natgillin/translations-raw huggingface dataset:
Qtrilmet skal straks seponeres hos patienter med mistænkt eller diagnosticeret DKA. 
In patients where DKA is suspected or diagnosed, treatment with Qtrilmet should be discontinued immediately.
- OCT2-hæmmere (såsom cimetidin, dolutegravir, ranolazin, trimethoprim, vandetanib, isavuconazol) kan reducere den renale udskillelse af metformin og dermed medføre en stigning i metforminkoncentrationen i plasma. 
Co-administration of metformin with: inhibitors of OCT1 (such as verapamil) may reduce efficacy of metformin; inducers of OCT1 (such as rifampicin) may increase gastrointestinal absorption and efficacy of metformin; inhibitors of OCT2 (such as cimetidine, dolutegravir, ranolazine, trimethoprime, vandetanib, isavuconazole) may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration; inhibitors of both OCT1 and OCT2 (such as crizotinib, olaparib) may alter efficacy and renal elimination of metformin.
Qtrilmet 1.000 mg/2,5 mg/5 mg depottabletter 
Qtrilmet 1,000 mg/2.5 mg/5 mg modified-release tablets
4.2, 4.4 og 5.2) - akutte tilstande med potentiale til at ændre nyrefunktionen såsom: o dehydrering o svær infektion o shock - akut eller kronisk sygdom, som kan forårsage vævshypoksi såsom: o hjerte- eller respirationssvigt o nyligt overstået myokardieinfarkt o shock - nedsat leverfunktion (se pkt. 
Qtrilmet is contraindicated in patients with: hypersensitivity to the active substances or to any of the excipients listed in section 6.1, history of a serious hypersensitivity reaction, including anaphylactic reaction, anaphylactic shock, and angioedema, to any dipeptidyl peptidase-4 (DPP-4) inhibitor or to any sodium-glucose co-transporter 2 (SGLT2) inhibitor (see sections 4.4, 4.8 and 6.1); any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis) (see sections 4.4 and 4.8); diabetic pre-coma (see section 4.4); severe renal failure (GFR < 30 mL/min) (see sections 4.2, 4.4 and 5.2); acute conditions with the potential to alter renal function such as: o dehydration, o severe infection, o shock; acute or chronic disease which may cause tissue hypoxia such as: o cardiac or respiratory failure, o recent myocardial infarction, o shock; hepatic impairment (see sections 4.2 and 5.2); acute alcohol intoxication, alcoholism (see section 4.5).
A Ikke Almindelig almindelig 
Common A Uncommon B Rare Very rare Not known
Depottabletter 
Modified-release tablets
- hvis du har alvorlige ledsmerter - hvis du tager pioglitazon for at nedsætte dit blodsukker, kan Qtrilmet måske ikke anbefales til dig - hvis du tager nogen af følgende lægemidler: glucokortikoider, beta-2-agonister, vanddrivende lægemidler (diuretika), carbamazepin, dexamethason, phenobarbital, phenytoin og rifampicin, da de kan nedsætte virkningen af Qtrilmet (se "Brug af anden medicin sammen med Qtrilmet") - hvis du er 75 år eller ældre - hvis blodprøver viser, at mængden af røde blodlegemer i dit blod er for høj. 
if you take any of the following medicines: glucocorticoids, beta-2 agonists, diuretics, carbamazepine, dexamethasone, phenobarbital, phenytoin, and rifampicin as they may reduce the effect of Qtrilmet (see “Other medicines and Qtrilmet”);
- Dehydrering, (tab af for meget væske fra kroppen), ikke almindelig (kan forekomme hos op til 1 ud af 100 personer) Tegn på dehydration: o meget tør eller klæbrig mund, udpræget tørst o udpræget søvnighed eller træthedsfølelse o meget lille eller ingen vandladning (urin) o hurtig hjerterytme. 
Signs of dehydration: o very dry or sticky mouth, feeling very thirsty, o feeling very sleepy or tired, o passing little or no water (urine), o fast heartbeat.
