natgillin/translations-raw huggingface dataset:
Sjældne:
Investigations Uncommon: alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased, blood urea increased, gamma-glutamyltransferase increased, weight increased.
Stigninger i blod- bilirubin, stigninger i blod- glukose.
Rare: blood bilirubin increased, blood glucose increased
* Baseret på analyser af kontrollerede kliniske langtidsundersøgelser med placebo og lægemidler, er selektive COX- 2 hæmmere blevet sat i forbindelse med en øget risiko for alvorlige arterielle thrombotiske hændelser, inklusive myokardieinfarkt og apopleksi.
* Based on analyses of long-term placebo and active controlled clinical trials, some selective COX-2 inhibitors have been associated with an increased risk of serious thrombotic arterial events, including myocardial infarction and stroke.
1. 100 patienter blev behandlet med lumiracoxib i analgetiske kliniske forsøg (smerter efter tandoperation, primær dysmenorré og smerter efter ortopædisk operation).
Approximately 1,100 patients were treated with lumiracoxib in analgesia clinical studies (post-surgical dental pain, primary dysmenorrhea, and post-orthopedic surgery pain).
Bivirkningsprofilen svarede generelt til den, der er rapporteret i OA - og RA- forsøg.
The undesirable effects profile was generally similar to that reported in the OA and RA studies.
Nefrotoksicitet inklusiv interstitiel nefritis og nefrotisk syndrom og
The following rare serious undesirable effects have been reported in association with the use of NSAIDs and cannot be ruled out for lumiracoxib: nephrotoxicity including interstitial nephritis and nephrotic syndrome and renal failure; hepatotoxicity including hepatic failure and jaundice; cutaneo- mucosal adverse effects and severe skin reactions.
Der er ingen klinisk erfaring med overdosering.
15 There is no clinical experience of overdose.
Der er administreret gentagne doser af lumiracoxib 1. 200 mg, én gang daglig i 4 uger, til patienter med rheumatoid arthritis uden klinisk signifikante bivirkninger.
Multiple doses of lumiracoxib 1,200 mg once daily have been administered to patients with rheumatoid arthritis for 4 weeks without clinically significant adverse effects.
Ved mistanke om overdosis skal der tages relevante, understøttende medicinske forholdsregler, så som eksempelvis ventrikeltømning, klinisk supervision og, hvis dette er nødvendigt, institueres 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.
Antiinflammatoriske og antirheumatiske lægemidler, non- steroid, coxiber, ATC- kode:
Anti-inflammatory and antirheumatic products, non-steroids, coxibs, ATC code:
Virkningsmekanisme Lumeracoxib er indenfor det kliniske dosisområde en oral aktiv selektiv cyclo- oxygenase- 2 (COX- 2) hæmmer.
Mode of Action Lumiracoxib is an orally active, selective cyclooxygenase-2 (COX-2) inhibitor within the clinical dose range.
Der er identificeret to isoformer, COX- 1 og COX- 2.
Two isoforms, COX-1 and COX-2 have been identified.
Forskellen i antithrombocytaktivitet mellem COX- 1- hæmmende NSAID og COX- 2 selektive hæmmere kan være af klinisk betydning for patienter med risiko for udvikling af thrombotiske 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 thromboxani blodpladerne.
COX-2 selective inhibitors reduce the formation of systemic (and therefore possibly endothelial) prostacyclin without affecting platelet thromboxane.
Den kliniske betydning af disse fund er endnu ikke klarlagt. I alle kliniske, farmakologiske undersøgelser forårsagede lumiracoxib, dosisafhængig hæmning af COX- 2 i plasma uden hæmning af COX- 1.
Across clinical pharmacology studies, lumiracoxib produced dose-dependent inhibition of COX-2 in plasma without inhibition of COX-1.
Selektiv hæmning af COX- 2 med lumiracoxib giver anti- inflammatorisk og analgetisk effekt.
Selective inhibition of COX-2 by lumiracoxib provides anti-inflammatory and analgesic effects.
