natgillin/translations-raw huggingface dataset:
• hvis du er allergisk over for bedaquilin eller et af de øvrige indholdsstoffer i dette lægemiddel (angivet i afsnit 6).
• you are allergic to bedaquiline or any of the other ingredients of this medicine (listed in section 6).
Hypromellose Polysorbat 20
Hypromellose Polysorbate 20
• smertende eller ømme muskler, der ikke skyldes motion
• aching or tender muscles, not caused by exercise
24 tabletter
24 tablets
Bedaquilins plasmaproteinbinding er > 99,9 % hos alle de undersøgte arter inklusive mennesker.
The plasma protein binding of bedaquiline is > 99.9% in all species tested, including human.
Hyppighedskategorierne defineres således: meget almindelig (≥ 1/10), almindelig (≥ 1/100 til < 1/10) og ikke almindelig (≥ 1/1.000 til
Frequency categories are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1,000 to < 1/100).
Der er ingen data, der understøtter en nedsat bedaquilindosis under sådanne omstændigheder.
There are no data to support a lowered bedaquiline dose in such circumstances.
• Endelig analyseklinisk studierapport 4. kvartal 2023
• Final analysis - Clinical Study Report 4Q 2023
Alle patienter, der døde af tuberkulose, med undtagelse af én havde ikke konverteret eller havde recidiveret.
All but one patients who died of tuberculosis had not converted or had relapsed.
Fortæl det straks til lægen, hvis du bliver svimmel.
Tell your doctor right away if you faint.
Det er ukendt, om bedaquilin eller dets metabolitter udskilles i human mælk.
It is not known whether bedaquiline or its metabolites are excreted in human milk.
• hvis du har fået at vide, at du har en leversygdom, eller hvis du regelmæssigt drikker alkohol
• you have liver disease or you drink alcohol on a regular basis;
Disse rapporter kan hjælpe lægen til at udvælge en kombination af antibakterielle lægemidler til behandlingen.
These reports should aid the physician in selecting a combination of antibacterial medicinal products for treatment.
Tag ikke SIRTURO, hvis dette gælder for dig.
Do not take SIRTURO if this applies to you.
SIRTURO's sikkerhed og virkning hos børn i alderen < 18 år er endnu ikke klarlagt.
The safety and efficacy of SIRTURO in children aged < 18 years have not yet been established.
Hver tablet indeholder 145 mg lactose (som monohydrat).
Each tablet contains 145 mg of lactose (as monohydrate).
SIRTURO tabletter bør synkes hele med vand.
SIRTURO tablets should be swallowed whole with water.
Hoveddemografien var som følger: 63,1 % var mænd, medianalderen var 34 år, 35 % var sorte, og 15 % var hiv-positive.
Main demographics were as follows: 63.1% were males, median age 34 years, 35% were Black, and 15% were HIV positive.
Der er udført dyrestudier af toksikologi med administration af bedaquilin i op til 3 måneder i mus, op til 6 måneder i rotter og op til 9 måneder i hunde.
Animal toxicology studies have been conducted with bedaquiline administration up to 3 months in mice, up to 6 months in rats, and up to 9 months in dogs.
Maksimal plasmakoncentration (Cmax) indtræffer sædvanligvis ca. 5 timer efter indgift af dosis.
Maximum plasma concentrations (Cmax) are typically achieved at about 5 hours post-dose.
Antibiotika er lægemidler, der dræber sygdomsfremkaldende bakterier.
Antibiotics are medicines that kill bacteria that cause disease.
I SIRTURO-gruppen opstod de fleste af disse stigninger under de 24 ugers behandling, og de var reversible.
In the SIRTURO treatment group, the majority of these increases occurred throughout the 24 weeks of treatment and were reversible.
• ekstrapulmonal tuberkulose (f.eks. i centralnervesystemet, knogler)
• extra-pulmonary tuberculosis (e.g. central nervous system, bone)
Det ene af de ti dødsfald i SIRTURO-gruppen (pga. alkoholforgiftning) indtraf i løbet af 24-ugers behandlingsperioden.
One of the ten deaths in the SIRTURO group (due to alcohol poisoning) occurred during the 24 week treatment period.
