qanastek/EMEA-V3 huggingface dataset:
In March 2006, the marketing authorisation holders (MAH) for Arcoxia (etoricoxib) submitted an application to extend the licensed indication to include treatment of ankylosing spondylitis (AS), at a recommended daily dose of 90mg.
F’ Marzu 2006, id- detenturi ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq (MAH) għal Arcoxia (etoricoxib) issottomettew applikazzjoni biex jestendu l- indikazzjoni liċenzjata biex tinkludi t - trattament ta ’ spondilite ankilosanti (AS), f’ doża ta ’ kuljum irrakkomandata ta ’ 90mg.
During the assessment of the procedure, concerns were raised over the long-term safety of etoricoxib 90mg in patients with AS.
Waqt il - proċedura ta ’ valutazzjoni tal- proċedura, tqajjem tħassib dwar is- sigurtà fit- tul ta ’ 90mg etoricoxib f’ pazjenti b’ AS.
Following concerns of a possible increased cardiovascular (CV) risk related to the use of the 90mg dose of etoricoxib, France considered that a review of the benefit/ risk profile of Arcoxia was needed.
Wara tħassib ta ’ żieda fir- riskju kardjovaskulari (KV) possibbli relatat ma ’ l- użu ta ’ doża ta ’ 90mg ta ’ etoricoxib, Franza ikkunsidrat li kien meħtieġ eżami mill- ġdid tal- profil benefiċċju/ riskju ta ’ Arcoxia.
Therefore, France sent a notification that was received by the EMEA on 19 September 2007 and a referral under Article 6 (12) of Commission Regulation EC No 1084/ 2003 was started on 20 September 2007.
Għalhekk, Franza bagħtet notifika li waslet għand l- EMEA fid- 19 ta ’ Settembru 2007 u fl- 20 ta ’ Settembru 2007, inbdiet referenza skond l- Artikolu 6( 12) tar- Regolament tal- Kummissjoni KE Nru 1084/ 2003.
The CHMP reviewed the data submitted by the marketing authorisation holders from clinical trials, drug utilisation studies and spontaneous reporting of adverse drug reactions.
Is- CHMP irreveda d- dejta sottomessa mid- detenturi ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq, minn provi kliniċi, studji ta ’ l- użu tal- mediċina u rapportaġġ spontanju ta ’ reazzjonijiet avversi tal - mediċina.
The CHMP assessed efficacy data submitted for AS and safety data collected regarding AS, and also in the rheumatoid arthritis population for which the same dose is approved for treatment.
Is- CHMP ivvaluta d- dejta ta ’ l- effikaċja sottomessa għal AS u d- dejta tas- sigurtà miġbura fir- rigward ta ’ AS, kif ukoll fil- popolazzjoni ta ’ l- artrite rewmatojde għal liema l- istess doża hija approvata għat- trattament.
The CHMP concluded on 26 June 2008 that the data confirm the known relatively adverse renovascular safety profile of etoricoxib (hypertension, oedema and congestive heart failure), but similar CV thrombotic risk as diclofenac and some degree of upper GI safety advantage over naproxen and diclofenac (though no particular lower GI safety advantage).
Fis- 26 ta ’ Ġunju 2008 is- CHMP ikkonkluda li d- dejta tikkonferma l- profil ta ’ sigurtà renovaskulari relattivament avvers magħruf ta ’ etoricoxib (ipertensjoni, edema u falliment konġestiv tal- qalb), iżda riskju trombotiku KV simili għal dak ta ’ diclofenac u ċertu grad ta ’ vantaġġ ta ’ sigurtà tal- parti GI ta ’ fuq, fuq naproxen u diclofenac (iżda l- ebda vantaġġ ta ’ sigurtà partikolari tal- parti GI t’ isfel).
There is little direct comparative safety data for individual NSAIDs other than diclofenac and naproxen and it is therefore difficult to determine risks for etoricoxib compared with ibuprofen, ketoprofen or other less-commonly used NSAIDs.
Hemm ftit dejta ta ’ tqabbil ta ’ sigurtà għal NSAIDs individwali għajr għal diclofenac u naproxen u għalhekk huwa diffiċli biex ikunu stabbiliti riskji għal etoricoxib meta mqabbel ma ’ ibuprofen, ketoprofen jew NSAIDs oħrajn użati b’ mod inqas komuni.
Drug utilisation data showed that some patients with high blood pressure are being initiated on etoricoxib.
Dejta ta ’ użu tal- mediċina wriet li xi pazjenti bi pressjoni għolja tad- demm qegħdin jinbdew fuq etoricoxib.
The CHMP therefore recommends the strengthening of the contraindication in hypertensive patients and alerts prescribers that blood pressure needs to be monitored, especially within 2 weeks of treatment initiation.
Is- CHMP għalhekk jirrakkomanda t- tisħiħ tal- kontraindikazzjoni f’ pazjenti ipertensivi u jwissi lil dawk li jippreskrivuh (jagħtuh b’ riċetta medika), li l- pressjoni jeħtieġ li tkun sorveljata, speċjalment fi żmien ġimagħtejn mill- bidu tat- trattament.
Healthcare professionals were to be reminded of these measures through a communication letter (DHCP).
Professjonisti fil- qasam tal- kura tas- saħħa kellhom jiġu mfakkrin b’ dawn il- miżuri permezz ta ’ ittra ta ’ komunikazzjoni (DHCP).
Data from clinical studies showed clinically meaningful treatment effect for the 90mg etoricoxib once daily dose for AS indications; however, some data are available to indicate that lower doses might also show effect.
Dejta minn studji kliniċi wriet effett ta ’ kura klinikament sinifikattiva għad- doża ta ’ 90mg etoricoxib darba kuljum għal indikazzjonijiet AS; madankollu, hemm xi dejta disponibbli li tindika li dożi iktar baxxi jistgħu wkoll juru effett.
The CHMP therefore recommends that dose finding studies are explored to conclude if treatment with 60mg once daily would also be adequate for some patients.
Għaldaqstant, is- CHMP jirrakkomanda li studji ta ’ tiftix tad- doża jkunu eżaminati bir- reqqa biex jikkonkludu jekk trattament b’ 60mg darba kuljum tkunx ukoll adegwata għal xi pazjenti.
Based on the review of the available data, the CHMP considers that the benefits of etoricoxib outweigh the risks in the treatment of ankylosing spondylitis.
Abbażi tar- reviżjoni tad- dejta disponibbli, is- CHMP ikkunsidra li l- benefiċċji ta ’ etoricoxib jegħlbu r - riskji fit- trattament ta ’ spondilite ankilosanti.
7 GROUNDS FOR AMENDMENT OF THE SUMMARY OF PRODUCT CHARACTERISTICS AND PACKAGE LEAFLET
7 RAĠUNIJIET GĦALL- EMENDA TAS- SOMMARJU TAL- KARATTERISTIĊI TAL - PRODOTT U L- FULJETT TA ’ TAGĦRIF
- The Committee considered the referral made under Article 6(12) of Commission Regulation EC No
- Il- Kumitat ikkunsidra r- referenza magħmula skond l- Artikolu 6( 12) tar- Regolament tal -
1084/ 2003, for Arcoxia and associated names.
