qanastek/EMEA-V3 huggingface dataset:
Experience in such patients is limited to cirrhotic patients (See 4.3, 4.4 and 5.2).
Truksta preparato vartojimo kepenu ciroze sergantiems pacientams patirties (žr.
20 Renal impairment:
Inkstu funkcijos sutrikimas.
Experience with celecoxib in patients with mild or moderate renal impairment is limited, therefore such patients should be treated with caution.
Rekomenduojama atsargiai celekoksibu gydyti pacientus, kuriems yra nesunkus ar vidutinio sunkumo inkstu funkcijos sutrikimas, nes stokojama tokiu ligoniu gydymo patirties (žr.
(See 4.3, 4.4 and 5.2).
4. 3, 4. 4 ir 5. 2 skyrius).
Celecoxib is not indicated for use in children.
Vaikams celekoksibo neskirti.
4.3 Contraindications History of hypersensitivity to the active substance or to any of the excipients (see 6.1).
6. 1 skyriu).
Known hypersensitivity to sulphonamides.
Padidejes jautrumas sulfonamidams.
Active peptic ulceration or gastrointestinal (GI) bleeding.
Aktyvi pepsine opa arba kraujavimas iš virškinimo trakto (VT).
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.
Astma, uminis rinitas, nosies polipai, angioneurozine edema, dilgeline arba kitokia alergine reakcija, kurios buvo pavartojus acetilsalicilo rugšties arba NVNU, iskaitant COX- 2 (ciklooksigenazes 2) inhibitorius.
In pregnancy and in women of childbearing potential unless using an effective method of contraception (See 4.5).
Preparato negalima vartoti ir vaisingo amžiaus moterims, nesinaudojancioms veiksmingu kontracepcijos metodu (žr.
Celecoxib has been shown to cause malformations in the two animal species studied (See 4.6 and 5.3).
4. 6 ir 5. 3 skyrius).
The potential for human risk in pregnancy is unknown, but cannot be excluded.
Galima rizika neštumo metu žmogui, nežinoma, bet jos negalima paneigti.
Breast feeding (See 4.6 and 5.3).
Žindymo laikotarpis (žr.
Severe hepatic dysfunction (serum albumin < 25 g/ l or Child-Pugh score ≥ 10).
Sunkus kepenu funkcijos sutrikimas (albumino koncentracija kraujo serume < 25 g/ l arba =10 balu pagal Child- Pugh).
Patients with estimated creatinine clearance < 30 ml/ min.
Kreatinino klirensas < 30 ml/ min.
Inflammatory bowel disease.
Stazinis širdies nepakankamumas (II- IV klases pagal NYHA).
Congestive heart failure (NYHA II-IV).
4. 4 Specialus ispejimai ir atsargumo priemones
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.
Celekoksiba vartojusiems pacientams nustatyta viršutines virškinimo trakto dalies komplikaciju kartais mirtinu (perforacijos, opos arba kraujavimas [POK]).
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.
Rekomenduojama atsargiai preparatu gydyti pacientus, kuriems vartojant NVNU gresia didesnis virškinimo trakto komplikaciju pavojus: senyviems žmonems, vartojantiems kartu kitu NVNU arba acetilsalicilo rugšti arba pacientams, kurie anksciau sirgo virškinimo trakto liga, pavyzdžiui, opalige arba VT kraujavimais.
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).
Celekoksiba vartojant kartu su acetilsalicilo rugštimi (net ir mažomis dozemis) dar labiau padideja nepageidaujamu reakciju (virškinimo trakto opu ar kitokiu virškinimo trakto komplikaciju) virškinimo trakte rizika.
NSAIDs + acetylsalicylic acid has not been demonstrated in long- term clinical trials (see 5.1).
5. 1 skyriu).
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).
Ilgalaikiu placebu kontroliuojamuju tyrimu duomenimis, 200 mg ir 400 mg celekoksibo doze du kartus per para vartojusiems asmenims, turejusiems pavieniu adenomatoziniu polipu, palyginti su
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).
5. 1 skyriu).
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).
Kadangi didinant celekoksibo doze ir vartojimo trukme gresia didesne širdies ir kraujagysliu sutrikimu rizika, reikia vartoti vaista kiek imanoma trumpiau ir mažiausia veiksminga paros doze.
COX-2 selective inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular
5. 1 skyriu).
21 thrombo-embolic diseases because of their lack of antiplatelet effects.
Selektyvuju COX- 2 inhibitoriu netinka vartoti vietoj acetilsalicilo rugšties širdies ir kraujagysliu trombemboliniu ligu profilaktikai, nes jie neveikia trombocitu funkcijos.
Therefore, antiplatelet therapies should not be discontinued (see section 5.1).
5. 1 skyriu).
As with other drugs known to inhibit prostaglandin synthesis fluid retention and oedema have been observed in patients taking celecoxib.
Organizme pacientu, vartojanciu celekoksiba, kaip ir kitu prostaglandinu sinteze slopinanciu preparatu, kaupiasi skysciai bei pasireiškia edema.
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.
Rekomenduojama atsargiai celekoksibu gydyti pacientus, kuriems yra širdies nepakankamumas, hipertenzija, sutrikusi kairiojo skilvelio veikla, bei tiems, kuriems edema atsirado del bet kuriu kitu priežasciu, nes slopinant prostaglandinu sinteze, gali sutrikti inkstu funkcija ir organizme kauptis skysciai.
Caution is also required in patients taking diuretic treatment or otherwise at risk of hypovolaemia.
