qanastek/EMEA-V3 huggingface dataset:
After first dilution of TORISEL 25 mg/ ml concentrate with 1.8 ml of withdrawn diluent, the mixture may be stored for up to 24 hours below 25°C and protected from light prior to further dilution.
Wara l- ewwel dilwizzjoni tal- konċentrat TORISEL 25 mg/ ml b’ 1. 8 ml ta ’ dilwent li jkun inġibed, it - taħlita tista ’ tinħażen f’ temperatura taħt il- 25°C sa 24 siegħa, u għandha tkun protetta mid- dawl qabel dilwizzjoni addizzjonali.
After further dilution of the concentrate-diluent mixture with sodium chloride 9 mg/ ml (0.9%) solution for injection, the solution may be stored for up to 6 hours below 25°C and protected from light.
31 Wara dilwizzjoni addizzjonali tat- taħlita tal- konċentrat- dilwent b’ sodium chloride 9 mg/ ml (0. 9%) soluzzjoni għall- injezzjoni, is- soluzzjoni tista ’ tinħażen sa 6 sigħat f’ temperatura taħt 25°C u tkun protetta mid- dawl.
What TORISEL contains
X’ fih TORISEL
The active substance is temsirolimus.
Is- sustanza attiva hi temsirolimus.
Each vial of 1.2 ml of TORISEL 25 mg/ ml concentrate contains 30 mg of temsirolimus.
Kull kunjett ta ’ 1. 2 ml ta ’ konċentrat TORISEL 25 mg/ ml fih 30 mg ta ’ temsirolimus.
The other ingredients in TORISEL are anhydrous ethanol, all-rac-α -tocopherol (E 307), propylene glycol and anhydrous citric acid (E 330).
Is- sustanzi l- oħra f’ TORISEL huma anhydrous ethanol, all- rac- ά- tocopherol (E 307), propylene glycol, u anhydrous citric acid (E 330).
The diluent contains polysorbate 80 (E 433) macrogol 400 and anhydrous ethanol.
Id- dilwent fih polysorbate 80 (E 433), macrogol 400, u anhydrous ethanol.
What TORISEL looks like and contents of the pack
Id- dehra ta ’ TORISEL u d- daqs tal- pakkett
TORISEL is a concentrate for infusion supplied with a diluent.
TORISEL hu konċentrat għall- infużjoni fornut b’ dilwent.
The concentrate is a clear, colourless to light-yellow solution.
Il- konċentrat hu soluzzjoni ċara, bla kulur sa safra ċara.
The diluent is a clear to slightly turbid, light-yellow to yellow solution.
Id- dilwent hu soluzzjoni ċara sa ftit imdardra, minn safra ċara sa safra.
The solutions are essentially free from visable particulates.
Is- soluzzjonijiet huma essenzjalment ħielsa minn frak viżibbli.
Each pack of TORISEL contains one vial of 1.2 ml concentrate and one vial of 2.2 ml diluent.
Kull pakkett ta ’ TORISEL fih kunjett wieħed ta ’ 1. 2 ml ta ’ konċentrat u kunjett wieħed ta ’ 2. 2 ml ta ’ dilwent.
Marketing Authorisation Holder Wyeth Europa Ltd Huntercombe Lane South Taplow, Maidenhead Berkshire SL6 0PH United Kingdom
Id- Detentur ta ’ l- Awtorizzazzjoni għat - Tqegħid fis- Suq Wyeth Europa Ltd Huntercombe Lane South Taplow, Maidenhead Berkshire SL6 0PH Ir- Renju Unit
Manufacturer Wyeth Lederle S. p. A.
Manifattur Wyeth Lederle S. p. A.
Via Franco Gorgone Zona Industriale 95100 Catania, Italy
Via Franco Gorgone Zona Industriale 95100 Catania, l- Italja
32 For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
32 Għal kull tagħrif dwar din il- mediċina, jekk jogħġbok ikkuntattja lir- rappreżentant lokali tad- detentur ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq:
33 Ελλάδα Wyeth Hellas A. E. B. E.
33 Ελλάδα Wyeth Hellas A. E. B. E.
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: http: / /www. emea. europa. eu/
Informazzjoni dettaljata dwar din il- mediċina tinsab fuq il- website ta ’ l- Aġenzija Ewropea dwar il - Mediċini (EMEA): http: // www. emea. europa. eu
34 _____________________________________________________________________________________
34 It- tagħrif li jmiss qed jingħata biss għall- professjonisti fil- qasam mediku:
Polyvinyl chloride (PVC) bags and medical devices must not be used for the administration of preparations containing polysorbate 80 because polysorbate 80 leaches di-2-ethylhexylphthalate (DEHP) from PVC.
Boroż magħmulin minn polyvinyl chloride (PVC) u tagħmir mediku ma jridux jintużaw għall- għoti ta ’ preparazzjonijiet li jkun fihom polysorbate 80, għax polysorbate 80 jerħi di- 2- ethylhexylphthalate (DEHP) mill- polyvinyl chloride (PVC).
TORISEL 25 mg/ ml concentrate must be diluted with 1.8 ml of withdrawn diluent before administration in sodium chloride 9 mg/ ml (0.9%) solution for injection.
Il- konċentrat TORISEL 25 mg/ ml irid ikun dilwit b’ 1. 8 ml ta ’ dilwent li jkun inġibed qabel l - għoti f’ soluzzjoni għall- injezzjoni ta ’ sodium chloride 9 mg/ ml (0. 9%).
In preparing the solution, the following two-step process must be carried out in an aseptic manner according to local standards for handling cytotoxic/ cytostatic drugs:
Meta tipprepara s- soluzzjoni, il- proċess li ġej li fih żewġ passi, irid jitwettaq b’ mod asettiku skont l - istandards lokali dwar l- immaniġġjar ta ’ mediċini ċitotossiċi/ ċitostatiċi:
DILUTION OF CONCENTRATE WITH THE SUPPLIED DILUENT
ID- DILWIZZJONI TAL- KONĊENTRAT BID- DILWENT FORNUT
• Withdraw 1.8 ml of the supplied diluent. • Inject the 1.8 ml of extracted diluent into the vial of TORISEL 25 mg/ ml concentrate, which contains 30 mg of temsirolimus (1.2 ml of concentrate). • Mix the diluent and the concentrate well by inversion of the vial.
Iġbed 1. 8 ml tad- dilwent fornut. • Injetta l- 1. 8 ml tad- dilwent li jkun inġibed ġol- kunjett tal- konċentrat TORISEL 25 mg/ ml, li • jkun fih 30 mg ta ’ temsirolimus (1. 2 ml ta ’ konċentrat).
Sufficient time should be allowed for air bubbles to subside.
Ħallat id- dilwent u l- konċentrat tajjeb billi taqleb il- kunjett ta ’ taħt fuq.
One vial of 1.2 ml of TORISEL 25 mg/ ml concentrate contains 30 mg of temsirolimus: when the 1.2 ml concentrate is combined with 1.8 ml of withdrawn diluent, a total volume of 3.0 ml is obtained and the concentration of temsirolimus will be 10 mg/ ml.
