FrancophonIA/ELRC3.0 huggingface dataset:
English: The MAH divided its argumentation into 2 parts: bioequivalence and safe switch, and pharmaceutical properties of Sandimmune Optoral and Ciclosporin IDL micro emulsions
Danish: Indehaveren af markedsføringstilladelsen opdelte sin argumentation i to dele: bioækvivalens og sikkert skifte samt farmaceutiske egenskaber for Sandimmun Optoral- og Ciclosporin IDLmikroemulsioner.
English: The upper 90% interval confidence limit for Cmax, which should be considered for safety issues, is below the accepted limit (111%) for NTI products.
Danish: Den øvre grænse for konfidensintervallet på 90 % for Cmax, som skal overvejes af hensyn til sikkerheden, er under den accepterede grænse (111 %) for lægemidler med et snævert terapeutisk indeks.
English: In the MAH view the same set of requirements should usually be applied in the case of studies under high fat fed conditions.
Danish: Ifølge indehaveren af markedsføringstilladelsen skulle de samme krav normalt gælde for undersøgelser foretaget efter et fedtrigt måltid.
English: The classification of ciclosporin as an NTI drug could have been based on the adverse events associated with its use or on the concomitant use of other drugs.
Danish: Klassificeringen af ciclosporin som et lægemiddel med et snævert terapeutisk indeks kunne være baseret på bivirkninger i forbindelse med brugen eller samtidig brug af andre lægemidler.
English: The MAH also stated that bioequivalence under fed conditions has not been shown, since the PK of Ciclosporin IDL formulation is considerably less affected by food than the reference product.
Danish: Indehaveren af markedsføringstilladelsen anførte endvidere, at bioækvivalens i ikkefastende tilstand ikke er blevet påvist, da PK for Ciclosporin IDL-formuleringen påvirkes betydeligt mindre af føde end referencelægemidlet.
English: The MAH answered that the reduced effect of food on generic ciclosporin pharmacokinetics as compared to the innovator formulation could be seen as an advantage over the reference product and a compelling argument for the acceptance of the former.
Danish: Indehaveren af markedsføringstilladelsen svarede, at kostens reducerede indvirkning på generisk ciclosporins farmakokinetik sammenlignet med det nye lægemiddels formulering kunne betragtes som en fordel i forhold til referencelægemidlet og et væsentligt argument for godkendelsen af førstnævnte.
English: They therefore advised that a generic ciclosporin product should be bioequivalent with the originator product both in the fasting and in the fed state.
Danish: Den anførte derfor, at et generisk ciclosporinlægemiddel bør være bioækvivalent med originalpræparatet, både i fastende og ikkefastende tilstand.
English: In the case of Ciclosporin IDL, the MAH argued that bioequivalence has been proven in the fasting state in CI (80-125%).
Danish: Hvad angår Ciclosporin IDL, anførte indehaveren af markedsføringstilladelsen at bioækvivalens er dokumenteret ved faste i konfidensintervallet (80-125 %).
English: In the ‘fasting' bioequivalence trial presented, the 90% confidence interval for Cmax does not meet the tighter 90-111% acceptance criteria.
Danish: I den fremlagte bioækvivalensundersøgelse for fastende opfylder konfidensintervallet på 90 % for Cmax ikke de skærpede godkendelseskriterier på 90-111 %.
English: The Marketing Authorisation Holder should conduct a new fasting and fed bioequivalence study showing the bioequivalence of Ciclosporin IDL under a tightened acceptance range (90-111%) for the 90% CI.
Danish: Indehaveren af markedsføringstilladelsen skal udføre en ny bioækvivalensundersøgelse ved faste og ikke-faste, som påviser bioækvivalensen for Ciclosporin IDL i et snævrere godkendelsesinterval (90111 %) for konfidensintervallet på 90 %.
English: The MAH answered that ciclosporin, in spite of being highly variable drug, is not to be considered a Narrow Therapeutic Index (NTI) drug because the clinical evidence for such a classification is lacking.
