qanastek/EMEA-V3 huggingface dataset:
Lymphoproliferative disease or lymphoma developed in 0.6% of patients receiving mycophenolate (2 g or 3 g daily) in combination with other immunosuppressants 6 in controlled clinical trials of renal (2 g data), cardiac and hepatic transplant patients followed for at least 1 year.
Mard limfoproliferattiv jew limfoma żviluppaw f’ 0. 6% ta ’ pazjenti li jkunu qegħdin jingħataw mycophenolate (2 g jew 3 g kuljum) f’ kumbinazzjoni ma ’ mediċini immunosoppressivi oħrajn fi provi kliniċi kkontrollati fuq pazjenti bi trapjanti tal- kliewi (2 g kuljum), tal- qalb u tal- fwied, li kienu seġwiti għal ta ’ l- anqas sena.
Non-melanoma skin carcinomas occurred in 3.6% of patients; other types of malignancy occurred in 1.1% of patients.
Karsinomi (mhux melanoma) tal - ġilda seħħew fi 3. 6% tal- pazjenti; tipi oħra ta ’ mard malinn seħħew f’ 1. 1%.
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 ’ siġurta fuq tliet snin f’ pazjenti bi trapjanti tal- kliewi u tal- qalb ma wrew l- ebda bidla mhux mistennija fl- inċidenza ta ’ mard malinn meta mqabbel ma ’ dejta ta ’ sena.
Hepatic transplant patients were followed for at least 1 year, but less than 3 years.
Pazjenti bi trapjanti tal- fwied kienu segwiti għal ta ’ l - anqas sena, iżda għal anqas minn 3 snin.
All transplant patients are at increased risk of opportunistic infections; the risk increased with total immunosuppressive load (see section 4.4).
Il- pazjenti kollha li għandhom trapjant għandhom riskju akbar ta ’ infezzjonijiet opportunistiċi; ir - riskju jikber aktar ma tikber it- tagħbija immunosoppressiva totali (ara sezzjoni 4. 4).
The most common opportunistic infections in patients receiving mycophenolate (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, cytomegalovirus (CMV) viraemia/ syndrome and Herpes simplex.
L- aktar infezzjonijiet opportunisti komuni f’ pazjenti li qegħdin jingħataw mycophenolate (2 g jew 3 g kuljum) ma ’ immunosoppressivi oħrajn fi provi kliniċi kkontrolati ta ’ pazjenti bi trapjanti tal- kliewi (dejta 2 g), tal- qalb u tal- fwied li kienu segwiti għal ta ’ l- anqas sena kienu candida mukokutanea, ċitomegalovajrus (CMV) viremja/ sindromu CMV u Herpes simplex.
The proportion of patients with CMV viraemia/ syndrome was 13.5%.
Il- proporzjon ta ’ pazjenti b’ viremja/ sindromu CMV kien ta ’ 13. 5%.
The type and frequency of adverse reactions in a clinical study, which recruited 92 paediatric patients aged 2 to 18 years who where given 600 mg/ m2 mycophenolate mofetil orally twice daily, were generally similar to those observed in adult patients given 1 g mycophenolate twice daily.
Tfal u adolexxenti; It- tip u l- frekwenza ta ’ reazzjonijiet avversi fi studju kliniku, fejn ġew ingaġġati 92 pazjent pedjatriku bejn l- etajiet ta ’ 2- 18- il sena li ngħataw 600mg/ m2 mycophenolate mofetil oralment darbtejn kuljum, kienu ġeneralment simili għal dawk osservati f’ pazjenti adulti li ngħataw 1 g mycophenolate darbtejn kuljum.
However, the 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, l- avvenimenti avversi relatati mat- trattament segwenti kienu aktar spissi fil - populazzjoni pedjatrika, partikolarment fi tfal taħt l- età ta ’ 6 snin, meta mqabbla ma ’ l- 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.
Pazjenti anzjani (> 65 sena) jistgħu ġeneralment ikunu f’ riskju akbar għal reazzjonijiet avversi minħabba immunosoppressjoni.
Elderly patients receiving Mycophenolate mofetil Teva 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.
7 infezzjonijiet (li jinkludu mard ta ’ invażjoni tat- tessuti minn cytomegalovirus) u possibilment t’ emorraġija gastrointestinali u edema pulmonarja, meta mqabblin ma ’ individwi aktar żgħar.
Other adverse reactions:
Reazzjonijiet avversi oħrajn:
Adverse reactions, probably or possibly related to mycophenolate, reported in of patients treated with mycophenolate in the controlled clinical trials of renal (2 g data), cardiac and hepatic transplant patients are listed in the following table.
Reazzjonijiet avversi, li probabilment jew possibilment huma relatati ma ’ mycophenolate, irraportati f’ ≥ 1/ 10 u f’ ≥1/ 100 sa < 1/ 10 ta ’ pazjenti trattati b’ mycophenolate fil- provi kliniċi kkontrollati ta ’ pazjenti bi trapjanti renali (dejta ta ’ 2 g), kardijaċi e epatiċi huma elenkati fit- tabella li ġejja.
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 from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness
Fi ħdan kull grupp ta ’ frekwenzi, l - effetti mhux mixtieqa huma ppreżentati f’ ordni fejn is- severità tagħhom tonqos.
