qanastek/EMEA-V3 huggingface dataset:
PROTELOS is not known to affect your ability to drive or use machines.
PROTELOS m’ għandu jkollu l- ebda effett fuq is- sewqan, l- użu minn għodda jew it- tħaddim ta’ magni.
Important information about some of the ingredients of PROTELOS:
Tagħrif importanti dwar xi wħud mis- sustanzi ta ’ PROTELOS:
PROTELOS contains aspartame.
PROTELOS fih aspartame.
HOW TO TAKE PROTELOS
KIF GĦANDEK TIEĦU PROTELOS
Always take PROTELOS exactly as your doctor has told you.
Dejjem għandek tieħu PROTELOS eżatt skond il- parir tat- tabib.
PROTELOS is for oral use.
PROTELOS huwa għal użu mill- ħalq.
It is recommended that you take PROTELOS at bedtime.
Huwa rakkomandat li tieħu PROTELOS qabel ir- raqda ta ’ bil- lejl.
You may lie down immediately after taking PROTELOS if you wish.
Tista ’ timtedd mill- ewwel wara li tieħu PROTELOS jekk tixtieq tagħmel dan.
PROTELOS can interact with milk and milk products, so it is important that you mix PROTELOS only with water to be sure it works properly.
PROTELOS jista ’ ma jaqbilx mal- ħalib jew prodotti magħmula mill- ħalib, għalhekk huwa importanti li tħawwad PROTELOS ma ’ l- ilma biss biex tkun ċert li jaħdem tajjeb.
Your doctor may advise you to take calcium and vitamin D supplements in addition to PROTELOS.
It- tabib tiegħek jista jirakkomandalek li tieħu supplimenti ta ’ calcium jew Vitamina D barra PROTELOS.
Do not take calcium supplements at bedtime, at the same time as PROTELOS.
Tieħux is- supplimenti ta’ calcium qabel ir- raqda ta ’ bil- lejl, fl- istess ħin ta ’ PROTELOS.
Your doctor will tell you how long you should continue to take PROTELOS.
It- tabib tieħek għandu jgħidlek kemm għandek iddum tieħu PROTELOS fit- tul.
It is important that you continue taking PROTELOS for as long as your doctor prescribes the medicine.
Huwa importanti li tibqa ’ tieħu PROTELOS sakemm it- tabib jibqa ’ jiktiblek il- mediċina.
If you take more PROTELOS than you should:
Jekk tieħu PROTELOS aktar milli suppost:
If you take too many sachets of PROTELOS, tell your doctor or pharmacist.
Jekk tieħu aktar qratas ta ’ PROTELOS milli suppost, kellem lit- tabib jew l- ispiżjar tiegħek.
If you forget to take PROTELOS:
Jekk tinsa tieħu PROTELOS:
Like all medicines, PROTELOS can cause side effects, although not everybody gets them.
Bħall kull mediċina oħra, PROTELOS jista ’ jkollu effetti sekondarji, għalkemm ma jidhrux fuq kulħadd.
The following side effects have also been reported by patients taking PROTELOS: vomiting, abdominal pain, oral irritation (such as mouth ulcers and gum inflammation), bone, muscle and/ or joint pain, muscle cramps, hypersensitivity syndromes (allergic reactions including rash and fever), itching, hives, angioedema (such as swollen face, tongue or throat, difficulty in breathing or swallowing), swelling in limbs, feeling confused.
Dawn l- effetti mhux mixtieqa ġew irraportati ukoll minn pazjenti li ħadu PROTELOS: remettar, uġigħ addominali, irritazzjoni orali (bħal ulċeri fil - ħalq u infjammazjoni fil- ħanek), uġigħ fl- għadam, fil - muskoli u/ jew fil- ġogi, bugħawwieġ, sindromi ta ’ sensittività eċċessiva (reazzjonijiet allerġiċi li jinkludu raxx u deni), ħakk, urtikarja, anġjoedema (bħal nefħa fil- wiċċ, ilsien jew griżmejn, diffikulta` biex tieħu n- nifs jew biex tibla), nefha fl- idejn u s- saqajn, tħossok konfuż.
Therefore you should immediately stop taking PROTELOS and see your doctor if you experience symptoms of angioedema or hypersensitivity syndrome.
Għalhekk għandek tieqaf tieħu PROTELOS immedjatament u għandek tara ’ t- tabib tiegħek jekk ikollok sintomi ta ’ anġjoedema jew sindromu ta ’ sensittività eċċessiva..
If you have stopped treatment due to hypersensitivity syndrome, it should be permanent and you should not re-start therapy with PROTELOS.
27 Jekk tkun waqqaft il- kura minħabba sindromu ta ’ sensittivita` aċċessiva, din għanda tkun għal dejjem u m’ għandekx terġa tibda l- kura bi PROTELOS.
HOW TO STORE PROTELOS
KIF TAĦŻEN PROTELOS
Do not use after the expiry date which is stated on the box and the sachet.
