qanastek/EMEA-V3 huggingface dataset:
Overall, in the two studies taken together, patients taking Volibris at a dose of 5 mg once a day could walk an average of 44.6 m further after 12 weeks of treatment, from a baseline of around 345 m at the start of the study.
Kumplessivament, fiż- żewġ studji meħudin flimkien, pazjenti li kienu qegħdin jieħdu Volibris f' doża ta '5 mg darba kuljum setgħu jimxu medja ta' 44. 6 m aktar wara 12- il ġimgħa ta 'trattament, mil- linja bażi ta' madwar 345 m fil- bidu ta 'l- istudju.
Patients taking placebo showed a reduction of 9.0 m after 12 weeks.
Pazjenti li kienu qegħdin jieħdu plaċebo wrew tnaqqis ta '9. 0 m wara 12- il ġimgħa.
Patients with class III disease and those with PAH caused by connective tissue disease gained a greater benefit from the 10 mg dose than from the 5 mg dose.
Pazjenti b' mard tal- klassi III u dawk bil- PAH ikkaġunata minn mard tat- tessut konnettiv ibbenefikaw aktar mid- doża ta '10 mg milli mid- doża ta' 5 mg.
What is the risk associated with Volibris?
X' inhu r- riskju assoċjat ma 'Volibris?
The most common side effects with Volibris (seen in more than 1 patient in 10) are headache (including sinus headache and migraine), peripheral oedema (swelling, especially of the ankles and feet) and fluid retention.
L- aktar effetti sekondarji komuni b' Volibris (li dehru f' aktar minn pazjent 1 f' 10) huma wġigħ ta 'ras (inklużi wġigħ ta' ras tas- sinus u emikranja), edema periferika (nefħa, speċjalment ta 'l- għekiesi u s - saqajn) u żamma ta' fluwidi.
For the full list of all side effects reported with Volibris, see the Package Leaflet.
Għal- lista sħiħa ta 'l- effetti sekondarji kollha rrapportati b' Volibris, ara l - Fuljett ta' Tagħrif.
Volibris should not be used in people who may be hypersensitive (allergic) to soya, ambrisentan or any of the other ingredients.
Volibris m' għandux jintuża f' nies li jistgħu jkunu ipersensittivi (allerġiċi) għas- sojja, ambrisentan jew għal kwalunkwe sustanza oħra tiegħu.
Because it might be able to cause birth defects, Volibris should not be used in pregnant women or in women who could become pregnant unless they are using reliable contraception.
Minħabba li jista 'jikkaġuna difetti fit- twelid, Volibris m' għandux jintuża f' nisa tqal jew f' nisa li jistgħu joħorġu tqal sakemm ma jkunux qegħdin jużaw kontraċezzjoni sikura.
It should not be used in patients who are breast feeding, who have severe liver problems or who have high levels of liver enzymes in the blood.
M' għandux jintuża f' pazjenti li jkunu qegħdin irreddgħu, li jkollhom problemi gravi tal- fwied jew li jkollhom livelli għoljin ta 'enzimi tal- fwied fid- demm.
Why has Volibris been approved?
Għaliex ġie approvat Volibris?
The Committee for Medicinal Products for Human Use (CHMP) decided that Volibris’ s benefits are greater than its risks for the treatment of patients with PAH classified as WHO functional class II and III, to improve exercise capacity.
Il- Kumitat għal Prodotti Mediċinali għal Użu tal- Bniedem (CHMP) iddeċieda li l- benefiċċji ta 'Volibris huma akbar mir- riskji tiegħu għat- trattament ta' pazjenti li jbatu mill- PAH ikklassifikati bħala ta 'klassi funzjonali II u III tad- WHO, biex ittejjeb il- kapaċità għall- eżerċizzju.
The Committee recommended that Volibris be given marketing authorisation.
Il- Kumitat irrakkomanda li Volibris jingħata awtorizzazzjoni għat- tqegħid fis- suq.
Which measures are being taken to ensure the safe use of Volibris?
X' miżuri qegħdin jittieħdu biex jassiguraw l- użu sikur ta 'Volibris?
The company that makes Volibris will set up a study in the European Union (EU) looking at how the medicine is used once it is on the market.
Il- kumpanija li tagħmel Volibris sejra tagħmel studju fl- Unjoni Ewropea (UE) li jeżamina kif il - mediċina tintuża ladarba din tkun fis- suq.
It will also agree on a system in each Member State to control the distribution of Volibris, and will prepare information packs to make sure that health care workers, patients, and the male partners of female patients are provided with information on the medicine’ s side effects and the need to avoid pregnancy.
Hija sejra taqbel ukoll fuq sistema f' kull Stat Membru biex tikkontrolla d- distribuzzjoni ta 'Volibris, u tħejji pakketti ta' tagħrif biex tassigura li operaturi fil- kura tas- saħħa, pazjenti, u s- sħab irġiel ta 'pazjenti nisa jkunu pprovduti b' tagħrif fuq l- effetti sekondarji tal - mediċina u l- ħtieġa li tiġi evitata t- tqala.
Other information about Volibris:
Aktar tagħrif dwar Volibris:
The European Commission granted a marketing authorisation valid throughout the EU for Volibris to Glaxo Group Ltd on 21 April 2008.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fuq is- suq fl- Unjoni Ewropea kollha, għal Volibris lil Glaxo Group Ltd fil- 21 ta 'April 2008.
The summary of opinion of the Committee for Orphan Medicinal Products for Volibris is available here.
Is- sommarju ta 'l- opinjoni tal- Kumitat għal Prodotti Mediċinali Orfni għal Volibris jinsab hawn.
The full EPAR for Volibris can be found here.
L- EPAR sħiħ għal Volibris jista 'jiġi kkonsultat hawn.
EU number EU/ 1/ 08/ 451/ 001 EU/ 1/ 08/ 451/ 002 EU/ 1/ 08/ 451/ 003 EU/ 1/ 08/ 451/ 004
Numru ta ’ l- EU EU/ 1/ 08/ 451/ 001 EU/ 1/ 08/ 451/ 002 EU/ 1/ 08/ 451/ 003 EU/ 1/ 08/ 451/ 004
Invented name Volibris Volibris Volibris Volibris
Isem ivvintat Volibris Volibris Volibris Volibris
Strength 5 mg 5 mg 10 mg 10 mg
Qawwa 5 mg 5 mg 10 mg 10 mg
Pharmaceutical Form Film coated tablets Film coated tablets Film coated tablets Film coated tablets
Għamla farmaċewtika Film coated tablets Film coated tablets Film coated tablets Film coated tablets
Route of administration Oral use Oral use Oral use Oral use
Mnejn jingħata Oral use Oral use Oral use Oral use
Packaging Blister (PVC/ PVdC/ Alu) Blister (PVC/ PVdC/ Alu) Blister (PVC/ PVdC/ Alu) Blister (PVC/ PVdC/ Alu)
Il- pakkett Blister (PVC/ PVdC/ Alu) Blister (PVC/ PVdC/ Alu) Blister (PVC/ PVdC/ Alu) Blister (PVC/ PVdC/ Alu)
Package size 10 tablets 30 tablets 10 tablets 30 tablets
Daqs tal- pakkett 10 tablets 30 tablets 10 tablets 30 tablets
Volibris 5 mg film-coated tablets
Volibris 5 mg pilloli miksija b' rita
Each tablet contains 5 mg of ambrisentan.
