natgillin/translations-raw huggingface dataset:
Behandlingens virkning blev hovedsagelig bedømt ved, hvor langt patienten kunne gå på 6 minutter (en måde at måle den fysiske kapacitet på), og undersøgelsen hos patienter med klasse II- sygdom så desuden nærmere på ændringen i lungekarmodstanden mod blodgennemstrømning (en markør for, hvor snævre blodkarrene er).
The main measure of effectiveness was how far the patient could walk in six minutes (a way of measuring exercise capacity), but the study in class II disease also looked at the change in the resistance to blood flow in the lungs’ blood vessels (a marker of how narrow the blood vessels are).
Der blev endvidere gennemført en undersøgelse med 19 børn i alderen tre til femten år.
A study was also carried out in 19 children aged between three and 15 years.
Der er ligeledes gennemført to undersøgelser med 312 patienter med systemisk sklerose og fingersår, hvor Tracleer blev sammenlignet med placebo.
In systemic sclerosis with digital ulcers, two studies have compared Tracleer with placebo in a total of 312 patients.
Behandlingens virkning blev hovedsagelig bedømt ved antallet af nye fingersår i løbet af undersøgelserne.
The main measure of effectiveness was based on the number of new digital ulcers developing during the studies.
En af undersøgelserne så desuden nærmere på Tracleers indvirkning på helingen hos 190 patienter ved at måle, hvor lang tid det tog for et bestemt fingersår hos hver patient at hele fuldstændigt.
One of the studies also looked at the effect of Tracleer on healing in 190 patients, by measuring the time taken for one selected digital ulcer in each patient to heal completely.
De to undersøgelser viste, at patienter med pulmonal arteriel hypertension i klasse III eller IV (der enten var primær eller forårsaget af sklerodermi), som blev behandlet med Tracleer, var i stand til at gå væsentligt længere efter 16 uger end patienter behandlet med placebo (44 meter længere i den største af de to undersøgelser).
In class III or IV PAH that was either primary or caused by scleroderma, the two studies showed that patients treated with Tracleer were able to walk significantly further than patients treated with placebo after 16 weeks (44 metres further in the larger study), but there were too few patients with class IV disease to support the use of the medicine in this group.
Dog var den afstand, patienterne kunne gå på 6 minutter, ens i de to grupper.
In patients with class II disease, Tracleer caused the resistance of the blood vessels to decrease by 23% compared with placebo after six months of treatment, but the distance the patients could walk over six minutes was similar in the two groups.
I den første undersøgelse fik de patienter, som blev behandlet med Tracleer, gennemsnitligt 1, 4 nye fingersår efter 16 uger, sammenlignet med 2, 7 hos de patienter, der fik placebo.
In the first study, patients taking Tracleer had an average of 1.4 new digital ulcers after 16 weeks, compared with 2.7 in the patients taking placebo.
Der blev opnået lignende resultater i den anden undersøgelse efter 24 uger, men Tracleer havde ikke nogen virkning på helingen af fingersår.
Similar results were seen in the second study after 24 weeks, but Tracleer did not have any effect on digital ulcer healing.
Den mest almindelige bivirkning ved Tracleer (som ses hos mere end 1 ud af 10 patienter) er hovedpine.
The most common side effect with Tracleer (seen in more than 1 patient in 10) is headache.
Tracleer medfører også ændringer i resultaterne af de tests, der gennemføres for at kontrollere leverfunktionen.
Tracleer also causes changes in the results of tests carried out to check liver function.
Af denne grund skal lægen måle indholdet af leverenzymer inden behandlingen med Tracleer og en gang om måneden under selve behandlingen.
Because of this, the doctor will measure the levels of liver enzymes before treatment, and every month during treatment with Tracleer.
Den fuldstændige liste over de indberettede bivirkninger for Tracleer fremgår af indlægssedlen.
For the full list of all side effects reported with Tracleer, see the Package Leaflet.
Virkningen af visse lægemidler (såsom p- piller) kan forstyrres, hvis man samtidigt tager Tracleer.
The effectiveness of some medicines (such as the contraceptive pill) can be affected by taking Tracleer at the same time.
