natgillin/translations-raw huggingface dataset:
Hvis nødvendigt kan patienten opbevare flasken ved stuetemperatur op til 25°C i en kort periode (24 timer).
If necessary, the patient may store the bottles at room temperatures up to 25 C for a short period of time (24 hours).
Ravfarvede type III glasflasker à 60 ml med sprøjteadapter og 30 ravfarvede doseringssprøjter i plastik.
60 ml type III amber glass bottles with syringe adapter and 30 amber, plastic dosing syringes.
Den korrekte mængde Rapamune tømmes fra sprøjten over i enten en glas - eller plastikbeholder med mindst 60 ml vand eller appelsinjuice.
Empty the correct amount of Rapamune from the syringe into only a glass or plastic container with at least 60 ml of water or orange juice.
Der må ikke anvendes andre væsker, inkl. grapefrugtjuice, til fortynding.
No other liquids, including grapefruit juice, should be used for dilution.
Beholderen fyldes igen med yderligere (minimum 120 ml) vand eller appelsinjuice, der omrøres kraftigt og drikkes med det samme.
Refill the container with an additional volume (minimum of 120 ml) of water or orange juice, stir vigorously, and drink at once.
14. marts 2001
14 March 2001 Date of latest renewal:
15. marts 2006
15 March 2006
Rapamune 1 mg overtrukne tabletter
Rapamune 1 mg coated tablets.
Hver tablet indeholder 1 mg sirolimus.
Each tablet contains 1 mg sirolimus.
Overtrukne tabletter
Coated tablet.
Hvide, trekantformede overtrukne tabletter mærket “ RAPAMUNE 1 mg ” på den ene side.
White coloured, triangular-shaped coated tablet marked “ RAPAMUNE 1 mg ” on one side.
Biotilgængeligheden er ikke fastlagt for tabletterne, hvis de knuses, tygges eller deles, og dette kan derfor ikke anbefales.
Bioavailability has not been determined for tablets after they have been crushed, chewed or split and therefore this cannot be recommended.
Foreslåede laveste cyclosporin koncentrationsniveauer i de første 2- 3 måneder efter transplantation er 150- 400 ng/ ml (monoklonal analyse eller tilsvarende teknik).
Suggested ciclosporin trough concentration ranges for the first 2-3 months after transplantation are 150 - 400 ng/ ml (monoclonal assay or equivalent technique).
Cyclosporin bør gradvis ophøre i løbet af 4- 8 uger, og dosis af Rapamune justeres for at opnå laveste helblodkoncentrationer på 12 til 20 ng/ ml (kromatografisk analyse; se Terapeutisk lægemiddelmonitorering).
Ciclosporin should be progressively discontinued over 4 to 8 weeks and the Rapamune dose should be adjusted to obtain whole blood trough levels of 12 to 20 ng/ ml
17 Anvendelse til sorte patienter:
Use in black recipients:
Anvendelse til børn og unge (< 18 år):
Use in children and adolescents ( 18 years):
Kliniske undersøgelser med Rapamune oral opløsning inkluderede ikke et tilstrækkeligt antal patienter > 65 år til at kunne afgøre, om de vil respondere anderledes end yngre patienter.
Clinical studies with Rapamune oral solution did not include a sufficient number of patients > 65 years of age to determine whether they will respond differently than younger patients.
Data for de laveste sirolimus blodkoncentrationer hos 35 nyretransplanterede patienter > 65 år var de samme som hos en voksenpopulation (n = 822) i alderen 18 til 65 år.
Sirolimus trough concentration data in 35 renal transplant patients > 65 years of age were similar to those in the adult population (n = 822) from 18 to 65 years of age.
Rapamune tabletter givet til 12 nyretransplanterede patienter > 65 år gav også samme resultater som hos voksne patienter (n= 167) i alderen 18 til 65 år.
Rapamune tablets administered to 12 renal transplant patients > 65 years of age also gave similar results to adult patients (n = 167) 18 to 65 years of age.
5. 2).
The clearance of sirolimus may be reduced in patients with impaired hepatic function (see section 5.2).
Hos patienter med svært nedsat hepatisk funktion anbefales det, at vedligeholdelsesdosen af Rapamune reduceres til omtrent det halve.
In patients with severe hepatic impairment, it is recommended that the maintenance dose of Rapamune be reduced by approximately one half.
