qanastek/EMEA-V3 huggingface dataset:
3 PHARMACEUTICAL FORM
ZALU FORMA
Capsule, hard.
Cietas kapsulas.
Opaque, white with two blue bands marked 7767 and 100 (INVENTED NAME 100 mg).
Necaurspidigas, baltas kapsulas ar zilu apmali, uz tam markejums 7767 un 100 (IZGUDROTAIS NOSAUKUMS 100 mg).
Opaque, white with two gold bands marked 7767 and 200 (INVENTED NAME 200 mg).
Necaurspidigas, baltas kapsulas ar zeltitu apmali, uz tam markejums 7767 un 200 (IZGUDROTAIS NOSAUKUMS 200 mg).
4 CLINICAL PARTICULARS
KLINISKA INFORMACIJA
4.1 Therapeutic indications Symptomatic relief in the treatment of osteoarthritis or rheumatoid arthritis.
Osteoartrita un reimatoida artrita radita iekaisuma un sapju simptomatiska terapija.
The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of the individual patient's overall risks (see sections 4.3, 4.4).
Lemums par selektivo COX- 2 inhibitoru ordinešanu japienem, izvertejot visparejo risku katram pacientam individuali (skatit apakšpunktus 4. 3 un 4. 4).
4.2 Posology and method of administration As the cardiovascular risks of celecoxib may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used.
Ta ka celekoksiba kardiovaskula rais risks var palielinaties, pieaugot devai un iedarbibas laikam, terapijas laikam jabut pec iespejas isakam un jalieto mazaka efektiva deva.
The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically, especially in patients with osteoarthritis (4.3, 4.4, 4.8 and 5.1).
Pacientiem, ipaši ar osteoartritu, periodiski jaizverte simptomu noveršanas nepieciešamiba un atbildes reakcija uz terapiju (skatit apakšpunktus 4. 3, 4. 4, 4. 8 un 5. 1).
Osteoarthritis:
Osteoartrits:
The usual recommended daily dose is 200 mg taken once daily or in two divided doses.
Parasta ieteicama dienas deva ir 200 mg, kas ienemama viena reize vai dalita divam ienemšanas reizem.
In some patients, with insufficient relief from symptoms, an increased dose of 200 mg twice daily may increase efficacy.
Dažiem pacientiem ar nepietiekošu simptomu zudumu devas palielinašana 200 mg divas reizes diena var paaugstinat terapijas efektivitati.
In the absence of an increase in therapeutic benefit after two weeks, other therapeutic options should be considered.
Ja arstešana nedod terapeitisku ieguvumu divu nedelu laika, tad ir jaapsver citas terapijas iespejas.
Rheumatoid arthritis:
Reimatoidais artrits:
The initial recommended daily dose is 200 mg taken in two divided doses.
Sakuma ieteicama dienas deva ir 200 mg, ko sadala divam ienemšanas reizem.
The dose may, if needed, later be increased to 200 mg twice daily.
Ja nepieciešama, devu velak var palielinat lidz 200 mg divas reizes diena.
The maximum recommended daily dose is 400 mg for both indications.
Maksimala ieteicama dienas deva abu indikaciju gadijumos ir 400 mg.
{Invented name}may be taken with or without food.
{Izgudrotais nosaukums} var ienemt ešanas laika vai starp edienreizem.
Elderly > 65 years:
20 Gados vecaki cilveki (> 65 gadi):
As in younger adults, 200 mg per day should be used initially.
Tapat ka jaunakiem pieaugušajiem, sakuma jalieto 200 mg diena.
(See 4.4 and 5.2).
Ipaša uzmaniba ir javelta gados vecakiem pacientiem, kuru kermena masa ir zem par 50 kg (skatit apakšpunktus 4. 4 un 5. 2).
Hepatic impairment:
Aknu darbibas traucejumi:
Treatment should be initiated at half the recommended dose in patients with established moderate liver impairment with a serum albumin of 25-35 g/ l.
Pacientiem ar mereni izteiktiem aknu funkciju traucejumiem (albumins seruma 25- 35 g/ l) arstešana jauzsak ar pusi no ieteicamas devas.
Experience in such patients is limited to cirrhotic patients (See 4.3, 4.4 and 5.2).
4. 3., 4. 4. un 5. 2.).
20 Renal impairment:
Nieru darbibas traucejumi:
Experience with celecoxib in patients with mild or moderate renal impairment is limited, therefore such patients should be treated with caution.
Pieredze celekoksiba lietošana pacientiem ar maz izteiktiem vai mereni izteiktiem nieru funkciju traucejumiem ir ierobežota, tadel šadi pacienti arstejami piesardzigi.
(See 4.3, 4.4 and 5.2).
4. 3., 4. 4. un 5. 2.)
Children:
Berni:
Celecoxib is not indicated for use in children.
Celekoksibs berniem nav indicets.
4.3 Contraindications History of hypersensitivity to the active substance or to any of the excipients (see 6.1).
Anamneze paaugstinats jutigums pret aktivo vielu vai jebkuru no paligvielam (skatit apakšpunktu 6. 1).
Known hypersensitivity to sulphonamides.
Zinama paaugstinata jutiba pret sulfanilamidiem.
Active peptic ulceration or gastrointestinal (GI) bleeding.
Aktiva peptiska ulceracija vai gastrointestinala (GI) asinošana.
Patients who have experienced asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic-type reactions after taking acetylsalicylic acid or NSAIDs including COX-2 (cyclooxygenase-2) inhibitors.
Pacienti, kuriem pec acetilsalicilskabes vai nesteroida pretiekaisuma lidzekla (NSPIL), tai skaita COX- 2 (ciklooksigenazes- 2) inhibitora ienemšanas radusies astma, akuts rinits, deguna polipi, angioneirotiska tuska, natrene vai cita alergiska tipa reakcija.
In pregnancy and in women of childbearing potential unless using an effective method of contraception (See 4.5).
Grutnieciba un sievietes, kuram var iestaties grutnieciba, ja vien tas nelieto efektivu kontracepcijas metodi (skatit apakšpunktu 4. 5).
Celecoxib has been shown to cause malformations in the two animal species studied (See 4.6 and 5.3).
Petijumos ar divu sugu dzivniekiem pieradits, ka celekoksibs šiem dzivniekiem izraisa malformacijas (skatit apakšpunktus 4. 6 un 5. 3).
The potential for human risk in pregnancy is unknown, but cannot be excluded.