Administration af 100 mg, 200 mg eller 400 mg, én gang daglig medfører > 90% maksimal hæmning af COX- 2.
Administration of 100 mg, 200 mg or 400 mg once daily leads to > 90% peak inhibition of COX-2.
Der er hos raske frivillige ingen signifikant hæmning af COX- 1 (vurderet som ex vivo hæmning af tromboxan B2) ved op til 800 mg.
There is no significant inhibition of COX-1 (assessed as ex vivo inhibition of thromboxane B2) up to 800 mg in healthy volunteers.
Lumiracoxib 800 mg daglig medførte ingen klinisk betydningsfuld hæmning af den gastriske prostaglandinsyntese og påvirkede ikke trombocytfunktionen.
Lumiracoxib at 800 mg daily did not lead to clinically meaningful inhibition of gastric prostaglandin synthesis and had no effect on platelet function.
Disse gavnlige
Efficacy In patients with osteoarthritis, lumiracoxib doses up to 200 mg once daily provided significant improvements in pain, stiffness, function, and patient assessments of disease status.
17 virkninger blev opretholdt i op til 52 uger.
These beneficial effects were maintained for up to 52 weeks.
Lumiracoxib 400 mg har i kliniske forsøg lindret smerte i akutte analgetiske modeller af post- operative tandsmerter, post- operative ortopædiske smerter og primær dysmenorré.
In clinical studies, lumiracoxib 400 mg relieved pain in acute analgesic models of post-operative dental pain, post-orthopaedic surgical pain, and primary dysmenorrhea.
I enkeltdosisforsøg med post - operative tandsmerter indtrådte den analgetiske effekt inden for 45 minutter og varede op til 24 timer efter dosering.
In single dose post-operative dental pain trials, the onset of analgesia occurred within 45 minutes and persisted for as long as 24 hours after dosing.
Lumiracoxib 400 mg, én gang daglig var effektivt smertelindrende i korterevarende kliniske forsøg med gentagne doser ved post- operative ortopædiske smerter og smerter fra primær dysmenorré.
In short-term, multiple-dose clinical studies of post-orthopaedic surgical pain and pain from primary dysmenorrhea, lumiracoxib 400 mg once daily was effective in relieving pain.
Sikkerhed The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) TARGET, et 12 måneders, dobbeltblindet, fase III studie inkluderende 18. 325 osteoarthrose patienter randomiseret til lumiracoxib 400 mg én gang daglig (to til fire gange den anbefalede dosis), naproxen 500 mg to gange daglig eller ibuprofen 800 mg tre gange daglig.
Safety The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET)
TARGET inkluderede patienter som fik lavdosis acetylsalicylsyre (75- 100 mg) til primær eller sekundær forebyggelse af koronar hjertelidelse.
16 TARGET, a 12-month, double-blind, phase III study included 18,325 OA patients randomized to lumiracoxib 400 mg once daily (two to four times the recommended OA dose), naproxen 500 mg twice daily or ibuprofen 800 mg three times daily.
- I studiepopulationen som ikke brugte lavdosis acetylsalicylsyre, var incidensen af
- In the population not using low-dose aspirin, the incidence of POBs was 14/ 6950 patients
POB 14/ 6. 950 patienter (0, 2%) for lumiracoxib mod 64/ 6. 968 patienter (0, 92%) for NSAID, med et risikoforhold (RF) på 0, 21 [95% konfidensinterval (KI) 0, 12- 0, 37] p < 0, 0001
(0.2%) for lumiracoxib versus 64/ 6968 patients (0.92%) for NSAIDs, with a hazard ratio (HR) of 0.21 [95% CI 0.12-0.37] p < 0.0001.
