qanastek/EMEA-V3 huggingface dataset:
Dose recommendations - Kidney transplantation Prophylaxis of transplant rejection Oral Advagraf therapy should commence at a dose of 0.20 - 0.30 mg/ kg/ day administered once daily in the morning.
Doża rikkmandata – trapjant tal- Kilwa Profilassi tar- riġezzjoni tat- trapjant Il- kura mill- ħalq b ’ Advagraf għandha tibda b’ doża ta’ 0. 20 – 0. 30 mg/ kg/ kuljum darba kuljum filgħodu.
Administration should commence within 24 hours after the completion of surgery.
Għandha tibda tingħata fi żmien 24 siegħa mill- operazzjoni.
Dose adjustment during post-transplant period Advagraf doses are usually reduced in the post-transplant period.
Normalment id- doża ta ’ Advagraf titnaqqas fiż- żmien ta ’ wara li jkun sar it- trapjant.
It is possible in some cases to withdraw concomitant immunosuppressive therapy, leading to Advagraf monotherapy.
Jista ’ jkun li f’ ċerti każi titwaqqaf xi kura immunosuppressiva oħra, li tkun qiegħed tingħata flimkien ma ’ Advagraf, u b’ hekk tgħaddi għal monoterapija ta ’ Advagraf.
Post-transplant improvement in the condition of the patient may alter the pharmacokinetics of tacrolimus and may necessitate further dose adjustments.
It- titjib fil- qagħda tal- pazjent wara t - trapjant jista ’ jkun li jibdel il- farmakokinetika ta ’ tacrolimus u jista ’ jkun meħtieġ aktar tibdiliet fid - doża.
Dose recommendations - Liver transplantation Prophylaxis of transplant rejection Oral Advagraf therapy should commence at a dose of 0.10 - 0.20 mg/ kg/ day administered once daily in the morning.
Doża rikkmandata – trapjant tal- Fwied Profilassi tar- riġezzjoni tat- trapjant Il- kura mill- ħalq b ’ Advagraf għandha tibda b’ doża ta’ 0. 10– 0. 20 mg/ kg/ kuljum darba kuljum filgħodu.
Administration should commence approximately 12-18 hours after the completion of surgery.
Għandha tibda tingħata minn bejn 12- il siegħa sa 18- il siegħa mill- operazzjoni.
It is possible in some cases to withdraw concomitant immunosuppressive therapy, leading to Advagraf monotherapy.
3 Advagraf u tgħaddi għal monoterapija ta ’ Advagraf.
Post-transplant improvement in the condition of the patient may alter the pharmacokinetics of tacrolimus and may necessitate further dose adjustments.
It- titjib fil- qagħda tal- pazjent wara t- trapjant jista ’ jkun li jibdel il- farmakokinetika ta ’ tacrolimus u jista ’ jwassal għal ħtieġa ta ’ aktar tibdil fid - doża.
Dose recommendations – Conversion of Prograf treated patients to Advagraf Allograft transplant patients maintained on twice daily Prograf capsules dosing requiring conversion to once daily Advagraf should be converted on a 1:1 (mg: mg) total daily dose basis.
Doża rikkmandata – Pazjenti kkurati b ’ Prograf jaqilbu għal Advagraf Pazjenti bi trapjant allograft li kienu fuq doża ta ’ kapsuli Prograf darbtejn kuljum u jkollhom bżonn jaqilbu għal Advagraf darba kuljum għandhom jibdew b’ doża totali ta ’ 1: 1 (mg: mg) kuljum.
Advagraf should be administered in the morning.
Advagraf għandu jingħata filgħodu.
Following conversion, tacrolimus trough levels should be monitored and if necessary dose adjustments made to maintain similar systemic exposure.
Wara li ssir il- bidla, għandhom jiġu ċċekkjati l- livelli ‘ trough ’ ta ’ tacrolimus u jekk ikun hemm bżonn isiru l- aġġustamenti meħtieġa biex tinżamm espożizzjoni sistemika simili.
3 Dose recommendations - Rejection therapy Increased doses of tacrolimus, supplemental corticosteroid therapy, and introduction of short courses of mono-/ polyclonal antibodies have all been used to manage rejection episodes.
Doża rikkmandata – Riġezzjoni tal- kura Żidiet fid- dożi ta ’ tacrolimus, terapija supplementari kortikosterojdika, kif ukoll l- introduzzjoni ta ’ korsijiet qosra ta ’ anti- korpi mono - / poliklonali kollha ntużaw biex jikkontrollaw episodji ta ’ riġezzjoni.
If signs of toxicity are noted (e. g. pronounced adverse reactions - see section 4.8) the dose of Advagraf may need to be reduced.
Jekk jidhru sinjali ta ’ tossiċita ’ (eż. reazzjonijiet kuntrarji qawwija - ara taqsima 4. 8) jista ’ jkun li d- doża ta ’ Advagraf jkollha titnaqqas.
For information on conversion from ciclosporin to Advagraf, see below under “ Dose adjustments in specific patient populations”.
Għal tagħrif dwar it- tibdil minn ciclosporin għal Advagraf, ara aktar ‘ l isfel “ Aġġustamenti tad- doża f’ certi pazjenti speċifiċi ”.
Kidney and liver transplantation For conversion from other immunosuppressants to once daily Advagraf, treatment should begin with the initial oral dose recommended in kidney and liver transplantation respectively for prophylaxis of transplant rejection.
Trapjant tal- kliewi jew tal- fwied Biex taqleb minn immunosuppressanti oħra għal Advagraf darba kuljum, trid tibda l- kura bid- doża orali rikkmandata fit- trapjant tal- kliewi u tal- fwied rispettivament għall- profilassi ta ’ riġezzjoni tat - trapjant.
Heart transplantation In adult patients converted to Advagraf, an initial oral dose of 0.15 mg/ kg/ day should be administered once daily in the morning.
Trapjant tal- Qalb F’ pazjenti adulti li jkunu qalbu għal Advagraf, għandha tingħata fil- bidu doża orali ta ’ 0. 15 mg/ kg/ kuljum, darba kuljum filgћodu.
Other allografts transplantation Although there is no clinical experience with Advagraf in lung-transplanted, pancreas-transplanted and intestine-transplanted patients, Prograf has been used in lung-transplanted patients at an initial oral dose of 0.10 - 0.15 mg/ kg/ day, in pancreas-transplanted patients at an initial oral dose of 0.2 mg/ kg/ day and in intestinal transplantation at an initial oral dose of 0.3 mg/ kg/ day.
Trapjanti oħra ta ’ allograft Għalkemm ma hemm ebda esperjenza klinika b ’ Advagraf f’ pazjenti li għamlu trapjant tal - pulmun, tal- pancreas u ta ’ l- intestini (msaren), Prograf intuża f’ pazjenti li kellhom trapjant tal - pulmun b’ doża mill- ħalq li bdiet bi 0. 10 - 0. 15 mg/ kg/ kuljum, fil- pazjenti bi tarpjant tal - pancreas b’ doża mill- ħalq li bdiet bi 0. 2 mg/ kg/ kuljum u f’ pazjenti bi trapjant intestinali b’ doża mill- ħalq li bdiet bi 0. 3 mg/ kg/ kuljum.
