qanastek/EMEA-V3 huggingface dataset:
The efficacy of Dynastat was established in studies of dental, gynaecologic (hysterectomy), orthopaedic (knee and hip replacement), and coronary artery bypass graft surgical pain.
L- effikaċja ta ’ Dynastat giet stabbilita fi studji dentali, ġinekoloġiċi (isterektomija), ortopediċi (trapjant ta ’ l- irkoppa u tal- ġenbejn (hip)) u uġigħ tal- coronary artery bypass graft.
The first perceptible analgesic effect occurred in 7 -13 minutes, with clinically meaningful analgesia demonstrated in 23-39 minutes and a peak effect within 2 hours following administration of single doses of 40 mg IV or IM Dynastat.
L- ewwel effett analġeżiku li jidher, seħħ f’ minn 7 sa 13- il minuta, b’ analġeżja klinikament valida murija minn 23 sa 39 minuta u bl- ogħla effett fi żmien sagħtejn wara l- amministrazzjoni ta ’ dożi waħda ta ’ 40 mg IV jew IM Dynastat.
The magnitude of analgesic effect of the 40 mg dose was comparable with that of ketorolac 60 mg IM or ketorolac 30 mg IV.
Id- daqs ta ’ l- effett analġeżiku tad- doża ta ’ 40 mg kien komparabbli ma ’ dak ta ’ ketorolac 60 mg IM jew ketorolac 30 mg IV.
After a single dose, the duration of analgesia was dose and clinical pain model dependent, and ranged from 6 to greater than 12 hours.
Wara doża waħda, id- dewmien ta ’ l- analġeżja kien dipendenti fuq id- doża u n- natura klinika ta ’ l- uġigħ u varja minn 6 sigħat sa aktar minn 12- il siegħa.
Opioid-sparing Effects:
Effetti ta ’ tnaqqis fl- użu ta ’ Opioids:
In a placebo-controlled, orthopedic and general surgery study (n =1050), patients received Dynastat at an initial parenteral dose of 40 mg IV followed by 20 mg twice daily for a minimum of 72 hours in addition to receiving standard care including supplemental patient controlled opioids.
Fi studju ta ’ kirurġija ortopedika u ġenerali kkontrollat bi plaċebo (n=1050), pazjenti inizjalment irċevew Dynastat b’ doża parenterali ta ’ 40mg IV, segwita minn doża ta ’ 20mg darbtejn kuljum għal 72 siegħa mill- inqas, mat- terapija standard li tinkludi teħid ta ’ opioids skond il- bżonn tal- pazjent.
The reduction in opioid use with Dynastat treatment on Days 2 and 3 was 7.2 mg
Kien hemm tnaqqis ta ’ 7. 2mg u 2. 8mg (37% u 28% rispettivament) fl- użu ta ’ opioids mat- trattament b’ Dynastat fit- 2 u 3 jum tat- terapija.
9 and 2.8 mg (37% and 28% respectively). This reduction in opioid use was accompanied by significant reductions in patient-reported opioid symptom distress.
Flimkien mat- tnaqqis fl- użu ta ’ l - opioids, kien hemm ukoll tnaqqis sinifikanti ta ’ rapporti mill- pazjenti ta ’ sintomi negattivi assoċċjati ma ’ l- użu ta ’ l- opioids.
Added pain relief compared to opioids alone was shown.
Ittafa iktar l- uġigħ meta kkumparat ma ’ l- użu ta ’ opioids waħedhom.
Additional studies in other surgical settings provided similar observations. There are no data indicating less overall adverse events associated with the use of parecoxib compared to placebo when used in conjunction with opioids.
M’ hemmx data li tindika tnaqqis ta ’ effetti aversi in ġenerali, assoċċjati ma ’ l- użu ta ’ parecoxib meta kkumparat mal- plaċebo, meta dan ikun użat ma ’ analġeżiċi opioid.
Gastrointestinal studies:
Studji Gastro- intestinali:
In short-term studies (7 days), the incidence of endoscopically observed gastroduodenal ulcers or erosions in healthy young and elderly (≥ 65 years) subjects administered Dynastat (5-21%), although higher than placebo (5-12%), was statistically significantly lower than the incidence observed with NSAIDs (66-90%).
Fi studji li ma ħadux fit- tul (7 ijiem), il- frekwenza ta ’ ulceri gastroduwodenali u erożjonijiet, li setgħu jidhru b’ endoskopju f’ persuni b’ saħħithom kemm żgħar kif ukoll anzjani (≥65 sena) li ingħataw Dynastat (5- 21%), għalkemm ogħla mill- plaċebo, kienet statistikament ferm inqas mill- frekwenza innutata bin- NSAIDs (66 sa 90%).
CABG post-operative Safety Studies:
Studji tas- Sigurtà wara operazzjoni tat- tip CABG:
In addition to routine adverse event reporting, pre-specified event categories, adjudicated by an independent expert committee, were examined in two placebo- controlled safety studies in which patients received parecoxib sodium for at least 3 days and then were transitioned to oral valdecoxib for a total duration of 10-14 days.
Il- pazjenti kollha rċevew analġeżja standard matul it- trattament.
All patients received standard of care analgesia during treatment Patients received low-dose acetylsalicylic acid prior to randomization and throughout the two CABG surgery studies.
Pazjenti rċevew doża baxxa ta ’ acetylsalicylic acid qabel tqassmu b’ mod każwali u matul iż- żewġ studji ta ’ kirurġija ta ’ CABG.
The first CABG surgery study evaluated patients treated with IV parecoxib sodium 40 mg bid for a minimum of 3 days, followed by treatment with valdecoxib 40 mg bid (parecoxib sodium/ valdecoxib group) (n=311) or placebo/ placebo (n=151) in a 14-day, double-blind placebo-controlled study.
L- ewwel studju fuq kirurġija CABG evalwa pazjenti kkurati bi parecoxib sodium 40 mg bid IV għal mill- inqas 3 ijiem, segwit bi trattament b’ valdecoxib 40 mg bid (grupp ta ’ parecoxib sodium/ valdecoxib) (n=311) jew plaċebo/ plaċebo (n=151) fi studju kkontrollat bi plaċebo double - blind ta ’ 14- il jum.
Nine pre-specified adverse event categories were evaluated (cardiovascular thromboembolic events, pericarditis, new onset or exacerbation of congestive heart failure, renal failure/ dysfunction, upper GI ulcer complications, major non-GI bleeds, infections, non-infectious pulmonary complications, and death).
Disa ’ kategorija ta ’ episodji avversi speċifikati minn qabel ġew evalwati (episodji tromboemboliċi, perikardite, bidu jew taħrix ta ’ insufiċjenza tal- qalb konġestiva, indeboliment renali/ funzjoni renali ħażina, kumplikazzjonijiet ta ’ ulċeri fil- parti ta ’ fuq tal - GI, fsada maġġuri mhux mill- GI maġġuri, infezzjonijiet, kumplikazzjonijiet pulmonari mhux infettużi, u mewt).