Kunjett wieħed ta ’ 1. 2 ml ta ’ konċentrat ta ’ TORISEL 25 mg/ ml fih 30 mg ta ’ temsirolimus: meta 1. 2 ml tal- konċentrat jitħallat ma ’ 1. 8 ml tad- dilwent li jkun inġibed, jinkiseb volum totali ta ’ 3. 0 ml, u l- konċentrazzjoni ta ’ temsirolimus ser tkun ta ’ 10 mg/ ml.
The concentrate-diluent mixture is stable below 25°C for up to 24 hours.
It- taħlita konċentrat- dilwent hi stabbli sa 24 siegħa f’ temperatura taħt il- 25°C.
ADMINISTRATION OF CONCENTRATE-DILUENT MIXTURE IN SODIUM CHLORIDE INFUSION
L- GĦOTI TAT- TAĦLITA TAL- KONĊENTRAT- DILWENT F’ INFUŻJONI TA ’ SODIUM CHLORIDE
• Withdraw the required amount of concentrate-diluent mixture (which contains temsirolimus 10 mg/ ml) from the vial; i. e., 2.5 ml for a temsirolimus dose of 25 mg. • Inject the withdrawn volume rapidly into 250 ml of sodium chloride 9 mg/ ml (0.9%) solution for injection to ensure adequate mixing.
Injetta l- volum li jkun inġibed malajr ġo 250 ml ta ’ sodium chloride 9 mg/ ml (0. 9%) • soluzzjoni għall- injezzjoni biex ikun żgurat taħlit adegwat.
The admixture should be mixed by inversion of the bag or bottle, avoiding excessive shaking, as this may cause foaming.
It- taħlita għandha titħallat billi l- borża jew il- flixkun jinqalbu ta ’ taħt fuq, u jiġi evitat ċaqliq eċċessiv, għax dan jista ’ jikkawża li tifforma r- ragħwa.
• Administration of the final diluted solution should be completed within six hours from the time that the TORISEL is first added to sodium chloride 9 mg/ ml (0.9%) solution for injection.
35 Kif Jingħata • L- għoti tas- soluzzjoni dilwita finali għandha titlesta fi żmien sitt sigħat mill- ħin li TORISEL l- ewwel ikun żdied ma ’ sodium chloride 9 mg/ ml (0. 9%) soluzzjoni għall- injezzjoni.
• Appropriate administration materials must be composed of glass, polyolefin, or polyethylene to avoid excessive loss of medicinal product and to decrease the rate of DEHP extraction.
• Il- materjal adattat ta ’ l- għoti irid ikun magħmul mill- ħġieġ, polyolefin, jew polyethylene biex jiġi evitat telf eċċessiv tal- prodott mediċinali u biex titnaqqas ir- rata ta ’ estrazzjoni ta ’ DEHP.
The administration materials must consist of non-DEHP, non-PVC tubing with appropriate filter.
Il- materjal ta ’ l- għoti għandu jikkonsisti minn non- DEHP, non- PVC tubing b’ filtru adattat.
An in-line polyethersulfone filter with a pore size of not greater than 5 microns is recommended for administration to avoid the possibility of particles bigger than 5 microns being infused.
Filtru in- line tal - polyethersulfone b’ daqs tal- pori ta ’ mhux aktar minn 5 mikrons hu rakkomandat għall- għoti biex tiġi evitata l- possibbiltà li partikuli ta ’ iktar minn 5 microns jiġu infużi.
If the administration set available does not have an in-line filter incorporated, a filter should be added at the end of the set (i. e., an end-filter) before the admixture reaches the vein of the patient.
Jekk is- sett li jkun disponibbli għall- għoti ma jkunx fih filtru in- line inkorporat, għandu jitwaħħal filtru fit- tarf tas- sett (i. e., end - filter) qabel ma t- taħlita tilħaq il- vina tal- pazjent.
Different end-filters can be recommended used ranging in filter pore size from 0.2 microns up to 5 microns.
End- filters differenti jistgħu jiġu rakkomandati biex jintużaw, li jvarjaw fid- daqs tal- pori tal- filtru minn 0. 2 microns sa 5 microns.
This incompatibility has to be considered during the preparation and administration of TORISEL.
Din l- inkompatibilità għandha tiġi kkunsidrata waqt il- preparazzjoni u l- għoti ta ’ TORISEL,.
It is important that the recommendations in sections 4.2 and 6.6 in the SPC be followed closely.
Huwa importanti li r- rakkomandazzjonijiet f’ sezzjonijiet 4. 2 u 6. 6 fil- SPC ikunu segwiti mill- qrib.
Any unused product or waste material should be disposed of in accordance with local requirements.
Rimi Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa ’ wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali.
TOVIAZ 4 mg prolonged-release tablets
TOVIAZ 4 mg, pilloli li jerħu l- mediċina bil- mod
Each prolonged-release tablet contains fesoterodine fumarate 4 mg corresponding to 3.1 mg of fesoterodine.
Ġo kull pillola li terħi l- mediċina bil- mod hemm 4 mg fesoterodine fumarate, dan jikkorrespondi għal 3. 1 mg ta ’ fesoterodine..
Excipients Each 4 mg prolonged-release tablet contains 0.525 mg of soya lecithin and 91.125 mg lactose monohydrate.
Sustanzi mhux attivi Ġo kull pillola li terħi l- mediċina bil- mod hemm 0. 525mg soya lecithin u 91. 125mg lactose monohydrate.
Prolonged-release tablets The 4 mg tablets are light blue, oval, biconvex, film-coated, and engraved on one side with the letters ‘ FS’.
Il- pilloli ta ’ 4 mg huma ta ’ kulur kaħlani ċar, ovali, imbuzzati, miksijin b’ rita u fuq naħa waħda għandhom imnaqqxin l- ittri ‘ FS ’.
Treatment of the symptoms (increased urinary frequency and/ or urgency and/ or urgency incontinence) that may occur in patients with overactive bladder syndrome.
Trattament tas- sintomi (żieda fil- frekwenza urinarja u/ jew urġenza u/ jew urġenza ta ’ nkontinenza) li jistgħu jinstabu f’ pazjenti li jbatu mill- problema ta ’ bużżieqa ta ’ l- awrina li hi attiva wisq.
Adults (including elderly) The recommended starting dose is 4 mg once daily.
Adulti (inkluż l- anzjani) Id- doża rakkomandata tal- bidu hi ta ’ 4 mg darba kuljum.
Based upon individual response, the dose may be increased to 8 mg once daily.
Skond kif l- individwu jirrispondi għat - trattament, id- doża tista ’ tiżdied għal 8 mg darba kuljum.
The maximum daily dose is 8 mg.
Id- doża massima li tista ’ tingħata kuljum hi ta ’ 8 mg.
Full treatment effect was observed between 2 and 8 weeks.
L- effett tat- trattament komplut ġie osservat bejn it- 2 u t- 8 ġimgħa.
Hence, it is recommended to re-evaluate the efficacy for the individual patient after 8 weeks of treatment.
Għalekk huwa rrikkmandat li l - effikaċja f’ kull pazjent individwali terġa tkun evalwata wara 8 ġimgħat ta ’ trattament.
Tablets are to be taken once daily with liquid and swallowed whole.
Il- pilloli għandhom jittieħdu darba kuljum ma ’ xi likwidu u għandhom jinbelgħu sħaħ.
TOVIAZ can be administered with or without food.
TOVIAZ jista jingħata ma ’ l- ikel jew mingħajr ikel.
