natgillin/translations-raw huggingface dataset:
Generelt var antallet af loratadin- eksponerede personer lille (47 til 93 personer), undersøgelsernes udformning var forskellig (prospektiv hhv. retrospektiv), og oplysningerne om undersøgelsen var begrænsede.
In general, the numbers of loratadine-exposed subjects were small (47 to 93 subjects), the study designs varied (prospective vs. retrospective), and the study details were limited.
CPMP konkluderede, at de tre anførte undersøgelser ikke tyder på øget risiko for medfødte misdannelser ved anvendelse af loratadin.
The CPMP concluded that the three cited studies do not indicate an increased risk of congenital malformations with loratadine use.
Disse undersøgelser omfatter imidlertid tilsammen mindre end 200 kvinder eksponeret for loratadin.
However, the total number of women exposed to loratadine in these studies is less than 200.
Prækliniske undersøgelser Udvikling af genitalia externa masculina og vigtigheden af androgener CPMP konkluderede, at antiandrogen aktivitet på nuværende tidspunkt er den eneste kendte ikke - genetiske mekanisme for fremkaldelse af hypospadi.
Preclinical studies External Male Genitalia Development and Importance of Androgens The CPMP concluded that antiandrogenic activity is the only currently known non-genetic mechanism for induction of hypospadias.
Alligevel findes der eksempler på, at der hos mennesker er påvist sammenhæng mellem hypospadi og anvendelse af lægemidler, f. eks insuliner og valproesyre.
Nevertheless, there are examples where an association between hypospadias and drug intake have been demonstrated in humans e. g. insulins and valproic acid.
I disse tilfælde er de mulige mekanismer ikke fastlagt, men er antagelig ikke direkte knyttet til antiandrogen aktivitet.
In these cases, possible mechanisms have not been established, but they are probably not directly related to antiandrogenic activity.
Desuden fandt CPMP, at der hverken i litteraturen eller i andre kilder var dokumentation for, at hypospadi, der er induceret via den kendte mekanisme, kan optræde uden tegn på andre hormonrelaterede virkninger, dvs. antiandrogen virkning.
Moreover, the CPMP considered that there is no evidence from the literature or other sources supporting that hypospadias induced via the known mechanism may occur without signs of other hormonally related effects i. e. signs of antiandrogenic actions.
Antiandrogene endepunkter i loratadin- undersøgelser CPMP vurderede en række parametre, der er relevante for antiandrogent potentiale, herunder hypospadi, i undersøgelser af reproduktiv toksicitet af loratadin.
Antiandrogenic endpoints in loratadine studies The CPMP assessed a number of parameters addressing antiandrogenic potential, including hypospadias in the loratadine reproductive toxicity studies.
En af disse undersøgelser var specielt tilrettelagt med henblik på at vurdere den mulige antiandrogene virkning af loratadin på rotters afkom af hankøn.
One of these studies was designed specifically to evaluate the potential antiandrogenic effect of loratadine in male rat offspring.
CPMP fandt, at resultaterne af undersøgelsen viste, at loratadin ikke fremkalder ændringer af udviklingen af tractus genitalis, herunder hypospadi, i F1- generationen hos rotter eksponeret gennem hele organogenesen og i den tidlige postnatale udvikling (indtil dag 4 post partum).
The CPMP considered that the results of this study demonstrated that loratadine did not affect the development of the male F1 genital tract, including hypospadias, in rats exposed throughout organogenesis and early postnatal development (up to day 4 post partum).
CPMP konkluderede, at der ikke var tegn på antiandrogen påvirkning af de undersøgte endepunkter.
The CPMP concluded that there was no indication of antiandrogenic effects in the studied endpoints.
CPMP/ 1333/ 03
CPMP/ 1333/ 03 OVERALL CONCLUSION ON BENEFIT/ RISK
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CPMP konkluderede, at signalet burde undersøges yderligere.
The CPMP concluded that the signal should be further investigated.
CPMP konkluderede, at loratadin har vist sig effektiv til bedring af symptomerne ved allergisk rhinitis og idiopatisk kronisk urticaria.
The CPMP concluded that loratadine has been shown to be effective in relieving the symptoms associated with Allergic Rhinitis and Chronic Idiopathic Urticaria.