There was a significantly (p < 0.05) greater incidence of cardiovascular/ thromboembolic events (myocardial infarction, ischemia, cerebrovascular accident, deep vein thrombosis and pulmonary embolism) detected in the parecoxib/ valdecoxib treatment group compared to the placebo/ placebo treatment group for the IV dosing period (2.2% and 0.0% respectively) and over the entire study period (4.8% and 1.3% respectively).
Kien hemm inċidenza ferm ikbar (p < 0. 05) ta ’ episodji kardjovaskulari/ tromboemboliċi (infart mikokardijaku, iskemja, inċident ċerebrovaskulari, trombożi profonda fil- vini u emboliżmu pulmonary) li dehru fil - grupp ta ’ trattament ta ’ parecoxib/ valdecoxib meta mqabbla mal- grupp ta ’ trattament tal - plaċebo/ plaċebo għall- perijodu ta ’ dożaġġ IV (2. 2% u 0. 0% rispettivament) u fuq il- perijodu kollu ta ’ l- istudju (4. 8% u 1. 3% rispettivament).
Surgical wound complications (most involving the sternal wound) were observed at an increased rate with parecoxib/ valdecoxib treatment.
Kumplikazzjonijiet f’ feriti kirurġiċi (ħafna minnhom jinvolvu feriti sternali) ġew osservati b’ rata ogħla bi trattament ta ’ parecoxib/ valdecoxib.
In the second CABG surgery study, four pre-specified event categories were evaluated (cardiovascular/ thromboembolic; renal dysfunction/ renal failure; upper GI ulcer/ bleeding; surgical wound complication).
Fit- tieni studju fuq kirurġija CABG, erba ’ kategoriji ta ’ episodji speċifikati minn qabel ġew evalwati (kardjovaskulari/ tromboemboliċi; indeboliment renali/ funzjoni renali ħażina; ulċeri fil- parti ta ’ fuq tal - GI/ fsada, kumplikazzjonijiet ta ’ feriti kirurġiċi).
Patients were randomized within 24-hours post-CABG surgery to: parecoxib initial dose of 40 mg IV, then 20 mg IV Q12H for a minimum of 3 days followed by valdecoxib PO (20 mg Q12H) (n=544) for the remainder of a 10 day treatment period; placebo IV followed by valdecoxib PO (n=544); or placebo IV followed by placebo PO (n=548).
Il- pazjenti tqassmu b’ mod każwali fi żmien 24 siegħa wara kirurġija CABG għal: doża inizjali ta ’ 40 mg parecoxib IV, imbagħad 20 mg IV Q12H għal mill - inqas 3 ijiem segwit b’ valdecoxib PO (20 mg Q12H) (n=544) għall- bqija tal- perijodu ta ’ trattament ta ’ 10 ijiem; plaċebo IV segwit b’ valdecoxib PO (n=544); jew plaċebo IV segwit bi plaċebo PO (n=548).
A significantly (p=0.033) greater incidence of events in the cardiovascular/ thromboembolic category was detected in the parecoxib / valdecoxib treatment group (2.0%) compared to the placebo/ placebo treatment group (0.5%).
10 Inkixfu ferm iktar inċidenzi (p=0. 033) ta ’ episodji fil- kategorija kardjovaskulari/ tromboemboliċi fil - grupp ta ’ trattament b’ parecoxib / valdecoxib treatment group (2. 0%) meta mqabbel mal- grupp ta ’ trattament plaċebo/ plaċebo (0. 5%).
Placebo/ valdecoxib treatment was also associated with a higher incidence of CV thromboembolic events versus placebo treatment, but this difference did not reach statistical significance.
Trattament bi plaċebo/ valdecoxib ġie assoċjat ukoll ma ’ inċidenza ogħla ta ’ episodji tromboemboliċi CV kontra trattament bi plaċebo, iżda din id- differenza ma laħqitx sinifikanza ta ’ statistika.
Three of the six cardiovascular thromboembolic events in the placebo/ valdecoxib treatment group occurred during the placebo treatment period; these patients did not receive valdecoxib.
Tlieta mis- sitt episodji tromboemboliċi kardjovaskulari fil- grupp ta ’ trattament ta ’ plaċebo/ valdecoxib seħħew matul il- perijodu ta ’ trattament bi plaċebo; dawn il- pazjenti ma rċevewx valdecoxib.
Pre-specified events that occurred with the highest incidence in all three treatment groups involved the category of surgical wound complications, including deep surgical infections and sternal wound healing events.
Episodji speċifikati minn qabel li seħħew ma ’ l- ogħla inċidenza fit- tliet gruppi ta ’ trattament involvew il- kategorija ta ’ kumplikazzjonijiet ta ’ feriti kirurġiċi, inkluż infezzjonijiet kirurġiċi fondi u episodji ta ’ fejqan ta ’ feriti sternali.
There were no significant differences between active treatments and placebo for any of the other pre- specified event categories (renal dysfunction/ failure, upper GI ulcer complications or surgical wound complications).
Ma kienx hemm differenzi sinifikanti bejn trattamenti attivi u plaċebo għal kwalunkwe kategorija oħra ta ’ avvenimenti speċifikati minn qabel (funzjoni ħażina/ indeboliment, renali, kumplikazzjonijiet b’ ulċeri fil- parti ta ’ fuq tal- GI jew kumplikazzjonijiet f’ feriti kirurġiċi).
General Surgery:
Kirurġija ġenerali:
There were no significant differences in the overall safety profile,
Fi prova ta ’ kirurġija ortopedika/ ġenerali maġġuri kbira (N=1050), pazjenti irċevew doża inizjali ta ’ parecoxib 40 mg IV, imbagħad 20 mg IV Q12H għal minimu ta ’ 3 ijiem u wara ngħataw valdecoxib PO (20 mg Q12H) (n=525) għall- bqija ta ’ perijodu ta ’ trattament ta ’ 10 ijiem, jew plaċebo IV segwit bi plaċebo PO (n=525).
10 including the four pre-specified event categories described above for the second CABG surgery study, for parecoxib sodium/ valdecoxib compared to placebo treatment in these post-surgical patients.
Ma kien hemm ebda differenzi sinifikanti fil - profil ta ’ sigurtà totali, inkluż l- erba ’ kategoriji ta ’ avvenimenti speċifikati minn qabel deskritti hawn fuq għat- tieni studju tal- kirurġija CABG, għal parecoxib sodium/ valdecoxib meta mqabbel ma ’ trattament bi plaċebo f’ dawn il- pazjenti wara kirurġija.
Platelet studies:
Studji tal- Plejtlets:
In a series of small, multiple dose studies in healthy young and elderly subjects, Dynastat 20 mg or 40 mg twice daily had no effect on platelet aggregation or bleeding compared to placebo.
F’ serje ta ’ studji b’ numru ta ’ dożi żgħar li saru fuq persuni b’ saħħithom, kemm żgħar kif ukoll anzjani, doża ta’ Dynastat 20 mg jew 40 mg darbtejn kuljum, ma kellha l- ebda effett fuq l- aggregazzjoni tal- plejtlets jew fuq il- fsada, kif imqabbla mal- plaċebo.
In young subjects, Dynastat 40 mg twice daily had no clinically significant effect on acetylsalicylic acid -mediated inhibition of platelet function (see section 4.5).
