qanastek/EMEA-V3 huggingface dataset:
In XPRESS serious bleeding rates were consistent with those observed in previous studies during the 28-day study period (days 0-28).
F’ XPRESS ir- rati ta ’ fsada serja matul il- perijodu ta ’ studju ta ’ 28 ġurnata (ġranet 0- 28) kienu konsistenti ma ’ dawk osservati f’ studji kliniċi preċedenti.
Prophylactic heparin did not increase the risk of serious bleeding compared to placebo (3.9% vs 5.2%, respectively), including CNS bleeding (1.0% vs 0.7%, respectively).
Eparina mgħotija bħala profilassi ma żiedetx ir- riskju ta ’ fsada serja meta mqabbla ma ’ plaċebo (3. 9% kontra 5. 2%, rispettivament), inkluż il- fsada fis- CNS (1. 0% kontra 0. 7%, rispettivament)
In the phase 1 studies, adverse events with a frequency of ≥ 5% included headache (30.9%), ecchymosis (23.0%), and pain (5.8%).
Fl- istudji ta ’ Fażi 1, il- każijiet avversi bi frekwenza ta ’ ≥ 5% jiġbru fihom l- uġigħ ta ’ ras (30. 9%), l - ekkimożi (23. 0%), u l- uġigħ (5. 8%).
In clinical trials and in post marketing experience there have been reports of accidental overdosing.
F’ studji kliniċi u mill- esperjenza wara li l- prodott tpoġġa fis- suq kien hemm xi rapporti ta ’ doża eċċessiva aċċidentali.
In the majority of cases, no reactions have been observed.
Fil- biċċa l- kbira tal- każijiet, ma kienet osservata l- ebda reazzjoni.
For the other reports, the observed events were consistent with known undesirable effects of the drug (see section 4.8), effects of the drug on laboratory tests (see section 4.4), or consequences of the underlying condition of sepsis.
Dwar ir - rapporti l- oħra, il- każijiet osservati kienu konsistenti fl- effetti avversi magħrufa tal- mediċina (ara Sezzjoni 4. 8), fl- effetti tal- mediċina waqt it- testijiet fil- laboratorju (ara Sezzjoni 4. 4), jew fil - konsegwenzi li ġġib magħha l- kondizzjoni tas- sepsis.
There is no known antidote for drotrecogin alfa (activated).
M’ hemm l- ebda antidotu magħruf għal drotrecogin alfa (attivat).
In case of overdose, immediately stop the infusion (see section 5.2).
Fil- każ ta ’ doża eċċessiva, waqqaf l - infużjoni minnufih (ara sezzjoni 5. 2).
B01AD10
Kategorija farmakoterapewtika: sustanzi antitrombotiċi, enżimi, Kodiċi ATC:
This means that for scientific reasons it has not been possible to obtain complete information on this medicinal product.
B01AD10 Dan il- prodott mediċinali ġie awtorizzat taħt “ Ċirkustanzi ta ’ Eċċezzjoni ”. Dan ifisser li minħabba raġunijiet xjentifiċi ma kienx possibbli li tinkiseb informazzjoni kompleta dwar dan il- prodott.
The European Medicines Agency (EMEA) will review any new information which may become available every year and this SPC will be updated as necessary.
Kull sena l- Aġenzija Ewropeja tal- Mediċini se tirrevedi kull informazzjoni ġdida li jista ’ jkun hemm u jekk ikun hemm il- bżonn dan l- SPC jiġi aġġornat.
Mechanism of Action Xigris is a recombinant version of the natural plasma-derived activated Protein C, from which it differs only by unique oligosaccharides in the carbohydrate portion of the molecule.
Mekkaniżmu ta ’ kif jaħdem Xigris huwa verżjoni rikombinanti tal- Proteina Ċ attivata derivata mill- plażma b’ mod naturali, u huwa differenti minnha biss minħabba l- oligosakkaridi uniċi fil- porzjoni tal- karboidrati tal- molekula.
Activated Protein C is a crucial coagulation regulator.
Il - Proteina Ċ attivata hija regulatur kruċjali tal- koagulazzjoni.
It limits thrombin formation by inactivating factors Va and VIIIa, thereby providing negative feedback regulation of coagulation.
Hija tillimita l- formazzjoni tat- trombina billi tinattiva l- fatturi Va u VIIIa, u b’ hekk tikkontrolla l- koagulazzjoni permezz ta ’ feedback negattiv.
Excessive coagulation activation in the microcirculatory bed plays a significant part in the pathophysiology of severe sepsis.
L- attivazzjoni eċċessiva tal- koagulazzjoni fil- livell mikroċirkolatorju għandha parti sinifikanti fil - patofiżjoloġija ta ’ sepsis gravi.
Furthermore, Activated Protein C is an important modulator of the systemic response to infection and has antithrombotic and profibrinolytic properties.
Barra minn hekk, il- Proteina Ċ attivata hija modulatur importanti tar - rispons sistemiku għall- infezzjoni u għandha karatteristiċi antitrombotiċi u profibrinolitiċi.
Xigris has similar properties to those of endogenous human Activated Protein C.
Xigris għandu l- istess karatteristiċi tal- Proteina Ċ attivata umana endoġena.
Pharmacodynamic Effects In placebo-controlled clinical trials in patients with severe sepsis, Xigris exerted an antithrombotic effect by limiting thrombin generation and improved sepsis-associated coagulopathy, as shown by a more rapid improvement in markers of coagulation and fibrinolysis.
Effetti farmakodinamiċi F’ studji kliniċi kkontrollati bi plaċebo f’ pazjenti b’ sepsis gravi, Xigris kellu effett antitrombotiku billi llimita l- formazzjoni tat- trombina u tejjeb il- koagulopatija assoċjata mas- sepsis, kif jidher minn titjib aktar mgħaġġel fl- indikaturi tal- koagulazzjoni u fibrinoliżi.
Xigris caused a more rapid decline in thrombotic markers such as D-dimer, prothrombin F1.2, and thrombin-antithrombin levels and a more rapid increase in Protein C and antithrombin levels.
Xigris ikkawża tnaqqis aktar rapidu fl - indikaturi trombotiċi bħal D- dimer, protrombina F1. 2, u livelli ta ’ trombina- antitrombina u żieda aktar mgħaġġla fil- livelli tal- Proteina Ċ u l- antitrombina.
Xigris also restored endogenous fibrinolytic potential, as evidenced by a more rapid trend toward normalisation in plasminogen levels and a more rapid decline in plasminogen activator inhibitor-1 levels.
Barra minn hekk, il -
Additionally, patients with severe sepsis treated with Xigris had a more rapid decline in interleukin-6 levels, a global marker of inflammation, consistent with a reduction in the inflammatory response.
8 pazjenti b’ sepsis gravi ikkurati b’ Xigris kellhom tnaqqis aktar mgħaġġel fil- livelli ta ’ interleukin- 6, li huwa indikatur globali ta ’ l- infjammazzjoni, flimkien ma ’ tnaqqis tar- rispons infjammatorju.
Clinical Efficacy Xigris was studied in one Phase 3 international, multi-centre, randomised, double-blind, placebo- controlled trial (PROWESS) in 1690 patients with severe sepsis.