Kummissjoni KE Nru 1084/ 2003, għal Arcoxia u ismijiet assoċjati.
- In view of the available data, the CHMP considered that the benefit/ risk balance for Arcoxia
- Mil- lat ta ’ dejta disponibbli, is- CHMP ikkunsidra li l- bilanċ benefiċċju/ riskju għad- doża ta ’ 90
(etoricoxib) 90mg dose in AS indication is positive; however, revisions to the contraindications and warnings sections have been added to the summary of product characteristics and package leaflet in relation to cardiorenal safety.
mg Arcoxia (etoricoxib) fl- indikazzjoni AS huwa wieħed pożittiv; madankollu, reviżjonijiet għas- sezzjonijiet ta ’ kontraindikazzjonijiet u twissijiet ġew miżjuda fis- sommarju tal - karatteristiċi tal- prodott u fil- fuljett ta ’ tagħrif fir- rigward tas- sigurtà kardjorenali.
The CHMP recommended the granting of the variation of the Marketing Authorisations for which the summaries of product characteristics, labelling and package leaflets are set out in Annex III and under the conditions set out in Annex IV.
Is- CHMP irrakkomanda l- għoti tal- varjazzjoni ta ’ l- Awtorizzazzjonijiet għat- Tqegħid fis- Suq għal liema, is- sommarji tal- karatteristiċi tal- prodott, it- tikketti u l- fuljetti ta ’ tagħrif huma stabbiliti fl - Anness III u skond il- kundizzjonijiet stabbiliti fl- Anness IV.
SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET
SOMMARJU TAL- KARATTERISTIĊI TAL- PRODOTT TIKKETTA U FULJETT TA ’ TAGĦRIF
9 SUMMARY OF PRODUCT CHARACTERISTICS
9 SOMMARJU TAL- KARATTERISTIĊI TAL- PRODOTT
< ARCOXIA (see Annex 1) > 30 mg film-coated tablets< ARCOXIA (see Annex 1) > 60 mg film-coated tablets< ARCOXIA (see Annex 1) > 90 mg film-coated tablets < ARCOXIA (see Annex 1) > 120 mg film-coated tablets [See Annex 1- To be completed nationally]
< ARCOXIA (ara l- Anness 1) > 30 mg pilloli miksijin b’ rita < ARCOXIA (ara l- Anness 1) > 60 mg pilloli miksijin b’ rita < ARCOXIA (ara l- Anness 1) > 90 mg pilloli miksijin b’ rita < ARCOXIA (ara l- Anness 1) > 120 mg pilloli miksijin b’ rita [Ara l- Anness 1 - Għandha timtela fuq livell nazzjonali]
Each film-coated tablet contains 30, 60, 90 or 120 mg of etoricoxib.
Kull pillola miksija b’ rita fiha 30, 60, 90 jew 120 mg ta ’ etoricoxib.
30 mg: lactose 1.4 mg 60 mg: lactose 2.8 mg 90 mg: lactose 4.2 mg 120 mg: lactose 5.6 mg
30 mg: lactose 1. 4 mg 60 mg: lactose 2. 8 mg 90 mg: lactose 4. 2 mg 120 mg: lactose 5. 6 mg
30 mg Tablets:
30 mg Pilloli:
Blue-green, apple-shaped biconvex tablets< debossed ‘101’ on one side and ‘ACX 30’ on the other side >.
Pilloli ġejjin għat- tond miż- żewġ naħat f’ għamla ta ’ tuffieħa blu fl- aħdar < imnaqqxin b ’ ‘ 101 ’ fuq naħa u b ’ ‘ ACX 30 ’ fuq in- naħa l- oħra >.
60 mg Tablets:
60 mg Pilloli:
Dark green, apple-shaped, biconvex tablets< debossed ‘200’ on one side and ‘ARCOXIA 60’ on the other side >.
Pilloli ġejjin għat- tond miż- żewġ naħat f’ għamla ta ’ tuffieħa ħodor skuri < imnaqqxin b ’ ‘ 200 ’ fuq naħa u b ’ ‘ ARCOXIA 60 ’ fuq in- naħa l- oħra >.
90 mg Tablets:
90 mg Pilloli:
White, apple-shaped, biconvex tablets< debossed ‘202’ on one side and ‘ARCOXIA 90’ on the other side >.
Pilloli ġejjin għat- tond miż- żewġ naħat f’ għamla ta ’ tuffieħa, bojod, < imnaqqxin b ’ ‘ 202 ’ fuq naħa u b ’ ‘ ARCOXIA 90 ’ fuq in- naħa l- oħra >.
120 mg Tablets:
120 mg Pilloli:
Pale-green, apple-shaped, biconvex tablets< debossed ‘204’ on one side and ‘ARCOXIA 120’ on the other side >.
Pilloli ġejjin għat- tond miż- żewġ naħat f’ għamla ta ’ tuffieħa ħodor ċari < imnaqqxin b ’ ‘ 204 ’ fuq naħa u b ’ ‘ ARCOXIA 120 ’ fuq in- naħa l- oħra >.
For the symptomatic relief of osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, and the pain and signs of inflammation associated with acute gouty arthritis.
Għas- serħan mis- sintomi ta ’ osetoartrite (OA), artrite rewmatojde (RA), ankylosing spondylitis u l - uġigħ u s- sinjali ta ’ infjammazzjoni assoċjati ma ’ artrite tal- gotta akuta.
The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of the individual patient's overall risks (see sections 4.3, 4.4).
Id- deċiżjoni jekk għandux jiġi preskritt inibitur selettiv COX- 2 għandha tkun ibbażata fuq valutazzjoni tar- riskji ġenerali tal- pazjenti individwali (ara sezzjonijiet 4. 3, 4. 4).
< ARCOXIA > is administered orally and may be taken with or without food.
< ARCOXIA > jingħata mill- ħalq u jista ’ jittieħed ma ’ l- ikel kif ukoll mhux ma ’ l- ikel.
The onset of the effect of the medicinal product may be faster when< ARCOXIA > is administered without food.
Il- bidu ta ’ l - effett tal- prodott mediċinali jista ’ jkun aktar veloċi meta < ARCOXIA > jingħata mingħajr ikel.
This should be considered when rapid symptomatic relief is needed.
Dan għandu jitqies meta jkun hemm bżonn ta ’ serħan rapidu mis- sintomi.
11 As the cardiovascular risks of etoricoxib may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used.
Il- ħtieġa tal -
The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically, especially in patients with osteoarthritis (see sections 4.3, 4.4, 4.8 and 5.1).
11 pazjent għal serħan mis- sintomi u għar- rispons għat- terapija għandhom jiġu evalwati mill- ġdid perjodikament f’ pazjenti b’ osteoartrite (ara sezzjonijiet 4. 3, 4. 4, 4. 8 u 5. 1).
Osteoarthritis The recommended dose is 30 mg once daily.
Osteoartrite Id- doża rakkomandata hija 30 mg darba kuljum.
