natgillin/translations-raw huggingface dataset:
I klinisk praksis vil dette betyde, at moxifloxacin skal bruges i kombination med et godkendt stof, der er aktivt imod fluoroquinolon- resistente N. gonorrhoeae- stammer (f. eks. cephalosporin) i forbindelse med empirisk behandling af PID, medmindre moxifloxacin- resistente N. gonorrhoeae- stammer kan udelukkes.
In clinical practice, this would mean that moxifloxacin should be used in combination with an approved agent active against fluoroquinolone resistant N. gonorrhoeae (e. g. a cephalosporin) for empirical treatment of PID unless moxifloxacin- resistant N. gonorrhoeae can be excluded.
For at dække alle stoffer med ætiologisk betydning for udvikling af PID skal en kombination med en anden gruppe af antibiotika såsom cephalosporiner (f. eks. ceftriaxon 250 mg intramuskulært (IM) i enkeltdosis) gives empirisk, hvilket svarer til fremgangsmåden ved andre anbefalede kombinationsbehandlinger.
To cover all etiologic agents of PID a combination with another antibiotic class such as the cephalosporins (e. g. ceftriaxone 250 mg intramuscular (IM) in a single dose) should be given empirically, which would be similar to other recommended treatment regimens given in combination.
Uagtet det anerkendes, at ca.
Although it is well known that monotherapy increases compliance, this example of combination therapy would not decrease compliance since the proposed cephalosporin would only have to be given once during the physician’ s visit and only moxifloxacin would have to be continued orally.
5% hovedsageligt fra en yngre population, som på langt sigt risikerer at opleve alvorlige følgevirkninger.
Although it is acknowledged that approximately 95% of the women with a PID might be ‘ overtreated’ by this combination therapy this fact outweighs the potential risk of not treating approximately 5% of a mainly very young population which could develop serious long-term sequelae.
I forbindelse med denne indbringelsesprocedure lagde CHMP vægt på risikoen for hyppigere forekomst af QT- forlængelse hos kvinder set i lyset af den forlængede behandling i forbindelse med PID (14 dage kontra 5- 10 dage), risikoen for samtidig administration af andre QT- påvirkende stoffer samt mulige uønskede bruskpåvirkninger i behandlingsgruppen.
5-10 days), on the risk of coadministration with other QT-affecting substances and on the possible adverse effects on cartilage in the treatment population.
QT- forlængelse er en kendt uønsket virkning af moxifloxacin.
QT-prolongation is a known undesirable effect of moxifloxacin.
De tilgængelige data indeholdt ingen dokumentation for øget hjertesygelighed i forbindelse med oral behandling med moxifloxacin i forhold til den antibiotikabehandling, der sammenlignes med, især hos den yngre kvindelige population, selv om QT- intervalforlængelse og torsades de pointes i andre undersøgelser var mere almindelige hos kvinder end hos mænd.
Available data demonstrated no evidence for increased cardiac morbidity related to oral moxifloxacin therapy when compared to comparator antibiotic therapy, especially in a younger female population, although in other trials QT interval prolongation and torsades de pointes were more common in women than in men.
Ud fra analysen af forekomsten af uønskede hjertehændelser kunne det ikke påvises, om nogen særlig undergruppe af PID- patienter har større risiko i forbindelse med behandling med moxifloxacin i forhold til behandling med sammenligningspræparater.
The analysis of the incidence of cardiac adverse events did not reveal any special subgroups of PID patients for whom moxifloxacin presents a greater risk than comparator treatments.
Desuden er risikoen for QT- forlængelse allerede tilstrækkeligt behandlet i produktoplysningerne, og indehaveren af markedsføringstilladelsen vil sørge for passende opfølgning på dette efter markedsføringen.
In addition, the risk of QT- prolongation is already sufficiently addressed in the Product Information and will be adequately followed up by the MAH in the post-marketing setting.
CHMP var dog af den opfattelse, at QT- forlængelse i forbindelse med PID skal behandles omhyggeligt af indehaveren af markedsføringstilladelsen i fremtidige PSUR' er.
The CHMP considered that QT-prolongation in PID should however be carefully addressed by the MAH in future PSURs.
