natgillin/translations-raw huggingface dataset:
Data om levertransplanterede patienter er baseret på i. v. behandling med CellCept i op til 14 dage efterfulgt af oral behandling.
Data in hepatic transplant patients are based on i. v. dosing of CellCept for up to 14 days followed by oral dosing.
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 kliniske studier med nyre - (2 g data) 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) and hepatic transplant patients are listed in the following table.
18 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- og leverstudier
18 Adverse Reactions, Probably or Possibly Related to CellCept, Reported in Patients Treated with CellCept in Renal 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).
- Acidose, hyperkaliæmi, hypokaliæmi, hyperglykæmi, hypomagnesæmi, hypocalcæmi, hyperkolesterolæmi, hyperlipæmi, hypophosphatæmi, anoreksi
Leucopenia, thrombocytopenia, anaemia Pancytopenia, leucocytosis - Acidosis, hyperkalaemia, hypokalaemia, hyperglycaemia, hypomagnesaemia, hypocalcaemia, hypercholesterolaemia, hyperlipidaemia, hypophosphataemia, anorexia
- Depression, abnorm tankevirksomhed, insomnia
- Depression, thinking abnormal, insomnia
Kramper, hypertoni, tremor, somnolens, hovedpine, paræstesier
- Convulsion, hypertonia, tremor, somnolence, headache, paraesthesia
Takykardi
- Tachycardia
- Hypotension, hypertension
- Hypotension, hypertension
Luftveje, thorax og mediastinum
Respiratory, thoracic and mediastinal disorders Gastrointestinal disorders
- Pleural effusion, dyspnø, hoste
- Pleural effusion, dyspnoea, cough Vomiting, abdominal pain, diarrhoea, nausea Gastrointestinal haemorrhage, peritonitis, ileus, colitis, gastric ulcer, duodenal ulcer, gastritis, oesophagitis, stomatitis, constipation, dyspepsia, flatulence
Mave - tarmkanalen
Hepatobiliary disorders
Opkastning, abdominalsmerter, diarré, kvalme Gastrointestinal blødning, peritonitis, ileus, colitis, mavesår, ulcus duodeni, gastritis, oesophagitis, stomatitis, obstipation, dyspepsi, flatulens
- Hepatitis
Lever og galdeveje
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
- Hepatitis
- Rash, acne, alopecia, - Arthralgia -
Udslæt, acne, alopeci
Adverse drug reactions
Meget almindelig
Renal impairment
Forhøjede leverenzymer, forhøjet serum- creatinin, forhøjet laktatdehydrogenase, forhøjede basiske phosphataser, vægttab
- Hepatic enzyme increased, blood creatinine increased, blood lactate dehydrogenase increased, blood alkaline phosphatase increased, weight decreased
501 (2 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 - og levertransplantation.
501 (2 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 and hepatic transplantation, respectively.
Uønskede hændelser som kunne tilskrives den perifere intravenøse infusion var phlebitis og tromboser som begge blev observeret hos 4% af de patienter, som blev behandlet med CellCept 500 mg pulver til koncentrat til infusionsvæske, opløsning.
Adverse reactions attributable to peripheral venous infusion were phlebitis and thrombosis, both observed at 4% in patients treated with CellCept 500 mg powder for concentrate for solution for infusion.
De uønskede hændelser, som er indberettet om CellCept efter markedsføringen svarer til dem, som er set i de kontrollerede nyre -, hjerte - og levertransplantationsstudier.
Adverse reactions reported during post-marketing with CellCept are similar to those seen in the controlled renal and hepatic transplant studies.
Andre uønskede hændelser, som er indberettet efter markedsføringen beskrives nedenfor, med frekvenserne angivet i parentes, hvis de er kendt.
Additional adverse reactions reported during post- marketing experience with CellCept are described below with the frequencies reported within brackets if known.
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.
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).
Hæmodialyse forventes ikke at kunne fjerne klinisk signifikante mængder MPA eller MPAG.
20 Haemodialysis would not be expected to remove clinically significant amounts of MPA or MPAG.
5. 2).
Bile acid sequestrants, such as cholestyramine, can remove MPA by decreasing the enterohepatic re- circulation of the drug (see section 5.2).
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.
Moderstoffet mycophenolatmofetil kan måles systemisk under intravenøs infusion; efter oral administration er det dog under kvantifikationsgrænsen (0, 4 μg/ ml).
The parent substance mycophenolate mofetil can be measured systemically during intravenous infusion; however, after oral administration it is below the limit of quantitation (0.4 μ g/ ml).
Som et resultat af det enterohepatiske kredsløb observeres sekundære stigninger i plasmakoncentrationen 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 med 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 phenolglucoronid af MPA (MPAG), som ikke er farmakologisk aktivt.
