natgillin/translations-raw huggingface dataset:
Endelig bemærkede PRAC, at den nuværende internationale konsensus om behandlingen af KOL og kronisk hypoksæmi (Global Initiative for Obstructive Lung Disease (GOLD) og andre praktiske anbefalinger) ikke længere nævner anvendelsen af almitrin.
Finally the PRAC noted that the current international consensus for the management of COPD and chronic hypoxemia (Global Initiative for Obstructive Lung Disease (GOLD) and other practical recommendation) does no longer refer to the use of almitrine.
De nationale kompetente myndigheder iværksætter rettidige tiltag med henblik på passende overgang af patienterne til andre behandlingsmuligheder.
The NCAs should undertake timely actions allowing an appropriate switching of patients to other therapeutic alternatives.
Dette var underbygget af det forhold, at der fra september 2003 til november 2012 fortsat blev indberettet tilfælde af perifer neuropati trods de iværksatte risikominimeringsforanstaltninger (anbefalinger om en sekventiel administrationsplan og initial dosisjustering, efterfulgt af kontraindikationer og advarsler).
This was supported by the fact that cases of peripheral neuropathy continued to be reported from September 2003 to November 2012 despite the implemented minimisation measures (recommendation for a sequential scheme of administration and dose adjustment initially, followed by contra-indications and warnings).
Indehaveren af markedsføringstilladelsen har aldrig udført forsøg eller undersøgelser til at dokumentere eller fastlægge virkningsmekanismen bag disse bivirkninger.
The MAH has never performed trials or investigations to document/establish the mechanism of action of these adverse effects.
Der er i alt spontant indberettet 2 304 tilfælde af perifer neuropati hos patienter, der blev eksponeret for almitrin siden produktets lancering (fra 1983 til december 2012).
With regards to peripheral neuropathy, a total of 2304 cases of peripheral neuropathy have been spontaneously reported in patients exposed to almitrine since the launch of the product (from 1983 to December 2012).
PRAC konstaterede, at det indberettede vægttab medførte seponering af almitrin i 90,9 % af tilfældene.
The PRAC noted that weight loss reported led to almitrine discontinuation in 90,9% of the cases.
I november 2012 nåede de kompetente franske nationale myndigheder frem til, at der trods de iværksatte risikominimeringsforanstaltninger ikke var fuld kontrol over ovennævnte sikkerhedsproblemer i klinisk praksis.
In November 2012 the French National Competent Authority considered that the above-mentioned major safety concerns were not fully controlled in clinical practice despite the risk minimisation measures in place.
PRAC konstaterede, at størstedelen af tilfældene af perifer neuropati indberettet fra september 2003 til december 2012 blev beskrevet som ikke restituerede eller restituerede med sequelae.
The PRAC noted that most cases of peripheral neuropathies reported from September 2003 to December 2012 were not recovered or recovered with sequelae.
I henhold til bestemmelserne i artikel 31 og 32 i direktiv 2001/83/EF anbefaler PRAC derfor tilbagekaldelse af markedsføringstilladelserne for alle lægemidler omhandlet i bilag I.
Therefore, in accordance with Articles 31 and 32 of Directive 2001/83/EC, the PRAC recommends the revocation of the marketing authorisations of the marketing authorisations for all medicinal products referred to in Annex I.
På baggrund af de 11 ovennævnte publicerede kliniske undersøgelser erkendes det, at undersøgelsernes resultater vedrørende virkning er indbyrdes modstridende, og at ekstrapolationer ikke er mulige.
In view of the 11 above mentioned published clinical studies, it is acknowledged that efficacy results among clinical studies are contradictory and extrapolations not feasible.
Antagelsen af, at langtidsoxygenterapi kan seponeres, forsinkes eller endog undgås med almitrin, bygger ikke på videnskabelig eller klinisk evidens.
Consideration that long-term oxygen therapy can be discontinued, delayed or even avoided with almitrine is not based on scientific or clinical evidence.
Der er endvidere rejst betænkelighed ved de potentielle risici for hepatobiliære sygdomme, hudsygdomme og cytopeni ved oral anvendelse af almitrin.
Concerns have also been raised with regards to the potential risks of hepatobilary disorders, skin disorders and cytopenia with the use of oral almitrine.
Hypoksæmi er i sig selv ikke tilstrækkelig til at forklare det svære vægttab, der indberettes med almitrin.
Hypoxemia alone is not sufficient to explain severe weight loss reported with almitrine.
Der blev gennemgået i alt 11 publicerede kliniske undersøgelser, som var blevet tilgængelige efter den oprindelige markedsføringstilladelse.
