qanastek/EMEA-V3 huggingface dataset:
ra 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 Quixidar 2. 5mg kuljum huma:
Cmax (mg/ l) - 0.39
Cmax (mg/ l) - 0. 39 na
e (31%), Tmax (h) - 2.8 (18%) and Cmin (mg/ l) -0.14 (56%).
(31%), Tmax (s) - 2. 8 (18%) u Cmin (mg/ l) - 0. 14 (56%).
In hip fracture patients, associated with their ng 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%). lo 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 no
Fit- trattament ta ’ DVT u PE, f ’ pazjenti li jieħdu fondaparinux 5 mg (piż < 50 kg), 7. 5 mg (piż 50- 100 ed
doses provide similar exposure across all body weight categories.
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.
The mean (CV%) steady state pharmacokinetic parameters estimates of fondaparinux in patients with VTE receiving the fondaparinux proposed dose regimen once daily are:
L- estimi medji (CV%) tal- parametri farmakokinetiċi fissi ta ’ fondaparinux f’ pazjenti b ’ VTE fuq id- dożaġġ propost ta ’ fondaparinux huma:
Cmax (mg/ l) - 1.41 (23%), Tmax (h) – 2.4 (8%) and Cmin (mg/ l) -0.52 (45%).
Cmax (mg/ l) - 1. 41 tm
Cmax (mg/ l), and 0.24 and 0.95 for Cmin (mg/ l). du
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). ot
In vitro, fondaparinux is highly and ro
In vitro, fondaparinux jeħel od
Fondaparinux does not bind lP
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).
significantly to other plasma proteins, including platelet factor 4 (PF4).
Pr
Since fondaparinux does not bind significantly to plasma proteins other than antithrombin, no na
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.
Although not fully evaluated, there is no evidence of fondaparinux metabolism and in particular no evidence for the formation of active metabolites. ed
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.
32 In vitro, fondaparinux ma inibixxix CYP450s (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 jew CYP3A4).
Thus, fondaparinux is not expected to interact with other medicinal M
Għalhekk, mhux mistenni li in vivo fondaparinux ma jaqbilx ma xi prodotti mediċinali oħra minħabba l- inibizzjoni ta ’ metaboliżmu medjat minn CYP.
products in vivo by inhibition of CYP-mediated metabolism.
Eskrezzjoni / Eliminazzjoni Il- half- life ta ’ eliminazzjoni (t½) huwa ta ’ madwar 17 il- siegħa f’ persuni żagħżagħ f’ saħħithom u
Excretion/ Elimination The elimination half-life (t½) is about 17 hours in healthy young subjects and about 21 hours in healthy elderly subjects.
t 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
30 Special populations
riz Gruppi ta ’ nies speċjali:
Paediatric patients - Fondaparinux has not been investigated in this population.
Pazjenti pedjatriċi: fondaparinux ma ġiex studjat f’ dan il- grupp.
Elderly patients - Renal function may decrease with age and thus, the elimination capacity for fondaparinux may be reduced in elderly.
to Pazjenti anzjani - L- eliminazzjoni ta ’ fondaparinux f’ anzjani jitnaqqas għaliex il- funzjoni renali
In patients > 75 years undergoing orthopaedic surgery and receiving fondaparinux 2.5 mg once daily, the estimated plasma clearance was 1.2 to 1.4 times lower than in patients < 65 years.
F’ pazjenti > 75 sena li jgħaddu minn kirurġija ortopedika, u fuq fondaparinux 2. 5 mg darba kuljum, l- estimu tal- clearance tal- plażma kienu minn 1. 2 sa 1. 4 l- darba iżjed baxx minn dak ta ’ pazjenti < 65 sena.
A similar pattern is observed in DVT and PE treatment patients.
L- istess huwa osservat f’ pazjenti fuq trattament għal DVT u PE.
d Renal impairment - Compared with patients with normal renal function (creatinine clearance
x Indeboliment renali - Il- clearance tal- plażma hija minn 1. 2 sa 1. 4 l- darba inqas f’ pazjenti b ’
e > 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
du 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 ħa minn kirurġija ortopedika u fuq fondaparinux 2. 5 mg kuljum.
In severe renal impairment (creatinine clearance < 30 ml/ min), plasma
F’ indeboliment renali serju (clearance tal- krejatinina < 30 ml/ min), il- clearance fil- plażma huwa bejn wieħed u ieħor 5 darbiet izjed baxx ’ g 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.