In subjects with normal renal and hepatic function receiving concomitant administration of potent CYP3A4 inhibitors, the maximum daily dose of TOVIAZ should be 4 mg once daily (see section 4.5).
Għal suġġetti li għandhom funzjoni normali renali u tal- fwied, li qed jieħdu waqt l- istess żmien inibituri potenti ta ’ CYP3A4, id- doża massima ta ’ kuljum ta ’ TOVIAZ li tista ’ tingħata hi ta ’ 4 mg kuljum (ara sezzjoni 4. 5).
During concomitant administration of a moderate CYP3A4 inhibitor, a dose increase to 8 mg should be preceded by an evaluation of the individual response and tolerability (see sections 4.4 and 4.5).
Waqt l- għoti flimkien ma inibitur moderat ta ’ CYP3A4, id- doża għandha tkun miżjuda għal 8mg wara evalwazzjoni tar- respons u t- tollerabilità ta ’ kull pazjent (ara sezzjonijiet 4. 4 u 4. 5).
Renal and hepatic impairment The following table provides the daily dosing recommendations for subjects with renal or hepatic impairment in the absence and presence of moderate and potent CYP3A4 inhibitors (see sections 4.3, 4.4, 4.5 and 5.2).
Indeboliment renali u tal- fwied It- tabella li ġejja tagħti rakkomandazjonijiet tad- doża li tista ’ tingħata kuljum lil pazjenti li għandhom indeboliment renali u epatiku fl- assenza u l- preżenza ta ’ inibituri moderati u qawwija ta ’ CYP3A4 (ara sezzjonijiet 4. 3, 4. 4, 4. 5 u 5. 2)
2 Moderate(3) or potent(4) CYP3A4 inhibitors
2 Inibituri ta’ CYP3A4 moderati( 3) jew qawwija( 4)
Potent
Qawwi
Renal impairment(1)
Indeboliment renali( 1)
Should be avoided
Għandu jiġi evitat
4→ 8 mg(2)
Kontra- indikat
4 mg
Serju
Contraindicated
4 mg
Should be
Għandu
Severe
jiġi evitat
4 mg
Kontra- indikat
(2)
4→8 mg( 2) Indeboliment epatiku
4→ 8 mg
Ħafif
avoided
Għandu jiġi evitat
Contraindicated
Kontra- indikat
(1) Mild GFR = 50-80 ml/ min; Moderate GFR = 30-50 ml/ min; Severe GFR = < 30 ml/ min (2) Cautious dose increase.
(1) GFR ħafif = 50- 80 ml/ min; GFR moderat = 30- 50 ml/ min; GFR serju = < 30 ml/ min (2) Żieda fid- doża għandha ssir b’ kawtela.
See sections 4.4, 4.5 and 5.2 (3) Studies with moderate CYP3A4 inhibitors have not been conducted.
Ara sezzjonijiet 4. 4, 4. 5 and 5. 2 (3) Għadhom ma sarux studju b’ inibituri moderati ta CYP3A4.
See section 4.5 (4) Potent CYP3A4 inhibitors.
Ara sezzjoni 4. 5 (4) Inibituri potenti ta ’ CYP3A4.
See sections 4.3, 4.4 and 4.5
Ara sezzjonijiet 4. 3, 4. 4 and 4. 5
TOVIAZ is contraindicated in subjects with severe hepatic impairment (see section 4.3).
TOVIAZ huwa kontraindikat f’ individwi li għandhom indeboliment serju tal- fwied (ara sezzjoni 4. 3).
Paediatric population TOVIAZ is not recommended for use in children and adolescents below 18 years of age due to lack of data on safety and efficacy (see section 5.2).
Popolazzjoni pedjatrika TOVIAZ m’ huwiex irrakkomandat għall- użu fi tfal u addoloxenti ta ’ taħt it- 18- il sena peress li m’ hemmx biżżejjed informazjoni dwar is- sigurtà u l- effikaċja (ara sezzjoni 5. 2)
• Hypersensitivity to the active substance or to peanut or soya or any of the excipients • Urinary retention • Gastric retention • Uncontrolled narrow angle glaucoma • Myasthenia gravis • Severe hepatic impairment (Child Pugh C) • Concomitant use of potent CYP3A4 inhibitors in subjects with moderate to severe hepatic or renal impairment • Severe ulcerative colitis • Toxic megacolon.
• Sensittività eċċessiva għas- sustanza attiva jew għall- karawett jew soja jew għal xi sustanzi mhux attivi • Żamma ta ’ l- awrina • Żamma tal- kontenut ta ’ l- istonku • Glawkoma ta ’ angolu dejjaq mhix ikkontrollata • Majestenja gravis • Indeboliment epatiku serju (Child Pugh C) • Użu fl- istess waqt ta ’ inibituri ta ’ CYP3A4 potenti f’ suġġetti li għandhom indeboliment epatiku jew renali minn moderat sa serju. • Kolite ulċerattiva serja • Megakolon tossiku.
TOVIAZ should be used with caution in patients with:
TOVIAZ għandu jintuża b’ kawtela f’ pazjenti bi:
- Clinically significant bladder outflow obstruction at risk of urinary retention (see section 4.3)
żamma ta ’ l- awrina (ara sezzjoni 4. 3)
- Gastrointestinal obstructive disorders (e. g. pyloric stenosis)
- Disturbi ta ’ mblukkar gastro- intestinali (eż. stenosi pilorika)
- Gastro-oesophageal reflux and/ or who are concurrently taking medicinal products (such as
- Rifluss gastro- esofagali u/ jew li qed jieħdu prodotti mediċinali fl- istess waqt (bħal
oral bisphosphonates) that can cause or exacerbate oesophagitis
bisphosphonates li jittieħdu mill- ħalq) li jistgħu jikkaġunaw jew iħarrxu l- esofaġite
- Decreased gastrointestinal motility
- Moviment gastro- intestinali mnaqqas
- Autonomic neuropathy
- Newropatija awtonomika
- Controlled narrow-angle glaucoma
- Glawkoma ta ’ angolu dejjaq ikkontrollata
Caution should be exercised when prescribing or uptitrating fesoterodine to patients in whom an increased exposure to the active metabolite (see section 5.1) is expected:
Għandha tiġi eżerċitata kawtela meta wieħed jikteb riċetta jew iżid id- doża ta ’ fesoterodine lil pazjenti li mistennija li jkunu aktar esposti għal metabolit attiv (ara sezzjoni 5. 1):
- Hepatic impairment (see sections 4.2, 4.3 and 5.2)
- Indeboliment epatiku (ara sezzjonijiet 4. 2, 4. 3 u 5. 2)
- Renal impairment (see section 4.2, 4.3 and 5.2)
- Indeboliment renali (ara sezzjoni 4. 2, 4. 3 u 5. 2)
- Concomitant administration of potent or moderate CYP3A4 inhibitors (see sections 4.2 and
- L- għoti fl- istess waqt ta ’ inibituri potenti jew moderati ta ’ CYP3A4 (ara sezzjonijiet 4. 2 u 4. 5)
4.5)
- L- għoti fl- istess waqt ta ’ inibitur potenti ta CYP2D6 (ara sezzjonijiet 4. 5 u 5. 2)
- Concomitant administration of a potent CYP2D6 inhibitor (see sections 4.5 and 5.2).
