natgillin/translations-raw huggingface dataset:
Patienterne blev inden for 24 timer efter CABG - operation randomiseret til: parecoxib initialdosis på 40 mg i. v., efterfulgt af 20 mg i. v. hver 12. time i mindst 3 dage, og derefter oral valdecoxib (20 mg hver 12. time) (n=544) i resten af den 10 dages behandlingsperiode; placebo i. v. blev efterfulgt af oral valdecoxib (n=544): eller placebo i. v. blev efterfulgt af oral placebo (n=548).
Patients were randomized within 24-hours post-CABG surgery to: parecoxib initial dose of 40 mg IV, then 20 mg IV Q12H for a minimum of 3 days followed by valdecoxib PO (20 mg Q12H) (n=544) for the remainder of a 10 day treatment period; placebo IV followed by valdecoxib PO (n=544); or placebo IV followed by placebo PO (n=548).
En signifikant (p=0, 033) højere hyppighed af hændelser i den kardiovaskulære/ tromboemboliske kategori ses i gruppen behandlet med parecoxib/ valdecoxib (2, 0%) sammenlignet med gruppen behandlet med placebo/ placebo (0, 5%).
A significantly (p=0.033) greater incidence of events in the cardiovascular/ thromboembolic category was detected in the parecoxib / valdecoxib treatment group (2.0%) compared to the placebo/ placebo treatment group (0.5%).
I gruppen behandlet med placebo/ valdecoxib ses også en øget hyppighed af kardiovaskulære tromboemboliske hændelser sammenlignet med placebo, men forskellen er ikke statistisk signifikant.
Placebo/ valdecoxib treatment was also associated with a higher incidence of CV thromboembolic events versus placebo treatment, but this difference did not reach statistical significance.
Disse patienter fik ikke valdecoxib.
Three of the six cardiovascular thromboembolic events in the placebo/ valdecoxib treatment group occurred during the placebo treatment period; these patients did not receive valdecoxib.
Præ- definerede hændelser, der opstod med højeste hyppighed i alle 3 behandlingsgrupper omfatter kategorier af sårkomplikationer efter operation, inklusive dybe operationsinfektioner og sårhelingskomplikationer i sternum.
Pre-specified events that occurred with the highest incidence in all three treatment groups involved the category of surgical wound complications, including deep surgical infections and sternal wound healing events.
Der ses ingen signifikante forskelle mellem aktive behandlinger og placebo for de øvrige præ - definerede hændelseskategorier (nedsat nyrefunktion/ nyresvigt, øvre gastrointestinale ulcus - komplikationer eller sårkomplikationer efter operation).
There were no significant differences between active treatments and placebo for any of the other pre- specified event categories (renal dysfunction/ failure, upper GI ulcer complications or surgical wound complications).
Almen kirurgi:
General Surgery:
I en stor undersøgelse (n=1050) ved større ortopædiske/ almen kirurgiske indgreb fik patienterne en initialdosis af parecoxib på 40 mg i. v., efterfulgt af 20 mg i. v. hver 12. time i mindst 3 dage, og derefter oral valdecoxib (20 mg hver 12. time) (n=525) i resten af den 10 dages behandlingsperiode, eller placebo i. v. efterfulgt af oral placebo (n=525).
There were no significant differences in the overall safety profile,
Der ses ingen signifikant forskel i den samlede sikkerhedsprofil, omfattende de 4 præ- definerede hændelseskategorier beskrevet ovenfor i den anden CABG- undersøgelse, ved parecoxibnatrium/ valdecoxib sammenlignet med placebobehandling hos disse post- operative patienter.
10 including the four pre-specified event categories described above for the second CABG surgery study, for parecoxib sodium/ valdecoxib compared to placebo treatment in these post-surgical patients.
Trombocytundersøgelser:
Platelet studies:
Hos unge forsøgspersoner havde Dynastat
In a series of small, multiple dose studies in healthy young and elderly subjects, Dynastat 20 mg or 40 mg twice daily had no effect on platelet aggregation or bleeding compared to placebo.
4. 5).
In young subjects, Dynastat 40 mg twice daily had no clinically significant effect on acetylsalicylic acid -mediated inhibition of platelet function (see section 4.5).
