qanastek/EMEA-V3 huggingface dataset:
Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.
Il- pazjenti għandhom jiġu idratati b’ mod adegwat u għandha tingħata kunsiderazzjoni għall- monitoraġġ tal - funzjoni tal- kliewi wara l- bidu ta ’ terapija konkomittanti, u perjodikament minn hemm ’ il quddiem.
In a 28-day clinical study in patients with lisinopril-controlled Stage I and II hypertension, administration of celecoxib 200 mg BID resulted in no clinically significant increases, when compared to placebo treatment, in mean daily systolic or diastolic blood pressure as determined using 24-hour ambulatory blood pressure monitoring.
Fi studju kliniku ta ’ 28 ġurnata fuq pazjenti bi pressjoni għolja ta ’ Stadju I u II ikkontrollata b’ lisinopril, l- għoti ta ’ celecoxib 200 mg BID ma rriżulta f’ ebda żidiet klinikament sinifikanti, meta mqabbel mat- trattament bil- plaċebo, fil- pressjoni sistolika jew dijastolika medja kuljum tad- demm kif stabbilita bl- użu ta ’ monitoraġġ ambulatorju tal- pressjoni tad- demm fuq 24 siegħa.
Among patients treated with celecoxib 200 mg BID, 48% were considered unresponsive to lisinopril at the final clinic visit (defined as either cuff diastolic blood pressure > 90 mmHg or cuff diastolic blood pressure increased > 10% compared to baseline), compared to 27% of patients treated with placebo; this difference was statistically significant.
Fost il- pazjenti ttrattati b’ celecoxib 200 mg BID, 48% tqiesu li ma rrispondewx għal lisinopril fl- aħħar żjara klinika (definita bħala cuff diastolic blood pressure > 90 mmHg jew żieda fil- cuff diastolic blood pressure > 10% pparagunata mal- linja bażi), meta mqabbel ma ’ 27% tal- pazjenti ttrattati bi plaċebo; din id - differenza kienet statistikament sinifikanti.
Co-administration of NSAIDs and ciclosporin D derivatives or tacrolimus have been suggested to increase the nephrotoxic effect of cyclosporin and tacrolimus.
Amministrazzjoni flimkien ta ’ NSAIDs u derivattivi taċ- ciclosporin D jew tacrolimus indikat żieda fl - effett nefrotossiku ta ’ cyclosporin u tacrolimus.
Renal function should be monitored when celecoxib and any of these medicinal products are combined.
Il- funzjoni renali trid tiġi mmonitorjata meta celecoxib jingħata flimkien ma ’ xi medicina minn dawn.
Celecoxib can be used with low dose acetylsalicylic acid, however it cannot be considered a substitute for acetylsalicylic acid for cardiovascular prophylaxis.
Celecoxib jista ’ jintuża b’ doża baxxa ta ’ acetlysalicyclic acid, iżda ma jistax jitqies bħala sostitut għal acetlysalicyclic acid għal profilassi kardjovaskolari.
As with other NSAIDs, an increased risk of gastrointestinal ulceration or other gastrointestinal complications compared to use of celecoxib alone was shown for concomitant administration of low-dose acetylsalicylic acid (see section 5.1).
Bħal b’ NSAIDs oħra, intwera riskju ogħla ta ’ ulċerazzjoni gastro- intestinali jew ta ’ kumplikazzjonijiet gastro- intestinali oħra meta mqabbla ma ’ l - użu ta ’ celecoxib waħdu għal għoti fl- istess ħin ta ’ acetylsalicylic acid ta ’ doża baxxa.
Pharmacokinetic interactions
Interazzjonijiet Farmakokinetiċi
Effects of celecoxib on other medicinal products Celecoxib is a weak inhibitor of CYP2D6.
Effetti ta ’ celecoxib fuq mediċini oħra Celecoxib huwa inibitur dgħajjef ta ’ CYP2D6.
During celecoxib treatment, the mean plasma concentrations of the CYP2D6 substrate dextromethorphan were increased by 136%.
Il -
The plasma concentrations of medicinal products that are substrates of this enzyme may be increased when celecoxib is used concomitantly.
5 konċentrazzjonijiet fil- plasma ta ’ mediċini li huma substrati ta ’ din l- enzima jistgħu jiżdiedu meta celecoxib jingħata fl- istess ħin magħhom.
Examples of medicines which are metabolised by CYP2D6 are antidepressants (tricyclics and SSRIs), neuroleptics, anti-arrhythmics, etc.
Eżempji ta ’ mediċini li huma metabolizzati b’ CYP2D6 huma mediċini kontra d- depressjoni (triċikliċi u SSRIs), newrolettiċi, anti- arritmiċi.
The dose of individually dose-titrated CYP2D6 substrates may need to be reduced when treatment with celecoxib is initiated or increased if treatment with celecoxib is terminated.
Id- doża ta ’ substrati CYP2D6 titrati individwalment tista ’ teħtieġ li titnaqqas meta jinbeda trattament, jew inkella li tiżdied jekk it- trattament b’ celecoxib jitwaqqaf.
In vitro studies have shown some potential for celecoxib to inhibit CYP2C19 catalysed metabolism.
Studji in vitro urew xi potenzjal għal celecoxib li jinibixxi metaboliżmu kkatalizzat minn CYP2C19.
The clinical significance of this in vitro finding is unknown.
Is- sinifikat kliniku ta ’ dan ir- riżultat in vitro mhuwiex magħruf.
Examples of medicinal products which are metabolised by CYP2C19 are diazepam, citalopram and imipramine.
Eżempji ta ’ prodotti mediċinali li huma metabolizzati minn CYP2C19 huma diazepam, citalopram u imipramine.
In an interaction study, celecoxib had no clinically relevant effects on the pharmacokinetics of oral contraceptives (1 mg norethistherone / 35 microg ethinylestradiol).
Fi studju tal- interazzjonijiet, celecoxib ma kellux effetti kliniċi rilevanti fuq il- farmakokinetiċi tal - kontraċettivi orali (1 mg norethistherone / 35 microg ethinylestradiol).
Celecoxib does not affect the pharmacokinetics of tolbutamide (CYP2C9 substrate), or glibenclamide to a clinically relevant extent.
Celecoxib ma jaffettwax il- farmakokinetiċi ta ’ tolbutamide (substrat ta ’ CYP2C9), jew glibenclamide f’ miżura klinikament rilevanti.
5 In patients with rheumatoid arthritis celecoxib had no statistically significant effect on the pharmacokinetics (plasma or renal clearance) of methotrexate (in rheumatologic doses).
F’ pazjenti bl- artrite rewmatika, celecoxib ma kellu ebda effett statistiku sinifikanti fuq il - farmakokinetiċi (tneħħija mill- plażma jew renali) ta ’ methotrexate (f’ dożi rewmatoloġiċi).
However, adequate monitoring for methotrexate-related toxicity should be considered when combining these two drugs.
Madankollu, għandu jiġi kkunsidrat monitoraġġ adegwat għat- tossiċità relatata ma ’ methotrexate meta dawn iż- żewġ mediċini jingħataw flimkien.
In healthy subjects, co-administration of celecoxib 200 mg twice daily with 450 mg twice daily of lithium resulted in a mean increase in Cmax of 16% and in AUC of 18% of lithium.