Riska potencials attieciba uz grutniecibu cilvekam nav zinams, tacu izslegt to nevar.
Breast feeding (See 4.6 and 5.3).
Berna zidišana (skatit apakšpunktus 4. 6 un 5. 3).
Severe hepatic dysfunction (serum albumin < 25 g/ l or Child-Pugh score ≥ 10).
Smaga aknu slimiba (seruma albumins < 25 g/ l vai Child- Pugh > 10).
Patients with estimated creatinine clearance < 30 ml/ min.
Pacienti, kuriem konstatets kreatinina klirens < 30 ml/ min.
Inflammatory bowel disease.
Iekaisiga zarnu slimiba.
Congestive heart failure (NYHA II-IV).
Sastreguma sirds mazspeja (NYHA II- IV).
Established ischaemic heart disease, peripheral arterial disease and/ or cerebrovascular disease.
Zinama sirds išemiska slimiba, perifero arteriju slimiba un/ vai cerebrovaskulara slimiba.
4.4 Special warnings and special precautions for use Upper gastrointestinal complications [perforations, ulcers or bleedings (PUBs)], some of them resulting in fatal outcome, have occurred in patients treated with celecoxib.
Ar celekoksibu arstetiem pacientiem noverotas gastrointestinala trakta augšejas dalas komplikacijas [perforacija, ulceracija vai asinošana (PUA)], daži gadijumi beigušies ar fatalu iznakumu.
Caution is advised with treatment of patients most at risk of developing a gastrointestinal complication with NSAIDs; the elderly, patients using any other NSAID or acetylsalicylic acid concomitantly or patients with a prior history of gastrointestinal disease, such as ulceration and GI bleeding.
Jaievero piesardziba, arstejot pacientus, kam pastav seviški augsts NSPIL izraisitu gastrointestinalo komplikaciju risks, tie ir: gados vecaki cilveki, pacienti, kuri vienlaikus lieto kadus citus NSPIL vai acetilsalicilskabi, ka ari pacienti ar gastrointestinalu ulceraciju un GI asinošanu anamneze.
There is further increase in the risk of gastrointestinal adverse effects for celecoxib (gastrointestinal ulceration or other gastrointestinal complications), when celecoxib is taken concomitantly with acetylsalicylic acid (even at low doses).
Tiek veicinats gastrointestinalo blakusparadibu paaugstinats risks (gastrointestinala culas slimiba vai citas gastrointestinalas komplikacijas), ja celekoksibu, lieto kombinacija ar acetilsalicilskabi (pat mazas devas).
A significant difference in GI safety between selective COX-2 inhibitors + acetylsalicylic acid vs.
Ilgtermina kliniskos petijumos nav ieguti rezultati, kas apliecinatu butisku atškiribu gastrointestinalas drošibas zina
NSAIDs + acetylsalicylic acid has not been demonstrated in long- term clinical trials (see 5.1).
21 lietojot selektivos COX- 2 inhibitorus + acetilsalicilskabi salidzinajuma ar NSPL + acetilsalicilskabe (skatit apakšpunktu 5. 1).
Increased number of serious cardiovascular events, mainly myocardial infarction, has been found in a long-term placebo-controlled study in subjects with sporadic adenomatous polyps treated with celecoxib at doses of 200mg BID and 400mg BID compared to placebo (see 5.1).
Ilgtermina placebo- kontroleta petijuma sporadiskas adenomatozas polipozes pacientiem, lietojot celekoksibu 200 mg divas reizes diena un 400 mg divas reizes diena, konstateja paaugstinatu nopietnu kardiovaskularo notikumu, galvenokart miokarda infarktu, skaitu salidzinajuma ar placebo (skatit 5. 1).
As the cardiovascular risks of celecoxib may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used.
Ta ka celekoksiba kardiovaskularais risks var pieaugt saistiba ar devas un iedarbibas ilguma pieaugumu, tad ir jalieto zemaka efektiva dienas deva pec iespejas isaku laiku.
The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically, especially in patients with osteoarthritis (4.2, 4.3, 4.8 and 5.1).
Periodiski arstešanas gaita, ipaši pacientiem ar osteoartritu, ir janoverte nepieciešamiba pacientam mazinat slimibas simptomus, ka ari reakcija uz terapiju (skatit apakšpunktus 4. 2, 4. 3, 4. 8 un 5. 1).
Patients with significant risk factors for cardiovascular events (e. g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with celecoxib after careful consideration (see 5.1).
Pacientus ar nozimigiem kardiovaskulariem riska faktoriem (piemeram, hipertensija, hiperlipidemija, cukura diabets, smekešana) celekoksibu var ordinet tikai pec rupigas apsveršanas (skatit apakšpunktu 5. 1).
COX-2 selective inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular
COX- 2 selektivos inhibitorus nevar izmantot acetilsalicilskabes vieta kardiovaskularas trombembolijas profilaksei, jo tiem nepiemit antitrombotiskais efekts.
Therefore, antiplatelet therapies should not be discontinued (see section 5.1).
Tadel antitrombocitara terapija nav japartrauc (skatit apakšpunktu 5. 1).
As with other drugs known to inhibit prostaglandin synthesis fluid retention and oedema have been observed in patients taking celecoxib.
Tapat ka ar citiem preparatiem, kas inhibe prostaglandinu sintezi, pacientiem, kuri lieto celekoksibu, noverota škidruma aizture un tuska.
Therefore, celecoxib should be used with caution in patients with history of cardiac failure, left ventricular dysfunction or hypertension, and in patients with pre-existing oedema from any other reason, since prostaglandin inhibition may result in deterioration of renal function and fluid retention.
Ši iemesla del celekoksibs lietojams piesardzigi pacientiem, kuriem anamneze ir sirds mazspeja, kreisa ventrikula disfunkcija vai hipertensija, ka ari pacientiem, kuriem ir jel kadas citas izcelsmes tuska, jo prostaglandinu inhibicijas rezultata var pavajinaties nieru funkcija un rasties škidruma retence.
Caution is also required in patients taking diuretic treatment or otherwise at risk of hypovolaemia.
Piesardziba nepieciešama ari tad, ja preparatu lieto pacientiem, kuri sanem diuretisku terapiju vai cita iemesla del paklauti hipovolemijas riskam.
Compromised renal or hepatic function and especially cardiac dysfunction are more likely in the elderly and therefore medically appropriate supervision should be maintained.