7 Adverse reactions, probably or possibly related to Mycophenolate, reported in patients treated with Mycophenolate in renal, cardiac and hepatic clinical trials when used in combination with ciclosporin and corticosteroids
Reazzjonijiet avversi, li b’ mod probabbli jew possibbli huma relatati ma ’ mycophenolate, irraportati f’ pazjenti trattati b’ mycophenolate fi provi renali, kardijaċi u epatiċi meta użati flimkien ma ’ ciclosporin u corticosteroids
System organ class
Sistema
Adverse drug reactions
Reazzjonijiet avversi għal mediċina
Investigations
tal- klassifikazzjoni tal- organi Investigazzjonijiet
increased, blood alkaline phosphatase increased, weight decreased
- Żieda fil- livell ta ’ enżima epatika, żieda fil- kreatinin tad- demm, żieda ta ’ lactate dehydrogenase fid- demm, żieda ta ’ urea fid- demm, żieda ta ’ alkaline phosphatase fid- demm, tnaqqis fil- piż
Cardiac
Disturbi kardijaċi
Tachycardia
- Takikardja
Leukopenia, thrombocytopenia, anaemia Pancytopenia, leukocytosis
Lewkopenija, tromboċitopenija, anemija Panċitopenija, lewkoċitosi
Nervous system
Disturbi tas- sistema nervuża
Convulsion, hypertonia, tremor, somnolence, myasthenic syndrome, dizziness, headache, paraesthesia, dysgeusia
- Aċċessjoni, ipertonija, tregħid, ħedla, sindromu mijasteniku, sturdamenti, uġigħ ta ’ ras, parestesija, disgewsja
Respiratory,
Disturbi respiratorji, toraċiċi u medjastinali
thoracic and mediastinal disorders
- Effużjoni plewrali, dispnea, sogħla
Pleural effusion, dyspnoea, cough
Disturbi gastro - intestinali
Gastrointestinal haemorrhage, peritonitis, ileus, colitis, gastric ulcer, duodenal ulcer, gastritis, oesophagitis,
Remettar, uġigħ addominali, dijarrea, dardir Emorraġija gastro- intestinali, peritonite, ileus, kolite, ulċeri fl- istonku, ulċeri duwodenali, gastrite, esofagite, stomatite, stitikezza, dispepsja, gass, tifwiq
stomatitis, constipation, dyspepsia, flatulence, eructation
Disturbi renali u tas- sistema urinarja Disturbi tal- ġilda u t- tessuti subkutanji Disturbi muskolu - skeletali u tat- tessut konnettiv
Very common
Komuni ħafna Komuni Komuni ħafna Komuni Komuni ħafna Komuni
Skin hypertrophy, rash, acne, alopecia
- Indeboliment renali - Ipertrofija tal- ġilda, raxx, akne, alopeċja - Artralġja
Adverse drug reactions
tal- klassifikazzjoni tal- organi
Metabolism
Disturbi marbuti
Acidosis, hyperkalaemia, hypokalaemia, hyperglycaemia,
mal- metaboliżmu u n- nutrizzjon
disorders
Komuni
hyperlipidaemia, hypophosphataemia, hyperuricaemia, gout, anorexia
Aċidosi, iperkalemija, ipokalemija, ipergliċemija, ipomagnesemija, ipokalċemija, iperkolesterolemija, iperlipidemija, ipofosfatemija, iperurikemija, gotta, anoreksja
Sepsis, gastrointestinal candidiasis, urinary tract infection, herpes simplex, herpes zoster
Sepsis, kandidjasi gastrointestinali, infezzjoni
Very common
infestazzjonijiet
Skin cancer, benign
tal- passaġġ urinarju, herpes simplex, herpes zoster Pnewmonja, influwenza, infezzjoni tal- passaġġ respiratorju, moniljasi respiratorja, infezzjoni gastrointestinali, kandidjasi, gastroenterite, infezzjoni, bronkite, farinġite, sinusite, infezzjoni fungali tal- ġilda, kandida tal- ġilda, kandidjasi vaġinali, rinite
malignant and unspecified (incl cysts and polyps)
Neoplażmi beninn, malinn u mhux speċifiċi (li jinkludu ċisti u polipi)
Hypotension, hypertension, vasodilatation
- Kanser tal- ġilda, neoplażmu beninn tal- ġilda
General
Disturbi vaskulari
Oedema, pyrexia, chills, pain, malaise, asthenia
- Ipotensjoni, ipertensjoni, vażodilazzjoni
administration site conditions
Disturbi ġenerali u kundizzjonijiet ta ’ mnejn jittieħed
disorders Psychiatric
- Edema, deni, tertir, uġigħ, telqa, astenja
hyperbilirubinaemia -
Disturbi epato - biljari Disturbi psikjattriċi
disorders
Komuni ħafna Komuni Komuni ħafna Komuni
Agitation, confusional state, depression, anxiety, thinking abnormal, insomnia
- Epatite, suffejra, iperbilirubinemija Aġitazzjoni, stat ta ’ konfużjoni, depressjoni, ansjetà, ħsibijiet mhux normali, nuqqas ta ’ rqad
501 (2 g mycophenolate daily), 289 (3 g mycophenolate daily) and 277 (2 g intravenous / 3 g oral mycophenolate daily) patients were treated in Phase III studies for the prevention of rejection in renal, cardiac and hepatic transplantation, respectively.
501 (2 g mycophenolate kuljum), 289 (3 g mycophenolate kuljum) u 277 (2 g intravenużi / 3 g mycophenolate orali kuljum) pazjenti ġew ittrattati fi studji ta ’ Fażi III għal prevenzjoni ta ’ riġettazzjoni fi trapjanti renali, kardijaċi u epatiċi rispettivament.
The following undesirable effects cover adverse reactions from post-marketing experience: the types of adverse reactions reported during post-marketing with mycophenolate are similar to those seen in the controlled renal, cardiac and hepatic transplant studies.
L- effetti mhux mixtieqa li ġejjin ikopru reazzjonijiet avversi skond esperjenzi ta ’ wara t- tqegħid fis - suq: it- tipi ta ’ reazzjonijet avversi rapportati wara t- tqegħid fis- suq b’ mycophenolate huma simili għal dawk li jidhru fi stħarriġ ikkontrollat li jinvolvi trapjanti 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 addizzjonali rrapportati fil- proċess ta ’ waqt it- tqegħid fis- suq huma mfissrin hawn taħt bil - frekwenzi rrapportati fil- parentesi jekk ikunu magħrufin.
Gastrointestinal: colitis including cytomegalovirus colitis, (common), pancreatitis, (common) and intestinal villous atrophy.
Gastrointestinali: kolite li tinkludi kolite minn ċitomegalovajrus, (kolite), (komuni) pankreatite, (komuni) u atrofija tal- villi intestinali.
Disorders related to immunosuppression: serious life-threatening infections including meningitis, endocarditis, tuberculosis and atypical mycobacterial infection.
Disturbi relatati ma ’ l- immunosoppressjoni: infezzjonijiet serji li jipperikolaw il- ħajja jinkludu meninġite, endokardite, tuberkulożi u infezzjonijiet b’ mikobatterja atipika.
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 Mycophenolate mofetil Teva.
9 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 Mycophenolate Mofetil Teva.
Agranulocytosis (uncommon) and neutropenia have been reported; therefore regular monitoring of patients taking Mycophenolate mofetil Teva is advised (see section 4.4). There have been reports of aplastic anaemia and bone marrow depression in patients treated with mycophenolate, some of which have been fatal.
