qanastek/EMEA-V3 huggingface dataset:
Cases of BK virus associated nephropathy, as well as cases of JC virus associated progressive multifocal leukoencephalopathy (PML), have been reported in patients treated with immunosuppressants, including Advagraf.
Każijiet ta ’ nefropatija assoċjata ma ’ virus BK, kif ukoll każijiet ta ’ lewkoenċefalopatija multifokali progressiva (PML) assoċjata ma ’ virus JC, ġew irrapportati f’ pazjenti kkurati b’ immunosuppressanti, inkluż Advagraf.
Injury, poisoning and procedural complications common:
Korriment, avvelenament u komplikazzjonijiet ta ’ xi proċedura komuni:
primary graft dysfunction
disfunzjoni tat- trapjant primarju
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 jigifieri bejn dik b’ rilaxx immedjat u dik b’ rilaxx prolungat ġew osservati.
A number of associated cases of transplant rejection have been reported (frequency cannot be estimated from available data).
Numru ta ’ każijiet assoċjati ta ’ rifjut ta ’ trapjanti kien irrapurtat (stima tal- frekwenza ma tistax tittieћed mill- informazzjoni disponibbli).
Patients receiving immunosuppressive therapy are at increased risk of developing malignancies.
Neoplażmi beninni, malinni u dawk mhux speċifikati (inklużi ċesti u polipi) Il- pazjenti li qed jieħdu kura immunosuppressiva għandhom riskju akbar li jiżviluppaw tkabbir malinn.
Benign as well as malignant neoplasms including EBV-associated lymphoproliferative disorders and skin malignancies have been reported in association with tacrolimus treatment.
Marbuta mal- kura b’ tacrolimus ġew rapportati neoplażmi beninji kif ukoll malinji li jinkludu disturbi limfoproliferattiv assoċjati ma ’ EBV kif ukoll tkabbir malinn fil- ġilda.
Vascular disorders very common: common:
Disturbi vaskulari komuni ħafna: komuni: mhux komuni:
hypertension haemorrhage, thromboembolic and ischaemic events, peripheral vascular disorders, vascular hypotensive disorders
pressjoni għolja emorraġija, inċidenti trombemboliċi u iskemiċi, disturbi vaskolari periferiċi, disturbi vaskolari ipotensivi infart, trombożi fonda ġol- vini fir- riġel, xokk
asthenic conditions, febrile disorders, oedema, pain and discomfort, blood alkaline phosphatase increased, weight increased, body temperature perception disturbed
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata kondizzjonijiet asteniċi, disturbi tad- deni, edema, uġigħ u skonfort, żieda tal - komuni: alkaline phosphatase fid- demm, żieda fil- piż, taqlib fit- temperatura tal- ġisem mhux komuni: rari:
multi-organ failure, influenza like illness, temperature intolerance, chest pressure sensation, feeling jittery, feeling abnormal, blood lactate dehydrogenase increased, weight decreased
diversi organi ma jaħdmux, mard qisu influwenza, intolleranza tat- temperatura, sensazzjoni ta ’ pressjoni fuq is- sider, tħossok abnormali, żieda tal- lactate dehydrogenase fid- demm, tinqis fil- piż għatx, wqigħ, sider magħfus, tnaqqis fil- mobbiltà, ulċera
thirst, fall, chest tightness, mobility decreased, ulcer fat tissue increased
tessut xaħmi miżjud
Immune system disorders Allergic and anaphylactoid reactions have been observed in patients receiving tacrolimus (see section 4.4).
Disturbi fis- sistema immuni F’ pazjenti jieħdu tacrolimus dehru reazzjonijiet allerġiċi u anafilaktojdi (ara taqsima 4. 4).
hepatic enzymes and function abnormalities, cholestasis and jaundice, hepatocellular damage and hepatitis, cholangitis
Disturbi fil- fwied u fil- marrara enżimi epatiċi u anormalità funzjonali, kolestasi u suffejra, ħsara epatoċellulari u komuni: epatite, kolanġite trombożi epatika ta ’ l- arterji, marda tal- vina magħluqa fil- fwied rari: rari ħafna:
hepatitic artery thrombosis, venoocclusive liver disease hepatic failure, bile duct stenosis
waqfien funzjonali tal- fwied, tidjiq tal- kanal tal- marrara
Reproductive system and breast disorders uncommon:
Disturbi fis- sistema riproduttiva u fis- sider mhux komuni:
dysmenorrhoea and uterine bleeding
uġigħ mestrwali u fsad fl- utru
Psychiatric disorders very common: common:
Disturbi psikjatriċi komuni ħafna: komuni:
insomnia anxiety symptoms, confusion and disorientation, depression, depressed mood, mood disorders and disturbances, nightmare, hallucination, mental disorders
insomnia (nuqqas ta ’ rqad) sintomi ta ’ ansjetà, konfużjoni u diżorjentament, depressjoni, burdata depressiva, disturbi u taqlib fil- burdata, ħmarillejl, alluċinazzjonijiet, disturbi mentali
4.9 Overdose
disturbi psikotiċi
psychotic disorder 10
Doża eċċessiva 4. 9
Experience with overdose is limited.
Ma tantx hemm esperjenza ta 'doża eċċessiva.
Several cases of accidental overdose have been reported with tacrolimus; symptoms have included tremor, headache, nausea and vomiting, infections, urticaria, lethargy, increased blood urea nitrogen and elevated serum creatinine concentrations, and increase in alanine aminotransferase levels.
Kien hemm bosta każi aċċidentali rapportati ta ’ doża eċċessiva b ’ tacrolimus; is- sintomi kienu jinkludu rogħda, uġigħ ta ’ ras, dardir u riġettar, infezzjonijiet, urtikarja, letarġija, żieda fl- urea nitroġena tad- demm u konċentrazzjonijiet tal - kreatinina fis- serum kif ukoll żieda fil- livelli ta ’ alanine aminotransferase.
No specific antidote to tacrolimus therapy is available.
Ma hemm l- ebda antidotu speċifiku għall- kura ta ’ tacrolimus.
If overdose occurs, general supportive measures and symptomatic treatment should be conducted.
Jekk ikun hemm każ ta ’ doża eċċessiva, għandha ssir kura simptomatika u jittieħdu passi ġenerali biex jgħinu.
Based on its high molecular weight, poor aqueous solubility, and extensive erythrocyte and plasma protein binding, it is anticipated that tacrolimus will not be dialysable.
