qanastek/EMEA-V3 huggingface dataset:
26 corresponding incidences in patients receiving the recommended regimen of enoxaparin in the 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.
Renal impairment The risk of bleeding increases with increasing renal impairment.
Indeboliment tal- kliewi Żieda fl- indeboliment tal- kliewi iżid ir- riskju ta ’ fsada.
Fondaparinux is known to be excreted mainly by the kidney.
Huwa magħruf li fondaparinux jitneħħa fil - 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 renal impairment and severe renal impairment were 3.0% (34/ 1,132), 4.4% (32/ 733), 6.6% (21/ 318), and 14.5% (8/ 55) respectively.
Każi ta ’ fsada f’ pazjenti li għandhom indeboliment renali ħafif, indeboliment renali moderat u indeboliment renali sever, li jieħdu d- dożaġġ rakkomandat fi trattament 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 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), 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. 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 ’ eparina mhux frazzjonata fit - trattament ta ’ PE kienu ta ’ 6. 9% (36/ 523), 3. 1% (11/ 352), 11. 1% (18/ 162) and 10. 7% (3/ 28), rispettivament.
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) 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) (see sections 4.2, 4.3 and 5.2).
It- tul tat- trattament m ’ għandux jiżboq dak studjat waqt il- prova klinika (medda ta ’ 7 t’ ijiem) (ara sezzjonijiet 4. 2, 4. 3 u 5. 2).
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 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).
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).
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).
Indeboliment sever tal - fwied 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).
Patients with Heparin Induced Thrombocytopenia Fondaparinux should be used with caution in patients with a history of HIT.
Pazjenti bi tromboċitopenja indotta bl ’ Eparina Fondaparinux għandu jintuża b’ kawtela f’ pazjenti li kellhom TIE fil- passat.
Fondaparinux does not bind to platelet factor 4 and does not cross-react with sera from patients with Heparin Induced Thrombocytopenia (HIT) type II.
Fondaparinux ma jintrabatx ma ’ l- fattur 4 tal- plejtlets u ma jirreaġixxix ma ’ serum minn pazjenti b ’ Tromboċitopenja Indotta bl ’ Eparina (HIT) tat- tip II.
In clinical studies performed with fondaparinux, oral anticoagulants (warfarin) did not interact with 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.
Fid- doża ta ’ fondaparinux (10 mg) li ntużat fl - 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.
30 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 not influence the bleeding time under acetylsalicylic acid or piroxicam treatment, nor the pharmacokinetics of digoxin at steady state.
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 trattament b ’ acetylsalicylic acid jew piroxicam, u lanqas fuq il- farmakokinetika ta ’ digoxin fi stat fiss.
27 4.6 Pregnancy and lactation
4. 6 Tqala u Treddigħ
The safety of fondaparinux has been evaluated in 2,517 patients treated for Venous Thrombo- Embolism and treated with fondaparinux for an average of 7 days.
Is- sigurtà ta ’ fondaparinux 2. 5 mg ġiet evalwata f’ 2, 517 pazjent li kienu fuq trattament b ’ fondaparinux għal medja ta ’ 7 t ’ ijiem għal Trombo- Emboliżmu Venuż.
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; 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.
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; rari ħafna < 1/ 10, 000) u fis- sistema tal- klassifika tal- organi, bil- gravita` ta ’ l- effett mhux mixtieq dejjem jonqos.
Undesirable effects in patients treated for VTE1
31 Effetti mhux mixtieqa f’ pazjenti fuq trattament Sistema tal- klassifika tal- organi fid - għal VTE1 database MedDRA
Common: bleeding (gastrointestinal, haematuria, haematoma, epistaxis, haemoptysis, utero-vaginal haemorrhage, haemarthrosis, ocular, purpura, bruise) Uncommon: anaemia, thrombocytopaenia Rare: other bleeding (hepatic, retroperitoneal, intracranial/ intracerebral), thrombocythaemia
Komuni: fsada (gastro- intestinali, ematurja, Disturbi tad- demm u tas- sistema ematoma, epistaxis, emoptisis, emorraġija uteru - limfatika vaġinali, emartrosis, okulari, purpura, tbenġil) Mhux komuni: anemija, tromboċitopenja Rari: fsada oħra (epatika, retroperitonjali, intrakranja/ intraċerebrali), tromboċitemija
Metabolism and nutrition disorders
Rari: reazzjonijiet allerġiċi Distubi fis- sistema immuni
Rare: non-protein-nitrogen (Npn) 2 increased
Disturbi fil- metaboliżmu u n- nutrizzjoni Rari: żieda fin- nitroġenu mhux minn proteini (Npn) 2
Uncommon: headache Rare: dizziness
Mhux komuni: uġigħ ta ’ ras Disturbi fis- sistema nervuża Rari: sturdament
Uncommon: abnormal liver function
Mhux komuni: funzjoni abnormali tal- fwied
Skin and subcutaneous tissue disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il - Rari: raxx bi ħmura ġilda
General disorders and administration site conditions
Mhux komuni: uġigħ, edema Disturbi ġenerali u kundizzjonijiet ta ’ mnejn jingħata Rari: reazzjoni fil- post ta ’ injezzjoni
(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.
