qanastek/EMEA-V3 huggingface dataset:
d fibrin specific lytics (77.3%), no reperfusion (22%), fibrin-specific lytics (0.3%), primary PCI (0.4%)),
Fl- istratum definit minn qabel li qabbel fondaparinux ma 'plaċebo (i. e. pazjenti trattati b' sustanzi litiċi mhux speċifiċi għal- fibrin (77. 3%), ebda reperfużjoni (22%), sustanzi litiċi speċifiċi għal- fibrin (0. 3%), PCI primarja (0. 4%), l- inċidenza ta ’ mewt/ re- MI f’ Jum 30 tnaqqset sinifikament minn 14. 0% fuq plaċebo għal 11. 3% (hazard ratio 0. 80, 95% CI, 0. 69.
In the predefined stratum comparing fondaparinux
Fl- istratum definit minn qabel li kkumpara fondaparinux ma ’ UFH (pazjenti trattati b’ PCI primarja (58. 5%), sustanzi litiċi speċifiċi għal- fibrin (13%), sustanzi litiċi li mhumiex speċifiċi għal- fibrin (2. 6%) u ebda reperfużjoni (25. 9%), l- effetti ta ’ fondaparinux u UFH fuq l- inċidenza ta ’ mewt/ re- MI f’ Jum 30 ma kienux statistikament differenti: rispettivament, 8. 3% vs 8. 7% (hazard ratio 0. 94, 95% CI, 0. 79, 1. 11 p = 0. 460).
ris to UFH (patients treated with primary PCI (58.5%), fibrin-specific lytics (13%), non-fibrin-specific lytics (2.6%) and no reperfusion (25.9%)), the effects of fondaparinux and UFH on the incidence of
Madankollu, f’ dan l- istratum, fis- sottogrupp tal- popolazzjoni indikata li kienu qegħdin jirċievu trombolitiċi jew ebda reperfużjoni (i. e. pazjenti li mhumiex qegħdin jgħaddu minn PCI primarja), l- inċidenza ta ’ mewt/ re- MI fit- 30 jum tnaqqset sinifikament minn 14. 3%
ho death/ re-MI at Day 30 were not statistically different: respectively, 8.3% vs 8.7% (hazard ratio 0.94, 95% CI, 0.79, 1.11 p = 0.460).
t fuq UFH għal 11. 5% b’ fondaparinux (hazard ratio 0. 79, 95% CI, 0. 64, 0. 98, p = 0. 03).
ut death/ re-MI at Day 30 was significantly reduced from 14.3% on UFH to 11.5% with fondaparinux (hazard ratio 0.79, 95% CI, 0.64, 0.98, p = 0.03).
za L- inċidenza tal- mortalita ’ mill- kawżi kollha fit- 30 jum tnaqqset ukoll sinifikament minn 8. 9% fil -
The
riz grupp ta ’ kontroll għal 7. 8% fil- grupp fondaparinux (hazard ratio 0. 87, 95% CI, 0. 77; 0. 98, p = 0. 02).
e difference in mortality was statistically significant in stratum 1 (placebo comparator) but not in ng stratum 2 (UFH comparator).
Id- differenza fil- mortalità kienet statistikament sinifikanti f’ stratum 1 (komparatur plaċebo) imma mhux f’ stratum 2 (komparatur UFH).
The mortality benefit shown in the fondaparinux group was maintained until the end of follow-up at Day 180. lo In patients who were revascularised with a thrombolytic, fondaparinux significantly reduced the incidence of death/ re-MI at Day 30 from 13.6% for the control group to 10.9% (hazard ratio 0.79, no
Il- benefiċċji ta ’ mortalita ’ li ntwera fil grupp fondaparinux
95%CI, 0.68; 0.93, p = 0.003).
to baqgħet hekk sa l- aħħar ta ’ l- insegwiment fil- 180 jum.
Among patients initially not reperfused, the incidence of death/ re-MI at Day 30 was significantly reduced from 15% for the control group to 12.1% for the fondaparinux group (hazard ratio 0.79, 95% CI, 0.65; 0.97, p = 0.023).
aw F’ pazjenti li kienu rivaskularizzati b’ sustanza trombolitika, fondaparinux naqqas l- inċidenza ta ’ mewt/ re- MI b’ mod sinifikanti fit- 30 jum minn 13. 6% fil- grupp ta ’ kontroll għal 10. 9% (hazard ratio 0. 79, 95% CI, 0. 68; 0. 93, p = 0. 003).
In patients treated with primary PCI, the incidence of death/ re-MI at Day 30 was not statistically different between the two groups [6.0% in fondaparinux ct
Fost il- pazjenti li għall- bidu ma kienux riperfużi, l- inċidenza ta ’ mewt/ re- MI tnaqqset b’ mod sinifikanti fit- 30 jum minn 15% fil- grupp ta ’ kontroll għal 12. 1% fil -
group vs 4.8% in the control group; hazard ratio 1.26, 95% CI, 0.96, 1.66)]. du
x grupp fondaparinux (hazard ratio 0. 79, 95% CI, 0. 65; 0. 97, p = 0. 023).
By Day 9, 1.1% of patients treated with fondaparinux and 1.4% of control patients experienced a severe haemorrhage.
du primarja l- inċidenza ta ’ mewt/ re- MI fit- 30 jum ma kienitx statistikament differenti bejn iż- żewġ gruppi (6. 0% fil- grupp fondaparinux kontra 4. 8% fil- grupp ta ’ kontroll; hazard ratio 1. 26, 95% CI, 0. 96, 1. 66).
In patients given a thrombolytic, severe haemorrhage occurred in 1.3% of the ro
ħa
fondaparinux patients and in 2.0% of controls.
Mad- 9 jum, 1. 1% ta ’ pazjenti trattati b’ fondaparinux u 1. 4% tal- pazjenti taħt kontroll esperjenzaw ’ g emorraġija qawwija.
In patients initially not reperfused, the incidence of severe haemorrhage was 1.2% for fondaparinux vs 1.5% for controls.
F’ pazjenti li ħadu sustanza trombolitika, emorraġija qawwija seħħet f’ 1. 3% tal - pazjenti b’ fondaparinux u f’ 2. 0% f’ pazjenti taħt kontroll.
For patients receiving primary lP
F’ pazjenti li għall- bidu ma kienux riperfużi, im
PCI, the incidence of severe haemorrhage was 1.0% for fondaparinux and 0.4% for controls.
F’ pazjenti li kienu fuq PCI primarja, l- inċidenza ta ’ emorraġija qawwija kienet ta ’ 1. 0% f’ dawk fuq fondaparinux u 0. 4% f’ dawk taħt kontroll. li l
The efficacy findings and results on severe haemorrhage were consistent across prespecified na
Dak li nstab dwar effikaċja u r- riżultati dwar emorraġija qawwija kienu konsistenti fis- sottogruppi speċifikati minn qabel, bħall- anzjani, pazjenti b’ indeboliment tal- kliewi, t- tip ta ’ impedituri na
subgroups such as elderly, renally impaired patients, type of concomitant platelet aggregation inhibitors (aspirin, thienopyridines). ici
konkomitanti kontra l- aggregazzjoni tal- plejtlets (aspirina, thienopyridines).
5.2 Pharmacokinetic properties ed
5. 2 Tagħrif farmakokinetiku iċi
Absorption After subcutaneous dosing, fondaparinux is completely and rapidly absorbed (absolute bioavailability 100%).