Taip pat rekomenduojama atsargiai celekoksibu gydyti pacientus, kurie vartoja diuretiku, bei tuos, kuriems del kokiu nors priežasciu gresia hipovolemija.
Compromised renal or hepatic function and especially cardiac dysfunction are more likely in the elderly and therefore medically appropriate supervision should be maintained.
Rekomenduojama atidžiai tikrinti senyvu pacientu bukle, nes jiems gresia didesne inkstu, kepenu arba širdies veiklos sutrikimu rizika.
Clinical trials with celecoxib have shown renal effects similar to those observed with comparator NSAIDs.
Klinikiniu tyrimu duomenimis, celekoksibo poveikis inkstams panašus i lyginamojo NVNU.
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.
Jei gydymo metu pablogeja kurios nors anksciau minetos paciento organu sistemos funkcija, reikia imtis atitinkamu priemoniu ir apsvarstyti, ar reikia nutraukti celekoksibo vartojima.
Celecoxib inhibits CYP2D6.
Celekoksibas slopina 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).
4. 5 skyriu).
Patients known to be CYP2C9 poor metabolisers should be treated with caution (see 5.2.).
5. 2 skyriu).
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).
Saugumo tyrimu po vaistinio preparato registracijos duomenimis, pacientams, vartojusiems celekoksiba, labai retai pasireiške sunkiu, kartais mirtinu odos reakciju, iskaitant eksfoliacini dermatita, Stivenso ir Džonsono sindroma ir toksine epidermio nekrolize (žr.
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.
Gydymo pradžioje tokiu reakciju tikimybe pacientui didesne: daugeliu atveju reakcijos prasideda per pirmaji gydymo menesi.
Serious hypersensitivity reactions (anaphylaxis and angioedema) have been reported in patients receiving celecoxib (see 4.8).
4. 8 skyriu).
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).
4. 3 skyriu).
Celecoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Reikia nutraukti celekoksibo vartojima, vos tik pasireiškus pirmiesiems odos išberimo, gleivines pažeidimo ar kitiems padidejusio jautrumo požymiams.
Celecoxib may mask fever and other signs of inflammation.
Celekoksibas gali slepti karšciavima ir kitus uždegimo požymius.
In patients on concurrent therapy with warfarin, serious bleeding events have occurred.
Pacientams, kartu vartojusiems varfarino, buvo sunkiu kraujavimo atveju.
Caution should be exercised when combining celecoxib with warfarin and other oral anticoagulants (See 4.5).
4. 5 skyriu).
{Invented Name}100 mg and 200 mg capsules contain lactose (149.7 mg and 49.8 mg, respectively).
{Sugalvotas pavadinimas} 100 mg ir 200 mg kapsulese yra laktozes (atitinkamai 149, 7 mg ir 49, 8 mg).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose- galactose malabsorption should not take this medicine.
Pacientams, kuriems yra paveldimas gliukozes netoleravimas, Lapp laktazes stoka ar gliukozes ir galaktozes malabsorbcija, šio preparato vartoti negalima.
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.
23 Farmakodinamine saveika Rekomenduojama tirti, ypac pirmasias kelias dienas nuo gydymo celekoksibu pradžios, pacientu, kurie vartoja varfarina arba kitu antikoaguliantu, antikoaguliacini aktyvuma, nes padideja kraujavimo pavojus, bei keisti celekoksibo doze.
Therefore, patients receiving oral anticoagulants should be closely monitored for their prothrombin time INR, particularly in the first few days when therapy with celecoxib is initiated or the dose of celecoxib is changed (see 4.4).
4. 4 skyriu).
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.
Del ilgo protrombino laiko pacientams, ypac senyviems, kurie vartojo celekoksiba kartu su varfarinu, prasidejo kraujavimas, kartais pasibaiges mirtimi.
NSAIDs may reduce the effect of diuretics and antihypertensive medicinal products.
NVNU gali slopinti diuretiku ir antihipertenziniu vaistiniu preparatu poveiki.
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.
Kaip ir vartojant kitokiu NVNU, kai kuriems ligoniams, kuriu inkstu funkcija sutrikusi (pvz., daug skysciu netekusiems ar senyviems pacientams), NVNU, iskaitant celekoksiba, vartojant kartu su AKF inhibitoriais ar angiotenzino II receptoriu antagonistais gresia didesne uminio inkstu nepakankamumo, dažniausiai grižtamojo, rizika.
Therefore, the combination should be administered with caution, especially in the elderly.
Taigi, minetus preparatus vartoti kartu reikia atsargiai, ypac senyviems pacientams.
Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.
Pacientas turi vartoti pakankamai skysciu, butina nuolatos stebeti jo inkstu funkcija pradejus kartu vartoti minetus preparatus ir reguliariai tikrinti tesiant gydyma.
22 Coadministration of NSAIDs and cyclosporin or tacrolimus have been suggested to increase the nephrotoxic effect of cyclosporin and tacrolimus.
Vartojant NVNU kartu su ciklosporinu arba takrolimusu, dideja nefrotoksinis ciklosporino ir takrolimuso poveikis.
Renal function should be monitored when celecoxib and any of these drugs are combined.
Reikia tirti inkstu funkcija pacientams, kurie vartoja celekoksiba kartu su minetais preparatais.
Celecoxib can be used with low-dose acetylsalicylic acid but is not a substitute for acetylsalicylic acid for cardiovascular prophylaxis.
Celekoksiba galima vartoti kartu su maža acetilsalicilo rugšties doze, bet netinka ji vartoti vietoj acetilsalicilo rugšties širdies bei kraujagysliu sistemos sutrikimu profilaktikai.
