natgillin/translations-raw huggingface dataset:
Patienter, som tidligere har haft symptomer på astma, akut rhinitis, nasale polypper, angioneurotisk ødem, urticaria eller anden type af allergisk reaktion efter at have taget acetylsalicylsyre eller NSAID herunder COX- 2 (cyclooxygenase- 2) hæmmere.
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.
4. 5).
In pregnancy and in women of childbearing potential unless using an effective method of contraception (See 4.5).
4. 6 og 5. 3).
Celecoxib has been shown to cause malformations in the two animal species studied (See 4.6 and 5.3).
En potentiel risiko under graviditet hos mennesker er uafklaret, men kan ikke udelukkes.
The potential for human risk in pregnancy is unknown, but cannot be excluded.
4. 6 og 5. 3).
Breast feeding (See 4.6 and 5.3).
Svær leverdysfunktion (serumalbumin < 25 g/ l eller Child- Pugh score ≥ 10).
Severe hepatic dysfunction (serum albumin < 25 g/ l or Child-Pugh score ≥ 10).
Patienter med estimeret kreatininclearance < 30 ml/ min.
Patients with estimated creatinine clearance < 30 ml/ min.
Der er set øvre gastrointestinale komplikationer (perforationer, ulcera og blødninger (PUB)), nogle med fatal udgang hos patienter behandlet med celecoxib.
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.
Der bør udvises forsigtighed ved behandling af patienter, der har høj risiko for at udvikle gastrointestinale komplikationer i forbindelse med NSAID: ældre, patienter som får andre NSAID eller acetylsalicylsyre samtidig, eller patienter der tidligere har haft en gastrointestinal sygdom, som f. eks. ulceration eller gastrointestinal blødning.
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.
Signifikant forskel i den gastrointestinale sikkerhed mellem selektive COX- 2 hæmmere + acetylsalicylsyre vs.
A significant difference in GI safety between selective COX-2 inhibitors + acetylsalicylic acid vs.
5. 1).
NSAIDs + acetylsalicylic acid has not been demonstrated in long- term clinical trials (see 5.1).
Der er set et øget antal alvorlige kardiovaskulære hændelser, hovedsagelig myokardieinfarkt, i placebokontrollerede langtidsstudier hos personer med sporadisk adenomatøs polypose
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).
Da den kardiovaskulære risiko ved brug af celecoxib kan øges med dosis og behandlingsvarighed bør den kortest mulige behandlingstid og den lavest effektive daglige dosis anvendes.
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.
4. 3, 4. 4, 4. 8 og 5. 1).
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).
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).
På grund af deres manglende virkning på trombocytfunktionen kan selektive COX- 2 hæmmere ikke erstatte acetylsalicylsyre som profylakse mod kardiovaskulær tromboembolisk sygdom.
COX-2 selective inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular
Ældre har hyppigere nedsat nyre - og leverfunktion og især nedsat hjertefunktion, og patienterne bør derfor kontrolleres løbende. celecoxib er i kliniske undersøgelser vist at have samme effekt på nyrerne som det NSAID, der blev sammenlignet med.
Clinical trials with celecoxib have shown renal effects similar to those observed with comparator NSAIDs.
Selv om det ikke er en kraftig hæmmer af dette enzym, kan en dosisnedsættelse blive nødvendig for individuelt dosistitrerede lægemidler, som metaboliseres af CYP2D6 (Se 4. 5).
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).
Patienter, som har svært ved at metabolisere via CYP2C9, bør behandles med forsigtighed (se 5. 2).
Patients known to be CYP2C9 poor metabolisers should be treated with caution (see 5.2.).
4. 8).
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).
Disse reaktioner optræder i de fleste tilfælde inden for den første måned af behandlingen.
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.
4. 3).
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).
Forsigtighed bør udvises, når celecoxib kombineres med warfarin og andre antikoagulantia (se 4. 5).
Caution should be exercised when combining celecoxib with warfarin and other oral anticoagulants (See 4.5).
24 {Navn} 100 mg og 200 mg kapsler indeholder lactose (henholdsvis 149, 7 mg og 49, 8 mg).
{Invented Name}100 mg and 200 mg capsules contain lactose (149.7 mg and 49.8 mg, respectively).
{navn} bør ikke anvendes til patienter med arvelig galactoseintolerans, en særlig form af hereditær lactasemangel (Lapp Lactase deficiency) eller glucose/ galactosemalabsorption.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose- galactose malabsorption should not take this medicine.
Antikoagulationsparametrene bør monitoreres især i de første dage efter behandlingsstart eller dosisændring af celecoxib hos patienter, som tager warfarin eller andre antikoagulantia, da disse patienter har en øget risiko for blødningskomplikationer.
