qanastek/EMEA-V3 huggingface dataset:
The potential risk for humans is unknown.
Ir- riskju potenzjali fuq l- umani mhuwiex magħruf.
Women of child-bearing potential should avoid pregnancy during treatment with dabigatran etexilate.
Nisa li jista ’ jkollhom it- tfal għandhom jevitaw li joħorġu tqal matul il- kura b’ dabigatran etexilate.
Pradaxa should not be used during pregnancy unless clearly necessary.
Pradaxa m’ għandhiex tintuża waqt it- tqala ħlief jekk ikun hemm bżonn ċar.
Lactation:
6 Treddigħ:
There are no clinical data of the effect of dabigatran on infants during breast feeding.
M’ hemm l- ebda dejta klinika dwar l- effett ta ’ dabigatran fuq trabi li jkunu qed jerdgħu.
Lactation should be discontinued during treatment with Pradaxa.
It- treddigħ għandu jitwaqqaf matul il- kura bi Pradaxa.
A total of 10.084 patients were treated in 4 actively controlled VTE prevention trials with at least one dose of the medicinal product.
Total ta ’ 10, 084 pazjent kienu kkurati f’ 4 provi ta ’ prevenzjoni ta ’ VTE kkontrollati attivament, b’ mill- inqas doża waħda tal- prodott mediċinali.
Of these 5419 were treated with 150 mg or 220 mg daily of Pradaxa, while 389 received doses less than 150 mg daily and 1168 received doses in excess of 220 mg daily.
Minn dawn, 5, 419 kienu kkurati b’ 150 mg jew 220 mg ta ’ Pradaxa kuljum, filwaqt li 389 irċivew dożi ta ’ inqas minn 150 mg kuljum u 1, 168 irċivew dożi ta ’ iktar minn 220 mg kuljum.
The most commonly reported adverse reactions are bleedings occurring in total in approximately 14% of patients; the frequency of major bleeds (including wound site bleedings) is less than 2%.
L- iktar reazzjonijiet avversi li kienu rrappurtati b’ mod komuni huma fsad li seħħ f’ total ta ’ madwar 14% tal - pazjenti; il- frekwenza ta ’ fsad maġġuri (li jinkludi fsad fis- sit tal- ferita) hu ta ’ inqas minn 2%.
6 The table 1 shows the number (%) of patients experiencing bleeding events during the treatment period in the VTE prevention in the two pivotal clinical trials, according to dose.
Tabella 1 turi n- numru (%) ta ’ pazjenti li kellhom avvenimenti ta ’ fsad matul il- perjodu tal- kura fil - prevenzjoni ta ’ VTE fiż- żewġ provi kliniċi importanti ħafna, skond id- doża
Table 1 Bleeding events broken down to major and any bleeding in the pivotal hip and knee study
Avvenimenti ta ’ fsad ikklassifikati skond jekk kinux maġġuri u kwalunkwe fsad fl- istudju importanti ħafna dwar il- ġenbejn u l- irkoppa.
Dabigatran etexilate 220 mg
Dabigatran etexilate Dabigatran etexilate 150 mg 220 mg
Treated Major Bleeding Any bleeding
Ikkurati Ħruġ Maġġuri tad- Demm Kwalunkwe fsad
1866(100.0) 24 (1.3) 258(13.8)
1866 (100. 0) 24 (1. 3) 258 (13. 8)
1825(100.0) 33 (1.8) 251(13.8)
1825 (100. 0) 33 (1. 8) 251 (13. 8)
1848(100.0) 27 (1.5) 247(13.4)
1848 (100. 0) 27 (1. 5) 247 (13. 4)
Table 2 shows the adverse reactions ranked under headings of SOC and frequency using the following convention: very common (≥ 1/ 10); common (≥ 1/ 100, < 1/ 10); uncommon (≥ 1/ 1,000, < 1/ 100); rare (≥ 1/ 10,000, < 1/ 1,000); very rare (< 1/ 10,000).
Tabella 2 turi r- reazzjonijiet avversi kklassifikati skond kategoriji ta ’ SOC u frekwenza bl- użu tal - konvenzjoni li ġejja: komuni ħafna (≥1/ 10); komuni (≥1/ 100, < 1/ 10); mhux komuni (≥1/ 1, 000, < 1/ 100); rari (≥1/ 10, 000, < 1/ 1, 000), rari ħafna (< 1/ 10, 000).
SOC / Preferred Term.
SOC/ Terminu Ppreferut.
Number of patients treated
Numru ta ’ pazjenti kkurati
Blood and lymphatic system disorders Common
Disturbi tad- demm u tas- sistema limfatika Komuni
110 (4.0)
110 (4. 0) Komuni
117 (4.4)
117 (4. 4)
141 (4.5)
141 (4. 5)
Vascular disorders Common
Disturbi vaskulari Komuni
Haematoma Traumatic haematoma Wound haemorhhage
Ematoma Ematoma trawmatika Emorraġija tal- ferita
38 (1.4) 37 (1.4) 35 (1.3)
38 (1. 4) 37 (1. 4) 35 (1. 3) Komuni
37 (1.4) 41 (1.5) 28 (1.0)
37 (1. 4) 41 (1. 5) 28 (1. 0)
55 (1.8) 51 (1.6) 31 (1.0)
55 (1. 8) 51 (1. 6) 31 (1. 0)
Haemorrhage
Emorraġija
18 (0.7)
18 (0. 7)
21 (0.7)
21 (0. 7)
Respiratory and thoracic system disorders Uncommon
Disturbi respiratorji u toraċiċi
Epistaxis
Enoxaparin
19 (0.7)
19 (0. 7) Komuni
15 (0.6)
15 (0. 6)
13 (0.4)
13 (0. 4)
Gastrointestinal haemorrhage
Emorraġija gastrointestinali
33 (1.2)
33 (1. 2) Mhux Komuni
17 (0.6)
17 (0. 6)
20 (0.6)
20 (0. 6)
Uncommon
Emorraġija tar- rektum Emorraġija tal- murliti Disturbi fil- fwied u fil- marrara
Rectal haemorrhage
12 (0. 4) 4 (0. 2) Mhux Komuni
12 (0.4)
15 (0. 6) 8 (0. 3)
1
5 (0. 2) 2 (0. 1)
Alaninine aminotransferase increased
Żieda f’ alaninine aminotransferase
18 (0.
