natgillin/translations-raw huggingface dataset:
• I et studie, der omfattede 1.183 tidligere ubehandlede patienter, blev det påvist, at de patienter, der fik Vectibix i kombination med FOLFOX, levede i gennemsnit 10,1 måneder, uden at sygdommen blev værre, sammenlignet med 7,9 måneder for dem, der fik FOLFOX alene.
• Patients receiving Vectibix in combination with FOLFOX lived for an average of 10.1 months without the disease getting worse in a study of 1,183 previously untreated patients compared with 7.9 months for those receiving FOLFOX alone.
Disse er på passende måde afspejlet i produktinformationen.
These are appropriately reflected in the product information.
Benefit/risk-forhold
Benefit/risk balance
Denne gennemgang blev foretaget af Udvalget for Risikovurdering inden for Lægemiddelovervågning (PRAC).
This review was conducted by the Pharmacovigilance Risk Assessment Committee (PRAC).
Bilag II Videnskabelige konklusioner og begrundelser for ændringen af betingelserne for markedsføringstilladelserne
Annex II Scientific conclusions and grounds for variation to the terms of the marketing authorisations
Diclofenac er et non-steroidt antiinflammatorisk lægemiddel (NSAID).
Diclofenac is a non-steroidal anti-inflammatory drug (NSAID).
Derudover anbefaledes proaktiv formidling af disse nye foranstaltninger gennem en direkte meddelelse til sundhedspersoner (DHPC).
Furthermore, a proactive communication of these new measures through a direct healthcare professional communication (DHPC) was recommended.
• PRAC konkluderede endvidere, at der er behov for yderligere risikominimeringsforanstaltninger såsom information til sundhedspersoner.
• The PRAC also concluded that there was need for further risk minimisation measures such as information to healthcare professionals.
Risikoen for større vaskulære hændelser var ca. 1/3 forhøjet med et coxib-præparat, (hyppighedsratio [RR] 1,37, 95 % sikkerhedsinterval [1,14; 1,66]; p=0,0009) og med diclofenac (1,41, [1,12; 1,78]; p=0,0036), hovedsagelig som følge af forhøjet forekomst af større koronare hændelser (for coxib-præparater: 1,76, [1.31; 2.37]; p=0,0001; for diclofenac: 1,70, [1,19; 2,37], p=0,0032).
Major vascular events were increased by about one third by a coxib (rate ratio [RR] 1.37, 95% confidence interval [CI] 1.14-1.66; p=0.0009) or diclofenac (1.41, 1.12-1.78; p=0.0036), mainly due to an increase in major coronary events (coxibs: 1.76, 1.31-2.37; p=0.0001; diclofenac: 1.70, 1.19-2.41; p=0.0032).
PRAC konkluderede, at diclofenac er effektivt til at reducere inflammation og smerter.
The PRAC concluded that diclofenac is effective in reducing inflammation and pain.
De foreliggende oplysninger om dosiseffekten af diclofenac er begrænsede.
The available information on the dose effect of diclofenac is limited.
Samlet resumé af den videnskabelige vurdering af systemiske lægemidler indeholdende diclofenac (se bilag I)
Overall summary of the scientific evaluation of diclofenac containing medicinal products (systemic formulations) (see Annex I)
Vedrørende kardiovaskulære risici bemærkede PRAC, at det indledende signal fra MEDALprogrammet bekræftedes af metaanalyser af randomiserede kliniske undersøgelser foretaget af Trelle et al (2011) og Chen og Ashcroft (2007).
With regards to cardiovascular risks, the PRAC noted that the initial signal from the MEDAL programme was confirmed by the meta-analyses of randomised clinical trials conducted by Trelle et al (2011) and Chen and Ashcroft (2007).
Nogle undersøgelser viser således også årsagssammenhæng ved lavere doser.
Some studies also report an association with lower doses.