L- istess huwa im
A similar pattern is observed in DVT and PE treatment patients.
osservat f’ pazjenti fuq trattament għal DVT u PE.
ut 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) li l
ra 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. na
e Race - Pharmacokinetic differences due to race have not been studied prospectively.
Razza - Id- differenzi farmakokinetiċi minħabba r- razza ma ġewx studjati b’ mod prospettiv.
However, studies ng performed in Asian (Japanese) healthy subjects did not reveal a different pharmacokinetic profile compared to Caucasian healthy subjects.
Ma nstabux differenzi iċi
Similarly, no plasma clearance differences were observed between black and Caucasian patients undergoing orthopaedic surgery. lo Hepatic impairment - Fondaparinux pharmacokinetics has not been evaluated in hepatic impairment. no
Indeboliment tal- fwied - Il- farmakokinetika ta ’ fondaparinux ma ’ ġietx studjata f’ indeboliment tal - fwied. tm
Non-clinical data reveal no special hazard for humans based on conventional studies of safety ct
Tagħrif ta ’ qabel l- użu kliniku magħmul fuq studji konvenzjonali ta ’ sigurtà farmakoloġika u effett ot
pharmacology and genotoxicity.
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 du
Studji fuq l- effett tossiku minn dożi ripetuti u fuq is- sistema riproduttiva, ma juru l- ebda periklu speċjali għall- bnedmin iżda ma provdew od
in the animal species. ro
Pr
PHARMACEUTICAL PARTICULARS lP
TAGĦRIF FARMAĊEWTIKU
6.1 List of excipients na
6. 1 Lista ta ’ sustanzi mhux attivi
Sodium chloride Water for injections Hydrochloric acid ici
Sodium chloride Ilma għall- injezzjoni Aċidu idrokloriku
Sodium hydroxide ed
t Idrossidu tas- sodju
6.2 Incompatibilities
za 6. 2 Inkompatibilitajiet
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal M
riz Minħabba li ma sarux studji li juru liema huma l- prodotti li ma jablux miegħu, dan il- prodott mediċinali m’ għandux jitħallat ma ’ prodotti mediċinali oħrajn.
6.3 Shelf life
to aw 6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
31 6.4 Special precautions for storage
x 6. 4 Prekawzjonijiet speċjali għall- ħażna
Type I glass barrel (1 ml) affixed with a 27 gauge x 12.7 mm needle and stoppered with a chlorobutyl elastomer plunger stopper.
du Tiffriżax ħa 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih ’ g 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. im
d Quixidar 5 mg/ 0.4 ml is available in pack sizes of 2, 7, 10 and 20 pre-filled syringes with an orange
Quixidar 5 mg/ 0. 4 ml jinstab f’ pakketti ta ’ 2, 7, 10, u 20 siringi mimlija lesti b ’ sistema awtomatika ta ’ sigurta ’ oranġjo.
Not all pack sizes may be marketed.
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali. li l
ris 6.6 Special precautions for disposal and other handling
6. 5 Struzzjonijiet għall- użu u maniġġar u għar- rimi na
ho 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
Soluzzjonijiet li jittieħdu b’ injezzjoni għandhom jiġu spezzjonati viżwalment għal frak u telf ta ’ kulur iċi
ut administration.
qabel ma ’ jittieħdu. ed
ra 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. tm
The Quixidar pre-filled syringe has been designed with an automatic needle protection system to
Is- siringa mimlija lesta ta ’ Quixidar hija diżinjata b ’ sistema protettiva tal- labra awtomatika biex tevita li wieħed jittaqqab bi żball wara l- injezzjoni. ot
e prevent needle stick injuries following injection. ng Any unused product or waste material should be disposed of in accordance with local requirements.
Kull fdal tal- prodott li ma jiġix użat jew skart li jibqa wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali. od
This medicinal product is for single use only. lo no
Din il- mediċina hija għall- użu ta ’ darba biss.
MARKETING AUTHORISATION HOLDER
ID- DETENTUR TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ Pr
Glaxo Group Ltd Greenford ct
Glaxo Group Ltd Greenford Middlesex UB6 0NN Renju Unit
MARKETING AUTHORISATION NUMBERS lP
NUMRU( I) TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
EU/ 1/ 02/ 207/ 009-011, 018 na
EU/ 1/ 02/ 206/ 009- 011, 018
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION ici
DATA TA ’ L- EWWEL AWTORIZZAZZJONI/ TIĠDID TA ’ L- AWTORIZZAZZJONI
Date of first authorisation:
t Data ta ’ l- ewwel awtorizzazzjoni:
21 March 2002 Date of latest renewal:
21 ta ’ Marzu 2002
21 March 2007 ed
21 ta ’ Marzu 2007
DATE OF REVISION OF THE TEXT M
DATA TA ’ META ĠIET RIVEDUTA L- KITBA
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu
to mediċini (EMEA) http: // www. emea. europa. eu
Quixidar 7.5 mg/ 0.6 ml solution for injection, pre-filled syringe.