18 (0. 7)
(0.3)
7 (0. 3)
28 (0.9)
28 (0. 9)
Aspartate aminotransferase increased
Żieda f’ aspartate aminotransferase
9 (0.3)
9 (0. 3)
(0.2)
5 (0. 2)
15 (0.5)
15 (0. 5)
Hepatic function abnormal/ Liver function Test
Funzjoni epatika anormali/ Test tal- Funzjoni Epatika b’ riżultat anormali
6 (0.2)
6 (0. 2)
10 (0.4)
10 (0. 4)
(0.2)
7 (0. 2)
Hepatic enzyme increased Hyperbilirubinaemia Transaminases increased
Żieda fl- enzimi epatiċi Iperbilirubinemja Żieda fit- transaminases
4 (0.2) 4 (0.1) 0 (0.0)
4 (0. 2) 4 (0. 1) 0 (0. 0)
5 (0.2) 3 (0.1) 2 (0.1)
5 (0. 2) 3 (0. 1) 2 (0. 1)
11 (0.4) 4 (0.1) 1 (0.0)
11 (0. 4) 4 (0. 1) 1 (0. 0)
Skin and subcutaneous tissue disorder Common
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Komuni
Skin haemorrhage
Emorraġija tal- ġilda
45 (1.6)
45 (1. 6)
57 (2.1)
57 (2. 1)
61 (2.0)
61 (2. 0)
Musculoskeletal and connective tissue and bone disorders Uncommon
Disturbi muskolu- skeltrali u tal- connective tissue u ta ’ l- għadam Mhux komuni
Haemarthrosis
Emartrożi
7 (
7 (0. 3)
Renal and urinary disorders Common
Disturbi fil- kliewi u fis- sistema urinarja Komuni
38 (1.4)
38 (1. 4)
33 (1.4)
33 (1. 4)
25 (0.8)
25 (0. 8)
General disorders and administration site conditions Uncommon
Disturbi ġenerali u kundizzjonijiet ta ’ mnejn jingħata Mhux Komuni
Injection site haemorrhage Bloody discharge Catheter site haemorrhage
Emorraġija fis- sit ta ’ l - injezzjoni
21 (0.8) 2 (0.1) 2 (0.1)
21 (0. 8)
19 (0.7) 6 (0.2) 1 (0.0)
19 (0. 7)
27 (0.9) 6 (0.2) 7 (0.2)
27 (0. 9)
Investigations Common
Investigazzjonijiet Komuni
35 (1.3)
35 (1. 3)
74 (2.4)
74 (2. 4)
Haematocrit decreased
Tnaqqis fl- ematokrit
0 (0.0)
0 (0. 0)
(0.2)
6 (0. 2)
(0.1)
(0. 1)
Injury, poisoning and procedural complications Common
Korriment, avvelenament u komplikazzjonijiet ta ’ xi proċedura Komuni
Wound secretion Anaemia postoperative Post procedural haematoma Post procedural haemorrhage
Tnixxija mill- ferita Anemija wara l- operazzjoni Ematoma wara l- proċedura
130 (4.8) 99 (3.6) 66 (2.4) 37 (1.4)
130 (4. 8) 99 (3. 6) 66 (2. 4)
130 87 45 54
130 (4. 9) 87 (3. 2) 45 (1. 7)
(3.0) (3.7) (2.5) (1.8)
(3. 0) (3. 7) (2. 5)
Post procedural discharge
Emorraġija wara
31 (1.1)
31 (1. 1) Mhux Komuni
34 (1.3)
34 (1. 3)
31 (1.0)
31 (1. 0)
Post procedural drainage Wound drainage
Tnixxija wara l- proċedura Tnixxija mill- ferita
Beyond the reported ALT findings the following laboratory chemistry data had been measured in phase 3 studies as presented in table 3.
Lilhemm mis- sejbiet ta ’ l- ALT irrappurtati, id- dejta kimika tal- laboratorju li ġejja kienet imkejla fi studji ta ’ fażi 3 kif ippreżentata f’ Tabella 3.
ALT findings the following laboratory chemistry
Is- sejbiet ta ’ l- ALT - id- dejta kimika tal- laboratorju
Total rates of Alaninine aminotransferase increased 3 x ULN
Rati totali żieda f’ alaninine aminotransferase 3 x ULN
58 (2.2)
68 (2. 5) 58 (2. 2)
95 (3.5)
95 (3. 5)
There is no antidote to dabigatran.
M’ hemm l- ebda antidot għal dabigatran.
Doses of dabigatran etexilate beyond those recommended, expose the patient to increased risk of bleeding.
Dożi ta ’ dabigatran etexilate lilhemm minn dawk rakkomandati, jesponu lill- pazjent għal żieda fir- riskju ta ’ fsad.
In the event of haemorrhagic complications, treatment must be discontinued and the source of bleeding investigated.
F’ każ ta ’ komplikazzjonijiet emorraġiċi, il- kura għandha titwaqqaf u s- sors ta ’ fsad ikun investigat.
Since dabigatran is excreted predominantly by the renal route adequate diuresis must be maintained.
Minħabba li dabigatran jitneħħa l- biċċa l- kbira mill- kliewi, għandha tinżamm dijuresi adegwata.
The initiation of appropriate treatment, e. g. surgical haemostasis or the transfusion of fresh frozen plasma should be considered.
Il- bidu ta ’ kura adattata, eż. emostasi kirurġika jew it- trasfużjoni ta ’ plażma friska ffriżata, għandhom ikunu kkunsidrati.
Dabigatran can be dialysed; there is no clinical experience to demonstrate the utility of this approach in clinical studies.
Dabigatran jista ’ jkun dijalizzat; m’ hemm l- ebda esperjenza klinika biex turi l- benefiċċju ta ’ din il - metodoloġija fl- istudji kliniċi.
Pharmacotherapeutic group: direct thrombine inhibitors, ATC code:
Kategorija farmakoterapewtika: inibituri thrombine diretti, Kodiċi ATC:
Dabigatran etexilate is a small molecule prodrug which does not exhibit any pharmacological activity.
Dabigatran etexilate hu prodrug ta ’ molekula żgħira li ma turi l- ebda attività farmakoloġika.
After oral administration, dabigatran etexilate is rapidly absorbed and converted to dabigatran by esterase- catalysed hydrolysis in plasma and in the liver.
Wara l- għoti mill- ħalq, dabigatran etexilate ikun assorbit malajr u jinbidel għal dabigatran permezz ta ’ idrolisi kkatalizzata minn esterase fil- plażma u fil- fwied.
Dabigatran is a potent, competitive, reversible direct thrombin inhibitor and is the main active principle in plasma.
Dabigatran hu inibitur potenti, kompetittiv, riversibbli u dirett tat - thrombin, u hu l- prinċipju attiv ewlieni fil- plażma.
Since thrombin (serine protease) enables the conversion of fibrinogen into fibrin during the coagulation cascade, its inhibition prevents the development of thrombus.
Minħabba li thrombin (serine protease) jippermetti l- bidla ta ’ fibrinogen għal fibrin waqt il- kaskata tal - koagulazzjoni, l- inibizzjoni tiegħu tevita l- iżvilupp ta ’ l- embolu.
Dabigatran also inhibits free thrombin, fibrin- bound thrombin and thrombin-induced platelet aggregation.
Dabigatran jinibixxi wkoll it- thrombin ħieles, it- thrombin imwaħħal mal- fibrin u l- aggregazzjoni tal- plejtlits ikkaġunata mit- thrombin.
In-vivo and ex-vivo animal studies have demonstrated antithrombotic efficacy and anticoagulant activity of dabigatran after intravenous administration and of dabigatran etexilate after oral administration in various animal models of thrombosis.
Studji in- vivo u ex- vivo fuq l- annimali wrew effikaċja antitrombotika u attività kontra l- koagulazzjoni ta ’ dabigatran wara l- għoti ġol- vina u ta ’ dabigatran etexilate wara l- għoti orali f’ mudelli varji tat- trombożi fl - annimali.
There is a clear correlation between plasma dabigatran concentration and degree of anticoagulant effect based on phase II studies.
9 Hemm korrelazzjoni ċara bejn il- konċentrazzjoni ta ’ dabigatran fil- plażma u l- grad ta ’ l- effett kontra l - koagulazzjoni, ibbażat fuq studji ta ’ fażi II.