- I lavdosis acetylsalicylsyregruppen var incidensen af POB 15/ 2. 167 (0, 69%) for
- In the low dose ASA group the incidence of POBs was 15/ 2167 patients (0.69%) for
lumiracoxib mod 19/ 2. 159 patienter (0, 88%) for NSAID, med et RF på 0, 79 [95% KI 0, 40- 1, 55] (ikke statistisk signifikant).
lumiracoxib versus 19/ 2159 patients (0.88%) for NSAIDs, with a HR of 0.79 [95% CI 0.40- 1.55] (not statistically significant).
- I den samlede studiepopulation var incidensen af POB 29/ 9. 117 (0, 32%) for
- In the overall population, the incidence of POBs was 29/ 9117 patients (0.32%) for lumiracoxib
lumiracoxib mod 83/ 9. 127 patienter (0, 91%) for NSAID med et RF på 0, 34 [95% KI 0, 22- 0, 52] p < 0, 0001
versus 83/ 9127 patients (0.91%) for NSAIDs, with a HR of 0.34 [95% CI 0.22-0.52] p < 0.0001.
Bekræftet eller sandsynligt myokardieinfarkt (klinisk eller ikke symptomgivende), slagtilfælde (iskæmisk eller haemoragisk) og KV- død.
Cardiovascular Effect in TARGET (12-month study) The primary cardiovascular (CV) endpoint studied was the Antiplatelet Trialists’ Collaboration (APTC) endpoint: confirmed or probable myocardial infarction (clinical or silent), stroke (ischemic or haemorrhagic) and CV death.
APTC- hændelsesraten var dog numerisk højere for lumiracoxib end for naproxen, men lavere end for ibuprofen.
However, the APTC event rate was numerically higher for lumiracoxib than for naproxen but lower than for ibuprofen.
- I studiepopulationen som ikke brugte lavdosis acetylsalicylsyre, var incidensen af
- In the population not using low-dose aspirin, the incidence of APTC events was
APTC- hændelser 35/ 6. 950 patienter (0, 50%) for lumiracoxib mod 27/ 6. 968 patienter (0, 39%) for NSAID med et RF på 1, 22 [95% KI 0, 74- 2, 02] p=0, 4343.
35/ 6950 patients (0.50%) for lumiracoxib versus 27/ 6968 patients (0.39%) for NSAIDs, with a HR of 1.22 [95% CI 0.74-2.02] p=0.4343.
Sammenlignet individuelt med ibuprofen og naproxen var RF respektivt 0, 94 [95% KI 0, 44- 2, 04] p=0, 8842 og 1, 49 [0, 95% KI 0, 76- 2, 92] p=0, 2417.
When compared separately to ibuprofen and naproxen, the HR were 0.94 [95% CI 0.44-2.04] p=0.8842 and 1.49 [95% CI 0.76-2.92] p=0.2417, respectively.
- I lavdosis acetylsalicylsyregruppen var incidensen af APTC- hændelser
- In the low-dose ASA group, the incidence of APTC events was 24/ 2167 patients (1.11%) for
24/ 2. 167 patienter (1, 11%) for lumiracoxib mod 23/ 2. 159 patienter (1, 07%) for NSAID, med et RF på 1, 04 [95% KI 0, 59- 1, 84] p=0, 8918.
lumiracoxib versus 23/ 2159 patients (1.07%) for NSAIDs, with a hazard ratio (HR) of 1.04 [95% CI 0.59-1.84] p=0.8918.
Sammenlignet individuelt med ibuprofen og naproxen var RF respektivt 0, 56 [95% KI 0, 20- 1, 54] p=0, 2603 og 1, 42 [95% KI 0, 70- 2, 90] p=0, 3368.
When compared separately to ibuprofen and naproxen, the HR were 0.56 [95% CI 0.20-1.54] p=0.2603 and 1.42 [95% CI 0.70-2.90] p=0.3368, respectively.