In some patients with insufficient relief from symptoms, an increased dose of 60 mg once daily may increase efficacy.
F’ xi pazjenti b’ serħan mis- sintomi insuffiċjenti, doża miżjuda ta ’ 60 mg darba kuljum tista ’ żżid l- effikaċja.
In the absence of an increase in therapeutic benefit, other therapeutic options should be considered.
Fin- nuqqas ta ’ żieda f’ benefiċċju terapewtiku, għandhom jiġu kkunsidrati opzjonijiet terapewtiċi oħrajn.
Rheumatoid arthritis The recommended dose is 90 mg once daily.
Artrite rewmatojde Id- doża rakkomandata hija 90 mg darba kuljum.
Acute gouty arthritis The recommended dose is 120 mg once daily.
Artrite tal- gotta akuta Id- doża rakkomandata hija 120 mg darba kuljum.
Etoricoxib 120 mg should be used only for the acute symptomatic period.
Etoricoxib 120 mg għandu jintuża għall- perjodu sintomatiku akut.
In clinical trials for acute gouty arthritis, etoricoxib was given for 8 days.
Fi provi kliniċi għal artrite tal- gotta akuta, etoricoxib ingħata għal 8 ijiem.
Ankylosing spondylitis The recommended dose is 90 mg once daily.
Ankylosing spondylitis Id- doża rakkomandata hija 90 mg darba kuljum
Doses greater than those recommended for each indication have either not demonstrated additional efficacy or have not been studied.
Dożi akbar minn dawk irrakkomandati għal kull indikazzjoni jew ma urewx effikaċja addizzjonali jew ma ġewx studjati.
Therefore:
Għalhekk:
The dose for OA should not exceed 60 mg daily The dose for RA and ankylosing spondylitis should not exceed 90 mg daily The dose for acute gout should not exceed 120 mg daily, limited to a maximum of 8 days treatment.
Id- doża għal OA ma għandhiex taqbeż 60 mg kuljum Id- doża għal RA u għal ankylosing spondylitis ma għandhiex taqbeż 90 mg kuljum Id- doża għal gotta akuta ma għandhiex taqbeż 120 mg kuljum, limitata għal kura massima ta ’ 8 ijiem.
Elderly No dosage adjustment is necessary for elderly patients.
L- anzjani Ebda aġġustament fid- doża ma huwa meħtieġ għal pazjenti anzjani.
As with other drugs, caution should be exercised in elderly patients (see section 4.4).
Bħal b’ kull mediċina oħra, għandha tingħata attenzjoni f’ pazjenti anzjani (ara sezzjoni 4. 4).
Hepatic insufficiency Regardless of indication, in patients with mild hepatic dysfunction (Child-Pugh score 5-6) a dose of 60 mg once daily should not be exceeded.
Indeboliment tal- fwied Minkejja l- indikazzjoni, f’ pazjenti b’ malfunzjonament ħafifa tal- fwied (skor Child- Pugh 5- 6), ma għandhiex tinqabeż doża ta ’ 60 mg darba kuljum.
In patients with moderate hepatic dysfunction (Child-Pugh score 7-9), regardless of indication, the dose of 60 mg every other day should not be exceeded; administration of 30 mg once daily can also be considered.
F’ pazjenti b’ malfunzjonament moderata tal- fwied (skor Child- Pugh ta ’ 7- 9), minkejja l- indikazzjoni, id- doża ta ’ 60 mg jum iva u jum le ma għandhiex tinqabeż; għoti ta ’ 30 mg darba kuljum jista ’ jiġi kkunsidrat ukoll.
Clinical experience is limited particularly in patients with moderate hepatic dysfunction and caution is advised.
Esperjenza klinika hija limitata b’ mod partikolari f’ pazjenti b’ malfunzjonament moderata tal- fwied u hija rrakkomandata l- kawtela.
There is no clinical experience in patients with severe hepatic dysfunction (Child-Pugh score ≥ 10); therefore, its use is contra-indicated in these patients (see sections 4.3, 4.4 and 5.2).
Ma hemm ebda esperjenza klinika f’ pazjenti b’ malfunzjonament severa tal- fwied (skor Child- Pugh ≥10); għalhekk, l- użu tiegħu huwa kontra- indikat f’ dawn il- pazjenti (ara sezzjonijiet 4. 3, 4. 4 u 5. 2).
Renal insufficiency No dosage adjustment is necessary for patients with creatinine clearance ≥ 30 ml/ min (see section 5.2).
Indeboliment tal- kliewi Ebda aġġustament fid- doża ma huwa meħtieġ għal pazjenti bi tneħħija tal- kreatinina ≥30 ml/ min (ara sezzjoni 5. 2).
The use of etoricoxib in patients with creatinine clearance < 30 ml/ min is contra-indicated (see sections 4.3 and 4.4).
L- użu ta ’ etoricoxib f’ pazjenti bi tneħħija tal- kreatinina < 30 ml/ min huwa kontra - indikat (ara sezzjonijiet 4. 3 u 4. 4).
Paediatric patients Etoricoxib is contra-indicated in children and adolescents under 16 years of age (see section 4.3).
Pazjenti tfal Etoricoxib huwa kontra- indikat fi tfal u adoloxxenti taħt is- 16- il sena (ara sezzjoni 4. 3).
Active peptic ulceration or active gastro-intestinal (GI) bleeding.
Ulċerazzjoni peptika attiva jew fsada gastro- intestinali (GI).
12 Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria, or allergic-type reactions after taking acetylsalicylic acid or NSAIDs including COX-2 (cyclooxygenase-2) inhibitors.
12 Pazjenti li esperjenzaw bronkospażmu, rinite akuta, qarnita nasali, edema anġjonewrotika, urtikarja jew reazzjonijiet tat- tip allerġiċi wara t- teħid ta ’ acetylsalicylic acid jew NSAIDs inkluż inibituri COX- 2 (cyclooxygenase- 2).
Pregnancy and lactation (see sections 4.6 and 5.3).
Tqala u treddigħ (ara sezzjonijiet 4. 6 u 5. 3).
Severe hepatic dysfunction (serum albumin < 25 g/ l or Child-Pugh score ≥ 10).
Malfunzjonament severa tal- fwied (albumina tas- serum < 25 g/ l jew skor Child- Pugh ≥10).
Estimated renal creatinine clearance < 30 ml/ min.
Stima tat- tneħħija tal- kreatina mill- kliewi < 30 ml/ min.
Children and adolescents under 16 years of age.
Tfal u adoloxxenti taħt l- età ta ’ 16- il sena.
Inflammatory bowel disease.
Mard infjammatorju ta ’ l- imsaren.
Congestive heart failure (NYHA II-IV).
Indeboliment konġestiv tal- qalb (NYHA II- IV).
Patients with hypertension whose blood pressure is persistently elevated above 140/ 90mmHg and has not been adequately controlled.
Pazjenti bi pressjoni għolja li l- pressjoni tad- demm tagħhom hija ogħla minn 140/ 90mmHg b’ mod persistenti u ma tkunx ġiet ikkontrollata b’ mod adegwat.
Established ischaemic heart disease, peripheral arterial disease, and/ or cerebrovascular disease.
