qanastek/EMEA-V3 huggingface dataset:
In clinical trials, etoricoxib was evaluated for safety in 7152 individuals, including 4614 patients with OA, RA, chronic low back pain or ankylosing spondylitis (approximately 600 patients with OA or RA were treated for one year or longer).
Fi provi kliniċi, etoricoxib ġie evalwat għas- sigurtà f’ 7152 individwu, inkluż 4614- il pazjent b’ OA, RA, uġigħ kroniku fil- parti ta ’ isfel tad- dahar jew ankylosing spondylitis (bejn wieħed u ieħor 600 pazjent b’ OA jew RA ġew ikkurati għal sena jew iktar).
In clinical studies, the undesirable effects profile was similar in patients with OA or RA treated with etoricoxib for one year or longer.
Fi studji kliniċi, il- profil ta ’ l- effetti mhux mixtieqa kien simili fil- pazjenti b’ OA jew RA ikkurati b’ etoricoxib għal sena jew aktar.
In a clinical study for acute gouty arthritis, patients were treated with etoricoxib 120 mg once daily for eight days.
17 Fi studju kliniku għal artrite tal- gotta akuta, il- pazjenti ġew ikkurati b’ etoricoxib 120 mg darba kuljum għal tmint ijiem.
The adverse experience profile in this study was generally similar to that reported in the combined OA, RA, and chronic low back pain studies.
Il- profil ta ’ l- esperjenza avversa f’ dan l- istudju kien ġeneralment simili għal dak irrapportat fl- OA, RA u studji dwar l- uġigħ kroniku fil- parti t’ isfel tad- dahar.
In a cardiovascular safety outcomes program of pooled data from three active comparator controlled trials, 17, 412 patients with OA or RA were treated with etoricoxib (60 mg or 90 mg) for a mean duration of approximately 18 months.
Fi programm dwar ir- riżultati tas- sigurtà kardjovaskulari ta ’ tagħrif kondiviż minn tliet provi kkontrollati attivi ta ’ tqabbil, 17, 412- il pazjent b’ OA jew RA ġew ikkurati b’ etoricoxib (60 mg jew 90 mg) għal tul ta ’ żmien medju ta ’ madwar 18- il xahar.
The safety data and details from this program are presented in section 5.1.
It- tagħrif tas- sigurtà u dettalji minn dan il - programm huma ppreżentati fis- sezzjoni 5. 1.
The following undesirable effects were reported at an incidence greater than placebo in clinical trials in patients with OA, RA, chronic low back pain or ankylosing spondylitis treated with etoricoxib 30 mg, 60 mg or 90 mg for up to 12 weeks, or in the MEDAL Program studies, or in post-marketing experience:
L- effetti mhux mixtieqa li ġejjin ġew irrapportati b’ inċidenza ikbar minn dawk ta ’ plaċebo fi provi kliniċi f’ pazjenti b’ OA, RA, uġigħ fil- parti t’ isfel tad- dahar jew b’ ankylosing spondylitis ikkurati b’ etoricoxib 30 mg, 60 mg jew 90 mg għal mhux aktar minn 12- il ġimgħa, jew fl- istudji tal- Programm MEDAL, jew f’ esperjenza ta ’ wara t- tqegħid fis- suq:
[Very Common (≥ 1/ 10) Common (≥ 1/ 100 to < 1/ 10) Uncommon (≥ 1/ 1000 to < 1/ 100) Rare (≥ 1/ 10,000 to < 1/ 1,000) Very rare (< 1/ 10,000), not known (cannot be estimated from the available data)]
[Komuni Ħafna (≥1/ 10) Komuni (≥1/ 100 sa < 1/ 10) Mhux komuni (≥1/ 1000 sa < 1/ 100) Rari (≥1/ 10, 000 sa < 1/ 1, 000) Rari ħafna (< 1/ 10, 000), mhux magħrufin (ma jistgħux jiġu stmati mit- tagħrif disponibbli)]
Uncommon: gastroenteritis, upper respiratory infection, urinary tract infection.
Mhux komuni: gastroenterite, infezzjoni respiratorja fil- parti ta ’ fuq, infezzjoni fil- passaġġ awrinarju.
Immune system disorder:
Disturbi fis- sistema immunitarja:
Very rare: hypersensitivity reactions, including angioedema, anaphylactic/ anaphylactoid reactions including shock.
Rari ħafna: reazzjonijiet ta ’ sensittività anafilattiċi/ anafilaktojde inkluż xokk.
17 Common: oedema/ fluid retention Uncommon: appetite increase or decrease, weight gain.
Komuni: edema/ żamma ta ’ fluwidu Mhux komuni: żieda jew tnaqqis fl- aptit, żieda fil- piż
Uncommon: anxiety, depression, mental acuity decreased.
Mhux komuni: ansjetà, depressjoni, ċarezza mentali mnaqqsa.
Very rare: confusion, hallucinations.
Rari ħafna: konfużjoni, alluċinazzjonijiet.
Nervous system disorder:
Disturbi fis- sistema nervuża:
Common: dizziness, headache.
Komuni: sturdament, uġigħ ta ’ ras.
Uncommon: dysgeusia, insomnia, paresthaesia/ hypaesthesia, somnolence.
Mhux komuni: disgwesja, nuqqas ta ’ rqad, paresteżja/ ipaesteżja, ngħas.
Uncommon: blurred vision, conjunctivitis.
Mhux komuni: viżta mċajpra, konġunktivite.
Uncommon: tinnitus, vertigo.
Mhux komuni: tinnite, vertiġini.
Cardiac disorders:
Disturbi kardijaċi:
Common: palpitations.
Komuni: palpitazzjonijiet.
Uncommon: atrial fibrillation, congestive heart failure, non-specific ECG changes, myocardial infarction∗.
Mhux komuni: fibrillazzjoni atrijali, kollass konġestiv tal- qalb, tibdil mhux speċifiku fl- ECG, infart mijokardijaku∗.
Common: hypertension.
Komuni: pressjoni għolja.
Uncommon: flushing, cerebrovascular accident∗, transient ischaemic attack.
Mhux komuni: fwawar, aċċident ċerebrovaskulari∗, attakk iskemiku temporanju.
Very rare: hypertensive crisis.
18 Rari ħafna: kriżi ipertensiva.
Uncommon: cough, dyspnoea, epistaxis.
Disturbi respiratorji, toraċiċi u medjastinali Mhux komuni: sogħla, dispnea, epistassi.
Common: gastrointestinal disorders (e. g., abdominal pain, flatulence, heartburn), diarrhea, dyspepsia, epigastric discomfort, nausea.
Komuni: disturbi gastrointestinali (eż. uġigħ addominali, gass, ħruq ta ’ stonku, dijarea, dispepsija, skumdità epigastrika, nawseja.
Uncommon: abdominal distention, acid reflux, bowel movement pattern change, constipation, dry mouth, gastroduodenal ulcer, irritable bowel syndrome, oesophagitis, oral ulcer, vomiting, gastritis.
Mhux komuni: distensjoni addominali, rifluss aċiduż, tibdil fil- mod kif jaħdmu l- imsaren, stitikezza, ħalq xott, ulċera gastroduwodenali, sindrome ta ’ imsaren irritabbli, esofaġite, ulċera fil- ħalq, rimettar, gastrite.
Very rare: peptic ulcers including gastrointestinal perforation and bleeding (mainly in the elderly).
Rari ħafna: ulċeri peptiċi inkluż perforazzjoni gastrointestinali u fsada (prinċipalment fl- anzjani).
