natgillin/translations-raw huggingface dataset:
På grund af den meget begrænsede eksponering in utero for natriumferrigluconat er der dog næppe risiko for abnormiteter hos nyfødte.
However, due to very limited exposure in utero to sodium ferric gluconate the risk for neonates of developing any abnormality seems unlikely.
Der var dog et tilfælde af grad IV (hjertestop), beskrevet i en artikel af Fishbane et al. (1996), og i hæmodialysepopulationen blev der i alt beskrevet 15 tilfælde af hypersensitivitet (7,3 %), hovedsagelig af grad II-III, (Haddad et al, 2009), som alle indtrådte under administration af testdosen.
Nevertheless, there was one grade IV (cardiac arrest) reported in Fishbane and colleagues (1996) publication and a total of fifteen hypersensitivity (7.3%) mainly grade II-III, reported in HD population (Haddad et al, 2009), all occurring during the test dose.
I henhold til Ring & Messmer-algoritmen blev 15 ikke-alvorlige tilfælde alle kodet enten som grad I eller II.
According to the Ring & Messmer algorithm, 15 non-serious cases were all coded as either Grade I or II cases.
CHMP vedtog desuden andre ændringer af produktinformationen, supplerende lægemiddelovervågning og risikominimeringsforanstaltninger over for hypersensitivitetshændelser hos alle patienter, herunder administration under graviditet.
Furthermore the CHMP agreed on other changes to the product information, additional pharmacovigilance activities and risk minimisation measures to address the risk of hypersensitivity events to all patients including administration in pregnancy.
Alle tilfælde i denne systemorganklasse er blevet klassificeret i henhold til Ring og Messmer.
All cases within this SOC have been classified according to the Ring and Messmer classification.
Størstedelen af de hypersensitivitetsrelaterede hændelser (15,1 %) indtrådte mellem 1 time og 24 timer efter behandlingen med jernsukrose, tæt efterfulgt af hypersensitivitetsrelaterede hændelser, der fandt sted efter mellem 5 og 30 minutter (13,9 %).
The majority of hypersensitivity associated events (15.1%) occurred between 1 hour and 24 hours after treatment with iron sucrose, closely followed by hypersensitivity associated events which occurred between 5 and 30 minutes (13.9%)
Heraf blev 3 klassificeret som anafylaktoide reaktioner.
Of these, 3 were classified as anaphylactoid reactions.
Pr. 29. februar 2012 var der modtaget i alt 26 rapporter om hypersensitivitet, svarende til en bivirkningsindberetningsfrekvens på 0,02 %.
As of 29 February 2012 a total of 26 case reports regarding hypersensitivity have been received yielding an ADR reporting rate of 0.02 %.
I de fleste publikationer blev størstedelen af de anafylaktoide reaktioner, der blev beskrevet med LMWID, klassificeret som Ring og Messmer sværhedsgrad I-II.
In most publications the majority of anaphylactoid reactions reported with LMWID were classified as grade I-II of severity according to Ring and Messmer classification.
Indehaverne af markedsføringstilladelse blev af CHMP anmodet om at give en detaljeret analyse, klassificeret efter Ring og Messmer, til brug ved gennemgangen af risikoen for allergiske reaktioner.
The MAHs were requested by the CHMP to provide a detailed analysis classified according to Ring and Messmer for the purpose of the review of the risk of allergic reactions.
Af de 20 patienter, der fik en anafylaktisk reaktion af grad IV, havde 35 % (7/20) hypersensitivitetsreaktioner i anamnesen.
Between the 20 patients who presented an anaphylactic reaction grade IV, 35% (7/20) patients had a medical history of hypersensitivity reactions.
Der blev i alt beskrevet 168 tilfælde (28,6 %), hvor primærhændelsen var i systemorganklasse immunsystemet; heraf var 147 alvorlige.
A total of 168 cases were reported with a primary event within the System Organ Class (SOC) of immune system disorders (28.6%) including 147 serious.
