natgillin/translations-raw huggingface dataset:
En kombination af disse med Aptivus og lavdosis ritonavir anbefales ikke (se pkt. 
Combination with Aptivus, coadministered with low dose ritonavir, is not recommended (see section 4.4)
Det skal du vide, før dit barn begynder at tage Aptivus Sådan skal dit barn tage Aptivus Bivirkninger 
What Aptivus is and what it is used for What you need to know before your child takes Aptivus How to take Aptivus
Dette kan være dødeligt. 
could be expected.
Proteasehæmmere 
Protease inhibitors
I fase III RESIST-studierne var frekvensen af forhøjet aminotransferase signifikant forøget i tipranavir med ritonavir-gruppen sammenlignet med komparatorgruppen. 
In Phase III RESIST trials, the frequency of transaminase elevations was significantly increased in the tipranavir with ritonavir arm compared to the comparator arm. Close monitoring is therefore needed in patients treated with Aptivus, co-administered with low dose ritonavir (see section
Zidovudin 300 mg x 2 (TPV/r 750/100 mg x 2) 
Zidovudine 300 mg BID (TPV/r 750/100 mg BID)
Atazanavir/ritonavir anbefales ikke samtidig med Aptivus givet med lavdosis ritonavir. 
The concomitant use of Aptivus, coadministered with low dose ritonavir, with atazanavir/ritonavir is not recommended.
Nedsat dosis af colchicin eller afbrydelse af colchicinbehandlingen anbefales ved samtidig administration af colchicin og Aptivus hos patienter med normal nyre- og leverfunktion (se pkt. 
In patients with normal renal and hepatic function, a reduction in colchicine dosage or an interruption of colchicine treatment is recommended in co-administration (see section 4.5).
Pravastatin Der er ikke udført interaktionsstudier. 
Pravastatin No interaction study performed
Teoretisk forventes det, at tipranavir plus lavdosis ritonavir øger plasmakoncentrationen af triazolam. 
Based on theoretical considerations, tipranavir, co-administered with low dose ritonavir, is expected to increase triazolam concentrations.
Emtricitabin Der er ikke udført interaktionsstudier. 
Emtricitabine No interaction study performed
Efter første dosis er P-gp-aktiviteten signifikant hæmmet, men der fantes en svag induktion ved steady state. 
P-gp activity is significantly inhibited after the first dose,
Rilpivirin 
Pyrexia
Saquinavir/ritonavir anbefales ikke samtidig med Aptivus givet med lavdosis ritonavir. 
The concomitant use of Aptivus, coadministered with low dose ritonavir, with saquinavir/ritonavir is not recommended.
Tipranavir/r hæmmer CYP3A4 og CYP2D6. 
Inhibition of CYP 3A4 and CYP 2D6 by tipranavir/r
Overskrides doseringstidspunktet med mere end 5 timer, bør dit barn vente med at tage en dosis til det næste planlagte doseringstidspunkt for Aptivus og ritonavir. 
If your child misses a dose of Aptivus or ritonavir by more than 5 hours, wait and then give the next dose of Aptivus and ritonavir at the regularly scheduled time.
Boehringer Ingelheim, Unipessoal, Lda Tel: +351 21 313 53 00 
Boehringer Ingelheim Italia S.p.A. Tel: +39 02 5355 1
Naturlægemidler indeholdende perikon må ikke anvendes samtidig med Aptivus og lavdosis ritonavir. 
Herbal preparations containing St. John's wort must not be combined with Aptivus, co-administered with low dose ritonavir.
Når Aptivus/ritonavir administreres 
recommended when coadministered with Aptivus/ritonavir.
- proteasehæmmere (PI): Aptivus sænker i høj grad plasmakoncentrationen af hiv-proteasehæmmerne amprenavir, atazanavir, lopinavir og saquinavir. 
- Protease Inhibitors (PIs): Taking Aptivus may cause large decreases in the blood levels of other HIV protease inhibitors.
Dit barn skal blive ved med at tage Aptivus, lige så længe, som lægen anbefaler det. Ved 12 år bør børn i behandling med Aptivus oral opløsning skiftes over til Aptivus kapsler. 