Wara dożaġġ subkutanju, fondaparinux huwa assorbit kompletament u malajr (biodisponibilità assoluta 100%).
Following a single subcutaneous injection of fondaparinux 2.5 mg to young healthy subjects, M
Wara injezzjoni subkutanja waħda ta ’ fondaparinux 2. 5 mg lil suġġetti żgħar u f’ saħħithom, konċentrazzjoni massima fil- plażma (medja Cmax = 0. 34 mg/ l) huwa ottenut 2 sigħat wara tm
peak plasma concentration (mean Cmax = 0.34 mg/ l) is obtained 2 hours post-dosing.
d- doża.
Plasma concentrations of half the mean Cmax values are reached 25 minutes post-dosing.
Konċentrazzjonijiet fil- plażma ta ’ nofs il- medja tal- valuri Cmax jintlaħqu 25 minuta wara d - doża. ot
In elderly healthy subjects, pharmacokinetics of fondaparinux are linear in the range of 2 to 8 mg by subcutaneous route.
F’ suġġetti anzjani f’ saħħithom, il- farmakokinetiċi ta ’ fondaparinux huma linejari ta ’ bejn 2 sa 8 mg mogħtija b’ mod subkutanju.
Following once daily subcutaneous dosing, steady state of plasma levels is obtained after 3 to 4 days with a 1.3-fold increase in Cmax and AUC.
3 sa 4 t’ ijiem b’ żieda ta ’ 1. 3- il darba fis- Cmax u AUC.
20 Mean (CV%) steady state pharmacokinetic parameters estimates of fondaparinux in patients undergoing hip replacement surgery receiving fondaparinux 2.5 mg once daily are:
Stimi tal- parametri farmakokinetiċi medji fissi (CV%) ta ’ fondaparinux f’ pazjenti għaddejjin minn Pr
Cmax (mg/ l) - 0.39 (31%), Tmax (h) - 2.8 (18%) and Cmin (mg/ l) -0.14 (56%).
Cmax (mg/ l) – 0. 39 (31%), Tmax (h) – 2. 8 (18%) u Cmin (mg/ l) - 0. 14 (56%).
In hip fracture patients, associated with their increased age, fondaparinux steady state plasma concentrations are:
F’ pazjenti bi frattura fil- ġenb, assoċjata ma ’ żieda fl- eta` tagħhom, il- konċentrazzjonijiet fissi ta ’ fondaparinux fil- plażma huma:
Cmax (mg/ l) - 0.50 (32%), Cmin (mg/ l) - 0.19 (58%).
Cmax (mg/ l) – 0. 50 (32%), Cmin (mg/ l) – 0. 19 (58%).
Distribution The distribution volume of fondaparinux is limited (7-11 litres).
22 Il- volum ta ’ distribuzzjoni ta ’ fondaparinux huwa limitat (7- 11 litri).
In vitro, fondaparinux is highly and specifically bound to antithrombin protein with a dose-dependant plasma concentration binding
In vitro fondaparinux huwa marbut ħafna u speċifikament mal- proteina antitrombin b’ mod dipendenti mad- doża u mal - konċentrazzjoni fil- plażma (98. 6% sa 97. 0% fil- firxa tal- konċentrazzjoni bejn 0. 5 sa 2 mg/ l).
e significantly to other plasma proteins, including platelet factor 4 (PF4).
Fondaparinux ma jorbotx b’ mod sinifikattiv ma ’ proteini tal- plażma oħrajn, inklużi fattur 4 tal - plejtlets (PF4).
ris Since fondaparinux does not bind significantly to plasma proteins other than ATIII, no interaction with other medicinal products by protein binding displacement are expected.
Peress illi fondaparinux ma jintrabatx b’ mod sinifikanti ma ’ proteini tal- plażma oħrajn minbarra
ho Metabolism Although not fully evaluated, there is no evidence of fondaparinux metabolism and in particular no
t ATIII, mhux mistennija l- ebda interazzjoni ma ’ prodotti mediċinali oħrajn li jikkawżaw spostament
ut evidence for the formation of active metabolites.
za ta ’ rbit ta ’ proteini.
ra Fondaparinux does not inhibit CYP450s (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4) in vitro.
to Fondaparinux ma jinibixxix CYP450s (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1
Thus, fondaparinux is not expected to interact with other medicinal products in vivo by inhibition of CYP-mediated metabolism.
Għalhekk fondaparinux mhux mistenni li jkollu interazzjoni ma ’ prodotti mediċinali in vivo bl- inibizzjoni ta ’ metaboliżmu medjat- CYP.
e Excretion/ Elimination
Eskrezzjoni/ Eliminazzjoni
ng
x Il- half life ta ’ l- eliminazzjoni (t1/ 2) hija madwar 17- il siegħa f’ suġġetti f’ saħħithom żgħażagħ u
The elimination half-life (t½) is about 17 hours in healthy young subjects and about 21 hours in healthy elderly subjects.
du madwar 21 siegħa f’ suġġetti anzjani f’ saħħithom.
Fondaparinux is excreted to 64 – 77% by the kidney as unchanged compound. lo Special populations no
64 – 77% ta ’ fondaparinux huwa mneħħi mill - kilwa bħala sustanza mhux mibdula. ħa Popolazzjonijiet speċjali: ’ g Pazjenti pedjatriċi - Fondaparinux ma ġiex investigat fuq din il- popolazzjoni. im
Paediatric patients - Fondaparinux has not been investigated in this population.
Pazjenti anzjani - Il- funzjoni renali tista ’ tonqos bl- età u għalhekk, il- ħila biex jitneħħa fondaparinux tista ’ tkun imnaqqsa fl- anzjani.
Elderly patients - Renal function may decrease with age and thus, the elimination capacity for ct
F’ pazjenti > 75 sena li jgħaddu minn kirurġija ortopedika, il- clearance tal- plażma ġiet stmata bħala 1. 2 sa 1. 4 drabi iktar baxxa milli f’ pazjenti ta ’ < 65 sena. li l
In patients > 75 years undergoing orthopaedic surgery, the estimated plasma clearance was 1.2 to 1.4 times lower than in patients < 65 years. du
Indeboliment renali - Pparagunati ma ’ pazjenti b’ funzjoni renali normali (clearance tal- krejatinina > 80 ml/ min), il- clearance tal- plażma hija minn 1. 2 sa 1. 4 drabi iktar baxxa f’ pazjenti b’ indeboliment na
Renal impairment - Compared with patients with normal renal function (creatinine ro
renali ħafif (clearance tal- krejatinina minn 50 sa 80 ml/ min) u fuq medja ta ’ darbtejn iktar baxxa f’ pazjenti b’ indeboliment renali moderat (clearance tal- krejatinina minn 30 sa 50 ml/ min).
clearance > 80 ml/ min), plasma clearance is 1.2 to 1.4 times lower in patients with mild renal impairment (creatinine clearance 50 to 80 ml/ min) and on average 2 times lower in patients with lP
F’ indeboliment renali sever (clearance tal- krejatinina < 30 ml/ min), il- clearance tal- plażma hi iċi
moderate renal impairment (creatinine clearance 30 to 50 ml/ min).
madwar 5 darbiet iktar baxxa milli meta jkun hemm funzjoni renali normali.
