natgillin/translations-raw huggingface dataset:
ris Hos patienter med atopisk dermatitis var bedringen af hudlæsioner under salvebehandling med tacrolimus ledsaget at reduceret Fc receptor expression på Langerhanske celler og en reduktion af
Tacrolimus ointment does not affect collagen synthesis
to deres hyperstimulerende effekt på T- celler.
The efficacy and safety of Protopy was assessed in
Tacrolimus salve har ingen effekt på kollagensyntesen hos mennesker.
than 13,500 patients treated with tacrolimus
au Resultater fra kliniske studier med patienter Effekt og tolerabilitet er blevet undersøgt i mere end 13. 500 patienter behandlet med tacrolimus salve i e fase I til fase III kliniske afprøvninger.
ointment in Phase I to Phase III clinical trials.
Data fra fire større afprøvninger bliver vist her. er I en seks- måneders multicenter, dobbelt- blind, randomiseret afprøvning blev 0, 1% tacrolimus salve administreret 2 gange om dagen til voksne med moderat til svær atopisk dermatitis, og blev ng
In a six-month multicentre double-blind randomised trial, 0.1% tacrolimus ointment was administered no
sammenlignet med lokal kortikosteroid behandling (0, 1% hydrokortison butyrat på kroppen og ekstremiteter og 1% hydrokortison acetat på ansigt og hals).
twice-a-day to adults with moderate to severe atopic dermatitis and compared to a topical corticosteroid based regimen (0.1% hydrocortisone butyrate on trunk and extremities, 1% hydrocortisone acetate on face and neck).
Den primære parameter var respons raten ved måned 3, defineret som delen af patientgruppen med mindst 60% forbedring i mEASI (modified læ
The primary endpoint was the response rate at month 3 ct
Eczema Area and Severity Index) fra baseline til måned 3.
defined as the proportion of patients with at least 60% improvement in the mEASI (modified Eczema Area and Severity Index) between baseline and month 3.
Respons raten i 0, 1% tacrolimus gruppen (71, 6%) var signifikant højere end den i gruppen med lokal kortikosteroid behandling (50, 8%, p < 0, 001; Tabel 1).
group (71.6%) was significantly higher than that in the topical corticosteroid based treatment group (50.8%; p < 0.001; Table 1).
Respons raten ved måned 6 svarede til resultaterne ved måned 3. e kk
The response rates at month 6 were comparable to the 3-month results. ro
Effekt ved måned 3 i
Efficacy at month 3 lp
er
a
kortikosteroidbehandling §
Topical corticosteroid regimen§
Respons rate på ≥ 60% bedring t
(N=485) Response rate of ≥ 60% in
i mEASI (Primær parameter) §§ le
improvement in mEASI (Primary ic
Forbedring ≥ 90% i lægens samlede vurdering id
Endpoint)§§ Improvement ≥ 90% in Physician’ s 28.5% ed
§ Lokal kortikosteroidbehandling = 0, 1% hydrokortison butyrat på krop og ekstremiteter, 1% m
Global Evaluation § Topical corticosteroid regimen = 0.1% hydrocortisone butyrate on trunk and extremities, 1% M
hydrokortison acetat på ansigt og hals. §§ højere værdi = større bedring ge
hydrocortisone acetate on face and neck §§ higher values = greater improvement
Brændende fornemmelse i huden, Læ
The incidence and nature of most adverse events were similar in the two treatment groups.
herpes simplex, alkoholintolerance (facial flushing eller øget hudfølsomhed efter alkoholindtagelse), prikken i huden, hyperæstesi, acne og fungal dermatitis forekom dog hyppigere i tacrolimus gruppen.
Skin burning, herpes simplex, alcohol intolerance (facial flushing or skin sensitivity after alcohol intake), skin tingling, hyperaesthesia, acne and fungal dermatitis occurred more often in the tacrolimus treatment group.
I den anden kliniske afprøvning blev børn i alderen 2 år til 15 år med moderat til svær atopisk dermatitis behandlet 2 gange om dagen i 3 uger med 0, 03% tacrolimus salve 0, 1% tacrolimus salve eller 1% hydrokortison acetat salve.