(ara sezzjoni 4. 5)
Following IV or IM injection, parecoxib is rapidly converted to valdecoxib, the pharmacologically active substance, by enzymatic hydrolysis in the liver.
Wara injezzjoni IV jew IM, parecoxib huwa malajr mibdul għal valdecoxib, is- sustanza farmakoloġikament attiva, b’ idroliżi enżimatika fil- fwied.
Absorption Exposure of valdecoxib following single doses of Dynastat, as measured by both the area under the plasma concentration vs. time curve (AUC) and peak concentration (Cmax), is approximately linear in the range of clinical doses.
Assorbiment L- esponiment ta ’ valdecoxib wara doża waħda ta ’ Dynastat, kif imkejjel kemm mill- erja taħt il- kurva tal- konċentrazzjoni fil- plażma kontra l- kurva tal- ħin (AUC) kif ukoll mill- konċentrazzjoni massima (Cmax), hija bejn wieħed u ieħor linjari fil- medda ta ’ dożi kliniċi.
AUC and Cmax following twice daily administration is linear up to 50 mg IV and 20 mg IM.
AUC u Cmax wara dożi darbtejn kuljum huma linjari sa 50 mg IV u 20 mg IM.
Steady state plasma concentrations of valdecoxib were reached within 4 days with twice daily dosing.
Konċentrazzjonijiet fil- plażma fi stat fiss ta ’ valdecoxib intlaħqu fi żmien 4 ijiem b’ dożi darbtejn kuljum.
Following single IV and IM doses of parecoxib sodium 20 mg, Cmax of valdecoxib is achieved in approximately 30 minutes and approximately 1 hour, respectively.
Wara doża waħda IV u IM ta ’ 20 mg parecoxib sodium, is- Cmax ta ’ valdecoxib huwa milħuq f’ madwar 30 min u siegħa rispettivament.
Exposure to parecoxib was similar after IV or IM administration in terms of AUC.
F’ termini ta ’ AUC l- esponiment għal parecoxib kien simili wara amministrazzjoni IV jew IM.
Average Cmax of parecoxib after IM dosing was lower compared to bolus IV dosing, which is attributed to slower extravascular absorption after IM administration.
Il- medja tas- Cmax ta ’ parecoxib, wara doża IM kienet anqas meta imqabbla ma ’ doża bolus IV, li huwa huwa attribwit għal- assorbiment ekstravaskulari iktar bil- mod, wara amministrazzjoni IM.
These decreases were not considered clinically important since Cmax of valdecoxib is comparable after IM and IV parecoxib sodium administration.
Dan it- tnaqqis ma kienx ikkunsidrat bħala klinikament importanti, peress li s- Cmax ta ’ valdecoxib jaqbel bejniethom, wara l- amministrazzjoni IM u IV ta ’ parecoxib sodium.
Distribution The volume of distribution of valdecoxib after its IV administration is approximately 55 litres.
Distribuzzjoni Il- volum ta ’ distribuzzjoni ta ’ valdecoxib wara li jiġi amministrat IV huwa bejn wieħed u ieħor ta ’ 55 litru.
Plasma protein binding is approximately 98% over the concentration range achieved with the highest recommended dose, 80 mg/ day.
L- irbit mal- proteini tal- plażma hija bejn wieħed u ieħor 98% aktar mill- firxa ta ’ konċentrazzjonijiet li jintlaħqu bl- aktar doża għolja rakkomandata, 80 mg / kuljum.
Valdecoxib, but not parecoxib, is extensively partitioned into erythrocytes.
Valdecoxib iżda mhux parecoxib, jiġi mqassam ħafna fl- eritroċiti..
Metabolism Parecoxib is rapidly and almost completely converted to valdecoxib and propionic acid in vivo with a plasma half-life of approximately 22 minutes.
Metaboliżmu Parecoxib huwa mibdul b’ mod mgħaġġel u kważi għal kollox f’ valdecoxib u propionic acid in vivo, b’ half life fil- plażma ta ’ madwar 22 min.
Elimination of valdecoxib is by extensive hepatic metabolism involving multiple pathways, including cytochrome P 450 (CYP) 3A4 and CYP2C9 isoenzymes and glucuronidation (about 20%) of the sulphonamide moiety.
L- eliminazzjoni ta ’ valdecoxib issir permezz ta ’ metaboliżmu epatiku estensiv li tinvolvi diversi triqat, inkluż iċ- ċitokromju P 450 (CYP) 3A4 u iżoenżimi CYP2C9 u glukuronidazzjoni (madwar 20%) ta ’ nofs il- biċċa (moiety) li fiha s - sulphonamide.
A hydroxylated metabolite of valdecoxib (via the CYP pathway) has been identified in human plasma that is active as a COX-2 inhibitor.
Metabolu hydroxylated ta ’ valdecoxib (permezz tal- pathway CYP) ġiet identifikata fi
It represents approximately 10% of the concentration of valdecoxib; because of this metabolite’ s low concentration, it is not expected to contribute a significant clinical effect after administration of therapeutic doses of parecoxib sodium.
Hija tirrapreżenta bejn wieħed u ieħor 10% tal - konċentrazzjoni ta ’ valdecoxib: minħabba l- konċentrazzjoni baxxa ta ’ dan il- metabolu, mhuwiex mistenni li din tikkontribwixxi effett kliniku importanti wara l- amministrazzjoni ta ’ doża terapewtika ta ’ parecoxib sodium.
Elimination Valdecoxib is eliminated via hepatic metabolism with less than 5% unchanged valdecoxib recovered in the urine.
Eliminazzjoni Valdecoxib huwa imneħħi permezz ta ’ metaboliżmu epatiku b’ inqas minn 5% ta ’ valdecoxib mhux mibdul jiġi rkuprat mill- urina.
No unchanged parecoxib is detected in urine and only trace amounts in the faeces.
Ma nstab l- ebda valdecoxib mhux mibdul fl- urina u traċċi zgħar biss instabu fl- ippurgar.
About 70% of the dose is excreted in the urine as inactive metabolites.
Madwar 70% tad- doża hija imneħħija fl- urina bħala metaboli inattivi.
Plasma clearance (CLp) for valdecoxib is about 6 l/ hr.
Il - clearance mill- plażma (CLp) għal valdecoxib hi ta ’ madwar 61/ hr.
After IV or IM dosing of parecoxib sodium, the elimination half-life (t1/ 2) of valdecoxib is about 8 hours.
Wara amministrazzjoni ta ’ dosaġġ IV u IM ta ’ parecoxib sodium, il- half life ta ’ l- eliminazzjoni ta ’ valdecoxib hija ta ’ madwar 8 sigħat.
Elderly Subjects:
Pazjenti Anzjani:
Dynastat has been administered to 335 elderly patients (65-96 years of age) in pharmacokinetic and therapeutic trials.
Fi provi farmakokinetiċi u terapewtiċi Dynastat ġie amministrat lil 335 pazjent anzjan( 65 sa 96 sena).
In healthy elderly subjects, the apparent oral clearance of valdecoxib was reduced, resulting in an approximately 40% higher plasma exposure of valdecoxib compared to healthy young subjects.