Huwa antiċipat li tacrolimus ma jkunx dijalisibbli ibbażat fuq piż molekulari għoli, fis- solubbiltà likwida fqir u r’ rabta estensiva eritrokita u proteina plażmatika tiegħu.
In isolated patients with very high plasma levels, haemofiltration or -diafiltration have been effective in reducing toxic concentrations.
F’ xi każi iżolati ta ’ pazjenti li kellhom livelli għolja fill- plażma, il- hemofiltrazzjoni jew id- dijafiltrazzjoni kienu effettivi biex inaqqsu l- konċentrazzjonijiet tossiċi.
In cases of oral intoxication, gastric lavage and/ or the use of adsorbents (such as activated charcoal) may be helpful, if used shortly after intake.
F’ każi ta ’ intossikazzjoni orali, tindif gastriku u/ jew l- użu ta ’ assorbenti (bħlama hu l- faħam attivat) jistgħu jgħinu, jekk jintużaw ftit wara lli jkun ittieħed.
PHARMACOLOGICAL PROPERTIES
11 TAGĦRIF FARMAKOLOĠIKU 5.
Calcineurin inhibitors, ATC code:
Kategorija farmakoterapewtika: inibituri ta ’ calcineurin, Kodiċi ATC:
Mechanism of action and pharmacodynamic effects At the molecular level, the effects of tacrolimus appear to be mediated by binding to a cytosolic protein (FKBP12) which is responsible for the intracellular accumulation of the compound.
Il- mekkaniżmu ta ’ kif jaħdem u l- effetti farmakodinamiċi Fil- livell molekulari, l- effetti ta ’ tacrolimus jidhru li jibdew billi jingħaqdu ma proteina ċistolika (FKBP12) li hi responsabbli għall- akkumulazzjoni intraċellulari tat- taħlita.
The FKBP12-tacrolimus complex specifically and competitively binds to and inhibits calcineurin, leading to a calcium-dependent inhibition of T-cell signal transduction pathways, thereby preventing transcription of a discrete set of lymphokine genes.
B’ dan il- mod iżżomm it- transkrizzjoni ta ’ sett ta ’ ġene diskreti limfokini.
Tacrolimus is a highly potent immunosuppressive agent and has proven activity in both in vitro and in vivo experiments.
Tacrolimus hu aġent immunosuppressiv qawwi ħafna u wera attività fl- esperimenti kemm in vitro kif ukoll in vivo.
In particular, tacrolimus inhibits the formation of cytotoxic lymphocytes, which are mainly responsible for graft rejection.
B’ mod partikolari tacrolimus iwaqqaf il- formazzjoni ta ’ limfoċiti ċitotossiċi, li huma ġeneralment responsabbli għar- riġezzjoni tat- trapjant.
Tacrolimus suppresses T-cell activation and T-helper-cell dependent B-cell proliferation, as well as the formation of lymphokines (such as interleukins-2, -3, and γ -interferon) and the expression of the interleukin-2 receptor.
Tacrolimus jissopprimi l- attivazzjoni tat- T- cell u t- tixrid tal - B- cell li hu dipendenti fuq it- T- helper- cell, kif ukoll il- formazzjoni ta ’ limfokini (bħal l- interlewkini 2, - 3, u l - γ- interferon) u l- espressjoni tar- reċettur interlewkin – 2.
Results from clinical trials performed with once-daily tacrolimus Advagraf Liver transplantation The efficacy and safety of Advagraf and Prograf, both in combination with corticosteroids, was compared in 471 de novo liver transplant recipients.
Riżultati minn provi kliniċi li saru b’ tacrolimus darba kuljum Advagraf Trapjant tal- fwied L- effikaċja u s- sigurta ’ ta ’ Advagraf u Prograf, meta ngћataw flimkien ma kortikosterojdi, ġie mqabbel f ’ 471 riċevitur de novo ta ’ trapjant tal- fwied.
The event rate of biopsy confirmed acute rejection within the first 24 weeks after transplantation was 32.6% in the Advagraf group (N=237) and 29.3% in the Prograf group (N=234).
Ir- rata ta ’ rifjut akut ikkonfermat b ’ bijopsija fl- ewwel 24 ġimgћa wara t- trapjant kien 32. 6% fil- grupp ta ’ l- Advagraf (N=237) u 29. 3% fil- grupp ta ’ l- Prograf (N=234).
The treatment difference (Advagraf – Prograf) was 3.3% (95% confidence interval [-5.7%, 12.3%]). The 12-month patient survival rates were 89.2% for Advagraf and 90.8% for Prograf; in the Advagraf arm 25 patients died (14 female, 11 male) and in the Prograf arm 24 patients died (5 female, 19 male).
Wara 12- il xahar mit- trapjant, 89. 2% tal- pazjenti li ћadu Advagraf u 90. 8% tal- pazjenti li ћadu Prograf għexu; fil- fergћa ta ’ l- Advagraf 25 pazjent mietu (14 nisa, 11 irġiel) u fil - fergћa ta ’ l- Prograf 24 pazjent mietu (5 nisa, 19 irġiel).
12-month graft survival was 85.3% for Advagraf and 85.6% for Prograf.
Wara 12- il xahar mit- trapjant, kien hemm sopravivenza tat- trapjant ta ’ 85. 3% gћal Advagraf u 85. 6% gћal Prograf.
Kidney transplantation The efficacy and safety of Advagraf and Prograf, both in combination with mycophenolate mofetil (MMF) and corticosteroids, was compared in 667 de novo kidney transplant recipients.
Trapjant tal- kliewi L- effikaċja u s- sigurta ’ ta ’ Advagraf u Prograf, meta ngћataw flimkien ma mycophenolate mofetil (MMF) u kortikosterojdi, ġie mqabbel f ’ 667 riċevitur de novo ta ’ trapjant tal- kliewi.
The event rate for biopsy-confirmed acute rejection within the first 24 weeks after transplantation was 18.6% in the Advagraf group (N=331) and 14.9% in the Prograf group (N=336).
Ir- rata ta ’ rifjut akut ikkonfermat b ’ bijopsija fl- ewwel 24 ġimgћa wara t- trapjant kien 18. 6% fil- grupp ta ’ l- Advagraf (N=331) u 14. 9% fil- grupp ta ’ l- Prograf (N=336).
The treatment difference (Advagraf-Prograf) was 3.8% (95% confidence interval [-2.1%, 9.6%]).
