qanastek/EMEA-V3 huggingface dataset:
or Frequencies are defined as very common (> 1/ 10), common (> 1/ 100 ,< 1/10) and uncommon (> 1/1 ,000, < 1/100).
Il- frekwenzi huma innutati bħala komuni ħafna (> 1/ 10), komuni (> 1/ 100, < 1/ 10) u mhux komuni (> 1/ 1, 000, < 1/ 100).
Within each frequency grouping, undesirable effects are presented in order of
Ma kull grupp ta ’ ċerta frekwenza, jitfaċcaw
th decreasing seriousness.
x effetti mhux mixtieqa iżda jonqsu fis- serjetà.
au General disorders and administration site conditions Very common:
du Mard ġenerali u kundizzjonijiet fil- parti ta 'mnejn jittieħed ħa Komuni ħafna:
Application site burning, application site pruritus Application site warmth, application site erythema, application site pain,
Ħruq mnejn jittieħed, ħakk mnejn jittieħed, Sħana mnejn jittieħed, ħmura mnejn jittieħed, uġigħ mnejn jittieħed, irritazzjoni mnejn jittieħed, paraesthesia mnejn jittieħed, raxx mnejn jittieħed. ’ g m
er application site irritation, application site paraesthesia, application site rash
Infezzjonijiet u infestazzjonijiet Komuni
Infections and infestations Common: ng Herpes viral infections (herpes simplex dermatitis [eczema herpeticum], herpes lo simplex [cold sores], Kaposi’ s varicelliform eruption) no
Infezzjonijiet bil- herpes (dermatite b’ herpes simplex [eczema herpeticum], herpes semplex [ħżiża], eruzzjoni variċelliforma ta 'Kaposi) li li
Skin and subcutaneous tissue disorders Common:
Mard tal- ġilda u tessuti taħta a
Uncommon:
Komuni
Folliculitis, pruritus Acne ct
Follikulite, ħakk in
Nervous system disorders du
Mard tas- sistema nervuża ed
Paraesthesias and dysaesthesias (hyperaesthesia, burning sensation) ro
Paraesthesia jew dysaesthesia (hyperaesthesia, sensazzjoni ta ’ ħruq)
Metabolism and nutrition disorders Common:
Mard marbut mal- metaboliżmu u nutrizzjoni tm
Alcohol intolerance (facial flushing or skin irritation after consumption of an lp
Intolleranza għall- alkoħol (ħmura tal- wiċċ jew irritazzjoni tal- ġilda wara xorb alkoħoliku)
alcoholic beverage)
Rosaċeja od
The following adverse reactions have been reported during post-marketing experience: a
Wara t- tqegħid fuq is- suq: f’ pazjenti li kienu qed jużaw l- ingwent tacrolimus kien hemm każijiet ta ’ xi Pr
Post-marketing: cases of malignancies, including cutaneous and other types of lymphoma, and skin cancers, have been reported in patients using tacrolimus ointment (see section 4.4). ed
malinjitajiet fil- ġilda u tipi oħra ta ’ limfoma, kif ukoll kanċer tal- ġilda (ara sezzjoni 4. 4).
Via its binding to a specific cytoplasmic immunophilin (FKBP12), tacrolimus inhibits calcium-
Minħabba li tacrolimus jintrabat ma 'immunophilin speċifiku taċ- ċellula (FKBP12), tacrolimus
ed dependent signal transduction pathways in T cells, thereby preventing the transcription and synthesis of IL-2, IL-3, IL-4, IL-5 and other cytokines such as GM-CSF, TNF-α and IFN-γ.
t za jinibixxi ġewwa T- cells sinjali tat- transduzzjoni, li jiddependu fuq il- kalċju, u b' hekk tiġi mwaqqfa t - transkrizzjoni u s- sinteżi ta 'IL- 2, IL- 3, IL- 4, IL- 5, u ta' ċitokini oħra bħal GM- CSF, TNF- α u IFN- γ.
In vitro, in Langerhans cells isolated from normal human skin, tacrolimus reduced the stimulatory
riz In vitro, f 'ċelluli ta' Langerhans li nkisbu minn ġilda normali, tacrolimus naqqas l- attività stimulatorja lejn it- T cells.
Tacrolimus has also been shown to inhibit the release of inflammatory
Intwera wkoll li tacrolimus inaqqas il- ħruġ ta 'aġenti ta' infjammazzjoni minn ċelluli mast, bażofili u eżinofili tal- ġilda.
In animals, tacrolimus ointment suppressed inflammatory reactions in experimental and spontaneous
to F 'annimali tacrolimus ingwent waqqaf l- infjammazzjoni f' każijiet ta 'dermatite sperimentali u
th dermatitis models that resemble human atopic dermatitis.
F 'annimali tacrolimus ma naqqasx il- ħxuna tal- ġilda u ma kkaġunax li l- ġilda togħlob.
Tacrolimus ointment did not reduce skin thickness and did not cause skin atrophy in animals.
F 'pazjenti b' dermatite atopika, waqt li l- marda tal- ġilda marret għall- aħjar wara trattament b 'tacrolimus ingwent, kien hemm riduzzjoni tal- qari tar- reċettur Fc fuq iċ- ċelluli ta' Langerhans u
au In patients with atopic dermatitis, improvement of skin lesions during treatment with tacrolimus ointment was associated with reduced Fc receptor expression on Langerhans cells and a reduction of their hyperstimulatory activity towards T cells.
x riduzzjoni ta 'l- istimulazzjoni qawwija tagħhom fuq ċelluli tat- tip T.
Tacrolimus ointment does not affect collagen synthesis
Tacrolimus ingwent ma jaffettwax
er in humans.
du is- sintesi tal- kollaġen fil- bniedem.
Results from clinical studies in patients
ħa Riżultati ta 'studji kliniċi fuq pazjenti L- effiċjenza u s- sigurtà ta' Protopy ġew studjati f 'aktar minn 13, 500 pazjent wara trattament bi ’ g Protopy ingwent fil Fasi I sa Fasi III ta ’ l- esperiment kliniku.
The efficacy and safety of Protopy was assessed in
Fi prova li ħa sitt xhur, li sar f 'aktar minn ċentru wiehed u li kien tat- tip "double blind randomised" 0. 1% Protopy ingwent ingħata darbtejn kuljum lil pazjenti kbar li kienu jsofru b' dermatite atopika ta 'qawwa moderata għal qalila.
than 13,500 patients treated with tacrolimus
It- trattament bi Protopy ġiet paragunata ma 'trattament b' corticosteroid li
In a six-month multicentre double-blind randomised trial, 0.1% tacrolimus ointment was administered no
applikat b’ mod topiku (0. 1% hydrocortisone butyrate fuq is- sider, fuq iż- żaqq, fuq l- idejn, fuq ir - li
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).