Hemm possibilità qawwija ta ’ effetti sekondarji antimuskariniċi li jiddependu
3 In patients with a combination of these factors, additional exposure increases are expected.
3 mid- doża.
In populations where the dose may be increased to 8 mg once daily, the dose increase should be preceded by an evaluation of the individual response and tolerability.
F’ popolazzjonijiet fejn id- doża tista ’ tiżdied sa ’ 8 mg darba kuljum, iż- żieda fid- doża għandha ssir wara evalwazjoni tar- respons u t- tollerabilità.
As with all medicinal products indicated for the treatment of overactive bladder, organic causes must be excluded before any treatment with antimuscarinics is considered.
Bħal prodotti mediċinali kollha li jintużaw għat- trattament tal- bużżieqa ta ’ l- awrina li hi attiva wisq, kawżi organiċi għandhom jiġu esklusi qabel ma jkun ikkunsidrat trattament b’ mediċini antimuskariniċi.
Safety and efficacy have not yet been established in patients with a neurogenic cause for detrusor overactivity.
Is- sigurtà u l- effikaċja għadhom ma ġewx stabbiliti f’ pażjenti li jbatu minn attivita eċċessiva fid- detrusor minħabba kawżi newroġeniċi.
Other causes of frequent urination (treatment of heart failure or renal disease) should be assessed before treatment with fesoterodine.
Kawżi oħra għal għemil ta ’ l- awrina ta ’ spiss (trattament ta ’ insuffiċjenza tal- qalb jew mard renali) għandhom ikunu valutati qabel ma jinbeda t- trattament b’ fesoterodine.
If urinary tract infection is present, an appropriate medical approach should be taken/ antibacterial therapy should be started.
Jekk hemm infezzjoni fil - passaġġ urinarju, wieħed għandu jikkonsidra li jieħu approċċ mediku xieraq/ jinbeda trattament antibatteriku.
The concomitant use of fesoterodine with a potent CYP3A4 inducer (i. e. carbamazepine, rifampicin, phenobarbital, phenytoin, St John’ s Wort) is not recommended (see section 4.5).
L- użu fl- istess żmien ta ’ Fesoterodine u mediċini potenti li jistimulaw is- CYP3A4 (i. e. carbamazepine, rifampicin, phenobarbital, phenytoin, St John’ s wort) m’ hux rakkomandat (ara sezzjoni 4. 5).
As with other antimuscarinics, fesoterodine should be used with caution in patients with risk for QT- prolongation (e. g. hypokalaemia, bradycardia and concomitant administration of medicines known to prolong QT interval) and relevant pre-existing cardiac diseases (e. g. myocardial ischaemia, arrhythmia, congestive heart failure), (see section 4.8).
Iskemja mijokardijaka, arritmija, insuffiċjenza tal- qalb konġestiva), (ara sezzjoni 4. 8).
This especially holds true when taking potent CYP3A4 inhibitors (see sections 4.2, 4.5 and 5.1).
Dan japplika speċjalment meta jittieħdu inibituri qawwija ta ’ CYP3A4 (ara sezzjonijiet 4. 2, 4. 5 u 5. 1).
Lactose TOVIAZ prolonged-release tablets contain lactose.
Lactose Il- pilloli li jerħu l- mediċina bil- mod ta ’ TOVIAZ fihom lactose.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Pazjenti li għandhom problemi ereditarji rari ta ’ intolleranza ta ’ galactose, defiċjenza ta ’ Lapp lactase jew li ma jistgħux jassorbu glucose- galactose m’ għandhomx jieħdu dan il- prodott medicinali.
Pharmacological interactions Caution should be exercised in coadministration of fesoterodine with other antimuscarinic agents and medicinal products with anticholinergic properties (e. g. amantadine, tri-cyclic antidepressants, certain neuroleptics) as this may lead to more pronounced therapeutic- and side-effects (e. g. constipation, dry mouth, drowsiness, urinary retention).
Interazzjonijiet farmakoloġiċi Kawtela għandha tiġi eżerċitata meta fesoterodine jingħata flimkien ma ’ mediċini antimuskariniċi oħra u prodotti mediċinali li għandhom karatteristiċi anti- kolinerġiċi (eż. amantadine, antidepressanti triċikliċi, xi newrolettiċi), għax dan jista ’ jwassal għal żieda fl- effett terapewtiku u fl- effetti sekondarji (eż. stitikezza ħalq xott, ngħas, żamma ta ’ l- awrina).
Fesoterodine may reduce the effect of medicinal products that stimulate the motility of the gastro- intestinal tract, such as metoclopromide.
Fesoterodine jista jnaqqas l- effectt ta ’ prodotti mediċinali li jistimulaw il- moviment tal- passaġġ gastrointestinali bħal metoclopromide.
Pharmacokinetic interactions In vitro data demonstrate that the active metabolite of fesoterodine does not inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4, or induce CYP1A2, 2B6, 2C9, 2C19, or 3A4 at clinically relevant plasma concentrations.
Interazzjonijiet farmakokinetiċi Dejta minn studji li saru in vitro juru li l- metabolit attiv ta ’ fesoterodine ma jimpedixxiex l- azzjoni ta ’ CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 jew 3A4 jew jistimula l- effett ta ’ CYP1A2, 2B6, 2C9, 2C19 jew 3A4 f’ konċentrazzjonijiet fil- plażma li huma klinikament rilevanti.
Thus fesoterodine is unlikely to alter the clearance of medicinal products that are metabolised by these enzymes.
Għalhekk fesoterodine mhux mistenni li jibdel it- tneħħija ta ’ prodotti medicinali li huma metaboliżżati minn dawn l- enzimi.
CYP3A4 Inhibitors
Impedituri CYP3A4
Potent CYP3A4 Inhibitors Following inhibition of CYP3A4 by co-administration of ketoconazole 200 mg twice daily, Cmax and AUC of the active metabolite of fesoterodine increased 2.0 and 2.3-fold in CYP2D6 extensive metabolisers and 2.1 and 2.5-fold in CYP2D6 poor metabolisers, respectively.
Impedituri Qawwija ta ’ CYP3A4 Wara inibizjoni ta ’ CYP3A4 li rriżulta wara l- għoti flimkien ta ’ 200mg ketoconazole darbtejn kuljum, is- Cmax u l- AUC tal- metabolit attiv ta ’ fesoterodine żdiedu b’ fatturi ta ’ 2. 0 u 2. 3 f’ metaboliżżaturi estensivi ta ’ CYP2D6 u b’ fatturi ta ’ 2. 1 u 2. 5 f’ metaboliżżaturi dgħajfin ta ’ CYP2D6 rispettivament.
Therefore, the maximum dose of fesoterodine should be restricted to 4 mg when used concomitantly with potent CYP3A4 inhibitors (e. g. atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir (and all ritonavir boosted PI-regimens), saquinivir and telithromycin (see sections 4.2 and 4.4)).
Għalhekk, id- doża massima ta ’ fesoterodine għandha tkun ristretta għal 4 mg, meta tittieħed ma ’ impedituri qawwija ta ’ CYP3A4 (eż. atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir (u l- korsijiet PI kollha li huma awmentati b’ ritonavir), saquinivir u telithromycin (ara sezzjonijiet 4. 2 u 4. 4)).