4. 5) og eller (3) hvis cyclosporindosis reduceres markant eller ophører, da disse patientgrupper mest sandsynligt har specielle doseringskrav.
(1) in patients with hepatic impairment; (2) when inducers or inhibitors of CYP3A4 are concurrently administered and after their discontinuation (see section 4.5); and/ or (3) if ciclosporin dosing is markedly reduced or discontinued, as these populations are most likely to have special dosing requirements.
5. 2).
To minimize variability, Rapamune should be taken at the same time in relation to ciclosporin, 4 hours after the ciclosporin dose, and consistently either with or without food (see section 5.2).
Patienterne kan skiftes fra opløsning til tabletformuleringen på en mg til mg basis.
Patients can be switched from the solution to the tablet formulation on a mg per mg basis.
Det anbefales, at laveste blodkoncentration måles 1 til 2 uger efter at have skiftet formulering eller tabletstyrke for at bekræfte, at laveste koncentration er inden for det anbefalede målområde.
It is recommended that a trough concentration be taken 1 or 2 weeks after switching formulations or tablet strength to confirm that the trough concentration is within the recommended target range.
Hvis behandling med cyclosporin ophører, anbefales det at sigte på et niveau for laveste koncentration i blodet på 12 til 20 ng/ ml (kromatografisk prøve).
Ciclosporin inhibits the metabolism of sirolimus, and
Cyclosporin hæmmer metaboliseringen af sirolimus, og følgelig vil sirolimusniveauerne falde ved ophør med cyclosporin, med mindre dosis af sirolimis øges.
19 consequently, sirolimus levels will decrease when ciclosporin is discontinued unless the sirolimus dose is increased.
18 Hvis yderlig( ere) dosisjustering( er) er nødvendig( e) i løbet af vedligeholdelsesbehandling (efter ophør af cyclosporin), kan disse justeringer hos de fleste patienter baseres på simple forhold: ny Rapamune dosis = nuværende dosis x (mål for koncentration/ nuværende koncentration).
If further dose adjustment(s) are required during maintenance therapy (after discontinuation of ciclosporin), in most patients these adjustments can be based on simple proportion: new Rapamune dose = current dose x (target concentration/ current concentration).
Indledende Rapamune dosis = 3 x (ny vedligeholdelsesbehandling - nuværende vedligeholdelsesbehandlingsdosis).
Rapamune loading dose = 3 x (new maintenance dose – current maintenance dose).
Den højeste Rapamune dosis givet på en hvilken som helst dag bør ikke overstige 40 mg.
The maximum Rapamune dose administered on any day should not exceed 40 mg.
Hos patienter med svært nedsat hepatisk funktion bør monitorering udføres hver 5. til 7. dag efter dosisjustering eller efter initialdosis, indtil 3 på hinanden følgende helblodsniveauer har vist stabile koncentrationer af sirolimus, da opnåelse af steady- state forsinkes på grund af den forlængede halveringstid.
In patients with severe hepatic impairment, monitoring should be performed every 5 to 7 days until 3 consecutive trough levels have shown stable concentrations of sirolimus after dose adjustment or after loading dose due to the delay in reaching steady state because of the prolonged half-life.
De koncentrationer, der opnås ved disse forskellige metodologier er ikke enstydige.
The concentration values obtained by these different methodologies are not interchangeable.
Når der bruges en navnebeskyttet prøvemetode (et varemærke), bør fremstilleres information for at korrelere værdier til en reference kromatografisk prøvemetode altid anvendes.
When using a proprietary immunoassay system, always refer to the manufacturer’ s information to correlate values to a reference chromatographic assay.
Justeringer af målområdet bør foretages i henhold til den anvendte prøvemetode der bliver brugt til bestemmelse af sirolimuskoncentrationen.
Adjustments to the targeted range should be made according to the assay being utilized to determine the sirolimus trough concentrations.
Rapamune, kan vaccination være mindre effektiv.
During treatment with immunosuppressants, including Rapamune, vaccination may be less effective.
Hos patienter med nedsat hepatisk funktion anbefales det, at sirolimusniveauerne i helblod monitoreres omhyggeligt.
20 In hepatically impaired patients, it is recommended that sirolimus whole blood trough levels be closely monitored.
4. 8).
