qanastek/EMEA-V3 huggingface dataset:
Ambrisentan is glucuronidated via several UGT isoenzymes (UGT1A9S, UGT2B7S and UGT1A3S) to form ambrisentan glucuronide (13%).
10 Ambrisentan jiġi glukuronidat permezz ta 'ħafna isoenżimi UGT (UGT1A9S, UGT2B7S u UGT1A3S) biex jifforma ambrisentan glucuronide (13%).
Ambrisentan also undergoes oxidative metabolism mainly by CYP3A4 and to a lesser extent by CYP3A5 and CYP2C19 to form 4-hydroxymethyl ambrisentan (21%) which is further glucuronidated to 4-hydroxymethyl ambrisentan glucuronide (5%).
Ambrisentan jgħaddi wkoll minn metaboliżmu ossidattiv prinċipalment b' CYP3A4 u ftit inqas minn hekk b' CYP3A5 u CYP2C19 biex jifforma 4- hydroxymethyl ambrisentan (21%) li jkompli jiġi glukurodinat għal 4- hydroxymethyl ambrisentan glucuronide (5%).
The binding affinity of 4-hydroxymethyl ambrisentan for the human endothelin receptor is 65-fold less than ambrisentan.
L- affinita 'tal- irbit ta' 4- hydroxymethyl ambrisentan għar- riċettur ta 'l- endotelina fil- bniedem hi 65 darba inqas minn ambrisentan.
Therefore at concentrations observed in the plasma (approximately 4% relative to parent ambrisentan), 4-hydroxymethyl ambrisentan is not expected to contribute to pharmacological activity of ambrisentan.
Għaldaqstant f' konċentrazzjonijiet osservati fil- plażma (madwar 4% relatati ma 'ambrisentan ġenitur), 4- hydroxymethyl ambrisentan mhux mistenni li jikkontribwixxi għal attività farmakoloġika ta' ambrisentan.
In vitro data have shown that at therapeutic concentrations, ambrisentan does not inhibit UGT1A1, UGT1A6, UGT1A9, UGT2B7 or cytochrome P450 enzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4.
Informazzjoni in vitro uriet li b' konċentrazzjonijiet terapewtiċi, ambrisentan ma jinibixxix lil UGT1A1, UGT1A6, UGT1A9, UGT2B7 jew enżimi taċ- ċitokrom P450 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 u 3A4.
Additional in vitro studies showed that ambrisentan does not inhibit NTCP, OATP or BSEP.
Studji in vitro oħra wrew li ambrisentan ma jinibixxix lil NTCP, OATP jew BSEP.
Furthermore, ambrisentan does not induce MRP2, Pgp or BSEP.
Barra dan, ambrisentan ma jinduċix MRP2, Pgp jew BSEP.
10 The effects of steady-state ambrisentan (10 mg once daily) on the pharmacokinetics and pharmacodynamics of a single dose of warfarin (25 mg), as measured by PT and INR, were investigated in 20 healthy volunteers.
L- effetti ta 'ambrisentan fi stat fiss (10 mg darba kuljum) fuq il- farmakokinetiċi u l- farmakodinamiċi ta' doża waħda ta 'warfarin (25 mg) kif imkejla b' PT u INR ġew investigati fuq 20 voluntieri b' saħħithom.
Ambrisentan did not have any clinically relevant effects on the pharmacokinetics or pharmacodynamics of warfarin.
Ambrisentan ma kellu l- ebda effetti ta 'rilevanza klinika fuq il- farmakokinetiċi jew il- farmakodinamiċi ta' warfarin.
Similarly, co-administration with warfarin did not affect the pharmacokinetics of ambrisentan (see section 4.5).
Bl- istess mod, l- għoti flimkien ma 'warfarin m' affettwax il- farmakokinetiċi ta' ambrisentan (ara sezzjoni 4. 5).
The effect of 7-day dosing of sildenafil (20 mg three times daily) on the pharmacokinetics of a single dose of ambrisentan, and the effects of 7-day dosing of ambrisentan (10 mg once daily) on the pharmacokinetics of a single dose of sildenafil were investigated in 19 healthy volunteers.
L- effett ta 'dożaġġ ta' 7- ijiem b' sildenafil (20 mg tlett darbiet kuljum) fuq il- farmakokinetiċi ta 'doża waħda ta' ambrisentan, u l- effetti ta 'dożaġġ ta' 7 ijiem ta 'ambrisentan (10 mg darba kuljum) fuq il- farmakokinetiċi ta' doża waħda ta 'sildenafil ġew investigati fuq 19 voluntieri b' saħħithom.
With the exception of a 13% increase in sildenafil Cmax following co-administration with ambrisentan, there were no other changes in the pharmacokinetic parameters of sildenafil, N-desmethyl-sildenafil and ambrisentan.
Bl- eċċezzjoni ta 'żieda ta' 13% ta 'Cmax ta' sildenafil wara li ngħata flimkien ma 'ambrisentan, ma kien hemm ebda tibdiliet oħra fil- parametri farmakokinetiċi ta' sildenafil, N- desmethyl- sildenafil u ambrisentan.
This slight increase in sildenafil Cmax is not considered clinically relevant (see section 4.5).
Din iż- żieda żgħira ta 'Cmax f' sildenafil m' hijiex meqjusa ta' rilevanza klinika (ara sezzjoni 4. 5).
The effects of steady-state ambrisentan (10 mg once daily) on the pharmacokinetics of a single dose of tadalafil, and the effects of steady-state tadalafil (40 mg once daily) on the pharmacokinetics of a single dose of ambrisentan were studied in 23 healthy volunteers.
L- effetti ta ’ ambrisentan meta jingħata fi stat stabbli (10mg darba kuljum) fuq il- farmakokinetika ta ’ doża waħda ta ’ tadalafil, u l- effetti ta ’ tadalafil fi stat stabbli (40mg darba kuljum) fuq il- farmakokinetika ta ’ doża waħda ta ’ ambrisentan ġew studjati fi 23 voluntiera b’ saħħithom.
Ambrisentan did not have any clinically relevant effects on the pharmacokinetics of tadalafil.
Ambrisentan ma kellux effetti klinikament rilevanti fuq il- farmakokinetika ta ’ tadalafil.
Similarly, co-administration with tadalafil did not affect the pharmacokinetics of ambrisentan (see section 4.5).
Bl- istess mod, it- tehid flimkien ma ’ tadalafil ma affettwatx il- farmakokinetika ta ’ ambrisentan (ara sezzjoni 4. 5).
The effects of repeat dosing of ketoconazole (400 mg once daily) on the pharmacokinetics of a single dose of 10 mg ambrisentan were investigated in 16 healthy volunteers.