A total of 11 published clinical studies which became available after the initial Marketing Authorisation were reviewed.
Endvidere foreligger der ingen data til støtte for en fordel ved almitrin til den indskrænkede indikation, der foreslås af indehaveren af markedsføringstilladelsen (patienter med PaO2: 55 mmHg< PaO2< 65 mmHg).
Moreover, no data is available to support any benefit of almitrine in the restrictive indication proposed by the MAH (patient with PaO2: 55 mmHg< PaO2< 65 mmHg).
På baggrund af det negative benefit/risk-forhold bør patienterne overgå til andre behandlinger.
In the view of the negative benefit risk balance, patients will need to be switched to alternative therapies.
Det af markedsføringstilladelsesindehaveren omtalte fald i indberetningen af perifer neuropati beror formodentlig hovedsagelig på nedgangen i salget gennem de seneste ti år.
The decrease in reporting of peripheral neuropathy mentioned by the MAH, is probably mainly related to the decrease in sales over the last 10 years.
I de publicerede kliniske undersøgelser med kontinuerlig administration 1234567, forekom der perifer neuropati og vægttab, når undersøgelsens varighed var over tre måneder, hvilket tyder at varigheden af kontinuerlig eksponering har haft betydning for deres opståen på,
In published clinical studies with continuous administration1234567, peripheral neuropathies and weight loss were encountered when the study duration was longer than 3 months, indicating that the duration of continuous exposure have played a role in their development.
Frankrig har truffet en række nationale foranstaltninger til minimering af risikoen for sådanne bivirkninger forbundet med oral anvendelse af almitrin.
France has taken a number of national regulatory actions to minimise the risk of these adverse reactions associated with almitrine for oral use.
Samlet resumé af PRAC's videnskabelige vurdering af orale lægemidler indeholdende almitrin
Overall summary of the scientific evaluation of Almitrine containing medicinal products for oral use by PRAC
Der bliver fortsat indberettet perifer neuropati selv efter indførelsen af den sekventielle behandlingsplan.
Spontaneous reports of peripheral neuropathies persist even after the introduction of sequential administration scheme.
I Frankrig har orale lægemidler indeholdende almitrin været under tæt overvågning som følge af alvorlige bivirkninger.
In France, almitrine containing medicinal products for oral use have been under close monitoring due to serious adverse reaction .
PRAC tillagde det betydning, at mange af publikationerne angav, at der ikke kunne konstateres klinisk fordel af oralt almitrin hvad angår forværringer eller indlæggelser, fysisk kapacitet, klinisk udfald, overlevelse eller livskvalitet.
The PRAC considered that many of the publications reported that a clinical benefit of oral almitrine could not be seen in terms of exacerbations or hospitalisation, exercise capacity, clinical outcome, survival, or quality of life.
Denne bivirkning er også klart blevet anerkendt i de undersøgelser, hvor almitrin i høje doser er blevet sammenlignet med placebo.
This adverse effect was also clearly recognised in the trials comparing almitrine at high doses to placebo.
Der er ikke påvist nogen fordel af almitrin som adjuverende behandling til denne intervention.
No benefit has been demonstrated when almitrine was used as an adjuvant of that intervention.
PRAC er den opfattelse, at almitrin ikke kan anses for at være et alternativ til langtidsoxygenterapi, med hvilken der er opnået nedsat mortalitet.
The PRAC is of the opinion that almitrine cannot be considered as an alternative to LTOT for which reduction in mortality has been achieved.
Hos patienter med respirationsinsufficiens er det iagttagne vægttab progressivt.
Weight loss observed in patients with respiratory insufficiency is progressive.
6 Marsac J. The assessment of almitrin bismesylate in the long-term treatment of chronic obstructive bronchitis.
6 Marsac J. The assessment of Almitrine bismesylate in the long-term treatment of chronic obstructive bronchitis.
En af de yderligere risikominimeringsforanstaltninger, der blev foreslået af indehaveren af markedsføringstilladelsen, var indskrænkning af indikationen til patienter med PaO2 mellem 55 mmHg og 65 mmHg eller som adjuverende behandling til langtidsoxygenterapi (LTOT).
One of the proposed further risk minimisation measures by the MAH was a restricted indication in patients with PaO2 between 55 mmHg and 65 mmHg or as adjuvant treatment to Long Term Oxygen Therapy (LTOT).
PRAC bemærkede dog, at det vægttab, der blev indberettet med almitrin, kan tænkes at være hurtigere og sværere end det, der sædvanligvis iagttages ved kronisk respirationsinsufficiens.