Id- differenza fit- trattament (Advagraf- Prograf) kien 3. 8% (95% confidence interval [- 2. 1%, 9. 6%]).
The 12-month patient survival rates were 96.9% for Advagraf and 97.5% for Prograf; in the Advagraf arm 10 patients died (3 female, 7 male) and in the Prograf arm 8 patients died (3 female, 5 male).
Wara 12- il xahar mit- trapjant, 96. 9% tal- pazjenti li ћadu Advagraf u 97. 5% tal- pazjenti li ћadu Prograf għexu; fil- grupp ta ’ l- Advagraf 10 pazjenti mietu (3 nisa, 7 irġiel) u fil- grupp ta ’ l- Prograf 8 pazjenti mietu (3 nisa, 5 irġiel).
12-month graft survival was 91.5% for Advagraf and 92.8% for Prograf.
Wara 12- il xahar mit - trapjant, kien hemm sopravivenza tat- trapjant ta ’ 91. 5% gћal Advagraf u 92. 8% gћal Prograf.
11 The efficacy and safety of Prograf, ciclosporin and Advagraf, all in combination with basiliximab antibody induction, MMF and corticosteroids, was compared in 638 de novo kidney transplant recipients.
L- effikaċja u s- sigurta ’ ta ’ Prograf, Ciclosporin u Advagraf, meta ngћataw flimkien ma ’ l- antikorp basiliximab indott, MMF u kortikosterojdi, ġie mqabbel f ’ 638 riċevitur de novo ta ’ trapjant tal - kliewi.
The incidence of efficacy failure at 12 months (defined as death, graft loss, biopsy- confirmed acute rejection, or lost to follow-up) was 14.0% in the Advagraf group (N=214), 15.1% in the Prograf group (N=212) and 17.0% in the ciclosporin group (N=212).
L- inċidenza ta ’ nuqqas ta ’ effikaċja wara 12- il xahar (definit bћala mewt, telf tal- graft, rifjut akut ikkonfermat b ’ bijopsija jew ma ġiex segwit) kien 14. 0% fil - fergћa ta ’ l- Advagraf (N=214), 15. 1% fil - fergћa ta ’ l- Prograf (N=212) u 17. 0% fil- grupp ta ’ ciclosporin (N=212).
The treatment difference was -3.0% (Advagraf-ciclosporin) (95.2% confidence interval [-9.9%, 4.0%]) for Advagraf vs. ciclosporin and -1.9% (Prograf-ciclosporin) (95.2% confidence interval [-8.9%, 5.2%]) for Prograf vs. ciclosporin.
Id- differenza fil - kura (Advagraf- Ciclosprin) kien - 3. 0% (95. 2% confidence interval [- 9. 9%, 4. 0%]) gћal Advagraf vs ciclosporin u - 1. 9% (Prograf- ciclosporin) (95. 2% confidence interval [- 8. 9%, 5. 2%]) gћal Prograf vs ciclosporin.
The 12-month patient survival rates were 98.6% for Advagraf, 95.7% for Prograf and 97.6% for ciclosporin; in the Advagraf arm 3 patients died (all male), in the Prograf arm 10 patients died (3 female, 7 male) and in the ciclosporin arm 6 patients died (3 female, 3 male).
Wara 12- il xahar mit- trapjant, 98. 6% tal- pazjenti li ћadu Advagraf, 95. 7% tal- pazjenti li ћadu Prograf u 97. 6% tal- pazjenti li ћadu ciclosporin għexu; fil - fergћa ta ’ l- Advagraf 3 pazjenti mietu (kollha rġiel), fil - fergћa ta ’ l- Prograf 10 pazjenti mietu (3 nisa, 7 irġiel) u fil - fergћa ta ’ ciclosporin 6 pazjenti mietu (3 nisa, 3 irġiel).
12-month graft survival was 96.7% for Advagraf, 92.9% for Prograf and 95.7% for ciclosporin.
Ma ’ 12- il xahar mit- trapjant, kien hemm sopravivenza tat- trapjant ta ’ 96. 7% gћal Advagraf, 92. 9% gћal Prograf u 95. 7% gћal ciclosporin.
Results from published data of tacrolimus administered twice daily as Prograf capsules in other primary organ transplantation Prograf has evolved into an accepted treatment as primary immunosuppressive medicinal product following pancreas, lung and intestinal transplantation.
12 Riżultati pubblikati minn tagħrif dwar l- għoti darbtejn kuljum ta ’ tacrolimus bħala kapsuli Prograf fi trapjanti ta ’ organi primarji Prograf żviluppa f’ kura aċċettata bħala prodott mediċinali immunosuppressiv primarju wara trapjant tal- pankreas, tal- pulmun u ta ’ l- intestini.
In prospective published studies oral Prograf was investigated as primary immunosuppressant in approximately 175 patients following lung, 475 patients following pancreas and 630 patients following intestinal transplantation.
Fi studji prospettivi pubblikati, Prograf orali kien investigat bħala immunsuppressant primarju f’ bejn wieħed u ieħor 175 pazjent wara trapjant tal- pulmun, f ’ 475 pazjent wara trapjant tal- pankreas u f ’ 630 pazjent wara trapjant intestinali.
Overall, the safety profile of oral Prograf in these published studies appeared to be similar to what was reported in the large studies, where Prograf was used as primary treatment in liver, kidney and heart transplantation.
Kollox ma ’ kollox, il - profil sigur f ’ Prograf orali li deher pubblikat f’ dawn l- istudji kien simili għal dak li deher fl- istudji l - kbar, fejn Prograf intuża bħala kura primarja għat- trapjanti tal- fwied, tal- kliewi u tal- qalb.
Efficacy results of the largest studies in each indication are summarised below.
L- effikaċja ta ’ l- akbar studji ta ’ riżultati f’ kull indikazzjoni qegħdin imqassra hawn taħt.
Lung transplantation The interim analysis of a recent multicentre study using oral Prograf discussed 110 patients who underwent 1:1 randomisation to either tacrolimus or ciclosporin.
Trapjant tal- pulmun Sadattant l- analiżi ta ’ studju reċenti minn diversi ċentri li użaw Prograf orali kien dwar 110 pazjenti li bl- addoċċ ta ’ 1: 1 ingħataw jew tacrolimus jew ciclosporin.
Tacrolimus was started as continuous intravenous infusion at a dose of 0.01 to 0.03 mg/ kg/ day and oral tacrolimus was administered at a dose of 0.05 to 0.3 mg/ kg/ day.