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).
5. 1 skyriu).
Pharmacokinetic interactions
Farmakokinetine saveika
Effects of celecoxib on other drugs Celecoxib is an inhibitor of CYP2D6.
Celekoksibo poveikis kitiems vaistiniams preparatams Celekoksibas slopina CYP2D6.
During celecoxib treatment, the plasma concentrations of the CYP2D6 substrate dextromethorphan were increased by 136%.
Vartojant celekoksiba, CYP2D6 metabolizuojamo dekstrometorfano koncentracija kraujo plazmoje padideja 136%.
The plasma concentrations of drugs that are substrates of this enzyme may be increased when celecoxib is used concomitantly.
Vartojant celekoksiba, gali smarkiai padideti kartu vartojamu preparatu, kuriuos metabolizuoja minetas fermentas, koncentracija kraujo plazmoje.
Examples of drugs which are metabolised by CYP2D6 are antidepressants (tricyclics and SSRIs), neuroleptics, anti- arrhythmic drugs, etc.
Pavyzdžiui, CYP2D6 metabolizuoja antidepresantus (triciklius ir SSRI), neuroleptikus, antiaritminius preparatus ir kt.
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.
Pradejus gydyti celekoksibu, kartais kai kuriu CYP2D6 metabolizuojamu preparatu jau nustatyta doze tenka sumažinti, o nutraukus gydyma celekoksibu — vel padidinti.
In vitro studies have shown some potential for celecoxib to inhibit CYP2C19 catalysed metabolism.
Tyrimais in vitro nustatyta, kad celekoksibas silpnai slopina CYP2C19 katalizuojama metabolizma.
The clinical significance of this in vitro finding is unknown.
Klinikine šio reiškinio svarba nežinoma.
Examples of drugs which are metabolised by CYP2C19 are diazepam, citalopram and imipramine.
CYP2C19 metabolizuoja diazepama, citaloprama ir imipramina.
In an interaction study, celecoxib had no clinically relevant effects on the pharmacokinetics of oral contraceptives (1 mg norethistherone / 35 microg ethinylestradiol).
Saveikos tyrimu duomenimis, celekoksibas nesukele klinikai reikšmingu geriamuju kontraceptiku farmakokinetikos pokyciu (1 mg noretisterono/ 35 µg etinilestradiolio).
Celecoxib does not affect the pharmacokinetics of tolbutamide (CYP2C9 substrate), or glibenclamide to a clinically relevant extent.
Celekoksibas klinikai reikšmingai neveike tolbutamido (metabolizuojamo CYP2C9) ar glibenklamido farmakokinetikos.
In patients with rheumatoid arthritis celecoxib had no statistically significant effect on the pharmacokinetics (plasma or renal clearance) of methotrexate (in rheumatologic doses).
Reumatoidiniu artritu serganciu pacientu organizme celekoksibas nekeite metotreksato, vartojamo doze, kuria gydomas reumatas, farmakokinetikos (klirenso plazmoje ar inkstuose).
However, adequate monitoring for methotrexate-related toxicity should be considered when combining these two drugs.
Visgi šiuos du preparatus kartu vartojancius pacientus reikia tinkamai stebeti del galimo metotreksato toksinio poveikio.
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.
Organizme sveiku asmenu, vartojanciu 200 mg celekoksibo du kartus per para kartu su 450 mg licio du kartus per para, licio Cmax padidejo vidutiniškai 16%, o AUC — 18%.
Therefore, patients on lithium treatment should be closely monitored when celecoxib is introduced or withdrawn.
Jei greta licio preparatu pradedama gydyti celekoksibu arba jo vartojimas nutraukiamas, pacienta reikia nuodugniai ištirti.
Effects of other drugs on celecoxib
Kitu preparatu poveikis celekoksibui
Since celecoxib is predominantly metabolised by CYP2C9 it should be used at half the recommended dose in patients receiving fluconazole.
24 Kadangi celekoksibas daugiausiai metabolizuojamas CYP2C9, reikia vartoti tik puse rekomenduojamos jo dozes pacientams, kurie gydomi flukonazoliu.
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%.
Vartojant vienkartine 200 mg celekoksibo doze kartu su stipriu CYP2C9 inhibitoriumi flukonazoliu (200 mg viena karta per para), celekoksibo Cmax padidejo 60%, o AUC — 130%.
Concomitant use of inducers of CYP2C9 such as rifampicin, carbamazepine and barbiturates may reduce plasma concentrations of celecoxib.
Kartu vartojant CYP2C9 sužadinanciu preparatu, pavyzdžiui, rifampicina, karbamazepina ir barbituratu, gali sumažeti celekoksibo koncentracija plazmoje.
Ketoconazole or antacids have not been observed to affect the pharmacokinetics of celecoxib.
Nustatyta, kad ketokonazolis ar antacidiniai preparatai neveikia celekoksibo farmakokinetikos.
4.6 Pregnancy and lactation No clinical data on exposed pregnancies are available for celecoxib.
Klinikiniu tyrimu duomenu apie celekoksibo vartojima neštumo metu nera.
Studies in animals (rats and rabbits) have shown reproductive toxicity, including malformations (see 4.3 and 5.3).
Su gyvunais (žiurkemis ir triušiais) atlikti tyrimai rodo, kad preparatas daro toksini poveiki reprodukcijai, iskaitant apsigimimus (žr.
The potential for human risk in pregnancy is unknown, but cannot be excluded.
Koks pavojus gresia žmogui, nežinoma, bet negalima jo paneigti.