Effikaċja klinika Xigris kien studjat f’ studju wieħed Fażi 3 internazzjonali, magħmul b’ mod arbitrarju, double - blind, multiċentriku, ikkontrollat bi plaċebo (PROWESS) f’ 1, 690 pazjent b’ sepsis gravi.
Severe sepsis is defined as sepsis associated with acute organ dysfunction.
Is- sepsis gravi hija definita bħala sepsis assoċjata ma ’ nuqqas akut fil- funzjoni ta ’ l- organi.
Patients meeting the clinical diagnosis of severe sepsis had a) known or suspected infection, b) clinical evidence of systemic response to infection including fever or hypothermia, leucopenia or leucocytosis, tachycardia and tachypnoea, and c) acute organ dysfunction.
Il- pazjenti li kkwalifikaw għad- dijanjożi klinika ta ’ sepsis gravi kellhom a) infezzjoni magħrufa jew suspettata, b) evidenza klinika ta ’ rispons sistemiku għall- infezzjoni inkluż deni jew ipotermja, lewkopenija jew lewkoċitożi, takikardija u takipnea, u c) nuqqas akut fil- funzjoni ta ’ l- organi.
Organ dysfunction was defined as shock, hypotension or the need for vasopressor support despite adequate fluid resuscitation, relative hypoxemia (ratio of partial pressure of oxygen in arterial blood in mmHg to the percentage of oxygen in the inspired air expressed as a decimal (PaO2/ FiO2 ratio) < 250), oliguria despite adequate fluid resuscitation, marked reduction in blood platelet counts, and/ or elevated lactic acid concentrations.
In- nuqqas fil- funżjoni ta ’ l- organi kien definit bħala xokk, pressjoni baxxa tad- demm jew il- ħtieġa għal għajnuna b’ vażopressuri, minkejja resuxxitazzjoni adegwata bil- fluwidi, ipoksemija relattiva (proporzjon ta ’ pressjoni parzjali ta ’ l- ossiġenu fid- demm fl- arterji f’ mmHg għall- perċentwal ta ’ l- ossiġenu fl- arja inspirata espress bħala deċimu (proporzjon ta ’ PaO2/ FiO2) < 250), oligurja minkejja resuxxitazzjoni adegwata bil - fluwidi, tnaqqis ġmielu fil- għadd tal- plejtlets, u/ jew livelli għoljin ta ’ konċentrazzjonijiet ta ’ aċidu lattiku.
Exclusion criteria encompassed patients at high risk of bleeding (see sections 4.3 and 4.4), patients who were not expected to survive for 28 days due to a pre-existing, non-sepsis related medical condition, HIV positive patients whose most recent CD4 count was ≤ 50/ mm3, patients on chronic dialysis, and patients who had undergone bone marrow, lung, liver, pancreas or small bowel transplantation, and patients with acute clinical pancreatitis without a proven source of infection.
Il- kriterji ta ’ esklużjoni inkludew pazjenti b’ riskju għoli ta ’ fsada (ara sezzjonijiet 4. 3 u 4. 4), pazjenti li ma kinux mistennija li jgħixu għal 28 jum minħabba kundizzjoni medika pri- eżistenti u mhix relatata mas- sepsis, pazjenti li kienu pożittivi għall- HIV li kellhom l- għadd ta ’ CD4 l - aktar reċenti tagħhom ta ’ ≤ 50/ mm3, pazjenti b’ dijaliżi kronika, u pazjenti li sarulhom trapjanti tal- mudullun, tal- pulmun, tal- fwied, tal- frixa jew tal- musrana ż- żgħira, kif ukoll pazjenti b’ pankreatite klinika akuta mingħajr kawża ppruvata ta ’ infezzjoni.
8 In the PROWESS trial, treatment was initiated within 48 hours of onset of the first sepsis-induced organ dysfunction.
Fl- istudju PROWESS, il- kura bdiet fi żmien 48 siegħa minn meta l- organu ma baqax jiffunzjona minħabba s- sepsis.
The median duration of organ dysfunction prior to treatment was 18 hours.
In- nuqqas ta ’ funzjoni ta ’ l- organu damet għal medja ta ’ 18- il siegħa qabel il- kura.
Patients were given a 96-hour constant rate infusion of Xigris at 24 µg/ kg/ hr (n=850) or placebo (n=840).
Il- pazjenti ngħataw infużjoni ta ’ 24 µg/ kg/ siegħa ta ’ Xigris b’ rata kostanti għal 96 siegħa (n=850) jew plaċebo (n=840).
Xigris was added to best standard care.
Xigris ingħata flimkien ma ’ l- aqwa kura indikata.
Best standard care includes adequate antibiotics, source control and supportive treatment (fluids, inotropes, vasopressors and support of failing organs, as required).
Il- kura msemmija kienet tinkludi antibijotiċi adegwati, kontroll tal- kawża tas- sepsis u kura ta ’ għajnuna (fluwidi, inotropi, vażopressuri u għajnuna għall- organi li ma kinux jiffunzjonaw tajjeb, kif meħtieġ).
Patients treated with Xigris experienced improved 28-day survival compared to those treated with placebo.
Il- pazjenti ikkurati b’ Xigris urew titjib fis- sopravvivenza f’ terminu ta ’ 28 ġurnata, aħjar minn dawk li ħadu l- plaċebo.
At 28 days, the overall mortality rates were 24.7% for the Xigris-treated group and 30.8% for the placebo-treated group (p=0.005).
Mat- 28 jum, ir- rata ta ’ mortalità ġenerali kienet ta ’ 24. 7% għall- grupp li ħa Xigris u ta ’ 30. 8% għall- grupp li ħa l- plaċebo (p=0. 005).
Significant absolute death reduction was limited to the subgroup of patients with greater disease severity i. e. baseline APACHE II score ≥ 25 or at least 2 acute organ dysfunctions at baseline.
It- tnaqqis sinifikanti assolut fl- imwiet kien limitat għas- sottogrupp ta ’ pazjenti b’ mard aktar gravi i. e., linja bażi ta ’ APACHE II > 25 jew dawk b’ mill- inqas żewġ organi li ma jiffunzjonawx b’ mod akut fil - linja bażi.
(The APACHE II score is designed to assess the risk of mortality based on acute physiology and chronic health evaluation).
(Il- marka ta ’ APACHE II hija maħsuba li tkejjel ir- riskju tal- mortalità a bażi ta ’ l - evalwazzjoni tal- fiżjoloġija akuta u tas- saħħa kronika).
In the subgroup of patients with an APACHE II score ≥ 25 at baseline, the mortality was 31% in the Xigris group (128 out of 414) and 44% in the placebo group (176 out of 403).
Fis- sottogrupp ta ’ pazjenti b’ marka bażi ta ’ APACHE II > 25, il- mortalità kienet ta ’ 31% fil- grupp Xigris (128 minn 414) u ta ’ 44% fil- grupp tal - plaċebo (176 minn 403).
No death reduction was observed in the subgroup of patients with lower disease severity.
L- ebda tnaqqis fl- imwiet ma kien osservat fis- sottogrupp ta ’ pazjenti b’ mard anqas gravi.
In the subgroup of patients with at least 2 acute organ dysfunctions at baseline, the mortality was 26.5% in the Xigris group (168 out of 634) and 33.9% in the placebo group (216 out of 637).
