natgillin/translations-raw huggingface dataset:
multiorgan svigt, influenza lignende symptomer, temperaturintolerans, trykken for brystet, nevøsitet, fremmedfølelse, øget blod lactatdehydrogenase, vægtfald
and administration site conditions asthenic conditions, febrile disorders, oedema, pain and discomfort, blood alkaline phosphatase increased, weight increased, body temperature perception disturbed
Sjældne:
uncommon:
Erfaringerne er begrænsede.
Experience with over dosage is limited.
Tremor, hovedpine, kvalme og opkastninger, infektioner, urticaria, lethargi, forhøjet blodurinstof samt forhøjet serumkreatinin og øget alanin- aminotransferase.
Several cases of accidental over dosage have been reported; symptoms have included tremor, headache, nausea and vomiting, infections, urticaria, lethargy, increased blood urea nitrogen and elevated serum creatinine concentrations, and increase in alanine aminotransferase levels.
Der findes ingen specifik antidot til < [(Sær) navn] > behandling.
No specific antidote to< Invented name > therapy is available.
I tilfælde af overdosering må man benytte almene understøttende midler og symptomatisk behandling.
If over dosage occurs, general supportive measures and symptomatic treatment should be conducted.
Som følge af den høje molekylevægt, den ringe vandopløselighed og stærke binding til erythrocytter og plasmaprotein vil < [(Sær) navn] > ikke være dialysabelt.
Based on its high molecular weight, poor aqueous solubility, and extensive erythrocyte and plasma protein binding, it is anticipated that tacrolimus will not be dialysable.
Ved peroral overdosering kan maveskylning og/ eller indgift aborberende sfoffer (så som medicinsk kul) forsøges kort tid efter indtagelse.
In cases of oral intoxication, gastric lavage and/ or the use of adsorbents (such as activated charcoal) may be helpful, if used shortly after intake.
Macrolid immunosuppressant, ATC- kode:
Macrolide immunosuppressant, ATC code:
Virkningsmekanisme og farmakodynamisk effekt På molekylært niveau synes virkningen af tacrolimus at være medieret af binding til cytosol protein (FKBP12), som også er ansvarlig for den intracellulære akkumulering af præparatet.
Mechanism of action and pharmacodynamic effects At the molecular level, the effects of tacrolimus appear to be mediated by binding to a cytosolic protein (FKBP12) which is responsible for the intracellular accumulation of the compound.
FKBP12- tacrolimus komplekset bindes specifikt, kompetitivt hæmmende til calcineurin, hvilket medfører en calciumafhængig hæmning af T- cellernes signaltransduktion, således at transkriptionen af visse lymfokingener forhindres.
The FKBP12-tacrolimus complex specifically and competitively binds to and inhibits calcineurin, leading to a calcium-dependent inhibition of T-cell signal transduction pathways, thereby preventing transcription of a discrete set of lymphokine genes.
Tacrolimus hæmmer specielt dannelsen af cytotoksiske lymfocytter, som er hovedansvarlig for transplantat afstødning.
26 In particular, tacrolimus inhibits the formation of cytotoxic lymphocytes, which are mainly responsible for graft rejection.
Tacrolimus hæmmer T- celleaktivering og T- hjælpercelle afhængig B - celleproliferation, samt dannelsen af lymfokiner (såsom interleukin- 2 og - 3 og γ- interferon) og nedreguleringen af interleukin- 2 receptorer.
Tacrolimus suppresses T-cell activation and T-helper-cell dependent B-cell proliferation, as well as the formation of lymphokines (such as interleukins-2, -3, and γ -interferon) and the expression of the interleukin-2 receptor.
Resultater fra publicerede data fra anden primær organtransplantation < [(Sær) navn] > er blevet en accepteret behandling som primært immunosuppressivum i forbindelse med pancreas, lunge og intestinale transplantationer.
Results from published data in other primary organ transplantation< Invented name > has evolved into an accepted treatment as primary immunosuppressive medicinal product following pancreas, lung and intestinal transplantation.
26 Lungetransplantation Interimanalysen af et nyligt afsluttet multicenterstudie omfatter 110 patienter der blev randomiseret i forholdet 1: 1 til enten tacrolimus eller ciclosporin.
Lung transplantation The interim analysis of a recent multicentre study discussed 110 patients who underwent 1:1 randomisation to either tacrolimus or ciclosporin.