Associated terminal half-life values were 29 h in moderate and 72 h in patients with na
Valuri tal- half life terminali assoċjati kienu 29 h fil- moderati u 72 h f’ pazjenti b’ indeboliment renali akut. ed
severe renal impairment.
Sess - Ma ġew osservati l- ebda differenzi minħabba s- sess wara li sar aġġustament tal- piż tal- ġisem. tm
Gender - No gender differences were observed after adjustment for body weight. ici
Razza - Differenzi farmakokinetiċi minħabba razza ma ġewx studjati prospettivament.
Race - Pharmacokinetic differences due to race have not been studied prospectively.
Iżda, studji magħmula fuq suġġetti f’ saħħithom Ażjatiċi (Ġappuniżi) ma wrewx profil farmakokinetiku differenti pparagunat ma ’ suġġetti f’ saħħithom Kawkasi.
However, studies ed
Bl- istess mod, ma ġewx osservati differenzi fil - ot
M
clearance tal- plażma bejn pazjenti suwed u Kawkasi li kienu għaddejjin minn kirurġija ortopedika. od
Body weight - Plasma clearance of fondaparinux increases with body weight (9% increase per 10 kg).
Pr
Hepatic impairment - Fondaparinux pharmacokinetics has not been evaluated in hepatic impairment.
Indeboliment tal- fwied - Il- farmakokinetika ta ’ fondaparinux ma ġietx evalwata f’ indeboliment tal - fwied.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, and genotoxicity.
Tagħrif ta ’ qabel l- użu kliniku magħmul fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku minn dożi ripetuti u effett tossiku fuq il- ġeni ma turi l- ebda periklu speċjali għall- bnedmin.
Animal studies are insufficient with respect to effects on toxicity to reproduction because of limited exposure.
23 Studji fuq l- annimali huma insuffiċjenti rigward l- effetti tossiku fuq is- sistema riproduttiva minħabba espożizzjoni limitata.
Sodium chloride Water for injections
t za Sodium Chloride Ilma għal injezzjonijiet
ris Hydrochloric acid Sodium hydroxide
riz Hydrochloric acid Sodium hydroxide
ho 6.2 Incompatibilities
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
ra 6.3 Shelf life
x du Sentejn
e 2 years. ng If fondaparinux sodium is added to a 0.9% saline minibag it should ideally be infused immediately, but can be stored at room temperature for up to 24 hours. lo 6.4 Special precautions for storage no
Jekk fondaparinux sodium jiġi miżjud ma ’ saline 0. 9% f’ borża żgħira, għandu idejalment jingħata ħa permezz ta ’ infużjoni immedjatament, imma jista ’ jinħażen f’ temperatura ambjentali sa 24 siegħa. ’ g 6. 4 Prekawzjonijiet speċjali għall- ħażna im
Do not freeze.
Tiffriżahx
6.5 Nature and contents of container ct
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih li l
Type I glass barrel (1 ml) affixed with a 27 gauge x 12.7 mm needle and stoppered with a bromobutyl du
Tubu ċilindriku tal- ħġieġ Tip1 (1 ml) mehmuż b ’ labra kalibru 27 ta ’ 12. 7 mm u magħluqa b’ tapp planġer tal- bromobutyl jew chlorobutyl elastomer. na
or chlorobutyl elastomer plunger stopper. ro
Quixidar huwa disponibbli f’ daqsijiet ta ’ pakketti ta ’ 2, 7, 10 u 20 siringi mimlija lesti b’ sistema ta ’ sikurezza awtomatika blu.
Not all pack sizes may be marketed. lP
kummerċjali. ed
6.6 Special precautions for disposal and other handling na
6. 6 Struzzjonijiet għall- użu u maniġġar u għar- rimi
The subcutaneous injection is administered in the same way as with a classical syringe.
L- amministrazzjoni ġol - tm
Intravenous administration should be through an existing intravenous line either directly or using a small volume (25 or 50ml) 0.9% saline minibag. ici
vina għandha ssir minn ġo linja intravenuża diġà eżistenti, direttament jew permezz ta ’ volum żgħir (25 ml jew 50 ml) ta ’ 0. 9% saline f’ borża żgħira. ot
Parenteral solutions should be inspected visually for particulate matter and discoloration prior to ed
Soluzzjonijiet parenterali għandhom jiġu miflija għal frak u telf ta ’ kulur qabel jingħataw. od
Instruction on self-administration by subcutaneous injection is included in the Package Leaflet.
Struzzjonijiet għal amministrazzjoni personali permezz ta ’ injezzjoni sub- kutanja huma inklużi fil - fuljett ta ’ tagħrif.
The needle protection system of the Quixidar pre-filled syringe has been designed with an automatic safety system to protect from needle stick injuries following injection.
Is- sistema ta ’ protezzjoni tal- labra tas- siringi mimlija lesti Quixidar giet diżinjata b’ sistema ta ’ sikurezza awtomatika biex tipproteġi minn feriti bil- labra wara l- injezzjoni.
22 7.
24 7.
d 8.
t za 8.
MARKETING AUTHORISATION NUMBERS
NUMRUI TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
e EU/ 1/ 02/ 207/ 001-004
riz EU/ 1/ 02/ 206/ 001- 004
ris ho 9.
to 9.
Date of first authorisation:
aw Data ta ’ l- ewwel awtorizzazzjoni:
21 March 2002
21 ta ’ Marzu 2002 Data ta ’ l- aħħar tiġdid:
ra 10.
x du 10.
e Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu ct du ro lP na ici ed M
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar ħa il- mediċini (EMEA) http: // www. emea. europa. eu ’ g im li l na iċi ed tm ot od Pr
Quixidar 5 mg/ 0.4 ml solution for injection, pre-filled syringe.
Quixidar 5 mg/ 0. 4 ml soluzzjoni għall- injezzjoni, siringa mimlija lesta
Each pre-filled syringe contains 5 mg of fondaparinux sodium in 0.4 ml solution for injection.
Kull siringa mimlija lesta fiha 5mg ta ’ fondaparinux sodium f ’ 0. 4 ml ta ’ soluzzjoni għall- injezzjoni.
d Excipient(s):
t za Sustanza( i):
Contains less than 1 mmol of sodium (23 mg) per dose, and therefore is essentially
Kull doża fiha anqas minn 1 mmol ta ’ sodium (23 mg) u għalhekk il- prodott huwa essenzjalment mingħajr sodium.
ris For a full list of excipients, see section 6.1.
riz Għal lista sħiħa ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
ut Solution for injection.
aw Soluzzjoni għall- injezzjoni.
The solution is a clear and colourless to slightly yellow liquid.
Is- soluzzjoni huwa likwidu ċar u mingħajr kulur għal ftit safrani.
ra 4.
x 4.
Treatment of acute Deep Vein Thrombosis (DVT) and treatment of acute Pulmonary Embolism (PE), lo except in haemodynamically unstable patients or patients who require thrombolysis or pulmonary embolectomy. no
du 4. 1 Indikazzjonijiet terapewtiċi ħa It- trattament ta ’ Trombożi akuta f’ Vina Fonda (DVT) u t- trattament ta ’ Emboliżmu Pulmonari (PE) akut, ħlief f’ pazjenti li huma emodinamikament instabli jew f’ pazjenti li għandhom bżonn tromboliżi ’ g jew embolektomija. im
The recommended dose of fondaparinux is 7.5 mg (patients with body weight ≥ 50, ≤ 100kg) once ct
Id- doża rakkomandata ta ’ fondaparinux hija ta ’ 7. 5 mg (f ’ pazjenti b’ piż ta ’ ≥ 50, ≥ 100 kg) darba kuljum li tingħata b’ injezzjoni subkutanja.