L- ewwel punt ta ’ l - a
The primary endpoint was the response rate at month 3 ct
evalwazzjoni kienet ir- rispons kliniku wara tlett xhur, definita bħala il- proporz tal- pazjenti li għaddew in
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.
għall- aħjar b 'mill- anqas 60% skond l- mEASI (modified Eczema Area and Severity Index) bejn il- bidu ta ’ l- esperiment u kif skadew 3 xhur.
The response rate in the 0.1% tacrolimus du
Ir- rata ta ’ rispons posittiv fil- grupp li ngħata 0. 1% Tacrolimus iċ
group (71.6%) was significantly higher than that in the topical corticosteroid based treatment group (50.8%; p < 0.001; Table 1).
Tabella 1).
The response rates at month 6 were comparable to the 3-month results. ro
Ir- riżultati ta 'wara 6 xhur kienu komparabbli ma' dawk ta 'wara 3 xhur.
Table 1
Tabella 1 tm
Efficacy at month 3 lp
Effiċjenza wara 3 xhur
a
ot
Topical corticosteroid regimen§
Reġimen ta ’ Corticosteroid applikat b’ mod topiku§ (N=485)
(N=485) Response rate of ≥ 60% in
Pazjenti li għaddew għal aħjar od
improvement in mEASI (Primary ic
mill- anqas ≥ 60% skond mEASI (l- ewwel punt wara 3 xhur) §§ Pazjenti li għaddew għal aħajar Pr
Endpoint)§§ Improvement ≥ 90% in Physician’ s 28.5% ed
28. 5%
Global Evaluation § Topical corticosteroid regimen = 0.1% hydrocortisone butyrate on trunk and extremities, 1% M
≥ 90% skond Physician’ s Global Evaluation § Corticosteroid applikat b’ mod topiku = 0. 1% hydrocortisone butyrate fuq is- sider, fuq iż- żaqq, fuq l - idejn, fuq ir- riġlejn u fuq is- saqajn, 1% hydrocortisone acetate fuq il- wiċċ u fuq l- għonq §§ valuri aktar għoljin = titjib akbar
hydrocortisone acetate on face and neck §§ higher values = greater improvement
Il- frekwenza u l- kwalità tal- biċċa ’ l kbira ta ’ l- effetti avversi kienu bejn wieħed u ieħor l- istess fiż - żewg gruppi.
The incidence and nature of most adverse events were similar in the two treatment groups.
6 aktar sikwit fil- grupp b 'trattament b' tacrolimus.
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.
Fit- tieni prova, tfal bejn 2 sa 15- il sena, li kienu jsofru minn dermatite atopika, moderata għal qalila, ġew mogħtija 0. 03% tacrolimus ingwent, 0. 1% tacrolimus ingwent u ingwent ta '1% hydrocortisone acetate darbtejn kuljum għal żmien ta' 3 ġimgħat.
Table 2
t za Tabella 2
Hydrocortisone acetate 1% (N=185)
Tacrolimus 0. 1%
ed Median mEASI as Percentage of Baseline mean AUC (Primary Endpoint)§
Il- medjan tal- mEASI bħala
is Improvement ≥ 90% in Physician’ s
to persentaġġ tal- medja tal- valur
15.7%
aw bażi AUC (l- endpoint Primarju) § Titjib ≥ 90% skond Physician’ s 15. 7% Global Evaluation
or Global Evaluation § lower values = greater improvement
x § valuri aktar baxxi = titjib akbar
th The incidence of local skin burning was higher in the tacrolimus treatment groups than in the
du Il- frekwenza ta 'ħruq tal- ġilda lokali kienet aktar għolja fil- gruppi b' trattament b' tacrolimus milli fil - ħa gruppi b 'trattament b' hydrocortisone.
There were no clinically relevant changes in the laboratory values or vital signs in either treatment group throughout the clinical trial.
Waqt il- prova klinika kollha ma kienx hemm ’ g tibdil kliniku relevanti fir- riżultati tal- laboratorju jew fis- sinjali vitali fil- pazjenti taż- żewg gruppi. m
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.
jew darbtejn kuljum fi tfal li kellhom dermatite atopika, moderata għal qalila, f 'paragun ma' 1% ingwent tal- hydrocortisone acetate li ġie applikat darbtejn kuljum.
Treatment duration was for up to three weeks. no
It- trattament damet sa tliet gimgħat. li a
Efficacy at week 3
Effiċjenza f’ ġimgħa 3 in
Hydrocortisone acetate 1% ct
Hydrocortisone acetate 1%
Tacrolimus 0.03% Once daily (N=207)
Tacrolimus 0. 03% Darba kuljum
Tacrolimus 0.03% Twice daily (N=210)
Tacrolimus 0. 03% Darbtejn kuljum
Median mEASI Percentage Decrease (Primary Endpoint)§ ro
(N=207) Tnaqqis fil- medja tal- mEASI (l - endpoint Primarju) § tm
Improvement ≥ 90% in Physician’ s Global Evaluation lp
Titjib ≥ 90% skond Physician’ s 13. 6% Global Evaluation ot
§ higher values = greater improvement a
§ valuri aktar għoljin = titjib akbar od
The primary endpoint was defined as the percentage decrease in mEASI from the baseline to end of in
L- endpoint primarju ġie definit bħala l- persentaġġ kif naqas il- mEASI mill- linja bażi sakemm spiċċat it- trattament.
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
Deher titjib statistikament sinifikanti b ’ 0. 03% tacrolimus ingwent, li ngħata darba u darbtejn kuljum, imqabbel ma ’ l- ingwent ta ’ hydrocortisone acetate mogħti darbtejn kuljum (p < 0. 001 Pr
both).
għat- tnejn).
Twice daily treatment with 0.03% tacrolimus ointment was more effective than once daily ed
It- trattament darbtejn kuljum b '0. 03% tacrolimus ingwent kienet aktar effettiva mill - applikazzjoni ta' darba kuljum (Tabella 3).
M
Waqt l- istudju kollu ma kienx hemm tibdil kliniku relevanti fir- riżultati tal- laboratorju jew fis- sinjali vitali fil- pazjenti taż- żewg gruppi.
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.
Fir- raba prova, kważi 800 pazjent (età ≥ 2 snin) irċevew trattament b '0. 1% tacrolimus ingwent, kontinwament jew b' intervalli, għal mhux aktar minn erba ’ snin, bl- iskop ta 'studju tas- sigurtà open - label fuq żmien twil ta' trattament.
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.