F’ suġġetti b’ saħħithom, it- teħid ta ’ 200 mg celecoxib darbtejn kuljum flimkien ma ’ 450 mg darbtejn kuljum ta ’ litju rriżulta f’ żieda medja fis - Cmax ta ’ 16% u fl- AUC ta ’ 18% ta ’ litju.
Therefore, patients on lithium treatment should be closely monitored when celecoxib is introduced or withdrawn.
Għaldaqstant pazjenti fuq trattament bil- litju għandhom jiġu immonitorati bir- reqqa meta celecoxib jibda jingħata jew jitwaqqaf.
Effects of other medicinal products on celecoxib
Effetti ta ’ prodotti mediċinali oħra fuq celecoxib
In individuals who are CYP2C9 poor metabolisers and demonstrate increased systemic exposure to celecoxib, concomitant treatment with CYP2C9 inhibitors could result in further increases in celecoxib exposure.
F’ individwi li mhumiex metabolizzaturi daqstant tajbin ta ’ CYP2C9 u juru esponiment sistemiku miżjud għal celecoxib, it- trattament simultanju b’ inibituri ta ’ CYP2C9 jista ’ jirriżulta f’ żidiet ulterjuri fl- esponiment għal celecoxib.
Such combinations should be avoided in known CYP2C9 poor metabolisers (see sections 4.2 and 5.2).
Tali kombinazzjonijiet għandhom jiġu evitati f’ metabolizzaturi magħrufa mhux daqstant tajbin ta ’ CYP2C9 (ara sezzjonijiet 4. 2 u 5. 2).
Since celecoxib is predominantly metabolised by CYP2C9 it should be used at half the recommended dose in patients receiving fluconazole.
Minħabba li celecoxib huwa fil- biċċa l- kbira metabolizzat minn CYP2C9, għandu jintuża f’ nofs id - doża rakkomandata f’ pazjenti li jkunu qed jingħataw flucanazole.
Concomitant use of 200 mg single dose of celecoxib and 200 mg once daily of fluconazole, a potent CYP2C9 inhibitor, resulted in a mean increase in celecoxib Cmax of 60% and in AUC of 130%.
It- teħid flimkien ta ’ doża waħdanija ta ’ 200 mg ta ’ celecoxib u ta ’ doża waħdanija ta ’ 200 mg ta ’ fluconazole, inibitur qawwi ta ’ CYP2C9, jirriżulta f’ żieda medja fis- Cmax ta ’ celecoxib ta ’ 60% u f’ AUC ta ’ 130%.
Concomitant use of inducers of CYP2C9 such as rifampicin, carbamazepine and barbiturates may reduce plasma concentrations of celecoxib.
It- teħid flimkien ta ’ indutturi ta ’ CYP2C9 bħal rifampicin, carbamaepine u barbiturates jista ’ jnaqqas il- konċentrazzjonijiet fil - plasma ta ’ celecoxib.
For celecoxib no clinical data on exposed pregnancies are available..
Għal celecoxib m’ hemmx tagħrif kliniku dwar l- użu waqt it- tqala.
Studies in animals (rats and rabbits) have shown reproductive toxicity (see sections 4.3 and 5.3).
Studji fuq il- bhejjem (firien u fniek) urew ħsara fuq is- sistema riproduttiva (ara sezzjoni 4. 3 u 5. 3).
Celecoxib, as with other medicinal products inhibiting prostaglandin synthesis, may cause uterine inertia and premature closure of the ductus arteriosus during the last trimester.
Celecoxib, bħal fil- każ ta ’ mediċini oħra li jinibixu s- sinteżi ta ’ prostaglandin, jista ’ jikkawża inerzja uterina u għeluq prematur tad- ductus arteriosus fl- aħħar tliet xhur tat- tqala.
Celecoxib is contraindicated in pregnancy and in women who can become pregnant unless using an effective method of contraception (see section 4.3).
Celecoxib huwa kontra- indikat fit- tqala u f’ nisa li jistgħu joħorġu tqal jekk ma jużawx metodu effettiv ta ’ kontraċezzjoni (ara sezzjoni 4. 3).
If a woman becomes pregnant during treatment, celecoxib should be discontinued.
Jekk mara toħroġ tqila waqt it- trattament, celecoxib għandu jitwaqqaf.
Celecoxib is excreted in the milk of lactating rats at concentrations similar to those in plasma.
Celecoxib joħroġ fil- ħalib ta ’ firien ireddgħu f’ konċentrazzjonijiet simili għal dawk fil- plażma.
Administration of celecoxib to a limited number of lactating women has shown a very low transfer of celecoxib into breast milk.
L - għoti ta ’ celecoxib lil numru limitat ta ’ nisa wera trasferiment baxx ħafna ta ’ celecoxib għal ġol- ħalib tas- sider.
Women who take celecoxib should not breastfeed.
In- nisa li jieħdu celecoxib m’ għandhomx ireddgħu.
No studies on the effect on the ability to drive and use machines have been performed.
6 Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni.
However, patients who experience dizziness, vertigo or somnolence while taking celecoxib should refrain from driving or operating machinery.
Madankollu, pazjenti li jesperjenzaw sturdament, vertigo jew ħedla m’ għandhomx isuqu jew iħaddmu magni.
Adverse reactions are listed by system organ class and ranked by frequency in Table 1, reflecting data from the following sources:
Ir- reazzjonijiet avversi huma elenkati skont is- sistema tal- klassifika tal- organi u mpoġġija skont il - frekwenza f’ Tabella 1, biex jirriflettu d- dejta mis- sorsi li ġejjin:
- Adverse reactions reported in osteoarthritis patients and rheumatoid arthritis patients at incidence rates
- Reazzjonijiet avversi rrappurtati f’ pazjenti bl- osteoartrite u f’ pazjenti bl- artrite rewmatika b’ rati ta ’
greater than 0.01% and greater than those reported for placebo during 12 placebo- and/ or active- controlled clinical trials of duration up to 12 weeks at celecoxib daily doses from 100 mg up to 800 mg.
inċidenza akbar minn 0. 01% u akbar minn dawk irrappurtati għall- plaċebo waqt 12- il prova klinika kkontrollati bil- plaċebo u/ jew bis- sustanza attiva li damu għaddejjin sa 12- il ġimgħa b’ dożi ta ’ celecoxib minn 100 mg sa 800 mg kuljum.
In additional studies using non-selective NSAID comparators, approximately 7400 arthritis patients have been treated with celecoxib at daily doses up to 800 mg, including approximately 2300 patients treated for 1 year or longer.
Fi studji addizzjonali bl- użu ta ’ komparaturi NSAID mhux selettivi, madwar 7400 pazjent bl- artrite ngħataw trattament b’ celecoxib f’ dożi sa 800 mg kuljum, fosthom madwar 2300 pazjent ikkurati għal sena jew aktar.
The adverse reactions observed with celecoxib in these additional studies were consistent with those for osteoarthritis and rheumatoid arthritis patients listed in Table 1.
Ir- reazzjonijiet avversi osservati b’ celecoxib f’ dawn l- istudji addizzjonali kienu konsistenti ma ’ dawk għall- pazjenti bl - osteoartrite u l- artrite rewmatika elenkati f ’ Tabella 1.