De fleste af de observerede ændringer indtraf efter længerevarende daglig indgift efterfulgt af stigninger i plasma- og vævskoncentrationer af det aktive stof.
Most of the observed changes occurred after prolonged daily dosing and subsequent increases in plasma and tissue concentrations of the active substance.
Det kaldes for multiresistent lungetuberkulose.
This is called multi-drug resistant pulmonary tuberculosis.
Den lange terminale eliminationsfase reflekterer sandsynligvis den langsomme frigivelse af bedaquilin og M2 fra perifere væv.
This long terminal elimination phase likely reflects slow release of bedaquiline and M2 from peripheral tissues.
Der sås normal spermatogenese og en normal mængde spermatozoer i bitestiklerne hos disse dyr.
Normal spermatogenesis and a normal amount of spermatozoa in the epidydimides were noted in these animals.
Bedaquilins elimination er ikke karakteriseret fuldstændigt in vivo.
The elimination of bedaquiline has not been fully characterised in vivo.
Relevansen af phospholipidosis hos mennesker kendes ikke.
The significance of phospholipidosis in humans is unknown.
Både i uge 24 og uge 120 var responsraterne højere hos patienter, der fik 3 eller flere aktive stoffer (in vitro) i deres baggrundsregime.
At both week 24 and week 120, responder rates were higher for patients on 3 or more active substances (in vitro) in their background regimen.
Dette studie inkluderede patienter fra alle tre resistenskategorier (MDRH&R-, præ-XDR- og XDR-TB).
This study included patients of all three resistance categories (MDRH&R-, pre-XDR- and XDR-TB).
• Der skal gå mindst 48 timer mellem to doser SIRTURO.
• There must be at least 48 hours in between each time you take SIRTURO.
Efter endt behandling med SIRTURO (dvs. efter uge 24) blev øgningerne af QTcF i SIRTURO-gruppen gradvist mindre udtalte.
After the end of SIRTURO treatment (i.e. after week 24), QTcF increases in the SIRTURO group gradually became less pronounced.
Der foreligger begrænsede data om anvendelse af SIRTURO til gravide kvinder.
There are limited data on the use of SIRTURO in pregnant women.
• Spring den glemte dosis over, og tag den næste dosis som sædvanligt.
• Skip the missed dose and take the next dose as usual
Der henvises til officielle vejledninger i korrekt anvendelse af antibakterielle midler.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Derfor bør bedaquilin indtages sammen med et måltid for at øge dens orale biotilgængelighed.
Therefore, bedaquiline should be taken with food to enhance its oral bioavailability.
• klinisk signifikant ventrikulær arytmi
• Clinically significant ventricular arrhythmia
Den samlede behandlingsvarighed med SIRTURO er 24 uger.
The total duration of treatment with SIRTURO is 24 weeks.
SIRTURO skal altid tages sammen med andre lægemidler til behandling af tuberkulose.
SIRTURO must always be taken together with other medicines for treating tuberculosis.
SIRTURO blev administreret som 400 mg en gang dagligt i de første 2 uger, og som 200 mg 3 gange om ugen i de følgende 22 uger.
SIRTURO was administered as 400 mg once daily for the first 2 weeks, and as 200 mg 3 times/week for the following 22 weeks.
• forhøjede leverenzymtal (i blodprøver)
• increased liver enzymes (shown in blood tests)
Patienterne bør monitoreres under hele behandlingsforløbet, eftersom stigningerne i leverenzymer var længe om at indtræffe og steg gradvist i løbet af de 24 uger.
Patients should be monitored throughout the treatment course, since the increases in liver enzymes were slow to appear and increased gradually during the 24 weeks.
Fjernelse af ikkeabsorberet bedaquilin kan fremmes ved administration af aktivt kul.
Removal of unabsorbed bedaquiline may be aided by the administration of activated charcoal.
Efter den 24 uger lange studieperiode fortsattes med baggrundsregimet for at gennemføre 18-24 måneders behandling for total multiresistent Mycobacterium tuberculosis.
After the 24-week investigational period, the background regimen was continued to complete 18 to 24 months of total multi-drug resistant Mycobacterium tuberculosis treatment.