Tacrolimus inbeda bħala doża infuża kontinwa fil- vini ta ’ minn 0. 01 għal 0. 03 mg/ kg/ kuljum u ngħata tacrolimus orali b’ doża ta ’ minn 0. 05 sa 0. 3 mg/ kg/ kuljum.
A lower incidence of acute rejection episodes for tacrolimus- versus ciclosporin-treated patients (11.5% versus 22.6%) and a lower incidence of chronic rejection, the bronchiolitis obliterans syndrome (2.86% versus 8.57%), was reported within the first year after transplantation.
Fl- ewwel sena wara t- trapjant kienu rappurtati inqas każi ta ’ episodji fejn kien hemm riġezzjoni akuta għal tacrolimus kontra pazjenti li ħadu ciclosporin (11. 5% kontra t - 22. 6%) u inqas inċidenza ta ’ riġezzjoni kronika, is- sindrome bronkolite obliterans (2. 86% versus 8. 57%).
The 1-year patient survival rate was 80.8% in the tacrolimus and 83% in the ciclosporin group (Treede et al., 3rd ICI San Diego, US, 2004; Abstract 22).
F’ sena kien hemm rata ta ’ 80. 8% tal- pazjenti li għexu wara li ħadu tacrolimus u 83% fil - grupp li ħadu ciclosporin (Treede et al., 3rd ICI San Diego, US, 2004; Abstract 22).
Another randomised study included 66 patients on tacrolimus versus 67 patients on ciclosporin.
Studju ieħor ‘ randomised ’ kien jinkludi 66 pazjent li ħadu tacrolimus kontra s- 67 pazjent li ħadu ciclosporin.
Tacrolimus was started as continuous intravenous infusion at a dose of 0.025 mg/ kg/ day and oral tacrolimus was administered at a dose of 0.15 mg/ kg/ day with subsequent dose adjustments to target trough levels of 10 to 20 ng/ ml.
Tacrolimus inbeda bħala infużjoni kontinwa ġol- vini b’ doża ta ’ 0. 025 mg/ kg/ kuljum u tacrolimus orali ingħata f’ doża ta ’ 0. 15 mg/ kg/ kuljum b’ aġġustamenti wara fid- doża biex jilħqu l - livelli ‘ trough ’ ta ’ minn 10 sa 20 ng/ ml.
The 1-year patient survival was 83% in the tacrolimus and 71% in the ciclosporin group, the 2-year survival rates were 76% and 66%, respectively.
F’ sena kien hemm 83% tal- pazjenti li għexu wara li ħadu tacrolimus u 71% fil- grupp li ħadu ciclosporin, fit- tieni sena kien hemm rispettivament 76% u 66% li għexu.
Acute rejection episodes per 100 patient-days were numerically fewer in the tacrolimus (0.85 episodes) than in the ciclosporin group (1.09 episodes).
Episodji ta ’ riġezzjoni akuta għal kull 100 jum- pazjent kienu numerikament inqas f’ dawk li ħadu tacrolimus (0. 85 episodji) milli dawk tal- grupp li ħadu ciclosporin (1. 09 episodji).
Obliterative bronchiolitis developed in 21.7% of patients in the tacrolimus group compared with 38.0% of patients in the ciclosporin group (p = 0.025).
Bronkjolite obliterattiva żviluppat f ’ 21. 7% tal- pazjenti tal- grupp li ħadu tacrolimus meta mqabbla mat- 38. 0% tal - pazjenti li kienu fil- grupp ta ’ ciclosporin (p = 0. 025).
Significantly more ciclosporin-treated patients (n = 13) required a switch to tacrolimus than tacrolimus-treated patients to ciclosporin (n = 2) (p = 0.02) (Keenan et al., Ann Thoracic Surg 1995; 60:580).
Sinifikattiv il- fatt li kien hemm aktar pazjenti li ħadu ciclosporin (n = 13) li kellhom jaqilbu għal tacrolimus milli pazjenti fuq tacrolimus li kellhom jaqilbu għal ciclosporin (n = 2) (p = 0. 02) (Keenan et al., Ann Thoracic Surg 1995; 60: 580).
In an additional two-centre study, 26 patients were randomised to the tacrolimus versus 24 patients to the ciclosporin group.
Fi studju ieħor f’ żewġ ċentri, 26 pazjent intgħażlu b- mod ‘ randomised ’ biex jieħdu tacrolimus kontra 24 pazjent fil- grupp ta ’ ciclosporin.
Tacrolimus was started as continuous intravenous infusion at a dose of 0.05 mg/ kg/ day and oral tacrolimus was administered at a dose of 0.1 to 0.3 mg/ kg/ day with subsequent dose adjustments to target trough levels of 12 to 15 ng/ ml.
Tacrolimus inbeda bħala infużjoni kontinwa intravenali b’ doża ta ’ 0. 05 mg/ kg/ kuljum u tacrolimus orali ingħata f’ doża ta ’ 0. 1 to 0. 3 mg/ kg/ kuljum b’ aġġustamenti wara fid- doża biex jilħqu l- livelli ‘ trough ’ ta ’ minn 12 sa 15 ng/ ml.
The 1-year survival rates were 73.1% in the tacrolimus versus 79.2% in the ciclosporin group.
F’ sena kien hemm 73. 1% tal- pazjenti li għexu wara li ħadu tacrolimus kontra 79. 2% fil- grupp li ħadu ciclosporin.
Freedom from acute rejection was higher in the tacrolimus group at 6 months (57.7% versus 45.8%) and at 1 year after lung transplantation (50% versus 33.3%) (Treede et al., J Heart Lung Transplant 2001; 20:511).
Ħelsien minn riġezzjoni akuta kien ikbar fil- grupp li ħadu tacrolimus wara sitt xhur (57. 7% versus 45. 8%) u wara sena li kienu għamlu t- trapjant tal- pulmun (50% kontra 33. 3%) (Treede et al., J Heart Lung Transplant 2001; 20: 511).
The three studies demonstrated similar survival rates.
It- tliet studji urew rati simili ta ’ pazjenti li għexu.
The incidences of acute rejection were numerically lower with tacrolimus in all three studies and one of the studies reported a significantly lower incidence of bronchiolitis obliterans syndrome with tacrolimus.
L- inċidenzi ta ’ riġezzjoni akuta kienu numerikament inqas fit- tliet studji kollha wara l- kura ta ’ tacrolimus u f’ wieħed mill- istudji kien hemm inċidenza sinifikament aktar baxxa tas - sindrome bronkolite obliterans bl- użu ta ’ tacrolimus.