L- effetti ta 'dożi ripetuti ta' ketoconazole (400 mg darba kuljum) fuq il- farmakokinetiċi ta 'doża waħda ta' 10 mg ta 'ambrisentan ġew investigati fuq 16 voluntieri b' saħħithom.
Exposures of ambrisentan as measured by AUC(0-inf) and Cmax were increased by 35% and 20%, respectively.
Esponimenti għal ambrisentan kif imkejjel fl- AUC( 0- inf) u Cmax ġew miżjuda b' 35% u 20% rispettivament.
This change in exposure is unlikely to be of any clinical relevance and therefore Volibris may be co-administered with ketoconazole.
Din il- bidla fl- esponiment mhux probabbli li għandha xi rilevanza klinika u għalhekk Volibris jista 'jingħata flimkien ma' ketoconazole.
The effects of repeat dosing of ambrisentan (10 mg) on the pharmacokinetics of single dose digoxin were studied in 15 healthy volunteers.
L- effetti ta 'dożi ripetuti ta' ambrisentan (10 mg) fuq il- farmakokinetiċi ta 'doża waħda ta' digoxin ġew studjati fuq 15 voluntieri b' saħħithom.
Multiple doses of ambrisentan resulted in slight increases in digoxin AUC0-last and trough concentrations, and a 29% increase in digoxin Cmax.
Dożi ripetuti ta 'ambrisentan wasslu għal żidiet zgħar fl- AUC0- last ta' digoxin u konċentrazzjonijiet baxxi, u żieda ta' 29% ta 'digoxin Cmax.
The increase in digoxin exposure observed in the presence of multiple doses of ambrisentan was not considered clinically relevant, and no dose adjustment of digoxin is warranted (see section 4.5).
Iż- żieda fl- esponiment ta 'digoxin osservata fil- preżenza ta' dożi ripetuti ta 'ambrisentan ma kienetx meqjusa ta' rilevanza klinika, u ma hemm bżonn ta 'l- ebda aġġustament fid- doża (ara sezzjoni 4. 5).
The effects of 12 days dosing with ambrisentan (10 mg once daily) on the pharmacokinetics of a single dose of oral contraceptive containing ethinyl estradiol (35 μ g) and norethindrone (1 mg) were studied in healthy female volunteers.
L- effetti ta ’ dożaġġ ta ’ 12- il ġurnata b’ ambrisentan (10mg darba kuljum) fuq il- farmakokinetika ta ’ doża waħda ta ’ kontraċettiv orali li fih ethinyl estradiol (35μg) u norethindrone (1mg) ġew studjati f’ voluntiera b’ saħħithom nisa.
The Cmax and AUC(0 –∞) were slightly decreased for ethinyl estradiol (8% and 4%, respectively), and slightly increased for norethindrone (13% and 14%, respectively).
Kien hemm tnaqqis zgħir fis - Cmax u AUC( 0– ∞) għal ethinyl estradiol (8% u 4% rispettivament), u żieda żgħira għal norethindrone (13% u 14%, rispettivament).
These changes in exposure to ethinyl estradiol or norethindrone were small and are unlikely to be clinically significant (see section 4.5).
Dan it- tibdil fl- espożizzjoni ta ’ ethinyl estradiol u norethindrone kien wieħed żgħir u għalhekk probabbilment mhux ta 'rilevanza klinika (ara sezzjoni 4. 5).
Ambrisentan and its metabolites are eliminated primarily in the bile following hepatic and/ or extra-hepatic metabolism.
11 Ambrisentan u l- metaboliti tiegħu jitneħħew primarjament fil- bili wara l- metaboliżmu fil- fwied u/ jew barra mill- fwied.
Approximately 22% of the administered dose is recovered in the urine following oral administration with 3.3% being unchanged ambrisentan.
Madwar 22% tad- doża li tingħata tispiċċa fl- awrina wara t- teħid mill- ħalq filwaqt li 3. 3% ikun ambrisentan mhux mibdul.
Plasma elimination half-life in humans ranges from 13.6 to 16.5 hours.
Il- half life ta ’ l- eliminazzjoni mill- plażma fil- bniedem tvarja minn 13. 6 sa 16. 5 sigħat.
Based on the results of a population pharmacokinetic analysis in healthy volunteers and patients with PAH, the pharmacokinetics of ambrisentan were not significantly influenced by gender or age (see section 4.2).
Fuq bażi tar- riżultati minn analiżi farmakokinetika ta 'popolazzjoni fuq voluntieri b' saħħithom u pazjenti b' PAH, il- farmakokinetiċi ta' ambrisentan ma ġewx influwenzati sostanzjalment mis- sess jew mill- età (ara sezzjoni 4. 2).
11 Ambrisentan does not undergo significant renal metabolism or renal clearance (excretion).
Ambrisentan ma jgħaddix minn proċess ta 'metaboliżmu sinifikanti tal- kliewi jew ta' tneħħija (eskrezzjoni) mill- kliewi.
In a population pharmacokinetic analysis, creatinine clearance was found to be a statistically significant covariate affecting the oral clearance of ambrisentan.
F' analiżi farmakokinetiku ta 'popolazzjoni, it- tneħħija ta' kreatinina instabet li kienet covariate statistikament sinifikanti li taffettwa it- tneħħija mill- ħalq ta 'ambrisentan.
The magnitude of the decrease in oral clearance is modest (20-40%) in patients with moderate renal impairment and therefore is unlikely to be of any clinical relevance.
Id- daqs tat- tnaqqis ta 'l- eliminazzjoni mill- ħalq hu ta' daqs modest (20- 40% f' pazjenti b' indebboliment moderat tal- kliewi u għalhekk mhux probabbli li jkollu xi rilevanza klinika.
However, caution should be used in patients with severe renal impairment (see section 4.2).
Madankollu, għandha tintuża l- kawtela f' pazjenti b' indebboliment sever tal- kliewi (ara s- sezzjoni 4. 2).
The main routes of metabolism of ambrisentan are glucuronidation and oxidation with subsequent elimination in the bile and therefore hepatic impairment would be expected to increase exposure (Cmax and AUC) of ambrisentan.
Billi ambrisentan jiġi immetaboliżżat primarjament b' glukoronidazzjoni u ossidazzjoni u wara jiġi eliminat fil- bili, u għalhekk l- indebboliment tal- fwied aktarx li jżid l- espożizzjoni (Cmax u l- AUC) ta 'ambrisentan.
In a population pharmacokinetic analysis, the oral clearance was shown to be decreased as a function of increasing bilirubin levels.
F' analiżi farmakokinetiku ta 'popolazzjoni, it- tneħħija mill- ħalq instabet li kienet anqas bħala funzjoni ta' livelli dejjem jiżdiedu ta 'bilirubin.