Kull pillola fiha 5 mg ta 'ambrisentan.
Each tablet contains lactose monohydrate (approximately 95 mg), Lecithin (Soya) (E322) (approximately 0.25 mg) and Allura red AC Aluminium Lake (E129) (approximately 0.11 mg).
Kull pillola fiha lactose monohydrate (bejn wieħed u ieħor 95 mg), Lecithin (Soya) (E322) (bejn wieħed u ieħor 0. 25 mg) u Allura red AC Aluminium Lake (E129) (bejn wieħed u ieħor 0. 11 mg).
Pale-pink, square, convex, film-coated tablet with “ GS ” debossed on one side and “ K2C” on the other side.
Pillola miksija b' rita, roża ċar, kwadra, b '"GS" imbuzzata fuq naħa waħda u "K2C" fuq in- naħa l- oħra.
Volibris is indicated for the treatment of patients with pulmonary arterial hypertension (PAH) classified as WHO functional class II and III, to improve exercise capacity (see section 5.1).
4. 1 Indikazzjonijiet terapewtiċi
Efficacy has been shown in idiopathic PAH (IPAH) and in PAH associated with connective tissue disease.
Intwera li jkun hemm effikaċja f' PAH idjopatika (IPAH) u f' PAH assoċjata ma 'mard tal- connective tissue.
Treatment must be initiated by a physician experienced in the treatment of PAH.
It- terapija għandha tinbeda biss minn tabib ta 'esperjenza fil- kura ta' PAH.
Volibris is to be taken orally at a dose of 5 mg once daily.
Volibris għandu jittieħed mill- ħalq f' doża ta '5 mg darba kuljum.
It is recommended that the tablet is swallowed whole and it can be taken with or without food.
Huwa rakkomandat li l- pillola tittieħed sħiħa u tista 'tittieħed ma ’ l- ikel jew fuq stonku vojt.
Some additional efficacy has been observed with 10 mg Volibris in patients with class III symptoms, however an increase in peripheral oedema has also been observed.
Kienet osservata ftit effikaċja akbar b' 10 mg ta ’ Volibris f’ pazjenti b' sintomi ta 'klassi III, madankollu kienet osservata wkoll żieda fl- edema periferali.
Patients with PAH associated with connective tissue disease may require 10 mg Volibris for optimal efficacy.
Pazjenti b ''PAH assoċjata ma 'mard tal- connective tissue jista' jkollhom bżonn 10 mg ta 'Volibris għall- aħjar effikaċja.
Confirm that the 5 mg dose is well tolerated before considering an increase in dose to 10 mg Volibris in these patients (see sections 4.4 and 4.8).
Ikkonferma li d- doża ta '5 mg hija ttollerata tajjeb qabel tiġi kkunsidrata żieda fid- doża għal 10 mg ta' Volibris f' dawn il- pazjenti (ara sezzjonijiet 4. 4 u 4. 8).
Limited data suggest that the abrupt discontinuation of Volibris is not associated with rebound worsening of PAH.
Informazzjoni limitata turi li l- waqfien f' daqqa ta 'Volibris m' huwiex assoċjat mal- fatt li l- PAH terġa tmur għall- agħar.
2 Volibris is not recommended for use in patients below 18 years of age due to a lack of data on safety and efficacy.
2 Volibris m' huwiex rakkomandat għall- użu fi tfal taħt it- 18 - il sena minħabba nuqqas ta 'dejta fuq sigurtà u effikaċja.
No dose adjustment is required in patients over the age of 65 (see section 5.2).
Ma hemmx għalfejn aġġustament fid- doża f' pazjenti 'il fuq minn 65 sena (ara s- sezzjoni 5. 2).
Patients with renal impairment
Pazjenti li jbatu minn indeboliment tal- kliewi.
No dose adjustment is required in patients with renal impairment (see section 5.2).
Ma hemmx għalfejn aġġustament fid- doża f' pazjenti b' indebboliment tal- kliewi (ara s- sezzjoni 5. 2).
There is limited experience with Volibris in individuals with severe renal impairment (creatinine clearance < 30 ml/ min); initiate therapy cautiously in this subgroup and take particular care if the dose is increased to 10 mg Volibris.
Hemm esperjenza limitata b' Volibris f' individwi b' indebboliment sever tal- kliewi (tneħħija ta 'kreatinina < 30 mL/ min); ibda l- kura b' attenzjoni f' dan is- sottogrupp u ħu aktar ħsieb jekk id- doża tiżdied għal 10 mg ta' Volibris.
Patients with hepatic impairment
Pazjenti li jbatu minn indeboliment tal- fwied.
Volibris has not been studied in individuals with severe hepatic impairment (with or without cirrhosis).
Volibris ma ġiex studjat f' persuni b' indeboliment qawwi tal- fwied (bi jew mingħajr ċirrożi).
Since the main routes of metabolism of ambrisentan are glucuronidation and oxidation with subsequent elimination in the bile, hepatic impairment would be expected to increase exposure (Cmax and AUC) to ambrisentan.
Billi ambrisentan jiġi immetaboliżżat primarjament b' glukoronidazzjoni u ossidazzjoni u wara jiġi eliminat fil- bil, tistenna li indebboliment tal- fwied iżid l- espożizzjoni (Cmax u l- AUC) ta 'ambrisentan.
Therefore Volibris should not be initiated in patients with severe hepatic impairment, or clinically significant elevated hepatic aminotransferases (greater than 3 times the Upper Limit of Normal (> 3xULN); see sections 4.3 and 4.4).
4. 3 Kontra- indikazzjonijiet
• Hypersensitivity to the active substance, to soya, or to any of the excipients (see sections 4.4 and 6.1).
• Sensittività eċċessiva għas- sustanzi attivi, għas- soya jew għal xi- sustanzi mhux attivi (ara s- sezzjonijiet 4. 4 u 6. 1).
• Pregnancy (see section 4.6).
• Tqala (ara sezzjoni 4. 6).
• Women of child-bearing potential who are not using reliable contraception (see sections 4.4 and 4.6).
Nisa li jista 'jkollhom it- tfal u li ma humiex qegħdin jużaw kontraċezzjoni ta' min joqgħod fuqha (ara sezzjonijiet 4. 4 u 4. 6).
• Lactation (see section 4.6).
Treddigħ (ara sezzjoni 4. 6).
• Severe hepatic impairment (with or without cirrhosis) (see section 4.2).
Indebboliment serju tal- fwied (bi jew mingħajr ċirrożi) (ara s- sezzjoni 4. 2)
• Baseline values of hepatic aminotransferases (aspartate aminotransferases (AST) and/ or alanine aminotransferases (ALT)) > 3xULN (see sections 4.2 and 4.4).
Valuri bażi ta 'aminotransferases tal- fwied (aspartate aminotransferases (AST)) u/ jew alanine aminotransferases (ALT)) > 3xGħLN (ara s- sezzjonijiet 4. 2 u 4. 4).