Nieru vai aknu un ipaši sirds funkciju ierobežojums biežak ir gados vecakiem cilvekiem, un mineto iemeslu del nepieciešama pienaciga mediciniska uzraudziba.
Clinical trials with celecoxib have shown renal effects similar to those observed with comparator NSAIDs.
Celekoksiba kliniskie petijumi pieradijuši, ka iedarbiba uz nierem ir vienada ka salidzinošiem NSPIL.
If during treatment, patients deteriorate in any of the organ system functions described above, appropriate measures should be taken and discontinuation of celecoxib therapy should be considered.
Ja arstešanas laika pacientam novero jebkuras augstak minetas organu sistemas funkcijas pasliktinašanos, tad ir attiecigi jarikojas un jaapsver iespeja partraukt terapiju ar celekoksibu.
Celecoxib inhibits CYP2D6.
Celekoksibs inhibe CYP2D6.
Although it is not a strong inhibitor of this enzyme, a dose reduction may be necessary for individually dose-titrated drugs that are metabolised by CYP2D6 (See 4.5).
Lai gan tas nav specigs ši enzima inhibitors, tomer var rasties nepieciešamiba reducet individuali pielagoto devu preparatiem, kurus metabolize CYP2D6 (skatit apakšpunktu 4. 5).
Patients known to be CYP2C9 poor metabolisers should be treated with caution (see 5.2.).
Pacienti, kuriem ir pavajinata CYP 2C9 aktivitate, jaarste seviški piesardzigi (skatit apakšpunktu 5. 2).
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use ofcelecoxib (see 4.8).
Sanemti loti reti zinojumi par nopietnam adas reakcijam, dažas no tam fatalas, tostarp, eksfoliativu dermatitu, Stivensa- Džonsona sindromu un toksisko epidermalo nekrolizi pacientiem, kuri lietoja celekoksibu (skatit apakšpunktu 4. 8).
Patients appear to be at highest risk for these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment.
Paaugstinatu šo reakciju risku pacientiem parasti novero terapijas kursa sakuma: lielakaja dala gadijumu reakcijas sakas terapijas pirmaja menesi.
Serious hypersensitivity reactions (anaphylaxis and angioedema) have been reported in patients receiving celecoxib (see 4.8).
Lietojot celekoksibu, tika zinots par smagam hipersensitivitates reakcijam (anafilaksi un angioneirotisko tusku) (skatit apakšpunktu 4. 8).
Patients with a history of sulphonamide allergy or any drug allergy may be at greater risk of serious skin reactions or hypersensitivity reactions (see 4.3).
Lielaks nopietnu adas reakciju vai hipersensivitates risks ir pacientiem, kuru anamneze ir alergija pret sulfanilamidiem vai jebkuram citam zalem (skatit apakšpunktu 4. 3).
Celecoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Celekoksiba lietošana japartrauc tiklidz uz adas paradas pirmie izsitumi, glotadas bojajumi vai jebkadas citas paaugstinatas jutibas pazimes.
Celecoxib may mask fever and other signs of inflammation.
Celekoksibs var masket drudzi un citas iekaisuma pazimes.
In patients on concurrent therapy with warfarin, serious bleeding events have occurred.
Pacientiem, kuri vienlaikus sanemuši terapiju ar varfarinu, noverotas smagu asinošanu epizodes.
Caution should be exercised when combining celecoxib with warfarin and other oral anticoagulants (See 4.5).
Jaievero piesardziba, celekoksibu kombinejot ar varfarinu vai citiem peroraliem antikoagulantiem (skatit apakšpunktu 4. 5).
{Invented Name}100 mg and 200 mg capsules contain lactose (149.7 mg and 49.8 mg, respectively).
22 {Izgudrotais nosaukums} 100 mg un 200 mg kapsulas satur laktozi (attiecigi 149, 7 mg un 49, 8 mg).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose- galactose malabsorption should not take this medicine.
Šis zales nevajadzetu lietot pacientiem ar retu iedzimtu galaktozes nepanesibu, ar Lapp laktazes deficitu vai glikozes- galaktozes malabsorbciju.
4.5 Interaction with other medicinal products and other forms of interaction Pharmacodynamic interactions Anticoagulant activity should be monitored particularly in the first few days after initiating or changing the dose of celecoxib in patients receiving warfarin or other anticoagulants since these patients have an increased risk of bleeding complications.
Farmakodinamiska mijiedarbiba Pacientiem, kuri lidztekus lieto varfarinu vai citus antikoagulantus, jakontrole antikoagulejošas terapijas efekts, it ipaši sakot arstešanos ar celekoksibu vai mainot ta devu, jo šiem pacientiem ir paaugstinats hemoragisku komplikaciju risks.
Bleeding events in association with increases in prothrombin time have been reported, predominantly in the elderly, in patients receiving celecoxib concurrently with warfarin, some of them fatal.
Zinots par asinošanas epizodem saistiba ar protrombina laika pieaugumu pacientiem, parsvara gados vecakiem cilvekiem, kuri celekoksibu sanemuši lidztekus varfarinam, dažas no tam fatalas.
NSAIDs may reduce the effect of diuretics and antihypertensive medicinal products.
NSPL var mazinat diuretisko lidzeklu un antihipertensivo zalu efektivitati.
As for NSAIDs, the risk of acute renal insufficiency, which is usually reversible, may be increased in some patients with compromised renal function (e. g. dehydrated patients or elderly patients)when ACE inhibitors or angiotensin II receptor antagonists are combined with NSAIDs, including celecoxib.
Dažiem pacientiem ar traucetu nieru funkciju (piemeram, dehidratetiem vai gados vecakiem pacientiem), lietojot NSPL, tai skaita celekoksibu, kombinacija ar AKE inhibitoriem vai angiotensina II receptoru antagonistiem, var but paaugstinats akutas nieru mazspejas risks, kas parasti ir atgriezenisks.
Therefore, the combination should be administered with caution, especially in the elderly.
Tapec ši kombinacija ir ordinejama piesardzigi, ipaši pacientiem gados.
Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.
Pacientiem ir jasanem adekvata hidratacija, jaapsver nieru funkciju monitorešana uzsakot paralelo terapiju, ka ari periodiski tas gaita.
22 Coadministration of NSAIDs and cyclosporin or tacrolimus have been suggested to increase the nephrotoxic effect of cyclosporin and tacrolimus.
Pastav noradijumi, ka NSPIL ievadišana kopa ar ciklosporiniem vai takrolimu pastiprina ciklosporinu un takrolima nefrotoksisko efektu.
