natgillin/translations-raw huggingface dataset:
4. 8 og 5. 1).
The available data on safety and efficacy are not sufficient to recommend the use of Rapamune in children and adolescents less than 18 years of age (see sections 4.8 and 5.1).
5. 2).
Limited pharmacokinetic information is available in children and adolescents (see section 5.2).
(> 65 år):
Use in elderly patients (> 65 years):
Kliniske undersøgelser af Rapamune inkluderede ikke et tilstrækkeligt antal patienter > 65 år til at kunne afgøre, om de vil respondere anderledes end yngre patienter.
Clinical studies of Rapamune 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.
Anvendelse til patienter med nyresvigt:
Use in patients with renal impairment:
5. 2).
No dosage adjustment is required (see section 5.2).
Anvendelse til patienter med hepatisk svækkelse:
Use in patients with hepatic impairment:
Sirolimus clearance kan være reduceret hos patienter med nedsat hepatisk funktion (se pkt.
The clearance of sirolimus may be reduced in patients with impaired hepatic function (see section 5.2).
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.
Det anbefales nøje at overvåge de laveste sirolimusniveauer i helblod hos patienter med nedsat hepatisk funktion (se Terapeutisk lægemiddelmonitorering).
It is recommended that sirolimus whole blood trough levels be closely monitored in patients with impaired hepatic function (see Therapeutic drug monitoring).
Det er ikke nødvendigt at ændre begyndelsesdosis af Rapamune.
It is not necessary to modify the Rapamune loading dose.
Terapeutisk lægemiddelmonitorering:
Therapeutic drug monitoring:
De fleste patienter, som fik 2 mg Rapamune 4 timer efter cyclosporin, havde laveste sirolimus helblodkoncentrationer i intervallet 4 til 12 ng/ ml (udtrykt som kromatografisk prøvemetodeværdi).
Most patients who received 2 mg of Rapamune 4 hours after ciclosporin had whole blood trough concentrations of sirolimus within the 4 to 12 ng/ ml target range (expressed as chromatographic assay values).
Optimal behandling kræver monitorering af terapeutisk lægemiddelkoncentration hos alle patienter.
Optimal therapy requires therapeutic drug concentration monitoring in all patients.
Sirolimusniveauer i helblod bør nøje monitoreres hos følgende patienter:
Whole blood sirolimus levels should be closely monitored in the following populations:
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.
Terapeutisk lægemiddelmonitorering bør ikke være den eneste årsag til at justere sirolimus behandling.
Therapeutic drug monitoring should not be the sole basis for adjusting sirolimus therapy.
Der bør være en nøje overvågenhed af kliniske tegn/ symptomer, vævsbiopsier og laboratorieparametre.
Careful attention should be made to clinical signs/ symptoms, tissue biopsies, and laboratory parameters.
5. 2).
To minimise 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).
Optimalt set bør regulering af Rapamune dosis være baseret på mere end en enkelt måling af laveste blodniveau målt > 5 dage efter en tidligere dosisændring.
Optimally, adjustments in Rapamune dosage should be based on more than a single trough level obtained > 5 days after a previous dosing change.
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).
Following the discontinuation of ciclosporin therapy, a target trough range of 12 to 20 ng/ ml (chromatographic assay) is recommended.
Cyclosporin hæmmer metaboliseringen af sirolimus, og følgelig vil sirolimusniveauerne falde ved ophør med cyclosporin, med mindre dosis af sirolimis øges.
Ciclosporin inhibits the metabolism of sirolimus, and consequently, sirolimus levels will decrease when ciclosporin is discontinued unless the sirolimus dose is increased.
Generelt vil det være nødvendigt at firedoble sirolimusdosis for at udligne både manglen på farmakokinetisk interaktion (dobbelt øgning) og det øgede immunsuppressive behov på grund af manglen på cyclosporin (dobbelt øgning).
On average, the sirolimus dose will need to be 4-fold higher to account for both the absence of the pharmacokinetic interaction (2-fold increase) and the augmented immunosuppressive requirement in the absence of ciclosporin (2-fold increase).
Dosis af sirolimus bør øges i samme takt, som cyclosporindosis ophører.
The rate at which the dose of sirolimus is increased should correspond to the rate of ciclosporin elimination.
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).
En indledende dosis bør overvejes i tillæg til en ny vedligeholdelsesdosis, når det er nødvendigt at øge laveste sirolimus koncentration væsentligt:
A loading dose should be considered in addition to a new maintenance dose when it is necessary to considerably increase sirolimus trough concentrations:
Indledende Rapamune dosis = 3 x (ny vedligeholdelsesbehandling - nuværende vedligeholdelsesbehandlingsdosis).