However, the magnitude of effect of bilirubin is modest (compared to the typical patient with a bilirubin of 0.6 mg/ dl, a patient with an elevated bilirubin of 4.5 mg/ dl would have approximately 30% lower oral clearance of ambrisentan).
Madankollu, l- effett ta 'bilirubin kien ta' kobor modest (meta mqabbel ma 'pazjent tipiku b' bilirubin ta' 0. 6 mg/ dl, pazjent b' bilirubin għoli ta '4. 5mg/ dl kien ikollu tneħħija ta' madwar 30% inqas ta 'ambrisentan).
The pharmacokinetics of ambrisentan in patients with severe hepatic impairment (with or without cirrhosis) has not been studied.
Il- farmakokinetiċi ta 'ambrisentan ma ġewx studjati f' persuni b' indeboliment qawwi tal- fwied (bi jew mingħajr ċirrożi).
Therefore Volibris should not be initiated in patients with severe hepatic impairment or clinically significant elevated hepatic aminotransferases (> 3xULN) (see sections 4.3 and 4.4).
Għalhekk Volibris m' għandux jinbeda f' pazjenti b' indebboliment sever tal- fwied, jew b' aminotransferases klinikament u b' mod sinifikanti għolja fil- fwied (> 3xULN) (ara s- sezzjonijiet 4. 3 u 4. 4).
Due to the class primary pharmacologic effect, a large single dose of ambrisentan (i. e. an overdose) could lower arterial pressure and have the potential for causing hypotension and symptoms related to vasodilation.
Minħabba effett farmakoloġiku primarju ta 'klassi, doża waħda għolja ta' ambrisentan (i. e. doża eċċessive) tista 'tbaxxi l- pressjoni arterjali u jkollha l- potenzjal li tikkawża pressjoni baxxa u sintomi relatati ma' vażodilatazzjoni.
Ambrisentan was not shown to be an inhibitor of bile acid transport or to produce overt hepatotoxicity.
Ambrisentan ma weriex li hu inibitur tat- trasport ta 'l- aċidu tal- bili jew li jagħmel xi tossiċita epatika fid- dieher.
Inflammation and changes in the nasal cavity epithelium have been seen in rodents after chronic administration at exposures below the therapeutic levels in humans.
Ġew osservati infjammazzjoni u tibdil fl- epitilju tal- ħofra fl- imnieħer fi ġrieden u firien f' esponimenti aktar baxxi mill- livelli terapewtiċi fil- bnedmin.
In dogs, slight inflammatory responses were observed following chronic high dose administration of ambrisentan at exposures greater than 20– fold that observed in patients.
Fil- klieb, ġew osservati risponsi infjammatorji minimi wara tehid kroniku ta 'doża għolja ta' ambrisentan f' esponimenti ta 'aktar minn 20 darba osservati fil- pazjenti.
Nasal bone hyperplasia of the ethmoid turbinates has been observed in the nasal cavity of rats treated with ambrisentan, at exposure levels 3-fold the clinical AUC.
Ġiet osservata iperplasja fl- għadam spirali etmojde ta 'l- imnieħer fil- ħofra ta' l- imnieħer ta 'firien trattati b' ambrisentan, b' livelli ta' esponiment 3- darbiet aktar mill- AUC kliniku.
Nasal bone hyperplasia has not been observed with ambrisentan in mice or dogs.
Ma ġietx osservata iperplasja ta 'l- għadma ta' l- imnieħer b' ambrisentan fi ġrieden jew klieb.
In the rat, hyperplasia of nasal turbinate bone is a recognised response to nasal inflammation, based on experience with other compounds.
Fil- far, iperplasja ta 'l- għadma spirali ta' l- imnieħer hija rispons magħruf għal infjammazzjoni ta 'l- imnieħer ibbażat fuq esperjenza b' sustanzi oħra.
Ambrisentan was clastogenic when tested at high concentrations in mammalian cells in vitro.
12 Ambrisentan kien klastoġeniku meta ttestjat in vitro f' konċentrazzjonijiet għoljin f' ċelloli mammeli.
No evidence for mutagenic or genotoxic effects of ambrisentan were seen in bacteria or in two in vivo rodent studies.
Ma kien hemm l- ebda evidenza ta 'effetti mutaġeniċi jew ġenotossiċi ta' ambrisentan f' mikrobi jew f' żewġ studji in vivo fil- ġrieden u l- firien.
There were no treatment-related increases in the incidence of tumours in 2 year oral studies in rats and mice.
Ma kien l- ebda żidiet fl- inċidenza ta 'tumuri relatati mat- trattament fi studji ta' sentejn mill- ħalq fi ġrieden u firien.
Testicular tubular atrophy, which was occasionally associated with aspermia, was observed in oral repeat dose toxicity and fertility studies with male rats and mice without safety margin.
Ġiet osservata atrofija tubulari tat- testikoli, kultant assoċjata ma 'aspermja fi studji orali ripetuti ta' tossiċità u fertilita 'fi firien u ġrieden irġiel mingħajr marġini ta' sigurtà.
The testicular changes were not fully recoverable during the off-dose periods evaluated.
Il- bdil fit- testikoli ma setgħux jittreġgħu lura għal kollox waqt il- perjodu mingħajr dożaġġ evalwat.
However no testicular changes were observed in dog studies of up to 39 weeks duration at an exposure 35– fold that seen in humans based on AUC.
Madankollu ma kienux osservati bdil fit- testikoli fi studji fi klieb sa tul ta '39 ġimgħa b' esponiment ta' 35 darba dak osservat fil- bniedem ibbażat fuq AUC.
The effect of ambrisentan on male human fertility is not known.
Mhux magħruf l- effett ta 'ambrisentan fuq il- fertilita' ta 'l- uman maskil.
12 Ambrisentan has been shown to be teratogenic in rats and rabbits.
Ambrisentan intwera li huwa teratoġeniku f' firien u fniek.
Abnormalities of the lower jaw, tongue, and/ or palate were seen at all doses tested.
Ġew osservati abnormalitajiet fix- xedaq ta 'isfel, l- ilsien u/ jew is- saqaf tal- ħalq fid- dożi kollha ttestjati.
In addition, interventricular septal defects, trunk vessel defects, thyroid and thymus abnormalities, ossification of the basisphenoid bone and increased incidence of left umbilical artery were seen in the rat study.
Barra minn hekk, fl- istudju fuq il- firien, ġew osservati difetti fis- septum interventrikulari, difetti fil- kanal prinċipali, anormalitajiet fit- tirojde u t- timu, ossifikazzjoni ta 'l- għadma bażifenojde, u inċidenza akbar fl- arterja umbilikali tax- xellug.