Renal function should be monitored when celecoxib and any of these drugs are combined.
Ja celekoksibs tiek kombinets ar kadu no šiem preparatiem, jaseko nieru funkcijai.
Celecoxib can be used with low-dose acetylsalicylic acid but is not a substitute for acetylsalicylic acid for cardiovascular prophylaxis.
Celekoksibu var lietot ar zemu devu acetilsalicilskabi, bet tas nav acetilsalicilskabes aizstajejs kardiovaskularai profilaksei.
In the submitted studies, 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 5.1).
Pec petijumu datiem, tapat ka citu NSPIL lietošanas gadijumos tad, ja celekoksibu lieto kombinacija ar mazam acetilsalicilskabes devam, gastrointestinalas ulceracijas un citu gastrointestinalo komplikaciju risks ir lielaks neka tad, ja celekoksibu lieto vienu pašu (skatit apakšpunktu 5. 1).
Pharmacokinetic interactions
Farmakokinetiska mijiedarbiba
Effects of celecoxib on other drugs Celecoxib is an inhibitor of CYP2D6.
Celekoksibs ir CYP2D6 inhibitors.
During celecoxib treatment, the plasma concentrations of the CYP2D6 substrate dextromethorphan were increased by 136%.
Celekoksiba terapijas laika CYP2D6 substrata dekstrometorfana koncentracija plazma pieauga par 136%.
The plasma concentrations of drugs that are substrates of this enzyme may be increased when celecoxib is used concomitantly.
Ja celekoksibs tiek lietots vienlaikus ar preparatiem, kas ir ši enzima substrati, to koncentracija plazma var but paaugstinata.
Examples of drugs which are metabolised by CYP2D6 are antidepressants (tricyclics and SSRIs), neuroleptics, anti- arrhythmic drugs, etc.
Preparati, kurus metabolize CYP2D6, ir, piemeram, antidepresanti (tricikliskie antidepresanti un selektivie serotonina atpakalsaistišanas inhibitori), neiroleptiskie lidzekli, antiaritmiskie preparati u. c.
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.
CYP2D6 substrata individuali noteikto devu var nakties samazinat, kad tiek sakta terapija ar celekoksibu, vai palielinat, ja terapija ar celekoksibu tiek partraukta.
In vitro studies have shown some potential for celecoxib to inhibit CYP2C19 catalysed metabolism.
Petijumos in vitro konstatets, ka celekoksibam piemit zinama speja inhibet CYP2C19 katalizeto metabolismu.
The clinical significance of this in vitro finding is unknown.
Šis in vitro atrades kliniska nozime nav zinama.
Examples of drugs which are metabolised by CYP2C19 are diazepam, citalopram and imipramine.
Preparati, kurus metabolize CYP2C19, ir, piemeram, diazepams, citaloprams un imipramins.
In an interaction study, celecoxib had no clinically relevant effects on the pharmacokinetics of oral contraceptives (1 mg norethistherone / 35 microg ethinylestradiol).
Mijiedarbibas petijuma celekoksibam nebija kliniski nozimiga efekta uz iekškigi lietojamo kontraceptivo lidzeklu (1 mg noretisterons/ 35 mikrogrami etinilestradiols) farmakokinetiku.
Celecoxib does not affect the pharmacokinetics of tolbutamide (CYP2C9 substrate), or glibenclamide to a clinically relevant extent.
Celekoksibam nav kliniski nozimigas ietekmes uz tolbutamida (CYP2D9 substrats) vai glibenklamida farmakokinetiku.
In patients with rheumatoid arthritis celecoxib had no statistically significant effect on the pharmacokinetics (plasma or renal clearance) of methotrexate (in rheumatologic doses).
23 Pacientiem ar reimatoido artritu celekoksibs neradija statistiski butisku ietekmi (plazmas vai nieru klirenss) uz metotreksata (lietojot reimatologiskas devas) farmakokinetiku.
However, adequate monitoring for methotrexate-related toxicity should be considered when combining these two drugs.
Tomer, butu javeic adekvats metotreksata saistitas toksicitates monitorings, kad šis zales lieto kombinacija.
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.
Veseliem subjektiem celekoksiba 200 mg divas reizes diena lidztekus lietošana ar litiju 450 mg divas reizes diena, radija litija videji Cmax 16% un AUC 18% pieaugumu.
Therefore, patients on lithium treatment should be closely monitored when celecoxib is introduced or withdrawn.
Tadel, pacienti, kas lieto litiju butu cieši janovero, kad uzsak vai beidz celekoksiba lietošanu.
Effects of other drugs on celecoxib
Citu preparatu ietekme uz celekoksibu
Since celecoxib is predominantly metabolised by CYP2C9 it should be used at half the recommended dose in patients receiving fluconazole.
Ta ka celekoksibu galvenokart metabolize CYP2C9, pacientiem, kuri vienlaikus sanem flukonazolu, to butu jalieto pusi no ieteicamas devas.
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%.
Celekoksiba (atseviškas 200 mg lielas devas) un CYP2C9 inhibitora flukonazola (200 mg reizi diena) vienlaiciga lietošana izraisija celekoksiba Cmax 60% un AUC 130% pieaugumu.
Concomitant use of inducers of CYP2C9 such as rifampicin, carbamazepine and barbiturates may reduce plasma concentrations of celecoxib.
Lidztekus lietoti CYP2C9 inducetaji, ka rifampicins, karbamazepins un barbiturati, var pazeminat celekoksiba koncentraciju plazma.
Ketoconazole or antacids have not been observed to affect the pharmacokinetics of celecoxib.
Nav noverots, ka ketokonazols vai antacidie lidzekli ietekmetu celekoksiba farmakokinetiku.
4.6 Pregnancy and lactation No clinical data on exposed pregnancies are available for celecoxib.
Nav pieejami nekadi kliniskie dati par ekspoziciju celekoksibam grutniecibas laika.
Studies in animals (rats and rabbits) have shown reproductive toxicity, including malformations (see 4.3 and 5.3).
Petijumos ar dzivniekiem (žurkam un trušiem) konstatets reproduktivs toksiskums, tai skaita malformacijas (skatit apakšpunktus 4. 3 un 5. 3).
The potential for human risk in pregnancy is unknown, but cannot be excluded.
Potencialais risks cilvekam grutniecibas laika nav zinams, tacu izslegt to nevar.