Indehaveren af markedsføringstilladelsen har påtaget sig at overvåge denne bivirkning i fremtidige PSUR' er og fremsende en opdateret risikostyringsplan, hvori den nye indikation let til moderat PID indgår.
The MAH committed to monitor this adverse event in the next PSURS and committed to provide an updated Risk Management Plan taking into account the new indication mild to moderate PID.
6 Overordnet var CHMP enig i, at der foreligger et positivt benefit/ risk- forhold for moxifloxacin til indikationen for PID over en periode på 14 dage.
Overall, the CHMP agreed that the benefit/ risk balance of moxifloxacin in the PID indication over 14 days is positive.
Afsnittene "Kontraindikationer" og "Særlige advarsler og forsigtighedsregler vedrørende brugen" i produktresuméet og i produktinformationen indeholder tilstrækkelige oplysninger om og anbefalinger for, hvilke forholdsregler der skal tages inden ordinering af moxifloxacin.
Information and recommendations regarding taking measures before prescribing moxifloxacin are adequately addressed in the ‘ contraindications’ and ‘ warnings-precaution of use’ sections of the SPC and PL.
12, i Kommissionens
6 GROUNDS FOR AMENDMENT OF THE SUMMARY OF PRODUCT CHARACTERISTICS AND PACKAGE LEAFLET
forordning (EF) nr.
- The Committee considered the Referral made under Article 6(12) of Commission Regulation (EC)
1084/ 2003, for Actira og tilknyttede navne (se bilag I).
No 1084/ 2003, for Actira and associated names (See Annex 1).
- Udvalget var af den opfattelse, at der eksisterer fyldestgørende data for virkningen af Actira i
- The Committee considered that robust data is available showing the efficacy of Actira in the
forbindelse med indikationen "Behandling af let til moderat PID (pelvic inflammatory disease), dvs. infektioner i de øvre genitaler, herunder salpingitis og endometritis", dog må moxifloxacin på grund af fremkomsten af resistens over for N. gonorrhoeae ikke anvendes i empirisk monoterapi, medmindre moxifloxacin- resistent N. gonorrhoeae kan udelukkes.
indication “ Treatment of mild to moderate pelvic inflammatory disease (PID), i. e. infections of upper genital tract, including salpingitis and endometritis”, however due to emerging resistance of N. gonorrhoeae, moxifloxacin should not be used in empirical monotherapy, unless moxifloxacin- resistant N. gonorrhoeae can be excluded.
- Udvalget var af den opfattelse, at der ikke forventes at fremkomme yderligere betænkeligheder
- The Committee considered that no additional safety concerns were expected with the claimed
vedrørende den ansøgte indikations sikkerhed i forhold til tidligere godkendte indikationer.
indication in comparison to the previously approved indications.
- Udvalget var på baggrund af de forelagte data for virkning og sikkerhed af den opfattelse, at
- The Committee, in view of the presented data on efficacy and safety, considered that the Benefit /
benefit/ risk- forholdet var positivt for Actira og tilknyttede navne i forbindelse med "Behandlingen af let til moderat PID (pelvic inflammatory disease), dvs. infektioner i de øvre genitaler, herunder salpingitis og endometritis", dog med de anførte restriktioner i forbindelse med empirisk monoterapi.
Risk balance for Actira and associated names in the “ The treatment of mild to moderate pelvic inflammatory disease (PID), i. e. infections of upper genital tract, including salpingitis and endometritis” with the restrictions concerning empirical monotherapy was favourable;
- CHMP anbefalede derfor, at der for Actira og tilknyttede navne (se bilag I) foretages ændring af
Characteristics sections 4.1, 4.2, 4.3, 4.4, 5.1 and 5.2 and Package Leaflet relevant sections as set out in Annex III for Actira and associated names (see Annex I).
afsnit 4. 1, 4. 2, 4. 3, 4. 4, 5. 1 og 5. 2 i produktresuméet samt relevante afsnit af indlægssedlen som beskrevet i bilag III.
AMENDMENTS TO SUMMARY OF PRODUCT CHARACTERISTICS AND PACKAGE LEAFLET (RELEVANT SECTIONS ONLY)
8 BILAG III
8 SUMMARY OF PRODUCT CHARACTERISTICS
9 PRODUKTRESUME
9 4.