PRAC anerkendte konklusionerne af de foregående gennemgange vedrørende den kardiovaskulære sikkerhed af diclofenac.
The PRAC acknowledged the conclusions of previous reviews with regards to the cardiovascular safety of diclofenac.
I henhold til bestemmelserne i artikel 31 og 32 i direktiv 2001/83/EF anbefaler PRAC derfor ændring af markedsføringstilladelserne for alle lægemidler omhandlet i bilag I, for hvilke ændringerne i produktinformationen fremgår af bilag III til anbefalingen.
Therefore in accordance with Articles 31 and 32 of Directive 2001/83/EC, the PRAC recommends the variation of the marketing authorisations for all medicinal products referred to in Annex I and for which the amendments to the product information are set out in annex III of the recommendation.
PRAC fandt, at anbefalingen om opdatering af produktinformationen bør gælde alle systemiske lægemidler indeholdende diclofenac, uanset dosis.
The PRAC considered that the recommendation for update of the product information should be applicable to all medicinal products containing diclofenac (systemic formulations), regardless of dose.
• PRAC fandt, at lægemidler indeholdende diclofenac er effektive til de godkendte indikationer
• The PRAC considered that diclofenac containing medicinal products are effective in their approved indications.
Krum et al 2012 foretog en post hoc-analyse af MEDALundersøgelsen og viste, at der ikke var nævneværdig forskel mellem etoricoxib og diclofenac hvad angår kardiovaskulære hændelser bortset fra bekræftet kronisk venstresidig hjerteinsufficiens.
The study by Krum et al 2012, a post hoc analysis of the MEDAL trial, showed that there was no significant differential effect between etoricoxib and diclofenac in relation to cardiovascular events, except for confirmed congestive heart failure.
Udvalget tog ligeledes i betragtning de oplysninger, som indehaverne af markedsføringstilladelse havde forelagt skriftligt og ved en mundtlig forklaring, samt relevante data stillet til rådighed af uafhængige forskere.
Data provided by the MAHs in writing and at an oral explanation and relevant data made available by independent researchers were also considered.
I gennemgangen indgik data fra en ny metaanalyse af randomiserede kliniske undersøgelser, der var udført af en uafhængig forskningsgruppe.
Evidence available from a new meta-analysis of randomised clinical trials conducted by an independent research group was included in the review.
NSAID såsom diclofenac anvendes til lindring af alle grader af smerter og inflammation ved en lang række lidelser, herunder arthritis, akutte muskuloskeletale sygdomme og andre smertefulde traumeforårsagede tilstande.
NSAIDs, such as diclofenac, are indicated in the relief of all grades of pain and inflammation associated with a wide range of conditions, including arthritic conditions, acute musculo-skeletal disorders and other painful conditions resulting from trauma.
De daværende foreliggende data (navnlig fra MEDAL-programmet1) tydede på, at risikoen for arterielle trombotiske hændelser med diclofenac var den samme som for coxib-præparater, men der kunne ikke drages endelige konklusioner, og der behøvedes flere epidemiologiske undersøgelser for at tilvejebringe yderligere data.
The data available (in particular data from the MEDAL1 programme) suggested that the risk of arterial thrombotic events with diclofenac was similar to that for coxibs, but firm conclusions could not be drawn and further epidemiological studies were needed to obtain additional data.
Til patienter med visse kardiovaskulære risikofaktorer (såsom hypertension, hyperlipidæmi, diabetes mellitus eller rygning) bør diclofenac desuden kun ordineres efter nøje overvejelse, hvorfor advarslerne skal opdateres, så de afspejler dette.
In addition, patients with certain cardiovascular risk factors (such as hypertension, hyperlipidaemia, diabetes mellitus or smoking) should only use diclofenac after careful consideration and therefore the warnings should also be updated to reflect this.
Skønt dataene tyder på, at den trombotiske risiko ved diclofenac er dosisafhængig, navnlig ved høje doser, er det vanskeligt at angive en klar skæringsdosis, ved hvilken risiciene stiger væsentligt.