Dose adjustments in specific patient populations Patients with liver impairment Dose reduction may be necessary in patients with severe liver impairment in order to maintain the blood trough levels within the recommended target range.
Aġġustamenti tad- doża f’ certi pazjenti speċifiċi Pazjenti b’ indeboliment tal- fwied F’ pazjenti li jkollhom indeboliment tal- fwied sever ikun jinħtieġ tnaqqis tad- doża biex ikunu jistgħu jinżammu l- livelli ‘ trough ’ tad- demm meħtieġa skond il- medda u l- mira rikkmandati.
Patients with kidney impairment As the pharmacokinetics of tacrolimus are unaffected by renal function, no dose adjustment should be required.
Pazjenti b’ indeboliment renali Billi l- farmakokinetika ta ’ tacrolimus mhux affettwat mill- funzjoni tal- kliewi, ma għandux ikun hemm bżonn ta ’ tibdil fid- doża.
However, owing to the nephrotoxic potential of tacrolimus careful monitoring of renal function is recommended (including serial serum creatinine concentrations, calculation of creatinine clearance and monitoring of urine output).
Madankollu minħabba l- potenzjal nefrotossiku ta ’ tacrolimus wieħed irid jieħu ħsieb u jiċċekkja sewwa kif ikunu qed jaħdmu l- kliewi (li jinkludu wkoll il- konċentrazzjoni tas - serial serum tal- kreatinina, il- kalkolu ta ’ kif qed titneħħa l- kreatinina u l- monitorġġ ta ’ kemm qed toħroġ awrina).
Race In comparison to Caucasians, black patients may require higher tacrolimus doses to achieve similar trough levels.
Ir- razza Meta tqabbel il- pazjenti negri ma ’ dawk Kawkażi, jista ’ jkun li jeħtieġu dożi ogħla ta ’ tacrolimus biex jilħqu livelli ‘ trough ’ simili.
Gender There is no evidence that male and female patients require different doses to achieve similar trough levels.
Il- ġens M ’ hemmx evidenza li l- pazjenti rġiel u nisa jeħtieġu dożi differenti biex jilħqu livelli ‘ trough ’ simili.
Elderly patients There is no evidence currently available to indicate that dosing should be adjusted in elderly patients.
Pazjenti anzjani S’ issa m ’ hemmx evidenza li d- doża fl- anzjani għandha tkun addattata għalihom.
Conversion from ciclosporin to Advagraf Care should be taken when converting patients from ciclosporin-based to tacrolimus-based therapy (see sections 4.4 and 4.5).
Bidla minn ciclosporin għal Advagraf Għandha tittieħed prekawzjoni partikolari meta pazjenti mdorrija fuq terapija mibnija fuq ciclosporin taqlibhom għall- kura mibnija fuq tacrolimus (ara taqsimiet 4. 4 u 4. 5).
Advagraf therapy should be initiated after considering ciclosporin blood concentrations and the clinical condition of the patient.
Il- kura b ’ Advagraf għandha tinbeda wara li jintqiesu l- konċentrazzjoni ta ’ ciclosporin fid- demm u l- kondizzjoni klinika tal - pazjent.
Dosing should be delayed in the presence of elevated ciclosporin blood levels.
Jekk ikun hemm livelli għolja ta ’ ciclosporin fid- demm id- dożaġġ għandu jitħalla għal aktar tard.
In practice, tacrolimus-based therapy has been initiated 12 - 24 hours after discontinuation of ciclosporin.
Il- kura bażata fuq tacrolimus, fil- prattika tibda minn bejn 12- il siegħa sa 24 siegħa wara li jkun
Monitoring of ciclosporin blood levels should be continued following conversion as the clearance of ciclosporin might be affected.
L - monitoraġġ tal- livelli ta ’ ciclosporin fid- demm għandhom jitkomplew wara l - qalba għax tista ’ tintlaqat it- tneħħija ta ’ ciclosporin mill- ġisem.
Target whole blood trough concentration recommendations Dosing should primarily be based on clinical assessments of rejection and tolerability in each individual patient aided by whole blood tacrolimus trough level monitoring.
Rakkomandazzjonijiet dwar kif għandhom jintlaħqu l- livelli ‘ trough ’ ta ’ konċentrazzjoni fid - demm sħiħ Id- dożaġġ għandu jinħadem primarjament fuq kemm klinikament jista ’ jkun hemm riġezzjoni jew tollerabbiltà individwalment f’ kull pazjent megħjun bil- monitoraġġ ta ’ l- livelli ‘ trough ’ ta ’ tacrolimus meħtieġa fid- demm sħiħ.
As an aid to optimise dosing, several immunoassays are available for determining tacrolimus concentrations in whole blood.
Bħala għajnuna biex id- doża tittieħed aħjar, hemm diversi immunasaġġi li jiddeterminaw il - konċentrazzjonijiet ta ’ tacrolimus fid- demm sħiħ.
Comparisons of concentrations from the published literature to individual values in clinical practice should be assessed with care and knowledge of the assay methods employed.
It- tqabbil tal- konċentrazzjonijiet minn dak li hemm pubblikat għal valuri miksuba individwalment fil- prattika klinika għandhom jintqiesu sewwa u jitħaddem l- għarfien tal- metodu ta ’ l- analiżi.
In current clinical practice, whole blood levels are monitored using immunoassay methods.
Fil- prattika klinika tal- lum, il- monitoraġġ tal- livelli fid - demm sħiħ isir bil- metodu ta ’ l- immunassaġġ.
The relationship between tacrolimus trough levels (C24) and systemic exposure (AUC 0-24) is similar between the two formulations Advagraf and Prograf.
Ir- relazzjoni li hemm bejn l- inqas livelli ta ’ tacrolimus (C24) u l- espożizzjoni sistemiku (AUC 0- 24) huma simili bejn iż- żewġ formulazzjonijiet ta ’ Advagraf u ta ’ Prograf.
Blood trough levels of tacrolimus should be monitored during the post-transplantation period.
Il- livelli ‘ trough ’ ta ’ tacrolimus fid- demm għandhom ikunu mmonitorjati matul iż- żmien ta ’ wara t- trapjant.
Blood trough levels for Advagraf should be drawn approximately 24 hours post-dosing, just prior to the next dose.
Il- livelli ‘ trough ’ fid- demm ta ’ Advagraf għandhom jittieħdu 24 siegħa wara li tittieħed id- doża, eżatt qabel id- doża li jkun imiss.
Frequent trough level monitoring in the initial two weeks post transplantation is recommended, 4 followed by periodic monitoring during maintenance therapy.
Tajjeb li jittieħdu sikwit il- livelli ‘ trough ’ fl- ewwel ġimagħtejn wara t- trapjant, u jkomplu perjodikament matul il- manutenzjoni tal- kura.