CPMP fandt derfor, at benefit/ risk- forholdet for lægemidler indeholdende loratadin er gunstigt for indikationen “ bedring af symptomerne ved allergisk rhinitis og idiopatisk kronisk urticaria ”, og anbefalede opretholdelse eller udstedelse af markedsføringstilladelser i overensstemmelse med produktresuméet i bilag III til CPMP’ s udtalelse med vægt på følgende:
Therefore the CPMP considered that the benefit/ risk balance of loratadine containing medicinal products is favourable for the indication “ relief of symptoms associated with Allergic Rhinitis and Chronic Idiopathic Urticaria” and recommended the maintenance or the granting of the Marketing Authorisations according to the Summary of Product Characteristics as set out in Annex III of the CPMP Opinion with emphasis to the following:
Afsnit 4. 6.
Section 4.6.
Graviditet og amning “ Loratadin var ikke teratogen i dyreundersøgelser.
Pregnancy and lactation “ Loratadine was not teratogenic in animal studies.
Det er ikke påvist, at det er sikkert at anvende loratadin under graviditet.
The safe use of loratadine during pregnancy has not been established.
Det anbefales derfor ikke at anvende {SÆRNAVN} under graviditet. ”
The use of {INVENTED NAME} during pregnancy is therefore not recommended .”
BEGRUNDELSE FOR ÆNDRING AF PRODUKTRESUMÉERNE
OF THE SUMMARIES OF
Ud fra følgende betragtninger:
CHARACTERISTICS
- Udvalget behandlede sagen, der er indbragt i henhold til artikel 31 i Rådets direktiv 2001/ 83/ EF,
- The Committee considered the referral made under article 31 of Directive 2001/ 83/ EC, as
med senere ændringer, for lægemidler indeholdende loratadin.
amended, for loratadine containing medicinal products;
- Udvalget konkluderede, at Medicinska födelseregistret giver et stærkt signal om, at eksponering
- The Committee concluded that the SMBR provides a robust signal that loratadine exposure
for loratadin under graviditeten øger risikoen for hypospadi.
during pregnancy increases the risk of hypospadia.
De foreliggende oplysninger giver hverken grundlag for at bekræfte eller udelukke en kausal sammenhæng.
Based on the available data, a causal relationship can neither be confirmed nor excluded.
Som sikkerhedsforanstaltning anbefalede CPMP, at produktresuméet for lægemidler indeholdende loratadin skulle ændres, så det indeholdt en angivelse af, at det ikke anbefales at anvende loratadin under graviditet.
As a precautionary measure the CPMP recommended, that the SPC for loratadine containing medicinal products should be amended to state that the use of loratadine during pregnancy is not recommended;
- Udvalget konkluderede, at signalet burde undersøges yderligere.
- The Committee concluded that the signal should be further investigated;
- Udvalgetvar af den opfattelse, at lægemidler indeholdende loratadin er effektive til lindring af
- The Committe considered that loratadine containing medicinal products are effective in the
symptomer forbundet med allergisk rhinitis og idiopatisk kronisk urticaria.
relief of symptoms associated with allergic rhinitis and chronic idiopathic urticaria;
- Udvalget fandt derfor, at benefit/ risk- forholdet for lægemidler indeholdende loratadin er
- The Committee, as a consequence considered the benefit/ risk balance of loratadine containing
gunstigt til lindring af symptomer forbundet med allergisk rhinitis og idiopatisk kronisk urticaria, anbefalede CPMP derfor udstedelse eller opretholdelse af ansøgninger/ markedsføringstilladelser for de lægemidler indeholdende loratadin, som er anført i bilag I som ændret i overensstemmelse med produktresuméet i bilag III.
As a consequence, the CPMP recommended the granting or maintenance of the Applications/ Marketing Authorisations for loratadine containing medicinal products referred in Annex I as amended in accordance with the SPC set out in Annex III.
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Dette er det SPC, der var bilag til Europa- Kommissionens beslutning vedrørende denne artikel 31 arbitreringssag vedrørende lægemidler indeholdende Loratadin.