Én patient med tidligere allergier og ikke nærmere beskrevne svære komplikationer efter administration af dextran døde efter en overdosis af natriumferrigluconat som følge af akut myokardieinfarkt samme dag som infusionen af natriumferrigluconat.
One patient with previous allergies and severe complications NOS after administration of dextran, received an overdose of sodium ferric gluconate and died from an acute myocardial infarction the day of sodium ferric gluconate infusion.
I markedsføringstilladelsesindehaverens database blev der i alt fundet 317 tilfælde af hypersensitivitet, der fandt sted ved en eksponering på 13 824 369 patientår (skæringsdato 31. december 2011).
A total of 317 cases of hypersensitivity were identified from the MAH database, which occurred in 13,824,369 patient years (cut-off date 31 December 2011).
Dette oplysningsmateriale skal indgå i risikostyringsplanen og skal fremhæve risici og advarsler i forbindelse med hypersensitivitetsreaktioner.
The latter should also be included in the risk management plan, highlighting the risks and warnings of hypersensitivity reactions.
Der er kun udført få prækliniske undersøgelser med lavmolekylære jerndextraner (LMWID) og jern(III)-isomaltosid 1000, og indehaverne af markedsføringstilladelse indsendte kun data fra undersøgelser med sikkerhedsmæssige resultater af relevans for immunogeniciteten.
Only a few preclinical studies with low molecular weight iron dextrans (LMWID), iron(III) isomaltoside 1000 have been carried out and only studies with safety findings relevant to immunogenicity were referenced in the data submission by the MAHs.
Størstedelen af de hypersensitivitetsrelaterede bivirkninger (26,1 %) indtrådte 5-30 minutter efter behandlingen med ferricarboxymaltose, tæt efterfulgt af hypersensitivitetsrelaterede bivirkninger, der indtrådte under infusion/injektion (15,9 %).
The majority of hypersensitivity associated AEs (26.1%) occurred between 5 to 30 minutes after treatment with ferric carboxymaltose, closely followed by hypersensitivity associated AEs which occurred during the infusion/injection (15.9%).
CHMP vedtog, at indehaverne af markedsføringstilladelse desuden årligt skal indsende samlede oversigter over indberetningsrapporter om hypersensitivitet, alle dødeligt tilfælde, alle graviditeter samt data om lægemiddelanvendelse, og at dette skal ske med samme skæringstidspunkt, samme definition af eksponering, samme definition af hændelse (bivirkning) og med sværhed klassificeret efter Ring og Messmer.
The CHMP also agreed that the MAHs should submit annual cumulative reviews of hypersensitivity case reports, all fatal cases and all pregnancy cases, together with usage data, using same data lock point, same exposure definition, same event definition and the severity classification according to Ring and Messmer classification.
Der forelå meget begrænsede oplysninger om sikkerheden ved graviditet og ved forstyrrelser i tarmabsorptionen.
Data provided regarding safety in pregnancy and intestinal absorption disorder was very limited.
Det må bemærkes, at hypotension, kvalme, opkastning og kramper ofte forekommer i forbindelse med hæmodialyse.
Of note, hypotension, nausea, vomiting and cramps are often symptoms associated with haemodialysis.
Allergi i anamnesen forekom i 8 af de i alt 51 livstruende tilfælde (15,7 %; 8/51 tilfælde, det ene klassificeret som grad IV).
In 8 cases of the total 51 life-threatening cases (15.7%; 8/51 cases, one graded as Grade IV), the patient presented with a history of allergy.
Seks tilfælde (4 %) blev klassificeret som grad IV (2 med anafylaktisk chok med dødeligt udfald, og 4 med anafylaktisk chok, der medførte hjertestop, men med fuld restitution).
Six cases (4%) were classified as grade IV (2 reported anaphylactic shock leading to a fatal outcome and 4 anaphylactic shock leading to cardiac arrest (all patients made full recovery).