Undersøgelser af miljørisikovurdering har vist, at bedaquilin potentielt kan være persistent, bioakkumulerende og giftigt for miljøet (se pkt.
Environmental risk assessment studies have shown that bedaquiline has the potential to be persistent, bioaccumulative and toxic to the environment (see section 6.6).
Behandling med regimets andre lægemidler bør fortsættes efter gennemførelse af behandlingen med SIRTURO.
Treatment with the other agents in the regimen should continue after completion of treatment with SIRTURO.
Resistens over for bedaquilin
Resistance to bedaquiline
Alle de undersøgte patienter havde et CD4+ celletal > 250 x 10
Those patients studied all had CD4+ cell counts greater than 250 x 10
Bedaquilin kan i mindre grad påvirke evnen til at føre motorkøretøj og betjene maskiner.
Bedaquiline may have a minor influence on the ability to drive and use machines.
Patienterne bør rådes til at tage SIRTURO nøjagtigt som anvist af lægen og til at gennemføre hele behandlingsforløbet.
Patients should be advised to take SIRTURO exactly as prescribed and to complete the full course of therapy.
Efflux-baserede mutationer er blevet set i prækliniske og kliniske isolater.
Efflux-based mutations have been seen in preclinical and clinical isolates.
Bedaquilin forlænger QTc-intervallet.
Bedaquiline prolongs the QTc interval.
I så fald må du ikke køre bil eller betjene maskiner.
If this happens do not drive or operate machinery.
Lægen fastsætter, hvilke andre lægemidler du skal tage sammen med SIRTURO.
Your doctor will decide which other medicines you should take with SIRTURO.
Plasmaproteinbindingen af metabolitten N-monodesmethyl (M2) hos mennesker er mindst 99,8 %.
The plasma protein binding of the N-monodesmethyl metabolite (M2) in humans is at least 99.8%.
Bedaquilin er et diarylquinolin.
Bedaquiline is a diarylquinoline.
Tabletterne er pakket i blister af aluminium/aluminiumsfolie.
Tablets are packaged in aluminium/aluminium foil blisters.
Der er ingen erfaring med behandling af akut overdosering med SIRTURO.
There is no experience with the treatment of acute overdose with SIRTURO.
Fald i legemsvægten hos afkommet kunne observeres i højdosis grupper under diegivningsperioden efter eksponering for bedaquilin gennem mælken og var ikke en følge af in utero-eksponering.
Body weight decreases in pups were noted in high dose groups during the lactation period after exposure to bedaquiline via milk and were not a consequence of in utero exposure.
Administration af bedaquilin med føde øgede den relative biotilgængelighed med ca. faktor 2 sammenlignet med administration under fastende betingelser.
Administration of bedaquiline with food increased the relative bioavailability by about 2-fold compared to administration under fasted conditions.
Farmakoterapeutisk klassifikation: Antimykobakterika, andre stoffer til behandling af tuberkulose, ATC-kode: J04AK05
Pharmacotherapeutic group: Antimycobacterials, drugs for treatment of tuberculosis, ATC code: J04AK05
SIRTURO må ikke gives til børn og unge (under 18 år).
Do not give this medicine to children and adolescents (under 18 years of age).
Der skal optages EKG, før behandlingen initieres og mindst en gang om måneden efter påbegyndt behandling med bedaquilin.
An electrocardiogram should be obtained before initiation of treatment and at least monthly after starting treatment with bedaquiline.
Kavernedannelse i den ene lunge sås hos 58 % af patienterne; og kavernedannelse i begge lunger sås hos 16 %.
Cavitation in one lung was seen in 58% of patients, and in both lungs in 16%.
Responsrater i uge 24 og uge 120 (det vil sige ca. 6 måneder efter ophør af al behandling) er vist i tabel 1.
Response rates at week 24 and week 120 (i.e. around 6 months after stopping all therapy) are presented in table 1.
Den skæve fordeling af dødsfald er ikke afklaret; der er ikke fundet bevis for en årsagssammenhæng med SIRTURO-behandling.
The imbalance in deaths is unexplained; no evidence has been found for a causal relationship with SIRTURO treatment.