Qtrilmet 1.000 mg/2,5 mg/5 mg tabletter metformin HCl/saxagliptin/dapagliflozin 
Qtrilmet 1,000 mg/2.5 mg/5 mg tablets metformin HCl/saxagliptin/dapagliflozin
Ikke kendt administration sstedet 
General disorders and administratio n site conditions
Qtrilmet 850 mg/2,5 mg/5 mg depottabletter og Qtrilmet 1.000 mg/2,5 mg/5 mg depottabletter fås i blisterpakninger. 
Qtrilmet 850 mg/2.5 mg/5 mg modified-release tablets and Qtrilmet 1,000 mg/2.5 mg/5 mg modified-release tablets are available in blister.
Tal med lægen, apotekspersonalet eller sygeplejersken, før du tager Qtrilmet, hvis noget af ovenstående gælder for dig (eller hvis du er i tvivl). 
If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist, or nurse before taking Qtrilmet.
Qtrilmet 850 mg/2,5 mg/5 mg depottabletter metforminhydrochlorid/saxagliptin/dapagliflozin 
Qtrilmet 850 mg/2.5 mg/5 mg modified-release tablets metformin hydrochloride/saxagliptin/dapagliflozin
Svampeinfekt ion 
Headache dizziness
Qtrilmet 1.000 mg/2,5 mg/5 mg depottabletter metforminhydrochlorid/saxagliptin/dapagliflozin 
Qtrilmet 1,000 mg/2.5 mg/5 mg modified-release tablets metformin hydrochloride/saxagliptin/dapagliflozin
Nykturi nedsat nyrefunktion 
Kidney function
Hvis du har taget for meget Qtrilmet 
If you take more Qtrilmet than you should
Symptomer på laktatacidose inkluderer: o opkastning o mavesmerter (abdominalsmerter) o muskelkramper o generel følelse af utilpashed med udtalt træthed o vejrtrækningsbesvær o nedsat kropstemperatur og langsom hjerterytme Hvis dette sker for dig, skal du omgående stoppe med at tage Qtrilmet og kontakte lægen eller nærmeste skadestue, da laktatacidose kan føre til koma. 
Symptoms of lactic acidosis include: o vomiting, o stomach ache (abdominal pain), o muscle cramps, o general feeling of not being well with severe tiredness, o difficulty in breathing, o reduced body temperature and slower heartbeat.
Tors. 
RHD).
Symptomerne omfatter mavesmerter, hurtig og dyb vejrtrækning, søvnighed, eller din ånde kan få en usædvanlig frugtagtig lugt. 
Symptoms include stomach pain, fast and deep breathing,
- hvis du har type 1-diabetes, må Qtrilmet ikke bruges til behandling af denne sygdom - hvis du har eller har haft en sygdom i bugspytkirtlen - hvis du har nedsat nyrefunktion eller leverproblemer - hvis din krops evne til at bekæmpe infektioner (immunitet) er nedsat, såsom ved en sygdom som aids, eller hvis du tager medicin efter en organtransplantation - hvis du har eller tidligere har haft en alvorlig allergisk reaktion, eller hvis lægen har fortalt dig, at du måske har haft én - hvis du har eller har haft en alvorlig hjertesygdom 
sleepiness, or your breath developing an unusual fruity smell; if you have ever had a diabetic coma; if you have severely reduced kidney function; if you have a severe infection; if you have lost a lot of water from your body (dehydration) - due to long-lasting or severe diarrhoea, or if you have vomited several times in a row (see “Warnings and precautions” below); if you have recently had a heart attack or if you have heart failure or serious problems with your blood circulation or difficulties in breathing; if you have problems with your liver; if you drink large amounts of alcohol, either every day or only from time to time (please see section “Qtrilmet with alcohol”).
Efter markedsføring af saxagliptin og dapagliflozin blev udslæt rapporteret som bivirkning. 
Rash was reported during the postmarketing use of saxagliptin and dapagliflozin.
Forskel i HbA1c-effekt Justeret gennemsnit (95 % CI) 
Difference in HbA1c effect
• stigende behandlingsvarighed (behandling >24 måneder) 
• the increasing duration of treatment (treated > 24 months),
Balancen mellem følsomhed og specificitet i dette interval skal omhyggeligt overvejes. 
