natgillin/translations-raw huggingface dataset:
Hvis ASAT eller ALAT overstiger 5 gange øvre grænse for normalområdet (ULN), bør behandlingen tages op til fornyet vurdering, og SIRTURO og/eller et eventuelt hepatotoksisk baggrundslægemiddel bør seponeres.
If AST or ALT exceeds 5 times the upper limit of normal then the regimen should be reviewed and SIRTURO and/or any hepatotoxic background medicinal product should be discontinued.
SIRTURO-behandlingen skal seponeres, hvis patienten får:
SIRTURO treatment must be discontinued if the patient develops:
Hos patienter, der fik SIRTURO alene uden andre QT-forlængende lægemidler, var den maksimale gennemsnitlige øgning af QTcF-forlængelsen i forhold til baseline 23,7 ms, og QT-varigheden var i intet tilfælde over 480 ms, mens patienter der fik mindst 2 andre QT-forlængende lægemidler udviklede en maksimal gennemsnitlig QTcF-forlængelse på 30,7 ms i forhold til baseline, hvilket hos den ene patient resulterede i en QTcF-varighed over 500 ms.
Patients receiving SIRTURO alone with no other QT prolonging medicinal product developed a maximal mean QTcF increase over baseline of 23.7 ms with no QT duration in excess of 480 ms, whereas patients with at least 2 other QT prolonging medicinal products developed a maximal mean QTcF prolongation of 30.7 ms over baseline, resulting in a QTcF duration in excess of 500 ms in one patient.
Behandling med SIRTURO bør indledes og monitoreres af en læge med erfaring i behandling af multiresistent Mycobacterium tuberculosis.
Treatment with SIRTURO should be initiated and monitored by a physician experienced in the management of multi-drug resistant Mycobacterium tuberculosis.
I et interaktionsstudie af bedaquilin og ketoconazol sås en større påvirkning af QTc efter gentagne doser bedaquilin og ketoconazol i kombination end efter gentagne doser af de to lægemidler hver for sig.
In an interaction study of bedaquiline and ketoconazole, a greater effect on QTc was observed after repeated dosing with bedaquiline and ketoconazole in combination than after repeated dosing with the individual medicinal products.
SIRTURO er hovedsageligt undersøgt hos personer med normal nyrefunktion.
SIRTURO has mainly been studied in patients with normal renal function.
Der foreligger ingen kliniske data om anvendelse af SIRTURO til behandling af:
There are no clinical data on the use of SIRTURO to treat:
Hvis der ikke foreligger in vitro-analyseresulter, kan der indledes behandling med SIRTURO i kombination med mindst fire andre lægemidler, som det er sandsynligt, at patientens isolat vil være følsomt over for.
If in vitro testing results are unavailable, treatment may be initiated with SIRTURO in combination with at least four medicinal products to which the patient's isolate is likely to be susceptible.
Hos dyr fordeler bedaquilin og dets aktive metabolit N-monodesmethyl (M2) sig i omfattende grad i de fleste væv, omend der sås lav optagelse i hjernen.
In animals, bedaquiline and its active N-monodesmethyl metabolite (M2) are extensively distributed to most tissues, however, brain uptake was low.
SIRTURO bruges til behandling af tuberkulose i lungerne, når sygdommen er blevet resistent (modstandsdygtig) over for andre antibiotika.
SIRTURO is used to treat tuberculosis that affects the lungs when the disease has become resistant to other antibiotics.
Uovertrukket, hvid til næsten hvid, rund bikonveks tablet, 11 mm i diameter, præget med "T" over "207" på den ene side og "100" på den anden side.
Uncoated, white to almost white round biconvex tablet, 11 mm in diameter, with debossing of "T" over "207" on one side and "100" on the other side.
Ældre (i alderen ≥ 65 år) Der foreligger begrænsede kliniske data (n = 2) om anvendelse af SIRTURO til ældre patienter.
Elderly population (≥ 65 years of age) There is limited clinical data (n = 2) on the use of SIRTURO in elderly patients.