Tużax PROTELOS wara d- data ta ’ skadenza li tidher fuq il- kartuna u il- qartas
What PROTELOS contains
X’ fih PROTELOS
What PROTELOS looks like and contents of the pack PROTELOS is available in sachets containing yellow granules for oral suspension.
Id- Dehra ta 'PROTELOS u l- kontenuti tal- pakkett PROTELOS jiġi fi qratas li fihom granijiet sofor għal suspensjoni orali.
PROTELOS is supplied in boxes of 7, 14, 28, 56, 84 or 100 sachets.
PROTELOS jinbiegħ f’ kaxxi ta ’ 7, 14, 28, 56, 84 jew 100 qartas.
29
29 Dan il- fuljett kien approvat l- aħħar f ’
Protopic 0.03% ointment
Protopic 0. 03% ingwent
1 g of Protopic 0.03% ointment contains 0.3 mg of tacrolimus as tacrolimus monohydrate (0.03%).
1 g ta 'Protopic 0. 03% ingwent fih 0. 3 mg ta' Tacrolimus bħala tacrolimus monohydrate (0. 03%).
A white to slightly yellowish ointment.
Ingwent abjad jagħti fl- isfar.
Treatment of moderate to severe atopic dermatitis in adults who are not adequately responsive to or are intolerant of conventional therapies such as topical corticosteroids.
Il- kura ta ’ dermatite atopika moderata jew severa fl- adulti li ma jkunux adegwatament responsivi għal jew intolleranti għal terapiji konvenzjonali bħalma huma l- kortikosterojdi topikali.
Treatment of moderate to severe atopic dermatitis in children (2 years of age and above) who failed to respond adequately to conventional therapies such as topical corticosteroids.
Kura moderata għal severa ta ’ dermatite atopika fit tfal (minn sentejn ‘ il fuq) li ma kellhomx respons adegwat għal kura konvenzjonali bħalma huma l- kortikosterojdi topikali.
Protopic should be initiated by physicians with experience in the diagnosis and treatment of atopic dermatitis.
Kura bi Protopic għandu jinbeda minn tabib li jkollu esperjenza fid- dijanjosi u l- kura tad- dermatite atopika.
Treatment should be intermittent and not continuous.
Il- kura ma tridx tkun kontinwa iżda intermittenti.
Protopic ointment should be applied as a thin layer to affected areas of the skin.
Protopic forma ta 'ingwent jiġi mdellek ħafif fuq il- parti tal- ġilda affettwata.
Protopic ointment may be used on any part of the body, including face, neck and flexure areas, except on mucous membranes.
Protopic forma ta ’ ingwent jista 'jiġi użat f' kull parti tal- ġisem, inklużi l- wiċċ, l- għonq, u partijiet fejn il- ġilda tintlewa, minbarra membrani mukużi.
Protopic ointment should not be applied under occlusion (see section 4.4).
Protopic forma ta 'ingwent m' għandux jintuża taħt faxxex (ara sezzjoni 4. 4).
Each affected region of the skin should be treated with Protopic until clearance occurs and then treatment should be discontinued.
Kull parti tal- ġilda affettwata għandha tiġi trattata bi Protopic sakemm il- marda tfieq, imbagħad it - trattament għandha tiġi mwaqqfa.
Generally, improvement is seen within one week of starting treatment.
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 għandu jaħseb f 'terapiji oħra.
Protopic can be used for short term and intermittent long term treatment.
Protopic jista 'jintuża għal żmien qasir jew ukoll għal żmien sakemm ikun hemm twaqqif għal xi perijodu żgħir.
At the first signs of recurrence (flares) of the disease symptoms, treatment should be re-initiated.
Malli jidher li ser jerġgħu jibdew is- sintomi (flares) tas - sintomi tal- marda, il- kura trid terġa ’ tibda.
Protopic is not recommended for use in children below age of 2 years until further data are available.
Protopic mhux rakkomandat għat- tfal taħt l- età ta ’ sentejn qabel ma jkun hemm aktar informazzjoni dwaru.
Use in children (2 years of age and above) Treatment should be started twice a day for up to three weeks.
Użu f 'tfal (ta' sentejn u akbar) Il- kura trid tinbeda darbtejn kuljum għal mhux aktar minn tliet ġimgħat.
Afterwards the frequency of application should be reduced to once a day until clearance of the lesion (see section 4.4).
Wara ma hemmx għalfejn tibqa ’ tingħata daqshekk spiss u tista ’ titnaqqas għal darba kuljum sakemm il- leżjoni tkun telqet sewwa (ara sezzjoni 4. 4).
Use in adults (16 years of age and above) Protopic is available in two strengths, Protopic 0.03% and Protopic 0.1% ointment.
2 Użu f 'persuni kbar (16 il- sena' l fuq) Protopic jiġi bħala ingwent fil- qawwa ta 'Protopic 0. 03% u ta' Protopic 0. 1%.
Treatment should be started with Protopic 0.1% twice a day and treatment should be continued until clearance of the lesion.
It- trattament tinbeda bi Protopic 0. 1% darbtejn kuljum sakemm il- ferita tfiq.