Efter i. v. eller i. m. injektion omdannes parecoxib hurtigt til valdecoxib, den farmakologisk aktive substans, ved enzymatisk hydrolyse i leveren.
Following IV or IM injection, parecoxib is rapidly converted to valdecoxib, the pharmacologically active substance, by enzymatic hydrolysis in the liver.
Absorption Eksponering for valdecoxib efter enkeltdoser af Dynastat målt ved både arealet under plasmakoncentrationskurven vs. tidskurven (AUC) og maksimal koncentration (Cmax), er omtrent lineær i området af kliniske doser.
Absorption Exposure of valdecoxib following single doses of Dynastat, as measured by both the area under the plasma concentration vs. time curve (AUC) and peak concentration (Cmax), is approximately linear in the range of clinical doses.
AUC og Cmax er efter dosering 2 gange dagligt lineær op til 50 mg i. v. og 20 mg i. m.
AUC and Cmax following twice daily administration is linear up to 50 mg IV and 20 mg IM.
1 time.
Following single IV and IM doses of parecoxib sodium 20 mg, Cmax of valdecoxib is achieved in approximately 30 minutes and approximately 1 hour, respectively.
Efter i. v. eller i. m. administration var eksponering af valdecoxib ens, udtrykt i AUC og Cmax.
Exposure to valdecoxib was similar in terms of AUC and Cmax following IV and IM administration.
Efter i. v. eller i. m. administration var eksponering af parecoxib ens, udtrykt i AUC.
Exposure to parecoxib was similar after IV or IM administration in terms of AUC.
Efter i. m. dosering var parecoxibs middel Cmax lavere sammenlignet med i. v. bolus dosering, hvilket skyldes langsommere ekstravaskulær absorption efter i. v. administration.
Average Cmax of parecoxib after IM dosing was lower compared to bolus IV dosing, which is attributed to slower extravascular absorption after IM administration.
Disse fald blev ikke betragtet som klinisk vigtige, idet valdecoxibs Cmax er sammenlignelig efter administration af parecoxibnatrium i. m. og i. v.
These decreases were not considered clinically important since Cmax of valdecoxib is comparable after IM and IV parecoxib sodium administration.
55 liter.
Distribution The volume of distribution of valdecoxib after its IV administration is approximately 55 litres.
98% i koncentrationsområdet opnået ved den højest anbefalede dosis, 80 mg/ dag.
Plasma protein binding is approximately 98% over the concentration range achieved with the highest recommended dose, 80 mg/ day.
22 minutter.
Metabolism Parecoxib is rapidly and almost completely converted to valdecoxib and propionic acid in vivo with a plasma half-life of approximately 22 minutes.
20%) af sulfonamiddelen.
Elimination of valdecoxib is by extensive hepatic metabolism involving multiple pathways, including cytochrome P 450 (CYP) 3A4 and CYP2C9 isoenzymes and glucuronidation (about 20%) of the sulphonamide moiety.
Der er blevet identificeret en hydroxyleret valdecoxibmetabolit i humant plasma (via CYP- vejen), som er aktiv som en COX- 2- hæmmer.
A hydroxylated metabolite of valdecoxib (via the CYP pathway) has been identified in human plasma that is active as a COX-2 inhibitor.
10% af valdecoxibkoncentrationen; på grund af denne metabolits lave koncentration forventes den ikke at bidrage med en klinisk signifikant effekt efter administration af parecoxibnatrium i terapeutiske doser.
It represents approximately 10% of the concentration of valdecoxib; because of this metabolite’ s low concentration, it is not expected to contribute a significant clinical effect after administration of therapeutic doses of parecoxib sodium.
Elimination Valdecoxib udskilles via levermetabolisme, og mindre end 5% uomdannet valdecoxib genfindes i urinen.
Elimination Valdecoxib is eliminated via hepatic metabolism with less than 5% unchanged valdecoxib recovered in the urine.
Ca.
No unchanged parecoxib is detected in urine and only trace amounts in the faeces.
70% af dosis udskilles i urinen som inaktive metabolitter.
About 70% of the dose is excreted in the urine as inactive metabolites.
6 l/ time.
Plasma clearance (CLp) for valdecoxib is about 6 l/ hr.
