FrancophonIA/ELRC3.0 huggingface dataset:
English: The recommended dosage is 13.1 mg amoxicillin (equivalent to 18.8 mg veterinary medicinal product) per kg body weight for 3 days or in severe cases for 5 days.
Danish: Den anbefalede dosis er 13,1 mg amoxicillin (svarende til 18,8 mg af præparatet) per kg legemsvægt i 3 dage eller i svære tilfælde i 5 dage.
English: Overall summary of the scientific evaluation of Valebo and associated names (see Annex I)
Danish: Samlet resumé af den videnskabelige vurdering af Valebo og relaterede navne (se bilag I)
English: The package leaflet should be amended accordingly.
Danish: Indlægssedlen bør ændres tilsvarende.
English: Studies on physical performance and balance
Danish: Undersøgelser af fysiske præstationer og balanceevne
English: The treatment effect was always significant when major reported trials were analysed together.
Danish: Behandlingseffekten var altid signifikant, når større beskrevne undersøgelser blev analyseret samlet.
English: These results are supported by two other studies published by Ringe and Schacht (2012, 2013).
Danish: Disse resultater støttes af to andre undersøgelser, der blev offentliggjort af Ringe og Schacht (2012,
English: Population pharmacokinetic modelling and simulation at steady state
Danish: Populationsfarmakokinetisk model og simulering ved steady state
English: Studies on reduction of falls and fall-related non-vertebral fractures
Danish: Undersøgelser af reduktion af fald og reduktion af faldrelaterede nonvertebrale frakturer
English: It is converted rapidly in the liver to 1,25 dihydroxyvitamin D, so called calcitriol.
Danish: Det omdannes i leveren hurtigt til 1,25 dihydroxyvitamin D (calcitriol).
English: The results showed a consistent odds ratio at around 0.65 in all analyses, suggesting a reliable estimated of treatment effect as compared to placebo.
Danish: Resultaterne viste samstemmende et odds ratio på omkring 0,65 i alle analyser, som tyder på en pålideligt estimeret behandlingseffekt i forhold til placebo.
English: The major concern raised by Spain could not be solved during the CMDh referral and the issue was therefore referred to the CHMP.
Danish: Den hovedbetænkelighed, der var rejst af Spanien, kunne ikke afklares ved indbringelsen for CMD(h), og sagen blev derfor indbragt for CHMP.
English: The decentralised procedure was closed on day 210, with most of the CMS agreeing with the conclusions of the reference member state except Spain which raised a potential serious risk to public health (PSRPH).
Danish: Den decentrale procedure blev afsluttet på dag 210, hvor konklusionerne i referencemedlemsstatens vurderingsrapport fik tilslutning fra størstedelen af de berørte medlemsstater bortset fra Spanien, som rejste betænkelighed ved en potentiel alvorlig risiko for den offentlige sundhed.
English: Both active substances are currently authorised either as monotherapy or in association (combination pack).
Danish: Begge aktive stoffer er godkendt enten som monoterapi eller som en del af en kombinationspakning.
English: The CHMP considered that the statement on falls should not be included in the section 4.1 of the SmPC.
Danish: CHMP fandt, at udtalelsen om fald ikke burde indgå i afsnit 4.1 af produktresuméet.
English: The open, multi-centre, prospective studies (Schacht and Ringe, 20121, Schacht and Ringe, 20112) demonstrated that treatment with alfacalcidol 1 μg resulted in significant increases in physical performance and balance in elderly women and men with and without an increased risk of falls as well as with and without Vitamin D insufficiency/deficiency.
Danish: De åbne, prospektive multicenterundersøgelser (Schacht og Ringe, 20121, Schacht og Ringe, 20112) viste, at behandling med alfacalcidol 1 μg medførte signifikante stigninger i fysiske præstationer og balanceevne hos ældre kvinder og mænd med og uden forhøjet risiko for fald såvel som med og uden vitamin D-insufficiens/mangel.
English: The proposed indication by the applicant for Valebo was the “Treatment of postmenopausal osteoporosis.
Danish: Den ansøgte indikation for Valebo var “behandling af postmenopausal osteoporose.
English: Bisphosphonates have strong pharmacodynamic action on osteoclast activity.
