natgillin/translations-raw huggingface dataset:
Naturligt forekommende mutationer i influenza A/ H1N1- virus med reduceret modtagelighed over for oseltamivir in vitro er set hos patienter, som baseret på den rapporterede information, ikke har været udsat for oseltamivir.
Naturally occurring mutations in influenza A/ H1N1 virus associated with reduced susceptibility to oseltamivir in vitro have been detected in patients who, based on the reported information, have not been exposed to oseltamivir.
Graden af reduceret modtagelighed over for oseltamivir og prævalensen af sådanne vira, forekommer at variere sæsonmæssigt og geografisk.
The extent of reduction in susceptibility to oseltamivir and the prevalence of such viruses appears to vary seasonally and geographically.
Behandling af influenzainfektion Oseltamivir er kun effektivt overfor sygdomme forårsaget af influenzavirus.
Treatment of influenza infection Oseltamivir is effective only against illnesses caused by influenza virus.
I den samlede behandlingspopulation, som omfattede både influenza- positive – og negative personer, reduceredes den primære effekt proportionalt med antallet af ikke smittede personer (ITT).
In the pooled treatment study population, which included both influenza-positive and -negative subjects (ITT), primary efficacy was reduced proportional to the number of influenza-negative individuals.
46% - 74%) af de rekrutterede patienter.
In the overall treatment population, influenza infection was confirmed in 67% (range 46% to 74%) of the recruited patients.
Af de ældre patienter var 64% influenza- positive og af de der havde kronisk hjerte - og/ eller luftvejslidelse var 62% influenza- positive.
Of the elderly subjects, 64% were influenza-positive and of those with chronic cardiac and/ or respiratory disease 62% were influenza-positive.
Voksne og unge, som var 13 år eller ældre:
Adults and adolescents 13 years of age and older:
Patienterne var valgbare, hvis de meldte sig senest 36 timer efter symptomerne var begyndt, havde feber ≥ 37, 8 ° C, ledsaget af mindst et respiratorisk symptom (hoste, nasale symptomer eller ondt i halsen) og mindst et systemisk symptom (myalgi, kulderystelser/ sveden, utilpashed, træthed eller hovedpine).
Patients were eligible if they reported within 36 hours of onset of symptoms, had fever ≥ 37.8 °C, accompanied by at least one respiratory symptom (cough, nasal symptoms or sore throat) and at least one systemic symptom (myalgia, chills/ sweats, malaise, fatigue or headache).
4, 0 – 4, 4 dage, p ≤ 0, 0001).
In a pooled analysis of all influenza-positive adults and adolescents (N = 2413) enrolled into treatment studies, oseltamivir 75 mg twice daily for 5 days reduced the median duration of influenza illness by approximately one day from 5.2 days (95% CI 4.9 – 5.5 days) in the placebo group to 4.2 days (95% CI 4.0 – 4.4 days; p ≤ 0.0001).
Antallet af patienter, som udviklede specificerede komplikationer i de nedre luftveje (hovedsageligt bronkitis), og som behandledes med antibiotika, nedsattes fra 12, 7% (135/ 1063) i placebogruppen til 8, 6% (116/ 1350) i oseltamivirgruppen (p ≤ 0, 0012).
The proportion of subjects who developed specified lower respiratory tract complications (mainly bronchitis) treated with antibiotics was reduced from 12.7% (135/ 1063) in the placebo group to 8.6% (116/ 1350) in the oseltamivir treated population (p = 0.0012).
Behandling af influenza i høj- risiko populationer:
Treatment of influenza in high risk populations:
Den mediane sygdomsvarighed hos ældre patienter (≥ 65 år) og hos patienter med kroniske hjerte - og/ eller åndedrætssygdomme, som fik 75 mg oseltamivir to gange daglig i 5 dage, nedsattes ikke signifikant.
The median duration of influenza illness in elderly subjects (≥ 65 years) and in subjects with chronic cardiac and/ or respiratory disease receiving oseltamivir 75 mg twice daily for 5 days was not reduced significantly.
Hos ældre, influenza- positive patienter nedsatte oseltamivir signifikant hyppigheden af specificerede nedre luftvejskomplikationer (hovedsageligt bronkitis), som behandledes med antibiotika, fra 19% (52/ 268) i placebogruppen til 12% (29/ 250) i oseltamivirgruppen (p = 0, 0156).