8 timer.
After IV or IM dosing of parecoxib sodium, the elimination half-life (t1/ 2) of valdecoxib is about 8 hours.
Ældre Dynastat er givet til 335 ældre patienter (65- 96 år) i farmakokinetiske og terapeutiske undersøgelser.
Dynastat has been administered to 335 elderly patients (65-96 years of age) in pharmacokinetic and therapeutic trials.
40% højere plasmaeksponering for valdecoxib til følge, sammenlignet med raske, unge forsøgspersoner.
In healthy elderly subjects, the apparent oral clearance of valdecoxib was reduced, resulting in an approximately 40% higher plasma exposure of valdecoxib compared to healthy young subjects.
4. 2).
When adjusted for body weight, steady state plasma exposure of valdecoxib was 16% higher in elderly females compared to elderly males (see section 4.2).
Nedsat nyrefunktion Hos patienter med varierende grader af nyreinsufficiens, som fik 20 mg Dynastat i. v., blev parecoxib hurtigt fjernet fra plasma.
In patients with varying degrees of renal impairment administered 20 mg IVDynastat, parecoxib was rapidly cleared from plasma.
4. 2).
Because renal elimination of valdecoxib is not important to its disposition, no changes in valdecoxib clearance were found even in patients with severe renal impairment or in patients undergoing dialysis (see section 4.2).
11 Nedsat leverfunktion Moderat nedsat leverfunktion resulterede ikke i reduceret hastighed eller omfang af omdannelse af parecoxib til valdecoxib.
Moderate hepatic impairment did not result in a reduced rate or extent of parecoxib conversion to valdecoxib.
Hos patienter med moderat nedsat leverfunktion (Child- Pugh score 7- 9) bør behandling initieres med halv sædvanlig anbefalet dosis af Dynastat, og den maksimale daglige dosis bør reduceres til 40 mg, da valdecoxib eksponering var mere end fordoblet hos disse patienter (130%).
In patients with moderate hepatic impairment (Child-Pugh score 7-9), treatment should be initiated with half the usual recommended dose of Dynastat and the maximum daily dose should be reduced to 40 mg since valdecoxib exposures were more than doubled (130%) in these patients.
4. 2 og 4. 3).
Patients with severe hepatic impairment have not been studied and therefore the use of Dynastat in patients with severe hepatic impairment is not recommended (see sections 4.2 and 4.3).
De ikke- kliniske data viser ingen særlig risiko for mennesker vurderet ud fra konventionelle undersøgelser af sikkerhedsfarmakologi eller toksicitet efter gentagne doser ved en eksponering for parecoxib, der er 2 gange den maksimale humane eksponering.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology or repeated dose toxicity at 2-fold the maximum human exposure to parecoxib.
0, 8 gange den systemiske eksponering hos ældre forsøgspersoner ved den maksimalt anbefalede terapeutiske dosis på 80 mg dagligt.
However, in the repeated dose toxicity studies in dogs and rats, the systemic exposures to valdecoxib (the active metabolite of parecoxib) were approximately 0.8-fold the systemic exposure in elderly human subjects at the maximum recommended therapeutic dose of 80 mg daily.
Højere doser er forbundet med forværring og forsinket helbredelse af hudinfektioner, en effekt der muligvis er forbundet med COX- 2- hæmning.
Higher doses were associated with aggravation and delayed healing of skin infections, an effect probably associated with COX-2 inhibition.
I reproduktionstoksicitetstests forekom incidensen af post- implantationstab, resorptioner og nedsat fostervægt ved doser, som ikke forårsagede maternal toksicitet i kaninforsøg.
In reproduction toxicity tests, the incidence of post-implantation losses, resorptions and foetal body weight retardation occurred at doses not producing maternal toxicity in the rabbit studies.
Der er ikke fundet nogen påvirkninger efter parecoxib af fertiliteten hos han - og hunrotter.
No effects of parecoxib on male or female fertilities were found in rats.
Virkningerne af parecoxibnatrium er ikke blevet undersøgt i sengraviditet eller i den præ - og postnatale periode.
The effects of parecoxib have not been evaluated in late pregnancy or in the pre- and postnatal period.