Fis- sottogrupp ta ’ pazjenti b’ mill- anqas żewġ organi li ma jiffunzjonawx b’ mod akut fil - linja bażi, il- mortalità kienet ta ’ 26. 5% fil- grupp ta ’ Xigris (168 minn 634) u ta ’ 33. 9% fil- grupp tal - plaċebo (216 minn 637).
No significant death reduction was observed in the subgroup of patients with less than 2 acute organ dysfunctions at baseline.
L- ebda tnaqqis sinifikanti fl- imwiet ma kien osservat fis- sottogrupp ta ’ pazjenti b’ anqas minn żewġ organi li ma jiffunzjonawx b’ mod akut fil- linja bażi.
A consistent treatment effect on mortality with Xigris administration was observed across patient subgroups defined by age, gender and infection type.
Kien osservat effett konsistenti fuq il- mortalità bil- kura ta ’ Xigris f’ sottogruppi ta ’ pazjenti magħżula bl- età, bis- sess u bit- tip ta ’ infezzjoni.
PROWESS Follow-up Study Survival status was assessed in a follow-up study of PROWESS survivors.
PROWESS Studju Sussegwenti L- istatus tas- sopravvivenza kien analizzat fi studju sussegwenti fuq is- sopravviventi ta ’ PROWESS.
In-hospital and 3 month survival status was reported for 98% and 94% of the 1690 PROWESS subjects respectively.
L- istatus tas- sopravvivenza fl- isptar u għat- 3 xhur ta ’ wara kien ta ’ 98% u ta ’ 94% ta ’ l- 1, 690 pazjent ta ’ PROWESS rispettivament.
In the overall population, the in-hospital mortality was significantly lower in patients on Xigris than in patients on placebo (29.4% vs.
Fil- popolazzjoni ġenerali, il- mortalità fl- isptar kienet aktar baxxa b’ mod sinifikanti f’ pazjenti li ħadu Xigris milli f’ pazjenti li ħadu l- plaċebo (29. 4% vs.
34.6%; p=0.023).
34. 6%; p=0. 023).
Survival through 3 months was also better in the Xigris group compared to placebo (log rank p=0.048).
Is- sopravvivenza wara 3 xhur kienet ukoll aħjar fil- grupp ta ’ Xigris milli f’ dawk li ħadu l - plaċebo (log rank p=0. 048).
These data confirmed that the benefit of Xigris is limited to the more severely affected sepsis patients such as patients with multiple organ failure and shock.
9 għall- pazjenti effettwati b’ sepsis gravi, bħal pazjenti li jkollhom aktar minn organu wieħed li ma jiffunzjonax u jkollhom xokk.
Further Clinical Experience In a Phase 3b international, single-arm, open-label clinical trial (ENHANCE), 2378 adult patients with severe sepsis received drotrecogin alfa (activated).
Aktar Esperjenza Klinika F’ studju kliniku Fażi 3b internazzjonali, b’ fergħa waħda, double- blind (ENHANCE), 2, 378 pazjent adult b’ sepsis gravi ħadu drotrecogin alfa (attivat).
The entry criteria were similar to those employed in PROWESS.
Il- kriterji tar- reġistrazzjoni kienu l- istess bħal dawk li ntużaw fi PROWESS.
Patients received drotrecogin alfa (activated) within 48 hours of onset of the first sepsis- induced organ dysfunction.
Il- pazjenti ħadu drotrecogin alfa (attivat) fi żmien 48 siegħa minn meta s - sepsis ikkawża n- nuqqas ta ’ funzjoni ta ’ l- organi.
The median duration of organ dysfunction prior to treatment was 25 hours.
Iż- żmien medju minn meta l- organi ma baqgħux jiffunzjonaw sa qabel il- kura kien ta ’ 25 siegħa.
At 28 days, the mortality rate in the Phase 3b study was 25.3%.
Mat- 28 ġurnata, ir- rata tal- mortalità fil- Fażi 3b ta ’ l - istudju kienet ta ’ 25. 3%.
The mortality rate was lower for patients treated within 24 hours of organ dysfunction compared to those treated after 24 hours, even after adjustment for differences in disease severity.
Ir- rata tal- mortalità kienet iktar baxxa għal dawk il- pazjenti li ħadu l- kura fi żmien 24 siegħa minn meta l- organi ma baqgħux jiffunzjonaw milli għal dawk li ħadu l- kura wara 24 siegħa, anki wara li sar l- aġġustament għall- gravità tal- mard.
A total of 2640 adult patients with severe sepsis who were at low risk of death (e. g. patients with APACHE II < 25 or with only one sepsis-induced organ failure) were enrolled in a randomised, double- blind, placebo-controlled trial (ADDRESS).
Għadd ta ’ 2, 640 pazjent b’ sepsis gravi li kellhom riskju baxx ta ’ mewt (p. e. pazjenti b’ APACHE II < 25 jew b’ organu wieħed li ma kienx jiffunzjona minħabba s- sepsis) iddaħħlu fi studju magħmul b’ mod arbitrarju, double- blind, ikkontrollat bi plaċebo (ADDRESS).
The trial was stopped after an interim analysis due to a low likelihood of demonstrating a significant difference in 28-day mortality by the end of the trial.
L- istudju twaqqaf wara analiżi ad interim minħabba li ftit kien hemm ċans li toħroġ differenza sinifikanti fil- mortalità f’ terminu ta ’ 28 ġurnata sa tmiem l- istudju.
25) and were more likely to have two organ dysfunctions (76% vs.
L- istudju ADDRESS irreġistra 872 pazjent li kellhom disfunzjoni ta ’ iktar minn organu wieħed Meta wieħed iqabbilhom ma ’ dawk ta ’ l- istudju PROWESS, il- pazjenti f’ ADDRESS kellhom l- organi ma jiffunzjonawx għal perjodu itwal qabel ħadu l- mediċina fl- istudju (medja ta ’ 25 vs 18- il siegħa), kellhom skors APACHE II aktar baxxi (medja ta ’ 20 vs 25) u aktarx kellhom żewġ organi li ma jiffunzjonawx (76% vs 43%).
At 28 days, the mortality rates for multiple organ dysfunction patients in ADDRESS were 20.7% versus 21.9% for drotrecogin alfa (activated)-treated and placebo-treated patients, respectively.
Mat- 28 ġurnata, ir- rata ta ’ mortalità għal pazjenti b’ aktar minn organu wieħed ma jiffunzjonax f’ ADDRESS kienet ta ’ 20. 7% għal pazjenti li ħadu drotrecogin alfa (attivat) kontra 21. 9% għal dawk bil- plaċebo.
In-hospital mortality rates were 23.1% and 25.3% respectively.
Ir- rata ta ’ mortalità fl- isptar kienet ta ’ 23. 1% u ta ’ 25. 3% rispettivament.
In the subgroup with two organ dysfunctions, the results were similar to those seen in the PROWESS trial.
Fis- sottogrupp b’ żewġ organi ma jiffunzjonawx, ir- riżultati kienu l- istess bħal dawk ta ’ l- istudju PROWESS.
9 In placebo controlled clinical trials, the treatment effect was most evident at sites enrolling larger numbers of patients.