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.
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 - trattament u biex tinstab il- kawża primarja.
Fondaparinux is a synthetic and selective inhibitor of activated Factor X (Xa).
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.
L- attivita` kontra t- trombożi 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.
Meta fondaparinux jeħel seletivament ma ’ antitrombin, huwa jsaħħaħ (għal madwar 300 darba) in- newtralizzazzjoni naturali ta ’ Fattur Xa permezz ta ’ antitrombin.
Neutralisation of Factor Xa interrupts the blood coagulation cascade and inhibits both thrombin formation and thrombus development.
In- newtralizzazzjoni 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 attivat) u m’ għandux effett fuq il- plejtlets.
At the doses used for treatment, fondaparinux does not, to a clinically relevant extent, affect routine 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 fibrinolytic activity.
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 (ACT) jew prothrombin time (PT) / International Normalised Ratio (INR) fuq il - plażma, u lanqas il - ħin biex jieqaf id- demm (bleeding time) jew l- attivita` fibrinolitika.
At the 10 mg dose used in interaction studies, fondaparinux did not significantly influence the anticoagulation activity (INR) of warfarin.
Fid- doża ta ’ 10 mg użata f ’ studji ta ’ interazzjoni, fondaparinux ma kellux effett sinifikanti fuq l- attivita` antikoagulanti (INR) ta ’ warfarin.
Fondaparinux does not cross-react with sera from patients with heparin-induced thrombocytopaenia.
Fondaparinux ma jirreaġixxix ma ’ serum minn pazjenti b ’ tromboċitopenja indotta bl’ eparina.
Clinical studies
Studji kliniċi
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 pulmonary embolism (PE).
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 4,874 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.
Treatment of Deep Venous Thrombosis 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 kg) or 10 mg (body weight > 100 kg) SC once daily was compared to enoxaparin sodium 1 mg/ kg SC twice daily.
Trattament ta ’ Trombożi f’ Vina Fonda Fi studju kliniku double- blind u randomised, f’ pazjenti b’ dijagnożi konfermata ta ’ DVT sintomatika akuta, 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 ’ enoxaparin sodium 1 mg/ kg SC darbtejn kuljum.
A total of 2,192 patients were treated; for both groups, patients were treated for at least 5 days and up to 26 days (mean 7 days).
Total ta ’ 2192 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 days, with regular dose adjustments to achieve an INR of 2-3.
Iż- żewġ ġruppi ta ’ trattament kienu jieħdu terapija b ’ 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 composite of confirmed symptomatic recurrent non-fatal VTE and fatal VTE reported up to Day 97.
L- effikaċja primarja finali ġiet minn ġabra 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 enoxaparin (VTE rates 3.9% and 4.1%, respectively).
Intwera li t- trattament ta ’ fondaparinux mhux inferjur għal dak b ’ enoxaparin (rati ta ’ VTE 3. 9% u 4. 1%, rispettivament).
Major bleeding during the initial treatment period was observed in 1.1% of fondaparinux patients, compared to 1.2% with enoxaparin.
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.
Treatment of Pulmonary Embolism A randomised, open-label, clinical trial was conducted in patients with acute symptomatic PE.
Trattament ta ’ Emboliżmu Pulmonari Studju kliniku open- label u randomised kien magħmul fuq pazjenti b ’ PE sintomatiku akut.
The diagnosis was confirmed by objective testing (lung scan, pulmonary angiography or spiral CT scan).
Id - dijanjosi kien konfermat b ’ testijiet oġġettivi (skan tal- pulmun, anġjografija pulmonari jew CT skan spirali).
Fondaparinux 5 mg (body weight< 50 kg), 7.5 mg (body weight ≥ 50kg, ≤ 100 kg) or 10 mg (body weight > 100 kg) SC once daily was compared to unfractionated heparin IV bolus (5,000 IU) followed by a continuous IV infusion adjusted to maintain 1.5– 2.5 times aPTT control value.
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
A total of 2,184 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).
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 ’ VTE 3. 8% u 5. 0%, rispettivament).
30 Major bleeding during the initial treatment period was observed in 1.3% of fondaparinux patients, compared to 1.1% with unfractionated heparin.
Fsada maġġuri fil- perjodu tal- bidu tat- trattament kienet osservata f ’ 1. 3% tal- pazjenti fuq 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.
Il- farmakokinetika ta ’ fondaparinux sodium hija miġbura minn konċentrazzjonijiet ta ’ fondaparinux fil- plażma mkejlin permezz ta ’ attivita` kontra fattur Xa.
Absorption After subcutaneous dosing, fondaparinux is completely and rapidly absorbed (absolute bioavailability 100%).
Assorbiment Wara li jittieħed minn taħt il- ġilda, fondaparinux huwa assorbit kompletament u malajr (biodisponibilita` assoluta ta ’ 100%).
Following a single subcutaneous injection of fondaparinux 2.5 mg to young healthy subjects, peak plasma concentration (mean Cmax = 0.34 mg/ l) is obtained 2 hours post-dosing.
