qanastek/EMEA-V3 huggingface dataset:
Patients treated with immunosuppressants, including CellCept, are at increased risk for opportunistic infections (bacterial, fungal, viral and protozoal), fatal infections and sepsis (see section 4.8).
Pazjenti kkurati b’ immunosoppressanti, inkluż CellCept, huma f’ riskju akbar għall- infezzjonijiet opportunistiċi (mill- batterja, moffa, virus u protożoa), infezzjonijiet fatali u sepsis (ara sezzjoni 4. 8).
Among the opportunistic infections are BK virus associated nephropathy and JC virus associated progressive multifocal leukoencephalopathy (PML).
Fost l- infezzjonijiet opportunistiċi hemm nefropatija assoċjata mal- virus BK u lewkoenċefalopatija multifokali progressiva assoċjata mal- virus JC (PML).
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 ħafna drabi huma relatati ma ’ esponiment immunosoppressiv totali għoli u jistgħu jwasslu għall- kundizzjonijiet serji jew fatali li t- tobba
3 Patients receiving CellCept should be monitored for neutropenia, which may be related to CellCept itself, concomitant medications, viral infections, or some combination of these causes.
Pazjenti li qed jirċievu CellCept għandhom jiġu sorveljati għal newtropenja, li tista tkun relatata ma ’ CellCept innifsu, mediċini fl- istess waqt, infezzjonijiet virali jew xi taħlita ta ’ dawn il- kawżi.
Patients taking CellCept should have complete blood counts weekly during the first month, twice monthly for the second and third months of treatment, then monthly through the first year.
Pazjenti li qed jieħdu CellCept għandhom jagħmlu test ta ’ l- għadd komplet taċ- ċelluli tad- demm kull ġimgħa waqt l - ewwel xahar, darbtejn fix- xahar fit- tieni u t- tielet xahar u wara darba fix- xahar matul l- ewwel sena ta ’ kura.
If neutropenia develops 3 (absolute neutrophil count < 1.3 x 10 / µl), it may be appropriate to interrupt or discontinue CellCept.
Jekk tiżvilluppa newtropenja, (għadd assolut ta ’ newtrofili < 1. 3 x 10³/ µl), jista ’ jkun xieraq li CellCept titwaqqaf għal xi żmien, jew għall- kollox.
Patients should be advised that during treatment with CellCept, vaccinations may be less effective and the use of live attenuated vaccines should be avoided (see section 4.5).
Il- pazjenti għandhom jiġu avżati li waqt il- kura b' CellCept, it- tilqim jista ’ jkun anqas effettiv u l- użu ta ’ tilqim b organiżmu ħaj għandu jiġi evitat (ara sezzjoni 4. 5).
Influenza vaccination may be of value.
Tilqim kontra l- influwenza jista 'jkun utli.
Prescribers should refer to national guidelines for influenza vaccination.
It - tobba għandhom jirreferu għall- linji gwida nazzjonali għat- tilqima kontra l- influwenza.
Because CellCept has been associated with an increased incidence of digestive system adverse events, including infrequent cases of gastrointestinal tract ulceration, haemorrhage and perforation, CellCept should be administered with caution in patients with active serious digestive system disease.
Peress li CellCept kien assoċjat ma ’ inċidenza għola ta ’ effetti avversi fuq is- sistema diġestiva, inklużi każijiet mhux frekwenti ta ’ ulċerazzjoni tal- apparat gastro- intestinali, emorraġija u perforazzjoni, CellCept għandu jingħata b' kawtela f' pazjenti b’ mard attiv serju tas- sistema diġestiva.
CellCept is an IMPDH (inosine monophosphate dehydrogenase) inhibitor.
CellCept huwa inibitur ta ’ l- enżima IMPDH (inosine monophosphate dehydrogenase).
On theoretical grounds, therefore, it should be avoided in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome.
Għalhekk fuq bażi teoretika, għandu jiġi evitat f’ pazjenti b’ nuqqas ereditarju, rari ta 'l- enżima hypoxanthine- guanine phosphoribosyl- transferase (HGPRT) bħas- sindromu Lesch- Nyhan u Kelley- Seegmiller.
It is recommended that CellCept should not be administered concomitantly with azathioprine because such concomitant administration has not been studied.
Huwa rakkomandat li CellCept ma jingħatax fl- istess ħin ma 'azathioprine, għaliex din l- għotja fl- istess ħin ma ġietx studjata.
In view of the significant reduction in the AUC of MPA by cholestyramine, caution should be used in the concomitant administration of CellCept with medicinal products that interfere with enterohepatic recirculation because of the potential to reduce the efficacy of CellCept.
Minħabba li cholestyramine inaqqas b’ mod sinifikanti l- AUC ta ’ MPA, għandu jkun hemm kawtela meta CellCept jingħata fl- istess ħin ma’ prodotti mediċinali li jfixxklu ċ- ċirkolazzjoni mill ġdid tad- demm tal - fwied, minħabba l- potenzjal li jnaqqsu l- effikaċja ta 'CellCept.
The risk: benefit of mycophenolate mofetil in combination with tacrolimus or sirolimus has not been established (see also section 4.5).
Ir- riskju: il- benefiċju ta ’ mycophenolate mofetil f’ taħlita ma ’ tacrolimus jew sirolimus ma ġiex stabbilit (ara wkoll sezzjoni 4. 5).
4.5 Interaction with other medicinal products and other forms of interaction
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarijiet oħra li jistgħu jibdlu l - effett farmaċewtiku tal- prodott
Interaction studies have only been performed in adults.
Studji dwar l- effett ta ’ mediċini jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku tal- prodott saru biss fl - adulti.
Aciclovir: higher aciclovir plasma concentrations were observed when mycophenolate mofetil was administered with aciclovir in comparison to the administration of aciclovir alone.
Aciclovir: livelli ogħla ta 'konċentrazzjonijiet ta ’ Aciclovir fil- plażma kienu osservati meta mycophenolate mofetil kien mogħti flimkien ma' aciclovir meta mqabbel ma ’ l- għotja ta ’ aciclovir waħdu.
The changes in MPAG (the phenolic glucuronide of MPA) pharmacokinetics (MPAG increased by 8%) were minimal and are not considered clinically significant.
It- tibdil fil - farmakokinetika ta ’ MPAG (il- phenolic glucuronide ta ’ MPA) kien minimu (MPAG żjied bi 8%) u m’ huwiex ikkunsidrat bħala klinikament rilevanti.
Because MPAG plasma concentrations are increased in the presence of renal impairment, as are aciclovir concentrations, the potential exists for mycophenolate mofetil and aciclovir, or its prodrugs, e. g. valaciclovir, to compete for tubular secretion and further increases in concentrations of both substances may occur.
Peress li fil- preżenza ta ’ indeboliment renali l - konċentrazzjonijiet fil- plażma ta 'MPAG u ta ’ aciclovir jiżdiedu, hemm il- potenzjal li mycophenolate mofetil u aciclovir, jew il- prodrugs tiegħu e. ż. valaciclovir jikkompetu għat- tneħħija mit- tubi tal- kliewi u dan iwassal għal aktar żieda fil- konċentrazzjoni taż- żewġ sustanzi.