Blood trough levels of tacrolimus should also be monitored following conversion from Prograf to Advagraf, dose adjustment, changes in the immunosuppressive regimen, or co-administration of substances which may alter tacrolimus whole blood concentrations (see section 4.5).
Għandu wkoll jittieħed l- inqas livell ta ’ tacrolimus fid- demm meta ssir il- bidla minn Prograf għal Advagraf, l- aġġustament fid- doża, bidliet fir- reġimen immunosuppressiv, jew għoti flimkien ma ’ sustanzi li jistgħu jibdlu l- konċentrazzjonijiet ta ’ tacrolimus fid- demm sħiħ (ara taqsima 4. 5).
The frequency of blood level monitoring should be based on clinical needs.
Il- frekwenza tal- monitoraġġ tal- livelli tad- demm għandha tkun ibbażata fuq il - ħtiġiet kliniċi.
As Advagraf is a medicinal product with low clearance, adjustments to the Advagraf dose regimen may take several days before steady state is achieved.
Billi Advagraf huwa prodott mediċinali li jitneħħa bil- mod, għandu mnejn li l - aġġustamenti meħtieġa fid- doża ta ’ Advagraf jieħdu bosta ġranet qabel ma jintlaħaq livell fiss.
Clinical study analysis suggests that the majority of patients can be successfully managed if tacrolimus blood trough levels are maintained below 20 ng/ ml.
L- analiżi ta ’ studji kliniċi juru li wieħed jista’ jirnexxilu jimmaniġġa l- parti l- kbira tal- pazjenti jekk il - livelli ‘ trough ’ ta ’ tacrolimus fid- demm jinżammu taħt l- 20 ng/ ml.
It is necessary to consider the clinical condition of the patient when interpreting whole blood levels.
Meta tipprova tifhem il- livelli fid - demm sħiħ trid tqis il- kondizzjoni klinika tal- pazjent.
In clinical practice, whole blood trough levels have generally been in the range 5 - 20 ng/ ml in liver transplant recipients and 10 - 20 ng/ ml in kidney and heart transplant patients in the early post- transplant period.
Fil- prattika klinika, il - livelli ‘ trough ’ fid- demm sħiħ kienu ġeneralment fil - medda ta’ bejn il- 5 u l - 20 ng/ ml f’ dawk li r evew trapjant tal - fwied u bejn l- 10 u l- 20 ng/ ml f’ dawk li ċevew trapjant tal -
During subsequent maintenance therapy, blood concentrations have generally been in the range of 5 - 15 ng/ ml in liver, kidney and heart transplant recipients.
Matul il- manutenzjoni tal- kura, il - konċentrazzjonijiet fid- demm kienuġeneralment fil - medda ta ’ bejn il- 5 u l- 15 ng/ ml f’ dawk il - pazjenti li rċevew trapjant tal- fwied, tal- kliewi u tal- qalb.
4.3 Contraindications
4. 3 Kontra - indikazzjonijiet
Hypersensitivity to tacrolimus or other macrolides or to any of the excipients.
Sensittività eċċessiva għal tacrolimus jew macrolidi oħra u kull sustanza oħra mhux attiva
4.4 Special warnings and precautions for use
Twissijiet speċjali u prekawzjonijiet għall - użu 4. 4
Medication errors, including inadvertent, unintentional or unsupervised substitution of immediate- or prolonged-release tacrolimus formulations, have been observed.
Żbalji fil- medikazzjoni, ta ’ tibdil b’ nuqqas ta ’ attenzjoni, bla intenzjoni jew mhux taћt osservazzjoni bejn il- formulazzjonijiet ta ’ tacrolimus jiġifieri bejn dik b’ rilaxx immedjat u dik b’ rilaxx prolungat ġew osservati.
This has led to serious adverse events, including graft rejection, or other side effects which could be a consequence of either under- or over- exposure to tacrolimus.
Dan wassal gћal reazzjonijiet avversi serji, li jinkludu rifjut tal- graft, jew effetti oћra mhux mixtieqa li jistgћu ikunu il- konsegwenza ta ’ jew nuqqas ta ’ espożizzjoni jew espożizzjoni żejda gћal tacrolimus.
Patients should be maintained on a single formulation of tacrolimus with the corresponding daily dosing regimen; alterations in formulation or regimen should only take place under the close supervision of a transplant specialist (see sections 4.2 and 4.8).
Pazjenti gћandhom jinżammu fuq formulazzjoni waћda ta ’ tacrolimus bid- doża xierqa ta ’ kuljum; tibdil fil- formulazzjoni jew fid- dożaġġ iridu iseћћu biss taћt superviżjoni mill- qrib tal- ispeċjalista tat- trapjanti (ara sezzjoni 4. 2 u 4. 8).
There is limited experience in non-Caucasian patients and patients at elevated immunological risk (e. g. retransplantation, evidence of panel reactive antibodies (PRA)).
Hemm esperjenza limitata f’ pazjenti mhux Kawkażi kif ukoll f’ pazjenti li għandhom riskju immunoloġiku elevat (per. eż. ritrapjant, evidenza ta ’ panel reattiv ta ’ antikorpi (PRA))
For treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products in adult patients clinical data are not yet available for the prolonged-release formulation Advagraf.
Għall- kura tar- riġezzjoni tal- allograft li kien reżistenti g at - trattament ma ’ prodotti mediċinali oħra ħ ħall - formulazzjoni immunosuppressivi f’ pazjenti adulti, ghad ma hemmx informazzjoni klinika g ta ’ Advagraf li jerħi il- mediċina bil- mod
For prophylaxis of transplant rejection in adult heart allograft recipients and for paediatric allograft recipients clinical data are not yet available for the prolonged-release formulation Advagraf.
5 Għall- profilassi tar- riġezzjoni tat- trapjant, f’ dawk li jkunu ser jieћdu allograft tal- qalb adult u għal dawk li jkunu ser jieћdu allograft pedjatriku, għad ma hemmx tagħrif kliniku għall- formulazzjoni ta ’ Advagraf li terћi l- mediċina bil- mod.
During the initial post-transplant period, monitoring of the following parameters should be undertaken on a routine basis: blood pressure, ECG, neurological and visual status, fasting blood glucose levels, electrolytes (particularly potassium), liver and renal function tests, haematology parameters, coagulation values, and plasma protein determinations.
Matul l- ewwel żmien ta ’ wara t- trapjant għandhom ikunu ċċekkjati regolarment dawn il- parametri: il - pressjoni tad- demm, l- ECG, il- qagħda viżwali u newroloġika, il- livelli taz- zokkor fid- demm waqt is - sawm, l- elektrolidi (l- aktar il- potassium) testijiet ta ’ kif qed jiffunzjonaw il- fwied u l- kliewi, il - parametri ematoloġiċi, kemm id- demm jagħqad malajr u d- determinazzjonijet tal- proteina fil- plażma.
If clinically relevant changes are seen, adjustments of the immunosuppressive regimen should be considered.
Jekk jitfaċcaw bidliet kliniċi rilevanti għandhom jintqiesu xi aġġustamenti fir - reġimen immunosuppressiv.