Mard tal- qalb iskemiku stabbilit, mard arterjali periferali, u/ jew mard ċerebrovaskulari.
Gastrointestinal effects Upper gastrointestinal complications [perforations, ulcers or bleedings (PUBs)], some of them resulting in fatal outcome, have occurred in patients treated with etoricoxib.
Effetti gastrointestinali Kumplikazzjonijiet gastrointestinali fil- parti ta ’ fuq [perforazzjonijiet, ulċeri jew fsada (PUBs)], li wħud minnhom irriżultaw f’ konsegwenzi fatali, seħħew f’ pazjenti ttrattati b’ etoricoxib.
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.
Hija rrakkomandata l- kawtela fil- kura ta ’ pazjenti li huma l- aktar f’ riskju li jiżviluppaw kumplikazzjoni gastrointestinali bl- NSAIDs; l- anzjani, pazjenti li jużaw kwalunkwe NSAID jew acetylsalicylic acid ieħor jew pazjenti bi storja preċedenti ta ’ mard gastrointestinali, bħall - ulċerazzjoni u fsada GI.
There is a further increase in the risk of gastrointestinal adverse effects (gastrointestinal ulceration or other gastrointestinal complications) when etoricoxib is taken concomitantly with acetylsalicylic acid (even at low doses).
Hemm żieda addizzjonali fir- riskju ta ’ effetti avversi gastrointestinali (ulċerazzjoni gastrointestinali jew kumplikazzjonijiet gastrointestinali) meta etoricoxib jittieħed fl- istess ħin ma ’ acetylsalicylic acid (anki f’ dożi baxxi).
A significant difference in GI safety between selective COX-2 inhibitors + acetylsalicylic acid vs.
Ma ntwerietx differenza sinjifikanti fis- sigurtà GI bejn inibituri COX- 2 selettivi + acetylsalicylic acid vs.
NSAIDs + acetylsalicylic acid has not been demonstrated in long-term clinical trials (see section 5.1).
NSAIDs + acetylsalicylic acid fi provi kliniċi fuq perjodu ta ’ żmien twil (ara sezzjoni 5. 1).
Cardiovascular effects Clinical trials suggest that the selective COX-2 inhibitor class of drugs may be associated with a risk of thrombotic events (especially myocardial infarction (MI) and stroke), relative to placebo and some NSAIDs.
Effetti kardjo vaskulari Provi kliniċi jissuġġerixxu li l- klassi ta ’ l- inibitur selettiv COX- 2 ta ’ mediċini tista ’ tkun assoċjata ma ’ riskju ta ’ episodji trombotiċi (b’ mod speċjali infart mijokardijaku (MI) u puplesija), meta mqabbla ma ’ plaċebo u ma ’ xi NSAIDs.
As the cardiovascular risks of etoricoxib may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used.
Minħabba li r- riskji kardjovaskulari ta ’ etoricoxib jistgħu jiżdiedu mad- doża u mat- tul ta ’ l- espożizzjoni, għandha tintuża l- iżgħar doża effettiva possibbli u għall- iqsar tul ta ’ żmien possibbli.
The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically, especially in patients with osteoarthritis (see sections 4.2, 4.3, 4.8 and 5.1).
Il- bżonn tal- pazjent għal serħan sintomatiku u r- rispons għat- terapija għandhom jiġu evalwati mill- ġdid perjodikament, b’ mod speċjali f’ pazjenti b’ osteoartrite (ara sezzjonijiet 4. 2, 4. 3, 4. 8 u 5. 1).
Patients with significant risk factors for cardiovascular events (e. g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with etoricoxib after careful consideration (see section 5.1).
Pazjenti b’ fatturi ta ’ riskju sinjifikanti għal episodji kardjovaskulari (eż. pressjoni għolja, lipidemija għolja, dijabete mellitus, tipjip) għandhom jiġu kkurati b’ etoricoxib wara kunsiderazzjoni attenta (ara sezzjoni 5. 1).
COX-2 selective inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular thrombo-embolic diseases because of their lack of antiplatelet effect.
Inibituri selettivi COX- 2 mhumiex sostituti għal acetylsalicylic acid għal profilassi ta ’ mard trombo - emboliku kardjovaskulari minħabba n- nuqqas ta ’ effett anti- pjastrini tagħhom.
Therefore antiplatelet therapies should not be discontinued (see sections above, 4.5 and 5.1.).
Għalhekk terpiji kontra l- pjastrini ma għandhomx jitwaqqfu (ara sezzjonijiet fuq, 4. 5 u 5. 1).
13 uncompensated heart failure, or cirrhosis.
13 Effetti renali Prostaglandini renali jista ’ jkollhom rwol kumpensatorju fiż- żamma ta ’ perfużjoni renali.
Monitoring of renal function in such patients should be considered.
Il- monitoraġġ ta ’ funzjoni renali fuq pazjenti bħal dawn għandu jiġi kkunsidrat.
Fluid retention, oedema and hypertension As with other medicinal products known to inhibit prostaglandin synthesis, fluid retention, oedema and hypertension have been observed in patients taking etoricoxib.
Żamma ta ’ fluwidu, edema u pressjoni għolja Bħal bi prodotti mediċinali oħrajn magħrufin li jinibixxu s- sintesi ta ’ prostaglandin, żamma tal - fluwidi, edema u pressjoni għolja ġew osservati f’ pazjenti li qegħdin jieħdu etoricoxib.
All Nonsteroidal Antiinflammatory Drugs (NSAIDs), including etoricoxib, can be associated with new onset or recurrent congestive heart failure.
Il- Mediċini Anti- infjammatorji Mhux- Sterojdali (NSAIDs) kollha nkluż etoricoxib jistgħu jkunu assoċjati ma ’ feġġa ta ’ jew ma ’ kollass konġestiv rikorrenti tal- qalb.
For information regarding a dose related response for etoricoxib see section 5.1.
Għal tagħrif dwar rispons relatat mad- doża għal etoricoxib ara sezzjoni 5. 1.
Caution should be exercised in patients with a history of cardiac failure, left ventricular dysfunction, or hypertension and in patients with pre-existing oedema from any other reason.
Għandha tiġi eżerċitata l- kawtela f’ pazjenti bi storja ta ’ indeboliment kardijaku, malfunzjonament ventrikulari xellugi, jew pressjoni għolja u f’ pazjenti b’ edema pre - eżistenti minn kwalunkwe raġuni oħra.
If there is clinical evidence of deterioration in the condition of these patients, appropriate measures including discontinuation of etoricoxib should be taken.
Jekk hemm evidenza klinika ta ’ deterjorament fil- kundizzjoni ta ’ dawn il- pazjenti, għandhom jittieħdu miżuri xierqa nkluż it- twaqqif ta ’ etoricoxib.
Etoricoxib may be associated with more frequent and severe hypertension than some other NSAIDs and selective COX-2 inhibitors, particularly at high doses.
Etoricoxib jista ’ jkun assoċjat ma ’ pressjoni għolja aktar frekwenti u severa minn xi NSAIDs oħrajn u inibituri COX- 2 selettivi, partikolarment f’ dożi għoljin.