If symptoms recur, twice daily treatment with Protopic 0.1% should be restarted.
Jekk is- sintomi jergħu jiġu, wieħed jerġa jibda trattament b' Protopic 0. 1% darbtejn kuljum.
An attempt should be made to reduce the frequency of application or to use the lower strength Protopic 0.03% ointment if the clinical condition allows.
Wieħed għandu jipprova inaqqas il- frekwenza ta ’ l- użu, jew juża Protopic 0. 03%, jekk il- kondizzjoni klinika tippermetti.
2 Use in elderly (65 years of age and above) Specific studies have not been conducted in elderly patients.
Użu fl- anzjani (65 sena u akbar) Għad m 'hemmx studji speċifiċi f’ pazjenti anzjani.
However, the clinical experience available in this patient population has not shown the necessity for any dosage adjustment.
Pero l- esperjenza klinika li għandna ma 'dawn il - pazjenti ma turix bżonn li d- doża għandha titbiddel.
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.
L- istudji kliniċi dwar l- effikaċja li saru ġew mwaqqfa f 'salt u għalhekk m' hemmx informazzjoni jekk ir- rata ta' rikorrenza tkunx anqas jekk it- trattament titwaqqaf bil- mod il- mod.
Hypersensitivity to macrolides in general, to tacrolimus or to any of the excipients.
Sensittività eċċessiva għal macrolides, għal tacrolimus jew għal xi sustanzi ohrajn.
Protopic should not be used in patients with congenital or acquired immunodeficiencies or in patients on therapy that cause immunosuppression.
Protopic 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.
The effect of treatment with Protopic ointment on the developing immune system of children, especially the young, has not yet been established and this should be taken into account when prescribing to this age group (see section 4.1).
L- effett tat- trattament bi Protopic ingwent fuq is- sistema immunitarja fit- tfal, speċjalment f 'tfal żgħar, għadu ma ġiex stabilit, u għalhekk wieħed għandu jaħseb f' dan il- fatt f' dan il- grupp ta 'pazjenti (ara sezzjoni 4. 1).
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 during use of Protopic ointment (see section 5.3).
Waqt l- użu ta 'Protopic ingwent wieħed għandu jevita li joqgħod espost għax- xemx u raġġi ultravjoletti (UV) ta' solarju kif ukoll dawk fit- trattament b 'UVB jew UVA b' kombinazzjoni ma 'psoralens (PUVA) (ara sezzjoni 5. 3).
Physicians should advise patients on appropriate sun 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.
Protopic ointment should not be applied to lesions that are considered to be potentially malignant or pre-malignant.
L- ingwent Protopic ma għandux jintuża fuq leżjonijiet meqjusa bħala potenzjalment malinji jew pre- malinji.
Emollients should not be applied to the same area within 2 hours of applying Protopic ointment.
Emoljenti ma jistgħux jintużaw fl- ewwel sagħtejn wara applikazzjoni ta 'Protopic.
Concomitant use of other topical preparations has not been assessed.
L- użu ta 'ingwenti oħrajn fl- istess ħin ma' Protopic 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 'Protopic ma' steroids sistemiċi jew ma 'mediċini immunosuppressivi.
Protopic ointment has not been evaluated for its efficacy and safety in the treatment of clinically infected atopic dermatitis.
Is- sigurtà u l- effiċenza ta 'Protopic ingwent għadhom ma ġewx eżaminati fit- trattament tad- dermatite atopika klinikament infettata.
Before commencing treatment with Protopic ointment, clinical infections at treatment sites should be cleared.
Qabel ma tibda trattament bi Protopic ingwent, wieħed għandu jara li infezzjoni tal- ġilda fil- partijiet relevanti tiġi mfejqa qabel.
Patients with atopic dermatitis are predisposed to superficial skin infections.
Pazjenti b 'dermatite atopika jista' jkollom ukoll infezzjoni superfiċjali tal- ġilda.
Treatment with Protopic may be associated with an increased risk of herpes viral infections (herpes simplex dermatitis [eczema herpeticum], herpes simplex [cold sores], Kaposi’ s varicelliform eruption).
Waqt it- trattament bi Protopic ir- riskju ta 'infezzjoni bil- herpes (dermatite sempliċi tal- herpes [eczema herpeticum], herpes simplex [ħżiża], eruzzjoni variċelliforma ta' Kaposi).
In the presence of these infections, the balance of risks and benefits associated with Protopic use should be evaluated.
Fil każ ta 'infezzjonijiet bħal dawn wieħed għandu jqies ir- riskji u l- ġid ta' trattament bi Protopic.
The potential for local immunosuppression (possibly resulting in infections or cutaneous malignancies) in the long term (i. e. over a period of years) is unknown (see section 5.1).
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).
Protopic contains the active substance tacrolimus, a calcineurin inhibitor.
Protopic fih is- sustanza attiva tacrolimus, inibitur kalċinewriniku.
In transplant patients, prolonged systemic exposure to intense immunosuppression following systemic administration of calcineurin inhibitors has been associated with an increased risk of developing lymphomas and skin malignancies.