Quixidar 7. 5 mg/ 0. 6 ml soluzzjoni għall- injezzjoni, siringa mimlija lesta
Each pre-filled syringe contains 7.5 mg of fondaparinux sodium in 0.6 ml solution for injection.
Kull siringa mimlija lesta fiha 7. 5mg ta ’ fondaparinux sodium f ’ 0. 6 ml ta ’ soluzzjoni għall- injezzjoni.
Excipient(s):
t Sustanza( i):
d sodium free.
za essenzjalment mingħajr sodium.
e For a full list of excipients, see section 6.1.
riz Għal lista sħiħa ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
Solution for injection.
aw Soluzzjoni għall- injezzjoni.
ut The solution is a clear and colourless to slightly yellow liquid.
Is- soluzzjoni huwa likwidu ċar u mingħajr kulur għal ftit safrani.
e 4.1 Therapeutic indications ng Treatment of acute Deep Vein Thrombosis (DVT) and treatment of acute Pulmonary Embolism (PE), except in haemodynamically unstable patients or patients who require thrombolysis or pulmonary lo embolectomy. no
x du 4. 1 Indikazzjonijiet terapewtiċi
4.2 Posology and method of administration
It- trattament ta ’ Trombożi akuta f’ Vina Fonda (DVT) u t- trattament ta ’ Emboliżmu Pulmonari (PE) ħa akut, ħlief f’ pazjenti li huma emodinamikament instabli jew f’ pazjenti li għandhom bżonn tromboliżi jew embolektomija. ’ g 4. 2 Pożoloġija u metodu ta ’ kif għandu jingħata im
The recommended dose of fondaparinux is 7.5 mg (patients with body weight ≥ 50, ≤ 100kg) once daily administered by subcutaneous injection.
Għal pazjenti b ’ piż ta ’ < 50 kg, id- doża rakkomandata hija ta ’ 5 mg.
For patients with body weight < 50 kg, the ct
Għal pazjenti b ’ piż ta ’ > 100 kg, id- doża rakkomandata hija ta ’ 10 mg. li l
For patients with body weight > 100 kg, the recommended dose is 10 mg. du
It- trattament għandu jitkompla għal mill- inqas 5 t’ ijiem u sakemm antikoagulazzjoni adekwata na
Treatment should be continued for at least 5 days and until adequate oral anticoagulation is established (International Normalised Ratio 2 to 3).
b’ antikoagulant orali tkun stabbilita b’ mediċina orali (International Normalised Ratio 2 sa 3).
as soon as possible and usually within 72 hours.
Trattament f’ istess ħin b ’ antikoagulant orali għandu jinbeda malajr kemm jista ’ jkun u s- soltu fi żmien 72 siegħa.
The average duration of administration in clinical trials was 7 days and the clinical experience from treatment beyond 10 days is limited. lP
mit- trattament għal aktar minn 10 t’ ijiem hija limitata. ed
Special populations na
Popolazzjonijiet speċjali
In patients ≥ 75 years, fondaparinux should be used with care, as renal function decreases with age (see section 4.4). ici
fondaparinux f’ pazjenti ≥ 75 sena għaliex il- funzjoni renali tonqos bl- eta` (ara sezzjoni 4. 4).
Renal impairment - Fondaparinux should be used with caution in patients with moderate renal impairment (see section 4.4). ed
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 renal impairment (creatinine clearance 30-50 ml/ min).
M’ hemmx esperjenza fis- sub- grupp ta ’ pazjenti li għandhom kemm piż tal- ġisem għoli (> 100 kg) kif ukoll indeboliment renali moderat (clearance tal- krejatinina 30- 50 ml/ min).
In this subgroup, after an initial 10 mg daily M
F’ dan is- sub- grupp, wara doża fil- bidu ta ’ 10 mg kuljum, tista ’ tiġi kunsidrata, meta bażata fuq mudell farmakokinetiku, tnaqqis Pr
dose, a reduction of the daily dose to 7.5 mg may be considered, based on pharmacokinetic modelling (see section 4.4).
tad- doża għal 7. 5 mg kuljum (ara sezzjoni 4. 4).
Hepatic impairment - No dosing adjustment is necessary.