[Lægemidlets navn] anvendes til behandling af følgende bakterielle infektioner:
[Invented name] 400 mg film-coated tablets are indicated for the treatment of the following bacterial infections:
- Ikke hospitalserhvervet lungebetændelse, med undtagelse af svære tilfælde
- Community acquired pneumonia, except severe cases
- Akut bakteriel sinuitis (adækvat diagnosticeret)
- Acute bacterial sinusitis (adequately diagnosed)
- Mild til moderat bækkenbetændelse (dvs. infektioner i de øvre genitialier hos kvinder, herunder
- Mild to moderate pelvic inflammatory disease (i. e. infections of female upper genital tract,
salpingitis og endometritis, uden en ledsagende abscess i æggestokkene eller bækkenet.
including salpingitis and endometritis), without an associated tubo-ovarian or pelvic abscess.
4. 4 og 5. 1)
[Invented name] 400 mg film-coated tablets are not recommended for use in monotherapy of mild to moderate pelvic inflammatory disease but should be given in combination with another appropriate antibacterial agent (e. g. a cephalosporin) due to increasing moxifloxacin resistance of Neisseria gonorrhoeae unless moxifloxacin-resistant Neisseria gonorrhoeae can be excluded (see sections 4.4 and 5.1).
5. 2 for detaljer).
Renal/ hepatic impairment No adjustment of dosage is required in patients with mild to severely impaired renal function or in patients on chronic dialysis i. e. haemodialysis and continuous ambulatory peritoneal dialysis (see section 5.2 for more details).
4. 3).
There is insufficient data in patients with impaired liver function (see section 4.3).
Børn og unge Moxifloxacin er kontraindiceret til børn samt unge (< 18 år).
Children and adolescents Moxifloxacin is contraindicated in children and adolescents (< 18 years).
4. 3).
Efficacy and safety of moxifloxacin in children and adolescents have not been established (see section 4.3).
Administration Tabletten skal synkes hel med tilstrækkelig mængde væske og kan indtages uafhængigt af måltider.
Method of administration The film-coated tablet should be swallowed whole with sufficient liquid and may be taken independent of meals.
Behandlingsvarighed Følgende behandlingsvarighed anbefales for [Lægemidlets navn] 400 mg filmovertrukne tabletter:
Duration of administration [Invented name] 400 mg film-coated tablets should be used for the following treatment durations:
- Akut forværring af kronisk bronkitis:
- Acute exacerbation of chronic bronchitis
5- 10 dage
5 - 10 days - days
- Ikke hospitalserhvervet lungebetændelse:
Community acquired pneumonia
10 dage
10
7 dage
Acute sinusitis 7 days
- Mild til moderat bækkenbetændelse:
Mild to moderate pelvic inflammatory disease
I kliniske studier har man undersøgt behandling med [Lægemidlets navn] 400 mg filmovertrukne tabletter i op til 14 dage.
10 [Invented name] 400 mg film-coated tablets have been studied in clinical trials for up to 14 days treatment.
11 4. 3 Kontraindikationer
4.3 Contraindications
- Overfølsomhed over for moxifloxacin, andre quinoloner eller over for et eller flere af
- Hypersensitivity to moxifloxacin, other quinolones or to any of the excipients.
4. 6).
- Pregnancy and lactation (see section 4.6).
- Patienter med tidligere tendo- sygdom / - lidelse relateret til quinolonbehandling.
- Patients with a history of tendon disease/ disorder related to quinolone treatment.
Både i prækliniske undersøgelser og i humane undersøgelser med moxifloxacin, er der observeret ændringer i hjertets elektrofysiologi i form af QT- forlængelse.
Both in preclinical investigations and in humans, changes in cardiac electrophysiology have been observed following exposure to moxifloxacin, in the form of QT prolongation.