En enkeltdosis parecoxibnatrium administreret intravenøst til diegivende rotter gav mælkekoncentra - tioner af parecoxib, valdecoxib og en aktiv valdecoxibmetabolit svarende til koncentrationer i maternel plasma.
Parecoxib sodium administered intravenously to lactating rats as a single dose showed concentrations of parecoxib, valdecoxib and a valdecoxib active metabolite in milk similar to that of maternal plasma.
Parecoxibnatriums karcinogene potentiale er ikke undersøgt.
The carcinogenic potential of parecoxib sodium has not been evaluated.
Phosphorsyre og/ eller natriumhydroxid (til pH- justering).
Powder Disodium hydrogen phosphate Phosphoric acid and/ or sodium hydroxide (for pH adjustment).
6. 6.
This medicinal product must not be mixed with other medicinal products except for those mentioned in section 6.6.
Brug af Ringer- lactat injektionsvæske eller Ringer- lactat med 50 g/ l (5%) glucose injektionsvæske til rekonstitution vil medføre udfældning af parecoxib, og det kan derfor ikke anbefales.
Use of Ringer-Lactate solution for injection or glucose 50 g/ l (5%) in Ringer Lactate solution for injection for reconstitution will cause the parecoxib to precipitate from solution and therefore is not recommended.
Brug af vand til injektionsvæsker anbefales ikke, da den færdige opløsning ikke vil være isotonisk.
Use of Sterile Water for Injection is not recommended, as the resulting solution is not isotonic.
Injicér ikke Dynastat i et i. v. drop, som anvendes til andre lægemidler. i. v. droppet skal skylles grundigt med en kendt forligelig opløsning (se pkt.
12 Do not inject Dynastat into an IV line delivering any other drug.
6. 6) både inden og efter injektion med Dynastat.
The IV line must be adequately flushed prior to and after Dynastat injection with a solution of known compatibility (see section 6.6).
6. 6, anbefales ikke, da der kan forekomme udfældning.
Injection into an IV line delivering glucose 50 g/ l (5%) in Ringer-Lactate solution for injection, or other IV fluids not listed in 6.6, is not recommended as this may cause precipitation from solution.
12 6. 3 Opbevaringstid
6.3 Shelf life
Kemisk og fysisk stabilitet for færdigtilberedt opløsning er vist i 24 timer ved 25°C.
Chemical and physical in-use stability of the reconstituted solution has been demonstrated for 24 hours at 25°C.
Ud fra et mikrobiologisk synspunkt skal det aseptisk fremstillede præparat anvendes straks.
From a microbiological point of view, the aseptically prepared product should be used immediately.
Hvis præparatet ikke anvendes straks, er opbevaringstid og - betingelser før anvendelse brugerens ansvar, og vil normalt ikke være længere end 12 timer ved 25°C, medmindre tilberedningen er sket under kontrollerede og validerede aseptiske forhold.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would not normally be longer than 12 hours at 25°C, unless reconstitution has taken place in controlled and validated aseptic conditions.
Dette lægemiddel kræver ingen særlige forholdsregler vedrørende opbevaringen før rekonstitution.
This medicinal product does not require special storing conditions prior to reconstitution.
Færdigtilberedt opløsning må ikke opbevares i køleskab eller nedfryses.
Do not refrigerate or freeze reconstituted solutions.
6. 3.
For storage conditions of the recosntituted medicinal product see section 6.3.
Parecoxibnatrium hætteglas 20 mg hætteglas:
Parecoxib sodium vials 20 mg vials:
Type I farveløst hætteglas (2 ml) med en lamineret gummiprop, lukket med en gul flip- off aluminiumkapsel.
Type I colourless glass vials (2 ml) with a laminated stopper, sealed with a yellow flip- off cap on the aluminium overseal.
Solvens til rekonstitution Anbefalet solvens til rekonstitution af Dynastat er:
Reconstitution solvents Acceptable solvents for reconstitution of Dynastat are:
natriumchloridopløsning 9 mg/ ml (0, 9%) glucose 50 g/ l (5%) infusionsvæske natriumchlorid 4, 5 mg/ l (0, 45%) og glucose 50 g/ l (5%) injektionsvæske
sodium chloride 9 mg/ ml (0.9%) solution glucose 50 g/ l (5%) solution for infusion sodium chloride 4.5 mg/ ml (0.45%) and glucose 50 g/ l (5%) solution for injection
Rekonstitutionsproces Benyt aseptisk teknik til opløsning af frysetørret parecoxib (som parecoxibnatrium).