F’ suġġetti anzjani b’ saħħithom, il- clearance apparenti ta ’ valdecoxib mill- ħalq kienet imnaqqsa, b’ riżultat ta ’ esponiment fil- plażma ta ’ valdecoxib madwar 40% ogħla meta mqabbla ma ’ suġġetti żagħżagħ b’ saħħithom.
When adjusted for body weight, steady state plasma exposure of valdecoxib was 16% higher in elderly females compared to elderly males (see section 4.2).
Meta adattat skond il- piż tal- ġisem, l- esponiment fi stat fiss fil - plażma ta ’ vadecoxib, kienet 16% ogħla f’ nisa anzjani meta mqabbla ma ’ rġiel anzjani (aAra sezzjoni 4. 2).
11 Renal Impairment:
Indeboliment renali:
In patients with varying degrees of renal impairment administered 20 mg IVDynastat, parecoxib was rapidly cleared from plasma.
F’ pazjenti bi gradi differenti ta ’ indeboliment renali li ġie amministrat lilhom 20 mg IV Dynastat, parecoxib ġie mneħħi malajr mill- plażma.
Because renal elimination of valdecoxib is not important to its disposition, no changes in valdecoxib clearance were found even in patients with severe renal impairment or in patients undergoing dialysis (see section 4.2).
Minħabba li t- tneħħija ta ’ valdecoxib mill- kliewi mhijiex importanti għad- dispożizzjoni tiegħu, ma nstab l- ebda tibdil fil- clearance ta ’ valdecoxib, lanqas f’ pazjenti li għandhom indeboliment serju ħafna tal- kliewi jew f’ pazjenti li jkollhom d- dijaliżi (Ara sezzjoni 4. 2).
Hepatic Impairment:
Indeboliment tal- Fwied:
Moderate hepatic impairment did not result in a reduced rate or extent of parecoxib conversion to valdecoxib.
Indeboliment epatiku moderat ma rriżultax f’ rata jew ammont imnaqqas ta ’ tibdil ta ’ parecoxib f' valecoxib.
In patients with moderate hepatic impairment (Child-Pugh score 7-9), treatment should be initiated with half the usual recommended dose of Dynastat and the maximum daily dose should be reduced to 40 mg since valdecoxib exposures were more than doubled (130%) in these patients.
F’ pazjenti b’ indeboliment tal- fwied moderat (Child- Pugh skala 7- sa 9), Dynastat għandu jinbeda b’ nofs id- doża normalment rakkomandata u d- doża massima ta ’ kuljum għandha tiġi mnaqqsa għal 40 mg, peress li l- esponimenti ta ’ valdecoxib żdiedu b’ aktar mid - doppju (130%) f’ dawn il- pazjenti.
Patients with severe hepatic impairment have not been studied and therefore the use of Dynastat in patients with severe hepatic impairment is not recommended (see sections 4.2 and 4.3).
Pazjenti b’ indeboliment tal- fwied serju ħafna ma ġewx studjati u għalhekk l- użu ta ’ Dynastat f’ dawn il- pazjenti mhuwiex rakkomandat (ara sezzjonijiet 4. 2 u 4. 3).
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology or repeated dose toxicity at 2-fold the maximum human exposure to parecoxib.
Tagħrif mhux kliniku magħmul fuq studji konvenzjonali ta ’ sigurtà farmakoloġika jew effett tossiku minn dożi ripetuti f’ livell doppju tal- massimu ta ’ l- esponiment uman għal parecoxib, ma ’ juri l- ebda periklu speċjali għall- bnedmin.
However, in the repeated dose toxicity studies in dogs and rats, the systemic exposures to valdecoxib (the active metabolite of parecoxib) were approximately 0.8-fold the systemic exposure in elderly human subjects at the maximum recommended therapeutic dose of 80 mg daily.
Iżda fl- istudju ta ’ l- effett tossiku ta ’ doża ripetuta fil- klieb u fil- firien, l- esponimenti sistematiċi għal valdecoxib (il- metabolu attiv ta ’ parecoxib) kienu bejn wieħed u ieħor 0. 8 aktar mill- esponiment sistematiku f’ persuni anzjani b’ doża terapewtikamassima rakkomandata ta ’ 80 mg kuljum.
Higher doses were associated with aggravation and delayed healing of skin infections, an effect probably associated with COX-2 inhibition.
Dożi ogħla ġew assoċjati ma ’ l- aggravament ta ’, jew ma ’ l- ittardjar fil- fejqan ta ’ infezzjonijiet tal- ġilda, effett probabilment marbut ma ’ l- inibizzjoni COX- 2.
In reproduction toxicity tests, the incidence of post-implantation losses, resorptions and foetal body weight retardation occurred at doses not producing maternal toxicity in the rabbit studies.
Fi provi tossiċi riproduttivi, l- inċidenza ta ’ telf ta ’ wara t- tnissil, risorbimenti u ritardjar biex iL- fetu jilħaq piż normali, rriżultaw b’ dożi li mhumiex tossiċi għall- ommijiet fi studji fuq il- fniek.
No effects of parecoxib on male or female fertilities were found in rats.
Fi studji fuq il- firien, ma nstab l- ebda effett ta ’ parecoxib fuq il- fertilità maskili jew femminili.
The effects of parecoxib have not been evaluated in late pregnancy or in the pre- and postnatal period.
L- effetti ta ’ parecoxib ma ġewx evalwati fl- aħhar żmien tat- tqala jew fil- perijodi qabel u wara t- twelid.
Parecoxib sodium administered intravenously to lactating rats as a single dose showed concentrations of parecoxib, valdecoxib and a valdecoxib active metabolite in milk similar to that of maternal plasma.
Parecoxib sodium amministrat b’ doża waħda fil- vina ta ’ firien li kienu qed ireddgħu, irriżulta f’ konċentrazzjoni ta ’ parecoxib, valdecoxib u metabolu attiv ta ’ valdecoxib fil- ħalib simili għal dak tal- plażma ta ’ l- omm.
The carcinogenic potential of parecoxib sodium has not been evaluated.
Il- potenzjal kanċeroġenu ta ’ parecoxib sodium ma ġiex evalwat.
Powder Disodium hydrogen phosphate Phosphoric acid and/ or sodium hydroxide (for pH adjustment).
12 Trab Dibasic sodium phosphate, heptahydrate Phosphoric acid u/ jew sodium hydroxide (biex jirranġa l- pH).
This medicinal product must not be mixed with other medicinal products except for those mentioned in section 6.6.
Dan il- prodott mediċinali m’ għandux jitħallat ma ’ prodotti mediċinali oħrajn ħlief dawk imsemmija f’ sezzjoni 6. 6.
Dynastat and opioids should not be administered together in the same syringe.
Dynastat u opjojdi m’ għandhomx jiġu amministrati flimkien fl- istess siringa.
Use of Ringer-Lactate solution for injection or glucose 50 g/ l (5%) in Ringer Lactate solution for injection for reconstitution will cause the parecoxib to precipitate from solution and therefore is not recommended.