Pancreas transplantation A multicentre study using oral Prograf included 205 patients undergoing simultaneous pancreas- kidney transplantation who were randomised to tacrolimus (n = 103) or to ciclosporin (n = 102).
Trapjant tal- Pankreas Studju f’ diversi ċentri bl- użu ta ’ Prograf orali inkluda 205 pazjent li għamlu f’ daqqa trapjant tal - pankreas u l- kliewi li ttieħdu bl- addoċċ għal (n = 103 pazjenti) bi- kura ta ’ tacrolimus jew għal (n = 102 pazjenti) bil- kura ta ’ ciclosporin.
The initial oral per protocol dose of tacrolimus was 0.2 mg/ kg/ day with subsequent dose adjustments to target trough levels of 8 to 15 ng/ ml by Day 5 and 5 to 10 ng/ mL after Month 6.
Id- doża orali fil- bidu ta ’ kull protokol ta ’ tacrolimus kienet ta ’ 0. 2 mg/ kg/ kuljum b’ aġġustamenti wara fid- doża biex ilaħħqu l- mira tal- livelli ‘ trough ’ ta ’ 8 sa 15 ng/ ml sal- ħames jum u 5 to 10 ng/ mL wara s- sitt xahar.
Pancreas survival at 1 year was significantly superior with tacrolimus:
Kienu ħafna aktar dawk li għexu wara sena mit- trapjant tal- pankreas, u ħadu tacrolimus:
91.3% versus 74.5% with ciclosporin (p < 0.0005), whereas renal graft survival was similar in both groups.
91. 3% kontra 74. 5% b ’ ciclosporin (p < 0. 0005), filwaqt li dawk li għexu wara trapjant tal- kliewi kien simili fiż- żewġ gruppi.
In total 34 patients switched treatment from
B’ kollox 34 pazjent qalbu l- kura minn ciclosporin għal tacrolimus, meta kienu sitta biss il- pazjenti b ’ tacrolimus li kellhom bżonn kura alternattiva.
Intestinal transplantation Published clinical experience from a single centre on the use of oral Prograf for primary treatment following intestinal transplantation showed that the actuarial survival rate of 155 patients (65 intestine alone, 75 liver and intestine, and 25 multivisceral) receiving tacrolimus and prednisone was 75% at 1 year, 54% at 5 years, and 42% at 10 years.
Trapjant Intestinali Esperjenza klinika pubblikata minn ċentru wieħed dwar l- użu ta ’ Prograf orali bħala l- ewwel kura wara trapjant intestinali wriet li r- rata attwarja ta ’ dawk li għexu kienet ta ’ 155 pazjent (65 l- intestini biss, 75 l- fwied u l- intestini, u 25 multivixxerali) jieħdu tacrolimus u prednisone kienet ta ’ 75%
In the early years the initial oral dose of tacrolimus was 0.3 mg/ kg/ day.
Fl- ewwel snin id- doża orali ta ’ tacrolimus nbdiet b ’ 0. 3 mg/ kg/ kuljum.
Results continuously improved with increasing experience over the course of 11 years.
Ir- riżultati baqgħu jitjiebu hekk kif zdiedet l- esperjenza matul il- 11- il sena ta ’ wara.
A variety of innovations, such as techniques for early detection of Epstein-Barr (EBV) and CMV infections, bone marrow augmentation, the adjunct use of the interleukin-2 antagonist daclizumab, lower initial tacrolimus doses with target trough levels of 10 to 15 ng/ ml, and most recently allograft irradiation were considered to have contributed to improved results in this indication over time (Abu- Elmagd et al., Ann Surg 2001; 234:404).
Kien hemm varjetà ta ’ innovazzjonijiet, bħalma hi t- teknika li tinduna kmieni bl- infezzjonijiet Epstein- Barr (EBV) u CMV, żieda fil- mudullun ta ’ l- għadam, iż- żieda fl- użu tal- antagonist interleukin- 2 daclizumab fl- istess waqt, dożi aktar baxxi fil- bidu ta ’ tacrolimus biex jintlaħqu l- livelli ‘ trough ’ ta ’ 10 sa 15 ng/ ml, u aktar reċenti l- irradjazzjoni tal- hallograft li nħass li għenet biex ikun hemm riżultati aħjar f’ din indikazzjoni aktar ma jgħaddi ż- żmien (Abu- Elmagd et al., Ann Surg 2001; 234: 404).
Absorption In man tacrolimus has been shown to be able to be absorbed throughout the gastrointestinal tract.
Assorbiment Fil- bniedem, tacrolimus deher li jista ’ jigi assorbit mill- kanal gastrointestinali.
Available tacrolimus is generally rapidly absorbed.
Tacrolimus li hawn ġeneralment jinxtorob malajr.
Advagraf is a prolonged-release formulation of tacrolimus resulting in an extended oral absorption profile with an average time to Cmax of approximately 2 hours.
Advagraf hija formula ta ’ kif jinħeles bil- mod tacrolimus bir- riżultat ta ’ profil ta ’ assorbiment orali estiż f ’ ħin medju sa Cmax ta ’ bejn wieħed u ieħor sagħtejn.
Absorption is variable and the mean oral bioavailability of tacrolimus (investigated with the Prograf formulation) is in the range of 20% - 25% (individual range in adult patients 6% - 43%).
L- assorbiment ivarja u l- medja biodisponibbli orali ta ’ tacrolimus (investigat bil- formulazzjoni ta ’ Prograf) qiegħda fil- medda ta ’ minn 20% sa 25% (il- medda individwali f’ pazjenti adulti hija ta ’ bejn 6% u 43%).
The oral bioavailability of Advagraf was reduced when it was administered after a meal.
Il- biodisponibbiltà orali ta ’ Advagraf tnaqqset meta ngħatat wara xi ikla.
Both the rate and extent of absorption of Advagraf were reduced when administered with food.
Kemm ir- rata u l- kwantità ta ’ assorbiment ta ’ Advagraf tnaqqsu meta ngħata ma ’ l- ikel.
Bile flow does not influence the absorption of tacrolimus and therefore treatment with Advagraf may commence orally.
Il- bili ma jinfluwenzawx l- assorbiment ta ’ tacrolimus u għaldaqstant il- kura b ’ Advagraf tista ’ tinbeda oralment.