Teratogenicity is a suspected class effect of ERAs.
Teratoġeniċità hija effett ta 'klassi suspettata ta' ERAs.
Administration of ambrisentan to female rats from late-pregnancy through lactation caused adverse events on maternal behaviour, reduced pup survival and impairment of the reproductive capability of the offspring (with observation of small testes at necropsy), at exposure 3-fold the AUC at the maximum recommended human dose.
L- għoti ta 'ambrisentan lil firien nisa mill- aħħar tat- tqala sa kemm jibdew ireddgħu ikkaġuna diversi effetti mhux mixtieqa fuq l- imġieba materna, naqqas minn numru ta' żgħar li baqgħu ħajjin u kkawża indebboliment tal- kapaċità riproddutiva fil- friegħ (bl- osservazzjoni ta 'testikoli zgħar f' nekroskopija), b' esponiment ta' 3- darbiet aktar mill- AUC bl- akbar doża rakkomandata għall- bniedem.
Tablet core Lactose monohydrate Microcrystalline cellulose Croscarmellose sodium Magnesium stearate
Lactose monohydrate Microcrystalline cellulose Croscarmellose sodium Magnesium stearate
Film coat Polyvinyl alcohol (Partially Hydrolyzed) Talc (E553b) Titanium dioxide (E171) Macrogol / PEG 3350 Lecithin (Soya) (E322) Allura red AC Aluminium Lake (E129)
Polyvinyl alcohol (Parzjalment Idroliżżat) Talc (E553b) Titanium dioxide (E171) Macrogol / PEG 3350 Lecithin (Soya) (E322) Allura red AC Aluminium Lake (E129)
PVC/ PVDC/ aluminium foil blisters.
Folji tal- PVC/ PVDC/ aluminjum.
Pack sizes of 10 or 30 film-coated tablets.
Daqs tal- pakketti ta '10 jew 30 pillola miksija b’ rita.
Glaxo Group Ltd Greenford Middlesex UB6 0NN United Kingdom
Glaxo Group Ltd Greenford Middlesex UB6 0NN Ir- Renju Unit
Date of first authorisation:
Data ta 'l- ewwel awtorizazzjoni:
21 April 2008
21 April 2008
Volibris 10 mg film-coated tablets
Volibris 10 mg pilloli miksija b' rita
Each tablet contains 10 mg of ambrisentan.
Kull pillola fiha 10 mg ta 'ambrisentan.
Each tablet contains lactose monohydrate (approximately 90 mg), Lecithin (Soya) (E322) (approximately 0.25 mg) and Allura red AC Aluminium Lake (E129) (approximately 0.45 mg).
Kull pillola fiha lactose monohydrate (bejn wieħed u ieħor 90 mg), Lecithin (Soya) (E322) (bejn wieħed u ieħor 0. 25 mg) u Allura red AC Aluminium Lake (E129) (bejn wieħed u ieħor 0. 45 mg).
Deep-pink, oval, convex, film-coated tablet with “ GS ” debossed on one side and “ KE3” on the other side.
Pillola miksija b' rita, roża skur, ovali, imbuzzati fuq iż- żewġ naħat b '"GS" imbuzzata fuq naħa waħda u "KE3" fuq in- naħa l- oħra.
15 Volibris is not recommended for use in patients below 18 years of age due to a lack of data on safety and efficacy.
15 Volibris m' huwiex rakkomandat għall- użu fi tfal taħt it- 18 - il sena minħabba nuqqas ta 'dejta fuq sigurtà u effikaċja.
16 Liver function abnormalities have been associated with PAH.
16 Abnormalitajiet tal- funzjoni tal- fwied ġew assoċċjati ma 'PAH.
17 Volibris tablets contain lactose monohydrate.
17 Il- pilloli ta 'Volibris fihom lactose monohydrate.
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.
18 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.
18 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).
Safety of Volibris has been evaluated in clinical trials of more than 483 patients with PAH (see section 5.1).
19 Is- sigurta 'ta ’ Volibris ġiet evalwata fi studji kliniċi ta' aktar minn 483 pazjent b' PAH (ara sezzjoni 5. 1).
3 Peripheral oedema was reported more frequently with 10 mg Volibris.
20 3 Edema periferali kienet rappurtata aktar spiss b' 10 mg ta 'Volibris.
20 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.
Ambrisentan is an orally active, propanoic acid-class, ERA selective for the endothelin A (ETA) receptor.
21 Ambrisentan huwa attiv meta jittieħed mill- ħalq, tal- klassi ta 'aċidi propanoiċi u ERA selettiv għar- riċettur ta' endotelina A( ETA).
21 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.
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.
22 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.
22 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).
Ambrisentan is glucuronidated via several UGT isoenzymes (UGT1A9S, UGT2B7S and UGT1A3S) to form ambrisentan glucuronide (13%).
23 Ambrisentan jiġi glukuronidat permezz ta 'ħafna isoenżimi UGT (UGT1A9S, UGT2B7S u UGT1A3S) biex jifforma ambrisentan glucuronide (13%).
23 The effects of steady-state ambrisentan (10 mg once daily) on the pharmacokinetics and pharmacodynamics of a single dose of warfarin (25 mg), as measured by PT and INR, were investigated in 20 healthy volunteers.
L- effetti ta 'ambrisentan fi stat fiss (10 mg darba kuljum) fuq il- farmakokinetiċi u l- farmakodinamiċi ta' doża waħda ta 'warfarin (25 mg) kif imkejla b' PT u INR ġew investigati fuq 20 voluntieri b' saħħithom.
Ambrisentan and its metabolites are eliminated primarily in the bile following hepatic and/ or extra-hepatic metabolism.
24 Ambrisentan u l- metaboliti tiegħu jitneħħew primarjament fil- bili wara l- metaboliżmu fil- fwied u/ jew barra mill- fwied.
24 Ambrisentan does not undergo significant renal metabolism or renal clearance (excretion).
Ambrisentan ma jgħaddix minn proċess ta 'metaboliżmu sinifikanti tal- kliewi jew ta' tneħħija (eskrezzjoni) mill- kliewi.
Ambrisentan was clastogenic when tested at high concentrations in mammalian cells in vitro.
25 Ambrisentan kien klastoġeniku meta ttestjat in vitro f' konċentrazzjonijiet għoljin f' ċelloli mammeli.
25 Ambrisentan has been shown to be teratogenic in rats and rabbits.
Ambrisentan intwera li huwa teratoġeniku f' firien u fniek.