Antacids with magnesium and aluminium hydroxides: absorption of mycophenolate mofetil was decreased when administered with antacids.
Antaċidi li fihom magnesium u aluminium hydroxide: l- assorbiment ta ’ mycophenolate mofetil naqas meta kien mogħti flimkien ma ’ antaċidi.
Cholestyramine: following single dose administration of 1.5 g of mycophenolate mofetil to normal healthy subjects pre-treated with 4 g TID of cholestyramine for 4 days, there was a 40% reduction in the AUC of MPA (see section 4.4 and section 5.2).
Cholestyramine: wara l- għotja ta ’ doża waħda ta '1. 5 g ta' mycophenolate mofetil lil individwi b' saħħithom li kienu kkuratati minn qabel b’ 4 g tliet darbiet kuljum ta ’ cholestyramine għal erbat ijiem, kien hemm tnaqqis ta ’ 40% fl- AUC ta ’ l- MPA (ara sezzjoni 4. 4 u sezzjoni 5. 2).
Caution should be used during concomitant administration because of the potential to reduce efficacy of CellCept.
Għandu jkun hemm kawtela waqt l- għotja flimkien minħabba l- potenzjal li tonqos l- effikaċja ta ’ CellCept.
Medicinal products that interfere with enterohepatic circulation: caution should be used with medicinal products that interfere with enterohepatic circulation because of their potential to reduce the efficacy of CellCept.
4 Prodotti mediċinali li jinterferixxu maċ- ċirkolazzjoni entero- epatika: għandu jkun hemm kawtela b’ mediċini li jinterferixxu maċ- ċirkolazzjoni entero- epatika minħabba l- potenzjal tagħhom li jnaqqsu l - effikaċja ta ’ CellCept.
4 Ciclosporin A: ciclosporin A (CsA) pharmacokinetics are unaffected by mycophenolate mofetil.
Ciclosporin A: il- farmakokinetika ta 'ciclosporin A (CsA) mhix affetwata minn mycophenolate mofetil.
In contrast, if concomitant ciclosporin treatment is stopped, an increase in MPA AUC of around 30% should be expected.
B’ kuntrast, jekk il- kura fl- istess ħin ta ’ ciclosporin titwaqqaf, għandha tkun mistennija żieda ta ’ madwar 30% fl- AUC ta ’ MPA.
Ganciclovir: based on the results of a single dose administration study of recommended doses of oral mycophenolate and IV ganciclovir and the known effects of renal impairment on the pharmacokinetics of CellCept (see section 4.2) and ganciclovir, it is anticipated that co-administration of these agents (which compete for mechanisms of renal tubular secretion) will result in increases in MPAG and ganciclovir concentration.
Ganciclovir: ibbażat fuq riżultati ta ’ studju b’ għotja ta ’ doża waħda ta ’ dożi rakkomandata ta ’ mycophenolate orali u ganciclovir IV u l- effetti magħrufa ta ’ indeboliment renali fuq il- farmakokinetika ta ’ CellCept (ara sezzjoni 4. 2) u ganciclovir, huwa mbassar li l- għotja flimkien ta ’ dawn is- sustanzi (li jikkompetu għall- mekkaniżmi ta ’ sekrezzjoni tubulari mill- kliewi) tirriżultaw f’ żieda fil - konċentrazzjonijiet ta ’ MPAG u ganciclovir.
No substantial alteration of MPA pharmacokinetics is anticipated and CellCept dose adjustment is not required.
Mhux mistennija bidla sostanzjali fil- farmakokinetika ta 'MPA u mhux meħtieġa bidla fid- doża ta' CellCept.
In patients with renal impairment in which CellCept and ganciclovir or its prodrugs, e. g. valganciclovir, are co-administered, the dose recommendations for ganciclovir should be observed and patients should be monitored carefully.
F' pazjenti b’ indeboliment renali li qed jingħataw CellCept flimkien ma ’ ganciclovir jew il- prodrugs tiegħu, (e. ż valganciclovir), għandhom jiġu osservati d - dożi rakkomandati għal ganciclovir u l- pazjenti għandhom jiġu sorveljati bir- reqqa.
Oral contraceptives: the pharmacokinetics and pharmacodynamics of oral contraceptives were unaffected by coadministration of CellCept (see also section 5.2).
Il- farmakokinetika u l- farmakodinamika ta ’ kontraċettivi orali ma kienux affetwati bl - għotja flimkien ta 'CellCept (ara wkoll sezzjoni 5. 2).
Rifampicin: in patients not also taking ciclosporin, concomitant administration of CellCept and rifampicin resulted in a decrease in MPA exposure (AUC0-12h) of 18% to 70%.
Rifampicin: f’ pazjenti li mhux qed jieħdu wkoll ciclosporin, l- għotja ta ’ CellCept flimkien ma ’ rifampicin wasslet għal tnaqqis ta ’ 18% sa 70% fl- esponiment għal MPA (AUC0- 12h).
It is recommended to monitor MPA exposure levels and to adjust CellCept doses accordingly to maintain clinical efficacy when rifampicin is administered concomitantly.
Għalhekk huwa rakkomandat li l- livelli ta ’ esponiment għal MPA jiġu sorveljati u li d- dożi ta ’ CellCept jiġu aġġustati kif meħtieġ biex tinżamm effikaċja klinika meta rifampicin jingħata fl- istess waqt.
Sirolimus: in renal transplant patients, concomitant administration of CellCept and CsA resulted in reduced MPA exposures by 30-50% compared with patients receiving the combination of sirolimus and similar doses of CellCept (see also section 4.4).
Sirolimus: f’ pazjenti li rċevew trapjant tal- kliewi, l- għotja ta ’ CellCept flimkien ma ’ CsA wasslet għal tnaqqis ta ’ 30- 50% fl- esponiment għal MPA meta mqabbel ma ’ pazjenti li rċevew sirolimus flimkien ma ’ dożi simili ta ’ CellCept (ara ukoll sezzjoni 4. 4).
Sevelamer: decrease in MPA Cmax and AUC0-12 by 30% and 25%, respectively, were observed when CellCept was concomitantly administered with sevelamer without any clinical consequences (i. e. graft rejection).
Sevelamer: tnaqqis f’ Cmax u fl- AUC0- 12 ta ’ MPA bi 30% u 25%, rispettivament, kien osservat meta CellCept ingħata flimkien ma ’ sevelamer mingħajr l- ebda konsegwenzi kliniċi (i. e tiċħid tat- trapjant).
It is recommended, however, to administer CellCept at least one hour before or three hours after sevelamer intake to minimise the impact on the absorption of MPA.
Madanakollu huwa rakkomandat li CellCept jiġi amministrat mill- anqas siegħa qabel jew tliet sigħat wara t- teħid ta ’ sevelamer biex jitnaqqas l- impatt fuq l- assorbiment ta ’ MPA.