Grænseværdier for mindste hæmmende koncentration (MIC) er følgende: Epidemiologiske cut-off-værdier (ECOFF)
Minimal inhibitory concentration (MIC) breakpoints are as follows: Epidemiological Cut-Off (ECOFF)
Der blev indberettet ét dødsfald i SIRTURO-gruppen og ét dødsfald i placebogruppen efter 120-ugers vinduet.
One death in the SIRTURO group and one death in the placebo group were reported after the week 120 window.
Baseret på de prækliniske studier elimineres hovedparten af den administrerede dosis i fæces.
Based on the preclinical studies, the bulk of the administered dose is eliminated in faeces.
Nedenfor vises eksempler på lægemidler, som kan tages af patienter med multiresistent tuberkulose, og som muligvis reagerer med SIRTURO:
The following are examples of medicines patients with multi-drug resistant tuberculosis may take and which may potentially interact with SIRTURO:
Hvis patienten glemmer en dosis i løbet af de første to ugers behandling, bør den glemte dosis ikke erstattes, men patienten skal fortsætte i henhold til den sædvanlige behandlingsplan.
If a dose is missed during the first two weeks of treatment, patients should not make up the missed dose, but should continue the usual dosing schedule.
Når de foreligger, skal klinisk mikrobiologisk laboratorium forsyne lægen med analyseresultaterne for in vitro-følsomhed af de antibakterielle lægemidler, der anvendes, som periodiske rapporter, der beskriver følsomhedsprofilen af hospitals- eller samfundserhvervede patogener.
When available, the clinical microbiology laboratory should provide the physician with the results of in vitro susceptibility test results for antimicrobial medicinal products used in resident hospitals as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens.
Ikke anvendt lægemiddel og rester heraf skal bortskaffes i overensstemmelse med lokale krav.
Any unused medicine should be disposed of in accordance with local requirements.
Hvis en dosis glemmes fra og med uge 3, skal patienten tage den glemte dosis på 200 mg snarest muligt og derefter genoptage behandlingsplanen med tre doser ugentligt.
If a dose is missed from week three onwards, patients should take the missed dose of 200 mg as soon as possible and then resume the three times a week regimen.
De øvrige ni dødsfald blandt dem, der blev behandlet med SIRTURO, indtraf efter gennemførelse af behandlingen med dette lægemiddel (interval 86-911 dage efter SIRTURO; median 344 dage).
The other nine deaths among those treated with SIRTURO occurred after completion of treatment with this agent (range 86 911 days post SIRTURO; median 344 days).
Der forelå ingen dokumenterede tilfælde af torsades de pointes i sikkerhedsdatabasen (se pkt.
There were no documented cases of Torsade de Pointes in the safety database (see section 4.4).
• hvis du har et unormalt hjertediagram (EKG) eller hjertesvigt
• you have had an abnormal heart reading (ECG) or heart failure;
Centrallaboratoriets analyseresultater for lægemiddelfølsomhed blev tilgængelige for en yderligere placeboforsøgsperson efter interimanalysen i uge 24
Central laboratory drug susceptibility testing results became available for one additional placebo subject after the week 24 interim analysis.
SIRTURO bør anvendes i kombination med mindst tre lægemidler, som patientens isolat har vist sig følsomt over for in vitro.
SIRTURO should be used in combination with at least three medicinal products to which the patient's isolate has been shown to be susceptible in vitro.
• Tag SIRTURO i forbindelse med et måltid.
• Take SIRTURO with food.
Den gennemsnitlige terminale eliminationshalveringstid både for bedaquilin og den aktive metabolit N-monodesmethyl (M2) er ca. 5 måneder (spændende fra 2 til 8 måneder).
The mean terminal elimination half-life of both bedaquiline and the active N-monodesmethyl metabolite (M2) is about 5 months (ranging from 2 to 8 months).
Af de 163 patienter, som responderede i uge 24, responderede 139 patienter (85,3 %) fortsat i uge 120.
Of the 163 patients who were responders at week 24, 139 patients (85.3%) were still responders at week 120.
Hvis fordelene opvejer risikoen, kan SIRTURO administreres med forsigtighed sammen med lopinavir/ritonavir.