This SPC is the one that was annexed to the Commission Decision on this Article 31 referral for loratadine containing medicinal products.
CPMP/ 1333/ 03 1.
CPMP/ 1333/ 03 1.
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{SÆRNAVN} {Styrke} {Lægemiddelform}
{INVENTED NAME} {Strength} {Pharmaceutical form}
< Hver < tablet > < overtrukket tablet > < filmovertrukket tablet > < brusetablet > < opløselig tablet > < smeltetablet > < smeltetabletter > indeholder 10 mg loratadin. > < Hver ml < syrup > < oral opløsning > < oral suspension > indeholder 1 mg loratadin.
< Each< tablet > < coated tablet > < film-coated tablet > < effervescent tablet > < soluble tablet > < oral lyophilisate > < oral dispersible tablet > contains 10 mg loratadine > < Each ml of < syrup > < oral solution > < oral suspension > contains 1 mg loratadine >
< Tablet > < Overtrukket tablet > < Filmovertrukket tablet > < Brusetablet > < Opløselig tablet > < Smeltetablet > < Smeltetabletter > < Syrup > < Oral opløsning > < Oral suspension >
< Tablet > < Coated tablet > < Film-coated tablet > < Effervescent tablet > < Soluble tablet > < Oral lyophilisate > < oral dispersible tablet > < Syrup > < Oral solution > < oral suspension >
< Visuel beskrivelse af produktet udfyldes nationalt >
< Visual description of the appearance of the product >
{SÆRNAVN} er indiceret til symptomatisk behandling af allergisk rinit og kronisk idiopatisk urticaria.
{INVENTED NAME} is indicated for the symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria.
Voksne og børn over 12 år:
Adults and children over 12 years of age:
10 mg 1 gang dagligt (< en < tablet > < overtrukket tablet > < filmovertrukket tablet > < brusetablet > < opløselig tablet > < smeltetablet > < smeltetabletter > > < 10 ml (10 mg) < syrup > < oral opløsning > < oral suspension > > 1 gang dagligt).
10 mg once daily (< one< tablet > < coated tablet > < film- coated tablet > < effervescent tablet > < soluble tablet > < oral lyophilisate > < oral dispersible tablet > > < 10 ml (10 mg) of the < syrup > < oral solution > < oral suspension > > once daily).
{Lægemiddelformen} kan tages uafhængigt af måltiderne.
The {pharmaceutical form} may be taken without regard to mealtime.
Børn 2 til 12 år gamle med:
Children 2 to 12 years of age with:
Legemsvægt mere end 30 kg:
Body weight more than 30 kg:
10 mg 1 gang dagligt (< en < tablet > < overtrukket tablet > < filmovertrukket tablet > < brusetablet > < opløselig tablet > < smeltetablet > < smeltetabletter > > < 10 ml (10 mg) < syrup > < oral opløsning > < oral suspension > > 1 gang dagligt).
10 mg once daily (< one< tablet > < coated tablet > < film-coated tablet > < effervescent tablet > < soluble tablet > < oral lyophilisate > < oral dispersible tablet > > < 10 ml (10 mg) of the < syrup > < oral solution > < oral suspension > > once daily).
< Legemsvægt 30 kg eller derunder:
< Body weight 30 kg or less:
5 ml (5 mg) < syrup > < oral opløsning > < oral suspension > 1 gang dagligt. > < 10 mg styrke < tablet > < overtrukket tablet > < filmovertrukket tablet > < brusetablet > < opløselig tablet > < smeltetablet > < smeltetabletter > er ikke hensigtsmæssige til børn med en legemsvægt mindre end 30 kg. >
5 ml (5 mg) of the< syrup > < oral solution > < oral suspension > once daily. > < The 10 mg strength < tablet > < coated tablet > < film-coated tablet > < effervescent tablet > < soluble tablet > < oral lyophilisate > < oral dispersible tablet > is not appropriate in children with a body weight less than 30 kg. >
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Til patienter med svær leverinsufficiens bør administreres en lavere initialdosis, da de kan have reduceret clearance af loratadin.
Patients with severe liver impairment should be administered a lower initial dose because they may have reduced clearance of loratadine.