F’ studji kliniċi kkontrollati bi plaċebo, l- effett tal- kura kien evidenti l- aktar f’ postijiet li rreġistraw għadd kbir ta ’ pazjenti.
Drotrecogin alfa (activated) and endogenous human Activated Protein C are inactivated in plasma by endogenous protease inhibitors but the mechanism by which they are cleared from plasma is unknown.
Drotrecogin alfa (attivat) u l- Proteina Ċ Attivata umana endoġena huma inattivati fil- plażma bl - inibituri endoġeni tal- proteażi iżda l- mekkaniżmu li bih jitneħħew mill- plażma mhuwiex magħruf.
Plasma concentrations of endogenous Activated Protein C in healthy subjects and patients with severe sepsis are usually below detection limits (< 5 ng/ ml) and do not significantly influence the pharmacokinetic properties of drotrecogin alfa (activated).
Konċentrazzjonijiet fil- plażma ta ’ Proteina Ċ Attivata endoġena f’ persuni u pazjenti b’ saħħithom u dawk b’ sepsis gravi ġeneralment ikunu taħt il- livelli li jistgħu jitkejlu (< 5 ng/ ml) u ma jeffettwawx b’ mod sinifikanti l- karatteristiċi farmakokinetiċi ta ’ drotrecogin alfa (attivat).
In healthy subjects, greater than 90% of the steady state condition is attained within 2 hours following the start of a constant-rate intravenous infusion of Xigris.
F’ persuni b’ saħħithom, aktar minn 90% tal- kundizzjoni fejn il- konċentrazzjoni tkun stabbli jintlaħaq fi żmien sagħtejn minn mindu tibda l- infużjoni fil- vina b’ rata kostanti ta ’ Xigris.
Following the completion of an infusion, the decline in plasma drotrecogin alfa (activated) concentrations is biphasic and is comprised of a rapid initial phase (t1/ 2 α =13 minutes) and a slower second phase (t1/ 2 β =1.6 hours).
Wara tmiem l - infużjoni, it- tnaqqis tal- konċentrazzjonijiet ta ’ drotrecogin alfa (attivat) fil- plażma jsir f’ żewġ fażijiet u jikkonsisti f’ fażi inizjali rapida (t1/ 2 α=13- il minuta) u t- tieni fażi aktar bil- mod (t1/ 2 β=1. 6 sigħat).
The short half-life of 13 minutes accounts for approximately 80% of the area under the plasma concentration curve and governs the initial rapid accrual of plasma drotrecogin alfa (activated) concentrations towards the steady-state.
Il- half life qasira ta ’ 13- il minuta tgħodd għal madwar 80% ta ’ l- erja taħt il- kurva tal- konċentrazzjoni tal - plażma u tirregola ż- żieda rapida inizjali tal- konċentrazzjonijiet ta ’ drotrecogin alfa (attivat) fil- plażma lejn stat stabbli.
Plasma drotrecogin alfa (activated) steady-state concentrations are proportional to the infusion rate over a range of infusion rates from 12 µg/ kg/ hr to 48 µg/ kg/ hr.
Il- konċentrazzjonijiet fi stat stabbli ta ’ drotrecogin alfa (attivat) fil- plażma huma proporzjonali għar- rata ta ’ infużjoni fi skala ta ’ rati ta ’ infużjoni minn 12 µg/ kg/ siegħa sa 48 µg/ kg/ siegħa.
The mean steady-state plasma concentration of drotrecogin alfa (activated) in healthy subjects receiving 24 µg/ kg/ hr is 72 ng/ ml.
Il- medja tal- konċentrazzjoni ta ’ drotrecogin alfa (attivat) fil- plażma fi stat stabbli f’ persuni b’ saħħithom li jieħdu 24 µg/ kg/ siegħa hija ta ’ 72 ng/ ml.
In patients with severe sepsis, infusion of drotrecogin alfa (activated) from 12 µg/ kg/ hr to 30 µg/ kg/ hr rapidly produced steady-state plasma concentrations that were proportional to infusion rates.
F’ pazjenti b’ sepsis gravi, l- infużjoni ta ’ drotrecogin alfa (attivat) ta ’ bejn 12 µg/ kg/ siegħa u 30 µg/ kg/ siegħa pproduċiet bil- ħeffa konċentrazzjonijiet ta ’ drotrecogin alfa (attivat) fil- plażma fi stat stabbli li kienu proporzjonati għar- rati ta ’ infużjoni.
In the Phase 3 trial, the pharmacokinetics of drotrecogin alfa (activated) were evaluated in 342 patients with severe sepsis administered a 96-hour continuous infusion at 24 µg/ kg/ hr.
Fl- istudju tal- Fażi 3, il- farmakokinetiċi ta ’ drotrecogin alfa (attivat) kienu evalwati fi 342 pazjent b’ sepsis gravi li ngħatatilhom infużjoni kontinwa għal 96 siegħa b’ rata ta ’ 24 µg/ kg/ siegħa.
The pharmacokinetics of drotrecogin alfa (activated) were characterised by attainment of steady-state plasma concentration within 2 hours following the start of the infusion.
Il- farmakokinetiċi ta ’ drotrecogin alfa (attivat) kienu karatterizzati minn konċentrazzjoni ta ’ plażma ta ’ stat stabbli fi żmien sagħtejn mill- bidu ta ’ l -
In the majority of patients, measurements of Activated Protein C beyond 2 hours after termination of the infusion were below the quantifiable limit, suggesting rapid elimination of drotrecogin alfa (activated) from the systemic circulation.
Fil- maġġoranza tal- pazjenti, il- kwantità ta ’ Proteina Ċ attivata wara aktar minn sagħtejn minn tmiem l- infużjoni kienet inqas mil- limitu kwantifikabbli, li jissuġġerixxi t- tneħħija mgħaġġla ta ’ drotrecogin alfa (attivat) miċ- ċirkolazzjoni sistemika.
The plasma clearance of drotrecogin alfa (activated) is approximately 41.8 l/ hr in sepsis patients as compared with 28.1 l/ hr in healthy subjects.
It- tneħħija mill- plażma ta ’ drotrecogin alfa (attivat) hija ta ’ madwar 41. 8 l/ siegħa għal pazjenti bis- sepsis meta nqabbluha ma ’ 28. 1 l/ siegħa f’ persuni b’ saħħithom.
In patients with severe sepsis, the plasma clearance of drotrecogin alfa (activated) was significantly decreased by renal impairment and hepatic dysfunction, but the magnitude of the differences in clearance (< 30%) does not warrant any dosage adjustment.
Fil- pazjenti b’ sepsis gravi, it- tneħħija ta ’ drotrecogin alfa (attivat) mill- plażma naqset b’ mod sinifikanti f’ min kellu mard fil- kliewi u l- fwied, iżda d- differenzi fit- tneħħija (< 30%) ma jiġġustifikawx tibdil fid- doża.
Changes observed in monkeys at, or in small excess of, the maximum human exposure during repeated dose studies, were all related to the pharmacological effect of Xigris and include beside the expected prolongation of APTT, decreases in haemoglobin, erythrocytes and haematocrit, and increases in reticulocyte count and PT.