There is no data on CellCept with phosphate binders other than sevelamer.
M’ hemmx tagħrif dwar CellCept flimkien ma ’ phosphate binders għajr sevelamer.
Trimethoprim/ sulfamethoxazole: no effect on the bioavailability of MPA was observed.
Trimethoprim / sulphamethoxazole: ma ġie osservat l- ebda effett fuq il- biodisponibiltà ta ’ MPA.
Norfloxacin and metronidazole: in healthy volunteers, no significant interaction was observed when CellCept was concomitantly administered with norfloxacin and metronidazole separately.
Norfloxacin u metronidazole: f’ voluntiera b’ saħħithom, ma kienet osservata l- ebda interazzjoni sinifikanti meta CellCept ingħata flimkien ma ’ norfloxacin u metronidazole separatament.
However, norfloxacin and metronidazole combined reduced the MPA exposure by approximately 30% following a single dose of CellCept.
Madanakollu, norfloxacin u metronidazole flimkien naqqsu l- esponiment għal MPA b’ madwar 30% wara doża waħda ta ’ CellCept.
Tacrolimus: in hepatic transplant patients initiated on CellCept and tacrolimus, the AUC and Cmax of MPA, the active metabolite of CellCept, were not significantly affected by coadministration with tacrolimus.
Tacrolimus: f’ pazjenti li rċevew trapjant tal- fwied li nbdew fuq CellCept u tacrolimus, l- AUC u Cmax ta ’ MPA, l- metabolit attiv ta ’ CellCept, ma kienux affettwati b’ mod sinifikanti mill- għotja fl- istess waqt ta ’ tacrolimus.
In, contrast, there was an increase of approximately 20% in tacrolimus AUC when multiple doses of CellCept (1.5 g BID) were administered to patients taking tacrolimus.
B’ kuntrast, kien hemm żjieda ta ’ madwar 20% fl- AUC ta ’ tacrolimus meta dożi multipli ta 'CellCept (1. 5 g BID) ingħataw lil pazjenti li kienu qed jieħdu tacrolimus.
However, in renal transplant patients, tacrolimus concentration did not appear to be altered by CellCept (see also section 4.4).
Iżda, f’ pazjenti bi trapjant renali, il- konċentrazzjoni ta ’ tacrolimus ma dehrietx li nbidlet minn CellCept (ara wkoll sezzjoni 4. 4).
Other interactions: co-administration of probenecid with mycophenolate mofetil in monkeys raises plasma AUC of MPAG by 3-fold.
Prodotti mediċinali oħra li jistgħu jbiddlu l- effett farmaċewtiku ta 'dan il- prodott: l- għotja flimkien ta ’ probenecid u mycophenolate mofetil lil xadini żiedet l- AUC fil- plażma ta ’ MPAG bi tliet darbiet.
Thus, other substances known to undergo renal tubular secretion may compete with MPAG, and thereby raise plasma concentrations of MPAG or the other substance undergoing tubular secretion.
Għalhekk sustanzi li huma magħrufa li jgħaddu minn tneħħijatubulari renali, jistgħu jikkompetu ma ’ MPAG u b’ hekk jgħollu l- konċentrazzjonijiet fil- plażma ta ’ MPAG jew tas- sustanza l- oħra li tkun qed tgħaddi minn sekrezzjoni tubulari.
Live vaccines: live vaccines should not be given to patients with an impaired immune response.
5 Vaċċini b' mikrobi ħajjin: vaċċini b’ mikrobi ħajjin m’ għandhomx jingħataw lil pazjenti b' indeboliment fir - rispons immunitarju.
The antibody response to other vaccines may be diminished (see also section 4.4).
Ir- rispons ta ’ l- antikorpi għal tilqim ieħor jista ’ jkun imnaqqas (ara wkoll sezzjoni 4. 4).
5 4.6 Pregnancy and lactation
4. 6 Tqala u Treddigħ
It is recommended that CellCept therapy should not be initiated until a negative pregnancy test has been obtained.
Huwa rakkomandat li t- terapija b’ CellCept ma tinbediex qabel ma jinkiseb eżami tat- tqala negattiv.
Effective contraception must be used before beginning CellCept therapy, during therapy, and for six weeks following discontinuation of therapy (see section 4.5).
Kontraċezzjoni effettiva għandha tintuża qabel ma tinbeda terapija b’ CellCept, waqt it- terapija u għal sitt ġimgħat wara li titwaqqaf it- terapija (ara sezzjoni 4. 5).
Patients should be instructed to consult their physician immediately should pregnancy occur.
F' każ ta 'tqala l- pazjenti għandhom jgħarrfu lit - tabib tagħhom mill- aktar fis possibbli.
The use of CellCept is not recommended during pregnancy and should be reserved for cases where no more suitable alternative treatment is available.
L- użu ta ’ CellCept mhux rakkomandat waqt it- tqala u għandu jiġi rriservat għall- każijiet fejn mhix disponibbli kura alternattiva xierqa.
CellCept should be used in pregnant women only if the potential benefit outweighs the potential risk to the foetus.
CellCept għandu jintuża f’ nisa tqal biss jekk il- benefiċċju potenzjali huwa akbar mir- riskju potenzjali għall- fetu.
There is limited data from the use of CellCept in pregnant women.
Hemm tagħrif limitat dwar l- użu ta ’ CellCept f’ nisa tqal.
However, congenital malformations including ear malformations, i. e. abnormally formed or absent external/ middle ear, have been reported in children of patients exposed to CellCept in combination with other immunosuppressants during pregnancy.
Madankollu, malformazzjonijiet konġenitali inkluż malformazzjonijiet tal- widnejn, i. e. widna ta ’ barra/ tan- nofs iffurmata b’ mod mhux normali jew nieqsa, ġew irrappurtati fi tfal ta ’ pazjenti esposti għal CellCept flimkien ma ’ immunosoppressivi oħra waqt it- tqala.
Cases of spontaneous abortions have been reported in patients exposed to CellCept.
Każijiet ta ’ abort spontanju ġew irrapportati f’ pazjenti esposti għal CellCept.
Studies in animals have shown reproductive toxicity (see section 5.3).
Studji fuq il- bhejjem urew ħsara fuq is- sistema riproduttiva (ara sezzjoni 5. 3).
Mycophenolate mofetil has been shown to be excreted in the milk of lactating rats.
Intwera li mycophenolate mofetil joħroġ fil- ħalib ta ’ firien li qed ireddgħu.
It is not known whether this substance is excreted in human milk.
M’ huwiex magħruf jekk din is- sustanza toħroġx fil- ħalib tas- sider uman.
Because of the potential for serious adverse reactions to mycophenolate mofetil in breast-fed infants, CellCept is contraindicated in nursing mothers (see section 4.3).
Minħabba l- potenzjal ta ’ effetti avversi serji għal mycophenolate mofetil fi trabi li jkunu qed jingħataw il- ħalib tas- sider, CellCept huwa kontra- indikat f’ nisa li qed ireddgħu (ara sezzjoni 4. 3).