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.
In patients using tacrolimus ointment, cases of malignancies, including cutaneous and other types of lymphoma, and skin cancers have been reported (see section 4.8).
F’ pazjenti li jużaw l - 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 Protopic have not been found to have significant systemic tacrolimus levels.
Ma nstabx li dawk il- pazjenti b’ dermatite atopika kkurati bi Protopic kellhom livelli sistemiċi sinifikanti ta ’ tacrolimus.
Lymphadenopathy was uncommonly (0.8%) reported in clinical trials.
Każijiet mhux komuni (0. 8%) ta ’ limfadenopatija kienu rapurtati fi provi kliniċi.
The majority of these cases related to infections (skin, respiratory tract, tooth) and resolved with appropriate antibiotic therapy.
Il- biċċa ’ l kbira 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 Protopic and who develop lymphadenopathy should be monitored to ensure that the lymphadenopathy resolves.
3 immunosuppressivi (per ezempju injezzjoni ta 'tacrolimus), għandhom ċans akbar li jiżviluppaw limfoma; Għalhekk pazjenti li qed jieħdu Protopic u tiżviluppalhom limfadenopatija għandhom jibqgħu taħt osservazzjoni biex jiġi aċċertat li l- limadenopatija tfieq.
Lymphadenopathy present at initiation of therapy should be investigated and kept under review.
Il- limfadenopatija li jkun hemm fil- bidu tal- kura għandha tkun investigata u tibqa ’ ċċekkjata regolarment.
In
Fil- każ li l- limfadenopatija ma tfieqx, il- kawża tal- limfadenopatija għandha tkun mistħarrġa.
3 the absence of a clear aetiology for the lymphadenopathy or in the presence of acute infectious mononucleosis, discontinuation of Protopic 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 Protopic.
Care should be taken to avoid contact with eyes and mucous membranes.
Għandha tingħata attenzjoni biex ma jseħħx kuntatt ma 'l- għajnejn jew ma ’ membrani mukużi.
If accidentally applied to these areas, the ointment should be thoroughly wiped off and/ or rinsed off with water.
Jekk aċċidentalment l- ingwent jiġi fuq dawn il- partijiet, wieħed għandu jimsaħ l- ingwent u jlaħlaħ il- parti bl- ilma.
The use of Protopic ointment under occlusion has not been studied in patients.
L- użu ta 'Protopic taħt faxxex għadu ma ġiex studjat f’ pazjenti.
Occlusive dressings are not recommended.
L- użu ta 'faxxex mhux rakkomandat.
As with any topical medicinal product, patients should wash their hands after application if the hands are not intended for treatment.
Kif jagħmlu wara l- użu ta ’ ingwenti u kremi mediċinali oħrajn, il- pazjenti għandhom jaħslu jdejhom jekk ma jkunux iridu jitrattawhom apposta.
Tacrolimus is extensively metabolised in the liver and although blood concentrations are low following topical therapy, the ointment should be used with caution in patients with hepatic failure (see section 5.2).
Ħafna minn tacrolimus jigi metabolizzat fil- fwied u għalkemm il- konċentrazzjoni fid- demm hi baxxa, l- ingwent għandu jiġi wżat b 'kawtela f' każ fejn ikun hemm insuffiċjenza tal- fwied (ara sezzjoni 5. 2).
The use of Protopic 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.
L- użu ta 'Protopic mhux rakkomandat f' pazjenti li jsofru minn difetti ġenetiċi li jaffettwaw l- ilqugħ tal- ġilda bħal Netherton' s syndrome minħabba il- periklu li tacrolimus jidħol b 'qawwa akbar fid- demm.
The safety of Protopic ointment has not been established in patients with generalised erythroderma.
Is- sigurtà ta 'l- użu ta' Protopic f 'pazjenti b' erythroderma ġeneralizzata għadha mhiex stabilita.
Care should be exercised if applying Protopic to patients with extensive skin involvement over an extended period of time, especially in children (see section 4.2).
Wieħed irid joqgħod attent ħafna meta juża Protopic fuq pazjenti li jkollhom firxa kbira ta ’ ġilda involuta għal perijodu ta ’ żmien fit- tul, speċjalment fit- tfal (ara sezzjoni 4. 2).
Formal topical drug interaction studies with tacrolimus ointment have not been conducted.
L- interazzjoni topika ta 'tacrolimus ingwent għadha ma ġietx studjata formalment.
Tacrolimus is not metabolised in human skin, indicating that there is no potential for percutaneous interactions that could affect the metabolism of tacrolimus.
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.
Systemically available tacrolimus is metabolised via the hepatic Cytochrome P450 3A4 (CYP3A4).
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 għalhekk ma tiġiex affettwata minn sustanzi kontra CYP3A4.
However, the 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 widespread and/ or erythrodermic disease should be done with caution.
Iżda wieħed ma jistgħax jeskludi l - 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.
A potential interaction between vaccination and application of Protopic ointment has not been investigated.
