neutrofillocyttal
micrograms Absolute Neutrophil Count
Trombocyttal
Platelet Count
< 50, 000/ mm3 > 25, 000/ mm3
< 50,000/mm3 > 25,000/ mm
< 25, 000/ mm3
< 25,000/ mm3
< 10 g/ dl og ≥8. 5 g/ dl
10 g/ dl, and < 8.5 g/ dl 8.5 g/ dl
< 8. 5 g/ dl
decrease < 12 g/ dl
Hæmoglobin - stabil hjertesygdom
stable cardiac disease
fald på ≥2 g/ dl i < 12 g/ dl trods 4 løbet af 4 uger ugers behandling med nedsat dosis
≥ 2 g/ dl during any 4 weeks
Leverfunktion Svingninger i abnorme leverfunktionstests er almindelige hos patienter med kronisk hepatitis C.
Liver function Fluctuations in abnormalities of liver function tests are common in patients with chronic hepatitis C.
Som tilfældet er for andre alfa- interferoner er der hos patienter, som er behandlet med Pegasys, inklusive patienter med virologisk respons, set forhøjelser af ALAT, i forhold til baseline (BL).
As with other alpha interferons, increases in ALT levels above baseline (BL) have been observed in patients treated with Pegasys, including patients with a virological response.
I de kliniske studier ved kronisk hepatitis C blev der hos 8 af 451 patienter, som fik kombinationsbehandling, set enkeltstående stigninger i ALAT (≥10 x øvre referencegrænse eller ≥2 x BL hos patienter med baseline- ALAT ≥10 x øvre referencegrænse), som normaliseredes uden justering af dosis.
In chronic hepatitis C clinical trials, isolated increases in ALT (≥ 10x ULN, or ≥ 2x BL for patients with a BL ALT ≥ 10x ULN) which resolved without dose-modification were observed in 8 of 451 patients treated with combination therapy.
Hvis ALAT- forhøjelserne progredierer eller persisterer, skal dosis initialt nedsættes til 135 mikrogram.
If ALT increase is progressive or persistent, the dose should be reduced initially to 135 micrograms.
4. 4).
When increase in ALT levels is progressive despite dose reduction, or is accompanied by increased bilirubin or evidence of hepatic decompensation, therapy should be discontinued (see section 4.4).
De kan afspejle immunclearance.
For chronic hepatitis B patients, transient flares of ALT levels sometimes exceeding 10 times the upper limit of normal are not uncommon, and may reflect immune clearance.
Hvis stigningerne overstiger 10 gange øvre referencegrænse, bør behandlingen normalt ikke påbegyndes.
Treatment should normally not be initiated if ALT is > 10 times the upper limit of normal.
4. 4).
If the Pegasys dose is reduced or withheld, therapy can be restored once the flare is subsiding (see section 4.4).
5. 2).
Elderly Adjustments in the recommended dosage of 180 micrograms once weekly are not necessary when instituting Pegasys therapy in elderly patients (see section 5.2).
Patienter under 18 år Sikkerhed og virkning af Pegasys er ikke dokumenteret hos denne population.
Patients under the age of 18 years The safety and efficacy of Pegasys have not been established in this population.
4. 3 og 4. 4).
Pegasys is contraindicated in neonates and young children up to 3 years old, because of the excipient benzyl alcohol (see sections 4.3 and 4.4).
5. 2).
Patients with renal impairment In patients with end stage renal disease, a starting dose of 135 micrograms should be used (see section 5.2).
Uanset initialdosis eller nyreinsufficiensens sværhedsgrad skal patienterne monitoreres, og der skal foretages passende reduktion af Pegasys- dosis under behandlingen, hvis der kommer bivirkninger.
Regardless of the starting dose or degree of renal impairment, patients should be monitored and appropriate dose reductions of Pegasys during the course of therapy should be made in the event of adverse reactions.
Child- Pugh A).
6 Patients with hepatic impairment In patients with compensated cirrhosis (eg, Child-Pugh A), Pegasys has been shown to be effective and safe.
4. 3).