Af sikkerhedshensyn er moxifloxacin derfor kontraindiceret til patienter med:
For reasons of drug safety, moxifloxacin is therefore contraindicated in patients with:
- medfødt eller erkendt erhvervet QT- forlængelse
- Congenital or documented acquired QT prolongation
- elektrolytforstyrrelser, specielt ukorrigeret hypokaliæmi
- Electrolyte disturbances, particularly in uncorrected hypokalaemia
- klinisk relevant bradykardi
- Clinically relevant bradycardia
- klinisk relevant hjertesvigt med nedsat venstre ventrikulær uddrivningsfraktion
- Clinically relevant heart failure with reduced left-ventricular ejection fraction
- tidligere anamnese med symptomatisk arytmi
- Previous history of symptomatic arrhythmias
4. 5).
Moxifloxacin should not be used concurrently with other drugs that prolong the QT interval (see also section 4.5).
Grundet begrænsede kliniske data er moxifloxacin også kontraindiceret til patienter med nedsat leverfunktion (Child- Pugh C) og til patienter med en stigning i transaminasen til mere end 5 gange øvre normalværdi (ULN).
Due to limited clinical data, moxifloxacin is also contraindicated in patients with impaired liver function (Child Pugh C) and in patients with transaminases increase > 5fold ULN.
- Overfølsomhedsreaktioner og allergiske reaktioner er blevet indberettet for fluoroquinoloner
- Hypersensitivity and allergic reactions have been reported for fluoroquinolones including
herunder moxifloxacin efter første administration.
moxifloxacin after first administration.
I disse tilfælde bør moxifloxacin seponeres og egnet behandling iværksættes (f. eks. behandling af shock).
In these cases moxifloxacin should be discontinued and suitable treatment (e. g. treatment for shock) initiated.
- Moxifloxacin har vist sig at kunne forlænge QTc- intervallet på elektrokardiogrammet hos nogle
- Moxifloxacin has been shown to prolong the QTc interval on the electrocardiogram in some
patienter.
patients.
Ved analyse af EKG’ er fra det kliniske undersøgelsesprogram var forlængelsen af QTc med moxifloxacin 6 msek. ± 26 msek.; 1, 4% sammenlignet med udgangsværdien.
In the analysis of ECGs obtained in the clinical trial program, QTc prolongation with moxifloxacin was 6 msec ± 26 msec, 1.4% compared to baseline.
4. 3).
Moxifloxacin should be used with caution in patients with ongoing proarrhythmic conditions, such as acute myocardial ischaemia or QT prolongation as this may lead to an increased risk for ventricular arrhythmias (incl. torsade de pointes) and cardiac arrest (see also section 4.3).
Størrelsen af QT- forlængelsen kan øges med stigende koncentrationer af lægemidlet.
The magnitude of QT prolongation may increase with increasing concentrations of the drug.
Fordelen ved moxifloxacin- behandling, specielt ved mindre alvorlige infektioner, bør vejes op imod informationen i afsnittet om advarsler og forsigtighedsregler.
The benefit of moxifloxacin treatment especially in infections with a low degree of severity should be balanced with the information contained in the warnings and precautions section.
- Tilfælde af fulminant hepatitis, som potentielt kan føre til livstruende leverinsufficiens, er blevet
- Cases of fulminant hepatitis potentially leading to life-threatening liver failure have been
indberettet ved brug af moxifloxacin (se pkt.
reported with moxifloxacin (see section 4.8).
Patienten skal rådes til at kontakte sin læge inden behandlingen fortsættes, hvis tegn og symptomer på fulminant hepatitis udvikler sig, som f. eks. hurtigt udviklende asteni forbundet med gulsot, mørk urin, tendens til blødning eller leverencefalopati.
Patients should be advised to contact their doctor prior to continuing treatment if signs and symptoms of fulminant hepatic disease develop such as rapidly developing asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy.
Test/ undersøgelse af leverfunktionen bør udføres ved tegn på nedsat leverfunktion.
Liver function tests/ investigations should be performed in cases where indications of liver dysfunction occur.
Præparatet bør anvendes med
Use should be with caution in patients with CNS
forsigtighed til patienter med CNS- forstyrrelser, som kan give krampeanfald eller nedsætte krampetærsklen.
disorders which may predispose to seizures or lower the seizure threshold.
