natgillin/translations-raw huggingface dataset:
Dette sammendrag blev sidst ajourført i 07- 2007.
This summary was last updated in 07-2007.
EMEA’ s procedurenr.
EMEA Procedure number
Indgivelsesvej
Route of administration Packaging
Paknings - størrelse
Package size
salve salve salve salve
Ointment Ointment Ointment Ointment
Brev (alu) Tube (alu) Tube (alu) Tube (alu)
Cutaneous use Sachet (alu) Cutaneous use Tube (alu) Cutaneous use Tube (alu) Cutaneous use Tube (alu)
0, 5 g 5g 10 g 15 g
0.5g 5g 10g 15g
12 breve 1 tube 1 tube 1 tube
12 sachets 1 tube 1 tube 1 tube
PRODUKTRESUME 1.
1 1.
Altargo 1% salve.
Altargo 1% ointment
1 g indeholder 10 mg retapamulin (1% w/ w).
1 g contains 10 mg retapamulin (1% w/ w).
Salve.
Ointment
Jævn, let gullig salve.
Smooth, off-white ointment.
Korttidsbehandling af følgende overfladiske hudinfektioner:
Short term treatment of the following superficial skin infections:
5. 1.
See sections 4.4 and 5.1 for important information regarding the clinical activity of retapamulin against different types of Staphylococcus aureus.
Der bør tages hensyn til officielle guidelines om hensigtsmæssig brug af antibakterielle midler.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Voksne (18- 65 år), unge (12- 17 år), spædbørn og børn (9 måneder - 11 år).
The area treated may be covered with sterile bandage or gauze dressing.
Et tyndt lag salve appliceres på det angrebne område 2 gang dagligt i 5 dage.
Safety and efficacy have not been established in the following:
Det behandlede område kan dækkes af steril bandage eller gazeforbinding.
• Impetiginous lesions > 10 in number and exceeding 100 cm2 in total surface area.
Sikkerhed og effekt er ikke klarlagt ved: • Impetigo- læsioner > 10 i antal og med et totalt overfladeareal på mere end 100 cm2. • Inficerede læsioner over 10 cm i længden eller med et totalt overfladeareal > 100 cm2.
• Infected lesions that exceed 10 cm in length or a total surface area > 100 cm2.
Hos patienter under 18 år må det behandlede områdes totale overfladeareal ikke overskride 2% af legemsoverfladen.
In patients aged less than 18 years the total surface area treated should be no more than 2% of the body surface area.
4. 4).
2 Patients not showing a clinical response within two to three days should be re-evaluated and alternative therapy should be considered (see section 4.4).
Spædbørn under 9 måneder.
Infants under nine months of age
Retapamulin salve bør ikke anvendes til spædbørn under 9 måneder pga. manglende dokumentation for sikkerhed og effekt.
The safety and efficacy of retapamulin ointment has not been established in paediatric patients less than nine months of age.
2 Ældre (over 65 år) Dosisjustering ikke nødvendigt.
Elderly (aged 65 and older)
Nedsat nyrefunktion Dosisjustering ikke nødvendigt.
No dosage adjustment is necessary.
Se pkt.
No dosage adjustment is necessary.
5. 3.
See section 5.3.
Nedsat leverfunktion Dosisjustering ikke nødvendigt.
No dosage adjustment is necessary.
Overfølsomhed over for det aktive stof retapamulin eller over for et eller flere af hjælpestofferne.
Known or suspected hypersensitivity to retapamulin or to the excipient.
I tilfælde af sensibilisering eller alvorlig lokal irritation ved brug af retapamulin salve skal behandlingen afbrydes, salven vaskes omhyggelig af og passende alternativ behandling af infektionen påbegyndes.
In the event of a sensitisation or severe local irritation from the use of retapamulin ointment, treatment should be discontinued, the ointment carefully wiped off, and appropriate alternative therapy for the infection instituted.
Undgå at indtage produktet.
Care must be taken to avoid ingestion.
5. 1).
Retapamulin should not be used to treat infections known or thought likely to be due to MRSA (see section 5.1).