Increased susceptibility to infection and the possible development of lymphoma and other malignancies, particularly of the skin, may result from immunosuppression (see section 4.8).
Patienter behandlet med immunsuppressiva, herunder Rapamune, har øget risiko for opportunistiske infektioner (bakteriel, svamp, viral og protozoal).
Patients treated with immunosuppressants, including Rapamune, are at increased risk for opportunistic infections (bacterial, fungal, viral and protozoal).
BK- virus associeret nephropati og JC- virus associeret progressiv multifokal leukoencefalopati (PML) er blandt disse infektioner.
Among these conditions are BK virus associated nephropathy and JC virus associated progressive multifocal leukoencephalopathy (PML).
Der har også været rapporter om væskeansamlinger, inkl. perifert ødem, lymfeødem, pleuraekssudat og perikardiale ekssudater (herunder hæmodynamisk signifikant ekssudat hos børn og voksne) hos patienter i behandling med Rapamune.
There have also been reports of fluid accumulation, including peripheral oedema, lymphoedema, pleural effusion and pericardial effusions (including haemodynamically significant effusions in children and adults), in patients receiving Rapamune.
Forebyggelse af cytomegalovirus (CMV) anbefales i 3 måneder efter transplantationen, specielt til patienter med forhøjet risiko for CMV sygdom.
21 Cytomegalovirus (CMV) prophylaxis is recommended for 3 months after transplantation, particularly for patients at increased risk for CMV disease.
Fordele og ulemper bør overvejes ved behandling af patienter med fastslået hyperlipidæmi, før immunhæmmende behandling
The risk/ benefit should be considered in patients with established hyperlipidemia before initiating an immunosuppressive regimen including Rapamune.
Under behandling med Rapamune bør patienter, som får en HMG- CoA reduktase- hæmmer og/ eller fibrat, kontrolleres for mulig udvikling af rhabdomyolyse eller andre bivirkninger, som er beskrevet i de respektive produktresuméer for disse stoffer.
During Rapamune therapy, patients administered an HMG-CoA reductase inhibitor and/ or fibrate, should be monitored for the possible development of rhabdomyolysis and other adverse effects as described in the respective Summary of Product Characteristics of these agents.
Hos patienter, hvor behandling med cyclosporin og Rapamune udover 3 måneder havde højere serumkreatininniveauer og lavere beregnede glomerulære filtrationsrater i sammenligning med kontrolpatienter behandlet med cyclosporin og placebo eller azathioprin.
Patients treated with ciclosporin and Rapamune beyond 3 months had higher serum creatinine levels and lower calculated glomerular filtration rates compared to patients treated with ciclosporin and placebo or azathioprine controls.
Samtidig brug af Rapamune og calcineurinhæmmer øger muligvis risikoen for calcineurinhæmmerinduceret hæmolytisk uræmisk syndrom/ trombotisk trombocytopenisk purpura/ trombotisk mikroangiopati (HUS/ TTP/ TMA).
The concomitant use of Rapamune with a calcineurin inhibitor may increase the risk of calcineurin inhibitor-induced haemolytic uraemic syndrome/ thrombotic thrombocytopenic purpura/ thrombotic microangiopathy (HUS/ TTP/ TMA).
Sirolimus tabletter indeholder sukrose og laktose.
Sirolimus tablets contain sucrose and lactose.
Hos patienter med en anamnese med sukrase insufficiens, isomaltase insufficiens, fruktose intolerans, glukose malabsorption, galaktose malabsorption, galaktose intolerans (f. eks. galaktosæmi) eller Lap laktase mangel bør der foretages en omhyggelig vurdering af fordele og ulemper, før sirolimus tabletter ordineres.
In those patients with a history of sucrase insufficiency, isomaltase insufficiency, fructose intolerance, glucose malabsorption, galactose malabsorption, galactose intolerance (e. g., galactosemia), or Lapp lactase deficiency, a careful risk/ benefit assessment should be performed prior to prescribing sirolimus tablets.
Sirolimus metaboliseres i vid udstrækning af CYP3A4 isozym i tarmvæggen og leveren.
Sirolimus is extensively metabolized by the CYP3A4 isozyme in the intestinal wall and liver.