Celecoxib, as with other drugs inhibiting prostaglandin synthesis, may cause uterine inertia and premature closure of the ductus arteriosus during the last trimester.
Celekoksibas, kaip ir kiti prostaglandinu sinteze slopinantys preparatai, gali sukelti gimdos inercija ir priešlaikini arterinio latako užakima trecia neštumo trimestre.
Celecoxib is contraindicated in pregnancy and in women who can become pregnant (see 4.3 and 4.4).
4. 3 ir 4. 4 skyrius).
If a woman becomes pregnant during treatment, celecoxib should be discontinued.
Jeigu moteris pastojo gydymo metu, celekoksibo vartojima reikia nutraukti.
23 There are no studies on the excretion of celecoxib in human milk.
Netirta, ar celekoksibo patenka i motinos piena.
Celecoxib is excreted in the milk of lactating rats at concentrations similar to those in plasma.
Tiriant žiurkes, nustatyta, kad celekoksibo koncentracija piene beveik prilygsta jo koncentracijai kraujo plazmoje.
Women who take celecoxib should not breastfeed.
Moterims, kurios vartoja celekoksiba, žindyti negalima.
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.
Pacientams, kuriems pavartojus celekoksibo, sukasi ar svaigsta galva bei apima mieguistumas, vairuoti ir valdyti mechanizmu negalima.
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.
Apie 2300 iš ju vartojo preparata vienerius metus arba ilgiau.
The following events have been reported in patients receiving celecoxib in 12 placebo and/ or active controlled trials.
Vartojusiuju celekoksiba grupeje nepageidaujamas poveikio dažnumas buvo panašus kaip placebo arba didesnis.
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.
7, 1% pacientu, vartojusiu celekoksiba, ir 6, 1% — placeba nutrauke gydyma del nepageidaujamo poveikio.
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.
Paskelbtos ir papildomos reakcijos, tokios kaip galvos skausmas, pykinimas, artralgija, bei labai reti ir pavieniai atvejai, išvardyti toliau kursyvu, kurie pasireiške, idiegus vaista i rinka ir pavartojus vaistini preparata daugiau kaip 70 milijonu 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)]
[Labai dažni (> 1/ 10), dažni (≥1/ 100, < 1/ 10), nedažni (≥1/ 1000, < 1/ 100), reti (≥1/ 10 000, < 1/ 1000) labai reti (< 1/ 10 000, iskaitant pavienius atvejus)].
Infections and infestations Common: sinusitis, upper respiratory tract infection Uncommon: urinary tract infection
Infekcijos ir infestacijos Dažni: sinusitas, viršutiniu kvepavimo taku infekcines ligos.
Blood and the lymphatic system disorders Uncommon: anaemia Rare: leucopenia, thrombocytopenia Very rare: pancytopenia.
Nedažni: šlapimo taku infekcines ligos.
Immune system disorders:
Kraujo ir limfines sistemos sutrikimai Nedažni: anemija.
Very rare: serious allergic reactions, anaphylactic shock
Labai reti: pancitopenija
Metabolism and nutrition disorders Uncommon: hyperkalaemia
Imunines sistemos sutrikimai Labai reti: sunkios alergines reakcijos, anafilaksinis šokas.
Psychiatric disorders Common: insomnia Uncommon: anxiety, depression, tiredness Very rare: confusion, hallucinations.
25 Metabolizmo ir mitybos sutrikimai Nedažni: hiperkaliemija.
Nervous system disorders Common: dizziness Uncommon: blurred vision, hypertonia, paraesthesia Rare: ataxia, taste alteration Very rare: aggravated epilepsy, meningitis aseptic, ageusia, anosmia
Labai reti: sumišimas, haliucinacijos.
Ear and labyrinth disorders Uncommon: tinnitus Very rare: decreased hearing
Nedažni: matymas lyg pro migla, hipertonija, parestezija.
Cardiac disorders Uncommon: myocardial infarction*, heart failure, palpitations
Labai reti: klausos susilpnejimas.
Vascular disorders Uncommon: hypertension, hypertension aggravated
Širdies sutrikimai Nedažni: miokardo infarktas *, širdies nepakankamumas, palpitacija.
24 Rare: ischaemic stroke* Very rare: vasculitis.
Labai reti: vaskulitas.
Respiratory, thoracic and mediastinal disorders Common: pharyngitis, rhinitis Uncommon: cough, dyspnoea Very rare: bronchospasm.
Labai reti: bronchu spazmas.
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.
Labai reti: kraujavimas iš virškinimo trakto, uminis pankreatitas, kolitas ir kolito pasunkejimas.
Hepato-biliary disorders Uncommon: abnormal hepatic function Very rare: hepatitis, jaundice, hepatic failure.
Labai reti: hepatitas, gelta, kepenu nepakankamumas.
Skin and subcutaneous tissue disorders Common: rash Uncommon: urticaria Rare: alopecia, photosensitivity Very rare: angioedema, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, epidermal necrolysis,
Labai reti: angioedema, eksfoliacinis dermatitas, daugiaforme eritema, Stivenso ir Džonsono sindromas, epidermio nekrolize.
Musculoskeletal and connective tissue disorders Uncommon: leg cramps Very rare: myositis
Labai reti: miozitas.
Renal and urinary disorders Very rare: acute renal failure, interstitial nephritis
Inkstu ir šlapimo taku sutrikimai Labai reti: uminis inkstu nepakankamumas, intersticinis nefritas.