Tabletter pakket i: - blister af aluminium/aluminiumsfolie: 3 år - hvid højdensitetspolyethylen (HDPE) beholder: 3 år
Tablets packaged in: - aluminium/aluminium foil blisters: 3 years - white high density polyethylene (HDPE) bottles: 3 years
Indvirkningen på mikrobiologiske resultater af høje MIC-værdier for bedaquilin ved baseline, tilstedeværelsen af Rv0689-baserede mutationer ved baseline og/eller øgede MIC-værdier for bedaquilin efter baseline er ikke tydelig på grund af den lave forekomst af sådanne tilfælde i fase II-forsøgene.
The impact of high baseline bedaquiline MICs, the presence of Rv0678 based mutations at baseline, and/or increased post-baseline bedaquiline MICs on microbiologic outcomes is unclear because of the low incidence of such cases in the Phase II trials.
Bedaquilin hæmmer specifikt mykobakteriel ATP-syntase (adenosin 5'-triphosphat-syntase), et essentielt enzym til generering af energi i Mycobacterium tuberculosis.
Bedaquiline specifically inhibits mycobacterial ATP (adenosine 5'-triphosphate) synthase, an essential enzyme for the generation of energy in Mycobacterium tuberculosis.
Studie C209 evaluerede sikkerhed, tolerabilitet og virkning af 24 ugers behandling med ikke-blindet SIRTURO som led i et individualiseret behandlingsregime hos 233 patienter, som havde positiv mikroskopi af ekspektorat inden for 6 måneder før screening.
Study C209 evaluated the safety, tolerability, and efficacy of 24 weeks treatment with open-label SIRTURO as part of an individualized treatment regimen in 233 patients who were sputum smear positive within 6 months prior to screening.
• QTcF-interval på > 500 ms (bekræftet af nyt elektrokardiogram).
• A QTcF interval of > 500 ms (confirmed by repeat electrocardiogram).
Der anbefales ikke at initiere behandling med SIRTURO hos patienter i følgende tilfælde, med mindre fordelene ved bedaquilin anses for at opveje den mulige risiko:
SIRTURO treatment initiation is not recommended in patients with the following, unless the benefits of bedaquiline are considered to outweigh the potential risks:
Naturligt resistente organismer Mycobacterium xenopi Mycobacterium novocastrense Mycobacterium shimoidei Non-mykobakterielle arter
Inherently resistant organisms Mycobacterium xenopi Mycobacterium novocastrense Mycobacterium shimoidei Non-mycobacterial species
Af de 42 patienter, som var non-respondere i uge 24, forekom der bekræftet dyrkningskonvertering efter uge 24 (dvs. efter afslutning af bedaquilin-dosering, men fortsat på baggrundsregime) hos 9 patienter (21,4 %), og dette var bibeholdt i uge 120.
Of the 42 patients who were non-responders at week 24, confirmed culture conversion after week 24 (i.e., after bedaquiline dosing ended but the background regimen was continued) occurred in 9 patients (21.4%) and was maintained at week 120.
Indehaveren af markedsføringstilladelsen vil vurdere yderligere data for bedaquilins effekt og sikkerhed i forskellige behandlingsregimer sammenlignet med et behandlingsregime, der ikke omfatter bedaquilin (bekræftende fase III studie) efter en aftalt protokol.
The MAH will evaluate additional efficacy and safety data of bedaquiline in different treatment regimen compared to a regimen that does not include bedaquiline (confirmatory phase III study) following an agreed protocol.
Hepatisk sikkerhed
Hepatic safety
Mycobacterium xenopi, Mycobacterium novocastrense, Mycobacterium shimoidei og non-mycobakterielle arter anses for naturligt resistente over for bedaquilin.
Mycobacterium xenopi, Mycobacterium novocastrense, Mycobacterium shimoidei and non-mycobacterial species are considered inherently resistant to bedaquiline.
Patienterne fik SIRTURO (n = 79) eller placebo (n = 81) i 24 uger, begge i kombination med et foretrukkent baggrundsregime (BR) bestående af 5 lægemidler, der omfattede ethionamid, kanamycin, pyrazinamid, ofloxacin og cycloserin/terizidon.
Patients received SIRTURO (n = 79) or placebo (n = 81) for 24 weeks, both in combination with a preferred 5-drug background regimen (BR) consisting of ethionamide, kanamycin, pyrazinamide, ofloxacin, and cycloserine/terizidone.