En initialdosis på 10 mg hver anden dag anbefales til voksne og børn, der vejer mere end 30 kg <, og til børn, der vejer 30 kg eller derunder, anbefales 5 ml (5 mg) hver anden dag >.
An initial dose of 10 mg every other day is recommended for adults and children weighing more than 30 kg<, and for children weighing 30 kg or less, 5 ml (5 mg) every other day is recommended >.
Dosisjustering er ikke nødvendig til ældre eller patienter med nyreinsufficiens.
No dosage adjustments are required in the elderly or in patients with renal insufficiency.
{SÆRNAVN} er kontraindiceret til patienter, som er hypersensitive overfor det aktive indholdsstof eller overfor et af hjælpestofferne i disse lægemiddelformer.
{INVENTED NAME} is contraindicated in patients who are hypersensitive to the active substance or to any of the excipients in these formulations.
4. 2).
{INVENTED NAME} should be administered with caution in patients with severe liver impairment (see 4.2).
< {SÆRNAVN} < syrup > < oral opløsning > < oral suspension > indeholder... g saccharose pr.... ml.
< {INVENTED NAME }< syrup > < oral solution > < oral suspension > contains … g of sucrose per … ml.
Dette bør tages i betragtning hos patienter med diabetes mellitus. >
This should be taken into account in patients with diabetes mellitus. >
< Andre advarsler nødvendige for indholdsstoffer eller tilbageblevne stoffer fra fremstillingsprocessen > [Udfyldes nationalt]
< Any other warnings necessary for excipients or residues from the manufacturing process > [To be completed nationally]
Administration af {SÆRNAVN} bør afbrydes mindst 48 timer før hudpriktest, da antihistaminer kan forhindre eller reducere ellers positive resultater på hudreaktionsindexet.
The administration of {INVENTED NAME} should be discontinued at least 48 hours before skin tests since antihistamines may prevent or reduce otherwise positive reactions to dermal reactivity index.
Administreret samtidig med alkohol, har {SÆRNAVN} ingen potenserende effekt, målt ved psychomotoriske udførelsesstudier.
When administered concomitantly with alcohol, {INVENTED NAME} has no potentiating effects as measured by psychomotor performance studies.
5. 2).
Due to the wide therapeutic index of loratadine no clinically relevant interactions are expected and none were observed in the conducted clinical trials (see 5.2).
Loratadin var ikke teratogent i dyreforsøg.
Loratadine was not teratogenic in animal studies.
Sikker anvendelse af loratadin under graviditet er ikke fastslået.
The safe use of loratadine during pregnancy has not been established.
Anvendelse af {SÆRNAVN} under graviditet kan derfor ikke anbefales.
The use of {INVENTED NAME} during pregnancy is therefore not recommended.
Loratadin udskilles i modermælk, hvorfor anvendelse af loratadin ikke anbefales til ammende mødre.
Loratadine is excreted in breast milk, therefore the use of loratadine is not recommended in breast- feeding women.
I kliniske studier, der bedømte evnen til at køre, opstod ingen forringelse hos patienter, der indtog loratadin.
In clinical trials that assessed driving ability, no impairment occurred in patients receiving loratadine.
Alligevel bør patienter informeres om, at nogle personer meget sjældent kan opleve søvnighed, hvilket kan influere på deres evne til at køre eller betjene maskiner.
However, patients should be informed that very rarely some people experience drowsiness, which may affect their ability to drive or use machines.
I kliniske studier i en pædiatrisk population med børn i alderen 2 til 12 år, var de almindelige bivirkninger, rapporteret hyppigere end ved placebo, hovedpine (2, 7%), nervøsitet (2, 3%) og træthed (1%).
In clinical trials in a paediatric population children aged 2 through 12 years, common adverse reactions reported in excess of placebo were headache (2.7%), nervousness (2.3%), and fatigue (1%).
I kliniske undersøgelser med voksne og unge, omfattende indikationerne allergisk rinit og kronisk idiopatisk urticaria, ved den anbefalede dosis på 10 mg dagligt, blev bivirkninger af loratadin rapporteret hos 2% flere patienter i forhold til patienter behandlet med placebo.