Kien hemm rapporti ta ’ anemija aplastika u depressjoni tal- mudullun f ’ pazjenti ttrattati b’ mycophenolate, li xi ftit minnhom kienu fatali.
9 Hypersensitivity: hypersensitivity reactions, including angioneurotic oedema and anaphylactic reaction have been reported.
4. 9 Doża eċċessiva
Reports of overdoses with mycophenolate mofetil have been received from clinical trials and during post-marketing experience.
Waslu rapporti ta ’ dożi eċċessivi b’ mycophenolate mofetil minn provi kliniċi u mill- esperjenza ta ’ wara t- tqegħid fis- suq.
In many of these cases, no adverse events were reported.
F’ ħafna minn dawn il- każijiet l- ebda każ avvers ma ġie rapportat.
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 meta każijiet avversi kienu rapportati, il- każijiet jaqgħu fil- profil ta ’ sigurtà magħrufa 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). If neutropenia develops, dosing with Mycophenolate mofetil Teva should be interrupted or the dose reduced (see section 4.4).
Jekk tiżviluppa n- newtropenja, Mycophenolate mofetil Teva għandu jiġi mwaqqaf jew id- doża mnaqqsa (ara sezzjoni 4. 4).
Haemodialysis would not be expected to remove clinically significant amounts of MPA or MPAG.
L- emodijalisi mhix mistennija li tneħħi ammonti sinifikanti ta ’ MPA jew 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 - aċidu biljari, bħal cholestyramine, jistgħu jnaqqsu MPA billi titnaqqas iċ- ċirkolazzjoni enteroepatika tal- mediċina (ara sezzjoni 5. 2).
Pharmacotherapeutic group: immunosuppressive agents ATC code:
Grupp farmakoterapewtiku: mediċini immunosoppressanti, Kodiċi ATC:
Mycophenolate mofetil is the 2-morpholinoethyl ester of mycophenolic acid (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 potenti, silettiv, mhux kompettitiv u impeditur reversibbli ta ’ inosine monophosphate dehydrogenase, u għalhekk jimpedixxi l- passaġġ de novo tas- sintesi ta ’ guanosine nucleotide mingħajr ma jinkorporah 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.
Peress li limfoċiti T - u B - huma kritikament dipendenti għall - proliferazzjoni tagħhom fuq sintesi de novo ta ’ purini mentri tipi ta ’ ċelloli oħrajn jistgħu jużaw passaġġi ta ’ salvataġġ, MPA għandu effetti ċitostatiċi aktar potenti fuq il- limfoċiti milli fuq ċelloli oħrajn.
Following oral administration, mycophenolate mofetil undergoes rapid and extensive absorption and complete presystemic metabolism to the active metabolite, MPA.
Wara teħid orali, mycophenolate mofetil iġarrab assorbiment rapidu u estensiv u metaboliżmu komplut presistematiku għall- metabolit attiv, MPA.
As evidenced by suppression of acute rejection following renal transplantation, the immunosuppressant activity of mycophenolate is correlated with MPA concentration.
Kif muri mis- soppressjoni ta ’ riġett akut wara trapjant tal- kliewi, l- attività immunosoppressanti ta ’ mycophenolate hija korrelata mal - konċentrazzjoni ta ’ MPA.
The mean bioavailability of oral mycophenolate mofetil, based on MPA AUC, is 94% relative to intravenous mycophenolate mofetil.
Il- bijodisponabilità medja ta ’ mycophenolate mofetil meħud oralment, ibbażata fuq MPA AUC, hija 94% relattiva ma ’ mycophenolate mofetil intravenuż.
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 m’ għandu l- ebda effett fuq kemm jiġi assorbit (MPA AUC) mycophenolate mofetil meta jingħata f’ dożi ta ’ 1. 5 g BID lill- pazjenti bi trattament tal- kliewi.
However, MPA C max was decreased by 40% in the presence of food.
Madankollu, MPA Cmax kienet imnaqqsa b’ 40% fil- preżenza ta ’ l- ikel.
Mycophenolate mofetil is not measurable systemically in plasma following oral administration.
Mycophenolate mofetil mhuwiex imkejjel sistemikament fil- plażma wara t- teħid orali.
MPA at clinically relevant concentrations, is 97% bound to plasma albumin.
MPA f’ konċentrazzjonijiet kliniċi relevanti, huwa 97% marbut ma ’ l- albumina fil- plażma.
As a result of enterohepatic recirculation, secondary increases in plasma MPA concentration are usually observed at approximately 6 – 12 hours post-dose.
10 Bħala riżultat ta ’ ċirkulazzjoni enteroepatika mill- ġdid, żjidiet sekondarji fil- konċentrazzjoni ta ’ MPA fil- plażma huma ġeneralment osservati bejn wieħed u ieħor minn 6- 12- il siegħa wara 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 ’ bejn wieħed u ieħor 40% huwa assoċjat ma ’ l- għoti konkomitanti ta ’ cholestyramine (4 g TID), li tindika li hemm ammont sinifikattiv ta ’ ċirkulazzjoni enteroepatika mill - ġdid.
MPA is metabolised principally by glucuronyl transferase to form the phenolic glucuronide of MPA (MPAG), which is not pharmacologically active.
L- MPA hu metabolizzat prinċipalment minn glucuronyl transferase sabiex jifforma l- phenolic glucuronide ta ’ MPA (MPAG), li mhux farmakoloġikament attiv.
10 A negligible amount of substance is excreted as MPA (< 1% of dose) in the urine.
Ammont negliġibbli ta ’ sustanza hija merħija bħala MPA (< 1% tad- doża) fl- awrina.
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 radjutikkettat mogħti oralment jirriżulta fi ġbir mill- ġdid komplut tad- doża li tkun ingħatat; b’ 93% tad- doża mgħotija miġbura mill- ġdid fl- awrina u 6% miġbura mill- ġdid mill- ippurgar.
Most (about 87%) of the administered dose is excreted in the urine as MPAG.
Il- parti l- kbira (madwar 87%) tad- doża mgħotija hija eliminata fl- awrina bħala MPAG.
At clinically encountered concentrations, MPA and MPAG are not removed by haemodialysis.
F’ konċentrazzjonijiet li niltaqgħu magħhom klinikament, MPA u MPAG mhumiex imneħħijin bl - emodialiżi.