Celecoxib, as with other drugs inhibiting prostaglandin synthesis, may cause uterine inertia and premature closure of the ductus arteriosus during the last trimester.
Celekoksibs tapat ka citi prostaglandinu sintezi kavetaji medikamenti var izraisit dzemdibu darbibas vajumu un ductus arteriosus priekšlaicigu slegšanos pedeja trimestri.
Celecoxib is contraindicated in pregnancy and in women who can become pregnant (see 4.3 and 4.4).
Celekoksibs ir kontrindicets grutniecibas laika un sievietem, kuram iespejama grutniecibas iestašanas (skatit apakšpunktus 4. 3 un 4. 4).
If a woman becomes pregnant during treatment, celecoxib should be discontinued.
Ja grutnieciba iestajas arstešanas laika, celekoksiba lietošana japartrauc.
23 There are no studies on the excretion of celecoxib in human milk.
Par celekoksiba ekskreciju mates piena petijumu nav.
Celecoxib is excreted in the milk of lactating rats at concentrations similar to those in plasma.
Celekoksibs izdalas zidošu žurku matišu piena tada paša koncentracija, kada tas ir plazma.
Women who take celecoxib should not breastfeed.
Sievietes, kuras lieto celekoksibu, nedrikst zidit bernu.
4.7 Effects on ability to drive and use machines Patients who experience dizziness, vertigo or somnolence while taking celecoxib should refrain from driving or operating machinery.
Pacientiem, kuri celekoksiba lietošanas laika jut apreibumu, reiboni vai miegainibu, jaatturas no transportlidzekla vadišanas vai mehanismu apkalpošanas.
4.8 Undesirable effects Approximately 7400 patients were treated with celecoxib in controlled trials and of those approximately 2300 have received it for 1 year or longer.
Kontroletos petijumos aptuveni 7400 pacientu tikuši arsteti ar celekoksibu un no tiem aptuveni 2300 to lietojuši 1 gadu vai ilgak.
The following events have been reported in patients receiving celecoxib in 12 placebo and/ or active controlled trials.
Sekojošas blakusparadibas zinotas no pacientiem, kuri lietojuši celekoksibu 12 placebo un/ vai aktivi kontroletos petijumos.
Side-effects listed have a rate equal or greater than placebo, and the discontinuation rate due to side effects was 7.1% in patients receiving celecoxib and 6.1% in patients receiving placebo.
Uzskaitito blakusparadibu biežums ir vienads vai lielaks par placebo grupa sastopamo blakusparadibu biežumu, del blakusparadibam partrauktas terapijas biežums bija 7, 1% pacientiem, kuri lietoja celekoksibu un 6, 1% pacientu, kuri sanema placebo.
Additional reactions reported from post-marketing experience in > 70 million treated patients include headache, nausea and arthralgia, and the reactions included as very rare, in italics in the list below.
Ieklautas papildus blakusparadibas no pecregistracijas uzraudziba sanemtiem zinojumiem, ieskaitot galvassapes, sliktu dušu un artralgiju un ieskaitot loti retas blakusparadibas, kas uzskaititas zemak kursiva, no > 70 miljoniem arstetu pacientu.
[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 including isolated cases)]
Loti bieži (> 1/ 10), bieži (> 1/ 100, < 1/ 10), retak (> 1/ 1000, < 1/ 100), reti (> 1/ 10000, < 1/ 1000), loti reti (< 1/ 10000, ieskaitot atseviškus gadijumus).
Infections and infestations Common: sinusitis, upper respiratory tract infection Uncommon: urinary tract infection
Infekcijas un parazitozes Bieži: sinusits, augšeja elpošanas trakta infekcijas
Blood and the lymphatic system disorders Uncommon: anaemia Rare: leucopenia, thrombocytopenia Very rare: pancytopenia.
24 Retak: urintrakta infekcijas
Immune system disorders:
Asins un limfatiskas sistemas traucejumi Retak: anemija Reti: leikopenija, trombocitopenija Loti reti: pancitopenija
Very rare: serious allergic reactions, anaphylactic shock
Imunas sistemas traucejumi Loti reti: nopietnas alergiskas reakcijas, anafilaktiskais šoks
Metabolism and nutrition disorders Uncommon: hyperkalaemia
Metabolisma un barošanas traucejumi Retak: hiperkaliemija
Psychiatric disorders Common: insomnia Uncommon: anxiety, depression, tiredness Very rare: confusion, hallucinations.
Psihiskie traucejumi Bieži: bezmiegs Retak: nemiers, depresija, nogurums Loti reti: apjukums, halucinacijas
Nervous system disorders Common: dizziness Uncommon: blurred vision, hypertonia, paraesthesia Rare: ataxia, taste alteration Very rare: aggravated epilepsy, meningitis aseptic, ageusia, anosmia
Nervu sistemas traucejumi Bieži: reibonis Retak: neskaidra redze, hipertonija, parestezija Reti: ataksija, garšas izmainas Loti reti: epilepsijas paasinajums, aseptisks meningits, ageuzija, anosmija
Ear and labyrinth disorders Uncommon: tinnitus Very rare: decreased hearing
Ausu un labirinta bojajumi Retak: tinnits Loti reti: dzirdes samazinašanas
Cardiac disorders Uncommon: myocardial infarction*, heart failure, palpitations
Sirds funkcijas traucejumi Retak: miokarda infarkts *, sirds mazspeja, sirdsklauves
Vascular disorders Uncommon: hypertension, hypertension aggravated
Asinsvadu sistemas traucejumi Retak: hipertensija, hipertensijas paasinajums Reti: išemisks insults * Loti reti: vaskulits
Respiratory, thoracic and mediastinal disorders Common: pharyngitis, rhinitis Uncommon: cough, dyspnoea Very rare: bronchospasm.
Respiratoras, krušu kurvja un videnes slimibas Bieži: faringits, rinits Retak: klepus, elpas trukums Loti reti: bronhospazma
Gastrointestinal disorders Common: abdominal pain, diarrhoea, dyspepsia, flatulence Uncommon: constipation, eructation, gastritis, stomatitis, vomiting, aggravation of gastrointestinal inflammation Rare: duodenal, gastricoesophageal, intestinal and colonic ulceration, dysphagia, intestinal perforation, oesophagitis, melaena Very rare: gastrointestinal haemorrhage, acute pancreatitis, colitis/ colitis aggravated.