At the age of 12 years, children treated with Aptivus should be switched from the oral solution to the capsules.
Teoretisk forventes det, at tipranvir plus lavdosis ritonavir øger koncentrationen af bosentan. 
Based on theoretical considerations, tipranavir, co-administered with low dose ritonavir, is expected to increase cisapride concentrations.
Aptivus. 
active.
Dit barn vil kun få ordineret abacavir og zidovudin, hvis det ikke kan tåle andre NRTI-midler - didanosin: Hvis dit barn er i behandling med didanosin depottabletter, skal disse tages mindst 2 
Your child's doctor will only prescribe them abacavir and zidovudine if they are unable to take other NRTIs.
- Lavdosis ritonavir (kombinationen er nødvendig, for at sikre optimal virkning af Aptivus i kroppen). 
low dose ritonavir (this helps Aptivus to reach a high enough level in your blood) other HIV medicines.
Ved akut krise anbefales det, at tabletterne tages før måltiderne." 
In case of acute crisis, it is recommended that the tablets are taken before meals.'
• udvalget behandlede den indbringelse, der var indledt af Det Forenede Kongerige i henhold til artikel 29, stk. 4, i direktiv 2001/83/EF, hvor Frankrig og Slovakiet rejste indvendinger, der blev betragtet som en potentiel alvorlig risiko for den offentlige sundhed 
• The Committee considered the notification of the referral triggered by the United Kingdom under Article 29(4) of Directive 2001/83/EC where France and the Slovakia raised objections that were considered to be a potential serious risk to public health;
Inden for de enkelte undersøgelser er der kun foretaget begrænsede sammenligninger. 
Limited within study comparisons are available.
De prædefinerede kriterier for bioækvivalens blev opfyldt for både Cmax og AUC. 
The pre-defined criteria for bioequivalence were met for both Cmax and AUC.
Ved den efterfølgende indbringelsesprocedure i CMDh var det ikke muligt at nå til enighed, da de indsigende medlemsstater fastholdt deres indsigelser, der blev anset for at udgøre en potentiel alvorlig risiko for den offentlige sundhed. 
During the CMDh referral procedure that followed, no consensus could be reached as the objecting EU Member States maintained their objections, which were considered to represent a potential serious risk to public health.
CHMP tilsluttede sig rådgivningen fra PKWP. 
The CHMP endorsed the PKWP's advice.
CMDh indbragte derfor sagen for CHMP ved en indbringelsesprocedure i henhold til artikel 29, stk. 4. 
The CMDh therefore referred the matter to the CHMP through an Article 29(4) referral procedure.
Som anmodet af CHMP foretog ansøgeren desuden en bibliografisk søgning i databaserne Medline og Embase. 
As requested by the CHMP, the applicant also performed a bibliographic search on the databases Medline and Embase.
Resultaterne af den sammenlignende biotilgængelighedsundersøgelse under fastende betingelser viser bioækvivalens mellem reference- og testproduktet hvad angår alle farmakokinetiske parametre. 
The results of the comparative bioavailability study under fasting conditions demonstrate bioequivalence between reference and test products for all pharmacokinetic parameters.
På CHMP's møde fremlagde ansøgeren mundtligt sine synspunkter. 
During the CHMP meeting the applicant presented their view in an oral explanation.
CHMP anser derfor benefit/risk-forholdet for at være negativt. 
Therefore, the CHMP is of the view that the benefit-risk is negative.
Udvalget anbefaler derfor afslag på ansøgninger om markedsføringstilladelse for Diclofenac (Altergon) i referencemedlemsstaten og de berørte medlemsstater. 
Therefore, the Committee recommends the refusal of the marketing authorisation of Diclofenac (Altergon) in the reference and concerned Member States.
Den gennemsnitlige iagttagne reduktion i Cmax ved fødeindtagelse er mellem 21 % og 69 %. 
The mean Cmax reduction observed with food ranges from 21% to 69%.
Der blev forelagt en sammenfatning af bioækvivalensundersøgelsen i fastende tilstand og en gennemgang af den forelagte litteratur. 