- Antibiotikarelateret kolitis (inklusive pseudomembranøs kolitis) er blevet indberettet i
- Antibiotic associated colitis (incl. pseudomembranous colitis) has been reported in association
Det er derfor vigtigt at overveje denne diagnose hos patienter, som udvikler alvorlig diaré under eller efter moxifloxacinbehandlingen.
with the use of broad spectrum antibiotics including moxifloxacin; therefore it is important to consider this diagnosis in patients who develop serious diarrhoea during or after the use of moxifloxacin.
Lægemidler, som hæmmer peristaltikken. er kontraindiceret i denne situation.
Drugs inhibiting peristalsis are contraindicated in this situation.
- Tendinitis og seneruptur kan forekomme ved behandling med quinoloner, herunder
- Tendon inflammation and rupture may occur with quinolone therapy including moxifloxacin,
moxifloxacin, specielt hos ældre patienter og patienter i samtidig behandling med kortikosteroider.
particularly in elderly patients and in those treated concurrently with corticosteroids.
- Ældre patienter med nyresygdomme bør anvende moxifloxacin med forsigtighed, hvis de ikke
- Elderly patients with renal disorders should use moxifloxacin with caution if they are unable to
kan opretholde et tilstrækkeligt væskeindtag, da dehydrering kan øge risikoen for nyresvigt.
maintain adequate fluid intake, because dehydration may increase the risk of renal failure.
- Hvis synet bliver nedsat, eller der opleves anden påvirkning af øjet, skal en øjenspecialist
- If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should
konsulteres med det samme.
be consulted immediately.
Studier
However, studies
har dog vist, at moxifloxacin har lav risiko for at inducere fotosensitivitet.
have shown that moxifloxacin has a lower risk to induce photosensitivity.
Ikke desto mindre bør patienter anbefales ikke at udsætte sig for UV- bestråling eller omfattende og/ eller stærkt sollys under behandling med moxifloxacin.
Nevertheless patients should be advised to avoid exposure to either UV irradiation or extensive and/ or strong sunlight during treatment with moxifloxacin.
- Patienter med kendt familiær disposition for eller erkendt glucose- 6- fosfat dehydrogenase -
- Patients with a family history of, or actual glucose-6-phosphate dehydrogenase deficiency are
mangel, har tendens til hæmolytiske reaktioner, når de behandles med quinoloner.
prone to haemolytic reactions when treated with quinolones.
- Patienter med sjælden arvelig galactoseintoleransforstyrrelse, Lapp laktasemangel eller med
- Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or
glucose- galactosemalabsorption bør ikke indtage dette lægemiddel.
glucose-galactose malabsorption should not take this medicine.
- [Lægemidlets navn] 400 mg filmovertrukne tabletter bør ikke anvendes til patienter med
or pelvic abscess), for whom an intravenous treatment is considered necessary, treatment with [Invented name] 400 mg film-coated tablets is not recommended.
kompliceret bækkenbetændelse (f. eks. forbundet med abscess i æggestokkene eller bækkenet), hvor intravenøs behandling skønnes nødvendig.
- Pelvic inflammatory disease may be caused by fluoroquinolone resistant Neisseria
I sådanne
gonorrhoeae.
tilfælde skal empirisk moxifloxacin derfor gives sammen med et andet passende antiboitikum (f. eks. cephalosporin), med mindre moxifloxacin- resistent Neisseria gonorrhoeae kan udelukkes.
Therefore in such cases empirical moxifloxacin should be co-administered with another appropriate antibiotic (e. g. a cephalosporin) unless moxifloxacin-resistant Neisseria gonorrhoeae can be excluded.
4. 3.) på
- Due to adverse effects on the cartilage in juvenile animals (see section 5.3) the use of
5. 3).
moxifloxacin in children and adolescents < 18 years is contraindicated (see section 4.3).
5. 1 Farmakodynamiske egenskaber
Pharmacotherapeutic group:
Virkningsmekanisme Moxifloxacin er in vitro- aktiv mod et bredt spektrum af grampositive og gramnegative patogene organismer.
Mechanism of action Moxifloxacin has in vitro activity against a wide range of Gram-positive and Gram-negative pathogens.