A strong correlation exists between AUC and whole blood trough levels at steady-state for Advagraf.
Hemm korrelazzjoni qawwija bejn l- AUC u l- livelli ‘ trough ’ tad- demm sħiħ f’ qagħda fissa għal Advagraf.
Monitoring of whole blood trough levels therefore provides a good estimate of systemic exposure.
Għaldaqstant il - monitoraġġ tal- livelli ‘ trough ’ tad- demm sħiħ għandu jagħti stima tajba tal- espożizzjoni sistemika.
Distribution and elimination In man, the disposition of tacrolimus after intravenous infusion may be described as biphasic.
Distribuzzjoni u tneħħija Fil- bniedem il- ħidma ta ’ tacrolimus wara l- infużjoni ġol- vini tista ’ tintqies li għandha żewġ stadji.
In the systemic circulation, tacrolimus binds strongly to erythrocytes resulting in an approximate 20:1 distribution ratio of whole blood/ plasma concentrations.
Fiċ- ċirkolazzjoni sistemika, tacrolimus jingħaqad mal- eritroċiti li jirriżulta f’ rata distributorja ta ’ bejn wieħed u ieħor 20: 1 tal- konċentrazzjonijiet tad- demm sħiħ / tal- plażma.
In plasma, tacrolimus is highly bound (> 98.8%) to plasma proteins, mainly to serum albumin and α -1-acid glycoprotein.
Fil- plażma, tacrolimus jaqbad sewwa (> 98. 8%) mal- proteini tal- plażma, l- aktar mas- serum albumin u l - α- 1- acid glycoprotein.
Tacrolimus is extensively distributed in the body.
Tacrolimus imqassam qatigħ mal- ġisem.
The steady-state volume of distribution based on plasma concentrations is approximately 1300 l (healthy subjects).
Il- qagħda fissa tal- volum tad- distribuzzjoni mibnija fuq il - konċentrazzjonijiet tal- plażma hija bejn wieħed u ieħor ta ’ 1300 l (soġgetti b’ saħħithom).
Corresponding data based on whole blood averaged 47.6 l.
Tagħrif li għandu x’ jaqsam ma ’ dan ibbażat fuq id- demm, sħiħ kellu medja ta’ 47. 6 l.
Tacrolimus is a low-clearance substance.
Tacrolimus hi sustanza li titneħħa bil- mod.
In healthy subjects, the average total body clearance estimated from whole blood concentrations was 2.25 l/ h.
F’ min hu b’ saħħtu, il- medja li biha titneħħa mill- ġisem kollu kalkulata mill- konċentrazzjonijiet kollha tad- demm sħiħ kienet ta ’ 2. 25 l/ h.
In adult liver, kidney and heart transplant patients, values of 4.1 l/ h, 6.7 l/ h and 3.9 l/ h, respectively, have been observed.
Fi trapjanti tal - fwied, tal- kliewi u tal- qalb f’ pazjenti adulti ħarġu rispettivament il- valuri ta ’ 4. 1 l/ h, 6. 7 l/ h u 3. 9 l/ h.
Factors such as low haematocrit and protein levels, which result in an increase in the unbound fraction of tacrolimus, or corticosteroid-induced increased metabolism are considered to be responsible for the higher clearance rates observed following transplantation.
Fatturi bħal livelli ‘ trough ’ ta ’ haematocrit u ta ’ proteini, li jirriżultaw f’ żieda ta ’ frazzjoni ta ’ tacrolimus mhux marbut, jew żieda fil- metboliżmu kaġunat mill- kortikosterojdi jintqiesu li huma responsabbli għar- rata ta ’ tisfija ogħla li kienet osservata wara t- trapjant.
The half-life of tacrolimus is long and variable.
Il- half life ta ’ tacrolimus hi twila u varjabbli.
In healthy subjects, the mean half-life in whole blood is approximately 43 hours.
F’ min hu b’ saħħtu, il- medja tal- half life ħajja fid- demm sħiħ hi bejn wieħed u ieħor ta ’ 43 siegħa.
Metabolism and biotransformation Tacrolimus is widely metabolised in the liver, primarily by the cytochrome P450-3A4.
Metaboliżmu u bijotransformazzjoni Tacrolimus jigi metabolizzat malajr fil- fwied, primarjament biċ- cytochrome P450- 3A4.
Tacrolimus is also considerably metabolised in the intestinal wall.
Tacrolimus jinħadem ukoll konsiderevolment fil- ħajt intestinali.
There are several metabolites identified.
Hemm bosta metaboliti identifikati.
Only one of these has been shown in vitro to have immunosuppressive activity similar to that of tacrolimus.
Waħda minn dawn biss dehret, in vitro, li għandha attività immunosuppressiva simili għal dik ta ’ tacrolimus.
The other metabolites have only weak or no immunosuppressive activity.
Il - metaboliti l- oħra għandhom biss jew attività fjakka jew l- ebda attività immunosuppressiva.
In systemic circulation only one of the inactive metabolites is present at low concentrations.
F’ ċirkolazzjoni sistemika hemm waħda biss mill- metaboliti inattivi, b ’ konċentrazzjoni baxxa.
Therefore, metabolites do not contribute to the pharmacological activity of tacrolimus.
Għaldaqstant, il- metaboliti ma jikkontribwixxux għall- attività farmakoloġika ta ’ tacrolimus.
13 Following intravenous and oral administration of 14C-labelled tacrolimus, most of the radioactivity was eliminated in the faeces.
Tneħħija mill- ġisem Wara li ngħata ġol- vini u ġol- ħalq tacrolimus 14C -, il- parti l- kbira tar- radjoattività tneħħiet mal- purgar.
Approximately 2% of the radioactivity was eliminated in the urine.
Bejn wieħed u ieħor 2% tar- radjoattività tneħħiet ma ’ l- awrina.
Less than 1% of unchanged tacrolimus was detected in the urine and faeces, indicating that tacrolimus is almost completely metabolised prior to elimination: bile being the principal route of elimination.
Inqas minn 1% ta ’ tacrolimus mhux mibdul deher fl- awrina u fil- ħmieġ (faeces), li kien ifisser li tacrolimus hu kważi kompletament metabolizzat qabel ma jkun eliminat: il- bili jidhru l- mod ewlieni kif jitneħħa.
5.3 Preclinical safety data
14 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurta ’ tal- mediċina 5. 3
The kidneys and the pancreas were the primary organs affected in toxicity studies performed in rats and baboons.