If the benefit outweighs the risk, SIRTURO may be used with caution when co-administered with lopinavir/ritonavir.
Cmax og arealet under plasmakoncentration-tidskurven (AUC) steg proportionalt op til de højeste undersøgte doser (700 mg som enkeltdosis og 400 mg en gang dagligt som gentagne doser).
Cmax and the area under the plasma concentration-time curve (AUC) increased proportionally up to the highest doses studied (700 mg single-dose and once daily 400 mg multiple doses).
Det forventes derfor ikke, at let eller moderat nedsat nyrefunktion vil have en klinisk relevant effekt på eksponeringen for bedaquilin.
It is therefore not expected that mild or moderate renal impairment will have a clinically relevant effect on the exposure to bedaquiline.
Der sås ingen virkninger efter behandling af moderdyr med bedaquilin uanset dosisniveau på seksuel modning, adfærdsmæssig modning, parringsadfærd, fertilitet eller reproduktionsevne hos dyr af F1-generationen.
There was no effect of maternal treatment with bedaquiline at any dose level on sexual maturation, behavioural development, mating performance, fertility or reproductive capacity of the F1 generation animals.
QT-interval og samtidig brug af clofazimin
QT interval and concomitant clofazimine use
Det anbefales at administrere SIRTURO under overvågning som DOT (directly observed therapy).
It is recommended that SIRTURO is administered by directly observed therapy (DOT).
Grundlaget for at vurdere årsagssammenhængen mellem bivirkninger og SIRTURO var ikke begrænset til disse studier, men blev også baseret på gennemgang af de poolede sikkerhedsdata fra fase I- og fase IIa-studier.
The basis of assessment of causality between the adverse drug reactions and SIRTURO was not restricted to these trials, but also on review of the pooled Phase I and Phase IIa safety data.
Der foreligger begrænsede oplysninger om risikoen for farmakodynamisk interaktion mellem bedaquilin og lægemidler, der forlænger QT-intervallet.
There is limited information available on the potential for a pharmacodynamic interaction between bedaquiline and medicinal products that prolong the QT interval.
SIRTURO indeholder det aktive stof bedaquilin.
SIRTURO contains the active substance bedaquiline.
Der foreligger ingen humane data om bedaquilins virkninger på fertilitet.
No human data on the effect of bedaquiline on fertility are available.
Andre hepatotoksiske lægemidler samt alkohol bør undgås under behandling med SIRTURO, især hos patienter med nedsat leverfunktion.
Other hepatotoxic medicinal products and alcohol should be avoided while on SIRTURO, especially in patients with diminished hepatic reserve.
Det primære effektmål var tid til konvertering af ekspektoratdyrkning under behandling med SIRTURO (median 57 dage for 205 patienter med tilstrækkelige data).
The primary efficacy endpoint was the time to sputum culture conversion during treatment with SIRTURO (median 57 days, for 205 patients with sufficient data).
I SIRTUROgruppen indtraf alle de fem dødsfald, der skyldtes tuberkulose, hos patienter, hvis status efter dyrkning af ekspektorat ved det sidste besøg var ‘ikke konverteret'.
In the SIRTURO group, all of the five deaths due to tuberculosis occurred in patients whose sputum culture status at last visit was ‘not converted'.
For patienter med omfattende lægemiddelresistens, hvor Sirturo anses for nødvendigt ud over 24 uger for at opnå helbredende behandling, kan en længere varighed af behandlingen kun overvejes fra sag til sag og under tæt overvågning af sikkerheden (se pkt.
In patients with extensive drug resistance, where SIRTURO is considered necessary beyond 24 weeks to obtain a curative treatment, a longer duration of therapy may be considered only on a case by case basis and under close safety surveillance (see section 4.8).
I MPS hos alle arter blev der også set hyperpigmenterede og/eller skummende makrofager i diverse væv, svarende til phospholipidosis.
In the MPS of all species, pigment-laden and/or foamy macrophages were also seen in various tissues, consistent with phospholipidosis.
Et in vitrostudie indikerede potentiale for, at bedaquilin hæmmer BCRP ved de koncentrationer, der opnås i tarmen efter oral administration.