However, at high MPAG plasma concentrations (> 100 g/ ml), small amounts of MPAG are removed.
Madankollu, f’ konċentrazzjonijiet ta ’ MPAG fil- plażma għoljin (> 100µg/ ml), ammonti żgħar ta ’ MPAG huma mneħħijin.
In the early post-transplant period (< 40 days post-transplant), renal, cardiac and hepatic transplant patients had mean MPA AUCs approximately 30% lower and C max approximately 40% lower compared to the late post-transplant period (3 - 6 months post-transplant).
Fil- perijodu bikri ta ’ wara t- trapjant (< 40 jum wara t- trapjant), pazjenti bi trapjanti tal- kliewi, tal- qalb u tal- fwied kellhom MPA AUCs medji bejn wieħed u ieħor 30% aktar baxxi u Cmax bejn wieħed u ieħor 40% aktar baxxa kkomparat mal- perijodu aktar tard 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 stħarriġ fuq doża ewlenija (6 suġġetti/ grupp), l- MPA AUC medju fil- plażma osservat f’ suġġetti b’ indeboliment kroniku tal- kliewi sever (rata tal- filtrazzjoni mill- glomeruli < 25 ml• min- 1• 1. 73 m- 2) kienet 28 – 75% aktar għolja relattivament mal- medji osservati f’ suġġetti normali u f’ saħħithom jew suġġetti bi gradi anqas ta ’ indeboliment tal- kliewi.
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.
Madankollu, il- MPAG AUC medju ta ’ doża ewlenija kien minn 3- 6 darbiet ogħla f’ suġġetti b’ indeboliment kroniku tal- kliewi sever milli f’ suġġetti b’ indeboliment tal- kliewi ħafif jew suġġetti normali u f’ saħħithom, konsistenti mat- tneħħija mill - kliewi ta ’ MPAG kif magħrufa.
Multiple dosing of mycophenolate mofetil in patients with severe chronic renal impairment has not been studied.
Dożaġġ multiplu ta ’ mycophenolate mofetil f’ pazjenti b’ indeboliment kroniku tal- kliewi sever għadu ma giex mistħarreġ.
No data are available for cardiac or hepatic transplant patients with severe chronic renal impairment.
L- ebda tagħrif ma jeżisti għal pazjenti bi trapjanti tal- qalb jew tal- fwied li jkollhom indeboliment kroniku tal- kliewi sever.
Delayed renal graft function:
Pazjenti b’ funzjoni mdewwma tal- graft:
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 b’ funzjoni mdewwma tal- graft tal- kilwa wara t- trapjant, l- MPA AUC (0- 12- il siegħa) medju kien komparabbli ma dak li jidher f’ pazjenti wara t- trapjant li ma kellhomx dewmien fil - funzjoni tal- graft.
Mean plasma MPAG AUC (0- 12h) was 2-3-fold higher than in post-transplant patients without delayed graft function.
L- MPAG AUC (0- 12- il siegħa) medju tal- plażma kien 2- 3 darbiet ogħla f’ pazjenti wara t- trapjant li ma kellhomx dewmien fil- funzjoni tal- graft.
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 għaddiena fil- frazzjoni ħielsa u fil- konċentrazzjoni tal- MPA fil- plażma f’ pazjenti b’ dewmien fil- funzjoni tal- graft tal- kilwa.
Dose adjustment of Mycophenolate mofetil Teva does not appear to be necessary.
Aġġustament fid- doża ta ’ Mycophenolate mofetil Teva ma jidhirx li huwa meħtieġ.
In volunteers with alcoholic cirrhosis, hepatic MPA glucuronidation processes were relatively unaffected by hepatic parenchymal disease.
F’ voluntieri b’ ċirrożi alkoħolika, proċessi ta ’ glukorinazzjoni ta ’ MPA epatiċi kienu relativament mhux effettwati minn mard epatiku parenkimali.
Effects of hepatic disease on this process probably depend on the particular disease.
Effetti ta ’ mard epatiku fuq dan il- proċess probabbilment jiddependui fuq il- marda partikolari.
However, hepatic disease with predominantly biliary damage, such as primary biliary cirrhosis, may show a different effect.
Madankollu, mard epatiku bi ħsara prinċipalment biljarja bħal ma ’ hija ċ- ċirrożi biljarja primarja, jista ’ juri effett differenti.
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 pazjenti pedjatriċi bi trapjant tal- kliewi li ngħataw 600mg/ m2 mycophenalate mofetil oralment darbtejn kuljum.
This dose achieved MPA AUC values similar to those seen in adult renal transplant patients receiving mycophenolate at a dose of 1 g BID in the early and late post-transplant period.
Din id- doża kisbet valuri ta ’ MPA AUC simili għal dawk li dehru f’ pazjenti adulti bi trapjanti tal- kliewi li kienu qegħdin jingħataw mycophenolate f’ doża ta ’ 1g BID fil- perijodi bikrin u dawk aktar tard ta ’ wara t- trapjant.
MPA AUC values across age groups were similar in the early and late post- transplant period.
Valuri ta ’ MPA AUC mifruxin fuq gruppi ta ’ etajiet kienu simili fil- perijodi ta ’ wara t- trapjant kemm bikrin u kemm tard.
Elderly patients ( 65 years):
11 Pazjenti anzjani (≥ 65 sena):
Pharmacokinetic behaviour of mycophenolate in the elderly has not been formally evaluated.
L- imġieba farmakokinetika ta ’ mycophenolate fl- anzjani ma ġietx formalment evalwata.
The pharmacokinetics of oral contraceptives were unaffected by co-administration of mycophenolate (see also section 4.5). A study of the co-administration of mycophenolate (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 immunosuppressants) over 3 consecutive menstrual cycles showed no clinically relevant influence of mycophenolate on the ovulation suppressing action of the oral contraceptives.
Studju dwar l- għoti konġunt ta ’ mycophenolate (1 g BID) u kontraċettivi orali kkombinati li jkun fihom ethinylestradiol (0. 02 mg sa 0. 04 mg) u levonorgestrel (0. 05 mg sa 0. 15 mg), desogestrel (0. 15 mg) jew gestodene (0. 05 mg to 0. 10 mg) magħmul fi 18- il mara li ma kellhomx trapjant (mhux qegħdin jieħdu immunosoppressanti oħrajn) fuq 3 ċiċkli menstruwali konsekuttivi ma wrew l- ebda influwenza klinikament relevanti ta ’ mycophenolate fuq l - azzjoni ta ’ trażżin ta ’ l- ovulazzjoni tal- kontraċettivi orali.
Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone were not significantly affected.
Livelli fis- sirum ta ’ l- ormon lewtanizzanti (LH), ormon li jistimula l- follikuli (FSH) u progesterone ma kinux sinifikattivament effettwati.
5.3 Preclinical safety data 11 In experimental models, mycophenolate mofetil was not tumourigenic.
F’ mudelli esperimentali, mycophenolate mofetil ma kienx tumuriġeniku.
The highest dose tested in the animal carcinogenicity studies resulted in approximately 2-3 times the systemic exposure (AUC or C max) observed in renal transplant patients as the recommended clinical dose of 2 g/ day and 1.3-2 times the systemic exposure (AUC or C max) observed in cardiac transplant patients at the recommended clinical dose of 3 g/ day.
L- ogħla doża ttestjata fi stħarriġ fuq il- karċinogenetiċità fl- annimali rriżultat f’ bejn wieħed u ieħor 2- 3 darbiet l- esponiment sistemiku (AUC jew Cmax) osservat f’ pazjenti bi trapjanti tal- kliewi f’ doża klinika rakkomandata ta ’ 2 g/ kuljum u 1. 3 – 2 darbiet l- esponimet sistemiku (AUC jew Cmax) osservat f’ pazjenti bi trapjanti tal - qalb f’ doża klinika rakkomandata ta ’ 3 g/ kuljum.
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 assaysi fuq ġenotossicità (assaġġ in vitro f’ limfoma tal- ġrieden u in vivo mikronuklejus test fil- mudullun tal- ġrieden) urew potenzjal ta ’ mycophenolate mofetil li jikkawża aberrazzjonijiet.
These effects can be related to the pharmacodynamics mode of action, i. e. inhibition of nucleotide synthesis in sensitive cells.
Dawn l- effetti jistgħu jiġu relatati għall- farmakodinamiċi tal- mod ta ’ l- azzjoni, i. e. impediment ta ’ sintesi tan- nukleotidi f’ ċelloli sensittivi.
Other in vitro tests for detection of gene mutation did not demonstrate genotoxic activity.
Testijiet in vitro oħrajn għall- ittestjar ta ’ mutazzjoni fil- ġene ma wrewx attività ġenotossika.
Mycophenolate mofetil had no effect on fertility of male rats at oral doses up to 20 mg kg-1 day-1. The systemic exposure at this dose represents 2-3 times the clinical exposure at the recommended clinical dose of 2 g/ day in renal transplant patients and 1.3-2 times the clinical exposure at the recommended clinical dose of 3 g/ day in cardiac transplant patients.
L- espożizzjoni sistemika f’ din id- doża tirrappreżenta 2- 3 darbiet l- espożizzjoni klinika fid- doża klinika rakkomandata ta ’ 2 g/ kuljum f’ pazjenti bi trapjanti tal- kliewi u 1. 3 – 2 darbiet l- espożizzjoni klinika fid- doża klinika rakkomandata ta ’ 3 g/ kuljum f’ pazjenti bi trapjanti tal- qalb.
In a female fertility and reproduction study conducted in rats, oral doses of 4.5 mg kg-1 day-1 caused malformations (including anophthalmia, agnathia and hydrocephaly) in the first generation offspring in the absence of maternal toxicity.
Fi stħarriġ fuq il - fertilità u r- riproduzzjoni magħmul fuq firien nisa, dożi orali ta ’ 4. 5mg• kg- 1• day- 1 ikkaġunaw malformazzjonijiet (inklużi anoftalmja, agnatija u idrokefali) f’ wild ta ’ l- ewwel ġenerazzjoni fl - assenza ta ’ tossiċità materna.
The systemic exposure at this dose was approximately 0.5 times the clinical exposure at the recommended clinical dose of 2 g/ day for renal transplant patients and approximately 0.3 times the clinical exposure at the recommended clinical dose of 3 g/ day for cardiac transplant patients.
L- espożizzjoni sistemika f’ din id- doża kienet bejn wieħed u ieħor ta ’ 0. 5 darbiet l- espożizzjoni klinika fid- doża klinika rakkomandata ta ’ 2 g/ kuljum għall- pazjenti bi trapjanti tal- kliewi u bejn wieħed u ieħor 0. 3 darbiet l- espożizzjoni klinika fid- doża klinika rakkomandata ta ’ 3 g/ kuljum f’ pazjenti bi trapjanti tal- qalb.
No effects on fertility or reproductive parameters were evident in the dams or in the subsequent generation.
L- ebda effett fuq il- fertilità jew il- parametri riproduttivi ma kienu evidenti fl- ommijiet jew fil- ġenerazzjonijiet sussegwenti.
In teratology studies in rats and rabbits, foetal resorptions and malformations occurred in rats at 6 mg kg-1 day-1 (including anophthalmia, agnathia, and hydrocephaly) and in rabbits at 90 mg kg-1 day-1 (including cardiovascular and renal anomalies, such as ectopia cordis and ectopic kidneys, and diaphragmatic and umbilical hernia), in the absence of maternal toxicity.
Fl- istudji teratoloġiċi fil- firien u fil- fniek, risorbiment tal- fetu u malformazzjonijiet seħħew fil- firien f’ 6 mg kg- 1 day- 1 (li jinkludu anoftalmja, agnatija u idrokefali) u fil- fniek f’ 90mg kg- 1 day- 1 (li jinkludu anomaliji kardjovaskularu u tal- kliewi, bħal ma huma ektopia kordis u kliewi ektopiċi, u ftuq dijafragmatiku u umbilikali), fl- assenza ta ’ tossicità materna.
The systemic exposure at these levels are approximately equivalent to or less than 0.5 times the clinical exposure at the recommended clinical dose of 2 g/ day for renal transplant patients and approximately 0.3 times the clinical exposure at the recommended clinical dose of 3 g/ day for cardiac transplant patients.
L- espożizzjoni sistemika f’ dawn il- livelli hija bejn wieħed u ieħor ekwivalenti għal jew anqas minn 0. 5 darbiet l- espożizzjoni klinika fid- doża klinikament rakkomandata ta ’ 2 g/ kuljum għall- pazjenti bi trapjanti tal- kliewi u bejn wieħed u ieħor 0. 3 darbiet l- esponiżizzjoni klinika fid- doża klinika rakkomandata ta ’ 3 g/ kuljum f’ pazjenti bi trapjanti tal- qalb.
