natgillin/translations-raw huggingface dataset:
Klinisk effekt (med delvist eller fuldstændigt respons, se neden for under Klinisk erfaring) er vist over for Aspergillus spp. herunder A. flavus, A. fumigatus, A. terreus, A. niger, A. nidulans, Candida spp., herunder C. albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis samt et begrænset antal af C. dubliniensis, C. inconspicua og C. guilliermondii, Scedosporium spp., herunder S. apiospermum, S. prolificans og Fusarium spp.
Microbiology Clinical efficacy (with partial or complete response, see below under Clinical Experience) has been demonstrated for Aspergillus spp. including A. flavus, A. fumigatus, A. terreus, A. niger, A. nidulans, Candida spp., including C. albicans, C. glabrata, C. krusei, C. parapsilosis and C. tropicalis and limited numbers of C. dubliniensis, C. inconspicua, and C. guilliermondii, Scedosporium spp., including S. apiospermum, S. prolificans and Fusarium spp.
Andre behandlede svampeinfektioner (med hyppigt delvist eller fuldstændigt respons) omfatter isolerede tilfælde af Alternaria spp., Blastomyces dermatitidis, Blastoschizomyces capitatus, Cladosporium spp., Coccidioides immitis, Conidiobolus coronatus, Cryptococcus neoformans, Exserholium rostratum, Exophiala spinifera, Fonsecaea pedrosoi, Madurella mycetomatis, Paecilomyces lilacinus, Penicillium spp. herunder P. marneffei, Phialophora richardsiae, Scopulariopsis brevicaulis og Trichosporon spp. herunder T. beigelii infektioner.
Other treated fungal infections (with often partial or complete response) included isolated cases of Alternaria spp., Blastomyces dermatitidis, Blastoschizomyces capitatus, Cladosporium spp., Coccidioides immitis, Conidiobolus coronatus, Cryptococcus neoformans, Exserohilum rostratum, Exophiala spinifera, Fonsecaea pedrosoi, Madurella mycetomatis, Paecilomyces lilacinus, Penicillium spp. including P. marneffei, Phialophora richardsiae, Scopulariopsis brevicaulis and Trichosporon spp. including T. beigelii infections.
In vitro aktivitet over for kliniske isolater er set over for Acremonium spp., Alternaria spp., Bipolaris spp., Cladophialophora spp., Histoplasma capsulatum, hvor de fleste stammer bliver hæmmet af voriconazolkoncentrationer i området fra 0, 05 til 2 μg/ ml.
In vitro activity against clinical isolates has been observed for Acremonium spp., Alternaria spp., Bipolaris spp., Cladophialophora spp., Histoplasma capsulatum, with most strains being inhibited by concentrations of voriconazole in the range 0.05 to 2µg/ ml.
In vitro aktivitet over for følgende patogener er vist, men den kliniske betydning er ukendt:
15 In vitro activity against the following pathogens has been shown, but the clinical significance is unknown:
15 Artsbestemmelse af svampekultur og andre relevante laboratorieundersøgelser (serologi, histopatologi) bør foretages før behandling for at isolere og identificere de sygdomsfremkaldende mikroorganismer.
Specimens for fungal culture and other relevant laboratory studies (serology, histopathology) should be obtained prior to therapy to isolate and identify causative organisms.
Kliniske isolater med nedsat følsomhed over for voriconazol er blevet identificeret.
Clinical isolates with decreased susceptibility to voriconazole have been identified.
Forhøjede mindste hæmmende koncentrationsværdier korrelerede ikke altid med klinisk svigt, og klinisk succes er set hos patienter inficeret med organismer, der er resistente over for andre azoler.
However, elevated minimum inhibitory concentrations did not always correlate with clinical failure and clinical success has been observed in patients infected with organisms resistant to other azoles.
Korrelationen mellem in vitro aktivitet og det kliniske resultat er vanskelig på grund af kompleksiteten hos de patienter, der er undersøgt i kliniske studier; ” breakpoints ” (følsomhedsgrænser) for voriconazol er endnu ikke fastslået.