De nærmere oplysninger herom fremgår af indlægssedlen.
See the Package Leaflet for full details.
Tracleer må ikke anvendes til patienter, som kan være overfølsomme (allergiske) over for bosentan eller andre af indholdsstofferne, som har leverenzymproblemer, som er eller kunne være gravide, eller som tager cyclosporin A (et lægemiddel, der indvirker på immunsystemet).
Tracleer should not be used in people who may be hypersensitive (allergic) to bosentan or any of the other ingredients, who have liver enzyme problems, who are or could be pregnant, or who are taking ciclosporin A (a medicine that acts on the immune system).
2/ 3 Hvorfor blev Tracleer godkendt?
2/ 3 ulcers in patients with systemic sclerosis and ongoing digital ulcer disease.
Udvalget anbefalede udstedelse af markedsføringstilladelse for Tracleer.
The Committee recommended that Tracleer be given marketing authorisation.
Tracleer blev oprindeligt godkendt under "særlige omstændigheder", da der på det oprindelige godkendelsestidspunktet kun forelå begrænsede oplysninger for pulmonal arteriel hypertension, eftersom denne sygdom er sjælden.
Tracleer was originally authorised under ‘ Exceptional Circumstances’, because, as PAH is rare, limited information was available at the time of its initial approval for this disease.
Efter at firmaet havde forelagt de supplerende oplysninger, det var blevet anmodet om, blev de "særlige omstændigheder" ophævet den 30. november 2004.
As the company had supplied the additional information requested, the ‘ Exceptional Circumstances ’ ended on 30 November 2004.
Hvilke foranstaltninger træffes der for at sikre en risikofri anvendelse af Tracleer?
Which measures are being taken to ensure the safe use of Tracleer?
Firmaet, der fremstiller Tracleer, vil til hver medlemsstat udarbejde et sæt informationsmateriale til sundhedsmedarbejdere og brochurer til patienterne med oplysning om lægemidlets sikkerhed (navnlig med hensyn til dets virkning på leveren og under graviditet) og interaktion med andre lægemidler.
The company that makes Tracleer will provide an educational kit for prescribers and an information booklet for patients in each Member State, explaining the safety of Tracleer (especially its effects on the liver and in pregnancy) and its interactions.
Andre oplysninger om Tracleer:
Other information about Tracleer:
Europa- Kommissionen udstedte en markedsføringstilladelse med gyldighed i hele Den Europæiske Union til Actelion Registration Ltd den 15. maj 2002.
The European Commission granted a marketing authorisation valid throughout the European Union to Actelion Registration Ltd on 15 May 2002.
Sammendragene af udtalelserne fra Udvalget for Lægemidler til Sjældne Sygdomme om Tracleer findes her (pulmonar arteriel hypertension) og her (systemisk sklerose).
The summaries of opinion of the Committee for Orphan Medicinal Products for Tracleer are available here (PAH) and here (systemic sclerosis).
Den fuldstændige EPAR for Tracleer findes her.
The full EPAR for Tracleer can be found here.
Emballage
EU-number
14 tabletter
Invented name
Filmovertrukket tablet
Pharmaceutical form
Filmovertrukket tablet
Route of administration
56 tabletter
Package size
EU/ 1/ 02/ 220/ 005
EU/ 1/ 02/ 220/ 001 EU/ 1/ 02/ 220/ 002 EU/ 1/ 02/ 220/ 003 EU/ 1/ 02/ 220/ 004 EU/ 1/ 02/ 220/ 005
125 mg
62.5 mg 62.5 mg 62.5 mg 125 mg 125 mg
Filmovertrukket tablet
Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet Film-coated tablet
Blisterpakning (PVC/ PE/ PVDC/ alu)
Blister (PVC/ PE/ PVDC/ alu) Blister (PVC/ PE/ PVDC/ alu) Blister (PVC/ PE/ PVDC/ alu) Blister (PVC/ PE/ PVDC/ alu) Blister (PVC/ PE/ PVDC/ alu)
112 tabletter
14 tablets 56 tablets 112 tablets 56 tablets 112 tablets
Tracleer 62, 5 mg filmovertrukne tabletter
Tracleer 62.5 mg film-coated tablets
Hver filmovertrukket tablet indeholder 62, 5 mg bosentan (som monohydrat).