Indeboliment tal- fwied - M’ hemmx bżonn aġġustament tad- doża.
33 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.
36 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 Fondaparinux huwa amministrat permezz ta ’ injezzjoni subkutanja fonda waqt li l- pazjent ikun mindud.
Sites of administration should alternate between the left and the right anterolateral and left and right posterolateral abdominal wall.
Il- postijiet ta ’ amministrazzjoni għandhom jalternaw bejn il- membrana ta ’ l- addome
To avoid the loss of medicinal product when using the pre-filled syringe do not expel the air bubble from the syringe before the injection.
t anterolaterali tax- xellug u tal- lemin u posterolaterali tax- xellug u tal- lemin.
The whole length of the
Biex tevita telf tal- prodott
d needle should be inserted perpendicularly into a skin fold held between the thumb and the forefinger;
It- tul kollu tal- labra għandu jiġi inserit b’ mod perpendikulari f’ tinja tal -
e the skin fold should be held throughout the injection.
riz ġilda miżmuma bejn is- saba ’ l- kbir u l- werrej; it- tinja tal- ġilda għandha tinżamm matul l- injezzjoni.
ris For additional instructions for use and handling and disposal see section 6.6.
Għal aktar struzzjonijiet għall- użu u maniġġar u għar- rimi ara sezzjoni 6. 6.
ho 4.3 Contraindications
to aw 4. 3 Kontra- indikazzjonijiet
ra
du
4.4 Special warnings and precautions for use
4. 4 Twissijiet speċjali u prekawzjonijiet speċjali għall- użu ħa Fondaparinux huwa intenzjonat għall- użu subkutanju biss.
Do not administer intramuscularly.
Tinjettax fil- muskoli. ’ g Hemm esperjenza limitata mit- trattament b ’ fondaparinux f’ pazjenti li m’ humiex stabbli im
There is limited experience from treatment with fondaparinux in haemodynamically unstable patients lo and no experience in patients requiring thrombolysis, embolectomy or insertion of a vena cava filter. no
emodinamikament u m’ hemm l- ebda esperjenza f’ pazjenti li għandhom bżonn tromboliżi, embolektomija jew li jiddaħħal filter ġol- vena cava.
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 ct
Fondaparinux għandu jintuża b’ attenzjoni f’ pazjenti b’ riskju ogħla ta ’ emorraġija, bħal dawk b’ mard ta 'fsada kemm konġenitali jew akkwistati (es. għadd ta ’ plejtlets < 50, 000 / mm3), mard gastro - na
ophthalmic surgery and in special patient groups as outlined below. du
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
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. ro
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. ed
Agents that may enhance the risk of haemorrhage should not be administered concomitantly with lP
Aġenti li jistgħu jżidu r- riskju ta ’ emorraġija m’ għandhomx jiġu amministrati flimkien ma ’ fondaparinux.
These agents include desirudin, fibrinolytic agents, GP IIb/ IIIa receptor antagonists, heparin, heparinoids, or Low Molecular Weight Heparin (LMWH).
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 na
Waqt trattament ta ’ VTE, f’ istess ħin għandha tingħata terapija b’ antagonista ta ’ vitamina K skond l- informazzjoni f ’ Sezzjoni 4. 5.
Other antiplatelet medicinal products (acetylsalicylic acid, dipyridamole, sulfinpyrazone, ticlopidine or clopidogrel), and NSAIDs should be used with caution.
ticlopidine jew clopidogrel), u NSAIDs għandhom jintużaw b’ attenzjoni.
If co- administration is essential, close monitoring is necessary. ici
Fil- każ li jkun essenzjali li jingħataw flimkien, jkun hemm bżonn ta ’ osservazzjoni mill- qrib. od
Spinal / Epidural anaesthesia ed
Anestesija Spinali / Epidurali F’ pazjenti li jieħdu fondaparinux għal trattament ta ’ VTE u mhux bħala profilassi, m’ għandiex tintuża Pr
M
anestesija spinali/ epidurali fil- każ ta ’ kirurġija.
Elderly patients The elderly population is at increased risk of bleeding.
37 Pazjenti anzjani In- nies anzjani huma f’ riskju akbar li jitilfu d- demm.
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, li jieħdu d- dożaġġ rakkomandat fit- trattament ta ’ DVT jew PE u kienu ta ’ 3. 0%, 4. 5% and 6. 5%, rispettivament.