Fi studji ripetuti dwar id- doża, it- tibdiliet osservati fix- xadini, meta kienu esposti għal doża simili jew ftit aktar għolja minn dik massima li jista ’ jkun espost għaliha l- bniedem, kienu kollha relatati ma ’ l - effett farmakoloġiku ta ’ Xigris u jinkludu, minbarra t- titwil mistenni ta ’ l- APTT, tnaqqis fl - emoglobina, fl- eritroċiti (fiċ- ċelluli ħomor tad- demm) u fl- ematokrit, u żidiet fl- għadd taċ- ċelluli retikuloċiti u fil- PT.
Drotrecogin alfa (activated) was not mutagenic in an in vivo micronucleus study in mice or in an in vitro chromosomal aberration study in human peripheral blood lymphocytes with or without rat liver metabolic activation.
Drotrecogin alfa (attivat) ma kienx mutaġeniku fi studju mikronuklejku in vivo li sar fuq il- ġrieden jew studju in vitro ta ’ aberrazzjoni kromożomali fil- linfoċiti tad- demm periferali tal- bniedem b’ attivazzjoni metabolika bil- fwied tal- firien jew mingħajrha.
Carcinogenicity studies and animal reproduction studies have not been conducted with Xigris.
Ma sarux studji b’ Xigris dwar il- karċinoġeniċità u dwar ir- riproduzzjoni fl- annimali.
However, with respect to the latter, the potential risk for humans being unknown, Xigris should not be used during pregnancy unless clearly necessary (see section 4.6).
Madanakollu, rigward din ta ’ l- aħħar, u minħabba li r- riskji għall- bnedmin mhumiex magħrufa, Xigris m’ għandux jintuża waqt it- tqala sakemm ma jkunx meħtieġ b’ mod ċar (ara sezzjoni 4. 6).
Sucrose Sodium chloride Sodium citrate Citric acid Hydrochloric acid Sodium hydroxide
Sucrose Sodium chloride Sodium citrate Citric acid Hydrochloric acid Sodium hydroxide.
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
Dan il- prodott mediċinali m’ għandux jitħallat ma ’ prodotti mediċinali oħra ħlief ma ’ dawk imsemmija f’ sezzjoni 6. 6.
After reconstitution, immediate use is recommended.
Wara r- rikostituzzjoni huwa rakkomandat li jintuża minnufih.
However, the reconstituted solution in the vial may be held for up to 3 hours at room temperature (15ºC-30ºC).
Madanakollu, s- soluzzjoni rikostitwita fil- kunjett tista ’ tinżamm sa 3 sigħat f’ temperatura ambjentali (15°C - 30ºC).
After preparation, the intravenous infusion solution can be used at room temperature (15ºC-30ºC) for a period up to 14 hours.
Wara l- preparazzjoni, s- soluzzjoni ta ’ infużjoni għal ġol- vina tista ’ tintuża f’ temperatura ambjentali (15°C - 30ºC) għal terminu sa 14- il siegħa.
Store in a refrigerator (2°C-8°C).
Aħżen fi friġġ (2°C - 8°C).
Powder in Type I glass vial.
Pakkett ta ’ kunjett wieħed.
Pack of 1 vial.
1.
Use appropriate aseptic technique during the preparation of Xigris for intravenous administration.
Uża teknika asettika xierqa matul il- preparazzjoni ta ’ Xigris għall- għoti minn ġol- vina
Calculate the dose and the number of Xigris vials needed.
Ikkalkula d- doża u l- għadd ta ’ kunjetti ta ’ Xigris meħtieġa.
Each Xigris vial contains 20 mg of drotrecogin alfa (activated).
Kull kunjett Xigris fih 20 mg drotrecogin alfa (attivat).
The vial contains an excess of drotrecogin alfa (activated) to facilitate delivery of the label amount.
Il- kunjett ikun fih drotrecogin alfa (attivat) żejjed biex jassigura li jkun hemm l- ammont imsemmi fuq it- tikketta.
Prior to administration, 20 mg vials of Xigris must be reconstituted with 10 ml of Sterile Water for Injection, resulting in a solution with a concentration of approximately 2 mg/ ml drotrecogin alfa (activated).
Qabel jingħata, il- kunjetti ta ’ 20 mg ta ’ Xigris għandhom jiġu rikostitwiti b’ 10 ml Ilma Sterili għall- Injezzjoni, li jirriżulta f’ soluzzjoni b’ konċentrazzjoni ta ’ madwar 2 mg/ ml drotrecogin alfa (attivat).
Slowly add the Sterile Water for Injection to the vial and avoid inverting or shaking the vial.
Żid l- Ilma Sterili għall- Injezzjoni bil- mod fil- kunjett u evita li taqleb ta ’ taħt fuq il- kunjett jew li tħawwad il- kunjet.
Gently swirl each vial until the powder is completely dissolved.
Dawwar bil- mod kull kunjett sakemm it- trab jinħall kompletament.
The solution of reconstituted Xigris must be further diluted with sterile 0.9% Sodium Chloride Injection to a final concentration of between 100 µg/ ml and 200 µg/ ml.
Is- soluzzjoni ta ’ Xigris rikostitwit trid tkompli tiġi dilwita b’ injezzjoni ta ’ soluzzjoni sterili ta ’ 0. 9% sodium chloride għal konċentrazzjoni finali li tkun bejn 100 µg/ ml u 200 µg/ ml..
Slowly withdraw the appropriate amount of reconstituted drotrecogin alfa (activated) solution from the vial.
Iġbed bil- mod l- ammont xieraq ta’ soluzzjoni ta ’ drotrecogin alfa (attivat) rikostitwit mill- kunjett.
Add the reconstituted drotrecogin alfa (activated) into a prepared infusion bag of sterile 0.9% Sodium Chloride Injection.
Żid d- drotrecogin alfa (attivat) rikostitwit f’ borża ta ’ infużjoni ppreparata b ’ 0. 9% sodium chloride sterili.
When adding the reconstituted drotrecogin alfa (activated) into the infusion 11 bag, direct the stream to the side of the bag to minimise the agitation of the solution.
Meta tkun qed iżżid d- drotrecogin alfa (attivat) rikostitwit fil- borża ta ’ infużjoni, iddirezzjona s- soluzzjoni lejn il- ġenb tal- borża biex tnaqqas kemm jista ’ jkun l- aġitazzjoni tas - soluzzjoni.
Gently invert the infusion bag to obtain a homogeneous solution.
Aqleb bil- mod il- borża rasha ’ l isfel biex ikollok soluzzjoni omoġena.
Do not transport the infusion bag between locations using mechanical delivery systems.
Tmexxix il - borża ta ’ infużjoni minn post għall- ieħor billi tuża sistemi tat- trasport mekkaniċi.
After reconstitution, immediate use is recommended.
Wara r- rikostituzzjoni, huwa rrakkomandat li l- prodott jintuża immedjatament.
However, the reconstituted solution in the vial may be held for up to 3 hours at room temperature (15 to 30ºC).
Madanakollu, s - soluzzjoni rikostitwita fil- kunjett tista ’ tinżamm sa 3 sigħat f’ temperatura ambjentali( 15 sa 30ºC).
After preparation, the intravenous infusion solution can be used at room temperature (15 to 30ºC) for a period up to 14 hours.