- Adverse drug reactions from post-marketing surveillance as spontaneously reported during a period in
- Reazzjonijiet avversi għall- mediċina mis- sorveljanza ta ’ wara t- tqegħid tal- prodott fis- suq kif
which an estimated > 70 million patients were treated with celecoxib (various doses, durations, and
irrappurtati b’ mod spontanju matul perjodu li fih madwar > 70 miljun pazjent ingħataw kura b’ celecoxib (diversi dożi, tul ta ’ żmien, u indikazzjonijiet).
Because not all adverse drug reactions are reported to the MAH and included in the safety database, the frequencies of these reactions cannot be reliably determined.
Billi mhux ir- reazzjonijiet avversi kollha għall- mediċina huma rrappurtati lill- MAH u inklużi fid- dejtabejż tas- sigurtà, il- frekwenzi ta ’ dawn ir- reazzjonijiet ma jistgħux jiġu stabbiliti b’ mod affidabbli.
Frequency Not
Mhix magħrufa l -
(≥ 1/ 100 to < 1/ 10)
(≥1/ 100 sa
(≥ 1/ 1000 to < 1/ 100)
(≥1/ 1000 sa
(≥ 1/ 10,000 to
(≥1/ 10, 000 sa
(Post-marketing experience)1
(Esperjenza ta ’ wara t- tqegħid fis- suq) 1
Sinusitis, upper respiratory tract infection, urinary tract infection
Sinożite, infezzjoni fil - parti ta ’ fuq tal - apparat respiratorju, infezzjoni fl - apparat urinarju
Blood and lymphatic
Disturbi tad - demm u tas - sistema limfatika
Leucopenia, thrombocytopenia
Lewkopenija, tromboċitopenija
Immune system
Disturbi fis - sistema immuni
Allergy aggravated
Allerġija aggravata
Serious allergic reactions, anaphylactic shock, anaphylaxis
Reazzjonijiet allerġiċi serji, xokk anafilattiku, anafilassi
Psychiatric
Disturbi psikjatriċi Disturbi fil - metaboliżmu u n- nutrizzjoni
Anxiety, depression, tiredness
Ansjetà, depressjoni, għeja Iperkalimja
Metabolism and nutrition
Alluċinazzjonijiet
Dizziness, hypertonia
Sturdament, ipertonija
Paraesthesia, somnolence
Parasteżija, ngħas
Ataxia, taste alteration
Atassja, bidla fit - togħma
Headache, aggravated epilepsy, meningitis aseptic, ageusia, anosmia, fatal intracranial haemorrhage
Uġigħ ta ’ ras, epilessija aggravata, meninġite asettika, agewżja, anosmija, emorraġija ġol - kranju fatali
Eye
Disturbi fl - għajnejn
Conjunctivitis, ocular haemorrhage, retinal artery or vein occlusion
Konġuntivite, emorraġija mill - għajnejn,
Ear and labyrinth
7
Tinnitus
okklużjoni tal - arterja jew tal- vina tar- retina
Decreased hearing
Disturbi fil - widnejn u fis - sistema labirintika
Cardiac
Żanżin tal - widnejn
Heart failure, palpitations, tachycardia
Tnaqqis fis- smigħ
Myocardial infarction2
Infart mijokardijaku2 Arritmija Disturbi fil- qalb
Arrhythmia
Insuffiċjenza tal - qalb, palpitazzjonijiet, takikardija
Vascular
Disturbi vaskulari
Hypertension, hypertension aggravate d
Pressjoni għolja, pressjoni għolja aggravata
Flushing, vasculitis
Fwawar, vaskulite
Respiratory, thoracic, and mediastinal
Disturbi respiratorji, toraċiċi, u medjastinali
Pharyngitis, rhinitis, cough
Farinġite, rinite, sogħla
Bronchospasm
Bronkospażmu
Gastrointestinal
Disturbi
Abdominal pain, diarrhoea,
Stitikezza, tifwiq,
Constipation, eructation, gastritis,
Ulċerazzjoni
Duodenal, gastric, oesophageal,
Dardir, pankreatite
Nausea, acute pancreatitis,
gastrointestinali
dyspepsia, flatulence
addominali, dijarea, dispepsja, gass fl- istonku
stomatitis, vomiting, aggravation of gastrointestinal inflammation
gastrite, stomatite, rimettar, aggravazzjoni tal - infjammazzjoni gastrointestinali
intestinal, and colonic gastrointestinal ulceration; dysphagia, haemorrhage, intestinal perforation; colitis/ colitis oesophagitis, aggravated melaena; pancreatitis
duwodenali, gastrika, akuta, emorraġija esofagali, intestinali u gastrointestinali, tal- musrana l- ħoxna; kolite/ kolite disfaġja, perforazzjoniaggravata intestinali, esofaġite, melena, pankreatite
Hepatobiliary
Disturbi fil - fwied u fil - marrara
Abnormal hepatic function, increased
Funzjoni abnormali epatika, żieda fis - SGOT u s- SGPT
Elevation of hepatic Hepatitis, enzymes hepatic failure
Żieda fl- enżimi Epatite, epatiċi insuffiċjenza tal - fwied, suffejra
Skin and subcutaneous
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
Rash, pruritus
Raxx, ħakk
Urticaria
Urtikarja
Alopecia, Ecchymosis, photosensitivity bullous eruption, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema
Alopeċja, Ekkimożi, imsiemer, fotosensittività dermatite esfoljattiva, eritema multiformi, sindrome ta ’ Stevens- Johnson, nekroliżi epidermika tossika, anġjoedema
Musculoskeletal and connective
Disturbi muskolu - skeltrali u tal - connective tissue
Leg cramps
Bugħawwieġ fis - saqajn
Arthralgia, myositis
Artralġja, mijosite
Renal and urinary
Disturbi fil - kliewi u fis - sistema urinarja
Increased creatinine, BUN increased
Żieda fil - kreatinina, żieda fil- BUN
Acute renal failure, interstitial nephritis, hyponatraemia
Insuffiċjenza renali akuta, nefrite interstizjali, iponatrimija
1
Disturbi fis - sistema riproduttiva u fis - sider
Reproductive and breast General
Disturb fil - mestrwazzjoni
Flu-like symptoms, peripheral oedema/ fluid retention
Disturbi ġenerali Sintomi bħall - influwenza, edema periferali/ żamma tal- fluwidu
Adverse drug reactions spontaneously reported to the safety surveillance database over a period in which an estimated > 70 million patients were treated with celecoxib (various doses, durations, and indications).
8 1 Reazzjonijiet avversi tal- mediċina rrappurtati b’ mod spontanju għad- dejtabejż dwar is- sorveljanza tas- sigurtà fuq perjodu li matulu xi > 70 miljun pazjent ingħataw kura b’ celecoxib (diversi dożi, tul ta ’ żmien, u indikazzjonijiet).
As a result, the frequencies of these adverse drug reactions cannot be reliably determined.
Minħabba f’ hekk, il- frekwenzi ta ’ dawn ir- reazzjonijiet avversi tal- mediċina ma jistgħux jiġu determinati b’ mod affidabbli.
Adverse drug reactions listed for the post-marketing population are only those that are not already listed for the arthritis trials (Table 1) or the polyp prevention trials (Table 2).