In the influenza-positive elderly, oseltamivir significantly reduced the incidence of specified lower respiratory tract complications (mainly bronchitis) treated with antibiotics from 19% (52/ 268) in the placebo group to 12% (29/ 250) in the oseltamivir treated population (p = 0.0156).
Hos influenza- positive patienter med kroniske hjerte - og/ eller åndedrætssygdomme var den samlede hyppighed af komplikationer i de nedre luftveje (hovedsaglig bronkitis) behandlet med antibiotika 17% (22/ 133) i placebogruppen og 14% (16/ 118) i Tamiflugruppen (p = 0, 5976).
In influenza-positive patients with chronic cardiac and/ or respiratory disease, the combined incidence of lower respiratory tract complications (mainly bronchitis) treated with antibiotics was 17% (22/ 133) in the placebo group and 14% (16/ 118) in the oseltamivir treated population (p = 0.5976).
Behandling af influenza hos børn:
Treatment of influenza in children:
5, 3 år), som havde feber (≥ 37. 8° C) plus enten hoste eller forkølelse var 67% af de influenza- positive patienter smittet med influenza A og 33% med influenza B.
In a study of otherwise healthy children (65% influenza-positive) aged 1 to 12 years (mean age 5.3 years) who had fever (≥ 37.8 °C) plus either cough or coryza, 67% of influenza-positive patients were infected with influenza A and 33% with influenza B.
Behandling med oseltamivir påbegyndt senest 48 timer efter symptomstart, nedsatte tiden indtil helbredelse af sygdommen signifikant (defineret som samtidig mildning af hoste, forstoppet næse, feber og forældrenes rapportering om barnets tilbagevenden til normalt helbred og normal aktivitet) med 1, 5 dag (95% konfidensinterval:
Oseltamivir
Oseltamivir nedsatte incidensen af akut otitis media fra 26, 5% (53/ 200) i placebogruppen til 16% (29/ 183) i oseltamivirgruppen (p = 0, 0013).
10 reduced the incidence of acute otitis media from 26.5% (53/ 200) in the placebo group to 16% (29/ 183) in the oseltamivir treated children (p = 0.013).
Et andet studie fuldførtes hos 334 astmatiske børn i alderen 6 til 12 år, af hvilke 53, 6% var smittet med influenza.
A second study was completed in 334 asthmatic children aged 6 to 12 years old of which 53.6% were influenza-positive.
Efter 6 dage (sidste behandlingsdag) øgedes FEV1 med 10, 8% i oseltamivirgruppen sammenlignet med 4, 7% i placebogruppen (p=0, 0148).
By day 6 (the last day of treatment) FEV1 had increased by 10.8% in the oseltamivir treated group compared to 4.7% on placebo (p = 0.0148) in this population.
10 Behandling af influenza B:
Treatment of influenza B infection:
I de enkelte studier spændte hyppigheden fra 1 – 33%.
Overall, 15% of the influenza-positive population were infected by influenza B, proportions ranging from 1 to 33% in individual studies.
0, 4 – 1, 7 dage, p < 0, 001).
Oseltamivir reduced the time to alleviation of all symptoms by 0.7 days (95% CI 0.1 – 1.6 days; p = 0.022) and the duration of fever (≥ 37.8 °C), cough and coryza by one day (95% CI 0.4 – 1.7 days; p < 0.001) compared to placebo.
Forebyggelse af influenza Effekten af oseltamivir mht. forebyggelse af naturligt optrædende influenza er påvist i et forebyggelsesstudie med husstande udsat for smitte og i to profylaktiske sæsonstudier.
Prevention of influenza The efficacy of oseltamivir in preventing naturally occurring influenza illness has been demonstrated in a post-exposure prevention study in households and two seasonal prevention studies.
Virulensen af influenzaepidemier kan ikke forudsiges og varierer i et område og fra sæson til sæson, hvorfor ” number needed to treat ”, som skal behandles for at forebygge et influenzatilfælde (NNT), varierer.
The virulence of influenza epidemics is not predictable and varies within a region and from season to season, therefore the number needed to treat (NNT) in order to prevent one case of influenza illness varies.