The balance between sensitivity and specificity in this range needs to be carefully considered.
Der er behov for at overveje, om regulatoriske tiltag er nødvendige som følge af de nye oplysninger. 
There is a need to consider whether regulatory action is necessary in light of the new elements.
De patienter, der overlever, har ofte alvorlig morbiditet forbundet med alvorlig og permanent invalidering. 
Patients who survive often have serious morbidity associated with serious and permanent disability.
10 tilfælde blev rapporteret i USA, mens hovedparten af de asymptomatiske tilfælde blev registreret i EU og resten af verden (83 %, 52/62). 
While 10 cases have been reported in the US, most of the asymptomatic cases were reported from EU/ROW (83%, 52/62).
Europa-Kommissionen bad agenturet om en udtalelse om, hvorvidt et regulatorisk tiltag vedrørende produktets markedsføringstilladelse er nødvendigt. 
The EC requested the Agency to give its opinion on whether a regulatory action with regard to the marketing authorisation for this product is necessary.
I lyset af ovenstående startede Europa-Kommissionen d. 29. april 2015 en procedure i henhold til artikel 20 i forordning (EF) nr. 726/2004 og bad agenturet om at vurdere ovenstående oplysninger og deres mulige indvirkning på benefit/risk-forholdet for Tysabri. 
In view of the above, on 29 April 2015 the European Commission triggered a procedure under Article 20 of Regulation (EC) No 726/2004, and asked the Agency to assess the above elements and their potential impact on the benefit-risk balance of Tysabri.
Følsomheden varierer meget lidt mellem indeksværdien 0,9 og 1,5, men specificiteten forbedres ved 1,5. 
Sensitivity differs very little between the index of 0.9 and 1.5 but there is improved specificity with 1.5.
Tidlig diagnosticering af PML synes at være forbundet med bedre udfald. 
Early diagnosis of PML appears to be associated with improved outcomes.
Ordlyden af et brev til sundhedspersonerne er vedtaget sammen med en kommunikationsplan. 
The wording of a Direct Healthcare Professional Communication has been adopted, together with a communication plan.
Den aktuelle evidens tyder på, at risikoen stiger med stigende antistof-indeks, men der er ikke nogen klar cut off-værdi. 
Current evidence suggests that risk increases with increasing antibody index but there is no clear cut off value.
Pr. maj 2015 har 142 958 patienter verden over fået natalizumab, og eksponeringen udgør i alt 432 814 patientår. 
As of May 2015, 142,958 patients had received natalizumab worldwide with 432,814 patient-years of exposure.
Da anmodningen bunder i en gennemgang af data fra lægemiddelovervågningsaktiviteter, skal udtalelsen vedtages af Udvalget for Lægemidler til Mennesker (CHMP) på grundlag af en anbefaling fra Udvalget for Risikovurdering inden for Lægemiddelovervågning (PRAC). 
As the request results from the evaluation of data resulting from pharmacovigilance activities, the opinion should be adopted by the Committee for Medicinal Products for Human Use (CHMP) on the basis of a recommendation from the Pharmacovigilance Risk Assessment Committee (PRAC).
Patienter, der har alle tre risikofaktorer, har en signifikant højere risiko for PML. 
Patients who have all three risk factors for PML have a significantly higher risk of PML.
På baggrund af dataene fra STRATIFY-2-studiet vedrørende antistof-indeks-stabilitet bør anbefalingen fastholdes. 
Based on the data on antibody index stability from STRATIFY-2 the recommendation should be maintained.
Siden natalizumab blev godkendt til markedsføring, er tre primære risikofaktorer for PML blevet identificeret: 
Since the auhtorisation of natalizumab, three main risk factors for PML have been identified:
PRAC har vedtaget en revideret version af risikostyringsplanen, der indeholder de ændringer, som blev aftalt i løbet af proceduren. 
The PRAC adopted a revised version of the Risk Management Plan (RMP) reflecting the amendments agreed during the procedure.