Reproductive system and breast disorders Very rare: menstrual disorder NOS
26 Lytines sistemos ir kruties sutrikimai Labai reti: menesiniu ciklo sutrikimai NOS.
General disorders and administration site conditions Common: peripheral oedema/ fluid retention
Bendri sutrikimai ir vartojimo vietos pažeidimai Nedažni: periferine edema ir skyscio kaupimasis.
Investigations Uncommon: increased SGOT and SGPT, increased creatinine, BUN increased
AST, ALT, kraujo šlapalo azoto, kreatinino koncentracijos padidejimas.
*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.
* 20 placebu kontroliuojamuju tyrimu, kuriuose dalyvavo osteoartritu ir reumatoidiniu artritu sergantys ligoniai, jungtines analizes duomenimis, ilgiau kaip 2 savaites ar iki vieneriu metu gydant 200- 400 mg celekoksibo doze 1000 ligoniu teko 0, 7 nepageidaujamu reiškiniu atveju daugiau (retai) nei vartojant placeba, o insulto perviršio nebuvo.
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).
Išankstiniais dvieju tyrimu, kuriuose dalyvavo storosios ir tiesiosios žarnos polipais sergantys ligoniai, duomenimis, trejus metus gydant 400 mg celekoksibo paros doze (žr.
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).
5. 1 skyriu) 1000 pacientu teko 7 miokardo infarkto atvejais daugiau (nedažnai) nei vartojant placeba.
For all strokes, there was no increased event rate with celecoxib compared with placebo.
Tu paciu tyrimu duomenimis, trejus metus gydant 400 mg celekoksibo paros doze 1000 pacientu teko 0, 5 išeminio insulto (išskyrus reiškinius, kai buvo hemoragiju arba nežinoma etiologija) atvejo daugiau (retai) nei vartojant placeba.
Single doses up to 1200 mg and multiple doses up to 1200
4. 9 Perdozavimas
25 mg twice daily have been administered to healthy subjects for nine days without clinically significant adverse effects.
Sveikiems žmonems vienkartines iki 1200 mg ir kartotines iki 1200 mg dozes du kartus per para, vartotos 9 dienas, kliniškai reikšmingo nepageidaujamo poveikio nesukele.
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.
Itarus perdozavima, skiriamos palaikomosios priemones, pavyzdžiui, plaunamas skrandis, stebima organizmo bukle ir, jeigu reikia, skiriamas simptominis gydymas.
Dialysis is unlikely to be an efficient method of drug removal due to high protein binding.
Dialize neefektyvi, nes celekoksibas stipriai susijungia su baltymais.
5 PHARMACOLOGICAL PROPERTIES
FARMAKOLOGINES SAVYBES
5.1 Pharmacodynamic properties Pharmacotherapeutic group:
Farmakoterapine grupe – koksibai.
M01AH01.
ATC kodas – MO1AH01.
Celecoxib is an oral, selective, cyclooxygenase-2 (COX-2) inhibitor within the clinical dose range (200-400 mg daily).
Celekoksibas, geriamas gydomosiomis dozemis (200- 400 mg per para), yra aktyvus selektyvusis ciklooksigenazes 2 (COX- 2) inhibitorius.
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.
Sveikiems savanoriams tokios preparato dozes statistiškai reikšmingai neslopino COX- 1 (tirtas tromboksano B2 [TxB2] sintezes slopinimas ex vivo).
Cyclooxygenase is responsible for generation of prostaglandins.
Žinomos dvi fermento izoformos — COX- 1 ir COX- 2.
Two isoforms, COX-1 and COX-2, have been identified.
Izoforma COX- 2 aktyvuoja uždegiminiai dirgikliai, ji pirmiausia skatina prostanoidiniu skausmo, uždegimo ir karšciavimo mediatoriu sinteze.
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.
Be to, COX- 2 daro itaka ovuliacijai, implantacijai ir arterinio latako užakimui, reguliuoja inkstu funkcija ir centrines nervu sistemos funkcijas (karšciavimo sužadinima, skausmo jutima, pažintine funkcija).
It may also play a role in ulcer healing.
Galbut ji skatina gyti opas.
COX-2 has been identified in tissue around gastric ulcers in man but its relevance to ulcer healing has not been established.
COX- 2 nustatyta audiniuose aplink žmogaus skrandžio opa, taciau neirodyta, kad ji skatintu opos gijima.
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.
Skirtingas NVNU slopinanciu COX- 1 ir selektyviuju COX- 2 inhibitoriu poveikis trombocitu funkcijai gali buti kliniškai reikšmingas tais atvejais, kai yra trombemboliniu komplikaciju pavojus.
COX-2 selective inhibitors reduce the formation of systemic (and therefore possibly endothelial) prostacyclin without affecting platelet thromboxane.
Selektyvieji COX- 2 inhibitoriai mažina sisteminio (taigi galbut ir endotelinio) prostaciklino susidaryma, neveikdamas trombocitu tromboksanui.
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).
Celekoksibas yra pirazolas su pakeista diarilo grupe, cheminiu požiuriu panašus i kitus ne arilamino sulfonamidus (pvz., tiazida, furozemida), bet skiriasi nuo arilamino sulfonamidu (pvz., sulfametoksizolio, kitu sulfonamidiniu antibiotiku).
A dose dependent effect on TxB2 formation has been observed after high doses of celecoxib.
27 Vartojant dideles celekoksibo dozes, nustatytas nuo dozes priklausomas poveikis TxB2 susidarymui.
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.
Taciau nedidelio kartotiniu doziu tyrimo duomenimis, sveiku asmenu organizme tris kartus per para vartojama 600 mg celekoksibo doze, palyginti su placebu, neveike trombocitu agregacijos ir kraujavimo laiko.