In clinical trials involving adults and adolescents in a range of indications including AR and CIU, at the recommended dose of 10 mg daily, adverse reactions with loratadine were reported in 2% of
CPMP/ 1333/ 03 Forstyrrelser i immunsystemet Sygdomme i nervesystemet Hjertesygdomme Gastrointestinale sygdomme Sygdomme i lever og galde Sygdomme i hud og subkutane væv Almene lidelser og reaktioner på indgivelsesstedet
CPMP/ 1333/ 03 patients in excess of those treated with placebo.
59/ 62 Anaphylaxia Svimmelhed Tachycardia, palpitation Kvalme, mundtørhed, gastritis Abnorm leverfunktion Udslæt, alopecia Træthed
58/ 61 The most frequent adverse reactions
EMEA 2004
 EMEA 2004 reported in
Overdosis af loratadin øger forekomsten af anticholinerge symptomer.
Overdosage with loratadine increased the occurrence of anticholinergic symptoms.
Somnolens, tachycardia og hovedpine er rapporteret ved overdosis.
Somnolence, tachycardia, and headache have been reported with overdoses.
I tilfælde af overdosering begyndes symptomatisk og støttende behandling og fortsættes så længe det er nødvendigt.
In the event of overdose, general symptomatic and supportive measures are to be instituted and maintained for as long as necessary.
Administration af aktivt kul suspenderet i vand kan forsøges.
Administration of activated charcoal as a slurry with water may be attempted.
Maveskylning kan overvejes.
Gastric lavage may be considered.
Loratadin fjernes ikke ved hæmodialyse og det vides ikke, om loratadin fjernes ved peritoneal dialyse.
Loratadine is not removed by haemodialysis and it is not known if loratadine is removed by peritoneal dialysis.
Medicinsk monitorering af patienten skal fortsættes efter den akutte behandling.
Medical monitoring of the patient is to be continued after emergency treatment.
Farmakoterapeutisk klassifikation: antihistaminer – H1 antagonist, ATC- kode:
Pharmacotherapeutic group: antihistamines – H1 antagonist, ATC code:
R06A X13.
R06A X13.
Loratadin, det aktive indholdsstof i {SÆRNAVN}, er et tricyklisk antihistamin med selektiv perifer H1 - receptoraktivitet.
Loratadine, the active ingredient in {INVENTED NAME}, is a tricyclic antihistamine with selective, peripheral H1-receptor activity.
Loratadin har ingen klinisk signifikante sedative eller anticholinerge egenskaber hos størstedelen af populationen og anvendt ved den anbefalede dosering.
Loratadine has no clinically significant sedative or anticholinergic properties in the majority of the population and when used at the recommended dosage.
Ved langtidsbehandling var der ingen klinisk signifikante ændringer i vitale funktioner, laboratorieværdier, fysiske parametre eller elektrokardiogrammer.
During long-term treatment there were no clinically significant changes in vital signs, laboratory test values, physical examinations or electrocardiograms.
Loratadin har ingen signifikant H2- receptor aktivitet.
Loratadine has no significant H2-receptor activity.
Det hæmmer ikke noradrenalinoptagelsen og har sædvanligvis ingen indflydelse på den kardiovaskulære funktion eller på hjertets pacemakeraktivitet.
It does not inhibit norepinephrine uptake and has practically no influence on cardiovascular function or on intrinsic cardiac pacemaker activity.
Efter oral administration absorberes loratadin hurtigt og godt og gennemgår en betydelig første- passage metabolisme, hovedsageligt af CYP3A4 og CYP2D6.
After oral administration, loratadine is rapidly and well absorbed and undergoes an extensive first pass metabolism, mainly by CYP3A4 and CYP2D6.
Hovedmetabolitten - desloratadin (DL) - er farmakologisk aktiv og ansvarlig for en stor del af den kliniske effekt.
The major metabolite-desloratadine (DL)- is pharmacologically active and responsible for a large part of the clinical effect.
Loratadin og DL opnår maksimale plasmakoncentrationer (Tmax) mellem henholdsvis 1- 1, 5 timer og 1, 5- 3, 7 timer efter administration.
Loratadine and DL achieve
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Loratadin er i høj grad (97- 99%) og dets aktive metabolit i moderat grad (73- 76%) bundet til plasmaproteiner.