Forebyggelse efter smitte:
Post-exposure prevention:
Behandlingen fortsattes i syv dage.
In a study in contacts (12.6% vaccinated against influenza) of an index case of influenza, oseltamivir 75 mg once daily was started within 2 days of onset of symptoms in the index case and continued for seven days.
Oseltamivir nedsatte signifikant hyppigheden af klinisk influenza hos de personer, som havde haft kontakt med personer med bekræftet influenza fra 24/ 200 (12%) i placebogruppen til 2/ 205 (1%) i oseltamivirgruppen (92% reduktion [95% KI 6 - 16, p ≤ 0, 0001]).
Oseltamivir significantly reduced the incidence of clinical influenza illness occurring in the contacts of confirmed influenza cases from 24/ 200 (12%) in the placebo group to 2/ 205 (1%) in the oseltamivir group (92% reduction [95% CI 6 – 16; p ≤ 0.0001]).
15- 19) i hele populationen (ITT), uanset infektionsstatus hos kontaktpersonerne.
The number needed to treat (NNT) in contacts of true influenza cases was 10 (95% CI 9 – 12) and was 16 (95% CI 15 – 19) in the whole population (ITT) regardless of infection status in the index case.
Effekten af oseltamivir ved forebyggelse af naturligt forekommende influenza er påvist i en post - eksponeringsundersøgelse med husstande udsat for smitte, der inkluderede voksne, unge og børn i alderen 1 til 12 år, både som indeks tilfælde og som familiekontakter.
The efficacy of oseltamivir in preventing naturally occurring influenza illness has been demonstrated in a post-exposure prevention study in households that included adults, adolescents, and children aged 1 to 12 years, both as index cases and as family contacts.
Den primære effektparameter for denne undersøgelse var forekomst af laboratorie- bekræftet klinisk influenza i husstandene.
The primary efficacy parameter for this study was the incidence of laboratory-confirmed clinical influenza in the households.
I den samlede population var der en reduktion i forekomsten af laboratoriebekræftet klinisk influenza i husstande fra 20% (27/ 136) i gruppen, der ikke fik forebyggelsesbehandling til 7% (10/ 135) i den gruppe, som fik forebyggelsesbehandling (62, 7% reduktion [95% konfidensinterval 26, 0- 81, 2, p=0, 0042]).
In the total population, there was a reduction in the incidence of laboratory-confirmed clinical influenza in households from 20% (27/ 136) in the group not receiving prevention to 7% (10/ 135) in the group receiving prevention (62.7% reduction [95% CI 26.0 – 81.2; p = 0.0042]).
I husstande med influenzasmittede indekstilfælde var der en reduktion i forekomsten af influenza fra 26% (23/ 89) i gruppen, der ikke fik forebyggelsesbehandling til 11% (9/ 84) i den gruppe, der fik forebyggelsesbehandling (58, 5% reduktion [95% konfidensinterval 15, 6- 79, 6, p=0, 0114]).
In households of influenza-infected index cases, there was a reduction in the incidence of influenza from 26% (23/ 89) in the group not receiving prevention to 11% (9/ 84) in the group receiving prevention (58.5% reduction [95% CI 15.6 – 79.6; p = 0.0114]).
Ifølge undergruppe analyser af børn i 1- 12 års alderen blev forekomsten af laboratoriebekræftet klinisk influenza signifikant reduceret fra 19% (21/ 111) i gruppen, der ikke fik forebyggelsesbehandling til 7% (7/ 104) i gruppen, der fik forebyggelsesbehandling (64, 4% reduktion [95% konfidensinterval 15, 8- 85, 0, p=0, 0188]).
According to subgroup analysis in children at 1 to 12 years of age, the incidence of laboratory- confirmed clinical influenza among children was significantly reduced from 19% (21/ 111) in the group not receiving prevention to 7% (7/ 104) in the group receiving prevention (64.4% reduction [95% CI 15.8 – 85.0; p = 0.0188]).
Blandt børn, som ikke allerede havde spredt virus ved baseline, reduceredes forekomsten af laboratorie - bekræftet klinisk influenza fra 21% (15/ 70) i gruppen, som ikke modtog forebyggelsesbehandling til 4% (2/ 47) i gruppen, som modtog forebyggelsesbehandling (80, 1% reduktion [95% konfidensinterval 22, 0 - 94, 9, p=0, 0206]).