The haematopoietic and lymphoid systems were the primary organs affected in toxicology studies conducted with mycophenolate mofetil in the rat, mouse, dog and monkey.
Is- sistemi ematopoetiċi u limfojdi kienu l- organi prinċipali effettwati fi stħarrig tossikoloġiku magħmul b’ mycophenolate mofetil fuq il- firien, il- ġrieden, il- klieb u x- xadini.
These effects occurred at systemic exposure levels that are equivalent to or less than the clinical exposure at the recommended dose of 2 g/ day for renal transplant recipients.
Dawn l- effetti seħħew f’ livelli ta ’ espożizzjoni sistemiċi li huma ekwivalenti għal jew għal anqas minn l- espożizzjoni klinika 12 f’ doża rakkomandata ta ’ 2 g/ kuljum għar- reċipjenti tat- trapjanti tal- kliewi.
Gastrointestinal effects were observed in the dog at systemic exposure levels equivalent to or less than the clinical exposure at the recommended doses.
Effetti gastrointestinali kienu osservati fil- klieb f’ livelli ta ’ espożizzjoni sistemiċi ekwivalenti għal jew anqas minn l - espożizzjoni klinika fid- dożi rakkomandati.
Gastrointestinal and renal effects consistent with dehydration were also observed in the monkey at the highest dose (systemic exposure levels equivalent to or greater than clinical exposure). The nonclinical toxicity profile of mycophenolate mofetil appears to be consistent with adverse events observed in human clinical trials which now provide safety data of more relevance to the patient population (see section 4.8).
Il- profil tat- tossiċità mhux kliniku ta ’ mycophenolate mofetil jidher li huwa konsistenti ma ’ każijiet avversi osservati fi provi kliniċi fuq il- bniedem li issa jipprovdu tagħrif ta ’ sigurtà li hija aktar ta ’ rilevanza għall- populazzjoni tal- pazjenti (ara sezzjoni 4. 8).
Capsule content:
X’ tikkonsisti l- kapsula:
Pregelatinised starch (maize) Povidone K-30 Croscarmellose sodium Magnesium stearate
Pregelatinised maize starch (qamħirrum) Povidone K- 30 Croscarmellose sodium Magnesium stearate
12 Capsule shell:
Il- qoxra tal- kapsuli:
Cap:
Ras:
Indigo carmine (E132) Titanium dioxide (E171) Gelatin Body:
Indigo carmine (E132) Titanium dioxide (E171) Gelatin Korp:
Red iron oxide (E172) Yellow iron oxide (E! 72) Titanium dioxide (E171) Gelatin Black ink containing: shellac, black iron oxide (E172), propylene glycol and potassium hydroxide.
Red iron oxide( E127) Yellow iron oxide (E110) Titanium dioxide (E171) Ġelatin Il- linka sewda tikkonsisti minn: shellac, black iron oxide (E172), propylene glycol u potassium hydroxide
This medicinal product does not require any special storage conditions
Dan il- prodott mediċinali m’ għandux kundizzjonijiet ta ’ ħażna speċjali.
Transparent PVC/ PVdC – aluminium blisters in pack sizes of 100 or 300 capsules per carton.
Pakketti trasparenti tal- PVC/ PVdC - folji ta ’ l- aluminju li fihom 100 jew 300 kapsula f’ kull kartuna.
Because mycophenolate mofetil has demonstrated teratogenic effects in rats and rabbit, Mycophenolate mofetil Teva capsules should not be opened or crushed.
Peress li mycophenolate mofetil wera effetti teratogeniċi fil- firien u l- fniek, il- kapsuli Mycophenolate mofetil Teva m’ għandhomx jinfetħu jew jiġu mitħunin.
Inhalation or direct contact with skin or mucous membranes of the powder contained in the capsules should be avoided.
Evita li tieħu n- nifs jew il- kuntatt mal- ġilda jew mar- riti mukużi tat- trab li jkun jinsab fil- kapsuli.
If such contact occurs, soap and water should be used to wash thoroughly and the eyes should be rinsed with plain water.
Jekk ikun hemm kuntatt bħal dan, laħlaħ sew bis- sapun u l- ilma; baħbaħ l- għajnejn bl- ilma biss.
Any unused product or waste material should be disposed of in accordance with local requirements.
13 Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali.
Computerweg 10 3542 DR Utrecht The Netherlands
Computerweg 10, 3542 DR Utrecht L- Olanda
EU/ 1/ 07/ 439/ 001 (100 capsules) EU/ 1/ 07/ 439/ 002 (300 capsules)
EU/ 1/ 07/ 439/ 001 (100 kapsula) EU/ 1/ 07/ 439/ 002 (300 kapsula)
13 Date of first authorisation:
Data ta ’ l- ewwel awtorizzazzjoni:
21 February 2008
21 ta ’ Frar 2008
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropea dwar il- Mediċini (EMEA) http: // www. emea. europa. eu
Mycophenolate mofetil Teva 500 mg film-coated tablets
Mycophenolate mofetil Teva 500 mg pilloli miksija b’ rita
Each tablet contains 500 mg mycophenolate mofetil For a full list of excipients, see section 6.1
Kull pillola fiha 500 mg mycophenolate mofetil Għal- lista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1
Film-coated tablet (tablet) Pale purple, oval shaped film-coated tablet, debossed with "M500" on one side and plain on the other side.
Pilloli miksija b’ rita (pillola) Pilloli miksija b’ rita ta ’ lewn il- lavanda pallida, f’ għamla ovali, intaljata b ’ “ M500 ” fuq naħa waħda u bla ebda disinn fuq in- naħa l- oħra.
Children and adolescents: the recommended dose of mycophenolate mofetil is 600 mg/ m2 administered orally twice daily (up to a maximum of 2 g daily).
Tfal u adolexxenti: id- doża rakkomandata ta ’ mycophenolate mofetil hija ta ’ 600 mg/ m2 li tingħata mill- ħalq darbtejn kuljum (sa ’ massimu ta ’ 2 g kuljum).
Mycophenolate mofetil Teva tablets should only be prescribed to patients with a body surface area greater than 1.5 m2, at a dose of 1 g twice daily (2 g daily dose).