4 Moderate CYP3A4 Inhibitors No study has been performed evaluating the effect of a moderate CYP3A4 inhibitor (e. g. amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, verapamil) on the pharmacokinetics of fesoterodine.
Impedituri Moderati ta ’ CYP3A4 Għadu ma sar ebda studju biex jevalwa l- effett ta ’ impedituri moderati ta ’ CYP3A4 (eż. amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, meraq tal- grejpfrut, verapamil) fuq il -
However, an increase in the exposure of the active metabolite of fesoterodine is expected, although a smaller increase than observed with a potent CYP3A4 inhibitor (see sections 4.2 and 4.4).
Madankollu, hu mistenni li jkun hemm żieda fl- espożizzjoni tal - metabolit attiv, għalkemm tkun inqas minn dik osservata b ’ impeditur potenti ta ’ CYP3A4 (ara sezzjonijiet 4. 2 u 4. 4).
CYP3A4 Inducers Following induction of CYP3A4 by coadministration of rifampicin 600 mg once a day, Cmax and AUC of the active metabolite of fesoterodine decreased by approximately 70% and 75%, respectively, after oral administration of fesoterodine 8 mg.
Stimulaturi ta ’ CYP3A4 Wara stimulazzjoni ta ’ CYP3A4 bl- għoti flimkien ta ’ rifampicin 600 mg darba kuljum, is- Cmax u l - AUC tal- metabolit attiv ta ’ fesoterodine naqas b’ madwar 70% u 75% rispettivament wara l- għoti orali ta ’ 8 mg fesoterodine
Induction of CYP3A4 may lead to subtherapeutic plasma levels.
Stimulazzjoni ta ’ CYP3A4 tista ’ tirriżulta f’ livelli sottoterapewtiċi fil- plażma.
Concomitant use with CYP3A4 inducers (e. g. carbamazepine, rifampicin, phenobarbital, phenytoin, St John’ s Wort) is not recommended (see section 4.4).
Użu fl- istess żmien ma ’ stimulaturi ta ’ CYP3A4 (eż. carbamazepine, rifampicin, phenobarbital, phenytoin, St John’ s Wort) m’ hux rakkomandat (ara sezzjoni 4. 4).
CYP2D6 Inhibitors The interaction with CYP2D6 inhibitors was not tested clinically.
Impedituri ta ’ CYP2D6 Ma sar l- ebda studju kliniku fuq l- interazzjoni ma ’ impedituri ta ’ CYP2D6.
Mean Cmax and AUC of the active metabolite are 1.7 and 2-fold higher, respectively, in CYP2D6 poor metabolisers as compared to extensive metabolisers.
Is- Cmax u l- AUC medji tal- metabolit attiv huma ogħla b’ fatturi ta ’ 1. 7 u 2 rispettivament, f’ metaboliżżaturi dgħajfin ta ’ CYP2D6, meta wieħed iqabbel ma ’ metaboliżżaturi estensivi.
Co-administration of a potent CYP2D6 inhibitor may result in increased exposure and adverse events.
L- għoti flimkien ta ’ impeditur potenti ta ’ CYP2D6 jista ’ jirriżulta f’ espożizzjoni ogħla u reazzjonijiet avversi.
A dose reduction to 4 mg may be needed (see section 4.4).
Tnaqqis fid- doża għal 4 mg jista ’ jkun meħtieġ (ara sezzjoni 4. 4).
Oral contraceptives Fesoterodine does not impair the suppression of ovulation by oral hormonal contraception.
Kontraċettivi orali Fesoterodine ma jimpedixxiex it- trażżin ta ’ l- ovulazzjoni b’ kontraċettivi ormonali orali.
In the presence of fesoterodine there are no changes in the plasma concentrations of combined oral contraceptives containing ethinylestradiol and levonorgestrel.
Fil- preżenza ta ’ fesoterodine ma hemm l- ebda tibdil fil- konċentrazjonijiet fil- plażma ta ’ kontraċettivi kumbinati li fihom ethinylestradiol u levonorgestrel.
Pregnancy There are no adequate data from the use of fesoterodine in pregnant women.
Tqala M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ fesoterodine waqt it- tqala.
Reproductive toxicity studies with fesoterodine in animals show minor embryotoxicity (see section 5.3).
Studji dwar tossiċità fis- sistema riproduttiva b’ fesoterodine fuq bhejjem urew tossiċità minuri fl- embriju (ara sezzjoni 5. 3).
TOVIAZ is not recommended during pregnancy.
TOVIAZ mhux rakkomandat waqt it- tqala.
Lactation It is not known whether fesoterodine is excreted into human milk; therefore, breast-feeding is not recommended during treatment with TOVIAZ.
Treddigħ M ’ hux magħruf hekk Fesoterodine jigiex eliminat fil- ħalib tal- bniedem; għalhekk, treddigħ mhux rakkomandat waqt trattament b’ TOVIAZ.
As with other antimuscarinic agents, caution should be exercised when driving or using machines due to possible occurrence of side effects such as blurred vision, dizziness, and somnolence (see section 4.8).
Bħal fil- każ ta ’ mediċini anti- muskariniċi oħrajn, attenzjoni speċjali għandha tittiehed waqt is- sewqan jew l- użu ta ’ magni minħabba il- possibilità ta ’ effetti sekondarji bħal vista mċajpra, sturdament u ngħas (ara sezzjoni 4. 8)
The safety of fesoterodine was evaluated in placebo-controlled clinical studies in a total of 2859 patients with overactive bladder, of which 780 received placebo.
Is- sigurtà ta ’ fesoterodine ġiet valutata fi studji kontrollati bi plaċebo f’ total ta ’ 2859 pazjent li kellhom il- bużżieqa ta ’ l- awrina attiva wisq, li minn dawn 780 irċevew plaċebo
Due to the pharmacological properties of fesoterodine, treatment may cause mild to moderate antimuscarinic effects like dry mouth, dry eye, dyspepsia and constipation.
Minħabba l- karatteristiċi farmakoloġiċi ta ’ fesoterodine, it- trattament jista ’ jirriżulta f’ effetti anti - muskariniċi minn ħfief sa moderati bħal ma huma ħalq xott, għajnejn xotti, dispepsja u stitikezza.
Dry mouth, the only very common event, occurred with a frequency of 28.8% in the fesoterodine group compared to 8.5% in the placebo group.
Il- ħalq xott, li kien l- uniku effett li kien komuni ħafna, seħħ bi frekwenza ta ’ 28. 8% fil- grupp li ħa Fesoterodine meta mqabbel ma ’ 8. 5% fil- grupp li ħa l- plaċebo.
The majority of ADRs occurred during the first month of treatment with the exception of cases classified as urinary retention or post void residual urine
Il- maġġoranza ta ’ reazzjonijiet avversi seħħew fl- ewwel xahar tat- trattament, bl- eċċezzjoni tal- każijiet ikklassifikati bħala żamma ta ’ l- awrina jew li kellhom volum ta ’ awrina residwali ogħla minn 200 ml wara l- iżvojtjar tal- bużżieqa li seta ’ jiġri wara żmien twil ta ’ trattament li kienu iktar komuni fl- irġiel milli fin- nisa.
The table below gives the frequency of treatment emergent adverse reactions from placebo-controlled clinical trials.