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.
Patienter, der får orale antikoagulantia, bør derfor monitoreres omhyggeligt med hensyn til INR, især i de første dage efter behandling med celecoxib er startet eller hvis dosis af celecoxib ændres (se 4. 4).
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).
Som for NSAID kan risikoen for akut nyreinsufficiens, som sædvanligvis er reversibel, muligvis være øget hos nogle patienter med kompromitteret nyrefunktion (f. eks. dehydrerede patienter eller ældre patienter), hvis ACE- hæmmere eller angiotension II receptor antagonister kombineres med NSAID, inklusive celecoxib.
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.
Samtidig behandling med NSAID og ciclosporin eller tacrolimus kan forøge den nyretoksiske effekt af ciclosporin og tacrolimus.
22 Coadministration of NSAIDs and cyclosporin or tacrolimus have been suggested to increase the nephrotoxic effect of cyclosporin and tacrolimus.
I de indsendte studier ses, som for andre NSAID, en øget risiko for gastrointestinal ulceration eller andre gastrointestinale komplikationer, når celecoxib kombineres med lavdosis acetylsalicylsyre (se 5. 1).
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).
Virkningen af celecoxib på andre lægemidler Celecoxib er en hæmmer af CYP2D6.
Effects of celecoxib on other drugs Celecoxib is an inhibitor of CYP2D6.
Under behandling med celecoxib steg plasmakoncentrationen af CYP2D6- substratet dextromethorphan med 136%.
During celecoxib treatment, the plasma concentrations of the CYP2D6 substrate dextromethorphan were increased by 136%.
Sådanne lægemidler, der metaboliseres af CYP2D6, omfatter antidepressiva (tricycliske og SSRI), neuroleptika, antiarrytmika og andre.
Examples of drugs which are metabolised by CYP2D6 are antidepressants (tricyclics and SSRIs), neuroleptics, anti- arrhythmic drugs, etc.
Doseringen af individuelt dosistitrerede CYP2D6- substrater, bør måske nedsættes, når samtidig behandling med celecoxib initieres, eller øges, hvis behandling med celecoxib afsluttes.
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.
In- vitro forsøg har vist mulighed for, at celecoxib kan hæmme CYP2C19 katalyseret metabolisme.
In vitro studies have shown some potential for celecoxib to inhibit CYP2C19 catalysed metabolism.
Den kliniske betydning af disse in- vitro fund er ikke kendt.
The clinical significance of this in vitro finding is unknown.
Celecoxib havde ingen klinisk relevant virkning på farmakokinetikken af orale antikonceptionsmidler (1 mg norethisteron/ 35 µg ethinylestradiol) i en udført interaktionsundersøgelse.
In an interaction study, celecoxib had no clinically relevant effects on the pharmacokinetics of oral contraceptives (1 mg norethistherone / 35 microg ethinylestradiol).
Hos patienter med rheumatoid arthritis havde celecoxib ingen signifikant effekt på farmakokinetikken (plasma - eller renal clearence) af methotrexat (i reumatologiske doser).
In patients with rheumatoid arthritis celecoxib had no statistically significant effect on the pharmacokinetics (plasma or renal clearance) of methotrexate (in rheumatologic doses).
25 Alligevel anbefales det at overveje passende monitorering af metotrexatrelateret toksicitet, når disse to lægemidler kombineres.
However, adequate monitoring for methotrexate-related toxicity should be considered when combining these two drugs.
Samtidig brug af 200 mg celecoxib taget som én enkelt dosis og 200 mg fluconazol, en potent CYP2C9- hæmmer, en gang daglig, resulterede i en gennemsnitlig stigning i celecoxibs Cmax på 60% og i AUC på 130%.
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%.
Der foreligger ingen kliniske data på graviditet og celecoxib.
4.6 Pregnancy and lactation No clinical data on exposed pregnancies are available for celecoxib.
Forsøg med dyr (rotter og kaniner) har vist reproduktionstoksicitet inklusiv misdannelser (se 4. 3 og 5. 3).
Studies in animals (rats and rabbits) have shown reproductive toxicity, including malformations (see 4.3 and 5.3).
Celecoxib er kontraindiceret under graviditet og til kvinder, som kan blive gravide (se 4. 3 og 4. 4).
Celecoxib is contraindicated in pregnancy and in women who can become pregnant (see 4.3 and 4.4).
Der er ingen undersøgelser om udskillelse af celecoxib i mælken hos ammende kvinder.
23 There are no studies on the excretion of celecoxib in human milk.
Patienter, som mærker svimmelhed, vertigo eller somnolens, bør undlade at føre bil eller betjene maskiner.