Reconstitution process Use aseptic technique to reconstitute lyophilised parecoxib (as parecoxib sodium).
Fjern den gule flip- off kapsel for at afdække den centrale del af 20 mg parecoxib hætteglassets gummiprop.
Remove the yellow flip-off cap to expose the central portion of the rubber stopper of the 20 mg parecoxib vial.
Tag med en steril nål og sprøjte 1 ml forligelig solvens og stik nålen ind gennem gummiproppens centrale del og overfør solvens til 20 mg parecoxib hætteglasset.
Withdraw, with a sterile needle and syringe, 1 ml of an acceptable solvent and insert the needle through the central portion of the rubber stopper transferring the solvent into the 20 mg vial.
Efter rekonstitution og før indgift skal Dynastat undersøges visuelt for partikler og misfarvning.
After reconstitution, Dynastat should be inspected visually for particulate matter and discoloration prior to administration.
6. 3), eller bortskaffes.
Dynastat should be administered within 24 hours of reconstitution (see section 6.3), or discarded.
Færdigtilberedt opløsning er isotonisk.
13 The reconstituted product is isotonic.
Forligelige opløsninger til i. v. drop Efter rekonstitution med anbefalet solvens må Dynastat kun injiceres i. v. eller i. m. eller i i. v. drop med:
IV line solution compatibility After reconstitution with acceptable solvents, Dynastat may only be injected IV or IM, or into IV lines delivering:
13 glucose 50 g/ l (5%) infusionsvæske natriumchlorid 4, 5 mg/ l (0, 45%) og glucose 50 g/ l (5%) injektionsvæske Ringer- lactat injektionsvæske
sodium chloride 9 mg/ ml (0.9%) solution glucose 50 g/ l (5%) solution for infusion sodium chloride 4.5 mg/ ml (0.45%) and glucose 50 g/ l (5%) solution for injection Ringer-Lactate solution for injection
Ikke anvendt lægemiddel samt affald heraf bør destrueres i henhold til lokale retningslinjer.
Any unusedproduct or waste material should be disposed of in accordance with local requirements.
EU/ 1/ 02/ 209/ 01
EU/ 1/ 02/ 209/ 001
22. marts 2002
22 March 2002 Date of first renewal:
Yderligere information om dette lægemiddel er tilgængelig på Det europæiske Lægemiddelagenturs (EMEAs) hjemmeside http: // www. emea. europa. eu /.
Detailed information on this product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu
Dynastat 20 mg pulver og solvens til injektionsvæske, opløsning.
Dynastat 20 mg powder and solvent for solution for injection
Hvidt/ råhvidt pulver.
Powder and solvent for solution for injection White to off-white powder.
Solvens: klar og farveløs opløsning.
Solvent: clear, colourless solution.
15 natriumchloridopløsning 0, 9 mg/ ml (0, 9%) glucose 50 g/ l (5%) infusionsvæske natriumchlorid 4, 5 mg/ l (0, 45%) og glucose 50 g/ l (5%) injektionsvæske Ringer- lactat injektionsvæske
15 IV line solution compatibility After reconstitution with acceptable solvents, Dynastat may only be injected IV or IM, or into IV lines delivering: sodium chloride 9 mg/ ml (0.9%) solution glucose 50 g/ l (5%) solution for infusion sodium chloride 4.5 mg/ ml (0.45%) and glucose 50 g/ l (5%) solution for injection Ringer-Lactate solution for injection
4. 4 og 5. 2).
In patients with severe renal impairment (creatinine clearance < 30 ml/ min.) or patients who may be predisposed to fluid retention parecoxib should be initiated at the lowest recommended dose and the patient's kidney function closely monitored (see sections 4.4 and 5.2).
Konstateret iskæmisk hjertesygdom, perifer arteriel sygdom og/ eller cerebrovaskulær sygdom.
16 Established ischaemic heart disease, peripheral arterial disease and/ or cerebrovascular disease.
4. 2).