6 In the second trial, children aged from 2 to 15 years with moderate to severe atopic dermatitis received twice daily treatment for three weeks of 0.03% tacrolimus ointment, 0.1% tacrolimus ointment or 1% hydrocortisone acetate ointment.
Bedring ≥ 90% i lægens samlede 15, 7%
is Improvement ≥ 90% in Physician’ s
s vurdering
48.4%
il § mindre værdier = større positiv effekt
or Global Evaluation § lower values = greater improvement
t et Incidensen af brændende følelse i huden var højere i gruppen der blev behandlet med tacrolimus end i hydrokortison gruppen.
th The incidence of local skin burning was higher in the tacrolimus treatment groups than in the
er gruppen.
au hydrocortisone group.
Der var ingen klinisk relevante ændringer i laboratorieværdier eller i puls og blodtryk i nogen af behandlingsgrupperne.
Pruritus decreased over time in the tacrolimus groups but not in the hydrocortisone group.
ris Formålet med det tredje multicenter, dobbelt- blind, randomiserede studie var at undersøge effekt og
There were no clinically relevant changes in the laboratory values or vital signs in either treatment group throughout the clinical trial.
to tolerabilitet af 0, 03% tacrolimus salve, når denne blev appliceret 1- 2 gange om dagen sammenlignet med administrering af 1% hydrokortison acetat 2 gange om dagen til børn med moderat til svær
er The purpose of the third multicentre, double-blind, randomised study was the assessment of efficacy ng and safety of 0.03% tacrolimus ointment applied once or twice a day relative to twice daily administration of 1% hydrocortisone acetate ointment in children with moderate to severe atopic lo dermatitis.
Behandlingens varighed var i indtil 3 uger.
Treatment duration was for up to three weeks. no
Hydrokortison acetat
Hydrocortisone acetate 1% ct
Tacrolimus 0, 03%
Tacrolimus 0.03% Once daily (N=207)
Tacrolimus 0, 03%
Tacrolimus 0.03% Twice daily (N=210)
En gang om dagen (N=207)
Twice daily (N=207) du
To gange om dagen (N=210)
Median mEASI Percentage Decrease (Primary Endpoint)§ ro
(N = 207)
47.2%
Bedring ≥ 90% i lægens 13, 6%
Improvement ≥ 90% in Physician’ s Global Evaluation lp
e
13.6%
samlede vurdering § højere værdi = større bedring kk
§ higher values = greater improvement a
Den primære parameter var defineret som den procentvise formindskelse af mEASI fra baseline og i
The primary endpoint was defined as the percentage decrease in mEASI from the baseline to end of in
indtil afslutning af behandlingen.
treatment.
0, 03% tacrolimus salve t
A statistically significant better improvement was shown for once daily and twice daily 0.03% tacrolimus ointment compared to twice daily hydrocortisone acetate ointment (p < 0.001 for ic
appliceret 2 gange om dagen var mere effektivt end applikation en gang om dagen Tabel 3). le
both).
Incidensen af brændende følelse i huden var højere i tacrolimus behandlingsgruppen end i id
Twice daily treatment with 0.03% tacrolimus ointment was more effective than once daily ed
hydrokortison gruppen.
administration (Table 3).
Der var ingen klinisk relevante ændringer i laboratorieværdier eller i puls og blodtryk i nogen af grupperne i løbet af studiets. m
The incidence of local skin burning was higher in the tacrolimus treatment groups than in the hydrocortisone group.
I det fjerde studie blev omkring 800 patienter (≥ 2 år gamle) behandlet intermitterende eller ge
M
På Læ
In the fourth trial, approximately 800 patients (aged ≥ 2 years) received 0.1% tacrolimus ointment intermittently or continuously in an open-label, long-term safety study for up to four years, with 300 patients receiving treatment for at least three years and 79 patients receiving treatment for a minimum of 42 months.
basis af ændringerne fra baseline i EASI og arealet af afficeret område havde patienterne, uanset alder, bedring af den atopiske dermatitis ved alle de følgende målinger.
Based on changes from baseline in EASI score and body surface area affected, patients regardless of age had improvement in their atopic dermatitis at all subsequent time points.