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.
2300 fået celecoxib i et år eller længere.
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.
De følgende hændelser er rapporteret for patienter, som fik celecoxib i 12 kontrollerede undersøgelser med placebo eller aktiv kontrol.
The following events have been reported in patients receiving celecoxib in 12 placebo and/ or active controlled trials.
Afbrydelse af behandlingen på grund af bivirkninger skete for 7, 1% af celecoxibpatienterne og for 6, 1% af placebopatienterne.
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.
Yderligere bivirkninger rapporteret efter markedsføring omfattende > 70 millioner behandlede patienter omfatter hovedpine, kvalme, artralgi samt de bivirkninger, som i følgende liste er skrevet med kursiv, og som er anført under meget sjælden.
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.
Meget almindelig (> 1/ 10), almindelig (> 1/ 100 og < 1/ 10), ikke almindelig (> 1/ 1000 og 1/ 100), sjælden (> 1/ 10. 000 og < 1/ 1000), meget sjælden (< 1/ 10. 000, inklusive enkeltstående rapporter).
[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)]
26 Infektioner og infestationer Almindelig: bihulebetændelse, øvre luftvejsinfektion Ikke almindelig: urinvejsinfektion
Infections and infestations Common: sinusitis, upper respiratory tract infection Uncommon: urinary tract infection
Forstyrrelser i immunsystemet Meget sjælden: alvorlige allergiske reaktioner, anafylaktisk shock
Very rare: serious allergic reactions, anaphylactic shock
Psykiske lidelser Almindelig: søvnmangel Ikke almindelig: angst, depression, træthed Meget sjælden: konfusion, hallucinationer
Psychiatric disorders Common: insomnia Uncommon: anxiety, depression, tiredness Very rare: confusion, hallucinations.
Lidelser i det centrale og perifere nervesystem Almindelig: svimmelhed Ikke almindelig: sløret syn, hypertoni, parestæsi Sjælden: ataksi, smagsforandringer Meget sjælden: forværret epilepsi, aseptisk meningitis, manglende eller nedsat smagsevne, anosmi
Nervous system disorders Common: dizziness Uncommon: blurred vision, hypertonia, paraesthesia Rare: ataxia, taste alteration Very rare: aggravated epilepsy, meningitis aseptic, ageusia, anosmia
27 Lidelser i myo -, endo -, perikardium og klapper Ikke almindelig: myokardieinfarkt *, hjertesvigt, hjertebanken
Cardiac disorders Uncommon: myocardial infarction*, heart failure, palpitations
Vaskulære (ekstrakardielle) lidelser Ikke almindelig: hypertension, forværring af allerede erkendt hypertension Sjælden: iskæmisk slagtilfælde * Meget sjælden: vaskulitis
Vascular disorders Uncommon: hypertension, hypertension aggravated
Gastrointestinale lidelser Almindelig: abdominalsmerter, diarré, dyspepsi, flatulens Ikke almindelig: obstipation, opstød, gastrit, stomatit, opkastning, forværring af gastrointestinal inflammation Sjælden: sår i spiserør, mavesæk, tolvfingertarmen, tyndtarmen og colon, synkebesvær, intestinal perforation, esophagitis, melæna Meget sjælden: gastroinstestinal blødning, akut pankreatitis, colitis/ forværret colitis
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.
Dermatologiske lidelser Almindelig: udslæt Ikke almindelig: nældefeber Sjælden: alopeci, lysfølsomhed Meget sjælden: angioødem, dermatitis exfoliativa, erythema multiforme, Stevens- Johnsons syndrom, epidermal nekrolyse
Skin and subcutaneous tissue disorders Common: rash Uncommon: urticaria Rare: alopecia, photosensitivity Very rare: angioedema, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, epidermal necrolysis,
Muskuloskeletale -, bindevævs - og knoglelidelser Ikke almindelig: lægkramper Meget sjælden: myositis
Musculoskeletal and connective tissue disorders Uncommon: leg cramps Very rare: myositis
Generelle symptomer og forstyrrelser ved applicationssted Almindelig: perifert ødem/ væskeretention
General disorders and administration site conditions Common: peripheral oedema/ fluid retention
1000 patienter (sjælden) og der ses ingen overrepræsentation af slagtilfælde.
Investigations Uncommon: increased SGOT and SGPT, increased creatinine, BUN increased
Foreløbige data fra 2 studier på patienter med kolorektale polypper behandlet med celecoxib 400 mg daglig (se pkt.
*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.
1000 patienter (ikke almindelig).
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).
1000 efter 3 år (sjælden).
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).