L- użu ta ’ soluzzjoni Ringer- Lactate għall- injezzjoni jew glucose 50 g/ l (5%) f’ soluzzjoni Ringer- Lactate għall- injezzjoni għar- rikostituzzjoni, iġġiegħel lil parecoxib jippreċipita u għalhekk mhuwiex rakkomandat.
Use of Sterile Water for Injection is not recommended, as the resulting solution is not isotonic.
L- użu ta ’ l- ilma Sterili għall- injezzjoni mhuwiex rakkomandat, għax is- soluzzjoni li tirriżulta ma tkunx iżotonika.
12 Do not inject Dynastat into an IV line delivering any other drug.
Tinjettax Dynastat f’ linja IV li qed tipprovdi xi mediċina oħra.
The IV line must be adequately flushed prior to and after Dynastat injection with a solution of known compatibility (see section 6.6).
Il- linja IV għandha tiġi mlaħalħa adegwatament qabel u wara injezzjoni ta ’ Dynastat b’ soluzzjoni li huwa mgħruf li hija kompatibbli (ara sezzjoni 6. 6).
Injection into an IV line delivering glucose 50 g/ l (5%) in Ringer-Lactate solution for injection, or other IV fluids not listed in 6.6, is not recommended as this may cause precipitation from solution.
Injezzjoni fit- tubu IV li jwassal il- glucose 50 g/ l (5%) f’ soluzzjoni Ringer- Lactate għall - injezzjoni, jew fluwidi IV oħra mhux imsemmija fi 6. 6, mhijiex rakkomondata għax din tista tikkawża preċipitazzjoni fis- soluzzjoni.
Chemical and physical in-use stability of the reconstituted solution has been demonstrated for 24 hours at 25°C.
Stabilità kimika u fiżika għall- użu intern (in- use) ta ’ soluzzjoni rikostitwita ġiet murija għal 24 siegħa bi 25˚C.
From a microbiological point of view, the aseptically prepared product should be used immediately.
Mil- lat mikrobijoloġiku, il- prodott imħejji asettikament għandu jiġi wżat immedjatment.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would not normally be longer than 12 hours at 25°C, unless reconstitution has taken place in controlled and validated aseptic conditions.
Jekk ma jiġix użat immedjatment il- ħinijiet ta ’ ħażna għall- użu intern u kundizzjonijiet eżistenti qabel l- użu, huma r- responsabilità ta ’ min juża u ma jkunux normalment itwal minn 12- il siegħa bi 25˚C, sakemm ir- rikostituzzjoni ma tkunx saret f’ kundizzjonijiet kontrollati u b’ mod asettikament validat.
This medicinal product does not require special storing conditions prior to reconstitution.
Dan il- prodott mediċinali ma jeħtieġx kundizzjonijiet speċjali ta ’ ħażna qabel rikostituzzjoni.
Do not refrigerate or freeze reconstituted solutions.
Taħżinx soluzzjonijiet rikostitwiti fi friġġ jew fi friża.
For storage conditions of the recosntituted medicinal product see section 6.3.
Għal kundizzjonijiet ta ’ ħażna tal- prodott mediċinali rikostitwit ara sezzjoni 6. 3.
Parecoxib sodium vials 20 mg vials:
Fjali ta ’ parecoxib sodium
Type I colourless glass vials (2 ml) with a laminated stopper, sealed with a yellow flip- off cap on the aluminium overseal.
Fjali 20 mg: fjali tal- ħġieġ bla kulur Tip Numru 1 (2 ml) b’ tapp laminat, issiġillat b’ għatu isfar li tiftħu b’ subgħajk (flip off) fuq kisja ta ’ l- aluminju.
Dynastat is available in packs containing 10 vials.
Dynastat jinstab f’ pakketti ta ’ 10 fjali.
6.6 Special precautions for disposal and other handling
13 6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema u għal immaniġġar ieħor
Dynastat must be reconstituted before use.
Dynastat irid jiġi rikostitwit qabel jintuża.
Dynastat is preservative free.
Dynastat ma fihx priservattivi.
Aseptic technique is required for its preparation.
Teknika asettika hija meħtieġa sabiex jiġi ppreparat.
Reconstitution solvents Acceptable solvents for reconstitution of Dynastat are:
Solventi xierqa għar- rikostituzzjoni ta ’ Dynastat huma:
sodium chloride 9 mg/ ml (0.9%) solution glucose 50 g/ l (5%) solution for infusion sodium chloride 4.5 mg/ ml (0.45%) and glucose 50 g/ l (5%) solution for injection
Soluzzjoni għall- injezzjoni ta ’ sodium chloride 4. 5 mg/ ml (0. 45%) u glucose 50 g/ l (5%).
Reconstitution process Use aseptic technique to reconstitute lyophilised parecoxib (as parecoxib sodium).
Uża teknika asettika biex tirrikostitwixxi parecoxib lajofilizzat (bħala parecoxib sodium).
Remove the yellow flip-off cap to expose the central portion of the rubber stopper of the 20 mg parecoxib vial.
Neħħi l- kappa safra li jinfetaħ b’ subgħajk b’ mod li tesponi l- parti ċentrali tat- tapp tal- gomma tal- fjala 20 mg tal- parecoxib.
Withdraw, with a sterile needle and syringe, 1 ml of an acceptable solvent and insert the needle through the central portion of the rubber stopper transferring the solvent into the 20 mg vial.
Iġbed permezz ta ’ labra sterili u siringa, 1ml ta ’ solvent xieraq u daħħal il- labra ġol- parti ċentrali tat- tapp tal- gomma, b’ mod li s- solvent jiġi trasferit ġol- fjala ta ’ 20 mg.
Dissolve the powder completely using a gentle swirling motion and inspect the reconstituted product before use.
Dewweb it- trab kompletament billi ddawru u ifli l- prodott rikostitwit qabel tużah.
The entire contents of the vial should be withdrawn for a single administration.
Dak kollu li jkun hemm fil- fjala għandu jiġi miġbud sabiex jiġi amministrat f’ darba.
After reconstitution, Dynastat should be inspected visually for particulate matter and discoloration prior to administration.
Is- soluzzjoni hija ċara u bla kulur.
The solution should not be used if discolored or cloudy, or if particulate matter is observed.
Qabel ma tiġi amministrata għandha tiġi miflija għal xi frak jew għal- telf ta ’ kulur.
Dynastat should be administered within 24 hours of reconstitution (see section 6.3), or discarded.
Is- soluzzjoni m’ għandiex tiġi wżata jekk tkun tilfet il- kulur jew imqallba jew jekk wieħed jinnota xi frak.
13 The reconstituted product is isotonic.
Il- prodott rikostitwit huwa iżotoniku.
IV line solution compatibility After reconstitution with acceptable solvents, Dynastat may only be injected IV or IM, or into IV lines delivering:
Dynastat jista jiġi injettat biss IV jew IM jew ġo tubi IV ta ’:
sodium chloride 9 mg/ ml (0.9%) solution glucose 50 g/ l (5%) solution for infusion sodium chloride 4.5 mg/ ml (0.45%) and glucose 50 g/ l (5%) solution for injection Ringer-Lactate solution for injection
soluzzjoni ta ’ sodium chloride 9 mg/ ml (0. 9%) soluzzjoni tal- glucose 50 g/ l (5%) għall- infużjoni soluzzjoni għall- injezzjoni ta ’ sodium chloride 4. 5 mg/ ml (0. 45%) u glucose 50 g/ l (5%) soluzzjoni Ringer- lactate għall- injezzjoni.