Pegasys has not been evaluated in patients with decompensated cirrhosis (eg, Child-Pugh B or C or bleeding oesophageal varices) (see section 4.3).
Child- Pugh- klassifikationen inddeler patienterne i gruppe A, B og C eller ” let ”, ” moderat ” og ” svær ” svarende til henholdsvis score 5- 6, 7- 9 og 10- 15.
The Child-Pugh classification divides patients into groups A, B, and C, or "Mild", "Moderate" and "Severe" corresponding to scores of 5-6, 7-9 and 10-15, respectively.
Modificeret vurdering Vurdering Encefalopati
Modified Assessment Assessment Encephalopathy
Grad af abnormalitet Ingen, grad 1- 2, grad 3- 4 *
Degree of abnormality None Grade 1-2 Grade 3-4*
Score 1 2 3
Score 1 2 3
S- bilirubin (mg/ dl)
S-Bilirubin (mg/ dl)
< 2, 2, 0- 3, > 3
< 2 2.0- 3> 3
SI - enheder = μmol / l
SI unit = μ mol/ l)
S- albumin (g/ dl)
S-Albumin (g/ dl)
> 3, 5 3, 5- 2, 8, < 2, 8
> 3.5 3.5-2.8 < 2.8
* graduering iht. til Trey, Burns og Saunders (1966)
*Grading according to Trey, Burns and Saunders (1966)
4. 4) • Påbegyndelse af Pegasys er kontraindiceret hos hiv- HCV- patienter med cirrose og en Child - Pugh- score ≥ 6
• Hypersensitivity to the active substance, to alpha interferons, or to any of the excipients • Autoimmune hepatitis • Severe hepatic dysfunction or decompensated cirrhosis of the liver • Neonates and young children up to 3 years old, because of the excipient benzyl alcohol (see section 4.4 for benzyl alcohol) • A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease in the previous six months (see section 4.4) • Initiation of Pegasys is contraindicated in HIV-HCV patients with cirrhosis and a Child-Pugh score ≥ 6
Vedrørende kontraindikationer for ribavirin henvises også til produktresuméet for ribavirin, når Pegasys skal anvendes i kombination med ribavirin.
For contraindications to ribavirin, please refer also to the ribavirin Summary of Product Characteristics (SPC) when Pegasys is to be used in combination with ribavirin.
7 4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen Psykiatri og centralnervesystemet (CNS):
Psychiatric and Central Nervous System (CNS):
Der er set svære symptomer fra centralnervesystemet, specielt depression, suicidale tanker og suicidalforsøg, hos nogle patienter, som er i behandling med Pegasys og selv efter behandlingen er stoppet, hovedsageligt under den 6- måneders follow- up periode.
Severe CNS effects, particularly depression, suicidal ideation and attempted suicide have been observed in some patients during Pegasys therapy, and even after treatment discontinuation mainly during the 6-month follow-up period.
Andre symptomer fra centralnervesystemet omfattende aggressiv adfærd (nogle gange rettet mod andre), konfusion og psykiske ændringer er observeret ved alfa- interferoner.
Other CNS effects including aggressive behaviour (sometimes directed against others), confusion and alterations of mental status have been observed with alpha interferons.
Patienterne skal kontrolleres nøje for tegn eller symptomer på psykiatriske sygdomme.
Patients should be closely monitored for any signs or symptoms of psychiatric disorders.
Hvis disse symptomer forekommer, skal den potentielle alvorlighed af disse bivirkninger vurderes af lægen og behovet for tilstrækkelig medicinsk behandling skal overvejes.
If psychiatric symptoms persist or worsen, or
Hvis de psykiatriske symptomer varer ved eller forværres eller sucidale tanker er konstateret anbefales det, at behandlingen med Pegasys stoppes, og patienten kontrolleres med psykiatrisk behandling som nødvendigt.
7 suicidal ideation is identified, it is recommended that treatment with Pegasys be discontinued, and the patient followed, with psychiatric intervention as appropriate.