The
Den højeste Rapamune dosis givet på en hvilken som helst dag bør ikke overstige 40 mg.
3 maximum Rapamune dose administered on any day should not exceed 40 mg.
Hvis en forventet daglig dosis overstiger 40 mg på grund af tilføjelse af en indledende dosis, så bør den indledende dosis gives over 2 dage.
If an estimated daily dose exceeds 40 mg due to the addition of a loading dose, the loading dose should be administered over 2 days.
De laveste sirolimus koncentrationer bør overvåges i mindst 3 til 4 dage efter en indledende dose( r).
Sirolimus trough concentrations should be monitored at least 3 to 4 days after a loading dose(s).
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
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 anbefalede laveste 24- timers koncentrationsintervaller for sirolimus er baseret på kromatografiske metoder.
The recommended 24-hour trough concentration ranges for sirolimus are based on chromatographic methods.
Adskillige prøvemetoder metodologier har været anvendt til at måle helblodskoncentrationer af sirolimus.
Several assay methodologies have been used to measure the whole blood concentrations of sirolimus.
I den nærværende kliniske praksis, bliver koncentrationen af sirolimus i helblod målt ved både kromatografiske og immunologiske metodologier.
Currently in clinical practice, sirolimus whole blood concentration are being measured by both chromatographic and immunoassay methodologies.
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 om 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.
Alle sirolimus koncentrationer, der er nævnt i dette produktresume, er enten målt ved at anvende kromatografiske metoder eller omsat til kromatografiske metodeækvivalenter.
All sirolimus concentrations reported in this Summary of Product Characteristics were either measured using chromatographic methods or have been converted to chromatographic method equivalents.
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 utilised to determine the sirolimus trough concentrations.
Andre overvejelser i forbindelse med anvendelse:
Other considerations for use:
4. 5).
Ciclosporin (microemulsion) and other medicinal or non-medicinal products may interact with sirolimus (see section 4.5).
5. 1).
Rapamune has not been adequately studied in patients at high immunological risk (see section 5.1).
Cyclosporin, azathioprin, mycophenolat mofetil, kortikosteroider og cytotoksiske antistoffer.
Concomitant use with other immunosuppressive agents Sirolimus has been administered concurrently with the following agents in clinical studies: ciclosporin, azathioprine, mycophenolate mofetil, corticosteroids and cytotoxic antibodies.
Sirolimus i kombination med andre immunhæmmende stoffer er ikke grundigt undersøgt.
Sirolimus in combination with other immunosuppressive agents has not been extensively investigated.
5. 1).
Based on information from subsequent clinical trials, the use of Rapamune, mycophenolate mofetil, and corticosteroids, in combination with IL-2 receptor antibody (IL2R Ab) induction, is not recommended in the de novo renal transplant setting (see section 5.1).
Rapamune, kan vaccinationen 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.
In hepatically impaired patients, it is recommended that sirolimus whole blood trough levels be closely monitored.
Hos patienter med svært nedsat hepatisk funktion anbefales en reduktion i vedligeholdelsesdosis til halv dosis på grund af den nedsatte clearance (se pkt.
In patients with severe hepatic impairment, reduction in maintenance dose by one half is recommended based on decreased clearance (see sections 4.2 and 5.2).
2. 4 og 5. 2).
Since half-life is prolonged in these patients, therapeutic drug monitoring after a loading dose or a change of dose should be performed for a prolonged period of time until stable concentrations are reached (see sections 4.2 and 5.2).
4. 5).
Co-administration of sirolimus with strong inhibitors of CYP3A4 (such as ketoconazole, voriconazole, itraconazole, telithromycin or clarithromycin) or inducers of CYP3A4 (such as rifampin, rifabutin) is not recommended (see section 4.5).
4. 8).
4 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).
Oversuppression af immunsystemet kan også øge modtageligheden for infektion, inkl. opportunistiske infektioner, fatale infektioner og sepsis.
Oversuppression of the immune system can also increase susceptibility to infection including opportunistic infections, fatal infections, and sepsis.
BK- virus associeret nephropati og JC- virus
Patients treated with immunosuppressants, including Rapamune, are at increased risk for opportunistic infections (bacterial, fungal, viral and protozoal).
4 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).
Disse infektioner er ofte relateret til en høj, total immunosuppressiv belastning og kan medføre alvorlige eller fatale tilstande, som læger bør vurdere ved en differentialdiagnose hos immunosuppressive patienter med forringet 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.
Sikkerhed og effekt af Rapamune som immunosuppressiv behandling er ikke fastslået hos lever - og lungetransplantationspatienter, og derfor anbefales denne brug ikke.