Among children who were not already shedding virus at baseline, the incidence of laboratory-confirmed clinical influenza was reduced from 21% (15/ 70) in the group not receiving prevention to 4% (2/ 47) in the group receiving prevention (80.1% reduction [95% CI 22.0 – 94.9; p = 0.0206]).
NNT for den samlede pædiatriske population var 9 (95% konfidensinterval 7- 24) og 8 (95% konfidensinterval 6, øvre grænse kan ikke estimeres) i henholdsvis den samlede population (ITT) og i pædiatriske kontakter af inficerede indekstilfælde (ITTII).
The NNT for the total paediatric population was 9 (95% CI 7 – 24) and 8 (95% CI 6, upper limit not estimable) in the whole population (ITT) and in paediatric contacts of infected index cases (ITTII), respectively.
Forebyggelse under en influenzaepidemi i befolkningen:
Prevention during an influenza epidemic in the community:
I en sammenlagt analyse af to andre studier hos ikke vaccinerede, i øvrigt raske voksne nedsatte 6 ugers behandling med oseltamivir, 75 mg en gang daglig, under en influenzaepidemi signifikant hyppigheden af klinisk influenza hos ikke - vaccinerede, i øvrigt raske voksne, fra 25/ 519 (4, 8%) i placebogruppen til 6/ 520 (1, 2%) i oseltamivirgruppen (76% reduktion [konfidensinterval 1, 6 - 5, 7, p = 0, 0006]).
In a pooled analysis of two other studies conducted in unvaccinated otherwise healthy adults, oseltamivir 75 mg once daily given for 6 weeks significantly reduced the incidence of clinical influenza illness from 25/ 519 (4.8%) in the placebo
NNT i dette studie var 28 (95% konfidensinterval:
The NNT in this study was 28 (95% CI 24 – 50).
I et studie hos ældre beboere i plejehjem, hvoraf 80% blev vaccineret i studieperioden, nedsatte 6 ugers behandling med oseltamivir, 75 mg en gang daglig, signifikant hyppigheden af klinisk influenza fra 12/ 272 (4, 4%) i placebogruppen til 1/ 276 (0, 4%) i oseltamivirgruppen (92% reduktion
A study in elderly residents of nursing homes, where 80% of participants received vaccine in the season of the study, oseltamivir 75 mg once daily given for 6 weeks significantly reduced the incidence of clinical influenza illness from 12/ 272 (4.4%) in the placebo group to 1/ 276 (0.4%) in the oseltamivir group (92% reduction [95% CI 1.5 – 6.6; p = 0.0015]).
23- 62).
The NNT in this study was 25 (95% CI 23 – 62).
Der er ikke udført specifikke studier om reduktion af risikoen for komplikationer.
Specific studies have not been conducted to assess of the reduction in the risk of complications.
Absorption Efter oral administration af oseltamivirphosphat (prodrug) absorberes oseltamivir hurtigt fra gastrointestinalkanalen og omdannes i stor udstrækning, overvejende af hepatiske esteraser, til den aktive metabolit (oseltamivircarboxylat).
Absorption Oseltamivir is readily absorbed from the gastrointestinal tract after oral administration of oseltamivir phosphate (pro-drug) and is extensively converted by predominantly hepatic esterases to the active metabolite (oseltamivir carboxylate).
Mindst 75% af en oral dosis når den systemiske cirkulation som den aktive metabolit.
At least 75% of an oral dose reaches the systemic circulation as the active metabolite.
Eksponeringen for prodrug er mindre end 5% i forhold til den aktive metabolit.
Exposure to the pro-drug is less than 5% relative to the active metabolite.
23 liter, et volumen som er ækvivalent med ekstracellulærvæsken.
Distribution The mean volume of distribution at steady state of the oseltamivir carboxylate is approximately 23 litres in humans, a volume equivalent to extracellular body fluid.
3%).
The binding of the oseltamivir carboxylate to human plasma protein is negligible (approximately 3%).