Very rare: hepatitis.
Rari ħafna: epatite.
Common: ecchymosis.
Komuni: ekkimożi.
Uncommon: facial oedema, pruritus, rash.
Mhux komuni: edema fil- wiċċ, prurite, raxx.
Very rare: urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Rari ħafna: urtikarja, is- sindrome ta ’ Stevens- Johnson, nekroliżi epidermali tossika.
Musculoskeletal, connective tissue and bone disorders:
Disturbi muskulo- skeletali, tal- connective tissue u tal- għadam:
Uncommon: muscular cramp/ spasm, musculoskeletal pain/ stiffness.
Mhux komuni: bugħawwiġ/ spażmi muskolari, uġigħ/ ebusija muskuloskeletali.
18 Uncommon: proteinuria.
Mhux komuni: proteinurja.
Very rare: renal insufficiency, including renal failure, usually reversible upon discontinuation of treatment (see section 4.4).
Rari ħafna: insuffiċjenza renali, inkluż indeboliment tal- kliewi, normalment riversibbli malli titwaqqaf il- kura (ara sezzjoni 4. 4).
Common: asthenia/ fatigue, flu-like disease.
Komuni: astenja/ għejja, marda simili għall- influwenza.
Uncommon: chest pain.
Mhux komuni: uġigħ fis- sider.
Uncommon: blood urea nitrogen increased, creatine phosphokinase increased, haematocrit decreased, haemoglobin decreased, hyperkalaemia, leukocytes decreased, platelets decreased, serum creatinine increased, uric acid increased.
Mhux komuni: żieda fin- nitroġenu fl- urea tad- demm, żieda fil- creatine phosphokinase, tnaqqis ematokritiku, tnaqqis fl- emoglobina, iperkalamija, tnaqqis fil- lewkoċiti, tnaqqis fil- pjastrini, żieda fil - kreatinina tas- serum, żieda fl- aċidu uriku.
Rare: blood sodium decreased.
Rari: tnaqqis fis- sodju tad- demm.
The following serious undesirable effects have been reported in association with the use of NSAIDs and cannot be ruled out for etoricoxib: nephrotoxicity including interstitial nephritis and nephrotic syndrome; hepatotoxicity including hepatic failure, jaundice and pancreatitis.
L- effetti serji mhux mixtieq li ġejjin ġew irrapportati f’ assoċjazzjoni ma ’ l- użu ta ’ NSAIDs u ma jistgħux ma jiġux ikkunsidrati għal etoricoxib: nefrotossiċità inkluż nefrite interstitjali u sindrome nefrotiku; tossiċità tal- fwied inkluż indeboliment epatiku, suffejra u pankreatite.
In clinical studies, administration of single doses of etoricoxib up to 500 mg and multiple doses up to 150 mg/ day for 21 days did not result in significant toxicity.
Fi studji kliniċi, l- għoti ta ’ dożi singoli ta ’ etoricoxib sa 500 mg u dożi multipli sa 150 mg/ jum għal 21 ġurnata ma rriżultawx f’ tossiċità sinjifikanti.
There have been reports of acute overdosage with etoricoxib, although adverse experiences were not reported in the majority of cases.
Kien hemm rapporti ta ’ doża eċċessiva akuta b’ etoricoxib, għalkemm esperjenzi avversi ma ġewx irrapportati fil- maġġoranza tal- każijiet.
The most frequently observed adverse experiences were consistent with the safety profile for etoricoxib (e. g. gastrointestinal events, cardiorenal events).
L- aktar esperjenzi avversi osservati b’ mod frekwenti kienu konsistenti mal- profil tas- sigurtà għal etoricoxib (eż. episodji gastrointestinali, episodji kardorenali).
In the event of overdose, it is reasonable to employ the usual supportive measures, e. g., remove unabsorbed material from the GI tract, employ clinical monitoring, and institute supportive therapy, if required.
19 Fil- każ ta ’ doża eċċessiva, jagħmel sens li jintużaw miżuri ta ’ appoġġ normali, eż. tneħħija ta ’ materjal li ma jkunx ġie assorbit mill- passaġġ GI, użu ta ’ monitoraġġ kliniku, u introduzzjoni ta ’ terapija ta ’ appoġġ, jekk ikun hemm bżonn.
Etoricoxib is not dialysable by haemodialysis; it is not known whether etoricoxib is dialysable by peritoneal dialysis.
Etoricoxib ma jiġix dijaliżabilizzat b’ emodijaliżi; mhuwiex magħruf jekk etoricoxib jiġix dijaliżabilizzat minn dijaliżi peritonejali.
Anti-inflammatory and antirheumatic products, non-steroids, coxibs, ATC Code:
Prodotti anti- infjammatorji u anti- rewmatiċi, mhux sterojde, coxibs, Kodiċi ATC:
Etoricoxib is an oral, selective cyclo-oxygenase-2 (COX-2) inhibitor within the clinical dose range.
Etoricoxib huwa inibitur cyclo- oxygenase- 2 (COX- 2) selettiv orali fi ħdan il- medda tad- dożaġġ kliniku.
Across clinical pharmacology studies ,< ARCOXIA > produced dose-dependent inhibition of COX-2 without inhibition of COX-1 at doses up to 150 mg daily.
Tul studji farmakoloġiċi kliniċi, < ARCOXIA > ipproduċa inibizzjoni dipendenti fuq id- doża ta ’ COX - 2 mingħajr inibizzjoni ta ’ COX- 1 f’ dożi ta ’ mhux aktar minn 150 mg kuljum.
Etoricoxib did not inhibit gastric prostaglandin synthesis and had no effect on platelet function.
Etoricoxib ma inibixxix sinteżi prostaglandin gastrika u ma kellux effet fuq il- funzjoni tal- pjastrini.
Cyclooxygenase is responsible for generation of prostaglandins.
Cyclooxygenase huwa responsabbli għall- ġenerazzjoni ta ’ prostaglandins.
Two isoforms, COX-1 and COX-2, have been identified.
Ġew identifikati żewġ isoforom, COX- 1 u COX - 2.
COX-2 is the isoform of the enzyme that has been shown to be induced by pro-inflammatory stimuli and has been postulated to be primarily responsible for the synthesis of prostanoid mediators of pain, inflammation, and fever.
COX- 2 hija l- isoformi ta ’ l- enzima li ntweriet li tiġi indotta minn stimuli pro- infjammatorji u ġiet postulata bħala li hija primarjament responsabbli għas- sinteżi ta ’ medjaturi prostanojde ta ’ l- uġigħ, infjammazzjoni u deni.
COX-2 is also involved in ovulation, implantation and closure of the ductus arteriosus, regulation of renal function, and central nervous system functions (fever induction, pain perception and cognitive function).
COX- 2 hija involuta wkoll fl- ovulazzjoni, impjantazzjoni u għeluq tad- ductus arteriosus, regolazzjoni tal- funzjoni renali, u funzjonijiet tas - sistema nervuża ċentrali (induzzjoni ta ’ deni, perċezzjoni ta ’ uġigħ u funzjonament konoxxittiv).
It may also play a role in ulcer healing.
Jista ’ jkollha rwol ukoll fil- fejqan minn ulċeri.
COX-2 has been identified in tissue around gastric ulcers in man but its relevance to ulcer healing has not been established.
COX- 2 ġiet identifikata fit- tessut madwar ulċeri gastriċi fil - bniedem iżda r- relevanza tagħha għall- fejqan mill- ulċeri għadha ma ġietx stabbilita.