However, the PRAC noted that weight loss reported with almitrine could occur faster and be more severe than what is commonly observed in chronic respiratory insufficiency.
Oral anvendelse af almitrin har været genstand for flere kliniske undersøgelser.
Almitrine for oral use was studied in several clinical studies.
PRAC bemærkede, at i de kliniske undersøgelser, hvor resultaterne er til fordel for almitrin, kan virkningen af almitrin være blevet overvurderet, da andelen af udtrædelser var højere i almitrin-gruppen end i placebogruppen (Voisin and al, 1987 samt størstedelen af alle de kliniske undersøgelser).
PRAC noted that in the clinical trials with results in favour of almitrine, effect of almitrine could have been overestimated as a high rate of patients withdrew predominantly in the almitrine group as compared to placebo (Voisin and al, 1987 and in most of all the clinical trials).
Ved kontinuerlige doser på 100-200 mg almitrin var der højere forekomst af bivirkninger og udtrædelser end med placebo.
The doses of 100-200 mg of almitrine continuously were associated with a higher incidence of adverse effects and withdrawals compared to placebo.
Den 27. november 2012 underrettede Frankrig Det Europæiske Lægemiddelagentur om, at det i medfør af artikel 31 i direktiv 2001/83/EF overvejede at revurdere benefit/risk-forholdet for oral anvendelse af almitrin til behandling af kroniske luftvejssygdomme baseret på en vurdering af lægemiddelovervågningsdata.
On 27 November 2012 France informed the European Medicines Agency, pursuant to Article 31 of Directive 2001/83/EC, of their consideration to review the benefit risk balance of almitrine for oral use in the treatment of chronic respiratory diseases resulting from the evaluation of data relating to pharmacovigilance.
Tilsammen omfattede disse kliniske undersøgelser 2 036 patienter (1 380 behandlet med almitrin, 656 med placebo).
Taken together, these clinical trials enrolled 2036 patients (1380 under almitrine, 656 under placebo).
De seneste undersøgelser blev udført med sekventiel behandling i et dobbeltblindet, placebokontrolleret design og omfatter 366 patienter.
The last trials, conducted with sequential treatment and following a double blind placebo controlled design, account for 366 patients.
At de tilfælde, der indberettet i perioden fra september 2003 til december 2012, synes en væsentlig del at være beskrevet som ikke restituerede (5 af de 7 indberettede tilfælde).
An important proportion of cases seems to have been reported with an outcome as not recovered during the period from September 2003 to December 2012 (5 cases of the 7 reported).
De første undersøgelser, hvor der blev anvendt non-sekventiel behandling, omfatter 1 670 patienter (1 006 i dobbeltblindet, placebokontrolleret design).
The first trials, conducted with non-sequential treatment, account for 1670 patients (1006 following a double blind, placebo controlled design).
Der er imidlertid ingen data til støtte for den indskrænkede indikation, der foreslås af indehaveren af markedsføringstilladelsen.
However, no data supports the restrictive indication proposed by the MAH.
Sequential treatment with low dose almitrin bismesylate in hypoxaemic chronic obstructive airways disease.
Sequential treatment with low dose Almitrine bismesylate in hypoxaemic chronic obstructive airways disease.
De indberettede reaktioner bestod hovedsagelig af perifer neuropati og vægttab.
The reported reactions consisted mainly of peripheral neuropathy and weight loss.
Selv om forekomsten af perifer neuropati hos KOL-patienter med tilknyttede sygdomme kan anses for en konfunderende faktor, tyder forekomsten af tilfælde fra erfaringerne efter markedsføring, hvor der var positiv reeksponering for almitrin, stærkt på en årsagssammenhæng mellem almitrin og perifer neuropati.
Even if occurrence of peripheral neuropathy in COPD patients with associated conditions could be considered as a confounding factor, the occurrence of cases with positive rechallenge with almitrine during the post-marketing experience is strongly in favour of a causal relationship between almitrine and peripheral neuropathies.
Ud over perifere neuropatier med abnorme føleindtryk i underekstremiteterne eller paræstesi og vægttab op til -6 % var følgende bivirkninger ligeledes hyppigere i almitrin-grupperne i de publicerede kliniske undersøgelser med kontinuerlig administration:
In addition to peripheral neuropathies with abnormal sensations in the lower limb or paraesthesia and weight loss up to -6%, in the publications reporting clinical studies with continuous administration, the following adverse events were also more frequent in the almitrine groups:
PRAC gennemgik de tidligere iværksatte risikominimeringsforanstaltninger (dosisreduktion og en sekventiel behandlingsplan) til afbødning af risikoen for neuropati og vægttab.