Danish: Bisphosphonater har stærk farmakodynamisk virkning på aktiviteten af osteoklaster.
English: In addition, the results of these studies, showing a significant reduction in fall-related non-vertebral fractures, have been confirmed by independent meta-analyses (Bischoff-Ferrari, 2004b6; BischoffFerrari, 20097; O'Donnell, 20088; Richy, 20089).
Danish: Resultaterne af disse undersøgelser, der viser signifikant reduktion faldrelaterede nonvertebrale frakturer, bekræftes desuden af uafhængige metaanalyser (Bischoff-Ferrari, 2004b6; Bischoff-Ferrari, 20097; O'Donnell, 20088; Richy, 20089).
English: The applicant claimed that alfacalcidol 1 μg daily and of calcitriol 0.25 μg twice a day are therapeutically equivalent, and therefore they considered that the results of this randomised clinical trial can be directly extrapolated to alfacalcidol.
Danish: Ansøgeren hævdede, at alfacalcidol, 1 µg dagligt og calcitriol, 0,25 µg to gange dagligt er terapeutisk ækvivalente, og mente derfor, at resultaterne fra denne randomiserede kliniske undersøgelse direkte kan ekstrapoleres til alfacalcidol.
English: The applicant performed a meta-analysis of the most relevant clinical studies (Gallagher, 2004; Dukas, 2004; Ringe, 201310 and Kaya, 201111) reporting the number of fallers following either alfacalcidol or calcitriol therapy.
Danish: Ansøgeren foretog en metaanalyse af de mest relevante kliniske undersøgelser (Gallagher, 2004; Dukas, 2004; Ringe, 201310 og Kaya, 201111), hvor der blev foretaget registrering af antal patienter, der falder efter behandling med enten alfacalcidol eller calcitriol.
English: The CHMP was of the opinion that results with calcitriol could be used as supportive data but not to conclude about the role of alfacalcidol in fall rate without confirmatory studies with alfacalcidol.
Danish: CHMP var af den opfattelse, at resultaterne med calcitriol kunne anvendes som støttende data, men ikke til at drage konklusioner om alfacalcidols betydning for faldtendensen uden bekræftende undersøgelser med alfacalcidol.
English: Evaluation
Danish: Vurdering
English: During the decentralised procedure, concerned member states (CMS) expressed the opinion that the role of alfacalcidol in the reduction in the fall rate has not been demonstrated.
Danish: Under den decentrale procedure var de berørte medlemsstater af den opfattelse, at alfacalcidols rolle i reduktion af forekomsten af fald ikke er påvist.
English: • The Committee reviewed all the data submitted by the applicant in order to support the role of alfacalcidol in the reduction of the fall rate.
Danish: • udvalget gennemgik alle de af ansøgeren forelagte data til dokumentation af alfacalcidols rolle i reduktion af faldtendens,
English: Gallagher et al (2004) examined the effects of calcitriol on falls in a randomised, double-blind, placebocontrolled study in 489 postmenopausal, Vitamin D replete/sufficient women with osteopenia.
Danish: Gallagher et al (2004) undersøgte virkningerne af calcitriol på fald i en randomiseret, placebokontrolleret dobbeltblindundersøgelse hos 489 postmenopausale kvinder med osteopeni og genoprettet/sufficient vitamin D-status.
English: Dukas et al (2004) presented a randomised, double-blind, placebo controlled trial with ‘number of fallers' as primary endpoint and an adequate number of patients.
Danish: Dukas et al (2004) beskrev en randomiseret, placebokontrolleret dobbeltblindundersøgelse med “antal patienter, der falder” som primært endepunkt og et tilstrækkeligt antal patienter.
English: • The Committee considered the notification of the referral triggered by Germany under Article 29(4) of Directive 2001/83/EC.
Danish: • udvalget behandlede anmeldelsen af den indbringelse, der var indledt af Tyskland i medfør af artikel 29, stk. 4, i direktiv 2001/83/EF, Spanien fandt, at udstedelsen af markedsføringstilladelsen udgør en potentiel alvorlig risiko for den offentlige sundhed,
English: In order to demonstrate the role of alfacalcidol in the reduction of falls, the applicant made reference to published clinical studies which support the effect of alfacalcidol alone and in combination with alendronic acid on the improvement of physical performance, the incidence of non-vertebral fractures and on falls.