300 pazjent irċevew trattament mill- anqas 3 snin u 79 pazjent irċevew trattament għal 42 xahar.
In addition, there was no evidence of loss of efficacy throughout the duration of the clinical trial.
Meta wieħed ikkonsidra it- tibdil bażat fuq il- linja bażi tal- punteġġ 7 EASI u fuq l- erja tal- ġilda affettwata, il- pazjenti b 'dermatite atopika kollha għaddew għall- aħjar f' kull fażi ta 'evalwazzjoni u indipendentement mill- età tagħhom.
The overall incidence of adverse events tended to decrease as the study progressed for all patients independent of age.
Barra minn hekk, ma kienx hemm evidenza li l- effiċenza tat- trattament tnaqqset waqt il- prova klinika.
The three most common adverse events reported were flu-like symptoms (cold, common cold,
Il- frekwenza ta 'effetti avversi kellha t - tendenza li tonqos meta tkompla l- istudju, b’ mod indipendenti mill- età tagħhom.
7 influenza, upper respiratory infection, etc.), pruritus and skin burning.
It- tliet effetti mhux mixtieqa, li kienu l- aktar komuni, kienu sintomi bħal ta ’ l- influwenza (riħ, riħ komuni, influwenza, infezzjoni tan- naħa ta ’ fuq ta ’ l- apparat respiratorju eċċ.), ħakk u ħruq tal- ġilda.
Clinical data have shown that tacrolimus concentrations in systemic circulation after topical administration are low and, when measurable, transient.
Informazzjoni klinika turi li l- konċentrazzjoni ta 'tacrolimus fiċ- ċirkolazzjoni tad- demm hi baxxa ħafna
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.
t za wara li tacrolimus ingwent jiġi applikat b’ mod topiku fuq il- ġilda, u, jekk il- livell ikun tant li jista 'jitkejjel, dan ikun biss għal żmien qasir.
ed Most atopic dermatitis patients (adults and children) treated with single or repeated application of tacrolimus ointment (0.03 - 0.1%), and infants from age of 5 months treated with tacrolimus ointment (0.03%) had blood concentrations < 1.0 ng/ ml.
riz Assorbiment Tagħrif kliniku li nkiseb minn bnedmin b’ saħħithom juri li jinstab ftit jew xejn tacrolimus fid- demm
When observed, blood concentrations exceeding
to wara applikazzjoni b’ mod topiku, ta 'darba jew iktar, ta' tacrolimus ingwent fuq il- ġilda.
is 1.0 ng/ ml were transient.
Konċentrazzjonijiet ogħla minn 1. 0 ng/ ml seħħew biss għal żmien qasir.
Systemic exposure increases with increasing treatment areas.
x jidħol fid- demm tikber aktar ma tkun kbira l- parti ta 'ġilda li tindilek.
However, both
Madankollu, kemm l- ammont kif
or the extent and the rate of topical absorption of tacrolimus decrease as the skin heals.
du ukoll ir- rata ta ’ assorbiment ta ’ tacrolimus jonqsu aktar ma tfiq il- ġilda.
AUC) of tacrolimus
u tfal) b 'tacrolimus ingwent għal żmien twil (sa sena).
th from Protopy is approximately 30-fold less than that seen with oral immunosuppressive doses in kidney and liver transplant patients.
Minħabba li meta tacrolimus ingwent ma jwassalx għal esponiment għoli fiċ- ċirkolazzjoni, l- irbit li
The lowest tacrolimus blood concentration at which systemic
qawwi ta ’ tacrolimus (> 98. 8%) mal- proteini tal- plażma mhuwiex meqjus bħala wieħed ta ’ rilevanza a
au effects can be observed is not known.
klinika. in
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
Meta tacrolimus ingwent jigi applikat lokalment, tacrolimus jgħaddi selettivament fil- ġilda, waqt li id - diffużjoni fiċ- ċirkolazzjoni tad- demm hi minima. iċ ed
Systemically available tacrolimus is ct
Metaboliżmu L- ammont ta ’ tacrolimus li jiġi metabolizzat mill- ġilda ma setgħax jitkejjel.
extensively metabolised in the liver via CYP3A4. du
Fid- demm, tacrolimus jiġi metabolizzat bil- qawwa fil- fwied permezz ta ’ CYP3A4. tm
The ro
Il- clearance ot
average total body clearance is approximately 2.25 l/ h.
totali mill- ġisem hi bejn wieħed u ieħor 2. 25 l/ h.
The hepatic clearance of systemically available tacrolimus could be reduced in subjects with severe hepatic impairment, or in subjects who are co- lp
Ir- rata tal- clearance ta ’ tacrolimus fid- demm mill - fwied tista tonqos f’ pazjenti li jsofru minn indeboliment tal- fwied, jew inkella jekk il- pazjenti ikunu od
treated with drugs that are potent inhibitors of CYP3A4.
jieħdu mediċini li jinibixxu bil- qawwa s- CYP3A4.
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
Meta l- ingwent jiġi applikat ripetutament il- medja tal- half life ta 'tacrolimus kienet stmata li tkun 75 Pr
5.3 Preclinical safety data ic
siegħa fil- kbar u 65 siegħa fit- tfal.
Repeated dose toxicity and local tolerance ed
5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina
M
Tossiċità minn dożi ripetuti u tolleranza lokali Meta tacrolimus ingwent jew il- komponenti bażi ta ’ l- ingwent jingħataw ripetutament fuq il- ġilda ta 'firien, fniek u fniek ta ’ l- indja wieħed jista' jara tibdil ħafif tal- ġilda bħal ħmura, edema jew ponot (papules).
Long-term topical treatment of rats with tacrolimus led to systemic toxicity including alterations of kidneys, pancreas, eyes and nervous system.
Dan it- tibdil seħħ minħabba l -
The changes were caused by high systemic exposure of rodents resulting from high transdermal absorption of tacrolimus.
8 esponiment għoli fiċ- ċirkolazzjoni tal- firien li rriżultat mill- assorbiment għoli ta ’ tacrolimus minn ġol - ġilda.
Carcinogenicity
Kanċeroġeniċità Studji sistemiċi kanċeroġeniċi fuq ġrieden (18 xahar) u firien (24 xahar) urew li tacrolimus m’ għandux
8 Systemic carcinogenicity studies in mice (18 months) and rats (24 months) revealed no carcinogenic potential of tacrolimus.
Fi studju dwar il- potenzjal kanċeroġenu fil- ġilda li dam sejjer 24 xahar, fi ġrieden li rċevew tacrolimus
In a 24-month dermal carcinogenicity study performed in mice with 0.1% ointment, no skin tumours were observed.
riz ingwent 0. 1%, ma dehrux tumuri tal- ġilda.