Although the data point towards a dose dependent effect on thrombotic risk associated with the use of diclofenac, particularly at high dose, it is difficult to establish a clear cut-off dose above which the risks become significantly increased.
PRAC anbefalede derfor en ændring af produktinformationen for diclofenac med en opdateret kontraindikation hos patienter med manifest venstresidig hjerteinsufficiens (NYHA II-IV), iskæmisk hjertesygdom, perifer arteriel sygdom og/eller cerebrovaskulær sygdom.
The PRAC therefore recommended an amendment to the product information for diclofenac to include an updated contraindication in patients with established congestive heart failure (NYHA II-IV), ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease.
De kendte risici ved behandling med NSAID i almindelighed, og med diclofenac i særdeleshed, er alvorlige gastrointestinale virkninger i form af perforation, ulcus og blødning, kardio-renale effekter, hepatiske effekter og hudreaktioner i form af Stevens Johnsons syndrom og toksisk epidermal nekrolyse.
Recognised risks associated with NSAID treatment in general, and with diclofenac treatment in particular, include serious gastrointestinal effects including PUB (perforation, ulcer, bleeding), cardio-renal effects, hepatic effects and skin reactions (including Stevens Johnson syndrome and toxic epidermal necrolysis).
Systemiske lægemidler indeholdende diclofenac findes som tabletter og kapsler til oral administration, suppositorier til rektal administration og injektionsvæsker (opløsning) til intravenøs og intramuskulær injektion.
Diclofenac containing medicinal products (systemic formulations) are available as tablets, capsules for oral administration, suppositories for rectal administration and solutions for intravenous or intramuscular injection.
Det konstateredes, at disse risici svarer til risiciene ved selektive COX-2-hæmmere
It was observed that these are similar to those of selective Cox-2 inhibitors.
Der blev indledt en ny gennemgang med henblik på de kardiovaskulære sikkerhedsproblemer ved diclofenac og betydningen heraf for benefit/risk-forholdet for systemiske lægemidler indeholdende diclofenac.
A new review was considered necessary and was initiated to address the cardiovascular safety concerns for diclofenac and their impact on the benefit-risk balance of diclofenac containing medicinal products (systemic formulations).
• PRAC fulgte proceduren i overensstemmelse med artikel 31 i direktiv 2001/83/EF på foranledning af lægemiddelovervågningsdata for systemiske lægemidler indeholdende diclofenac
• The PRAC considered the procedure under Article 31 of Directive 2001/83/EC resulting from pharmacovigilance data, for diclofenac containing medicinal products (systemic formulations).
På grundlag af de foreliggende data konkluderede PRAC derfor, at der ikke kan udelukkes kardiovaskulær tromboserisiko ved nogen dosis af diclofenac, navnlig ikke hos patienter med præeksisterende komorbiditet.
Based on the available data to date, the PRAC therefore concluded that the cardiovascular thrombotic risk cannot be excluded across all doses of diclofenac, especially in patients with pre-existing co-morbidities.
I betragtning af, at der iagttages samme forhøjelse af den kardiovaskulære risiko med diclofenac som med selektive COX-2-hæmmere, bør enhver foranstaltning til minimering af kardiovaskulær risiko, der finder anvendelse for COX-2-hæmmere, også finde anvendelse for diclofenac.
Considering that an increased cardiovascular risk with diclofenac is observed, and this appears similar to that of selective Cox-2 inhibitors, it therefore follows that any risk minimisation in place for Cox-2 inhibitors with respect to cardiovascular risk should also apply to diclofenac.
I 2012 foretog CHMP endnu en gennemgang2 af al foreliggende evidens fra metaanalyse af kliniske undersøgelser og observationsundersøgelser samt fra epidemiologiske undersøgelser.
Another evaluation conducted by the CHMP in 20122 considered all available published evidence to date from meta-analysis of clinical trials and observational studies, and also epidemiological studies.