No studies on the effects on the ability to drive and use machines have been performed.
Ma saru l- ebda studji dwar l- effetti fuq il- ħila biex issuq u tħaddem magni.
The pharmacodynamic profile and the reported adverse reactions indicate that an effect is unlikely.
Il- profil farmakodinamiku u r - rapporti ta ’ reazzjonijiet avversi, jindikaw li effett mhux probabbli.
The following undesirable effects cover adverse reactions from clinical trials:
L- effetti mhux mixtieqa segwenti jkopru reazzjonijiet avversi minn provi kliniċi:
The principal adverse reactions associated with the administration of CellCept in combination with ciclosporin and corticosteroids include diarrhoea, leucopenia, sepsis and vomiting, and there is evidence of a higher frequency of certain types of infections (see section 4.4).
L- effetti mhux mixtieqa prinċipali assoċjati ma ’ l- għotja ta ’ CellCept flimkien ma 'ciclosporin u kortikosterojdi jinkludu dijarea, lewkopenja, sepsis u rimettar u hemm evidenza ta ’ frekwenza aktar għolja ta ’ ċertu tipi ta ’ infezzjonijiet (ara sezzjoni 4. 4).
Malignancies:
Tumuri malinni:
Patients receiving immunosuppressive regimens involving combinations of medicinal products, including CellCept, are at increased risk of developing lymphomas and other malignancies, particularly of the skin (see section 4.4).
Pazjenti li qed jingħataw programmi ta ’ dożaġġ immunosoppressivi li jinvolvu taħlitiet ta ’ prodotti mediċinali nkluż CellCept, huma f' riskju akbar li jiżviluppaw limfomi u tipi oħra ta 'tumuri malinni, speċjalment tal- ġilda (ara sezzjoni 4. 4).
Lymphoproliferative disease or lymphoma developed in 0.6% of patients receiving CellCept (2 g or 3 g daily) in combination with other immunosuppressants in controlled clinical trials of renal (2 g data), cardiac and hepatic transplant patients followed for at least 1 year.
Fi provi kliniċi kkontrollati, b’ pazjenti bi trapjant renali (tagħrif ta ’ 2g), tal- qalb u epatiku li ġew segwiti għal minn ta ’ l- anqas sena, żviluppa mard limfoproliferattiv jew limfoma f' 0. 6% tal- pazjenti li kienu qed jingħataw CellCept (2 g jew 3 g kuljum) flimkien ma ’ immunosoppressanti oħra.
Non-melanoma skin carcinomas occurred in 3.6% of patients; other types of malignancy occurred in 1.1% of patients.
Carċinoma mhux melanoma tal- ġilda seħħet f’ 3. 6% tal- pazjenti, waqt li tipi oħra ta 'tumuri malinni seħħew f' 1. 1% tal- pazjenti.
Three-year safety data in renal and cardiac transplant patients did not reveal any unexpected changes in incidence of malignancy compared to the 1-year data.
Tagħrif ta ’ tliet snin dwar is- sigurtá f’ pazjenti bi trapjanti tal- kliewi u tal- qalb, ma żvelax bidliet mhux mistennija fl- inċidenza tat- tumuri malinni meta mqabbla mat- tagħrif ta ’ l- istudju ta 'sena.
Hepatic transplant patients were followed for at least 1 year, but less than 3 years.
Pazjenti bi trapjant tal- fwied baqgħu taħt osservazzjoni għal iktar minn sena iżda inqas minn tliet snin.
Opportunistic infections:
Infezzjonijiet opportunistiċi:
All transplant patients are at increased risk of opportunistic infections; the risk increased with total immunosuppressive load (see section 4.4).
Il- pazjenti li jirċievu trapjant kollha huma f' riskju akbar ta 'infezzjonijiet opportunistiċi; ir- riskju jiżdied bl- għotja totali ta ’ l- immunosoppressiv (ara sezzjoni 4. 4).
The most common opportunistic infections in patients receiving CellCept (2 g or 3 g daily) with other immunosuppressants in controlled clinical trials of renal (2 g data), cardiac and hepatic transplant patients followed for at least 1 year were candida mucocutaneous, CMV viraemia/ syndrome and Herpes simplex.
Il- proporzjon ta '
The proportion of patients with CMV viraemia/ syndrome was 13.5%.
6 pazjenti viremija/ sindromu b’ CMV kien ta 13. 5%.
Children and adolescents (aged 2 to 18 years):
Tfal u adoloxxenti (b’ età minn 2 sa '18- il sena):
However, the
Fi studju kliniku fuq 92 pazjent pedjatriku b’ età minn sentenjn sa 18- il sena li ngħataw mycophenolate mofetil 600 mg / m2 mill- ħalq darbtejn kuljum, instab li t- tip u l- frekwenza tar- reazzjonijiet avversi ġeneralment kienu simili għal dawk osservati f’ pazjenti adulti li ngħataw 1 g ta 'CellCept darbtejn kuljum.
6 following treatment-related adverse events were more frequent in the paediatric population, particularly in children under 6 years of age, when compared to adults: diarrhoea, sepsis, leucopenia, anaemia and infection.
Madankollu r- reazzjonijiet avversi relatati mal- kura li ġejjin kienu aktar komuni fil- popolazzjoni pedjatrika, speċjalment tfal taħt l- età ta ’ sitt snin, meta mqabbla ma ’ adulti: dijarea, sepsis, lewkopenja, anemija u infezzjoni.
Elderly patients (≥ 65 years):
Pazjenti anzjani (≥ 65 sena):
Elderly patients (≥ 65 years) may generally be at increased risk of adverse reactions due to immunosuppression.
Ġeneralment, pazjenti anzjani (≥ 65 sena) jistgħu jkunu f' riskju akbar ta 'reazzjonijiet avversi minħabba immunosoppressjoni.
Elderly patients receiving CellCept as part of a combination immunosuppressive regimen, may be at increased risk of certain infections (including cytomegalovirus tissue invasive disease) and possibly gastrointestinal haemorrhage and pulmonary oedema, compared to younger individuals.
Pazjenti anzjani li qed jirċievu CellCept bħala parti minn kors immunosoppressiv kombinat, jistgħu jkunu f' riskju akbar ta 'ċertu infezzjonijiet (inkluż mard b’ cytomegalovirus invasiv fit - tessut) u possibilment emorraġija gastro- intestinali u edima fil- pulmun meta mqabbla ma' individwi iżgħar.
Other adverse reactions:
Reazzjonijiet avversi oħra:
Adverse reactions, probably or possibly related to CellCept, reported in ≥ 1/ 10 and in ≥ 1/ 100 to < 1/ 10 of patients treated with CellCept in the controlled clinical trials of renal (2 g data), cardiac and hepatic transplant patients are listed in the following table.
