natgillin/translations-raw huggingface dataset:
Hos patienter med nedsat nyrefunktion, som får CellCept og ganciclovir, eller dets prodrugs, f. eks. valganciclovir, samtidig, bør dosisanbefalingerne for ganciclovir følges og patienterne bør monitoreres omhyggeligt.
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.
5. 2).
Oral contraceptives: the pharmacokinetics and pharmacodynamics of oral contraceptives were unaffected by coadministration of CellCept (see also section 5.2).
Hos patienter, som ikke fik ciclosporin, sås ved samtidig administration af CellCept og rifampicin et fald på 18- 70% i MPA- eksponeringen (AUC0- 12 timer).
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%.
For at opretholde den kliniske effekt bør MPA- eksponeringen overvåges, og CellCept- doserne justeres i forhold til dette, når rifampicin administreres samtidigt.
It is recommended to monitor MPA exposure levels and to adjust CellCept doses accordingly to maintain clinical efficacy when rifampicin is administered concomitantly.
4. 4).
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).
Når CellCept blev administreret samtidig med sevelamer, faldt MPA- Cmax og AUC0- 12 timer med henholdsvis 30% og 25%, dog uden at dette havde kliniske konsekvenser (f. eks. i form af transplantatafstødning).
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).
CellCept bør imidlertid administreres mindst én time før eller tre timer efter indtagelsen af sevelamer for at minimere dets indvirkning på MPA- absorptionen.
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.
Der er ingen data for administrationen af CellCept med andre phosphatbindere end sevelamer.
There is no data on CellCept with phosphate binders other than sevelamer.
Der blev ikke observeret nogen virkning på MPAs biotilgængelighed.
Trimethoprim/ sulfamethoxazole: no effect on the bioavailability of MPA was observed.
Der blev ikke observeret nogen signifikant interaktion hos raske frivillige, når CellCept blev administreret samtidigt med norfloxacin og metronidazol hver for sig.
Norfloxacin and metronidazole: in healthy volunteers, no significant interaction was observed when CellCept was concomitantly administered with norfloxacin and metronidazole separately.
30% efter én CellCept- dosis.
However, norfloxacin and metronidazole combined reduced the MPA exposure by approximately 30% following a single dose of CellCept.
Hos levertransplanterede patienter, der indledningsvis blev behandlet med CellCept og tacrolimus samtidigt, blev MPAs Cmax og AUC - CellCepts aktive metabolit - ikke signifikant påvirket af den samtidige administration af tacrolimus.
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.
20%, når flere CellCept- doser (1, 5 g to gange daglig) blev givet til patienter, som fik 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.
4. 4).
However, in renal transplant patients, tacrolimus concentration did not appear to be altered by CellCept (see also section 4.4).
Samtidig administration af probenecid og mycophenolatmofetil forhøjer MPAG' s plasma- AUC 3 gange hos aber.
Other interactions: co-administration of probenecid with mycophenolate mofetil in monkeys raises plasma AUC of MPAG by 3-fold.
Levende vacciner må ikke gives til patienter med nedsat immunforsvar.
Live vaccines: live vaccines should not be given to patients with an impaired immune response.
4. 4).
The antibody response to other vaccines may be diminished (see also section 4.4).
4. 6 Graviditet og amning
5 4.6 Pregnancy and lactation
Det anbefales, at behandling med CellCept ikke initieres før en negativ graviditetstest foreligger.
It is recommended that CellCept therapy should not be initiated until a negative pregnancy test has been obtained.
Effektiv antikonception skal anvendes før behandling med CellCept påbegyndes, under behandlingen
Effective contraception must be used before beginning CellCept therapy, during therapy, and for six weeks following discontinuation of therapy (see section 4.5).
Patienter bør instrueres i straks at kontakte deres læge, hvis graviditet opstår.
Patients should be instructed to consult their physician immediately should pregnancy occur.
Anvendelse af CellCept anbefales ikke under graviditet og bør begrænses til tilfælde, hvor der ikke findes andre, mere passende behandlinger.
The use of CellCept is not recommended during pregnancy and should be reserved for cases where no more suitable alternative treatment is available.
CellCept bør kun anvendes til gravide kvinder, hvis den potentielle fordel er større end den potentielle risiko for fostret.