Danish: Indehaveren af markedsføringstilladelsen svarede, at ciclosporin, selv om det er et foranderligt lægemiddel, ikke kan betegnes som et lægemiddel med et snævert terapeutisk indeks, da der ikke foreligger kliniske data for en sådan klassificering.
English: The CHMP maintained its conclusion that bioequivalence of Ciclosporin IDL to the originator has not been adequately demonstrated, either in fed or fasted conditions.
Danish: CHMP fastholdt sin konklusion om, at bioækvivalens mellem Ciclosporin IDL og originallægemidlet ikke var blevet tilstrækkeligt påvist, hverken for den fastende eller den ikkefastende tilstand.
English: The data submitted showed that the 90% CI for Cmax fell outside the standard (80-125%) acceptance range in the fed state and outside a narrowed (90-111%) acceptance range in the fasted state and the respective value for AUC exceeds the narrowed acceptance range in the fed state.
Danish: De forelagte data viste, at konfidensintervallet på 90 % for Cmax faldt uden for godkendelsesintervallets standard (80 - 125 %) i ikkefastende tilstand og udenfor et mere snæver (90 - 111%) godkendelsesinterval i fastende tilstand, og at den respektive værdi for AUC overstiger det mere snævre godkendelsesintervallet i ikkefastende tilstand.
English: The CHMP acknowledged that a therapeutic index (TI) calculation has not been reported for ciclosporin but disagreed with the statement from MAH that it is based on the adverse events profile.
Danish: CHMP medgav, at beregningen af det terapeutiske indeks for ciclosporin ikke er indberettet, men erklærede sig uenigt i indehaveren af markedsføringstilladelsens udtalelse om, at den er baseret på bivirkningsprofilen.
English: There is emerging data indeed to suggest that appropriate therapeutic monitoring may radically reduce the incidence of acute rejection in de-novo recipients and ameliorate chronic rejection and secondary effects in maintenance transplant patients, as for ciclosporin, the patients inter and intra-variability is actually more problematic than the therapeutic index.
Danish: Der foreligger nye data, som antyder, at passende terapeutisk monitorering kan reducere hyppigheden af akut afstødning markant hos nyligt transplanterede patienter og hindre afstødning samt sekundære bivirkninger hos transplanterede patienter under vedligeholdelsesbehandling.
English: The CHMP considered that similar argumentation (using TDM) must not be used to excuse any failed bioequivalence for any generic product.
Danish: CMPH vurderede, at lignende argumentation (brug af terapeutisk monitorering af lægemidler) ikke må bruges som undskyldning for manglende bioækvivalens for et generisk lægemiddel.
English: - the Scope of the Referral was about the bioequivalence (BE) of the generic Ciclosporin IDL to the originator.
Danish: - formålet med indbringelsen af sagen omhandlede bioækvivalens for generisk Ciclosporin IDL over for originalpræparatet,
English: The CHMP acknowledged that the food effect seen on Ciclosporin IDL is lower then the effect on the innovator and that it may represent an advantage for a product that can be administered with or without food.
Danish: CHMP anerkendte, at kostens indvirkning er mindre på Ciclosporin IDL end på originalpræparatet, og at dette kan være en fordel for et lægemiddel, som kan gives med eller uden et måltid.
English: The CHMP noted that MAH stressed the need for routine TDM and from experienced physicians to prescribe ciclosporin, but these arguments could not counterbalance any failed bioequivalence for any compound being proposed as generic of the reference product.
Danish: CHMP bemærkede, at indehaveren af markedsføringstilladelsen understregede behovet for rutinemæssig terapeutisk monitorering af lægemidler, og at ciclosporin skal ordineres af erfarne læger, men disse argumenter opvejer ikke den manglende bioækvivalens for et stof, der foreslås som en generisk form af referencelægemidlet.
English: OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF CICLOSPORIN IDL Ciclosporin is a calcineurin inhibitor and as such an immunosuppressive drug.
Danish: Ciclosporin er en calcineurinhæmmer og som sådan et immunosuppressivt lægemiddel.