5 It- tabella t’ hawn taħt turi l- frekwenza ta ’ effetti avversi li tfaċċaw waqt studji kontrollati bi plaċebo.
The adverse reactions reported in this table are those events that were very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10) or uncommon (≥ 1/ 1,000 to < 1/ 100).
L - effetti avversi rrapportati f’ din it- tabella huma kklassifikati bħala komuni ħafna (≥1/ 10), komuni (≥1/ 100 sa < 1/ 10) jew mhux komuni (≥1/ 1, 000 sa < 1/ 100).
System Organ Class
Klassifika
Very common
tas- Sistema ta ’
Uncommon*
Mhux Komuni *
Cardiac disorders
l- Organi Disturbi kardijaċi
Tachycardia
Takikardja
Nervous system disorders
Disturbi fis- sistema nervuża Disturbi fl- għajnejn Disturbi fil- widnejn u s - sistema labirintika
Dysgeusia; Somnolence
Sturdament; Uġigħ ta ’ ras Għajnejn xotti
Vertigo
Disgewsja; Ngħas Vertigo
Dry throat
Griżmejn xotti
Pharyngolaryngeal pain; Cough; Nasal dryness
Uġigħ faringolarinġejali; Sogħla; L- imnieħer xott
Dry mouth
Ħalq xott
Abdominal pain; Diarrhoea; Dyspepsia; Constipation; Nausea
Uġigħ addominali; Dijarrea; Dispepsja; Stitikezza; Dardir
Abdominal discomfort; Flatulence
Dwejjaq addominali; Gass
Renal and urinary disorders
Disturbi renali u fis - sistema urinarja
Dysuria
Disurja
Urinary retention (including feeling of residual urine; micturition disorder); Urinary hesitation
Disturb fil- passaġġ ta ’ l- awrina); Eżitazzjoni urinarja
Rash; Dry skin
Raxx; Ġilda xotta
Infections and infestations General disorders and administration site conditions
Infezzjonijiet u infestazzjonijiet Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata
Urinary tract infection Fatigue
Infezzjoni tal- passaġġ urrinarju Għejja
ALT increased; GGT increased
Żieda fl- ALT; Żieda fil- GGT
Psychiatric disorders *5 or more cases
Disturbi psikjatriċi * 5 każijiet jew aktar
In clinical trials of fesoterodine, cases of markedly elevated liver enzymes were reported with the occurrence frequency no different from the placebo group.
Fi studji kliniċi b’ fesoterodine, każijiet ta ’ enzimi tal- fwied elevati sew kienu rrapportati mingħajr ebda differenza fil- frekwenza ta ’ każijiet mill- grupp li ħa l- plaċebo.
The relation to fesoterodine treatment is unclear.
Ir- relazzjoni mat- trattament ta ’ Fesoterodine m’ hix ċara
Electrocardiograms were obtained from 782 patients treated with 4 mg, 785 treated with 8 mg, 222 treated with 12 mg fesoterodine and 780 with placebo.
Elekrokardjogrammi ttieħdu minn fuq 782 pazjent li kienu trattati b’ 4 mg, 785 trattati bi 8 mg, 222 trattati bi 12 mg fesoterodine u 780 bi plaċebo.
The heart rate corrected QT interval in fesoterodine treated patients did not differ from that seen in placebo treated patients.
L- intervall tal- QT, ikkoreġut skond ir- rata tal- qalb, f’ pazjenti li ħadu fesoterodine ma kienx differenti minn dak ta ’ pazjenti li ħadu l- plaċebo.
The incidence rates of QTc ≥ 500 ms post baseline or QTc increase of ≥ 60 ms is 1.9%, 1.3%, 1.4% and 1.5%, for fesoterodine 4 mg, 8 mg, 12 mg and placebo, respectively.
6 1. 9%, 1. 3%, 1. 4% u 1. 5%, għal Fesoterodine 4 mg, 8 mg, 12 mg u plaċebo rispettivament.
The clinical relevance of these findings will depend on individual patient risk factors and susceptibilities present (see section 4.4).
Ir- rilevanza klinika ta ’ dawn ir- riżultati tiddependi fuq il- fatturi tar- riskju u suxxettibilita ’ ta ’ kull pazjent individwali (ara sezzjoni 4. 4).
Overdose with antimuscarinic agents, including fesoterodine can result in severe anticholinergic effects.
Doża eċċessiva b’ mediċini anti- muskarinici, li jinkludu fesoterodine tista ’ tirriżulta f’ effetti anti - kolinergiċi qawwijin ħafna.
Treatment should be symptomatic and supportive.
It- trattament għandu jkun sintomatiku u ta ’ appoġġ.
6 is recommended; standard supportive measures for managing QT prolongation should be adopted.
Fil- każ ta ’ doża eċċessiva huwa rakkomandat li l- ECG ikun monitorat; miżuri ta ’ appoġġ standard għall- immaniġġar tat- titwil ta ’ l- intervall QT għandhom jiġu adottati.
Fesoterodine has been safely administered in clinical studies at doses up to 28 mg/ day.
Fesoterodine ingħata mingħajr periklu fi studji kliniċi f’ dożi sa 28 mg/ jum.
In the event of fesoterodine overdose, treat with gastric lavage and give activated charcoal.
F’ każ ta ’ doża eċċessiva ta ’ fesoterodine, ittratta b’ ħasil ta ’ l- istonku u agħti charcoal attivat.
Treat symptoms as follows:
Is - sintomi għandhom ikunu trattati kif ġej:
Convulsions or pronounced excitation: treat with benzodiazepines Respiratory insufficiency: treat with artificial respiration Tachycardia: treat with beta-blockers Urinary retention: treat with catheterisation Mydriasis: treat with pilocarpine eye drops and/ or place patient in dark room.
− Effetti anti- kolinergiċi ċentrali qawwijin ħafna (eż. alluċinazjonijiet, eċitament kbir): ittratta b’ physostigmine − Konvulżjonijiet jew eċitament qawwi ħafna: ittratta b’ benzodiazepines − Insuffiċjenza respiratorja: ittratta b’ respirazzjoni artifiċjali − Takikardja: ittratta b’ mediċini li jimblukkaw ir- riċetturi beta. − Żamma ta ’ l- awrina: ittratta billi ddaħħal kateter − Midrijasi: ittratta bi qtar tal- għajnejn pilocarpine u/ jew poġġi l- pazjent f’ kamra mudlama.
Urinary antispasmodics, ATC code:
Antispasmodiċi urrinarji, Kodiċi ATC:
Fesoterodine is a competitive, specific muscarinic receptor antagonist.
Fesoterodine huwa antagonist kompetittiv speċifiku tar- riċettur muskariniku.
It is rapidly and extensively hydrolysed by non-specific plasma esterases to the 5-hydroxymethyl derivative, its primary active metabolite, which is the main active pharmacological principle of fesoterodine.
Huwa idroliżżat malajr u estensivament minn esterase mhux speċifiku fil- plażma u jifforma id- derivat 5- hydroxymethyl, il - prodott attiv primarju tal- metaboliżmu, li huwa wkoll il- prinċipju farmakoloġiku attiv ewlieni ta ’ fesoterodine.
The efficacy of fixed doses of fesoterodine 4 mg and 8 mg was evaluated in two Phase 3 randomised, double-blind, placebo-controlled, 12-week studies.