MPA is metabolised principally by glucuronyl transferase to form the phenolic glucuronide of MPA (MPAG), which is not pharmacologically active.
Oralt administreret, radioaktivt mærket mycophenolatmofetil resulterede i fuldstændig genfinding af den administrerede dosis med 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 faeces.
MPA og MPAG i kliniske koncentrationer fjernes ikke med hæmodialyse.
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).
Efter intravenøs indgift af CellCept (1 g to gange daglig) til nyretransplanterede patienter i den tidlige posttransplantationsperiode var værdierne for MPA- AUC sammenlignelige med værdierne efter oral indgift af CellCept (1 g to gange daglig).
MPA AUC values obtained following administration of 1 g BID intravenous CellCept to renal transplant patients in the early post- transplant phase are comparable to those observed following 1 g BID oral CellCept.
Hos levertransplanterede patienter var MPA- AUC- værdierne efter i. v. administration af CellCept (1 g to gange daglig) efterfulgt af 1, 5 g to gange daglig oralt sammenlignelige med værdierne hos nyretransplanterede patienter, der fik oral CellCept (1 g CellCept to gange daglig).
In hepatic transplant patients, administration of 1 g BID intravenous CellCept followed by 1.5 g BID oral CellCept resulted in MPA AUC values similar to those found in renal transplant patients administered 1 g CellCept BID.
21 Nyreinsufficiens:
Renal impairment:
I en enkelt- dosis undersøgelse (6 patienter pr. gruppe) blev middel plasma MPA- AUC hos personer 2 med svær, kronisk nyreinsufficiens (glomerulær filtrationsrate < 25 ml• min- 1• 1, 73 m -) 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 21 renal impairment than in subjects with mild renal impairment or normal healthy subjects, consistent with the known renal elimination of MPAG.
Der findes ingen data for levertransplanterede patienter med svær, kronisk nyreinsufficiens.
No data are available for hepatic transplant patients with severe chronic renal impairment.
Hos patienter med forsinket renal transplantatfunktion post- transplantativt var middel MPA- AUC0 12 timer sammenlignelig med, hvad man så hos posttransplantations- patienter uden forsinket transplantatfunktion.
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.
CellCept' s farmakokinetik hos ældre er ikke blevet formelt undersøgt.
Pharmacokinetic behaviour of CellCept in the elderly has not been formally evaluated.
2 - 3 gange den systemiske eksponering (AUC eller Cmax) der er observeret hos nyretransplanterede patienter der fik den anbefalede kliniske dosis på 2 g daglig.
The highest dose tested in the animal carcinogenicity studies resulted in approximately 2 – 3 times the systemic exposure (AUC or Cmax) observed in renal transplant patients at the recommended clinical dose of 2 g/ day.
Den systemiske eksponering af denne dosis repræsenterer 2 til 3 gange den kliniske eksponering ved den anbefalede kliniske dosis på 2 g daglig.
The systemic exposure at this dose represents 2 – 3 times the clinical exposure at the recommended clinical dose of 2 g/ day.
0, 5 gange den kliniske eksponering af den anbefalede kliniske dosis på 2 g daglig.
The systemic exposure at this dose was approximately 0.5 times the clinical exposure at the recommended clinical dose of 2 g/ day.
22 Ved teratologiske undersøgelser på rotter og kaniner forekom der føtal resorption og misdannelser hos rotter ved 6 mg• kg- 1• dag- 1 (inkl. anophthalmi, agnathi og hydrocephalus) og hos kaniner ved 90 mg• kg- 1• dag- 1 (inkl. kardiovaskulære og nyre anomalier, såsom cordis ectopia og ectopiske nyrer og diafragma og umbilical brok) med fravær af maternel toksicitet.
The systemic
Den systemiske eksponering på disse niveauer er omtrent lig med eller mindre end 0, 5 gange den kliniske eksponering ved den anbefalede dosis på 2 g daglig.
22 exposure at these levels is approximately equivalent to or less than 0.5 times the clinical exposure at the recommended clinical dose of 2 g/ day.
Disse effekter forekom ved systemiske eksponeringsniveauer som er lig med eller mindre end de kliniske niveauer ved den anbefalede dosis på 2 g daglig.
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.
Den ikke- kliniske toksikologiske profil af mycophenolatmofetil forekommer i overenstemmelse med bivirkninger observerede i de humane kliniske undersøgelser som nu fremviser bivirkningsdata der er mere relevante for en patientpopulation (se 4. 8).
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).
Polysorbat 80 citronsyre saltsyre natriumchlorid
CellCept 500 mg powder for concentrate for solution for infusion: polysorbate 80 citric acid hydrochloric acid sodium chloride.