For patients with body weight < 50 kg, the du
Għal pazjenti b ’ piż ta ’ < 50 kg, id- doża rakkomandata hija li l
recommended dose is 5 mg.
ta ’ 5 mg.
For patients with body weight > 100 kg, the recommended dose is 10 mg.
Għal pazjenti b ’ piż ta ’ > 100 kg, id- doża rakkomandata hija ta ’ 10 mg. na
Treatment should be continued for at least 5 days and until adequate oral anticoagulation is established ro
It- trattament għandu jitkompla għal mill- inqas 5 t’ ijiem u sakemm antikoagulazzjoni adekwata b’ antikoagulant orali tkun stabbilita b’ mediċina orali (International Normalised Ratio 2 sa 3).
Concomitant oral anticoagulation treatment should be initiated as soon as possible and usually within 72 hours.
żmien 72 siegħa.
trials was 7 days and the clinical experience from treatment beyond 10 days is limited.
Il- tul medju tat- trattament fi studji kliniċi kien ta ’ 7 t’ ijiem u l- esperjenza klinika mit- trattament għal aktar minn 10 t’ ijiem hija limitata. ed
Special populations na
Popolazzjonijiet speċjali tm
Elderly patients - No dosing adjustment is necessary.
Pazjenti anzjani - M’ hemmx bżonn aġġustament fid- doża.
In patients ≥ 75 years, fondaparinux should be used with care, as renal function decreases with age (see section 4.4). ici
Għandha tittieħed attenzjoni bl- użu ta ’ fondaparinux f’ pazjenti ≥ 75 sena għaliex il- funzjoni renali tonqos bl- eta` (ara sezzjoni 4. 4). ot
Renal impairment - Fondaparinux should be used with caution in patients with moderate renal ed
Indeboliment tal- kliewi - Għandha tittieħed attenzjoni bl- użu ta ’ fondaparinux f’ pazjenti b’ indeboliment moderat tal- kliewi (ara sezzjoni 4. 4). od
There is no experience in the subgroup of patients with both high body weight (> 100 kg) and moderate M
F’ dan is- sub- grupp, wara Pr
In this subgroup, after an initial 10 mg daily dose, a reduction of the daily dose to 7.5 mg may be considered, based on pharmacokinetic modelling (see section 4.4).
doża fil- bidu ta ’ 10 mg kuljum, tista ’ tiġi kunsidrata, meta bażata fuq mudell farmakokinetiku, tnaqqis tad- doża għal 7. 5 mg kuljum (ara sezzjoni 4. 4).
Fondaparinux should not be used in patients with severe renal impairment (creatinine clearance < 30 ml/ min) (see section 4.3).
Fondaparinux m’ għandux jintuża f’ pazjenti b’ indeboliment sever tal- kliewi (clearance tal- krejatinina < 30ml/ min) (ara sezzjoni 4. 3).
24 Hepatic impairment - No dosing adjustment is necessary.
26 Indeboliment tal- fwied - M’ hemmx bżonn aġġustament tad- doża.
In patients with severe hepatic impairment, fondaparinux should be used with care (see section 4.4).
(ara sezzjoni 4. 4)
Paediatric population - Fondaparinux is not recommended for use in children below 17 years of age due to a lack of data on safety and efficacy.
Popolazzjonijiet pedjatriċi - Fondaparinux mhux rakkomandat għall- użu fi tfal ta ’ taħt is- 17- il sena minħabba nuqqas ta ’ tagħrif dwar is- sikurezza u l- effikaċja.
Method of administration Fondaparinux is administered by deep subcutaneous injection while the patient is lying down.
Metodu ta ’ amministrazzjoni
Sites of administration should alternate between the left and the right anterolateral and left and right
t Fondaparinux huwa amministrat permezz ta ’ injezzjoni subkutanja fonda waqt li l- pazjent ikun
d posterolateral abdominal wall.
za mindud.
To avoid the loss of medicinal product when using the pre-filled
Biex tevita telf tal- prodott
The whole length of the needle should be inserted perpendicularly into a skin fold held between the thumb and the forefinger;
riz mediċinali waqt l- użu ta ’ l- injezzjoni mimlija lesta m’ għandekx tespella l- buzzieqa ta ’ l- arja minn ġos- siringa qabel l- injezzjoni.
ris the skin fold should be held throughout the injection.
It- tul kollu tal- labra għandu jiġi inserit b’ mod perpendikulari f’ tinja tal - ġilda miżmuma bejn is- saba ’ l- kbir u l- werrej; it- tinja tal- ġilda għandha tinżamm matul l- injezzjoni.
ho For additional instructions for use and handling and disposal see section 6.6.
to Għal aktar struzzjonijiet għall- użu u maniġġar u għar- rimi ara sezzjoni 6. 6.
4.3 Contraindications
aw 4. 3 Kontra- indikazzjonijiet
- hypersensitivity to the active substance or to any of the excipients
- Sensittività eċċessiva għal fondaparinux jew għal xi sustanzi mhux attivi
- active clinically significant bleeding
- Fsada attiva li tkun klinikament sinifikattiva
- acute bacterial endocarditis
- Endokardite akuta kawżata minn batterji
- severe renal impairment defined by creatinine clearance < 30 ml/ min.
- Indeboliment sever tal- kliewi definit bi clearance tal- krejatinina ta ’ < 30 ml/ min.
Special warnings and precautions for use
ħa 4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu ’ g Fondaparinux huwa intenzjonat għall- użu subkutanju biss.
Fondaparinux is intended for subcutaneous use only.
Tinjettax fil- muskoli. im
and no experience in patients requiring thrombolysis, embolectomy or insertion of a vena cava filter.
Hemm esperjenza limitata mit- trattament b ’ fondaparinux f’ pazjenti li m’ humiex stabbli emodinamikament u m’ hemm l- ebda esperjenza f’ pazjenti li għandhom bżonn tromboliżi, embolektomija jew li jiddaħħal filter ġol- vena cava. li l
Haemorrhage Fondaparinux should be used with caution in patients who have an increased risk of haemorrhage, ct
Emorraġija Fondaparinux għandu jintuża b’ attenzjoni f’ pazjenti b’ riskju ogħla ta ’ emorraġija, bħal dawk b’ mard na
such as those with congenital or acquired bleeding disorders (e. g. platelet count < 50,000/ mm3), active ulcerative gastrointestinal disease and recent intracranial haemorrhage or shortly after brain, spinal or du
ta 'fsada kemm konġenitali jew akkwistati (es. għadd ta ’ plejtlets < 50, 000 / mm3), mard gastro - intestinali ulċerattiv attiv u emorraġija riċenti fil- kranju jew ftit wara kirurgija fil- moħħ, is- sinsla jew l- għajnejn u fi gruppi speċjali ta ’ pazjenti li jissemmew hawn taħt. iċi
ophthalmic surgery and in special patient groups as outlined below. ro
Bħal kull antikoagulant ieħor, fondaparinux għandu jintuża b’ attenzjoni f’ pazjenti li għaddew minn ed
As for other anticoagulants, fondaparinux should be used with caution in patients who have undergone recent surgery (< 3 days) and only once surgical haemostasis has been established. lP
kirurġija riċenti (< 3 t’ ijiem) u jintuża biss meta jiġi stabbilit emostasi kirurġiku.
