natgillin/translations-raw huggingface dataset:
4. 4 og pkt.
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).
Der skal iagttages forsigtighed ved samtidig administration pga. muligheden for nedsat effekt af mycophenolatmofetil.
Caution should be used during concomitant administration because of the potential to reduce efficacy of mycophenolate mofetil.
Der skal iagttages forsigtighed med lægemidler, som interfererer med den enterohepatiske cirkulation pga. risikoen for nedsat effekt af mycophenolatmofetil.
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.
Ciclosporin A' s (CsA) farmakokinetik påvirkes ikke af mycophenolatmofetil.
Ciclosporin A: ciclosporin A (CsA) pharmacokinetics were unaffected by mycophenolate mofetil.
Der forudses ingen væsentlig ændring af MPA’ s farmakokinetik og dosisjustering af mycophenolatmofetil er ikke nødvendig.
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 No substantial alteration of MPA pharmacokinetics is anticipated and mycophenolate mofetil dose adjustment is not required.
Hos patienter med nedsat nyrefunktion, som får Mycophenolate mofetil Teva og ganciclovir, eller deres prodrugs, f. eks. valganciclovir, samtidig bør dosisanbefalingerne for ganciclovir følges og patienterne monitoreres omhyggeligt.
In patients with renal impairment in which Mycophenolate mofetil Teva and ganciclovir or its prodrugs, e. g. valganciclovir, are co-administered the dose recommendations for ganciclovir should be observed and patients monitored carefully.
5. 2).
Oral contraceptives: the pharmacokinetics and pharmacodynamics of oral contraceptives were unaffected by co-administration of mycophenolate (see also section 5.2).
For at opretholde den kliniske effekt bør MPA- eksponeringen overvåges, og Mycophenolate mofetil Teva - doserne justeres i forhold til dette, når rifampicin administreres samtidigt.
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%. It is recommended to monitor MPA exposure levels and to adjust Mycophenolate mofetil Teva doses accordingly to maintain clinical efficacy when rifampicin is administered concomitantly.
4. 4).
Sirolimus: in renal transplant patients, concomitant administration of mycophenolate mofetil and CsA resulted in reduced MPA exposures by 30-50% compared with patients receiving the combination of sirolimus and similar doses of mycophenolate mofetil (see also section 4.4).
Mycophenolate mofetil Teva bør imidlertid administreres mindst én time før eller tre timer efter indtagelsen af sevelamer for at minimere dets indvirkning på MPA - absorptionen.
Sevelamer: decrease in MPA C max and AUC 0-12 by 30% and 25%, respectively, were observed when mycophenolate mofetil was concomitantly administered with sevelamer without any clinical consequences (i. e. graft rejection). It is recommended, however, to administer Mycophenolate mofetil Teva at least one hour before or three hours after sevelamer intake to minimise the impact on the absorption of MPA.
Der er ingen data for administrationen af mycophenolatmofetil med andre phosphatbindere end sevelamer.
There is no data on mycophenolate mofetil with phosphate binders other than sevelamer.
Der blev ikke observeret nogen virkning på MPA' s biotilgængelighed.
Trimethoprim/ sulfamethoxazole: no effect on the bioavailability of MPA was observed.
Der blev ikke observeret nogen signifikant interaktion hos raske frivillige, når mycophenolatmofetil blev administreret samtidigt med norfloxacin og metronidazol hver for sig.
Norfloxacin and metronidazole: in healthy volunteers, no significant interaction was observed when mycophenolate mofetil was concomitantly administered with norfloxacin and metronidazole separately.
30% efter én mycophenolatmofetil- dosis.
However, norfloxacin and metronidazole combined reduced the MPA exposure by approximately 30% following a single dose of mycophenolate mofetil.
Hos levertransplanterede patienter, der indledningsvis blev behandlet med mycophenolatmofetil og tacrolimus samtidigt, blev MPAs Cmax og AUC – mycophenolatmofetils aktive metabolit - ikke signifikant påvirket af den samtidige administration af tacrolimus.