Der blev også fundet forhøjet risiko ved diclofenac i de undersøgelser med indlejrede kontroller, der var en del af SOS-projektet, og som blev udført på tværs af alle databaser for både myokardieinfarkt og iskæmisk apopleksi.
An increased risk with diclofenac was also observed in the SOS nested-cases control studies across all databases and for both myocardial infarction and ischaemic stroke.
• PRAC tog hensyn til alle foreliggende data vedrørende den kardiovaskulære sikkerhed af lægemidler indeholdende diclofenac, idet udvalget anerkendte konklusionerne af tidligere gennemgange foretaget af CHMP, markedsføringstilladelsesindehavernes skiftlige oplysninger og mundtlige forklaring samt nye data fra uafhængige forskere
• The PRAC considered the totality of the data available in relation to the cardiovascular safety of diclofenac containing medicinal products, acknowledging the conclusions from previous reviews by the CHMP, the submissions by marketing authorisation holders in writing and at an oral explanation, and emerging data from independent researchers.
• PRAC konkluderede, at på baggrund af de foreliggende sikkerhedsdata og med henblik på opretholdelse af et positivt benefit/risk-forhold bør lægemidler indeholdende diclofenac være kontraindiceret hos patienter med manifest venstresidig hjerteinsufficiens (NYHA II-IV), iskæmisk hjertesygdom, perifer arteriel sygdom og/eller cerebrovaskulær sygdom.
• The PRAC concluded that in view of the currently available safety data in order to maintain a favourable benefit/risk, diclofenac containing medicinal products should be contraindicated in patients with established congestive heart failure (NYHA II-IV), ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease.
Efter at have gennemgået PRAC's anbefaling af 13. juni 2013 i medfør af artikel 107, stk. 1 og 2, i direktiv 2001/83/EF tillsluttede CMDh sig ændring af markedsføringstilladelserne for lægemidler indeholdende diclofenac, for hvilke ændringerne af produktinformationen fremgår af bilag III.
The CMDh, having considered the PRAC recommendation dated 13 June 2013 pursuant to Article 107k(1) and (2) of Directive 2001/83/EC, reached a position on the variation of the marketing authorisations of diclofenac containing medicinal products for which the amendments to the product information are set out in annex III.
Der blev dengang indført risikominimeringsforanstaltninger for COX-2-hæmmere (i form af kontraindikationer og advarsler i produktinformationen).
Risk minimisation measures (in the form of contraindications and warnings in the product information) were implemented at the time for Cox-2 inhibitors.
Analysen gennemgik mere end 600 randomiserede kliniske undersøgelser og konkluderede, at de vaskulære risici med diclofenac i høje doser svarer til risiciene med COX-2-hæmmerne.
The study, which looked at more than 600 randomised clinical trials, concluded that the vascular risks of high dose diclofenac are comparable to Cox-2 inhibitors.
Metaanalyser af observationsdata og individuelle observationsundersøgelser tydede ligeledes samstemmende på, at risikoen ved diclofenac er af samme grad som ved COX-2-hæmmere.
Meta-analyses of observational data and individual observational studies also consistently indicated that diclofenac is associated with a similar level of risk as Cox-2 inhibitors.
Afsnittet om dosering i produktinformationen bør derudover konsekvent nævne den generelle regel om, at NSAID bør anvendes i lavest mulige dosering i kortest mulig tid
Moreover, the general rule that NSAIDs should be used at the lowest dose for the shortest duration possible should be consistently implemented in the posology section of the product information.
På baggrund af alt det ovennævnte konkluderede PRAC, at benefit/risk-forholdet for systemiske lægemidler indeholdende diclofenac fortsat er positivt under forudsætning af de vedtagne begrænsninger, advarsler, andre ændringer i produktinformationen og supplerende risikominimeringsforanstaltninger i form af en direkte meddelelse til sundhedspersoner.