English: Ciclosporin is considered a NTI drugs, and the MAH accepted this in the grounds for re-examination.
Danish: Ciclosporin betegnes som et lægemiddel med et snævert terapeutisk indeks, og indehaveren af markedsføringstilladelsen accepterede dette i begrundelsen for revurdering.
English: The CHMP concluded that bioequivalence has not been satisfactorily demonstrated, the benefit/risk ratio is considered negative and Ciclosporin IDL cannot be recommended for approval.
Danish: CHMP konkluderede, at benefit-/risk-forholdet må anses for negativt, og at Ciclosporin IDL ikke kan anbefales til godkendelse, da bioækvivalens ikke er blevet tilfredsstillende påvist.
English: The effect of food on the blood concentrations, the large variation of the blood levels, and the resultant adverse events might well be other reasons for branding the reference product a NTI drug.
Danish: Kostens virkning på koncentrationen i blodet, den store variation i indholdet i blodet og de deraf følgende bivirkninger kan være årsagen til, at lægemidlet får betegnelsen "lægemiddel med et snævert terapeutisk indeks".
English: The MAH summarized previous studies showing that the size of the emulsion droplets and concomitant food intake have an effect on the absorption of ciclosporin from the small intestine when orally administered, which may have an influence on the drugs' pharmacokinetic parameters The MAH compared Neoral and 3 batches of Ciclosporin IDL.
Danish: Indehaveren af markedsføringstilladelsen opsummerede tidligere undersøgelser, der påviser, at størrelsen af emulsionsdråber og samtidig fødeindtagelse kan have en indvirkning på absorptionen af ciclosporin gennem tyndtarmen ved peroral indgift, hvilket kan påvirke lægemidlernes farmakokinetiske parametre.
English: For ciclosporin IDL, it was argued that because the differences observed between test and reference products under fed conditions were not due to the test product, but to the very profound effect of food on the blood levels of the reference product, no safety concern arose and the upper 90% confidence limit for comparison of Cmax (137%) was acceptable (see 4 below).
Danish: For ciclosporin IDL blev det fremført, at der ikke var anledning til sikkerhedsmæssige betænkeligheder, og at den øvre grænse for konfidensintervallet på 90 % til sammenligning af Cmax (137 %) var acceptabel (se punkt 4 nedenfor), fordi de observerede forskelle mellem test- og referencelægemidlerne i ikkefastende tilstand ikke skyldtes testlægemidlet, men derimod fødens udtalte indvirkning på indholdet af referencelægemidlet i blodet.
English: - On the efficacy side not achieving therapeutic levels may lead to devastating consequences and therefore the SPC clearly states that monitoring blood levels are essential during treatment with ciclosporin and when switching to another formulation.
Danish: Denne begrundelse er baseret på kliniske vurderinger med udgangspunkt i både virkning og sikkerhed: - Når det gælder virkning, kan manglende opnåelse af det terapeutiske niveau få katastrofale konsekvenser, og derfor fremgår det tydeligt af produktresuméet, at monitorering af indholdet i blodet er nødvendig under behandling med ciclosporin, og når der skiftes til en anden formulering.
English: The CHMP agreed with the EWP PK expert group position that if ciclosporin is considered a narrow therapeutic index drug, a narrowed (90-111%) acceptance range should be applied for AUC.
Danish: CHMP erklærede sig enigt med den farmakokinetiske ekspertgruppe under Arbejdsgruppen vedrørende virkninger i, at der bør anvendes et mere snævert godkendelsesinterval (90-111 %) for AUC, hvis ciclosporin betegnes som et lægemiddel med et snævert terapeutisk indeks.
English: The EWP PK expert group advised that since ciclosporin may be given either with or without food, the requirements with regard to bioequivalence should be the same in both fasted and fed states.
Danish: Den farmakokinetiske ekspertgruppe under Arbejdsgruppen vedrørende virkninger anførte, at kravene i forbindelse med bioækvivalens skal være de samme i fastende tilstand og i ikkefastende tilstand, eftersom ciclosporin kan gives med eller uden et måltid.
