natgillin/translations-raw huggingface dataset:
Begrundelse fra indehaveren af markedsføringstilladelsen for, at risikoen for myopati i forbindelse med cerivastatin 0, 1- 0, 3 mg ikke er større end ved andre ækvipotente doser af de øvrige statiner.
MAH Justification that the risk of myopathy with cerivastatin 0.1-0.3mg does not exceed that of other equipotent dosages of the other statins.
Data fra 8. 804 patienter, som deltog i kliniske undersøgelser, og som fik 0, 025- 0, 4 mg cerivastatin, indikerer, at procentdelen af patienter med forhøjet CPK ≥ 10xULN er ens for alle doser og placebo.
Data from 8,804 patients enrolled in clinical studies who received cerivastatin 0.025mg up to 0.4mg for 8-24 weeks suggest that the percentage of patients with elevations of CPK ≥ 10xULN are similar at all the dosages and with placebo.
Langtidseksposition (> 24 uger) viser en svag stigning for cerivastatin 0, 4 mg sammenlignet med de lavere doser eller andre statiner.
Long term exposure (> 24weeks) show a slight increase for cerivastatin 0.4mg compared with that of the lower dosages or other statins.
Indehaveren af markedsføringstilladelsen fremførte, at der er størst sandsynlighed for, at rabdomyolyse indtræffer i de første 6- 12 uger af terapien, og at korttidsdataene derfor er mest relevante.
Data from published clinical trials suggest that the risk of unconfirmed rhabdomyolysis (including cases in which increased CPK or muscle symptoms occur alone) with cerivastatin is similar to that of the other statins.
Indberetningsfrekvensen for bekræftede tilfælde af rabdomyolyse ved monoterapi med 0, 2- 0, 8 mg cerivastatin er højere end for de øvrige statiner.
The reporting rates of confirmed cases of rhabdomyolysis in association with 0.2mg to 0.8mg cerivastatin monotherapy are greater than those with any of the other statins.
Indberetningsfrekvensen for monoterapi med cerivastatin i doser på 0, 2- 0, 4 mg er højere end for ækvipotente doser af henholdsvis simvastatin og atorvastatin.
The reporting rates for cerivastatin monotherapy at doses of 0.2mg and 0.4mg are higher than those for equipotent dosages of simvastatin and atorvastatin, respectively.
Indberetningsfrekvensen for cerivastatin brugt i kombination med gemfibrozil i doser på 0, 4 og 0, 8 mg er væsentlig højere end ved ækvipotente doser af simvastatin og atorvastatin.
The reporting rates for cerivastatin when used in combination with gemfibrozil at doses of 0.4mg and 0.8mg are greatly elevated compared with equipotent dosages of simvastatin and atorvastatin.
Data for patienter, der behandles med cerivastatin og clopidogrel samtidig, indikerer en højere indberetningsfrekvens for bekræftet rabdomyolyse.
Data on patients receiving concomitant cerivastatin and clopidogrel indicate an increased reporting rate of confirmed rhabdomyolysis.
Uden for USA var det samlede antal bekræftede tilfælde af rabdomyolyse 16 med samtidig brug af cerivastatin og clopidogrel, hvoraf fire var døde.
In non-US countries, the total number of confirmed cases of rhabdomyolysis was 16 with combined cerivastatin-clopidogrel use, of which 4 were deaths.
Der blev ikke indberettet andre tilfælde af bekræftet rabdomyolyse med samtidig brug af clopidogrel i forbindelse med de øvrige statiner undtagen simvastatin, hvor der blev indberettet tre tilfælde, men ingen dødsfald.
No cases of confirmed rhabdomyolysis with clopidogrel co-administration were reported with the other statins, except for 3 cases with simvastatin, but no fatalities.
Når ekspositions data tages i betragtning var indberetningsfrekvensen væsentlig højere for cerivastatin
When exposure data are considered, the reporting rate is considerably higher with cerivastatin.
I USA var det samlede antal bekræftede tilfælde af rabdomyolyse 49 med samtidig brug af cerivastatin og clopidogrel Indberetningsfrekvensen for cerivastatin var væsentlig højere end for simvastatin og pravastatin i kombination med clopidrogel.