Il- pilloli Mycophenolate mofetil Teva għandhom jiġu preskritti biss lil pazjenti b’ erja superfiċjali korporali ta ’ aktar minn 1. 5m2, f’ doża ta ’ 1 g darbtejn kuljum (doża ta ’ 2 g kuljum).
As some adverse reactions occur with greater frequency in this age group (see section 48) compared with adults, temporary dose reduction or interruption may be required; these will need to take into account relevant clinical factors including severity of reaction.
Peress li xi reazzjonijiet avversi jiġru bi frekwenza akbar f’ dan il- grupp ta ’ età (ara sezzjoni 4. 8) meta mqabbel ma ’ l- adulti, tnaqqis temporanju jew twaqqif tad- doża jista ’ jkun meħtieġ; dawn għandhom jiġu kkunsidrati ma ’ fatturi kliniċi relevanti li jinkludu s- severità tar- reazzjoni.
Adults: oral Mycophenolate mofetil Teva should be initiated within 5 days following transplantation.
Mycophenolate mofetil Teva mogħti mill- ħalq għandu jiġi mibdi fi żmien 5 ijiem wara t - trapjant.
15 Children and adolescents: no data are available for paediatric cardiac transplant patients, therefore use in this patients group is not recommended until further data to support this is available.
15 Tfal u adoloxxenti: m’ hemm l- ebda tagħrif disponibbli għal pazjenti tfal bi trapjant kardijaku, għalhekk l- użu f’ dan il- grupp ta ’ pazjenti mhux rakkomandat sakemm ikun hemm aktar tagħrif li jappoġġja dan.
Children and adolescents: no data are available for paediatric hepatic transplant patients, therefore use in this patient group is not recommended until further data to support this is available.
Tfal u adoloxxenti: l- ebda tagħrif mhu disponibbli għal pazjenti pedjatri bi trapjant tal- fwied, għalhekk l- użu f’ dan il- grupp ta ’ pazjenti mhux rakkomandat sakemm ikun hemm aktar tagħrif li jappoġġja dan.
Use in elderly ( 65 years)
Użu fl- anzjani (≥ 65 sena):
Use in renal impairment
Użu f’ indeboliment tal- kliewi:
In renal transplant patients with severe chronic renal impairment (glomerular filtration rate < 25 ml min-1 1.73 m-2), outside the immediate post-transplant period, doses greater than 1 g administered twice a day should be avoided.
F’ pazjenti bi trapjanti tal- kliewi b’ indeboliment kroniku sever tal- kliewi (rata ta ’ filtrazzjoni glomerulari < 25 ml min- 1 1. 73 m- 2), barra milli fil- perijodu immedjat ta ’ wara t- trapjant, dożi akbar minn 1 g mogħtijin darbtejn kuljum għandhom jiġu evitati.
Use in severe hepatic impairment
Użu f’ indeboliment tal- fwied sever:
Mycophenolate mofetil Teva is contraindicated in women who are breast-feeding (see section 4.6).
Sensittività eċċessiva għas- sustanza attiva, għal mycophenolic acid jew għal xi sustanzi mhux attivi Mycophenolate mofetil Teva huwa kontra- indikat f’ nisa li qed ireddgħu (ara sezzjoni 4. 6).
Patients receiving immunosuppressive regimens involving combinations of medicinal products, including Mycophenolate mofetil Teva, are at increased risk of developing lymphomas and other malignancies, particularly of the skin (see section 4.8).
Pażjenti li qegħdin fuq reġimens immunosoppressivi li jinvolvu kumbinazzjonijiet ta ’ prodotti mediċinali, li jinkludu Mycophenolate mofetil Teva, huma f’ riskju akbar li jiżviluppaw limfomi u tumuri malinni oħrajn, b’ mod partikolari dawk tal- ġilda (Ara sezjoni 4. 8).
The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent.
Ir- riskju jidher li huwa aktar relatat ma ’ l- intensità u t- tul tal- immunosoppressjoni milli mill- użu ta ’ xi mediċina speċifika.
As general advice to minimise the risk for skin cancer, exposure to sunlight and ultra-violet (UV) light should be limited by wearing protective clothing and using a sunscreen with a high protection factor.
Bħala rakkomandazzjoni ġenerali biex jitnaqqas ir- riskju għal kanċer tal- ġilda, espożizzjoni għad- dawl tax - xemx u d- dawl ultra vjola (UV) għandu jkun ristrett billi jintlibsu ħwejjeġ protettivi u billi jintuża sunskrin b’ fattur ta ’ protezzjoni għoli.
16 Patients receiving Mycophenolate mofetil Teva should be instructed to report immediately any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression.
16 Pazjenti li jirċievu Mycophenolate mofetil Teva għandhom jiġu mogħtija istruzzjonijiet biex jirraportaw minnufih kull evidenza ta ’ infezzjoni, tbenġil mhux mistenni, fsada jew xi manifestazzjoni oħra ta ’ dipressjoni tal- mudullun.
Patients receiving Mycophenolate mofetil Teva should be monitored for neutropenia, which may be related to Mycophenolate mofetil Teva itself, concomitant medicinal products, viral infections, or some combination of these causes.
Pazjenti li jirċievu Mycophenolate mofetil Teva għandhom jiġu sorveljati għan- newtropenija, li tista ’ tkun relatata ma ’ Mycophenolate mofetil Teva innifsu, prodotti mediċinali konkomitanti, infezzjonijiet minn vajrusis, jew xi kumbinazzjoni ta ’ dawn il- kawżi.
If neutropenia develops (absolute neutrophil count < 1.3 x 103/ l) it may be appropriate to interrupt or discontinue Mycophenolate mofetil Teva.
Jekk tiżviluppa n- newtropenija (għadd ta ’ newtrofils assolut < 1. 3 x 103/ µl) jkun aħjar li Mycophenolate mofetil Teva jiġi interrot jew imwaqqaf.
It is recommended that Mycophenolate mofetil Teva should not be administered concomitantly with azathioprine because such concomitant administration has not been studied.
Huwa rakkomandat li Mycophenolate mofetil Teva ma jingħatax flimkien ma ’ azathioprine minħabba li l- għoti konkomittanti bħal dan ma ġiex studjat.