Patienter med eksisterende eller svære psykiatriske sygdomme i anamnesen:
Patients with existence of, or history of severe psychiatric conditions:
Hvis behandling med Pegasys er vurderet at være nødvendig hos patienter, som har eller tidligere har haft svære psykiatriske lidelser, bør behandlingen kun påbegyndes, når den psykiatriske lidelse er individuelt diagnosticeret og behandlet på passende måde.
If treatment with Pegasys is judged necessary in 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.
Der henvises også til produktresuméet (SPC) for ribavirin, når Pegasys anvendes i kombination med ribavirin.
Please refer also to the ribavirin Summary of Product Characteristics (SPC) when Pegasys is to be used in combination with ribavirin.
Alle patienter i studierne omhandlende kronisk hepatitis C fik foretaget en leverbiopsi før inklusion, men for specielle patienter (f. eks. patienter med genotype 2 eller 3) er behandling mulig uden histologisk bekræftelse.
All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (ie, patients with genotype 2 or 3), treatment may be possible without histological confirmation.
Gældende behandlingsvejledninger bør konsulteres for hvorvidt foretagelse af leverbiopsi er nødvendig inden behandlingen påbegyndes.
Current treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing treatment.
Hos patienter med normal ALAT sker udviklingen af fibrose i gennemsnit med en lavere hastighed end hos patienter med forhøjede ALAT.
In patients with normal ALT, progression of fibrosis occurs on average at a slower rate than in patients with elevated ALT.
HCV- genotype, patientens alder, tilstedeværelse af ekstrahepatiske tegn, risiko for overførsel af smitte osv.
This should be considered in conjunction with other factors, such as HCV genotype, age, extrahepatic manifestations, risk of transmission, etc. which influence the decision to treat or not.
Pegasys er kontraindiceret hos nyfødte eller børn op til 3 år på grund af hjælpestoffet benzylalkohol.
Pegasys is contraindicated in infants or young children up to 3 years old because of the excipient benzyl alcohol.
Laboratorieundersøgelser før og under behandlingen Før behandlingen med Pegasys påbegyndes, anbefales det at foretage hæmatologiske og biokemiske laboratorieundersøgelser på alle patienter.
Laboratory tests prior to and during therapy Prior to beginning Pegasys therapy, standard haematological and biochemical laboratory tests are recommended for all patients.
- Trombocyttal ≥90000/ mm3
- Platelet count ≥ 90,000/ mm3
- Absolut neutrofillocyttal ≥1500/ mm3
- Absolute neutrophil counts ≥ 1500/ mm3
Yderligere prøver skal tages periodisk under behandlingen.
Additional testing should be performed periodically during therapy.
Efter 8 ugers behandling var yderligere fald sjældent.
In clinical trials, Pegasys treatment was associated with decreases in both total white blood cell (WBC) count and absolute neutrophil count (ANC), usually starting within the first 2 weeks of treatment (see section 4.8).
I de kliniske studier med Pegasys var faldet i ANC reversibelt efter dosisreduktion eller ophør af behandlingen (se pkt.
Progressive decreases after 8 weeks of therapy were infrequent.
4. 2), opnåede normale værdier efter 8 uger hos hovedparten af patienterne og vendte tilbage til baseline hos alle patienter efter 16 uger.
The decrease in ANC was reversible upon dose reduction or cessation of therapy (see section 4.2), reached normal values by 8 weeks in the majority of patients and returned to baseline in all patients after about 16 weeks.
4. 8).
Pegasys treatment has been associated with decreases in platelet count, which returned to pre- treatment levels during the post-treatment observation period (see section 4.8).
4. 2).
In some cases, dose modification may be necessary (see section 4.2).
8 I de kliniske studier om kombineret behandling af Pegasys med ribavirin er der set anæmi (hæmoglobin < 10 g/ dl) hos op til 15% af patienterne med kronisk hepatitis C.
The occurrence of anaemia (haemoglobin < 10 g/ dl) has been observed in up to 15% of chronic hepatitis C patients in clinical trials on the combined treatment of Pegasys with ribavirin.
4. 8).