Pulver til koncentrat til infusionsvæske, opløsning:
Powder for concentrate for solution for infusion:
Rekonstitueret opløsning og infusionsopløsning:
Reconstituted solution and infusion solution:
Hvis infusionsopløsningen ikke er fremstillet umiddelbart før administrationen skal infusion af infusionsopløsningen påbegyndes senest 3 timer efter rekonstituering og fortynding af lægemidlet.
If the infusion solution is not prepared immediately prior to administration, the commencement of administration of the infusion solution should be within 3 hours from reconstitution and dilution of the medicinal product.
Opbevares ved temperaturer mellem 15- 30 °C.
Store at 15 – 30°C.
20 ml type I klare hætteglas med grå butylgummiprop og aluminiumhætte med plastikafrivningshætte.
20 ml type I clear glass vials with grey butyl rubber stopper and aluminium seals with plastic flip-off caps.
23 CellCept 500 mg pulver til koncentrat til infusionsvæske, opløsning, findes i pakninger med 4 hætteglas.
CellCept 500 mg powder for concentrate for solution for infusion is available in packs containing 4 vials.
6. 6 Regler for destruktion og anden håndtering
23 6.6 Special precautions for disposal and other handling
Fremstilling af infusionsopløsning (6 mg/ ml)
Preparation of Infusion Solution (6 mg/ ml)
CellCept 500 mg pulver til koncentrat til infusionsvæske, opløsning, indeholder ikke et antibakterielt konserveringsmiddel; derfor bør rekonstituering og fortynding af lægemidlet foregå under aseptiske forhold.
CellCept 500 mg powder for concentrate for solution for infusion does not contain an antibacterial preservative; therefore, reconstitution and dilution of the product must be performed under aseptic conditions.
CellCept 500 mg pulver til koncentrat til infusionsvæske, opløsning, skal fremstilles over to trin; første trin er rekonstituering med 5% glucose intravenøs infusionsvæske og andet trin er fortynding med 5% glucose intravenøs infusionsvæske.
CellCept 500 mg powder for concentrate for solution for infusion must be prepared in two steps: the first step is a reconstitution step with glucose intravenous infusion 5% and the second step is a dilution step with glucose intravenous infusion 5%.
Trin 1. a) Der skal anvendes 2 hætteglas CellCept 500 mg pulver til koncentrat til infusionsvæske, opløsning, til at fremstille en dosis på 1 g.
Two vials of CellCept 500 mg powder for concentrate for solution for infusion are used for preparing each 1 g dose.
Rekonstituer indholdet af hvert hætteglas ved at injicere 14 ml 5% glucose intravenøs infusionsvæske.
Reconstitute the content of each vial by injecting 14 ml of glucose intravenous infusion 5%.
Trin 2. a) Derefter fortyndes indholdet af de 2 rekonstiuerede hætteglas (ca.
Further dilute the content of the two reconstituted vials (approx.
2 x 15 ml) med 140 ml 5% glucose intravenøs infusionsvæske.
2 x 15 ml) into 140 ml of glucose intravenous infusion 5%.
Den endelige koncentration af opløsningen er 6 mg mycophenolatmofetil per ml.
The final concentration of the solution is 6 mg/ ml mycophenolate mofetil.
Da mycophenolatmofetil har demonstreret fosterbeskadigende virkning på rotter og kaniner, skal direkte kontakt af hud og slimhinder med opløsninger af CellCept 500 mg pulver til koncentrat til infusionsvæske, opløsning, undgås.
Because mycophenolate mofetil has demonstrated teratogenic effects in rats and rabbits, avoid direct contact of prepared solutions of CellCept 500 mg powder for concentrate for solution for infusion with skin or mucous membranes.
24 8.
24
14, februar 1996 Dato for sidste fornyelse af tilladelsen:
14 February 1996 Date of latest renewal:
CellCept 1 g/ 5 ml pulver til oral suspension.
CellCept 1 g/ 5 ml powder for oral suspension.
5 ml af den rekonstituerede suspension indeholder 1 g mycophenolatmofetil.
5 ml of the reconstituted suspension contains 1 g of mycophenolate mofetil.
CellCept 1 g/ 5 ml pulver til oral suspension er, i kombination med ciclosporin og kortikosteroider, indiceret til forebyggelse af akut transplantatafstødning hos patienter, der modtager allogene nyre -, hjerte - eller levertransplantater.
CellCept 1 g/ 5 ml powder for oral suspension is indicated in combination with ciclosporin and corticosteroids for the prophylaxis of acute transplant rejection in patients receiving allogeneic renal, cardiac or hepatic transplants.
Anvendelse ved nyretransplantation:
Use in renal transplant:
Oralt dosis af CellCept 1 g/ 5 ml pulver til oral suspension bør gives inden for 72 timer efter transplantation.
Adults: oral CellCept 1 g/ 5 ml powder for oral suspension should be initiated within 72 hours following transplantation.