5 Tacrolimus: in liver transplant recipients initiated on mycophenolate mofetil and tacrolimus, the AUC and C max of MPA, the active metabolite of mycophenolate mofetil, were not significantly affected by trough tacrolimus level.
Hos nyretransplanterede patienter blev tacrolimuskoncentrationen imidlertid tilsyneladende ikke påvirket af mycophenolatmofetil.
In renal transplant patients, the tacrolimus concentration did not appear to be altered by mycophenolate mofetil.
4. 4).
However, in hepatic transplant patients, there was an increase of approximately 20% in tacrolimus AUC when multiple doses of mycophenolate mofetil (1.5 g taken twice a day [BID], morning and evening]) were administered to patients taking tacrolimus (see also section 4.4).
Derfor kan andre stoffer, der vides at udskilles ved renal tubulær sekretion, konkurrere med MPAG og derved forhøje plasmakoncentrationerne af MPAG eller andre stoffer, der udskilles ved tubulær sekretion.
Other interactions: co-administration of probenecid with mycophenolate mofetil in monkeys raises plasma AUC of MPAG by 3-fold. 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.
Det anbefales, at behandling med Mycophenolate mofetil Teva ikke initieres før en negativ graviditetstest foreligger.
It is recommended that Mycophenolate mofetil Teva therapy should not be initiated until a negative pregnancy test has been obtained.
Patienter bør instrueres i straks at kontakte deres læge, hvis graviditet opstår.
Effective contraception must be used before beginning mycophenolate mofetil therapy, during therapy, and for six weeks following discontinuation of therapy (see section 4.5). Patients should be instructed to consult their physician immediately should pregnancy occur.
Anvendelse af Mycophenolate mofetil Teva anbefales ikke under graviditet og bør begrænses til tilfælde, hvor der ikke findes andre, mere passende behandlinger.
The use of Mycophenolate mofetil Teva is not recommended during pregnancy and should be reserved for cases where no more suitable alternative treatment is available.
Mycophenolate mofetil Teva bør kun anvendes til gravide kvinder, hvis den potentielle fordel er større end den potentielle risiko for fostret.
Mycophenolate mofetil Teva should be used in pregnant women only if the potential benefit outweighs the potential risk to the foetus.
Der er begrænset data om brugen af mycophenolatmofetil hos gravide kvinder.
There is limited data from the use of mycophenolate mofetil in pregnant women.
Medfødte misdannelser, herunder øremisdannelser dvs. abnormt dannet, eller manglende ydre øre/ mellemøre, er imidlertid blevet rapporteret hos børn af patienter, som under graviditeten er blevet behandlet med mycophenolatmofetil i kombination med andre immunosuppressiva.
However, congenital malformations including ear malformations, i. e. abnormally formed or absent external/ middle ear have been reported in children of patients exposed to mycophenolate mofetil in combination with other immunosuppressants during pregnancy.
Tilfælde af spontane aborter er set hos patienter, der blev behandlet med mycophenolatmofetil.
Cases of spontaneous abortions have been reported in patients exposed to mycophenolate mofetil.
4. 3).
Because of the potential for serious adverse reactions to mycophenolate mofetil in breast-fed infants, Mycophenolate mofetil Teva is contraindicated in breast-feeding mothers (see section 4.3).
Den farmakodynamiske profil og de rapporterede uønskede reaktioner peger på, at en påvirkning er usandsynlig.
The pharmacodynamics profile and the reported adverse reactions indicate that an effect is unlikely.
4. 4).
The principal adverse reactions associated with the administration of mycophenolate 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).
Patienter, der får immunosuppressiv behandling med kombinationer af lægemidler, inklusive mycophenolatmofetil, har forøget risiko for at udvikle lymfomer og andre maligne lidelser, især i huden (se pkt.