Steady state (after day 3) dabigatran peak plasma concentration, measured 2 - 4 hours after 220 mg dabigatran etexilate administration, is expected to be around 270 ng/ ml, with an expected range of 80 - 460 ng/ ml.
L- istat fiss (wara jum 3) tal- konċentrazzjoni massima ta ’ dabigatran fil- plażma, imkejla 2 - 4 sigħat wara l - għoti ta ’ 220 mg ta ’ dabigatran etexilate, hu mistenni li jkun madwar 270 ng/ ml, b’ medda mistennija ta ’ 80 - 460 ng/ ml.
The dabigatran trough concentration, measured at the end of the dosing interval (24 hours after the last 220 mg dabigatran dose), is expected to be around 40 ng/ ml, with expected range of 10-90 ng/ ml.
L- inqas konċentrazzjoni ta ’ dabigatran, imkejla fit- tmiem ta ’ l- intervall tad- dożaġġ (24 siegħa wara l- aħħar doża ta ’ 220 mg ta ’ dabigatran), hi mistennija li tkun ta ’ madwar 40 ng/ ml, b’ medda mistennija ta ’ 10- 90 ng/ ml.
Ethnic origin:
Oriġini etnika:
More than 99% of efficacy and safety data were generated in Caucasians.
Iktar minn 99% tad- dejta dwar l- effikaċja u s- sigurtà inħolqot f’ nies Kawkasi.
Clinical trials in Venous Thromboembolism (VTE) prophylaxis following major joint replacement surgery:
Provi kliniċi fil- profilassi ta ’ Tromboemboliżmu Venuż (VTE) wara operazzjoni maġġuri tas- sostituzzjoni tal- ġogi:
Totals of 2076 patients (knee) and 3494 (hip) were treated respectively.
F’ 2 provi kbar biex jikkonfermaw id- doża, li kienu randomized, parallel grupp u double- blind, il- pazjenti li kienet qed issirilhom operazzjoni ortopedika maġġuri mhux urġenti (waħda għall- operazzjoni tas - sostituzzjoni ta ’ l- irkoppa u waħda għall- operazzjoni tas- sostituzzjoni tal- ġenbejn), irċivew Pradaxa 75 mg jew 110 mg fi żmien 1- 4 sigħat mill- operazzjoni, segwiti minn 150 jew 220 mg kuljum wara dan il- perjodu, wara li kienet inkisbet l- emostasi, jew enoxaparin 40 mg fil- jum ta ’ qabel l- operazzjoni u kuljum wara l - operazzjoni.
Composite of total VTE (including PE, proximal and distal DVT, whatever symptomatic or asymptomatic detected by routine venography) and all-cause mortality constituted the primary end-point for both studies.
Kompost ta ’ VTE totali (li jinkludi PE u DVT prossimali u distali, kemm sintomatika jew asintomatika, osservata permezz ta ’ venografija ta ’ rutina) u mortalità mill- kawżi kollha, ikkostitwixxa l- punt aħħari primarju għaż- żewġ studji.
9 Composite of major VTE (including PE and proximal DVT, whatever symptomatic or asymptomatic detected by routine venography) and VTE-related mortality constituted a secondary end-point and is considered of better clinical relevance.
Kompost ta ’ VTE totali (li jinkludi PE u DVT prossimali, kemm sintomatika jew asintomatika, osservata permezz ta ’ venografija ta ’ rutina) u mortalità marbuta ma ’ VTE, ikkostitwixxa punt aħħari sekondarju, u hu kkunsidrat li hu ta ’ rilevanza klinika aħjar.
Results of both studies showed that the antithrombotic effect of Pradaxa 220 mg and 150 mg were statistically non-inferior to that of enoxaparin on total VTE and all-cause mortality.
Ir- riżultati taż- żewġ studji wrew li l- effett antitrombotiku ta ’ Pradaxa 220 mg u 150 mg kien statistikament mhux inferjuri għal dak ta ’ enoxaparin fuq il- VTE totali u l- mortalità mill- kawżi kollha.
The point estimate for incidence of Major VTE and VTE related mortality for the 150 mg dose was slightly worse than enoxaparin (table 4).
Il- point estimate għall- inċidenza ta ’ VTE maġġuri u mortalità marbuta ma ’ VTE għad- doża ta ’ 150 mg kien ftit agħar minn dak ta ’ enoxaparin (Tabella 4).
Better results were seen with the 220mg dose where the point estimate of Major VTE was slightly better than enoxaparin (table 4). "
Riżultati aħjar kienu osservati bid- doża ta ’ 220 mg fejn il- point estimate ta ’ VTE maġġuri kien ftit aħjar minn dak ta ’ enoxaparin (Tabella 4). "
The clinical studies have been conducted in a patient population with a mean age > 65 years.
L- istudji kliniċi saru f’ popolazzjoni ta ’ pazjenti b’ età medja > 65 sena.
There were no differences in the phase 3 clinical studies for efficacy and safety data between men and women.
Ma kien hemm l- ebda differenzi fl- istudji kliniċi ta ’ fażi 3 għad- dejta dwar l- effikaċja u s- sigurtà bejn l- irġiel u n- nisa.
In the studied patient population of RE-MODEL and RE-NOVATE (5539 patients treated), 51% suffered from concomitant hypertension, 9% from concomitant diabetes, 9% from concomitant coronary artery disease and 20% had a history of venous insufficiency.
Fil- popolazzjoni ta ’ pazjenti li kienu studjati ta ’ RE- MODEL u RE- NOVATE (5539 pazjenti kkurati), 51% kienu jbatu minn pressjoni għolja fl- istess ħin, 9% minn dijabete fl- istess ħin; 9% minn mard ta ’ l- arterji koronarji fl- istess ħin, u 20% kellhom storja medika ta ’ insuffiċjenza venuża.
None of these diseases showed an impact on the effects of dabigatran on VTE-prevention or bleeding rates.
L- ebda waħda minn dawn il - mardiet ma wriet impatt fuq l- effetti ta ’ dabigatran fuq il- prevenzjoni ta ’ VTE jew ir- rati ta ’ fsad.
Data for the major VTE and VTE-related mortality endpoint were homogeneous with regards to the primary efficacy endpoint and are shown in table 4.
Dejta għall- VTE maġġuri u r- riżultat aħħari tal- mortalità assoċjata ma ’ VTE, kienu omoġenji fir- rigward tar - riżultat aħħari ta ’ l- effikaċja primarja, u hi murija f’ Tabelli 4.
Data for the total VTE and all cause mortality endpoint are shown in table 5.
Dejta għall- VTE totali u r- riżultat aħħari tal- mortalità mill- kawżi kollha, huma murija f’ Tabella 5.
Data for adjudicated major bleeding endpoints are shown in tables 6 below.
Dejta għar- riżultati aħħarin ta ’ fsad maġġuri li kienu ġġudikati, huma murija f’ Tabella 6 hawn taħt.