19 Efficacy
Effikaċja
In patients with osteoarthritis (OA), etoricoxib 60 mg once daily provided significant improvements in pain and patient assessments of disease status.
F’ pazjenti b’ osteoartrite (OA), etoricoxib 60 mg darba kuljum ta titjib sinjifikanti fil- valutazzjonijiet ta ’ l- istatus tal- marda fir- rigward ta ’ l- uġigħ u tal- pazjent.
These beneficial effects were observed as early as the second day of therapy and maintained for up to 52 weeks.
Dawn l- effetti ta ’ benefiċċju ġew osservati sa mit- tieni jum ta ’ kura u nżammu sa 52 ġimgħa.
Studies with etoricoxib 30 mg once daily demonstrated efficacy superior to placebo over a 12 week treatment period (using similar assessments as the above studies).
Studji b’ etoricoxib 30 mg darba kuljum urew effikaċja superjuri għal plaċebo fuq perjodu ta ’ kura ta ’ 12- il ġimgħa (permezz ta ’ valutazzjonijiet simili bħall- istudji ta ’ fuq).
In a dose ranging study, etoricoxib 60 mg demonstrated significantly greater improvement than 30 mg for all 3 primary endpoints over 6 weeks of treatment.
Fi studju b’ doża li tvarja, etoricoxib 60 mg wera titjib ferm iktar sinjifikanti milli 30 mg għat- 3 punti ta ’ tmiem kollha fuq 6 ġimgħat ta ’ kura.
The 30 mg dose has not been studied in osteoarthritis of hands.
Id- doża ta ’ 30 mg ma ġietx studjata f’ osteoartrite ta ’ l- idejn.
In patients with rheumatoid arthritis (RA), etoricoxib 90 mg once daily provided significant improvements in pain, inflammation, and mobility.
F’ pazjenti b’ artrite rewmatojde (RA), etoricoxib 90 mg kuljum ipprovda titjib sinjifikanti fl- uġigħ, infjammazzjoni u mobilità.
These beneficial effects were maintained over the 12-week treatment periods.
Dawn l- effetti ta ’ benefiċċju nżammu għal perjodi ta ’ kura ta ’ 12- il ġimgħa.
In patients experiencing attacks of acute gouty arthritis, etoricoxib 120 mg once daily over an eight-day treatment period, relieved moderate to extreme joint pain and inflammation comparable to indomethacin 50 mg three times daily.
F’ pazjenti li esperjenzaw attakki ta ’ artrite tal- gotta akuta, etoricoxib 120 mg darba kuljum fuq perjodu ta ’ kura ta ’ 8 ijiem, serraħ minn uġigħ u infjammazzjoni fil- ġogi moderat għal sever komparabbli għal indomethacin 50 mg tliet darbiet kulujm.
Pain relief was observed as early as four hours after initiation of treatment.
Is- serħan mill- uġigħ ġie osservat sa wara erba ’ sigħat mill- bidu tal- kura.
In patients with ankylosing spondylitis, etoricoxib 90 mg once daily provided significant improvements in spine pain, inflammation, stiffness and function.
F’ pazjenti b’ ankylosing spondylitis, etoricoxib 90 mg darba kuljum ta titjib sinjifikanti fl- uġigħ ta ’ l - ispina, infjammazzjoni, ebusija u funzjoni.
The clinical benefit of etoricoxib was observed as early as the second day of therapy after initiation of treatment and was maintained throughout the 52-week treatment period.
Il- benefiċċju kliniku ta ’ etoricoxib ġie osservat sa mit- tieni jum wara l- bidu tal- kura u dan inżamm tul il- perjodu ta ’ 52 ġimgħa kollu.
In studies specifically designed to measure the onset of action of etoricoxib, the onset of action occurred as early as 24 minutes after dosing.
20 Fi studji mfasslin speċifikament sabiex ikejlu l- bidu ta ’ azzjoni ta ’ etoricoxib, il- bidu ta ’ l- azzjoni seħħ sa minn wara 24 minuta wara d- doża.
Safety
Sigurtà
Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) Program The MEDAL Program was a prospectively designed Cardiovascular (CV) Safety Outcomes Program of pooled data from three randomized, double-blind active comparator controlled trials, the MEDAL study, EDGE II and EDGE.
Il- Programm Multinational Etoricoxib and Diclofenac Arthritis Long- term (MEDAL) Il- Programm MEDAL kien Programm tar- Riżultati tas- Sigurtà Kardjovaskulari (CV) imfassal prospettivament ta ’ tagħrif miġbur flimkien minn tliet provi randomizzati, double- blind ikkontrollati b’ komparatur, l- istudju MEDAL, EDGE II u EDGE.
The MEDAL Study, was an endpoint driven CV Outcomes study in 17,804 OA and 5,700 RA patients treated with etoricoxib 60 (OA) or 90 mg (OA and RA) or diclofenac 150 mg daily for a mean period of 20.3 months (maximum of 42.3 months, median 21.3 months).
L- Istudju MEDAL, kien studju tar- riżultati CV immexxi minn punt ta ’ tmiem fi 17, 804 pazjenti OA u 5, 700 pazjent RA ikkurati b’ etoricoxib 60 (OA) jew 90 mg (OA u RA) jew diclofenac 150 mg kuljum għal perjodu medju ta ’ 20. 3 xahar (massimu ta ’ 42. 3 xahar, medjan ta ’ 21. 3 xahar).
In this trial, only serious adverse events and discontinuations due to any adverse events were recorded.
F’ din il- prova, ġew irrekordjati biss episodji avversi serji u diskontinwi dovuti għal kwalunkwe episodju avvers.
The EDGE and EDGE II studies compared the gastrointestinal tolerability of etoricoxib versus diclofenac.
L- istudji EDGE u EDGE II qabblu t- tollerabilità gastrointestinali ta ’ etoricoxib kontra diclofenac.
The EDGE study included 7111 OA patients treated with a dose of etoricoxib 90 mg daily (1.5 times the dose recommended for OA) or diclofenac 150 mg daily for a mean period of 9.1 months (maximum 16.6 months, median 11.4 months).
L - istudju EDGE nkluda 7111- il pazjent OA ikkurati b’ doża ta ’ etoricoxib 90 mg kuljum (1. 5 drabi d - doża rakkomandata għall- OA) jew diclofenac 150 mg kuljum għal perjodu medju ta ’ 9. 1 xhur (massimu 16. 6 xahar, medjan ta ’ 11. 4 xahar).
The EDGE II study included 4086 RA patients treated with etoricoxib 90 mg daily or diclofenac 150 mg daily for a mean period of 19.2 months (maximum 33.1 months, median 24 months).
L- istudju EDGE II inkluda 4086 pazjent RA ikkurati b’ etoricoxib 90 mg kuljum jew diclofenac 150 mg kuljum għal perjodu medju ta ’ 19. 2 xahar (massimu ta ’ 33. 1 xhur, medjan ta ’ 24 xahar).
In the pooled MEDAL Program, 34,701 patients with OA or RA were treated for a mean duration of 17.9 months (maximum 42.3 months, median 16.3 months) with approximately 12,800 patients receiving treatment for more than 24 months.
Fil- Programm MEDAL bit- tagħrif kollu miġbur flimkien, 34, 701 pazjent b’ OA jew b’ RA kienu kkurati għal tul ta ’ żmien medju ta ’ 17. 9 xahar (masismu ta ’ 42. 3 xahar, medjan ta ’ 16. 3 xahar) b’ bejn wieħed u ieħor 12, 800 pazjent jirċievi kura għal aktar minn 24 xahar.