The safety and efficacy of Rapamune as immunosuppressive therapy have not been established in liver or lung transplant patients, and therefore, such use is not recommended.
I to kliniske studier med de novo levertransplantationspatienter blev brugen af sirolimus plus cyclosporin eller tacrolimus forbundet med en stigning i hepatisk arterietrombose, oftest medførende afstødning eller død.
In two clinical studies in de novo liver transplant patients the use of sirolimus plus ciclosporin or tacrolimus was associated with an increase in hepatic artery thrombosis, mostly leading to graft loss or death.
Der har været rapporter om forringet eller forsinket sårheling hos patienter i behandling med Rapamune, herunder lymfocele og sårruptur.
There have been reports of impaired or delayed wound healing in patients receiving Rapamune, including lymphocele and wound dehiscence.
Baseret på data fra den medicinske litteratur kan patienter med et BMI på mere end 30 kg/ m2 have forøget risiko for unormal sårheling.
Patients with a BMI greater than 30 kg/ m2 may be at increased risk of abnormal wound healing based on data from the medical literature.
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.
Tilfælde af bronkial anastomose insufficiens, oftest fatal, er rapporteret hos de novo lungetransplanterede patienter, hvor sirolimus er brugt som del af en immunosuppressiv behandling.
Cases of bronchial anastomotic dehiscence, most fatal, have been reported in de novo lung transplant patients when sirolimus has been used as part of an immunosuppressive regimen.
4. 8).
Hypersensitivity reactions, including anaphylactic/ anaphylactoid reactions, angioedema, exfoliative dermatitis, and hypersensitivity vasculitis, have been associated with the administration of sirolimus (see section 4.8).
I sjældne tilfælde har samtidig administration af sirolimus og ACE- hæmmere medført angioneurotiske, ødemlignende reaktioner.
In rare cases, the concomitant administration of sirolimus and ACE inhibitors has resulted in angioneurotic oedema-type reactions.
Som normalt for patienter med øget risiko for hudkræft bør udsættelse for sollys og UV- lys begrænses ved at have beskyttende tøj på og bruge solfilter med høj beskyttelsesfaktor.
As usual for patients with increased 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.
Tilfælde af Pneumocystis carinii pneumoni er rapporteret hos patienter, der ikke modtog antimikrobisk profylakse.
Cases of Pneumocystis carinii pneumonia have been reported in patients not receiving antimicrobial prophylaxis.
Antimikrobisk profylakse bør derfor gives for Pneumocystis carinii i de første 12 måneder efter transplantationen.
Therefore, antimicrobial prophylaxis for Pneumocystis carinii pneumonia should be administered for the first 12 months following transplantation.
Forebyggelse af cytomegalovirus (CMV) anbefales i 3 måneder efter transplantationen, specielt til patienter med forhøjet risiko for CMV sygdom.
Cytomegalovirus (CMV) prophylaxis is recommended for 3 months after transplantation, particularly for patients at increased risk for CMV disease.
Anvendelse af Rapamune til nyretransplanterede patienter var forbundet med forhøjet serum - kolesterol og - triglycerid, som kan kræve behandling.
The use of Rapamune in renal transplant patients was associated with increased serum cholesterol and triglycerides that may require treatment.
Patienter, der får Rapamune, bør kontrolleres med laboratorieundersøgelser for hyperlipidæmi, og hvis hyperlipidæmi opdages, bør iværksættes efterfølgende intervention som f. eks. diæt, motion og lipid- sænkende stoffer.
Patients administered Rapamune should be monitored for hyperlipidemia using laboratory tests and if hyperlipidemia is detected, subsequent interventions such as diet, exercise, and lipid-lowering agents should be initiated.
Fordele og ulemper bør overvejes ved behandling af patienter med fastslået hyperlipidæmi, før immunhæmmende behandling inkl.
The risk/ benefit should be considered in patients with established hyperlipidemia before initiating an immunosuppressive regimen including
Rapamune påbegyndes.
5 Rapamune.
Tilsvarende bør fordele og ulemper ved fortsat behandling med Rapamune revurderes ved alvorlig refraktær hyperlipidæmi.
Similarly the risk/ benefit of continued Rapamune therapy should be re-evaluated in patients with severe refractory hyperlipidemia.
I kliniske undersøgelser viste samtidig administration af Rapamune og HMG- CoA reduktase - hæmmere og/ eller fibrater at være vel tolereret.
In clinical trials, the concomitant administration of Rapamune and HMG-CoA reductase inhibitors and/ or fibrates was well tolerated.
Under behandling med Rapamune bør patienter, der 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.
Nyrefunktionen bør monitoreres ved samtidig administration af Rapamune og cyclosporin.