- I den samlede studiepopulation var incidensen af APTC- hændelser
- In the overall population, the incidence of APTC events was 59/ 9117 patients (0.65%) for
59/ 9. 117 (0, 65%) for lumiracoxib mod 50/ 9. 127 patienter (0, 55%) for NSAID med et RF på 1, 14 [95% KI 0, 78- 1, 66] p=0, 5074.
lumiracoxib versus 50/ 9127 patients (0.55%) for NSAIDs, with a HR of 1.14 [95% CI 0.78- 1.66] p=0.5074.
Sammenlignet individuelt med ibuprofen og naproxen, var RF respektivt 0, 76 [95% KI 0, 41- 1, 40] p=0, 3775 og 1, 46 [95% KI 0, 89- 2, 37] p=0, 1313.
When compared separately to ibuprofen and naproxen, the HR were 0.76 [95% CI 0.41-1.40] p=0.3775 and 1.46 [95% CI 0.89-2.37] p=0.1313, respectively.
18 Der var ingen statistisk signifikant forskel i incidensen af MI (klinisk MI og ikke symptomgivende MI) mellem lumiracoxib og NSAID.
MI events in TARGET (12-month study) There was no statistically significant difference between lumiracoxib and NSAIDs for incidence of MI (clinical MI and silent MI).
- I studiepopulationen som ikke brugte lavdosis acetylsalicylsyre, var incidensen af
- In the population not using low-dose aspirin, the incidence of MI events was 14/ 6950 patients
MI- hændelser 14/ 6. 950 patienter (0, 20%) for lumiracoxib mod 9/ 6. 968 patienter (0, 13%) for NSAID med et RF på 1, 47 [95% KI 0, 63- 3, 39] p=0, 3706.
(0.20%) for lumiracoxib versus 9/ 6968 patients (0.13%) for NSAIDs, with a HR of 1.47 [95% CI 0.63-3.39] p=0.3706.
Sammenlignet individuelt med ibuprofen og naproxen var RF respektivt 0, 75 [95% KI 0, 20- 2, 79] p=0, 6669 og 2, 37 [0, 95% KI 0, 74- 7, 55] p=0, 1454.
When compared separately to ibuprofen and naproxen, the HR were 0.75 [95% CI 0.20-2.79] p=0.6669 and 2.37 [95% CI 0.74-7.55] p=0.1454, respectively.
- I lavdosis acetylsalicylsyregruppen var incidensen af MI- hændelser
- In the low-dose ASA group, the incidence of MI events was 9/ 2167 patients (0.42%) for
9/ 2. 167 patienter (0, 42%) for lumiracoxib mod 8/ 2. 159 patienter (0, 37%) for NSAID, med et RF på 1, 14 [95% KI 0, 44- 2, 95] p=0, 7899.
lumiracoxib versus 8/ 2159 patients (0.37%) for NSAIDs, with a HR of 1.14 [95% CI 0.44-2.95] p=0.7899.
Sammenlignet individuelt med ibuprofen og naproxen var RF respektivt 0, 47 [95% KI 0, 04- 5, 14] p=0, 5328 og 1, 36 [95% KI 0, 47- 3, 93] p=0, 5658.
When compared separately to ibuprofen and naproxen, the HR were 0.47 [95% CI 0.04-5.14] p=0.5328 and 1.36 [95% CI 0.47-3.93] p=0.5658, respectively.
- I den samlede studiepopulation var incidensen af MI- hændelser 23/ 9. 117 (0, 25%)
- In the overall population, the incidence of MIs was 23/ 9117 patients (0.25%) for lumiracoxib
for lumiracoxib mod 17/ 9. 127 patienter (0, 19%) for NSAID med et RF på 1, 31 [95% KI 0, 70- 2, 45] p=0, 4012.
versus 17/ 9127 patients (0.19%) for NSAIDs, with a HR of 1.31 [95% CI 0.70-2.45] p=0.4012.
Sammenlignet individuelt med ibuprofen og naproxen, var RF respektivt 0, 66 [95% KI 0, 21- 2, 09] p=0, 4833 og 1, 77 [95% KI 0, 82- 3, 84] p=0, 1471.