I henhold til Ring og Messmer-klassifikationen blev tre tilfælde klassificeret som anafylaktoide reaktioner af grad II, og et tilfælde som grad III.
According to the Ring and Messmer classification, three cases were classified as grade II anaphylactoid reactions and one case as grade III.
I 2011 blev den franske lægemiddelstyrelse (ANSM) betænkelig ved risikoen for hypersensitivitetsreaktioner over for intravenøst administrerede jernholdige lægemidler, der er indiceret ved jernmangel, når oral administration er utilstrækkelig eller tolereres dårligt, navnlig hos hæmodialysepatienter med kronisk nyresygdom, men også præ- eller postoperativt og ved forstyrrelser i absorptionen fra tarmen.
In 2011 the French medicines agency (ANSM) had concerns with regards to the risk of hypersensitivity reactions of intravenous iron containing products indicated in iron deficiency situations when the oral route is insufficient or poorly tolerated especially in chronic kidney disease (CKD) patients (haemodialysis), but also in pre- or post-operative situations, or in case of intestinal absorption disorders.
Der iagttoges højere total bivirkningsforekomst per patient og eksponering i LMWID end i jernsukrosegruppen, men ingen forskel mellem jernsukrose og jerngluconat i populationen med kronisk nyresygdom (Ganguli et al 2008).
A higher incidence of total adverse events (AEs) per patient and exposure within LMWID compared to iron sucrose group was identified but no difference between iron sucrose and iron gluconate (Ganguli et al 2008) in CKD population was observed.
Der blev udført én hovedundersøgelse og én støttende kontrolleret undersøgelse hos voksne til vurdering af virkningen og sikkerheden af natriumferrigluconat som førstevalgsbehandling af jernmangelanæmi hos patienter, der er i renal hæmodialyse og får tilskud af rekombinant humant erythropoietin.
One pivotal and one supportive controlled studies were conducted in adults to assess the efficacy and safety of sodium ferric gluconate as first line treatment for iron deficiency anaemia in renal haemodialysis patients on supplemental recombinant human erythropoietin.
For patienter med kendt allergi og immunbetingede eller inflammatoriske sygdomme (f.eks. systemisk lupus erythematosus, og reumatoid arthritis) kan disse produkter øge risikoen for forværring af sygdommen og bør kun gives, når fordelene skønnes at opveje risiciene.
Patients with known allergies and with immune or inflammatory conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis) may enhance their risk when given these products as their condition may worsen unless it is deemed that the benefit outweighs the risks for these patients.
For jerngluconat (natriumferrigluconat) blev der forelagt en oversigt over det toksikologiprogram, der var gennemført fra 1970'erne og indtil 1996 som dokumentation til registreringsansøgningen for natriumferrigluconatkomplekset.
For iron gluconate (sodium ferric gluconate) an overview of the toxicology program performed between 1970's and 1996 to support the registration of sodium ferric gluconate complex was submitted.
Der er således fundet fire tilfælde af allergiske reaktioner med mulig sammenhæng med jern(III)-isomaltosid 1000 i undersøgelserne.
Thus, four cases of allergic reactions possibly related to iron (III) isomaltoside 1000 have been found in the trials.
Foranstaltninger til risikominimering og andre lægemiddelovervågningsaktiviteter Som led i risikominimeringsforanstaltningerne fandt CHMP, at der bør gøres brug af al relevant information om sikker anvendelse af disse produkter for alle godkendte produkter, og vedtog derfor en ordlyd til alle relevante afsnit om risikoen for hypersensitivitetsreaktioner, herunder afsnittene om graviditet.
As part of the risk minimisation measures the CHMP considered there was a need to ensure that all relevant information for the safe use of these products should be applied across authorised products and therefore agreed on the wording for all relevant sections dealing with the risk of hypersensitivity reactions including the sections on pregnancy.
CHMP bestemte, at der skal udsendes en direkte meddelelse til fagfolk i sundhedssektoren (DHPC) om resultatet af denne gennemgang.