In vitro- og in vivo-genotoksicitetstests indikerede, at bedaquilin ikke udviste mutagene eller clastogene effekter.
In vitro and in vivo genotoxicity tests indicated that bedaquiline did not have any mutagenic or clastogenic effects.
4.5 under "QT-interval og samtidig brug af clofazimin" for yderligere oplysninger om samtidig anvendelse af clofazimin.
See section 4.5, QT interval and concomitant clofazimine use, for further information regarding patients using clofazimine concomitantly.
• hvis du eller nogen i din familie har en hjertelidelse kaldet “medfødt langt QT-syndrom”
• you have a personal or family history of a heart problem called “congenital long QT syndrome”;
Publicerede data fra patienter behandlet med bedaquilin som del af en behandling for lægemiddelresistent TB og lopinavir/ritonavirbaseret antiretroviral behandling har vist, at eksponeringen (AUC) for bedaquilin over 48 timer steg cirka 2 gange.
Published data on patients treated with bedaquiline as part of therapy for drugresistant TB and lopinavir/ritonavir-based ART have shown that bedaquiline exposure (AUC) over 48 hours was increased approximately 2 fold.
I SIRTURO-gruppen observeredes ingen eller kun mindre forskelle i tid til konvertering af dyrkningsprøver og konverteringsrater for dyrkningsprøver mellem patienter med præ-XDR-TB og patienter med MDRH&R-TB.
In the SIRTURO group, no or only minor differences in time to culture conversion and culture conversion rates were observed between patients with pre-XDR-TB and patients with MDRH&R-TB.
Forholdet mellem farmakokinetik/farmakodynamik
Pharmacokinetic/pharmacodynamic relationship
Bedaquilin er bakteriostatisk for mange non-tuberkuløse mykobakterielle arter.
Bedaquiline is bacteriostatic for many non-tuberculous mycobacterial species.
Hos de resterende forsøgspersoner, der fik SIRTURO, var dødsårsagerne alkoholforgiftning, hepatitis/levercirrose, septisk chok/peritonitis, cerebrovakulær hændelse og ulykke med motorkøretøj.
The causes of death in the remaining SIRTURO subjects were alcohol poisoning, hepatitis/hepatic cirrhosis, septic shock/peritonitis, cerebrovascular accident and motor vehicle accident.
Der foreligger ingen kliniske data om anvendelse af SIRTURO som led i kombinationsregime til at behandle lægemiddelfølsomt Mycobacterium tuberculosis.
There are no clinical data on the use of SIRTURO as part of combination regimens used to treat drug-susceptible Mycobacterium tuberculosis.
Hos rotter sås ingen bivirkninger i et præ- og postnatalt udviklingsstudie efter eksponering af maternel plasma (AUC) svarende til eksponeringen hos mennesker, og eksponering af afkommet var 3 gange højere end hos voksne mennesker.
In the rat, no adverse effects were observed in a pre- and post-natal development study at maternal plasma exposure (AUC) similar to humans and exposure in the offspring 3-fold higher than in adult humans.
Hæmning af ATP-syntase medfører bactericide virkninger på både replikerende og ikke-replikerende tuberkelbaciller.
The inhibition of ATP synthase leads to bactericidal effects for both replicating and non-replicating tubercle bacilli.
Der foreligger begrænsede kliniske data (n = 2) om anvendelse af SIRTURO til tuberkulosepatienter i alderen > 65 år.
There is limited clinical data (n = 2) on the use of SIRTURO in tuberculosis patients aged 65 years and older.
Graden af resistens baseret på centrallaboratoriets analyseresultater for lægemiddelfølsomhed var ikke tilgængelig for 32 forsøgspersoner i mITT-populationen.
Extent of resistance based on central laboratory drug susceptibility testing results was not available for 32 subjects in the mITT population.
Hvis du springer doser over eller ikke gennemfører hele behandlingen:
Skipping doses or not completing the full course of therapy may:
Bedaquilin og M2 hæmmede ikke transportørerne P-gp, OATP1B1, OATP1B3, BCRP, OAT1, OAT3, OCT1, OCT2, MATE1 og MATE2 in vitro ved klinisk relevante koncentrationer.