CYP3A4 hæmmere (som f. eks. ketoconazol, voriconazol, itraconazol, telithromycin eller clarithromycin) nedsætter metaboliseringen af sirolimus og øger sirolimus niveauerne.
22 telithromycin, or clarithromycin) decrease the metabolism of sirolimus and increase sirolimus levels.
Sirolimus absorptionshastighed og – mængde blev signifikant øget af cyclosporin A (CsA).
The rate and extent of sirolimus absorption was significantly increased by ciclosporin A (CsA).
21 (microemulsion) farmakokinetik hos sunde frivillige personer ved indgivelse samtidig eller med 4 timers mellemrum.
Single-dose sirolimus did not affect the pharmacokinetics of ciclosporin (microemulsion) in healthy volunteers when administered simultaneously or 4 hours apart.
Rifampicin (CYP3A4 fremmer):
Rifampicin (CYP3A4 inducer):
4, 4 gange, 1, 4 gange og 10, 9 gange.
Multiple-dose ketoconazole administration significantly affected the rate and extent of absorption and sirolimus exposure from Rapamune oral solution as reflected by increases in sirolimus Cmax, tmax, and AUC of 4.4-fold, 1.4-fold, and 10.9-fold, respectively.
Diltiazem (CYP3A4 hæmmer):
Diltiazem (CYP3A4 inhibitor):
Ingen klinisk signifikant, farmakokinetisk interaktion blev observeret mellem Rapamune oral opløsning og 0, 3 mg norgestrel/ 0, 03 mg etinyløstradiol.
No clinically significant pharmacokinetic interaction was observed between Rapamune oral solution and 0.3 mg norgestrel/ 0.03 mg ethinyl estradiol.
Skønt resultaterne af interaktionsundersøgelser med en enkelt dosering med et oralt antikonceptionsmiddel ikke tyder på farmakokinetisk interaktion, kan resultaterne ikke udelukke ændringer i farmakokinetikken, som kan påvirke effekten af orale antikonceptionsmidler ved langtidsbehandling med Rapamune.
Although the results of a single dose drug interaction study with an oral contraceptive suggest the lack of a pharmacokinetic interaction,
Andre mulige interaktioner Moderate og svage CYP3A4 hæmmere kan nedsætte metaboliseringen af sirolimus og øge sirolimusniveauet (f. eks. kalcium- blokkere: verapamil; antisvampemidler: clotrimazol, fluconazol; antibiotika: troleandomycin; andre stoffer: bromocriptin, cimetidin, danazol, protease- hæmmere).
23 the results cannot exclude the possibility of changes in the pharmacokinetics that might affect the efficacy of the oral contraceptive during long term treatment with Rapamune.
John’ s urt (Hyperikum perforatum) antikrampemidler: carbamazepin, phenobarbital, phenytoin).
John's wort, (Hypericum perforatum), anticonvulsants: carbamazepine, phenobarbital, phenytoin).
Skønt sirolimus hæmmer det humane levermikrosomale cytokrom P450, CYP2C9, CYP2C19, CYP2D6 og CYP3A4/ 5 in vitro, forventes det aktive indholdsstof ikke at hæmme aktiviteten af disse isozymer in vivo, eftersom de sirolimus koncentrationer, som er nødvendige for hæmningen er meget højere end koncentrationerne set hos patienter, der får terapeutiske doser af Rapamune.
Although sirolimus inhibits human liver microsomal cytochrome P450 CYP2C9, CYP2C19, CYP2D6, and CYP3A4/ 5 in vitro, the active substance is not expected to inhibit the activity of these isozymes in vivo since the sirolimus concentrations necessary to produce inhibition are much higher than those observed in patients receiving therapeutic doses of Rapamune.
22 Grapefrugtjuice påvirker CYP3A4 formidlet metabolisering og bør derfor undgås.
Grapefruit juice affects CYP3A4 mediated metabolism and should therefore be avoided.
De hyppigst rapporterede bivirkninger (forekommer hos > 10% af patienterne) er trombocytopeni, anæmi, pyreksi, hypertension, hypokaliæmi, hypofosfatæmi, urinvejsinfektion, hyperkolesterolæmi, hyperglykæmi, hypertriglyceridæmi, abdominalsmerter, lymfocele, perifert ødem, artralgi, akne, diarré, smerte, forstoppelse, kvalme, hovedpine, øget kreatinin i blodet og øget laktatdehydrogenase (LDH).