Wara doża waħda subkutanja ta ’ Arixtra 2. 5 mg f’ persuni żagħżagħ u f’ saħħithom, l- ogħla konċentrazzjoni fil- plażma (medja Cmax = 0. 34 mg/ l) intlaħħqet sagħtejn wara d- doża.
Plasma 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 id- doża.
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.
Mean (CV%) steady state pharmacokinetic parameters estimates of fondaparinux in patients undergoing hip replacement surgery receiving fondaparinux 2.5 mg once daily are:
L- estimi medji (CV%) tal- parametri farmakokinetiċi fissi ta ’ fondaparinux f’ pazjenti li jgħaddu minn kirurġija tat- tibdil fil- għadma tal - ġenbejn li jieħdu fondaparinux 2. 5mg kuljum huma:
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 (s) - 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 ksur fil- għadma tal- ġenbejn, marbuta ma ’ l- eta` avvanzati tagħhom, il- konċentrazzjonijiet fissi fil- plażma ta ’ fondaparinux kienu ta ’:
Cmax (mg/ l) - 0.50 (32%), Cmin (mg/ l) - 0.19 (58%).
Cmax (mg/ l) - 0. 50 (32%), Cmin (mg/ l) - 0. 19 (58%).
In DVT and PE treatment, patients receiving fondaparinux 5 mg (body weight< 50 kg), 7.5 mg (body weight 50- 100 kg inclusive) and 10 mg (body weight > 100 kg) once daily, the body weight-adjusted doses provide similar exposure across all body weight categories.
Fit- trattament ta ’ DVT u PE, f ’ pazjenti li jieħdu fondaparinux 5 mg (piż < 50 kg), 7. 5 mg (piż 50- 100 kg inklużi), u 10 mg (piż > 100 kg) kuljum, kien hemm esponiment simili f’ kull kategorija ta ’ piż meta d- dożi ta ’ kuljum kienu aġġustati għall- piż.
Cmax (mg/ l) - 1.41 (23%), Tmax (h) – 2.4 (8%) and Cmin (mg/ l) -0.52 (45%).
Cmax (mg/ l) - 1. 41 (23%), Tmax (s) – 2. 4 (8%) u Cmin (mg/ l) - 0. 52 (45%).
The associated 5th and 95th percentiles are, respectively, 0.97 and 1.92 for Cmax (mg/ l), and 0.24 and 0.95 for Cmin (mg/ l).
Il- ħames u l- ħamsa u disgħin percentiles assoċjati kienu, rispettivament, 0. 97 and 1. 92 for Cmax (mg/ l), u 0. 24 u 0. 95 għal Cmin (mg/ l).
In vitro, fondaparinux is highly and specifically bound to antithrombin protein with a dose-dependant plasma concentration binding (98.6% to 97.0% in the concentration range from 0.5 to 2 mg/ l).
In vitro, fondaparinux jeħel ħafna u speċifikament ma ’ l - proteina antitrombin u jilħaq konċentrazzjonijiet fil- plażma li jiddependi mid - doża (98. 6% sa 97. 0% fil- medda ta ’ konċentrazzjonijiet minn 0. 5 sa 2 mg/ l).
Fondaparinux does not bind significantly to other plasma proteins, including platelet factor 4 (PF4).
Fondaparinux ma jeħilx sinifikament ma ’ proteini tal- plażma oħrajn, bħal fattur 4 tal- plejtlets (PF4).
Since fondaparinux does not bind significantly to plasma proteins other than antithrombin, no interaction with other medicinal products by protein binding displacement are expected.
Peress li fondaparinux ma jeħilx sinifikament ma ’ proteini fil- plażma għajr antitrombin, mhux mistenni li jkun hemm xi effett fuq mediċinali oħra għax jieħu post oħrajn biex jeħel ma ’ l - proteini.
Metabolism Although not fully evaluated, there is no evidence of fondaparinux metabolism and in particular no evidence for the formation of active metabolites.
34 Metaboliżmu Għalkemm ma ġiex studjat bi sħiħ, m’ hemm ebda evidenza li fondaparinux jiġi metaboliżżat u partikolarment li jifformaw xi prodotti tal- metaboliżmu attivi.
Fondaparinux does not inhibit CYP450s (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4) in vitro.
In vitro, fondaparinux ma inibixxix CYP450s (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 jew CYP3A4).
Thus, fondaparinux is not expected to interact with other medicinal products in vivo by inhibition of CYP-mediated metabolism.
Għalhekk, mhux mistenni li in vivo fondaparinux ma jaqbilx ma xi prodotti mediċinali oħra minħabba l- inibizzjoni ta ’ metaboliżmu medjat minn CYP.
Excretion/ Elimination The elimination half-life (t½) is about 17 hours in healthy young subjects and about 21 hours in healthy elderly subjects.
Eskrezzjoni / Eliminazzjoni Il- half- life ta ’ eliminazzjoni (t½) huwa ta ’ madwar 17 il- siegħa f’ persuni żagħżagħ f’ saħħithom u madwar 21 siegħa f ’ persuni anzjani f’ saħħithom.
Fondaparinux is excreted to 64 – 77% by the kidney as unchanged compound.