John’ s Wort (Hypericum perforatum) or other herbal preparations should be avoided when taking Advagraf due to the risk of interactions that lead to decrease in blood concentrations of tacrolimus and reduced clinical effect of tacrolimus (see section 4.5).
Ma għandhomx jittieħdu preparazzjonijiet ta ’ ħxejjex li jkollhom il- fexfiex (Hypericum perforatum) jew preparazzjonijiet ta ’ ħxejjex oħra meta jkun qed jittieħed Advagraf minħabba xi riskju ta ’ interazzjoni li jista ’ jwassal għat- tnaqqis fil- konċentrazzjoni ta ’ tacrolimus fid- demm u b’ hekk inaqqas l- effett kliniku ta ’ tacrolimus (ara taqsima 4. 5).
Since levels of tacrolimus in blood may significantly change during diarrhoea episodes, extra monitoring of tacrolimus concentrations is recommended during episodes of diarrhoea.
Billi waqt perijodu ta ’ dijarrea l- livelli ta ’ tacrolimus fid- demm jistgħu jinbidlu, għandu jsir aktar monitoraġġ tal- konċentrazzjoni ta ’ tacrolimus meta jkun hemm dawn l- episodji tad- dijarrea.
The combined administration of ciclosporin and tacrolimus should be avoided and care should be taken when administering tacrolimus to patients who have previously received ciclosporin (see sections 4.2 and 4.5).
Ciclosporin u tacrolimus ma għandhomx jingħataw flimkien u għandha tittieħed attenzjoni speċjali meta jingħata tacrolimus lill- pazjenti li qabel kienu jieħdu ciclosporin (ara taqsimiet 4. 2 u 4. 5).
Ventricular hypertrophy or hypertrophy of the septum, reported as cardiomyopathies, have been observed in Prograf treated patients on rare occasions and may therefore also occur with Advagraf.
L- ipertrofija ventrikolari jew tas- septum, rapportati bħala cardjomijopatċi, tfaċċaw f’ xi okkażjonijiet rari f’ pazjenti li kienu jieħdu Prograf u allura jistgħu ukoll jidhru f’ dawk li jieħdu Advagraf.
Most cases have been reversible, occurring with tacrolimus blood trough concentrations much higher than the recommended maximum levels.
Il- parti l - kbira tal- każi huma riversibbli, meta jiġru b’ konċentrazzjonijiet ‘ trough ’ ta ’ tacrolimus fid- demm bil - wisq ogħla mill- massimu tal- livelli rikkmandati.
Other factors observed to increase the risk of these clinical 5 conditions included pre-existing heart disease, corticosteroid usage, hypertension, renal or hepatic dysfunction, infections, fluid overload, and oedema.
Fatturi oħra osservati li żiedu r- riskju ta ’ dawn il - kondizzjonijiet kliniċi kienu l- mard tal- qalb li kien hemm minn qabel, l- użu tal- kortikosterojdi, il - pressjoni għolja, meta l- fwied jew il- kliewi ma jaħdmux normali, l- infezzjonijiet, l- ilma żejjed, u edema.
Accordingly, high-risk patients receiving substantial immunosuppression should be monitored, using such procedures as echocardiography or ECG pre- and post-transplant (e. g. initially at 3 months and then at 9 -12 months).
Għalhekk pazjenti li għandhom riskju għoli u qed jieħdu immunosuppressjoni sostanzjali għandhom ikunu ċċekkjati, bl- użu ta ’ proċeduri bħal l- ekokardjografija jew l- ECG qabel u wara t - trapjant (eż. fil- bidu mat- 3 xhur u wara mad- 9 xhur u t- 12- il xahar).
If abnormalities develop, dose reduction of Advagraf therapy, or change of treatment to another immunosuppressive agent should be considered.
Jekk jiżviluppaw xi anormalitajiet irid jintqies it- tnaqqis fil- kura ta ’ Advagraf jew bidla fil- kura għall- aġent immunosuppressiv ieħor.
Tacrolimus may prolong the QT interval but at this time lacks substantial evidence for causing Torsades de Pointes.
Tacrolimus jista ’ jtawwal l- intervall QT imma għalissa jonqsu evidenza suffiċjenti li jikkaġuna Torsades de Pointes.
Caution should be exercised in patients with diagnosed or suspected Congenital Long QT Syndrome.
Għandha tittieħed prekawzjoni speċjali f’ pazjenti li għandhom jew jista ’ jkollhom il- Congenital Long QT Syndrome.
Patients treated with tacrolimus have been reported to develop EBV-associated lymphoproliferative disorders.
Pazjenti li qed jieħdu tacrolimus dehru li żviluppaw disturbi limfoproliferattiv marbutin ma ’ l- EBV.
A combination of immunosuppressives such as antilymphocytic antibodies given concomitantly increases the risk of EBV-associated lymphoproliferative disorders.
Taħlita ta ’ immunosuppressivi bħalma huma antikorpori antilimfoċitiċi, mogħtija flimkien ikabbru r - riskju tad- distrubi limfoproliferattivi marbutin ma ’ l- EBV.
EBV-Viral Capsid Antigen (VCA)-negative patients have been reported to have an increased risk of developing lymphoproliferative disorders.
Pazjenti negattivi għall- EBV- Kapsida Antigena Virali (VCA) dehru li żiedu r- riskju li jiżviluppaw dawn id- disturbi limfoproliferattiv.
Therefore, in this patient group, EBV-VCA serology should be ascertained before starting treatment with Advagraf.
Għaldaqstant, f’ dan il- grupp ta ’ pazjenti, trid l- ewwel tkun aċcertata s- seroloġija EBV- VCA qabel ma tibda l- kura b ’ Advagraf.
During treatment, careful monitoring with EBV- PCR is recommended.
Matul il- kura għandu jsir monitoraġġ akkurat bil- EBV- PCR.
Positive EBV-PCR may persist for months and is per se not indicative of lymphoproliferative disease or lymphoma.
L- EBV- PCR pożittiv jista ’ jdum għal xhur sħaħ u minnu nnifsu mhux indikattiv tal- marda limfoproliferattiva jew tal- limfoma.
Patients treated with immunosuppressants, including Advagraf are at increased risk for opportunistic infections (bacterial, fungal, viral and protozoal).
Pazjenti kkurati b’ immunosuppressanti, inkluż Advagraf huma f’ riskju akbar għal infezzjonijiet opportunistiċi (batterjali, fungali, virali u protżoali).
Among these conditions are BK virus associated nephropathy and JC virus associated progressive multifocal leukoencephalopathy (PML).
Fost dawn il- kundizzjonijiet hemm nefropatija assoċjata ma ’ virus BK u lewkoenċefalopatija multifokali progressiva (PML) assoċjata ma ’ virus JC.
These infections are often related to a high total immunosuppressive burden and may lead to serious or fatal conditions that physicians should consider in the differential diagnosis in immunosuppressed patients with deteriorating renal function or neurological symptoms.