The most commonly reported adverse drug reactions (occuring in > 10% of patients) are thrombocytopenia, anaemia, pyrexia, hypertension, hypokalaemia, hypophosphataemia, urinary tract infection, hypercholesterolaemia, hyperglycaemia, hypertriglyceridaemia, abdominal pain, lymphocoele, peripheral oedema, arthralgia, acne, diarrhoea, pain, constipation, nausea, headache, increased blood creatinine, and increased blood lactate dehydrogenase (LDH).
I nedenstående tabel angives de bivirkninger, der er baseret på erfaringer fra kliniske forsøg og erfaringer fra perioden efter markedsføringen, efter organklasse og hyppighed.
24 Adverse reactions based on experience from clinical trials and postmarketing experience are presented in the following table by system organ class and frequency of occurrence.
Sepsis Lungebetændelse Pyelonephritis Herpes simplex Svampe -, virale og bakterielle
Sepsis Pneumonia Pyelonephritis Herpes simplex Fungal, viral, and bacterial infections (such as mycobacterial infections, including tuberculosis, Epstein-Barr virus, CMV, and Herpes zoster)
Lymfom/ lymfoproli ferative sygdomme efter transplantation
Lymphoma / post transplant lymphoproliferative disorder
Trombotisk trombocytopenisk purpura/ hæmolytisk uræmisk syndrom Leukopeni Neutropeni
Thrombotic thrombocytopenic purpura/ haemolytic uraemic syndrome Leukopenia Neutropenia
4. 4)
Hypersensitivity reactions, including anaphylactic/ anaphylactoid reactions, angioedema, exfoliative dermatitis, and hypersensitivity vasculitis (see section 4.4)
Metabolisme og ernæring
25 System Organ Class
Hypokaliæmi Hypofosfatæmi Hypercholesterolæmi Hyperglykæmi Hypertriglyceridæmi
Very common ( 1/ 10)
Takykardi
Metabolism and Hypokalaemia nutrition disorders
Perikardialt ekssudat (inkl. hæmodynamisk signifikant ekssudat hos børn og voksne)
Hypophosphataemia Hypercholesterolaemia Hyperglycaemia Hypertriglyceridaemia
Vaskulære sygdomme
Nervous system disorders
Lymfocele Hypertension
Headache
Dyb venetrombose
Cardiac disorders
Lungeemboli
Tachycardia
Lymfeødem
Pericardial effusion (including haemodynamically significant effusions in children and adults)
Luftveje, thorax og mediastinum
Vascular disorders Respiratory, thoracic, and mediastinal disorders
Stomatitis 24
Stomatitis
Unormale lever - funktionsprøver
Liver function tests abnormal
Knogler, led, muskler og bindevæv
Musculoskeletal Arthralgia and connective tissue disorders
Almene symptomer og reaktioner på administra - tionsstedet
Renal and urinary disorders General Oedema peripheral disorders and Pyrexia administration Pain site conditions
Perifert ødem Pyreksi Smerte
Proteinuria Impaired healing Oedema
Nedsat heling Ødem
Nephrotic syndrome (see section 4.4)
Øget laktatdehydrogenase Øget kreatinin i blodet
Investigations Blood lactate dehydrogenase increased Blood creatinine increased
Øget aspartataminotransf erase Øget alaninaminotransfer ase
Aspartate aminotransferase increased Alanine aminotransferase increased
Hos patienter behandlet med immunsuppressiva, herunder Rapamune, er der rapporteret tilfælde af både BK- virus associeret nephropati og JC- virus associeret progressiv multifokal leukoencefalopati (PML).
26 Cases of BK virus associated nephropathy, as well as cases of JC virus associated progressive multifocal leukoencephalopathy (PML), have been reported in patients treated with immunosuppressants, including Rapamune.
Risikoen kan øges, når det laveste sirolimusniveau stiger.
The risk may increase as the trough sirolimus level increases.
Sjældne tilfælde af fatal hepatisk nekrose er rapporteret, når det laveste sirolimusniveau stiger.
Rare reports of fatal hepatic necrosis have been reported with elevated trough sirolimus levels.
Samtidig brug af sirolimus og calcineurinhæmmer øger muligvis risikoen for calcineurinhæmmerinduceret HUS/ TTP/ TMA.