CellCept should be used in pregnant women only if the potential benefit outweighs the potential risk to the foetus.
Der foreligger en begrænset mængde data om brugen af CellCept hos gravide kvinder.
There is limited data from the use of CellCept 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 CellCept 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 CellCept in combination with other immunosuppressants during pregnancy.
Tilfælde af spontane aborter er set hos patienter, der blev behandlet med CellCept.
Cases of spontaneous abortions have been reported in patients exposed to CellCept.
Det er påvist, at mycophenolat mofetil udskilles i mælken hos diegivende rotter.
Mycophenolate mofetil has been shown to be excreted in the milk of lactating rats.
4. 3).
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).
Følgende bivirkninger omfatter uønskede hændelser fra de kliniske undersøgelser:
The following undesirable effects cover adverse reactions from clinical trials:
4. 4).
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).
Maligniteter:
Malignancies:
4. 4).
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).
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% af de patienter som fik CellCept (2 eller 3 g daglig) sammen med andre immunsuppressive stoffer.
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.
Non - melanom hudcancer indtraf hos 3, 6% af patienterne og andre maligniteter hos 1, 1%.
Non-melanoma skin carcinomas occurred in 3.6% of patients; other types of malignancy occurred in 1.1% of patients.
Sammenlignet med data efter 1 år viste sikkerhedsdata for 3 år ingen uventede ændringer mht. hyppighed af malignitet hos nyre - og hjertetransplanterede patienter.
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.
Opportunistiske infektioner:
Opportunistic infections:
I kontrollerede kliniske studier hos nyre - (2 g data), hjerte - og levertransplanterede patienter, som blev fulgt i mindst 1 år, var de almindeligste opportunistiske infektioner hos patienter, som fik CellCept (2 g eller 3 g daglig) sammen med andre immunsupprimerende stoffer, mukokutane candidainfektioner, CMV- viræmi/ syndrom og herpes simplex- infektioner.
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.
Andelen af patienter med CMV- viræmi/ syndrom var 13, 5%.
The proportion of patients with CMV viraemia/ syndrome was 13.5%.
Børn og unge (2- 18 år):
Children and adolescents (aged 2 to 18 years):
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 CellCept to gange daglig.
However, the
Imidlertid var følgende behandlingsrelaterede bivirkninger hyppigere i den pædiatriske population, især hos børn under 6 år, sammenlignet med voksne: diarré, sepsis, leukopeni, anæmi og infektion.
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.
6 Ældre patienter (≥ 65 år):
Elderly patients (≥ 65 years):
Ældre patienter, som får CellCept som led i et kombinationsimmunsuppressivt 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 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.
Andre uønskede hændelser:
Other adverse reactions:
Uønskede hændelser, som var ” sandsynligt relateret ” eller ” muligt relateret ” til CellCept, og som rapporteredes hos ≥ 1/ 10 og hos ≥ 1/ 100 til < 1/ 10 af de patienter, der blev behandlet med CellCept 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 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.
Uønskede hændelser, som var ” sandsynligt relateret ” eller ” muligt relateret ” til CellCept, og som rapporteredes hos patienter, som blev behandlet med CellCept i kombination med ciclosporin og kortikosteroider i de kliniske nyre -, hjerte - og leverstudier
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
Inden for hver systemorganklasse er bivirkninger opstillet efter frekvens under anvendelse af følgende kategorier: meget almindelig (≥ 1/ 10); almindelig (≥ 1/ 100 til < 1/ 10); ikke almindelig (≥ 1/ 1. 000 til < 1/ 100); sjælden (≥ 1/ 10. 000 til < 1/ 1. 000); meget sjælden (< 1/ 10. 000), ikke kendt (kan ikke estimeres ud fra forhåndenværende data).
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).