When compared separately to ibuprofen and naproxen, the HR were 0.66 [95% CI 0.21-2.09] p=0.4833 and 1.77 [95% CI 0.82-3.84] p=0.1471, respectively.
Kardiorenal effekt i TARGET (12 måneders studie) For det systoliske blodtryk var den gennemsnitlige ændring fra basislinien +0, 4 mmHg for lumiracoxib og +2, 1 mmHg for NSAID (p < 0, 0001).
17 For systolic blood pressure, mean change from baseline were +0.4 mmHg for lumiracoxib and +2.1 mmHg for NSAIDs (p < 0.0001).
For det diastole blodtryk var den gennemsnitlige ændring fra basislinien - 0, 1 mmHg for lumiracoxib og +0, 5 mmHg for NSAID (p < 0, 0001).
For diastolic blood pressure, mean change from baseline were - 0.1 mmHg for lumiracoxib and +0.5 mmHg for NSAIDs (p < 0.0001).
Absorption Lumiracoxib absorberes hurtigt efter oral administration.
Absorption Lumiracoxib is rapidly absorbed following oral administration.
15 minutter efter administration af 400 mg, når plasmakoncentrationen 0, 6 µg/ ml, hvilket er tilstrækkeligt til at opnå mere end 90% hæmning af COX- 2.
At 15 minutes post 400 mg dose, the plasma concentration reached 0.6 µg/ ml, which is sufficiently high to achieve over 90% inhibition of COX-2.
2 timer efter dosering.
Median tmax is about 2 hours post dose.
Over dosisspændet 25- 800 mg, øges omfanget af optagelsen (AUC) dosisproportionalt, og maksimal plasma- koncentration (Cmax) er omtrent dosis - proportional.
Over the range of 25 to 800 mg, extent of exposure (AUC) increases in a dose-proportional manner and the peak plasma concentration (Cmax) was roughly dose-proportional.
31 µg t/ ml.
Following 400 mg once daily dosing, Cmax was about 9 µg/ ml and AUC was about 31 µg h/ ml.
74%.
The absolute bioavailability of lumiracoxib is approximately 74%.
{Særnavn} filmovertrukne tabletter kan administreres uden hensyntagen til måltider.
{Invented Name} film- coated tablets can be administered without regard to timing of meals.
Distribution Lumiracoxib bindes i udstrakt grad til plasmaproteiner (≥98%), og bindingen er koncentrationsuafhængig over spændet 0, 1- 100 µg/ ml.
Distribution Lumiracoxib is highly bound to plasma proteins, (≥ 98%), and binding is independent of concentration over a range of 0.1 to 100 µg/ mL.
5 timer efter dosering er koncentrationen af lumiracoxib i human synovialvæske hos patienter med rheumatoid arthritis højere end i plasma og vedbliver at være betragteligt højere i resten af dosisintervallet (AUC12- 24 i synovialvæske er 2, 6 gange højere end i plasma).
By about 5 hour post dose, concentrations of lumiracoxib in human synovial fluid of rheumatoid arthritis patients were higher than plasma and remained substantially higher for the remainder of the dose interval (AUC12-24 in synovial fluid was 2.6 times higher than that for plasma).
Der er ikke observeret forskelle i omfanget af lumiracoxib- proteinbinding i synovialvæske sammenlignet med plasma.
No difference was observed in the extent of lumiracoxib protein binding in synovial fluid compared to plasma.
19 I en rotte- inflammationsmodel påvistes, 1 time efter oral administration af 14[ C] - mærket lumiracoxib, radioakivitetsratio målt ved inflammationsstedet versus radioakivitetsratio målt i blod i forholdet 2: 1 og 8: 1 fire timer efter dosering.
One hour after oral administration of 14[C]-labeled lumiracoxib in a rat model of inflammation, the ratio of radioactivity detected at the site of inflammation versus that detected in the blood was 2:1, and was 8:1 four hours post dose.
Dette indikerer, at lumiracoxib og/ eller dets metabolitter fordeles og forbliver med forskellige præferencer i inflammeret væv.