Because of the possibility for increased adverse reactions at higher doses of parecoxib, other COX-2 inhibitors and NSAIDs, patients treated with parecoxib should be reviewed following dose increase and, in the absence of an increase in efficacy, other therapeutic options should be considered (see section 4.2).
Behandlingen med parecoxib bør seponeres ved den første forekomst af hududslæt, slimhinde - affektioner, eller andre tegn på overfølsomhed.
17 Parecoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Rapporteringshyppigheden af alvorlige hudreaktioner synes dog at være højere for valdecoxib (den aktive metabolit af parecoxib) sammenlignet med andre selektive COX- 2- hæmmere.
However, the reported rate of serious skin events appears to be greater for valdecoxib (the active metabolite of parecoxib) as compared to other COX-2 selective inhibitors.
Samtidig administration af parecoxibnatrium og heparin påvirkede ikke heparins farmakodynamik (aktiveret partiel thromboplastintid) sammenlignet med heparin administreret alene.
18 Co-administration of parecoxib sodium and heparin did not affect the pharmacodynamics of heparin (activated partial thromboplastin time) compared to heparin alone.
NSAID- præparater kan reducere virkningen af diuretika og antihypertensiva.
NSAIDs may reduce the effect of diuretics and antihypertensive medicinal products.
18 Det tyder på, at samtidig indgift af NSAID- præparater og ciclosporin eller tacrolimus kan øge den nefrotoksiske virkning af ciclosporin og tacrolimus.
Co-administration of NSAIDs and cyclosporin or tacrolimus has been suggested to increase the nephrotoxic effect of cyclosporin and tacrolimus.
Samtidig administration af valdecoxib og glibenclamid (CYP3A4 substrat) påvirkede hverken glibenclamids farmakokinetik (eksponering) eller farmakodynamik (blodsukker og insulinniveauer).
19 Co-administration of valdecoxib with glibenclamide (CYP3A4 substrate) did not affect either the pharmacokinetics (exposure) or the pharmacodynamics (blood glucose and insulin levels) of glibenclamide.
Injicerbare anæstetika:
Injectable anaesthetics:
19 Inhalationsanæstetika:
Inhalation anaesthetics:
4. 3, 5. 1 og 5. 3).
Parecoxib sodium is suspected to cause serious birth defects when administered during the last trimester of pregnancy because as with other medicinal products known to inhibit prostaglandin synthesis, it may cause premature closure of the ductus arteriosus or uterine inertia (see sections 4.3, 5.1 and 5.3).
Følgende bivirkninger havde en hyppighed større end placebo og er set blandt 1543 patienter, der har fået Dynastat 20 mg eller 40 mg som en enkelt eller flere doser (op til 80 mg/ dag) i 12 placebokon - trollerede undersøgelser, inklusive tandkirurgi, gynækologisk kirurgi, ortopædkirurgi eller koronar bypassoperation såvel som præ- operativ administration ved tandkirurgi og ortopædkirurgi.
The
Sepone - ringshyppighedenpå grund af bivirkninger i disse undersøgelser var 5, 0% for patienter, der fik Dynastat og 4, 3% for patienter, der fik placebo.
20 discontinuation rate due to adverse events in these studies was 5.0% for patients receiving Dynastat and 4.3% for patients receiving placebo.
[Meget almindelig (≥ 1/ 10), almindelig (≥ 1/ 100, < 1/ 10), ikke almindelig (≥ 1/ 1000, < 1/ 100), sjælden (≥ 1/ 10. 000, < 1/ 1000), meget sjælden (< 1/ 10. 000), ikke kendt (kan ikke estimeres ud fra forhåndenværende data)]
[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), not known (cannot be estimated from the available data)] Infections and infestations Uncommon: abnormal sternal serous wound drainage, wound infection.
Infektiøse og parasitære sygdomme Ikke almindelig: abnorm serøs sekretion i sternumdræn, sårinfektion
Blood and lymphatic system disorders Common: post-operative anaemia Uncommon: thrombocytopenia
Blod og lymfesystem Almindelig: postoperativ anæmi Ikke almindelig: trombocytopeni
Metabolism and nutrition disorders Common: hypokalaemia