The frequency depends on the treatment duration and the dose of ribavirin (see section 4.8,).
Som det er tilfældet med andre interferoner, skal der iagttages forsigtighed, hvis Pegasys kombineres med andre potentielt myelosuppresive stoffer.
As with other interferons, caution should be exercised when administering Pegasys in combination with other potentially myelosuppressive agents.
Brugen af Pegasys og ribavirin i kombinationsbehandling hos kroniske hepatitis C- patienter, hvor tidligere behandling har svigtet, er ikke blevet undersøgt tilstrækkeligt hos patienter, som har afbrudt tidligere behandling på grund af hæmatologiske uønskede hændelser.
The use of Pegasys and ribavirin combination therapy in chronic hepatitis C patients who failed prior treatment has not been adequately studied in patients who discontinued prior therapy for
Det endokrine system Abnorm thyreoideafunktion eller forværring af thyreoideasygdomme er rapporteret efter anvendelse af alfa- interferoner, inklusive Pegasys.
Endocrine system Thyroid function abnormalities or worsening of pre-existing thyroid disorders have been reported with the use of alpha interferons, including Pegasys.
Før Pegasys- behandlingen påbegyndes, skal niveauet af TSH og T4 undersøges.
Prior to initiation of Pegasys therapy, TSH and T4 levels should be evaluated.
Behandlingen med Pegasys kan påbegyndes/ fortsættes, hvis TSH- niveauet kan holdes normalt med medicin.
Pegasys treatment may be initiated or continued if TSH levels can be maintained in the normal range by medication.
4. 8).
TSH levels should be determined during the course of therapy if a patient develops clinical symptoms consistent with possible thyroid dysfunction (see section 4.8).
4. 8).
As with other interferons, hypoglycaemia, hyperglycaemia and diabetes mellitus have been observed with Pegasys (see section 4.8).
Patienter med disse tilstande, som ikke effektivt kan kontrolleres med medicinering, bør ikke påbegynde hverken Pegasys monoterapi eller Pegasys/ ribavirin kombinationsbehandling.
Patients with these conditions who cannot be effectively controlled by medication should not begin Pegasys monotherapy nor Pegasys/ ribavirin combination therapy.
Patienter, der udvikler disse tilstande under behandlingen, og som ikke kan kontrolleres med medicinering, bør afbryde behandlingen med Pegasys eller Pegasys/ ribavirin.
Patients who develop these conditions during treatment and cannot be controlled with medication should discontinue Pegasys or Pegasys/ ribavirin therapy.
Det kardiovaskulære system Behandling med alfa- interferoner, inklusive Pegasys, er blevet sat i forbindelse med hypertension, supraventrikulære arytmier, kongestiv hjertesygdom, brystsmerter og myokardieinfarkt.
Cardiovascular system Hypertension, supraventricular arrhythmias, congestive heart failure, chest pain and myocardial infarction have been associated with alpha interferon therapies, including Pegasys.
Det anbefales, at patienter med hjerteabnormaliteter får taget elektrokardiogram før behandlingen med Pegasys påbegyndes.
It is recommended that patients who have pre-existing cardiac abnormalities have an electrocardiogram prior to initiation of Pegasys therapy.
4. 2).
In patients with cardiovascular disease, anaemia may necessitate dose reduction or discontinuation of ribavirin (see section 4.2).
Leverfunktion Behandlingen med Pegasys skal stoppes hos patienter, som får tegn på leverdekompensation under behandlingen.
Liver function In patients who develop evidence of hepatic decompensation during treatment, Pegasys should be discontinued.
Som tilfældet er for andre alfa- interferoner, er der set stigninger af ALAT, i forhold til baseline, hos patienter, som behandles med Pegasys, inklusive patienter med viralt respons.
As with other alpha interferons, increases in ALT levels above baseline have been observed in patients treated with Pegasys, including patients with a viral response.
4. 2 og 4. 8).
When the increase in ALT levels is progressive and clinically significant, despite dose reduction, or is accompanied by increased direct bilirubin, therapy should be discontinued (see sections 4.2 and 4.8).