Reazzjonijiet avversi, possibilment jew probabilment relatati ma 'CellCept, irrappurtati f ’ ≥ 1/ 10 u f ’ ≥1/ 100 sa < 1/ 10 tal- pazjenti kkurati b’ CellCept fil- provi kliniċi kkontrollati f’ pazjenti bi trapjant renali (tagħrif ta ’ 2 g), tal - qalb u tal- fwied huma mniżżla fit- tabella taħt:
Adverse Reactions, Probably or Possibly Related to CellCept, Reported in Patients Treated with CellCept in Renal, Cardiac and Hepatic Clinical Trials when Used in Combination with Ciclosporin and Corticosteroids
Reazzjonijiet avversi, Possibilment jew Probabilment Relatati ma 'CellCept, irrapportati F’ pazjenti Kkurati B’ CellCept Fi provi Kliniċi Tal- Kliewi, Tal- Qalb u Tal- Fwied Meta Użat Flimkien Ma ’ Ciclosporin U Kortikosterojdi:
Within the system organ classes, undesirable effects are listed under headings of frequency, using the following categories: 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 form the available data).
Fis- sistema tal- klassifika tal- organi, effetti mhux mixtieqa huma mniżżla taħt it- titli ta ’ frekwenza, bl- użu tal- kategoriji li ġejjin: komuni ħafna (≥1/ 10); komuni (≥1/ 100 sa < 1/ 10); mhux komuni (≥1/ 1, 000 sa < 1/ 100); rari (≥1/ 10, 000 sa < 1/ 1, 000); rari ħafna (< 1/ 10, 000), mhux magħruf (ma jistax jiġi stmat mit - tagħrif disponibbli).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa għandhom jitniżżlu skond is - serjeta ’ tagħhom.
System organ class
Sistema tal- klassifika ta ’ l- organi
Adverse drug reactions
Reazzjonijiet avversi tal- mediċina
Infections and infestations
Infezzjonijiet u infestazzjonijiet
Sepsis, gastrointestinal candidiasis, urinary tract infection, herpes simplex, herpes zoster
Sepsis, kandidajażi gastro- intestinali, infezzjoni fl- apparat ta ’ l- awina, herpes simplex, herpes zoster
Pneumonia, influenza, respiratory tract infection, respiratory moniliasis, gastrointestinal infection, candidiasis, gastroenteritis, infection, bronchitis, pharyngitis, sinusitis, fungal skin infection, skin candida, vaginal candidiasis, rhinitis
Pnewmonja, influwenza, infezzjoni fl- apparat respiratorju, monolijażi respiratorja, infezzjoni gastro- intestinali, kandidajażi, gastroenterite, infezzjoni, bronkite, farinġite, sinusite, infezzjoni tal- ġilda mill- moffa, kandida tal - ġilda, kandidajażi tal- vaġina, rinite
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplażmi beninni, malinni u dawk mhux speċifikati (inkluż ċesti u polipi)
Very common Common
Komuni ħafna Komuni
- Skin cancer, benign neoplasm of skin
- Kanċer fil- ġilda, neoplażma beninna tal- ġilda
Blood and lymphatic system disorders Metabolism and nutrition disorders
Disturbi tad- demm u tas- sistema limfatika Disturbi fil- metaboliżmu u n - nutrizzjoni
Very common Common Very common Common
Komuni ħafna Komuni Komuni ħafna Komuni
Leucopenia, thrombocytopenia, anaemia Pancytopenia, leucocytosis - Acidosis, hyperkalaemia, hypokalaemia, hyperglycaemia, hypomagnesaemia, hypocalcaemia, hypercholesterolaemia, hyperlipidaemia, hypophosphataemia, hyperuricaemia, gout, anorexia
Lewkopenja, tromboċitopenja, anemija Panċitopenja, lewkoċitożi - Aċidożi, iperkalimja, ipokalimja, ipergliċemija, ipomagnesimja, ipokalċimja, iperkoleserolimja, iperlipidimja, ipofosfatimja, iperurikimja, gotta, anoressija
Tachycardia
Aġitazzjoni, stat konfuż, depressjoni, ansjetà, ħsibijiet mhux normali, nuqqas ta ’ rqad
Vascular disorders
Disturbi fis- sistema nervuża
Very common
Komuni ħafna - Komuni
-
Konvulżjoni, ipertonija, rogħda, ħedla ta ’ ngħas, sindromu mijasteniku, sturdament, uġigħ ta ’ ras, parasteżija, disġeusja
Common
Disturbi fil- qalb Disturbi vaskulari Disturbi respiratorji, toraċiċi u
Hypotension, hypertension, vasodilatation
Komuni ħafna - Komuni Komuni ħafna - Komuni Komuni ħafna -
Respiratory, thoracic and mediastinal disorders Gastrointestinal disorders
Takikardja Ipotensjoni, ipertensjoni, vażodilazzjoni
Very common Common Very common Common
Komuni
- Pleural effusion, dyspnoea, cough Vomiting, abdominal pain, diarrhoea, nausea Gastrointestinal haemorrhage, peritonitis, ileus, colitis, gastric ulcer, duodenal ulcer, gastritis, oesophagitis, stomatitis, constipation, dyspepsia, flatulence, eructation
Effużjoni fil- plewra, qtugħ ta ’ nifs, sogħla
Hepatobiliary disorders
Disturbi gastro- intestinali
Very common Common
Disturbi fil- fwied u fil- marrara
- Hepatitis, jaundice, hyperbilirubinaemia
Komuni ħafna - Komuni Epatite, suffejra, iperbilirubinimja
Skin and subcutaneous tissue disorders Musculoskeletal and connective Tissue disorders Renal and urinary disorders
Disturbi fil- ġilda u fit- tessuti ta ’ Komuni ħafna - taħt il- ġilda Disturbi muskolu- skeletrali u
Very common Common Very common Common Very common Common
Komuni Komuni ħafna -
- Skin hypertrophy, rash, acne, alopecia, - Arthralgia - Renal impairment
Ipertrofija tal- ġilda, raxx, akne, alopeċja
General disorders and administration site conditions
tat- tessut konnettiv Disturbi fil- kliewi u fis- sistema
Very common Common
Common Komuni ħafna -
- Oedema, pyrexia, chills, pain, malaise, asthenia,
Komuni Komuni ħafna -
Investigations
Indeboliment renali
Very common Common
Komuni Komuni ħafna - Komuni
- Hepatic enzyme increased, blood creatinine increased, blood lactate dehydrogenase increased, blood urea increased, blood alkaline phosphatase increased, weight decreased
Edima, deni, tertir, uġigħ, tħossok ma tiflaħx, astenja Żieda ta ’ l- enżima epatika, żieda fil- krejatinina fid- demm, żieda tal- lactate dehydrogenase fid - demm, żieda fil- urea fid- demm, żieda tal - alkaline phosphatase fid- demm, tnaqqis fil- piż
501 (2 g CellCept daily), 289 (3 g CellCept daily) and 277 (2 g IV / 3 g oral CellCept daily) patients were treated in Phase III studies for the prevention of rejection in renal, cardiac and hepatic transplantation, respectively.