English: Whereas
Danish: Fastende
English: Ciclosporin IDL 100 mg 100 mg capsule, soft
Danish: Ciclosporin IDL 100 mg 100 mg kapsel, blød oral anvendelse
English: The CHMP in principle agreed that a decreased sensitivity of the ciclosporin absorption to food intake could be seen as an advantage, however a generic product should be bioequivalent and possible to be used interchangeably with an originator product based on bioequivalence and this has not been demonstrated.
Danish: Et generisk lægemiddel skal dog være bioækvivalent og kunne anvendes substituerbart med et originalpræparat baseret på bioækvivalens, og dette er ikke blevet påvist.
English: Ciclosporin IDL 50 mg 50 mg capsule, soft
Danish: Ciclosporin IDL 50 mg 50 mg kapsel, blød oral anvendelse
English: Ciclosporin IDL 25 mg 25 mg capsule, soft
Danish: Ciclosporin IDL 25 mg 25 mg kapsel, blød oral anvendelse
English: The CHMP considered that as ciclosporin is NTI drug, narrowing the Confidence Interval (CI) range to 90-111%, would minimize the risk of over or under exposure.
Danish: CHMP fandt, at en indsnævring af konfidensintervallet til 90-111 % ville minimere risikoen for overeller undereksponering, eftersom ciclosporin er et lægemiddel med et snævert terapeutisk indeks.
English: - clinical evidence-based classification of Ciclosporin as a NTI drug was still lacking, difficult to calculate, and based only on the adverse events for which an explanation was already given,
Danish: En sådan var svær at beregne og kunne udelukkende baseres på bivirkninger, der allerede var blevet redegjort for.
English: The procedure included an oral explanation, at which the MAH presented their views that:
Danish: Listen indeholdt følgende punkter:
English: Applicant
Danish: Styrke
English: 25 mg capsule
Danish: 100 mg
English: Ciclosporin IDL 25 mg
Danish: Ciclosporina IDL 100 mg
English: Ciklosporin IDL 100 mg 100 mg capsule
Danish: FRANKRIG Ciklosporin IDL 100 mg100 mg
English: Ciklosporin IDL 25 mg 25 mg capsule
Danish: FRANKRIG Ciklosporin IDL 25 mg 25 mg
English: Ciklosporin IDL 50 mg 50 mg capsule
Danish: FRANKRIG Ciklosporin IDL 50 mg 50 mg
English: Ciclosporina IDL 50 mg 50 mg capsule
Danish: FRANKRIG Ciclosporina IDL 50 mg 50 mg
English: Ciclosporin IDL 100 mg 100 mg capsule
Danish: FRANKRIG Ciclosporin IDL 100 mg100 mg
English: Ciclosporina IDL 25 mg 25 mg capsule
Danish: FRANKRIG Ciclosporina IDL 25 mg 25 mg
English: Ciclosporin IDL 50 mg 50 mg capsule
Danish: FRANKRIG Ciclosporin IDL 50 mg 50 mg
English: In the MAH view even if Ciclosporin was to be considered a NTI drug, the normal 80-125% acceptance range should be used.
Danish: Ifølge indehaveren af markedsføringstilladelsen burde det normale godkendelsesinterval (80-125 %) anvendes, selv om ciclosporin var betegnet som et lægemiddel med et snævert terapeutisk indeks.
English: Ciclosporin IDL 25 mg 25 mg capsule
Danish: FRANKRIG Ciclosporin IDL 25 mg 25 mg
English: MA (EU) number (Invented) name Strength Pharmaceutical Form Route of Administration
Danish: Styrke Lægemiddelform Administration Emballage
English: • over about 1 hour.
Danish: • i løbet af ca. 1 time.
English: • once each day
Danish: • en gang dagligt
English: Date of first authorization: 11 February 2016
Danish: Dato for første markedsføringstilladelse: 11 februar 2016
English: Caution is advised when treating this age group.
Danish: Forsigtighed tilrådes ved behandling af denne aldersgruppe.
English: Ask your doctor for more information.