Patients receiving immunosuppressive regimens involving combinations of medicinal products, including mycophenolate, are at increased risk of developing lymphomas and other malignancies, particularly of the skin (see section 4.4).
I kontrollerede undersøgelser hos nyre - (2 g data), hjerte - og levertransplanterede patienter som kontrolleredes i mindst 1 år udvikledes lymfoproliferativ sygdom eller lymfomer hos 0, 6
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.
6% af de patienter som fik mycophenolatmofetil (2 eller 3 g daglig) sammen med andre immunsuppressive stoffer.
Non-melanoma skin carcinomas occurred in 3.6% of patients; other types of malignancy occurred in 1.1% of patients.
Levertransplanterede patienter fulgtes i mindst 1 år, men i mindre 3 år.
Hepatic transplant patients were followed for at least 1 year, but less than 3 years.
I kontrollerede kliniske studier hos nyre - (2 g data), hjerte - og levertransplantationspatienter, som blev fulgt i mindst 1 år, var de almindeligste opportunistiske infektioner hos patienter, som fik mycophenolatmofetil (2 g eller 3 g daglig) sammen med andre immunsupprimerende stoffer, mukokutane candidainfektioner, cytomegalovirus (CMV) viræmi/ syndrom og herpes simplex infektioner.
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.
Andelen af patienter med CMV viræmi/ syndrome var 13, 5%.
The proportion of patients with CMV viraemia/ syndrome was 13.5%.
I et klinisk studie, som rekrutterede 92 børn i alderen 2- 18 år, og som fik 600 mg/ m2 mycophenolatmofetil oralt to gange daglig, var arten og hyppigheden af uønskede hændelser generelt den samme som dem, der observeredes hos voksne patienter, som fik 1 g mycophenolatmofetil to gange daglig.
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.
Ældre patienter (≥ 65 år):
Elderly patients ( 65 years):
Ældre patienter (≥ 65 år) har i almindelighed større risiko for uønskede hændelser pga. immunsuppresion.
Elderly patients ( 65 years) may generally be at increased risk of adverse reactions due to immunosuppression.
Ældre patientersom får Mycophenolate mofetil Teva som led i et kombinations immunsuppressivt regi, kan have større risiko for visse infektioner (inklusive vævsinvasiv sygdom forårsaget af cytomegalovirus) og muligvis gastrointestinal blødning og lungeødem, sammenlignet med yngre individer.
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.
Uønskede hændelser, som var ” sandsynligt relateret ” eller ” muligt relateret ” til mycophenolatmofetil, og som rapporteredes hos de patienter, der blev behandlet med mycophenolatmofetil i de kontrollerede studier med nyre - (2 g data), hjerte - og levertransplanterede patienter er anført i den følgende tabel. ´
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.
Inden for hver frekvensgruppering er bivirkningerne opstillet efter faldende alvorlighed.