Each film-coated tablet contains 62.5 mg bosentan (as monohydrate).
Filmovertrukket tablet:
Film-coated tablet:
Orange- hvide, runde, bikonvekse, filmovertrukne tabletter, med “ 62, 5 ” præget på den ene side.
Orange-white, round, biconvex, film-coated tablets, embossed with “ 62,5 ” on one side.
Effektivitet er blevet påvist ved: • Primær (idiopatisk og familiær) PAH • PAH sekundært til sklerodermi uden signifikant interstitiel pulmonalsygdom • PAH associeret med kongenit systemisk til pulmonal shunt og Eisenmengers fysiologi
Efficacy has been shown in: • Primary (idiopathic and familial) PAH • PAH secondary to scleroderma without significant interstitial pulmonary disease • PAH associated with congenital systemic-to-pulmonary shunts and Eisenmenger’ s physiology
5. 1).
Some improvements have also been shown in patients with PAH WHO functional class II (see section 5.1).
5. 1).
Tracleer is also indicated to reduce the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease (see section 5.1).
Pulmonal arteriel hypertension.
Pulmonary arterial hypertension
Behandling med Tracleer bør påbegyndes med en dosis på 62, 5 mg to gange dagligt i 4 uger, hvorefter dosis forhøjes til en vedligeholdelsesdosis på 125 mg to gange dagligt.
Tracleer treatment should be initiated at a dose of 62.5 mg twice daily for 4 weeks and then increased to the maintenance dose of 125 mg twice daily.
Tabletterne indtages peroralt morgen og aften i forbindelse med eller uden føde.
Tablets are to be taken orally morning and evening, with or without food.
I tilfælde af klinisk forværring (f. eks. mindst 10% reduktion i 6- minutters gangtest i sammenligning med målinger inden behandlingens start) på trods af Tracleer behandling i mindst 8 uger (måldosis i mindst 4 uger), bør alternativ behandling overvejes.
In the case of clinical deterioration (e. g., decrease in 6-minute walk test distance by at least 10% compared with pre-treatment measurement) despite Tracleer treatment for at least 8 weeks (target dose for at least 4 weeks), alternative therapies should be considered.
Hvis det besluttes at seponere Tracleer, skal dette ske gradvist, mens der introduceres en alternativ behandling.
If the decision to withdraw Tracleer is taken, it should be done gradually while an alternative therapy is introduced.
I tilfælde af sen klinisk forværring på trods af behandling med Tracleer (dvs. efter flere måneders behandling) skal behandlingen revurderes.
In the case of late clinical deterioration despite treatment with Tracleer (i. e., after several months of treatment), the treatment should be re-assessed.
Nogle patienter, der ikke responderer godt på 125 mg Tracleer to gange dagligt, kan forbedre deres arbejdskapacitet lidt, hvis dosis øges til 250 mg to gange daglig.
Some patients not responding well to 125 mg twice daily of Tracleer may slightly improve their exercise capacity when the dose is increased to 250 mg twice daily.
4. 4 og 5. 1).
A careful risk/ benefit assessment should be made, taking into consideration that the liver toxicity is dose dependent (see sections 4.4 and 5.1).
2 Behandlingsophør
2 Discontinuation of treatment
Der er begrænset erfaring med pludselig seponering af Tracleer.
There is limited experience with abrupt discontinuation of Tracleer.
For at undgå mulig forekomst af skadelig, klinisk forværring, der skyldes potentiel rebound - effekt, bør gradvis nedsættelse af dosis (halvering af dosis i 3 til 7 dage) dog overvejes.
However, to avoid the possible occurrence of harmful clinical deterioration due to potential rebound effect, gradual dose reduction (halving the dose for 3 to 7 days) should be considered.
Tracleerbehandling bør initieres med en dosis på 62, 5 mg 2 gange dagligt i 4 uger og derefter øges til vedligeholdesesdosis 125 mg 2 gange dagligt.