Meget
Very common
Sepsis, gastrointestinal candidiasis, urinvejsinfektioner, herpes
Sepsis, gastrointestinal candidiasis, urinary tract infection, herpes simplex, herpes zoster
parasitære sygdomme
Common
simplex, herpes zoster Pneumoni, influenza, infektion i luftrøret, respiratorisk moniliasis, gastrointestinal infektion, candidiasis, gastroenteritis, infektion, bronkitis, pharyngitis, sinuitis, svampeinfektion i huden, hud candidiasis, vaginal candidiasis, rhinitis
Pneumonia, influenza, respiratory tract infection, respiratory moniliasis, gastrointestinal infection, candidiasis, gastroenteritis, infection, bronchitis, pharyngitis, sinusitis, fungal skin infection, skin candida, vaginal candidiasis, rhinitis
tumorer (inkl. cyster og polypper)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hudkræft, benignt neoplasme af huden
- Skin cancer, benign neoplasm of skin
Leukopeni, trombocytopeni, anæmi Pancytopeni, leukocytose
Blood and lymphatic system disorders Metabolism and nutrition disorders
Meget almindelig Almindelig
Very common Common Very common Common
- Acidose, hyperkaliæmi, hypokaliæmi, hyperglykæmi, hypomagnesæmi, hypocalcæmi, hyperkolesterolæmi, hyperlipæmi, hypophosphatæmi, hyperuricæmi, ægte gigt, anoreksi
Leucopenia, thrombocytopenia, anaemia Pancytopenia, leucocytosis - Acidosis, hyperkalaemia, hypokalaemia, hyperglycaemia, hypomagnesaemia, hypocalcaemia, hypercholesterolaemia, hyperlipidaemia, hypophosphataemia, hyperuricaemia, gout, anorexia
- Agitation, konfusion, depression, angst, abnorm tankevirksomhed, insomnia
- Agitation, confusional state, depression, anxiety, thinking abnormal, insomnia
Meget almindelig
Nervous system disorders
Kramper, hypertoni, tremor, somnolens, muskelsvaghed, svimmelhed, hovedpine, paræstesier, smagsforstyrrelser
- Convulsion, hypertonia, tremor, somnolence, myasthenic syndrome, dizziness, headache, paraesthesia, dysgeusia
Meget almindelig
Cardiac disorders
Takykardi
-
Meget
Common
sygdomme
Tachycardia
Luftveje, thorax
Vascular disorders
og mediastinum
Common
Pleural effusion, dyspnø, hoste
Hypotension, hypertension, vasodilatation
Mave - tarmkanalen
Respiratory, thoracic and mediastinal disorders Gastrointestinal disorders
Opkastning, abdominalsmerter, diarré, kvalme Gastrointestinal blødning, peritonitis, ileus, colitis, mavesår, ulcus duodeni, gastritis, oesophagitis, stomatitis, obstipation, dyspepsi, flatulens, opstød
- 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
- Hepatitis, icterus, hyperbilirubinæmi
- Hepatitis, jaundice, hyperbilirubinaemia
Hud og subkutane væv
Skin and subcutaneous tissue disorders Musculoskeletal and connective Tissue disorders Renal and urinary disorders
Meget almindelig Almindelig
Very common Common Very common Common Very common Common
- Hud hypertrofi, udslæt, acne, alopeci
- Skin hypertrophy, rash, acne, alopecia, - Arthralgia - Renal impairment
reaktioner på administrations - stedet
General disorders and administration site conditions
Ødemer, feber, kulderystelser, smerter, utilpashed, asteni
- Oedema, pyrexia, chills, pain, malaise, asthenia,
Forhøjede leverenzymer, forhøjet serum- creatinin, forhøjet laktatdehydrogenase, forhøjet serum- carbamid, forhøjede basiske phosphataser, vægttab
- Hepatic enzyme increased, blood creatinine increased, blood lactate dehydrogenase increased, blood urea increased, blood alkaline phosphatase increased, weight decreased
Note:
Note:
501 (2 g CellCept dagligt), 289 (3 g CellCept dagligt) og 277 (2 g i. v. / 3 g oral CellCept dagligt) patienter i fase III studier blev behandlet med henblik på forebyggelse af afstødelse efter henholdsvis nyre -, hjerte - og levertransplantation.
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.
Følgende bivirkninger omfatter uønskede hændelser fra erfaringer efter markedsføring:
The following undesirable effects cover adverse reactions from post-marketing experience:
De uønskede hændelser, som er indberettet om CellCept efter markedsføringen svarer til dem, som er set i de kontrollerede nyre -, hjerte - og levertransplantationsstudier.
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.
Mave- tarmkanalen: colitis inklusive cytomegalovirus colitis, (≥ 1/ 100 til < 1/ 10), pancreatitis, (≥ 1/ 100 til < 1/ 10) og intestinal villøs atrofi.