In a photocarcinogenicity study, albino hairless mice were chronically treated with tacrolimus ointment and UV radiation.
Fi studju dwar il- fotokanċeroġeniċità, tacrolimus ingwent u raġġi ta ’ l- UV ingħataw f’ daqqa għal
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.
aw ġilda (squamous cell carcinoma) żviluppa iktar malajr b’ mod statistikament sinifikanti u l- annimali kellhom ukoll numru akbar ta ’ tumuri.
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.
Ir- riskju għal bniedem ma jistax jitħalla barra għal kollox għax il- potenzjal għal immunosuppressjoni lokali meta jintuża fit- tul l- ingwent tacrolimus
ed Reproduction toxicity Embryo/ foetal toxicity was observed in rats and rabbits, but only at doses that caused significant
x għadu mhux magħruf.
Reduced sperm function was noted in male rats at high subcutaneous
du Effett tossiku fuq is- sistema riproduttiva ħa Kien hemm effett ħazin fuq l- embrijoni/ feti ta 'fniek u firien biss, meta d- doża ta' tacrolimus kienet tossika fl- annimali li kienu tqal.
or doses of tacrolimus.
Tnaqqis fil- funzjoni ta ’ l- isperma dehret f’ firien ta ’ sess maskili b’ dożi għolja mogħtija taħt il- ġilda. ’ g m
PHARMACEUTICAL PARTICULARS
TAGĦRIF FARMAĊEWTIKU li
au 6.1 List of excipients
6. 1 Lista ta 'sustanzi mhux attivi li a
er White soft paraffin Liquid paraffin Propylene carbonate White beeswax ng lo Hard paraffin no
Liquid paraffin Propylene carbonate iċ
6.2 Incompatibilities
6. 2 Inkompatibilitajiet tm
Not applicable. ct
Ma jghoddx f' dan il- każ. ot
6.3 Shelf life du
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali od
3 years ro
3 snin Pr
6.4 Special precautions for storage lp
6. 4 Prekawzjonijiet speċjali għall- ħażna
Do not store above 25°C. a
Taħżinx f' temperatura 'l fuq minn 25°C.
6.5 Nature and contents of container in ic
6. 5 In- natura tal- kontenitur u ta 'dak li hemm ġo fih
Laminate tube with an inner lining of low-density-polyethylene fitted with a white polypropylene screw cap. ed
Tubu li fuq ġewwa għandu saff ta 'low density polyethylene u li għandu kappa bajda b’ kamin tal - propylene.
Package sizes:
9 Daqsijiet tal- pakkett:
M
Jista 'jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall - skop kummerċjali.
9 7.
t 7.
Astellas Pharma GmbH Neumarkter Str.
za Astellas Pharma GmbH
8.
to aw 8.
EU/ 1/ 02/ 202/ 001
EU/ 1/ 02/ 202/ 001
ed EU/ 1/ 02/ 202/ 002 EU/ 1/ 02/ 202/ 005
du EU/ 1/ 02/ 202/ 005
is or 9.
ħa 9.
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION
DATA TA 'L- EWWEL AWTORIZZAZZJONI/ TIĠDID TA' L- AWTORIZZAZZJONI ’ g Data ta ’ l- ewwel awtorizzazzjoni:
28/ 02/ 2002 Date of renewal:
28/ 02/ 2002 m
20/ 11/ 2006
20/ 11/ 2006 li
DATE OF REVISION OF THE TEXT
DATA TA 'META ĠIET RIVEDUTA L- KITBA li a
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
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar ed
in
il- mediċini (EMEA) http: // www. emea. europa. eu tm ot od Pr
Protopy 0.1% ointment
Protopy 0. 1% ingwent
1 g of Protopy 0.1% ointment contains 1.0 mg of tacrolimus as tacrolimus monohydrate (0.1%).
1 g ta 'Protopy 0. 1% ingwent fih 1. 0 mg ta' Tacrolimus bħala tacrolimus monohydrate (0. 1%).
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
du Il- kura ta ’ dermatite atopika moderata jew severa fl- adulti li ma jkunux adegwatament responsivi għal ħa jew intolleranti għal terapiji konvenzjonali bħalma huma l- kortikosterojdi topikali. ’ g 4. 2 Pożoloġija u metodu ta 'kif għandu jingħata m
Protopy should be initiated by physicians with experience in the diagnosis and treatment of atopic dermatitis. ct
Kura bi Protopy għandu jinbeda minn tabib li jkollu esperjenza fid- dijanjosi u l- kura tad- dermatite atopika. li
Treatment should be intermittent and not continuous. du
Il- kura ma tridx tkun kontinwa iżda intermittenti. li a
Protopy ointment may be used on any part of the body, including face, neck and flexure areas, except on mucous membranes. ro
Protopy forma ta ’ ingwent in
Protopy ointment should not be applied under occlusion (see section 4.4). lp
Protopy forma ta 'ingwent m' għandux jintuża taħt faxxex (ara sezzjoni 4. 4). iċ ed
Each affected region of the skin should be treated with Protopy until clearance occurs and then treatment should be discontinued.
Kull parti tal- ġilda affettwata għandha tiġi trattata bi Protopy sakemm il- marda tfieq, imbagħad it - trattament għandha tiġi mwaqqfa.
Generally, improvement is seen within one week of starting a
Il- parti tal- ġilda affettwata għandha tmur għall- aħjar fi żmien ġimgħa wara l- bidu tat- trattament.
If no signs of improvement are seen after two weeks of treatment, further treatment options should be considered.
Jekk wara ħmistax il- ġurnata ma jkunx hemm progress, wieħed tm
At the in
Protopy jista 'jintuża għal żmien qasir jew ukoll għal żmien sakemm ikun hemm twaqqif għal xi perijodu żgħir.
first signs of recurrence (flares) of the disease symptoms, treatment should be reinitiated. ic
Malli jidher li ser jerġgħu jibdew is- sintomi (flares) tas - sintomi tal- marda, il- kura trid terġa ’ tibda. ot
Protopy is not recommended for use in children below age of 2 years until further data are available. ed
Protopy mhux rakkomandat għat- tfal taħt l- età ta ’ sentejn qabel ma jkun hemm aktar informazzjoni od
Use in adults (16 years of age and above) M
Pr
Protopy is available in two strengths, Protopy 0.03% and Protopy 0.1% ointment.
Użu f 'persuni kbar (16 il- sena' l fuq) Protopy jiġi bħala ingwent fil- qawwa ta 'Protopy 0. 03% u ta' Protopy 0. 1%.
Use in elderly (65 years of age and above) Specific studies have not been conducted in elderly patients.