Kliniske studier af åbne, sekundært inficerede sår viste utilstrækkelig virkning af retapamulin hos patienter, der var inficerede med methicillin- resistente Staphylococcus aureus (MRSA).
In clinical studies of secondarily infected open wounds, the efficacy of retapamulin was inadequate in patients with infections caused by methicillin-resistant Staphylococcus aureus (MRSA).
Årsagen til den reducerede virkning, der blev observeret hos disse patienter er ukendt.
The reason for the reduced clinical efficacy observed in these patients is unknown.
Hvis der ikke ses forbedringer, eller hvis infektionen forværres efter 2- 3 dages behandling, bør man overveje alternativ behandling.
Alternative therapy should be considered if there is no improvement or a worsening in the infected area after 2-3 days of treatment.
Retapamulin salve indeholder butylhydroxytoluen, som kan give lokalt hududslæt (f. eks. kontakteksem) eller irritation af øjne og slimhinder.
Retapamulin ointment contains butylated hydroxytoluene, which may cause local skin reaction (e. g. contact dermatitis), or irritation to the eyes and mucous membranes.
I lighed med andre antibakterielle produkter kan længere tids anvendelse af retapamulin resultere i vækst af ikke- følsomme mikroorganismer, inklusive svampe.
As with other antibacterial agents, prolonged use of retapamulin may result in overgrowth of non-susceptible micro-organisms, including fungi.
Effekten ved samtidig administration af retapamulin og andre produkter til kutan anvendelse på samme hudområde er ikke undersøgt og kan ikke anbefales.
The effect of concurrent application of retapamulin and other topical products to the same area of skin has not been studied, and is not recommended.
I humane levermikrosomer er retapamulin en stærk hæmmer af CYP3A4.
3 In human liver microsomes, retapamulin was a strong inhibitor of CYP3A4.
5. 2).
Based on the low plasma concentration achieved in humans after topical application to abraded skin or infected superficial wounds, a clinically relevant inhibition is not expected in vivo (see section 5.2)
Ved samtidig administration af oral ketoconazol 200 mg 2 gange dagligt og retapamulin salve 1% på skadet hud blev retapamulins gennemsnitlige AUC( 0- 24) og Cmax øget med 81% hos voksne, raske mænd.
Co-administration of oral ketoconazole 200mg twice daily increased mean retapamulin AUC(0-24) and Cmax by 81% after topical application of retapamulin 1% ointment on the abraded skin of healthy adult males.
På grund af den lave systemiske optagelse efter kutan anvendelse er det ikke nødvendigt at justere dosis, når retapamulin påføres huden ved samtidig systemisk behandling med CYP3A4 - hæmmere.
Due to low systemic exposure following topical application in patients, dosage adjustments are considered to be unnecessary when topical retapamulin is applied during systemic treatment with CYP3A4 inhibitors.
Graviditet Der foreligger ingen kliniske data om eksponering for retapamulin under graviditet.
Pregnancy No clinical data on exposed pregnancies are available.
5. 3).
Animal studies have shown reproductive toxicity after oral administration and are insufficient with respect to effects on parturition and fetal/ postnatal development (see Section 5.3).
Brugen af retapamulin salve er at foretrække frem for systemisk antibakteriel behandling.
Retapamulin ointment should only be used in pregnancy when topical antibacterial therapy is clearly indicated and the use of retapamulin is considered to be preferable to administration of a systemic antibacterial agent.
Amning Det er uvist, om retapamulin udskilles i modermælken.
Lactation It is unknown whether retapamulin is excreted in human breast milk.
En beslutning om at fortsætte/ stoppe amning eller fortsætte/ stoppe behandling med Altargo bør afveje barnets fordele ved amningen med kvindens fordele ved behandlingen med Altargo.
A decision on whether to continue/ discontinue breast-feeding or to continue/ discontinue therapy with Altargo should be made taking into account the benefit of breast-feeding to the child and the benefit of Altargo therapy to the woman.
Da Altargo er til kutan anvendelse, er det usandsynligt, at det har virkning på evnen til at føre motorkøretøj eller betjene maskiner.
Altargo is administered topically and is unlikely to have an effect on the ability to drive or use machines.
1% af patienterne.