Patients enrolled in the Program had a wide range of cardiovascular and gastrointestinal risk factors at baseline.
Pazjenti rreġistrati fil- Programm kellhom firxa wiesgħa ta ’ fatturi ta ’ riskju kardjovaskulari u gastrointestinali fil- linja bażi.
Patients with a recent history of myocardial infarction, coronary artery bypass grafting or percutaneous coronary intervention within 6 months preceding enrollment were excluded.
Pazjenti bi storja reċenti ta ’ infart mijokardijaku, grafting tal- bypass ta ’ l- arterja koronarja jew intervent koronarju perkutanju fi żmien 6 xhur qabel ir- reġistrazzjoni ġew esklużi.
Use of gastroprotective agents and low dose aspirin were permitted in the studies.
L- użu ta ’ sustanzi gastroprotettivi u aspirina ta ’ doża baxxa kien permess fl- istudji.
Overall Safety:
Sigurtà Ġenerali:
20 There was no significant difference between etoricoxib and diclofenac in the rate of cardiovascular thrombotic events.
Ma kien hemm ebda differenza sinjifikanti bejn etoricoxib u diclofenac fir- rata ta ’ episodji trombotiċi kardjovaskulari.
Cardiorenal adverse events were observed more frequently with etoricoxib than with diclofenac, and this effect was dose-dependent (see specific results below).
Episodji kardjorenali avversi ġew osservati b’ mod aktar frekwenti b’ etoricoxib aktar milli b’ diclofenac, u dan l- effett kien dipendenti fuq id- doża (ara r- riżultati speċifiċi taħt).
Gastrointestinal and hepatic adverse events were observed significantly more frequently with diclofenac than etoricoxib.
Episodji gastrointestinali u epatiċi avversi ġew osservati b’ mod ferm aktar frekwenti b’ diclofenac milli b’ etoricoxib.
The incidence of adverse experiences in EDGE and EDGE II and of adverse experiences considered serious or resulting in discontinuation in the MEDAL study was higher with etoricoxib than diclofenac.
L- inċidenza ta ’ esperjenzi avversi f’ EDGE u EDGE II u ta ’ esperjenzi avversi meqjusin serji jew li jirriżultaw fi twaqqif ta ’ l- istudju MEDAL kienu ogħla b’ etoricoxib milli b’ diclofenac.
Cardiovascular safety results:
Riżultati tas- sigurtà kardjovaskulari:
The rate of confirmed thrombotic cardiovascular serious adverse events (consisting of cardiac, cerebrovascular, and peripheral vascular events) was comparable between etoricoxib and diclofenac, and data are summarized in the table below.
Ir- rata ta ’ l- episodji avversi serji kardjovaskulari trombotiċi (li jikkonsistu minn episodji kardijaċi, ċerebrovaskulari u episodji vaskulari periferali) kienet komporabbli bejn etoricoxib u diclofenac, u t - tagħrif huwa mogħti fil- qosor fit- tabella t’ hawn taħt.
There were no statistically significant differences in thrombotic event rates between etoricoxib and diclofenac across all subgroups analyzed including patient categories across a range of baseline cardiovascular risk.
Ma kien hemm ebda differenza statistikament sinjifikanti fir- rati ta ’ episodji trombotiċi bejn etoricoxib u diclofenac fis- subgruppi kollha analizzati nkluż kategoriji ta ’ pazjenti tul firxa ta ’ riskji kardjovaskulari tal- linja bażi.
When considered separately, the relative risks for confirmed thrombotic cardiovascular serious adverse events with etoricoxib 60 mg or 90 mg compared with diclofenac 150 mg were similar.
Meta kkunsidrati separatament, ir- riskji relattivi għal episodji avversi serji kardjovaskulari trombotiċi kkonfermati b’ etoricoxib 60 mg jew 90 mg meta mqabbla ma ’ diclofenac 150 mg kienu simili.
Rates of Confirmed Thrombotic CV Events (Pooled MEDAL Program)
Rati ta ’ Episodji CV Trombotiċi Konfermati (Programm MEDAL Konġunt)
Treatment
Tqabbil tal- Kura
25836 Patient- Years
25836 Pazjent -
24766 Patient- Years
24766 Pazjent -
Comparison
Rata †
Rate† (95% CI)
Rata † (95% CI)
Relative Risk (95% CI)
Riskju Relattiv (95% CI)
Confirmed Thrombotic Cardiovascular Serious Adverse Events
Episodji Avversi Kardjovaskulari Trombotiċi Kkonfermati Serji
Per-protocol Intent-to-treat
Per- protokoll
1.24 (1.11, 1.38) 1.25 (1.14, 1.36)
1. 24 (1. 11, 1. 38)
1.30 (1.17, 1.45) 1.19 (1.08, 1.30)
1. 30 (1. 17, 1. 45)
0.95 (0.81, 1.11) 1.05 (0.93, 1.19)
0. 95 (0. 81, 1. 11)
Confirmed Cardiac Events
Intenzjoni għall - 1. 25 (1. 14, 1. 36) kura Episodji Kardijaċi Kkonfermati
Per-protocol Intent-to-treat
1. 19 (1. 08, 1. 30)
0.78 (0.68, 0.90) 0.70 (0.62, 0.79)
1. 05 (0. 93, 1. 19)
0.90 (0.74, 1.10) 0.99 (0.84, 1.17)
Per- protokoll 0. 71 (0. 61, 0. 82) Intenzjoni għall - 0. 69 (0. 61, 0. 78) kura Episodji Ċerebrovaskulari Kkonfermati
Confirmed Cerebrovascular Events
0. 78 (0. 68, 0. 90) 0. 70 (0. 62, 0. 79)
Per-protocol Intent-to-treat
0. 90 (0. 74, 1. 10) 0. 99 (0. 84, 1. 17)
0.32 (0.25, 0.40) 0.29 (0.24, 0.35)
Per- protokoll 0. 34 (0. 28, 0. 42) Intenzjoni għall - 0. 33 (0. 28, 0. 39) kura Episodji Vaskulari Periferali Kkonfermati
1.08 (0.80, 1.46) 1.12 (0.87, 1.44)
0. 32 (0. 25, 0. 40) 0. 29 (0. 24, 0. 35)
Per-protocol Intent-to-treat †
1. 08 (0. 80, 1. 46) 1. 12 (0. 87, 1. 44)
0.20 (0.15, 0.27) 0.24 (0.20, 0.30)
Per- protokoll 0. 20 (0. 15, 0. 27) Intenzjoni għall - 0. 24 (0. 20, 0. 30) kura †
0.22 (0.17, 0.29) 0.23 (0.18, 0.28)
0. 22 (0. 17, 0. 29) 0. 23 (0. 18, 0. 28)
0.92 (0.63, 1.35) 1.08 (0.81, 1.44)
0. 92 (0. 63, 1. 35) 1. 08 (0. 81, 1. 44)
Events per 100 Patient-Years; CI=confidence interval N=total number of patients included in Per-protocol population
Episodji għal kull 100 Pazjent- Sena; CI=intervall ta ’ fiduċja N=numru totali ta ’ pazjenti nklużi fil- popolazzjoni Per- protokoll
Per-protocol: all events on study therapy or within 14 days of discontinuation (excluded: patients who took< 75% of their study medication or took non-study NSAIDs > 10% of the time).