L- effikaċja ta ’ dożi fissi ta ’ fesoterodine 4 mg u 8 mg kienet valutata f’ żewg studji randomised, double blind, u bi plaċebo bħala kontroll ta ’ Fażi 3 mifruxa fuq 12- il ġimgħa.
Female (79%) and male (21%) patients with a mean age of 58 years (range 19-91 years) were included.
Pazjenti nisa (79%) u rġiel (21%) b’ età medja ta 58 sena (etajiet bejn 19- il- sena u 91 sena) kienu inklużi.
A total of 33% of patients were ≥ 65 years of age and 11% were ≥ 75 years of age.
B’ kollox 33% tal - pazjenti kienu ≥65 sena u 11% kienu ≥75 sena.
Fesoterodine treated patients had statistically significant mean reductions in the number of micturitions per 24 hours and in the number of urge incontinence episodes per 24 hours at the end of treatment compared to placebo.
Pazjenti trattati b’ fesoterodine kellhom tnaqqis statistikament sinifikanti medju fl- għadd ta ’ mikturizzjonijiet kull 24 siegħa u fl- għadd ta ’ episodji mqanqla ta ’ inkontinenza kull 24 siegħa fit - tmiem tat- trattament meta mqabblin ma dawk li hadu l- plaċebo.
Likewise, the response rate (% of patients reporting that their condition has been “ greatly improved” or “ improved” using a 4-point Treatment Benefit Scale) was significantly greater with fesoterodine compared to placebo.
Hekk ukoll, ir- rata ta ’ respons (% ta ’ pażjenti li rrapportaw li l- kondizjoni tagħhom “ tjiebet ħafna ” jew “ tjiebet ”, ikkalkulata skond l- Iskala Ta ’ Siwi tat- Trattament ta ’ 4 punti) kienet sinifikament ogħla b’ fesoterodine meta mqabbla ma ’ plaċebo.
Furthermore, fesoterodine improved the mean change in the voided volume per micturition, and the mean change in the number of continent days per week (see Table 1 below).
Barra minn hekk, fesoterodine tejjeb il- bidla medja tal- volum ta ’ l- awrina li kien prodott ma ’ kull mikturazjoni, u l- bidla fil- medja fl- għadd ta ’ jiem li ma kellhomx episodji ta ’ inkontinenza fil - ġimgħa (ara Tabella 1 taħt).
Mean changes from Baseline to end of treatment for primary and selected secondary endpoints
Tibdiliet medji mil- linji bażi ta ’ Referenza sa tmiem it- trattament għal endpoints primarji u sekondarji magħżula
Fesoterodine Fesoterodine
Plaċebo Fesoterodine Fesoterodine Komparatur Plaċebo Fesoterodine Fesoterodine 4 mg 8 mg Attiv 4 mg 8 mg
Number of micturitions per 24 hours#
Għadd ta ’ mikturizzjonijiet kull 24 siegħa #
N=283
N=276 N=283
N=266
N=266 7
Baseline Change from baseline
Linja bażi
12.0 -1.02
Bidla mil - linjabażi
11.6 -1.74
- 1. 02
11.9 -1.94
- 1. 74
11.5 -1.69
- 1. 94
12.2 -1.02
- 1. 69 - 1. 02
12.9 -1.86
- 1. 86
12.0 -1.94
- 1. 94
p-value
valur- p
< 0.001
< 0. 001 < 0. 001
< 0.001
0. 032
Responder rate (treatment response)#
Rata ta ’ respons (respons għat- trattament) #
Responder rate
Rata ta ’ respondaturi
79.0%
53. 4%
72.4%
74. 7%
45.1%
79. 0%
63.7%
72. 4%
74.2%
45. 1%
7 p-value
63. 7%
< 0.001 < 0.001 < 0.001
< 0. 001 < 0. 001 < 0. 001
Number of urge incontinence episodes per 24 hours
Għadd ta’ episodji ta ’ impuls qawwi ta ’ inkontinenza kull 24 siegħa
Baseline Change from baseline
Linja bażi Bidla mil- linja bażi
3.7 -1.20
3. 7 - 1. 20
3.8 -2.06
3. 8 - 2. 06
3.7 3.8 -2.27 -1.83
3. 7 3. 8 - 2. 27 - 1. 83
3.7 -1.00
3. 7 - 1. 00
3.9 -1.77
3. 9 - 1. 77
3.9 -2.42
3. 9 - 2. 42
0.003
0. 003
Number of continent days per week
Għadd ta ’ ġranet mingħajr episodji ta ’ inkontinenza fil- ġimgħa
0.8 2.1
0. 8 2. 1
0.8 2.8
0. 8 2. 8
0.6 0.6 3.4 2.5
0. 6 0. 6 3. 4 2. 5
0.6 1.4
0. 6 1. 4
0.7 2.4
0. 7 2. 4
0.7 2.8
0. 7 2. 8
< 0.001
0. 007
Voided volume per micturition (ml)
Volum żvojtjat kull mikturizzjoni (ml)
< 0.001
0. 150
# primary end points
# end points primarji
Cardiac electrophysiology:
Elektrofisjoloġija kardijaka:
The effect of fesoterodine 4 mg and 28 mg on the QT interval was thoroughly evaluated in a double-blind, randomised, placebo- and positive-controlled (moxifloxacin 400 mg) parallel group study with once-daily treatment over a period of 3 days in 261 male and female subjects aged 45 to 65 years.
L- effett ta ’ fesoterodine 4 mg u 28 mg fuq l- intervall ta ’ QT kien valutat sew fi studju double- blind, parallel, randomised, b’ kontroll pożittiv (moxifloxacin 400mg) u bil- plaċebo b’ trattamentt ta ’ darba kuljum li dam tliet ijiem, u li sar fuq 261 raġel u mara li kellhom bejn il- 45 u 65 sena.
Change from baseline in QTc based on the Fridericia correction method did not show any differences between the active treatment and placebo group.
Bidla mill- linja bażi fi QTc, bażata fuq il- metodu ta ’ korrezzjoni Fridericia, ma wriet l- ebda differenza bejn it- trattament attiv u l- grupp li ħa l- plaċebo.
Absorption After oral administration, due to rapid and extensive hydrolysis by non-specific plasma esterases, fesoterodine was not detected in plasma.
Assorbiment Wara l- għoti mill- ħalq, minħabba idrolizi ta ’ malajr u estensiva minn esterases mhux speċifiċi fil - plażma, l- ebda traċċa ta ’ fesoterodine ma ġiet osservata fil- plażma.
Bioavailability of the active metabolite is 52%.
Il- bijodisponibilità tal- metabolit attiv hi ta ’ 52%.
After single or multiple-dose oral administration of fesoterodine in doses from 4 mg to 28 mg, plasma concentrations of the active metabolite are proportional to the dose.
Wara t- teħid orali ta ’ darba jew iktar ta ’ fesoterodine b’ dożi bejn 4mg u 28mg, il- konċentrazzjonijiet fil- plażma tal- metabolit attiv huma proporzjonali għad- doża li ngħatat.
Maximum plasma levels are reached after approximately 5 hours.
Il- livelli massimi fil- plażma jintlaħqu wara bejn wieħed u ieħor 5 sigħat.