Danish: Spørg lægen om yderligere information.
English: Not Recommended
Danish: Anbefales ikke
English: The safety information on treatment durations longer than 4 weeks is limited.
Danish: Information vedrørende sikkerhed ved behandlingsvarighed over 4 uger er begrænset.
English: From a microbiological point of view, the product should be used immediately.
Danish: Af mikrobiologiske grunde bør produktet anvendes straks.
English: If you weigh more than 80 kg, you may need a different dose.
Danish: Hvis De vejer mere end 80 kg, skal De måske have en anden dosis.
English: Duration of treatment
Danish: Varighed af behandling
English: Efficacy was a secondary endpoint in this study.
Danish: Effekt var et andet sekundært endpoint i denne undersøgelse.
English: Twentyfour patients had neutropaenia.
Danish: 24 patienter havde neutropeni.
English: This stops the infection from spreading and gives the body's natural defences a chance to completely get rid of the infection.
Danish: Dette forhindrer infektionen i at sprede sig og giver kroppens naturlige forsvar en chance for helt at komme af med infektionen.
English: A similar effect could be expected for other medicinal products that induce metabolic enzymes.
Danish: En lignende effekt kan forventes for andre lægemidler, der inducerer metaboliske enzymer.
English: The plasma concentrations decrease with increasing weight.
Danish: Plasmakoncentrationerne falder med øget vægt.
English: • if you have ever had any other medical problem.
Danish: • De nogensinde har haft andre helbredsmæssige problemer.
English: Reconstituted concentrate: should be used immediately.
Danish: Rekonstitueret koncentrat: Skal anvendes straks.
English: The mechanism of resistance has not been established.
Danish: Resistensmekanismen er ikke fastlagt.
English: Your doctor will monitor how well the medicine works for you.
Danish: Lægen vil kontrollere, hvordan medicinen virker hos Dem.
English: An additional gamma-phase also occurs with a half-life of 45 hours.
Danish: Der opstår ligeledes yderligere en gamma-fase med en halveringstid på 45 timer.
English: These limited data are supported by the outcome of the empirical therapy study.
Danish: Disse begrænsede data støttes af resultatet af undersøgelsen af empirisk behandling.
English: Generally the increase was modest and not large enough to warrant dosage adjustment.
Danish: Generelt var øgningen beskeden og ikke tilstrækkelig til at nødvendiggøre dosisjustering.
English: Fever and chills that do not respond to an antibiotic are the most common signs of this type of infection.
Danish: Feber og kuldegysninger, som ikke reagerer på antibiotika, er de mest almindelige tegn på denne type infektion.
English: The number of neutropenic patients enrolled in this study was also limited (8.0 %).
Danish: Antallet af patienter med neutropeni var også begrænset i denne undersøgelse (8,0%).
English: • you are allergic to any other medicines
Danish: • De er allergisk over for anden medicin
English: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Danish: På grund af manglende kompatibilitetsstudier må dette lægemiddel ikke blandes med andre lægemidler.
English: A small amount of caspofungin is excreted unchanged in urine (approximately 1.4 % of dose).
Danish: En lille mængde af caspofungin udskilles uændret i urinen (ca. 1,4% af dosis).
English: The mechanism of interaction could possibly be due to an initial inhibition and subsequent induction of transport proteins.
Danish: Interaktionsmekanismen kan muligvis skyldes en initial hæmning og efterfølgende induktion af transportproteiner.
English: A favourable response required both symptom resolution and microbiological clearance of the Candida infection.
Danish: Et gunstigt respons krævede både resolution af symptomer og mikrobiologisk clearance af candida-infektionen.
English: Caspofungin should not be used during pregnancy unless clearly necessary.
Danish: Caspofungin må ikke anvendes under graviditet, med mindre dette er klart nødvendigt.
English: These cases have been associated with poor clinical outcomes.
Danish: Disse tilfælde har været associeret med dårlige kliniske resultater.
English: Read all of this leaflet carefully before you or your child are given this medicine because it contains important information for you.