The CHMP endorsed a Dear healthcare professional communication (DHPC), to communicate the outcome of the present review.
Begrundelse for ændringen af betingelserne for markedsføringstilladelsen Ud fra følgende betragtninger:
Grounds for the variation to the terms of the marketing authorisation
Indehaverne af markedsføringstilladelse har kun udført to undersøgelser med lavmolekylært jern(III)hydroxid-dextrankompleks.
Only two MAH studies have been conducted with low molecular weight iron (III)-hydroxide dextran complex.
Det vigtigste grundlag for CHMP's vurdering og konklusioner var sikkerhedsdata efter markedsføring for alle jernkomplekserne.
The main safety data which were used in the CHMP assessment and conclusions were post-marketing data for all complexes.
• udvalget understregede desuden, at intravenøse, jernholdige lægemidler kun bør administreres, når der på behandlingsstedet umiddelbart forefindes personale, som er oplært i at vurdere og håndtere anafylaktiske/anafylaktoide reaktioner, samt genoplivningsudstyr.
The Committee in addition stressed that the intravenous iron products should only be administered when staff trained to evaluate and manage anaphylactic/anaphylactoid reactions as well as resuscitation facilities are immediately available.
Kun tre undersøgelser med jern(III)-isomaltosid 1000 er afsluttet, mens 11 undersøgelser stadig pågår.
There are only three completed studies involving iron (III) isomaltoside 1000 and eleven are still ongoing.
Der er udført en systematisk gennemgang af den relevante publicerede litteratur, der indbefattede alle randomiserede kliniske undersøgelser og andre undersøgelsesdesign, herunder ukontrollerede, retrospektive og prospektive undersøgelser, som beskrev uønskede lægemiddelreaktioner i forbindelse med anvendelse af lavmolekylært jerndextran- (LMWID-) kompleks.
A systematic review of the relevant published literature has been performed and randomised clinical study and other study designs including uncontrolled retrospective and prospective studies have been included if they reported on ADRs associated with the use of low molecular weight iron dextran (LMWID) complex.
• udvalget fandt, at risikoen for hypersensitivitet er øget hos patienter med kendte allergier (herunder lægemiddelallergi) og hos patienter med immunbetingede eller inflammatoriske sygdomme (f.eks. systemisk lupus erythematosus, reumatoid arthritis) eller med anamnese med svær astma, eksem eller anden atopisk allergi.
The Committee considered that the risk of hypersensitivity is increased in patients with known allergies (including drug allergies) and in patients with immune or inflammatory conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis) as well as in patients with a history of severe asthma, eczema or other atopic allergy.
Desuden anmodede PRAC om, at der sammen med indsendelse af risikostyringsplanen forelægges en protokol til en sikkerhedsundersøgelse efter markedsføring (PASS) til nærmere karakterisering af sikkerhedsproblemerne i forbindelse med hypersensitivitetsreaktionerne.
Furthermore the PRAC requested that the protocol of a Post-Authorisation Safety Study (PASS) should be submitted within the risk management plan submission, to better characterize the safety concerns for the hypersensitivity reactions.
CHMP anmodede desuden om, at der udføres en PASS til nærmere vurdering af sikkerhedsproblemer med hypersensitivitetsreaktioner, og at der udarbejdes passende informationsmateriale til patienter og ordinerende læger,
Furthermore the CHMP requested that a PASS will be conducted to further evaluate the safety concern of the hypersensitivity reactions, as well as adequate educational materials to be developed for patients and prescribers.
Tilfælde af hypersensitivitetsreaktioner forekom også hos gravide kvinder.
Pregnant women were among the cases with hypersensitivity reactions.
Specielt for graviditet anbefalede CHMP, at intravenøst administrerede jernkomplekser ikke gives til kvinder i de tidlige stadier af graviditeten, da orale jernpræparater kan være veltolererede i første trimester.