Il- possibilità ta 'interazzjoni bejn Protopic ingwent u t- tilqim għadha mhiex studjata.
Because of the potential risk of vaccination failure, vaccination should be administered prior to commencement of treatment, or during a treatment-free interval with a period of 14 days between the last application of Protopic and the vaccination.
Minħabba li t - tilqima tista ’ ma tirnexxix, it- tilqima għandha ssir qabel tibda t- trattament bi Protopic, jew inkella f ’ perijodu meta t- trattament bi Protopic tkun imwaqqfa u jkun hemm intervall ta ’ 14- il ġurnata bejn Protopic u t- tilqima.
In case of live attenuated vaccination, this period should be extended to 28 days or the use of alternative vaccines should be considered.
Fil- każ ta 'tilqima bil- mikrobi newtralizzati (attenuated) ħajjin, dan l- spazju għandu jkun estiż għal 28 jum jew inkella wieħed għandu juża tipi ta ’ tilqim oħrajn.
There are no adequate data from the use of tacrolimus ointment in pregnant women.
Ma hemmx tagħrif biżżejjed dwar l- użu ta ’ l- ingwent tacrolimus fuq nisa tqal.
Studies in animals 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.
Ir- riskju li jista ’ jkun hemm għal bniedem mhux magħruf.
Protopic ointment should not be used during pregnancy unless clearly necessary.
Protopic ingwent m' għandux jintuża waqt it- tqala sakemm ma jkunx verament meħtieġ.
Human data demonstrate that, after systemic administration, tacrolimus is excreted into breast milk.
Għalkemm tagħrif kliniku juri li l- konċentrazzjoni ta 'tacrolimus fid- demm tkun baxxa wara li
Although clinical data have shown that systemic exposure from application of tacrolimus ointment is low, breast-feeding during treatment with Protopic ointment is not recommended.
4 tacrolimus jintuża bħala ingwent fuq il- ġilda, mhux rakkomandat li Protopic ingwent jintuża f 'pazjenti nisa li jkunu għadhom jreddu.
4 No studies on the effects on the ability to drive and use machines have been performed.
Dawn l- effetti għadhom ma ġewx studjati.
Protopic ointment is administered topically and is unlikely to have an effect on the ability to drive or use machines.
L- ingwent Protopic jista ’ jintuża topikament u aktarx li ma jkollu ebda effett 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.
Madwar 50% tal- pazjenti kellhom xi tip ta ’ irritazzjoni avversa tal- ġilda fil- parti fejn ġie applikat l - ingwent.
Burning sensation and pruritus were very common, usually mild to moderate in severity and tended to resolve within one week of starting treatment.
Ħruq u ħakk kienu komuni ħafna, b 'intensità ħafifa għal moderata, u ġeneralment kienu jfiequ fi żmien ġimgħa wara li kienet bdiet it- trattament.
Erythema was a common skin irritation adverse reaction.
Eritema kienet reazzjoni ta ’ irritazzjoni avversa tal- ġilda komuni wkoll.
Sensation of warmth, pain, paraesthesia and rash at the site of application were also commonly observed.
Ħafna drabi seħħew ukoll sensazzjoni ta ’ sħana, uġigħ, paraesthesia (wieħed ma jkunx iħoss) u raxx fil- partijiet fejn ġie applikat l- ingwent.
Alcohol intolerance (facial flushing or skin irritation after consumption of an alcoholic beverage) was common.
Ta ’ spiss kien hemm ukoll intolleranza lejn ix- xorb alkoħoliku (ħmura tal- wiċċ jew ħruq tal- ġilda wara xarba alkoħolika).
Patients may be at an increased risk of folliculitis, acne and herpes viral infections.
Il- pazjenti jista ’ jkollhom ukoll riskju akbar ta ’ follikulite, akne jew infezzjonijiet virali bil- herpes.
Adverse reactions with suspected relationship to treatment are listed below by system organ class.
Reazzjonijiet avversi li dehru li kellhom x 'jaqsmu mat- trattament huma elenkati hawn taħt, skond il - klassi ta ’ l- organu tas- sistema.
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 decreasing seriousness.
Ma kull grupp ta ’ ċerta frekwenza, jitfaċcaw effetti mhux mixtieqa iżda jonqsu fis- serjetà.
General disorders and administration site conditions Very common:
Mard ġenerali u kundizzjonijiet fil- parti ta 'mnejn jittieħed Komuni ħafna:
Application site burning, application site pruritus Application site warmth, application site erythema, application site pain, application site irritation, application site paraesthesia, application site rash
Ħruq mnejn jittieħed, ħakk mnejn jittieħed, Sħana mnejn jittieħed, ħmura mnejn jittieħed, uġigħ mnejn jittieħed, irritazzjoni mnejn jittieħed, paraesthesia mnejn jittieħed, raxx mnejn jittieħed.