This indicates lumiracoxib and/ or its metabolites are preferentially distributed and retained in inflamed tissue.
Biotransformation Hos mennesker metaboliseres lumiracoxib i udstrakt grad via leveren.
Biotransformation In humans, lumiracoxib undergoes extensive hepatic metabolism.
Den oxidative metabolisme af lumiracoxib er primært medieret af CYP2C9.
The oxidative metabolism of lumiracoxib is mainly CYP2C9 mediated.
Der er identificeret 3 større metabolitter i plasma:
Three major metabolites were identified in plasma:
4 ’ - hydroxy- lumiracoxib, 5 - carboxy- lumiracoxib og 4 ’ - hydroxy- 5- carboxy- lumiracoxib.
4’ -hydroxy-lumiracoxib, 5-carboxy-lumiracoxib and 4’ - hydroxy-5-carboxy-lumiracoxib.
4 ’ - hydroxymetabolitten har samme potens og COX- 2 selektivitet som lumiracoxib.
The 4’ -hydroxy metabolite has similar potency and COX-2 selectivity to lumiracoxib.
Koncentrationen af 4 ’ - hydroxymetabolitten i plasma og synovialvæsken er lav, og bidrager dermed med al sandsynlighed ikke til effekten.
The concentration of 4’ -hydroxy metabolite in plasma and synovial fluid is low, thus it is unlikely to contribute to efficacy.
Andre metabolitter er ikke aktive som COX- 1 eller COX- 2 hæmmere.
Other metabolites are not active as COX-1 or COX-2 inhibitors.
Elimination Lumiracoxib elimineres primært via hepatisk metabolisme.
Elimination Lumiracoxib is eliminated predominantly via hepatic metabolism.
Efter administration af enkeltdosis lumiracoxib 400 mg til raske frivillige, udskiltes 54% af det lægemiddelrelaterede materiale i urinen og 43% i fæces.
After administration of a single dose of lumiracoxib 400 mg to healthy subjects, 54% of drug-related material was excreted in urine
Kun ca.
18 and 43% in feces.
5% af den administrerede dosis kunne genfindes i ekskreterne som uomdannet lumiracoxib.
Only about 5% of the administered dose was recovered in excreta as unchanged lumiracoxib.
Plasma- clearance er 7, 7 l/ t.
Plasma clearance is 7.7 L/ h.
4 timer.
The mean plasma half-life of lumiracoxib is approximately 4 hours.
Lumiracoxib akkumuleres ikke i plasma ved administration 1 eller 2 gange daglig, og steady- state opnås på første administrationsdag uden stigning i Cmax eller AUC efter forlænget dosering.
Lumiracoxib does not accumulate in plasma under once or twice daily administration and steady state is achieved on the first day of administration with no increase in Cmax or AUC after extended dosing.
Der er ingen forskel i optagelse af lumiracoxib hos mænd og kvinder.
There is no difference in exposure of lumiracoxib in men and women.
Lumiracoxibs farmakokinetik er ens hos patienter af asiatisk, negroid og kaukasisk afstamning.
The pharmacokinetics of lumiracoxib are similar in Asians, Blacks and Caucasians.
CYP2C9- polymorfisme:
CYP2C9 polymorphism:
Der er på baggrund af såvel plasmaoptagelsen af lumiracoxib som farmakogenetiske analyser, ikke fundet tegn på, at lumiracoxiboptagelsen er øget hos patienter med CYP2C9- genotyper forbundet med nedsat metabolisk clearance.
On the basis of both plasma exposure to lumiracoxib and pharmacogenetic analysis, no evidence has been found to suggest that exposure to lumiracoxib is increased in subjects with genotypes of CYP2C9 associated with reduced metabolic clearance.
Dosisjustering er ikke nødvendig hos patienter med nedsat CYP2C9 - metabolisme.
No dose adjustment is necessary in patients known to be CYP2C9 poor metabolisers.