Therefore, hypertension should be controlled before treatment with etoricoxib (see section 4.3) and special attention should be paid to blood pressure monitoring during treatment with etoricoxib.
Għalhekk il- pressjoni għolja għandha tiġi kkontrollata qabel il- kura b’ etoricoxib (ara sezzjoni 4. 3) u għandha tingħata attenzjoni speċjali għall - monitoraġġ tal- pressjoni tad- demm matul trattatment b’ etoricoxib.
Blood pressure should be monitored within two weeks after initiation of treatment and periodically thereafter.
Il- pressjoni tad- demm għandha tiġi mmonitorjata fi żmien ġimagħtejn wara l- bidu tat- trattament u minn hemm 'il quddiem perjodikament.
If blood pressure rises significantly, alternative treatment should be considered.
Jekk il- pressjoni tad- demm tiżdied b’ mod sinjifikanti, għandha tiġi kkunsidrata kura alternattiva.
Hepatic effects Elevations of alanine aminotransferase (ALT) and/ or aspartate aminotransferase (AST) (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials treated for up to one year with etoricoxib 30, 60 and 90 mg daily.
Effetti epatiċi Żidiet ta ’ alanine aminotransferase (ALT) u/ jew aspartate aminotransferase (AST) (bejn wieħed u ieħor tliet darbiet u iktar il- limitu ta ’ fuq tan- normal) ġew irrapportati f’ madwar 1% tal- pazjenti fi provi kliniċi kkurati għal sena b’ etoricoxib 30, 60 u 90 mg kuljum.
Any patients with symptoms and/ or signs suggesting liver dysfunction, or in whom an abnormal liver function test has occurred, should be monitored.
Kull pazjent b’ sintomi u/ jew sinjali li jissuġġerixxu malfunzjonament tal- fwied, jew li sar test tal - funzjoni tal- fwied fuqhom u dan irriżulta bħala mhux normali, għandhom jiġu mmonitorjati.
If signs of hepatic insufficiency occur, or if persistently abnormal liver function tests (three times the upper limit of normal) are detected, etoricoxib should be discontinued.
Jekk iseħħu sinjali ta ’ insuffiċjenza tal- fwed, jew jekk jirriżultaw testijiet tal- funzjoni tal- fwied mhux normali b’ mod persistenti (tliet darbiet il- limitu ta ’ fuq tan- normal), etoricoxib għandu jitwaqqaf.
General If during treatment, patients deteriorate in any of the organ system functions described above, appropriate measures should be taken and discontinuation of etoricoxib therapy should be considered.
Ġenerali Jekk matul it- trattament, pazjenti jmorru għall- agħar fi kwalunkwe funzjoni tas- sistema ta ’ l- organi deskritta fuq, għandhom jittieħdu miżuri xierqa u għandu jiġi kkunsidrat it- twaqqif tal- kura b’ etoricoxib.
Medically appropriate supervision should be maintained when using etoricoxib in the elderly and in patients with renal, hepatic, or cardiac dysfunction.
Meta jkun qiegħed jintuża etoricoxib, għandha tinżamm sorveljanza medika xierqa fl - anzjani u fil- pazjenti b’ malfunzjonament renali, epatika jew kardijaka.
Caution should be used when initiating treatment with etoricoxib in patients with dehydration.
Għandha tintuża l- kawtela meta jinbeda trattament b’ etoricoxib f’ pazjenti b’ deidratazzjoni.
It is advisable to rehydrate patients prior to starting therapy with etoricoxib.
Huwa rrakkomandat li pazjenti jiġu re- idratati qabel jibdew il- kura b’ etoricoxib.
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 of NSAIDs and some selective COX-2 inhibitors during post-marketing surveillance (see section 4.8).
Reazzjonijiet serji tal- ġilda, uħud minnhom fatali, inkluż dermatite esfoljattiva, is- sindrome ta ’ Stevens- Johnson, u nekroliżi epidermali tossika, ġew irrapportati fuq bażi rari ħafna f’ assoċjazzjoni ma ’ l- użu ta ’ NSAIDs u xi inibituri selettivi ta ’ COX- 2 matul sorveljanza ta ’ wara t- tqegħid fis- suq (ara sezzjoni 4. 8).
Patients appear to be at highest risk for these reactions early in the course of therapy with the onset of the reaction occurring in the majority of cases within the first month of treatment.
Il- pazjenti jidhru li jkunu fl- akbar riskju għal dawn ir- reazzjonijiet kmieni fil- kors tal- kura bil- feġġa tar- reazzjoni sseħħ, fil- maġġoranza tal- każijiet, fl- ewwel xahar tal- kura.
Serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported in patients receiving etoricoxib (see section 4.8).
Reazzjonijiet serji ta ’ sensittività eċċessiva (bħal anafilassi u anġjoedema) ġew irrapportati f’ pazjenti li jirċievu etoricoxib (ara sezzjoni 4. 8).
Some selective COX- 2 inhibitors have been associated with an increased risk of skin reactions in patients with a history of any drug allergy.
Xi inibituri selettivi ta ’ COX- 2 ġew assoċjati ma ’ żieda fir - reazzjonijiet tal- ġilda f’ pazjenti bi storja ta ’ xi allerġija għal mediċina.
Etoricoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Etoricoxib għandu jitwaqqaf ma ’ l- ewwel dehra ta ’ raxx tal- ġilda, leżjonijiet mukosali, jew ta ’ xi sinjali oħrajn ta ’ sensittività eċċessiva.
Etoricoxib may mask fever and other signs of inflammation.
14 Etoricoxib jista ’ jaħbi d- deni u sinjali oħrajn ta ’ infjammazzjoni.
Caution should be exercised when co-administering etoricoxib with warfarin or other oral anticoagulants (see section 4.5).
Għandha tiġi eżerċitata l- kawtela meta etoricoxib jingħata flimkien mal- warfarina jew ma ’ antikoagulanti orali oħrajn (ara sezzjoni 4. 5).
The use of etoricoxib, as with any medicinal product known to inhibit cyclooxygenase / prostaglandin synthesis, is not recommended in women attempting to conceive (see sections 4.6, 5.1, and 5.3).
L- użu ta ’ etoricoxib, bħal b’ kull prodott mediċinali ieħor magħruf li jinibixxi sinteżi ta ’ cyclooxygenase / prostaglandin, mhuwiex rakkomandat f’ nisa li jkunu qegħdin jipprovaw ikollhom it - tfal (ara sezzjonijiet 4. 6, 5. 1, u 5. 3).
14< ARCOXIA > tablets contain lactose.
Il- pilloli ta ’ < ARCOXIA > fihom il- lactose.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Pazjenti bi problemi ereditarji rari ta ’ intolleranza għall - glucose, Lapp lactase deficiency jew assorbiment ħażin ta ’ glucose- galactose ma għandhomx jieħdu din il- mediċina.
Oral anticoagulants:
Antikoagulanti orali:
In subjects stabilised on chronic warfarin therapy, the administration of etoricoxib 120 mg daily was associated with an approximate 13% increase in prothrombin time International Normalised Ratio (INR).