The 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
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 -
34 the recommended regimen of UFH in the treatment of PE were 5.5%, 6.6% and 7.4%, respectively.
t każi f’ pazjenti li jieħdu d- dożaġġ rakkomandat ta ’ UFH fit- trattament ta ’ PE kienu ta ’ 5. 5%, 6. 6%
Low body weight Clinical experience is limited in patients with body weight < 50 kg.
riz Piż tal- ġisem baxx 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
Fondaparinux is known to be
to għandu jintuża b’ attenzjoni f ’ dan il- grupp ta ’ pazjenti (ara sezzjoni 4. 2 u 5. 2).
d excreted mainly by the kidney.
aw Indeboliment tal- kliewi Żieda fl- indeboliment tal- kliewi iżid ir- riskju ta ’ fsada.
Incidences of bleeding events in patients receiving the recommended
Huwa magħruf li fondaparinux jitneħħa fil - biċċa l- kbira mill- kliewi.
e 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/ 1132), 4.4% (32/ 733), 6.6% (21/ 318),
Każi ta ’ fsada f’ pazjenti li għandhom indeboliment renali ħafif, indeboliment renali moderat u indeboliment renali sever, li jieħdu d- dożaġġ rakkomandat fi trattament
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)
x ta ’ DVT jew PE, kienu ta ’ 3. 0% (34/ 1132), 4. 4% (32/ 733), 6. 6% (21/ 318), u 14. 5% (8/ 55),
ho 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 ’ ħa 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. ’ g Fondaparinux huwa kontra- indikat f’ indeboliment renali sever (clearance tal - krejatinina < 30ml/ min) im
ra should be used with caution in patients with moderate renal impairment (creatinine clearance 30-50 ml/ 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). li l
e 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).
Fondaparinux għandu jintuża na
Fondaparinux should be used with care in these patients.
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, lo 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). iċi
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
riskju ogħla ta ’ fsada minħabba nuqqas ta ’ fatturi ta ’ koagulazzjoni (ara sezzjoni 4. 2). tm
Patients with Heparin Induced Thrombocytopenia Fondaparinux does not bind to platelet factor 4 and does not cross-react with sera from patients with du
L- effikaċja u s- sigurta` ta ’ fondaparinux ma ot
The efficacy and safety of fondaparinux have not been formally studied in patients with HIT type II. ro
ġewx studjati formalment f’ pazjenti b ’ HIT tat- tip II. od
4.5 Interaction with other medicinal products and other forms of interaction lP
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott Pr
Bleeding risk is increased with concomitant administration of fondaparinux and agents that may enhance the risk of haemorrhage (see section 4.4). na
Ir- riskju ta ’ fsada jiżdied bl- amministrazzjoni konkomitanti ta ’ fondaparinux u aġenti li jistgħu jżidu r- riskju ta ’ emorraġija (ara sezzjoni 4. 4).
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 ici
F ’ studji kliniċi li saru b ’ fondaparinux, antikoagulanti li jittieħdu mill- ħalq (warfarin) ma kellhom ebda effett fuq il- farmakokinetika ta ’ fondaparinux.
did not influence the anticoagulation monitoring (INR) activity of warfarin. ed
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.
38 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 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 trattament b ’ acetylsalicylic acid jew piroxicam, u lanqas fuq il- farmakokinetika ta ’ digoxin fi stat fiss.
4.6 Pregnancy and lactation
t 4. 6 Tqala u Treddigħ
No clinical data on exposed pregnancies are available.
za 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.
riz biżżejjed rigward l- effetti fuq it- tqala u fuq l - iżvilupp ta ’ l- embriju/ fetu, ħlas u żvilupp wara t- twelid.
35 Fondaparinux is excreted in rat milk but it is not known whether fondaparinux is excreted in human milk.
to Fondaparinux jitneħħa fil- ħalib tal- far imma m’ hemmx tagħrif dwar l- eskrezzjoni ta ’ fondaparinux fil - ħalib tas- sider fil- bniedem.
Breast-feeding is not recommended during treatment with fondaparinux.
Fit -
Oral absorption by the child is however unlikely.
aw tarbija l- assorbiment mill- ħalq huwa improbabli.
No studies on the effect on the ability to drive and to use machines have been performed.
x Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni.
The most common adverse
du 4. 8 Effetti mhux mixtieqa ħa Is- sigurta ’ 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.
ris reactions were bleeding complications (see section 4.4).