Diagnosticering af PML før udvikling af kliniske symptomer 
Diagnosis of PML before development of clinical symptoms
Derudover er advarselskortet til patienterne og formularerne til behandlingsiværksættelse og -fortsættelse også blevet opdateret, og der introduceres en ny formular til behandlingsseponering. 
In addition, the patient alert card and the treatment initiation and continuation forms are also updated, and a new treatment discontinuation form is introduced.
Tysabri (natalizumab) blev godkendt i EU den 27. juni 2006, og det er i øjeblikket indiceret som sygdomsmodificerende enkeltstofbehandling af højaktiv recidiverende remitterende multipel sklerose. 
Tysabri (natalizumab) was approved in the EU on 27 June 2006 and is currently indicated as single disease modifying therapy in highly active relapsing remitting multiple sclerosis (MS).
I alt 566 tilfælde af PML er rapporteret verden over pr. 4. juni 2015, hvoraf 133 patienter er døde (svarende til 23,5 % af patienterne med PML). 
A total of 566 PML cases have been reported globally as of 04 June 2015, of which 133 patients died (23.5 % 0f PML patients).
Det er imidlertid uklart, om det er muligt at identificere et enkelt cut-punkt i indekset inden for intervallet af vurderede indeksgrænser, som kan give et optimalt klinisk grundlag for behandlingsbeslutninger. 
However, it is unclear whether a single index cut-point can be identified within the range of index thresholds assessed that will provide optimal clinical utility in terms of treatment decisions.
Der er i stigende grad evidens for, at T2-FLAIR er den mest følsomme sekvens til detektion af PML. 
Increasing evidence indicates that T2-FLAIR is the most sensitive sequence for detecting PML.
Alle tilfælde af PML hos patienter, der var i behandling med natalizumab, forekom inden for 6 måneder efter sidste infusion. 
All PML cases in patients who had received natalizumab occurred within 6 months of the last infusion.
Nylige bestræbelser på at identificere potentielle biomarkører er lovende, men har endnu ikke medført identificering af nye markører, der kan anvendes i klinisk praksis til at forbedre den eksisterende stratificering af PML-risikoen. 
Recent efforts to identify potential biomarkers are promising but have not resulted, to date, in the identification of new markers that can be used in clinical practice to enhance the existing PML risk stratification.
Hos patienter med immunsupprimerende behandling i anamnesen, blev der ikke observeret nogen signifikant forskel i det mediane indeks mellem PML-patienter og ikke-PML-patienter. 
For patients with prior immunosuppressant treatment, no significant difference was observed in median index between non-PML and PML patients.
I betragtning af de data fra den virkelige verden, som UNILABS har leveret for fire EU-lande, og som viser, at den øvre årlige frekvens af serostatusændring (negativ til positiv) kan være helt op til 16 %, er der behov for at opdatere den årlige frekvens af serostatusændring i lægeinformationen og behandlingsvejledningen. 
Considering real world data from UNILABS from four EU countries showing that the upper annual serostatus change rate can be as high as 16%, the annual (negative to positive) serostatus change rate in the Physician Information and Management Guidelines needs to be updated.
Den kortere tid til diagnosticering for asymptomatiske patienter sammenlignet med symptomatiske patienter kan have muliggjort tidligere rekonstituering af immunsystemet efter seponering af natalizumab. 
The shorter time to diagnosis of asymptomatic patients compared with symptomatic patients may have enabled earlier immune reconstitution following discontinuation of natalizumab.
Hos 62 PML-patienter (10,9 %) er der observeret asymptomatisk debut. 
In sixty-two PML patients (10.9%) asymptomatic onset PML has been reported.
PRAC anerkender behovet for at ændre lægeinformationen og behandlingsvejledningen og foretage tilsvarende opdateringer af de relevante dele af undervisningsmaterialet. 
The PRAC agreed on the need to amend the physician information and management guideline and updated the key elements of the educational material accordingly.
Udvikling af PML hos patienter med multipel sklerose har en alvorlig indvirkning på prognosen, da det medfører døden hos ca. 20 % af patienterne eller alvorlig invalidering hos 40 % af de patienter, der overlever. 