A summary of the bioequivalence study in the fasted state was presented as well as a review of the literature submitted.
Ansøgningen om markedsføringstilladelse for Diclofenac (epolamin) 50 mg, tabletter med umiddelbar frigivelse, blev indgivet i henhold til artikel 10, stk. 1, i direktiv 2001/83/EF. 
The marketing authorisation application (MAA) for Diclofenac (epolamine) 50 mg immediate release tablets was submitted according to Article 10(1) of Directive 2001/83/EC.
For natrium- og kaliumsaltet og syren ses i de fleste undersøgelser en effekt af fødeindtagelse. 
For the sodium and potassium salt, and the acid, a food effect is evident in most studies.
Betænkeligheden ved den potentielle alvorlige risiko for den offentlige sundhed blev fastholdt, og referencemedlemsstaten indbragte proceduren for CMDh. 
The potential serious risk to public health (PSRPH) concern was maintained, and the procedure was referred by the RMS to the CMDh.
Undersøgelsen var en åben, randomiseret 2x2 overkrydsningsundersøgelse med enkeltdosering med acceptabelt design. 
This was a single-dose openlabel randomised 2x2 crossover study of acceptable design.
De indsigende EU-medlemsstater hævdede imidlertid, at virkningen af fødeindtagelse på Cmax kan være formuleringsafhængig for diclofenacs vedkommende, og at den foreliggende evidens viser, at den potentielle forskel i biotilgængelighed (mindskelse af Cmax med op til 70 %) kan være så stor, at den berører lægemidlets sikkerhed og effektivitet. 
However the objecting EU Member States argued that the effect of food on Cmax may be formulationdependent in the case of diclofenac, and that from the available evidence the potential difference in bioavailability (Cmax decrease of up to 70%) may reach such a high level so as to compromise the safe and effective use of the drug.
I betragtning heraf blev det hævdet, at der måtte anmodes om en postprandial undersøgelse for at udelukke al risiko for manglende bioækvivalens ved postprandiale betingelser. 
Considering this, it was argued that it was necessary to request a fed study in order to rule out any risk of bio-in-equivalence under fed conditions.
Punkt 4.2 i det foreslåede produktresumé for Diclofenac (epolamin) 50 mg, tabletter med umiddelbar frigivelse, er i overensstemmelse med referenceproduktet og anbefaler, at: "... tabletterne skal synkes hele med et glas vand, fortrinsvis sammen med eller efter et måltid. 
Section 4.2 of the proposed SmPC for Diclofenac (epolamine) 50 mg immediate release tablets is in line with the reference product, and recommends that: '… tablets should be swallowed whole with a glass of water, preferably during or after meals.
Diclofenac er et non-steroidt antiinflammatorisk lægemiddel (NSAID), der hæmmer prostaglandinsyntesen gennem hæmning af både COX-1- og COX-2-isoenzymer i arachidonsyremetabolismen. 
Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits prostaglandin synthesis via inhibition of both COX-1 and COX-2 isoenzymes of the arachidonic acid pathway.
• udvalget gennemgik de data, der er forelagt af ansøgeren til støtte for produktet Diclofenac (Altergon) 50 mg, tabletter 
• The Committee reviewed the data submitted by the applicant in support of this particular medicinal product Diclofenac (Altergon) 50mg tablets;
På baggrund af den stærke evidens for en effekt af fødeindtagelse på Cmax og Tmax konkluderes det, at denne effekt er både lægemiddelstof- og formuleringsafhængig. 
Given the strong evidence of a food effect on the Cmax and Tmax, this effect is concluded to be both drug substance and formulation dependent.
Sammenfattende kunne det af ansøgerens litteraturgennemgang vedrørende omfanget af fødeindtagelses virkning på absorptionsgraden for diclofenac-formuleringer med umiddelbar frigivelse konkluderes, at Cmax i gennemsnit blev 50 % nedsat og tmax i vekslende grad forsinket uden tab i omfanget af den systemiske eksponering. 