Volibris has not been studied in a sufficient number of patients to establish the benefit/ risk balance in WHO functional class I PAH.
Volibris ma ġiex studjat f' biżżejjed pazjenti biex jiġi stabbilit il- bilanċ ta 'benefiċċju/ risku fil- klassi funzjonali I ta' PAH skond WHO.
The efficacy of Volibris as monotherapy has not been established in patients with WHO functional class IV PAH.
L- effikaċja ta ’ Volibris bħala monoterapija ma ġietx stabbilita f’ pazjenti bi klassi funzjonali IV ta 'PAH skond WHO.
Therapy that is recommended at the severe stage of the disease (e. g. epoprostenol) should be considered if the clinical condition deteriorates.
Għandha tiġi kkunsidrata terapija (e. ż. epoprostenol) li hija rrakkomandata fl- istadju sever tal- marda jekk il- kondizzjoni klinika tmur għall- agħar.
3 Liver function abnormalities have been associated with PAH.
3 Abnormalitajiet tal- funzjoni tal- fwied ġew assoċċjati ma 'PAH.
Hepatic enzyme elevations potentially related to therapy have been observed with endothelin receptor antagonists (ERAs) (see section 5.1).
Ġiet osservata żieda fl- enżimi tal- fwied li potenzjalment għandha x' taqsam mat- terapija ma 'antagonisti tal- riċettur ta' l- endotelina (ERAs) (ara sezzjoni 5. 1).
Therefore hepatic aminotransferases (ALT and AST) should be evaluated prior to initiation of Volibris.
Għalhekk għandhom jiġu evalwati l- aminotransferases (ALT u AST) tal- fwied qabel jinbeda Volibris.
Volibris treatment should not be initiated in patients with baseline values of ALT and/ or AST > 3xULN (see section 4.3).
M' għandiex tinbeda kura b' Volibris f' pazjenti b' valuri ta 'linja bażi ta' ALT u/ jew AST > 3xULN (ara s- sezzjoni 4. 3).
Monthly monitoring of ALT and AST is recommended.
Huwa rrakkomandat osservazzjoni kull xahar ta 'ALT u AST.
If patients develop sustained, unexplained, clinically significant ALT and/ or AST elevation, or if ALT and/ or AST elevation is accompanied by signs or symptoms of hepatic injury (e. g. jaundice), Volibris therapy should be discontinued.
Jekk il- pazjenti jiżviluppaw żieda sostenuta, mhux spjegabbli u klinikament sinifikanti ta 'ALT u/ jew AST, jew jekk żieda f' ALT u/ jew AST hija akkumpanjata b' sinjali jew sintomi ta' ħsara fil- fwied (e. ż. suffejra), għandha titwaqqaf il- kura b' Volibris.
In patients without clinical symptoms of hepatic injury or of jaundice, re-initiation of Volibris may be considered following resolution of hepatic enzyme abnormalities.
F' pazjenti mingħajr sintomi kliniċi ta 'ħsara fil- fwied jew suffejra, tista tiġi kkunsidrata il- possibilita' li jerġa jinbeda Volibris wara li l- abnormalitajiet fl- enżimi tal- fwied jitranġaw.
Haemoglobin concentration
Konċentrazzjoni ta 'emoglobina
Reductions in haemoglobin concentrations and haematocrit have been associated with ERAs including Volibris (see section 4.8).
Tnaqqis fil- konċentrazzjonijiet ta 'emoglobina u l- ematokrit ġew assoċċjati ma' ERAs inkluż Volibris (ara sezzjoni 4. 8).
Most of these decreases were detected during the first 4 weeks of treatment and haemoglobin generally stabilised thereafter.
Ħafna mit- tnaqqis kien osservat fl- ewwel 4 ġimgħat ta 'kura u l- emoglobina ġeneralment stabiliżżat wara.
Initiation of Volibris is not recommended for patients with clinically significant anaemia.
M' huwiex rakkomandat bidu ta 'kura b' Volibris f' pazjenti b' anemija klinikament sinifikanti.
It is recommended that haemoglobin and/ or haematocrit levels are measured during treatment with Volibris, for example at 1 month, 3 months and periodically thereafter in line with clinical practice.
Hu rrakomandat li l- livelli ta 'l- emoglobinba u/ jew il- hematocrit jiġu iċċekkjata waqt il- kura b' Volibris, per eżempju wara xahar, 3 xhur u perjodikament wara skond il- prattika klinika.
If a clinically significant decrease in haemoglobin or haematocrit is observed, and other causes have been excluded, dose reduction or discontinuation of treatment should be considered.
Għandu jiġi kkunsidrat tnaqqis fid- doża jew twaqqif tal- kura jekk jiġi osservat tnaqqis klinikament sinifikanti fl- emoglobina jew il- hematocrit u kawżi oħra ikunu ġew esklużi.
Fluid retention
Ritenzjoni ta 'fluwidu
Peripheral oedema has been observed with ERAs including ambrisentan.
Kienet osservata edema periferali b' ERAs inkluż ambrisentan.
Most cases of peripheral oedema in clinical studies with ambrisentan were mild to moderate in severity, although it appeared to occur with greater frequency and severity in patients ≥ 65 years.
Ħafna mill- każijiet ta 'edema periferali fi studji kliniċi b' ambrisentan kienu ta' severita 'ħafifa għal moderata għalkemm dehret li tiġri bi frekwenza u severita akbar f' pazjenti ≥65 sena.
Peripheral oedema was reported more frequently with 10 mg ambrisentan (see section 4.8).
Edema periferali kienet rappurtata aktar spiss b' 10 mg ta 'ambrisentan (ara sezzjoni 4. 8).
Post-marketing reports of fluid retention occurring within weeks after starting ambrisentan have been received and, in some cases, have required intervention with a diuretic or hospitalisation for fluid management or decompensated heart failure.
Ġew riċevuti rapporti wara t- tqegħid fis- suq ta 'ritenzjoni ta' fluwidu li ġrat ġimgħat wara li nbeda ambrisentan u, f' xi każijiet kien hemm bżonn ta 'intervent b' dijuretiku jew dħul l- isptar għall- immaniġġar tal- fluwidu jew falliment tal- qalb mhux kompensat.
If patients have pre-existing fluid overload, this should be managed as clinically appropriate prior to starting ambrisentan.
Jekk il- pazjenti diġa għandhom eċċess ta 'fluwidu, dan għandu jkun immaniġġjat kif klinikament appropjat qabel ma jinbeda ambrisentan.
If clinically significant fluid retention develops during therapy with ambrisentan, with or without associated weight gain, further evaluation should be undertaken to determine the cause, such as ambrisentan or underlying heart failure, and the possible need for specific treatment or discontinuation of ambrisentan therapy.
Jekk tiżviluppa ritenzjoni ta 'fluwidu klinikament sinifikanti waqt kura b' ambrisentan, b' żieda fil- piż jew mingħajr, għandu jkun hemm aktar evalwazzjoni biex tinstab il- kawża bħal ambrisentan jew xi insuffiċjenza tal- qalb moħbija u il- possibilita' ta 'bżonn għal kura speċifika jew twaqqif ta' kura b' ambrisentan.