Correlation of in vitro activity with clinical outcome is difficult owing to the complexity of the patients studied in clinical trials; breakpoints for voriconazole remain to be established.
Positivt resultat defineres i dette afsnit som fuldstændigt eller delvis respons.
Clinical Experience Successful outcome in this section is defined as complete or partial response.
Aspergillus- infektioner – effekt hos aspergillose patienter med dårlig prognose Voriconazol har in vitro fungicid aktivitet over for Aspergillus spp.
Aspergillus infections – efficacy in aspergillosis patients with poor prognosis Voriconazole has in vitro fungicidal activity against Aspergillus spp.
Der sås tilfredstillende globalt respons (fuldstændig eller delvis resolution af alle tilhørende symptomer, radiografiske/ bronkoskopiske abnormaliteter ved baseline) hos 53% af de voriconazolbehandlede patienter sammenlignet med 31% af patienterne behandlet med komparatoren.
A satisfactory global response (complete or partial resolution of all attributable symptoms signs, radiographic/ bronchoscopic abnormalities present at baseline) was seen in 53% of voriconazole-treated patients compared to 31% of patients treated with comparator.
Dette studie bekræftede fund fra et tidligere prospektivt studie, hvor der sås positivt resultat hos patienter med risikofaktorer for dårlig prognose, herunder graft- versus- host sygdom og i særdeleshed cerebrale infektioner (normalt forbundet med næsten 100% mortalitet).
This study confirmed findings from an earlier, prospectively designed study where there was a positive outcome in subjects with risk factors for a poor prognosis, including graft versus host disease, and, in particular, cerebral infections (normally associated with almost 100% mortality).
Disse studier omfatter cerebral, sinusrelateret, pulmonal og dissemineret aspergillose hos knoglemarvs - og organtransplanterede patienter, patienter med maligne hæmatologiske lidelser, cancer og AIDS.
The studies included cerebral, sinus, pulmonary and disseminated aspergillosis in patients with bone marrow and solid organ transplants, haematological malignancies, cancer and AIDS.
Effekten af voriconazol sammenlignet med behandling med amphotericin B efterfulgt af fluconazol i primær behandling af candidæmi, blev vist i et åbent komparativt studie.
Candidaemia in non-neutropenic patients The efficacy of voriconazole compared to the regimen of amphotericin B followed by fluconazole in the primary treatment of candidaemia was demonstrated in an open, comparative study.
Heraf blev 248 behandlet med voriconazol.
Three hundred and seventy non-neutropenic patients (above 12 years of age) with documented candidaemia were included in the study, of whom 248 were treated with voriconazole.
I den primære analyse var succesfuld respons, i følge en ” Data Review Committee ” (DRC), der var blindet over for studiemedicinen, defineret som resolution/ forbedring i alle kliniske tegn og symptomer på infektion med eradikation af Candida fra blodet og infektion i dybtliggende vævssteder 12 uger efter endt behandling (EOT).
In the primary analysis, successful response as assessed by a Data Review Committee (DRC) blinded to study medication was defined as resolution/ improvement in all clinical signs and symptoms of infection with eradication of Candida from blood and infected deep tissue sites at 12 weeks after the end of therapy (EOT).
I denne analyse var der succesfuld respons hos 41% af patienterne i begge behandlingsarme.
In this analysis a successful response was seen in 41% of patients in both treatment arms.
I en anden analyse, hvor DRCs vurderinger anvendes ved det seneste evaluerbare tidspunkt (EOT eller 2, 6 eller 12 uger efter EOT) havde voriconazol og amphotericin B efterfulgt af fluconazol en succesfuld responsrate på henholdsvis 65% og 71%.
In a secondary analysis, which utilised DRC assessments at the latest evaluable time point (EOT, or 2, 6, or 12 weeks after EOT) voriconazole and the regimen of amphotericin B followed by fluconazole had successful response rates of 65% and 71%, respectively.
16
The Investigator’ s assessment of successful outcome at each of these time points is shown in the following table.