L- effetti mhux mixtieqa l - ’ g iżjed komuni kienu kumplikazzjonijiet ta ’ fsada (ara sezzjoni 4. 4). im
ho 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
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 li l
ut class by decreasing order of seriousness.
dejjem jonqos. na iċi ed tm ot od Pr
e Blood and lymphatic system disorders ng Common: bleeding (gastrointestinal, haematuria, haematoma, epistaxis, haemoptysis, utero-vaginal haemorrhage, haemarthrosis, ocular, purpura, lo bruise) Uncommon: anaemia, thrombocytopaenia no
Komuni: fsada (gastro- intestinali, ematurja, ematoma, epistaxis, emoptisis, emorraġija uteru - vaġinali, emartrosis, okulari, purpura, tbenġil)
Rare: other bleeding (hepatic, retroperitoneal, intracranial/ intracerebral), thrombocythaemia ct
t za Mhux komuni: anemija, tromboċitopenja Rari: fsada oħra (epatika, retroperitonjali,
Rare: allergic reaction
riz intrakranja/ intraċerebrali), tromboċitemija
Metabolism and ro
to Rari: reazzjonijiet allerġiċi Distubi fis- sistema immuni
nutrition disorders lP
x du Mhux komuni: uġigħ ta ’ ras Disturbi fis- sistema nervuża Rari: sturdament ħa
ici
’ g
Uncommon: nausea, vomiting
Mhux komuni: dardir, rimettar
M
im
General disorders and administration site conditions
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il - Rari: raxx bi ħmura ġilda na
(2) Npn stands for non-protein-nitrogen such as urea, uric acid, amino acid, etc.
(2) Npn iffisser nitroġenu mhux minn proteini bħal urea, aċidu uriku, amino aċidi, etc.
36 4.9 Overdose
4. 9 Doża eċċessiva ot
There is no known antidote to fondaparinux.
M’ hemmx antidotu għal fondaparinux.
Initiation of appropriate therapy such as surgical haemostasis, blood replacements, fresh plasma transfusion, plasmapheresis should be considered.
Għandu jitqies l- bidu ta ’ trattament addattat bħal emastasi kirurġiku, tibdil ta ’ demm, trasfużjoni ta ’ plażma ġdida u plażmafereżi.
ris 5.1 Pharmacodynamic properties
5. 1 Tagħrif farmakodinamiku
ut Pharmacodynamic effects
t Effetti farmakodinamiċi
ra Fondaparinux is a synthetic and selective inhibitor of activated Factor X (Xa).
za Fondaparinux huwa inibitur sintetiku u selettiv ta ’ Fattur X attivat (Xa).
By binding selectively to antithrombin, fondaparinux potentiates (about 300 times) the
In- newtralizzazzjoni
e innate neutralization of Factor Xa by antithrombin.
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.
Neutralisation of Factor Xa interrupts the blood ng coagulation cascade and inhibits both thrombin formation and thrombus development.
Fondaparinux ma ’ jinattivax trombin (Fattur II
Fondaparinux does not inactivate thrombin (activated Factor II) and has no effects on platelets. lo 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) no
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
or prothrombin time (PT)/ International Normalised Ratio (INR) tests in plasma nor bleeding time or fibrinolytic activity.
x (ACT) jew prothrombin time (PT) / International Normalised Ratio (INR) fuq il - plażma, u lanqas il -
At the 10 mg dose used in interaction studies, fondaparinux did not significantly influence the anticoagulation activity (INR) of warfarin. ct
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
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 4874 patients were studied in controlled Phase II and III clinical studies. na
Iżjed minn 4874 pazjent kienu studjati f’ studji kliniċi kontrollati f ’ Fażi II u III. li l
Treatment of Deep Venous Thrombosis In a randomised, double-blind, clinical trial in patients with a confirmed diagnosis of acute ici
Trattament ta ’ Trombożi f’ Vina Fonda na
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 ed
Total ta ’ 2192 iċi
Both treatment groups received Vitamin K antagonist therapy usually initiated within 72 hours after the first study drug administration and continued for 90 ± 7 M
Iż- żewġ ġruppi ta ’ trattament kienu jieħdu terapija b ’ ed
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 tm
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). ot
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. od
37 Treatment of Pulmonary Embolism A randomised, open-label, clinical trial was conducted in patients with acute symptomatic PE.
Id - Pr
Patients who required thrombolysis or embolectomy or vena cava filter were excluded.
Pazjenti li kellhom bżonn tromboliżi, embolektomija jew li jiddaħħal filter ġol- vena cava kienu esklużi.
Randomised 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 excluded.
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
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
d of 2184 patients were treated; for both groups, patients were treated for at least 5 days and up to 22
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
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.