Kienu il- kliewi u l- pankreas l- organi primarji, li ntlaqtu fl- istudji tossiċi li saru fuq il- firien u l- babuni.
In rats, tacrolimus caused toxic effects to the nervous system and the eyes.
Tacrolimus ħoloq effetti tossiċi fis- sistema nervuża u fl- għajnejn tal- firien.
Reversible cardiotoxic effects were observed in rabbits following intravenous administration of tacrolimus.
Effetti kardjotossiċi riversibbli dehru fil- fniek wara li ngħataw tacrolimus ġol- vini.
Embryofoetal toxicity was observed in rats and rabbits and was limited to doses that caused significant toxicity in maternal animals.
Tossiċità embrijofetali ġiet osservata fil- firien u fil- fniek u kienet limitata għal dożi li kkaġunaw tossiċità sinifikanti f’ annimali materni.
In rats, female reproductive function including birth was impaired at toxic doses and the offspring showed reduced birth weights, viability and growth.
Fil- firien, il- funzjoni riproduttiva inkluż it- twelid intlaqtet b’ dożi tossiċi u l- wild wera nuqqas fil- piż fit- twelid, vijabbiltà u tkabbir.
A negative effect of tacrolimus on male fertility in the form of reduced sperm counts and motility was observed in rats.
Fil- firien irġiel, deher ukoll li kien hemm nuqqas fl- għadd u moviment ta ’ sperma, b’ effett negattiv fuq il- fertilità.
Capsule content:
X’ fiha l- kapsula:
Hypromellose Ethylcellulose Lactose monohydrate Magnesium stearate.
Hypromellose Ethylcellulose Lactose monohydrate Magnesium stearate.
Capsule shell:
Il- qoxra tal- kapsula:
Titanium dioxide (E 171) Yellow iron oxide (E 172) Red iron oxide (E 172) Gelatin.
Titanium dioxide (E 171) Yellow iron oxide (E 172) Red iron oxide (E 172) Gelatin.
Shellac Lecithin (soya) Simethicone Red iron oxide (E 172) Hydroxypropyl Cellulose.
Linka stampata (Opacode S- 1- 15083) Shellac Lecithin (soya) Simethicone Red iron oxide (E 172) Hydroxypropyl Cellulose
6.2 Incompatibilities
6. 2 Inkompatibbiltajiet
Tacrolimus is not compatible with PVC.
Tacrolimus mhux compatibbli mal- PVC.
Tubing, syringes and other equipment used to prepare a suspension of Advagraf capsule contents should not contain PVC.
Tubi, siringi u strumenti oħra li jintużaw biex titlesta suspenzzjoni tal- mediċina tal- kapsula Advagraf ma ghandux ikun fihom PVC.
1 year
La darba tinfetaħ il- qoxra ta ’ l- aluminju: sena
Store in the original package and in a dry place in order to protect from moisture.
Aħżen fil- pakkett oriġinali u f’ post xott sabiex tilqa ’ mill- umdità.
14 Transparent PVC/ PVDC aluminium blister wrapped in an aluminium pouch with a desiccant.
Folja transparenti PVC/ PVDC ta ’ l- aluminju mgeżwer f’ borża ta ’ l- aluminju pouch b ’ desikkant.
Ten capsules per blister.
Għaxar kapsuli kull folja.
Pack sizes:
Pakketti ta ’:
30, 50 and 100 prolonged-release capsules.
30, 50 u 100 kapsula li jerћu l- mediċina bil- mod
Not all pack sizes may be marketed.
15 Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
6.6 Special precautions for disposal
Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema 6. 6
Elisabethhof 19 2353 EW Leiderdorp Netherlands
Elisabethhof 19 2353 EW Leiderdorp L- Olanda
Advagraf 1 mg Prolonged-release hard capsules
Advagraf 1 mg Kapsuli iebsin li jerћu l- mediċina bil- mod
Each prolonged-release capsule contains 1 mg of tacrolimus.
Kull kapsula li terћi l- mediċina bil- mod fiha 1 mg ta ’ tacrolimus.
Each prolonged-release capsule contains 107.28 mg of lactose monohydrate
Kull kapsula li terћi l- mediċina bil- mod fiha 107. 28 mg ta ’ lactose monohydrate
White-orange gelatin capsules imprinted in red with “ 1 mg” on the white capsule cap and “ the orange capsule body, containing white powder.
Kapsuli tal- ġelatina, ta ’ lewn abjad- aranġjo b ’ “ 1 mg ” miktuba bl- aħmar fuq l- għatu abjad tal- kapsula u b ’ “  677 ” fuq l- għatu aranġjo tal- kapsula, mimlija trab abjad.
In stable patients converted from Prograf (twice daily) to Advagraf (once daily) on a 1:1 (mg: mg) total daily dose basis the systemic exposure to tacrolimus (AUC0-24) for Advagraf was approximately 10% lower than that for Prograf.
17 F’ pazjenti stabbli li qalbu minn Prograf (darbtejn kuljum) għal Advagraf (darba kuljum) fuq bażi ta ’ doża totali kuljum ta ’ 1: 1 (mg: mg), l- esponiment sistemiku għal tacrolimus (AUC0- 24) fl- Advagraf kien bejn wieħed u ieħor 10% inqas minn dak ta ’ Prograf.
The relationship between tacrolimus trough levels (C24) and systemic 16 exposure (AUC0-24) for Advagraf is similar to that of Prograf.
Ir- relazzjoni bejn il- livelli ‘ trough ’ ta ’ tacrolimus (C24) u l - espożizzjoni sistemika (AUC0- 24) għal Advagraf tixbaћ ħafna lil dik ta ’ Prograf.
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 ’
17 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.
Frequent trough level monitoring in the initial two weeks post transplantation is recommended, 18 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.
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.
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.
20 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.
Other factors observed to increase the risk of these clinical 19 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.
Patients treated with tacrolimus have been reported to develop posterior reversible encephalopathy syndrome (PRES).
21 Saru rapporti li pazjenti ttrattati b’ tacrolimus jiżviluppaw is- sindrome tal- enċefalopatija riversibbli posterjuri (posterior reversible encephalopathy syndrome - PRES).
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.
22 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.
Protein binding considerations 21 Tacrolimus is extensively bound to plasma proteins.
Konsiderazzjonijiet dwar l- irbit mal- proteini Tacrolimus jingħaqqad estensivament mal- proteini tal- plażma.