De tre mest almindelige bivirkninger, der blev rapporteret, var influenzalignende symptomer (snue, forkølelse, influenza, infektioner i de øvre luftveje o. s. v.) kløe og en brændende fornemmelse i huden.
The three most common adverse events reported were flu-like symptoms (cold, common cold,
Absorption Data fra sunde forsøgspersoner indicerer, at der kun er ringe eller ingen systemisk eksponering af
Absorption Data from healthy human subjects indicate that there is little or no systemic exposure to tacrolimus following single or repeated topical application of tacrolimus ointment.
al Flertallet af de patienter med atopisk dermatitis (voksne og børn), der er blevet behandlet med en enkelt eller med gentagen applikation af tacrolimus salve (0, 03 - 0, 1%), og spædbørn fra 5 måneders
When observed, blood concentrations exceeding
I de tilfælde
is 1.0 ng/ ml were transient.
il man fandt blodkoncentrationer > 1 ng/ ml var disse kun af kort varighed.
Systemic exposure increases with increasing treatment areas.
Den systemiske eksponering
However, both
Men både størrelsen og hastigheden af den lokale absorption falder i takt med, at huden heler.
or the extent and the rate of topical absorption of tacrolimus decrease as the skin heals.
et overflade, er den systemiske eskponering (dvs AUC) af tacrolimus fra Protopy cirka 30- gange mindre
AUC) of tacrolimus
er end hvad man finder ved orale immunosuppressive doser i nyre - og levertransplanterede patienter.
th from Protopy is approximately 30-fold less than that seen with oral immunosuppressive doses in kidney and liver transplant patients.
Det vides ikke hvor lave tacrolimus blodkoncentrationer, der vil kunne give systemisk effekt.
The lowest tacrolimus blood concentration at which systemic
ris Der har ikke været tegn på systemisk akkumulation af tacrolimus i patienter (voksne og børn), der er blevet behandlet med tacrolimus salve i længere perioder (op til 1 år).
There was no evidence of systemic accumulation of tacrolimus in patients (adults and children) treated for prolonged periods (up to one year) with tacrolimus ointment.
Efter lokal applikation af tacrolimus salve, bliver tacrolimus selektivt optaget i huden med minimal diffusion til den systemiske cirkulation. e er Metabolisme ng
er Distribution ng As systemic exposure is low with tacrolimus ointment, the high binding of tacrolimus (> 98.8%) to plasma proteins is considered not to be clinically relevant. lo Following topical application of tacrolimus ointment, tacrolimus is selectively delivered to the skin with minimal diffusion into the systemic circulation. no
Der er ikke tegn på, at tacrolimus metaboliseres af human hud.
Metabolism Metabolism of tacrolimus by human skin was not detectable.
Systemisk tilgængeligt tacrolimus er extensivt metaboliseret i leveren via CYP3A4. læ
Systemically available tacrolimus is ct
Eliminering Efter intravenøs administrering er tacrolimus vist at være et stof med lav clearance.
The ro
Den gennemsnitlige totale clearance fra kroppen er omkring 2, 25 l/ time.
average total body clearance is approximately 2.25 l/ h.
systemisk tilgængeligt tacrolimus kan vær nedsat hos patienter med svær nedsættelse af kk
The hepatic clearance of systemically available tacrolimus could be reduced in subjects with severe hepatic impairment, or in subjects who are co- lp
leverfunktionen, eller ved samtidig behandling med lægemidler, der er potente inhibitorer af CYP3A4.
treated with drugs that are potent inhibitors of CYP3A4.
Efter gentagen lokal applikation af salven, beregnede man halveringstiden til 75 timer for voksne og i
Following repeated topical application of the ointment the average half-life of tacrolimus was estimated to be 75 hours for adults and 65 hours for children. a in
Prækliniske sikkerhedsdata t le
5.3 Preclinical safety data ic
Kronisk toksicitet og lokal tolerabilitet Gentagen lokal administrering af enten tacrolimus salve eller af salvegrundlag til rotter, kaniner og id
Repeated dose toxicity and local tolerance ed
Langtids lokalbehandling af rotter med tacrolimus salve medførte systemisk toksicitet med m
M
Forandringerne skyldtes kraftig ge
Long-term topical treatment of rats with tacrolimus led to systemic toxicity including alterations of kidneys, pancreas, eyes and nervous system.
systemisk eksponering i gnavere på grund af udtalt transdermal absorption af tacrolimus.