Wara l- preparazzjoni, is- soluzzjoni għall- infużjoni fil- vina tista ’ tintuża f’ temperatura ambjentali (15 sa 30ºC) għal perijodu sa 14- il siegħa.
Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration.
Prodotti tal- mediċina parenterali għandhom ikunu spezzjonati viżwalment għal xi frak u xi tibdil fil- kulur qabel jingħataw.
It is recommended that Xigris be infused with an infusion pump to accurately control the infusion rate.
Huwa rrakkomandat li Xigris jiġi infuż b’ pompa għall- infużjoni sabiex tiġi kkontrollata bi preċiżjoni r- rata ta ’ infużjoni.
The solution of reconstituted Xigris should be diluted into an infusion bag containing sterile 0.9% Sodium Chloride Injection to a final concentration of between 100 µg/ ml and 200 µg/ ml.
Is- soluzzjoni ta ’ Xigris rikostitwit għandha tiġi dilwita f’ borża ta ’ infużjoni li fiha injezzjoni sterili ta ’ 0. 9% Sodium Chloride sakemm tintlaħaq konċentrazzjoni finali ta ’ bejn 100µg/ ml u 200µg/ ml.
When administering drotrecogin alfa (activated) at low flow rates (less than approximately 5 ml/ hr), the infusion set must be primed for approximately 15 minutes at a flow rate of approximately 5 ml/ hr.
Meta jingħata drotrecogin alfa (attivat) b’ rati baxxi ta ’ infużjoni (inqas minn madwar 5 ml/ siegħa), is- sett ta ’ l- infużjoni għandu jkun imħejji għal madwar 15- il minuta b’ rata ta’ infużjoni ta ’ madwar 5 ml/ siegħa.
Xigris should be administered via a dedicated intravenous line or a dedicated lumen of a multilumen central venous catheter.
Xigris għandu jingħata permezz ta ’ linja minn ġol- vina apposta jew lumen apposta ta ’ kateter ċentrali fil- vina multilumen.
The ONLY other solutions that can be administered through the same line are 0.9% Sodium Chloride Injection, Lactated Ringer’ s Injection, Dextrose or Dextrose and Saline mixtures.
Injezzjoni ta ’ 0. 9% Sodium Chloride, Injezzjoni ta ’ Ringer Lactated, Dextrose jew taħlititiet ta ’ Dextrose u Ilma bil- Melħ.
Avoid exposing drotrecogin alfa (activated) solutions to heat and/ or direct sunlight.
Evita li tesponi s- soluzzjoni ta ’ drotrecogin alfa (attivat) għas- sħana u/ jew għad- dawl dirett tax - xemx.
No incompatibilities have been observed between drotrecogin alfa (activated) and glass infusion bottles or infusion bags made of polyvinylchloride, polyethylene, polypropylene, or polyolefin.
L- ebda inkompatibilitajiet ma kienu osservati bejn drotrecogin alfa (attivat) u l- fliexken ta ’ l- infużjoni tal- ħġieġ jew boroż ta ’ l- infużjoni magħmula mill- polyvinylchloride,
The use of other types of infusion sets could have a negative impact on the amount and potency of drotrecogin alfa (activated) administered.
L- użu ta ’ tipi oħrajn ta ’ settijiet ta ’ l- infużjoni jista ’ jkollhom impatt negattiv fuq l- ammont u l- qawwa ta ’ drotrecogin alfa (attivat) li jingħata.
Care should be taken to administer Xigris at the appropriate rate, calculated based on kg of bodyweight and infused for the correct duration.
Trid tittieħed attenzjoni biex Xigris jingħata b’ rata adatta, ikkalkulata fuq bażi tal- piż tal- ġisem f’ kg u infuża għal tul ta ’ żmien korrett.
It is recommended that the bag be labelled accordingly.
Huwa rrakkomandat li l- borża jkollha t- tikketta kif xieraq.
Eli Lilly Nederland B. V., Grootslag 1-5, 3991 RA, Houten, The Netherlands
Eli Lilly Nederland B. V., Grootslag 1- 5, 3991 RA, Houten, l- Olanda
Date of latest renewal:
22 ta ’ Awissu 2002 Data ta ’ l- aħħar tiġdid:
Detailed information on this product is available on the website of the European Medicines Agency (EMEA): http: / /www. emea. europa. eu/ 12 1.
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il- Mediċini (EMEA) http: // www. emea. europa. eu /.
Xigris 5 mg powder for solution for infusion
Xigris 5 mg trab għal soluzzjoni għall- infużjoni
Each vial contains 5 mg of Drotrecogin alfa (activated).
Kull kunjett fih 5 mg ta ’ Drotrecogin alfa (attivat)
After reconstitution with 2.5 ml of Water for Injection each ml contains 2 mg of Drotrecogin alfa (activated).
Wara r- rikostituzzjoni b’ 2. 5 ml ta ’ Ilma għall- Injezzjonijiet kull ml fih 2 mg ta ’ Drotrecogin alfa.
Drotrecogin alfa (activated) is a recombinant version of the endogenous activated Protein C and is produced by genetic engineering from an established human cell line.
Drotrecogin alfa (attivat) huwa tip rikombinat tal- Proteina Ċ endoġena attivata u huwa magħmul b’ inġinerija ġenetika minn razza stabbilita ta ’ ċelloli umani stabbilita.
Each vial contains approximately 17 mg sodium.
Kull kunjett fih madwar 17 mg ta ’ sodium.
For a full list of excipients, see 6.1.
Għal lista kompleta ta ’ sustanzi mhux attivi, ara Sezzjoni 6. 1.
No dose adjustments are required in adult patients with severe sepsis with regard to age, gender, hepatic function (as measured by transaminase levels), renal function, obesity or co-administration of prophylactic heparin.
Mhux meħtieġ tibdil fid- doża għal pazjenti adulti b’ sepsis gravi għal dik li hi età, sess, il- funzjoni tal - fwied (imkejla skond il- livelli transaminażi), il- funzjoni renali, obeżità jew it- teħid fl- istess żmien ma ’ eparina mgħotija għal skop profilattiku.
Paediatrics:
Pazjenti f’ età pedjatrika:
Data from a placebo-controlled clinical trial which was stopped for futility after 477 patients 0 to 17 years-old had received the study treatment did not establish efficacy of Xigris in paediatric patients and showed a higher rate of central nervous system bleeding in the Xigris versus
Skond l- informazzjoni li ħarġet minn studju kliniċi kkontrollati bi plaċebo, li twaqqfu minħabba l- inutilità wara li 477 pazjent bejn it- twelid u s- 17- il sena kienu ngħataw il- kura għal skopijiet ta ’ studju, instab li Xigris ma kinitx effikaċi f’ pazjenti żgħar, u wriet li dawk li ħadu
13 placebo group.
14 Xigris kellhom rata ogħla ta ’ fsada fis- sistema nervuża ċentrali minn dawk li ħadu l- plaċebo.
Because drotrecogin alfa (activated) may increase the risk of bleeding, Xigris is contraindicated in the following situations:
Minħabba li drotrecogin alfa (attivat) jista ’ jżid ir- riskju ta ’ fsada, Xigris m’ għandux jintuża f’ dawn iċ - ċirkostanzi:
For procedures with an inherent bleeding risk, discontinue Xigris for 2 hours prior to the start of the procedure.