Agents that may enhance the risk of haemorrhage should not be administered concomitantly with fondaparinux.
Aġenti li jistgħu jżidu r- riskju ta ’ emorraġija m’ għandhomx jiġu amministrati flimkien ma ’ tm
heparin, heparinoids, or Low Molecular Weight Heparin (LMWH).
Dawn l- aġenti jinkludu desirudin, aġenti fibrinolitiċi, antagonisti ta ’ riċetturi GP IIb/ IIIa, heparin, heparinoids, jew Heparin ta ’ Piż Molekulari Baxx (LMWH).
During treatment of VTE, concomitant therapy with vitamin K antagonist should be administered in accordance with the information of Section 4.5.
Waqt trattament ta ’ VTE, f’ istess ħin għandha tingħata terapija b’ antagonista ta ’ vitamina K skond l- informazzjoni f ’ ot
sulfinpyrazone, ticlopidine or clopidogrel), and NSAIDs should be used with caution.
Fil- każ li jkun essenzjali li od
If co- administration is essential, close monitoring is necessary. ed
jingħataw flimkien, jkun hemm bżonn ta ’ osservazzjoni mill- qrib.
Spinal / Epidural anaesthesia In patients receiving fondaparinux for treatment of VTE rather than prophylaxis, spinal/ epidural M
Anestesija Spinali / Epidurali Pr
anaesthesia in case of surgical procedures should not be used.
F’ pazjenti li jieħdu fondaparinux għal trattament ta ’ VTE u mhux bħala profilassi, m’ għandiex tintuża anestesija spinali/ epidurali fil- każ ta ’ kirurġija.
Elderly patients The elderly population is at increased risk of bleeding.
Pazjenti anzjani In- nies anzjani huma f’ riskju akbar li jitilfu d- demm.
As renal function generally decreases with age, elderly patients may show reduced elimination and increased exposure of fondaparinux (see section 5.2).
Il- funzjoni renali ġeneralment tonqos bl- eta`, u għalhekk pazjenti anzjani jistgħu jkollhom eliminazzjoni mnaqqsa u esponiment akbar ta ’ fondaparinux (ara sezzjoni 5. 2).
Incidences of bleeding events in patients receiving the recommended regimen in the treatment of DVT or PE and aged< 65 years, 65-75 and > 75 years were 3.0%, 4.5% and 6.5%, respectively.
Każi ta ’ fsada f’ pazjenti li kellhom < 65 sena, 65- 75 sena u > 75 sena,
The corresponding incidences in patients receiving the recommended regimen of enoxaparin in the
27 li jieħdu d- dożaġġ rakkomandat fit- trattament ta ’ DVT jew PE u kienu ta ’ 3. 0%, 4. 5% and 6. 5%, rispettivament.
25 treatment of DVT were 2.5%, 3.6% and 8.3% respectively, while the incidences in patients receiving the recommended regimen of UFH in the treatment of PE were 5.5%, 6.6% and 7.4%, respectively.
Meta maqsumin f’ gruppi fl- istess mod, il- każi f’ pazjenti li jieħdu d- dożaġġ rakkomandat ta ’ enoxaparin fit- trattament ta ’ DVT kienu ta ’ 2. 5%, 3. 6% u 8. 3% rispettivament, u l - każi f’ pazjenti li jieħdu d- dożaġġ rakkomandat ta ’ UFH fit- trattament ta ’ PE kienu ta ’ 5. 5%, 6. 6% and 7. 4% rispettivament.
Fondaparinux should be used with caution in elderly patients (see section 4.2).
Fondaparinux għandu jintuża b’ attenzjoni f ’ pazjenti anzjani (ara sezzjoni 4. 2).
Low body weight Clinical experience is limited in patients with body weight < 50 kg.
za L- esperjenza klinika hija limitata f’ pazjenti b ’ piż < 50 kg.
Fondaparinux should be used with caution at a daily dose of 5 mg in this population (see sections 4.2 and 5.2).
Fondaparinux f’ doża ta ’ 5mg kuljum għandu jintuża b’ attenzjoni f ’ dan il- grupp ta ’ pazjenti (ara sezzjoni 4. 2 u 5. 2).
d The risk of bleeding increases with increasing renal impairment.
riz Indeboliment tal- kliewi Żieda fl- indeboliment tal- kliewi iżid ir- riskju ta ’ fsada.
Fondaparinux is known to be
Huwa magħruf li fondaparinux jitneħħa fil -
e excreted mainly by the kidney.
to biċċa l- kbira mill- kliewi.
Incidences of bleeding events in patients receiving the recommended regimen in the treatment of DVT or PE with normal renal function, mild renal impairment, moderate
Każi ta ’ fsada f’ pazjenti li għandhom indeboliment renali ħafif, indeboliment renali moderat u indeboliment renali sever, li jieħdu d- dożaġġ rakkomandat fi trattament
ris renal impairment and severe renal impairment were 3.0% (34/ 1132), 4.4% (32/ 733), 6.6% (21/ 318), and 14.5% (8/ 55) respectively.
aw ta ’ DVT jew PE, kienu ta ’ 3. 0% (34/ 1132), 4. 4% (32/ 733), 6. 6% (21/ 318), u 14. 5% (8/ 55), rispettivament.
The corresponding incidences in patients receiving the recommended
Meta maqsumin f’ gruppi fl- istess mod, il- każi f’ pazjenti li jieħdu d- dożaġġ rakkomandat ta ’ enoxaparin fit- trattament ta ’ DVT kienu ta ’ 2. 3% (13/ 559), 4. 6% (17/ 368), 9. 7% (14/ 145) u 11. 1% (2/ 18), rispettivament, u l- każi f’ pazjenti li jieħdu d- dożaġġ rakkomandat ta ’
ho regimen of enoxaparin in the treatment of DVT were 2.3% (13/ 559), 4.6% (17/ 368), 9.7% (14/ 145) and 11.1% (2/ 18) respectively, and in patients receiving the recommended regimen of unfractionated heparin in the treatment of PE were 6.9% (36/ 523), 3.1% (11/ 352), 11.1% (18/ 162) and 10.7% (3/ 28),
x eparina mhux frazzjonata fit- trattament ta ’ PE kienu ta ’ 6. 9% (36/ 523), 3. 1% (11/ 352), 11. 1%
ut respectively.
du (18/ 162) and 10. 7% (3/ 28), rispettivament.
ra Fondaparinux is contra-indicated in severe renal impairment (creatinine clearance < 30 ml/ min) and should be used with caution in patients with moderate renal impairment (creatinine clearance 30-50 ml/ min).
Fondaparinux huwa kontra- indikat f’ indeboliment renali sever (clearance tal - krejatinina < 30ml/ min) ħa u jrid jintuża b’ attenzjoni f ’ pazjenti f’ indeboliment renali moderat (clearance tal - krejatinina 30- 50 ml/ min).
The duration of treatment should not exceed that evaluated during clinical trial (mean 7 days)
It- tul tat- trattament m ’ għandux jiżboq dak studjat waqt il- prova klinika (medda ta ’ 7 t’ ijiem) ’ g (ara sezzjonijiet 4. 2, 4. 3 u 5. 2). im
e (see sections 4.2, 4.3 and 5.2). ng There is no experience in the subgroup of patients with both high body weight (> 100 kg) and moderate renal impairment (creatinine clearance 30-50 ml/ min).