Infections and infestations 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 semplex [ħżiża], eruzzjoni variċelliforma ta 'Kaposi)
Uncommon:
Mard tal- ġilda u tessuti taħta Komuni Mhux komuni
Folliculitis, pruritus Acne
Follikulite, ħakk Akne
Nervous system disorders Common:
Mard tas- sistema nervuża Komuni
Paraesthesias and dysaesthesias (hyperaesthesia, burning sensation)
Paraesthesia jew dysaesthesia (hyperaesthesia, sensazzjoni ta ’ ħruq)
Metabolism and nutrition disorders Common:
Mard marbut mal- metaboliżmu u nutrizzjoni Komuni
Alcohol intolerance (facial flushing or skin irritation after consumption of an alcoholic beverage)
Intolleranza għall- alkoħol (ħmura tal- wiċċ jew irritazzjoni tal- ġilda wara xorb alkoħoliku)
The following adverse reactions have been reported during post-marketing experience:
Kien hemm dawn ir- reazzjonijiet avversi matul l- esperjenza ta ’ wara t- tqegħid fis- suq:
Rosacea
Rosaċeja
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).
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).
Overdosage following topical administration is unlikely.
Dan il- periklu mhux probabli, jekk l- ingwent jiġi biss applikat fuq il- ġilda.
If ingested, general supportive measures may be appropriate.
Jekk forsi l- ingwent jittiekel, ikun hemm bżonn ta 'miżuri kif jixraq.
These may include monitoring of vital signs and observation of clinical status.
Dan jista 'jinkludi monitoraġġ tas - sinjali vitali u ħarsien ta ’ l- istat kliniku tal- pazjent.
Due to the nature of the ointment vehicle, induction of vomiting or gastric lavage is not recommended.
Minħabba n- natura ta ’ l- ingwent użat, mhux rakkomandat ir- riġettar jew ħasil gastriku.
5 Pharmacotherapeutic group:
Kategorija farmakoterapewtika:
Other dermatologicals, ATC code:
Prodotti mediċinali tal- ġilda, kodiċi ATC:
Mechanism of action and pharmacodynamic effects The mechanism of action of tacrolimus in atopic dermatitis is not fully understood.
Il- mod ta 'l- azzjoni u l- effetti farmakodinamiċi Il- mod ta' l- azzjoni ta 'tacrolimus f' każ ta 'dermatite atopica għadu mhux mifhum għal kollox.
While the following have been observed, the clinical significance of these observations in atopic dermatitis is not known.
Wieħed innota l- fatti li ser jissemew, għalkemm is- sinifikanza klinika ta 'dawn il- fatti f' każ ta 'dermatite atopika għadha mhiex magħrufa.
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.
Minħabba li tacrolimus jintrabat ma 'immunophilin speċifiku taċ- ċellula (FKBP12), tacrolimus 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 activity towards T cells.
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 mediators from skin mast cells, basophils and eosinophils.
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 dermatitis models that resemble human atopic dermatitis.
F 'annimali tacrolimus ingwent waqqaf l- infjammazzjoni f' każijiet ta 'dermatite sperimentali u spontanji li kienu jixbhu d- dermatite atopika tal- bniedem.
Tacrolimus ointment did not reduce skin thickness and did not cause skin atrophy in animals.
F 'annimali tacrolimus ma naqqasx il- ħxuna tal- ġilda u ma kkaġunax li l- ġilda togħlob.
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 riduzzjoni ta 'l- istimulazzjoni qawwija tagħhom fuq ċelluli tat- tip T.
Tacrolimus ointment does not affect collagen synthesis in humans.
Tacrolimus ingwent ma jaffettwax is- sintesi tal- kollaġen fil- bniedem.
Results from clinical studies in patients The efficacy and safety of Protopic was assessed in more than 13,500 patients treated with tacrolimus ointment in Phase I to Phase III clinical trials.
Riżultati ta 'studji kliniċi fuq pazjenti L- effiċjenza u s- sigurtà ta' Protopic ġew studjati f 'aktar minn 13, 500 pazjent wara trattament bi Protopic 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.
In a six-month multicentre double-blind randomised trial, 0.1% tacrolimus ointment was administered 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).
It- trattament bi Protopic ġiet paragunata ma 'trattament b' 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).
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 Area and Severity Index) between baseline and month 3.
L- ewwel punt ta ’ l - evalwazzjoni kienet ir- rispons kliniku wara tlett xhur, definita bħala il- proporz tal- pazjenti li għaddew 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 group (71.6%) was significantly higher than that in the topical corticosteroid based treatment group (50.8%; p < 0.001; Table 1).
Ir- rata ta ’ rispons posittiv fil- grupp li ngħata 0. 1% Tacrolimus (71. 6%) kienet aktar għolja minn dik tal- grupp li ngħata corticosteroid b’ mod topiku (50. 8%; p < 0. 001; Tabella 1).
The response rates at month 6 were comparable to the 3-month results.
Ir- riżultati ta 'wara 6 xhur kienu komparabbli ma' dawk ta 'wara 3 xhur.