Danish: Læs denne indlægsseddel grundigt, inden De eller Deres barn får dette lægemiddel, da den indeholder vigtige oplysninger.
English: If this occurs, Caspofungin should be discontinued and appropriate treatment administered.
Danish: Hvis dette forekommer, skal caspofungin seponeres, og passende behandling administreres.
English: However, no systematic dosage adjustment is required.
Danish: Systematisk dosisjustering er dog ikke nødvendig.
English: Paediatric patients (12 months to 17 years)
Danish: Pædiatrisk population (12 måneder til 17 år)
English: A short alpha-phase occurs immediately post-infusion, followed by a beta-phase with a halflife of 9 to 11 hours.
Danish: Der opstår en kortvarig alfa-fase umiddelbart efter infusion, efterfulgt af en beta-fase med en halveringstid på 9-11 timer.
English: Xellia Pharmaceuticals ApS Dalslandsgade 11, København S, 2300, Denmark
Danish: Xellia Pharmaceuticals ApS Dalslandsgade 11, København S, 2300, Danmark
English: An increase in the incidence of cervical ribs was also noted.
Danish: Der sås også en øgning i forekomsten af cervikale ribben.
English: Therefore, elimination occurs in the absence of a distribution equilibrium, and a true estimate of the volume of distribution of caspofungin is currently impossible to obtain.
Danish: Derfor sker eliminationen uden en distributionsligevægt, og et estimat af det sande fordelingsvolumen for caspofungin er i øjeblikket umuligt at opnå.
English: Distribution, rather than excretion or biotransformation, is the dominant mechanism influencing plasma clearance.
Danish: Distribution er, frem for ekskretion og biotransformation, den dominerende mekanisme der påvirker plasmaclearance.
English: • you have ever had liver problems - you might need a different dose of this medicine
Danish: • De nogensinde har haft leverproblemer - De skal måske have en anden dosis af lægemidlet
English: Each pack contains one vial of powder.
Danish: Hver pakning indeholder 1 hætteglas med pulver.
English: The requirements for submission of periodic safety update reports for this medicinal product are set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any subsequent updates published on the European medicines web-portal.
Danish: Kravene til fremsendelse af periodiske, opdaterede sikkerhedsindberetninger for dette lægemiddel fremgår af listen over EU-referencedatoer (EURD list), som fastsat i artikel 107c, stk. 7, i direktiv 2001/83/EF, og og alle efterfølgende opdateringer offentliggjort på den europæiske webportal for lægemidler.
English: After signs and symptoms of invasive candidiasis have improved and cultures have become negative, a switch to oral antifungal therapy may be considered.
Danish: Når tegn og symptomer på invasiv candidiasis er forbedrede, og kulturer er blevet negative, kan skift til oral antimykotisk behandling overvejes.
English: Caspofungin Accord is used to treat the following infections in children, adolescents and adults:
Danish: Caspofungin Accord anvendes til at behandle følgende infektioner hos børn, unge og voksne:
English: Approximately 75 % of a radioactive dose was recovered during 27 days: 41 % in urine and 34 % in faeces.
Danish: Ca. 75% af en radioaktivt mærket dosis blev genfundet i løbet af 27 dage: 41% i urinen og 34% i fæces.
English: The following adverse reactions were reportedduring clinical studies and/or post-marketing use:
Danish: Følgende bivirkninger er rapporteret under kliniske studier og/eller efter markedsføring:
English: Once Caspofungin Accord has been prepared, it should be used straight away.
Danish: Når Caspofungin Accord er tilberedt, skal det anvendes med det samme.
English: Among patients with extrapulmonary disease, 2 of 8 patients who also had definite, probable, or possible CNS involvement had a favourable response.
Danish: Blandt patienterne med ekstrapulmonal sygdom havde 2 ud af 8 patienter, der også havde verificeret, sandsynlig eller mulig CNS-inddragning, gunstigt respons.
English: As with any prescription medicine, some side effects may be serious.
Danish: Som med al anden receptmedicin, kan nogle bivirkninger være alvorlige.