F’ suġġetti stabilizzati fuq terapija ta ’ warfarina kronika, l- għoti ta ’ etoricoxib 120 mg kuljum kien assoċjat ma ’ żieda ta ’ madwar 13% fil- prothrombin time International Normalised Ratio (INR).
Therefore, patients receiving oral anticoagulants should be closely monitored for their prothrombin time INR, particularly in the first few days when therapy with etoricoxib is initiated or the dose of etoricoxib is changed (see section 4.4).
Għalhekk, il- pazjenti li jirċievu antikoagulanti orali għandhom jiġu mmonitorjati mill- qrib għall- prothrombin time INR tagħhom, b’ mod partikolari fl- ewwel ftit jiem meta tkun inbdiet il- kura b’ etoricoxib jew meta din tinbidel (ara sezzjoni 4. 4).
Diuretics, ACE inhibitors and Angiotensin II Antagonists:
Dijuretiċi, inibituri ACE u Antagonisti Angiotensin II:
NSAIDs may reduce the effect of diuretics and other antihypertensive drugs.
NSAIDs jistgħu jnaqqsu l- effett ta ’ dijuretiċi u ta ’ mediċini oħrajn ta ’ kontra l- pressjoni għolja.
In some patients with compromised renal function (e. g. dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor or Angiotensin II antagonist and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible.
F’ xi pazjenti b’ funzjoni renali kompromessa (eż. pazjenti deidrati jew pazjenti anzjani b’ funzjoni renali kompromessa), l- għoti fl- istess ħin ta ’ inibitur ACE jew antagonista Angiotensin II u aġenti li jinibixxu cyclo- oxygenase jistgħu jirriżultaw f’ aktar deterjorament tal- funzjoni renali, inkluż il- possibbiltà ta ’ kollass renali akut, li normalment ikun wieħed riversibbli.
These interactions should be considered in patients taking etoricoxib concomitantly with ACE inhibitors or angiotensin II antagonists.
Dawn l- interazzjonijiet għandhom jiġu kkunsidrati f’ pazjenti li jkunu qegħdin jieħdu etoricoxib fl- istess ħin ma ’ inibituri ACE jew antagonisti angiotensin.
Therefore, the combination should be administered with caution, especially in the elderly.
Għalhekk, il- kombinazzjoni għandha tingħata b’ kawtela, b’ mod speċjali fuq l- anzjani.
Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.
Il- pazjenti għandhom jiġu idratati b’ mod adegwat u għandha tingħata kunsiderazzjoni għall- monitoraġġ tal - funzjoni renali wara l- bidu ta ’ terapija konkomittanti, u perjodikament minn hemm ’ il quddiem.
Acetylsalicylic Acid:
Acetylsalicylic Acid:
In a study in healthy subjects, at steady state, etoricoxib 120 mg once daily had no effect on the anti-platelet activity of acetylsalicylic acid (81 mg once daily).
Fi studju b’ suġġetti b’ saħħithom, fi stat fiss, etoricoxib 120 mg kuljum ma kellu ebda effett fuq l- attività kontra l- pjastrini ta ’ acetylsalicylic acid (81 mg darba kuljum).
Etoricoxib can be used concomitantly with acetylsalicylic acid at doses used for cardiovascular prophylaxis (low-dose acetylsalicylic acid).
Etoricoxib jista ’ jintuża fl- istess ħin ma ’ acetylsalicylic acid f’ dożi użati għal profilassi kardjovaskulari (acetylsalicylic acid ta ’ doża baxxa).
However, concomitant administration of low-dose acetylsalicylic acid with etoricoxib may result in an increased rate of GI ulceration or other complications compared to use of etoricoxib alone.
Madankollu, għoti fl- istess ħin ta ’ acetylsalicylic acid b’ etoricoxib b’ doża baxxa jista ’ jirriżulta f’ rata miżjuda ta ’ ulċerazzjoni GI jew kumplikazzjonijiet oħrajn meta mqabbla ma ’ l- użu ta ’ etoricoxib waħdu.
Concomitant administration of etoricoxib with doses of acetylsalicylic acid above those for cardiovascular prophylaxis or with other NSAIDs is not recommended (see sections 5.1 and 4.4.).
Għoti fl- istess ħin ta ’ etoricoxib ma ’ dożi ta ’ acetylsalicylic acid ogħla minn dawk għal profilassi kardjovaskulari jew ma ’ NSAIDs oħrajn mhuwiex rakkomandat (ara sezzjonijiet 5. 1 u 4. 4.).
Cyclosporin and tacrolimus:
Cyclosporin u tacrolimus:
Although this interaction has not been studied with etoricoxib, coadministration of cyclosporin or tacrolimus with any NSAID may increase the nephrotoxic effect of cyclosporin or tacrolimus.
Għalkemm din l- interazzjoni ma ġietx studjata ma ’ etoricoxib, l- għoti fl - istess ħin ta ’ cyclosporin jew tacrolimus ma ’ kwalunkwe NSAID jista ’ jirriżulta f’ żieda fl- effett nefrotossiku ta ’ cyclosporin jew tacrolimus.
Renal function should be monitored when etoricoxib and either of these drugs is used in combination.
Il- funzjoni renali għandha tiġi mmonitorjata meta etoricoxib u waħda minn dawn il- mediċini jintużaw flimkien.
The effect of etoricoxib on the pharmacokinetics of other drugs
L- effett ta ’ etoricoxib fuq il- farmakokinetiċi ta ’ mediċini oħrajn
Lithium:
Litju:
NSAIDs decrease lithium renal excretion and therefore increase lithium plasma levels.
NSAIDs inaqqsu t- tneħħija tal- litju mill- kliewi u għalhekk iżidu l- livelli tal- plasma tal- litju.
If necessary, monitor blood lithium closely and adjust the lithium dosage while the combination is being taken and when the NSAID is withdrawn.
Jekk ikun hemm bżonn, immonitorja l- litju tad- demm mill- qrib u aġġusta d- dożaġġ tal- litju waqt li l - kombinazzjoni tkun qiegħda tittieħed u waqt li jkun irtirat l- NSAID.
Methotrexate:
15 Methotrexate:
Two studies investigated the effects of etoricoxib 60, 90 or 120 mg administered once daily for seven days in patients receiving once-weekly methotrexate doses of 7.5 to 20 mg for rheumatoid arthritis.
Żewġ studji investigaw l- effetti ta ’ etoricoxib 60, 90 jew 120 mg mogħti darba kuljum għal sebat ijiem f’ pazjenti li jirċievu dożi ta ’ methotrexate ta ’ 7. 5 sa 20 mg darba fil- ġimgħa għal artrite rewmatojde.
Etoricoxib at 60 and 90 mg had no effect on methotrexate plasma concentrations or renal clearance.
Etoricoxib f’ 60 u 90 mg ma kellu ebda effett fuq il- konċentrazzjonijiet tal- plasma jew fuq it- tneħħija mill- kliewi ta ’ methotrexate.