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
Uønskede hændelser, som var ” sandsynligt relateret ” eller ” muligt relateret ” til mycophenolatmofetil, ogsom rapporteredes hos patienter, som blev behandlet med mycophenolatmofetil i kombination med ciclosporin og kortikosteroider i de kliniske nyre -, hjerte - og leverstudier
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
7 Systemorgan - klasse
System organ class
forhøjet serum- creatinin, forhøjet
Hepatic enzyme increased, blood creatinine increased, blood lactate dehydrogenase increased, blood urea
laktatdehydrogenase, forhøjet serum- carbamid, forhøjede basiske phosphataser, vægttab
increased, blood alkaline phosphatase increased, weight decreased
almindelig
disorders
Blod og
Blood and lymphatic system disorders
Leukopeni, trombocytopeni, anæmi
Leukopenia, thrombocytopenia, anaemia Pancytopenia, leukocytosis
lymfesystem
Nervous system
almindelig Almindelig
Very common
Pancytopeni, leukocytose
-
-
Convulsion, hypertonia, tremor, somnolence, myasthenic syndrome, dizziness, headache, paraesthesia, dysgeusia
almindelig
Respiratory,
Kramper, hypertoni, tremor, somnolens, muskelsvaghed, svimmelhed, hovedpine, paræstesier, smagsforstyrrelser
-
Meget almindelig Almindelig
Common
- Pleural effusion, dyspnø, hoste
Pleural effusion, dyspnoea, cough
Almindelig
disorders
Gastrointestinal blødning, peritonitis, ileus, colitis,
Gastrointestinal haemorrhage, peritonitis, ileus, colitis, gastric ulcer, duodenal ulcer, gastritis, oesophagitis,
mavesår, ulcus duodeni, gastritis, oesophagitis, stomatitis, obstipation, dyspepsi, flatulens, opstød Nyrer og urinveje
stomatitis, constipation, dyspepsia, flatulence, eructation
almindelig
urinary
Hud og subkutane væv
disorders
Knogler, led, muskler og
Musculoskeletal
bindevæv
Common
Almindelig
Arthralgia
Arthralgi
Frequency
almindelig Almindelig
Common
Acidose, hyperkaliæmi, hypokaliæmi, hyperglykæmi, hypomagnesæmi, hypocalcæmi, hyperkolesterolæmi,
Acidosis, hyperkalaemia, hypokalaemia, hyperglycaemia,
hyperlipæmi, hypophosphatæmi, hyperuricæmi, ægte gigt, anoreksi Infektioner og
disorders
Meget
hypomagnesaemia, hypocalcaemia, hypercholesterolaemia,
Sepsis, gastrointestinal candidiasis, urinvejsinfektioner,
hyperlipidaemia, hypophosphataemia, hyperuricaemia, gout, anorexia
almindelig
Very common
Herpes simplex, herpes zoster
Sepsis, gastrointestinal candidiasis, urinary tract infection, herpes simplex, herpes zoster
Pneumoni, influenza, infektion i luftrøret, respiratorisk moniliasis, gastrointestinal infektion, candidiasis,
Pneumonia, influenza, respiratory tract infection, respiratory moniliasis, gastrointestinal infection, candidiasis, gastroenteritis, infection, bronchitis, pharyngitis, sinusitis, fungal skin infection, skin candida, vaginal candidiasis, rhinitis
gastroenteritis, infektion, bronkitis, pharyngitis, sinuitis, svampeinfektion i huden, hud candidiasis, vaginal candidiasis, rhinitis Benigne, maligne
Neoplasms
og uspecificerede
benign,
tumorer (inkl. cyster og polypper)
Skin cancer, benign
Almindelig
neoplasm of skin
Hudkræft, benignt neoplasme af huden
malignant and unspecified (incl cysts and polyps)
8
disorders
Hypotension, hypertension, vasodilatation
Hypotension, hypertension, vasodilatation
Almene symptomer og
General
reaktioner på administrations - stedet
disorders and
- Hepatitis, icterus, hyperbilirubinæmi
-
Psykiske
disorders Psychiatric
Meget
Common Very common
-
Hepatitis, jaundice,
forstyrrelser
hyperbilirubinaemia -
almindelig Almindelig
disorders
501 (2 g mycophenolatmofetil dagligt), 289 (3 g mycophenolatmofetil dagligt) og 277 (2 g intravenøs / 3 g oral mycophenolatmofetil dagligt) patienter i fase III studier blev behandlet med henblik på forebyggelse af afstødelse efter henholdsvis nyre -, hjerte - og levertransplantation.
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.
De uønskede hændelser, som er indberettet om mycophenolatmofetil efter markedsføringen svarer til dem, som er set i de kontrollerede nyre -, hjerte - og levertransplantationsstudier.
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.
Gastrointestinale: colitis inklusive cytomegalovirus colitis, (almindelig), pancreatitis, (almindelig) og intestinal villøs atrofi.