Treatment with
Intwera li t- trattament ta ’ fondaparinux mhux inferjur għal dak b ’ enoxaparin (rati ta ’
ho fondaparinux was demonstrated to be non-inferior to unfractionated heparin (VTE rates 3.8% and 5.0%, respectively).
za Fsada maġġuri fil- perjodu tal- bidu tat- trattament kienet osservata f ’ 1. 3% tal- pazjenti fuq
ut 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.
ra 5.2 Pharmacokinetic properties
5. 2 Tagħrif farmakokinetiku
e The pharmacokinetics of fondaparinux sodium are derived from fondaparinux plasma concentrations ng quantified via anti factor Xa activity.
to Il- farmakokinetika ta ’ fondaparinux sodium hija miġbura minn konċentrazzjonijiet ta ’ fondaparinux
As a result, the concentration of fondaparinux is expressed as milligrams (mg). lo Absorption no
Għalhekk, il- konċentrazzjoni ta ’ fondaparinux tidher bħala milligrammi (mg).
After subcutaneous dosing, fondaparinux is completely and rapidly absorbed (absolute bioavailability 100%).
x du 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 ’ 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.
Plasma concentrations of half the mean Cmax values are reached 25 minutes post-dosing. ct du
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 subcutaneous route.
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. ro
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
Mean (CV%) steady state pharmacokinetic parameters estimates of fondaparinux in patients lP
Cmax (mg/ l) - 0. 39 na
Cmax (mg/ l) - 0.39 (31%), Tmax (h) - 2.8 (18%) and Cmin (mg/ l) -0.14 (56%).
(31%), Tmax (s) - 2. 8 (18%) u Cmin (mg/ l) - 0. 14 (56%).
Cmax (mg/ l) - 0.50 (32%), na
F’ pazjenti bi ksur fil- għadma tal- ġenbejn, marbuta ma ’ l- eta` avvanzati tagħhom, il- konċentrazzjonijiet fissi fil- plażma ta ’ fondaparinux kienu ta ’:
Cmin (mg/ l) - 0.19 (58%).
Cmax (mg/ l) - 0. 50 (32%), Cmin (mg/ l) - 0. 19 (58%). iċi
In DVT and PE treatment, patients receiving fondaparinux 5 mg (body weight < 50 kg), 7.5 mg (body ici
Fit- trattament ta ’ DVT u PE, f ’ pazjenti li jieħdu fondaparinux 5 mg (piż < 50 kg), 7. 5 mg (piż 50- 100 ed
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.
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.
The mean (CV%) steady state ed
Cmax (mg/ l) - 1. 41 tm
Cmax (mg/ l) - 1.41 (23%), Tmax (h) – 2.4 (8%) and Cmin (mg/ l) -0.52 (45%).
(23%), Tmax (s) – 2. 4 (8%) u Cmin (mg/ l) - 0. 52 (45%).
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). ot
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).
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).
Pr
38 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.
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.
42 In vitro, fondaparinux ma inibixxix CYP450s (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 jew CYP3A4).
Thus, fondaparinux is not expected to interact with other medicinal
Għalhekk, mhux mistenni li in vivo fondaparinux ma jaqbilx ma xi prodotti mediċinali oħra minħabba l- inibizzjoni ta ’ metaboliżmu medjat minn CYP.
d products in vivo by inhibition of CYP-mediated metabolism.
Eskrezzjoni / Eliminazzjoni Il- half- life ta ’ eliminazzjoni (t½) huwa ta ’ madwar 17 il- siegħa f’ persuni żagħżagħ f’ saħħithom u
ris The elimination half-life (t½) is about 17 hours in healthy young subjects and about 21 hours in healthy elderly subjects.
t madwar 21 siegħa f ’ persuni anzjani f’ saħħithom.
ho Special populations
riz Gruppi ta ’ nies speċjali:
ut Paediatric patients - Fondaparinux has not been investigated in this population.
Pazjenti pedjatriċi: fondaparinux ma ġiex studjat f’ dan il- grupp.
ra Elderly patients - Renal function may decrease with age and thus, the elimination capacity for fondaparinux may be reduced in elderly.
to Pazjenti anzjani - L- eliminazzjoni ta ’ fondaparinux f’ anzjani jitnaqqas għaliex il- funzjoni renali
In patients > 75 years undergoing orthopaedic surgery and receiving fondaparinux 2.5 mg once daily, the estimated plasma clearance was 1.2 to 1.4 times lower
F’ pazjenti > 75 sena li jgħaddu minn kirurġija ortopedika, u fuq fondaparinux 2. 5 mg darba kuljum, l- estimu tal- clearance tal- plażma kienu minn 1. 2 sa 1. 4 l- darba iżjed baxx minn dak ta ’ pazjenti < 65 sena.
e than in patients < 65 years.
x Indeboliment renali - Il- clearance tal- plażma hija minn 1. 2 sa 1. 4 l- darba inqas f’ pazjenti b ’
A similar pattern is observed in DVT and PE treatment patients. ng 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 lo 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 no
du 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 ħa 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 ’ g minn dak f ’ funzjoni renali normali.