11 Użu fl- anzjani (65 sena u akbar) Għad m 'hemmx studji speċifiċi f’ pazjenti anzjani.
4.4 Special warnings and precautions for use
t za 4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu
Protopy should not be used in patients with congenital or acquired immunodeficiencies or in patients on therapy that cause immunosuppression.
riz Protopy ma għandhiex tintuża fuq pazjenti li jkollhom immunodefiċjenzi konġenitali jew li jkunu ħaduhom jew f’ pazjenti li jkunu għaddejjin b’ kura li tista ’ tikkaġuna l- immunosuppressjoni.
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
to Waqt l- użu ta 'Protopy ingwent wieħed għandu jevita li joqgħod espost għax- xemx u raġġi ultravjoletti
Physicians should advise patients on appropriate sun
aw (UV) ta 'solarju kif ukoll dawk fit- trattament b' UVB jew UVA b 'kombinazzjoni ma' psoralens (PUVA) (ara sezzjoni 5. 3).
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.
It- tobba għandhom jagħtu parir lil- pazjenti biex jużaw protezzjoni xierqa kontra x- xemx, bħal żmien qasir fix- xemx, użu ta 'xi prodott li jilqa ’ mir- raġġi tax- xemx (sunscreen) kif ukoll ilbies xieraq.
Protopy ointment should not be applied to lesions that
L- ingwent Protopy ma għandux jintuża fuq leżjonijiet meqjusa bħala
th are considered to be potentially malignant or pre-malignant.
x potenzjalment malinji jew pre- malinji.
au Emollients should not be applied to the same area within 2 hours of applying Protopy ointment.
du Emoljenti ma jistgħux jintużaw fl- ewwel sagħtejn wara applikazzjoni ta 'Protopy.
Concomitant use of other topical preparations has not been assessed.
L- użu ta 'ingwenti ħa oħrajn fl- istess ħin ma' Protopy għadu ma ġiex stmat.
There is no experience with concomitant use of systemic steroids or immunosuppressive agents.
Għad m' hemmx tagħrif dwar l- użu ta 'Protopy ma' steroids sistemiċi jew ma 'mediċini immunosuppressivi. ’ g Is- sigurtà u l- effiċenza ta' Protopy ingwent għadhom ma ġewx eżaminati fit- trattament tad- dermatite m
er Protopy ointment has not been evaluated for its efficacy and safety in the treatment of clinically ng infected atopic dermatitis.
Qabel ma tibda trattament bi Protopy ingwent, wieħed għandu jara li infezzjoni tal- ġilda fil- partijiet relevanti tiġi mfejqa qabel.
Before commencing treatment with Protopy ointment, clinical infections at treatment sites should be cleared.
Pazjenti b 'dermatite atopika jista' jkollom ukoll infezzjoni superfiċjali tal- ġilda.
Patients with atopic dermatitis are predisposed to superficial skin lo infections.
Waqt it- trattament bi Protopy ir- riskju ta 'infezzjoni bil- herpes li
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
(dermatite sempliċi tal- herpes [eczema herpeticum], herpes simplex [ħżiża], eruzzjoni variċelliforma ta 'li
eruption).
Kaposi).
The potential for local immunosuppression (possibly resulting in infections or cutaneous ct
Fil każ ta 'infezzjonijiet bħal dawn wieħed għandu jqies ir- riskji u l- ġid ta' trattament bi a
malignancies) in the long term (i. e. over a period of years) is unknown (see section 5.1). du
Il- potenzjal għall- immunosuppressjoni lokali (li aktarx toħloq infezzjonijiet jew ġilda malinja) ma nafux x’ inhu meta jgħaddi ħafna żmien (ngħidu aħna wara perijodu ta ’ snin) (ara sezzjoni 5. 1). iċ ed
In transplant patients, prolonged systemic exposure to intense immunosuppression following systemic administration of ro
F’ pazjenti bi trapjant, l- esponiment sistemiku fit- tul għall- immunosuppressjoni intensa wara għoti sistemika ta ’ inibituri kalċinewriniċi ġiet assoċjata ma ’ żieda fir- riskju li jiżviluppaw limfomi u malinjitajiet fil- ġilda.
calcineurin inhibitors has been associated with an increased risk of developing lymphomas and skin malignancies.
F’ pazjenti li jużaw l - tm
other types of lymphoma, and skin cancers have been reported (see section 4.8).
ingwent tacrolimus, kien hemm rapportati każi ta ’ malinjitajiet, inklużi l- limfoma fil- ġilda u tipi oħra ta ’ limfoma, kif ukoll kanċer tal- ġilda (ara sezzjoni 4. 8).
Patients with atopic dermatitis treated with Protopy have not been found to have significant systemic tacrolimus levels. a
Ma nstabx li dawk il- pazjenti b’ dermatite atopika kkurati bi Protopy kellhom livelli sistemiċi sinifikanti ta ’ tacrolimus. ot
The majority of these cases in
Il- biċċa ’ l kbira od
related to infections (skin, respiratory tract, tooth) and resolved with appropriate antibiotic therapy. ic
kellhom x 'jaqsmu ma' infezzjonijiet (tal- ġilda, ta ’ l- apparat respiratorju, u tas- snien) u tfejjqu b 'trattament antibijotika xierqa.
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
immunosuppressivi (per ezempju injezzjoni ta 'tacrolimus), għandhom ċans akbar li jiżviluppaw limfoma; Għalhekk pazjenti li qed jieħdu Protopy u tiżviluppalhom limfadenopatija għandhom jibqgħu taħt osservazzjoni biex jiġi aċċertat li l- limadenopatija tfieq.
In M
Il- limfadenopatija li jkun hemm fil- bidu tal- kura għandha tkun investigata u tibqa ’ ċċekkjata regolarment.
case of persistent lymphadenopathy, the aetiology of the lymphadenopathy should be investigated.
Fil- każ li l- limfadenopatija ma tfieqx, il- kawża tal- limfadenopatija għandha tkun mistħarrġa.
In the absence of a clear aetiology for the lymphadenopathy or in the presence of acute infectious mononucleosis, discontinuation of Protopy should be considered.
Jekk il- kawża tal- limfadenopatija ma tkunx ċara, jew jekk ikun hemm il- marda infectious mononucleosis akuta, wieħed għandu jikkonsidra li jwaqqaf it- trattament bi Protopy.
Care should be taken to avoid contact with eyes and mucous membranes.
12 Għandha tingħata attenzjoni biex ma jseħħx kuntatt ma 'l- għajnejn jew ma ’ membrani mukużi.
The use of Protopy ointment under occlusion has not been studied in patients.