The onset of PML in MS has serious prognostic implications, as it leads to death in about 20% of patients or to serious disability in 40% of survivors.
Med hensyn til udfald er det vigtigt at bemærke, at asymptomatiske patienter lod til at blive mindre invaliderede over tid og havde højere overlevelsesrater end symptomatiske patienter (95 % vs. 74 %). 
Most importantly, in terms of outcomes, asymptomatic patients appeared to have less accrual of disability over time and higher survival rates compared with symptomatic patients (95% vs. 74%).
Supplerende fremstillinger af PML-risikoen på grundlag af forskellige metoder kan komplementere oplysningerne inden for den nuværende algoritme og kan bidrage med yderligere information til lægerne, når de skal drøfte benefit/risk-forholdet med deres patienter. 
Supplemental presentations of PML risk using different methodologies may be complementary to the information within the current algorithm and will provide additional information to physicians as they engage in benefit/risk discussions with their patients.
Inklusion af en KaplanMeier-analyse af PML-risikoen sammen med algoritmen vil navnlig gøre det muligt at præsentere den kumulative risiko for PML over tid. 
In particular, the inclusion of a KaplanMeier analysis of PML risk alongside the algorithm would allow to present cumulative risk of PML over time.
Asymptomatiske PML-tilfælde blev identificeret via rutinemæssig MR-scanning. 
Asymptomatic PML cases were identified via routine MRI.
Biomarkører for PML-udvikling 
Biomarkers for PML development
Natalizumab er et humaniseret monoklonalt antistof, der er rettet mod α-kæden i α4β1adhæsionsmolekylet. 
Natalizumab is a humanized monoclonal antibody targeting the α-chain of the α4β1 adhesion molecule.
Det er vigtigt at opdatere indlægssedlen med risikoen for PML i op til 6 måneder efter seponering af Tysabri. 
It is important to update the package leaflet concerning the risk of PML up to 6 months following Tysabri discontinuation.
• tidligere immunsupprimerende behandling. 
• a history of immunosuppressive therapy.
Natalizumab er forbundet med udvikling af progressiv multifokal leukoencefalopati (PML), der skyldes John Cunningham-virus (JCV). 
Natalizumab is associated with the onset of progressive multifocal leukoencephalopathy (PML), which is caused by John Cunningham Virus (JCV).
Den videnskabelige evidens for progressiv multifokal leukoencefalopati (PML) hos patienter i behandling med Tysabri vokser hurtigt. 
Scientific evidence on progressive multifocal leukoencephalopathy (PML) in patients treated with Tysabri is rapidly growing.
Den aktuelt tilgængelige evidens tyder på, at risikoen for PML er lav ved et indeks lig med eller lavere end 0,9 (og lavere end tidligere estimeret) og stiger væsentligt over 1,5 for patienter, som er blevet behandlet med Tysabri i mere end to år. 
Currently available evidence suggests that the risk of PML is low at an index equal to or below 0.9 (and lower than previously estimated) and increases substantially above 1.5 for patients who have been on treatment with Tysabri for longer than 2 years.
Derfor skal undervisningsmaterialet omfatte relevant vejledning, og andre redskaber til deling af MR-billeder (f.eks. webbaserede) og høring af andre eksperter kan også overvejes. 
Thus, adequate guidance needs to be provided in the educational materials, and other tools may also be explored (e.g. web-based) for sharing MRIs and consultation of additional expertise.
Disse fund understøtter den aktuelle anbefaling i produktresuméet om, at lægerne fortsat skal være opmærksomme på tegn og symptomer på PML i ca. 6 måneder efter seponering af natalizumab, og at den samme monitoreringsstrategi skal anvendes i op til 6 måneder efter seponering. 
These findings support the current SmPC recommendation that physicians should remain vigilant for signs and symptoms of PML for approximately 6 months after natalizumab discontinuation, and that the same monitoring strategy should apply for up to 6 months after discontinuation.
Hos patienter behandlet i mere end to år er risikoen for PML lav ved indeksværdier på 0,9 eller derunder, og den stiger signifikant ved værdier over 1,5. 