Analysis of major VTE and VTE-related mortality during the treatment period in the RE-MODEL and the RE-NOVATE orthopeadic surgery studies
Analiżi ta ’ VTE maġġuri u mortalità assoċjata ma ’ VTE matul il- perjodu tal- kura fl- istudji dwar l - operazzjonijiet ortopediċi f’ RE- MODEL u RE- NOVATE
Trial RE-NOVATE (hip)
Prova RE- NOVATE (ġenbejn)
Incidences (%) Risk ratio over
N Inċidenzi (%) Proporzjon tar- riskju fuq enoxaparin
38 (4.3)
909 888 28 (3. 1) 38 (4. 3) 0. 78 1. 09
36 (3.9)
917 36 (3. 9)
95% CI RE-MODEL (knee)
95% CI RE- MODEL (irkoppa)
0.70, 1.70
0. 48, 1. 27 0. 70, 1. 70
20 (3.8)
506 527 13 (2. 6) 20 (3. 8) 0. 73 1. 08
18 (3.5)
511 18 (3. 5)
0.58, 2.01
0. 36, 1. 47 0. 58, 2. 01
Analysis of total VTE and all cause mortality during the treatment period in the RE-NOVATE and the RE-MODEL orthopaedic surgery studies
Analiżi ta ’ VTE totali u mortalità mill- kawżi kollha matul il- perjodu tal- kura fl- istudji dwar l - operazzjonijiet ortopediċi f’ RE- NOVATE u RE- MODEL
Incidences (%) Risk ratio over enoxaparin
Inċidenzi (%) Proporzjon tar- riskju fuq enoxaparin
53 (6.0) 0.9
53 (6. 0) 0. 9
75 (8.6) 1.28
75 (8. 6) 1. 28
60 (6.7)
60 (6. 7)
(0.63, 1.29)
(0. 63, 1. 29)
(0.93, 1.78)
(0. 93, 1. 78)
183 (36.4) 0.97
183 (36. 4) 0. 97
213 (40.5) 1.07
213 (40. 5) 1. 07
193 (37.7)
193 (37. 7)
(0.82, 1.13)
(0. 82, 1. 13)
(0.92, 1.25)
(0. 92, 1. 25)
Major bleeding events by treatment in the individual RE-MODEL and the RE-NOVATE studies
Avvenimenti maġġuri ta ’ fsad skond il- kura fl- istudji individwali RE- MODEL u RE- NOVATE
Treated patients N Number of MBE N(%) RE-MODEL (knee)
Pazjenti kkurati N Numru ta ’ MBE N (%) RE- MODEL (irkoppa)
1163 15 (1.3)
1146 1163 23 (2. 0) 15 (1. 3)
1154 18 (1.6)
1154 18 (1. 6)
Treated patients N Number of MBE N(%)
Pazjenti kkurati N Numru ta ’ MBE N (%)
703 9 (1.3)
679 703 10 (1. 5) 9 (1. 3)
694 9 (1.3)
694 9 (1. 3)
After oral administration, dabigatran etexilate is rapidly and completely converted to dabigatran, which is the active form in plasma.
Wara l- għoti mill- ħalq, dabigatran etexilate jinbidel malajr u kompletament għal dabigatran, li hu s- sura attiva fil- plażma.
The cleavage of the prodrug dabigatran etexilate by esterase-catalysed hydrolysis to the active principle dabigatran is the predominant metabolic reaction.
Il- qsim tal- prodrug dabigatran etexilate permezz ta ’ idrolisi kkatalizzata minn esterase
The absolute bioavailability of dabigatran following oral administration of Pradaxa was approximately 6.5%.
Il- bijodisponibilità assoluta ta ’ dabigatran wara l- għoti mill- ħalq ta ’ Pradaxa kienet ta ’ madwar 6. 5%.
After oral administration of Pradaxa in healthy volunteers, the pharmacokinetic profile of dabigatran in plasma is characterized by a rapid increase in plasma concentrations with Cmax attained within 0.5 and 2.0 hours post administration.
Wara l- għoti mill- ħalq ta ’ Pradaxa f’ voluntiera b’ saħħithom, il- profil farmakokinetiku ta ’ dabigatran fil - plażma hu kkaratterizzat minn żieda mgħaġġla fil- konċentrazzjonijiet fil- plażma bis- Cmax li jinkiseb fi żmien nofs siegħa u sagħtejn wara l- għoti.
A study evaluating post-operative absorption of dabigatran etexilate, 1-3 hours following surgery, demonstrated relatively slow absorption compared with that in healthy volunteers, showing a smooth plasma concentration-time profile without high peak plasma concentrations.
Studju li jevalwa l- assorbiment ta ’ wara l- operazzjoni ta ’ dabigatran etexilate, 1- 3 sigħat wara l- operazzjoni, wera assorbiment relattivament bil- mod meta mqabbel ma ’ dak f’ voluntiera b’ saħħithom, u juri profil lixx tal- konċentrazzjoni tal- plażma- ħin, mingħajr konċentrazzjonijiet massimi għoljin fil- plażma.
Peak plasma concentrations are reached at 6 hours following administration in a postoperative period due to contributing factors such as anesthesia, gastrointestinal paresis, and surgical effects independent of the oral medicinal product formulation.
Il - konċentrazzjonijiet massimi fil- plażma jintlaħqu 6 sigħat wara l- għoti fil- perjodu ta ’ wara l- operazzjoni minħabba fatturi li jikkontribwixxu, bħal loppju, paresi gastrointestinali, u l- effetti kirurġiċi indipendentement mill- formulazzjoni orali tal- prodott mediċinali.
It was demonstrated in a further study that slow and delayed absorption is usually only present on the day of surgery.
Intwera fi studju addizzjonali, li assorbiment bil- mod u assorbiment li jdum ma jseħħ hu normalment preżenti biss fil- jum ta ’ l- operazzjoni.
On subsequent days absorption of dabigatran is rapid with peak plasma concentrations attained 2 hours after medicinal product administration.
Fil- jiem ta ’ wara, l- assorbiment ta ’ dabigatran hu mgħaġġel, bil- konċentrazzjonijiet massimi fil- plażma li jintlaħqu sagħtejn wara l- għoti tal- prodott mediċinali.
Food does not affect the bioavailability of dabigatran etexilate but delays the time to peak plasma concentrations by 2 hours.
L- ikel ma jaffettwax il- bijodisponibilità ta ’ dabigatran etexilate iżda jdewwem il- ħin sakemm jintlaħqu l - konċentrazzjonijiet massimi fil- plażma b’ sagħtejn.
Low (34-35%) concentration independent binding of dabigatran to human plasma proteins was observed.
Kien osservat li dabigtran jeħel ftit (34- 35%) mal- proteini tal- plażma umana u dan hu indipendenti mill - konċentrazzjoni.
The volume of distribution of dabigtran of 60 – 70 L exceeded the volume of total body water indicating moderate tissue distribution of dabigatran.
Il- volum tad- distribuzzjoni ta ’ dabigtran ta ’ 60 – 70 L qabeż il- volum ta ’ l- ilma totali tal - ġisem, li jindika distribuzzjoni moderata ta ’ dabigatran fit- tessut.
Cmax and the area under the plasma concentration-time curve were dose proportional.
Is- Cmax u ż- żona taħt il- kurva konċentrazzjoni- ħin kienu proporzjonali mad- doża.
Plasma concentrations of dabigatran showed a biexponential decline with a mean terminal half-life of 12 - 14 hours in healthy volunteers and 14 – 17 hours in patients undergoing major orthopaedic surgery.
Il- konċentrazzjonijiet fil - plażma ta ’ dabigatran urew tnaqqis bi- esponenzjali bil- medja tal- half- life terminali ta ’ 12 - 14- il siegħa f’ voluntiera b’ saħħithom u ta ’ 14 – 17- il- siegħa f’ pazjenti li kienet qed issirilhom operazzjoni ortopedika maġġuri.