Ir- reazzjonijiet avversi tal- mediċina elenkati għall- popolazzjoni ta ’ wara t- tqegħid tal- prodott fis- suq huma biss dawk li mhumiex diġà elenkati għall- provi dwar l- artrite (Tabella 1) jew il- provi għall- prevenzjoni tal - polipi (Tabella 2). 2).
2 In a pooled analysis of 20 placebo-controlled studies with duration greater than 2 weeks up to 1 year in patients with OA and RA, the excess rate of myocardial infarction in patients treated with celecoxib 200 or 400 mg daily over placebo was 0.7 events per 1000 patients (Rare) and there was no excess of strokes.
2 F’ analiżi miġbura ta ’ 20 studju kkontrollati bil- plaċebo li damu aktar minn ġimagħtejn sa sena f’ pazjenti b’ OA u RA, ir- rata żejda ta ’ infart mijokardijaku fil- pazjenti kkurati b’ celecoxib 200 jew 400 mg kuljum fuq il- plaċebo kienet ta ’ 0. 7 episodji għal kull 1000 pazjent (Rari) u ma kien hemm ebda eċċess ta ’ puplesiji.
The additional adverse reactions listed by system organ class and ranked by frequency in Table 2 were reported at incidence rates greater than placebo for subjects treated with celecoxib 400 mg to 800 mg daily in long-term polyp prevention trials of duration up to 3 years (the APC and PreSAP trials; see Section 5.1, Pharmacodynamic properties:
Ir- reazzjonijiet avversi addizzjonali elenkati skont is- sistema tal- klassifika tal- organi u mpoġġija skont il- frekwenza f’ Tabella 2 ġew irrappurtati b’ rati ta ’ inċidenza akbar mill- plaċebo fil- każ tal- persuni ttrattati b’ celecoxib 400 mg sa 800 mg kuljum fil- provi fuq perjodu fit- tul għall- prevenzjoni tal- polipi li damu sa 3 snin (il- provi APC u PreSAP; ara Sezzjoni 5. 1, Tagħrif Farmakodinamiku:
Cardiovascular Safety – Long-Term Studies Involving Patients With Sporadic Adenomatous Polyps).
Sigurtà Kardjovaskulari – Studji fuq Perjodu fit- Tul li Jinvolvu Pazjenti b’ Polipi Adenomatużi Sporadiċi).
Common Common
Komuni Komuni
(≥ 1/ 10)
Ħafna (≥1/ 10)
(≥ 1/ 100 to < 1/ 10)
(≥1/ 100 sa < 1/ 10)
(≥ 1/ 1000 to < 1/ 100)
(≥1/ 1000 sa < 1/ 100)
Ear infection, fungal infection (fungal infections were primarily nonsystemic)
Infezzjoni fil- widnejn, infezzjoni fungali (l - infezzjonijiet fungali kienu prinċipalment mhux sistemiċi)
Helicobacter infection, herpes zoster, erysipelas, wound infection, gingival infection, labrynthitis, bacterial infection
Infezzjoni tal- helicobacter, herpes zoster, irsipla, infezzjoni fil- ferita, infezzjoni fil- ħniek, labirintite
Neoplasms Psychiatric Nervous system Eye
Neoplażmi Disturbi psikjatriċi
Lipoma Sleep disorder Cerebral infarction Vitreous floaters; conjunctival hemorrhage
Lipoma Disturb tal- irqad
Ear and labyrinth
Disturbi fis - sistema nervuża
Hypoacusis
Infart ċerebrali;
Cardiac
Disturbi fil- qalb
Angina pectoris; myocardial infarction
Angina pectoris; infart mijokardijaku
Angina unstable, aortic valve incompetence, coronary artery atherosclerosis, sinus bradycardia, ventricular hypertropy
Anġina instabbli, inkompetenza tal- valv aortiku, aterosklerożi tal- arterja koronarja, sinus bradycardia, ipertrofija ventrikulari
Hypertension *
Pressjoni għolja *
Deep vein thrombosis; hematoma
Trombożi fil- vini fondi; ematoma
Dysphonia
Disfonja
Gastrointestinal
Disturbi gastrointestinali Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
Diarrhoea*
Dijarea *
Nausea, gastroesophageal reflux disease, diverticulum, vomiting, * dysphagia, irritable bowel syndrome
Dardir, mard tar- rifluss gastroesofagali, divertikulu, rimettar, * disfaġja, sindrome tal- imsaren irritabbli
Haemorrhoidal haemorrhage, frequent bowel movements, mouth ulceration, stomatitis
Emorraġija mill- murliti, movimenti frekwenti tal - imsaren, ulċera tal- ħalq, stomatite Dermatite allerġika
Skin and subcutaneous
Disturbi muskolu - skeltrali u tal - connective tissue
Dermatitis allergic
Spażmi fil- muskoli
Musculoskeletal nd connective
Disturbi fil- kliewi
Muscle spasms
Nefrolitjasi, żieda fil -
Ganglion
Nokturja
Renal and urinary
fis- sistema
Nephrolithiasis, blood creatinine increased
kreatinina fid- demm
Nocturia
urinarja
Reproductive and breast
Disturbi fis- sistema riproduttiva u fis - sider Disturbi ġenerali u kundizzjonijiet ta ’ mnejn jingħata
Benign prostatic hyperplasia, prostatitis, prostatic specific antigen increased
Iperplasija beninna tal - prostata, infjammazzjoni tal- prostata, żieda fl - antiġens speċifiċi għall - prostata Edema
Vaginal haemorrhage, breast tenderness, dysmenorrhea, ovarian cyst, menopausal symptoms
Emorraġija mill- vaġina, sensibilità fis- sider, mestrwazzjoni diffiċli jew li tweġġa ’, ċista fl- ovarju, sintomi tal- menopawsa
Blood levels increased: potassium, sodium, hemoglobin Blood levels decreased: hematocrit, testosterone
Żieda fil- livelli fid- demm: potassju, sodju, emoglobina Tnaqqis tal- livelli fid- demm: ematokrit, testosteron
Injury, poisoning, procedural
Korriment, avvelenament, kumplikazzjonijiet ta ’ xi proċedura
Foot fracture, lower limb fracture, epicondylitis, tendon rupture, fracture
Ksur fis- saqajn, ksur fir- riġlejn, epikondilite, ftuq tal- għeruq, ksur
* Hypertension, vomiting and diarrhoea are included in Table 2 because they were reported more frequently in these studies, which were of 3-year duration, compared to Table 1, which includes adverse reactions from studies of 12-week duration.
* Il- pressjoni għolja, ir- rimettar u d- dijarea huma inklużi f’ Tabella 2 minħabba li ġew irrappurtati b’ mod aktar frekwenti f’ dawn l- istudji, li damu għaddejjin 3 snin, meta mqabbel ma ’ Tabella 1, li tinkludi reazzjonijiet avversi minn studji li damu għaddejjin 12- il ġimgħa.
In final data (adjudicated) from the APC trial in patients treated with celecoxib 800 mg daily for up to 3 years, the excess rates over placebo were 11 events per 1000 patients for myocardial infarction (common); and 5 events per 1000 patients for stroke (uncommon; types of stroke not differentiated).