Danish: Til påvisning af alfacalcidols rolle i reduktion af forekomsten af fald henviste ansøgeren til publicerede kliniske undersøgelser, der støtter virkningen af alfacalcidol alene og i kombination med alendronsyre med hensyn til forbedring af fysiske præstationer, forekomsten af nonvertebrale frakturer og fald.
English: These studies demonstrated the efficacy of the vitamin D analogues alfacalcidol and calcitriol on falls in elderly men and women and in postmenopausal women without diagnosed vitamin D insufficiency.
Danish: Disse undersøgelser godtgjorde virkningen af vitamin D-analogerne alfacalcidol og calcitriol på fald hos ældre mænd og kvinder og hos postmenopausale kvinder uden diagnosticeret vitamin D-mangel.
English: Valebo is a combination package consisting of tablets containing 70 mg of alendronate sodium (alendronic acid) and soft capsules containing 1µg of alfacalcidol.
Danish: Valebo er en kombinationspakning bestående af tabletter med 70 mg natriumalendronat (alendronsyre) og bløde kapsler med 1 µg alfacalcidol.
English: Alfacalcidol is a vitamin D analogue which acts as a regulator of calcium and phosphate metabolism.
Danish: Alfacalcidol er en vitamin D-analog, der virker som regulator af calcium- og fosfatstofskiftet.
English: Having considered that data submitted by the applicant, the CHMP considered that there is sufficient evidence to conclude that in some clinical studies, alfacalcidol has been shown to reduce the risk of falls in the elderly.
Danish: Efter gennemgang af de af ansøgeren forelagte data fandt CHMP, at der var tilstrækkelig evidens til at konkludere, at det i nogle kliniske undersøgelser er påvist, at alfacalcidol nedsætter risikoen for fald blandt ældre.
English: To support the inclusion of this indication the application should be based on parallel-group, randomised, double-blind, placebo or comparator controlled clinical trials with an adequate number of patients.
Danish: For at underbygge denne indikation bør ansøgningen være baseret på randomiserede kliniske dobbeltblindundersøgelser med parallelle grupper med placebokontrol eller aktivt sammenligningspræparat og med et tilstrækkeligt antal patienter.
English: The applicant has analysed pharmacokinetics data of alfacalcidol and calcitriol dosed independently from two bioequivalence studies.
Danish: Ansøgeren har analyseret farmakokinetiske data for alfacalcidol og calcitriol indgivet hver for sig fra to bioækvivalensundersøgelser.
English: Other studies had been performed to specifically investigate the efficacy and safety of alfacalcidol in monotherapy and combination therapy on the reduction of falls in elderly and patients with PMO (Dukas, 20043; Gallagher, 20044; Ringe, 20075).
Danish: Andre undersøgelser vedrørte specifikt virkningen og sikkerheden af alfacalcidol som monoterapi og kombinationsterapi til reduktion af fald hos ældre og patienter med postmenopausal osteoporose (Dukas, 20043; Gallagher, 20044; Ringe, 20075).
English: Systemic levels are shown to be equivalent at steady state under scaled dosing and there is no significant difference in predicted AUC's (Area Under the Curve) at six months between alfacalcidol 1 μg once-aday (QD) and calcitriol 0.25 μg twice-daily (BID).
Danish: Den systemiske koncentration ved steady state er påvist at være ækvivalent under skaleret dosering, og der er ingen signifikant forskel i de forventede AUC-værdier (Area Under the Curve) efter 6 måneder mellem alfacalcidol 1 μg én gang dagligt og calcitriol 0,25 μg to gange dagligt.
English: The results over 36 weeks showed that alfacalcidol treatment was associated with fewer non-significantly fallers than placebo (OR (Odds ratio) 0.69, 95% CI (confidence interval): 0.41-1.16).
Danish: Resultaterne gennem 36 uger viste, at behandling med alfacalcidol er forbundet med et ikke-signifikant lavere antal patienter, der falder, end behandling med placebo (OR (Odds ratio) 0,69, 95 % SI (sikkerhedsinterval): [0,41; 1,16]).
English: Alendronic acid is a bisphosphonate with high affinity for the hydroxylapatite of the bone.