Dawn l- infezzjonijiet huma spiss relatati ma ’ tagħbija immunosuppressiva totali għolja u jistgħu jwasslu għal kundizzjonijiet serji jew fatali li t- tobba għandhom jikkunsidraw fid- dijanjożi differenti f’ pazjenti immunosoppressi b’ funzjoni renali indebolita jew b’ sintomi newroloġiċi.
As with other immunosuppressive agents, owing to the potential risk of malignant skin changes, exposure to sunlight and UV light should be limited by wearing protective clothing and using a sunscreen with a high protection factor.
Minħabba l- potenzjal tar- riskju ta ’ tibdil malinn fil- ġilda, kif jagħmlu agenti oħra immunosuppressivi, l- espożizzjoni għax- xemx jew għad- dawl UV għandha tkun limitata billi jintlibsu ħwejjeġ protettivi u jintuża dlik bi skrin b’ fattur protettiv qawwi.
As with other potent immunosuppressive compounds, the risk of secondary cancer is unknown (see section 4.8).
Bħal fil- każ ta ’ komponenti potenti immunosuppressivi oћra, mhux magħruf x’ riskju jista ’ jkun hemm ta ’ kanċer sekondarju (ara taqsima 4. 8).
Patients treated with tacrolimus have been reported to develop posterior reversible encephalopathy syndrome (PRES).
6 Saru rapporti li pazjenti ttrattati b’ tacrolimus jiżviluppaw is- sindrome tal- enċefalopatija riversibbli posterjuri (posterior reversible encephalopathy syndrome - PRES).
If patients taking tacrolimus present with symptoms indicating PRES such as headache, altered mental status, seizures, and visual disturbances, a radiological procedure (e. g.
Jekk il- pazjenti li jieħdu tacrolimus jippreżenataw b’ sintomi li jindikaw PRES bħal uġigħ ta 'ras, status mentali mibdul, puplesija u disturbi fil- viżta, għandha ssir proċedura radjoloġika (eż.
If PRES is diagnosed, adequate blood pressure and seizure control and immediate discontinuation of systemic tacrolimus is advised.
Jekk issir dijanjożi ta ’ PRES, huwa rrakkomandat kontroll adegwat tal- pressjoni tad- demm u tal- puplesija u waqfien minnufih ta ’ tacrolimus sistemiku.
Most patients completely recover after appropriate measures are taken.
Ħafna pazjenti jirkupraw għal kollox wara li jittieħdu miżuri xierqa.
As Advagraf prolonged-release capsules contain lactose, special care should be taken in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Billi Advagraf, kapsuli li jerħu l- mediċina bil- mod fihom lactose, għandha tittieħed attenzjoni speċjali f’ pazjenti li jkollhom problemi ereditarji rari ta ’ intolleranza ta ’ galattosi, defiċjenza ta ’ lattasi Lapp jew ma jassorbux tajjeb glukosju- galattosju.
Metabolic interactions Systemically available tacrolimus is metabolised by hepatic CYP3A4.
Interazzjonijiet Metaboliċi Tacrolimus li hu disponibbli fis- sistema jimmetabolizza bil- CYP3A4 tal- fwied.
There is also evidence of gastrointestinal metabolism by CYP3A4 in the intestinal wall.
Hemm ukoll evidenza ta ’ metaboliżmu gastrointestinali bil- CYP3A4 fil- ħajt intestinali.
Concomitant use of medicinal products or herbal remedies known to inhibit or induce CYP3A4 may affect the metabolism of tacrolimus and thereby increase or decrease tacrolimus blood levels.
L- użu flimkien ta ’ prodotti mediċinali jew rimedji tal- ħxejjex magħrufa li jinibixxu jew jinduċu l- CYP3A4 jistgħu jeffettwaw il - metaboliżmu ta ’ tacrolimus u allura jżidu jew inaqqsu l- livelli ta ’ tacrolimus fid- demm.
It is therefore recommended to monitor tacrolimus blood levels whenever substances which have the potential to alter CYP3A metabolism are used concomitantly and to adjust the tacrolimus dose as appropriate in order to maintain similar tacrolimus exposure (see sections 4.2 and 4.4).
Għaldaqshekk tajjeb li jkunu ċċekkjati l- livelli ta ’ tacrolimus fid- demm kull meta sustanzi li jista ’ jkollhom il - potenzjal li jibdlu il- metaboliżmu ta ’ CYP3A jintużaw flimkien u biex jaġġustaw id- doża ta ’ tacrolimus sewwa ħalli tinżamm l- espożizzjoni ta ’ tacrolimus simili (ara taqsimiet 4. 2 u 4. 4).
Inhibitors of metabolism Clinically the following substances have been shown to increase tacrolimus blood levels:
Impedituri tal- metaboliżmu Klinikament dawn is- sustanzi li se nsemmu huma magħrufa li jżidu l- livelli ta ’ tacrolimus fid- demm:
Strong interactions have been observed with antifungal agents such as ketoconazole, fluconazole, itraconazole and voriconazole, the macrolide antibiotic erythromycin or HIV protease inhibitors (e. g.
Interazzjonijiet qawwija kienu osservati ma aġenti antifungali bħalma huma ketoconazole, fluconazole, itraconazole u voriconazole, antibijotiku macrolide erythromycin jew HIV protease inhibitors (eż. ritonavir).
Concomitant use of these substances may require decreased tacrolimus doses in nearly all patients.
L- użu f’ daqqa ta ’ dawn is- sustanzi jista ’ jkun jinħtieġ dożi inqas ta ’ tacrolimus kważi fil- pazjenti kollha.
Pharmacokinetics studies have indicated that the increase in blood levels is mainly a result of increase in oral bioavailability of tacrolimus owing to the inhibition of gastrointestinal metabolism.
Studji farmakokinetiċi wrew li ż- żieda fil- livelli tad- demm hi fil - biċċa l- kbira riżultat taż- żieda fil- bijodisponibiltà orali ta ’ tacrolimus minħabba l- inibizzjoni tal - metaboliżmu gastrointestinali.
Effect on hepatic clearance is less pronounced.
L- effett fuq il- mogħdija epatika mhux daqshekk kbir.
Weaker interactions have been observed with clotrimazole, clarithromycin, josamycin, nifedipine, nicardipine, diltiazem, verapamil, danazol, ethinylestradiol, omeprazole and nefazodone.
Kien hemm interazzjonijiet aktar fjakki b ’ clotrimazole, b ’ clarithromycin, b ’ josamycin, b ’ nifedipine, b ’ nicardipine, b ’ diltiazem, b ’ verapamil, b ’ danazol, b ’ ethinylestradiol, b ’ omeprazole u b ’ nefazodone.
In vitro the following substances have been shown to be potential inhibitors of tacrolimus metabolism: bromocriptine, cortisone, dapsone, ergotamine, gestodene, lidocaine, mephenytoin, miconazole, midazolam, nilvadipine, norethindrone, quinidine, tamoxifen, (triacetyl)oleandomycin.