The half-life was independent of dose.
Il- half- life kienet indipendenti mid- doża.
Metabolism and elimination:
Metaboliżmu u tneħħija:
Metabolism and excretion of dabigatran were studied following a single intravenous dose of radiolabeled dabigatran in healthy male subjects.
Il- metaboliżmu u t- tneħħija ta ’ dabigatran kienu studjati wara doża waħda ġol- vina ta ’ dabigatran radjutikkettat f’ pazjenti rġiel b’ saħħithom.
After an intravenous dose, the dabigatran-derived radioactivity was eliminated primarily in the urine (85%).
Wara doża ġol- vina, ir- radjuattività miksuba minn dabigatran kienet eliminata primarjament fl- awrina (85%).
Faecal excretion accounted for 6% of the administered dose.
It- tneħħija permezz ta ’ l- ippurgar kienet ta ’ 6% tad- doża mogħtija.
Recovery of the total radioactivity ranged from 88 - 94% of the administered dose by 168 hours post dose.
L- irkuprar tar- radjuattività totali varja minn 88 - 94% tad- doża mogħtija sa 168 siegħa wara l- għoti tad- doża.
Dabigatran is subject to conjugation forming pharmacologically active acylglucuronides.
Dabigatran hu suġġett għal konjugazzjoni li tifforma acylglucuronides farmakoloġikament attivi.
Four positional isomers, 1-O, 2-O, 3-O, 4-O-acylglucuronide exist, each accounts for less than 10% of total dabigatran in plasma.
Jeżistu erba ’ positional isomers, 1- O, 2- O, 3- O, 4- O- acylglucuronide, u kull wieħed minnhom fih inqas minn 10% mit- total ta ’ dabigatran fil- plażma.
Traces of other metabolites were only detectable with highly sensitive analytical methods.
Traċċi ta ’ metaboliti oħrajn instabu biss b’ metodi analatiċi li kienu sensittivi ħafna.
Dabigatran is eliminated primarily in the unchanged form in the urine, at a rate of approximately 100 ml/ min corresponding to the glomerular filtration rate.
Dabigatran hu eliminat primarjament fis- sura mhux mibdula fl- awrina, b’ rata ta ’ madwar 100 ml/ min, li tikkorrispondi għar- rata tal- filtrazzjoni glomerulari.
The exposure (AUC) of dabigatran after the oral administration of Pradaxa is approximately 2.7 fold higher in volunteers with moderate renal insufficiency (CrCL between 30 – 50 ml/ min) than in those without renal insufficiency.
L- espożizzjoni (AUC) ta ’ dabigatran wara l- għoti mill- ħalq ta ’ Pradaxa hi ta ’ madwar 2. 7 darba ogħla f’ voluntiera b’ insuffiċjenza moderata renali (CrCL bejn 30 - 50 ml/ min) milli f’ dawk mingħajr insuffiċjenza renali.
In a small number of volunteers with severe renal insufficiency (CrCL 10 - 30 ml/ min), the exposure (AUC) to dabigatran was approximately 6 times higher and the half-life approximately 2 times longer than that observed in a population without renal insufficiency (see sections 4.2, 4.3 and 4.4).
F’ numru żgħir ta ’ voluntiera b’ insuffiċjenza severa renali (CrCL 10 - 30 ml/ min), l- espożizzjoni (AUC) għal dabigatran kienet ta ’ madwar 6 darbiet ogħla u l- half- life ta ’ madwar darbtejn itwal minn dik osservata f’ popolazzjoni mingħajr insuffiċjenza renali (ara sezzjonijiet 4. 2, 4. 3 u 4. 4).
Elderly patients:
12 Pazjenti anzjani:
Specific pharmacokinetic studies with elderly subjects showed an increase of 40 to 60% in the AUC and of more than 25% in Cmax compared to young subjects.
Studji speċifiċi dwar il- farmakokinetika fuq pazjenti anzjani urew żieda ta ’ 40% sa 60% fl- AUC, u ta ’ iktar minn 25% fis- Cmax meta mqabbla ma ’ pazjenti żgħażagħ.
Population-based pharmacokinetic studies have evaluated the pharmacokinetics of dabigatran after repeated doses in patients (up to 88 years).
Studji farmakokinetiċi bbażati fuq il- popolazzjoni evalwaw il- farmakokinetika ta ’ dabigatran wara dożi ripetuti f’ pazjenti (sa 88 sena).
The observed increase of dabigatran exposure correlated with the age-related reduction in creatinine clearance (see sections 4.2 and 4.4).
Iż- żieda osservata ta ’ l - espożizzjoni għal dabigatran ikkorrelat mat- tnaqqis marbut ma ’ l- età fit- tneħħija tal- krejatinina (ara sezzjonijiet 4. 2 u 4. 4).
No change in dabigatran exposure was seen in 12 subjects with moderate hepatic insufficiency (Child Pugh B) compared to 12 controls (see sections 4.2 and 4.4).
L- ebda bidla fl- espożizzjoni għal dabigatran ma kienet osservata fi 12- il pazjent b’ insuffiċjenza epatika moderata (Child Pugh B) meta mqabbla mat- 12- il pazjent tal- kontroll (ara sezzjonijiet 4. 2 u 4. 4).
Population pharmacokinetic studies have evaluated the pharmacokinetics of dabigatran in patients of 48 to 120 kg body weight.
Piż tal- ġisem Studji dwar il- farmakokinetika tal- popolazzjoni evalwaw il- farmakokinetika ta ’ dabigatran f’ pazjenti li kienu jiżnu minn 48 sa 120 kg.
Body weight had a minor effect on the plasma clearance of dabigatran resulting in higher exposure in patients with low body weight (see section 4.2 and 4.4).
Il- piż tal- ġisem kellu effett żgħir fuq it- tneħħija tal- plażma ta ’ dabigatran li tirriżulta f’ espożizzjoni ogħla f’ pazjenti b’ piż baxx tal- ġisem (ara sezzjonijiet 4. 2 u 4. 4).
Active substance exposure in female patients is about 40% to 50% higher than in male patients and no dose adjustment is recommended.
L- espożizzjoni tas- sustanza attiva f’ pazjenti nisa hi madwar 40% sa 50% ogħla milli f’ pazjenti rġiel, u l- ebda aġġustament fid- doża mhu rakkomandat.
12 Ethnic origin:
Oriġini etnika:
The pharmacokinetics of dabigatran was investigated in Caucasian and Japanese volunteers after single and multiple doses.
Il- farmakokinetika ta ’ dabigatran kienet investigata f’ voluntiera Kawkasi u Ġappuniżi wara dożi waħidhom u multipli.
Ethnic origin does not affect the pharmacokinetics of dabigatran in a clinically relevant manner.
L- oriġini etnika ma taffettwax il- farmakokinetika ta ’ dabigatran b’ mod li hu klinikament rilevanti.
No pharmacokinetic data in black patients are available.
L- ebda dejta farmakokinetika dwar pazjenti suwed mhi disponibbli.
Pharmacokinetic interactions:
Interazzjonijiet tal- farmakokinetika:
In vitro interaction studies did not show any inhibition or induction of the principal isoenzymes of cytochrome P450.
Studji in vitro dwar l- interazzjoni ma wrew l- ebda inibizzjoni jew induzzjoni ta ’ l- isoenzimi prinċipali ta ’ ċitokrom P450.