Women of child-bearing potential
Nisa li jista 'jkollhom tfal
Volibris treatment must not be initiated in women of child-bearing potential unless the result of a pre-treatment pregnancy test is negative and reliable contraception is practiced.
Kura b' Volibris m' għandhiex tinbeda f' nisa li jista 'jkollhom tfal, sakemm ir- riżultat ta' test tat- tqala qabel il- kura jiġi negattiv u jiġi użat kontraċettiv ta 'min joqgħod fuqu.
If there is any doubt on what contraceptive advice should be given to the individual patient, consultation with a gynaecologist should be considered.
Jekk ikun hemm xi dubju fuq x' parir dwar kontraċettiv għandu jingħata lil pazjenti individwali, għandha tiġi kkunsidrata konsulta mal- ġinekologu.
Monthly pregnancy tests during treatment with Volibris are recommended (see sections 4.3 and 4.6).
Huma rakkommandati testijiet tat- tqala kull xahar waqt kura b' Volibris (ara sezzjonijiet 4. 3 u 4. 6).
4 Volibris tablets contain lactose monohydrate.
4 Il- pilloli ta 'Volibris fihom lactose monohydrate.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Pazjenti bi problemi ereditarji rari ta 'intolleranza ta' galattosju, id- defiċjenza tal- lattasju Lapp jew assorbiment mhux siwi ta 'glukosju u galattosju m' għandhomx jieħdu din il- mediċina.
Volibris tablets contain the azo colouring agent Allura red AC Aluminium Lake (E129), which can cause allergic reactions.
Il- pilloli ta 'Volibris fihom is- sustanza azo li tagħti l- kulur Allura red AC Aluminium Lake (E129), li tista ’ tikkawża reazzjonijiet allerġiċi.
Ambrisentan does not inhibit or induce phase I or II drug metabolizing enzymes at clinically relevant concentrations in in vitro and in vivo non-clinical studies, suggesting a low potential for ambrisentan to alter the profile of medicinal products metabolized by these pathways.
Ambrisentan ma jinibixxix jew jinduċi enżimi tal- metaboliżmu ta 'mediċina f' fażi I jew II f' konċentrazzjonijiet klinikament rilevanti fi studji mhux kliniċi kemm in vitro kif ukoll in vivo, li tissuġġerixxi li ambrisentan għandu potenzjal baxx li jibdel il- profil ta' mediċini immetaboliżżati minn dawn il- passaġġi.
The potential for ambrisentan to induce CYP3A4 activity was explored in healthy volunteers with results suggesting a lack of inductive effect of ambrisentan on the CYP3A4 isoenzyme.
Il- potenzjal 'li ambrisentan jinduċi attivita' f' CYP3A4 ġiet esplorata f' voluntieri b' saħħithom b' riżultati li jissuġġerixxu nuqqas ta 'effett induttiv ta' ambrisentan fuq l- isoenzyme CYP3A4.
Co-administration of ambrisentan with a phosphodiesterase inhibitor, either sildenafil or tadalafil (both substrates of CYP3A4) in healthy volunteers did not significantly affect the pharmacokinetics of the phosphodiesterase inhibitor or ambrisentan (see section 5.2).
It- tehid flimkien ta 'ambrisentan ma' inibitur ta 'phosphodiesterase, jew sildenafil jew tadalafil (it- tnejn substratti ta' CYP3A4) f' voluntiera b' saħħithom m' affettwatx b' mod sinifikattiv il- farmakokinetika ta 'l- inibitur ta' phosphodiesterase jew ambrisentan (ara sezzjoni 5. 2).
Steady state administration of ketoconazole (a strong inhibitor of CYP3A4) did not result in a clinically significant increase in exposure to ambrisentan (see section 5.2).
L- għoti ta 'ketoconazole (inibitur qawwi ta' CYP3A4) fi stat fiss ma rriżultax f 'żieda klinikament sinifikanti meta kien hemm espożizzjoni għal ambrisentan (ara sezzjoni 5. 2).
The impact of the co-administration of Volibris with inducers of CYP3A4 and 2C19 is unknown.
M' huwiex magħruf l- impatt ta 'l- għoti flimkien ta' Volibris ma 'sustanzi li jinduċu CYP3A4 u 2C19.
Ambrisentan had no effects on the steady state pharmacokinetics and anti-coagulant activity of warfarin in a healthy volunteer study (see section 5.2).
Ambrisentan ma kellu l- ebda effett fuq il- farmakokinetika fi stat fiss u l- attivita 'anti- koagulattiva ta' warfarin fi studju f' voluntiera b' saħħithom (ara sezzjoni 5. 2).
Warfarin also had no clinically significant effects on the pharmacokinetics of ambrisentan.
Warfarin ukoll ma kellu l- ebda effect klinikament sinifikanti fuq il- farmakokinetika ta 'ambrisentan.
In addition, in patients, ambrisentan had no overall effect on the weekly warfarin-type anticoagulant dose, prothrombin time (PT) and international normalized ratio (INR).
Barra minn hekk, fil- pazjenti, ambrisentan ma kellu l- ebda effett fuq kollox fuq id- doża ta 'warfarin tat- tip li tingħata kull ġimgħa, il- prothrombin time (PT) u l- international normalized ratio (INR).
Cyclosporine A is an inhibitor of multiple metabolic enzymes and transporters.
Cyclosporine A hu inibitur ta 'ħafna enżimi u trasportaturi metaboliċi.
Use caution when Volibris is co-administered with cyclosporine A.
Uża l- kawtela meta Volibris jingħata flimkien ma 'cyclosporine A.
In a clinical study in healthy volunteers, steady-state dosing with ambrisentan 10 mg once daily did not significantly affect the single-dose pharmacokinetics of the ethinyl estradiol and norethindrone components of a combined oral contraceptive (see section 5.2).
Fi studju kliniku f’ voluntiera b’ saħħithom, dożaġġ fi stat stabbli b’ ambrisentan 10mg darba kuljum ma affettwax b’ mod sinifikattiv il- farmakokinetika ta ’ doża waħda ta ’ komponenti ta ’ ethinly estradiol u norethindrone ta ’ kontraċettiv orali kombinat (ara sezzjoni 5. 2).
Based on this pharmacokinetic study, ambrisentan would not be expected to significantly affect exposure to oestrogen- or progestogen- based contraceptives.
Fuq bażi ta ’ dan l- istudju farmakokinetiku, ambrisentan ma jkunx mistenni li jaffettwa b’ mod sinifikattiv l- espożizzjoni għal kontraċettivi ibbażati fuq estroġeni jew proġestoġeni.
The efficacy and safety of Volibris when co-administered with other treatments for PAH (e. g. prostanoids and phosphodiesterase type V inhibitors) has not been specifically studied in controlled clinical trials (see section 5.1).
L- effikaċċja u s- sigurta 'ta' Volibris meta jingħata ma 'kuri oħra għall- PAH (e. ż prostanoids, inibituri ta' phoshodiesterase tip V) ma ġiewx studjata speċifikament fi studji kliniċi kontrollati (ara sezzjoni 5. 1).
Therefore, caution is recommended in the case of co-administration.
Għalhekk hi rakkomandata kawtela f' każ li jittieħdu flimkien.