For pregnancy specifically, as oral iron may be well tolerated in the first trimester of the pregnancy, the CHMP advised that the intravenous iron complexes are not given to pregnant women in the early stages.
Indehaverne af markedsføringstilladelsen skal derudover ændre deres risikostyringsplan, i risikostyringsplanen forelægge protokol til en PASS til karakterisering af sikkerhedsproblemerne ved hypersensitivitetsreaktioner og desuden udlevere oplysningsmateriale til ordinerende læger og patienter.
The MAHs also should amend their risk management plan, provide a protocol of a PASS within the risk management plan submission to characterise the safety concerns on the hypersensitivity reactions and also provide educational material for prescribers and patients.
I en population med inflammatorisk tarmsygdom fik 6 % af patienterne anafylaktoide reaktioner, Ring og Messmer grad I-II (Khalil et al, 2011).
In inflammatory bowel disease population, according to Khalil et al (2011), 6% of IBD patients experienced anaphylactoid reactions (Ring and Messmer grade I-II).
Der var tre publikationer vedrørende jernmangelanæmi, og ingen af disse omtalte anafylaktoide reaktioner.
In iron deficiency anaemia there were three publications with no anaphylactoid reactions reported.
Hyppigheden af hypersensitivitetsrelaterede hændelser med jernsukrose (0,27 %) i de analyserede kliniske undersøgelser var væsentligt lavere end risikoen for hypersensitivitetshændelser i de pågældende baggrundspopulationer (1,2-16,8 %).
The frequency of hypersensitivity related events reported with iron sucrose in the analysed clinical trials (0.27%) was considerably less than the hypersensitivity event risk for the respective background populations (1.2
Analysen omfatter kun de tilfælde, hvor natriumferrigluconat blev indgivet parenteralt.
Only the cases in which sodium ferric gluconate was given parenterally were taken into account.
Den overvejende del af dem vedrørte patienter med kronisk nyresygdom og behandling af patienter i kronisk hæmodialyse.
The vast majority of these concerned patients in chronic kidney disease (CKD) and treatment in patients undergoing chronic haemodialysis (HD).
• udvalget fandt, at i betragtning af de på nuværende tidspunkt tilgængelige sikkerhedsdata og for at opretholde et gunstigt benefit/risk-forhold bør sådanne intravenøst administrerede jernholdige lægemidler være kontraindiceret, når der i anamnesen er hypersensitivitet eller reaktioner over for det aktive indholdsstof eller nogen af hjælpestofferne eller tidligere allergisk reaktion over for andre parenterale jernholdige produkter.
The Committee considered that in view of the currently available safety data in order to maintain a favourable benefit-risk balance, these intravenous iron containing medicinal products should be contraindicated in patients with history of hypersensitivity reactions to the active substance or any of the excipients of these products, as well as to patients who experienced allergic reactions to other parenteral iron containing products.
Desuden anmodede CHMP indehaverne af markedsføringstilladelsen om årligt at indsende en samlet gennemgang af hypersensitivitetsindberetninger, alle dødelige tilfælde og alle tilfælde af graviditet, samt oplysninger om lægemiddelanvendelse.
In addition the CHMP requested the MAHs to submit annual cumulative reviews of hypersensitivity case reports, all fatal cases and all pregnancy cases, together with usage data yearly.
Der ses intet sammenhængende mønster eller nogen forudsigelig dosis, og højere enkeltdoser synes ikke at være korreleret med øget bivirkningsfrekvens eller -sværhed.
No consistent pattern or predictive dose appears and the higher individual doses do not appear to be correlated with increased frequency or severity of events.
De foreliggende prækliniske data førte imidlertid ikke til afklaring af punktet immunogenicitet og gav derfor ikke mulighed for at drage endelige konklusioner.
However the discussion of the existing preclinical data did not clear the immunogenic point, therefore the existing pre-clinical data do not allow for any firm conclusions; the CHMP conclusions were reached based on clinical and pharmacovigilance data.