Sa 64- 77% ta ’ fondaparinux jitneħħa mill- kliewi f’ forma mhux mibdula.
31 Special populations
Gruppi ta ’ nies speċjali:
Elderly patients - Renal function may decrease with age and thus, the elimination capacity for fondaparinux may be reduced in elderly.
Pazjenti anzjani - L- eliminazzjoni ta ’ fondaparinux f’ anzjani jitnaqqas għaliex il- funzjoni renali tonqos biż- żmien.
Renal impairment - Compared with patients with normal renal function (creatinine clearance > 80 ml/ min) undergoing orthopaedic surgery and receiving fondaparinux 2.5 mg once daily, 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 moderate renal impairment (creatinine clearance 30 to 50 ml/ min).
Indeboliment renali - Il- clearance tal- plażma hija minn 1. 2 sa 1. 4 l- darba inqas f’ pazjenti b ’ indeboliment renali ħafif (clearance tal- krejatinina minn 50 sa 80 ml/ min) u medja ta ’ darbtejn inqas f’ pazjenti b’ indeboliment renali moderat (clearance tal- krejatinina minn 30 sa 50 ml/ min), meta mqabbla ma pazjenti b’ funzjoni renali normali (clearance tal- krejatinina > 80 ml/ min), li jgħaddu minn kirurġija ortopedika u fuq fondaparinux 2. 5 mg kuljum.
In severe renal impairment (creatinine clearance < 30 ml/ min), plasma clearance is approximately 5 times lower than in normal renal function.
F’ indeboliment renali serju (clearance tal - krejatinina < 30 ml/ min), il- clearance fil- plażma huwa bejn wieħed u ieħor 5 darbiet izjed baxx minn dak f ’ funzjoni renali normali.
Associated terminal half-life values were 29 h in moderate and 72 h in patients with severe renal impairment.
Il- valuri assoċjati ma ’ half- life terminali kienu ta ’ 29 siegħa f ’ indeboliment renali moderat u 72 siegħa f ’ pazjenti b’ indeboliment renali serju.
Body weight - Plasma clearance of fondaparinux increases with body weight (9% increase per 10 kg).
Piż tal- ġisem - Il- clearance tal- plażma ta ’ fondaparinux jiżdied mall- piż (żieda ta ’ 9% kull 10 kg)
Gender - No gender differences were observed after adjustment for body weight.
Sess - Ma dehrux differenzi fis- sessi, wara li kien hemm arranġamenti għall- piż tal- ġisem.
However, studies performed in Asian (Japanese) healthy subjects did not reveal a different pharmacokinetic profile compared to Caucasian healthy subjects.
Madanakollu, studji li saru fuq persuni f’ saħħithom Asjatiċi (Jappuniżi) ma wrewx profil farmakokinetiku differenti meta mqabbla ma ’ persuni Kawkasi f’ saħħithom.
Similarly, no plasma clearance differences were observed between black and Caucasian patients undergoing orthopaedic surgery.
Ma nstabux differenzi fil - clearance tal- plażma bejn pazjenti suwed u Kawkasi li għamlu kirurġija ortopedika.
5.3 Preclinical safety data
35 5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology and genotoxicity.
Tagħrif ta ’ qabel l- użu kliniku magħmul fuq studji konvenzjonali ta ’ sigurtà farmakoloġika u effett tossiku fuq il- ġeni, ma juru l- ebda periklu speċjali għall- bnedmin.
The repeated dose and reproduction toxicity studies did not reveal any special risk but did not provide adequate documentation of safety margins due to limited exposure in the animal species.
Studji fuq l- effett tossiku minn dożi ripetuti u fuq is- sistema riproduttiva, ma juru l- ebda periklu speċjali għall- bnedmin iżda ma provdew ebda dokumentazzjoni adekwati fuq marġini ta ’ sigurta` minħabba esponiment limitat fuq l- ispeċi ta ’ l- annimali.
Sodium chloride Water for injections Hydrochloric acid Sodium hydroxide
Sodium chloride Ilma għall- injezzjoni Aċidu idrokloriku Idrossidu tas- sodju
Type I glass barrel (1 ml) affixed with a 27 gauge x 12.7 mm needle and stoppered with a chlorobutyl elastomer plunger stopper.
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.
Arixtra 5 mg/ 0.4 ml is available in pack sizes of 2, 7, 10 and 20 pre-filled syringes.
Arixtra 5 mg/ 0. 4 ml jinstab f’ pakketti ta ’ 2, 7, 10, u 20 siringi mimlija lesti.
There are two types of syringes: • syringe with a orange plunger and an automatic safety system • syringe with orange plunger and a manual safety system.
siringa bi planġer oranġjo u b’ sistema awtomatika ta ’ sigurtà.. siringa bi planġer oranġjo u b’ sistema manwali ta ’ sigurtà
The subcutaneous injection is administered in the same way as with a classical syringe.
L- injezzjoni subkutaneja tittieħed bl- istess mod ta ’ siringa klassika.
Parenteral solutions should be inspected visually for particulate matter and discoloration prior to administration.