Tidspunkt
16 Timepoint _
EOT 2 uger efter EOT 6 uger efter EOT 12 uger efter EOT
EOT 2 weeks after EOT
Alvorlige refraktære Candida- infektioner Studiet omfatter 55 patienter med alvorlige refraktære systemiske Candida- infektioner (herunder candidæmi, dissemineret og andre invasive candidiasis), hvor tidligere antimykotisk behandling, især med fluconazol ikke har været effektiv.
Serious refractory Candida infections The study comprised 55 patients with serious refractory systemic Candida infections (including candidaemia, disseminated and other invasive candidiasis) where prior antifungal treatment, particularly with fluconazole, had been ineffective.
I fluconazol- resistente ikke albicans arter er et succesfuldt resultat set hos 3/ 3 C. krusei (fuldstændigt respons) og 6/ 8 C. glabrata (5 med fuldstændigt, 1 med delvist respons) infektioner.
In fluconazole-resistant non albicans species, a successful outcome was seen in 3/ 3 C. krusei (complete responses) and 6/ 8 C. glabrata (5 complete, 1 partial response) infections.
Data vedrørende klinisk effekt bliver understøttet af begrænsede data for følsomhed.
The clinical efficacy data were supported by limited susceptibility data.
Scedosporium og Fusarium- infektioner Voriconazol har vist sig effektivt over for følgende sjældne patogene svampe:
Scedosporium and Fusarium infections Voriconazole was shown to be effective against the following rare fungal pathogens:
Succesrigt respons på voriconazolbehandling blev set hos 16 (6 med fuldstændigt, 10 med delvist respons) ud af 28 patienter med S. apiospermum og hos 2 (begge med delvist respons) ud af 7 patienter med S. prolificans infektion.
Successful response to voriconazole therapy was seen in 16 (6 complete, 10 partial responses) of 28 patients with S. apiospermum and in 2 (both partial responses) of 7 patients with S. prolificans infection.
7 (3 med fuldstændigt, 4 med delvist respons) ud af 17 patienter blev succesrigt behandlet med voriconazol.
Seven (3 complete, 4 partial responses) of 17 patients were successfully treated with voriconazole.
Yderligere 4 patienter havde en fusarium- infektion forårsaget af adskillige organismer; 2 af dem havde et succesrigt resultat.
Four additional patients with fusariosis had an infection caused by several organisms; two of them had a successful outcome.
Varighed af behandlingen I kliniske studier fik 561 patienter voriconazolbehandling i mere end 12 uger, heraf fik 136 patienter voriconazol i over 6 måneder.
Duration of treatment In clinical trials, 561 patients received voriconazole therapy for greater than 12 weeks, with 136 patients receiving voriconazole for over 6 months.
Erfaring med pædiatriske patienter 61 pædiatriske patienter i alderen 9 måneder til 15 år, som havde fået diagnosticeret eller sandsynligvis havde invasiv svampeinfektion, blev behandlet med voriconazol.
Experience in paediatric patients Sixty one paediatric patients aged 9 months up to 15 years who had definite or probable invasive fungal infections, were treated with voriconazole.
Denne population inkluderede 34 patienter i aldersgruppen 2 til < 12 år og 20 patienter i aldersgruppen 12- 15 år.
This population included 34 patients 2 to < 12 years old and 20 patients 12-15 years of age.
Hovedparten (57/ 61) havde ikke haft succes med tidligere svampebehandling.
The majority (57/ 61) had failed previous antifungal therapies.
Kliniske studier inkluderede 5 patienter i alderen 12- 15 år, de resterende patienter fik voriconazol i specielle kliniske programmer (” compassionate use ”).
Therapeutic studies included 5 patients aged 12-15 years, the remaining patients received voriconazole in the compassionate use programmes.
De tilgrundliggende sygdomme hos disse patienter omfattede ondartede hæmatologiske sygdomme og aplastisk anæmi (27 patienter) og kronisk granulomatose (14 patienter).
Underlying diseases in these patients included haematological malignancies and aplastic anaemia (27 patients) and chronic granulomatous disease (14 patients).
Den oftest behandlede svampeinfektion var aspergillose (43/ 61; 70%).