The PRAC considered the risk minimisations measures already implemented (reduction of the dose and implementation of a sequential treatment scheme) to mitigate the risk of neuropathies and weight loss.
Baseret på data fra kliniske undersøgelser og erfaringer efter markedsføring er de to vigtigste sikkerhedsproblemer ved almitrin perifer neuropati og vægttab.
Based on the data from clinical studies and post-marketing experience, the two main safety concerns with almitrine are peripheral neuropathy and weight loss.
Eur J Respir Dis 1983; 64(Suppl 126):323-330 (PE10377) 3 Bakran I., Vrhovac B., Stangl B., Tabori D., Ivicevic A., Todic V., Kandare F. Double- blind placebo controlled clinical trial of almitrin bismesylate in patients with chronic respiratory insufficiency.
Eur J Respir Dis 1983; 64(Suppl 126):323-330 (PE10377) 3 Bakran I., Vrhovac B., Stangl B., Tabori D., Ivicevic A., Todic V., Kandare F. Double- blind placebo controlled clinical trial of Almitrine bismesylate in patients with chronic respiratory insufficiency.
• PRAC fulgte proceduren i overensstemmelse med artikel 31 i direktiv 2001/83/EF som følge af lægemiddelovervågning af produkter til oral anvendelse af almitrin (se bilag I).
• The PRAC considered the procedure under Article 31 of Directive 2001/83/EC resulting from pharmacovigilance data, for almitrine containing products for oral administration (see Annex I).
Foruden publikationer af kliniske undersøgelser gennemgik PRAC data efter markedsføring, som blev forelagt af indehaveren af markedsføringstilladelsen.
In addition to publications of clinical studies, the PRAC reviewed post marketing data provided by the MAH.
Totalt finder PRAC det uacceptabelt, at der er et betydeligt antal tilfælde med udfald, der indberettes som ikke restituerede eller restituerede med sequelae.
Overall, a significant number of cases with outcomes reported as not recovered or recovered with sequelae is not acceptable to the PRAC.
Desuden bemærkede PRAC, at vi i dag ved væsentligt mere om patofysiologien og behandlingen af KOL (herunder den forventede levetid ved KOL).
Besides, the PRAC also noted that the knowledge in physiopatholigical mechanism and management of COPD (including life expectancy in COPD) has been considerably improved.
PRAC bemærkede, at der er usikkerhed omkring virkningsmekanismen bestående i vasokonstriktion af lungevaskulaturen (som er omvendt i forhold til den gavnlige virkning af langtidsoxygenterapi på lungearterietrykket).
The uncertainties relating to the mechanisms of action implying the vasoconstriction of pulmonary vasculature (which is inverse to the beneficial effect of LTOT on pulmonary arterial pressure) was noted by the PRAC.
PRAC konkluderede derfor, at benefit/risk-forholdet for lægemidler indeholdende almitrin til oral anvendelse ikke er positivt.
The PRAC therefore concluded that the benefit-risk balance of almitrine containing medicinal products for oral administration is not favourable.
Heri indgik data fra medlemsstaterne og publicerede data, der blev tilgængelige efter de oprindelige markedsføringsgodkendelser, samt besvarelsen fra indehaveren af markedsføringstilladelsen.
This included data from the Member States and published literature data which became available since the original marketing authorisations and the MAH's response.
• På grundlag af de foreliggende data konkluderede PRAC derfor, at risiciene for alvorlige bivirkninger i form af perifer neuropati og vægttab overstiger de begrænsede fordele ved anvendelse af orale lægemidler indeholdende almitrin til behandling af respirationsinsufficiens med hypoksæmi ved obstruktiv bronkitis.
• The PRAC therefore concluded, in view of the available data, that the risks of serious peripheral neuropathy and weight loss adverse reactions associated with the use of almitrine-containing medicinal products for oral administration in the treatment of respiratory failure with hypoxemia related to obstructive bronchitis outweigh the limited benefits.
• hændelser relateret til fordøjelsessystemet (kvalme, halsbrand, epigastrisk tyngdefornemmelse, dyspepsi)
• Digestive events (nausea, burning sensation and sensation of epigastric heaviness, dyspepsia),
Eur J Respir Dis 1986; 69(Suppl 146):685-693 (PE10387)
Respir Dis 1986; 69(Suppl 146):685-693 (PE10387)
• På grundlag af en vurdering af virkningen af de gennemførte risikominimeringsforanstaltninger (dosisreduktion og indførelse af en sekventiel behandlingsplan) og af den publicerede litteratur fandt udvalget, at de risikominimeringsforanstaltninger, der påtænkes af indehaveren af markedsføringstilladelsen, ikke vil kunne mindske risiciene for alvorlige bivirkninger til et klinisk acceptabelt niveau.