Fid- dejta finali (aġġudikata) mill- prova APC f’ pazjenti ttrattati b’ celecoxib 800 mg kuljum sa perjodu ta ’ 3 snin, ir- rati ta ’ eċċess fuq il- plaċebo kienu 11- il episodju għal kull 1000 pazjent fil- każ tal- infart mijokardijaku (komuni); u 5 episodji għal kull 100 pazjent fil- każ tal- puplesija (mhux komuni; ma saritx differenza bejn it- tipi ta ’ puplesija).
There is no clinical experience of overdose in clinical trials.
M’ hemm l- ebda esperjenza klinika ta ’ doża eċċessiva fil- provi kliniċi.
Single doses up to 1200 mg and multiple doses up to 1200 mg twice daily have been administered to healthy subjects for nine days without clinically significant adverse events.
Dożi waħdenin sa 1200 mg u dożi multipli sa 1200 mg darbtejn kuljum ingħataw lil persuni b’ saħħithom għal disat ijiem mingħajr ebda episodji avversi klinikament sinifikanti.
In the event of suspected overdose, appropriate supportive medical care should be provided e. g. by eliminating the gastric contents, clinical supervision and, if necessary, the institution of symptomatic treatment.
F’ każ ta ’ suspett ta ’ doża eċċessiva, għandha tiġi provduta kura medika ta ’ appoġg xierqa eż. bit- tneħħija tal- kontenut gastriku, superviżjoni klinika u, jekk neċċessarju, istituzjoni ta ’ trattament simtomatiku.
Dialysis is unlikely to be an efficient method of medicinal product removal due to high protein binding.
Id- dijaliżi għandu mnejn ma jkunx il- metodu ideali li tneħħi l- prodott mediċinali minħabba tagħqid mall- proteini għoli.
Antineoplastic, ATC code:
Antineoplastics, Kodiċi ATC:
Celecoxib is a diaryl-substituted pyrazole, chemically similar to other non-arylamine sulfonamides (e. g. thiazides, furosemide) but differing from arylamine sulfonamides (e. g. sulfamethoxizole and other sulfonamide antibiotics).
Celecoxib huwa pyrazole sostitwit fil- parti diarili, huwa kimikament simili għal sulfonamidi oħra li m’ għandhomx arylamine (eż. thiazides, furosemide) imma li huma differenti minn sulfonamidi li għandhom arylamine (eż. sulphamethoxizole u antibijotiċi sulfonamidi oħra).
9 Celecoxib is an oral, selective cyclooxygenase-2 (COX-2) inhibitor.
Celecoxib huwa inibitur selettiv attiv ta ’ ċiklo- ossiġenażi- 2 (COX- 2) li jittieħed mill- ħalq.
No statistically significant inhibition of COX-1 (assessed as ex vivo inhibition of thromboxane B2 [TxB2] formation) was observed in healthy volunteers at the FAP therapeutic dose of 400 mg BID.
L- ebda inibizzjoni statistikament sinifikanti ta ’ COX- 1 (stmata bħala inibizzjoni ex vivo ta ’ formazzjoni ta ’ thromboxane B2) ma ġiet osservata f‘ volontiera b’ saħħithom fid- doża terapewtika għal FAP ta ’ 400 mg BID.
Cyclooxygenase is responsible for generation of prostaglandins.
Cyclooxygenase huwa responsabbli għall- ġenerazzjoni ta ’ prostaglandini.
Two isoforms, COX-1 and COX-2, have been identified.
COX- 2 hija l- iżoforma ta ’ l- enzim li nterwa li jiġi indott minn stimuli li jiffavorixxu l- infjammazzjoni u ġie postulat li huwa responsabbli b’ mod ewlieni għas- sinteżi ta ’
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.
10 medjaturi prostanojdi ta ’ l- uġigħ, infjammazzjoni u deni.
Elevated levels of COX-2 are found in many pre-malignant lesions (such as adenomatous colorectal polyps) and epithelial cancers.
Livelli għoljin ta ’ COX- 2 jinstabu f’ ħafna feriti pre- malinji (polipi adenomatużi kolorettali) u kanċer epiteljali.
Familial Adenomatous Polyposis (FAP) is a genetic disease resulting from an autosomal dominant genetic alteration of a tumor suppressor gene, the adenomatous polyposis coli (APC) gene.
Polipożi Familjali Adenomatuża (FAP) hija marda ġenetika li tirriżulta minn alterazzjoni ġenetika dominanti autosomal ta ’ ġene li jrażżan it- tumuri, il- ġene Koli Adenomatuż Polipożi (APC).
Polyps with the APC mutation overexpress COX-2 and left untreated, these polyps continue to form and enlarge in the colon or rectum resulting in essentially a 100% chance of developing colorectal cancer.
Polipi li għandhom il- mutazzjoni APC jesprimu COX- 2 iżżejjed u jekk jitħallew mhux trattati, dawn il- polipi jibqgħu jiffurmaw u jikbru fil - kolon u fir- rettum b’ riżultat ta ’ 100% żvilupp ta ’ kanċer kolorettali.
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).
Huwa maħsub ukoll li COX- 2 hija involuta fl- ovulazzjoni, impjantazzjoni u għeluq tad- ductus arteriosus, regolament tal- funzjoni renali u funzjonijiet tas- sistema nervuża ċentrali (bidu ta ’ deni, perċezzjoni ta ’ uġigħ u funzjoni konjittiva).
It may also play a role in ulcer healing.
Jista ’ jkun li għandha rwol fil- fejqan ta ’ l- 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 f’ tessuti madwar ulċeri gastriċi fil- bniedem iżda r- rilevanza tagħha fil- fejqan ta ’ l- ulċeri gastriċi għadu ma ġiex stabbilit.
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.
Id- differenza fl- attività kontra l- plejtlits bejn xi COX- 1 li jinibixxu NSAIDs u inibituri selettivi COX - 2 tista ’ tkun ta ’ sinifikanza klinika f’ pazjenti b’ riskju ta ’ reazzjonijiet tromboemboliċi.
COX-2 inhibitors reduce the formation of systemic (and therefore possibly endothelial) prostacyclin without affecting platelet thromboxane.
Inibituri ta ’ COX- 2 inaqqsu l- formazzjoni ta ’ prostacyclin sistemiku (u allura possibilment endoteljali) mingħajr ma jaffetwaw it- thromboxane tal- plejtlits.
A dose-dependent effect on TxB2 formation has been observed after high doses of celecoxib.
Effett li jiddependi fuq id- doża fuq il- formazzjoni ta ’ TxB2 ġie osservat wara li ngħataw dożi għoljin ta ’ celecoxib.
However, in small multiple dose studies in healthy subjects with 600 mg BID celecoxib had no effect on platelet aggregation and bleeding time compared to placebo.
Madankollu, fi studji żgħar b’ dożi multipli fuq suġġetti b’ saħħithom b’ 600 mg BID, celecoxib ma kellu l- ebda effett fuq l- aggregazzjoni tal- plejtlits u l- ħin ta ’ telf ta ’ demm meta imqabbel ma ’ plaċebo.
Experimental evidence shows that the mechanism(s) of action by which celecoxib leads to tumour death may be related to induction of apoptosis and inhibition of angiogenesis.