M’ hemmx esperjenza fis- sub- grupp ta ’ pazjenti li għandhom kemm piż għoli (> 100 kg), kif ukoll indeboliment renali moderat (clearance tal - krejatinina 30- 50 ml/ min).
Fondaparinux should be used with care in these lo patients.
Fondaparinux għandu jintuża b’ attenzjoni f’ dawn il- pazjenti.
After an initial 10 mg daily dose, a reduction of the daily dose to 7.5 mg may be considered, based on pharmacokinetic modelling (see section 4.2). no
Wara doża fil- bidu ta ’ 10 mg kuljum, tista ’ tiġi kunsidrata meta bażata fuq mudell farmakokinetiku, tnaqqis fid- doża għal 7. 5 mg kuljum, (ara sezzjoni 4. 2). li l
Severe hepatic impairment The use of fondaparinux should be considered with caution because of an increased risk of bleeding due to a deficiency of coagulation factors in patients with severe hepatic impairment (see section 4.2). ct du
Fondaparinux għandu jintuża b’ attenzjoni f ’ pazjenti b’ indeboliment sever tal- fwied għaliex hemm riskju ogħla ta ’ fsada minħabba nuqqas ta ’ fatturi ta ’ koagulazzjoni (ara sezzjoni 4. 2). iċi
Patients with Heparin Induced Thrombocytopenia Fondaparinux does not bind to platelet factor 4 and does not cross-react with sera from patients with Heparin Induced Thrombocytopenia (HIT) type II.
Pazjenti bi tromboċitopenja indotta bl ’ Eparina Fondaparinux ma jintrabatx ma ’ l- fattur 4 tal- plejtlets u ma jirreaġixxix ma ’ serum minn pazjenti b ’ ed
been formally studied in patients with HIT type II. lP
Tromboċitopenja Indotta bl ’ Eparina (HIT) tat- tip II.
4.5 Interaction with other medicinal products and other forms of interaction
L- effikaċja u s- sigurta` ta ’ fondaparinux ma ġewx studjati formalment f’ pazjenti b ’ HIT tat- tip II. tm
Bleeding risk is increased with concomitant administration of fondaparinux and agents that may na
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott ot
enhance the risk of haemorrhage (see section 4.4).
Ir- riskju ta ’ fsada jiżdied bl- amministrazzjoni konkomitanti ta ’ fondaparinux u aġenti li jistgħu jżidu r- riskju ta ’ emorraġija (ara sezzjoni 4. 4). od
In clinical studies performed with fondaparinux, oral anticoagulants (warfarin) did not interact with ici
F ’ studji kliniċi li saru b ’ fondaparinux, antikoagulanti li jittieħdu mill- ħalq (warfarin) ma kellhom ebda effett fuq il- farmakokinetika ta ’ fondaparinux.
the pharmacokinetics of fondaparinux; at the 10 mg dose used in the interaction studies, fondaparinux did not influence the anticoagulation monitoring (INR) activity of warfarin. ed
istudji ta ’ interazzjoni, fondaparinux ma kellu ebda effett fuq l- attivita` ta ’ l- osservazzjoni ta ’ antikoagulazzjoni (INR) ta ’ warfarin.
Platelet inhibitors (acetylsalicylic acid), NSAIDs (piroxicam) and digoxin did not interact with the pharmacokinetics of fondaparinux.
Inibituri tal- plejtlets (acetylsalicylic acid), NSAIDs (piroxicam) u digoxin ma kellhomx effett fuq il - farmakokinetika ta ’ fondaparinux.
At the 10 mg dose used in the interaction studies, fondaparinux did M
Fid- doża ta ’ fondaparinux (10 mg) li ntużat fl- istudji ta ’ interazzjoni, fondaparinux ma kellu ebda effett fuq il- ħin biex jieqaf id- demm (bleeding time) waqt
not influence the bleeding time under acetylsalicylic acid or piroxicam treatment, nor the pharmacokinetics of digoxin at steady state.
28 trattament b ’ acetylsalicylic acid jew piroxicam, u lanqas fuq il- farmakokinetika ta ’ digoxin fi stat fiss.
26 4.6 Pregnancy and lactation
4. 6 Tqala u Treddigħ
No clinical data on exposed pregnancies are available.
M’ hemmx tgħarif biżżejjed dwar l- użu ta ’ fondaparinux waqt it- tqala.
Animal studies are insufficient with respect to effects on pregnancy, embryo/ foetal development, parturition and postnatal development because of limited exposure.
Studji fuq bhejjem m’ humiex biżżejjed rigward l- effetti fuq it- tqala u fuq l - iżvilupp ta ’ l- embriju/ fetu, ħlas u żvilupp wara t- twelid.
Fondaparinux should not be prescribed to pregnant women unless clearly necessary.
t Fondaparinux m’ għandux jintuża waqt it- tqala jekk m’ hemmx bżonn ċar.
Fondaparinux is excreted in rat milk but it is not known whether fondaparinux is excreted in human milk.
za Fondaparinux jitneħħa fil- ħalib tal- far imma m’ hemmx tagħrif dwar l- eskrezzjoni ta ’ fondaparinux fil -
Breast-feeding is not recommended during treatment with fondaparinux.
It- treddiegħ mhux rakkomandat waqt trattament b ’ fondaparinux.
Oral absorption by the child is however unlikely.
Fit - tarbija l- assorbiment mill- ħalq huwa improbabli.
Effects on ability to drive and use machines
to 4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
ris No studies on the effect on the ability to drive and to use machines have been performed.
aw Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni.
ho 4.8 Undesirable effects
4. 8 Effetti mhux mixtieqa
The safety of fondaparinux has been evaluated in 2,517 patients treated for Venous Thrombo-
x Is- sigurta ’ ta ’ fondaparinux 2. 5 mg ġiet evalwata f’ 2, 517 pazjent li kienu fuq trattament b ’
ut Embolism and treated with fondaparinux for an average of 7 days.
du fondaparinux għal medja ta ’ 7 t’ ijiem għal Trombo- Emboliżmu Venuż.