501 (2 g ta 'CellCept kuljum), 289 (3 g ta' CellCept kuljum) u 277 (2 g IV / 3 g mill- ħalq ta 'CellCept kuljum) pazjent kienu kkurati fl- istudji tat- III fażi għall- prevenzjoni ta ’ tiċħid ta' trapjant tal - kliewi, tal- qalb u tal- fwied rispettivament.
The following undesirable effects cover adverse reactions from post-marketing experience:
L- effetti mhux mixtieqa li ġejjin ikopru reazzjonijiet avversi minn esperjenza wara t- tqegħid fis- suq:
The types of adverse reactions reported during post-marketing with CellCept are similar to those seen in the controlled renal, cardiac and hepatic transplant studies.
It- tipi ta ’ reazzjonijiet avversi rrappurtati b’ CellCept wara t- tqegħid fis- suq, kienu simili għal dawk li dehru, fl- istudji kontrollati bi trapjant tal- kliewi, tal- qalb u tal- fwied.
Additional adverse reactions reported during post-marketing are described below with the frequencies reported within brackets if known.
Reazzjonijiet avversi oħrajn irrappurtati wara t- tqegħid fis- suq huma deskritti hawn taħt bil- frekwenzi rrappurtati fil- parentesi, jekk magħrufa.
Gastrointestinal: colitis including cytomegalovirus colitis, (≥ 1/ 100 to < 1/ 10), pancreatitis, (≥ 1/ 100 to < 1/ 10) and intestinal villous atrophy.
Kolite (inkluż kolite b’ cytomegalovirus), (≥1/ 100 sa < 1/ 10), pankrejatite, (≥1/ 100 sa < 1/ 10) u atrofija tal- villi fl- imsaren.
Disorders related to immunosuppression: serious life-threatening infections including meningitis, endocarditis, tuberculosis and atypical mycobacterial infection.
Disturbi relatati ma ’ immunosoppressjoni: infezzjonijiet serji li jipperikolaw il- ħajja inkluż meninġite, endokardite, tuberkulożi, u infezzjonijiet atipiċi mycobacteria.
Cases of BK virus associated nephropathy, as well as cases of JC virus associated progressive multifocal leucoencephalopathy (PML), have been reported in patients treated with immunosuppressants, including CellCept.
Każijiet ta ’ newropatija assoċjata mal- virus BK, kif ukoll każijiet ta ’ lewkoenċefalopatija multifokali progressiva (PML) assoċjata mal- virus JC, kienu rrapportati f’ pazjenti kkurati b’ immunosoppressanti, inkluż CellCept.
Agranulocytosis (≥ 1/ 1000 to < 1/ 100) and neutropenia have been reported; therefore, regular monitoring of patients taking CellCept is advised (see section 4.4).
8 Kienu rrapportati agranuloċitożi (≥1/ 1000 sa < 1/ 100) u newtropenja; għalhekk hija rakkomandata osservazzjoni regolari ta ’ pazjenti li qed jirċievu CellCept (ara sezzjoni 4. 4).
There have been reports of aplastic anaemia and bone marrow depression in patients treated with CellCept, some of which have been fatal.
Kien hemm rapporti ta ’ anemija aplastika u depressjoni tal- mudullun f’ pazjenti kkurati b’ CellCept, li wħud minnhom kienu fatali.
Hypersensitivity:
Sensittività Eċċessiva:
Hypersensitivity reactions, including angioneurotic oedema and anaphylactic reaction, have been reported.
Kienu rrapportati reazzjonijiet ta ’ sensittività eċċessiva inkluż edima anġjonewrotika u reazzjoni anafilattika.
Congenital disorders: see further details in section 4.6.
Disturbi konġenitali: ara sezzjoni 4. 6 għal aktar dettalji.
8 4.9 Overdose
4. 9 Doża eċċessiva
Reports of overdoses with mycophenolate mofetil have been received from clinical trials and during post-marketing experience.
Rapporti ta ’ dożi eċċessivi b’ mycophenolate mofetil waslu minn provi kliniċi u waqt l- esperjenza ta ’ wara t- tqegħid fuq is- suq.
In many of these cases, no adverse events were reported.
F’ ħafna minn dawn il- każijiet, ma kienux irrappurtati avveniment avversi.
In those overdose cases in which adverse events were reported, the events fall within the known safety profile of the medicinal product.
F’ dawk il- każijiet ta ’ doża eċċessiva fejn kienu rrappurtati avveniment avversi, l- avveniment jaqgħu fi ħdan il- profil tas- sigurtà magħruf tal- prodott mediċinali.
It is expected that an overdose of mycophenolate mofetil could possibly result in oversuppression of the immune system and increase susceptibility to infections and bone marrow suppression (see section 4.4).
Huwa mistenni li doża eċċessiva ta ’ mycophenolate mofetil tista ’ possibilment twassal għal soppressjoni żejda tas- sistema mmuni u żieda fis- suxxettibilità għall- infezzjonijiet u soppressjoni tal- mudullun (ara sezzjoni 4. 4).
If neutropenia develops, dosing with CellCept should be interrupted or the dose reduced (see section 4.4).
Jekk tiżviluppa newtropenja, id- dożaġġ b’ CellCept għandu jitwaqqaf jew id- doża titnaqqas (ara sezzjoni 4. 4).
Haemodialysis would not be expected to remove clinically significant amounts of MPA or MPAG.
L- emodijalisi mhuwiex mistenni li jneħħi ammonti klinikament sinifikanti ta ’ MPA jew ta ’ MPAG.
Bile acid sequestrants, such as cholestyramine, can remove MPA by decreasing the enterohepatic re- circulation of the drug (see section 5.2)..
Sekwestranti ta ’ l- aċidi tal- bili, bħal cholestyramine, jistgħu jneħħu MPA billi jnaqqsu iċ- ċirkulazzjoni enteroepatika mill- ġdid tal- mediċina (ara sezzjoni 5. 2).
Pharmacotherapeutic group: immunosuppressive agents ATC code L04AA06
LO4AA06.
Mycophenolate mofetil is the 2-morpholinoethyl ester of MPA.
Mycophenolate mofetil huwa l- ester 2- morpholinoethyl ta ’ MPA.
MPA is a potent, selective, uncompetitive and reversible inhibitor of inosine monophosphate dehydrogenase, and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA.
MPA huwa impeditur qawwi, selettiv, mhux kompetittiv u riversibli ta ’ inosine monofosfat dehydrogenase, u għalhekk jimpedixxi r- rotta de novo tas- sintesi tan- nuklejotida guanosine mingħajr inkorporazzjoni fid- DNA.
Because T- and B-lymphocytes are critically dependent for their proliferation on de novo synthesis of purines whereas other cell types can utilise salvage pathways, MPA has more potent cytostatic effects on lymphocytes than on other cells.
Minħabba li limfoċiti T - u B - jiddependu kritikament fuq is- sintesi tal- purines de novo għall- proliferazzjoni tagħhom, waqt li tipi oħra ta 'ċelluli jistgħu jutilizzaw ir- rotot ta' salvataġġ, MPA għandu effetti ċitostatiċi aktar qawwija fuq il - limfoċiti milli fuq ċelluli oħrajn.