15 Għal proċeduri b’ riskju inerenti ta ’ fsada, waqqaf Xigris sagħtejn qabel tibda l- proċedura.
Xigris may be restarted 12 hours after major invasive procedures or surgery if adequate haemostasis has been achieved.
Xigris jista ’ jinbeda 12- il siegħa wara l- kirurġija jew proċeduri invażivi maġġuri jekk tkun intlaħqet emostażi xierqa.
The incidence of serious bleeding events with Xigris was higher in patients with recent [within 30 days] surgery than in “ medical” patients without surgery (see section 4.8).
L- inċidenza ta ’ każijiet serji ta ’ fsada b’ Xigris kienu ogħla f’ pazjenti li kellhom kirurġija reċenti [fi żmien 30 ġurnata] milli f’ pazjenti ‘ tal- mediċina ’ li ma kellhom ebda kirurġija (ara sezzjoni 4. 8).
Paediatric patients Xigris is not recommended in children below the age of 18 and therefore it should not be used in children.
Xigris mhuwiex rakkomandat għal tfal taħt it- 18- il sena u għalhekk m’ għandux jintuża għat- tfal.
15 Data from a placebo-controlled clinical trial did not establish efficacy of Xigris in paediatric patients suffering from severe sepsis, acute infection, systemic inflammation and respiratory and cardiovascular organ dysfunction.
L- informazzjoni minn testijiet kliniċi kkontrollati bil- plaċebo ma wrietx li Xigris huwa effikaċi fil - kura ta ’ tfal li jbatu b’ sepsis gravi, infezzjoni akuta, infjammazzjoni sistematika u nuqqas ta ’ funzjoni ta ’ l- organi respiratorji u kardjovaskulari.
To be taken into consideration by patients on a controlled sodium diet.
Dan il- prodott mediċinali fih madwar 17 mg ta ’ sodium. Pazjenti li qegħdin fuq dieta ta ’ restrizzjoni ta ’ sodium għandhom jagħtu kas ta ’ dan il- fatt.
4.6 Pregnancy and lactation
17 4. 6 Tqala u Treddigħ
The Phase 3 international, multi-centre, randomised, double-blind, placebo-controlled clinical trial (PROWESS) involved 850 drotrecogin alfa (activated)-treated and 840 placebo-treated patients.
Fl- istudju kliniku Fażi 3 internazzjonali, multiċentriku, magħmul b’ mod arbitrarju, double- blind, ikkontrollat bi plaċebo (PROWESS) ħadu sehem 850 pazjent li ħadu drotrecogin alfa (attivat) u 840 li ħadu l- plaċebo.
During the infusion period in PROWESS and ENHANCE the incidence of serious bleeding events with Xigris was numerically higher in patients with recent [within 30 days] surgery than in patients without surgery (PROWESS:
Waqt il- perijodu ta ’ infużjoni fi PROWESS u ENHANCE, l- inċidenza ta ’ każijiet serji ta ’ fsada bi Xigris kienet numerikament ogħla f’ pazjenti li kellhom kirurġija reċenti [fi żmien 30 ġurnata] milli f’ pazjenti li ma kellhom ebda kirurġija (PROWESS:
18 In the open-label ENHANCE study, the incidence of serious bleeding events during the 28-day study period was 6.5%, and the incidence of CNS bleeds during the 28-day study period was 1.5%.
19 Fl- istudju bil- miftuħ ENHANCE, l- inċidenza ta ’ każijiet serji ta ’ fsada matul il- perijodu ta ’ studju ta ’ 28 ġurnata kienet ta ’ 6. 5%, u l- inċidenza ta ’ fsada fis- CNS fl- istess perijodu ta ’ żmien kienet ta ’ 1. 5%.
Xigris also restored endogenous fibrinolytic potential, as evidenced by a more rapid trend toward normalisation in plasminogen levels and a more rapid decline in plasminogen activator inhibitor-1 levels.
Xigris radd lura wkoll il- potenzjal fibrinolitiku endoġenu, kif jidher minn tendenza aktar mgħaġġla lejn in- normalizzazzjoni fil- livelli tal- plażminoġen u tnaqqis aktar mgħaġġel fil- livelli ta ’ l- inibitur- 1 ta ’ l- attivatur tal- plażminoġen.
Additionally, patients with severe
Barra minn hekk, il -
19 sepsis treated with Xigris had a more rapid decline in interleukin-6 levels, a global marker of inflammation, consistent with a reduction in the inflammatory response.
20 pazjenti b’ sepsis gravi ikkurati b’ Xigris kellhom tnaqqis aktar mgħaġġel fil- livelli ta ’ interleukin- 6, li huwa indikatur globali ta ’ l- infjammazzjoni, flimkien ma ’ tnaqqis tar- rispons infjammatorju.
In the PROWESS trial, treatment was initiated within 48 hours of onset of the first sepsis-induced organ dysfunction.
Fl- istudju PROWESS, il- kura bdiet fi żmien 48 siegħa minn meta l- organu ma baqax jiffunzjona minħabba s- sepsis.
These data confirmed that the benefit of Xigris is limited to the more severely affected sepsis patients such as patients with multiple organ failure and shock.
21 għall- pazjenti effettwati b’ sepsis gravi, bħal pazjenti li jkollhom aktar minn organu wieħed li ma jiffunzjonax u jkollhom xokk.
20 Further Clinical Experience In a Phase 3b international, single-arm, open-label clinical trial (ENHANCE), 2378 adult patients with severe sepsis received drotrecogin alfa (activated).
Aktar Esperjenza Klinika F’ studju kliniku Fażi 3b internazzjonali, b’ fergħa waħda, double- blind (ENHANCE), 2, 378 pazjent adult b’ sepsis gravi ħadu drotrecogin alfa (attivat).
In placebo controlled clinical trials, the treatment effect was most evident at sites enrolling larger numbers of patients.
F’ studji kliniċi kkontrollati bi plaċebo, l- effett tal- kura kien evidenti l- aktar f’ postijiet li rreġistraw għadd kbir ta ’ pazjenti.
21 In patients with severe sepsis, the plasma clearance of drotrecogin alfa (activated) was significantly decreased by renal impairment and hepatic dysfunction, but the magnitude of the differences in clearance (< 30%) does not warrant any dosage adjustment.
Fil- pazjenti b’ sepsis gravi, it- tneħħija ta ’ drotrecogin alfa (attivat) mill- plażma naqset b’ mod sinifikanti f’ min kellu mard fil- kliewi u l- fwied, iżda d- differenzi fit- tneħħija (< 30%) ma jiġġustifikawx tibdil fid- doża.
Sucrose, Sodium chloride Sodium citrate Citric acid Hydrochloric acid Sodium hydroxide
Sucrose Sodium chloride Sodium citrate Citric acid Hydrochloric acid Sodium hydroxide.
However, the reconstituted solution in the vial may be held for up to 3 hours at room temperature (15ºC - 30ºC).
Madanakollu, s- soluzzjoni rikostitwita fil- kunjett tista ’ tinżamm sa 3 sigħat f’ temperatura ambjentali (15°C - 30ºC).
After preparation, the intravenous infusion solution can be used at room temperature (15ºC - 30ºC) for a period up to 14 hours.