Lumiracoxiboptagelsen ændredes ikke hos patienter med moderat leverinsufficiens (Child- Pugh score 7- 8) sammenlignet med raske frivillige.
Compared to healthy subjects, exposure to lumiracoxib was not changed in patients with moderate hepatic impairment (Child-Pugh score 7-8).
Der sås ingen forskel i plasma- proteinbindingen mellem de 2 grupper.
No difference was observed in the plasma protein binding between the two groups.
Lumiracoxibs farmakokinetik er ikke undersøgt hos patienter med svær leverinsufficiens (Child- Pugh > 9).
The pharmacokinetics of lumiracoxib have not been studied in patients with severe hepatic impairment (Child-Pugh > 9).
20 Der er set 33% fald i lumiracoxib Cmax og 27% fald i AUC ved administration af lumiracoxib til patienter med terminal nyresygdom sammenlignet med raske frivillige.
When lumiracoxib was administered to patients with end-stage renal disease, a 33% decrease in lumiracoxib Cmax and a 27% decrease in AUC were observed compared to healthy subjects.
Gennemsnitlig eksponering for den aktive 4 '- hydroxy- lumiracoxibmetabolit var stort set uændret.
Mean exposure to the active 4'-hydroxy-lumiracoxib metabolite was largely unaffected.
Plasma- proteinbindingen af lumiracoxib hos patienter med terminal nyresygdom svarede til den hos raske frivillige.
Plasma protein binding of lumiracoxib was similar in healthy subjects and in patients with end-stage renal disease.
4. 4).
While renal insufficiency does not significantly influence the pharmacokinetics of lumiracoxib and its active metabolite, use of lumiracoxib in patients with moderate to severe renal insufficiency is contraindicated because of potential further deterioration of renal function due to cyclooxygenase inhibition (see section 4.3 and 4.4).
Lumiracoxibs farmakokinetik er ikke undersøgt hos børn.
The pharmacokinetics of lumiracoxib in paediatric patients have not been studied.
Der er induceret kromosomafvigelser i V79- celller ved høje, cytotoksiske koncentrationer af lumiracoxib, som ikke anses som værende biologisk relevante for mennesker.
Chromosome aberrations were induced in V79 cells at high, cytotoxic concentrations of lumiracoxib,
Der var ingen indikation af genotoksisk potentiale i 3 in vivo rotteforsøg (mikronukleus- test i knoglemarv og lever samt lever comet- assay).
There was no indication of genotoxic potential in three in vivo rat studies (micronucleus tests in bone marrow and liver and liver comet assay).
Der sås hos rotter (26 ugers forsøg) og aber (39 ugers forsøg) ingen uønskede hændelser i disse organer ved systemisk optagelse af henholdsvis 6, 5 og 22 gange større end hos mennesker efter en dosis på 200 mg.
Systemic exposure at levels with no adverse effect for these targets in rat (26-week study) and monkey (39-week study) were 6.5 and 22 times that in man following a 200 mg therapeutic dose, respectively.
Lumiracoxib var ikke teratogent i reproduktionstoksicitetforsøg med rotter og kaniner ved doser svarende til systemisk optagelse 10, 4 (rotter) og 38 (kaniner) gange større end det humane terapeutiske niveau efter en dosis på 200 mg.
Lumiracoxib was not teratogenic in reproduction toxicity studies conducted in rats and rabbits at doses representing systemic exposure 10.4 (rat) and 38 (rabbit) times greater than the human therapeutic level after a 200 mg dose.
Hos rotter var forekomsten af præ- implantationstab øget ved en dosis på 100 mg/ kg/ dag (10, 4 gange den humane terapeutiske optagelse efter en dosis på 200 mg), som forårsagede maternal toksicitet.
In rats the incidence of pre-implantation loss was increased at a dose of 100 mg/ kg/ day, (10.4 times the human therapeutic exposure following a dose of 200 mg), which caused maternal toxicity.