An in vitro study indicated a potential for bedaquiline to inhibit BCRP at the concentrations achieved in the intestine after oral administration.
I det åbne fase IIb-studie (C209) døde 6,9 % (16/233) af patienterne.
In the Phase IIb, open label study (C209), 6.9% (16/233) patients died.
• Genoptag behandlingen med 3 doser om ugen.
• Resume the three times a week schedule.
• anamnestisk torsades de pointes
• A history of Torsade de Pointes;
Under studiet blev der ikke påvist forudgående signifikant QT-forlængelse eller klinisk signifikant dysrytmi hos de patienter, der afgik ved døden.
During the trial, there was no evidence of antecedent significant QT prolongation or clinically significant dysrhythmia in any of the patients that died.
Hvid beholder af HDPE med børnesikret lukke af polypropylen (PP) med aluminumsforsegling indeholdende 188 tabletter.
White HDPE bottle with child-resistant polypropylene (PP) closure with aluminium induction seal liner containing 188 tablets.
Bedaquilin var associeret med påvirkning af målorganerne, der omfattede monocyt og fagocyt systemet (MPS), skeletmuskulatur, lever, mave, pancreas og hjertemuskel.
Bedaquiline was associated with effects in target organs which included monocytic phagocytic system (MPS), skeletal muscle, liver, stomach, pancreas and heart muscle.
• Interim IDMCanbefaling, når halvdelen af patienterne når uge 76: 4. kvartal
• Interim IDMC recommendation when half of the patients reach W76: 4Q2020
Der foreligger ingen sikkerhedsdata fra studier med gentagne doser bedaquilin, hvor doseringen var højere end den indicerede dosis.
There are no safety data from bedaquiline multiple dose trials which utilised a dose higher than the indicated dose.
Erhvervede resistensmekanismer, der påvirker bedaquilins MIC-værdi, inkluderer mutationer i atpEgenet, som koder for target for ATP-syntase, og i Rv0678-genet, som regulerer ekspressionen af MmpS5-MmpL5-effluxpumpen.
Acquired resistance mechanisms that affect bedaquiline MICs include mutations in the atpE gene, which codes for the ATP synthase target, and in the Rv0678 gene, which regulates the expression of the MmpS5-MmpL5 efflux pump.
SIRTURO er ikke undersøgt hos patienter med svært nedsat leverfunktion, og det anbefales ikke til denne population.
SIRTURO has not been studied in patients with severe hepatic impairment and is not recommended in this population.
Der ses kun ubetydelig renal udskillelse af uomdannet bedaquilin (< 0,001 %).
Renal excretion of unchanged bedaquiline is insignificant (< 0.001%).
Der skal bestemmes serumværdier af kalium, calcium og magnesium ved baseline, og abnorme værdier bør korrigeres.
Serum potassium, calcium, and magnesium should be obtained at baseline and corrected if abnormal.
In vitro hæmmer bedaquilin ikke i væsentlig grad aktiviteten af de testede CYP-enzymer (CYP1A2, CYP2A6, CYP2C8/9/10, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A4/5 og CYP4A), ligesom det ikke inducerer aktivitet af CYP1A2, CYP2C9 eller CYP2C19.
In vitro, bedaquiline does not significantly inhibit the activity of any of the CYP450 enzymes tested (CYP1A2, CYP2A6, CYP2C8/9/10, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A4/5 and CYP4A) and does not induce CYP1A2, CYP2C9 or CYP2C19 activities.
• QT-interval korrigeret med Fridericia-metoden (QTcF) > 450 ms (bekræftet af gentaget elektrokardiogram)
• QT interval as corrected by the Fridericia method (QTcF) > 450 ms (confirmed by repeat electrocardiogram);
Grad af resistens baseret på centrallaboratoriets analyseresultater for lægemiddelfølsomhed var ikke tilgængelig for 20 forsøgspersoner i mITT-populationen (12 i SIRTURO-gruppen og 8 i placebogruppen).
Extent of resistance based on central laboratory drug susceptibility testing results was not available for 20 subjects in the mITT population (12 in the SIRTURO group and 8 in the placebo group).