In one study, etoricoxib 120 mg had no effect, but in the other study, etoricoxib 120 mg increased methotrexate plasma concentrations by 28% and reduced renal clearance of methotrexate by 13%.
Fi studju wieħed, etoricoxib 120 mg ma kellu ebda effett, iżda fi studju ieħor, etoricoxib 120 mg żied il- konċentrazzjonijiet ta ’ plasma ta ’ methotrexate bi 28% u naqqas it- tneħħija mill- kliewi ta ’ methotrexate bi 13%.
Adequate monitoring for methotrexate-related toxicity is recommended when etoricoxib and methotrexate are administered concomitantly.
Huwa rrakkomandat monitoraġġ adegwat għal tossiċità relatata ma ’ methotrexate meta etoricoxib u methotrexate jingħataw fl- istess ħin.
Etoricoxib 60 mg given concomitantly with an oral contraceptive containing 35 micrograms ethinyl estradiol (EE) and 0.5 to 1 mg norethindrone for 21 days increased the steady state AUC0-24hr of EE by 37%.
Etoricoxib 60 mg mogħti fl- istess ħin ma ’ kontraċettiv orali li fih 35 mikrogrammi ta ’ ethinyl estradiol (EE) u 0. 5 sa 1 mg norethindrone għal 21 jum żied l- AUC0- 24hr b’ rata fissa ta ’ EE b’ 37%.
Etoricoxib 120 mg given with the same oral contraceptive concomitantly or separated by 12 hours, increased the steady state AUC0-24hr of EE by 50 to 60%.
Etoricoxib 120 mg mogħti ma ’ l- istess kontraċettiv orali fl- istess ħin jew b’ differenza ta ’ 12- il siegħa bejniethom, żied l- AUC0- 24hr ta 'stat fiss ta ’ EE b’ 50 sa 60%.
This increase in EE concentration should be considered when selecting an oral contraceptive for use with etoricoxib.
Din iż- żieda fil- konċentrazzjoni ta ’ l- EE għandha tiġi kkunsidrata meta jintagħżel kontraċettiv orali sabiex jintuża ma ’ etoricoxib.
An 15 increase in EE exposure can increase the incidence of adverse events associated with oral contraceptives (e. g., venous thrombo-embolic events in women at risk).
Żieda fl- espożizzjoni ta ’ EE tista ’ żżid l- inċidenza ta ’ episodji avversi assoċjati ma ’ kontraċettivi orali (eż. episodji trombo- emboliċi venużi f’ nisa li jkunu f’ riskju).
Hormone Replacement Therapy (HRT):
Terapija ta ’ Sostituzzjoni ta ’ l- Ormoni (HRT):
Administration of etoricoxib 120 mg with hormone replacement therapy consisting of conjugated estrogens (0.625 mg PREMARINTM) for 28 days, increased the mean steady state AUC0-24hr of unconjugated estrone (41%), equilin (76%), and 17-β -estradiol (22%).
L- għoti ta ’ etoricoxib 120 mg b’ terapija ta ’ sostituzzjoni ta ’ l- ormoni magħmula minn estroġeni konjugati (0. 625 mg PREMARINTM) għal 28 jum, naqqas l- AUC0- 24hr fl- istat fiss medju ta ’ estrone mhux konjugat (41%), equilin (76%), u 17- β - estradiol (22%).
The effect of the recommended chronic doses of etoricoxib (30, 60, and 90 mg) has not been studied.
L- effett tad- dożi kroniċi rrakkomandati (30, 60 u 90 mg) ma ġiex studjat.
The effects of etoricoxib 120 mg on the exposure (AUC0-24hr) to these estrogenic components of PREMARIN were less than half of those observed when PREMARIN was administered alone and the dose was increased from 0.625 to 1.25 mg.
L- effetti ta ’ etoricoxib 120 mg fuq l- espożizzjoni (AUC0- 24hr) għal dawn il- komponenti estroġeniċi ta ’ PREMARIN kienu inqas minn nofs ta ’ dawk osservati meta PREMARIN ingħata waħdu u d- doża żdiedet minn 0. 625 għal 1. 25 mg.
The clinical significance of these increases is unknown, and higher doses of PREMARIN were not studied in combination with etoricoxib.
Is- sinjifikat kliniku ta ’ dawn iż- żidiet mhuwiex magħruf, u doża ogħla ta ’ PREMARIN ma ġewx studjati f’ kombinazzjoni ma ’ etoricoxib.
These increases in estrogenic concentration should be taken into consideration when selecting post-menopausal hormone therapy for use with etoricoxib because the increase in oestrogen exposure might increase the risk of adverse events associated with HRT.
Dawn iż- żidiet fil- konċentrazzjoni estroġenika għandhom jiġu kkunsidrati meta tintagħżel terapija ta ’ l- ormoni ta ’ wara l- menopawża għal użu ma ’ etoricoxib minħabba li ż- żieda fl- espożizzjoni għall- oestroġenu tista ’ żżid ir- riskju ta ’ l - episodji avversi assoċjati ma ’ HRT.
Prednisone/ prednisolone:
Prednisone/ prednisolone:
In drug-interaction studies, etoricoxib did not have clinically important effects on the pharmacokinetics of prednisone/ prednisolone.
Fi studji ta ’ interazzjoni tal- mediċina, etoricoxib ma kellux effetti klinikament importanti fuq il- farmakokinetiċi ta ’ prednisone/ prednisolone.
Etoricoxib 120 mg administered once daily for 10 days to healthy volunteers did not alter the steady-state plasma AUC0-24hr or renal elimination of digoxin.
Etoricoxib 120 mg mogħti darba kuljum għal 10 ijiem lil voluntiera b’ saħħithom ma biddilx l- AUC0- 24hr tal- plasma fi stat fiss jew l- eliminazzjoni renali tad- digoxin.
There was an increase in digoxin Cmax (approximately 33%).
Kien hemm żieda f’ digoxin Cmax (bejn wieħed u ieħor 33%).
This increase is not generally important for most patients.
Din iż- żieda mhijiex ġeneralment importanti għal ħafna mill- pazjenti.
However, patients at high risk of digoxin toxicity should be monitored for this when etoricoxib and digoxin are administered concomitantly.
Madankollu, pazjenti f’ riskju għoli ta ’ tossiċità tad- digoxin għandhom jiġu mmonitorjati għal dan meta etoricoxib u digoxin jingħata fl- istess ħin.
Effect of etoricoxib on drugs metabolised by sulfotransferases
L- effett ta ’ etoricoxib fuq mediċini metabolizzati minn sulfotransferases
Etoricoxib is an inhibitor of human sulfotransferase activity, particularly SULT1E1, and has been shown to increase the serum concentrations of ethinyl estradiol.
Etoricoxib huwa inibitur ta ’ l- attività ta ’ sulfotransferase umana, b’ mod partikolari SULT1E1, u ntwera li jżid il- konċentrazzjonijiet tas- serum ta 'ethinyl estradiol.
While knowledge about effects of multiple sulfotransferases is presently limited and the clinical consequences for many drugs are still being examined, it may be prudent to exercise care when administering etoricoxib concurrently with other drugs primarily metabolised by human sulfotransferases (e. g., oral salbutamol and minoxidil).