Tracleer treatment should be initiated at a dose of 62.5 mg twice daily for 4 weeks and then increased to the maintenance dose of 125 mg twice daily.
Tabletterne skal indtages peroralt morgen og aften sammen med mad eller uden for måltider.
Tablets are to be taken orally morning and evening, with or without food.
5. 1).
Controlled clinical trial experience in this indication is limited to 6 months (see section 5.1).
Patientens respons på behandling og behov for fortsat behandling bør revurderes regelmæssigt.
The patient ’ s response to treatment and need for continued therapy should be re-evaluated on a regular basis.
4. 4 og 4. 8).
A careful risk/ benefit assessment should be made, taking into consideration the liver toxicity of bosentan (see sections 4.4 and 4.8).
Dosering ved nedsat leverfunktion
Dosage in hepatic impairment
Child- Pugh klasse A) (se pkt.
No dose adjustment is needed in patients with mild hepatic impairment (i. e., Child-Pugh class A) (see section 5.2).
4. 3, 4. 4 og 5. 2).
Tracleer is contraindicated in patients with moderate to severe liver dysfunction (see sections 4.3, 4.4 and 5.2).
Dosering ved nedsat nyrefunktion
Dosage in renal impairment
Der kræves ingen dosisjustering til patienter med nedsat nyrefunktion.
No dose adjustment is required in patients with renal impairment.
5. 2).
No dose adjustment is required in patients undergoing dialysis (see section 5.2).
Dosering til ældre patienter
Dosage in elderly patients
- Pulmonal arteriel hypertension:
Pulmonary arterial hypertension:
Sikkerhed og virkning hos børn under 12 år er ikke tilstrækkeligt dokumenteret.
Safety and efficacy in patients under the age of 12 years have not been substantially documented.
Følgende doseringsplan blev anvendt i studiet AC- 052- 356 (BREATHE- 3):
Initiation Dose (4 weeks)
Legemsvægt (kg)
Maintenance Dose
Startdosis (4 uger)
31.25 mg once daily
Vedligeholdelsesdosis
31.25 mg twice daily
10 20
20
≤ × ≤ 20 < × ≤ 40 > 40
< × ≤ 40> 40
31, 25 mg en gang daglig 31, 25 mg to gange daglig 62, 5 mg to gange daglig
31.25 mg twice daily 62.5 mg twice daily
31, 25 mg to gange daglig 62, 5 mg to gange daglig 125 mg to gange daglig
62.5 mg twice daily 125 mg twice daily
Dette studie var primært designet til vurdering af farmakokinetikken hos børn.
This study was primarily designed to assess pharmacokinetics in children.
Antallet af patienter undersøgt i hver dosisgruppe var utilstrækkeligt til at fastlægge en optimal dosisplan for patienter under
The number of patients studied in each dose group was insufficient to establish the optimal dosing regimen in patients under the age of 12 years (see also section 5.1).
De farmakokinetiske resultater viste, at systemisk eksponering var lavere end hos voksne med pulmonal hypertension (se pkt.
The pharmacokinetic findings showed that systemic exposure was lower than in adults with pulmonary hypertension (see section 5.2) which may provide
5. 2), som kan give en suboptimal virkning på det pulmonale karsystem.
3 sub-optimal effect on pulmonary vasculature.
Sikkerheden ved højere doser er imidlertid ikke undersøgt hos børn.
However the safety of higher doses has not been established in children.
Der er ingen erfaring med børn under 3 år.
There is no experience in children below 3 years.
- Systemisk sklerose med eksisterende fingersår:
Systemic sclerosis with ongoing digital ulcer disease:
Der foreligger ingen data vedrørende sikkerhed og virkning hos patienter under 18 år.
data on the safety and efficacy in patients under the age of 18 years.
Der foreligger begrænset erfaring med patienter med en legemsvægt under 40 kg.
There is limited experience in patients with a body weight below 40 kg.