The most commonly treated fungal infection was aspergillosis (43/ 61; 70%).
Kliniske studier, der undersøger QT- intervallet Et placebokontrolleret, randomiseret, enkeltdosis, crossover studie, der undersøgte effekten på QT - intervallet hos raske frivillige forsøgspersoner, blev udført med 3 orale doser af voriconazol og ketoconazol.
Clinical Studies Examining QT Interval A placebo-controlled, randomized, single-dose, crossover study to evaluate the effect on the QT interval of healthy volunteers was conducted with three oral doses of voriconazole and ketoconazole.
De placebo- justerede gennemsnitlige maksimale stigninger i QTc i forhold til baseline efter 800 mg, 1200 mg og 1600 mg voriconazol var henholdsvis 5, 1 msek., 4, 8 msek. og 8, 2 msek. og
The placebo-adjusted mean maximum increases in QTc from baseline after 800, 1200 and 1600 mg of voriconazole were 5.1, 4.8, and 8.2 msec, respectively and 7.0 msec for ketoconazole 800 mg.
Ingen forsøgspersoner i nogen af grupperne havde en stigning i QTc på ≥60 msek. i forhold til baseline.
No 17 subject in any group had an increase in QTc of ≥ 60 msec from baseline.
Generelle farmakokinetiske karakteristika Voriconazols farmakokinetik er beskrevet hos raske forsøgspersoner, specielle populationer og patienter.
General pharmacokinetic characteristics The pharmacokinetics of voriconazole have been characterised in healthy subjects, special populations and patients.
Ved oral administration af 200 mg eller 300 mg 2 gange dagligt i 14 dage hos patienter med risiko for aspergillose (hovedsageligt patienter med ondartede svulster i det lymfatiske eller hæmatopoetiske væv) svarede de observerede farmakokinetiske karakteristika af hurtig og ensartet absorption, akkumulering og ikke- lineær farmakokinetik til, hvad man har observeret hos raske forsøgspersoner.
During oral administration of 200 mg or 300 mg twice daily for 14 days in patients at risk of aspergillosis (mainly patients with malignant neoplasms of lymphatic or haematopoietic tissue), the observed pharmacokinetic characteristics of rapid and consistent absorption, accumulation and non- linear pharmacokinetics were in agreement with those observed in healthy subjects.
Voriconazols farmakokinetik er ikke- lineær på grund af mætning af dets metabolisme.
The pharmacokinetics of voriconazole are non-linear due to saturation of its metabolism.
Det er skønnet, at en gennemsnitlig stigning i den orale dosis fra 200 mg 2 gange dagligt til 300 mg 2 gange dagligt fører til en 2, 5 gange stigning i eksponering (AUCτ).
It is estimated that, on average, increasing the oral dose from 200 mg twice daily to 300 mg twice daily leads to a 2.5-fold increase in exposure (AUCτ).
Uden initialdosis forekommer akkumulering ved 2 gange dagligt dosering indtil steady state plasma voriconazolkoncentrationer, som hos de fleste forsøgspersoner er opnået på dag 6.
Without the loading dose, accumulation occurs during twice daily multiple dosing with steady- state plasma voriconazole concentrations being achieved by day 6 in the majority of subjects.
Absorption Voriconazol absorberes hurtigt og næsten fuldstændigt efter oral administration med maksimale plasmakoncentrationer (Cmax) 1- 2 timer efter dosisindtagelse.
Absorption Voriconazole is rapidly and almost completely absorbed following oral administration, with maximum plasma concentrations (Cmax) achieved 1-2 hours after dosing.
Hvis flere doser voriconazol indtages sammen med meget fede måltider, vil Cmax og AUCτ blive reduceret med henholdsvis 34% og 24%.
When multiple doses of voriconazole are administered with high fat meals, Cmax and AUCτ are reduced by 34% and 24%, respectively.
Distribution Steady state fordelingsvolumen af voriconazol er anslået til at være 4, 6 l/ kg, hvilket indikerer udbredt fordeling ud i vævene.