Per- protokoll: l- episodji kollha dwar terapija ta ’ studju jew fi żmien 14- il jum mit- twaqqif (għajr: pazjenti li ħadu < 75% tal- medikazzjoni ta ’ studju tagħhom jew li ħadu NSAIDs mhux ta ’ l- istudju > 10% tal- ħin).
Intent-to-treat: all confirmed events up to the end of the trial (included patients potentially exposed to non-study interventions following discontinuation of study medication).
Intenzjoni għall- kura: l- episodji kkonfermati kollha sa tmiem il- prova (inkluż pazjenti li huma potenzjalment esposti għal interventi mhux ta ’ l- istudju wara t- twaqqif tal - medikazzjoni ta ’ l- istudju).
Total number of patients randomised, n= 17412 on etoricoxib and 17289 on diclofenac.
Numru totali ta ’ pazjenti randomizzati, n= 17412 fuq etoricoxib u 17289 fuq diclofenac.
CV mortality, as well as overall mortality, was similar between the etoricoxib and diclofenac treatment groups.
Il- mortalità CV, kif ukoll il- mortalità in ġenerali, kienet simili bejn il- grupp bil- kura b’ etoricoxib u dak bil- kura b’ diclofenac
Cardiorenal Events:
Episodji Kardjorenali:
Approximately 50% of patients enrolled in the MEDAL study had a history of hypertension at baseline.
Bejn wieħed u ieħor 50% tal- pazjenti rreġistrati fl- istudju MEDAL kellhom storja ta ’ pressjoni għolja fil- linja bażi.
In the study, the incidence of discontinuations due to hypertension-related adverse events was statistically significantly higher for etoricoxib than for diclofenac.
Fl- istudju, l- inċidenza ta ’ twaqqif dovut għal episodji avversi relatati ma ’ pressjoni għolja kienet statistikament ferm ogħla għal etoricoxib milli għal diclofenac.
21 diclofenac 150 mg but was higher for etoricoxib 90 mg compared to diclofenac 150 mg (statistically significant for 90 mg etoricoxib vs.
L- inċidenza ta ’ episodji avversi ta ’ kollass konġestiv tal- qalb (twaqqif u episodji serji) seħħew f’ rati simili fuq etoricoxib 60 mg meta mqabbel ma ’ diclofenac 150 mg iżda kienet ogħla għal etoricoxib 90 mg meta mqabbel ma ’ diclofenac 150 mg (statistikament sinjifikanti għal 90 mg etoricoxib vs.
150 mg diclofenac in MEDAL OA cohort).
150 mg diclofenac fil- ko- orti OA ta ’ MEDAL).
The incidence of confirmed congestive heart failure adverse events (events that were serious and resulted in hospitalisation or a visit to an emergency department) was non-significantly higher with etoricoxib than diclofenac 150 mg, and this effect was dose-dependent.
L- inċidenza ta ’ episodji avversi ta ’ kollass konġestiv tal- qalb ikkonfermati (episodji li kienu serji u rriżultaw f’ kura l- isptar jew fi żjara f’ dipartiment ta ’ l- emerġenza) kienet ogħla iżda mhux b’ mod sinjifikanti b’ etoricoxib milli b’ diclofenac 150 mg, u dan l- effett kien dipendenti fuq id - doża.
The incidence of discontinuations due to edema-related adverse events was higher for etoricoxib than diclofenac 150 mg, and this effect was dose-dependent (statistically significant for etoricoxib 90 mg, but not for etoricoxib 60 mg).
L- inċidenza ta ’ twaqqif dovut għal episodji avversi relatati ma ’ edema kienet ogħla għal etoricoxib milli għal diclofenac 150 mg, u dan l- effett kien dipendenti fuq id- doża (statistikament sinjifikanti għal etoricoxib 90 mg, iżda mhux għal etoricoxib 60 mg).
The cardiorenal results for EDGE and EDGE II were consistent with those described for the MEDAL Study.
Ir- riżultati kardjorenali għal EDGE u EDGE II kienu konsistenti ma ’ dawk deskritti għall- Istudju ta ’ MEDAL.
In the individual MEDAL Program studies, for etoricoxib (60 mg or 90 mg), the absolute incidence of discontinuation in any treatment group was up to 2.6% for hypertension, up to 1.9% for edema, and up to 1.1% for congestive heart failure, with higher rates of discontinuation observed with etoricoxib 90 mg than etoricoxib 60 mg.
22 Fl- istudji tal- Programm MEDAL individwali, għal etoricoxib (60 mg jew 90 mg), l- inċidenza assoluta ta ’ waqfien fi kwalunkwe grupp ta ’ kura kien sa 2. 6% għal pressjoni għolja, sa 1. 9% għal edema, u sa 1. 1% għal kollass konġestiv tal- qalb, b’ rati ogħla ta ’ waqfien osservati b’ etoricoxib 90 mg milli b’ etoricoxib 60 mg.
MEDAL Program Gastrointestinal Tolerability Results:
Ir- Riżultati tat- Tollerabilità Gastrointestinali tal- Programm MEDAL:
A significantly lower rate of discontinuations of treatment for any clinical (e. g., dyspepsia, abdominal pain, ulcer) GI adverse event was observed with etoricoxib compared with diclofenac within each of the three component studies of the MEDAL Program.
Rata ferm aktar baxxa ta ’ waqfien tal- kura minħabba xi episodju GI kliniku avvers (eż. dispepsija, uġigħ addominali, ulċera) ġiet osservata b’ etoricoxib meta mqabbla ma ’ diclofenac fi ħdan kull wieħed mit- tliet studji komponenti tal- Programm MEDAL.
The rates of discontinuations due to adverse clinical GI events per hundred patient-years over the entire period of study were as follows:
Ir- rati ta ’ waqfien dovuti għal episodji GI kliniċi avversi għal kull mitt pazjent- snin fuq il- perjodu kollu ta ’ l- istudju kienu kif ġej:
3.23 for etoricoxib and 4.96 for diclofenac in the MEDAL Study; 9.12 with etoricoxib and 12.28 with diclofenac in the EDGE study; and 3.71 with etoricoxib and 4.81 with diclofenac in the EDGE II study.
3. 23 għal etoricoxib u 4. 96 għal diclofenac fl- Istudju MEDAL; 9. 12 b’ etoricoxib u 12. 28 b’ diclofenac fl- istudju EDGE; u 3. 71 b’ etoricoxib u 4. 81 b’ diclofenac fl- istudju EDGE II.
MEDAL Program Gastrointestinal Safety Results:
Ir- Riżultati tas- Sigurtà Gastrointestinali tal- Programm MEDAL:
Overall upper GI events were defined as perforations, ulcers and bleeds.
B’ kollox ma ’ kollox, l- episodji GI ta ’ fuq kienu definiti bħala perforazzjonijiet, ulċeri u fsada.
The subset of overall upper GI events considered complicated included perforations, obstructions, and complicated bleeding; the subset of upper GI events considered uncomplicated included uncomplicated bleeds and uncomplicated ulcers.
Is - subsett ta ’ l- episodji GI ta ’ fuq ġenerali meqjusin bħala kkumplikati kien jinkludi perforazzjonijiet, ostruzzjonijiet u fsada kkomplikata; is- subsett ta 'episodji GI ta' fuq meqjusin bħala mhux ikkumplikati inkludew fsada mhux ikkumplikata u ulċeri mhux ikkumplikati.
A significantly lower rate of overall upper GI events was observed with etoricoxib compared to diclofenac.
Rata ferm aktar baxxa ta ’ episodji GI ta ’ fuq ġenerali ġiet osservata b’ etoricoxib meta mqabbla ma ’ diclofenac.