This has been confirmed by in vivo studies with healthy volunteers, who did not show any interaction between this treatment and the following active substances: atorvastatin (CYP3A4), digoxin (P- glycoprotein transporter interaction) and diclofenac (CYP2C9).
Dan kien ikkonfermat minn studji in vivo f’ voluntiera b’ saħħithom, li ma wrew l- ebda interazzjoni bejn din il- kura u s- sustanzi attivi li ġejjin: atorvastatin (CYP3A4), digoxin (interazzjoni tal- P - glycoprotein tat- trasportatur) u diclofenac (CYP2C9).
Dabigatran exposure in healthy subjects was increased by 60% in the presence of amiodarone.
L- espożizzjoni għal dabigatran f’ pazjenti b’ saħħithom żdiedet b’ 60% fil- preżenza ta ’ amiodarone.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.
5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurtà tal- mediċina Tagħrif ta ’ qabel l- użu kliniku bbażat fuq studji konvenzjonali dwar is- sigurtà farmakoloġika, it- tossiċità ta ’ dożi ripetuti u l- ġenotossiċità, ma żvela l- ebda periklu speċjali għall- bnedmin.
Effects observed in the repeat-dose toxicity studies were due to the exaggerated pharmacodynamic effect of dabigatran.
L- effetti osservati fl- istudji dwar it- tossiċità minn dożi ripetuti kienu minħabba l- effett farmakodinamiku esaġerat ta ’ dabigatran.
An effect on female fertility was observed in the form of a decrease in implantations and an increase in pre- implantation loss at 70 mg/ kg (5-fold the plasma exposure level in patients).
Effett fuq il- fertilità tan- nisa kien osservat fis- sura ta ’ tnaqqis fl- impjantazzjonijiet u żieda fit- telf ta ’ qabel l - impjantazzjoni f’ doża ta ’ 70 mg/ kg (5 darbiet iktar mil- livell ta ’ l- espożizzjoni tal- plażma fil- pazjenti).
At doses that were toxic to the mothers (5 to 10-fold the plasma exposure level in patients), a decrease in foetal body weight and viability along with an increase in foetal variations were observed in rats and rabbits.
F’ dożi li kienu tossiċi għall- ommijiet (minn 5 sa 10 darbiet tal- livell ta ’ l- espożizzjoni tal- plażma fil - pazjenti), tnaqqis fil- piż tal- ġisem u fil- vijabilità tal- fetu flimkien ma ’ żieda fil- varjazzjonijiet tal- fetu kienu osservati fil- firien u fil- fniek.
In the pre- and post-natal study, an increase in foetal mortality was observed at doses that were toxic to the dams (a dose corresponding to a plasma exposure level 4-fold higher than observed in patients).
Fi studji qabel u wara t- twelid, kienet osservata żieda fil- mortalità tal- fetu f’ dożi li kienu tossiċi għall- ommijiet (doża li tikkorrispondi għal- livell ta ’ espożizzjoni tal- plażma li hu 4 darbiet ogħla minn dak osservat fil- pazjenti).
Carcinogenicity studies have not yet been completed with dabigatran.
Ma sarux studji b’ dabigatran dwar il- karċinoġeneċità.
Capsule fill • Tartaric acid • Acacia • Hypromellose • Dimeticone 350 • Talc • Hydroxypropylcellulose
Mili tal- kapsula • Tartaric acid • Acacia • Hypromellose • Dimeticone 350 • Talc • Hydroxypropylcellulose
Capsule shell • Carrageenan • Potassium Chloride • Titanium Dioxide • Indigo Carmine (E132) • Sunset Yellow (E110) • Hypromellose • Water purified
Qoxra tal- kapsula • Carrageenan • Potassium Chloride • Titanium Dioxide • Indigo Carmine (E132) • Sunset Yellow (E110) • Hypromellose • Ilma ppurifikat
13 Black printing ink • Shellac • N-Butyl alcohol • Isopropyl alcohol • Industrial methylated spirit • Iron oxide black (E172) • Purified water • Propylene glycol
Shellac N- Butyl alcohol Isopropyl alcohol Industrial methylated spirit Iron oxide black (E172) Ilma ppurifikat Propylene glycol
Blister and bottle:
Folja u flixkun:
Once the bottle is opened, the product must be used within 30 days
Ġaladarba l- flixkun jinfetaħ, il- prodott għandu jintuża fi żmien 30 jum
Store in the original package in order to protect from moisture.
Aħżen fil- pakkett oriġinali sabiex tilqa ’ mill- umdità
Bottle:
Flixkun:
6.5 Nature and contents of container
14 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
Cartons containing 1, 3, or 6 blister strips (10 x 1, 30 x 1, 60 x 1) in perforated aluminium unit dose blisters.
Kaxxi tal- kartun li fihom 1, 3, jew 6 strixxi tal- folji (10 x 1, 30 x 1, 60 x 1) f’ folji tad- doża ta ’ l- unità ta ’ l - aluminju.
The blister consists of an aluminium lidding foil coated with polyvinylchloride-polyvinylacetate copolymer- acrylate (PVCAC acrylate) in contact with the product and an aluminium bottom foil with polyvinylchloride (PVC) in contact with the product.
Il- folja tikkonsisti f’ għatu tal- fojl miksi b’ polyvinylchloride- polyvinylacetate copolymer- acrylate (PVCAC acrylate) li jmiss mal- prodott, u fojl tal- qiegħ ta ’ l- aluminju bil- polyvinylchloride (PVC) li jmiss mal- prodott.
Polypropylene bottle with a screw cap containing 60 hard capsules.
Flixkun tal- polypropylene b’ għatu bil- kamini li fih 60 kapsuli iebsin.
When taking Pradaxa capsules out of the blister pack, the following instructions should be followed:
Meta tkun qed toħroġ il- kapsuli Pradaxa mill- pakkett tal- folji, jekk jogħġbok osserva l- istruzzjonijiet li ġejjin:
• The hard capsules should be taken out of the blister card by peeling off the backing foil. • The hard capsules should not be pushed through the blister foil. • The blister foil should only be peeled off, when a hard capsule is required.
• Il- kapsuli iebsin għandhom jinħarġu mill- kard tal- folja billi tqaxxar il- fojl ta ’ wara. • Il- kapsuli iebsin m’ għandux jiġu mbuttati minn ġol- fojl tal- folja. • Il- fojl tal- folja għandha titqaxxar biss meta jkollok bżonn ta ’ kapsula iebsa Pradaxa.
When taking a hard capsule out of the bottle, please observe the following instructions:
Meta tkun qed toħroġ kapsula iebsa mill- flixkun, jekk jogħġbok osserva l- istruzzjonijiet li ġejjin:
• The cap opens by pushing and turning.
• L- għatu jinfetaħ billi timbuttah u ddawru.
14 Any unused product or waste material should be disposed of in accordance with local requirements.
Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa ’ wara l- użu tal- prodott għandu jintrema kif jitolbu l - liġijiet lokali.
18 March 2008
18 ta 'Marzu, 2008
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/.
15 Dejta dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropea dwar il- Mediċini (EMEA) http: // www. emea. europa. eu /.