Bedaquiline and M2 did not inhibit the transporters P-gp, OATP1B1, OATP1B3, BCRP, OAT1, OAT3, OCT1, OCT2, MATE1 and MATE2 at clinically relevant concentrations in vitro.
Den tilsvarende plasmaeksponering (AUC) var 2 gange så høj hos rotter i forhold til hos mennesker.
The corresponding plasma exposure (AUC) was 2-fold higher in rats compared to humans.
I musemodellen for TB-infektion har bedaquilin udvist baktericide og steriliserende virkninger.
In the mouse model for TB infection, bedaquiline has demonstrated bactericidal and sterilizing activities.
Bedaquilin metaboliseres af CYP3A4.
Bedaquiline is metabolised by CYP3A4.
Størstedelen af isolater, der er fenotype resistente over for bedaquilin, er krydsresistente over for clofazimin.
The majority of isolates that are phenotypically resistant to bedaquiline are cross-resistant to clofazimine.
Æske, der indeholder 4 tryk-ud blisterstrip (med 6 tabletter per strip).
A carton containing 4 push-through blister strips (containing 6 tablets per strip).
Metabolitten N-monodesmethyl (M2) menes ikke at bidrage i væsentlig grad til den kliniske virkning på grund af den lavere gennemsnitlige eksponering for denne metabolit (23 % til 31 %) hos mennesker og begrænsede virkning mod mykobakterier (3-6 gange lavere) sammenlignet med moderstoffet.
The N-monodesmethyl metabolite (M2) is not thought to contribute significantly to clinical efficacy given its lower average exposure (23% to 31%) in humans and lower antimycobacterial activity (3- to 6-fold lower) compared to the parent compound.
5.1 for yderligere oplysninger om dødsfald i C209-studiet.
For additional information on deaths in the C209 trial, see section 5.1.
efavirenz, etravirin, lopinavir/ritonavir til at behandle hiv-infektioner (antiretrovirale non-nukleosid revers transkriptasehæmmere, antiretrovirale proteasehæmmere)
efavirenz, etravirine, lopinavir/ritonavir to treat HIV infection (antiretroviral non-nucleoside reverse transcriptase inhibitors, antiretroviral protease inhibitors)
Udskillelse i urinen af uomdannet bedaquilin udgjorde < 0,001 % af dosis i kliniske studier, hvilket indikerer, at kun en ubetydelig del af det aktive stof udskilles uomdannet gennem nyrerne.
The urinary excretion of unchanged bedaquiline was < 0.001% of the dose in clinical studies, indicating that renal clearance of unchanged active substance is insignificant.
• Uge 3-24: 200 mg (2 tabletter a 100 mg) tre gange ugentligt (med mindst 48 timers interval mellem doserne).
• Weeks 3-24: 200 mg (2 tablets of 100 mg) three times per week (with at least 48 hours between doses).
clofazimin mod visse infektioner såsom lepra
clofazimine to treat some infections like leprosy
Der sås ingen strukturelle forandringer i testikler og bitestikler efter op til 6 måneders behandling med bedaquilin.
No structural abnormalities in the testes and epididymides were seen after up to 6-months of bedaquiline treatment.
Tre af 24 hanrotter behandlet med højdosis bedaquilin fik intet afkom i fertilitetsstudiet.
Three of 24 male rats treated with high bedaquiline doses failed to produce offspring in the fertility study.
Der kunne ikke observeres et påviseligt mønster mellem død og konvertering af ekspektoratatdyrkning, recidiv, følsomhed over for andre lægemidler mod tuberkulose, hiv-status eller sygdommens sværhedsgrad.
No discernible pattern between death and sputum culture conversion, relapse, sensitivity to other medicinal products used to treat tuberculosis, human immunodeficiency virus status, or severity of disease could be observed.
Det er ikke nødvendigt at justere dosis af isoniazid eller pyrazinamid under samtidig administration af bedaquilin.
No dose-adjustment of isoniazid or pyrazinamide is required during co-administration with bedaquiline.
Brug ikke lægemidlet efter den udløbsdato, der står på pakningen efter Exp. Udløbsdatoen er den sidste dag i den nævnte måned.
Do not use this medicine after the expiry date which is stated on the carton after “EXP”.
Der foreligger kun begrænsede data om bedaquilins virkning på hiv-inficerede patienter, der ikke får antiretrovirale (ARV) midler.