Den baktericide effekt af moxifloxacin fremkommer ved hæmning afbegge type II - topoisomeraser (DNA- gyrase og topoisomerase IV), som er nødvendig for bakteriel DNA - replikation, - transskription og - reparation.
The bactericidal action of moxifloxacin results from the inhibition of both type II topoisomerases (DNA gyrase and topoisomerase IV) required for bacterial DNA replication, transcription and repair.
C8- methoxy- gruppen synes at bidrage til en øget aktivitet og lav selektion af resistente mutanter af grampositive bakterier sammenlignet med C8- H- gruppen.
It appears that the C8-methoxy moiety contributes to enhanced activity and lower selection of resistant
Tilstedeværelsen af den rumlige bicycloaminsubstituent i position C- 7 forhindrer aktiv udstrømning forbundet med nor- A - eller pmr- A - generne set i visse grampositive bakterier.
The presence of the bulky bicycloamine substituent at the C-7 position prevents active efflux, associated with the norA or pmrA genes seen in certain Gram-positive bacteria.
Interferens med dyrkningsdiagnostik Behandling med moxifloxacin kan give falsk negativt dyrkningsresultat for Mycobacterium spp. ved undertrykkelse af mycobacteriel vækst.
Interference with culture test Moxifloxacin therapy may give false negative culture results for Mycobacterium spp. by suppression of mycobacterial growth.
13 Effekt på tarmfloraen hos mennesker Følgende forandringer blev observeret i tarmfloraen hos frivillige forsøgspersoner efter oral administration af moxifloxacin:
Effect on the intestinal flora in humans The following changes in the intestinal flora were seen in volunteers following oral administration of moxifloxacin:
Escherichia coli, Bacillus spp., Enterococcus spp., og Klebsiella spp. blev reduceret, ligesom de anaerobe Bacteroides vulgatus, Bifidobacterium spp., Eubacterium spp. og Peptostreptococcus spp..
Escherichia coli, Bacillus spp., Enterococcus spp., and Klebsiella spp. were reduced, as were the anaerobes Bacteroides vulgatus, Bifidobacterium spp., Eubacterium spp., and Peptostreptococcus spp..
For Bacteroides fragilis observeredes en stigning.
For Bacteroides fragilis there was an increase.
Resistensmekanisme Resistensmekanismer, som inaktiverer penicilliner, cephalosporiner, aminoglykosider, makrolider og tetracykliner, påvirker ikke moxifloxacins antibakterielle aktivitet.
Mechanism of resistance Resistance mechanisms that inactivate penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines do not interfere with the antibacterial activity of moxifloxacin.
In vitro- resistens mod moxifloxacin udvikles langsomt via trinvise processer medieret af target- site - mutationer i begge type II topoisomeraser, DNA gyrase og topoisomerase IV.
In vitro resistance to moxifloxacin is acquired through a stepwise process by target site mutations in both type II topoisomerases, DNA gyrase and topoisomerase IV.
Moxifloxacin er et dårligt substrat for aktiv effluks- mekanismer i Grampositive organismer.
Moxifloxacin is a poor substrate for active efflux mechanisms in Gram-positive organisms.
In vitro- følsomhedsdata
In vitro Susceptibility Data
EUCAST clinical MIC breakpoints for moxifloxacin (31. 01. 2006):
EUCAST clinical MIC breakpoints for moxifloxacin (31.01.2006):
Organisme Staphylococcus spp.
Organism Staphylococcus spp.
S. pneumoniae Streptococcus gruppe A, B, C, G H. influenzae og M. catarrhalis Enterobacteriaceae Ikke- artsrelateret brydningspunkt * ≤
S. pneumoniae Streptococcus Groups A, B, C, G H. influenzae and M. catarrhalis Enterobacteriaceae Non-species related breakpoints* * Non-species related breakpoints have been determined
Følsomhed ≤ 0. 5 mg/ l ≤ 0. 5 mg/ l ≤ 0. 5 mg/ l ≤ 0. 5 mg/ l ≤ 0. 5 mg/ l 0. 5 mg/ l
≤ 0.5 mg/ l ≤ 0.5 mg/ l ≤ 0.5 mg/ l ≤ 0.5 mg/ l ≤ 0.5 mg/ l mainly on the basis of