Dawn is- sustanzi li se nsemmu wrew in vitro li huma inibituri potenzjali tal- metaboliżmu ta ’ tacrolimus: bromocriptine, cortisone, dapsone, ergotamine, gestodene, lidocaine, mephenytoin, miconazole, midazolam, nilvadipine, norethindrone, quinidine, tamoxifen, (triacetyl) oleandomycin.
Grapefruit juice has been reported to increase the blood level of tacrolimus and should therefore be avoided.
Il- meraq tal- grejpfrut jidher li jgħolli l- livell tad- demm ta ’ tacrolimus u għalhekk għandu jkun evitat.
Lansoprazol and ciclosporin may potentially inhibit CYP3A4-mediated metabolism of tacrolimus and thereby increase tacrolimus whole blood concentrations.
Lansoprazol u ciclosporin jista ’ jkun li potenzjalment jinibixxu l- metaboliżmu bil- CYP3A4 ta ’ tacrolimus u b’ hekk iżid il- konċentrazzjonijiet ta ’ tacrolimus fid- demm sħiħ.
Inducers of metabolism Clinically the following substances have been shown to decrease tacrolimus blood levels:
Stimoli tal- metaboliżmu Klinikament is- sustanzi li ġejjin urew li jnaqqsu l- livelli ta ’ tacrolimus fid- demm:
John’ s Wort (Hypericum perforatum) which may require increased tacrolimus doses in almost all patients.
Dehru interazzjonijiet qawwija ma ’ rifampicin, ma ’ phenytoin, mal- fuxfiex (Hypericum perforatum) u b’ hekk jista ’ jkun jinħtieġ dożaġġ ta ’ tacrolimus ogħla kważi fil- pazjenti kollha.
Clinically significant interactions have also been observed with phenobarbital.
Interazzjonijiet kliniċi sinifikanti dehru wkoll ma ’ phenobarbital.
Maintenance doses of corticosteroids have been shown to reduce tacrolimus blood levels.
Dożaġġ ta ’ manteniment bil- kortikosterojdi wera li l- livelli ta ’ tacrolimus fid- demm jonqsu.
High dose prednisolone or methylprednisolone administered for the treatment of acute rejection have the potential to increase or decrease tacrolimus blood levels.
Doża qawwija ta ’ prednisolone jew ta ’ methylprednisolone moghtija għall- kura ta ’ riġezzjoni akuta għandhom il- potenzjal li jżidu jew inaqqsu l- livelli ta ’ tacrolimus fid- demm.
Carbamazepine, metamizole and isoniazid have the potential to decrease tacrolimus concentrations.
Carbamazepine, metamizole u isoniazid għandhom il- potenzjal li jnaqqsu l- konċentrazzjonijiet ta ’ tacrolimus.
Effect of tacrolimus on the metabolism of other medicinal products Tacrolimus is a known CYP3A4 inhibitor; thus concomitant use of tacrolimus with medicinal products known to be metabolised by CYP3A4 may affect the metabolism of such medicinal products.
7 Tacrolimus hu magħruf bħala inibitur ta ’ CYP3A4; għaldaqstant l- użu ta ’ tacrolimus flimkien ma ’ prodotti mediċinali magħrufa li jigu metabolizzati b ’ CYP3A4 jista ’ jeffettwa l- metaboliżmu ta ’ dawn il- prodotti mediċinali.
The half-life of ciclosporin is prolonged when tacrolimus is given concomitantly.
Il- half life ta ’ ciclosporin titwal meta flimkien miegħu jingħata tacrolimus.
In addition, synergistic/ additive nephrotoxic effects can occur.
Jistgħu wkoll jinħolqu effetti sinerġistiċi/ addittivi nefrotossiċi.
For these reasons, the combined administration of ciclosporin and tacrolimus is not recommended and care should be taken when administering tacrolimus to patients who have previously received ciclosporin (see sections 4.2 and 4.4).
Għal dawn ir- raġunijiet mhux rikkmandat li ciclosporin u tacrolimus jingħataw flimkien, u wieħed għandu joqgħod attent meta jingħata tacrolimus lill- pazjenti li qabel ikunu ħadu ciclosporin (ara taqsimiet 4. 2 and 4. 4).
Tacrolimus has been shown to increase the blood level of phenytoin.
Tacrolimus wera li jgħolli l- livelli ta ’ phenytoin fid- demm.
As tacrolimus may reduce the clearance of steroid-based contraceptives leading to increased hormone exposure, particular care should be exercised when deciding upon contraceptive measures.
Billi tacrolimus jista ’ jnaqqas it- tneħħija ta ’ kontraċettivi bażati fuq sterojdi u jwassal għal espożizzjoni ormonali akbar, għandha tittieħed attenzjoni speċjali meta wieħed jiġi biex jieħu deċiżjonijiet dwar kontraċettivi.
Limited knowledge of interactions between tacrolimus and statins is available.
Hemm ftit għarfien dwar l- interazzjoni bejn tacrolimus u statini.
Clinical data suggest that the pharmacokinetics of statins are largely unaltered by the co-administration of tacrolimus.
L- informazzjoni klinika li hawn, tagħti x’ tifhem li l- farmakokinetika ta ’ statini ġeneralment ma tinbidilx bil- koamministrazzjoni ta ’ tacrolimus.
Animal data have shown that tacrolimus could potentially decrease the clearance and increase the half- life of pentobarbital and antipyrine.
Informazzjoni mill- annimali turi li tacrolimus jista ’ potenzjalment inaqqas din it- tneħħija u jżid il- half life ta ’ pentobarbital u antipyrine.
Other potential interactions that may increase systemic exposure of tacrolimus Prokinetic agents such as metoclopramide and cisapride.
Interazzjonijiet oħra li jistgħu jżidu l- esponiment sistemiku ta ’ tacrolimus Aġenti prokinetiċi bħalma huma metoclopramide u cisapride.
Cimetidine.
Cimetidine.
Magnesium-aluminum-hydroxide.
Magnesium- aluminum- hydroxide.
Other interactions which have led to clinically detrimental effects Concurrent use of tacrolimus with medicinal products known to have nephrotoxic or neurotoxic effects may increase these effects (e. g., aminoglycosides, gyrase inhibitors, vancomycin, cotrimoxazole, NSAIDs, ganciclovir or aciclovir).
Interazzjonijiet oħra li wasslu għal effetti klinikament detrimentali L- użu ta ’ tacrolimus flimkien ma prodotti mediċinali oħra magħrufa li għandhom effetti nefrotossiċi jew newrotossiċi jista ’ jżid dawn l- effetti (eż. aminoglycosides, gyrase inhibitors, vancomycin, cotrimoxazole, NSAIDs, ganciclovir jew aciclovir).
Enhanced nephrotoxicity has been observed following the administration of amphotericin B and ibuprofen in conjunction with tacrolimus.
Dehret żieda ta ’ nefrotossiċita meta ngħata amphotericin B u ibuprofen flimkien ma ’ tacrolimus.