Danish: Alendronsyre er et biphosphonat med høj affinitet for hydroxyapatit i knoglevæv.
English: However, the CHMP agreed to provide the respective information in the section 5.1 of the SmPC “In some clinical studies, alfacalcidol has been shown to reduce the risk of falls in the elderly”.
Danish: CHMP tilsluttede sig imidlertid, at oplysningerne gives i produktresuméets afsnit 5.1: “Det er i nogle kliniske undersøgelser påvist, at alfacalcidol nedsætter risikoen for fald hos ældre”.
English: Alfacalcidol is indicated in various conditions where there is a disturbance of calcium or phosphorus metabolism.
Danish: Alfacalcidol er indiceret til forskellige sygdomme med forstyrrelser i calcium- eller fosfatstofskiftet.
English: the CHMP has recommended the granting of the marketing authorisations for which the summary of product characteristics, labelling and package leaflet remain as per the final versions achieved during the Coordination group procedure with the amendment as mentioned in Annex III for Valebo and associated names (see Annex I).
Danish: Udvalget fandt imidlertid, at erklæringen om reduktion af faldtendens hos ældre ikke burde indgå i indikationen, men tilsluttede sig, at disse oplysninger gives i afsnit 5.1 af produktresuméet og afsnit 1 af indlægssedlen, anbefaler CHMP, at der udstedes markedsføringstilladelser, for hvilke produktresumé, etikettering og indlægsseddel er de endelige udgaver, der er fremkommet ved koordinationsgruppens procedure med ændringen, som anført i bilag III for Valebo og relaterede navne (se bilag I).
English: Ringe et al (2007) presented a randomised trial, where three treatments were compared ‘alfacalcidol alone', ‘alfacalcidol + alendronate' and ‘alendronate + vitamin D + calcium'.
Danish: Ringe et al (2007) beskrev en randomiseret undersøgelse af tre behandlinger: “alfacalcidol alene”, “alfacalcidol + alendronat”, og “alendronat + vitamin D + calcium”.
English: Hence, the treatment effect in a grouped meta-analysis, even with trials where ‘fallers' was not always the primary endpoint, remains significant independent of study design differences.
Danish: Selv i undersøgelser, hvor antal patienter, der falder, ikke altid var det primære endepunkt, er behandlingseffekten ved grupperet metaanalyse fortsat signifikant uanset forskelle i undersøgelsesdesign.
English: Alfacalcidol alone was slightly superior to alendronate + plain Vitamin D + calcium after two years (MW = 0.5422; CI-LB = 0.4838; p = 0.0785).
Danish: Alfacalcidol alene var efter to år let overlegent i forhold til alendronat + almindeligt vitamin D + calcium (MW = 0,5422; undergrænse af sikkerhedsinterval = 0,4838; p = 0,0785).
English: Alendronic acid reduces the risk of vertebral and hip fractures, whilst a significant reduction in the fall rate has been demonstrated for alfacalcidol in the elderly”.
Danish: Alendronsyre nedsætter risikoen for vertebral- og hoftefrakturer, og alfacalcidol er påvist at mindske forekomsten af fald væsentligt blandt ældre”.
English: The applicant also provided a population modelling and simulation of results to demonstrate that there is no difference between alfacalcidol and calcitriol treatments at appropriate and equivalent dosing.
Danish: Ansøgeren fremlagde også en populationsmodel og simulering af resultater til påvisning af, at der ved korrekt og ækvivalent dosering ikke er forskel mellem behandling med alfacalcidol og calcitriol.
English: The analysis was done using population pharmacokinetic modelling to confirm the exchangeability of alfacalcidol and calcitriol when administrated at appropriately scaled doses.
Danish: Analysen blev foretaget med en populationsfarmakokinetisk model for at bekræfte, at alfacalcidol og calcitriol kan erstatte hinanden ved administration i korrekt skalerede doser.
English: Alendronic acid is indicated in the treatment of postmenopausal osteoporosis (PMO).
Danish: Alendronsyre er indiceret til behandling af postmenopausal osteoporose.
English: Effects of Alfacalcidol on falls and balance in elderly people with Vitamin D deficiency.
Danish: 11 Kaya U et al. Effects of Alfacalcidol on falls and balance in elderly people with Vitamin D deficiency.