The changes were caused by high systemic exposure of rodents resulting from high transdermal absorption of tacrolimus.
Læ
Slightly lower body weight gain in females was the only systemic change observed in micropigs at high ointment concentrations (3%).
8 Carcinogenicitet Systemiske carcinogenicitets undersøgelser i mus (18 måneder) og rotter (24 måneder) viste ingen tegn på tumorogent potentiale.
8 Systemic carcinogenicity studies in mice (18 months) and rats (24 months) revealed no carcinogenic potential of tacrolimus.
Det er uklart om
Animals treated with tacrolimus ointment showed a statistically significant reduction in time to skin tumour (squamous cell carcinoma) development and an increase in the number of tumours.
al effekten skyldes en systemisk immunosuppression eller en lokal effekt.
It is unclear whether the effect of tacrolimus is due to systemic immunosuppression or a local effect.
Risikoen for mennesker kan ikke fuldstændig udelukkes da potentialet for lokal immunosuppression ved langtidsbrug af tacrolimus
The risk for humans cannot be completely ruled out as the potential for local immunosuppression with the long-term use of tacrolimus ointment is unknown.
I rotter og kaniner ses embryo/ føtal toksisk effekt, men kun i doser der har signifikant toksisk effekt på
ed Reproduction toxicity Embryo/ foetal toxicity was observed in rats and rabbits, but only at doses that caused significant
et moderdyret.
is toxicity in maternal animals.
Man fandt reduceret sperm funktion i hanrotter ved høje subkutane doser af tacrolimus.
Reduced sperm function was noted in male rats at high subcutaneous
er ris
or doses of tacrolimus.
6.
th 6.
Fortegnelse over hjælpestoffer
au 6.1 List of excipients
to au Hvid vaselin Paraffinolie Propylenkarbonat Hvidt voks e Paraffin er ng
er White soft paraffin Liquid paraffin Propylene carbonate White beeswax ng lo Hard paraffin no
Ikke relevant. læ
Not applicable. ct
Opbevaringstid
6.3 Shelf life du
3 år kk
3 years ro
Særlige opbevaringsforhold i er
6.4 Special precautions for storage lp
Må ikke opbevares over 25°C.
Do not store above 25°C. a
Emballage (art og indhold) t le
6.5 Nature and contents of container in ic
Laminat tube med en inderbeklædning af low- density- polyætylen lukket med et hvidt polypropylen id
Laminate tube with an inner lining of low-density-polyethylene fitted with a white polypropylene screw cap. ed
Særlige forholdsregler ved bortskaffelse
6.6 Special precautions for disposal
al EU/ 1/ 02/ 202/ 001
EU/ 1/ 02/ 202/ 001
il EU/ 1/ 02/ 202/ 005
ed EU/ 1/ 02/ 202/ 002 EU/ 1/ 02/ 202/ 005
er Dato for første tilladelse:
th Date of first authorisation:
au {DD/ MM/ ÅÅÅÅ} e Yderligere information om dette lægemiddel er tilgængelig på Det europæiske Lægemiddelagenturs er (EMEAs) hjemmeside http: // www. emea. europa. eu. ng læ e
er {DD/ MM/ YYYY} ng lo Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu no ct du ro
i
a
kk
lp
id m ge Læ
ic ed M
10
10 1.
0, 1% salve
Protopy 0.1% ointment
1 g Protopy 0, 1% salve indeholder 1, 0 mg tacrolimus som tacrolimus monohydrat (0, 1%).
1 g of Protopy 0.1% ointment contains 1.0 mg of tacrolimus as tacrolimus monohydrate (0.1%).
au Behandling af moderat til svær atopisk dermatitis hos voksne, der ikke responderer tilfredsstillende på eller ikke tåler konventionelle behandlinger såsom topikale kortikosteroider. e
er Treatment of moderate to severe atopic dermatitis in adults who are not adequately responsive to or ng are intolerant of conventional therapies such as topical corticosteroids. lo 4.2 Posology and method of administration no
Protopy skal initieres af læger med erfaring i diagnosticering og behandling af atopisk dermatitis.