As tacrolimus treatment may be associated with hyperkalaemia, or may increase pre-existing hyperkalaemia, high potassium intake, or potassium-sparing diuretics (e. g., amiloride, triamterene, or spironolactone) should be avoided.
Billi l- kura ta ’ tacrolimus tista ’ tkun assoċjata ma ’ l- iperkalemija, jew tista ’ żżid iperkalemija prieżistenti, għandu jiġi evitat it- teħid ta ’ ammont kbir ta ’ potassium, jew dijuretiċi potassium- sparing (eż. amiloride, triamterene, jew spironolactone).
Immunosuppressants may affect the response to vaccination and vaccination during treatment with tacrolimus may be less effective.
L- immunosuppressanti jistgħu jeffettwaw ir- respons għall- vaċċinazzjoni u għalhekk it- tilqim matul il - kura b’ tacrolimus jista ’ jkun inqas effettiv.
The use of live attenuated vaccines should be avoided.
Tilqim ħaj attenwat għandu jiġi evitat.
Protein binding considerations 7 Tacrolimus is extensively bound to plasma proteins.
Konsiderazzjonijiet dwar l- irbit mal- proteini Tacrolimus jingħaqqad estensivament mal- proteini tal- plażma.
Possible interactions with other medicinal products known to have high affinity for plasma proteins should be considered (e. g., NSAIDs, oral anticoagulants, or oral antidiabetics).
NSAIDs, antikoagulanti jew antidijabetiċi orali).
Human data show that tacrolimus crosses the placenta.
Tagħrif mill- bniedem juri li tacrolimus jaqsam il- plaċenta.
Limited data from organ transplant recipients show no evidence of an increased risk of adverse events on the course and outcome of pregnancy under tacrolimus treatment compared with other immunosuppressive medicinal products.
Tagħrif limitat minn pazjenti ta ’ trapjanti ta ’ organi ma juri ebda żieda fir- riskju ta ’ effetti avversi fuq it- tqala u fuq ir- riżultat tat- tqala bil- kura ta ’ tacrolimus meta mqabbel ma ’ prodotti oħra mediċinali immunosuppressivi..
To date, no other relevant epidemiological data are available.
Sa llum, m’ hemm l - ebda tagћrif epidemjoloġiku rilevanti ieħor.
Tacrolimus treatment can be considered in pregnant women, when there is no safer alternative and when the perceived benefit justifies the potential risk to the foetus.
F’ każ ta ’ espożizzjoni in utero, monitoraġġ tat- tarbija mwielda għal xi effetti avversi potenzjali ta ’ tacrolimus huwa rikkmandat (speċjalment effetti fuq il- kliewi).
In case of in utero exposure, monitoring of the newborn for the potential adverse events of tacrolimus is recommended (in particular effects on the kidneys). There is a risk for premature delivery (< 37 week) as well as for hyperkalaemia in the newborn (incidence 8 of 111 neonates, i. e.
Hemm ir- riskju tat - twelid qabel iż- żmien (< 37 ġimgħa) kif ukoll lit - tarbija mwielda ikollha l- iperkalemija, (inċidenza ta ’ 8 minn 111 il- tarbija mwielda, jiġifieri.
7.2%) which, however normalises spontaneously.
7. 2%) li madankollu tinnormalizza ruħha spontanjament.
In rats and rabbits, tacrolimus caused embryofoetal toxicity at doses which demonstrated maternal toxicity (see section 5.3).
(ara taqsima 5. 3).
Tacrolimus affected fertility in male rats (see section 5.3).
Tacrolimus effettwa l- fertilità fil- firien rġiel (ara taqsima 5. 3).
Lactation Human data demonstrate that tacrolimus is excreted in breast milk.
Treddigħ Tagħrif mill- bniedem juri li tacrolimus jitneħħa fil- ħalib.
As detrimental effects on the newborn cannot be excluded, women should not breast-feed whilst receiving Advagraf.
Billi ma jistgħux jiġu esklużi effetti ħżiena fuq l- imwieled ġdid, in- nisa ma għandhomx ireddgħu meta jkunu qed jieħdu Advagraf.
4.7 Effects on ability to drive and use machines
8 4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
Tacrolimus may cause visual and neurological disturbances.
Tacrolimus jista ’ jikkaġuna diffikultajiet newroloġiċi u fil- vista.
This effect may be enhanced if Advagraf is administered in association with alcohol.
Dawn l- effetti jistgħu jikbru jekk Advagraf jingħata ma ’ l- alkoħol
The adverse reaction profile associated with immunosuppressive agents is often difficult to establish owing to the underlying disease and the concurrent use of multiple medications.
Bosta drabi diffiċli tistabbilixxi l- profil tar- reazzjonijiet kuntrarji assoċjati ma ’ l- aġenti immunosuppressivi minħabba l- marda li tkun u d- diversi mediċini użata flimkien għaliha.
Many of the adverse reactions stated below are reversible and/ or respond to dose reduction.
Ħafna mir- reazzjonijiet avversi msemmija hawn taħt huma riversibbli u/ jew jirrispondu għat- tnaqqis tad- doża.
Adverse reactions are listed below in descending order by frequency of occurrence: very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000), not known (cannot be estimated from the available data).
Ir- reazzjonijiet avversi msemmija hawn taħt huma elenkati f’ ordni ta ’ tinqis fil- frekwenza tal- okkorrenza: komuni ħafna (≥ 1/ 10); komuni (≥ 1/ 100 sa < 1/ 10); mhux komuni (≥ 1/ 1, 000 sa < 1/ 100); rari (≥ 1/ 10, 000 to < 1/ 1, 000); rari ħafna (< 1/ 10, 000), mhux magħruf (ma tistax tittieћed stima mid- data disponnibli).