There are only limited clinical data on the efficacy of bedaquiline in HIV-infected patients not receiving antiretroviral (ARV) therapy.
Recidiv blev i dette studie defineret som positiv ekspektoratdyrkning efter eller under behandlingen efter tidligere konvertering af ekspektoratdyrkning.
Relapse was defined in the trial as having a positive sputum culture after or during treatment following prior sputum culture conversion.
Hver tablet indeholder bedaquilinfumarat svarende til 100 mg bedaquilin.
Each tablet contains bedaquiline fumarate equivalent to 100 mg bedaquiline.
Den største gennemsnitlige øgning af baselineværdier af QTcF under de 24 ugers behandling med SIRTURO var 15,7 ms (i uge 18).
The largest mean increase from baseline values in QTcF during the 24 weeks of SIRTURO treatment was 15.7 ms (at week 18).
• infektioner, der skyldes andre arter af mykobakterier end Mycobacterium tuberculosis
• infections due to mycobacterial species other than Mycobacterium tuberculosis
Efter at have nået Cmax faldt bedaquilins plasmakoncentration tre-eksponentielt.
After reaching Cmax, bedaquiline concentrations decline tri-exponentially.
SIRTURO's bivirkninger blev påvist i poolede data fra kliniske fase IIb-studier (såvel kontrollerede som ikke kontrollerede), der omfattede 335 patienter, som fik SIRTURO i kombination med et baggrundsregime af tuberkulostatika.
Adverse drug reactions for SIRTURO were identified from pooled Phase IIb clinical trial data (both controlled and uncontrolled) containing 335 patients who received SIRTURO in combination with a background regimen of tuberculosis medicinal products.
Et placebokontrolleret, dobbeltblindt, randomiseret fase IIb-studie (C208) evaluerede SIRTURO's antibakterielle virkning, sikkerhed og tolerabilitet hos nydiagnosticerede patienter med pulmonal MDRH&R- og præ-XDR-TB med mikroskopi-positive ekspektorater.
A Phase IIb, placebo-controlled, double-blind, randomised trial (C208) evaluated the antibacterial activity, safety, and tolerability of SIRTURO in newly diagnosed patients with sputum smear-positive pulmonary MDRH&R- and pre-XDR-TB.
Brug af SIRTURO sammen med alkohol Undgå at drikke alkohol under behandlingen med SIRTURO.
SIRTURO with alcohol You should not drink alcohol while taking SIRTURO.
Det primære resultatparameter var tid til konvertering af ekspektoratprøver (dvs. interval mellem den første indgift af SIRTURO og den første af to på hinanden følgende dyrkningsnegative flydende ekspektoratprøver udtaget med mindst 25 dages mellemrum) under behandling med SIRTURO eller placebo (median tid til konvertering var 83 døgn for SIRTURO-gruppen, 125 døgn for placebogruppen (hazard ratio, 95 % CI: 2,44 [1,57; 3,80]), p < 0,0001).
The primary outcome parameter was the time to sputum culture conversion (i.e. the interval between the first SIRTURO intake and the first of two consecutive negative liquid cultures from sputum collected at least 25 days apart) during treatment with SIRTURO or placebo (median time to conversion was 83 days for the SIRTURO group, 125 days for the placebo group (hazard ratio, 95% CI: 2.44 [1.57; 3.80]), p < 0.0001).
En børnesikret beholder indeholder 188 tabletter.
A plastic bottle containing 188 tablets.
Bedaquilin er virksomt mod Mycobacterium tuberculosis med en MIC-værdi (minimal inhibitory concentration) for såvel lægemiddelfølsomme som lægemiddelresistente stammer (multiresistente stammer, herunder præ-ekstremt og ekstremt resistente stammer i området ≤ 0,008-0,12 mg/l.
Bedaquiline has activity against Mycobacterium tuberculosis with a minimal inhibitory concentration (MIC) for drug-sensitive as well as drug-resistant strains (multi-drug resistant including preextensively drug resistant strains, extensively drug resistant strains) in the range of ≤ 0.008-0.12 mg/l.
Patienterne bør monitoreres for symptomer og have udført laboratorieundersøgelser (ALAT, ASAT, basisk fosfatase og bilirubin) ved baseline, hver måned under behandlingen og ellers efter behov.