English: The combination ‘alendronate + alfacalcidol' showed a significant superiority in reduction of falls compared to ‘alendronate + plain Vitamin D + calcium' after two years (MannWhitney (MW) = 0.5506; Confidence interval Lower bound (CI-LB) = 0.4937; p=0.0407) but not superiority to ‘alfacalcidol alone'.
Danish: Kombinationen “alendronat + alfacalcidol” var efter to år signifikant overlegen hvad angår reduktion af fald i forhold til “alendronat + almindeligt vitamin D + calcium” (Mann-Whitney (MW) = 0,5506; undergrænse af sikkerhedsintervallet = 0,4937; p=0,0407) men ikke overlegen i forhold til “alfacalcidol alene”.
English: Furthermore, the applicant claimed that these results on alfacalcidol monotherapy have been confirmed in a post-approval trial of the combination package of 70 mg alendronate weekly and 1 μg
Danish: Ansøgeren hævdede, at disse resultater af alfacalcidol-monoterapi desuden bekræftes af en undersøgelse efter markedsføring af kombinationspakningen med 70 mg alendronat pr. uge og 1 µg alfacalcidol dagligt (Tevabone).
English: The analysis has demonstrated that there is no difference in calcitriol exposure at steady state after administration of either alfacalcidol or calcitriol at appropriate and equivalent dosing.
Danish: Analysen viste, at der ved steady state ikke er forskel i eksponeringen for calcitriol efter indgift af henholdsvis alfacalcidol og calcitriol i korrekt og ækvivalent dosering.
English: Treatment with calcitriol 0.25 μg twice daily significantly reduced the number of fallers (OR 0.54 (95% CI 0.31-0.94, p<0.03) and decreased the incidence of falls compared to placebo (0.27 versus 0.43, p=0.0015) in this 3 years trial.
Danish: I denne undersøgelse, der strakte sig over 3 år, medførte behandling med calcitriol, 0,25 µg to gange dagligt, signifikant reduktion i antallet af patienter, der faldt (OR 0,54 (95 % SI [031; 0,94], p<0,03) og mindskede forekomsten af fald i forhold til placebo (0,27 mod 0,43, p=0,0015).
English: Significant fall reduction in alfacalcidol-treated subject with a total calcium intake of more than 512 mg/d (median Ca intake in the study) (OR 0.45; 95% CI 0.21-0.97, p=0.042) was observed but not in those with less Ca intake than 512 mg/d (OR 1.00, 95% CI 0.47-2.11, p=0.998).
Danish: En post hoc-analyse baseret på medianværdier af totalt calciumindtag viste statistisk signifikante forskelle: Hos personer behandlet med alfacalcidol var der signifikant reduktion i fald ved et totalt calciumindtag over 512 mg/d (som var det mediane calciumindtag i undersøgelsen) (OR 0,45; 95 % SI [0,21; 0,97], p=0,042), men ikke ved calciumindtag under 512 mg/d (OR 1,00, 95 % SI [0,47; 2,11], p=0,998).
English: • The Committee is of the opinion that, based on available results of clinical trials and metaanalyses, the efficacy of alfacalcidol in combination with alendronic acid has been adequately demonstrated.
Danish: • udvalget finder, at virkningen af alfacalcidol i kombination med alendronsyre er tilstrækkeligt godtgjort på grundlag af de foreliggende resultater af kliniske undersøgelser og metaanalyser.
English: In addition, 500 mg of calcium daily was added in each arm. Amongst other parameters the authors compared the rate of falls between the three groups.
Danish: Blandt andre parametre sammenlignede forfatterne faldtendensen i de tre grupper.
English: The applicant claimed that since no significant difference in numbers of falls was found between the groups treated with the combination of ‘alendronate + alfacalcidol' and ‘alfacalcidol alone', this underlines the efficacy of alfacalcidol as monotherapy as well as in combination with alendronate for the reduction of falls.
Danish: Ansøgeren hævdede, at den manglende signifikante forskel i antal fald mellem grupperne ved behandling med kombinationen af “alendronat + alfacalcidol” og “alfacalcidol alene” understreger
English: The applicant further performed a meta-analysis of trials with alfacalcidol and calcitriol investigating fallers.