In view of the significant reduction in the area under the curve (AUC) of MPA by cholestyramine, caution should be used in the concomitant administration of Mycophenolate mofetil Teva with medicinal products that interfere with enterohepatic recirculation because of the potential to reduce the efficacy of Mycophenolate mofetil Teva.
In vista tat- tnaqqis sinifikattiv fl- erja taħt il- kurva (AUC) jew MPA minn cholestyramine, għandha tiġi użata l- kawtela fl- użu konkomitanti ta ’ Mycophenolate mofetil Teva ma ’ prodotti mediċinali li jiddisturbaw iċ- ċirkulazzjoni mill- ġdid enteroepatika minħabba l- potenzjal li jnaqqas l- effikaċja ta ’ Mycophenolate mofetil Teva.
4.5 Interaction with other medicinal products and other forms of interaction
Il- proporzjon dwar ir- riskju għal benefiċċju ta ’ teħid ta mycophenolate mofetil ma ’ tacrolimus jew sirolimus għadu ma ġiex stabbilit (ara wkoll sezzjoni 4. 5).
The changes in MPAG (the phenolic glucuronide of MPA) pharmacokinetics (MPAG increased by 8%) were minimal and are not considered clinically significant.
It- tibdiliet fil - farmakokinetiċi MPAG (phenolic glucorinide ta ’ MPA) (MPAG tiżdied bi 8%) huma minimi u mhumiex ikkunsiderati klinikament sinifikattivi.
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 konċentrazzjonijiet fil- plażma ta ’ MPAG jiżdiedu fil- preżenza ta ’ indeboliment tal- kliewi, kif jiġri lill- konċentrazzjonijiet ta ’ aciclovir, jeżisti l - potenzjal għal mycophenolate mofetil u aciclovir, jew il- prodrugs tiegħu, eż. valaciclovir, li jikkompetu għat- tnixxija tubulari u jista ’ jkun hemm aktar żidiet fil- konċentrazzjonijiet taż- żewġ sustanzi.
17 Antacids with magnesium and aluminium hydroxides: absorption of mycophenolate mofetil was decreased when administered with antacids.
Antacids b’ magnesium u aluminium hydroxides: assorbiment ta ’ mycophenolate mofetil ġie mnaqqas meta mogħti ma ’ l- antacids.
Cholestyramine: following single dose administration 1.5 g of mycophenolate mofetil to normal healthy subjects pre-treated with 4 g three times a day (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- għoti ta ’ doża waħdanija ta ’ 1. 5 g ta ’ mycophenolate mofetil lil soġġetti normali f’ saħħithom li jkunu diġa ġew trattati b’ 4 g tliet darbiet kuljum (TID) ta ’ cholestyramine għal 4 ijiem, kien hemm tnaqqis ta ’ 40% fl- AUC ta ’ MPA (ara sezzjoni 4. 4 u sezzjoni 5. 2).
Caution should be used during concomitant administration because of the potential to reduce efficacy of Mycophenolate mofetil Teva.
Għandha tintuża l- kawtela waqt l- għoti konkomitanti minħabba l- potenzjal li titnaqqas l- effikaċja ta ’ Mycophenolate mofetil Teva.
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 mycophenolate mofetil.
Prodotti mediċinali li jfixklu ċ- ċirkulazzjoni enteroepatika: għandha tintuża l- kawtela bi prodotti mediċinali li jiddisturbaw iċ- ċirkulazzjoni enteroepatika minħabba l- potenzjal tagħhom li jnaqqsu l - effikaċja ta ’ mycophenolate mofetil.
Ciclosporin A: ciclosporin A (CsA) pharmacokinetics were unaffected by mycophenolate mofetil.
Ciclosporoin A: il- farmakokinetiċi ta ’ ciclosporoin A (CsA) ma kienux affettwati b’ mycophenolate mofetil.
Ganciclovir: based on the results of a single dose administration study of recommended doses of oral mycophenolate and intravenous ganciclovir and the known effects of renal impairment on the pharmacokinetics of mycophenolate (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 ir- riżultati ta ’ stħarriġ b’ għoti ta ’ doża ewlenija tad- dożi rakkomandati ta ’ mycophenolate b’ mod orali u ganciclovir intravenuż u l- effetti magħrufa dwar l- indeboliment tal - kliewi fuq il- farmakokinetiċi ta ’ mycophenolate (ara sezzjoni 4. 2) u ganciclovir, huwa antiċipat li l - għoti konkomittanti ta ’ dawn iż- żewġ mediċini (li jikkompetu għall- mekaniżmi ta ’ tnixxija mit- tubuli tal- kliewi) tirriżulta f’ żidiet fil- konċentrazzjonijiet ta ’ MPAG u ganciclovir.
No substantial alteration of MPA pharmacokinetics is anticipated and Mycophenolate mofetil Teva dose adjustment is not required.
L- ebda tibdil sostanzjali ma huwa antiċipat u aġġustament tad- doża ta ’ Mycophenolate mofetil Teva mhux meħtieġ.
In patients with renal impairment in which mycophenolate mofetil and ganciclovir or its prodrugs, e. g. valganciclovir, are co-administered the dose recommendations for ganciclovir should be observed and patients monitored carefully.
F’ pazjenti b’ indeboliment tal- kliewi fejn mycophenolate mofetil u ganciclovir jew il- prodrugs tagħha, eż. valganciclovir, huma mgħotijin konkomitantement ir- rakkomandazzjonijiet tad- doża għal ganciclovir għandhom jiġu osservati u l- pażjenti moniterjati bir- reqqa.
Oral contraceptives: the pharmacokinetics and pharmacodynamics of oral contraceptives were unaffected by co-administration of mycophenolate (see also section 5.2).
Kontraċettivi orali: il- farmakokinetiċi u l- farmakodinamiċi ta ’ kontraċettivi orali ma kinux effettwati mill- għoti konkomitanti ta ’ mycophenolate (ara wkoll sezzjoni 5. 2).
Rifampicin: in patients not also taking ciclosporin, concomitant administration of mycophenolate mofetil and rifampicin resulted in a decrease in MPA exposure (AUC 0-12h) of 18% to 70%.
Rifampicin: f’ pazjenti li mhux qed jieħdu wkoll ciclosporin, it- teħid konkomitanti ta ’ mycophenolate mofetil u rifamicin irriżulta fi tnaqqis fl- espożizzjoni għal MPA (AUC 1- 12h) ta ’ 18% sa 70%.