Evidenza sperimentali tindika li l- mekkaniżmu( i) ta ’ azzjoni li bih( om) celecoxib iwassal għall- mewta tat- tumur tista ’ tkun relatata ma ’ l- induzzjoni ta ’ apoptożi u inibizjoni ta ’ anġjoġenesi.
Inhibition of COX-2 may have consequences on tumour viability that are unrelated to inflammation.
Inibizzjoni ta ’ COX- 2 jista ’ jkollha konsegwenzi fuq il- vijabilità tat- tumur li mhumiex relatati ma ’ infjammazzjoni.
Celecoxib inhibits tumour formation in preclinical models of colon cancer, which overexpress COX-2, whether induced by chemical (rat AOM model) or genetic (MIN mouse model) mutation.
Celecoxib jinibixxi formazzjoni tat- tumur f’ mudelli preklinikali ta ’ kanċer tal- kolon, li jespremu COX- 2, kemm jekk hu indott b’ mutazzjoni kimika (mudell AOM tal- firien) kif ukoll jekk indott b’ mutazzjoni ġenetika (mudell MIN tal- ġurdien)
Celecoxib has been shown to reduce the number and size of adenomatous colorectal polyps.
Intwera li celecoxib inaqqas in- numru u d- daqs ta ’ polipi adenomatużi kolorettali.
A randomized double-blind placebo controlled study was conducted in 83 patients with FAP.
Sar studju b’ mod każwali fejn la t- tabib u lanqas il- pazjent ma kienu jafu x’ qed jingħata, ikkontrollat bil- plaċebo fi 83 pazjent bl- FAP.
The study population included 58 patients with a prior subtotal or total colectomy and 25 patients with an intact colon.
Il- popolazzjoni ta ’ l- istudju kienet tinkludi 58 pazjent b’ kolektomija subtotali preċedenti jew totali u 25 pazjent b’ kolon intatt.
Thirteen patients had the attenuated FAP phenotype.
Tlettax- il pazjent kellhom il- fenotip FAP attenwat.
The mean reduction in the number of colorectal polyps following six months of treatment was 28% (SD + 24%) for celecoxib 400 mg BID which was statistically superior to placebo (mean 5%, SD +16%).
It - tnaqqis medju fin- numru ta ’ polipi kolorettali wara sitt xhur kura kien ta ’ 28% (SD + 24%) għal celecoxib 400 mg BID li kien statistikament superjuri għal plaċebo (medja ta ’ 5%, SD +16%).
A meaningful reduction in duodenal adenoma area was also observed compared with placebo (14.5% celecoxib 400 mg BID versus 1.4% placebo), which however was not statistically significant.
Ġie osservat tnaqqis sinifikanti fl- erja ta ’ l- adenoma dwodenali meta mqabbel ma ’ plaċebo (14. 5% celecoxib 400 mg BID kontra 1. 4% plaċebo), li madankollu ma kienx statistikament sinifikanti.
Pilot Study in Juvenile FAP Patients:
Studju Pilota fuq Pazjenti FAP Minorenni:
A total of 18 children 10 to 14 years of age who had genotype or phenotype positive FAP were treated with celecoxib 4 mg/ kg/ day (4 patients, compared to 2 patients treated with placebo), celecoxib 8 mg/ kg/ day (4 patients, compared to 2 patients treated with placebo), or celecoxib 16 mg/ kg/ day (4 patients, compared to 2 patients treated with placebo).
Total ta ’ 18- il tifel/ tifla ta ’ 10 sa 14- il sena li kellhom FAP pożittiv ta ’ ġenotip jew fenotip ingħataw kura b’ celecoxib 4 mg/ kg/ kuljum (4 pazjenti, meta mqabbel ma ’ 2 pazjenti ttrattati bi plaċebo), celecoxib 8 mg/ kg/ kuljum (4 pazjenti, meta mqabbel ma ’ 2 pazjenti ttrattati bi plaċebo), jew celecoxib 16 mg/ kg/ kuljum (4 pazjenti, meta mqabbel ma ’ 2 pazjenti ttrattati bi plaċebo).
Results demonstrated a statistically significant reduction in polyp burden in all celecoxib treatment groups compared to the corresponding placebo treatment groups.
Ir- riżultati wrew tnaqqis statistiku sinifikanti fil- problema tal- polipi fil- gruppi kollha tat- trattament b’ celecoxib meta mqabbel mal- gruppi korrispondenti li kienu qegħdin jiġu trattati bi plaċebo.
The greatest reduction was observed in patients treated with celecoxib 16 mg/ kg/ day, which corresponds to the recommended adult FAP dose of 800 mg daily.
L- akbar tnaqqis kien osservat f’ pazjenti ttrattati b’ celecoxib 16 mg/ kg/ kuljum, li tikkorrispondi għad- doża rakkomandata ta ’ 800 mg kuljum għal FAP fl- adulti.
Safety data were reviewed in detail by a Data Safety Monitoring Committee, which concluded that celecoxib 16 mg/ kg/ day was a safe dose to recommend for further studies in juvenile FAP patients.
L- informazzjoni dwar is- sigurtà ġiet eżaminata b’ reqqa minn Kumitat għall- Monitoraġġ tad- Dejta dwar is- Sigurtà, li kkonkluda li celecoxib 16 mg/ kg/ kuljum kienet doża sigura biex tiġi rakkomandata għal aktar studji f’ pazjenti FAP minorenni.
The long-term cardiovascular toxicity in children exposed to celecoxib has not been evaluated and it is unknown if the long-term risk may be similar to that seen in adults exposed to celecoxib or other COX-2 selective and non-selective NSAIDs (see section 4.4; cardiovascular effects.).
It- tossiċità kardjovaskulari fuq perjodu fit- tul fi tfal esposti għal celecoxib ma ġietx evalwata u mhux magħruf jekk ir- riskju fuq perjodu fit- tul jistax ikun simili għal dak li deher f’ persuni adulti esposti għal celecoxib jew NSAIDs oħra COX- 2 selettivi u mhux selettivi (ara sezzjoni 4. 4; effetti kardjovaskulari).
10 Cardiovascular Safety – Long-Term Studies Involving Subjects With Sporadic Adenomatous Polyps:
11 Sigurtà Kardjovaskulari – Studji fuq Perjodu fit- Tul li Jinvolvu Persuni b’ Polipi Adenomatużi Sporadiċi:
Two studies involving subjects with sporadic adenomatous polyps were conducted with celecoxib i. e., the APC trial (Adenoma Prevention with Celecoxib) and the PreSAP trial (Prevention of Spontaneous Adenomatous Polyps).
Saru żewġ studji b’ celecoxib li kienu jinvolvu persuni b’ polipi adenomatużi sporadiċi, jiġifieri l- prova APC (Prevenzjoni tal- Adenomi b’ Celecoxib) u l- prova PreSAP (Prevenzjoni tal - Polipi Adenomatużi Spontanji).
In theAPC trial, there was a dose-related increase in the composite endpoint of cardiovascular death, myocardial infarction, or stroke (adjudicated) with celecoxib compared to placebo over 3 years of treatment.