Filwaqt li fil- preżent, it- tagħrif dwar l- effetti ta ’ sulfotransferases multipli huwa limitat u l- konsegwenzi kliniċi għal bosta mediċini għad iridu jiġu eżaminati, jista ’ jkun prudenti li tiġi eżerċitata l- kawtela meta etoricoxib jingħata fl - istess ħin ma ’ mediċini oħrajn metabolizzati primarjament minn sulfotransferases umani (eż. salbutamol u minoxidil orali).
Effect of etoricoxib on drugs metabolised by CYP isoenzymes
L- effett ta ’ etoricoxib fuq mediċini metabolizzati minn isoenzimi CYP
Based on in vitro studies, etoricoxib is not expected to inhibit cytochromes P450 (CYP) 1A2, 2C9, 2C19, 2D6, 2E1 or 3A4.
Fuq il- bażi ta ’ studji in vitro, etoricoxib mhuwiex mistenni li jinibixxi cytochromes P450 (CYP) 1A2, 2C9, 2C19, 2D6, 2E1 jew 3A4.
In a study in healthy subjects, daily administration of etoricoxib 120 mg did not alter hepatic CYP3A4 activity as assessed by the erythromycin breath test.
Fi studju f’ suġġetti b’ saħħithom, l- amministrazzjoni ta 'kuljum ta ’ etoricoxib 120 mg ma bidlitx l- attività CYP3A4 epatika kif ivvalutata mit- test tan- nifs ta ’ erythromycin.
Effects of other drugs on the pharmacokinetics of etoricoxib
16 Effetti ta ’ mediċini oħrajn fuq il- farmakokinetiċi ta 'etoricoxib
The main pathway of etoricoxib metabolism is dependent on CYP enzymes.
Il- mogħdija ewlenija tal- metaboliżmu ta ’ etoricoxib hija dipendenti fuq l- enzimi CYP.
CYP3A4 appears to contribute to the metabolism of etoricoxib in vivo.
CYP3A4 jidher li jikkontribwixxi għall- metaboliżmu ta ’ etoricoxib in vivo.
In vitro studies indicate that CYP2D6, CYP2C9, CYP1A2 and CYP2C19 also can catalyse the main metabolic pathway, but their quantitative roles have not been studied in vivo.
Studji in vitro jindikaw li CYP2D6, CYP2C9, CYP1A2 u CYP2C19 ukoll jistgħu jikkatalizzaw il- mogħdija metabolika prinċipali, iżda l - irwoli kwantitattivi tagħhom ma ġewx studjati in vivo.
Ketoconazole, a potent inhibitor of CYP3A4, dosed at 400 mg once a day for 11 days to healthy volunteers, did not have any clinically important effect on the single-dose pharmacokinetics of 60 mg etoricoxib (43% increase in AUC).
Ketoconazole, inibitur qawwi ta ’ CYP3A4, iddożat f’ 400 mg darba kuljum għal 11- il jum lil voluntiera b’ saħħithom, ma kellux xi effett klinikament importanti fuq il- farmakokinetiċi ta 'doża waħda ta ’ 60 mg etoricoxib (żieda ta ’ 43% fl- AUC).
Co-administration of etoricoxib with rifampicin, a potent inducer of CYP enzymes, produced a 65% decrease in etoricoxib plasma concentrations.
L- għoti fl- istess ħin ta ’ etoricoxib ma ’ rifampicin, induttur qawwi ta ’ enzimi CYP, ipproduċa tnaqqis ta ’ 65% fil- konċentrazzjonijiet fil- plasma ta ’ etoricoxib.
This interaction may result in recurrence of symptoms when etoricoxib is co-administered with rifampicin.
Din l- interazzjoni tista ’ tirriżulta fir- rikorrenza tas- sintomi meta etoricoxib jingħata ma ’ rifampicin.
While this information may suggest an increase in dose, doses of etoricoxib greater than those listed for each indication have not been studied in combination with rifampicin and are therefore not recommended (see section 4.2).
Filwaqt li din l - informazzjoni tista ’ tissuġġerixxi żieda fid- doża, dożi ta ’ etoricoxib ikbar minn dawk elenkati għal kull indikazzjoni ma ġewx studjati f’ kombinazzjoni ma ’ rifampicin u għalhekk mhumiex rakkomandati (ara sezzjoni 4. 2).
Antacids do not affect the pharmacokinetics of etoricoxib to a clinically relevant extent.
Antaċidi ma jaffettwawx il- farmakokinetiċi ta ’ etoricoxib sa punt li huwa klinikament relevanti.
16 4.6 Pregnancy and lactation
4. 6 Tqala u Treddigħ
The use of etoricoxib, as with any drug substance known to inhibit COX-2, is not recommended in women attempting to conceive.
L- użu ta ’ etoricoxib, bħal kull mediċina oħra magħrufa li tinibixxi COX- 2, mhuwiex rakkomandat f’ nisa li qegħdin jipprovaw ikollhom it- tfal.
No clinical data on exposed pregnancies are available for etoricoxib.
Ebda tagħrif kliniku fuq tqala esposta ma huwa disponibbli għal etoricoxib.
The potential for human risk in pregnancy is unknown.
Ir- riskju potenzjali għall- bnedmin matul tqala mhuwiex magħruf.
Etoricoxib, as with other medicinal products inhibiting prostaglandin synthesis, may cause uterine inertia and premature closure of the ductus arteriosus during the last trimester.
Etoricoxib, bħal kull mediċina oħra li tinibixxi s- sinteżi ta ’ prostaglandin, jista ’ jikkawża inerzja ta ’ l- utru u għeluq prematur tad- ductus arteriosus matul l- aħħar tliet xhur tat- tqala.
Etoricoxib is contraindicated in pregnancy (see section 4.3).
Etoricoxib huwa kontraindikat matul it- tqala (ara sezzjoni 4. 3).
If a woman becomes pregnant during treatment, etoricoxib must be discontinued.
Jekk mara tinqabad tqila waqt it- trattament, etoricoxib għandu jitwaqqaf.
It is not known whether etoricoxib is excreted in human milk.
Mhuwiex magħruf jekk etoricoxib joħroġx fil- ħalib uman.
Etoricoxib is excreted in the milk of lactating rats.
Etoricoxib kien eliminat fil- ħalib ta ’ firien li kienu qegħdin irreddgħu.
Women who use etoricoxib must not breast feed (see sections 4.3 and 5.3).
Nisa li jużaw etoricoxib ma għandhomx ireddgħu (ara sezzjonijiet 4. 3 u 5. 3).
No studies on the effect of etoricoxib on the ability to drive or use machines have been performed.
Ma sar l- ebda studju fuq l- effett ta ’ etoricoxib fuq il- ħila biex issuq u tħaddem magni.
However, patients who experience dizziness, vertigo or somnolence while taking etoricoxib should refrain from driving or operating machinery.
Madankollu, pazjenti li jesperjenzaw sturdament, vertiġini jew ngħas meta jieħdu etoricoxib ma għandhomx isuqu jew iħaddmu makkinarju.