Effect of ambrisentan on xenobiotic transporters
L- effett ta 'ambrisentan fuq trasportaturi xenobijotiċi
In vitro, ambrisentan has no inhibitory effect on the P-glycoprotein (Pgp)-mediated efflux of digoxin and is a weak substrate for Pgp-mediated efflux.
5 Ambrisentan m' għandu l- ebda effett inbitorju fuq l- effluss medjat minn glikoproteina- P (Pgp) ta 'digoxin u huwa sustrat debboli għall- effluss medjat minn Pgp in vitro.
Additional in vitro studies in rat and human hepatocytes showed that ambrisentan did not inhibit sodium-taurocholate co-transporter (NTCP), organic anion export pump (OATP), bile salt export pump (BSEP) and multi-drug resistance protein isoform-2 (MRP2).
Studji oħra in vitro f' ċelloli tal- fwied fil- far u fil- bniedem urew li ambrisentan ma inibixxix il- ko- trasportatur ta 'sodium taurocholate (NTCP), il- pompa organika ta' esportazzjoni anjonika (OATP), il- pompa ta 'esportazzjoni tal- melħ tal- bil (BSEP) u l- isoform 2 tal- proteina ta' reżistenza għal- mediċini multipli (MRP2).
In vitro studies in rat hepatocytes also showed that ambrisentan has no inductive effects on Pgp, BSEP or MRP2.
Fi studji in vitro f' ċelloli tal- fwied fil- firien urew ukoll li ambrisentan m' għandux effetti induttivi fuq Pgp, BSEP jew MRP2.
5 Steady-state administration of ambrisentan in healthy volunteers had no clinically relevant effects on the single-dose pharmacokinetics of digoxin, a substrate for Pgp (see section 5.2).
It- tehid fi stat fiss ta 'ambrisentan f' voluntiera b' saħħithom ma kellux effetti klinikament rilevanti fuq il- farmakokinetika ta' doża waħda ta 'digoxin, substratt għal Pgp (ara sezzjoni 5. 2).
Volibris is contraindicated in pregnancy (see section 4.3).
Volibris m' għandux jingħata fit- tqala (ara sezzjoni 4. 3).
Animal studies have shown that ambrisentan is teratogenic.
Studji fl- annimali urew li ambrisentan huwa teratoġeniku.
There is no experience in humans.
Ma hemmx esperjenza fil- bnedmin.
Monthly pregnancy tests during treatment with Volibris are recommended.
Huma rakkommandati testijiet tat- tqala kull xahar waqt kura b' Volibris.
Women receiving Volibris must be advised of the risk of foetal harm and alternative therapy initiated if pregnancy occurs (see sections 4.3, 4.4 and 5.3).
Nisa li jkunu fuq Volibris għandhom jingħataw parir fuq ir- riskju ta 'ħsara lil- fetu u jekk ikun hemm tqala għandha tinbeda kura oħra (ara s- sezzjonijiet 4. 3, 4. 4 u 5. 3).
It is not known whether ambrisentan is excreted in human breast milk.
Mhuwiex magħruf jekk ambrisentan jgħaddix fil- ħalib tas- sider tal- bniedem.
The excretion of ambrisentan in milk has not been studied in animals.
L- eskrezzjoni ta 'ambrisentan fil- ħalib ma ġietx studjata f' annimali.
Therefore lactation is contraindicated in patients taking Volibris (see section 4.3).
It- treddigħ huwa kontra- indikat f' pazjenti li jieħdu Volibris (ara sezzjoni 4. 3).
Male fertility
Fertilita 'fl- irġiel
The development of testicular tubular atrophy in male animals has been linked to the chronic administration of ERAs, including ambrisentan (see section 5.3).
L- iżvilupp ta 'atrofija fit- tubi tat- testikoli f' annimali rġiel kien ikkollegat ma' l- għoti kroniku ta 'ERAs inkluż ambrisentan (ara sezzjoni 5. 3).
The effect on male human fertility is not known.
Mhux magħruf l- effett fuq il- fertilita 'ta' l- uman maskil.
Chronic administration of ambrisentan was not associated with a change in plasma testosterone in clinical studies.
L- għoti kroniku ta 'ambrisentan ma kienx assoċċjat ma' bdil fit- testosterone fil- plażma fi studji kliniċi.
Experience from clinical studies
Esperjenza minn studji kliniċi
Safety of Volibris has been evaluated in clinical trials of more than 483 patients with PAH (see section 5.1).
6 Is- sigurta 'ta ’ Volibris ġiet evalwata fi studji kliniċi ta' aktar minn 483 pazjent b' PAH (ara sezzjoni 5. 1).
Adverse drug reactions (ADR) identified from 12 week placebo controlled clinical trial data are listed below by system organ class and frequency.
L- effetti avversi tal- mediċina (ADR) li nstabu minn studju kliniku ta '12- il ġimgħa kkontrollat bi plaċebo huma elenkati skond is- sistema tal- klassi ta ’ l- organi u l- frekwenza.
With longer observation in uncontrolled studies (mean observation of 79 weeks), the safety profile was similar to that observed in the short term studies.
Il- profil ta 'sigurta' f' osservazzjoni aktar fit- tul fi studji mhux kontrollati (medja ta 'osservazzjoni ta' 79 ġimgħa), kien simili għal dak osservata fi studji li saru fuq żmien qasir.
Frequencies are defined as: very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000).
Il- frekwenzi huma mfissra bħala komuni ħafna (> 1/ 10), komuni (> 1/ 100, < 1/ 10), mhux komuni (> 1/ 1, 000, < 1/ 100), rari (> 1/ 10, 000, < 1/ 1, 000) rari ħafna (< 1/ 10, 000).
For dose-related adverse reactions the frequency category reflects the higher dose of Volibris.
Għal effetti avversi relatati mad- doża il- kategorija ta 'frekwenza tirrifletti id- doża aktar għolja ta' Volibris.
Frequency categories do not account for other factors including varying study duration, pre-existing conditions and baseline patient characteristics.
Il- kategoriji ta 'frekwenza ma jikkunsidrawx fatturi oħra bħal tul ta' studju differenti, kondizzjonijiet li kienu hemm qabel u karatteristiċi tal- linja bażi tal- pazjent.
Adverse reaction frequency categories assigned based on clinical trial experience may not reflect the frequency of adverse events occurring during normal clinical practice.
Il- kategoriji ta 'frekwenza ta' effetti mhux mixtieqa assenjati bbażati fuq esperjenza minn studji kliniċi jista 'ma jirriflettux il- frekwenza ta' effetti avversi li jiġru waqt il- prattika klinika normali.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F' kull sezzjoni ta 'frekwenza, l- effetti mhux mixtieqa għandhom jitniżżlu skond is- sigurta' tagħhom.