Gastrointestinal: colitis including cytomegalovirus colitis, (common), pancreatitis, (common) and intestinal villous atrophy.
Tilfælde af BK- virus associeret med nefropati såvel som tilfælde af JC- virus associeret med progessiv multifokal leukoencefalopati (PML) er blevet rapporteret hos patienter, der behandles med immunosuppressiva herunder Mycophenolate mofetil Teva.
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.
Der har været indberetninger om aplastisk anæmi og knoglemarvsdepression hos patienter behandlet med mycophenolatmofetil, hvor nogle har været fatale.
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.
4. 9 Overdosering
9 Hypersensitivity: hypersensitivity reactions, including angioneurotic oedema and anaphylactic reaction have been reported.
4. 4).
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).
5. 2).
5.
Farmakoterapeutisk klassifikation: immunsuppressive midler ATC kode L04AA06
LO4A A06
MPA er en potent, selektiv, ikke- kompetitiv og reversibel inhibitor af inosin- monophosfat- dehydrogenase og hæmmer derfor de novo vejen for en guanosin- nucleotid - syntese uden inkorporering i DNA.
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.
Da T - og B - lymfocytter i deres proliferation, i modsætning til andre celletyper, der kan anvende alternative veje, er helt afhængige af en de novo syntese af puriner, har MPA en mere potent cytostatisk virkning på lymfocytter end på andre celler.
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.
Som vist ved suppression af akut afstødning efter nyretransplantation er den immunosuppressive virkning af mycophenolatmofetil korreleret til MPA koncentrationen.
As evidenced by suppression of acute rejection following renal transplantation, the immunosuppressant activity of mycophenolate is correlated with MPA concentration.
Oral mycophenolatmofetils gennemsnitlige biotilgængelighed, baseret på MPA AUC, er 94% i forhold til intravenøs mycophenolatmofetil.
The mean bioavailability of oral mycophenolate mofetil, based on MPA AUC, is 94% relative to intravenous mycophenolate mofetil.
Føde har ingen effekt på absorptionen (MPA AUC) af mycophenolatmofetil, når det gives i doser på 1, 5 g to gange daglig til nyretransplantaterede patienter.
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.
MPA C max var dog nedsat med 40% i nærvær af føde.
However, MPA C max was decreased by 40% in the presence of food.
MPA metaboliseres hovedsageligt af glucuronyltransferase til et phenolglucuronid af MPA 8MPAG), som ikke er farmakologisk aktiv.
MPA is metabolised principally by glucuronyl transferase to form the phenolic glucuronide of MPA (MPAG), which is not pharmacologically active.
Ubetydelige mængder af stoffet udskilles som MPA (< 1% af dosis) i urinen.
10 A negligible amount of substance is excreted as MPA (< 1% of dose) in the urine.
93% af den administrerede dosis genfundet i urinen og 6% genfundet i fæces.
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.
Ved høje MPAG - koncentrationer (> 100 µg/ ml) fjernes dog mindre mængder MPAG.
However, at high MPAG plasma concentrations (> 100 g/ ml), small amounts of MPAG are removed.
40% lavere sammenlignet med den sene posttransplantationsperiode (3 – 6 måneder efter transplantationen).
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).
I en enkelt- dosis undersøgelse (6 personer per gruppe) blev middel plasma MPA AUC hos personer med svær, kronisk nyreinsufficiens (glomerulær filtrationsrate < 25 ml min- 1 1, 73 m- 2) observeret til 28- 75% højere i forhold til middelværdierne hos normale, sunde personer eller personer med mindre grad af nyreinsufficiens.
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.
Imidlertid var middel enkelt- dosis MPAG AUC 3- 6 gange højere hos personer med svær nyreinsufficiens end hos personer med let nyreinsufficiens eller normale, sunde personer svarende til den kendte renale udskillelse af MPAG.
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.