Any unusedproduct or waste material should be disposed of in accordance with local requirements.
Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa ’ wara l- użu tal - prodott għandu jintrema kif jitolbu l- liġijiet lokali.
Pfizer Limited Sandwich Kent CT13 9NJ United Kingdom
Pfizer Limited Sandwich Kent CT13 9NJ Ir- Renju Unit
22 March 2002 Date of first renewal:
22 ta ’ Marzu 2002 Data ta ’ l- ewwel tiġdid:
22 March 2007
22 ta ’ Marzu 2007
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 Ewropea dwar il - Mediċini( EMEA) http: // www. emea. europa. eu
Dynastat 20 mg powder and solvent for solution for injection
Dynastat 20 mg trab u solvent għal soluzzjoni għall- injezzjoni
When reconstituted in sodium chloride 9 mg/ ml (0.9%) solution, Dynastat contains approximately 0.22 mEq of sodium per vial.
Meta rikostitwit f’ soluzzjoni ta ’ 9 mg/ ml (0. 9%) ta ’ sodium chloride, Dynastat ikun fih bejn wieħed u ieħor 0. 22 mEq ta ’ sodium f ’ kull fjala.
Powder and solvent for solution for injection White to off-white powder.
Trab abjad ikanġi fl- offwajt.
Solvent: clear, colourless solution.
Solvent: soluzzjoni ċara u mingħajr kulur.
The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of the individual patient's overall risks (see sections 4.3 and 4.4).
Id- deċiżjoni li jiġi preskritt inibitur selettiv ta ’ COX- 2 għandha tkun ibbażata fuq valutazzjoni tar - riskji in ġenerali tal- pazjent individwali (ara sezzjonijiet 4. 3 u 4. 4).
15 IV line solution compatibility After reconstitution with acceptable solvents, Dynastat may only be injected IV or IM, or into IV lines delivering: sodium chloride 9 mg/ ml (0.9%) solution glucose 50 g/ l (5%) solution for infusion sodium chloride 4.5 mg/ ml (0.45%) and glucose 50 g/ l (5%) solution for injection Ringer-Lactate solution for injection
16 Kompatibilità tas- soluzzjoni f’ linja IV Wara rikostituzzjoni b’ solventi aċċettabbli, Dynastat jista ’ jiġi injettat biss IV jew IM, jew f’ linji IV bl- għoti ta ’: soluzzjoni ta ’ 9 mg/ ml (0. 9%) ta ’ sodium chloride soluzzjoni għall- infużjoni ta ’ 50 g/ l (5%) ta ’ glucose soluzzjoni għal injezzjoni ta ’ 4. 5 mg/ ml (0. 45%) ta ’ sodium chloride u ta ’ 50 g/ l (5%) ta ’ glucose soluzzjoni għal injezzjoni Ringer- Lactate
In patients with severe renal impairment (creatinine clearance < 30 ml/ min.) or patients who may be predisposed to fluid retention parecoxib should be initiated at the lowest recommended dose and the patient's kidney function closely monitored (see sections 4.4 and 5.2).
F’ pazjenti li għandhom indeboliment renali serju ħafna (clearance ta ’ Creatinine < 30 ml/ min) jew pazjenti li jistgħu ikunu predisposti li jżommu l- fluwidi, parecoxib għandu jinbeda bl - inqas doża rrikmandata, u l- funzjoni tal- kliewi tal- pazjent għandha tkun immonitorjata sew (ara sezzjoni 4. 4 u 5. 2).
16 Established ischaemic heart disease, peripheral arterial disease and/ or cerebrovascular disease.
17 Mard tal- qalb iskemiku stabbilit, mard arterjali periferali u/ jew mard ċerebrovaskulari.
Because of the possibility for increased adverse reactions at higher doses of parecoxib, other COX-2 inhibitors and NSAIDs, patients treated with parecoxib should be reviewed following dose increase and, in the absence of an increase in efficacy, other therapeutic options should be considered (see section 4.2).
Minħabba l- possibiltà li jkun hemm żieda fir- reazzjonijiet avversi meta jittieħdu dożi akbar ta ’ parecoxib, impedituri COX- 2 oħra u NSAIDs, il- pazjenti li jkunu qed jingħataw il- kura b’ parecoxib għandhom ikunu osservati wara li tiżdiedilhom id- doża u, fl- assenza ta ’ żieda fl- effikaċja, għandhom jiġu kkunsidrati għażliet terapewtiċi oħra (ara sezzjoni 4. 2).
Appropriate measures should be taken and discontinuation of parecoxib therapy should be considered if there is clinical evidence of deterioration in the condition of specific clinical symptoms in these patients (see section 5.1).
Għandhom jittieħdu miżuri adegwati u l- waqfien tat- terapija b’ parecoxibgħandu jiġi kkunsidrat jekk ikun hemm biżżejjed evidenza klinika ta ’ deterjorazzjoni fil- kundizzjoni ta ’ sintomi kliniċi speċifiċi f’ dawn il- pazjenti (ara sezzjoni 5. 1).
17 Parecoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
18 Parecoxib għandu jitwaqqaf ma ’ l- ewwel feġġa ta ’ raxx tal- ġilda, feriti bil- mukus, jew ma ’ kwalunkwe sinjal ieħor ta ’ sensittività eċċessiva.
Serious skin reactions are known to occur with NSAIDs including COX-2 selective inhibitors as well as other medications.
Reazzjonijiet serji tal- ġilda huma magħrufin li jseħħu b’ NSAIDs inkluż inibituri selettivi ta ’ COX- 2 kif ukoll medikazzjonijiet oħra.
However, the reported rate of serious skin events appears to be greater for valdecoxib (the active metabolite of parecoxib) as compared to other COX-2 selective inhibitors.
Madankollu, ir- rata rrapportata ta ’ episodji serji tal- ġilda tidher li hija ikbar għal valdecoxib (il- metabolit attiv ta ’ parecoxib) hekk kif imqabbel ma ’ inibituri selettivi oħra ta ’ COX- 2.
Dynastat had no effect on acetylsalicylic acid-mediated inhibition of platelet aggregation or bleeding times.
19 Dynastat ma għandu l- ebda effett fuq l- inibizzjoni ta ’ l- aggregazzjoni ta ’ plejtlets, medjata permezz ta ’ acetylsalicylic acid jew fuq perijodi ta ’ fsada.
Clinical trials indicate that Dynastat can be given with low dose acetylsalicylic acid (≤ 325 mg).
Provi kliniċi juru li Dynastat jista ’ jiġi amministrat ma ’ doża baxxa ta ’ acetylsalicylic acid (≤ 325 mg).
18 Co-administration of parecoxib sodium and heparin did not affect the pharmacodynamics of heparin (activated partial thromboplastin time) compared to heparin alone.