4. 4, 4. 5 og 4. 6)
• Hypersensitivity to the active substance or to any of the excipients • Child-Pugh Class B or C, i. e., moderate to severe hepatic impairment (see section 5.2) • Baseline values of liver aminotransferases, i. e., aspartate aminotransferases (AST) and/ or alanine aminotransferases (ALT), greater than 3 times the upper limit of normal (see section 4.4) • Concomitant use of cyclosporine A (see section 4.5) • Pregnancy • Women of childbearing potential who are not using reliable methods of contraception (see sections 4.4, 4.5 and 4.6)
4. 2).
Transfer to a therapy that is recommended at the severe stage of the disease (e. g., epoprostenol) should be considered if the clinical condition deteriorates (see section 4.2).
Balancen mellem fordele/ risici for bosentan er ikke undersøgt hos patienter med WHO klasse I funktionsstatus ved pulmonal arteriel hypertension.
The benefit/ risk balance of bosentan has not been established in patients with WHO class I functional status of pulmonary arterial hypertension.
Forøgelser af leveraminotransferaser, dvs. aspartat - og alaninaminotransferaser (ASAT og/ eller ALAT) i forbindelse med bosentan er dosisafhængige.
Elevations in liver aminotransferases, i. e., aspartate and alanine aminotransferases (AST and/ or ALT), associated with bosentan are dose dependent.
4. 3 og 4. 5) samtidigt med bosentan, men der er kun begrænsede data herom til rådighed.
Liver dysfunction risk may also be increased when medicinal products that are inhibitors of the bile salt export pump (BSEP), e. g., rifampicin, glibenclamide and cyclosporine A (see sections 4.3 and 4.5), are co- administered with bosentan, but limited data are available.
4 Anbefalinger i tilfælde af forøgelse af ALAT/ ASAT
Recommendations in case of ALT/ AST elevations
ALAT/ ASAT niveauer Anbefalet behandling og overvågning > 3 og ≤ 5 × ULN
4 ALT/ AST levels > 3 and ≤ 5 × ULN
4. 2); undersøg aminotransferaseniveauer mindst hver anden uge.
Treatment and monitoring recommendations Confirm by another liver test; if confirmed, reduce the daily dose or stop treatment (see section 4.2), monitor aminotransferase levels at least every 2 weeks.
Hvis aminotransferaseniveauer retableres til de samme niveauer som inden behandlingen, kan det overvejes at fortsætte behandlingen eller genintroducere Tracleer i henhold til nedenstående betingelser.
If the aminotransferase levels return to pre-treatment values consider continuing or re-introducing Tracleer according to the conditions described below.
> 5 og ≤ 8 × ULN
> 5 and ≤ 8 × ULN
Hvis aminotransferaseniveauer retableres til de samme niveauer som inden behandlingen, kan det overvejes at genintroducere Tracleer i henhold til nedenstående betingelser.
If the aminotransferase levels return to pre-treatment values consider re-introducing Tracleer according to the conditions described below.
> 8 × ULN
> 8 × ULN
Behandlingen skal afbrydes, og genintroduktion af Tracleer skal ikke overvejes.
Treatment must be stopped and re-introduction of Tracleer is not to be considered.
I tilfælde af associerede kliniske symptomer på leverskader, dvs. kvalme, opkastning, feber, mavesmerter, gulsot, usædvanlig apati eller træthed, influenza- lignende syndrom (arthralgia, myalgia, feber), skal behandlingen afbrydes, og en reintroduktion af Tracleer skal ikke overvejes.
In case of associated clinical symptoms of liver injury, i. e., nausea, vomiting, fever, abdominal pain, jaundice, unusual lethargy or fatigue, flu-like syndrome (arthralgia, myalgia, fever), treatment must be stopped and re-introduction of Tracleer is not to be considered.
Reintroduktion af behandlingen Reintroduktion af behandling med Tracleer bør kun overvejes, hvis de potentielle fordele ved behandling med Tracleer opvejer de potentielle risici, og hvis leveraminotransferaseniveauerne er inden for de samme værdier som før behandlingens start.
Re-introduction of treatment Re-introduction of treatment with Tracleer should only be considered if the potential benefits of treatment with Tracleer outweigh the potential risks and when liver aminotransferase levels are within pre-treatment values.