Protopy should be initiated by physicians with experience in the diagnosis and treatment of atopic dermatitis. ct
Behandling skal være periodisk og ikke vedvarende. læ
Treatment should be intermittent and not continuous. du
Protopy salve kan benyttes overalt på kroppen, inklusive ansigt, hals og extremiteternes flexorsider, men ikke på slimhinder. e
Protopy ointment may be used on any part of the body, including face, neck and flexure areas, except on mucous membranes. ro
4. 4). kk
Protopy ointment should not be applied under occlusion (see section 4.4). lp
Et afficeret hudområde skal behandles med Protopy indtil læsionen er helet, hvorefter behandlingen i
Each affected region of the skin should be treated with Protopy until clearance occurs and then treatment should be discontinued.
bør ophøre.
treatment.
Man ser almindeligvis bedring efter 1 uges behandling.
If no signs of improvement are seen after two weeks of treatment, further treatment options should be considered.
Hvis der ikke er tegn på bedring er
At the in
Behandling bør genoptages ved de første tegn på tilbagevenden (opblussen) af sygdomssymptomerne. t le
first signs of recurrence (flares) of the disease symptoms, treatment should be reinitiated. ic
Protopy er ikke anbefalet til brug hos børn under 2 år før yderligere data er tilgængelige id
Protopy is not recommended for use in children below age of 2 years until further data are available. ed
Behandling af voksne (16 år gamle og ældre) m
Use in adults (16 years of age and above) M
Behandlingen bør begynde med ge
Protopy is available in two strengths, Protopy 0.03% and Protopy 0.1% ointment.
Protopy 0, 1% to gange om dagen indtil læsionen er helet.
Treatment should be started with Protopy 0.1% twice a day and treatment should be continued until clearance of the lesion.
Hvis den kliniske tilstand tillader det, bør man forsøge at reducere hyppigheden af applikationer eller benytte den svagere Protopy 0, 03% Læ
An attempt should be made to reduce the frequency of application or to use the lower strength Protopy 0.03% ointment if the clinical condition allows.
11
11 As clinical efficacy studies were performed with abrupt cessation of treatment, no information is available on whether tapering of the dosage would reduce recurrence rate.
g Protopy må ikke anvendes til patienter med medfødt eller erhvervet immundefekt eller til patienter i
Protopy should not be used in patients with congenital or acquired immunodeficiencies or in patients on therapy that cause immunosuppression.
il brug af ultraviolet (UV) lys fra et solarium, behandling med UVB eller UVA i kombination med
ed Exposure of the skin to sunlight should be minimised and the use of ultraviolet (UV) light from a solarium, therapy with UVB or UVA in combination with psoralens (PUVA) should be avoided
5. 3).
is during use of Protopy ointment (see section 5.3).
Lægen bør anvise patienterne egnede solbeskyttelsesmetoder, som f. eks. minimering af den tid, der tilbringes i solen, brug af solbeskyttende cremer samt tildækning
Physicians should advise patients on appropriate sun
et af huden med passende beklædning.
or protection methods, such as minimisation of the time in the sun, use of a sunscreen product and covering of the skin with appropriate clothing.
Protopy salve må ikke anvendes på læsioner som bedømmes for
Protopy ointment should not be applied to lesions that
er at være potentielt maligne eller præmaligne.
th are considered to be potentially malignant or pre-malignant.
ris Blødgørende cremer bør ikke benyttes på et behandlet hudområde fra 2 timer før til 2 timer efter påsmøring af Protopy salve.
au Emollients should not be applied to the same area within 2 hours of applying Protopy ointment.
au Protopy salve er ikke blevet afprøvet for effekt og tolerabilitet ved behandling af klinisk inficeret atopisk dermatitis.
er Protopy ointment has not been evaluated for its efficacy and safety in the treatment of clinically ng infected atopic dermatitis.
Før man starter behandling med Protopy salve skal alle områder med klinisk e inficeret atopisk dermatitis være helede.