Fil- prova APC, kien hemm żieda relatata mad- doża fl- endpoint kompost ta ’ mewt kardjovaskulari, infart mijokardijaku, jew puplesija (aġġudikati) b’ celecoxib meta mqabbel ma ’ plaċebo fuq 3 snin ta ’ kura.
The PreSAP trial did not demonstrate a statistically significant increased risk for the same composite endpoint.
Il- prova PreSAP ma wrietx żieda statistika sinifikanti fir - riskju għall- istess endpoint kompost.
In the APC trial, the relative risks compared to placebo for a composite endpoint (adjudicated) of cardiovascular death, myocardial infarction, or stroke were 3.4 (95% CI 1.4 - 8.5) with celecoxib 400 mg twice daily and 2.8 (95% CI 1.1 - 7.2) with celecoxib 200 mg twice daily.
Fil- prova APC, ir- riskji relattivi meta mqabbla mal- plaċebo għal endpoint kompost (aġġudikat) ta ’ mewt kardjovaskulari, infart mijokardijaku, jew puplesija kienu 3. 4 (95% CI 1. 4 - 8. 5) b’ celecoxib 400 mg darbtejn kuljum u 2. 8 (95% CI 1. 1 - 7. 2) b’ celecoxib 200 mg darbtejn kuljum.
Cumulative rates for this composite endpoint over 3 years were 3.0% (20/ 671 subjects) and 2.5% (17/ 685 subjects), respectively, compared to 0.9% (6/ 679 subjects) for placebo.
Ir- rati kumulattivi għal dan l- endpoint kompost fuq 3 snin kienu 3. 0% (20/ 671 persuna) u 2. 5% (17/ 685 persuna), rispettivament, meta mqabbel ma ’ 0. 9% (6/ 679 persuna) għall- plaċebo.
The increases for both celecoxib dose groups versus placebo were mainly due to an increased incidence of myocardial infarction.
Iż- żidiet għaż- żewġ gruppi fuq dożi ta ’ celecoxib kontra l- plaċebo kienu dovuti prinċipalment għal inċidenza akbar ta ’ infart mijokardijaku.
In the PreSAP trial, the relative risk compared to placebo for this same composite endpoint (adjudicated) was 1.2 (95% CI 0.6 - 2.4) with celecoxib 400 mg once daily compared to placebo.
Fil- prova PreSAP, ir- riskju relattiv ipparagunat mal- plaċebo għal dan l- istess endpoint kompost (aġġudikat) kien ta ’ 1. 2 (95% CI 0. 6 - 2. 4) b’ celecoxib 400 mg darba kuljum meta mqabbel ma ’ plaċebo.
Cumulative rates for this composite endpoint over 3 years were 2.3% (21/ 933 subjects) and 1.9% (12/ 628 subjects), respectively.
Ir- rati kumulattivi għal dan l- endpoint kompost fuq 3 snin kienu 2. 3% (21/ 933 persuna) u 1. 9% (12/ 628 persuna), rispettivament.
The incidence of myocardial infarction (adjudicated) was 1.0% with (9/ 933 subjects) with celecoxib 400 mg once daily and 0.6% (4/ 628 subjects) with placebo.
L- inċidenza tal- infart mijokardijaku (aġġudikata) kienet ta ’ 1. 0% (9/ 933 persuna) b’ celecoxib 400 mg darba kuljum u 0. 6% (4/ 628 persuna) bi plaċebo.
Data from a third long-term study, ADAPT (The Alzheimer's Disease Anti-inflammatory Prevention Trial), did not show a significantly increased cardiovascular risk with celecoxib 200mg BID compared to placebo.
Informazzjoni mit- tielet studju fuq perjodu fit- tul, ADAPT (The Alzheimer' s Disease Anti - inflammatory Prevention Trial), ma wrietx żieda sinifikanti fir- riskju kardjovaskulari b’ celecoxib 200mg BID meta mqabbel ma ’ plaċebo.
The relative risk compared to placebo for a similar composite endpoint (CV death, MI, stroke) was 1.14 (95% CI 0.61 - 2.12) with celecoxib 200 mg twice daily.
Ir- riskju relattiv ipparagunat mal- plaċebo għal endpoint simili kompost (mewt kardjovaskulari, infart mijokardijaku, puplesija) kien ta ’ 1. 14 (95% CI 0. 61 - 2. 12) b’ celecoxib 200 mg darbtejn kuljum.
The incidence of myocardial infarction was 1.1% (8/ 717 patients) with celecoxib 200 mg twice daily and 1.2% (13/ 1070 patients) with placebo.
L- inċidenza ta ’ infart mijokardijaku kienet ta ’ 1. 1% (8/ 717 pazjent) b’ celecoxib 200 mg darbtejn kuljum u 1. 2% (13/ 1070 pazjent) bi plaċebo.
Data from pooled analysis of controlled randomized trials also suggest that cardiovascular risk may be associated with the use of celecoxib compared to placebo, with evidence for differences in risk based on celecoxib dose.
Tagħrif mill- analiżi miġbura ta ’ provi randomised kkontrollati jissuġġerixxi wkoll li r- riskju kardjovaskulari jista ’ jkun assoċjat mal- użu ta ’ celecoxib meta mqabbel ma ’ plaċebo, b’ evidenza għal differenzi fir- riskju bbażati fuq id- doża ta ’ celecoxib.
This medicinal product has been authorised under “ Exceptional Circumstances”.
Dan il- prodott mediċinali kien awtorizzat taħt ‘ Ċirkustanzi ta ’ Eċċezzjoni ’.
This means that due to the rarity of the disease it has not been possible to obtain complete information on this medicinal product.
Dan ifisser li minħabba li l- marda li qed tbati minnha hija rari ma kienx possibbli li tinkiseb informazzjoni kompleta dwar il - benefiċċji u r- riskji ta ’ dan il- prodott mediċinali.
The European Medicines Agency (EMEA) will review any new information which may become available every year and this SPC will be updated as necessary.
L- Aġenzija Ewropeja dwar il- Mediċini (EMEA) ser tirrevedi kull tip ta ’ informazzjoni ġdida li toħroġ kull sena u ser taġġorna dan is- Sommarju tal - Karatteristiċi tal- Prodott, skond il- bżonn.
Celecoxib is well absorbed reaching peak plasma concentrations after approximately 2-3 hours.
L- assorbiment ta ’ celecoxib huwa tajjeb bl- akbar konċentrazzjonijiet fil- plażma jintlaħqu wara bejn wieħed u ieħor 2- 3 sigħat.
Dosing with food (high fat meal) delays absorption by about 1 hour with an increase in total absorption (AUC) of 10 to 20%.
Id- dożaġġ ma ’ l- ikel (ikla b’ kontenut xaħmi għoli) jittardja l- assorbiment b’ madwar siegħa b’ żieda fl- assorbiment totali (AUC) ta ’ 10 sa 20%.
Celecoxib is mainly eliminated by metabolism.
Celecoxib huwa eliminat primarjament bil- metaboliżmu.
Less than 1% of the dose is excreted unchanged in urine.
Inqas minn 1% tad- doża jitneħħa mhux mibdul fl- awrina.
The inter-subject variability in the exposure of celecoxib is about 10-fold.
Il- varjabilità bejn suġġett u ieħor fl- esponiment ta ’ celecoxib hija ta ’ xi 10 darbiet.