Several clinical studies have been performed confirming efficacy and safety in osteoarthritis and rheumatoid arthritis.
Atlikti keli klinikiniai celekoksibo efektyvumo ir saugumo tyrimai, kuriu metu buvo gydomi osteoartritu ir reumatoidiniu artritu sergantys pacientai.
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.
Gydymo celekoksibu poveikis uždegimui ir skausmui ivertintas 12 savaiciu trukmes placebu ir (arba) aktyviai kontroliuojamais tyrimais, kuriuose dalyvavo 4200 kelio ir klubo osteoartritu serganciu pacientu, ir 24 savaiciu trukmes tokiais pat tyrimais, kuriuose dalyvavo apie 2100 pacientu, serganciu reumatoidiniu artritu.
Celecoxib at daily doses of 200 mg – 400 mg provided pain relief within 24 hours of dosing.
200- 400 mg celekoksibo paros doze per 24 valandas sumažino skausma.
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).
Maždaug 4500 opu netureje pacientai dalyvavo penkiuose atsitiktiniu imciu kontroliuojamuosiuose dvigubai akluose tyrimuose (skirta nuo 50 mg iki 400 mg celekoksibo doze du kartus per para), kuriu metu atlikta planine viršutines virškinimo trakto dalies endoskopija.
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).
12 savaiciu trukusiu endoskopijos tyrimu duomenimis, pacientams, vartojusiesiems celekoksiba (100- 800 mg per para), skrandžio ir dvylikapirštes žarnos opu pavojus buvo reikšmingai mažesnis nei vartojusiesiems naproksena (1000 mg per para) ir ibuprofena (2400 mg per para).
The data were inconsistent in comparison with diclofenac (150 mg per day).
Celekoksibo ir diklofenako (150 mg per para) lyginamieji duomenys prieštaringi.
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.
Dvieju 12 savaiciu trukmes tyrimu duomenimis, endoskopijos budu diagnozuoto skrandžio ir dvylikapirštes žarnos išopejimo dažnumas grupese pacientu, vartojusiu placeba, 200 mg bei 400 mg celekoksibo du kartus per para, skyresi nereikšmingai.
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).
Vieni ju gydyti 400 mg celekoksibo doze du kartus per para (atitinkamai 4 ir 2 kartus didesne už rekomenduojama osteoartritui ir reumatoidiniam artritui gydyti), kiti — 800 mg ibuprofeno tris kartus per para, treti — 75 mg diklofenako du kartus per para (abieju preparatu doze gydomoji).
Twenty-two percent of enrolled patients took concomitant low-dose acetylsalicylic acid (≤ 325 mg/ day), 26 primarily for cardiovascular prophylaxis.
22 procentai pacientu daugiausia širdies ir kraujagysliu sutrikimu profilaktikai kartu gere maža acetilsalicilo doze (=325 mg per para).
For the primary endpoint complicated ulcers (defined as gastrointestinal bleeding, perforation or obstruction) celecoxib was not significantly different than either ibuprofen or diclofenac individually.
Pirminis ivertis rodo, kad opu komplikaciju (kraujavimas iš virškinimo trakto, perforacija ar nepraeinamumas) dažnumas celekoksibo, ibuprofeno ir diklofenako grupese skyresi statistiškai nereikšmingai.
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).
Jungtineje NVNU grupeje statistiškai reikšmingo opu komplikaciju skirtumo nebuvo (santykine rizika — 0, 77, 95% PI 0, 41- 1, 46, remiantis viso tyrimo duomenimis).
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.
Jungtinis ivertis rodo, kad opu komplikaciju ir simptomu celekosibo grupeje buvo reikšmingai mažiau nei NVNU grupeje (santykine rizika — 0, 66, 95% PI 0, 45- 0, 97), bet ne tarp celekoksibo ir diklofenako.
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.
Tiems pacientams, kurie vartojo celekoksiba kartu su maža acetilsalicilo doze, opu komplikaciju buvo 4 kartus dažniau nei vartojusiesiems vien celekoksiba.
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.
Kartojant hemoglobino koncentracijos tyrima nustatyta, kad pacientams, kurie vartojo celekoksiba, kliniškai reikšmingai hemoglobino koncentracija sumažejo (> 2 g/ dl) reciau nei NVNU vartojusiuju grupeje (santykine rizika — 0, 29, 95% PI 0, 17- 0, 48).
The significantly lower incidence of this event with celecoxib was maintained with or without acetylsalicylic acid use.
Šio reiškinio pavojus vartojant celekoksiba mažesnis ir tais atvejais, kai kartu geriama acetilsalicilo rugšties, ir tais, kai negeriama.
Ongoing Clinical Trials:
Tebevykstantys klinikiniai tyrimai.
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.
Gauti išankstiniai duomenys triju tebevykstanciu ilgalaikiu celekoksibo saugumo klinikiniu tyrimu, kuriuose dalyvauja ligoniai, turintys pavieniu storosios žarnos adenomatoziniu polipu arba predispozicija susirgti Alzheimerio liga.
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.
Prevention of Sporadic Colorectal Adenomas with Celecoxib, APC), nustatytas nuo dozes priklausomas (200 mg ir 400 mg dozes du kartus per para, palyginti su placebu) širdies ir kraujagysliu sistemos sutrikimu (daugiausia miokardo infarkto, MI) padažnejimas.
The increased risk became apparent after approximately 1 year of treatment.
Rizikos padidejimas pastebetas maždaug po vieneriu metu gydymo.
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.