Having noted all of the above, the PRAC concluded that the benefit-risk balance for diclofenac containing medicinal products (systemic formulations) remains favourable subject to the agreed restrictions, warnings, other changes to the product information and additional risk minimisation measures, in the form of a DHPC letter.
Udvalget for Lægemidler til Mennesker (CHMP) har tidligere gennemgået de kardiovaskulære risici ved NSAID, herunder diclofenac, på grundlag af data fra epidemiologiske og kliniske undersøgelser.
Epidemiological and clinical trial data on the cardiovascular risks of NSAIDs, including diclofenac, were previously reviewed by the Committee for Medicinal Products for Human Use (CHMP).
Den nye dokumentation, der blev fremlagt af indehaverne af markedsføringstilladelse, herunder data fra nye case-kontrolundersøgelser og retrospektive undersøgelser, giver yderligere evidens for, at der er større risiko med diclofenac end med andre NSAID, og at risikoen med diclofenac svarer til risikoen med coxib-præparater.
The new evidence provided by marketing authorisation holders including evidence from new casecontrol studies and retrospective studies add to the evidence of an increased risk with diclofenac
(2011) undersøgte data om risici i relation til eksponeringsvarighed og fandt, at risiciene ved diclofenac på alle tidspunkter nøje svarede til risiciene ved coxib-præparater.
Schjerning Olsen et al (2011) provided data on risks in relation to duration of exposure and found that the risks associated with diclofenac were very similar to those of coxibs at all time points.
• vedrørende risikoen for arterielle tromboser fandt PRAC, at det kan konkluderes, at diclofenac er forbundet med øgede kardiovaskulære risici, hvilket er baseret på de foreliggende data fra randomiserede kliniske undersøgelser, observationsundersøgelser og individuelle epidemiologiske undersøgelser samt metaanalyse heraf.
• The PRAC considered that with regards to the arterial thrombotic risks of diclofenac, the data available to date from randomised clinical trials, observational studies and individual epidemiological studies, including meta-analysis thereof, allow the conclusion that diclofenac is associated with increased cardiovascular risks.
Hovedelementerne i en direkte meddelelse til sundhedspersoner blev vedtaget tillige med en tidsplan for udsendelsen konkluderede PRAC, at benefit/risk-forholdet for systemiske lægemidler indeholdende diclofenac fortsat er positivt under forudsætning af de vedtagne begrænsninger, advarsler, andre ændringer i produktinformationen og supplerende risikominimeringsforanstaltninger i form af en direkte meddelelse til sundhedspersoner.
The PRAC concluded that the benefit-risk balance for diclofenac containing medicinal products (systemic formulations) remains favourable subject to the agreed restrictions, warnings, other changes to the product information and additional risk minimisation measures, in the form of a communication letter.
Af de foreliggende data kan der ikke drages konklusioner om de konkrete mekanismer bag de kardiovaskulære trombotiske risici ved diclofenac, skønt de er forsøgt nærmere udredt i flere undersøgelser.
The data available today do not allow conclusion on the specific mechanisms underlying the cardiovascular thrombotic risks of diclofenac, although several studies have explored different options and it can be noted that is unlikely that one single mechanism would explain the risk.
I 2006 konkluderedes det, at det ikke kunne udelukkes, at klassen af NSAID som helhed medfører en let forhøjelse af den absolutte risiko for trombotiske hændelser, navnlig i høje doser ved langvarig behandling.
In 2006 it was concluded that a small increase in the absolute risk of thrombotic events could not be excluded for NSAIDs as a class, especially when used at high-doses and long-term therapy, although the risk was considered to be higher for the selective cyclooxygenase-2 (Cox-2) inhibitors (also known as coxibs) compared to NSAIDs.
gennemgangen: http://www.ema.europa.eu/docs/en_GB/document_library/Report/2010/01/WC500054344.pdf.