The reporting rate for cerivastatin was greatly in excess of that seen with simvastatin and pravastatin in combination with clopidogrel.
Der ver ingen indberetninger for de andre statiner.
There were no reports for the other statins
Tabel 8 viser en oversigt over rabdomyolysedødstilfælde i forbindelse med de forskellige statiner, som blev indberettet til FDA inden 26. juni 2001, og som for nylig blev offentliggjort i New England Journal of Medicine.
Fatal rhabdomyolysis reported to the FDA before June 26, 2001 and associated with the different statins are summarized in the table 8, recently published in the New England Journal of Medicine.
Indberettede rabdomyolysedødstilfælde i forbindelse med alle statiner, som er udleveret i USA, siden disse produkter blev lanceret.
Reported cases of fatal rhabdomyolysis for all statins dispensed in the USA since these products were launched
Cerivastatin
Cerivastatin
Fluvastatin
Fluvastatin
Lovastatin
Lovastatin
Simvastatin
Simvastatin
Godkendelsesdato
Date approved
26. 06. 97
06.26.97
17. 12. 96
12.17.96
31. 12. 93
12.31.93
31. 08. 87
08.31.87
31. 10. 91
10.31.91
23. 12. 91
12.23.91
Dødstilfælde af rabdomyo - lyse
of
19 3
19 3
Indberetningsfrekvens (pr.
Reporting rate (per
3, 16 1 million recepter)
million prescriptions)
0, 04 0
0.04 0
0, 19 0, 04
0.19 0.04
Rabdomyolyse med dødelig udgang er sjælden blandt statinbrugere, idet indberetningsfrekvensen er langt under et dødsfald pr. million recepter for de fleste statiners vedkommende.
Fatal rhabdomyolysis is a rare event among statin users, with reporting rates much lower than 1 death per million prescriptions in the case of most statins.
Frekvensen af rabdomyolyse med dødelig udgang i forbindelse med cerivastatinterapi er imidlertid 16- 80 gange så høj som for de øvrige statiner.
The rate of fatal rhabdomyolysis associated with cerivastatin therapy, however, is 16 to 80 times as high as the rates of any other statin.
10- 50 gange så høj som frekvensen for de øvrige statiner.
After the exclusion of the cases in which gemfibrozil was co-administered, the reporting rate of fatal rhabdomyolysis is 1.9 per million prescriptions, 10 to 50 times higher than the rates associated with the other statins.
Antallet af dødstilfælde uden samtidig ordinering af clopidogrel fremgår ikke af dette dokument.
The number of fatal cases without clopidogrel co-medication were not presented in this paper.
US Pacific Healthcare- undersøgelsen Der er modtaget en endelig rapport over 3rd PacifiCare/ Prescription Solutions undersøgelsen.
US PACIFIC HEALTHCARE STUDY A final study report of the 3rd PacifiCare/ Prescription Solutions was received.
Den foreløbige rapport var inkluderet i den første rapport fra indehaveren af markedsføringstilladelsen.
The preliminary report was included in the MAH's initial submission.
Den primære forskel mellem den endelige og den foreløbige rapport er definitionen af nyresvigt, som er medtaget i definitionen af et tilfælde.
The principal difference between the final report and the preliminary study report lies in the definition of renal failure included in the case definition.
Mens alle tilfælde af nyresvigt er med i den foreløbige rapport, er definitionen denne gang mere snæver og giver et lidt lavere antal tilfælde.
Whereas all renal failure cases had been included in the preliminary report, the case definition this time was more restricted and resulted in a slightly lower number of cases.
Der var flere
However, overall the results were entirely consistent with previous reports.
CPMP/ 811/ 02 oplysninger om co- morbiditet, co- medicinering, dødsfald, leverreaktioner og mortalitet.
Unadjusted risk of myopathy ranged from 0.59% with lovastatin to 0.27% with pravastatin.
De overordnede resultater var dog helt i overensstemmelse med tidligere rapporter.
The risk for cerivastatin was 0.54%.
Samtidig ordinering af gemfibrozil forekom i 3, 2% af kohorten.
The adjusted odds ratio for myopathy for concurrent cerivastatin and gemfibrozil compared with pravastatin was 10.5 (95% CI 4.2 to 26.2).