Efficacy at month 3
Effiċjenza wara 3 xhur
Topical corticosteroid regimen§ (N=485)
Reġimen ta ’ Corticosteroid applikat b’ mod topiku§ (N=485)
Tacrolimus 0.1% (N=487)
Tacrolimus 0. 1% (N=487)
Response rate of ≥ 60% improvement in mEASI (Primary Endpoint)§§
Pazjenti li għaddew għal aħjar mill- anqas ≥ 60% skond mEASI (l- ewwel punt wara 3 xhur) §§
71.6%
71. 6%
Improvement ≥ 90% in Physician’ s 28.5% Global Evaluation
Pazjenti li għaddew għal aħajar ≥ 90% skond Physician’ s Global Evaluation
47.7%
47. 7%
§ Topical corticosteroid regimen = 0.1% hydrocortisone butyrate on trunk and extremities, 1% hydrocortisone acetate on face and neck §§ higher values = greater improvement
§ 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
The incidence and nature of most adverse events were similar in the two treatment groups.
Il- frekwenza u l- kwalità tal- biċċa ’ l kbira ta ’ l- effetti avversi kienu bejn wieħed u ieħor l- istess fiż - żewg gruppi.
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.
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 aktar sikwit fil- grupp b 'trattament b' tacrolimus.
There were no clinically relevant changes in the laboratory values or vital signs in either treatment group throughout the study.
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% 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.
The primary endpoint was the area-under-the-curve (AUC) of the mEASI as a percentage of baseline averaged over the treatment period.
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.
The results of this multicentre, 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).
Efficacy at week 3
Effiċenza fit- 3 ġimgħa
Hydrocortisone acetate 1% (N=185)
Hydrocortisone acetate 1% (N=185)
Tacrolimus 0.03% (N=189)
Tacrolimus 0. 03% (N=189)
Tacrolimus 0.1% (N=186)
Tacrolimus 0. 1% (N=186)
Median mEASI
Il- medjan tal- mEASI bħala persentaġġ tal- medja tal- valur bażi AUC (l- endpoint Primarju) §
64.0%
64. 0%
44.8%
44. 8%
39.8%
39. 8%
Baseline mean AUC (Primary Endpoint)§ Improvement ≥ 90% in Physician’ s Global Evaluation § lower values = greater improvement
Titjib ≥ 90% skond Physician’ s 15. 7% Global Evaluation § valuri aktar baxxi = titjib akbar
38.5%
38. 5%
48.4%
48. 4%
The incidence of local skin burning was higher in the tacrolimus treatment groups than in the hydrocortisone group.
Il- frekwenza ta 'ħruq tal- ġilda lokali kienet aktar għolja fil- gruppi b' trattament b' tacrolimus milli fil - gruppi b 'trattament b' hydrocortisone.
Pruritus decreased over time in the tacrolimus groups but not in the hydrocortisone group.
Il- ħakk biż- żmien naqas fil- gruppi b 'trattament b' tacrolimus imma mhux fil- grupp 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 tibdil kliniku relevanti fir- riżultati tal- laboratorju jew fis- sinjali vitali fil- pazjenti taż- żewg gruppi.
The purpose of the third multicentre, double-blind, randomised study was the assessment of efficacy 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 dermatitis.
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 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.
Efficacy at week 3
Effiċjenza f’ ġimgħa 3
Hydrocortisone acetate 1% Twice daily (N=207)
Hydrocortisone acetate 1% Darbtejn kuljum (N=207)
Tacrolimus 0.03% Once daily (N=207)
Tacrolimus 0. 03% Darba kuljum (N=207)
Tacrolimus 0.03% Twice daily (N=210)
Tacrolimus 0. 03% Darbtejn kuljum (N=210)
Median mEASI
Tnaqqis fil- medja tal- mEASI (l - endpoint Primarju) §
47.2%
47. 2%
70.0%
70. 0%
78.7%
78. 7%
Decrease (Primary Endpoint)§ Improvement ≥ 90% in Physician’ s Global Evaluation
Titjib ≥ 90% skond Physician’ s 13. 6% Global Evaluation
27.8%
27. 8%
36.7%
36. 7%
§ higher values = greater improvement
§ valuri aktar għoljin = titjib akbar
The primary endpoint was defined as the percentage decrease in mEASI from the baseline to end of treatment.
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 both).
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 għat- tnejn).
Twice daily treatment with 0.03% tacrolimus ointment was more effective than once daily administration (Table 3).
It- trattament darbtejn kuljum b '0. 03% tacrolimus ingwent kienet aktar effettiva mill - applikazzjoni ta' darba kuljum (Tabella 3).
The incidence of local skin burning was higher in the tacrolimus treatment groups than in the hydrocortisone group.
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.
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.
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 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.
In addition, there was no evidence of loss of efficacy throughout the duration of the clinical trial.
Barra minn hekk, ma kienx hemm evidenza li l- effiċenza tat- trattament tnaqqset waqt il- prova klinika.
The overall incidence of adverse events tended to decrease as the study progressed for all patients independent of age.
Il- frekwenza ta 'effetti avversi kellha t - tendenza li tonqos meta tkompla l- istudju, b’ mod indipendenti mill- età tagħhom.
The three most common adverse events reported were flu-like symptoms (cold, common cold, 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.