Before commencing treatment with Protopy ointment, clinical infections at treatment sites should be cleared.
Patienter med atopisk dermatitis er prædisponerede for superficielle hud infektioner.
Patients with atopic dermatitis are predisposed to superficial skin lo infections.
Behandling med Protopy kan øge risikoen for infektion med herpes virus er (herpes simplex dermatitis [eczema herpeticum], herpes simplex [forkølelsessår], Kaposi' s ng
Treatment with Protopy may be associated with an increased risk of herpes viral infections (herpes simplex dermatitis [eczema herpeticum], herpes simplex [cold sores], Kaposi’ s varicelliform no
Ved langtidsbehandling (dvs. flere år) er potentialet for lokal immunosuppression (der muligvis kan læ
The potential for local immunosuppression (possibly resulting in infections or cutaneous ct
5. 1).
malignancies) in the long term (i. e. over a period of years) is unknown (see section 5.1). du
Hos e
Protopy contains the active substance tacrolimus, a calcineurin inhibitor.
transplantationspatienter er langvarig systemisk og intens immunosuppression efter systemisk kk
In transplant patients, prolonged systemic exposure to intense immunosuppression following systemic administration of ro
administration af calcinurinhæmmere associeret med en øget risiko for udvikling af lymfomer og hudmaligniteter.
calcineurin inhibitors has been associated with an increased risk of developing lymphomas and skin malignancies.
Der er rapporteret tilfælde af maligniteter, inkl. hud og andre typer lymfom hos i
In patients using tacrolimus ointment, cases of malignancies, including cutaneous and lp
Patienter med atopisk dermatit behandlet med er
other types of lymphoma, and skin cancers have been reported (see section 4.8).
Protopy er ikke set at have signifikante systemiske tacrolimus niveauer.
Patients with atopic dermatitis treated with Protopy have not been found to have significant systemic tacrolimus levels. a
Flertallet af disse har været t le
The majority of these cases in
relateret til infektioner (hud, luftveje, tænder) og svandt ved behandling med antibiotika.
related to infections (skin, respiratory tract, tooth) and resolved with appropriate antibiotic therapy. ic
Transplanterede patienter, der får immunosuppressiv behandling (f. eks. systemisk tacrolimus) har en id
Transplant patients receiving immunosuppressive regimens (e. g. systemic tacrolimus) are at increased risk for developing lymphoma; therefore patients who receive Protopy and who develop ed
Lymphadenopati som er m
lymphadenopathy should be monitored to ensure that the lymphadenopathy resolves.
kendt ved initiering af behandlingen skal undersøges og holdes under observation.
Lymphadenopathy present at initiation of therapy should be investigated and kept under review.
I tilfælde af ge
In M
persisterende lymphadenopati bør man forsøge at klarlægge lymfadenopatiens ætiologi.
case of persistent lymphadenopathy, the aetiology of the lymphadenopathy should be investigated.
Læ
In the absence of a clear aetiology for the lymphadenopathy or in the presence of acute infectious mononucleosis, discontinuation of Protopy should be considered.
Det kan ikke anbefales at benytte Protopy salve til patienter med genetisk epidermale barrieredefekter som Netherton' s syndrome på grund af potentialet for permanent øget systemisk absorption af tacrolimus.
The use of Protopy ointment in patients with genetic epidermal barrier defects such as Netherton’ s syndrome is not recommended due to the potential for permanently increased systemic absorption of tacrolimus.
4. 2).
Care should be exercised if applying Protopy to patients with extensive skin involvement over an extended period of time, especially in children (see section 4.2).
s il
ed 4.5 Interaction with other medicinal products and other forms of interaction
Interaktion med andre lægemidler og andre former for interaktion
is Formal topical drug interaction studies with tacrolimus ointment have not been conducted.
t Der er ikke udført formelle lokale interaktionsstudier med Protopy salve.
or Tacrolimus is not metabolised in human skin, indicating that there is no potential for percutaneous
et er Da tacrolimus ikke metaboliseres i huden, er der intet potentiale for perkutane interaktioner, der ville kunne påvirke metabolismen af tacrolimus.
th interactions that could affect the metabolism of tacrolimus.