Ujusteret risiko for myopati varierede mellem 0, 59% i forbindelse lovastatin og 0, 27% i forbindelse med pravastatin.
significantly raised odds ratios compared with pravastatin in concomitant treatment.
Justeret OR for myopati ved samtidig behandling med cerivastatin og gemfibrozil sammenlignet med pravastatin var 10, 5% (95% CI 4, 2- 26, 2).
The adjusted odds ratio for myopathy for monotherapy cerivastatin compared with pravastatin was 1.4 (95% CI 1.09 to 1.74).
Fluvastatin og atorvastatin havde tilsvarende øgede OR sammenlignet med pravastatin i monoterapi.
Fluvastatin and atorvastatin had similarly raised odds ratios compared with pravastatin in monotherapy.
Heraf var hovedparten (42%) i behandling med cerivastatin, og det var mere sandsynligt, at de samtidig var i behandling med gemfibrozil, end dem, der blev indlagt med myopati og blev behandlet med andre statiner.
Of the myopathy cases, 6.2% were hospitalised: of those diagnosed as inpatients, the largest proportion (42%) were taking cerivastatin and more likely to have concurrent gemfibrozil than those with hospitalised myopathy and other statins.
Af de patienter, som oplevede myopati i forbindelse med cerivastatin, fik 61% ≤ 0, 4 mg, hvor 1% var titreret fra en lav til en høj dosis, og 37% skiftede fra et andet statin til en lav dosis cerivastatin.
Of those patients who experienced myopathy on cerivastatin, 61% were on ≤ 0.4mg, with 1% having been titrated from a low to a high dose and 37% switched from another statin to low dose cerivastatin.
Der var ingen forskel mellem den observerede og den forventede dødelighed i forbindelse med forskellige statiner.
There was no difference between observed and expected rates of death across different statins.
GPRD Det foreløbige resultat af undersøgelsen blev fremsendt sammen med det indledende svar fra indehaveren af markedsføringstilladelsen.
GPRD The preliminary report of the study was submitted as part of the MAH’ s initial response.
Den endelige rapport omfattede flere patienter og øgede antallet af personår til analyse.
This final study report included additional patients and increased the person-years available for analysis.
10. 000.
The overall incidence rate for community acquired acute renal failure from all cases was 1.4 per 10,000.
Forekomsten af akut nyresvigt i forbindelse med de forskellige statiner var ikke statistisk forskellig.
The incidence rate of acute renal failure was not statically different among different statins.
Kun et tilfælde af akut nyresvigt, som blev vurderet til at være en følge af et knusningssyndrom havde kliniske symptomer på rabdomyolyse.
Only one case of acute renal failure assessed to be due to a crush injury presented with clinical symptoms of rhabdomyolysis.
Dette gav en forekomst af erhvervet rabdomyolyse i patientgruppen på 2, 9 pr. million personår.
This yielded a community-acquired incidence rate of rhabdomyolysis of 2.9 per million person-years.
Der forekom ingen tilfælde af fulminant leversvigt i studiepopulationen under opfølgningen.
No cases of fulminant hepatic failure occurred during follow-up in the study population.
Den ukorrigerede mortalitetsrate var 11, 9 pr.
A total of 2,826 deaths from all causes occurred.
1. 000 personår for simvastatin, 12, 2 for cerivastatin, 11, 0 for atorvastatin, 10, 8 for pravastatin og 12, 1 for fluvastatin sammenlignet med 7, 9 for fibrater, 5, 5 i den ubehandlede gruppe og 17, 5 i afvigelsesperioden for patienter, som på et tidspunkt var blevet behandlet med hypolipidæmiske midler.
The crude mortality rates were 11.9 per 1000 person- years for simvastatin, 12.2 for cerivastatin, 11.0 for atorvastatin, 10.8 for pravastatin, and 12.1 for fluvastatin, as compared with 7.9 for fibrates, 5.5 in the untreated group and 17.5 during the non- compliance period of patients treaded with hypolipidaemic agents at some point.
Mortalitetsanalysen var begrænset af manglende kontrol af hjerte- kar- risikofaktorer såsom rygning, diabetes og hypertension.