In summary this review of literature by the applicant about the magnitude of the food-effect on the rate of absorption with diclofenac immediate release formulations, allowed to conclude that it reached on average, 50% decrease on Cmax and various delays on tmax, without any loss in the amount of systemic exposure.
CHMP var enig med ansøgeren i, at virkningen af fødeindtagelse på Cmax for diclofenac både afhænger af lægemiddelstoffet og formuleringen, baseret på en litteraturgennemgang, der omfatter både kaliumog natriumsalt og syren. 
The CHMP agreed with the applicant that the food effect on Cmax of diclofenac is both drug substance and formulation dependent, based on the review of the literature, which includes potassium and sodium salts, and the acid.
Diclofenac 50 mg, tabletter, indeholder diclofenacepolamin, der er et salt af diclofenac dannet ved kombination af diclofenacsyre med den tertiære amin N-(2-hydroxyethyl)-pyrrolidin. 
Diclofenac 50 mg Tablets contain diclofenac epolamine, a salt of diclofenac, formed by the combination of diclofenamic acid with the tertiary amine N-(2-hydroxyethyl)-pyrrolidine.
Begrundelse for CHMP's udtalelse 
Grounds for the CHMP opinion Whereas
Der blev ikke fundet undersøgelser af effekten af fødeindtagelse på diclofenacepolamin. 
No food-effect study was identified with Diclofenac epolamine.
Chen et al (2015)2 beskrev en reduktion i postprandial i forhold til fastende tilstand på 69 % i Cmax for en bufret kaliumopløsning, og en reduktion på 28 % for en kaliumtablet. 
Chen et al (2015)2 reported a 69% reduction in Cmax for a buffered potassium solution vs a 28% reduction for a potassium tablet, in the fed state vs. fasted state.
Der blev imidlertid ikke til underbygning af ansøgningen forelagt data, der viser effekten af fødeindtagelse for henholdsvis test- og referenceproduktet, skønt det i produktresuméets punkt 4.2 anbefales, at Diclofenacepolamin, tabletter, synkes hele med et glas vand, fortrinsvis under eller efter et måltid. 
However no data was submitted to show the food effect between test and reference product to support this application, given that the SmPC recommendation in section 4.2 is that Diclofenac epolamine tablets should be swallowed whole with a glass of water, preferably during or after meals.
• udvalget var den opfattelse, at der i dette tilfælde også skulle påvises bioækvivalens af Diclofenac, tabletter, 50 mg med referenceproduktet, Flector, granulat til oral opløsning, i postprandial tilstand, hvilket har baggrund i den foreliggende litteratur, der viser, at Cmax for forskellige formuleringer af diclofenac påvirkes forskelligt i postprandial tilstand 
• The Committee was of the view that in this case bioequivalence of Diclofenac 50 mg tablets vs. the reference product Flector granules for oral solution should be demonstrated in fed conditions as well, in view of the available literature demonstrating that the Cmax of different formulations of diclofenac is affected differently in fed conditions;
Ved en sammenlignende opløselighedstest ved pH 5,5 blev der desuden påvist umiddelbar frigivelse fra test- og referenceproduktet. 
Furthermore, comparative dissolution testing at pH 5.5 demonstrated immediate release from test and reference product, which was used to support the comparative rate and extent of absorption in vivo in the fed state.
CHMP er derfor af den opfattelse, at der ikke er påvist bioækvivalens af Diclofenacepolamin, tabletter, med referenceproduktet diclofenacepolamin, granulat til opløsning, med henblik på denne markedsføringstilladelsesansøgning i henhold til artikel 10, stk. 1, da der ikke kan drages en konklusion om bioækvivalens uden en bioækvivalensundersøgelse i postprandial tilstand. 
Therefore the CHMP is of the opinion that the bioequivalence of Diclofenac epolamine tablets and the reference product diclofenac epolamine granules for solution has not been demonstrated for this Article 10(1) marketing authorisation application, since bioequivalence cannot be concluded in the absence of a bioequivalence study in the fed state.
Ansøgeren har forelagt data fra en undersøgelse af bioækvivalensen af diclofenacepolamin, tabletter, med Flector, granulat til oral opløsning, hos raske frivillige under fastende betingelser. 