ra The adverse reactions reported by the investigator as at least possibly related to fondaparinux are presented within each frequency grouping (very common ≥ 1/ 10; common: ≥ 1/ 100 to < 1/ 10;
L- effetti mhux mixtieqa l - iżjed komuni kienu kumplikazzjonijiet ta ’ fsada (ara sezzjoni 4. 4). ħa L- effetti mhux mixtieqa li ġew irrapurtati mill- investigatur bħala dawk li ta ’ l- inqas għandhom possibilment x’ jaqsmu ma ’ fondaparinux huma rranġati f’ kull grupp ta ’ frekwenza (komuni ħafna: ≥ 1/ 10; komuni: ≥1/ 100 sa < 1/ 10; mhux komuni: ≥ 1/ 1, 000 sa ≤ 1/ 100; rari: ≥ 1/ 10, 000 sa ≤1/ 1, 000; ’ g rari ħafna ≤1/ 10, 000) u fis- sistema tal- klassifika tal- organi, bil- gravita` ta ’ l- effett mhux mixtieq im
e uncommon: ≥ 1/ 1,000 to ≤ 1/ 100; rare: ≥ 1/ 10,000 to ≤ 1/ 1,000; very rare ≤ 1/ 10,000) and system organ class by decreasing order of seriousness. ng lo no ct du ro lP na ici ed M
dejjem jonqos. li l na iċi ed tm ot od Pr
System organ class MedDRA
Sistema tal- klassifika tal- organi fid - database MedDRA
Undesirable effects in patients treated for VTE1
Effetti mhux mixtieqa f’ pazjenti fuq trattament għal VTE1
Common: bleeding (gastrointestinal, haematuria, haematoma, epistaxis, haemoptysis, utero-vaginal haemorrhage, haemarthrosis, ocular, purpura, bruise)
Komuni: fsada (gastro- intestinali, ematurja, ematoma, epistaxis, emoptisis, emorraġija uteru - vaġinali, emartrosis, okulari, purpura, tbenġil)
e Rare: other bleeding (hepatic, retroperitoneal,
t za Mhux komuni: anemija, tromboċitopenja Rari: fsada oħra (epatika, retroperitonjali,
ris intracranial/ intracerebral), thrombocythaemia
riz intrakranja/ intraċerebrali), tromboċitemija
Metabolism and nutrition disorders
to Rari: reazzjonijiet allerġiċi Distubi fis- sistema immuni
Rare: non-protein-nitrogen (Npn) 2 increased
aw Disturbi fil- metaboliżmu u n - Rari: żieda fin- nitroġenu mhux minn proteini (Npn) 2 nutrizzjoni
ra
x du Mhux komuni: uġigħ ta ’ ras Disturbi fis- sistema nervuża Rari: sturdament ħa
Uncommon: headache
’ g
e Rare: dizziness
Mhux komuni: dardir, rimettar
Gastrointestinal ng Uncommon: nausea, vomiting disorders lo Hepatobiliary disorders Uncommon: abnormal liver function no
im
Skin and subcutaneous tissue disorders
Disturbi fil- fwied u fil- marrara li l
Rare: rash erythematous
Mhux komuni: funzjoni abnormali tal- fwied
General disorders and administration site
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il - Rari: raxx bi ħmura ġilda na
Uncommon: pain, oedema, Rare: reaction at injection site
Mhux komuni: uġigħ, edema iċi
conditions ro
Disturbi ġenerali u kundizzjonijiet ta ’ mnejn jingħata Rari: reazzjoni fil- post ta ’ injezzjoni ed
(1) Isolated AEs have not been considered except if they were medically relevant.
(1) Effetti mhux mixtieqa iżolati ma kienux kunsidrati ħlief meta kienu relevanti f’ mod mediku. tm
(2) Npn stands for non-protein-nitrogen such as urea, uric acid, amino acid, etc. lP
(2) Npn iffisser nitroġenu mhux minn proteini bħal urea, aċidu uriku, amino aċidi, etc.
4.9 Overdose na
4. 9 Doża eċċessiva ot
Fondaparinux doses above the recommended regimen may lead to an increased risk of bleeding.
Dożi ta ’ fondaparinux akbar minn dawk rakkomandati jistgħu jwasslu għal riskju ogħla ta ’ fsada. od
There is no known antidote to fondaparinux. ici
M’ hemmx antidotu għal fondaparinux.
Overdose associated with bleeding complications should lead to treatment discontinuation and search for the primary cause.
Doża eċċessiva assoċjata ma ’ kumplikazzjonijiet ta ’ fsada għandhom iwasslu għal waqfien tat - Pr
M
Għandu jitqies l- bidu ta ’ trattament addattat bħal emastasi kirurġiku, tibdil ta ’ demm, trasfużjoni ta ’ plażma ġdida u plażmafereżi.
ATC code:
Kategorija farmakoterapewtika: mediċina kontra t- trombożi Kodiċi ATC:
28 Pharmacodynamic effects
t Effetti farmakodinamiċi
Fondaparinux is a synthetic and selective inhibitor of activated Factor X (Xa).
za Fondaparinux huwa inibitur sintetiku u selettiv ta ’ Fattur X attivat (Xa).
The antithrombotic activity of fondaparinux is the result of antithrombin III (antithrombin) mediated selective inhibition of Factor Xa.
riz ta ’ fondaparinux huwa riżultat ta ’ l- inibizzjoni selettiva ta ’ Fattur Xa medjat minn antitrombin III (antitrombin).
By binding selectively to antithrombin, fondaparinux potentiates (about 300 times) the innate neutralization of Factor Xa by antithrombin.
In- newtralizzazzjoni
Neutralisation of Factor Xa interrupts the blood coagulation cascade and inhibits both thrombin formation and thrombus development.
to ta ’ Fattur Xa jinterrompi l- katina ta ’ reazzjonijiet fil- koagulazzjoni tad- demm u jinibixxi kemm il - formazzjoni ta ’ trombin u l- iżvilupp ta ’ trombus.
Fondaparinux does not inactivate thrombin (activated Factor II) and has no effects on platelets.
Fondaparinux ma ’ jinattivax trombin (Fattur II
d At the doses used for treatment, fondaparinux does not, to a clinically relevant extent, affect routine
Fid- doza li tintuża fit- trattament, fondaparinux m’ għandux effett klinikament relevanti fuq testijiet tal - koagulazzjoni ta ’ rutina bħal activated partial thromboplastin time (aPTT), activated clotting time
e coagulation tests such as activated partial thromboplastin time (aPTT), activated clotting time (ACT) or prothrombin time (PT)/ International Normalised Ratio (INR) tests in plasma nor bleeding time or
x (ACT) jew prothrombin time (PT) / International Normalised Ratio (INR) fuq il - plażma, u lanqas il -
ris fibrinolytic activity.
du ħin biex jieqaf id- demm (bleeding time) jew l- attivita` fibrinolitika.
At higher doses, moderate changes in aPTT can occur.
F’ dożi ogħla, jista ’ jkun hemm tibdil moderati f ’ aPTT.
At the 10 mg dose used in interaction studies, fondaparinux did not significantly influence the anticoagulation activity (INR) of
Fid- doża ta ’ 10 mg użata f ’ studji ta ’ interazzjoni, fondaparinux ma kellux effett sinifikanti fuq l- attivita` antikoagulanti (INR) ta ’ warfarin. ħa Fondaparinux ma jirreaġixxix ma ’ serum minn pazjenti b ’ tromboċitopenja indotta bl’ eparina. ’ g Studji kliniċi im
ra The fondaparinux clinical program in treatment of Venous Thromboembolism was designed to demonstrate the efficacy of fondaparinux for the treatment of deep vein thrombosis (DVT) and
Il- programm kliniku ta ’ fondaparinux fi trattament ta ’ Tromboemboliżmu Venuż kien iddiżinjat biex juri l- effikaċja ta ’ fondaparinux fit- trattament ta ’ trombożi f ’ vina fonda (DVT) u emboliżmu pulmonari (PE).
Over 4874 patients were studied in controlled Phase II and III clinical studies.
Iżjed minn 4874 pazjent kienu studjati f’ studji kliniċi kontrollati f ’ Fażi II u III. li l
Treatment of Deep Venous Thrombosis
Trattament ta ’ Trombożi f’ Vina Fonda na
In a randomised, double-blind, clinical trial in patients with a confirmed diagnosis of acute symptomatic DVT, fondaparinux 5 mg (body weight < 50 kg), 7.5 mg (body weight ≥ 50 kg, ≤ 100 no
Total ta ’ 2192 iċi
A total of 2192 patients were treated; for both groups, patients were treated for at least 5 days and up to 26 days (mean 7 days).
pazjent kienu trattati; fiż- żewgt gruppi, pazjenti kienu trattati għal mill- inqas 5 t’ ijiem u għal mhux iżjed minn 26 ġurnata (medja ta ’ 7 t’ ijiem).