Kunga- zarnu trakta traucejumi Bieži: sapes vedera, caureja, dispepsija, meteorisms Retak: aizcietejums, atraugas, gastrits, stomatits, vemšana, gastrointestinala iekaisuma paasinajums Reti: duodena, kunga, baribas vada, tievo zarnu un resnas zarnas ulceracija, disfagija, zarnu perforacija, ezofagits, melena Loti reti: gastrointestinala hemoragija, akuts pankreatits, kolits/ kolita paasinajums
Hepato-biliary disorders Uncommon: abnormal hepatic function Very rare: hepatitis, jaundice, hepatic failure.
Aknu un/ vai žultscelu traucejumi Retak: trauceta aknu funkcija Loti reti: hepatits, dzelte, aknu mazspeja
Skin and subcutaneous tissue disorders Common: rash Uncommon: urticaria Rare: alopecia, photosensitivity Very rare: angioedema, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, epidermal necrolysis,
25 Bieži: izsitumi Retak: natrene Reti: alopecija, fotosensitivitate Loti reti: angioedema, eksfoliatifs dermatits, multiforma eritema, Stivensa - Džonsona sindroms, epidermala nekrolize
Musculoskeletal and connective tissue disorders Uncommon: leg cramps Very rare: myositis
Skeleta- muskulu un saistaudu sistemas bojajumi Retak: krampji kajas Loti reti: miozits
Renal and urinary disorders Very rare: acute renal failure, interstitial nephritis
Nieru un urincelu traucejumi Loti reti: akuta nieru mazspeja, intersticials nefrits
Reproductive system and breast disorders Very rare: menstrual disorder NOS
Loti reti: menstruala cikla traucejumi (nespecifiski)
General disorders and administration site conditions Common: peripheral oedema/ fluid retention
Vispareji traucejumi un reakcijas ievadišanas vieta Bieži: perifera tuska / škidruma retence
Investigations Uncommon: increased SGOT and SGPT, increased creatinine, BUN increased
Izmeklejumi Retak: palielinats ALAT un ASAT, palielinats kreatinins, paaugstinats urinvielas slapeklis asinis (BUN)
*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.
* Divu nedelu lidz 1 gadam ilgu 20 placebo kontroleto petijumu kopeja analize, pacientiem ar osteoartritu un reimatoido artritu, kurus arsteja ar celekoksibu 200 mg vai 400 mg diena, miokarda infarkts bija 0, 7 gadijumos uz 1000 pacientiem (Reti), kas ir vairak neka placebo, bet insultu skaits nebija lielaks.
In preliminary data from two studies in patients with colorectal polyps treated with celecoxib 400 mg daily (see Section 5.1) the excess rate over placebo of myocardial infarction over 3 years was 7 events per 1000 patients (Uncommon).
Preliminarie dati no diviem petijumiem, kuros pacienti ar kolorektaliem polipiem, kurus arsteja ar celekoksibu 400 mg diena (skatit apakšpunktu 5. 1), miokarda infarkts 3 gados bija 7 gadijumi uz 1000 pacientiem, kas ir vairak neka placebo (Retak).
In the same studies, the excess rate for clearly identified ischaemic stroke for the 400 mg daily dose (not including events that were haemorrhagic or of unknown aetiology) was 0.5 event per 1000 over 3 years (Rare).
Tajos pašos petijumos ilgakos par 3 gadiem lietojot 400 mg devu diena, skaidri identificets išemisks insults (netika ieklauti hemoragiski un nezinamas etiologijas gadijumi) bija 0, 5 gadijumos uz 1000 pacientiem (Reti).
For all strokes, there was no increased event rate with celecoxib compared with placebo.
Celekoksiba grupa salidzinot ar placebo nenoveroja palielinatu jebkadu insultu biežumu.
4.9 Overdose There is no clinical experience of overdose.
Attieciba uz pardozešanu kliniskas pieredzes nav.
Single doses up to 1200 mg and multiple doses up to 1200
Veseliem cilvekiem viena atseviška lidz 1200 mg liela deva un atkartotas lidz 1200 mg lielas devas divas reizes diena devinas dienas pec kartas kliniski nozimigus nelabveligus efektus neradija.
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.
Ja iespejama pardozešana, javeic stavoklim atbilstoši mediciniskie pasakumi, piemeram, kunga satura evakuacija, kliniska noverošana un, ja nepieciešams simptomatiska terapija stacionara.
Dialysis is unlikely to be an efficient method of drug removal due to high protein binding.
Nav sagaidams, ka dialize bus efektiva metode preparata izvadišanai, jo tas liela mera ir saistijies pie proteiniem.
5 PHARMACOLOGICAL PROPERTIES
FARMAKOLOGISKAS IPAŠIBAS
5.1 Pharmacodynamic properties Pharmacotherapeutic group:
5. 1 Farmakodinamiskas ipašibas
ATC code:
Farmakoterapeitiska grupa:
M01AH01.
ATK kods – M01AH01.
Celecoxib is an oral, selective, cyclooxygenase-2 (COX-2) inhibitor within the clinical dose range (200-400 mg daily).
Celekoksibs ir perorali lietojams selektivs ciklooksigenazes- 2 (COX- 2) inhibitors, ar klinisko devu diapazonu (200- 400 mg diena).
No statistically significant inhibition of COX-1 (assessed as ex vivo inhibition of thromboxane B2 [TxB2] formation) was observed in this dose range in healthy volunteers.
Nekada statistiski nozimiga COX- 1 inhibicija (novertets pec tromboksana B2 [TxB2] veidošanas kavejuma ex vivo) šaja devu diapazona veseliem brivpratigajiem netika noverota.
Cyclooxygenase is responsible for generation of prostaglandins.
26 Ciklooksigenaze ir enzims, kas nepieciešams prostaglandinu sintezes procesa.
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.
Pieradits, ka enzima izoforma COX- 2 induce iekaisumu veicinošie faktori un tieši ta ir atbildiga par sapju, iekaisuma un drudža prostanoido mediatoru sintezi.
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 iesaistas ari ovulacijas, implantacijas un ductus arteriosus slegšanas procesos, ta piedalas nieru darbibas kontrole un centralas nervu sistemas funkcijas (induce drudzi, nodrošina sapju percepciju un kognitivo funkciju).
It may also play a role in ulcer healing.
Tai varetu but nozime ari culas sadzišanas procesa.
COX-2 has been identified in tissue around gastric ulcers in man but its relevance to ulcer healing has not been established.