There was no significant difference between etoricoxib and diclofenac in the rate of complicated events.
Ma kien hemm ebda differenza sinjifikanti bejn etoricoxib u diclofenac fir- rata ta ’ episodji kkumplikati.
For the subset of upper GI hemorrhage events (complicated and uncomplicated combined), there was no significant difference between etoricoxib and diclofenac.
Għas - subsett ta ’ episodji ta ’ emorraġija GI ta ’ fuq (ikkumplikati u mhux ikkumplikati flimkien), ma kien hemm ebda differenza sinjifikanti bejn etoricoxib u diclofenac.
The upper GI benefit for etoricoxib compared with diclofenac was not statistically significant in patients taking concomitant low-dose aspirin (approximately 33% of patients).
Il- benefiċċju GI ta ’ fuq għal etoricoxib meta mqabbel ma ’ diclofenac ma kienx statistikament sinjifikanti f’ pazjenti li kienu qegħdin jieħdu aspirina ta ’ doża baxxa fl- istess ħin (bejn wieħed u ieħor 33% tal- pazjenti).
The rates per hundred patient-years of confirmed complicated and uncomplicated upper GI clinical events (perforations, ulcers and bleeds (PUBs)) were 0.67 (95% CI 0.57, 0.77) with etoricoxib and 0.97 (95% CI 0.85, 1.10) with diclofenac, yielding a relative risk of 0.69 (95% CI 0.57, 0.83).
Ir- rati għal kull mitt pazjent sena ta ’ episodji kliniċi GI ta 'fuq ikkomplikati u mhux ikkomplikati kkonfermati (perforazzjonijiet, ulċeri u fsada (PUBs)) kienu 0. 67 (95% CI 0. 57, 0. 77) b’ etoricoxib u 0. 97 (95% CI 0. 85, 1. 10) b’ diclofenac, u dan ta ’ riskju relattiv ta ’ 0. 69 (95% CI 0. 57, 0. 83).
The rate for confirmed upper GI events in elderly patients was evaluated and the largest reduction was observed in patients ≥ 75 years of age (1.35 [95% CI 0.94, 1.87] vs.
Ir- rata għal episodji GI ikkonfermati f’ pazjenti anzjani ġiet evalwata u l- akbar tnaqqis ġie osservat f’ pazjenti ≥ 75 sena (1. 35 [95% CI 0. 94, 1. 87] vs.
2.78 [95% CI 2.14, 3.56] events per hundred patient-years for etoricoxib and diclofenac, respectively.
2. 78 [95% CI 2. 14, 3. 56] (episodji għal kull mitt pazjent- sena għal etoricoxib u diclofenac, rispettivament).
The rates of confirmed lower GI clinical events (small or large bowel perforation, obstruction, or hemorrhage, (POBs)) were not significantly different between etoricoxib and diclofenac.
Ir- rati ta 'episodji kliniċi GI baxxi kkonfermati (perforazzjoni żgħira jew kbira ta ’ l- imsaren, ostruzzjoni, jew emorraġija, (POBs)) ma kinux ferm differenti bejn etoricoxib u diclofenac.
MEDAL Program Hepatic Safety Results:
Ir- Riżultati tas- Sigurtà Epatika tal- Programm MEDAL:
Etoricoxib was associated with a statistically significantly lower rate of discontinuations due to hepatic- related adverse experiences than diclofenac.
Etoricoxib kien assoċjat ma ’ rata li statistikament kienet ferm aktar baxxa ta ’ waqfien dovut għal esperjenzi avversi relatati mal- fwied milli għal diclofenac.
In the pooled MEDAL Program, 0.3% of patients on etoricoxib and 2.7% of patients on diclofenac discontinued due to hepatic-related adverse experiences.
Fil- Programm MEDAL bit- tagħrif miġbur flimkien, 0. 3% tal- pazjenti fuq etoricoxib u 2. 7% tal- pazjenti fuq diclofenac waqfu minħabba esperjenzi avversi relatati mal- fwied.
The rate per hundred patient-years was 0.22 on etoricoxib and 1.84 for diclofenac (p-value was < 0.001 for etoricoxib vs. diclofenac).
Ir- rata għal kull mitt pazjent- snin kienet 0. 22 għal etoricoxib u 1. 84 għal diclofenac (valur- p kien < 0. 001 għal etoricoxib vs. diclofenac).
However, most hepatic adverse experiences in the MEDAL Program were non-serious.
Madankollu, ħafna mill - esperjenzi avversi epatiċi fil- Programm MEDAL ma kinux serji.
Additional Thrombotic Cardiovascular Safety Data In clinical studies excluding the MEDAL Program Studies, approximately 3100 patients were treated with etoricoxib ≥ 60 mg daily for 12 weeks or longer.
Tagħrif Addizzjonali dwar is- Sigurtà Kardjovaskulari Trombotika Fi studji kliniċi għajr l- Istudji tal- Programm MEDAL, madwar 3100 pazjent ġew trattati b’ etoricoxib ≥60 mg kuljum għal 12- il ġimgħa jew aktar.
There was no discernible difference in the rate of confirmed serious thrombotic cardiovascular events between patients receiving etoricoxib ≥ 60 mg, placebo, or non-
Ma kien hemm ebda differenza kbira fir- rata ta ’ episodji kardjovaskulari trombotiċi serji kkonfermati bejn pazjenti li rċevew etoricoxib ≥60 mg, plaċebo, jew NSAIDs mhux naproxen.
However, the rate of these events was higher in patients receiving etoricoxib compared with those receiving naproxen 500 mg twice daily.
Madankollu, ir- rata ta ’ dawn l- episodji kienet ogħla f’ pazjenti li jirċievu etoricoxib meta mqabbla ma ’ dawk li jirċievu naproxen 500 mg darbtejn kuljum.
The difference in antiplatelet activity between some COX-1 inhibiting NSAIDs and selective COX-2 inhibitors may be of clinical significance in patients at risk of thrombo-embolic events.
Id- differenza fl - attività kontra l- pjastrini bejn xi NSAIDs li jinibixxu COX- 1 u inibituri COX- 2 selettivi tista ’ tkun ta ’ sinjifikat klinikali f’ pazjenti f’ riskju ta ’ episodji trombo- emboliċi.
Selective COX-2 inhibitors reduce the formation of systemic (and therefore possibly endothelial) prostacyclin without affecting platelet thromboxane.
Inibituri COX- 2 selettivi jnaqqsu l - formazzjoni ta ’ prostacyclin sistemiku (u għalhekk possibbilment endoteljali) mingħajr ma jaffettwaw it- thromboxane tal- pjastrini.
Additional Gastrointestinal Safety Data In two 12-week double-blind endoscopy studies, the cumulative incidence of gastroduodenal ulceration was significantly lower in patients treated with etoricoxib 120 mg once daily than in patients treated with either naproxen 500 mg twice daily or ibuprofen 800 mg three times daily.
23 Tagħrif Addizzjonali dwar is- Sigurtà Gastrointestinali F’ żewġ studji ta ’ endoskopija double- blind ta ’ 12- il ġimgħa, l- inċidenza kumulattiva ta ’ ulċerazzjoni gastroduwodenali kienet ferm inqas fil- pazjenti kkurati b’ etoricoxib 120 mg darba kuljum milli f’ pazjenti kkurati jew b’ naproxen 500 mg darbtejn kuljum jew b’ ibuprofen 800 mg tliet darbiet kuljum.