• The PRAC considered, based on the assessment of the impact of risk minimisation measures already implemented (reduction of the dose and implementation of a sequential treatment scheme) and on the published literature, that the additional risk minimisation measures proposed by the Marketing Authorisation Holder and discussed during the assessment would not be able to adequately reduce the risks of serious adverse reactions to a clinically acceptable level.
Til langvarig anvendelse af almitrinbismesylat anbefales på nuværende tidspunkt et dosisniveau på 50-100 mg dagligt og begrænsning af dosis til 50 mg dagligt hos patienter med legemsvægt under 50 kg.
Long-term use of almitrine bismesylate is currently recommended at a dose level of 50 to 100 mg per day with limitation of the dose at 50 mg per day in patients with body weight less than 50 kg. After 3-month treatment, maintenance therapy of the sequential type is recommended: a 1-month interval for every 2 months treatment.
Under drøftelserne overvejede desuden supplerende risikominimeringsforanstaltninger såsom yderligere ændringer af produktinformationen (indskrænkning af indikationen samt kontraindikationer), kommunikationsmateriale (direkte meddelelse til sundhedspersoner) og begrænset ordination.
Further risk minimisation measures such as additional amendments to the product information (restriction of the indication and contra-indications), communication material (dear Health Care Professional Communication) and restricted prescription were also considered during the discussions.
• PRAC gennemgik samtlige foreliggende data for produkter indeholdende almitrin vedrørende risikoen for perifer neuropati og vægttab.
• The PRAC considered the totality of the data available for almitrine containing products for oral administration in relation to the risk of peripheral neuropathy and weight loss.
Under drøftelserne overvejede desuden yderligere risikominimeringsforanstaltninger, der blev foreslået af indehaveren af markedsføringstilladelsen, såsom yderligere ændringer af produktinformationen (indskrænkning af indikationen samt kontraindikationer), kommunikationsmateriale (direkte meddelelse til sundhedspersoner) og begrænset recept (begrænsning til en måned for lungespecialister og hospitalsanvendelse).
Further risk minimisation measures, as proposed by the MAH, such as additional amendments to the product information (restriction of the indication and contra-indications), communication material (dear Health Care Professional Communication) and restricted prescription (restriction to one month for pneumologists and hospital's use) were also considered during the discussions.
4 Bardsley P.A., Howard P., De-Backer W., Vermeire P., Mairesse M., Ledent C., Radermecker M., Bury T., Ansquer J.. Two years treatment with almitrin bismesylate in patients with hypoxic chronic obstructive airways disease.
Bardsley P.A., Howard P., De-Backer W., Vermeire P., Mairesse M., Ledent C., Radermecker M., Bury T., Ansquer J.. Two years treatment with Almitrine bismesylate in patients with hypoxic chronic obstructive airways disease.
Trods et sekventielt dosisregime og ændringer af produktresuméet konstaterede PRAC, at der fortsat blev indberettet alvorlige tilfælde af neuropati og vægttab, herunder tilfælde med positiv reeksponering, og undertiden med sequelae.
Despite sequential doses regimen and amendments in the SmPC, the PRAC noted serious cases of neuropathy and weight loss continued to be reported, including some cases with positive rechallenge, and leading sometimes to sequelae.
På baggrund af den publicerede litteratur og undersøgelser efter markedsføring er PRAC af den opfattelse, at de af markedsføringstilladelsesindehaveren foreslåede risikominimeringsforanstaltninger ikke vil kunne reducere risiciene for alvorlige bivirkninger til et klinisk acceptabelt niveau: Risiciene for neuropati og vægttab er i forvejen velkendt af de ordinerende læger, og eventuel yderligere information herom vil ikke bidrage til sikrere anvendelse af produktet.
Based on the published literature and post marketing data, the PRAC is of the view that the risk minimisation measures proposed by the MAH would not be able to adequately reduce the risks of serious adverse reactions to a clinically acceptable level: any additional communication on risks of neuropathies and weight loss, already well known to prescribers, would not contribute to a safer use of the product.
På grundlag af de foreliggende publicerede data og data fra spontane indberetninger finder PRAC, at anvendelse af almitrin er forbundet med alvorlige tilfælde af perifer neuropati, nogle ved positiv
Overall, based on the available published data and data from spontaneous reports, the PRAC considers that almitrine use is associated with serious cases of peripheral neuropathy, some with positive rechallenge, and weight loss.