4.7 Effects on ability to drive and use machines
23 Effetti fuq il- ħila biex issuq u tħaddem magni 4. 7
tremor, headache seizures, disturbances in consciousness, paraesthesias and dysaesthesias, peripheral neuropathies, dizziness, writing impaired, nervous system disorders 22
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
dyspnoea, parenchymal lung disorders, pleural effusion, pharyngitis, cough, nasal congestion and inflammations
24 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
23 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
psychotic disorder 24
Doża eċċessiva 4. 9
PHARMACOLOGICAL PROPERTIES
26 TAGĦRIF FARMAKOLOĠIKU 5.
25 The efficacy and safety of Prograf, ciclosporin and Advagraf, all in combination with basiliximab antibody induction, MMF and corticosteroids, was compared in 638 de novo kidney transplant recipients.
L- effikaċja u s- sigurta ’ ta ’ Prograf, Ciclosporin u Advagraf, meta ngћataw flimkien ma ’ l- antikorp basiliximab indott, MMF u kortikosterojdi, ġie mqabbel f ’ 638 riċevitur de novo ta ’ trapjant tal - kliewi.
Results from published data of tacrolimus administered twice daily as Prograf capsules in other primary organ transplantation Prograf has evolved into an accepted treatment as primary immunosuppressive medicinal product following pancreas, lung and intestinal transplantation.
27 Riżultati pubblikati minn tagħrif dwar l- għoti darbtejn kuljum ta ’ tacrolimus bħala kapsuli Prograf fi trapjanti ta ’ organi primarji Prograf żviluppa f’ kura aċċettata bħala prodott mediċinali immunosuppressiv primarju wara trapjant tal- pankreas, tal- pulmun u ta ’ l- intestini.
26 ciclosporin to tacrolimus, whereas only 6 tacrolimus patients required alternative therapy (Bechstein et al., Transplantation 2004; 77:1221).
Trapjant Intestinali Esperjenza klinika pubblikata minn ċentru wieħed dwar l- użu ta ’ Prograf orali bħala l- ewwel kura wara trapjant intestinali wriet li r- rata attwarja ta ’ dawk li għexu kienet ta ’ 155 pazjent (65 l- intestini
Intestinal transplantation Published clinical experience from a single centre on the use of oral Prograf for primary treatment following intestinal transplantation showed that the actuarial survival rate of 155 patients (65 intestine alone, 75 liver and intestine, and 25 multivisceral) receiving tacrolimus and prednisone was 75% at 1 year, 54% at 5 years, and 42% at 10 years.
28 biss, 75 l- fwied u l- intestini, u 25 multivixxerali) jieħdu tacrolimus u prednisone kienet ta ’ 75% f’ sena, 54% f’ 5 snin, u 42% f’ 10 snin.
27 Following intravenous and oral administration of 14C-labelled tacrolimus, most of the radioactivity was eliminated in the faeces.
Tneħħija mill- ġisem Wara li ngħata ġol- vini u ġol- ħalq tacrolimus 14C -, il- parti l- kbira tar- radjoattività tneħħiet mal- purgar.
5.3 Preclinical safety data
29 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurta ’ tal- mediċina 5. 3
28 Transparent PVC/ PVDC aluminium blister wrapped in an aluminium pouch with a desiccant.
Folja transparenti PVC/ PVDC ta ’ l- aluminju mgeżwer f’ borża ta ’ l- aluminju pouch b ’ desikkant.
30, 50, 60 and 100 prolonged-release capsules.
30, 50, 60 u 100 kapsula li jerћu l- mediċina bil- mod
Not all pack sizes may be marketed.
30 Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
Advagraf 5 mg Prolonged-release hard capsules
Advagraf 5 mg Kapsuli iebsin li jerћu l- mediċina bil- mod
Each prolonged-release capsule contains 5 mg of tacrolimus.
Kull kapsula li terћi l- mediċina bil- mod fiha 5 mg ta ’ tacrolimus.
Each prolonged-release capsule contains 536.4 mg of lactose monohydrate
Kull kapsula li terћi l- mediċina bil- mod fiha 536. 4 mg ta ’ lactose monohydrate
Greyish red-orange gelatin capsules imprinted in red with “ 5 mg” on the greyish red capsule cap and ” 687” on the orange capsule body, containing white powder.
Kapsuli tal- ġelatina, ta ’ lewn aħmar jagħti fil- griż- oranġjo b ’ “ 5 mg ” miktuba bl- aħmar fuq l- għatu aħmar jagħti fil- griż u b ’ “  687 ” fuq l- għatu aranġjo tal- kapsula, mimlija trab abjad.
In stable patients converted from Prograf (twice daily) to Advagraf (once daily) on a 1:1 (mg: mg) total daily dose basis the systemic exposure to tacrolimus (AUC0-24) for Advagraf was approximately 10% lower than that for Prograf.
32 F’ pazjenti stabbli li qalbu minn Prograf (darbtejn kuljum) għal Advagraf (darba kuljum) fuq bażi ta ’ doża totali kuljum ta ’ 1: 1 (mg: mg), l- esponiment sistemiku għal tacrolimus (AUC0- 24) fl- Advagraf kien bejn wieħed u ieħor 10% inqas minn dak ta ’ Prograf.
The relationship between tacrolimus trough levels (C24) and systemic 30 exposure (AUC0-24) for Advagraf is similar to that of Prograf.
Ir- relazzjoni bejn il- livelli ‘ trough ’ ta ’ tacrolimus (C24) u l - espożizzjoni sistemika (AUC0- 24) għal Advagraf tixbaћ ħafna lil dik ta ’ Prograf.
31 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.
Frequent trough level monitoring in the initial two weeks post transplantation is recommended, 32 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.
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.
35 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.
Other factors observed to increase the risk of these clinical 33 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.
Patients treated with tacrolimus have been reported to develop posterior reversible encephalopathy syndrome (PRES).
36 Saru rapporti li pazjenti ttrattati b’ tacrolimus jiżviluppaw is- sindrome tal- enċefalopatija riversibbli posterjuri (posterior reversible encephalopathy syndrome - PRES).
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.
37 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.
Protein binding considerations 35 Tacrolimus is extensively bound to plasma proteins.
Konsiderazzjonijiet dwar l- irbit mal- proteini Tacrolimus jingħaqqad estensivament mal- proteini tal- plażma.
4.7 Effects on ability to drive and use machines
38 Effetti fuq il- ħila biex issuq u tħaddem magni 4. 7