L- amministrazzjoni flimkien ta ’ parecoxib sodium u heparin m ’ affettwawx il- farmakodinamika ta ’ heparin (ħin tat- tromboplastina parzjalment attivata) kif imqabbla ma ’ heparin waħidha.
NSAIDs may reduce the effect of diuretics and antihypertensive medicinal products.
In- NSAIDs jistgħu jnaqqsu l- effett tad- dijuretiċi u prodotti mediċinali anti- ipertensivi.
In interaction studies in rheumatoid arthritis patients receiving weekly methotrexate intramuscularly, orally administered valdecoxib (40 mg twice daily) did not have a clinically significant effect on the plasma concentrations of methotrexate.
20 Fi studji ta ’ interazzjonijiet li saru f’ pazjenti li jbatu minn artrite rewmatika, li kienu qed jingħataw metrotrexate fil- muskolu darba fil- ġimgħa, valdecoxib mogħti mil- ħalq ma kellu l- ebda effett kliniku sinifikanti fuq il- konċentrazzjonijiet fil- plażma ta ’ methotrexate.
However, adequate monitoring of methotrexate-related toxicity should be considered when co-administering these two medicinal products.
Madankollu sorveljanza kif jixraq tat- tossiċità relatata ma ’ methotrexate, għandha tigi kunsidrata meta wieħed ikun qed jagħti dawn iż - żewg prodotti mediċinali flimkien.
19 Co-administration of valdecoxib with glibenclamide (CYP3A4 substrate) did not affect either the pharmacokinetics (exposure) or the pharmacodynamics (blood glucose and insulin levels) of glibenclamide.
L- amministrazzjoni ta ’ valdecoxib flimkien ma ’ glibenclamide (sustrat ta ’ CYP3A4) ma affettwatx la l- farmakokinetiċi (esponiment) u lanqas il- farmakodinamiċi (livelli ta ’ glucose fid- demm u ta ’ l - insulina) ta ’ glibenclamide.
Injectable anaesthetics:
Anestetiċi li jistgħu jiġu injettati:
Parecoxib sodium is suspected to cause serious birth defects when administered during the last trimester of pregnancy because as with other medicinal products known to inhibit prostaglandin synthesis, it may cause premature closure of the ductus arteriosus or uterine inertia (see sections 4.3, 5.1 and 5.3).
Hemm suspetti li parecoxib sodium jikkawża difetti serji fit- twelid meta mogħti matul l- aħħar tliet xhur tat- tqala, għax bħal fil- każ ta ’ prodotti oħra mediċinali li huma magħrufa li jinibixxu s- sinteżi ta ’ prostaglandin, jista ’ jikkawża l- għeluq prematur tad- ductus arteriosus u inerzja ta ’ l- utru (ara Sezzjonijiet 4. 3, 5. 1 u 5. 3).
However, patients who experience dizziness, vertigo or somnolence after receiving Dynastat should refrain from driving or operating machines.
Iżda pazjenti li jsofru minn sturdament, vertigo jew tħeddil, wara li jiġi amministrat lilhom Dynastat, m’ għandhomx isuqu jew
4.8 Undesirable effects
22 4. 8 Effetti mhux mixtieqa
The
L- effetti mhux mixtieqa imsemmija hawn taħt kellhom rata akbar mill- plaċebo u ġew rappurtati fost 1543 pazjent li ngħata l- kura bi 20 jew 40 mg Dynastat f’ doża singola jew f’ diversi dożi (sa 80 mg/ kuljum) fi 12- il studju kontrollat bil- plaċebo, li jinkludu kirurġiji dentali, ġinekoloġici, ortopediċi jew coronary artery bypass graft, kif ukoll l- amministrazzjoni qabel l- operazzjoni f’ operazzjonijiet dentali u ortopediċi.
20 discontinuation rate due to adverse events in these studies was 5.0% for patients receiving Dynastat and 4.3% for patients receiving placebo.
F’ dawn l- istudji r- rata ta ’ twaqqif minħabba effetti avversi, kienet ta ’ 0. 5% f’ pazjenti b’ Dynastat u 4. 3% f’ pazjenti bil- plaċebo.
[Very Common (≥ 1/ 10), Common (≥ 1/ 100, < 1/ 10) Uncommon (≥ 1/ 1000, < 1/ 100) Rare (≥ 1/ 10,000, < 1/ 1000) Very rare (< 1/ 10,000), not known (cannot be estimated from the available data)] Infections and infestations Uncommon: abnormal sternal serous wound drainage, wound infection.
[Komuni ħafna (> 1/ 10), Komuni ((≥1/ 100, < 1/ 10) Mhux komuni (≥1/ 1000, < 1/ 100) Rari (≥1/ 10, 000, < 1/ 1000) Rari ħafna (< 1/ 10, 000) mhux magħruf (ma jistax jiġi stmat mit- tagħrif disponibbli)]
Renal and urinary disorders Common: oliguria
Disturbi tal- kliewi u tas- sistema urinarja
General disorders and administration site conditions Common: peripheral oedema
23 Komuni: oligurja
Investigations Common: blood creatinine increased Uncommon:
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jittieħed Komuni: edema periferali
21 Following coronary artery bypass graft surgery, patients administered Dynastat have a higher risk of adverse events, such as cardiovascular/ thromboembolic events, deep surgical infections and sternal wound healing complications.
Wara coronary artery bypass graft pazjenti li jkun ġie amministrat lilhom Dynastat, jista ’ jkollhom riskju ogħla ta ’ effetti avversi, bħal episodji kardjovaskulari/ trmoboemboliċi, infezzjonijiet kirurġiċi fondi u kumplikazzjoni fil- fejqan ta ’ ferita sternali.
The difference in antiplatelet activity between some COX-1 inhibiting NSAIDs and COX-2 selective inhibitors may be of clinical significance in patients at risk of thrombo-embolic reactions.
24 Id- differenza fl- attività ta ’ kontra l- plejtlets ta ’ bejn xi NSAIDs li jimpedixxu COX- 1 u mpedituri selettivi COX- 2 tista ’ tkun ta ’ sinifikat kliniku f’ pazjenti li għandhom riskju ta ’ reazzjonijiet trombo - embolitiċi.
In a placebo-controlled, orthopedic and general surgery study (n =1050), patients received Dynastat at an initial parenteral dose of 40 mg IV followed by 20 mg twice daily for
Fi studju ta ’ kirurġija ortopedika u ġenerali kkontrollat bi plaċebo (n=1050), pazjenti inizjalment irċevew Dynastat b’ doża parenterali ta ’ 40mg IV, segwita minn doża ta ’ 20mg darbtejn kuljum għal 72 siegħa mill- inqas, mat- terapija standard li tinkludi teħid ta ’ opioids skond il- bżonn tal- pazjent.
22 a minimum of 72 hours in addition to receiving standard care including supplemental patient controlled opioids.
Kien hemm tnaqqis ta ’ 7. 2mg u 2. 8mg (37% u 28% rispettivament) fl- użu ta ’ opioids mat- trattament b’ Dynastat fit- 2 u 3 jum tat- terapija.