The mortality analysis was limited by a lack of control for cardiovascular risk factors such as smoking, diabetes and hypertension.
Det kan konkluderes, at undersøgelsen ikke viste en signifikant statistisk forskel mellem risikoen for erhvervet akut nyresvigt i patientgruppen og cerivastatinmortalitet af alle årsager sammenlignet med simvastatin.
In conclusion, this study did not show a significant statistical difference between the risk of community-acquired acute renal failure or all-cause mortality for cerivastatin when compared with simvastatin.
Der blev ikke identificeret statinrelateret rabdomyolyse.
No statin related rhabdomyolysis was identified.
I betragtning af den lille population eksponeret for cerivastatin (3. 309 patienter) og statiner i almindelighed kan der ikke konkluderes noget om dosisafhængig svær muskeltoksicitet eller sammenligning af muskeltoksicitet i forbindelse med de forskellige statiner på baggrund af denne undersøgelse.
However, given the small population exposed to cerivastatin (3,309 patients) and to statins in general, no conclusions can be drawn from this study concerning dose dependent severe myotoxicity or comparison of myotoxicity between the different statins.
DISKUSSION De mest almindelige bivirkninger i forbindelse med statiner er ikke- alvorlige bivirkninger såsom mave - og tarmforstyrrelser, hovedpine, muskelsmerter, forstyrrelser i centralnervesystemet samt søvn forstyrrelser.
The most common adverse drug reactions associated with statins are non-serious reactions such as gastrointestinal disturbances, headache, myalgia, CNS disturbances and sleep disorders.
Levertoksicitet og myopatier er de klinisk vigtigste bivirkninger.
Hepatoxicity and myopathies are the most clinically important adverse reactions.
Sikkerhedsprofilen for cerivastatin, med undtagelse af risikoen for myopati, lader til at være på linje med sikkerhedsprofilen for de øvrige statiner.
The safety profile of cerivastatin, with the exception of the risk of myopathy, appears to be similar to that of the other statins.
Sammenligningsdata fra offentliggjorte kliniske undersøgelser viser, at risikoen for leverrelaterede og alvorlige hændelser/ bivirkninger kan være lavere for cerivastatin.
Comparative data from published clinical trials suggest that the risk of hepatic and serious adverse events may be lower with cerivastatin.
Data fra den samlede analyse af kliniske undersøgelser vedrørende cerivastatin viser, at forekomsten af bivirkninger, som indikerer muskelskader, herunder CPK ≥ 10xULN, stiger dosisafhængigt.
Data from the pooled analysis of cerivastatin clinial trials show that the incidence of adverse events indicative of muscle damage, including CPK ≥ 10xULN increases dose dependently.
For 0, 8 mg cerivastatin er forekomsten af CPK > 10xULN tre gange større end for cerivastatin 0, 4 mg (2, 0%
For 0.8mg cerivastatin the incidence of CPK > 10xULN is 3 fold greater than that with cerivastatin 0.4mg (2.0% vs 0.6%) and 6 fold greater than that with other statins (2.0 vs 0.35%).
CPMP/ 811/ 02 sammenlignet med 0, 6%) og seks gange større end for andre statiner (2, 0% sammenlignet med 0, 35%).
This is particularly marked with the 0.8mg formulation, for which the incidence of rhabdomyolysis is between 4 and 10 fold greater than that of the other statins, though the CPMP/ 8
Dette er særlig markant i forbindelse med formuleringen på 0, 8 mg, hvor rabdomyolyseforekomsten er 4- 10 gange større end for de øvrige statiner, selvom rabdomyolyseforekomsten i forbindelse med cerivastatin 0, 4 mg er dobbelt så stor som for de øvrige statiner.
incidence of rhabdomyolysis with cerivastatin 0.4mg is 2 fold greater than with other statins.
Det synspunkt, som indehaveren af markedsføringstilladelsen har fremført om, at der er indberettet meget få tilfælde af rabdomyolyse fra kliniske undersøgelser, og at den øgede forekomst i forbindelse med cerivastatin i forhold til de øvrige statiner derfor skal tolkes forsigtigt, godtages.