Cardiac disorders
Disturbi vaskulari Palpitazzjoni
Anaemia (decreased haemoglobin, decreased haematocrit)
Anemija (nuqqas fl- emoglobina, nuqqas fil- ematokrit)
Nervous system disorders
Disturbi tas- sistema nervuża Uġigħ ta 'ras (li tinkludi uġigħ ta' ras minħabba sinus, emikranja) 1)
Respiratory, thoracic and mediastinal disorders
Disturbi respiratorji, toraċiċi, u medjastinali Komuni Parti respiratorja ta 'fuq (e. ż. nasali2, sinus), konġestjoni, sinużite, nasofarinġite, flissjoni
Upper respiratory (e. g. nasal2, sinus) congestion, sinusitis, nasopharyngitis, rhinitis
Disturbi gastro- intestinali Ugigħ tal- addome Stitikezza
Gastrointestinal disorders
Disturbi vaskulari
Common Common
Fawra
General disorders and administration site conditions
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Komuni ħafna Edema periferali, żamma ta 'ilma3
Immune system disorders
Disturbi fis- sistema immuni Reazzjonijiet ta ’ sensittività eċċessiva (e. ż. anġjoedema, raxx)
1 The frequency of headache appeared higher with 10 mg Volibris.
1 Il- frekwenza ta 'uġigħ ta' ras dehret aktar b' 10 mg ta 'Volibris.
2 The incidence of nasal congestion was dose related during Volibris therapy.
2 L- inċidenza ta 'konġestjoni fl- imnieħer kienet relatata mad- doża waqt kura b' Volibris.
3 Peripheral oedema was reported more frequently with 10 mg Volibris.
7 3 Edema periferali kienet rappurtata aktar spiss b' 10 mg ta 'Volibris.
In clinical studies peripheral oedema was reported more commonly and tended to be more severe in patients ≥ 65 years (see section 4.4).
Fi studji kliniċi edema periferali kienet rappurtata b' mod aktar komuni u kien hemm tendenza li tkun aktar severa f' pazjenti ≥65 sena (ara sezzjoni 4. 4).
Decreased haemoglobin (see section 4.4).
Nuqqas fl- emoglobina (ara sezzjoni 4. 4).
The frequency of decreased haemoglobin (anaemia) was higher with 10 mg Volibris.
Il- frekwenza ta 'nuqqas fl- emoglobina (anemija) dehret aktar b' 10 mg ta' Volibris.
Across the 12 week placebo controlled Phase III clinical studies, mean haemoglobin concentrations decreased for patients in the Volibris groups and were detected as early as week 4 (decrease by 0.83 g/ dl); mean changes from baseline appeared to stabilise over the subsequent 8 weeks.
Matul l- istudji kliniċi Fażi III, fuq 12- il ġimgħa, kkontrollati bi plaċebo, il- medja ta 'konċentrazzjoni ta' emoglobina naqset għal pazjenti fil- gruppi ta 'Volibris u ndunaw bihom kmieni mir- 4 ġimgħa (nuqqas b' 0. 83 g/ dL); il- medja ta' bdil mill- linja bażi dehret li stabbilit ruħha fuq it- 8 ġimgħat ta 'wara.
A total of 17 patients (6.5%) in the Volibris treatment groups had decreases in haemoglobin of ≥ 15% from baseline and which fell below the lower limit of normal.
Fil- gruppi ta ’ trattament ta 'Volibris total ta' 17- il pazjent (6. 5%) kellhom nuqqas fl- emoglobina ta '≥15% mill- linja bażi u li waqgħat taħt il- limitu l- aktar baxx tan- normal
Post-marketing data
Dejta wara t- tqegħid fis- suq
7 In addition to adverse reactions identified from clinical studies, the following adverse reactions were identified during post-approval use of Volibris.
Barra mill- eventi avversi identifikati minn studji kliniċi ġew identifikati dawn l- effetti avversi li ġejjin waqt użu wara l- approvazzjoni ta 'Volibris.
Frequencies are defined as: ‘ not known’ (cannot be estimated from the available data).
Il- frekwenzi huma definiti bħala 'mhux magħrufa' (li ma jistgħux ikunu ikkalkulati mid- dejta disponibbli).
Cardiac disorders
Disturbi vaskulari Ma jgħoddx f’ dan il- każ.
Cardiac failure4
Falliment tal- qalb4
Respiratory, thoracic and mediastinal disorders
Disturbi respiratorji, toraċiċi, u medjastinali Ma jgħoddx f’ dan il- każ.
Dyspnoea5
Qtigh ta 'nifs5
4 Most of the reported cases of cardiac failure were associated with fluid retention.
4 Ħafna mill- każijiet irrappurtati ta 'falliment tal- qalb ġew assoċċjati ma' ritenzjoni ta 'fluwidu.
5 Cases of worsening dyspnoea of unclear aetiology have been reported shortly after starting Volibris therapy.
5 Ġew irrapurtati każijiet ta 'qtigħ ta' nifs li mar għall- agħar li l- kawża tiegħu ma kienetx ċara ftit wara li nbdiet il- kura b' Volibris.
There is no experience in PAH patients of Volibris at daily doses greater than 10 mg.
Ma hemmx esperjenza f' pazjenti b' PAH ta 'Volibris f' dożi ta' kuljum ta 'aktar minn 10 mg.
In healthy volunteers, single doses of 50 and 100 mg (5 to 10 times the maximum recommended dose) were associated with headache, flushing, dizziness, nausea and nasal congestion.
F' voluntiera b' saħħithom, dożi waħedhom ta '50 u 100 mg (5 sa 10 darbiet id- doża massima rakkommandata) kienu assoċjati ma' uġigħ ta 'ras, fawra, sturdament dardir u sadda fl- imnieħer.
Due to the mechanism of action, an overdose of Volibris could potentially result in hypotension (see section 5.3).
Minħabba l- mod li jaħdem, doża eċċessiva ta 'Volibris tista' tirriżulta fi pressjoni baxxa (ara sezzjoni 5. 3).
In the case of pronounced hypotension, active cardiovascular support may be required.
F' kas ta 'pressjoni baxxa ħafna, jista' jkun hemm bżonn sapport kardjovaskulari attiv.
No specific antidote is available.
Ma hemmx antidot speċifiku disponibbli.
Pharmacotherapeutic group: other anti-hypertensives, ATC code:
Kategorija farmakoterapewtika: mediċini oħra li jbaxxu l- pressjoni, Kodiċi ATC:
Ambrisentan is an orally active, propanoic acid-class, ERA selective for the endothelin A (ETA) receptor.
8 Ambrisentan huwa attiv meta jittieħed mill- ħalq, tal- klassi ta 'aċidi propanoiċi u ERA selettiv għar- riċettur ta' endotelina A( ETA).
Endothelin plays a significant role in the pathophysiology of PAH.
L- endotelina għandha rwol importanti fil- patofisjoloġija ta 'PAH.
• Ambrisentan blocks the ETA receptor subtype, localized predominantly on vascular smooth muscle cells and cardiac myocytes.
• Ambrisentan jimblokka s- sottotip tar- riċettur ETA, li jinstab l- aktar fuq ċelloli lixxi tal- muskolu vaskulari u ċelloli tal- muskolu tal- qalb.
This prevents endothelin-mediated activation of second messenger systems that result in vasoconstriction and smooth muscle cell proliferation. • The selectivity of ambrisentan for the ETA over the ETB receptor is expected to retain ETB receptor mediated production of the vasodilators nitric oxide and prostacyclin.