Film coat Polyvinyl alcohol (Partially Hydrolyzed) Talc (E553b) Titanium dioxide (E171) Macrogol / PEG 3350 Allura red AC Aluminium Lake (E129) Lecithin (Soya) (E322)
Polyvinyl alcohol (Parzjalment Idroliżżat) Talc (E553b) Titanium dioxide (E171) Macrogol / PEG 3350 Allura red AC Aluminium Lake (E129) Lecithin (Soya) (E322)
6.4 Special precautions for storage
26 6. 4 Prekawzjonijiet speċjali għall- ħażna
KG Industriestrasse 32-36 D-23843 Bad Oldesloe Germany
KG Industriestrasse 32- 36 D- 23843 Bad Oldesloe Il- Ġermanja
The MAH shall set up a post-marketing surveillance study as per the synopsis in the EU-Risk Management Plan.
L- MAH ser iwaqqaf studju ta 'sorveljanza wara t- tqegħid fis- suq skond is- sinopsi fil- Pjan ta' Maniġġjar ta 'Riskju.
Details of the implementation of the post-marketing surveillance study should be agreed with the National Competent Authorities in each member state and put in place prior to marketing of the product.
Dettalji ta 'l- implementazzjoni ta' l- istudju ta 'sorveljanza għandu jiġu miftehmin ma' l- Awtoritajiet Kompetenti Nazzjonali f' kull stat membru u jkun implimentat qabel il- prodott jitqiegħed fis- suq.
The MAH must agree the details of a controlled distribution system with the National Competent Authorities and must implement such programme nationally to ensure that prior to prescribing (and where appropriate and in agreement with the National Competent Authority, dispensing) all health care professionals who intend to prescribe (and where appropriate, dispense) Volibris have been provided with the following:
L- MAH għandu jiftiehem id- dettalji ta 'sistema ta' distribuzzjoni kontrollata ma 'l- Awtoritajiet Kompetenti Nazzjonali u għandu jimplementa programm nazzjonali bħal dan biex jassigura li qabel ikun preskritt (u fejn hu xieraq u bi ftehim ma' l- Awtorita 'Kompetenti Nazzjoni, tqassim) kull professjonist fil- qasam tas- saħħa li bi ħsiebu jippreskrivi (u fejn hu xieraq, iqassam) Volibris ġie provdut b' dan li ġej:
• Product information (Summary of Product Characteristics (SPC) and Package Leaflet) • Healthcare professional information regarding Volibris • Pre-prescription checklist for physicians • Information about the post marketing surveillance study • Information booklets for patients • Information booklets for male partners of female patients with child-bearing potential • Patient reminder cards • Pregnancy reporting forms • Adverse drug reaction reporting forms
• Informazzjoni fuq il- Prodott (Sommarju tal- Karatteristiċi tal- Prodott (SPC) u Fuljett tal- Pakkett) • Informazzjoni fuq Volibris lil professjonist fil- qasam tas- saħħa • Lista biex it- tabib jiċċekkja qabel jippreskrivi • Informazzjoni fuq l- istudju ta 'sorveljanza wara t- tqegħid fis- suq • Kotba żgħar ta' informazzjoni għall- pazjenti • Kotba żgħar ta 'informazzjoni lil sieħba rġiel ta' pazjenti nisa li jista 'jkollhom it- tfal • Cards biex ifakkru l- pazjenti • Formoli biex tirraporta waqt it- tqala • Formoli biex tirraporta reazzjonijiet avversi b' xi mediċina
Health care Professional information
Informazzjoni għal Professjonist fil- qasam tas- Saħħa
The healthcare professional information regarding Volibris should contain the following key elements:
L- informazzjoni fuq Volibris lil professjonist fil- qasam tas- saħħa għandu jkollha dawn l- elementi kruċjali li ġejjin:
Obligations of health care professionals in relation to the prescribing of Volibris:
Obligazzjonijiet tal- professjonisti fil- qasam tas- saħħa fejn għandu x’ jaqsam preskrizzjoni ta 'Volibris:
29 • That patients should be capable of complying with the requirements for the safe use of Volibris. • The need to provide comprehensive advice and counselling to patients. • The need to provide patients with the appropriate information booklet(s) and patient reminder card. • Should consider monthly prescription of 30 day supply to ensure that patients and key test results are reviewed prior to further prescription. • That the safety database of Volibris is limited and physicians are encouraged to enrol patients in a post marketing surveillance study. • To report suspected adverse reactions and pregnancy.
29 • Li l- pazjenti ikun kapaċi li jħarsu il- ħtiġijiet għall- użu mingħajr periklu ta 'Volibris. • Il- bżonn li jkun provdut tagħrif u parir komprensiv lill- pazjent. • Il- bżonn li l- pazjenti ikunu provduti bi ktieb/ kotba żgħar ta ’ informazzjoni adatti u l- card biex tfakkar lil- pazjent. • Għanda tkun ikkonsidrata riċetta ta ’ xahar għal provediment ta ’ 30 ġurnata biex ikun assigurat li l- pazjenti u r- riżultati ta ’ testijiet importanti ikunu ċċekkjati qabel riċetti oħra jingħataw. • Li d- database ta ’ sigurta ’ ta ’ Volibris huwa limitat u li t- tobba ikunu mħeġġa biex idaħħlu aktar pazjenti fi studju ta ’ sorveljanza wara t- tqegħid fis- suq. • Biex jirrapurtaw effetti avversi suspetti u tqala.
That Volibris is teratogenic
Li Volibris huwa teratoġeniku
• Volibris is contraindicated in pregnancy and in women of child-bearing potential who are not using reliable contraception. • That women receiving Volibris should be advised of the risk of foetal harm. • Guidance for identifying women of child-bearing potential and the actions the physician should take if unsure.
• Volibris huwa kontraindikat fit- tqala u f’ nisa li jista 'jkollhom it- tfal u li ma humiex qegħdin jużaw kontraċezzjoni ta' min joqgħod fuqha. • Li nisa li jkunu qegħdin jieħdu Volibris għandhom ikunu mwissija fuq ir- riskju ta ’ ħsara lil- fetu. • Gwida biex ikunu identifikati nisa li jista ’ jkollhom it- tfal u l- azzjonijiet li għandu jieħu t- tabib jekk ma jkunx ċert.
For women with child-bearing potential:
Għal nisa li jista 'jkollhom tfal:
• Exclusion of pregnancy prior to treatment initiation and monthly pregnancy testing during treatment. • The need to advise women (even if a woman has amenorrhoea) on the use of reliable contraception during treatment and for one month following permanent discontinuation of treatment. • Definition of reliable contraception and the need to seek expert advice if unsure what is suitable for an individual patient. • That if a woman of child-bearing potential needs to change or stop her method of contraception she should inform the physician prescribing her contraception that she is taking Volibris. • That if a women of child-bearing potential needs to change or stop her method of contraception she should inform the physician prescribing Volibris. • That the patient should contact her doctor immediately if pregnancy is suspected and that alternative therapy should be initiated if pregnancy confirmed. • The need to refer patients who become pregnant to a physician specialised or experienced in teratology and its diagnosis for evaluation and advice. • To report all cases of pregnancy occurring during therapy.