Gastrointestinal: colitis including cytomegalovirus colitis, (≥ 1/ 100 to < 1/ 10), pancreatitis, (≥ 1/ 100 to < 1/ 10) and intestinal villous atrophy.
Sygdomme relateret til immunsuppression: alvorlige livstruende infektioner inklusive meningitis, endocarditis, tuberkulose og atypisk mycobakteriel infektion.
Disorders related to immunosuppression: serious life-threatening infections including meningitis, endocarditis, tuberculosis and atypical mycobacterial infection.
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 CellCept.
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.
4. 4).
Agranulocytosis (≥ 1/ 1000 to < 1/ 100) and neutropenia have been reported; therefore, regular monitoring of patients taking CellCept is advised (see section 4.4).
Der har været indberetninger om aplastisk anæmi og knoglemarvsdepression hos patienter behandlet med CellCept, hvor nogle har været fatale.
There have been reports of aplastic anaemia and bone marrow depression in patients treated with CellCept, some of which have been fatal.
8 Hypersensitivitet:
Hypersensitivity:
4. 6
Congenital disorders: see further details in section 4.6.
4. 9 Overdosering
8 4.9 Overdose
I de tilfælde af overdosis, hvor der var uønskede hændelser, fandtes disse at være indenfor den kendte sikkerhedsprofil for lægemidlet.
In those overdose cases in which adverse events were reported, the events fall within the known safety profile of the medicinal product.
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).
4. 4).
If neutropenia develops, dosing with CellCept should be interrupted or the dose reduced (see section 4.4).
5. 2).
Bile acid sequestrants, such as cholestyramine, can remove MPA by decreasing the enterohepatic re- circulation of the drug (see section 5.2)..
Farmakoterapeutisk klassifikation: immunsuppressive midler ATC kode L04AA06
Pharmacotherapeutic group: immunosuppressive agents ATC code L04AA06
Mycophenolatmofetil er 2- morpholinoethyl- esteren af MPA.
Mycophenolate mofetil is the 2-morpholinoethyl ester of MPA.
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.
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 CellCept korreleret til MPA- koncentrationen.
As evidenced by suppression of acute rejection following renal transplantation, the immunosuppressant activity of CellCept is correlated with MPA concentration.
Oral mycophenolatmofetils gennemsnitlige biotilgængelighed, baseret på MPA- AUC, er 94% i forhold til i. v. mycophenolatmofetil.
The mean bioavailability of oral mycophenolate mofetil, based on MPA AUC, is 94% relative to IV 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 nyretransplanterede 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 Cmax var dog nedsat med 40% i nærvær af føde.
However, MPA Cmax was decreased by 40% in the presence of food.
MPA er ved klinisk relevante koncentrationer for 97% 's vedkommende bundet til plasma- albumin.
MPA at clinically relevant concentrations is 97% bound to plasma albumin.
Som et resultat af det enterohepatiske kredsløb observeres sekundære stigninger i plasma - koncentrationen af MPA sædvanligvis omkring 6- 12 timer efter indgift.
As a result of enterohepatic recirculation, secondary increases in plasma MPA concentration are usually observed at approximately 6 – 12 hours post-dose.
40% er associeret til den samtidige administration af colestyramin (4 g tre gange daglig), hvilket indikerer, at der er en betragtelig enterohepatisk recirkulation.
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.
MPA metaboliseres hovedsageligt af glucuronyltransferase til et phenolglucuronid af MPA (MPAG), 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.
A negligible amount of substance is excreted as MPA (< 1% of dose) in the urine.
Det meste (ca.
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.
87%) af den administrerede dosis udskilles i urinen som MPAG.
Most (about 87%) of the administered dose is excreted in the urine as MPAG.
MPA og MPAG i kliniske koncentrationer fjernes ikke med hæmodialyse.
9 At clinically encountered concentrations, MPA and MPAG are not removed by haemodialysis.
Ved høje MPAG- koncentrationer (> 100 μg/ ml) fjernes dog mindre mængder MPAG.
However, at high MPAG plasma concentrations (> 100µg/ 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 Cmax approximately 40% lower compared to the late post-transplant period (3 – 6 months post-transplant).