CHMP konkluderede, at benefit/risk-forholdet for intravenøst administrerede jernholdige lægemidler er gunstigt, da fordelene fortsat overstiger risiciene til behandling af jernmangel, når oral administration er utilstrækkelig eller ikke tolereres.
The CHMP concluded that the benefit-risk balance of intravenous iron containing medicinal products is favourable as the benefits continue to outweigh the risks in the treatment of iron deficiency when the oral route is insufficient or poorly tolerated.
Alle indehavere af markedsføringstilladelse for disse produkter skal årligt indsende kumulative indberetninger om hypersensitivitetsreaktioner.
Cumulative annual reporting of hypersensitivity reactions should be undertaken by all MAHs of these products.
Lancet intravenøst administrerede jernholdige præparater over for anti-dextranantistoffer bestemt ved omvendt radial immundiffusion.
In addition in vitro reactivity of various marketed intravenous iron preparations towards anti-dextran antibodies was tested in a reverse radial immunodiffusion assays.
Der er i alt inkluderet 13 134 patienter i 29 fase 1- til 3-undersøgelser, der var sponsoreret af indehaveren af markedsføringstilladelsen og omfattede forskellige behandlingsområder (nefrologi, gynækologi, gastroenterologi, neurologi, kardiologi og jernmangelanæmi).
A total of 13,134 patients have been included in 29 MAH sponsored Phase 1 to 3 studies in different therapeutic areas (nephrology, gynaecology, gastroenterology, neurology, cardiology and iron deficiency anaemia), of which 6,608 have received ferric carboxymaltose and compared with those receiving other parenteral irons.
Der ser ikke ud til at være noget ensartet mønster eller nogen forudsigelig dosis eller infusionshastighed, der har sammenhæng med risikoen for indtræden af disse bivirkninger, og vigtigt ser højere enkeltdoser ikke ud til at være korreleret med øget bivirkningsfrekvens eller -sværhed.
There does not appear to be a consistent pattern or predictive dose or rate of infusion that relates to the chance of these events occurring and importantly the higher individual doses do not appear to be correlated with increased frequency or severity of events.
Jerngluconat (natriumferrigluconat)
Iron gluconate (sodium ferric gluconate)
Både for jerncarboxymaltose og jernsukrose sås en klar hudreaktion efter administration af dextran (positiv kontrol) til marsvin, der havde fået indgivet immunserum indeholdende jerndextran-antistoffer.
For ferric carboxymaltose as well as iron sucrose in animal studies in guinea pigs that had been administered immune serum containing iron-dextran antibodies, a clear skin reaction after the administration of dextran was observed (positive control).
Endelig anmodede CHMP om, at der som en del af risikostyringsplanen forelægges oplysningsmateriale til både ordinerende læger og patienter, hvor risici og advarsler vedrørende hypersensitivitetsreaktioner fremhæves (f.eks. gennem en tjekliste, der indføres på nationalt plan).
Finally educational material for prescribers as well for patients highlighting the risks and warnings of hypersensitivity reactions (by e.g. a checklist, to be implemented at national level) have been requested by the CHMP for submission within the risk management plan.
Natriumferrigluconat
Sodium ferric gluconate
Udvalget konkluderede, at i jernmangelsituationer, hvor oralt jern ikke er tilstrækkeligt eller ikke er veltolereret, er benefit/risk-forholdet for intravenøst administrerede jernholdige lægemidler fortsat positivt under normale anvendelsesbetingelser under forudsætning af de vedtagne betingelser, advarsler og ændringer i produktinformationen og de vedtagne supplerende lægemiddelovervågningsog risikominimeringsforanstaltninger.
The Committee concluded that the benefit-risk balance of intravenous iron containing medicinal products in the iron deficiency situations where the oral iron is not sufficient or tolerated remains positive under normal conditions of use, subject to the restrictions, warnings, changes to the product information, additional pharmacovigilance activities and risk minimisation measures agreed.