Etoricoxib had a higher incidence of ulceration as compared to placebo.
Etoricoxib kellu inċidenza ogħla ta ’ ulċerazzjoni meta mqabbel ma ’ plaċebo.
Renal Function Study in the Elderly A randomized, double-blind, placebo-controlled, parallel-group study evaluated the effects of 15 days of treatment of etoricoxib (90 mg), celecoxib (200 mg bid), naproxen (500 mg bid) and placebo on urinary sodium excretion, blood pressure, and other renal function parameters in subjects 60 to 85 years of age on a 200-mEq/ day sodium diet.
L- Istudju dwar il- Funzjoni Renali fl- Anzjani Studju bi grupp parallel, ikkontrollat bi plaċebo, double- blind, randomizzat evalwa l- effetti ta '15- il jum ta ’ kura ta ’ etoricoxib (90 mg), celecoxib (200 mg bid), naproxen (500 mg bid) u plaċebo fuq it - tneħħija ma ’ l- awrina tas- sodju, pressjoni tad- demm, u parametric oħrajn tal- funzjoni renali f’ suġġetti ta ’ bejn 60 u 85 sena fuq dieta ta ’ sodju ta ’ 200- mEq/ kuljum.
Etoricoxib, celecoxib, and naproxen had similar effects on urinary sodium excretion over the 2 weeks of treatment.
Etoricoxib, celecoxib, u naproxen kellhom effetti simili fuq it- tneħħija tas- sodju ma ’ l- awrina fuq iż- 2 ġimgħat tal- kura.
All active comparators showed an increase relative to placebo with respect to systolic blood pressures; however, etoricoxib was associated with a statistically significant increase at Day 14 when compared to celecoxib and naproxen (mean change from baseline for systolic blood pressure: etoricoxib 7.7 mmHg, celecoxib 2.4 mmHg, naproxen 3.6 mmHg).
Il- komparaturi attivi kollha wrew żieda meta mqabbla ma 'plaċebo fir- rigward ta' pressjonijiet sistoliċi fid- demm; madankollu, etoricoxib kien assoċjat ma 'żieda statistikament sinjifikanti f’ Jum 14 meta mqabbel ma' celecoxib u naproxen (bidla medja mil- linja bażi għal pressjoni sistolika tad- demm: etoricoxib 7. 7 mmHg, celecoxib 2. 4 mmHg, naproxen 3. 6 mmHg).
Absorption Orally administered etoricoxib is well absorbed.
Assorbiment Etoricoxib mogħti mill- ħalq huwa assorbit sewwa.
The absolute bioavailability is approximately 100%.
Il- bijodisponibbiltà assoluta hija madwar 100%.
Following 120 mg once-daily dosing to steady state, the peak plasma concentration (geometric mean Cmax = 3.6 µg/ ml) was observed at approximately 1 hour (Tmax) after administration to fasted adults.
Wara dożaġġ ta ’ 120 mg darba kuljum b’ rata fissa, il- konċentrazzjoni massima tal- plasma (medja ġeometrika Cmax = 3. 6 µg/ ml) kienet osservata wara madwar siegħa (Tmax) wara li ngħatat lil adulti msajmin.
The geometric mean area under the curve (AUC0-24hr) was 37.8 µg• hr/ ml.
L- erja medja ġeometrika taħt il- kurva (AUC0- 24hr) kienet 37. 8 µg• hr/ ml.
The pharmacokinetics of etoricoxib are linear across the clinical dose range.
Il- farmakokinetiċi ta ’ etoricoxib huma lineari tul il- medda klinika kollha tad- doża.
Dosing with food (a high-fat meal) had no effect on the extent of absorption of etoricoxib after administration of a 120-mg dose.
Id- doża ma ’ ikel (ikla b’ ħafna xaħam) ma kellhiex effett fuq l- ammont ta ’ assorbiment ta ’ etoricoxib wara għoti ta ’ doża ta ’ 120 mg.
The rate of absorption was affected, resulting in a 36% decrease in Cmax and an increase in Tmax by 2 hours.
Ir- rata ta ’ assorbiment kienet affettwata, u rriżultat fi tnaqqis ta ’ 36% f’ Cmax u f’ żieda fit- Tmax b’ sagħtejn.
These data are not considered clinically significant.
Dan it- tagħrif mhuwiex meqjus bħala klinikament sinjifikanti.
In clinical trials, etoricoxib was administered without regard to food intake.
Fi provi kliniċi, etoricoxib ingħata mingħajr ma tqies it- teħid ta ’ l- ikel.
Distribution Etoricoxib is approximately 92% bound to human plasma protein over the range of concentrations of 0.05 to 5 µg/ ml.
Distribuzzjoni Etoricoxib huwa bejn wieħed u ieħor 92% marbut mal- proteina tal- plasma umana fuq il- medda ta ’ konċentrazzjonijiet ta ’ 0. 05 sa 5 µg/ ml.
The volume of distribution at steady state (Vdss) was approximately 120 l in humans.
Il- volum tad- distribuzzjoni f’ rata fissa (Vdss) kien bejn wieħed u ieħor 120 l fl- umani.
Etoricoxib crosses the placenta in rats and rabbits, and the blood-brain barrier in rats.
Etoricoxib jaqsam il- plaċenta f’ firien u fniek, u l- barriera tad- demm u l- moħħ fil- firien.
Metabolism Etoricoxib is extensively metabolised with < 1% of a dose recovered in urine as the parent drug.
Metaboliżmu Etoricoxib huwa metabolizzat b’ mod estensiv b ’ < 1% tad- doża rkuprata fl- awrina bħala l- mediċina prinċipali.
The major route of metabolism to form the 6’ -hydroxymethyl derivative is catalyzed by CYP enzymes.
Ir- rotta maġġuri tal- metaboliżmu biex tifforma d- derivattiv 6 ’ - hydroxymethyl hija kkatalizzata mill- enzimi ta ’ CYP.
In vitro studies indicate that CYP2D6, CYP2C9, CYP1A2 and CYP2C19 also can catalyse the main metabolic pathway, but their quantitative roles in vivo have not been studied.
Studji in vitro jindikaw li CYP2D6, CYP2C9, CYP1A2 u CYP2C19 ukoll jistgħu jikkatalizzaw il- mogħdija metabolika prinċipali, iżda l- irwoli kwantitattivi tagħhom ma ġewx studjati in vivo.
Five metabolites have been identified in man.
Ħames metaboliti ġew identifikati fil- bniedem.
The principal metabolite is the 6’ -carboxylic acid derivative of etoricoxib formed by further oxidation of the 6’ -hydroxymethyl derivative.
Il- metabolit prinċipali huwa d- derivattiv 6 ’ - carboxylic acid ta ’ etoricoxib iffurmat b’ ossidazzjoni ulterjuri tad- derivattiv 6 ’ - hydroxymethyl.
These principal metabolites either demonstrate no measurable activity or are only weakly active as COX-2 inhibitors.
Dawn il - metaboliti prinċipali jew ma juru ebda attività li titkejjel jew huma biss attivi b’ mod debboli bħala inibituri ta ’ COX- 2.
None of these metabolites inhibit COX-1.
Ebda minn dawn il- metaboliti ma jinibixxu COX- 1.
23 Following administration of a single 25-mg radiolabeled intravenous dose of etoricoxib to healthy subjects, 70% of radioactivity was recovered in urine and 20% in faeces, mostly as metabolites.