A similar pattern is observed in DVT and PE treatment patients. ct
osservat f’ pazjenti fuq trattament għal DVT u PE.
Body weight - Plasma clearance of fondaparinux increases with body weight (9% increase per 10 kg). du
Piż tal- ġisem - Il- clearance tal- plażma ta ’ fondaparinux jiżdied ma ’ l - piż (żieda ta ’ 9% kull 10 kg) li l
Gender - No gender differences were observed after adjustment for body weight. ro
Sess - Ma dehrux differenzi fis- sessi, wara li kien hemm arranġamenti għall - piż tal- ġisem. na
Race - Pharmacokinetic differences due to race have not been studied prospectively.
Razza - Id- differenzi farmakokinetiċi minħabba r- razza ma ġewx studjati b’ mod prospettiv.
However, studies lP
Ma nstabux differenzi iċi
Similarly, no plasma clearance differences were observed between black and Caucasian patients undergoing orthopaedic surgery. na
fil- clearance tal- plażma bejn pazjenti suwed u Kawkasi li għamlu kirurġija ortopedika. ed
Hepatic impairment - Fondaparinux pharmacokinetics has not been evaluated in hepatic impairment. ici
Indeboliment tal- fwied - Il- farmakokinetika ta ’ fondaparinux ma ’ ġietx studjata f’ indeboliment tal - fwied. tm
5.3 Preclinical safety data ed
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 ot
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 M
Studji fuq l- effett tossiku minn dożi ripetuti u fuq is- sistema riproduttiva, ma juru l- ebda periklu speċjali għall- bnedmin iżda ma provdew od
in the animal species.
Pr
Sodium chloride Water for injections Hydrochloric acid Sodium hydroxide
Sodium chloride Ilma għall- injezzjoni Aċidu idrokloriku
d 6.2 Incompatibilities
za 6. 2 Inkompatibilitajiet
e In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
riz Minħabba li ma sarux studji li juru liema huma l- prodotti li ma jablux miegħu, dan il- prodott mediċinali m’ għandux jitħallat ma ’ prodotti mediċinali oħrajn.
ho 6.3 Shelf life
to aw 6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
ut 6.4 Special precautions for storage
x 6. 4 Prekawzjonijiet speċjali għall- ħażna
e 6.5 Nature and contents of container ng Type I glass barrel (1 ml) affixed with a 27 gauge x 12.7 mm needle and stoppered with a chlorobutyl elastomer plunger stopper. lo Quixidar 7.5 mg/ 0.6 ml is available in pack sizes of 2, 7, 10 and 20 pre-filled syringes with a magenta no
du Tiffriżax ħa 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih ’ g 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. im
automatic safety system.
Quixidar 7. 5 mg/ 0. 6 ml jinstab f’ pakketti ta ’ 2, 7, 10, u 20 siringi mimlija lesti b ’ sistema awtomatika ta ’ sigurta ’ ta ’ kulur maġenta.
Not all pack sizes may be marketed.
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għal skop kummerċjali. li l
6.6 Special precautions for disposal and other handling ct
6. 5 Struzzjonijiet għall- użu u maniġġar u għar- rimi na
The subcutaneous injection is administered in the same way as with a classical syringe. du
L- injezzjoni subkutaneja tittieħed bl- istess mod ta ’ siringa klassika. iċi
Parenteral solutions should be inspected visually for particulate matter and discoloration prior to administration. ro
Soluzzjonijiet li jittieħdu b’ injezzjoni, għandhom jiġu spezzjonati viżwalment għal frak u telf ta ’ kulur qabel ma ’ jittieħdu. ed
Instruction for self-administration is mentioned in the Package Leaflet. lP
L- istruzzjonijiet biex wieħed ikun jista ’ jieħu hu stess l- injezzjoni huma mniżżlin fil- Fuljett ta ’ Tagħrif. tm
The Quixidar pre-filled syringe has been designed with an automatic needle protection system to prevent needle stick injuries following injection. na
Is- siringa mimlija lesta ta ’ Quixidar hija diżinjata b ’ sistema protettiva tal- labra awtomatika biex tevita li wieħed jittaqqab bi żball wara l- injezzjoni. ot