Soluzzjonijiet li jittieħdu b’ injezzjoni għandhom jiġu spezzjonati viżwalment għal frak u telf ta ’ kulur qabel ma ’ jittieħdu.
Instruction for self-administration is mentioned in the Package Leaflet.
L- istruzzjonijiet biex wieħed ikun jista ’ jieħu hu stess l- injezzjoni huma mniżżlin fil- Fuljett ta ’ Tagħrif.
The Arixtra pre-filled syringes have been designed with a needle protection system to prevent needle stick injuries following injection.
Is- siringi mimlijin lesti ta ’ Arixtra huma ddiżinjati b’ sistema protettiva tal- labra biex tevita li wieħed jittaqqab bi żball wara l- injezzjoni.
This medicinal product is for single use only.
36 Din il- mediċina hija għall- użu ta ’ darba biss.
Arixtra 7.5 mg/ 0.6 ml solution for injection, pre-filled syringe.
Arixtra 7. 5 mg/ 0. 6 ml soluzzjoni għall- injezzjoni, siringa mimlija lesta
Treatment should be continued for at least 5 days and until adequate oral anticoagulation is established (International Normalised Ratio 2 to 3).
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).
The average duration of administration in clinical 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.
35 Hepatic impairment - No dosing adjustment is necessary in patients with either mild or moderate hepatic impairment.
Indeboliment tal- fwied - M’ hemmx bżonn aġġustament tad- doża f’ pazjenti b’ indeboliment tal- fwied ħafif jew moderat.
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.
38 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.
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.
Bħal kull antikoagulant ieħor, fondaparinux għandu jintuża b’ attenzjoni f’ pazjenti li għaddew minn kirurġija riċenti (< 3 t’ ijiem) u jintuża biss meta jiġi stabbilit emostasi kirurġiku.
The
Meta maqsumin f’ gruppi fl- istess mod, il- każi f’ pazjenti li jieħdu d- dożaġġ
36 corresponding incidences in patients receiving the recommended regimen of enoxaparin in the 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.
39 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.
The duration of treatment should not exceed that evaluated during clinical trial (mean 7 days) (see sections 4.2, 4.3 and 5.2).
It- tul tat- trattament m ’ għandux jiżboq dak studjat waqt il- prova klinika (medda ta ’ 7 t ’ ijiem) (ara sezzjonijiet 4. 2, 4. 3 u 5. 2).
37 4.6 Pregnancy and lactation
40 4. 6 Tqala u Treddigħ
The safety of fondaparinux has been evaluated in 2,517 patients treated for Venous Thrombo- Embolism and treated with fondaparinux for an average of 7 days.
Is- sigurtà ta ’ fondaparinux 2. 5 mg ġiet evalwata f’ 2, 517 pazjent li kienu fuq trattament b ’ fondaparinux għal medja ta ’ 7 t’ ijiem għal Trombo- Emboliżmu Venuż.
The most common adverse reactions were bleeding complications (see section 4.4).
L- effetti mhux mixtieqa l- iżjed komuni kienu kumplikazzjonijiet ta ’ fsada (ara sezzjoni 4. 4).
Undesirable effects in patients treated for VTE1
41 Effetti mhux mixtieqa f’ pazjenti fuq trattament Sistema tal- klassifika tal- organi fid - għal VTE1 database MedDRA
39 Pharmacodynamic effects
Effetti farmakodinamiċi
Over 4,874 patients were studied in controlled Phase II and III clinical studies.
Iżjed minn 4, 874 pazjent kienu studjati f’ studji kliniċi kontrollati f ’ Fażi II u III.
A total of 2,192 patients were treated; for both groups, patients were treated for at least 5 days and up to 26 days (mean 7 days).
Total ta ’ 2, 192 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).
Fondaparinux 5 mg (body weight< 50 kg), 7.5 mg (body weight ≥ 50kg, ≤ 100 kg) or 10 mg (body weight > 100 kg) SC once daily was compared to unfractionated heparin IV bolus (5,000 IU) followed by a continuous IV infusion adjusted to maintain 1.5– 2.5 times aPTT control value.
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 -
A total of 2,184 patients were treated; for both groups, patients were treated for at least 5 days and up to 22 days (mean 7 days).
Total ta ’ 2, 184 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).
40 Major bleeding during the initial treatment period was observed in 1.3% of fondaparinux patients, compared to 1.1% with unfractionated heparin.
Fsada maġġuri fil- perjodu tal- bidu tat- trattament kienet osservata f ’ 1. 3% tal- pazjenti fuq fondaparinux meta mqabbel ma ’ 1. 1% fil- pazjenti fuq heparin mhux frazzjonat.
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.
Mean (CV%) steady state pharmacokinetic parameters estimates of fondaparinux in patients undergoing hip replacement surgery receiving fondaparinux 2.5 mg once daily are:
L- estimi medji (CV%) tal- parametri farmakokinetiċi fissi ta ’ fondaparinux f’ pazjenti li jgħaddu minn kirurġija tat- tibdil fil- għadma tal - ġenbejn li jieħdu Arixtra 2. 5mg kuljum huma:
Since fondaparinux does not bind significantly to plasma proteins other than antithrombin, no interaction with other medicinal products by protein binding displacement are expected.