1 For more details on the MEDAL programme, including its components, please refer to the assessment report for the review conducted in 2006 at http://www.ema.europa.eu/docs/en_GB/document_library/Report/2010/01/WC500054344.pdf.
CMDh (koordinationsgruppen vedrørende gensidig anerkendelse og decentraliserede procedurer (human)) har gennemgået PRAC's (Udvalget for Risikovurdering inden for Lægemiddelovervågning) anbefaling af 13. juni 2013 for systemiske lægemidler indeholdende diclofenac.
The CMDh, having considered the PRAC recommendation dated 13 June 2013 with regards to diclofenac containing medicinal products (systemic formulations), agrees with the recommendation therein as stated below:
Ved gennemgangen konkluderedes, at de foreliggende data samstemmende tyder på en mindre fordelagtig kardiovaskulær risikoprofil af diclofenac end af andre NSAID, og at risiciene svarer til risiciene ved COX-2-hæmmere.
Results of the ‘safety of non-steroidal anti-inflammatory drugs' (SOS) research project funded by the European Commission under the Seventh Framework Programme were considered in the review that concluded that available evidence regarding diclofenac seemed to consistently point towards a less favourable cardiovascular risk profile compared to other NSAIDs, and similar risks as those of Cox-2 inhibitors.
Disse infektioner er sædvanligvis nemme at behandle.
These infections are usually easily treated.
Ud fra et mikrobiologisk synspunkt bør lægemidlet anvendes med det samme.
From a microbiological point of view, the product should be used immediately.
Børn og unge Dette lægemiddel bør ikke gives til børn og unge under 18 år.
Children and adolescents This medicine should not be given to children and adolescents less than 18 years of age.
Hvis din partner bliver gravid inden for tre måneder efter din behandling, skal du straks fortælle det til lægen.
If your partner becomes pregnant within three months of your treatment, you must immediately tell your doctor.
Tilstanden bedres af sig selv eller ved behandling af infektionen.
The condition gets better on its own or with treatment of the infection.
Tilstanden fortog sig i løbet af tre dage.
The case resolved within three days.
Samtidig administration skal ske med forsigtighed, og tæt overvågning anbefales.
Co-administration should be done with caution and close monitoring is recommended.
Alle disse forandringer vurderedes at være tilfældige og var sandsynligvis relateret til den intravenøse administrationsprocedure.
All these changes were considered to be incidental and probably related to the intravenous administration procedure.
Injektionen varer i 10 minutter.
The injection lasts 10 minutes.
Alle stadier af spermatogenese er imidlertid observeret hos dyr.
However, all stages of spermatogenesis have been observed in animal.
Fase III-undersøgelse (PCM301)
Phase III Study (PCM301)
• Forklaring af, hvilke bivirkninger patienterne kan forvente, og sandsynligheden for, at de får dem
• Explain what side effects the Patient might expect and the likelihood of him getting them
Indsendelse af endelige resultater af studiet:
Submission of final study results:
Alle patienter havde en Gleason-score ≤ 3 + 3 ved baseline.
All patients had Gleason score ≤ 3 + 3 at baseline.
Opbevares i køleskab (2-8 °C).
Store in a refrigerator (2°C-8°C).
Du kan også være nødt til ikke at tage visse lægemidler i flere dage efter VTP-proceduren.
You may also be required to not take certain medicines for several days after the VTP procedure.
Hvis det ikke anvendes med det samme, er opbevaringstiden og opbevaringsforholdene før ibrugtagning brugerens ansvar.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.
- Feber, smerter og hævelse i operationsområdet kan forekomme efter proceduren.
- Fever, pain and swelling in the area of the operation might occur after the procedure.
Det var ikke nødvendigt at operere nogen af disse patienter for inkontinens.
None of these patients required an operation for incontinence.
Hos 5 patienter (2,5 %) vurderedes infektionen at være alvorlig.
In 5 (2.5 %) patients, the infection was considered serious.