Cilvekiem COX- 2 konstateta audos ap kunga culam, tacu tas saistiba ar culu dzišanu nav pieradita.
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.
Atškiribas dažu COX- 1 inhibejošo NSPIL un selektivo COX- 2 inhibitoru antitrombocitara aktivitate var but kliniski svarigas pacientiem ar trombembolisku komplikaciju risku.
COX-2 selective inhibitors reduce the formation of systemic (and therefore possibly endothelial) prostacyclin without affecting platelet thromboxane.
COX- 2 inhibitori nomac sistemiska (un tadejadi, iespejams, ari endoteliala) prostaciklina veidošanos, neietekmejot trombocitos esošo tromboksanu.
Celecoxib is a diaryl-substituted pyrazole, chemically similar to other non-arylamine sulfonamides (e. g. thiazides, furosemide) but differs from arylamine sulfonamides (e. g. sulfamethoxizole and other sulfonamide antibiotics).
Celekoksibs ir diaril- aizvietots pirazola atvasinajums, kas kimiski lidzigs citiem ne- arilaminetiem sulfanilamidiem (piemeram, tiazidiem, furosemidam), bet atškirigs no arilamina grupu saturošiem sulfanilamidiem (piemeram, sulfametoksizola un citiem sulfanilamidiem ar antibakterialu darbibu).
A dose dependent effect on TxB2 formation has been observed after high doses of celecoxib.
Pec lielam celekoksiba devam noverota no devas atkariga ietekme uz TxB2 veidošanos.
However, in healthy subjects, in small multiple dose studies with 600 mg BID (three times the highest recommended dose) celecoxib had no effect on platelet aggregation and bleeding time compared to placebo.
Tomer dažos nelielos multiplu devu petijumos veseliem subjektiem 600 mg celekoksiba divas reizes diena (tris reizes parsniedz maksimalo ieteicamo devu), salidzinajuma ar placebo neietekmeja ne trombocitu agregaciju, ne asinošanas laiku.
Several clinical studies have been performed confirming efficacy and safety in osteoarthritis and rheumatoid arthritis.
Veikti vairaki kliniskie petijumi, kuri apliecina iedarbigumu un drošumu osteoartrita un reimatoida artrita pacientiem.
Celecoxib was evaluated for the treatment of the inflammation and pain of OA of the knee and hip in approximately 4200 patients in placebo and active controlled trials of up to 12 weeks duration.
Placebo un aktivi kontroletos lidz 12 nedelu ilgos petijumos celekoksibs tika lietots cela un gužas osteoartrita iekaisuma un sapju gadijuma aptuveni 4200 pacientiem.
It was also evaluated for treatment of the inflammation and pain of RA in approximately 2100 patients in placebo and active controlled trials of up to 24 weeks duration.
Tas tika lietots ari placebo un aktivi kontroleta lidz 24 nedelu ilga petijuma reimatoida artrita iekaisuma un sapju terapija aptuveni 2100 pacientiem.
Celecoxib at daily doses of 200 mg – 400 mg provided pain relief within 24 hours of dosing.
Celekoksibs dienas deva 200 mg – 400 mg uzradija sapju atvieglojumu 24 stundas no devas ienemšanas briža.
Five randomised double-blind controlled studies have been conducted including scheduled upper gastrointestinal endoscopy in approximately 4500 patients free from initial ulceration (celecoxib doses from 50 mg-400 mg BID).
Veikti pieci randomizeti, dubultakli, kontroleti petijumi, ietverot kunga- zarnu trakta augšejas dalas planveida endoskopiju, kuros piedalijas ap 4500 pacientu bez culam sakumstavokli (celekoksiba devas bija no 50 lidz 400 mg divas reizes diena).
In twelve week endoscopy studies celecoxib (100-800 mg per day) was associated with a significantly lower risk of gastroduodenal ulcers compared with naproxen (1000 mg per day) and ibuprofen (2400 mg per day).
Divpadsmit nedelu endoskopiskos petijumos celekoksibs (100- 800 mg diena) tika saistits ar butiski zemaku gastroduodenalo culu risku salidzinajuma ar naproksenu (1000 mg diena) un ibuprofenu (2400 mg diena).
The data were inconsistent in comparison with diclofenac (150 mg per day).
Dati salidzinajuma ar diklofenaku (150 mg diena) bija pretrunigi.
In two of the 12-week studies the percentage of patients with endoscopic gastroduodenal ulceration were not significantly different between placebo and celecoxib 200 mg BID and 400 mg BID.
Divos 12- nedelu petijumos procentualais pacientu skaits ar endoskopiski konstatetam gastroduodenalam culam placebo grupa un celekoksiba grupas, lietojot 200 mg divas reizes diena un 400 mg divas reizes diena, bija bez butiskas atškiribas.
In a prospective long-term safety outcome study (6 to 15 month duration, CLASS study), 5,800 OA and 2,200 RA patients received celecoxib 400 mg BID (4-fold and 2-fold the recommended OA and RA doses, respectively), ibuprofen 800 mg TID or diclofenac 75 mg BID (both at therapeutic doses).
Perspektiva ilgtermina drošibas petijuma (6 lidz 15 menešu ilgs, CLASS petijums) 5800 osteoartrita un 2200 reimatoida artrita pacienti sanema 400 mg celekoksibu divas reizes diena (4- kartigi un 2- kartigi parsniedz attiecigi osteoartrita un reimatoida artrita ieteicamas devas), ibuprofenu 800 mg tris reizes diena vai diklofenaku 75 mg tris reizes diena (abi terapeitiskajas devas).
Twenty-two percent of enrolled patients took concomitant low-dose acetylsalicylic acid (≤ 325 mg/ day), 26 primarily for cardiovascular prophylaxis.
Divdesmit divi procenti ieklauto pacientu lidztekus sanema zemu devu acetilsalicilskabi (=325 mg/ diena), galvenokart kardiovaskularai profilaksei.
For the primary endpoint complicated ulcers (defined as gastrointestinal bleeding, perforation or obstruction) celecoxib was not significantly different than either ibuprofen or diclofenac individually.
Celekoksiba grupa primarais galapunkts – komplicetu culu (definetu ka gastrointestinala asinošana, perforacija vai obstrukcija) biežums butiski neatškiras no ibuprofena grupas vai diklofenaka grupas.
Also for the combined NSAID group there was no statically significant difference for complicated ulcers (relative risk 0,77, 95% CI 0.41-1.46, based on entire study duration).