Distribution The volume of distribution at steady state for voriconazole is estimated to be 4.6 l/ kg, suggesting extensive distribution into tissues.
Prøver af cerebrospinalvæsken fra 8 patienter i et særligt klinisk program (” compassionate use ”) viste målbare voriconazolkoncentrationer hos alle patienter.
Cerebrospinal fluid samples from eight patients in a compassionate programme showed detectable voriconazole concentrations in all patients.
Metabolisme In vitro forsøg har vist, at voriconazol metaboliseres via leverens cytokrom P450- isoenzymer CYP2C19, CYP2C9 og CYP3A4.
Metabolism In vitro studies showed that voriconazole is metabolised by the hepatic cytochrome P450 isoenzymes, CYP2C19, CYP2C9 and CYP3A4.
Den inter- individuelle variabilitet af voriconazols farmakokinetik er høj.
The inter-individual variability of voriconazole pharmacokinetics is high.
For eksempel forventes det, at det hos 15- 20% af de asiatiske populationer metaboliseres dårligt.
For example, 15-20% of Asian populations may be expected to be poor metabolisers.
Blandt kaukasiere og personer af negroid afstamning er prævalensen af personer med dårlig metaboliseringsevne 3- 5%.
For Caucasians and Blacks the prevalence of poor metabolisers is 35%.
Personer, som er heterozygotisk kraftigt metaboliserende har gennemsnitligt fordoblet voriconazol eksponering i forhold til deres homozygotisk kraftigt metaboliserende modparter.
Subjects who are heterozygous extensive metabolisers have on average 2- fold higher voriconazole exposure than their homozygous extensive metaboliser counterparts.
Hovedmetabolitten af voriconazol er N- oxid, der står for 72% af de cirkulerende radioaktivt mærkede metabolitter i plasma.
The major metabolite of voriconazole is the N-oxide, which accounts for 72% of the circulating radiolabelled metabolites in plasma.
Udskillelse Voriconazol udskilles ved levermetabolisme, hvor mindre end 2% af dosis udskilles uforandret i urinen.
Excretion Voriconazole is eliminated via hepatic metabolism with less than 2% of the dose excreted unchanged in the urine.
18 Efter administration af en radioaktivt mærket dosis af voriconazol bliver næsten 80% af radioaktiviteten genfundet i urinen efter gentagne intravenøse doser, og 83% i urinen efter gentagne orale doser.
18 is recovered in the urine after multiple intravenous dosing and 83% in the urine after multiple oral dosing.
Størstedelen (> 94%) af den totale radioaktivitet bliver udskilt i de første 96 timer efter både oral og intravenøs dosering.
The majority (> 94%) of the total radioactivity is excreted in the first 96 hours after both oral and intravenous dosing.
6 timer ved 200 mg (oralt).
The terminal half-life of voriconazole depends on dose and is approximately 6 hours at 200 mg (orally).
Grundet ikke- lineær farmakokinetik er halveringstiden ikke anvendelig i forudsigelsen af akkumuleringen eller udskillelsen af voriconazol.
Because of non-linear pharmacokinetics, the terminal half-life is not useful in the prediction of the accumulation or elimination of voriconazole.
Farmakokinetiske – farmakodynamiske relationer I 10 kliniske studier var medianen for gennemsnitlige og maksimale plasmakoncentrationer hos individuelleforsøgspersoner personer på tværs af studierne henholdsvis 2425 ng/ ml (inter- kvartil fra 1193 til 4380 ng/ ml) og 3742 ng/ ml (inter- kvartil fra 2027 til 6302 ng/ ml).
Pharmacokinetic-Pharmacodynamic relationships In 10 therapeutic studies, the median for the average and maximum plasma concentrations in individual subjects across the studies was 2425 ng/ ml (inter-quartile range 1193 to 4380 ng/ ml) and 3742 ng/ ml (inter-quartile range 2027 to 6302 ng/ ml), respectively.
En positiv sammenhæng mellem middel, maksimum og minimum plasmavoriconazolkoncentration og effekt i kliniske studier blev ikke fundet.
A positive association between mean, maximum or minimum plasma voriconazole concentration and efficacy in therapeutic studies was not found.