In clinical studies in which 2150 patients with superficial skin infections applied Altargo, the most commonly reported adverse reaction was application site irritation, which affected approximately 1% of patients.
(≥ 1/ 100 og < 1/ 10) (≥ 1/ 1000 og < 1/ 100)
> 1/ 100 to< 1/10 > 1/1000 to< 1/100
Systemorganklasse Almene symptomer og reaktioner på administrationsstedet
General disorders and administration site conditions
Almindelig Reaktioner på applikationsstedet
Application site reactions
Ikke almindelig Reaktioner på applikationsstedet
Application site reactions
Irritation
Irritation
Smerter Hudkløe Erytem
Pain Pruritus Erythema
Kontakteksem
Contact dermatitis
4 4. 9 Overdosering
4.9 Overdose
Der bør gives symptomatisk behandling ved tegn og symptomer på overdosering efter kutan anvendelse, eller hvis retapamulin- salve indtages ved et uheld.
Any signs or symptoms of overdose, either topically or by accidental ingestion, should be treated symptomatically.
Hudmidler, ATC- kode:
Dermatologicals
Dette site adskiller sig fra de sites, som andre ikke- pleuromutilin antibakterielle midler, der virker ved at interagere med ribosomet, binder sig til.
Retapamulin selectively inhibits bacterial protein synthesis by interacting at a unique site on the 50S subunit of the bacterial ribosome that is distinct from the binding sites of other non- pleuromutilin antibacterial agents that interact with the ribosome.
Data indikerer, at bindingen sker til det ribosomale protein L3, og at bindingsstedet er i området af ribosomets P- site og peptidyl transferasecenter.
Data indicate that the binding site involves ribosomal protein L3 and is in the region of the ribosomal P site and peptidyl transferase centre.
Ved at binde til dette site hæmmer pleuromutilin peptidyl transfer, blokerer P- site- interaktioner og forhindrer den normale funktion af ribosomets aktive 50S- del.
By virtue of binding to this site, pleuromutilins inhibit peptidyl transfer, partially block P-site interactions, and prevent normal formation of active 50S ribosomal subunits.
Det lader derfor til, at pleuromutilin hæmmer bakteriernes proteinsyntese gennem forskellige mekanismer.
Therefore the pleuromutilins appear to inhibit bacterial protein synthesis by multiple mechanisms.
Retapamulin er fortrinsvis bakteriostatiske mod S. aureus og S. pyogenes.
Retapamulin is predominantly bacteriostatic against S. aureus and S. pyogenes.
Resistensmekanisme
Mechanism of Resistance
På grund af retapamulins særlige virkemekanisme er der ikke vist specifik krydsresistens med andre klasser af antibakterielle midler.
Due to its distinct mechanism of action, retapamulin does not demonstrate target specific cross-resistance with other classes of antibacterial agents.
In vitro er der identificeret to mekanismer, hvorved følsomheden over for retapamulin reduceres.
In vitro, two mechanisms have been identified which reduce susceptibility to retapamulin.
Den ene mekaniske skyldes en mutation i det ribosomale protein L3, mens den anden er en non- specifik efflux- mekanisme (ABC transporter vgaAv).
One involves mutations in ribosomal protein L3, the other is a non- specific efflux mechanism (ABC transporter vgaAv).
Det er også vist, at denne non- specifikke efflux mekanisme reducerer in vitro- aktiviteten af streptogramin A.
This non-target specific efflux mechanism has also been demonstrated to reduce the in vitro activity of streptogramin A.
Alle kliniske isolater blev hæmmet ved retapamulinkoncentrationer på ≤ 2µg/ ml.
5 No development of resistance was observed during treatment with retapamulin in the clinical study programme and all clinical isolates were inhibited by retapamulin concentrations of < 2µg/ ml.
Specielt ved behandling af alvorlige infektioner bør man indhente lokal information on resistens.
The prevalence of acquired resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections.
I tilfælde, hvor den lokale prævalens af resistens tyder på, at præparatets virkning ved nogle typer af infektioner er tvivlsom, bør den behandlende læge søge ekspertrådgivning.
As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infection is questionable.