The concomitant use of sirolimus with a calcineurin inhibitor may increase the risk of calcineurin inhibitor-induced HUS/ TTP/ TMA.
Der var en højere frekvens af alvorlige bivirkninger inkl.
In an ongoing study evaluating the safety and efficacy of conversion from calcineurin inhibitors to sirolimus (target levels of 12 - 20 ng/ mL) in maintenance renal transplant patients, enrollment was stopped in the subset of patients (n=90) with a baseline glomerular filtration rate of less than 40 mL/ min (see section 5.1).
25 pneumoni, akut afstødelse, graft- tab og død i gruppen behandlet med sirolimus (n=60, mediantid efter transplantation 36 måneder).
There was a higher rate of serious adverse events including pneumonia, acute rejection, graft loss and death in this sirolimus treatment arm (n=60, median time post-transplant 36 months).
Sikkerheden blev vurderet i et kontrolleret klinisk forsøg, hvor der var inkluderet nyretransplanterede patienter på < 18 år, som ansås for at have en høj immunologisk risiko, defineret som havende én eller flere akutte episoder med allograftafstødning i anamnesen og/ eller med tilstedeværelsen af kronisk allograftnefropati bekræftet ved nyrebiopsi (se afsnit 5. 1).
Safety was assessed in a controlled clinical trial enrolling renal transplant patients  18 years of age considered of high-immunologic risk, defined as a history of one or more acute allograft rejection episodes and/ or the presence of chronic allograft nephropathy on a renal biopsy (see section 5.1).
Brugen af Rapamune i kombination med calcineurinhæmmere og kortikosteroider blev forbundet med en øget risiko for svækkelse af nyrefunktionen, abnorme niveauer af serumlipider (herunder, men ikke begrænset til, forhøjede niveauer af serumtriglycerider og serumkolesterol) samt urinvejsinfektioner.
The use of Rapamune in combination with calcineurin inhibitors and corticosteroids was associated with an increased risk of deterioration of renal function, serum lipid abnormalities (including but not limited to increased serum triglycerides and cholesterol), and urinary tract infections.
Af de 89 patienter, der var konstateret EBV- seronegative inden transplantationen, udviklede 13 (15, 6%) PTLD.
27 Among 89 patients known to be EBV seronegative prior to transplantation, 13 (15.6%) were reported to have developed PTLD.
I måned 12, 24 og 36 var graft - og patientoverlevelsen den samme for begge grupper.
At 12, 24 and 36 months, graft and patient survival were similar for both groups.
Den gennemsnitlige beregnede glomerulære filtrationshastighed (GFR) i måned 12, 24, 36, 48 og 60 var signifikant større for de patienter, som fik Rapamune efter cyclosporin- elimination end hos den behandlingsgruppe, som fik Rapamune med cyclosporin.
The mean calculated glomerular filtration rate (GFR) at 12, 24, 36, 48 and 60 months was significantly higher for patients receiving Rapamune following ciclosporin elimination than for those in the Rapamune
Efter 60 måneder var forekomsten af cancer, som ikke var hudcancer, signifikant højere i den patientgruppe, som fortsatte med at tage cyclosporin, end i den patientgruppe, hvor cyclosporin blev seponeret (henholdsvis 8, 4% over for 3, 8%).
By 60 months, the incidence of non-skin malignancies was significantly higher in the cohort who continued ciclosporin as compared with the cohort who had ciclosporin withdrawn (8.4% vs.
27 I to kliniske multicenterforsøg havde de novo nyretransplanterede patienter, som blev behandlet med Rapamune, mycophenolat mofetil, kortikosteroider og en IL- 2- receptorantagonist, en signifikant højere akut rejektionsfrekvens og en numerisk højere dødsfrekvens end de patienter, som blev behandlet med en calcineurinhæmmer, mycophenolat mofetil, kortikosteroider og en IL- 2 - receptorantagonist (se pkt.
In two multi-centre clinical studies, de novo renal transplant patients treated with Rapamune, mycophenolate mofetil (MMF), corticosteroids, and an IL-2 receptor antagonist had significantly higher acute rejection rates and numerically higher death rates compared to patients treated with a calcineurin inhibitor, MMF, corticosteroids, and an IL-2 receptor antagonist (see section 4.4).