The applicant submitted data from one bioequivalence study of diclofenac epolamine tablets vs. Flector granules for oral solution in healthy volunteers under fasted conditions.
Ansøgeren gjorde ud fra den forelagte litteratur gældende, at manglende bioækvivalens i fastende tilstand er prædiktiv for manglende bioækvivalens i postprandial tilstand, men CHMP fandt, at man ikke uden underbyggende evidens tilsvarende kunne slutte, at bioækvivalens i fastende tilstand er prædiktiv for bioækvivalens i postprandial tilstand. 
Although it was argued by the applicant that a failure of bioequivalence under fasting state is predictive of a failure of bioequivalence under fed state based on the submitted literature, the CHMP was of the view that the reverse argument could not be upheld i.e that bioequivalence under fasting state is predictive of bioequivalence under fed state, without any evidence to support it.
• udvalget konkluderede derfor, at der savnedes tilstrækkelige data til dokumentation af et positivt benefit/risk-forhold for lægemidlet Diclofenac 50 mg, tabletter finder udvalget følgelig, at benefit/risk-forholdet for Diclofenac ikke er positivt. 
• The Committee therefore concluded that there was a lack of appropriate data to support the positive benefit-risk of this medicinal product Diclofenac 50mg tablets.
(2015)1 medførte indtagelse i postprandial i forhold til fastende tilstand en reduktion af Cmax på 60 % for en kapsel med diclofenacsyre, og 43 % for en kaliumtablet. 
According to Desjardins et al (2015)1, there was 60% decrease in Cmax for a diclofenac acid capsule, compared to a 43% decrease in Cmax for a potassium tablet, in the fed state vs fasted.
I dette tilfælde kan der derfor kun konkluderes at foreligge bioækvivalens, hvis dette påvises ved både postprandiale og fastende betingelser, fordi Diclofenacepolamin, tabletter, og referenceproduktet diclofenacepolamin, granulat til opløsning, er forskellige orale farmaceutiske formuleringer, og fordi litteraturdata viser, at effekten af fødeindtagelse på Cmax for diclofenac ikke kun afhænger af lægemiddelstoffet, men også af formuleringen. 
Therefore as Diclofenac epolamine tablets and the reference product diclofenac epolamine granules for solution are different oral pharmaceutical formulations, and because literature data show that the food effect on Cmax of diclofenac is not only dependent on the drug substance but also on the formulation, in this case, bioequivalence can only be concluded if bioequivalence is shown under fed as well as fasted conditions.
Ved proceduren konsulteredes desuden arbejdsgruppen vedrørende farmakokinetik (PKWP). 
The advice of PKWP was also sought during this procedure.
Forholdet mellem Cmax i postprandial/fastende tilstand var mellem 26 og 73 % for de forskellige formuleringer. 
In summary, the view of the PKWP was that under fed conditions the Cmax is highly variable; Cmax ratio fed/fasted ranged from 26-73% for the different formulations, and formulations that are bioequivalent in the fasted state may not be bioequivalent in the fed state, especially if the dosage form is different.
Vurdering af benefit/risk-forholdet og diskussion 
Benefit-risk assessment and discussion
Heterogeniteten kan også spille en rolle i de to studier. 
The heterogeneity could also play a role in the two studies.
Den terapeutiske indikation for Lartruvo er som følger: 
The therapeutic indication of Lartruvo is:
Kommissionen anmodede CHMP om at udtale sig om, hvorvidt markedsføringstilladelsen for dette produkt bør bevares, ændres, suspenderes eller tilbagekaldes. 
The EC requested the CHMP to give its opinion on whether the marketing authorisation for this product should be maintained, varied, suspended or revoked.
I henhold til artikel 116 i direktiv 2001/83/EF anbefaler udvalget derfor tilbagekaldelse af markedsføringstilladelsen for Lartruvo. 
Therefore, pursuant to Article 116 of Directive 2001/83/EC, the Committee recommends the revocation of the marketing authorisation for Lartruvo.
Resultaterne af ANNOUNCE-studiet bekræftede sikkerhedsprofilen fra det tidligere fase II-studie. 