Both treatment groups received Vitamin K antagonist therapy usually initiated within 72 hours after the first study drug administration and continued for 90 ± 7 ct
Iż- żewġ ġruppi ta ’ trattament kienu jieħdu terapija b ’ ed
days, with regular dose adjustments to achieve an INR of 2-3.
antagonista ta ’ Vitamina K s- soltu jinbeda fi żmien 72 siegħa wara l- ewwel doża ta ’ l- istudju u jitkompla għal 90± 7 ġurnata, b’ aġġustamenti reġolari fid- doża biex jintlaħaq INR ta ’ 2- 3.
The primary efficacy endpoint was the du
L- effikaċja primarja finali ġiet minn ġabra ta ’ kazi confirmati ta ’ VTE sintomatiku mhux fatali rikorrenti u VTE tm
composite of confirmed symptomatic recurrent non-fatal VTE and fatal VTE reported up to Day 97.
fatali rappurtati sa Ġurnata 97.
Treatment with fondaparinux was demonstrated to be non-inferior to enoxaparin (VTE rates 3.9% and 4.1%, respectively). ro
Intwera li t- trattament ta ’ fondaparinux mhux inferjur għal dak b ’ enoxaparin (rati ta ’ VTE 3. 9% u 4. 1%, rispettivament). ot
Major bleeding during the initial treatment period was observed in 1.1% of fondaparinux patients, lP
Fsada maġġuri fil- perjodu tal- bidu tat- trattament kienet osservata f ’ 1. 1% tal- pazjenti fuq fondaparinux meta mqabbel ma ’ 1. 2% fil- pazjenti fuq enoxaparin. od
compared to 1.2% with enoxaparin.
Id - Pr
The diagnosis was confirmed by objective testing (lung scan, pulmonary angiography or spiral CT scan).
dijanjosi kien konfermat b ’ testijiet oġġettivi (skan tal- pulmun, anġjografija pulmonari jew CT skan spirali).
Randomised ici
Pazjenti li kellhom bżonn tromboliżi, embolektomija jew li jiddaħħal filter ġol- vena cava kienu esklużi.
patients could have been pre-treated with UFH during the screening phase but patients treated for more than 24 hours with therapeutic dose of anticoagulant or with uncontrolled hypertension were ed
Pazjenti li ntgħażlu bla ħsieb jista ’ jkun li ġew trattati qabel b’ UFH waqt il- fażi ta ’ screening iżda ġew esklużi pazjenti trattati għal iżjed minn 24 siegħa b’ doża terapewtika ta ’ antikoagulant jew pazjenti li kellhom pressjoni għolja mhux kontrollata.
A total M
Fondaparinux 5 mg (piż < 50 kg), 7. 5 mg (piż ≥ 50 kg, ≤ 100 kg) jew 10 mg (piż > 100 kg) SC darba kuljum kien mqabbel ma ’ l - eparina mhux frazzjonata IV bolus (5000IU) segwit minn infużjoni IV kontinwu li kien aġġustat biex
of 2184 patients were treated; for both groups, patients were treated for at least 5 days and up to 22 days (mean 7 days).
Total ta ’ 2184 pazjent kienu trattati; fiż- żewgt gruppi, pazjenti kienu trattati għal mill- inqas 5 t’ ijiem u għal mhux iżjed minn 22 ġurnata (medja ta ’ 7 t’ ijiem).
Both treatment groups received Vitamin K antagonist therapy usually initiated within 72 hours after the first study drug administration and continued for 90 ± 7 days, with regular dose adjustments to achieve an INR of 2-3.
Iż- żewġt ġruppi ta ’ trattament kienu jieħdu terapija b ’ antagonista ta ’ Vitamina K li s- soltu jinbeda fi żmien 72 siegħa wara l- ewwel doża ta ’ l- istudju u jitkompla għal 90 ± 7 ġurnata, b’ aġġustamenti reġolari tad- doża biex jintlaħaq INR ta ’ 2- 3.
The primary efficacy endpoint was the composite of confirmed symptomatic recurrent non-fatal VTE and fatal VTE reported up to Day 97.
L- effikaċja primarja finali ġiet minn ġabra ta ’ ta ’ kazi confirmati ta ’ VTE sintomatiku mhux fatali rikorrenti u VTE fatali rappurtati sa Ġurnata 97.
Treatment with fondaparinux was demonstrated to be non-inferior to unfractionated heparin (VTE rates 3.8% and 5.0%, respectively).
Intwera li t- trattament ta ’ fondaparinux mhux inferjur għal dak b ’ enoxaparin (rati ta ’
29 Major bleeding during the initial treatment period was observed in 1.3% of fondaparinux patients, compared to 1.1% with unfractionated heparin.
riz fondaparinux meta mqabbel ma ’ 1. 1% fil- pazjenti fuq heparin mhux frazzjonat.
The pharmacokinetics of fondaparinux sodium are derived from fondaparinux plasma concentrations quantified via anti factor Xa activity.
to Il- farmakokinetika ta ’ fondaparinux sodium hija miġbura minn konċentrazzjonijiet ta ’ fondaparinux
Only fondaparinux can be used to calibrate the anti-Xa assay (the international standards of heparin or LMWH are not appropriate for this use).
Fondaparinux biss jista ’ jintuża biex jikkalibra l- assay li jkejjel l- attivita` kontra fattur Xa (l- istandard internazzjonali ta ’ heparin jew LMWH humiex tajbin għal dan l- użu).
As a result, the concentration of fondaparinux is expressed as milligrams (mg).
Għalhekk, il- konċentrazzjoni ta ’ fondaparinux tidher bħala milligrammi (mg).
After subcutaneous dosing, fondaparinux is completely and rapidly absorbed (absolute bioavailability
x du Assorbiment Wara li jittieħed minn taħt il- ġilda, fondaparinux huwa assorbit kompletament u malajr (biodisponibilita` assoluta ta ’ 100%).
Plasma
Wara doża waħda subkutanja ta ’ Quixidar 2. 5 mg f’ persuni ħa żagħżagħ u f’ saħħithom, l- ogħla konċentrazzjoni fil- plażma (medja Cmax = 0. 34 mg/ l) intlaħħqet sagħtejn wara d- doża.
ho concentrations of half the mean Cmax values are reached 25 minutes post-dosing.
Konċentrazzjonijiet ta ’ nofs il- medja Cmax intlaħħqet 25 minuta wara li ttieħdet ’ g id- doża. im
In elderly healthy subjects, pharmacokinetics of fondaparinux is linear in the range of 2 to 8 mg by
F’ pazjenti anzjani f’ saħħithom, il- farmakokinetika ta ’ fondaparinux b’ injezzjoni subkutanja hija linejari fil- medda ta ’ 2 sa 8 mg.
Following once daily dosing, steady state of plasma levels is obtained after 3 to 4 days with a 1.3-fold increase in Cmax and AUC.
Meta tibda tittieħed id - doża darba kuljum, livelli fissi fil- plażma jintlaħqu wara 3 sa 4 t’ ijiem, b’ żieda ta ’ 1. 3 darba iżjed f ’ Cmax u AUC. li l