Peress li fonaparinux ma jeħilx sinifikament ma ’ proteini fil- plażma għajr antitrombin, mhux mistenni li jkun hemm xi effett fuq mediċinali oħra għax jieħu post oħrajn biex jeħel ma ’ l - proteini.
Metabolism Although not fully evaluated, there is no evidence of fondaparinux metabolism and in particular no evidence for the formation of active metabolites.
44 Metaboliżmu Għalkemm ma ġiex studjat bi sħiħ, m’ hemm ebda evidenza li fondaparinux jiġi metaboliżżat u partikolarment li jifformaw xi prodotti tal- metaboliżmu attivi.
Excretion/ Elimination The elimination half-life (t½) is about 17 hours in healthy young subjects and about 21 hours in healthy elderly subjects.
Eskrezzjoni / Eliminazzjoni Il- half- life ta ’ eliminazzjoni (t½) huwa ta ’ madwar 17- ilsiegħa f’ persuni żagħżagħ f’ saħħithom u madwar 21 siegħa f ’ persuni anzjani f’ saħħithom.
41 Special populations
Gruppi ta ’ nies speċjali:
In severe renal impairment (creatinine clearance < 30 ml/ min), plasma clearance is approximately 5 times lower than in normal renal function.
F’ indeboliment renali serju (clearance tal - krejatinina < 30 ml/ min), il- clearance fil- plażma huwa bejn wieħed u ieħor 5 darbiet izjed baxx minn dak b ’ funzjoni renali normali.
Associated terminal half-life values were 29 h in moderate and 72 h in patients with severe renal impairment.
Il- valuri assoċjati ma ’ half- life terminali kienu ta ’ 29 siegħa b ’ indeboliment renali moderat u 72 siegħa f ’ pazjenti b’ indeboliment renali serju.
5.3 Preclinical safety data
45 5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina
Arixtra 7.5 mg/ 0.6 ml is available in pack sizes of 2, 7, 10 and 20 pre-filled syringes.
Arixtra 7. 5 mg/ 0. 6 ml jinstab f’ pakketti ta ’ 2, 7, 10, u 20 siringi mimlija lesti.
There are two types of syringes: • syringe with a magenta plunger and an automatic safety system • syringe with magenta plunger and a manual safety system.
siringa bi planġer ta ’ kulur maġenta u b’ sistema awtomatika ta ’ sigurtà. siringa bi planġer ta ’ kulur maġenta u b’ sistema manwali ta ’ sigurtà
Parenteral solutions should be inspected visually for particulate matter and discoloration prior to administration.
Soluzzjonijiet li jittieħdu b’ injezzjoni, għandhom jiġu spezzjonati viżwalment għal frak u telf ta ’ kulur qabel ma ’ jittieħdu.
The Arixtra pre-filled syringes have been designed with a needle protection system to prevent needle stick injuries following injection.
Is- siringi mimlijin lesti ta ’ Arixtra huma ddiżinjati b ’ sistema protettiva tal- labra biex tevita li wieħed jittaqqab bi żball wara l- injezzjoni.
This medicinal product is for single use only.
46 Din il- mediċina hija għall- użu ta ’ darba biss.
Arixtra 10 mg/ 0.8 ml solution for injection, pre-filled syringe.
Arixtra 10 mg/ 0. 8 ml soluzzjoni għall- injezzjoni, siringa mimlija lesta
Elderly patients - No dosing adjustment is necessary.
Pazjenti anzjani – M’ hemmx bżonn aġġustament fid- doża.
Renal impairment - Fondaparinux should be used with caution in patients with moderate renal impairment (see section 4.4).
Indeboliment tal- kliewi – Għandha tittieħed attenzjoni bl- użu ta ’ fondaparinux f’ pazjenti b’ indeboliment moderat tal- kliewi (ara sezzjoni 4. 4).
45 Hepatic impairment - No dosing adjustment is necessary in patients with either mild or moderate hepatic impairment.
Indeboliment tal- fwied – M’ hemmx bżonn aġġustament tad- doża f’ pazjenti b’ indeboliment tal- fwied ħafif jew moderat.
In patients with severe hepatic impairment, fondaparinux should be used with care as this patient group has not been studied (see sections 4.4 and 5.2).
Għandha tittieħed attenzjoni bl- użu ta ’ fondaparinux f’ pazjenti b’ indeboliment sever tal- fwied għaliex dan il- grupp ta ’ pazjenti ma ġiex studjat (ara sezzjonijiet 4. 4 u 5. 2).
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
48 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.
Haemorrhage Fondaparinux should be used with caution in patients who have an increased risk of haemorrhage, 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 ophthalmic surgery and in special patient groups as outlined below.
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.
These agents include desirudin, fibrinolytic agents, GP IIb/ IIIa receptor antagonists, 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).
46 corresponding incidences in patients receiving the recommended regimen of enoxaparin in the 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.
49 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.
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 renal impairment and severe renal impairment were 3.0% (34/ 1,132), 4.4% (32/ 733), 6.6% (21/ 318), and 14.5% (8/ 55) respectively.