Ivertinus jungtini galutini rodikli (mirtis nuo širdies ir kraujagysliu sistemos sutrikimu, MI ar insulto), nustatyta, kad vartojant celekoksiba santykine rizika (SR), palyginti su placebu, buvo didesne: vartojant didesne celekoksibo doze - 3, 4 (95%, PI 1, 4- 8, 5), o mažesne - 2, 5 (95%, PI 1, 0- 6, 4).
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.
Jungtinio galutinio rodiklio absoliucioji rizika, vartojant celekoksiba, atitinkamai - 3, 0% (didesnei celekoksibo dozei) ir 2, 2% (mažesnei celekoksibo dozei), o placeba – 0, 9%.
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.
28 Išankstiniais kitu dvieju tyrimu duomenimis, vartojant 200 mg celekoksibo doze du kartus per para ir 400 mg celekoksibo doze viena karta per para, palyginti su placebu, širdies ir kraujagysliu reiškiniu rizika reikšmingai nepadidejo.
This information will be updated as final data become available.
Ši informacija bus atnaujinta, kai tik bus gauti galutiniai duomenys.
5.2 Pharmacokinetic properties Celecoxib is well absorbed reaching peak plasma concentrations after approximately 2-3 hours.
Celekoksibas gerai absorbuojamas ir didžiausia jo koncentracija kraujo plazmoje susidaro maždaug po 2- 3 valandu.
Dosing with food (high fat meal) delays absorption by about 1 hour.
Celekoksibas, vartojamas su maistu (labai riebiu), absorbuojamas maždaug viena valanda ilgiau.
Celecoxib is mainly eliminated by metabolism.
Didele celekoksibo dalis metabolizuojama.
Less than 1% of the dose is excreted unchanged in urine.
Mažiau kaip 1% nepakitusio preparato išsiskiria su šlapimu.
The inter-subject variability in the exposure of celecoxib is about 10-fold.
Ivairiu žmoniu organizme celekoksibo farmakokinetika skiriasi apie 10 kartu.
Celecoxib exhibits dose- and time-independent pharmacokinetics in the therapeutic dose range.
Gydomuju celekoksibo doziu farmakokinetika nepriklauso nuo dozes ir laiko.
Plasma protein binding is about 97% at therapeutic plasma concentrations and the drug is not preferentially bound to erythrocytes.
Kai kraujo plazmoje susidaro gydomoji celekoksibo koncentracija, apie 97% preparato jungiasi su plazmos baltymais, bet nesijungia su eritrocitais.
Elimination half-life is 8-12 hours.
Pusines eliminacijos laikas — 8- 12 valandu.
Steady state plasma concentrations are reached within 5 days of treatment.
Pusiausvyrine koncentracija kraujo plazmoje susidaro per 5 dienas.
Pharmacological activity resides in the parent drug.
Nepakites preparatas yra farmakologiškai aktyvus.
The main metabolites found in the circulation have no detectable COX-1 or COX-2 activity.
Pagrindiniai kraujyje cirkuliuojantys celekoksibo metabolitai neslopina COX- 1 arba COX- 2.
Celecoxib is metabolised in the liver by hydroxylation, oxidation and some glucuronidation.
Celekoksibas metabolizuojamas kepenyse hidroksilinimo, oksidacijos ir konjugacijos su gliukurono rugštimi budais.
The phase I metabolism is mainly catalysed by CYP2C9.
Pirmosios fazes metu daugiausia preparato metabolizuojama, dalyvaujant CYP2C9.
There is a genetic polymorphism of this enzyme.
Nustatytas genetinis šio fermento polimorfizmas.
Less than 1% of the population are poor metabolisers and have an enzyme with decreased activity.
Mažiau kaip 1% žmoniu organizme preparatas metabolizuojamas silpnai del mažo fermento aktyvumo.
Plasma concentrations of celecoxib are probably markedly increased in such patients.
Tokiu pacientu kraujo plazmoje susidaro daug didesne celekoksibo koncentracija.
Patients known to be CYP2C9 poor metabolisers should be treated with caution.
Atsargiai preparatu reikia gydyti pacientus, kuriu organizme CYP2C9 metabolizuoja silpnai.
No clinically significant differences were found in PK parameters of celecoxib between elderly African-Americans and Caucasians.
Juodosios rases pacientu kraujo plazmoje susidaro didesne celekoksibo koncentracija negu baltosios rases pacientu.
The plasma concentration of celecoxib is approximately 100% increased in elderly women (> 65 years).
Senyvu moteru (> 65 metu) kraujo plazmoje susidaro maždaug 100% didesne celekoksibo koncentracija.
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.
Pacientu, kuriems yra nesunkus kepenu funkcijos sutrikimas, celekoksibo Cmax kraujo plazmoje 53%, o AUC 26% didesne, palyginti su susidarancia sveiku asmenu kraujyje.
The corresponding values in patients with moderate hepatic impairment were 41% and 146% respectively.
Rodmenys pacientu, kuriems yra vidutinio sunkumo kepenu funkcijos sutrikimas, — atitinkamai 41% ir 146%.
The metabolic capacity in patients with mild to moderate impairment was best correlated to their albumin values.
Metabolizmo pajegumas pacientu, serganciu nesunkiu ir vidutinio sunkumo kepenu sutrikimu, organizme susijes su albumino koncentracija.
Treatment should be initiated at half the recommended dose in patients with moderate liver impairment (with serum albumin 25-35g/ L).
Pacientus, kurie serga vidutinio sunkumo kepenu sutrikimu (albumino koncentracija kraujo serume 25— 35 g/ l), reikia pradeti gydyti puse rekomenduojamos dozes.