Therapeutic plasma levels are achieved after the first administration of fesoterodine.
Livelli terapewtiċi fil- plażma jintlaħqu wara l- ewwel għotja ta ’ fesoterodine.
No accumulation occurs after multiple-dose administration.
Ma jkun hemm l- ebda akkumulazjoni wara l- għoti ta ’ dożi multipli.
Distribution Plasma protein binding of the active metabolite is low with approximately 50% bound to albumin and alpha-1-acid glycoprotein.
Distribuzzjoni L- irbit tal- metabolit attiv mal- proteini tal- plażma huwa baxx, b’ 50% tal- metabolit marbut ma ’ l - albumina u mal- alpha- 1- acid glycoprotein.
The mean steady-state volume of distribution following intravenous infusion of the active metabolite is 169 l.
Il- medja tal- volum ta ’ distribuzzjoni fiss wara infużjoni ġol- vina tal- metabolit attiv hu 1691.
Metabolism After oral administration, fesoterodine is rapidly and extensively hydrolysed to its active metabolite.
8 Metaboliżmu Wara l- għoti mill- ħalq, fesoterodine huwa idrolizzat malajr u estensivament biex jifforma l- metabolit attiv.
The active metabolite is further metabolised in the liver to its carboxy, carboxy-N-desisopropyl, and
Il- metabolit attiv ikompli jkun metaboliżżat ġol- fwied u jifforma l- metaboliti carboxy, carboxy- N- desisopropyl u N- desisopropyl bl- involviment ta ’ CYPD6 u CYP3A4.
None of these metabolites contribute significantly to the antimuscarinic activity of fesoterodine.
L- ebda wieħed minn dawn il- metaboliti m’ għandu effett sinifikativ fuq l- attività anti- muskarinika ta ’ fesoterodine.
Mean Cmax and AUC of the active metabolite are 1.7 and 2-fold higher, respectively, in CYP2D6 poor metabolisers as compared to extensive metabolisers.
Is- Cmax medju u l- AUC tal- metabolit attiv huma ogħla b’ fatturi ta ’ 1. 7 u 2, rispettivament, f’ dawk il- metaboliżżaturi dgħajfin ta ’ CYP2D6 meta mqabblin ma’ metaboliżżaturi estensivi.
Elimination Hepatic metabolism and renal excretion contribute significantly to the elimination of the active metabolite.
Eliminazzjoni Il- metaboliżmu epatiku u l- eliminazzjoni renali jikkontribwixxu b’ mod sinifikanti għall- eliminazzjoni tal- metabolit attiv.
After oral administration of fesoterodine, approximately 70% of the administered dose was recovered in urine as the active metabolite (16%), carboxy metabolite (34%), carboxy-N- desisopropyl metabolite (18%), or N-desisopropyl metabolite (1%), and a smaller amount (7%) was recovered in faeces.
Wara li fesoterodine jittieħed mill- ħalq, madwar 70% tad- doża mogħtija ġiet rkuprata mill- awrina bħala l- metabolit attiv (16%), metabolit carboxy (34%), metabolit carboxy- N - desisopropyl (18%), jew metabolit N- desisopropyl (1%), u ammont iżgħar (7%) ġie rkuprat fl - ippurgar.
The terminal half-life of the active metabolite following oral administration is approximately 7 hours and is absorption rate-limited.
Il- half- life terminali tal- metabolit attiv wara li jittieħed mill- ħalq hi ta ’ madwar 7 sigħat u hi ristretta bir- rata ta ’ assorbiment.
Age and gender No dose adjustment is recommended in these subpopulations.
Età u sess L- ebda bidla fid- doza m ’ hi rakkomandata f’ dawn is- sub- popolazzjonijiet.
The pharmacokinetics of fesoterodine are not significantly influenced by age and gender.
Il- farmakokinetika ta ’ fesoterodine m’ hix affettwata b’ mod sinifikanti minn età u sess.
Paediatric patients The pharmacokinetics of fesoterodine have not been evaluated in paediatric patients.
Pazjenti pedjatriċi Il- farmakokinetiċi ta ’ fesoterodine għadhom ma ġewx evalwati f’ pazjenti pedjatriċi.
Renal impairment In patients with mild or moderate renal impairment (GFR 30 – 80 ml/ min), Cmax and AUC of the active metabolite increased up to 1.5 and 1.8-fold, respectively, as compared to healthy subjects.
Indeboliment renali F’ pazjenti li għandhom indeboliment ħafif jew moderat tal- kliewi (GFR 30 – 80 ml/ min), is- Cmax u l - AUC tal- metabolit attiv ogħlew sa 1. 5 u 1. 8 darba, rispettivament, meta mqabblin ma ’ suġġetti b’ saħħithom.
In patients with severe renal impairment (GFR < 30 ml/ min), Cmax and AUC are increased 2.0 and 2.3- fold, respectively.
F’ pazjenti li għandhom indeboliment renali serju (GFR < 30 ml/ min), is- Cmax u l- AUC huma ogħla 2. 0 u 2. 3 drabi, ispettivament.
Hepatic impairment In patients with moderate hepatic impairment (Child Pugh B), Cmax and AUC of the active metabolite increased 1.4 and 2.1-fold, respectively, as compared to healthy subjects.
Indeboliment epatiku F’ pazjenti b’ indeboliment epatiku moderat (Child Pugh B), is- Cmax u l- AUC tal- metabolit attiv żdied b’ 1. 4 u 2. 1- drabi rispettivament, meta mqabblin ma individwi b’ saħħithom.
Pharmacokinetics of fesoterodine in patients with severe hepatic impairment have not been studied.
Il- farmakokinetiċi ta ’ fesoterodine f’ pazjenti li għandhom indeboliment epatiku serju ma ġewx studjati.
In non-clinical safety pharmacology, general toxicity, genotoxicity and carcinogenicity studies no clinically relevant effects have been observed, except those related to the pharmacological effect of the active substance.
Informazzjoni li mhix klinika, magħmula fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku, effett tossiku fuq il- ġeni, riskju ta ’ kanċer, l- ebda effett kliniku rilevanti ma ġie osservat, ħlief dawk relatati ma ’ l- effett farmakoloġiku għas- sustanza attiva.
Reproduction studies have shown minor embryotoxicity at doses close to maternally toxic ones (increased number of resorptions, pre-implantation and post-implantation losses).
Studji fuq ir- riproduzzjoni wrew tossiċità embrijonika minuri meta ngħataw dożi li kważi laħqu dawk tossiċi għall- omm (żieda fin- numru ta ’ riassorbimenti, u telf ta ’ qabel l- impjantazzoni u wara l - impjantazzjoni).
Supratherapeutic concentrations of the active metabolite of fesoterodine, have been shown to inhibit K+ current in cloned human ether-à-go-go-related gene (hERG) channels and prolong action potential duration (70% and 90% repolarisation) in canine isolated Purkinje fibres.
Konċentrazzjonijiet supraterapewtiċi tal- metabolit attiv ta ’ fesoterodine, urew li jimpedixxu l- kurrent K+ f’ kanali fil- ġene uman ikklownjat ether- à- go- go (hERG) u wkoll żieda fit- tul ta ’ l- azzjoni potenzjali (ripolariżazzjoni 70% u 90%) fil- fibri ta ’ Purkinje iżolati mill- klieb.