Dan iwaqqaf attivazzjoni medjata mill- endotelina tas- sistema tat- tieni messaġier li jwassal għal vażokonstrizzjoni u proliferazzjoni taċ- ċelloli lixxi tal- muskolu. • Is- selettività ta 'ambrisentan għal ETA fuq ir- riċettur ETB hija mistennija li żżomm il- produzzjoni ta' vażodilataturi bħal nitric oxide u prostacyclin li tiġi medjata minn ETB.
8 Two randomised, double-blind, multi-centre, placebo controlled, Phase 3 pivotal studies were conducted (ARIES-1 and 2).
Saru żewġ studji pivotali (ARIES 1 u 2), tal- Fażi 3, kontrollati bi plaċebo, f' ħafna ċentri, double blind u randomised.
ARIES-1 included 201 patients and compared Volibris 5 mg and 10 mg with placebo.
ARIES 1 kien jinkludi 201 pazjenti u pparaguna Volibris 5 mg u 10 mg ma 'plaċebo.
ARIES-2 included 192 patients and compared Volibris 2.5 mg and 5 mg with placebo.
ARIES 2 kien jinkludi 192 pazjenti u pparaguna Volibris 2. 5 mg u 5 mg ma 'plaċebo.
In both studies, Volibris was added to patients’ supportive/ background medication, which could have included a combination of digoxin, anticoagulants, diuretics, oxygen and vasodilators (calcium channel blockers, ACE inhibitors).
Fiż- żewġ studji, Volibris ġie miżjud mal- mediċina ta 'sapport/ li jieħdu s- soltu, fejn setgħa jkun hemm kombinazzjoni ta' digoxin, antikoagulanti, dijuretiċi ossiġnu u vażodilataturi (imblokkaturi tal- kanali tal- kalċju, inibituri ACE).
Patients enrolled had IPAH or PAH associated with connective tissue disease.
Il- pazjenti li ħadu sehem kellhom IPAH jew PAH assoċċjata ma 'mard tal- connective tissue.
The majority of patients had WHO functional Class II (38.4%) or Class III (55.0%) symptoms.
Il- maġġoranza ta 'pazjenti kellhom sintomi Klassi funzjonali WHO II (38. 4%) jew Klassi III (55. 0%).
Patients with pre-existent hepatic disease (cirrhosis or clinically significantly elevated aminotransferases) and patients using other targeted therapy for PAH (e. g. prostanoids) were excluded.
Kienu esklużi pazjenti li diġa jbatu minn mard tal- fwied (ċirrożi jew żieda klinikament sinifikanti ta 'aminotransferases) u pazjenti li jużaw terapija immirata għal PAH (e. ż. prostanoids).
Haemodynamic parameters were not assessed in these studies.
Ma kienux assessjati parametri emodinamiċi f' dawn l- istudji.
The primary endpoint defined for the Phase 3 studies was improvement in exercise capacity assessed by change from baseline in 6 minute walk distance (6MWD) at 12 weeks.
L- endpoint primarju definit fl- istudji Fażi 3 kien titjib fil- kapaċita 'ta' eżerċizzju assessjata permezz ta 'bidla mill- linja bażi f' mixjiet ta' 6 minuti (6MWD) fi 12- il ġimgħa.
In both studies, treatment with Volibris resulted in a significant improvement in 6MWD for each dose of Volibris.
Fiż- żewġ studji, il- kura b' Volibris irriżultat f' titjib sinifikanti fis- 6MWD għal kull doża ta 'Volibris.
The placebo-adjusted improvement in mean 6MWD at week 12 compared to baseline was 30.6 m (95% CI:
It- titjib aġġustat skond il- plaċebo fil- medja ta '6MWD f' ġimgħa 12 meta mqabbla mal- linja bażi kien ta' 30. 6 m (95% CI:
29.6 to 89.3; p < 0.001) for the 5 mg group, in ARIES 1 and 2 respectively.
2. 9 to 58. 3; p=0. 008) u 59. 4 m (95% CI: minn 29. 6 sa 89. 3; p < 0. 001) għall- grupp ta '5 mg, f' ARIES 1 u 2 rispettivament.
26.6 to 76.2; p < 0.001).
It- titjib aġġustat skond il- plaċebo fil- medja ta '6MWD f' ġimgħa 12 f' pazjenti fil- grupp ta' 10 mg f' ARIES 1 kien ta '51. 4 m (95% CI: minn 26. 6 sa 76. 2; p < 0. 001).
A pre-specified combined analysis of the Phase 3 studies (ARIES-C) was conducted.
Saret analiżi kombinata u speċifikata minn qabel ta 'studji f' Fażi 3 (ARIES C).
28.8 to 76.2; p < 0.001) for the 10 mg dose.
It- titjib aġġustat skond il- plaċebo fil- medja ta '6MWD kien ta' 44. 6 m (95% CI: minn 24. 3 sa 64. 9; p < 0. 001) għad- doża ta '5 mg, u 52. 5 m (95% CI: minn 28. 8 sa 76. 2; p < 0. 001) għad- doża ta' 10 mg.
47% to 92%).
F' ARIES 2, Volibris (grupp tad- doża kombinata) dewwem sinifikament iż- żmien li PAH tmur għall- agħar klinikament meta mqabbel ma 'plaċebo (p < 0. 001), il- proporzjon ta' riskju wera tnaqqis ta '80% (95% CI: minn 47% sa 92%).
The measure included: death, lung transplantation, hospitalisation for PAH, atrial septostomy, addition of other PAH therapeutic agents and early escape criteria.
Il- miżura inkludiet mewt, transpjant tal- pulmun, dħul l- isptar minħabba PAH, septostomija ta 'l- atrium, żieda ta' aġenti tal- kura oħra għall- PAH u kriterji ta 'ħelsien kmieni.
A statistically significant increase (3.41 ± 6.96) was observed for the combined dose group in the physical functioning scale of the SF-36 Health Survey compared with placebo (-0.20 ± 8.14, p=0.005).
Kienet osservata żieda statistikament sinifikanti (3. 41 ± 6. 96) għal grupp tad- doża kombinata fl- iskala ta 'funzjoni fiżika tas- Survey tas- Saħħa SF 36 meta mqabbla ma' plaċebo (0. 20 ± 8. 14; p=0. 005).
Treatment with Volibris led to a statistically significant improvement in Borg Dyspnea Index (BDI) at week 12 (placebo-adjusted BDI of -1.1 (95% CI: -1.8 to -0.4; p=0.019; combined dose group)).
Kura b' Volibris wasslet għal titjib statistikament sinifikanti fl- Indiċi tad- Dispnea Borg (BDI) f' ġimgħa 12 (BDI aġġustat bil- plaċebo ta '- 1. 1 (95% CI: minn - 1. 8 sa - 0. 4; p=0. 019; grupp tad- doża kombinata)).
Long term data
Dejta fuq tul ta 'żmien
Patients enrolled into ARIES 1 and 2 were eligible to enter a long term open label extension study ARIES E (n=383).
Pazjenti irreġistrati f' ARIES 1 u 2 kienu eliġibli li jidħlu fi studju ta 'estensjoni open label fuq tul ta' żmien ARIES E (n=383).
The effect of Volibris on the outcome of the disease is unknown.