Pradaxa 110 mg hard capsules
Pradaxa 110 mg, kapsuli iebsin
Each hard capsule contains 110 mg of dabigatran etexilate (as mesilate) Excipients:
Sustanzi mhux attivi:
Each hard capsule contains 3 micrograms sunset yellow (E110)
Kull kapsula iebsa fiha 2 mikrogrammi ta ’ sunset yellow (E110)
Imprinted capsules with light blue, opaque cap and cream-coloured, opaque body of size 1 filled with yellowish pellets.
Kapsuli stampati b’ għatu blu ċar u opak, u korp opak mil- lewn il- krema ta ’ daqs 1 mimli bi pritkuni jagħtu fl- isfar.
The cap is imprinted with the Boehringer Ingelheim company symbol, the body with “ R110”.
L- għatu hu stampat bis- simbolu tal- kumpanija Boehringer Ingelheim, u l- korp stampat b ’ “ R110 ”.
Prevention of Venous Thromboembolism (VTE) in patients following elective knee replacement surgery:
Prevenzjoni ta ’ Tromboemboliżmu Venuż (VTE) fil- pazjenti wara operazzjoni mhux urġentitas- sostituzzjoni ta ’ l- irkoppa:
Treatment should be initiated orally within 1 – 4 hours of completed surgery with a single capsule and continuing with 2 capsules once daily thereafter for a total of 10 days.
Il- kura għandha tinbeda mill- ħalq fi żmien 1 – 4 sigħat mit- tmiem ta ’ l- operazzjoni, b’ kapsula waħda u mbagħad titkompla b’ 2 kapsuli darba kuljum wara dan il- perjodu, għal total ta ’ 10 ijiem.
Prevention of Venous Thromboembolism (VTE) in patients following elective hip replacement surgery:
Għall- prevenzjoni ta ’ Tromboemboliżmu Venuż (Venous Thromboembolism - VTE) fil- pazjenti wara operazzjoni mhux urġentitas- sostituzzjoni tal- ġenbejn:
16 In patients with moderate renal impairment (creatinine clearance 30-50 ml/ min), there is limited clinical experience.
17 F’ pazjenti b’ indeboliment renali moderat (tneħħija tal- krejatinina ta ’ 30- 50 ml/ min), hemm esperjenza klinika limitata.
These patients should be treated with caution.
Dawn il- pazjenti għandhom jiġu kkurati bl - attenzjoni.
Patients at risk for bleeding or patients at risk of overexposure, notably patients with moderate renal impairment (creatinine clearance 30 – 50 ml/ min), should be treated with caution (see sections 4.4 and 5.1).
Pazjenti li qegħdin f’ riskju għal fsad jew pazjenti f’ riskju ta ’ espożizzjoni eċċessiva, b’ mod speċjali pazjenti b’ indeboliment renali moderat (tneħħija tal- krejatinina ta ’ 30 – 50 ml/ min), għandhom ikunu kkurati bl - attenzjoni (ara sezzjonijiet 4. 4 u 5. 1).
Concomitant use of Pradaxa with Amiodarone:
18 L- użu fl- istess ħin ta ’ Pradaxa ma ’ Amiodarone:
17 Switching from parenteral anticoagulants treatment to Pradaxa:
Kif taqleb minn mediċina antikoagulanti parentali għal Pradaxa:
Agents that may enhance the risk of haemorrhage should not be administered concomitantly or should be administered with caution with Pradaxa (see section 4.5).
19 Mediċini li jistgħu jżidu r- riskju ta ’ emorraġija m’ għandhomx jingħataw fl- istess ħin, jew għandhom jingħataw bl- attenzjoni ma ’ Pradaxa (ara sezzjoni 4. 5).
18 Spinal anaesthesia/ epidural anaesthesia/ lumbar puncture:
Loppju fil- kolonna vertebrali/ loppju epidurali/ titqiba fis- sinsla:
The following treatments are not recommended concomitantly with Pradaxa: unfractionated heparins and heparin derivatives, low molecular weight heparins (LMWH), fondaparinux, desirudin, thrombolytic agents, GPIIb/ IIIa receptor antagonists, clopidogrel, ticlopidine, dextran, sulfinpyrazone and vitamin K antagonists.
Il- kuri li ġejjin m’ għandhomx mhumiex rakkomandati li jingħataw fl- istess ħin ma ’ Pradaxa: eparini mhux frazzjonati u derivattivi tal- heparin, eparini b’ piż molekulari baxx (low molecular weight heparins - LMWH), fondaparinux, desirudin, sustanzi trombolitiċi, antagonisti tar- riċettur GPIIb/ IIIa, clopidogrel, ticlopidine, dextran, sulfinpyrazone u antagonisti tal- vitamina K.
NSAIDs:
20 NSAIDs:
19 Dosing should be reduced to 150 mg Pradaxa daily in patients who received concomitantly dabigatran etexilate and amiodarone (see section 4.2).
Id- dożaġġ għandu jitnaqqas għal 150 mg ta ’ Pradaxa kuljum f’ pazjenti li jkunu rċivew dabigatran etexilate u amiodarone fl- istess ħin (ara sezzjoni 4. 2).
There are no adequate data from the use of Pradaxa in pregnant women.
M’ hemmx tagħrif biżżejjed mill- użu ta ’ Pradaxa f’ nisa tqal.
Lactation:
21 Treddigħ:
20 The table 1 shows the number (%) of patients experiencing bleeding events during the treatment period in the VTE prevention in the two pivotal clinical trials, according to dose.
Tabella 1 turi n- numru (%) ta ’ pazjenti li kellhom avvenimenti ta ’ fsad matul il- perjodu tal- kura fil - prevenzjoni ta ’ VTE fiż- żewġ provi kliniċi importanti ħafna, skond id- doża
(0.3) 7 (0.3)
7 (0. 3)
ALT findings the following laboratory chemistry
Is- sejbiet ta ’ l- ALT - dejta kimika tal- laboratorju
22 4.9 Overdose
4. 9 Doża eċċessiva
There is a clear correlation between plasma dabigatran concentration and degree of anticoagulant effect based on phase II studies.
24 Hemm korrelazzjoni ċara bejn il- konċentrazzjoni ta ’ dabigatran fil- plażma u l- grad ta ’ l- effett kontra l - koagulazzjoni, ibbażat fuq studji ta ’ fażi II.
23 Composite of major VTE (including PE and proximal DVT, whatever symptomatic or asymptomatic detected by routine venography) and VTE-related mortality constituted a secondary end-point and is considered of better clinical relevance.
Kompost ta ’ VTE totali (li jinkludi PE u DVT prossimali, kemm sintomatika jew asintomatika, osservata permezz ta ’ venografija ta ’ rutina) u mortalità marbuta ma ’ VTE, ikkostitwixxa punt aħħari sekondarju, u hu kkunsidrat li hu ta ’ rilevanza klinika aħjar.
Table 4:
25 Tabella 4:
N Incidences (%) Risk ratio over
N Inċidenzi (%) Proporzjon tar- riskju fuq enoxaparin
888 38 (4.3)
909 888 28 (3. 1) 38 (4. 3) 0. 78 1. 09
917 36 (3.9)
917 36 (3. 9)
527 20 (3.8)
506 527 13 (2. 6) 20 (3. 8) 0. 73 1. 08
511 18 (3.5)
511 18 (3. 5)
25 Distribution:
Distribuzzjoni:
Low (34-35%) concentration independent binding of dabigatran to human plasma proteins was observed.