5 Almindeligvis følsomme organismer Staphylococcus aureus* $Streptococcus pyogenes * Streptococcus agalactiae Organismer med erhvervet resistens Enterobacteriaceae Pseudomonas aeruginosa Enterococcus faecalis $In vitro var retapamulin lige aktiv mod methicillin- følsomme og methicillin- resistente stammer af S. aureus.
$In vitro, retapamulin was equally active against methicillin-susceptible and methicillin- resistant strains of S. aureus.
4. 4 og nedenstående med hensyn til den kliniske effekt mod MRSA.
However, see section 4.4 and below regarding clinical efficacy against MRSA.
Information fra kliniske studier
Information from clinical trials
Kun få MRSA blev isoleret ved studier med impetigo og alle var kliniske succeser (100%:
Very few MRSA were isolated in studies in impetigo and all were clinical successes (100%:
I studier med impetigo og i to studier med sekundært åbne, inficerede sår (SIOW), var den kliniske succesrate høj for retapamulin hos patienter med mupirocin- resistente S. aureus (100%:
In studies in impetigo and in two studies of secondarily infected open wounds (SIOW), clinical success rates were high for retapamulin in patients with mupirocin-resistant S. aureus (100%:
11/ 11) eller fusidinsyre- resistente S. aureus (96, 7% 29/ 30).
29/ 30).
De to studier, der omfattede patienter med SIOW, viste dog en utilstrækkelig effekt af retapamulin ved infektioner forårsaget af MRSA (75, 7%).
However, in the two studies that enrolled patients with SIOW the efficacy of retapamulin in infections due to MRSA was inadequate (75.7%).
In vitro blev der ikke observeret forskelle i aktiviteten af retapamulin mod S. aureus, uanset om isolaterne var methicillin- følsomme eller methicillin - resistente.
No differences were observed in the in vitro activity of retapamulin versus S. aureus whether the isolates were susceptible or resistant to methicillin.
Årsagen til den mindre kliniske effekt mod MRSA ved SIOW er ukendt, men kan muligvis skyldes tilstedeværelsen af en speciel MRSA- klon.
The explanation for lower clinical efficacy against MRSA in SIOW is unclear and it may have been influenced by the presence of a particular MRSA clone.
Panton- Valentine Leukocidin) i betragtning.
In the case of treatment failure associated with S. aureus, the presence of strains possessing additional virulence factors (such as Panton-Valentine Leukocidin) should be considered.
Klinisk succesrate ved opfølgning af SIOW- patienter med S. aureus
6 Clinical Success Rates at Follow up for SIOW patients with S. aureus
Fænotype /
Phenotype/ PFGE
Retapamulin
RETAPAMULIN
Cephalexin
Cephalexin
PFGE- type
type
Success - rate (%)
Success 95% Exact n/ N
95% Exact CI
n/ N Success 95% Exact n/ N
n/ N
CI
Success - rate (%)
Rate (%)
S. aureus (alle) MRSA$ MSSA
S. aureus (all) MRSA $MSSA
88, 9 75, 7 90, 4
88.9 75.7 90.4
(85, 3, 91, 9) (58, 8, 88, 2) (86, 7, 93, 3)
(85.3,91.9) (58.8,88.2) (86.7,93.3)
155/ 186 21/ 26 133/ 159
155/ 186 21/ 26 133/ 159
Konfidensinterval.
CI: confidence interval.
Responsraten for MRSA på grund af PVL+MRSA var 8/ 13 (62%).
Exact CI is calculated using the F-distribution method. $: the response rate for MRSA due to PVL+ MRSA was 8/ 13 (62%)
I et studie af raske voksne personer blev retapamulin salve 1% påført dagligt på ubeskadiget hud og på skadet hud under okklusion i op til 7 dage.
In a study of healthy adult subjects, 1% retapamulin ointment was applied daily to intact and to abraded skin under occlusion for up to 7 days.
Den maksimale individuelle systemiske eksponering (Cmax) blev målt til 22, 1 ng/ ml.
The geometric mean Cmax value in plasma after application to 200 cm2 of abraded skin was 9.75 ng/ ml on day 1 and 8.79 ng/ ml on day 7 and the maximum individual systemic exposure (Cmax) recorded was 22.1 ng/ ml.