Mhux magħruf l- effett ta 'Volibris fuq l- iżvilupp tal- marda.
The observed probability of survival at 1 year for subjects receiving Volibris (combined Volibris dose group) was 95% and at 2 years was 84%.
Il- probabilita 'ta' sopravivenza osservata wara sena għal suġġetti li rċevew Volibris (grupp ta 'doża kombinata ta' Volibris) kien ta '95% u ta' 84% wara 2 snin.
In an open label study (AMB222), Volibris was studied in 36 patients to evaluate the incidence of increased serum aminotransferase concentrations in patients who had previously discontinued other ERA therapy due to aminotransferase abnormalities.
9 Fi studju open label (AMB222), Volibris ġie studjat f' 36 pazjent biex tkun evalwata l- inċidenza ta 'konċentrazzjonijiet miżjuda ta' aminotransferase fis- serum f' pazjenti li f' xi żmien qabel kienu waqqfu t- terapija ERA minħabba abnormalitajiet ta 'aminotransferase.
During a mean of 53 weeks of treatment with Volibris, none of the patients enrolled had a confirmed serum ALT > 3xULN that required permanent discontinuation of treatment.
Matul medja ta '53 ġimgħa ta' kura b' Volibris, ebda wieħed mill- pazjenti reġistrati ma kellu serum ALT > 3xULN konfermat li kien jeħtieġ li l- kura titwaqqaf permanentament.
Fifty percent of patients had increased from 5 mg to 10 mg Volibris during this time.
Matul dan iż- żmien ħamsin fil- mija tal- pazjenti kienu żiedu Volibris minn 5 mg sa 10 mg.
The cumulative incidence of serum aminotransferase abnormalities > 3xULN in all Phase 2 and 3 studies (including respective open label extensions) was 17 of 483 subjects over a mean exposure duration of 79.5 weeks.
L- inċidenza kumulativa ta 'abnormalitajiet ta' aminotransferase fis- serum > 3xULN fl- istudji kollha f' Fażi 2 u 3 (li jinkludu estensjonijiet open label rispettivi) kienu 17 minn 483 suġġett matul medja ta 'espożizzjoni ta' 79. 5 ġimgħa.
This is an event rate of 2.3 events per 100 patient years of exposure for Volibris.
Din hija rata ta 'eventi ta' 2. 3 eventi kull 100 sena pazjent ta 'espożizzjoni għal Volibris.
Other clinical information
Informazzjoni klinika oħra
9 An improvement in haemodynamic parameters was observed in patients with PAH after 12 weeks (n=29) in a Phase 2 study (AMB220).
Kien osservat titjib fil- parametri emodinamiċi f' pazjenti b' PAH wara 12 il- ġimgħa (n=29) fi studju Fażi 2 (AMB220).
Treatment with Volibris resulted in an increase in mean cardiac index, a decrease in mean pulmonary artery pressure, and a decrease in mean pulmonary vascular resistance.
Kura b' Volibris irriżultat f' żieda fil- medja ta 'l- indiċi kardijaku, tnaqqis fil- medja tal- pressjoni ta' l- arterja tal- pulmun, u tnaqqis fil- medja ta 'reżistenza vaskulari fil- pulmun.
No clinically meaningful effects on the pharmacokinetics of ambrisentan or sildenafil were seen during a drug-drug interaction study in healthy volunteers, and the combination was well tolerated.
Ma kien hemm l- ebda effetti ta 'valur kliniku fuq il- farmakokinetika ta' ambrisentan jew sildenafil waqt studju fuq interazzjonijiet bejn mediċina u oħra f' voluntiera b' saħħithom u l- kumbinazzjoni kienet tolerata tajjeb.
The number of patients who received concomitant Volibris and sildenafil in ARIES-E and AMB222 was 22 patients (5.7%) and 17 patients (47%), respectively.
In- numru ta 'pazjenti li rċevew Volibris u sildenafil flimkien f' ARIES E u AMB222 kien ta' 22 pazjent (5. 7%) u 17- il pazjent rispettivament.
No additional safety concerns were identified in these patients.
Ma kienux identifikati tħassib fuq sigurta 'f' dawn il- pazjenti.
Ambrisentan is absorbed rapidly in humans.
Ambrisentan jiġi assorbit malajr fil- bniedem.
After oral administration, maximum plasma concentrations (Cmax) of ambrisentan typically occur around 1.5 hours post-dose under both fasted and fed conditions.
Wara li jkun ittieħed mill- ħalq, konċentrazzjonijiet massimi ta 'ambrisentan fil- plażma (Cmax) jintlaħqu tipikament madwar 1. 5 sigħat wara t- teħid tad- doża kemm waqt sawma u kemm le.
Cmax and area under the plasma concentration-time curve (AUC) increase dose proportionally over the therapeutic dose range.
Cmax u l- erja taħt il- kurva tal- konċentrazzjoni fil- plażma (AUC) u ż- żmien jiżdiedu proporzjonament skond id- doża tul il- medda tad- doża terapewtika.
Steady-state is generally achieved following 4 days of repeat dosing.
Stat stabbli ġeneralment jinkiseb wara 4 ijiem ta 'dożaġġ ripetut.
A food-effect study involving administration of ambrisentan to healthy volunteers under fasting conditions and with a high-fat meal indicated that the Cmax was decreased 12% while the AUC remained unchanged.
Studju dwar effetti mill- ikel li jinvolvi għoti ta 'ambrisentan lil voluntieri b' saħħithom waqt sawma u fuq ikla b' ħafna xaħam wera li Cmax naqas bi 12% waqt li l- AUC baqa ma nbidilx.
This decrease in peak concentration is not clinically significant, and therefore ambrisentan can be taken with or without food.
Dan it- tnaqqis tal- konċentrazzjonijiet massimi m' għandux sinifikanza klinika, u għalhekk ambrisentan jista 'jittieħed kemm ma' l- ikel u kemm le.
Ambrisentan is highly plasma protein bound.
Ambrisentan jeħel ħafna mal- proteini tal- plażma.
The in vitro plasma protein binding of ambrisentan was, on average, 98.8% and independent of concentration over the range of 0.2 – 20 microgram/ ml.
It- twaħħil tal- proteini fil- plażma in vitro ta 'ambrisentan kien, bħala medja, 98. 8% u indipendenti minn konċentrazzjoni tul il- medda ta' 0. 2 - 20mikrogrammi/ ml.
Ambrisentan is primarily bound to albumin (96.5%) and to a lesser extent to alpha1-acid glycoprotein.
Ambrisentan jeħel primarjament ma 'l- albumina (96. 5%) u ftit anqas minn hekk mal- glikoproteina alpha1- acid.
The distribution of ambrisentan into red blood cells is low, with a mean blood: plasma ratio of 0.57 and 0.61 in males and females, respectively.
Id- distribuzzjoni ta 'ambrisentan f' ċelloli ħomor tad- demm hi baxxa, b' medja proporzjonali demm: plażma ta' 0. 57 u 0. 61 f' nisa u rġiel rispettivament.
Ambrisentan is a non-sulphonamide (proprionic acid) ERA.
Ambrisentan hu ERA mhux sulphonamide (propionic acid).