• Għandha tiġi eskluża t- tqala qabel ma tinbeda l- kura u għandhom isiru testijiet tat- tqala kull xahar waqt il- kura. • Il- bżonn li jingħata parir lin- nisa (ukoll jekk mara ikollha amenorrea) fuq l- użu ta ’ kontraċezzjoni ta ’ min joqgħod fuqha waqt il- kura u għal xahar wara li l- kura tieqaf għal kollox. • Definizzjoni ta ’ kontraċezzjoni ta ’ min joqgħod fuqha u l- bżonn li jitfittex parir espert fejn ma jkunx hemm ċertezza ta ’ x’ inhu adatt għal pazjent individwali. • Li jekk mara li jista ’ jkollha t- tfal ikollha bżonn tibdel jew twaqqaf il- metodu ta ’ kontraċezzjoni tagħha hi għandha tinforma it- tabib li jippreskrivi l- kontraċezzjoni li qed tieħu Volibris. • Li jekk mara li jista ’ jkollha t- tfal ikollha bżonn tibdel jew twaqqaf il- metodu ta ’ kontraċezzjoni tagħha hi għandha tinforma it- tabib li ppreskriva Volibris. • Li l- pazjenta għandha tikkuntatja lit- tabib tagħha immedjatament jekk tissusspetta li ħarġet tqila u għandha tinbeda kura oħra jekk tkun konfermata t- tqala. • Il- bżonn li jirreferu pazjenti li joħorġu tqal għand tabib speċjaliżżat jew b’ esperjenza fit- teratoloġija u d- dijanjożi tagħha għal evalwazzjoni u parir. • Biex jirrapurtaw il- każi kollha ta ’ tqala li jseħħu waqt il- kura.
That Volibris is potentially hepatotoxic
Li Volibris hu potenzjalment tossiku għall fwied
• Contraindication in patients with severe hepatic impairment (with or without cirrhosis) and in patients with baseline values of hepatic aminotransferases (AST and/ or ALT) > 3X ULN. • Hepatic aminotransferases (ALT and/ or AST) should be evaluated prior to initiation of ambrisentan. • During therapy, monthly monitoring of ALT and AST is recommended. • Discontinuation of ambrisentan therapy 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). • In subjects without clinical symptoms of hepatic injury or jaundice, reinitiation of ambrisentan may be considered following resolution of hepatic enzyme abnormalities.
• Mhux indikat f’ pazjenti b' indeboliment sever tal- fwied (bi jew mingħajr ċirrożi) u f’ pazjenti li għandhom il- valuri bażi ta ’ aminotransferases tal- fwied (AST u/ jew ALT) > 3xULN. • Għandhom jiġu evalwati l- aminotransferases (ALT u AST) qabel jinbeda ambrisentan. • Waqt il- kura, huwa rrakkomandat osservazzjoni kull xahar ta 'ALT u AST. • Twaqqif ta' kura b' ambrisentan 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). • F' suġġetti mingħajr sintomi kliniċi ta 'ħsara fil- fwied jew suffejra, tista tiġi kkunsidrata il- possibilita' li jerġa jinbeda ambrisentan wara li l- abnormalitajiet fl- enżimi tal- fwied jitranġaw.
That treatment with Volibris often causes a decrease in haemoglobin and haematocrit
Il- kura b’ Volibris ħafna drabi tikkawża nuqqas fl- emoglobina u l- ematokrit
30 • Initiation of Volibris is not recommended for patients with clinically significant anaemia. • Patients taking Volibris should have their haemoglobin and/ or haematocrit levels measured regularly. • If tests show a clinically significant decrease in haemoglobin or haematocrit, and other causes have been excluded, consider reducing the dose of Volibris, or stopping treatment.
30 • M' huwiex rakkomandat bidu ta 'kura b' Volibris f' pazjenti b' anemija klinikament sinifikanti. • Pazjenti li qed jieħdu Volibris għandu jkollhom il- livelli ta ’ emoglobina u/ jew ematokrit iċċekkjati regolarment. • Għandu jiġi kkunsidrat tnaqqis fid- doża ta ’ Volibris jew twaqqif tal- kura jekk testijiet juru tnaqqis klinikament sinifikanti fl- emoglobina jew il- ematokrit u kawżi oħra ikunu ġew esklużi.
That treatment with Volibris causes peripheral oedema and fluid retention
Li l- kura b’ Volibris tagħmel edema periferali u ritenzjoni ta ’ fluwidu
• If a patient develops clinically significant peripheral oedema, with or without associated weight gain, carry out further evaluation to determine the cause and if appropriate consider discontinuation of Volibris.
• Jekk pazjent jiżviluppa edema klinikament sinifikanti periferali, bi jew mingħajr żieda assoċjata fil- piż, għamel aktar evalwazzjoni biex issib il- kawża u jekk ikun hemm bżonn ikkunsidra li twaqqaf Volibris.
That chronic administration of Volibris in animals has been linked to testicular tubular atrophy and impaired fertility.
L- għoti kroniku ta ’ Volibris fl- annimali ġie assoċjat ma ’ atrofija tat- tubi tat- testikoli u nuqqas ta ’ fertilita ’.
The effect of Volibris on human testicular function and male fertility is not known.
Mhux magħruf l- effett ta 'Volibris fuq il- funzjoni tat- testikoli umani u l- fertilita' ta 'l- uman maskil.
That Volibris should be initiated with caution in patients with severe renal impairment.
Li Volibris għandu jinbeda b’ kawtela f’ pazjenti b’ indebboliment sever tal- kliewi.
That hypersensitivity reactions, although uncommon, have been reported with Volibris.
Li ġew irrapurtati reazzjonijiet ta ’ sensittività eċċessiva, għalkemm mhux komuni, b’ Volibris.
Physician checklist
Lista biex jiċċekkja it- tabib
The physician pre-prescription checklist will highlight the contraindications to the use of ambrisentan and important pre-prescription assessments including:
Il- lista li juża t- tabib biex jiċċekkja qabel tingħata ir- riċetta turi aktar biċ- ċar il- kontraindikazzjonijiet għal użu ta ’ ambrisentan u affarijiet importanti li għandhom ikunu iċċekkjati qabel ir- riċetta li jinkludu:
• Liver function tests. • Determination of child-bearing potential in female patients. • Pregnancy test if female patient with child-bearing potential. • That women of child-bearing potential are on reliable contraception.