Metabolisme Oseltamivir omdannes overvejende til oseltamivircarboxylat af esteraser som fortrinsvis findes i leveren.
Metabolism Oseltamivir is extensively converted to oseltamivir carboxylate by esterases located predominantly in the liver.
In vitro- studier har vist at hverken oseltamivir eller den aktive metabolit er substrat for eller hæmmer af cytokrom P450 - isoenzymer.
In vitro studies demonstrated that neither oseltamivir nor the active metabolite is a substrate for, or an inhibitor of, the major cytochrome P450 isoforms.
Elimination Absorberet oseltamivir elimineres primært (> 90%) ved omdannelse til oseltamivircarboxylat.
Elimination Absorbed oseltamivir is primarily (> 90%) eliminated by conversion to oseltamivir carboxylate.
Peak- plasmakoncentrationerne af oseltamivir carboxylat falder med en halveringstid på 6 til 10 timer hos de fleste forsøgspersoner.
Peak plasma concentrations of oseltamivir carboxylate decline with a half-life of 6 to 10 hours in most subjects.
Det tyder på at der udover den glomerulære filtration også finder en tubulær sekretion sted.
Renal clearance (18.8 l/ h) exceeds glomerular filtration rate (7.5 l/ h) indicating that tubular secretion occurs in addition to glomerular filtration.
Mindre end 20% af en oral, radioaktivt markeret dosis udskilles i fæces.
Less than 20% of an oral radiolabelled dose is eliminated in faeces.
Nyreinsufficiens Administration af 100 mg oseltamivirphosphat to gange daglig i fem dage til patienter med varierende grad af nyreinsufficiens har vist at eksponeringen overfor oseltamivircarboxylat er omvendt proportional med nyrefunktionen.
Renal impairment Administration of 100 mg oseltamivir phosphate twice daily for 5 days to patients with various degrees of renal impairment showed that exposure to oseltamivir carboxylate is inversely proportional to declining renal function.
4. 2.
For dosing, see section 4.2.
4. 2).
Hepatic impairment In vitro studies have concluded that exposure to oseltamivir is not expected to be increased significantly nor is exposure to the active metabolite expected to be significantly decreased in patients with hepatic impairment (see section 4.2).
Ældre Eksponeringen overfor den aktive metabolit i steady state, efter sammenlignelige doser oseltamivir, var 25 til 35% højere hos ældre (fra 65 til 78 år) sammenlignet med voksne under 65 år.
Elderly Exposure to the active metabolite at steady state was 25 to 35% higher in elderly (age 65 to 78 years) compared to adults less than 65 years of age given comparable doses of oseltamivir.
De observerede halveringstider hos ældre svarede til dem som er set hos unge voksne.
Half-lives observed in the elderly were similar to those seen in young adults.
4. 2).
On the basis of drug exposure and tolerability, dosage adjustments are not required for elderly patients unless there is evidence of severe renal impairment (creatinine clearance below 30 ml/ min) (see section 4.2).
Børn Oseltamivirs farmakokinetik er undersøgt i et enkeltdosis farmakokinetisk studie med børn i alderen 1 til 16 år.
12 Children The pharmacokinetics of oseltamivir have been evaluated in single-dose pharmacokinetic studies in children aged 1 to 16 years.
Multipel dosisfarmakokinetik undersøgtes hos et mindre antal børn, som indgik i et klinisk
Multiple-dose pharmacokinetics were studied in a small number of children enrolled in a clinical efficacy study.
Yngre børn udskilte både prodrug’ en og dens aktive metabolit hurtigere end voksne, resulterende i en lavere eksponering for en given mg/ kg- dosis.
The pharmacokinetics of oseltamivir in children over 12 years of age are similar to those in adults.
De prækliniske data viser ingen særlig risiko for mennesker vurderet ud fra konventionelle undersøgelser af sikkerhedsfarmakologi, toksicitet efter gentagne doser og genotoksicitet.
Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity and genotoxicity.
1500 mg/ kg/ dag og 500 mg/ kg/ dag.
Teratology studies have been conducted in rats and rabbits at doses of up to 1500 mg/ kg/ day and 500 mg/ kg/ day, respectively.
I et fertilitetsstudie på rotte med en dosis op til 1500 mg/ kg/ dag blev der, uanset køn, ikke påvist bivirkninger.