Eliminazzjoni Wara għoti ta ’ doża ġol- vini radju- tikkettjata ta ’ 25 mg waħdanija ta ’ etoricoxib lil suġġetti b’ saħħithom, 70% tar- radju- attività ġiet irkuprata fl- awrina u 20% fil- feċi, l- aktar bħala metabolite.
Less than 2% was recovered as unchanged drug.
Inqas minn 2% ġiet irkuprata bħala mediċina mhux mibdula.
Elimination of etoricoxib occurs almost exclusively through metabolism followed by renal excretion.
24 L- eliminazzjoni ta ’ etoricoxib isseħħ kważi esklussivament permezz ta ’ metaboliżmu segwit minn tneħħija mill- kliewi.
Steady state concentrations of etoricoxib are reached within seven days of once daily administration of 120 mg, with an accumulation ratio of approximately 2, corresponding to a half-life of approximately 22 hours.
Konċentrazzjonijiet ta ’ stat fiss ta ’ etoricoxib jintlaħqu fi żmien sebat ijiem ta ’ għoti ta ’ darba kuljum ta ’ 120 mg, bi proporzjon ta ’ akkumulazzjoni ta ’ madawar 2, li jikkorrespondi għal half- life ta ’ madwar 22 siegħa.
The plasma clearance after a 25-mg intravenous dose is estimated to be approximately 50 ml/ min.
It- tneħħija mill- plasma wara doża ġol- vini ta ’ 25 mg hija stmata li tkun madwar 50 ml/ min.
Characteristics in patients
Karatteristiċi fil- pazjenti
Elderly:
L- anzjani:
Pharmacokinetics in the elderly (65 years of age and older) are similar to those in the young.
Il- farmakokinetiċi fl- anzjani (65 sena jew aktar) huma simili għal dawk fiż- żgħażagħ.
The pharmacokinetics of etoricoxib are similar between men and women.
Il- farmakokinetiċi ta ’ etoricoxib huma simili bejn l- irġiel u n- nisa.
Hepatic insufficiency:
Indeboliment tal- fwied:
Patients with mild hepatic dysfunction (Child-Pugh score 5-6) administered etoricoxib 60 mg once daily had an approximately 16% higher mean AUC as compared to healthy subjects given the same regimen.
Pazjenti b’ malfunzjonament ħafif tal- fwied (skor ta 'Child- Pugh ta' 5- 6) mogħtijin etoricoxib 60 mg darba kuljum kellhom AUC medju li kien madwar 16% ogħla meta mqabbel ma 'dak ta' suġġetti b' saħħihom mogħtijin l- istess reġimen.
Patients with moderate hepatic dysfunction (Child-Pugh score 7-9) administered etoricoxib 60 mg every other day had similar mean AUC to the healthy subjects given etoricoxib 60 mg once daily; etoricoxib 30 mg once daily has not been studied in this population.
Pazjenti b’ malfunzjonament moderat tal- fwied (skor ta ’ Child- Pugh 7- 9) mogħtijin etoricoxib 60 mg darba iva u darba le kellhom AUC medju simili għal dak ta ’ suġġetti b’ saħħithom li ngħataw etoricoxib 60 mg darba kuljum; etoricoxib 30 mg darba kuljum ma ġiex studjat f' din il- popolazzjoni.
There are no clinical or pharmacokinetic data in patients with severe hepatic dysfunction (Child-Pugh score ≥ 10).
Ma hemm ebda tagħrif kliniku jew farmakokinetiku f’ pazjenti b’ malfunzjonament sever tal- fwied (skor ta ’ Child- Pugh ≥10).
(See sections 4.2 and 4.3.)
(Ara Sezzjonijiet 4. 2 u 4. 3).
Renal insufficiency:
Indeboliment tal- kliewi:
The pharmacokinetics of a single dose of etoricoxib 120 mg in patients with moderate to severe renal insufficiency and patients with end-stage renal disease on hemodialysis were not significantly different from those in healthy subjects.
Il- farmakokinetiċi ta ’ doża waħda ta ’ etoricoxib 120 mg f’ pazjenti b’ indeboliment renali moderat għal sever u pazjenti b’ mard tal- kliewi fil- fażi finali fuq emodijaliżi ma kinux ferm differenti minn dawk f' suġġetti b' saħħithom.
Hemodialysis contributed negligibly to elimination (dialysis clearance approximately 50 ml/ min).
L- emodijaliżi kkontribwiet b’ mod negliġibbli għall- eliminazzjoni (tneħħija b’ dijaliżi ta ’ madwar 50 ml/ min).
(See sections 4.3 and 4.4.)
(Ara Sezzjonijiet 4. 3 u 4. 4.)
The pharmacokinetics of etoricoxib in paediatric patients (< 12 years old) have not been studied.
Il- farmakokinetiċi ta ’ etoricoxib f’ pazjenti pedjatriċi (< 12- il sena) ma ġewx studjati.
In a pharmacokinetic study (n=16) conducted in adolescents (aged 12 to 17) the pharmacokinetics in adolescents weighing 40 to 60 kg given etoricoxib 60 mg once daily and adolescents > 60 kg given etoricoxib 90 mg once daily were similar to the pharmacokinetics in adults given etoricoxib 90 mg once daily.
Fi studju farmakokinetiku (n=16) li sar fuq adoloxxenti (ta ’ bejn 12 u 17- il sena) il- farmakokinetiċi fl - adoloxxenti li jiżnu bejn 40 u 60 kg mogħtijin etoricoxib 60 mg darba kuljum u adoloxxenti > 60 kg mogħtijin etoricoxib 90 mg darba kuljum kienu simili għall- farmakokinetiċi fl- adulti mogħtijin etoricoxib 90 mg darba kuljum.
Safety and effectiveness of etoricoxib in paediatric patients have not been established (see section 4.2).
Is- sigurtà u l- effettività ta ’ etoricoxib f’ pazjenti pedjatriċi għadhom ma ġewx stabbiliti (ara sezzjoni 4. 2).
In preclinical studies, etoricoxib has been demonstrated not to be genotoxic.
Fi studji prekliniċi, etoricoxib intwera li ma kienx ġenotossiku.
Etoricoxib was not carcinogenic in mice.
Etoricoxib ma kienx karċinoġeniku fil- ġrieden.
Rats developed hepatocellular and thyroid follicular cell adenomas at > 2-times the daily human dose [90 mg] based on systemic exposure when dosed daily for approximately two years.
Il- firien żviluppaw adenomi epatoċellulari u taċ- ċelloli follikulari tat- tirojde bi kważi > darbtejn id- doża umana ta ’ kuljum [90 mg] abbażi ta ’ espożizzjoni sistemika meta ddożati kuljum għal madwar sentejn.
Hepatocellular and thyroid follicular cell adenomas observed in rats are considered to be a consequence of rat-specific mechanism related to hepatic CYP enzyme induction.
Adenomi epatoċellulari u taċ- ċelloli follikulari tat- tirojde osservati fil- firien huma meqjusin bħala konsegwenza ta ’ mekkaniżmu speċifiku għall- firien relatat ma ’ induzzjoni ta ’ enzim CYP tal- fwied.
Etoricoxib has not been shown to cause hepatic CYP3A enzyme induction in humans.
Etoricoxib ma ntweriex li jikkawża induzzjoni ta ’ enzim CYP3A epatiku fil - bniedem.
In the rat, gastrointestinal toxicity of etoricoxib increased with dose and exposure time.
Fil- firien, it- tossiċità gastrointestinali ta ’ etoricoxib żdiedet mad- doża u mal- ħin ta ’ espożizzjoni.