Reintroduktion skal følge de retningslinier, som er anført i pkt.
Re-introduction must follow the guidelines detailed in section 4.2.
ULN = Upper Limit of Normal (Øvre grænse for normalt område)
ULN= Upper Limit of Normal
4. 8).
Treatment with bosentan has been associated with dose-related decreases in haemoglobin concentration (see section 4.8).
I placebo- kontrollerede studier var bosentan- relateret fald i hæmoglobinkoncentrationen ikke progressivt og stabiliseredes efter de første 4– 12 ugers behandling.
In placebo-controlled studies, bosentan-related decreases in haemoglobin concentration were not progressive, and stabilised after the first 4– 12 weeks of treatment.
I perioden efter markedsføring har der været rapporteret tilfælde af anæmi, som krævede transfusion af røde blodlegemer (se pkt. 4. 8).
In the post-marketing period, cases of anaemia requiring red blood cell transfusion have been reported (see section 4.8).
Anvendelse til kvinder i den fødedygtige alder
Use in women of child-bearing potential
4. 6).
Tracleer treatment must not be initiated in women of child-bearing potential unless they practice reliable contraception (see section 4.5) and the result of the pre-treatment pregnancy test is negative (see section 4.6).
Graviditet skal udelukkes, før der indledes behandling med Tracleer hos kvinder i den fødedygtige alder, der skal gives passende rådgivning om pålidelige præventionsmetoder, og pålidelig prævention skal være iværksat.
Before the initiation of Tracleer treatment in women of child-bearing potential, the absence of pregnancy should be checked, appropriate advice on reliable methods of contraception provided, and reliable contraception initiated.
Patienten og den ordinerende læge skal være opmærksom på, at Tracleer, på grund af de mulige farmakokinetiske interaktioner, kan gøre de hormonelle præventionsmetoder uvirksomme (se pkt.
Patients and prescribers must be aware that, due to potential pharmacokinetic interactions, Tracleer may render hormonal contraceptives ineffective (see section 4.5).
Kvinder i den fødedygtige alder må derfor ikke anvende hormonelle præventionsmetoder (herunder orale, injicérbare, transkutane og implantable former), som eneste præventionsmetode, men skal anvende en supplerende eller en alternativ pålidelig præventionsmetode.
Therefore, women of child-bearing potential must not use hormonal contraceptives (including oral, injectable, transdermal, and implantable forms) as the sole method of contraception but should use an additional or an alternative reliable method of contraception.
Hvis der hos den individuelle patient er nogen som helst tvivl om, hvilken form for præventionsrådgivning, der skal gives, bør rådgivning finde sted hos en gynækolog.
If there is any doubt on what contraceptive advice should be given to the individual patient, consultation with a gynaecologist is recommended.
5 Da hormonel prævention muligvis ikke er effektiv under behandling med Tracleer, og også på grund af risikoen for at pulmonal hypertension forværres alvorligt under graviditet, anbefales det, at der udføres månedlige graviditetsprøver under behandlingen med Tracleer for at opdage en graviditet tidligst muligt.
Because of possible hormonal contraception failure during Tracleer treatment and also bearing in mind the risk that pulmonary hypertension severely deteriorates with pregnancy, monthly pregnancy tests during treatment with Tracleer are recommended to allow early detection of pregnancy.
Pulmonal veno- okklusiv sygdom
5 Pulmonary veno-occlusive disease
Tilfælde af pulmonært ødem har været rapporteret i forbindelse med vasodilatatorer (især prostacykliner), når de anvendes til patienter med pulmonær veno- okklusiv sygdom.
Cases of pulmonary oedema have been reported with vasodilators (mainly prostacyclins) when used in patients with pulmonary veno-occlusive disease.
Skulle der forekomme tegn på pulmonært ødem, når Tracleer administreres til patienter med PAH, bør muligheden for associeret veno - okklusiv sygdom derfor tages i betragtning.
Consequently, should signs of pulmonary oedema occur when Tracleer is administered in patients with PAH, the possibility of associated veno-occlusive disease should be considered.