Renal function should be monitored during concomitant administration of Rapamune and ciclosporin.
Passende regulering af den immunhæmmende behandling bør overvejes hos patienter med forhøjede serum - kreatinin niveauer.
Appropriate adjustment of the immunosuppression regimen should be considered in patients with elevated serum creatinine levels.
Der bør udvises forsigtighed ved samtidig indgivelse af disse stoffer, som er kendt for at have en skadelig virkning på nyrefunktionen.
Caution should be exercised when co-administering other agents that are known to have a deleterious effect on renal function.
5 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.
Patienter, som med held ophørte med cyclosporin, havde lavere serumkreatininniveauer og højere beregnede glomerulære filtrationsrater, samt lavere hyppighed af malignitet, i sammenligning med patienter i vedligeholdelsesbehandling med cyclosporin.
Patients who were successfully withdrawn from ciclosporin had lower serum creatinine levels and higher calculated glomerular filtration rates, as well as lower incidence of malignancy, compared to patients remaining on ciclosporin.
Fortsat, samtidig administration af cyclosporin og Rapamune som vedligeholdelsesbehandling kan ikke anbefales.
The continued co-administration of ciclosporin and Rapamune as maintenance therapy cannot be recommended.
Hos patienter med forsinket virkning af transplantatet, kan sirolimus forsinke genoprettelsen af nyrefunktionen.
In patients with delayed graft function, sirolimus may delay recovery of renal function.
Periodisk, kvantitativ monitorering af udskillelse af urinprotein anbefales.
Periodic quantitative monitoring of urinary protein excretion is recommended.
5. 1).
In a study evaluating conversion from calcineurin inhibitors to Rapamune in maintenance renal transplant patients, increased urinary protein excretion was commonly observed at 6 to 24 months after conversion to Rapamune (see section 5.1).
Ny fremkomst af nefrosis (nefrotisk syndrom) blev også rapporteret i 2% af patienterne i undersøgelsen (se pkt.
New onset nephrosis (nephrotic syndrome) was also reported in 2% of the patients in the study (see section 4.8).
Sikkerhed og effekt ved skift fra calcineurin hæmmere til Rapamune til nyretransplanterede patienter i vedligeholdelsesbehandling er ikke fastslået.
The safety and efficacy of conversion from calcineurin inhibitors to Rapamune in maintenance renal transplant patients have not been established.
Samtidig brug af Rapamune og calcineurinhæmmer øger muligvis risikoen for calcineurinhæmmer - induceret 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 metaboliseres i vid udstrækning af CYP3A4 isozym i tarmvæggen og leveren.
Sirolimus is extensively metabolised by the CYP3A4 isozyme in the intestinal wall and liver.
Sirolimus er også substrat for multistofudstrømningspumpen, P- glycoprotein (P- GP), i tyndtarmen.
Sirolimus is also a substrate for the multidrug efflux pump, P-glycoprotein (P-gp) located in the small intestine.
CYP3A4 hæmmere (som f. eks. ketoconazol, voriconazol, itraconazol, telithromycin eller clarithromycin) nedsætter metaboliseringen af sirolimus og øger sirolimus niveauerne.
Inhibitors of CYP3A4 (such as ketoconazole, voriconazole, itraconazole, telithromycin, or clarithromycin) decrease the metabolism of sirolimus and increase sirolimus levels.
CYP3A4 fremmere (som f. eks. rifampin eller rifabutin) øger metaboliseringen af sirolimus og nedsætter sirolimus niveauerne.
Inducers of CYP3A4 (such as rifampin or rifabutin) increase the metabolism of sirolimus and decrease sirolimus levels.
4. 4.).
Co-administration of sirolimus with strong inhibitors of CYP3A4 or inducers of CYP3A4 is not recommended (see section 4.4).
Cyclosporin (CYP3A4 substrat):
Ciclosporin (CYP3A4 substrate):
Absorptionshastighed og – mængde for sirolimus blev signifikant øget af cyclosporin A (CsA).
The rate and extent of sirolimus absorption was significantly increased by ciclosporin A (CsA).
183%, 141% og 80%.
Sirolimus administered concomitantly (5 mg), and at 2h (5 mg) and 4h (10 mg) after CsA (300 mg) resulted in increased sirolimus AUC by approximately 183%, 141% and 80% respectively.
Effekten af CsA afspejledes også i øget sirolimus Cmax og tmax.
The effect of CsA was also reflected by increases in sirolimus Cmax and tmax.
Indgivet 2 timer før administration af CsA påvirkede ikke sirolimus Cmax og AUC.
When given 2 hours before CsA administration, sirolimus Cmax and AUC were not affected.