Salidzinot ari ar kombinetu NSPIL grupu nebija statistiski ticamas atškiribas komplicetu culu biežuma (relativais risks 0, 77, 95% ticamibas intervals 0, 41 – 1, 46, balstits uz pilnu petijuma laiku).
For the combined endpoint, complicated and symptomatic ulcers, the incidence was significantly lower in the celecoxib group compared to the NSAID group, relative risk 0.66, 95% CI 0.45-0.97 but not between celecoxib and diclofenac.
Celekoksiba grupa kombinetais galapunkts – komplicetu un simptomatisku culu biežums, bija butiski zemaks salidzinot ar NSPIL grupu, relativais risks 0, 66, 95% ticamibas intervals 0, 45 – 0, 97, bet ne starp celekoksiba un diklofenaka grupam.
Those patients on celecoxib and concomitant low- dose acetylsalicylic acid experienced 4 fold higher rates of complicated ulcers as compared to those on celecoxib alone.
Tiem pacientiem, kuri lietoja lidztekus celekoksibu un acetilsalicilskabi zema deva, noveroja 4 reizes lielaku komplicetu culu sastopamibu neka tiem, kuri lietoja tikai celekoksibu.
The incidence of clinically significant decreases in haemoglobin (> 2 g/ dL), confirmed by repeat testing, was significantly lower in patients on celecoxib compared to the NSAID group, relative risk 0.29, 95% CI 0.17- 0.48.
Pacientiem celekoksiba grupa bija butiski zemaka kliniski nozimiga hemoglobina samazinašanas incidence, apstiprinata atkartotos merijumos, salidzinot ar NSPIL grupu, relativais risks 0, 29, 95% ticamibas intervals 0, 17 – 0, 48.
The significantly lower incidence of this event with celecoxib was maintained with or without acetylsalicylic acid use.
Šo gadijumu butiski zemaka sastopamiba tika noverota lietojot celekoksibu ar vai bez lidztekus acetilsalicilskabes lietošanu.
Ongoing Clinical Trials:
27 Kliniskie petijumi, kas turpinas:
Preliminary safety information from three long-term studies involving patients with Sporadic Adenomatous Polyps or who were predisposed to developing Alzheimer’ s disease treated with celecoxib is available.
Ir pieejama pirmatneja informacija par celekoksiba terapijas drošibu tris ilgermina petijumos pacientiem ar sporadiskiem adenomatoziem polipiem vai pacientiem, kuri predisponeti Alzheimer slimibas attistibai.
In one of the three studies, the APC (Prevention of Sporadic Colorectal Adenomas with Celecoxib), there was a dose-related increase in cardiovascular events (mainly myocardial infarction, MI) at celecoxib doses of 200 mg BID and 400 mg BID compared to placebo.
Viena no šiem tris petijumiem (sporadiskas kolorektalas adenomas profilakse ar celekoksibu), lietojot celekoksibu devas 200 mg divas reizes un 400 mg divas reizes diena salidzinajuma ar placebo, konstateja devas atkarigu kardiovaskularo notikumu (galvenokart miokarda infarkta – MI) pieaugumu.
The increased risk became apparent after approximately 1 year of treatment.
Riska pieaugums kluva acimredzams apmeram pec 1 gada terapijas.
The relative risk (RR) for the composite endpoint (cardiovascular death, MI or stroke) was 3.4 (95% CI 1.4 - 8.5) for the higher dose and 2.5 (95% CI 1.0 - 6.4) for the lower dose of celecoxib, compared to placebo.
Kombineta galamerka (kardiovaskulara nave, MI vai insults) relativais risks (RR) bija 3, 4 (95% ticamibas intervals 1, 4- 8, 5) celekoksiba lielakai devai un 2, 5 (95% ticamibas intervals 1, 0- 6, 4) mazakai devai, salidzinajuma ar placebo.
The absolute risk for the composite endpoint was 3.0% for the higher dose of celecoxib, 2.2% for the lower dose of celecoxib, and 0.9% for placebo.
Kombineta galamerka absolutais risks bija 3, 0% celekoksiba augstakajai devai, 2, 2% celekoksiba zemakajai devai un 0, 9% placebo.
Preliminary data from the other two long-term studies did not show a significantly increased cardiovascular risk with celecoxib 200mg BID and 400mg QD compared to placebo.
P irmatnejie dati no citiem diviem ilgtermina petijumiem neuzrada ticami paaugstinatu kardiovaskularo risku, lietojot celekoksibu 200 mg divas reizes un 400 mg vienu reizi, salidzinajuma ar placebo.
This information will be updated as final data become available.
Ši informacija tiks papildinata tiklidz bus pieejami gala rezultati.
5.2 Pharmacokinetic properties Celecoxib is well absorbed reaching peak plasma concentrations after approximately 2-3 hours.
Celekoksibs labi uzsucas, maksimalo koncentraciju plazma sasniedzot pec apmeram 2- 3 stundam.
Dosing with food (high fat meal) delays absorption by about 1 hour.
Preparata ienemšana kopa ar uzturu (treknas maltites laika) palenina ta absorbciju par apmeram 1 stundu.
Celecoxib is mainly eliminated by metabolism.
Celekoksiba eliminacija galvenokart notiek, tam metabolizejoties.
Less than 1% of the dose is excreted unchanged in urine.
Neizmainita forma ar urinu izdalas mazak par 1% no devas.
The inter-subject variability in the exposure of celecoxib is about 10-fold.
Celekoksiba ekspozicija dažadiem cilvekiem var atškirties par aptuveni 10 reizem.
Celecoxib exhibits dose- and time-independent pharmacokinetics in the therapeutic dose range.
Celekoksibam terapeitisko devu diapazona piemit no devas un la ika neatkariga farmakokinetika.
Plasma protein binding is about 97% at therapeutic plasma concentrations and the drug is not preferentially bound to erythrocytes.
Saistišanas ar plazmas olbaltumvielam pie terapeitiskam koncentracijam plazma ir ap 97%, un medikaments netiek parsvara piesaistits pie eritrocitiem.
Elimination half-life is 8-12 hours.
Pusizvadišanas periods ir 8- 12 stundas.
Steady state plasma concentrations are reached within 5 days of treatment.
Vienmerigas koncentracijas limenis plazma tiek sasniegts 5 terapijas dienu laika.
Pharmacological activity resides in the parent drug.
Farmakologiska aktivitate piemit neparveidotam savienojumam.