Monitor symptoms and laboratory tests (ALT, AST, alkaline phosphatase, and bilirubin) at baseline, monthly while on treatment, and as needed.
Forsigtighed tilrådes ved ordination af bedaquilin samtidig med lægemidler med kendt risiko for QT-forlængelse.
Caution is recommended when prescribing bedaquiline concomitantly with medicinal products with a known risk of QT prolongation.
For en sikkerheds skyld skal SIRTURO undgås under graviditeten, medmindre fordelene ved behandlingen anses at opveje risikoen.
As a precautionary measure, avoid the use of SIRTURO during pregnancy unless the benefit of therapy is considered to outweigh the risks.
Sammenlignet med de eksponeringer (AUC), der observeredes hos individer med MDR-TB i fase IIforsøgene med bedaquilin, var eksponeringerne (AUC) hos rotter ved høje doser sammenlignelige hos hanner og 2 gange så høj hos hunner for bedaquilin og 3 gange så høj hos hanner og 2 gange så høj hos hunner for M2.
Compared to the exposures (AUC) observed in subjects with MDR-TB in the bedaquiline phase II trials, the exposures (AUC) in rats at high doses were similar in males and 2-fold higher in females for bedaquiline, and 3-fold higher in males and 2-fold higher in females for M2.
Tag ikke SIRTURO:
Do not take SIRTURO if:
Bedaquilins farmakokinetiske egenskaber blev evalueret hos voksne raske forsøgspersoner og voksne patienter inficeret med multiresistent tuberkulose.
The pharmacokinetic properties of bedaquiline have been evaluated in adult healthy subjects and in adult multi-drug resistant tuberculosis-infected patients.
Mikrokrystallinsk cellulose Croscarmellosenatrium Silica, vandfri kolloid Magnesiumstearat
Microcrystalline cellulose Croscarmellose sodium Silica, colloidal anhydrous Magnesium stearate
For patienter med fuld resistensundersøgelse var 76 % (84/111) inficeret med en MDRH&R-TB-stamme, og 24 % (27/111) med en præ-XDR-TB-stamme.
For patients with full characterisation of resistance status, 76% (84/111) were infected with an MDRH&R-TB strain and 24% (27/111) with a pre-XDR-TB strain.
I en populationfarmakokinetisk analyse af tuberkulosepatienter, der blev behandlet med SIRTURO, var eksponeringen for bedaquilin lavere hos sorte patienter end hos patienter af andre racer.
In a population pharmacokinetic analysis of tuberculosis patients treated with SIRTURO, exposure to bedaquiline was found to be lower in Black patients than in patients from other race categories.
Pædiatriske patienter SIRTURO's farmakokinetik er ikke blevet evalueret hos pædiatriske patienter.
Paediatric patients The pharmacokinetics of SIRTURO in paediatric patients have not been evaluated.
Det Europæiske Lægemiddelagentur har udsat forpligtelsen til at fremlægge resultaterne af studier med SIRTURO i en eller flere undergrupper af den pædiatriske population ved behandling af multiresistent Mycobacterium tuberculosis (se pkt.
The European Medicines Agency has deferred the obligation to submit the results of studies with SIRTURO in one or more subsets of the paediatric population in the treatment of multi-drug resistant Mycobacterium tuberculosis (see section 4.2 for information on paediatric use).
I C208, som er et 120-ugers studie, hvor SIRTURO blev administreret i 24 uger i kombination med et baggrundsregime, forekom der flere dødsfald i SIRTURO-gruppen end i placebogruppen (se pkt.
In the 120-week C208 trial where SIRTURO was administered for 24 weeks in combination with a background regimen, more deaths occurred in the SIRTURO treatment group than in the placebo group (see section 5.1).
Bivirkningerne er opstillet efter systemorganklasse og hyppighed.
Adverse drug reactions are listed by system organ class (SOC) and frequency.
Inden for det koncentrationsområde, som opnås med den terapeutiske dosis, blev der ikke observeret et forhold mellem farmakokinetik og farmakodynamik hos patienterne.
Within the concentration range achieved with the therapeutic dose, no pharmacokinetic/pharmacodynamic relationship was observed in patients.