Każi ta ’ fsada f’ pazjenti li għandhom indeboliment renali ħafif, indeboliment renali moderat u indeboliment renali sever, li jieħdu d- dożaġġ rakkomandat fi trattament ta ’ DVT jew PE, kienu ta ’ 3. 0% (34/ 1, 132), 4. 4% (32/ 733), 6. 6% (21/ 318), u 14. 5% (8/ 55), rispettivament.
47 4.6 Pregnancy and lactation
50 4. 6 Tqala u Treddigħ
Fondaparinux is excreted in rat milk but it is not known whether fondaparinux is excreted in human milk.
Fondaparinux jitneħħa fil- ħalib tal- far imma m’ hemmx tagħrif dwar l- eskrezzjoni ta ’ fondaparinux fil- ħalib tas- sider fil- bniedem.
Undesirable effects in patients treated for VTE1
51 Effetti mhux mixtieqa f’ pazjenti fuq trattament Sistema tal- klassifika tal- organi fid - għal VTE1 database MedDRA
49 Pharmacodynamic effects
Effetti farmakodinamiċi
A total of 2,192 patients were treated; for both groups, patients were treated for at least 5 days and up to 26 days (mean 7 days).
Total ta ’ 2, 192 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).
Fondaparinux 5 mg (body weight< 50 kg), 7.5 mg (body weight ≥ 50kg, ≤ 100 kg) or 10 mg (body weight > 100 kg) SC once daily was compared to unfractionated heparin IV bolus (5,000 IU) followed by a continuous IV infusion adjusted to maintain 1.5– 2.5 times aPTT control value.
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 (5, 000IU) segwit minn infużjoni IV kontinwu li kien aġġustat biex
50 Major bleeding during the initial treatment period was observed in 1.3% of fondaparinux patients, compared to 1.1% with unfractionated heparin.
Fsada maġġuri fil- perjodu tal- bidu tat- trattament kienet osservata f ’ 1. 3% tal- pazjenti fuq fondaparinux meta mqabbel ma ’ 1. 1% fil- pazjenti fuq heparin mhux frazzjonat.
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 (s) – 2. 8 (18%) u Cmin (mg/ l) - 0. 14 (56%).
Cmax (mg/ l) - 1.41 (23%), Tmax (h) – 2.4 (8%) and Cmin (mg/ l) -0.52 (45%).
Cmax (mg/ l) – 1. 41 (23%), Tmax (s) – 2. 4 (8%) u Cmin (mg/ l) - 0. 52 (45%).
Metabolism Although not fully evaluated, there is no evidence of fondaparinux metabolism and in particular no evidence for the formation of active metabolites.
54 Metaboliżmu Għalkemm ma ġiex studjat bi sħiħ, m’ hemm ebda evidenza li fondaparinux jiġi metaboliżżat u partikolarment li jifformaw xi prodotti tal- metaboliżmu attivi.
Excretion/ Elimination The elimination half-life (t½) is about 17 hours in healthy young subjects and about 21 hours in healthy elderly subjects.
Eskrezzjoni / Eliminazzjoni Il- half- life ta ’ eliminazzjoni (t½) huwa ta ’ madwar 17- il siegħa f’ persuni żagħżagħ f’ saħħithom u madwar 21 siegħa f ’ persuni anzjani f’ saħħithom.
51 Special populations
Gruppi ta ’ nies speċjali:
Elderly patients - Renal function may decrease with age and thus, the elimination capacity for fondaparinux may be reduced in elderly.
Pazjenti anzjani – L- eliminazzjoni ta ’ fondaparinux f’ anzjani jitnaqqas għaliex il- funzjoni renali tonqos biż- żmien.
Renal impairment - Compared with patients with normal renal function (creatinine clearance > 80 ml/ min) undergoing orthopaedic surgery and receiving fondaparinux 2.5 mg once daily, 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 moderate renal impairment (creatinine clearance 30 to 50 ml/ min).
Indeboliment renali – Il- clearance tal- plażma hija minn 1. 2 sa 1. 4 l- darba inqas f’ pazjenti b ’ indeboliment renali ħafif (clearance tal- krejatinina minn 50 sa 80 ml/ min) u medja ta ’ darbtejn inqas f’ pazjenti b’ indeboliment renali moderat (clearance tal- krejatinina minn 30 sa 50 ml/ min), meta mqabbla ma pazjenti b’ funzjoni renali normali (clearance tal- krejatinina > 80 ml/ min), li jgħaddu minn kirurġija ortopedika u fuq fondaparinux 2. 5 mg kuljum.
Body weight - Plasma clearance of fondaparinux increases with body weight (9% increase per 10 kg).
Piż tal- ġisem – Il- clearance tal- plażma ta ’ fondaparinux jiżdied ma ’ l- piż (żieda ta ’ 9% kull 10 kg)
Gender - No gender differences were observed after adjustment for body weight.
Sess – Ma dehrux differenzi fis- sessi, wara li kien hemm arranġamenti għall- piż tal- ġisem.
Race - Pharmacokinetic differences due to race have not been studied prospectively.