In patients treated for longer than 2 years, the risk of PML is low at index values of 0.9 or less, and increases substantially at values above 1.5.
• PRAC har gennemgået alle de data vedrørende risikoen for progressiv multifokal leukoencefalopati (PML), som indehaveren af markedsføringstilladelsen for Tysabri har lagt frem, såvel som de øvrige data, der er gjort tilgængelige i løbet af proceduren, samt de holdninger, der er blevet fremlagt af den videnskabelige rådgivende gruppe inden for neurologi. 
• The PRAC reviewed all data presented by the MAH on the risk of PML in association with Tysabri, as well as other data made available during the procedure and the views expressed by the neurology scientific advisory group.
Der synes at herske enighed blandt eksperterne om, at rutinemæssig MR-screening for formodede PML-læsioner kan udføres uden brug af gadolinium-kontrast. 
There seems to be consensus among experts that routine MRI screening for suspected PML lesions can be conducted without gadolinium-enhancement.
• PRAC anbefaler som konsekvens heraf, at hyppigere MR-screening for PML (f.eks. hver 3.6. måned) med anvendelse af en forkortet MRI-protokol bør overvejes hos patienter med høj risiko for udvikling af PML. 
• As a consequence, the PRAC recommended that more frequent MRI screening for PML (e.g. every 3-6 months) using an abbreviated MRI protocol should be considered in patients at higher risk of development of PML.
Derudover er det nødvendigt at tydeliggøre, at patienter, der på et givet tidspunkt testes positive for anti-JCV-antistoffer, bør anses for at have en øget risiko for PML, uanset resultatet af tidligere eller efterfølgende antistof-test. 
In addition, it needs to be clarified that patients who test anti-JCV antibody positive at any time should be considered to beat an increased risk of PML, independent of any prior or subsequent antibody test result.
Den kliniske præsentation af natalizumabrelateret PML anses for at være den samme som ved klassisk PML og består af kognitive forstyrrelser hos mere end halvdelen af patienterne samt motoriske symptomer, ataksi, synsnerveforstyrrelser og dysfasi eller agnosi i mere end 40 % af tilfældene. 
The clinical presentation of natalizumab-associated PML is considered not distinct from classical PML, and consists in cognitive disorders in more than half of the patients together with motor symptoms, ataxia, neurovisual disturbances, and dysphasia or agnosia in more than 40% of cases.
• PRAC konkluderer, at PML, der er klinisk asymptomatisk ved diagnosticeringen, oftere fremstår som lokaliseret sygdom på MR-scanninger og har en højere overlevelsesrate med bedre klinisk udfald end symptomatisk PML. 
• The PRAC concluded that PML which is clinically asymptomatic at diagnosis represents more frequently localised disease in MRI, with a higher survival rate and better clinical outcome as compared to symptomatic PML.
Det anbefales i øjeblikket, at patienter, som er anti-JCV-antistof-negative, bør testes for serokonvertering to gange om året. 
Currently it is recommended that patients who are anti-JCV antibody negative should be tested for seroconversion twice yearly.
Selvom patienter med asymptomatisk PML generelt set havde samme kliniske baseline-karakteristika som symptomatiske patienter, havde en højere andel af de asymptomatiske patienter en mere lokaliseret sygdom (64 % havde PML i én hjernelap) på MRbilleder på diagnosticeringstidspunktet sammenholdt med symptomatiske PML-patienter (36 %). 
Although asymptomatic PML patients had generally similar baseline clinical characteristics compared with symptomatic patients, a higher proportion of asymptomatic patients presented with more localized disease (64% unilobar PML) on Magnetic Resonance Image (MRI) at the time of diagnosis compared to symptomatic PML patients (36%).
Udvikling af PML efter seponering af natalizumab 
PML development after discontinuation of natalizumab
Formodningen om, at 55 % af patienterne i den samlede natalizumab-behandlede population, der anvendes i beregningerne af risikoalgoritmen for PML, har en positiv serostatus, er fortsat acceptabel. 
The assumption of 55% positive serostatus for the overall natalizumab-treated population utilized in the PML risk algorithm calculations remains acceptable.