No adverse events previously unreported in shorter duration and/ or previous studies were observed in this long-term study.
F 'dan l- istudju twil ma dehrux effetti avversi ġodda fuq dawk li dehru waqt studji aktar qosra jew fi studji oħra ta ’ qabel.
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 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.
7 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.
Assorbiment Tagħrif kliniku li nkiseb minn bnedmin b’ saħħithom juri li jinstab ftit jew xejn tacrolimus fid- demm wara applikazzjoni b’ mod topiku, ta 'darba jew iktar, ta' tacrolimus ingwent fuq il- ġilda.
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.
Ħafna mill- pazjenti li jbatu minn dermatite atopika (kbar u żgħar) kkurati b’ applikazzjoni waħda jew ripetuta ta ’ ingwent tacrolimus (0. 03 - 0. 1%), kif ukoll trabi minn ħames xhur ikkurati bl- ingwent tacrolimus (0. 03%) kellhom konċentrazzjonijiet fid- demm ta ’ < 1. 0 ng/ ml.
When observed, blood concentrations exceeding 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.
Il- probabilità li tacrolimus jidħol fid- demm tikber aktar ma tkun kbira l- parti ta 'ġilda li tindilek.
However, both the extent and the rate of topical absorption of tacrolimus decrease as the skin heals.
Madankollu, kemm l- ammont kif ukoll ir- rata ta ’ assorbiment ta ’ tacrolimus jonqsu aktar ma tfiq il- ġilda.
In both adults and children with an average of 50% body surface area treated, systemic exposure (i. e.
Fi kbar u fi tfal b’ medja ta ’ 50% tal- ġilda trattata, l- esponiment fiċ- ċirkolazzjoni tad- demm (i. e.
AUC) of tacrolimus from Protopic is approximately 30-fold less than that seen with oral immunosuppressive doses in kidney and liver transplant patients.
AUC) ta ’ tacrolimus minn Protopic hu madwar 30% inqas minn dak ta 'mediċina immunosuppressiva li tingħata mill- ħalq lill pazjenti li kellhom trapjant ta' kilwa jew fwied.
The lowest tacrolimus blood concentration at which systemic effects can be observed is not known.
Mhux magħruf kemm hi l- anqas konċentrazzjoni fid - demm li biha jkun hemm effett ġenerali fis- sistema tal- ġisem.
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.
Ma kienx hemm evidenza ta 'akkumulazzjoni ta' tacrolimus fid- demm wara trattament ta 'pazjenti (kbar u tfal) b' tacrolimus ingwent għal żmien twil (sa sena).
Distribution 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.
8 Minħabba li meta tacrolimus ingwent ma jwassalx għal esponiment għoli fiċ- ċirkolazzjoni, l- irbit qawwi ta ’ tacrolimus (> 98. 8%) mal- proteini tal- plażma mhuwiex meqjus bħala wieħed ta ’ rilevanza klinika.
Following topical application of tacrolimus ointment, tacrolimus is selectively delivered to the skin with minimal diffusion into the systemic circulation.
Meta tacrolimus ingwent jigi applikat lokalment, tacrolimus jgħaddi selettivament fil- ġilda, waqt li id - diffużjoni fiċ- ċirkolazzjoni tad- demm hi minima.
Metabolism Metabolism of tacrolimus by human skin was not detectable.
Metaboliżmu L- ammont ta ’ tacrolimus li jiġi metabolizzat mill- ġilda ma setgħax jitkejjel.
Systemically available tacrolimus is extensively metabolised in the liver via CYP3A4.
Fid- demm, tacrolimus jiġi metabolizzat bil- qawwa fil- fwied permezz ta ’ CYP3A4.
Elimination When administered intravenously, tacrolimus has been shown to have a low clearance rate.
Eliminazzjoni Meta tacrolimus jingħata permezz ta 'injezzjoni fil- vina, hu juri rata ta ’ clearnce baxxa.
The average total body clearance is approximately 2.25 l/ h.
Il- clearance 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- treated with drugs that are potent inhibitors of CYP3A4.
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 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.
Meta l- ingwent jiġi applikat ripetutament il- medja tal- half life ta 'tacrolimus kienet stmata li tkun 75 siegħa fil- kbar u 65 siegħa fit- tfal.
Repeated dose toxicity and local tolerance Repeated topical administration of tacrolimus ointment or the ointment vehicle to rats, rabbits and micropigs was associated with slight dermal changes such as erythema, oedema and papules.
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.
Meta tacrolimus ingħata fit- tul fuq il- ġilda tal- firien, dawn kellhom sinjali ta 'tossiċità fis- sistema ġenerali b' tibdil fil- kliewi, pankrejas, għajnejn u s- sistema nervuża.
The changes were caused by high systemic exposure of rodents resulting from high transdermal absorption of tacrolimus.
Dan it- tibdil seħħ minħabba l - esponiment għoli fiċ- ċirkolazzjoni tal- firien li rriżultat mill- assorbiment għoli ta ’ tacrolimus minn ġol - ġilda.