6 En plasmaprøve blev indhentet fra hver af de 516 voksne og børn, der modtog kutan behandling med retapamulin salve 1% 2 gange dagligt i 5 dage for behandling af sekundært inficerede traumatiske læsioner.
Single plasma samples were obtained from 516 adult and paediatric patients who received topical treatment with retapamulin 1% ointment twice daily for 5 days for the treatment of secondarily infected traumatic lesions.
Prøverne blev taget før administration hos voksne på dag 3 eller 4 og mellem 0- 12 timer efter sidste påsmøring hos børn på dag 3 eller 4.
Sampling occurred pre-dose for adult subjects on days 3 or 4, and between 0-12 hours after the last application for paediatric subjects on days 3 or 4.
Størstedelen af prøverne (89%) lå under kvantiseringsgrænsen (0, 5 ng/ ml).
The majority of samples (89%) were below the lower limit of quantitation (0.5 ng/ ml).
Af de prøver, hvor det var muligt at måle koncentrationen, havde 90% en retapamulinkoncentration på under 2, 5 ng/ ml.
Of the samples that had measurable concentrations 90% had retapamulin concentrations less than 2.5 ng/ ml.
Den maksimale målte plasmakoncentration af retapamulin var 10, 7 ng/ ml hos voksne og 18, 5 ng/ ml hos børn.
The maximum measured plasma concentration of retapamulin was 10.7 ng/ ml in adults and 18.5 ng/ ml in paediatric patients.
Distribution
Distribution
In vitro er retapamulin vist at være substrat og hæmmer af P- glycoprotein (Pgp).
In vitro, retapamulin was shown to be a P-glycoprotein (Pgp) substrate and inhibitor.
Den maksimale systemiske eksponering i mennesker efter kutan anvendelse af salve 1% på 200 cm2 skadet hud (Cmax = 22 ng/ ml; AUC( 0- 24) = 238 ng* h/ ml) var dog 660 gange lavere end retapamulins IC50 for Pgp- hæmning.
However, the maximum individual systemic exposure in humans following topical application of 1% ointment on 200 cm2 of abraded skin (Cmax= 22 ng/ ml; AUC(0-24) = 238 ng. h/ ml) was 660-fold lower than the retapamulin IC50 for Pgp inhibition.
94% bundet til humane plasmaproteiner.
Retapamulin is approximately 94% bound to human plasma proteins.
4. 5).
The in vitro oxidative metabolism of retapamulin in human liver microsomes was primarily mediated by CYP3A4 with minor contributions from CYP2C8 and CYP2D6 (see section 4.5).
Elimination
Elimination
Specielle patientpopulationer
7 Special Patient Populations
Ingen farmakokinetiske data er tilgængelig for børn under 2 år eller for patienter med nedsat nyre - eller leverfunktion.
No pharmacokinetic data are available in children aged less than 2 years, or in patients with renal or hepatic impairment.
På grund af de lave systemiske plasmaniveauer regnes der ikke med sikkerhedsproblemer af nogen art.
However, due to the low systemic plasma levels that have been observed, no safety problems are foreseen.
I 14 dages (50, 150, 450 mg/ kg) orale toksicitetsstudier af rotter var der tegn på adaptive lever - og thyroidforandringer.
In 14-day (50, 150 or 450 mg/ kg) oral toxicity studies in rats there was evidence of adaptive hepatic and thyroid changes.
Hos aber, der blev doseret oralt (50, 150, 450 mg/ kg) i 14 dage var der dosis- relaterede opkastninger.
In monkeys dosed orally (50, 150 or 450 mg/ kg) for 14 days there was dose-related emesis.
Dette gælder både vurdering in vitro for genmutation og/ eller kromosomal effekter i en muselymfomcelletest, i dyrkede humane perifere lymfocytter såvel som vurdering in vivo for kromosomale effekter i en mikronukleustest udført i rotter.
There was no evidence of genotoxicity when evaluated in vitro for gene mutation and/ or chromosomal effects in the mouse lymphoma cell assay, in cultured human peripheral blood lymphocytes, or when evaluated in vivo for chromosomal effects in a rat micronucleus test.