Cardiac disorders common: uncommon:
Disturbi fil- qalb komuni: mhux komuni: rari:
ischaemic coronary artery disorders, tachycardia ventricular arrhythmias and cardiac arrest, heart failures, cardiomyopathies, ventricular hypertrophy, supraventricular arrhythmias, palpitations, ECG investigations abnormal, heart rate and pulse investigations abnormal
disturbi iskemiku fl- arterji koronarji, takikardija arritmea ventrikolari u waqfien kardijaku, waqfien tal- qalb, kardjomijopatite, ipertrofija ventrikolari, arritmea supraventrikolari, palpitazzjonijiet, investigazzjonijiet anormali ta ’ l- ECG, taħbit anormali tal- qalb u investigazzjonijiet anormali tal- polz effużjoni perikardjali
rare: very rare:
rari ħafna:
pericardial effusion echocardiogram abnormal
ekokardjogramma anormali
Blood and lymphatic system disorders common:
Disturbi tad- demm u
uncommon:
tas- sistema limfatika
coagulopathies, coagulation and bleeding analyses abnormal, pancytopenia, neutropenia
anemija, lewkopenija, tromboċitopenija, lewkoċitożi, analiżi anormali taċ- ċelluli komuni: ħomor tad- demm koagulopatite, analiżi tal- koagulazzjoni u tad- dmija anormali, panċitopenija, mhux komuni: newtropenija rari: tromboċitopenia trombotika purpura, ipoprotrombinemija
Nervous system disorders very common: common:
Disturbi fis- sistema nervuża komuni ħafna: komuni: mhux komuni:
tremor, headache seizures, disturbances in consciousness, paraesthesias and dysaesthesias, peripheral neuropathies, dizziness, writing impaired, nervous system disorders 8
rogħda, uġigħ ta ’ ras attakk ta ’ puplesija, disturbi meta f’ sensik, parestesija u disestesija, newropatiji periferali, sturdamenti, nuqqas ta ’ ħila fil- kitba, disturbi fis- sistema nervuża kôma, emorragiji fis- sistema nervuża ċentrali u diżgrazzji ċerebrovaskolari, paraliżi u pareżi, enċefalopatija, anormalitajiet fil- lingwa u d- diskors, amneżija
rare: very rare:
rari: rari ħafna:
hypertonia myasthenia
ipertonija mijastenija
common: uncommon: rare:
Disturbi fl- għajnejn viżjoni mċajpra, fotofobija, disturbi fl- għajnejn komuni: mhux komuni: rari:
vision blurred, photophobia, eye disorders cataract blindness
katarretti għama
Ear and labyrinth disorders common: uncommon: rare: very rare:
Disturbi fil- widnejn u fis- sistema labirintika komuni: mhux komuni: rari: rari ħafna:
tinnitus hypoacusis deafness neurosensory hearing impaired
tisfir ipoakusis turxien newrosensorju smigħ difettuż
Respiratory, thoracic and mediastinal disorders common:
Disturbi respiratorji, toraċiċi u medjastinali
dyspnoea, parenchymal lung disorders, pleural effusion, pharyngitis, cough, nasal congestion and inflammations
9 dispnoea, disturbi parenkimali pulmonari, effuzzjoni pleurali, farinġite, sogħla, komuni: konġestjoni ta ’ l- imnieħer u infjammazzjonijiet nuqqasijiet respiratorji, taħwid fil- kanal tan- nifs, ażma mhux komuni: rari: sindrome ta ’ għeja respiratorja akuta
Gastrointestinal disorders very common: common:
Disturbi gastro- intestinali komuni ħafna: komuni: mhux komuni:
diarrhoea, nausea gastrointestinal inflammatory conditions, gastrointestinal ulceration and perforation, gastrointestinal haemorrhages, stomatitis and ulceration, ascites, vomiting, gastrointestinal and abdominal pains, dyspeptic signs and symptoms, constipation, flatulence, bloating and distension, loose stools, gastrointestinal signs and symptoms
dijarrea, dardir kondizzjonijiet gastrointestinali infjammatorji, ulċerazzjonijiet u perforazzjonijiet gastrointestinali, emorraġiji gastrointestinali, stomatite u ulċerazzjoni, axxite, riġettar, uġigħ gastrointestinali u addomenali, sintomi u sinjali dispeptiċi, kostipazzjoni, uġigħ ta ’ gas fl- istonku, nefħa u tkabbir, purgar maħlul, sintomi u sinjali gastrointestinali ileus paralitiku, peritonite, pankreatite akuta u kronika, żieda tal- amylase fid - demm, marda ta ’ rifluss gastroosofaġeali, dewmin fl- iżvojtar gastriku
rare:
rari:
subileus, pancreatic pseudocyst
subileus, pseudoċista pankratika
Renal and urinary disorders very common: common:
Disturbi fil- kliewi komuni ħafna: komuni:
renal impairment renal failure, renal failure acute, oliguria, renal tubular necrosis, nephropathy toxic, urinary abnormalities, bladder and urethral symptoms
u fis- sistema urinarja indeboliment renali waqfien funzjonali tal- kliewi, waqfien funzjonali tal- kliewi akut, oligurija, nekrożi tubulari tal- kliewi, nefropatija tossika, anormalitajiet urinarji, sintomi tal- bużżieqa u tal- kanal ta ’ l- awrina
uncommon: very rare:
mhux komuni: rari ħafna:
anuria, haemolytic uraemic syndrome nephropathy, cystitis haemorrhagic
anuria, sindrome uremika emolitika nefropatite, ċistite emorraġika
Skin and subcutaneous tissue disorders common: uncommon: rare: very rare:
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda ħakk, raxx, alopeċja, akne, żieda fl- għaraq komuni: mhux komuni: rari:
pruritus, rash, alopecias, acne, sweating increased dermatitis, photosensitivity toxic epidermal necrolysis (Lyell’ s syndrome) Stevens Johnson syndrome
dermatite, fotosensittività nekroliżi tossika tal- ġilda (Lyell’ s syndrome)
Musculoskeletal and connective tissue disorders common: uncommon:
sindrome Stevens Johnson
arthralgia, muscle cramps, pain in limb, back pain joint disorders
Disturbi muskolu- skeltrali u tal- connective tissue artralgija, krampi muskolari, uġigħ fis- saqajn u d- dirgħajn, uġigħ fid- dahar komuni: mhux komuni:
Endocrine disorders rare: hirsutism
disturbi fil- ġogi
Metabolism and nutrition disorders very common: common:
Irsutiżmu
hyperglycaemic conditions, diabetes mellitus, hyperkalaemia hypomagnesaemia, hypophosphataemia, hypokalaemia, hypocalcaemia, hyponatraemia, fluid overload, hyperuricaemia, appetite decreased, anorexia,
Distrubi fil- metaboliżmu u n- nutrizzjoni komuni ħafna: komuni:
9 metabolic acidoses, hyperlipidaemia, hypercholesterolaemia, hypertriglyceridaemia, other electrolyte abnormalities
kondizzjonijiet ipergliċemiċi, dijabete, iperkalemija ipomagnesemija, ipofosfatemija, ipokalemija, ipokalċemija, iponatremija, fluwidu żejjed, iperuriċemija, nuqqas ta ’ aptit, anoressija, aċidożi metabolika, iperlipidemija, iperkolesterolemija, ipertrigliċeridemija, anormalitajiet elektroliti oħra
uncommon:
mhux komuni:
dehydration, hypoproteinaemia, hyperphosphataemia, hypoglycaemia
deidrazzjoni, ipoprotenemija, iperfosfatemija, ipogliċemija
Infections and infestations As is well known for other potent immunosuppressive agents, patients receiving tacrolimus are frequently at increased risk for infections (viral, bacterial, fungal, protozoal).
Infezzjonijiet u infestazzjonijiet Kifinhu magħruf li jiġri b’ aġenti qawwija immunosuppressivi qawwija oħra, il- pazjenti li jieħdu tacrolimus ġeneralment ikunu f’ riskju akbar li jieħdu infezzjonijiet (virali, batteriċi, fungali, protozoali).
The course of pre- existing infections may be aggravated.
Jista ’ jkun li l- infezzjonijiet li jkunu ġa hemm isiru aktar gravi.
Both generalised and localised infections can occur.
Jistgħu jitfaċċaw kemm infezzjonijiet ġeneralizzati kif ukoll lokalizzati.