The MAH’ s point of view that very few cases of rhabdomyolysis have been reported during clinical trials, and therefore the higher incidence seen with cerivastatin compared with the other statins should be interpreted with caution, is accepted.
På grund af undersøgelsernes og patientgruppens omfang (nøje udvalgt og overvåget) er det lille antal tilfælde dog ikke uventet.
However due to the size of the studies and the patient population (highly selected and carefully monitored) the small number of cases is not unexpected.
De opdaterede data fra FDA- databasen viser, at indberetningsfrekvensen for bekræftede tilfælde af rabdomyolyse ved monoterapi med 0, 2- 0, 8 mg cerivastatin er større end for de øvrige statiner.
The updated data from the FDA database suggests that the reporting rates of confirmed cases of rhabdomyolysis in association with 0.2mg to 0.8mg cerivastatin monotherapy are greater than those with any of the other statins.
Indberetningsfrekvensen for 0, 4 mg and 0, 8 mg cerivastatin brugt i kombination med gemfibrozil er meget højere end ved ækvipotente doser af simvastatin og atorvastatin.
The reporting rates for 0.4mg and 0.8mg cerivastatin when used in combination with gemfibrozil are much higher than those seen with equipotent dosages of simvastatin and atorvastatin.
Data for patienter, der behandles med cerivastatin og clopidogrel samtidig, viser en højere indberetningsfrekvens for bekræftet rabdomyolyse.
Data on patients receiving concomitant cerivastatin and clopidogrel indicate an increased reporting rate of confirmed rhabdomyolysis.
De farmakoepidemiologiske undersøgelser, der er gennemført i USA og Det Forenede Kongerige, indikerer ikke øget risiko for myopati i forbindelse med cerivastatin sammenlignet med de øvrige statiner, når det bruges som monoterapi.
The pharmacoepidemiological studies conducted in the US and the UK do not suggest an increased risk of myopathy with cerivastatin compared with the other statins when used as monotherapy.
Der var dog en vis bekymring over metoden, som gør det svært at drage konklusioner vedrørende risikoforholdet mellem statiner.
However, there were some concerns over the methodology which make conclusions regarding the relative risk between statins difficult.
De amerikanske undersøgelser bekræfter, at der er øget risiko for myopati, når cerivastatin bruges i kombination med gemfibrozil.
The US studies confirm an increased risk of myopathy when cerivastatin was used in combination with gemfibrozil.
De tilgængelige data fra Princess- undersøgelsen og spontane indberetninger indikerer kraftigt, at der er øget risiko for rabdomyolyse, når cerivastatin og clopidogrel bruges samtidig, og at denne øgede risiko sandsynligvis skyldes interaktion mellem de to stoffer.
The available data from the PRINCESS study and spontaneous reports strongly suggest that the risk of rhabdomyolysis is increased when cerivastatin and clopidogrel are administered concomitantly, and that this increased risk is likely to be due to an interaction between these two substances.
Selv om der ikke er gennemført formelle undersøgelser af raske frivillige, som bekræfter en farmakokinetisk interaktion, er der på nuværende tidspunkt ingen grund til at tro, at der sandsynligvis er tale om en farmakodynamisk interaktion.
Though no formal healthy volunteer studies have been conducted to confirm a pharmacokinetic interaction, there is currently no reason to believe that this is likely to be a pharmacodynamic interaction.
Desuden kendes den mekanisme, som skaber den mulige interaktion, endnu ikke.
Furthermore, the mechanism by which this possible interaction may occur remains unknown.
Det er tydeligt, at interaktionen mellem cerivastatin og gemfibrozil eller clopidogrel ikke kunne forudsiges på grundlag af det nuværende kendskab til deres metabolisme.
What is apparent is that the interactions between cerivastatin and gemfibrozil or clopidogrel could not have been predicted based on what is currently known about their metabolism.
På trods af tilbagekaldelsen af cerivastatinlicenserne har mangelen på en definitiv mekanisme, hvormed cerivastatin fremkalder rabdomyolyse og interagerer med gemfibrozil og clopidogrel, alligevel stor betydning for risk/ benefit - forholdet i forbindelse med cerivastatin.