Following oral administration, mycophenolate mofetil undergoes rapid and extensive absorption and complete presystemic metabolism to the active metabolite, MPA.
Wara għotja mill- ħalq, mycophenolate mofetil jgħaddi minn assorbiment rapidu u estensiv u metaboliżmu pre- sistemiku komplet għall- metabolit attiv, MPA.
As evidenced by suppression of acute rejection following renal transplantation, the immunosuppressant activity of CellCept is correlated with MPA concentration.
Kif intwera bis- suppressjoni tat- tiċħid akut wara trapjant renali, l- attività immunosoppressanti ta ’ CellCept hija ikkorrelata mal- konċentrazzjoni ta ’ MPA.
The mean bioavailability of oral mycophenolate mofetil, based on MPA AUC, is 94% relative to IV mycophenolate mofetil.
Il- biodisponibilità medja ta ’ mycophenolate mofetil li jittieħed mill- ħalq, ibbażata fuq l- AUC ta ’ l- MPA, hija ta '94% meta mqabbel ma ’ mycophenolate mofetil IV.
Food had no effect on the extent of absorption (MPA AUC) of mycophenolate mofetil when administered at doses of 1.5 g BID to renal transplant patients.
L- ikel ma kellu l- ebda effet fuq il- vastità tal - assorbiment (AUC ta ’ MPA) ta ’ Mycophenolate mofetil meta mogħti f’ dożi ta ’ 1. 5 g BID lil pazjenti bi trapjanti renali.
However, MPA Cmax was decreased by 40% in the presence of food.
Iżda, Cmax ta ’ MPA tnaqqas b’ 40% fil- preżenza ta ’ l- ikel.
Mycophenolate mofetil is not measurable systemically in plasma following oral administration.
Mycophenolate mofetil ma jistax jitkejjel sistematikament fil- plażma wara li jittieħed mill- ħalq.
MPA at clinically relevant concentrations is 97% bound to plasma albumin.
F’ konċentrazzjonijiet li huma klinikament relevanti MPA huwa 97% maqgħud mal- albumina tal- plażma.
As a result of enterohepatic recirculation, secondary increases in plasma MPA concentration are usually observed at approximately 6 – 12 hours post-dose.
Bħala riżultat tar- riċirkolazzjoni entero- epatika, żidiet sekondarji fil- konċentrazzjoni tal- plażma ta ’ MPA normalment huma osservati f’ madwar 6 – 12- il siegħa wara li tingħata d- doża.
A reduction in the AUC of MPA of approximately 40% is associated with the co-administration of cholestyramine (4 g TID), indicating that there is a significant amount of enterohepatic recirculation.
Tnaqqis fl- AUC ta ’ MPA ta ’ madwar 40% huwa assoċjat ma ’ amministrazzjoni flimkien ma ’ cholestyramine (4 g TID), li jindika li hemm ammont sinifikanti ta ’ riċirkolazzjoni entero- epatika.
MPA is metabolised principally by glucuronyl transferase to form the phenolic glucuronide of MPA (MPAG), which is not pharmacologically active.
9 MPA huwa metabolizzat l- aktar minn glucuronyl transferase biex jifforma il - glucuronide fenoliku ta ’ l - MPA (MPAG), li mhuwiex attiv farmakoloġikament.
A negligible amount of substance is excreted as MPA (< 1% of dose) in the urine.
Ammont negliġibbli tas- sustanza jitneħħa fl- awrina bħala MPA (< 1% tad- doża).
Orally administered radiolabelled mycophenolate mofetil results in complete recovery of the administered dose with 93% of the administered dose recovered in the urine and 6% recovered in the faeces.
Mycophenolate mofetil radjutikketjat mogħti mill- ħalq jiġi rkuprat kompletament b’ 93% tad- doża amministrata rkuprata fl - awrina u 6% tad- doża rkuprata fl- ippurgar.
Most (about 87%) of the administered dose is excreted in the urine as MPAG.
Il- maġġoranza (madwar 87%) tad- doża amministrata hija mneħħija fl- awrina bħala MPAG.
9 At clinically encountered concentrations, MPA and MPAG are not removed by haemodialysis.
F’ konċentrazzjonijiet li jintużaw klinikament, MPA u MPAG ma jitneħħewx bl- emodijalisi.
However, at high MPAG plasma concentrations (> 100µg/ ml), small amounts of MPAG are removed.
Iżda, f’ konċentrazzjonijiet ta ’ MPAG għoljin fil- plażma (> 100 µg/ ml), jitneħħew ammonti żgħar ta ’ MPAG.
In the early post-transplant period (< 40 days post-transplant), renal, cardiac and hepatic transplant patients had mean MPA AUCs approximately 30% lower and Cmax approximately 40% lower compared to the late post-transplant period (3 – 6 months post-transplant).
Fil- perijodu bikri ta ’ wara t- trapjant (< 40 ġurnata wara t- trapjant), pazjenti bi trapjant renali, tal- qalb u epatiku kellhom medja ta ’ l- AUC ta ’ MPA ta ’ madwar 30% aktar baxxa u Cmax ta ’ madwar 40% aktar baxxa meta mqabbel mal- perijodu tard ta ’ wara t- trapjant (3 - 6 xhur wara t- trapjant).
In a single dose study (6 subjects/ group), mean plasma MPA AUC observed in subjects with severe chronic renal impairment (glomerular filtration rate < 25 ml• min-1• 1.73 m-2) were 28 – 75% higher relative to the means observed in normal healthy subjects or subjects with lesser degrees of renal impairment.
Fi studju ta ’ doża waħda (6 individwi/ grupp), il- medja tal- AUC fil- plażma ta ’ MPA osservata f’ persuni b’ indeboliment kroniku renali sever (rata ta ’ filtrazzjoni glomerulari < 25 ml• min- 1• 1. 73 m- 2), kienu 28 – 75% ogħla meta mqabbla ma ’ medja osservati f’ individwi normali b’ saħħithom jew individwi b’ indeboliment renali ta ’ gradi inqas gravi.
However, the mean single dose MPAG AUC was 3 – 6-fold higher in subjects with severe renal impairment than in subjects with mild renal impairment or normal healthy subjects, consistent with the known renal elimination of MPAG.
Iżda il- medja tal- AUC ta ’ doża waħda ta ’ MPAG kienet 3 – 6 darbiet ogħla f’ individwi b’ indeboliment renali sever milli f’ persuni b’ indeboliment renali ħafif jew f’ persuni normali b’ saħħithom, kosistenti ma ’ l- eliminazzjoni renali magħrufa ta ’ MPAG.
Multiple dosing of mycophenolate mofetil in patients with severe chronic renal impairment has not been studied.
Ma sarx studju ta ’ dożi multipli ta 'mycophenolate mofetil f’ pazjenti b' indeboliment renali kroniku sever.
No data are available for cardiac or hepatic transplant patients with severe chronic renal impairment.