Wara l- preparazzjoni, s- soluzzjoni ta ’ infużjoni għal ġol- vina tista ’ tintuża f’ temperatura ambjentali (15°C - 30ºC) għal terminu sa 14- il siegħa.
Keep the vial in the outer carton in order to protect it from light.
Żomm il- kunjett fil- kartuna ta ’ barra sabiex tilqa ’ mid- dawl.
6.6 Special precautions for disposal and other handling
Uża teknika asettika xierqa matul il- preparazzjoni ta ’ Xigris għall- għoti minn ġol- vina.
Calculate the dose and the number of Xigris vials needed.
Ikkalkula d- doża u n- numru ta ’ kunjetti ta ’ Xigris meħtieġa.
Each Xigris vial contains 5 mg of drotrecogin alfa (activated).
Kull kunjett Xigris fih 5 mg drotrecogin alfa (attivat).
The vial contains an excess of drotrecogin alfa (activated) to facilitate delivery of the label amount.
Il- kunjett fih drotrecogin alfa (attivat) żejjed biex jiffaċilita li jingħata l- ammont imsemmi fuq it- tikketta.
Prior to administration, 5 mg vials of Xigris must be reconstituted with 2.5 ml of Sterile Water for Injection, resulting in a solution with a concentration of approximately 2 mg/ ml drotrecogin alfa (activated).
Qabel jingħataw, il- kunjetti ta ’ 5 mg ta ’ Xigris għandhom jiġu rikostitwiti ma ’ 2. 5 ml Ilma Sterili għall- Injezzjoni, li jirriżulta f’ soluzzjoni b ’ konċentrazzjoni ta ’ madwar 2 mg/ ml drotrecogin alfa (attivat).
Slowly add the Sterile Water for Injection to the vial and avoid inverting or shaking the vial.
Żid l- ilma Sterili għall- Injezzjoni fil- kunjett bil- mod u evita li taqleb ta ’ taħt fuq jew li tħawwad il- kunjett.
The solution of reconstituted Xigris must be further diluted with sterile 0.9% Sodium Chloride Injection to a final concentration of between 100 µg/ ml and 200 µg/ ml.
Is- soluzzjoni ta ’ Xigris rikostitwit trid tkompli tiġi dilwita b’ injezzjoni ta ’ soluzzjoni sterili ta ’ 0. 9% sodium chloride għal konċentrazzjoni finali li tkun bejn 100 µg/ ml u 200 µg/ ml.
Slowly withdraw the appropriate amount of reconstituted drotrecogin alfa (activated) solution from the vial.
Iġbed bil - mod l- ammont xieraq ta’ soluzzjoni ta ’ drotrecogin alfa (attivat) rikostitwit mill- kunjett.
Add the reconstituted drotrecogin alfa (activated) into a prepared infusion bag of sterile 0.9% Sodium Chloride Injection.
Żid d - drotrecogin alfa (attivat) rikostitwit f’ borża ta ’ infużjoni ppreparata b ’ 0. 9% sodium chloride sterili.
When adding the reconstituted drotrecogin alfa (activated) into the infusion bag, direct the stream to the side of the bag to minimise the agitation of the solution.
Meta tkun qed iżżid d- drotrecogin alfa (attivat) rikostitwit fil- borża ta ’ infużjoni, iddirezzjona s- soluzzjoni lejn il- ġenb tal- borża biex tnaqqas kemm jista ’ jkun l- aġitazzjoni tas - soluzzjoni.
Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration.
Prodotti mediċinali parenterali għandhom jiġu spezzjonati viżwalment għal xi frak u tibdil fil - kulur qabel jingħataw.
The solution of reconstituted Xigris should be diluted into an infusion bag containing sterile 0.9% Sodium Chloride Injection to a final concentration of between 100 µg/ ml and 200 µg/ ml.
Huwa rrakkomandat li Xigris jiġi infuż b’ pompa għall- infużjoni sabiex tiġi kkontrollata bi preċiżjoni r- rata ta ’ infużjoni. Is- soluzzjoni ta ’ Xigris rikostitwit għandha tiġi dilwita f’ borża ta ’ infużjoni li fiha injezzjoni sterili ta ’ 0. 9% Sodium Chloride sakemm tintlaħaq konċentrazzjoni finali ta ’ bejn 100µg/ ml u 200µg/ ml.
When administering drotrecogin alfa (activated) at low flow rates (less than approximately 5 ml/ hr), the infusion set must be primed for approximately 15 minutes at a flow rate of approximately 5 ml/ hr.
Meta jingħata drotrecogin alfa (attivat) b’ rati ta ’ infużjoni baxxi (inqas minn madwar 5 ml/ siegħa), is- sett ta ’ l- infużjoni għandu jkun imħejji għal perijodu ta ’ madwar 15- il minuta b’ rata ta ’ infużjoni ta ’ madwar 5 ml/ siegħa.
Avoid exposing drotrecogin alfa (activated) solutions to heat and/ or direct sunlight.
Evita li tesponi s- soluzzjoni ta ’ drotrecogin alfa (attivat) għas- sħana u/ jew id- dawl tax- xemx dirett.
No incompatibilities have been observed between drotrecogin alfa (activated) and glass infusion bottles or infusion bags made of polyvinylchloride, polyethylene, polypropylene, or polyolefin.
Ma ġewx innutati inkompatibilitajiet bejn drotrecogin alfa (attivat) u fliexken ta ’ l - infużjoni tal- ħġieġ jew boroż ta ’ l- infużjoni magħmulin minn polyvinylchloride, polyethylene,
The use of other types of infusion sets could have a negative impact on the amount and potency of drotrecogin alfa (activated) administered.
L- użu ta ’ tipi oħra ta ’ settijiet ta ’ l- infużjoni jista ’ jkollhom impatt negattiv fuq l- ammont u l- qawwa ta ’ drotrecogin alfa (attivat) li jiġi mogħti.
MARKETING AUTHORISATION HOLDER
ID_ DETENTUR TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
Eli Lilly Nederland B. V., Grootslag 1-5, 3991 RA, Houten, The Netherlands
Eli Lilly Nederland B. V., Grootslag 1- 5, 39991 RA, Houten L- Olanda
Date of latest renewal:
Data ta ’ l- ewwel awtorizzazzjoni: 22 ta’ Awissu 2002 Data ta ’ l- aħħar tiġdid
Detailed information on this product is available on the website of the European Medicines Agency (EMEA): http: / /www. emea. europa. eu/
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il- Mediċini (EMEA) http: // www. emea. europa. eu /.
24 ANNEX II
25 ANNESS II
101 International Drive Portsmouth New Hampshire 03801-2815 USA
101 International Drive Portsmouth New Hampshire 03801- 2815 Stati Unitu ta ’ L- Amerika
KG Teichweg 3 D-35396 Giessen Germany
KG Teichweg 3 D- 35396 Giessen Ġermanja
The holder of this marketing authorisation must inform the European Commission about the marketing plans for the medicinal product authorised by this decision.
Id- detentur ta ’ din l- awtorizzazzjoni għat- tqegħid fis- suq għandu jagħti tagħrif lill- Kummissjoni Ewropeja dwar il- pjanijiet kummerċjali tal- prodott mediċinali awtorizzat b' din id- deċiżjoni.