• Testijiet tal- funzjoni tal- fwied. • Determinazzjoni tal- potenzjal li pazjenti nisa jkollhom it- tfal. • Test tat- tqala jekk pazjenta mara jista 'jkollha t- tfal. • Li nisa li jista' jkollhom tfal qegħdin fuq kontraċezzjoni ta 'min joqgħod fuqha.
Patient information
Informazzjoni għal pazjent
The information for patients should include the following information:
L- informazzjoni għall- pazjenti għandha tinkludi l- informazzjoni li ġejja:
• That Volibris may cause serious birth defects in unborn babies conceived before, during, or within a month after stopping treatment. • That Volibris cannot be initiated if patient is pregnant. • Women with child-bearing potential must have a pregnancy test immediately prior to the first prescription and at monthly intervals whilst taking Volibris. • The need to ensure that women of child-bearing potential are using reliable contraception and that patients should inform their doctors of any possibility of pregnancy before a new prescription is issued. • That if a women of child-bearing potential needs to change or stop her method of contraception she should inform the physician prescribing her contraception that she is taking Volibris. • That if a women of child-bearing potential needs to change or stop her method of contraception she should inform the physician prescribing Volibris. • The need for female patients to contact their treating doctor immediately if they suspect that they might be pregnant. • The need for the patient to discuss with her doctor if she is planning to become pregnant. • That Volibris may cause liver injury. • That because of the potential for liver injury and anaemia, patients should have regular blood tests and also tell their doctor if experiencing any symptoms of liver injury. • That the patient should not give Volibris to any other person. • That the patient should tell their doctor about any adverse event.
31 • Li Volibris jista 'jagħmel difetti serji lil- trabi mhux imwielda li l- konċepiment tagħhom ikun sar qabel, waqt jew fi żmien xahar wara li jkun twaqqaf it- trattament. • Li Volibris ma jistax jinbeda jekk il- pazjenta tkun tqila. • Nisa li jista' jkollhom it- tfal, għandhom jagħmlu test tat- tqala immedjatament qabel l- ewwel riċetta u kull xahar waqt li jkunu qed jieħdu Volibris. • Il- bżonn li jkun żgurat li nisa li jista 'jkollhom tfal qed jużaw ta' kontraċettiv ta 'min joqgħod fuqu u l- pazjenti għandhom jinfurmaw lit- tabib tagħhom dwar xi possibilita ’ ta ’ tqala qabel toħroġ kull riċetta ġdida. • Li jekk mara li jista ’ jkollha t- tfal ikollha bżonn tibdel jew twaqqaf il- metodu ta ’ kontraċezzjoni tagħha hi għandha tinforma it- tabib li jippreskrivi l- kontraċezzjoni tagħha li qed tieħu Volibris. • Li jekk mara li jista ’ jkollha t- tfal ikollha bżonn tibdel jew twaqqaf il- metodu ta ’ kontraċezzjoni tagħha hi għandha tinforma it- tabib li ppreskriva Volibris. • Il- bżonn ta ’ pazjenti nisa biex jikkuntatjaw lit- tabib kuranti tagħhom immedjatament jekk jissusspettaw li jistgħu ikunu tqal. • Il- bżonn li pazjenta tiddiskuti mat- tabib tagħha jekk qed tippjana li toħroġ tqila. • Li Volibris jista ’ jagħmel ħsara fil- fwied. • Li minħabba il- possibilita ’ ta ’ ħsara fil- fwied u anemija, il- pazjenti għandu jkollhom testijiet regolari tad- demm u jgħidu lit- tabib tagħhom ukoll jekk jesperjenzaw xi sintomi ta ’ ħsara tal- fwied. • Li l- pazjent m’ għandux jagħti Volibris lil xi persuna oħra. • Li l- pazjent għandu jgħid lit- tabib tiegħu fuq xi event avvers.
31 Booklet for male partners of women with child-bearing potential
Kotba żgħar ta 'nformazzjoni lil sieħba rġiel ta' nisa li jista 'jkollhom it- tfal
The information for male partners of women with child-bearing potential should include the following information:
Kotba żgħar ta 'nformazzjoni lil sieħba rġiel ta' nisa li jista 'jkollhom it- tfal għandu jkollhom din l- informazzjoni li ġejja:
• That Volibris may cause serious birth defects in unborn babies conceived before, during, or within a month after stopping treatment. • The need to ensure that women of child-bearing potential are using reliable contraception. • That Volibris cannot be taken if a woman is or might become pregnant.
• Li Volibris jista 'jagħmel difetti serji lil- trabi mhux imwielda li l- konċepiment tagħhom ikun sar qabel, waqt jew fi żmien xahar wara li jkun twaqqaf it- trattament. • Il- bżonn li tassigura li nisa li jista' jkollhom it- tfal qegħdin jużaw kontraċezzjoni ta 'min joqgħod fuqha. • Li Volibris ma jistax jittieħed jekk pazjenta tkun jew tista ’ toħroġ tqila.
Patient reminder card
Card biex tfakkar lill- pazjent
This should include key messages regarding the need for regular blood and pregnancy tests and provide spaces for the dates of appointments and the results of tests.
Din għandu jkollha messaġġi kruċjali fuq il- bżonn ta ’ testijiet regolari tad- demm u tat- tqala u jkollha postijiet għad- dati ta ’ l- appuntamenti u r- riżultati tat- testijiet.
The MAH must ensure that the system of pharmacovigilance, as described in version 6.2 presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
L- MAH għandu jassikura li s- sistema ta 'farmakoviġilanza, kif deskritta f' verżjoni 6. 2 u ppreżentata f' Module 1. 8. 1. ta' l- Applikazzjoni ta 'l- Awtorizzazzjoni għat- tqegħid fis- Suq, tkun stabbilita u qegħda taħdem qabel u waqt li l- prodott qiegħed fis- suq.
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 3.0 of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by the CHMP.
L- MAH jikkommetti ruħu li jagħmel studji u attivitajiet oħra ta 'farmakoviġilanza ddettaljati fil- Pjan tal- Farmakoviġilanza, kif stabbilit f' verżjoni 3. 0 tal- Pjan għall- Immaniġġjar ta' Riskju (RMP) ppreżentat f' Module 1. 8. 2 ta 'l- Applikazzjoni ta' l- Awtorizzazzjoni għat- tqegħid fis- Suq u xi aġġornamenti sosegwenti ta 'l- RMP kif miftiehem mill- CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
32 Skond il- linji gwida ta 'CHMP fuq Sistemi ta' Mmaniġġjar tar- Riskju għal prodotti mediċinali għall- użu fil- bniedem, il- PMR ta 'l- aħħar għandu jiġi sottomess fl- istess żmien tar- Rapport Perjodiku ta' Aġġornament dwar Sigurta '(PSUR) li jmiss.