L- użu ta 'Protopy taħt faxxex għadu ma ġiex studjat f’ pazjenti.
The safety of Protopy ointment has not been established in patients with generalised erythroderma.
L- użu ta 'Protopy mhux rakkomandat f' pazjenti li jsofru minn difetti ġenetiċi li jaffettwaw l- ilqugħ tal -
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).
t za ġilda bħal Netherton' s syndrome minħabba il- periklu li tacrolimus jidħol b 'qawwa akbar fid- demm.
ed 4.5 Interaction with other medicinal products and other forms of interaction
Is - sigurtà ta 'l- użu ta' Protopy f 'pazjenti b' erythroderma ġeneralizzata għadha mhiex stabilita.
is Formal topical drug interaction studies with tacrolimus ointment have not been conducted.
riz Wieħed irid joqgħod attent ħafna meta juża Protopy fuq pazjenti li jkollhom firxa kbira ta ’ ġilda involuta għal perijodu ta ’ żmien fit- tul, speċjalment fit- tfal (ara sezzjoni 4. 2).
or Tacrolimus is not metabolised in human skin, indicating that there is no potential for percutaneous
to aw 4. 5 Prodotti mediċinali oħra li ma jaqblux ma 'dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
th interactions that could affect the metabolism of tacrolimus.
L- interazzjoni topika ta 'tacrolimus ingwent għadha ma ġietx studjata formalment.
au Systemically available tacrolimus is metabolised via the hepatic Cytochrome P450 3A4 (CYP3A4).
x du Tacrolimus ma jiġiex metabolizzat fil- ġilda umana, u għalhekk m’ hemmx periklu ta 'interazzjoni fil - livell tal- ġilda li jista' jaffettwa l- metaboliżmu ta 'tacrolimus. ħa Tacrolimus fid- demm jiġi metabolizzat permezz taċ- Ċitokromju tal- fwied P450 3A4 (CYP3A4).
Systemic exposure from topical application of tacrolimus ointment is low (< 1.0 ng/ ml) and is unlikely to be affected by concomitant use of substances known to be inhibitors of CYP3A4.
Il - konċentrazzjoni ta 'tacrolimus fid- demm wara użu fuq il- ġilda hi baxxa (inqas minn 1. 0 ng/ ml) u ’ g għalhekk ma tiġiex affettwata minn sustanzi kontra CYP3A4.
However, the
Iżda wieħed ma jistgħax jeskludi l - m
er possibility of interactions cannot be ruled out and the concomitant systemic administration of known CYP3A4 inhibitors (e. g. erythromycin, itraconazole, ketoconazole and diltiazem) in patients with ng widespread and/ or erythrodermic disease should be done with caution. lo A potential interaction between vaccination and application of Protopy ointment has not been investigated.
possibiltà ta 'interazzjoni u għalhekk hemm bżonn ta' attenzjoni fl- użu konkomitanti ta 'sustanzi kontra CYP3A4 (erythromycin, itraconazole, ketoconazole u diltiazem) f' pazjenti li għandhom mard tal- ġilda mifrux ħafna u/ jew f 'pazjenti bil- marda eritrodermika. li li
Because of the potential risk of vaccination failure, vaccination should be administered no
tilqima tista ’ ma tirnexxix, it- tilqima għandha ssir qabel tibda t- trattament bi Protopy, jew inkella f ’ in
prior to commencement of treatment, or during a treatment-free interval with a period of 14 days between the last application of Protopy and the vaccination.
Fil- każ ta 'tilqima bil- mikrobi newtralizzati (attenuated) ħajjin, dan l- spazju iċ
In case of live attenuated vaccination, this period should be extended to 28 days or the use of alternative vaccines should be considered. ct
għandu jkun estiż għal 28 jum jew inkella wieħed għandu juża tipi ta ’ tilqim oħrajn. ed
4.6 Pregnancy and lactation du
4. 6 Tqala u Treddigħ tm
Studies in animals ro
Ma hemmx tagħrif biżżejjed dwar l- użu ta ’ l- ingwent tacrolimus fuq nisa tqal.
have shown reproductive toxicity following systemic administration (see section 5.3).
L- istudji fuq l- annimali wrew tossiċità riproduttiva wara li ngħata sistemikament (ara sezzjoni 5. 3).
The potential risk for humans is unknown. lp
Ir- riskju li jista ’ jkun hemm għal bniedem mhux magħruf. ot
Protopy ointment should not be used during pregnancy unless clearly necessary. a
Protopy ingwent m' għandux jintuża waqt it- tqala sakemm ma jkunx verament meħtieġ. od
Although clinical data have shown that systemic exposure from application of tacrolimus ointment is ic
Pr
low, breast-feeding during treatment with Protopy ointment is not recommended. ed
Għalkemm tagħrif kliniku juri li l- konċentrazzjoni ta 'tacrolimus fid- demm tkun baxxa wara li tacrolimus jintuża bħala ingwent fuq il- ġilda, mhux rakkomandat li Protopy ingwent jintuża f' pazjenti nisa li jkunu għadhom jreddu.
4.7 Effects on ability to drive and use machines M
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
In clinical studies approximately 50% of patients experienced some type of skin irritation adverse reaction at the site of application.
13 Madwar 50% tal- pazjenti kellhom xi tip ta ’ irritazzjoni avversa tal- ġilda fil- parti fejn ġie applikat l - ingwent.
Frequencies are defined as very common (> 1/ 10), common (> 1/ 100 ,< 1/10) and uncommon (> 1/1 ,000, < 1/100).
Il- frekwenzi huma innutati bħala komuni ħafna (> 1/ 10), komuni
General disorders and administration site conditions Very common:
riz Mard ġenerali u kundizzjonijiet fil- parti ta 'mnejn jittieħed Komuni ħafna:
Application site burning, application site pruritus
Ħruq mnejn jittieħed, ħakk mnejn jittieħed,
ed Common:
to Komuni
Application site warmth, application site erythema, application site pain, application site irritation, application site paraesthesia, application site rash
Sħana mnejn jittieħed, ħmura mnejn jittieħed, uġigħ mnejn jittieħed, irritazzjoni
is Infections and infestations
aw mnejn jittieħed, paraesthesia mnejn jittieħed, raxx mnejn jittieħed.