A rat fertility study up to a dose of 1500 mg/ kg/ day demonstrated no adverse effects on either sex.
I præ - og postnatale studier blev der set forlængelse af fødslen i doser på 1500 mg/ kg/ dag: sikkerhedsmarginen mellem human eksponering og den højeste uvirksomme dosis hos rotte (500 mg/ kg/ dag) er en faktor 480 for oseltamivir og en faktor 44 for den aktive metabolit.
In pre- and post-natal rat studies, prolonged parturition was noted at 1500 mg/ kg/ day: the safety margin between human exposure and the highest no-effect dose (500 mg/ kg/ day) in rats is 480-fold for oseltamivir and 44-fold for the active metabolite, respectively.
15 til 20% af eksponeringen hos moderen.
Foetal exposure in the rats and rabbits was approximately 15 to 20% of that of the mother.
0, 01 mg/ dag og 0, 3 mg/ dag.
It is not known whether oseltamivir or the active metabolite is excreted in human milk, but extrapolation of the animal data provides estimates of 0.01 mg/ day and 0.3 mg/ day for the respective compounds.
Ca.
A potential for skin sensitisation to oseltamivir was observed in a "maximisation" test in guinea pigs.
50% af dyrene, som behandledes med det uformulerede aktive stof fik erytem efter provokation af de testede dyr.
Approximately 50% of the animals treated with the unformulated active ingredient showed erythema after challenging the induced animals.
Meget høje enkeltdoser af oseltamivirphosphat havde ingen effekt hos voksne rotter, men resulterede derimod i toxicitet, herunder dødsfald, hos (juvenile) 7 dage gamle rotteunger.
Whereas very high oral single doses of oseltamivir phosphate had no effect in adult rats, such doses resulted in toxicity in juvenile 7-day-old rat pups, including death.
Denne virkning forekom ved doser på 657 mg/ kg og højere.
These effects were seen at doses of 657 mg/ kg and higher.
Ved 500 mg/ kg sås ingen bivirkninger, ej heller ved kronisk behandling (500 mg / kg / dag givet fra dag 7 til dag 21 post partum).
At 500 mg/ kg, no adverse effects were seen, including upon chronic treatment (500 mg/ kg/ day administered from 7 to 21 days post partum).
Kapselindhold:
Capsule core:
Prægelatineret stivelse (udvundet af majsstivelse) Talcum Povidon Croscarmellosenatrium Natriumstearylfumarat
Pregelatinized starch (derived from maize starch) Talc Povidone Croscarmellose sodium Sodium stearyl fumarate
Gelatine Gul jernoxid (E172) Rød jernoxid (E172) Titandioxid (E171)
Gelatin Yellow iron oxide (E172) Red iron oxide (E172) Titanium dioxide (E171)
13 Det påtrykte blæk:
13 Printing ink:
Shellak Titandioxid (E171) FD og C Blue 2 (indigokarmin, E132)
Shellac Titanium dioxide (E171) FD and C Blue 2 (indigo carmine, E132)
Dette lægemiddel kræver ingen særlige forholdsregler vedrørende opbevaringen
This medicinal product does not require any special storage condition.
En pakning indeholder 10 kapsler i en triplex blisterpakke (PVC/ PE/ PVDC, forseglet med aluminiumfolie).
One box contains 10 capsules in a triplex blister pack (PVC/ PE/ PVDC, sealed with aluminium foil).
20. juni 2002 Dato for seneste fornyelse:
20 June 2002 Date of last renewal:
Tamiflu 45 mg hårde kapsler.
Tamiflu 45 mg hard capsule.
Hårde kapsler De hårde kapsler består af en grå, ugennemsigtig krop, påtrykt ” ROCHE ” og en grå, ugennemsigtig hætte, påtrykt ” 45 mg ”.
Hard capsule The hard capsule consists of a grey opaque body bearing the imprint “ ROCHE” and a grey opaque cap bearing the imprint “ 45 mg”.
Behandling af influenza Til patienter, som er 1 år eller ældre, med typiske symptomer på influenza når der er influenza i området.
Treatment of influenza In patients one year of age and older who present with symptoms typical of influenza, when influenza virus is circulating in the community.