Razza – Id- differenzi farmakokinetiċi minħabba r- razza ma ġewx studjati b’ mod prospettiv.
Hepatic impairment - Following a single, subcutaneous dose of fondaparinux in subjects with moderate hepatic impairment (Child-Pugh Category B), total (i. e., bound and unbound) Cmax and AUC were decreased by 22% and 39%, respectively, as compared to subjects with normal liver function.
Indeboliment tal- fwied – Wara doża waħda mogħtija taħt il- ġilda ta ’ fondaparinux, f’ suġġetti b’ indeboliment tal- fwied moderat (Child- Pugh Category B), Cmax totali (jiġifieri marbut u mhux marbut) u AUC tnaqqsu b’ 22% u 39%, rispettivament, meta mqabbla ma ’ suġġetti b’ funzjoni tal - fwied normali.
5.3 Preclinical safety data
55 5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurtà tal- mediċina
Arixtra 10 mg/ 0.8 ml is available in pack sizes of 2, 7, 10 and 20 pre-filled syringes.
Arixtra 10 mg/ 0. 8 ml jinstab f’ pakketti ta ’ 2, 7, 10, u 20 siringi mimlija lesti.
There are two types of syringes: • syringe with a violet plunger and an automatic safety system • syringe with violet plunger and a manual safety system.
siringa bi planġer vjola u b’ sistema awtomatika ta ’ sigurtà. siringa bi planġer vjola u b’ sistema manwali ta ’ sigurtà.
The subcutaneous injection is administered in the same way as with a classical syringe.
L- injezzjoni subkutaneja titieħed bl- istess mod ta ’ siringa klassika.
This medicinal product is for single use only.
56 Din il- mediċina hija għall- użu ta ’ darba biss.
54 ANNEX II
57 ANNESS II
Glaxo Wellcome Production 1, rue de l’ Abbaye F-76960 Notre Dame de Bondeville France
Glaxo Wellcome Production 1, rue de l’ Abbaye F- 76960 Notre Dame de Bondeville Franza
• CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON THE MARKETING AUTHORISTION HOLDER
• KUNDIZZJONIJIET JEW RESTRIZZJONIJIET FUQ IL- FORNIMENT U L- UŻU IMPOSTI FUQ ID- DETENTUR TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS - SUQ
Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance, as described in the June 2006 version 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 L- MAH għandu jiżgura li s- sistema ta ’ farmakoviġilanza, kif deskritta fil- verżjoni ta ’ Ġunju 2006 preżentata fit- Taqsima 1. 8. 1 ta ’ l- Applikazzjoni għall- Awtorizzazzjoni għat- Tqegħid fis- Suq, qiegħda f’ postha u tiffunzjona qabel ma l- prodott jitqiegħed fis- suq u waqt li l- prodott ikun fis- suq.
Risk Management Plan The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 1.2 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 il- Maniġġjar ta ’ Riskju L- MAH jimpenja ruħu li jwettaq l- istudji u l- attivitajiet addizzjonali ta ’ farmakoviġilanza dettaljati fil - Pjan ta ’ Farmakoviġilanza, kif miftiehem fil- verżjoni 1. 2 tal- Pjan dwar il- Maniġġjar ta ’ Riskju (RMP) preżentat fit- Taqsima 1. 8. 2 ta ’ l- Applikazzjoni għall- Awtorizzazzjoni għat- Tqegħid fis- Suq u fl - aġġornamenti sussegwenti tal- RMP mifthema mas- CHMP.
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.
Barra minn hekk, RMP aġġornat għandu jiġi ppreżentat: • Meta tasal informazzjoni ġdida li jista ’ jkollha effett fuq l- ispeċifikazzjoni tas- sigurta` kurrenti, fuq il- Pjan ta ’ Farmakoviġilanza kurrenti jew fuq l- attivitajiet għat- tnaqqis tar- riskji. • F’ żmien ta ’ 60 ġurnata wara li tkun tlaħqet xi mira importanti (ta ’ farmakoviġilanza jew ta ’ tnaqqis ta 'riskji) • Fuq talba ta ’ l- EMEA
56 ANNEX III
59 ANNESS III
58 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
61 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
Arixtra 1.5 mg/ 0.3 ml solution for injection Fondaparinux sodium
Fondaparinux sodium
One pre-filled syringe (0.3 ml) contains 1.5 mg fondaparinux sodium.
Siringa waħda mimlija lesta (0. 3 ml) fiha 1. 5 mg fondaparinux sodium.
Also contains: sodium chloride, water for injections, hydrochloric acid, sodium hydroxide.
Fiha wkoll: sodium chloride, ilma għal injezzjonijiet, hydrochloric acid, sodium hydroxide.
Solution for injection, 2 pre-filled syringes with an automatic safety system Solution for injection, 7 pre-filled syringes with an automatic safety system Solution for injection, 10 pre-filled syringes with an automatic safety system Solution for injection, 20 pre-filled syringes with an automatic safety system
Soluzzjoni għall- injezzjoni, 20 siringa mimlija lesta b’ sistema ta ’ sikurezza awtomatika.