28 Undersøgelser Ikke almindelig: forhøjet ASAT og ALAT, forhøjet se- kreatinin, forhøjet se- carbamid
4.9 Overdose There is no clinical experience of overdose.
4. 9 Overdosering
Single doses up to 1200 mg and multiple doses up to 1200
Enkeltdoser op til 1200 mg og gentagne doser op til 1200 mg to gange daglig er blevet givet til raske personer i 9 dage uden klinisk betydende bivirkninger.
25 mg twice daily have been administered to healthy subjects for nine days without clinically significant adverse effects.
Ved mistanke om overdosering skal relevant medicinsk behandling iværksættes for eksempel ventrikeltømning, klinisk overvågning og hvis nødvendigt iværksættes symptomatisk behandling.
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.
FARMAKOLOGISKE OPLYSNINGER
5 PHARMACOLOGICAL PROPERTIES
5. 1 Farmakodynamiske egenskaber
5.1 Pharmacodynamic properties Pharmacotherapeutic group:
Farmakoterapeutisk gruppe:
ATC code:
M 01 AH 01
M01AH01.
Celecoxib er inden for det kliniske dosisinterval (200- 400 mg daglig) en oral, selektiv cyclooxygenase- 2 (COX- 2) hæmmer.
Celecoxib is an oral, selective, cyclooxygenase-2 (COX-2) inhibitor within the clinical dose range (200-400 mg daily).
Inden for dette dosisinterval er der hos raske frivillige personer ikke observeret nogen statistisk signifikant hæmning af COX- 1 (vurderet som ex vivo hæmning af tromboxan B2 (TxB2) dannelse).
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.
Der er identificeret 2 iso - former, COX- 1 og COX- 2.
Two isoforms, COX-1 and COX-2, have been identified.
Det er vist, at COX- 2 er isoformen af det enzym, som induceres af pro- inflammatoriske stimuli, og som man mener, hovedsagelig har ansvaret for syntese af prostanoide mediatorer af smerte, inflammation og feber.
COX-2 is the isoform of the enzyme that has been shown to be induced by pro- inflammatory stimuli and has been postulated to be primarily responsible for the synthesis of prostanoid mediators of pain, inflammation, and fever.
COX- 2 er også involveret i ovulation, implantation og lukning af ductus arteriosus, regulering af nyrefunktionen og funktioner i centralnervesystemet (induktion af feber, smerteopfattelse og cognitive funktioner).
COX-2 is also involved in ovulation, implantation and closure of the ductus arteriosus, regulation of renal function, and central nervous system functions (fever induction, pain perception and cognitive function).
Forskellen i antitrombocytaktivitet mellem COX- 1 hæmmende NSAID og COX- 2 selektive hæmmere kan være af klinisk betydning for patienter med risiko for udvikling af tromboemboliske hændelser.
The difference in antiplatelet activity between some COX-1 inhibiting NSAIDs and COX-2 selective inhibitors may be of clinical significance in patients at risk of thrombo-embolic reactions.
COX- 2 selektive hæmmere reducerer dannelsen af systemiske (og dermed muligvis endotel- deriveret) prostacyclin uden at påvirke thromboxan i blodpladerne.
COX-2 selective inhibitors reduce the formation of systemic (and therefore possibly endothelial) prostacyclin without affecting platelet thromboxane.
Celecoxib er en diaryl- substitueret pyrazol med kemisk lighed med andre non- arylamin sulfonamider (f. eks. thiazider, furosemid) men adskiller sig fra arylaminsulfonamider (f. eks. sulfamethoxizol og andre sulfonamid- antibiotika).
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).
4200 patienter i kliniske undersøgelser i op til 12 ugers varighed med placebo og aktiv kontrol.
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.
2100 patienter i kliniske undersøgelser i op til 24 ugers varighed med placebo og aktiv kontrol.
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.
Daglig dosis på 200- 400 mg celecoxib gav smertelindring inden for 24 timer efter indtagelsen.
Celecoxib at daily doses of 200 mg – 400 mg provided pain relief within 24 hours of dosing.
4500 patienter uden primært mavesår bekræftet ved øvre gastroskopi (celecoxibdoser på 50- 400 mg 2 gange daglig).
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).
Endoskopiforsøg over 12 uger med celecoxib (100- 800 mg daglig) viste en signifikant lavere risiko for mavesår i forhold til naproxen (1000 mg daglig) og ibuprofen (2400 mg daglig).
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).
I to 12- ugers forsøg var andelen af patienter med endoskopisk mavesår ikke signifikant forskellig mellem placebo og celecoxib 200 mg 2 gange daglig eller 400 mg 2 gange daglig.
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.