or Common:
Infezzjonijiet u infestazzjonijiet Komuni
Herpes viral infections (herpes simplex dermatitis [eczema herpeticum], herpes simplex [cold sores], Kaposi’ s varicelliform eruption)
Infezzjonijiet bil- herpes (dermatite b’ herpes simplex [eczema herpeticum], herpes
th Skin and subcutaneous tissue disorders
x semplex [ħżiża], eruzzjoni variċelliforma ta 'Kaposi)
Uncommon:
du Mard tal- ġilda u tessuti taħta ħa Komuni Mhux komuni
er Nervous system disorders Common:
Mard tas- sistema nervuża m
Metabolism and nutrition disorders ng lo Common:
Mard marbut mal- metaboliżmu u nutrizzjoni li
Alcohol intolerance (facial flushing or skin irritation after consumption of an alcoholic beverage) no
Intolleranza għall- alkoħol (ħmura tal- wiċċ jew irritazzjoni tal- ġilda wara xorb li
Rosacea ct
alkoħoliku) a in
Post-marketing: cases of malignancies, including cutaneous and other types of lymphoma, and skin du
Kien hemm dawn ir- reazzjonijiet avversi matul l- esperjenza ta ’ wara t- tqegħid fis- suq:
cancers, have been reported in patients using tacrolimus ointment (see section 4.4). ro
Wara t- tqegħid fuq is- suq: f’ pazjenti li kienu qed jużaw l- ingwent tacrolimus kien hemm każijiet ta ’ xi malinjitajiet fil- ġilda u tipi oħra ta ’ limfoma, kif ukoll kanċer tal- ġilda (ara sezzjoni 4. 4). tm
4.9 Overdose lp
4. 9 Doża eċċessiva
Overdosage following topical administration is unlikely.
Dan il- periklu mhux probabli, jekk l- ingwent jiġi biss applikat fuq il- ġilda. ot
Due to the nature of the ointment vehicle, induction of a
Minħabba n- natura ta ’ l- ingwent użat, mhux od
vomiting or gastric lavage is not recommended. in ic
Pr
PHARMACOLOGICAL PROPERTIES ed
TAGĦRIF FARMAKOLOĠIKU
5.1 Pharmacodynamic properties M
5. 1 Tagħrif farmakodinamiku
Via its binding to a specific cytoplasmic immunophilin (FKBP12), tacrolimus inhibits calcium- dependent signal transduction pathways in T cells, thereby preventing the transcription and synthesis of IL-2, IL-3, IL-4, IL-5 and other cytokines such as GM-CSF, TNF-α and IFN-γ.
t za jinibixxi ġewwa T- cells sinjali tat- transduzzjoni, li jiddependu fuq il- kalċju, u b' hekk tiġi mwaqqfa t - transkrizzjoni u s- sinteżi ta 'IL- 2, IL- 3, IL- 4, IL- 5, u ta' ċitokini oħra bħal GM- CSF, TNF- α u IFN- γ.
14 In vitro, in Langerhans cells isolated from normal human skin, tacrolimus reduced the stimulatory activity towards T cells.
riz In vitro, f 'ċelluli ta' Langerhans li nkisbu minn ġilda normali, tacrolimus naqqas l- attività stimulatorja lejn it- T cells.
In animals, tacrolimus ointment suppressed inflammatory reactions in experimental and spontaneous dermatitis models that resemble human atopic dermatitis.
to F 'annimali tacrolimus ingwent waqqaf l- infjammazzjoni f' każijiet ta 'dermatite sperimentali u
In patients with atopic dermatitis, improvement of skin lesions during treatment with tacrolimus ointment was associated with reduced Fc receptor expression on Langerhans cells and a reduction of their hyperstimulatory activity towards T cells.
F 'pazjenti b' dermatite atopika, waqt li l- marda tal- ġilda marret għall- aħjar wara trattament b 'tacrolimus ingwent, kien hemm riduzzjoni tal- qari tar- reċettur Fc fuq iċ- ċelluli ta' Langerhans u
Tacrolimus ointment does not affect collagen synthesis in humans.
Tacrolimus ingwent ma jaffettwax
ed Results from clinical studies in patients The efficacy and safety of Protopy was assessed in more than 13,500 patients treated with tacrolimus ointment in Phase I to Phase III clinical trials.
ħa Riżultati ta 'studji kliniċi fuq pazjenti L- effiċjenza u s- sigurtà ta' Protopy ġew studjati f 'aktar minn 13, 500 pazjent wara trattament bi ’ g Protopy ingwent fil Fasi I sa Fasi III ta ’ l- esperiment kliniku.
Data from four major trials are presented here.
Hawn ser jingħata t- tagħrif miġbur minn erba ’ provi kliniċi maġġuri. m
is In a six-month multicentre double-blind randomised trial, 0.1% tacrolimus ointment was administered
Fi prova li ħa sitt xhur, li sar f 'aktar minn ċentru wiehed u li kien tat- tip "double blind randomised" 0. 1% Protopy ingwent ingħata darbtejn kuljum lil pazjenti kbar li kienu jsofru b' dermatite atopika ta 'qawwa moderata għal qalila.
or 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%
applikat b’ mod topiku (0. 1% hydrocortisone butyrate fuq is- sider, fuq iż- żaqq, fuq l- idejn, fuq ir - li
th hydrocortisone acetate on face and neck).
riġlejn u fuq is- saqajn, 1% hydrocortisone acetate fuq il- wiċċ u fuq l- għonq).
The primary endpoint was the response rate at month 3 defined as the proportion of patients with at least 60% improvement in the mEASI (modified Eczema
għall- aħjar b 'mill- anqas 60% skond l- mEASI (modified Eczema Area and Severity Index) bejn il- bidu ta ’ l- esperiment u kif skadew 3 xhur.
au Area and Severity Index) between baseline and month 3.
(71. 6%) kienet aktar għolja minn dik tal- grupp li ngħata corticosteroid b’ mod topiku (50. 8%; p < 0. 001; ed
The response rate in the 0.1% tacrolimus group (71.6%) was significantly higher than that in the topical corticosteroid based treatment group (50.8%; p < 0.001; Table 1).
Tabella 1).
er Table 1
Tabella 1 tm
ng
ot
Topical corticosteroid lo (N=485)
Reġimen ta ’ Corticosteroid applikat b’ mod topiku§ (N=485)
Response rate of ≥ 60%
Pazjenti li għaddew għal aħjar od
50.8% no
50. 8%
improvement in mEASI (Primary Endpoint)§§
mill- anqas ≥ 60% skond mEASI (l- ewwel punt wara 3 xhur) §§ Pazjenti li għaddew għal aħajar Pr
Improvement ≥ 90% in Physician’ s 28.5% ct
28. 5%
Global Evaluation § Topical corticosteroid regimen = 0.1% hydrocortisone butyrate on trunk and extremities, 1% du
≥ 90% skond Physician’ s Global Evaluation § Corticosteroid applikat b’ mod topiku = 0. 1% hydrocortisone butyrate fuq is- sider, fuq iż- żaqq, fuq l - idejn, fuq ir- riġlejn u fuq is- saqajn, 1% hydrocortisone acetate fuq il- wiċċ u fuq l- għonq §§ valuri aktar għoljin = titjib akbar
Skin lp
Il- frekwenza u l- kwalità tal- biċċa ’ l kbira ta ’ l- effetti avversi kienu bejn wieħed u ieħor l- istess fiż - żewg gruppi.