Celecoxib exhibits dose- and time-independent pharmacokinetics in the therapeutic dose range.
Celecoxib juri farmakokinetiċi indipendenti mid- doża u l- ħin fil- medda tad- doża terapewtika.
Plasma protein binding is about 97% at therapeutic plasma concentrations and celecoxib is not preferentially bound to erythrocytes.
It - twaħħil mal- proteini tal- plasma hu madwar 97% f’ konċentrazzjonijiet terapewtiċi fil- plasma u celecoxib ma jaqbadx b’ mod preferenzjali ma ’ l- eritroċiti.
Elimination half-life is 8-12 hours.
Il- half- life ta ’ l- eliminazzjoni hija 8- 11– il siegħa.
Steady state plasma concentrations are reached within 5 days of treatment.
Konċentrazzjonijiet stabbli fil- plażma jintlaħqu fi żmien 5 ijiem ta ’ kura.
Pharmacological activity resides in the parent substance.
L- attività farmakoloġika tinsab fis- sustanza oriġinali.
The main metabolites found in the circulation have no detectable COX-1 or COX-2 activity.
Il- metaboliti prinċipali li jinstabu fiċ- ċirkulazzjoni m’ għandhom l- ebda attività COX- 1 jew COX- 2 rilevabbli.
Celecoxib metabolism is primarily mediated via cytochrome P450 CYP2C9.
Il- metaboliżmu ta ’ celecoxib huwa medjat prinċipalment permezz taċ- ċitokromu P450 CYP2C9.
Three metabolites, inactive as COX-1 or COX-2 inhibitors, have been identified in human plasma i. e., a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate.
Tliet metaboliti, inattivi bħall- inibituri COX- 1 jew COX- 2, ġew identifikati fil- plażma umana, jiġifieri
Cytochrome P450 CYP2C9 activity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity, such as those homozygous for the CYP2C9*3 polymorphism.
L- attività taċ - ċitokromu P450 CYP2C9 hija mnaqqsa f’ individwi li għandhom polimorfiżmi ġenetiċi li jwasslu għal attività ridotta tal- enzimi, bħal dawk omozigoti għall- polimorfiżmu ta ’ CYP2C9* 3.
11 In a pharmacokinetic study of celecoxib 200 mg administered once daily in healthy volunteers, genotyped as either CYP2C9*1/ *1, CYP2C9*1/ *3, or CYP2C9*3/ *3, the median Cmax and AUC 0-24 of celecoxib on day 7 were approximately 4-fold and 7-fold, respectively, in subjects genotyped as CYP2C9*3/ *3 compared to other genotypes.
Fi studju farmakokinetiku ta ’ celecoxib 200 mg mogħti darba kuljum lil voluntiera b’ saħħithom, ġenotipati bħala CYP2C9* 1 / * 1, CYP2C9* 1 / * 3, jew CYP2C9* 3 / * 3, il- Cmax u l- AUC 0- 24 medjan ta ’ celecoxib f’ jum 7 kienu bejn wieħed u ieħor 4 darbiet aktar u 7 darbiet aktar, rispettivament, f’ individwi ġenotipati bħala CYP2C9* 3 / * 3 meta mqabbel ma ’ ġenotipi oħra.
In three separate single dose studies, involving a total of 5 subjects genotyped as CYP2C9*3/ *3, single-dose AUC 0-24 increased by approximately 3-fold compared to normal metabolizers.
Fi tliet studji separati b’ doża waħda, li kienu jinvolvu total ta ’ 5 persuni ġenotipati bħala CYP2C9* 3 / * 3, l- AUC 0- 24 ta ’ doża waħda żdiedet b’ madwar 3 darbiet meta pparagunat ma ’ metabolizzaturi normali.
It is estimated that the frequency of the homozygous *3/ *3 genotype is 0.3-1.0% among different ethnic groups.
Huwa stmat li l- frekwenza tal- ġenotip omozigota * 3 / * 3 huwa 0. 3- 1. 0% fost gruppi etniċi differenti.
Patients who are known or suspected to be CYP2C9 poor metabolizers based on previous history/ experience with other CYP2C9 substrates should be administered celecoxib with caution (see Section 4.2).
Il- pazjenti magħrufin jew issuspettati li mhumiex metabolizzaturi daqstant tajbin ta ’ CYP2C9 fuq il - bażi tal- istorja/ esperjenza preċedenti b’ substrati oħra ta ’ CYP2C9 għandhom jingħataw celecoxib b’ kawtela (ara Sezzjoni 4. 2).
No clinically significant differences were found in pharmacokinetic parameters of celecoxib between African-Americans and Caucasians.
Ma nstabu l- ebda differenzi klinikament sinifikanti fil- parametri farmakokinetiċi ta ’ celecoxib bejn persuni Afro- Amerikani u Kawkasi.
The plasma concentration of celecoxib is approximately 100% increased in elderly women (> 65 years).
Il- konċentrazzjoni ta ’ celecoxib fil- plażma hija madwar 100% ogħla f’ nisa anzjani (> 65 sena).
Compared to subjects with normal hepatic function, patients with mild hepatic impairment had a mean increase in Cmax of 53% and in AUC of 26% of celecoxib.
Meta mqabbla ma ’ suġġetti b’ funzjoni normali tal- fwied, il- pazjenti b’ indeboliment ħafif tal- fwied kellhom żieda medja fil- Cmax ta ’ 53% u fl- AUC ta ’ 26% ta ’ celecoxib.
When dosed at 200 mg per day the corresponding values in patients with moderate hepatic impairment were 41% and 146% respectively.
Meta ngħataw doża ta ’ 200 mg kuljum, il- valuri korrispondenti f’ pazjenti b’ indeboliment moderat tal- fwied kienu 41% u 146% rispettivament.
The metabolic capacity in patients with mild to moderate impairment was best correlated to their albumin values.
Il- kapaċità metabolika f’ pazjenti b’ indeboliment tal- fwied ħafif għal moderat kienet korrelatata l- aħjar mal- valuri ta ’ l- albumina tagħhom.
In FAP patients with moderate hepatic impairment (serum albumin of 25-35 g/ l), the daily recommended dose of celecoxib should be reduced by 50%.
F’ pazjenti FAP b’ indeboliment moderat tal - fwied (albumina fis- serum ta ’ 25- 35 g / l), id- doża ta ’ kuljum rakkomandata ta ’ celecoxib għandha titnaqqas b’ 50%.
Patients with severe hepatic impairment (serum albumin < 25 g/ l) have not been studied and celecoxib is contraindicated in this patient group.
Pazjenti b’ indeboliment tal- fwied serju ħafna (albumina fis- serum < 25 gramma / litru) ma ġewx studjati u celecoxib huwa kontra- indikat f’ dan il- grupp ta ’ pazjenti.
The pharmacokinetics of celecoxib has not been studied in patients with renal impairment but is unlikely to be markedly changed in these patients since it is mainly eliminated by hepatic metabolism.
Il- farmakokinetika ta ’ celecoxib ma ġietx studjata f’ pazjenti b’ indeboliment tal- kliewi iżda mhux probabbli li jkun hemm tibdil markat f’ dawn il- pazjent minħabba li jiġi eliminat primarjament bil - metaboliżmu tal- fwied.