Patients with severe hepatic impairment (serum albumin < 25 g/ l) have not been studied and celecoxib is contraindicated in this patient group.
Netirti pacientai, kuriems yra sunkus kepenu funkcijos sutrikimas (albumino koncentracija kraujo serume < 25 g/ l), todel jiems vartoti celekoksiba draudžiama.
There is little experience of celecoxib in renal impairment.
Pacientu, kuriu inkstu funkcija sutrikusi, gydymo celekoksibu patirties stinga.
The pharmacokinetics of celecoxib has not
Celekoksibo farmakokinetika organizme ligoniu, kuriems yra inkstu funkcijos sutrikimas, netirta, bet tiketina, kad ji labai pakinta.
27 been studied in patients with renal impairment but is unlikely to be markedly changed in these patients.
Taigi, jei paciento inkstu funkcija sutrikusi, preparatu reikia gydyti atsargiai.
Thus caution is advised when treating patients with renal impairment.
Pacientams, sergantiems sunkiu inkstu funkcijos sutrikimu, preparata vartoti draudžiama.
Severe renal impairment is contraindicated.
5. 3 Ikiklinikiniu saugumo tyrimu duomenys
5.3 Preclinical safety data Conventional embryo-fetal toxicity studies resulted in dose dependent occurrences of diaphragmatic hernia in rat fetuses and of cardiovascular malformations in rabbit fetuses at systemic exposures to free drug approximately 5X (rat) and 3X (rabbit) higher than those achieved at the maximum recommended daily human dose (400 mg).
Iprastiniais preparato toksinio poveikio embrionui ir vaisiui tyrimais nustatyta, kad parenteraliai duodant žiurkems maždaug 5 kartus, o triušiams maždaug 3 kartus didesne paros doze už didžiausia rekomenduojama žmogui (400 mg), žiurkiu jaunikliams pasireiške nuo dozes priklausoma diafragmos išvarža, o triušiu — širdies bei kraujagysliu sistemos sklaidos ydu.
Diaphragmatic hernia was also seen in a peri-post natal toxicity study in rats, which included exposure during the organogenetic period.
Tiriant preparato toksini poveiki žiurkems perinataliniu, postnataliniu bei organogenezes laikotarpiais, taip pat nustatyta diafragmos išvarža.
In the latter study, at the lowest systemic exposure where this anomaly occurred in a single animal, the estimated margin relative to the maximum recommended daily human dose was 3X.
Mažiausia šio tyrimo metu duota parenterine paros doze, sukelusi mineta apsigimima vienam gyvunui, buvo 3 kartus didesne už didžiausia rekomenduojama žmogui.
In animals, exposure to celecoxib during early embryonic development resulted in pre-implantation and post-implantation losses.
Duodant celekoksibo gyvunams ankstyvuoju embrioniniu laikotarpiu, ivyko persileidimu prieš implantacija ir po jos.
These effects are expected following inhibition of prostaglandin synthesis.
Manoma, kad toks poveikis pasireiškia del slopinamos prostaglandinu sintezes.
Celecoxib was excreted in rat milk.
29 Celekoksibo patenka i žiurkes piena.
In a peri-post natal study in rats, pup toxicity was observed.
Tiriant žiurkes perinataliniu ir postnataliniu laikotarpiais, nustatyta, kad preparatas sukelia toksini poveiki ju jaunikliams.
Based on conventional studies, genotoxicity or carcinogenicity, no special hazard for humans was observed, beyond those addressed in other sections of the SmPC.
Remiantis iprastiniais kartotiniu doziu toksinio, genotoksinio arba kancerogeninio poveikio tyrimu duomenimis, kitokio žmogui žalingo poveikio nenustatyta, išskyrus ta, kuris aprašytas kituose preparato charakteristiku santraukos skyriuose.
In a two-year toxicity study an increase in nonadrenal thrombosis was observed in male rat at high doses.
Dvejus metus trukusiu preparato toksinio poveikio tyrimu duomenimis, žiurkiu patinams, gavusiems dideles preparato dozes, padaugejo neadrenaliniu tromboziu.
6 PHARMACEUTICAL PARTICULARS
FARMACINE INFORMACIJA
6.1 List of excipients Capsules 100 mg contain lactose monohydrate, sodium lauryl sulphate, povidone K30, croscarmellose sodium and magnesium stearate.
Laktozes monohidratas, natrio laurilo sulfatas, povidonas K30, kroskarmeliozes natrio druska ir magnio stearatas.
Capsule shells contain gelatin, titanium dioxide E171; ink contains indigotine E132
Kapsuleje yra želatinos, titano dioksido E171; dažuose yra indigotino E132.
Capsules 200 mg contain lactose monohydrate, sodium lauryl sulphate, povidone K30, croscarmellose sodium and magnesium stearate.
Laktozes monohidratas, natrio laurilo sulfatas, povidonas K30, kroskarmeliozes natrio druska ir magnio stearatas.
Capsule shells contain gelatin, titanium dioxide E171; ink contains iron oxide E172.
Kapsuleje yra želatinos, titano dioksido E171; dažuose yra geležies oksido E172.
6.2 Incompatibilities Not applicable.
6. 3 Tinkamumo laikas
6.3 Shelf-life 3 years.
3 metai.
6.4 Special precautions for storage Do not store above 30oC.
Laikyti ne aukštesneje kaip 30°C temperaturoje.
6.5 Nature and content of container Clear or opaque PVC blisters or aluminium cold-formed blisters.
Permatomos arba nepermatomos PVC lizdines plokšteles arba aliuminio folijos lizdines plokšteles.