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 a
Ħruq tal- ġilda, herpes semplex, intolleranza lejn l- akoħol (ħmura tal- wiċċ jew sensitività tal- ġilda wara xorb alkoħoliku), tingiz tal- ġilda, hyperaesthesia, akne u dermatite tal- fungus seħħew
treatment group.
15 aktar sikwit fil- grupp b 'trattament b' tacrolimus.
There were no clinically relevant changes in the laboratory values or vital signs in in
Waqt l- istudju kollu ma kienx hemm tibdil kliniku rilevanti fir- riżultati tal- laboratorju jew fis- sinjali vitali fil- pazjenti taż- żewg gruppi.
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% ed
Fit- tieni prova, tfal bejn 2 sa 15- il sena, li kienu jsofru minn dermatite atopika, moderata għal qalila, ġew mogħtija 0. 03% tacrolimus ingwent, 0. 1% tacrolimus ingwent u ingwent ta '1% hydrocortisone acetate darbtejn kuljum għal żmien ta' 3 ġimgħat.
The results of this multicentre, M
L- ewwel punt ta ’ l- evalwazzjoni kienet l- erja taħt il - kurva (AUC = area under the curve) tal- mEASI bħala persentaġġ tal- valur bażi fuq it- tul tat- trattament.
double-blind, randomised trial showed that tacrolimus ointment, 0.03% and 0.1%, is significantly more effective (p < 0.001 for both) than 1% hydrocortisone acetate ointment (Table 2).
Ir- riżultati ta 'din il- prova double blind u randomised, urew li tacrolimus ingwent f' konċentrazzjoni ta '0. 03% u ta' 0. 1% hu sinifikament aktar effettiv (p < 0. 001 għat- tnejn) minn ingwent ta '1% hydrocortisone acetate (Tabella 2).
15 Table 2
t za Tabella 2
Median mEASI
Il- medjan tal- mEASI bħala
as Percentage of
64. 0%
64.0%
44. 8%
44.8%
39. 8%
39.8%
to persentaġġ tal- medja tal- valur
Baseline mean AUC (Primary Endpoint)§ Improvement ≥ 90% in Physician’ s Global Evaluation § lower values = greater improvement
aw bażi AUC (l- endpoint Primarju) § Titjib ≥ 90% skond Physician’ s 15. 7% Global Evaluation
15.7%
38. 5%
38.5%
48. 4%
48.4%
x § valuri aktar baxxi = titjib akbar
ed The incidence of local skin burning was higher in the tacrolimus treatment groups than in the hydrocortisone group.
du Il- frekwenza ta 'ħruq tal- ġilda lokali kienet aktar għolja fil- gruppi b' trattament b' tacrolimus milli fil - ħa gruppi b 'trattament b' hydrocortisone.
There were no clinically relevant changes in the laboratory values or vital signs
Waqt il- prova klinika kollha ma kienx hemm ’ g tibdil kliniku relevanti fir- riżultati tal- laboratorju jew fis- sinjali vitali fil- pazjenti taż- żewg gruppi. m
or The purpose of the third multicentre, double-blind, randomised study was the assessment of efficacy
L- iskop tat- tielet studju tat- tip "double- blind randomised", li ġie magħmul f 'aktar minn ċentru wieħed, kienet l- evalwazzjoni ta ’ l- effiċjenza u tas- sigurtà ta' 0. 03% tacrolimus ingwent, li ġie applikat darba li
th 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
jew darbtejn kuljum fi tfal li kellhom dermatite atopika, moderata għal qalila, f 'paragun ma' 1% ingwent tal- hydrocortisone acetate li ġie applikat darbtejn kuljum.
Treatment duration was for up to three weeks.
It- trattament damet sa tliet gimgħat. li a
er
iċ
Hydrocortisone acetate 1% Twice daily (N=207)
Hydrocortisone acetate 1%
ng lo Median mEASI Percentage Decrease (Primary Endpoint)§
(N=207) Tnaqqis fil- medja tal- mEASI (l - endpoint Primarju) § tm
Improvement ≥ 90% in Physician’ s Global Evaluation
Titjib ≥ 90% skond Physician’ s 13. 6% Global Evaluation ot
§ higher values = greater improvement ct
§ valuri aktar għoljin = titjib akbar od
The primary endpoint was defined as the percentage decrease in mEASI from the baseline to end of du
L- endpoint primarju ġie definit bħala l- persentaġġ kif naqas il- mEASI mill- linja bażi sakemm spiċċat it- trattament.
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 ro
Deher titjib statistikament sinifikanti b ’ 0. 03% tacrolimus ingwent, li ngħata darba u darbtejn kuljum, imqabbel ma ’ l- ingwent ta ’ hydrocortisone acetate mogħti darbtejn kuljum (p < 0. 001 Pr
The incidence of local skin burning was higher in the tacrolimus treatment lp
Il- frekwenza ta 'ħruq tal- ġilda fil- parti ta ’ l- applikazzjoni kienet aktar għolja fil- gruppi bit- trattament b' tacrolimus milli f' dawk b 'trattament b' hydrocortisone.
There were no clinically relevant changes in the laboratory values or vital signs in either treatment group throughout the study. a in
Waqt l- istudju kollu ma kienx hemm tibdil kliniku relevanti fir- riżultati tal- laboratorju jew fis- sinjali vitali fil- pazjenti taż- żewg gruppi.
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 ic
Fir- raba prova, kważi 800 pazjent (età ≥ 2 snin) irċevew trattament b '0. 1% tacrolimus ingwent, kontinwament jew b' intervalli, għal mhux aktar minn erba ’ snin, bl- iskop ta 'studju tas- sigurtà open - label fuq żmien twil ta' trattament.
patients receiving treatment for at least three years and 79 patients receiving treatment for a minimum ed
300 pazjent irċevew trattament mill- anqas 3 snin u 79 pazjent irċevew trattament għal 42 xahar.
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.
Meta wieħed ikkonsidra it- tibdil bażat fuq il- linja bażi tal- punteġġ 16 EASI u fuq l- erja tal- ġilda affettwata, il- pazjenti b 'dermatite atopika kollha għaddew għall- aħjar f' kull fażi ta 'evalwazzjoni u indipendentement mill- età tagħhom.