The reduction in opioid use with Dynastat treatment on Days 2 and 3 was 7.2 mg and 2.8 mg (37% and 28% respectively). This reduction in opioid use was accompanied by significant reductions in patient-reported opioid symptom distress.
Flimkien mat- tnaqqis fl- użu ta ’ l - opioids, kien hemm ukoll tnaqqis sinifikanti ta ’ rapporti mill- pazjenti ta ’ sintomi negattivi assoċċjati ma ’ l- użu ta ’ l- opioids.
Additional studies in other surgical settings provided similar observations.
Studji oħra fl- ambjent kirurġiku wrew osservazzjonijiet simili.
There are no data indicating less overall adverse events associated with the use of parecoxib compared to placebo when used in conjunction with opioids.
M’ hemmx data li tindika tnaqqis ta ’ effetti aversi in ġenerali, assoċċjati ma ’ l- użu ta ’ parecoxib meta kkumparat mal- plaċebo, meta dan ikun użat ma ’ analġeżiċi opioid.
In addition to routine adverse event reporting, pre-specified event categories, adjudicated by an independent expert committee, were examined in two placebo- controlled safety studies in which patients received parecoxib sodium for at least 3 days and then were transitioned to oral valdecoxib for a total duration of 10-14 days.
Barra mir- rapportar ta ’ episodji avversi ta ’ rutina, kategoriji ta ’ episodji speċifikati minn qabel, meqjusin minn kumitat espert indipendenti, ġew eżaminati f’ żewġ studji tas- sigurtà kkontrollati bi plaċebo li fihom, il- pazjenti rċevew parecoxib sodium għal mill- inqas 3 ijiem u mbagħad inqelbu għal valdecoxib orali għal perjodu totali ta ’ 10- 14 - il ġurnata.
All patients received standard of care analgesia during treatment.
Il- pazjenti kollha rċevew analġeżija standard matul it- trattament.
Patients received low-dose acetylsalicylic acid prior to randomization and throughout the two CABG surgery studies.
Pazjenti rċevew doża baxxa ta ’ acetylsalicylic acid qabel it- tqassim b’ mod każwali u matul iż- żewġ studji ta ’ kirurġija CABG.
The first CABG surgery study evaluated patients treated with IV parecoxib sodium 40 mg bid for a minimum of 3 days, followed by treatment with valdecoxib 40 mg bid (parecoxib sodium/ valdecoxib group) (n=311) or placebo/ placebo (n=151) in a 14-day, double-blind placebo-controlled study.
L- ewwel studju fuq kirurġija CABG evalwa pazjenti kkurati bi parecoxib sodium 40 mg bid IV għal mill- inqas 3 ijiem, segwit bi trattament b’ valdecoxib 40 mg bid (grupp parecoxib sodium/ valdecoxib) (n=311) jew plaċebo/ plaċebo (n=151) fi studju kkontrollat bi plaċebo double- blind ta ’ 14- il jum.
Nine pre-specified adverse event categories were evaluated (cardiovascular thromboembolic events, pericarditis, new onset or exacerbation of congestive heart failure, renal failure/ dysfunction, upper GI ulcer complications, major non-GI bleeds, infections, non-infectious pulmonary complications, and death).
Disa ’ kategorija ta ’ episodji avversi speċifikati minn qabel ġew evalwati (episodji tromboemboliċi, perikardite, bidu jew taħrix ta ’ insufiċjenza tal- qalb konġestiva, indeboliment renali/ funzjoni renali ħażina, kumplikazzjonijiet ta ’ ulċeri GI fil- parti ta ’ fuq, fsada mhux GI maġġuri, infezzjonijiet, kumplikazzjonijiet pulmonari mhux infettużi, u mewt).
There was a significantly (p < 0.05) greater incidence of cardiovascular/ thromboembolic events (myocardial infarction, ischemia, cerebrovascular accident, deep vein thrombosis and pulmonary embolism) detected in the parecoxib/ valdecoxib treatment group compared to the placebo/ placebo treatment group for the IV dosing period (2.2% and 0.0% respectively) and over the entire study period (4.8% and 1.3% respectively).
Kien hemm inċidenza ferm ikbar (p < 0. 05) ta ’ episodji kardjovaskulari/ tromboemboliċi (infart mikokardjali, iskemja, inċident ċerebrovaskulari, trombożi profonda fil- vini u emboliżmu pulmonary) mikxufin fil- grupp ta ’ trattament parecoxib/ valdecoxib meta mqabbla mal- grupp ta ’ trattament plaċebo/ plaċebo għall- perjodu ta ’ dożaġġ IV (2. 2% u 0. 0% rispettivament) u fuq il- perjodu kollu ta ’ l- istudju (4. 8% u 1. 3% rispettivament).
In the second CABG surgery study, four pre-specified event categories were evaluated (cardiovascular/ thromboembolic; renal dysfunction/ renal failure; upper GI ulcer/ bleeding; surgical wound complication).
Fit- tieni studju fuq kirurġija CABG, erba ’ kategoriji ta ’ episodji speċifikati minn qabel ġew evalwati (kardjovaskulari/ tromboemboliċi; indeboliment renali/ funzjoni renali ħażina; ulċeri GI fil- parti ta ’ fuq/ fsada, kumplikazzjonijiet ta ’ feriti kirurġiċi).
Patients were randomized within 24-hours post-CABG surgery to: parecoxib initial dose of 40 mg IV, then 20 mg IV Q12H for a minimum of 3 days followed by valdecoxib PO (20 mg Q12H) (n=544) for the remainder of a 10 day treatment period; placebo IV followed by valdecoxib PO (n=544); or placebo IV followed by placebo PO (n=548).
25 10 ijiem; plaċebo IV segwit bi valdecoxib PO (n=544); jew plaċebo IV segwit bi plaċebo PO (n=548).
A significantly (p=0.033) greater incidence of events in the cardiovascular/ thromboembolic category was detected in the parecoxib / valdecoxib treatment group (2.0%) compared to the placebo/ placebo treatment group (0.5%).
Inkixfu ferm iktar inċidenzi (p=0. 033) ta ’ episodji fil- kategorija kardjovaskulari/ tromboemboliċi fil - grupp ta ’ trattament parecoxib / valdecoxib treatment group (2. 0%) meta mqabbel mal- grupp ta ’ trattament plaċebo/ plaċebo (0. 5%).
Placebo/ valdecoxib treatment was also associated with a higher incidence of CV thromboembolic events versus placebo treatment, but this difference did not reach statistical significance.
Trattament plaċebo/ valdecoxib ġie assoċjat ukoll ma ’ inċidenza ogħla ta ’ episodji tromboemboliċi CV kontra trattament bi plaċebo, iżda din id- differenza ma laħqitx sinifikanza statistika.
Three of the six cardiovascular thromboembolic events in the placebo/ valdecoxib treatment group occurred during the placebo treatment period; these patients did not receive valdecoxib.
Tlieta mis- sitt episodji tromboemboliċi kardjovaskulari fil- grupp ta ’ trattament plaċebo/ valdecoxib seħħew matul il- perjodu ta ’ trattament bi plaċebo; dawn il- pazjenti ma rċevewx valdecoxib.