7 Der var ikke tegn på svækket fertilitet hos han - eller hunrotter efter oral administration af 50, 150 eller 450 mg/ kg/ dag, hvilket resulterede i en eksponeringsmargin på optil 5 gange den højeste, estimerede humane eksponering (kutan anvendelse på 200 cm2 skadet hud:
There was no evidence of impaired fertility in male or female rats at oral doses of 50, 150, or 450 mg/ kg/ day, resulting in exposure margins of up to 5-times the highest human estimated exposure (topical application to 200 cm2 abraded skin:
AUC 238 ng* h* ml).
AUC 238 ng. h/ ml).
Et embryotoksicitetsstudie af rotter viste udviklingstoksicitet (nedsat fosterkropsvægt og forsinket skeletal ossifikation) og maternal toksicitet efter orale doser på ≥ 150 mg/ kg/ dag (svarende til ≥ 3 gange den estimerede humane eksponering (se ovenstående)).
In an embryotoxicity study in rats, developmental toxicity (decreased fetal body weight and delayed skeletal ossification) and maternal toxicity were observed at oral doses of ≥ 150 mg/ kg/ day (corresponding to ≥ 3 times the human estimated exposure (see above).
Der var ingen behandlingsrelaterede malformationer hos rotter.
There were no treatment-related malformations in rats.
Maternal toksicitet blev vist ved dosering ≥ 7, 2 mg/ kg/ dag svarende til ≥ 8 gange den estimerede humane eksponering (se ovenstående).
Maternal toxicity was demonstrated at dosages of ≥ 7.2 mg/ kg/ day corresponding to ≥ 8 times the estimated human exposure (see above).
Der var ingen behandlingsrelateret effekt på embryoets/ fostrets udvikling.
There was no treatment-related effect on embryo-fetal development.
Ingen studier har evalueret effekten af retapamulin på den præ - / postnatale udvikling.
No studies to evaluate effects of retapamulin on pre-/ postnatal development were performed.
Der var derimod ingen systemisk effekt hos unge rotter efter påsmøring af retapamulin salve.
However, there were no systemic effects on juvenile rats with topical application of retapamulin ointment.
Hvid blød paraffin Butylhydroxytoluen
Butylated hydroxytoluene
6. 3 Opbevaringstid
8 6.3 Shelf life
Åbnet:
In-use:
Må ikke opbevares over 25 oC.
Do not store above 25°C.
0, 5 g brev af aluminiumsfolie.
0.5 g aluminium foil sachet.
Æske med 12 breve.
Carton of 12 sachets.
Aluminiumstube med plastik skruelåg indeholdende 5g, 10g eller 15g.
5 g, 10 g and 15 g aluminium tubes with a plastic screw cap.
Æske med 1 tube.
Carton of 1 tube.
Glaxo Group Ltd Glaxo Wellcome House Berkeley Avenue, Greenford Middlesex UB6 0NN United Kingdom
Glaxo Group Ltd Glaxo Wellcome House Berkeley Avenue Greenford Middlesex UB6 0NN United Kingdom
DATO FOR FØRSTE MARKEDSFØRINGSTILLADELSE
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION
Yderligere information om dette lægemiddel er tilgængelig på Det europæiske Lægemiddelagenturs (EMEAs) hjemmeside http: // www. emea. europa. eu /
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: http: / /www. emea. europa. eu/.
(trdg as Glaxo Wellcome Operations) Harmire Road Barnard Castle Durham, DL12 8DT United Kingdom
(trdg as Glaxo Wellcome Operations) Harmire Road Barnard Castle Durham, DL12 8DT United Kingdom
Indehaveren af markedsføringstilladelsen skal sikre, at pharmacovigilancesystemet, som beskrevet i Modul 1. 8. 1 i version 6. 2 af ansøgningsmaterialet til markedsføringstilladelsen, er oprettet og fungerer, før produktet frigives på markedet og lige så længe produktet er på markedet.
The MAH must ensure that the system of pharmacovigilance, as described in version 6.2 presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before the product is placed on the market and for as long as the marketed product remains in use.
Risk Management- plan
Risk Management plan