Loratadine is highly bound (97% to 99%) and its active metabolite moderately bound (73% to 76%) to plasma proteins.
Hos raske personer er plasmahalveringstiden i distributionsfasen for loratadin og dets aktive metabolit henholdsvis 1 og 2 timer.
In healthy subjects, plasma distribution half-lives of loratadine and its active metabolite are approximately 1 and 2 hours, respectively.
Den gennemsnitlige halveringstid i eliminationsfasen hos raske voksne personer var 8, 4 timer (strækkende fra 3 til 20 timer) for loratadin og 28 timer (strækkende fra 8, 8 til 92 timer) for dets aktive hovedmetabolit.
The mean elimination half-lives in healthy adult subjects were 8.4 hours (range = 3 to 20 hours) for loratadine and 28 hours (range = 8.8 to 92 hours) for the major active metabolite.
Cirka 40% af dosis udskilles i urinen og 42% i fæces over en 10 dages periode og det hovedsageligt i form af konjugerede metabolitter.
Approximately 40% of the dose is excreted in the urine and 42% in the faeces over a 10 day period and mainly in the form of conjugated metabolites.
Cirka 27% af dosis elimineres i urinen i løbet af de første 24 timer.
Approximately 27% of the dose is eliminated in the urine during the first 24 hours.
Mindre end 1% af den aktive substans udskilles uomdannet i aktiv form som loratadin eller DL.
Less than 1% of the active substance is excreted unchanged in active form, as loratadine or DL.
Biotilgængeligheden af loratadin og dets aktive metabolit er dosisproportionale.
The bioavailability parameters of loratadine and of the active metabolite are dose proportional.
Den farmakokinetiske profil af loratadin og dets metabolitter er sammenlignelig for raske voksne personer og raske geriatriske personer.
The pharmacokinetic profile of loratadine and its metabolites is comparable in healthy adult volunteers and in healthy geriatric volunteers.
Samtidig indtagelse af føde kan forsinke absorptionen af loratadin lidt dog uden at influere på den kliniske effekt.
Concomitant ingestion of food can delay slightly the absorption of loratadine but without influencing the clinical effect.
Hos patienter med kronisk nyreinsufficiens øgedes både AUC og den maksimale plasmakoncentration (Cmax) for loratadin og dets aktive metabolit sammenlignet med AUC og den maksimale plasmakoncentration (Cmax) hos patienter med normal nyrefunktion.
In patients with chronic renal impairment, both the AUC and peak plasma levels (Cmax) increased for loratadine and its metabolite as compared to the AUCs and peak plasma levels (Cmax) of patients with normal renal function.
Gennemsnitshalveringstiderne i eliminationsfasen for loratadin og dets metabolit var ikke signifikant forskellige fra dem der var observeret hos raske personer.
The mean elimination half-lives of loratadine and its metabolite were not significantly different from that observed in normal subjects.
Hæmodialyse har ingen effekt på loratadin og dets aktive metabolits farmakokinetik hos patienter med kronisk nyreinsufficiens.
Haemodialysis does not have an effect on the pharmacokinetics of loratadine or its active metabolite in subjects with chronic renal impairment.
Hos patienter med kronisk alkoholisk leversygdom var AUC og den maksimale plasmakoncentration (Cmax) for loratadin fordoblet, mens den farmakokinetiske profil af den aktive metabolit ikke var signifikant ændret i forhold til patienter med normal leverfunktion.
In patients with chronic alcoholic liver disease, the AUC and peak plasma levels (Cmax) of loratadine were double while the pharmacokinetic profile of the active metabolite was not significantly changed from that in patients with normal liver function.
Eliminationshalveringstiderne for loratadin og dets metabolit var henholdsvis 24 timer og 37 timer, og forhøjedes ved forhøjet sværhedsgrad af leversygdommen.
The elimination half-lives for loratadine and its metabolite were 24 hours and 37 hours, respectively, and increased with increasing severity of liver disease.
Loratadin og dets aktive metabolit udskilles i modermælken hos ammende kvinder.
Loratadine and its active metabolite are excreted in the breast milk of lactating women.