Ma hemm l - ebda tagħrif disponibbli għal pazjenti bi trapjant tal- qalb jew epatiku b’ indeboliment renali kroniku sever.
Delayed renal graft function:
Dewmien tal- funzjoni bi trapjant renali:
In patients with delayed renal graft function post-transplant, mean MPA AUC (0– 12h) was comparable to that seen in post-transplant patients without delayed graft function.
F’ pazjenti li l- kliewi tagħhom idumu biex jibdew jaħdmu wara li jsir it- trapjant, l- AUC medja ta ’ MPA (0- 12- il siegħa) kienet simili għal dik osservata f’ pazjenti wara t- trapjant mingħajr dewmien sal- funzjoni tat- trapjant.
Mean plasma MPAG AUC (0-12h) was 2 – 3-fold higher than in post-transplant patients without delayed graft function.
L- AUC medja fil- plażma ta ’ MPAG (0- 12- il siegħa) kienet darbtejn sa tliet darbiet ogħla minn f’ pazjenti wara t- trapjant mingħajr dewmien sal- funzjoni tat- trapjant.
There may be a transient increase in the free fraction and concentration of plasma MPA in patients with delayed renal graft function.
Jista ’ jkun hemm żieda għal ftit żmien fil- frazzjoni ħielsa u l- konċentrazzjoni ta ’ MPA fil- plażma f’ pazjenti b’ dewmien sal- funzjoni tat- trapjant.
Dose adjustment of CellCept does not appear to be necessary.
Ma jidhirx li huwa meħtieġ aġġustament fid- doża ta ’ CellCept.
In volunteers with alcoholic cirrhosis, hepatic MPA glucuronidation processes were relatively unaffected by hepatic parenchymal disease.
Il- proċessi ta ’ glucoronidation epatika ta ’ MPA relattivament ma kienux affettwati mill- marda epatika parenkimali f’ voluntiera b’ ċirrożi alkoħolika.
Effects of hepatic disease on this process probably depend on the particular disease.
Effetti ta ’ mard epatiku fuq dan il- proċess probabilment jiddependi mil- marda partikolari.
However, hepatic disease with predominantly biliary damage, such as primary biliary cirrhosis, may show a different effect.
Iżda, mard epatiku bi ħsara predominanti tal- biljari, bħal ċirrożi biljari primarja, jistgħu juru effett differenti.
Children and adolescents (aged 2 to 18 years):
Tfal u adoloxxenti (b’ età minn 2- 18- il sena):
Pharmacokinetic parameters were evaluated in 49 paediatric renal transplant patients given 600 mg/ m2 mycophenolate mofetil orally twice daily.
Parametri farmakokinetiċi kienu evalwati f’ 49 pazjent pedjatriku bi trapjant renali li ngħataw 600 mg/ m2 ta 'mycophenolate mofetil mill- ħalq darbtejn kuljum.
This dose achieved MPA AUC values similar to those seen in adult renal transplant patients receiving CellCept at a dose of 1 g bid in the early and late post- transplant period.
Din id- doża laħqet valuri fl- AUC ta ’ MPA simili għal dawk osservati f’ pazjenti adulti bi trapjant renali li jirċievu doża ta ’ CellCept ta ’ 1 g bid fil- perijodu bikri jew tard wara t- trapjant.
MPA AUC values across age groups were similar in the early and late post- transplant period.
Il- valuri ta ’ l- AUC ta ’ MPA fil- gruppi ta 'età differenti kienu simili fil - perijodu bikri u tard wara t- trapjant.
Pharmacokinetic behaviour of CellCept in the elderly has not been formally evaluated.
Il- farmakokinetika ta ’ CellCept fl- anzjani ma kienitx evalwata formalment.
Oral contraceptives:
Kontraċettivi orali:
The pharmacokinetics of oral contraceptives were unaffected by coadministration of CellCept (see also section 4.5).
Il- farmakokinetika ta ’ kontraċettivi orali ma ġewx affettwati bl- għotja flimkien ta ’ CellCept (ara ukoll sezzjoni 4. 5).
A study of the coadministration of CellCept (1 g bid) and combined oral contraceptives containing ethinylestradiol (0.02 mg to 0.04 mg) and levonorgestrel (0.05 mg to 0.15 mg), desogestrel (0.15 mg) or gestodene (0.05 mg to 0.10 mg) conducted in 18 non-transplant women (not taking other immunosupressants) over 3 consecutive menstrual cycles showed no clinically relevant influence of CellCept on the ovulation suppressing action of the oral contraceptives.
10 immunosoppressanti oħrajn) fuq medda ta ’ tliet ċikli menstruwali ma wrew l- ebda influwenza klinikament relevanti ta ’ CellCept fuq l- azzjoni ta ’ soppressjoni ta ’ l- ovulazzjoni tal- kontraċettivi orali.
Serum levels of LH, FSH and progesterone were not significantly affected.
Il- livelli fis - serum ta ’ LH, FSH u proġesterone ma kinux affettwati sinifikament.
In experimental models, mycophenolate mofetil was not tumourigenic.
F’ mudelli esperimentali, mycophenolate mofetil ma kienx tumuroġeniku.
The highest dose tested in the animal carcinogenicity studies resulted in approximately 2 – 3 times the systemic exposure (AUC or Cmax) observed in renal transplant patients at the recommended clinical dose of 2 g/ day and 1.3 – 2
L- ogħla doża eżaminata fl - istudji dwar il- karċinoġeniċità fuq l- annimali wasslu għal esponimenti madwar 2 – 3 darbiet ogħla mill - esponimenti sistemiċi (AUC jew Cmax) li kienu osservati f’ pazjenti bi trapjant renali fid- doża rakkomandata klinikament ta ’ 2 g/ jum u 1. 3 – 2 darbiet l- eponimenti sistemiċi (AUC jew Cmax) osservati f’ pazjenti bi trapjant tal- qalb fid- doża rakkomandata klinikament ta ’ 3 g/ jum.
Two genotoxicity assays (in vitro mouse lymphoma assay and in vivo mouse bone marrow micronucleus test) showed a potential of mycophenolate mofetil to cause chromosomal aberrations.
Żewġ analiżi tal- ġenotossiċità (analiżi ta ’ limfoma tal- ġurdien in vitro u t- test tal- mikronukleju tal - mudullun tal- ġurdien) urew li mycophenolate mofetil għandu potenzjal li jikkawża aberrazzjonijiet fil - kromosomi.
These effects can be related to the pharmacodynamic mode of action, i. e. inhibition of nucleotide synthesis in sensitive cells.
Dawn l- effetti jistgħu jkunu relatati mal- mod ta ’ azzjoni farmakodinamika, i. e. impediment tas- sintesi tan- nucleotida f’ ċelluli sensittivi.
Other in vitro tests for detection of gene mutation did not demonstrate genotoxic activity.
Testijiet oħrajn in vitro għas- sejba ta ’ mutazzjoni tal- ġeni ma wrewx attività ġenotossika.