In addition, an updated RMP should be submitted
Barra minn dan għandu jiġi sottomess il- PMR ta 'l- aħħar
• When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities • Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached • At the request of the EMEA.
• Meta tiġi rċevuta informazzjoni ġdida li tista tagħmel impatt fuq l- Ispeċifikazzjoni ta 'Sigurta' ta 'issa, Pjan ta' Farmakoviġilanza jew attivitajiet biex inaqqsu r- riskju • Fi żmien 60 ġurnata li tista 'tintlaħaq mira importanti (ta' farmakoviġilanza jew ta 'tnaqqis ta' riskju) • Fuq talba ta 'EMEA.
33 A.
33 ANNESS III
Each tablet contains 5 mg ambrisentan
Kull pillola fiha 5 mg ta 'ambrisentan
Contains lactose, lecithin (soya) (E322) and Allura red AC Aluminium Lake (E129).
Fiha lactose, lecithin (soya) (E322) u Allura red AC Aluminium Lake (E129).
See leaflet for further information
Ara il- fuljett għal aktar informazzjoni
10 film-coated tablets.
10 pillola miksija b’ rita.
Each tablet contains 10 mg ambrisentan
Kull pillola fiha 10 mg ta 'ambrisentan
40 MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
41 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ IL- FOLJI JEW FUQ L- ISTRIXXI
Blister Pack
Pakkett Blister
Volibris 5 mg tablets
Volibris 5 mg pilloli
41 MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
42 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ IL- FOLJI JEW FUQ L- ISTRIXXI
Volibris 10 mg tablets
Volibris 10 mg pilloli
Volibris 5 mg film-coated tablets Volibris 10 mg film-coated tablets ambrisentan
Volibris 5 mg pilloli miksija b' rita Volibris 10 mg pilloli miksija b' rita ambrisentan
What Volibris is and what it is used for 2.
X’ inhu Volibris u għalxiex jintuża 2.
Before you take Volibris 3.
Qabel ma tieħu Volibris 3.
How to take Volibris 4.
Kif għandek tieħu Volibris 4.
How to store Volibris 6.
Kif taħżen Volibris 6.
WHAT VOLIBRIS IS AND WHAT IT IS USED FOR
X’ INHU VOLIBRIS U GĦALXIEX JINTUŻA
Volibris is used to treat pulmonary arterial hypertension (PAH).
Volibris jintuża biex jikkura pazjenti b' ipertensjoni arterjali tal- pulmun (PAH).
PAH is high blood pressure in the blood vessels (the pulmonary arteries) that carry blood from the heart to the lungs.
PAH hija pressjoni għolja tad- demm fl- arterji tad- demm (l- arterji tal- pulmun) li jġorru d- demm mill- qalb għall- pulmun.
In people with PAH, these arteries get narrower, so the heart has to work harder to pump blood through them.
F' nies li jbatu minn PAH dawn l- arterji dejjem jidjiequ, għalhekk il- qalb trid taħdem aktar biex tippompja d- demm minnhom.
This causes people to feel tired, dizzy and short of breath.
Dan iġiegħel lin- nies iħossuhom għajjiena, storduti u b' nifishom maqtugħ.
Volibris widens the pulmonary arteries, making it easier for the heart to pump blood through them.
Volibis iwessa 'l- arterji tal- pulmun u jagħmilha aktar faċli għall- qalb biex tippompja d- demm minnhom.
This lowers the blood pressure and relieves the symptoms.
Dan ibaxxi l- pressjoni tad- demm u jtaffi s- sintomi.
BEFORE YOU TAKE VOLIBRIS
QABEL MA TIEĦU VOLIBRIS
Do n't take Volibris: • if you are allergic (hypersensitive) to ambrisentan, soya, or any of the other ingredients of Volibris (listed in Section 6). • if you are pregnant, if you are planning to become pregnant, or if you could become pregnant because you are not using reliable birth control (contraception).
Tieħux Volibris: jekk inti allerġiku( għandek sensittività eċċessiva) għal ambrisentan, soya jew xi wieħed • mill- ingredjenti ta 'Volibris (mniżżla f' Sezzjoni 6). jekk inti tqila, jekk qed tippjana biex toħroġ tqila, jew jekk inti tista' toħroġ tqila għaliex • m' intix qegħda tuża kontroll tat- twelid ta 'min joqgħod fuqu (kontraċezzjoni).
Please read the information under ‘ Pregnancy and Breast feeding’. • if you are breast feeding. • if you have liver disease.
Jekk jogħġbok aqra l- informazzjoni taħt 'Tqala u Treddigħ'. jekk qed tredda. • jekk inti għandek mard tal- fwied.
Talk to your doctor, who will decide whether Volibris is suitable for you. • if you are under 18 years old.
Kellem lit- tabib tiegħek biex jiddeċiedi jekk Volibris • huwiex tajjeb għalik. jekk inti taħt it- 18- il sena. •
If any of these apply to you:
Jekk xi wieħed minn dawn japplikaw għalik:
→ Tell your doctor and don ’ t take Volibris.
45 Għid lit- tabib tiegħek u tieħux Volibris.
44 Take special care with Volibris: • if you have anaemia (a reduced number of red blood cells).
Oqgħod attent ħafna b’ Volibris: jekk għandek anemija (numru anqas ta 'ċelloli ħomor tad- demm). •
→ Tell your doctor, who will decide whether Volibris is suitable for you.
Għid lit- tabib tiegħek, biex jiddeċiedi jekk Volibris huwiex tajjeb għalik.
You will need regular blood tests Before you start taking Volibris, and at regular intervals while you ’ re taking it, your doctor will take blood tests to check:
Ikollok bżonn testijiet tad- demm regolari Qabel ma tibda tieħu Volibris, u regolarment waqt li tkun qed tieħdu, it- tabib jeħodlok it- testijiet tad- demm biex jiċċekkja:
• whether you have anaemia (a reduced number of red blood cells) • whether your liver is working properly.
• jekk għandek anemija (numru anqas ta 'ċelloli ħomor tad- demm) • jekk il- fwied tiegħek hux qiegħed jaħdem sew.
→ It is important that you have these regular blood tests for as long as you are taking Volibris.
Huwa mportanti li tieħu dawn it- testijiet regolari tad- demm sakemm iddum tieħu Volibris.
Signs that your liver may not be working properly include:
Sinjali li l- fwied tiegħek jista ma jkunx qiegħed jaħdem sew jinkludu: