natgillin/translations-raw huggingface dataset:
5 Det tyder på, at samtidig indgift af NSAID- præparater og ciclosporin eller tacrolimus kan øge den nefrotoksiske virkning af ciclosporin og tacrolimus.
Co-administration of NSAIDs and cyclosporin or tacrolimus has been suggested to increase the nephrotoxic effect of cyclosporin and tacrolimus.
Nyrefunktionen bør monitoreres, når parecoxibnatrium og et af disse stoffer gives samtidig.
Renal function should be monitored when parecoxib sodium and any of these medicinal products are co-administered.
I de kliniske forsøg var det daglige behov for p. n. opioider signifikant reduceret, når opioider blev anvendt sammen med paracoxib
In clinical trials, the daily requirement for PRN opioids was significantly reduced when coadministered with parecoxib.
Andre lægemidlers virkning på parecoxibs (eller dets aktive substans valdecoxibs) farmakokinetik Parecoxib hydrolyseres hurtigt til den aktive substans valdecoxib.
Effects of other medicinal products on the pharmacokinetics of parecoxib (or its active metabolite valdecoxib) Parecoxib is rapidly hydrolysed to the active metabolite valdecoxib.
Plasmaeksponering (AUC og Cmax) for valdecoxib blev øget (henholdsvis 62% og 19%), når det blev administreret sammen med fluconazol (hovedsagelig en CYP2C9 hæmmer), hvilket viser, at dosis af parecoxibnatrium bør reduceres hos de patienter, der er i fluconazolbehandling.
Plasma exposure (AUC and Cmax) to valdecoxib was increased (62% and 19%, respectively) when co- administered with fluconazole (predominantly a CYP2C9 inhibitor), indicating that the dose of parecoxib sodium should be reduced in those patients who are receiving fluconazole therapy.
Dosisjustering bør imidlertid ikke generelt være nødvendig hos patienter, der får ketoconazol.
Plasma exposure (AUC and Cmax) to valdecoxib was increased (38% and 24%, respectively) when co- administered with ketoconazole (CYP3A4 inhibitor), however, a dosage adjustment should not generally be necessary for patients receiving ketoconazole.
Valdecoxibs metabolisme kan øges, når det administreres sammen med enzyminducere, såsom rifampicin, phenytoin, carbamazepin eller dexamethason.
The metabolism of valdecoxib may increase when co-administered with enzyme inducers such as rifampicin, phenytoin, carbamazepine or dexamethasone.
Parecoxibs (eller dets aktive substans valdecoxibs) virkning på andre lægemidlers farmakokinetik Behandling med valdecoxib (40 mg 2 gange dagligt i 7 dage) gav en 3 gange så stor stigning i plasmakoncentrationerne af dextromethorphan (CYP2D6 substrat).
Effect of parecoxib (or its active metabolite valdecoxib) on the pharmacokinetics of other medicinal products Treatment with valdecoxib (40 mg twice daily for 7 days) produced a 3-fold increase in plasma concentrations of dextromethorphan (CYP2D6 substrate).
Forsigtighed bør derfor udvises, når Dynastat administreres sammen med lægemidler, som hovedsagelig metaboliseres via CYP2D6, og som har et smalt terapeutisk vindue (f. eks. flecainid, propafenon, metoprolol).
Therefore, caution should be observed when co-administering Dynastat and medicinal products that are predominantly metabolised by CYP2D6 and which have narrow therapeutic margins (e. g. flecainide, propafenone, metoprolol).
Plasmaeksponeringen af omeprazol (CYP 2C19 substrat) 40 mg 1 gang dagligt blev øget med 46% efter administration af valdecoxib 40 mg 2 gange dagligt i 7 dage, mens plasmaeksponeringen af valdecoxib var upåvirket.
Plasma exposure of omeprazole (CYP 2C19 substrate) 40 mg once daily was increased by 46% following administration of valdecoxib 40 mg twice daily for 7 days, while the plasma exposure to valdecoxib was unaffected.
Forsigtighed bør derfor udvises ved administration af Dynastat sammen med lægemidler, som er CYP2C19 substrater (f. eks. phenytoin, diazepam eller imipramin).
Therefore, caution should be observed when administering Dynastat with medicinal products known to be substrates of CYP2C19 (e. g. phenytoin, diazepam, or imipramine).
I interaktionsundersøgelser med patienter med reumatoid artritis, der ugentligt fik methotrexat intramuskulært, havde oralt administreret valdecoxib (40 mg 2 gange dagligt) ingen klinisk signifikant virkning på plasmakoncentrationenerne af methotrexat.
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.
Passende monitorering af methotrexatrelateret toksicitet bør imidlertid overvejes nøje, når disse to lægemidler kombineres.
However, adequate monitoring of methotrexate-related toxicity should be considered when co-administering these two medicinal products.
Samtidig administration af valdecoxib og lithium medførte signifikante fald i lithiums serumclearance (25%) og renaleclearance (30%) med en 34% højere serumeksponering sammenlignet med lithium alene.
Co-administration of valdecoxib and lithium produced significant decreases in lithium serum clearance (25%) and renal clearance (30%) with a 34% higher serum exposure compared to lithium alone.
Serumkoncentrationen af lithium bør monitoreres tæt, når behandling med parecoxibnatrium initieres eller ændres hos patienter, der behandles med lithium.
Lithium serum concentration should be monitored closely when initiating or changing parecoxib sodium therapy in patients receiving lithium.
Samtidig administration af valdecoxib og glibenclamid (CYP3A4 substrat) påvirkede hverken glibenclamids farmakokinetik (eksponering) eller farmakodynamik (blodsukker og insulinniveauer).
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.
Injicerbare anæstetika:
6 Injectable anaesthetics:
Samtidig administration af parecoxibnatrium 40 mg i. v. og propofol (CYP2C9 substrat) eller midazolam (CYP3A4 substrat) påvirker hverken farmakokinetikken (metabolisme og eksponering) eller farmakodynamikken (EEG påvirkninger, psykomotoriske tests og opvågning fra sedation) for propofol i. v. eller midazolam i. v.
Coadministration of IV parecoxib sodium 40 mg with propofol (CYP2C9 substrate) or midazolam (CYP3A4 substrate) did not affect either the pharmacokinetics (metabolism and exposure) or the pharmacodynamics (EEG effects, psychomotor tests and waking from sedation) of IV propofol or IV midazolam.
Derudover har samtidig administration af valdecoxib ingen klinisk effekt på hepatisk eller intestinal CYP 3A4- medieret metabolisme af oralt administreret midazolam.
Additionally, coadministration of valdecoxib had no clinically significant effect on the hepatic or intestinal CYP 3A4-mediated metabolism of orally administered midazolam.
(CYP3A4 substrater).
Administration of IV parecoxib sodium 40 mg had no significant effect on the pharmacokinetics of either IV fentanyl or IV alfentanil (CYP3A4 substrates).
6 Inhalationsanæstetika:
Inhalation anaesthetics:
5. 1).
In surgery studies in which parecoxib sodium was administered pre-operatively, no evidence of pharmacodynamic interaction was observed in patients receiving parecoxib sodium and the inhalation anaesthetic agents nitrous oxide and isoflurane (see section 5.1).
4. 3, 5. 1 og 5. 3).
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).
4. 3) i sidste graviditetstrimester.
Dynastat is contraindicated (see section 4.3) in the last trimester of pregnancy.
4. 4, 5. 1 og 5. 3).
Like other medicinal products that inhibit COX-2, Dynastat is not recommended in women attempting to conceive (see sections 4.4, 5.1 and 5.3).
Der er ikke tilstrækkelige data fra brugen af parecoxibnatrium hos gravide kvinder eller under fødsel.
There are no adequate data from the use of parecoxib sodium in pregnant women or during labour.
5. 1 og 5. 3).
Studies in animals have shown reproductive toxicity (see sections 5.1 and 5.3).
Dynastat bør ikke anvendes i de to første graviditetstrimestre, medmindre det er klart nødvendigt (dvs. de potentielle fordele for patienten opvejer den potentielle risiko for fostret).
Dynastat should not be used during the first two trimesters of pregnancy unless clearly necessary (i. e. the potential benefit to the patient outweighs the potential risk to the foetus).
Parecoxib, valdecoxib (dets aktive metabolit) og en aktiv valdecoxibmetabolit udskilles i mælken hos rotter.
Parecoxib, valdecoxib (its active metabolite) and a valdecoxib active metabolite are excreted in the milk of rats.
Det vides ikke, om valdecoxib udskilles i modermælken hos mennesker.
It is not known whether valdecoxib is excreted in human milk.
4. 3 og 5. 3).
Dynastat should not be administered to women who breast-feed (see sections 4.3 and 5.3).
Der er ikke foretaget undersøgelser af virkningen på evnen til at føre motorkøretøj eller betjene maskiner.
No studies on the effect of Dynastat on the ability to drive or use machines have been performed.
Patienter, der oplever svimmelhed eller søvnighed efter at have fået Dynastat, bør imidlertid undgå at føre motorkøretøj eller betjene maskiner.
However, patients who experience dizziness, vertigo or somnolence after receiving Dynastat should refrain from driving or operating machines.
1962 af patienterne, der blev behandlet med Dynastat i de kontrollerede undersøgelser, var patienter med post- operative smerter.
Of the Dynastat treated patients in controlled trials, 1962 were patients with post-surgical pain.
Følgende bivirkninger havde en hyppighed større end placebo og er set blandt 1543 patienter, der har fået Dynastat 20 mg eller 40 mg som en enkelt eller flere doser (op til 80 mg/ dag) i 12 placebokon - trollerede undersøgelser, inklusive tandkirurgi, gynækologisk kirurgi, ortopædkirurgi eller koronar bypassoperation såvel som præ- operativ administration ved tandkirurgi og ortopædkirurgi.
The following undesirable effects had a rate greater than placebo and have been reported among 1543 patients administered Dynastat 20 or 40 mg as a single or multiple dose (up to 80 mg/ day) in 12 placebo controlled studies, including dental, gynaecologic, orthopaedic surgery or coronary artery bypass graft surgery as well as pre-operative administration in dental and orthopaedic surgeries.
Sepone - ringshyppigheden på grund af bivirkninger i disse undersøgelser var 5, 0% for patienter, der fik Dynastat og 4, 3% for patienter, der fik placebo.
The discontinuation rate due to adverse events in these studies was 5.0% for patients receiving Dynastat and 4.3% for patients receiving placebo.
[Meget almindelig (≥ 1/ 10), almindelig (≥ 1/ 100, < 1/ 10), ikke almindelig (≥ 1/ 1000, < 1/ 100), sjælden (≥ 1/ 10. 000, < 1/ 1000), meget sjælden (< 1/ 10. 000), ikke kendt (kan ikke estimeres ud fra forhåndenværende data)]
7 [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)]
Infektiøse og parasitære sygdomme Ikke almindelig: abnorm serøs sekretion i sternumdræn, sårinfektion
Infections and infestations Uncommon: abnormal sternal serous wound drainage, wound infection.
Blod og lymfesystem Almindelig: postoperativ anæmi Ikke almindelig: trombocytopeni
Blood and lymphatic system disorders Common: post-operative anaemia Uncommon: thrombocytopenia
7 Metabolisme og ernæring Almindelig: hypokalæmi
Metabolism and nutrition disorders Common: hypokalaemia
Psykiske forstyrrelser Almindelig: agitation, insomnia
Common: agitation, insomnia
Nervesystemet Almindelig: hypæstesi Ikke almindelig: cerebrovaskulær forstyrrelse
Nervous system disorders Common: hypoaesthesia Uncommon: cerebrovascular disorder
Hjerte Ikke almindelig: bradykardi
Cardiac disorders Uncommon: bradycardia
Vaskulære sygdomme Almindelig: hypertension, hypotension Ikke almindelig: forværret hypertension
Vascular disorders Common: hypertension, hypotension Uncommon: aggravated hypertension
Luftveje, thorax og mediastinum Almindelig: respiratorisk insufficiens, pharyngitis
Respiratory, thoracic and mediastinal disorders Common: respiratory insufficiency, pharyngitis
Mave- tarmkanalen Almindelig: alveolær osteitis (tør tandalveole), dyspepsi, flatulens Ikke almindelig: gastroduodenal ulceration
Gastrointestinal disorders Common: alveolar osteitis (dry socket), dyspepsia, flatulence Uncommon: gastroduodenal ulceration
Hud og subkutane væv Almindelig: pruritus Ikke almindelig: blodudtrædning
Skin and subcutaneous tissue disorders Common: pruritus Uncommon: ecchymosis
Knogler, led, muskler og bindevæv Almindelig: rygsmerter
Musculoskeletal and connective tissue disorders Common: back pain
Nyrer og urinveje Almindelig: oliguri
Renal and urinary disorders Common: oliguria
Almene symptomer og reaktioner på administrationsstedet Almindelig: perifere ødemer
General disorders and administration site conditions Common: peripheral oedema
Undersøgelser Almindelig: serum- kreatininstigning Ikke almindelig: øget ALAT, øget ASAT, øget serum- carbamid
SGOT increased, SGPT increased, blood urea nitrogen increased.
Følgende sjældne bivirkninger er rapporteret i forbindelse med brugen af NSAID- præparater, og kan ikke udelukkes for Dynastat: bronkospasmer og hepatitis.
The following rare, serious adverse events have been reported in association with the use of NSAIDs and cannot be ruled out for Dynastat: bronchospasm and hepatitis.
Efter koronar bypassoperation har patienter, der får Dynastat en øget risiko for uønskede hændelser som f. eks. kardiovaskulære/ tromboemboliske hændelser, dybe sårinfektioner og sternale sårhelings - komplikationer.
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 8 wound healing complications.
5. 1).
Cardiovascular/ thromboembolic events include myocardial infarction, stroke/ TIA, pulmonary embolus and deep vein thrombosis (see section 4.3 and 5.1).
Efter markedsføring er følgende bivirkninger rapporteret i forbindelse med brug af parecoxib:
In post-marketing experience, the following reactions have been reported in association with the use of parecoxib:
Sjælden: akut nyresvigt, nedsat nyrefunktion, myokardieinfarkt, venstresidig hjerteinsufficiens, abdominalsmerter, kvalme, opkastning, dyspnø, takykardi og Stevens- Johnson syndrom.
Rare: acute renal failure, renal failure, myocardial infarction, congestive heart failure, abdominal pain, nausea, vomiting, dyspnoea, tachycardia and Stevens-Johnson syndrome.
4. 4).
Very rare: erythema multiforme, exfoliative dermatitis and hypersensitivity reactions including anaphylaxis and angioedema (see section 4.4).
4. 4).
In post marketing experience, the following reaction has been reported in association with the use of valdecoxib, and cannot be ruled out for parecoxib: toxic epidermal necrolysis (see section 4.4).
Der er ikke rapporteret tilfælde af overdosering med parecoxib.
No case of parecoxib overdose has been reported.
Coxib, ATC kode:
Coxib, ATC code:
Valdecoxib er inden for det kliniske dosisinterval en oral, selektiv cyclooxygenase- 2 (COX- 2) hæmmer.
Valdecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor within the clinical dose range.
Der er identificeret 2 iso- former, COX- 1 og COX- 2.
Two isoforms, COX-1 and COX-2, have been identified.
Det er vist, at COX- 2 er isoformen af det enzym, som induceres af proinflammatoriske stimuli, og som man mener, hovedsagelig har ansvaret for syntese af prostanoide mediatorer af smerte, inflammation og feber.
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 er også involveret i ovulation, implantation og lukning af ductus arteriosus, regulering af nyrefunktionen og funktioner i centralnervesystemet (induktion af feber, smerteopfattelse og kognitive funktioner).
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 er påvist i vævet omkring gastriske ulcera hos mennesker, men dets relevans ved heling af ulcera er ikke fastslået.
COX-2 has been identified in tissue around gastric ulcers in man but its relevance to ulcer healing has not been established.
Forskellen i antitrombocytaktivitet mellem COX- 1- hæmmende NSAID- præparater og COX- 2 selektive hæmmere kan være af klinisk betydning for patienter med risiko for udvikling af tromboemboliske hændelser.
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.
COX- 2 selektive hæmmere reducerer dannelsen af systemiske (og dermed muligvis endotel- deriveret) prostacyclin uden at påvirke tromboxan i blodpladerne.
COX-2 selective inhibitors reduce the formation of systemic (and therefore possibly endothelial) prostacyclin without affecting platelet thromboxane.
Dynastats effekt er fastslået i undersøgelser af smerter efter dentale, gynækologiske (hysterektomi), ortopædiske (knæ - og hofteudskiftning) og koronar bypassoperationer.
The efficacy of Dynastat was established in studies of dental, gynaecologic (hysterectomy), orthopaedic (knee and hip replacement), and coronary artery bypass graft surgical pain.
Den første mærkbare analgetiske virkning indtræder i løbet af 7- 13 minutter med klinisk meningsfuld analgesi i løbet af 23 - 39 minutter og maksimal effekt inden for 2 timer efter administration af enkeltdoser på 40 mg Dynastat i. v. eller i. m.
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.
Omfanget af den analgetiske virkning af en 40 mg dosis er sammenlignelig med ketorolac 60 mg i. m. eller ketorolac 30 mg i. v.
The magnitude of analgesic effect of the 40 mg dose was comparable with that of ketorolac 60 mg IM or ketorolac 30 mg IV.
Opioid- besparende effekt:
Opioid-sparing Effects:
I et placebo- kontrolleret forsøg (n=1050) med ortopædiske/ almen kirurgiske indgreb fik patienterne en initialdosis af Dynastat på 40 mg i. v. efterfulgt af 20 mg i. v.
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.
2 gange dagligt i mindst 72 timer som tillæg til standardbehandling, herunder supplerende patientkontrollerede opioider.
The reduction in opioid use with Dynastat treatment on Days 2 and 3 was 7.2 mg
Reduktion i brugen af opioider i forbindelse med Dynastat- behandling var 7, 2 mg på dag 2 og 2, 8 mg på dag 3 (henholdsvis 37% og 28%).
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.
Der er ingen data, der indikerer, at der samlet er færre bivirkninger forbundet med brugen af paracoxib sammenlignet med placebo, når paracoxibanvendes sammen med opioider.
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.
Gastrointestinale undersøgelser:
Gastrointestinal studies:
I korttids- endoskopiundersøgelser (7 dage) med raske unge og ældre (> 65 år) resulterede behandling med Dynastat i en forekomst af endoskopisk observerede gastroduodenale sår eller erosioner (5- 21%), der selv om tallet er højere end for placebo (5- 12%), er statistisk signifikant lavere end forekomsten observeret med NSAID- præparater (66- 90%).
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%).
9 CABG post- operative sikkerhedsundersøgelser:
CABG post-operative Safety Studies:
Alle patienter fik standard smertelindrings - behandling under forløbet.
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.
Patienterne fik lav- dosis acetylsalicylsyre forud for randomisering og gennem begge de 2 CABG - undersøgelser.
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.
I den første CABG- undersøgelse evaluerede man patienter, der fik i. v. parecoxibnatrium 40 mg 2 gange dagligt i mindst 3 dage, efterfulgt af behandling med valdecoxib 40 mg 2 gange dagligt (parecoxibnatrium/ valdecoxib gruppe) (n=311) eller placebo/ placebo (n=151) i en 14 dages dobbeltblind, placebokontrolleret undersøgelse.
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.
9 præ- definerede uønskede hændelseskategorier blev undersøgt (kardiovaskulære tromboemboliske hændelser, hjertehindebetændelse, debut af eller forværring af kronisk hjerteinsufficiens, nedsat nyrefunktion/ nyresvigt, øvre gastrointestinal kompliceret ulcus, større ikke- gastrointestinale blødninger, infektioner, ikke- infektiøse pulmonale komplikationer og død).
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).
Der ses en signifikant (p < 0, 05) større hyppighed af kardiovaskulære/ tromboemboliske hændelser (myokardieinfarkt, iskæmi, cerebrovaskulær hændelse, dybe venetromboser og lungeemboli) i gruppen behandlet med parecoxib/ valdecoxib sammenlignet med den placebo/ placebo- behandlede gruppe i perioden med i. v. - behandling (henholdsvis 2, 2% og 0, 0%) og gennem hele behandlingsperioden (henholdsvis 4, 8% og 1, 3%).
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).
Sårkomplikationer efter operation (hyppigst omfattende sternumsår) ses hyppigere i gruppen behandlet med parecoxib/ valdecoxib.
Surgical wound complications (most involving the sternal wound) were observed at an increased rate with parecoxib/ valdecoxib treatment.
I den anden CABG- undersøgelse blev 4 præ- definerede hændelseskategorier undersøgt (kardiovaskulær/ tromboembolisk hændelse, nedsat nyrefunktion/ nyresvigt, øvre gastrointestinal ulcus/ blødning, sårkomplikation efter operation).
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).