The results of the ANNOUNCE study confirmed the safety profile seen in the previous phase II study.
Det er plausibelt, at forskellig forekomst af en række histologier mellem de to studier kan have haft betydning for den observerede forskel i effekt. 
It is plausible that a different rate of several histologies between the two studies could have had an impact in the dissimilar efficacy observed.
Selv behandlingen efter seponering er balanceret. 
Even the post-discontinuation therapy is balanced.
Patient- og sygdomskarakteristika ved baseline syntes generelt at være i god balance. 
Baseline patient and disease characteristics appeared overall well balanced.
Derudover sås der ingen klinisk gavn, hvad angår de centrale sekundære endepunkter. 
Furthermore, there was no clinical benefit in key secondary efficacy endpoints.
Alle de anafylaktiske reaktioner opstod under den første olaratumabinfusion. 
All anaphylactic reactions occurred during the first olaratumab infusion.
Ugunstige virkninger 
Unfavourable effects
Den 25. januar 2019 indledte Europa-Kommissionen en procedure i henhold til artikel 20 i forordning (EF) nr. 726/2004 og bad CHMP om at vurdere ovenstående problemstillinger og disses betydning for benefit/risk-forholdet for Lartruvo. 
On 25 January 2019 the European Commission (EC) triggered a procedure under Article 20 of Regulation (EC) No 726/2004, and requested the CHMP to assess the above concerns and their impact on the benefit-risk balance of Lartruvo.
Sikkerhedsanalyse pr. alderskategori (< 65 vs. ≥ 65 år) viste højere toksicitet hos ældre patienter, om end dette sås i samme omfang i de to grupper. 
Safety analysis by age category (<65 vs >=65 years) showed higher toxicity in older subjects, although this occurred equally in both arms.
Delgruppeanalyserne viser ingen delgruppe af interesse, hvor der kunne være en fordel. 
The subgroup analyses do not reveal any subgroup of interest where there could be some benefit.
Der sås ingen forskel for nogen af de andre sekundære endepunkter, der blev analyseret i ITTpopulationen. 
No difference was observed in any of the other secondary endpoints analysed in the ITT population.
Styrken af evidensen i fase III-studiet ANNOUNCE er i sagens natur højere som følge af et større antal patienter og det blindede design uden overkrydsning. 
The strength of the evidence from the phase III ANNOUNCE study is necessarily higher due to higher patient numbers and the blinded design with no cross-over.
Baselinekarakteristikaene synes at være ligeligt fordelt, både med hensyn til histologi og sygdom ved randomisering. 
The baseline characteristics appear to be evenly balanced, both in histology and disease at randomization.
De forskellige eksponeringer for doxorubicin mellem den eksperimentelle gruppe og kontrolgruppen blev bemærket. 
The different exposure to doxorubicin between investigational arm and the control group was noted.
Sidstnævnte studie viste en uventet overlevelsesfordel hos patienter med fremskredent/metastatisk bløddelssarkom, der var rekrutteret i USA. 
The latter showed an unexpected survival gain in patients with advanced/metastatic STS recruited in the United States.
I januar 2019 fremsendte indehaveren af markedsføringstilladelsen de foreløbige højniveauresultater fra JGDJ-studiet til Det Europæiske Lægemiddelagentur. 
In January 2019, the marketing authorisation holder communicated to the European Medicines Agency high level preliminary results of the JGDJ study.
Studiet gav anledning til bekymring på grund af manglende effekt, idet det ikke opfyldte det primære formål, der var at forlænge overlevelsen hos den samlede population eller i leiomyosarkomdelpopulationen. 
The study gave rise to concerns about lack of efficacy, because it did not meet the primary objective to prolong survival in the overall population or in the leiomyosarcoma sub-population.
Gavnlige virkninger 
Favourable effects
Infusionsrelaterede reaktioner, hjertearytmier og hjertedysfunktion anses for at være hændelser af særlig interesse for olaratumab. 
Infusion related reactions, cardiac arrhythmia and cardiac dysfunction are considered events of special interest for olaratumab.