Danish: Ansøgeren udførte desuden en metaanalyse af undersøgelser, hvor der er anvendt alfacalcidol og calcitriol og foretaget registrering af personer, der falder.
English: Meta-analysis of trials on alfacalcidol and calcitriol investigating fallers
Danish: Metaanalyse af undersøgelser med alfacalcidol og calcitriol med registrering af patienter, der falder
English: Higher performance in functional tests is associated with a significantlylower number of fallers and risk of falls, therefore the positive effects of alfacalcidol treatment on physical performance should be considered for the assessment of the results of alfacalcidol in the reduction of falls in elderly and in patients with PMO.
Danish: Den positive virkning af alfacalcidol på fysiske præstationer bør derfor tages i betragtning ved vurderingen af resultaterne af anvendelse af alfacalcidol til reduktion af fald hos ældre og hos patienter med postmenopausal osteoporose.
English: Date of first authorisation: 06/11/2015.
Danish: Dato for første markedsføringstilladelse: 06/11/2015.
English: Half-life was comparable for the intravenous and oral routes at 12 and 11 days, respectively.
Danish: Halveringstiden var sammenlignelig for intravenøs og oral indgift ved henholdsvis dag 12 og 11.
English: Sarolaner was determined to have low clearance (0.12 ml/min/kg) and a moderate volume of distribution (2.81 l/kg).
Danish: Det blev fundet, at sarolaner havde en lav clearance (0,12 ml/min./kg) og et moderat fordelingsvolumen (2,81 l/kg).
English: One carton contains one blister of 1, 3 or 6 tablets.
Danish: En æske indeholder en blisterpakning med 1, 3 eller 6 tabletter.
English: Treatment should be continued until skin scrapings are negative on at least two consecutive occasions one month apart.
Danish: Behandlingen bør forsættes, indtil hudskrabning er negativ i mindst 2 på hinanden følgende prøver med 1 måneds mellenrum.
English: For each strength, the chewable tablets are available in the following pack sizes: carton with 1 blister of 1, 3 and 6 tablets.
Danish: Tyggetabletterne fås i de forskellige styrker i pakninger af følgende størrelser: æske med en blisterpakning med 1, 3 og 6 tabletter.
English: In a margin of safety study, the veterinary medicinal product was administered orally to 8 week old Beagle puppies at doses of 0, 1, 3, and 5 times the maximum exposure dose of 4 mg/kg at 28 day intervals for 10 doses.
Danish: I forbindelse med en undersøgelse af sikkerhedsmarginen for produktet blev veterinærlægemidlet administreret oralt til 8 uger gamle beaglehvalpe i doser på 0, 1, 3 og 5 gange den maksimale eksponeringsdosis på 4 mg/kg i 28 dages intervaller med 10 doser.
English: During clinical field trials, no interactions between Simparica chewable tablets for dogs and routinely used veterinary medicinal products were observed.
Danish: I forbindelse med kliniske feltstudier blev der ikke observeret interaktion mellem Simparicatyggetabletter til hunde og rutinemæssigt anvendte veterinærlægemidler.
English: PACKAGE LEAFLET: Simparica chewable tablets for dogs
Danish: INDLÆGSSEDDEL Simparica tyggetabletter til hunde
English: EU/2/15/191/011 (40 mg, 3 tablets) EU/2/15/191/012 (40 mg, 6 tablets) EU/2/15/191/013 (80 mg, 1 tablet) EU/2/15/191/014 (80 mg, 3 tablets) EU/2/15/191/015 (80 mg, 6 tablets) EU/2/15/191/016 (120 mg, 1 tablet) EU/2/15/191/017 (120 mg, 3 tablets) EU/2/15/191/018 (120 mg, 6 tablets)
Danish: EU/2/15/191/011 (40 mg, 3 tabletter) EU/2/15/191/012 (40 mg, 6 tabletter) EU/2/15/191/013 (80 mg, 1 tablet) EU/2/15/191/014 (80 mg, 3 tabletter) EU/2/15/191/015 (80 mg, 6 tabletter) EU/2/15/191/016 (120 mg, 1 tablet) EU/2/15/191/017 (120 mg, 3 tabletter) EU/2/15/191/018 (120 mg, 6 tabletter)