Farmkokinetiske- farmakodynamiske analyser af kliniske data identificerede positiv forbindelse mellem plasma voriconazolkoncentrationer og både abnorme leverfunktionsværdier og synsforstyrrelser.
Pharmacokinetic-Pharmacodynamic analyses of clinical trial data identified positive associations between plasma voriconazole concentrations and both liver function test abnormalities and visual disturbances.
Køn I et oralt flerdosisstudie med raske, unge kvinder var Cmax og AUCτ henholdsvis 83% og 113% højere, end hos raske, unge mænd (18- 45 år).
Pharmacokinetics in special patient groups Gender In an oral multiple dose study, Cmax and AUCτ for healthy young females were 83% and 113% higher, respectively, than in healthy young males (18-45 years).
Ældre I et oralt flerdosisstudie med raske, ældre mænd (≥ 65 år) var Cmax og AUCτ henholdsvis 61% og 86% højere end hos raske, unge mænd (18- 45 år).
Elderly In an oral multiple dose study Cmax and AUCτ in healthy elderly males (≥ 65 years) were 61% and 86% higher, respectively, than in healthy young males (18-45 years).
Der blev ikke observeret nogen signifikante forskelle i Cmax og AUCτ mellem raske, ældre kvinder (≥ 65 år) og raske, unge kvinder (18- 45 år).
No significant differences in Cmax and AUCτ were observed between healthy elderly females (≥ 65 years) and healthy young females (18- 45 years).
4. 2).
The safety profile of voriconazole in young and elderly patients was similar and, therefore, no dosage adjustment is necessary for the elderly (see section 4.2).
Børn Den anbefalede orale dosis for børn er baseret på en farmakokinetisk populationsanalyse af data fra 47 immunkompromitterede pædiatriske patienter i alderen 2 til < 12 år, som blev evalueret i et farmakokinetisk studie på multiple orale suspensionsdoser på 4 og 6 mg/ kg 2 gange om dagen.
Paediatric The recommended oral dose in paediatrics is based on a population pharmacokinetic analysis of data obtained from 47 immunocompromised paediatric patients aged 2 to < 12 years old who were evaluated in a pharmacokinetic study examining multiple oral suspension doses of 4 and 6 mg/ kg twice daily.
En sammenligning af de farmakokinetiske populationsdata fra børn og voksne indikerer at, for at opnå sammenlignelige eksponeringer fra de der er opnået hos voksne, efter en vedligeholdelsesdosis på 200 mg 2 gange dagligt, er 200 mg oral suspension 2 gange dagligt påkrævet hos pædiatriske patienter, uafhængig af legemsvægt.
A comparison of the paediatric and adult population pharmacokinetic data indicated that in order to obtain comparable exposures to those obtained in adults following a maintenance dose of 200 mg twice daily, 200 mg of oral suspension twice daily is required in paediatric patients, independent of body weight.
Hos pædiatriske patienter er der en generel trend mod lavere oral biotilgængelighed ved lavere legemsvægt og højere oral biotilgængelighed ved højere legemsvægt (nærmende sig den udstrækning der er vist hos voksne).
In paediatric patients there is a general trend towards low bioavailability at lower body weights and high bioavailability at higher body weights (approaching the extent demonstrated in adults).
Baseret på den farmakokinetisk populationsanalyse er dosisjustering ikke nødvendig, ud fra alder eller vægt, for patienter i alderen 2 til < 12 år, ved doseringen 200 mg oral suspension 2 gange dagligt.
Based on the population pharmacokinetic analysis, no dosage adjustment according to age or weight is warranted in patients aged 2 to < 12 years old at the 200 mg b. i. d. oral suspension dosing regimen.
En initialdosis er ikke indiceret til pædiatriske patienter.
A loading dose is not indicated in paediatric patients.
Hos pædiatriske patienter, med malabsorption og meget lav legemsvægt, for deres alder, kan oral biotilgængelighed være begrænset.
Oral bioavailability may, however, be limited in paediatric patients with malabsorption and very low body weight for their age.