Despite the cancellation of the cerivastatin licences, the lack of a definitive mechanisms by which cerivastatin induces rhabdomyolysis and interacts with gemfibrozil and clopidogrel does have important implications for the balance of risks and benefits for cerivastatin.
Cerivastatin reducerer effektivt og dosisafhængigt den samlede mængde kolesterol, LDL- kolesterol, triglycerider og apolipoprotein B samt øger mængden af HDL- kolesterol.
Cerivastatin effectively and dose-dependently reduces total cholesterol, LDL – cholesterol, triglycerides and apolipoprotein B and increases HDL-cholesterol.
Atorvastatin og simvastatin kan være mere virkningsfulde ved de højere tilladte doser.
Atorvastatin and simvastatin may be more efficacious at the higher licensed dosages.
Til forskel fra nogle af de øvrige statiner er der ingen data, som påviser cerivastatins effekt i forbindelse med primær eller sekundær forebyggelse af koronare hjertesygdomme, men der er ingen grund til at antage, at det ikke ville være gavnligt.
Unlike some of the other statins, there are no data to demonstrate the efficacy of cerivastatin in either primary or secondary prevention of coronary heart disease but there is no reason to assume that it would not be beneficial.
Der er overbevisende dokumentation for, at risikoen for rabdomyolyse i forbindelse med cerivastatin er dosisafhængig.
Data from pharmacoepidemiological studies do not support an increased risk with cerivastatin monotherapy.
Analysen af spontane data indikerer, at risikoen for muskeltoksicitet stiger især fra 0, 4 mg og opefter.
The risk of rhabdomyolysis when cerivastatin is used in combination with gemfibrozil or clopidogrel is greatly increased.
Dette resultat påvirkes ikke af, at indberetninger om interagerende lægemidler udelades.
important implications for the balance of risks and benefits.
I lyset af erfaringerne fra USA anses det for at være urealistisk at undgå samtidig ordinering af andre potentielt interagerende produkter.
Given the US experience, avoiding co- prescription with other potentially interacting products, is considered unrealistic.
CPMP konkluderede derfor, at risk/ benefit- forholdet i forbindelse med cerivastatin er negativt ved normal brug i alle tidligere tilladte doser.
The CPMP therefore concluded that the balance of risks and benefits for cerivastatin is negative under normal conditions of use at all previously authorised doses.
BEGRUNDELSE FOR TILBAGEKALDELSE AF MARKEDSFØRINGSTILLADELSEN( ERNE)
GROUNDS FOR WITHDRAWAL OF THE MARKETING AUTHORISATION(S)
- Uanset at indehaverne af markedsføringstilladelsen har til hensigt at tilbagekalde alle
- Notwithstanding the intention of the Marketing Authorisation Holders to withdraw all Marketing
markedsføringstilladelser for lægemidler indeholdende cerivastatin, som er tilladt i henhold til den gensidige anerkendelsesprocedure, besluttede CPMP at fortsætte behandlingen af sagen, som var indbragt i henhold til artikel 36 i direktiv 2001/ 83/ EF, da et folkesundhedsspørgsmål skulle drøftes.
Authorisations for cerivastatin containing medicinal products authorised under the Mutual Recognition Procedure, the CPMP decided to continue the referral made under Article 36 of Directive 2001/ 83/ EC as there was a public health matter to be discussed.
- Udvalget var enigt om, at lægemidler indeholdende cerivastatin er effektive i behandlingen af
- the Committee agreed that cerivastatin containing medicinal products are effective in the treatment of
hyperlipidæmi, men ikke frembyder en specifik terapeutisk fordel i forhold til sammenlignelige præparater.
hyperlipidaemia but do not present a specific therapeutic benefit in relation to comparable compounds.
- Udvalget var enigt om, at sikkerhedsprofilen for lægemidler indeholdende cerivastatin gav anledning
- the Committee agreed that there were concerns related to the safety profile of cerivastatin containing
til betænkeligheder, især for så vidt angår risikoen for rabdomyolyse.
medicinal products, in particular the risk of rhabdomyolysis.
- Risikoen for rabdomyolyse øges betydeligt, når cerivastatin bruges i kombination med gemfibrozil
- the risk of rhabdomyolysis is greatly increased when cerivastatin is used concomitantly with