Kien osservat li dabigtran jeħel ftit (34- 35% mal- proteini tal- plażma umana u dan hu indipendenti mill - konċentrazzjoni.
Elderly patients:
27 Pazjenti anzjani:
26 Ethnic origin:
Oriġini etnika:
27 Black printing ink • Shellac • N-Butyl alcohol • Isopropyl alcohol • Industrial methylated spirit • Iron oxide black (E172) • Purified water • Propylene glycol
Shellac N- Butyl alcohol Isopropyl alcohol Industrial methylated spirit Iron oxide black (E172) Ilma ppurifikat Propylene glycol
6.5 Nature and contents of container
29 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
28 Any unused product or waste material should be disposed of in accordance with local requirements.
Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa ’ wara l- użu tal- prodott għandu jintrema kif jitolbu l - liġijiet lokali
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/.
30 Dejta dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropea dwar il- Mediċini (EMEA) http: // www. emea. europa. eu /.
KG Binger Strasse 173 D-55216 Ingelheim am Rhein Germany
Boehringer Ingelheim Pharma GmbH & Co. KG Binger Strasse 173 55216 Ingelheim am Rhein Il- Ġermanja.
Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance, as described in version 5.0 dated 09 October 2008 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.
Sistema ta ’ farmakoviġilanza Id- Detentur ta ’ l- Awtorizzazzjoni tal- Manifattura jrid jiżgura li s- sistema ta ’ farmakoviġilanza, kif deskritt f’ verżjoni 5. 0 bid- data tad- 9 ta ’ Ottubru, 2008, ippreżentata f’ Modulu 1. 8. 1. ta ’ l- Applikazzjoni għall - Awtorizzazzjoni għat- Tqegħid fis- Suq, tkun implimentata u taħdem qabel u waqt li l- prodott jitpoġġa fuq is - suq.
Risk Management Plan The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 01 dated 11 January 2007 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.
Pjan dwar l- Immaniġġjar tar- Riskju Id- Detentur ta ’ l- Awtorizzazzjoni tal- Manifattura jrid ikun obbligat li jwettaq l- istudji u attivitajiet addizzjonali ta ’ farmakoviġilanza deskritti fil- Pjan tal- Farmakoviġilanza, kif maqbul f’ verżjoni 01 bid- data tal- 11 ta ’ Jannar, 2007, tal- Pjan dwar l- Immaniġġjar tar- Riskju (Risk Management Plan - RMP) ippreżentat f’ Modulu 1. 8. 2. ta ’ l- Applikazzjoni ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq, u kwalunkwe aġġornamenti sussegwenti tal- RMP li kienu maqbula mis- 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).
Skond il- Linja Gwida dwar is- Sistemi ta ’ l- Immaniġġjar tar- Riskju għal prodotti mediċinali għall- użu uman tas CHPM, l- RMP aġġornat għandu jkun sottomess fl- istess ħin mar- Rapport Perjodiku dwar l- Aġġornament tas- Sigurtà (Periodic Safety Update Report - PSUR) li jkun imiss.
In addition, an updated RMP should be submitted • 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
Flimkien ma ’ dan, RMP aġġornat għandu jkun sottomess • Meta dejta ġdida tkun irċevuta li jista ’ jkollha impatt fuq l- Ispeċifikazzjoni tas- Sigurtà kurrenti, fuq il - Pjan tal- Farmakoviġilanza jew fuq attivitajiet li jimminimizzaw ir- riskju. • Fi żmien 60 jum minn meta tintlaħaq milestone importanti (tal- farmakoviġilanza jew minimizzazzjoni tar- riskju) • Fuq talba tal- EMEA
FOLDING BOX FOR BLISTER for 75 mg
KAXXA LI TINTEWA GĦALL- FOLJA għal 75 mg
Pradaxa 75 mg hard capsules Dabigatran etexilate
Pradaxa 75 mg kapsuli iebsin Dabigatran etexilate
Each hard capsule contains 75 mg dabigatran etexilate (as mesilate)
Kull kapsula iebsa fiha 75 mg ta ’ dabigatran etexilate (bħala mesilate)
Contains sunset yellow (E 110) (see leaflet for further information)
Fih sunset yellow (E 110) (ara l- fuljett għal tagħrif addizzjonali)
10 x 1 hard capsules 30 x 1 hard capsules 60 x 1 hard capsules
10 x 1 kapsula iebsa 30 x 1 kapsula iebsa 60 x 1 kapsula iebsa
Oral use Do not chew Read the package leaflet before use
Użu orali Tomgħodx Aqra l- fuljett ta ’ tagħrif qabel l- użu.
EXP MM YYYY
JIS XX SSSS
Store in the original package in order to protect from moisture
Aħżen fil- pakkett oriġinali sabiex tilqa ’ mill- umdità.
Any unused product or waste material should be disposed of in accordance with local requirements
Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa ’ wara l- użu tal- prodott għandu jintrema kif jitolbu l - liġijiet lokali
FOLDING BOX FOR BLISTER for 110 mg
KAXXA LI TINTEWA GĦALL- FOLJA għal 110 mg
Pradaxa 110 mg hard capsules Dabigatran etexilate
Pradaxa 110 mg kapsuli iebsin Dabigatran etexilate
Each hard capsule contains 110 mg dabigatran etexilate (as mesilate)
Kull kapsula iebsa fiha 110 mg ta ’ dabigatran etexilate (bħala mesilate)
BLISTER FOR 75 mg
FOLJA GĦAL 75 mg
Peel back
Qaxxar lura
38 MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
40 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ IL- FOLJI JEW FUQ L- ISTRIXXI
BLISTER FOR 110 mg
FOLJA GĦAL 110 mg
39 PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE PACKAGING
41 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA JEW U FUQ IL- PAKKETT LI JMISS MAL- PRODOTT
FOLDING BOX AND LABEL FOR BOTTLE for 75 mg
KAXXA LI TINTEWA U TIKKETTA GĦALL- FLIXKUN għal 75 mg
Contains sunset yellow (E110) (see leaflet for further information)
Fih sunset yellow (E110) (ara l- fuljett għal tagħrif addizzjonali)
EXP MM YYYY Once opened, the product must be used within 30 days
JIS XX SSSS Ġaladarba jinfetaħ, il- prodott għandu jintuża fi żmien 30 jum
Any unused product or waste material should be disposed of in accordance with local requirements
Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa ’ wara l- użu tal- prodott għandu jintrema kif jitolbu l - liġijiet lokali.
Pradaxa 75 mg (only applicable for folding box, not applicable for bottle label)
Pradaxa 75 mg (japplika biss għall- folding box, mhux applikabbli għat- tikketta tal- flixkun)
41 PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE PACKAGING.
43 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA U FUQ IL- PAKKETT LI JMISS MAL- PRODOTT
FOLDING BOX AND LABEL FOR BOTTLE for 110 mg
KAXXA LI TINTEWA U TIKKETTA GĦALL- FLIXKUN għal 110 mg
Pradaxa 110 mg (only applicable for folding box, not applicable for bottle label)
Pradaxa 110 mg (japplika biss għall- folding box, mhux applikabbli għat- tikketta tal- flixkun)
Pradaxa 75 mg hard capsules Pradaxa 110 mg hard capsules dabigatran etexilate
Pradaxa 75 mg kapsuli iebsin Pradaxa 110 mg kapsuli iebsin dabigatran etexilate