Den anbefalede dosis til nyretransplanterede patienter er 1 g administreret to gange daglig (døgndosis, 2 g), dvs.
The recommended dose in renal transplant patients is 1 g administered twice daily (2 g daily dose), i. e.
5 ml oral suspension to gange daglig.
5 ml oral suspension twice daily.
Den anbefalede dosis af CellCept 1 g/ 5 ml pulver til oral suspension er 600 mg/ m2 administreret to gange daglig (højst 2 g/ 10 ml oral suspension daglig).
Children and adolescents (aged 2 to 18 years): the recommended dose of CellCept 1 g/ 5 ml powder for oral suspension is 600 mg/ m2 administered twice daily (up to a maximum of 2 g/ 10 ml oral suspension daily).
Anvendelse ved hjertetransplantation:
Use in cardiac transplant:
Oralt CellCept skal gives senest 5 dage efter transplantationen.
Adults: oral CellCept should be initiated within 5 days following transplantation.
Den anbefalede dosis til hjertetransplanterede patienter er 1, 5 g to gange daglig (døgndosis, 3 g).
The recommended dose in cardiac transplant patients is 1.5 g administered twice daily (3 g daily dose).
Der er ingen data vedrørende hjertetransplantationer hos børn.
Children: no data are available for paediatric cardiac transplant patients.
26 Voksne:
26 Use in hepatic transplant:
Den anbefalede dosis til levertransplanterede patienter er 1, 5 g to gange daglig (døgndosis, 3 g).
The recommended oral dose in hepatic transplant patients is 1.5 g administered twice daily (3 g daily dose).
Den anbefalede dosis på 1 g to gange daglig til nyretransplanterede patienter og 1, 5 g to gange daglig til hjerte - eller levertransplanterede patienter er passende til ældre.
Use in elderly (≥ 65 years): the recommended dose of 1 g administered twice a day for renal transplant patients and 1.5 g twice a day for cardiac or hepatic transplant patients is appropriate for the elderly.
Hos nyretransplanterede patienter med svær, kronisk nyreinsufficiens (glomerulær filtration < 25 ml• min- 1• 1, 73 m- 2), bortset fra i den umiddelbare post- transplantationsperiode, skal doser på mere end 1 g to gange dagligt undgås.
Use in renal impairment: 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.
Dosisregulering er ikke nødvendig hos patienter, der oplever forsinket nyretransplantatfunktion postoperativt (se pkt.
No dose adjustments are needed in patients experiencing delayed renal graft function post-operatively.
Der findes ingen data om hjerte - eller levertransplanterede patienter med svær, kronisk nyreinsufficiens.
No data are available for cardiac or hepatic transplant patients with severe chronic renal impairment.
Det er ikke nødvendigt med dosisjusteringer hos nyretransplanterede patienter med svær leverparenchymlidelse.
Use in severe hepatic impairment: no dose adjustments are needed for renal transplant patients with severe hepatic parenchymal disease.
Der findes ingen data for hjertetransplanterede patienter med svær leverparenchymlidelse
No data are available for cardiac transplant patients with severe hepatic parenchymal disease.
Behandling under afstødningsperioder:
Treatment during rejection episodes:
Afstødning af nyretransplantat medfører ikke ændringer af MPAs farmakokinetik; dosisreduktion eller afbrydelse af CellCept er ikke nødvendig.
Renal transplant rejection does not lead to changes in MPA pharmacokinetics; dosage reduction or interruption of CellCept is not required.
Bemærk Om nødvendigt kan CellCept 1 g/ 5 ml pulver til oral suspension gives via en næsesonde af minimum størrelse på 8 French (den indre diameter skal være mindst 1, 7 mm).
Note If required, CellCept 1 g/ 5 ml powder for oral suspension can be administered via a nasogastric tube with a minimum size of 8 French (minimum 1.7 mm interior diameter).
Generelt må det tilrådes, for at minimere risikoen for hudkræft, at udsættelse for sollys og UV- lys begrænses ved at bære beskyttende beklædning og anvende en solblokker med en høj beskyttelsesfaktor.
As general advice to minimise the risk for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing and using a sunscreen with a high protection factor.
Blandt de opportunistiske infektioner er BK- virus associeret med nefropati og JC- virus associeret med progressiv multifokal leukoencefalopati (PML).
Among the opportunistic infections are BK virus associated nephropathy and JC virus associated progressive
27 tage dette i betragtning i differentialdiagnosen hos immunosupprimerede patienter med svækket nyrefunktion eller neurologiske symptomer.
These infections are often related to a high total immunosuppressive burden and may lead to serious or fatal conditions that physicians should consider in the differential diagnosis in immunosuppressed patients with deteriorating renal function or neurological symptoms.