Tacrolimus blev startet som kontinuerlig intravenøs infusion i doser på 0, 01 mg – 0, 03 mg/ kg/ dag derpå blev peroral tacrolimus administreret i doser på 0, 05 – 0, 3 mg/ kg/ dag.
Tacrolimus was started as continuous intravenous infusion at a dose of 0.01 to 0.03 mg/ kg/ day and oral tacrolimus was administered at a dose of 0.05 to 0.3 mg/ kg/ day.
Det første år efter transplantationen blev der rapporteret en lavere incidens af akutte afstødningsepisoder for tacrolimus - versus ciclosporinbehandlede patienter (11, 5% versus 22, 6%) og en lavere incidens af kronisk afstødning, bronchiolitis obliterans syndromet (2, 86% versus 8, 57%).
A lower incidence of acute rejection episodes for tacrolimus- versus ciclosporin- treated patients (11.5% versus 22.6%) and a lower incidence of chronic rejection, the bronchiolitis obliterans syndrome (2.86% versus 8.57%), was reported within the first year after transplantation.
Tacrolimus blev startet som kontinuerlig intravenøs infusion med doser på 0, 025 mg/ kg/ dag, peroral tacrolimus blev administreret i doser på 0, 15 mg/ kg/ dag med følgende dosisjustering for at nå dalkoncentrationer på10- 20 ng/ ml.
Tacrolimus was started as continuous intravenous infusion at a dose of 0.025 mg/ kg/ day and oral tacrolimus was administered at a dose of 0.15 mg/ kg/ day with subsequent dose adjustments to target trough levels of 10 to 20 ng/ ml.
Man så obliterativ bronchiolitis i 21, 7% af patienterne i tacrolimus sammenlignet med 38, 0% af patienterne i ciclosporingruppen (p=0, 025).
Obliterative bronchiolitis developed in 21.7% of patients in the tacrolimus group compared with 38.0% of patients in the ciclosporin group (p = 0.025).
Signifikant flere patienter i ciclosporingruppen (n=13) måtte overføres til tacrolimus end tacrolimusbehandlede patienter, der måtte overføres til ciclosporin (n=2) (p=0, 02) (Keenan et al.; Ann Thoracic Surg 1995; 60: 580).
Significantly more ciclosporin-treated patients (n = 13) required a switch to tacrolimus than tacrolimus-treated patients to ciclosporin (n = 2) (p = 0.02) (Keenan et al., Ann Thoracic Surg 1995; 60:580).
I yderligere et 2- center studie, blev 26 patienter randomiseret til tacrolimus versus 24 patienter til ciclosporin.
In an additional two-centre study, 26 patients were randomised to the tacrolimus versus 24 patients to the ciclosporin group.
Tacrolimus startede som kontinuerlig intravenøs infusion med doser på 0, 05 mg/ kg/ dag hvorefter oral tacrolimus blev administreret i doser på 0, 1 – 0, 3 mg/ kg/ dag med følgende dosisjustering for at nå dalkoncentrationer på 12 – 15 ng/ ml.
Tacrolimus was started as continuous intravenous infusion at a dose of 0.05 mg/ kg/ day and oral tacrolimus was administered at a dose of 0.1 to 0.3 mg/ kg/ day with subsequent dose adjustments to target trough levels of 12 to 15 ng/ ml.
1- års overlevelsesrater var 73, 1% i tacrolimusgruppen versus 79, 2% i ciclosporingruppen.
The 1-year survival rates were 73.1% in the tacrolimus versus 79.2% in the ciclosporin group.
Fravær af akut afstødning var højere i tacrolimusgruppen ved 6 måneder (57, 7% versus 45, 8%) og 1 år efter lungetransplantationen (50% versus 33, 3%) (Treede et al., J Heart Lung Transplant 2001; 20: 511).
Freedom from acute rejection was higher in the tacrolimus group at 6 months (57.7% versus 45.8%) and at 1 year after lung transplantation (50% versus 33.3%) (Treede et al., J Heart Lung Transplant 2001; 20:511).
Pancreastransplantation Et multicenter studie, hvori der indgik 205 patienter, der gennemgik simultan pancreas - nyretransplantation blev randomiseret til tacrolimus (n=103) eller til ciclosporin (n=102).
Pancreas transplantation A multicentre study included 205 patients undergoing simultaneous pancreas-kidney transplantation who were randomised to tacrolimus (n=103) or to ciclosporin (n=102).
Den initiale orale per protokol dosis af tacrolimus var 0, 2 mg/ kg/ dag med følgende dosisjustering for at opnå dalkoncentrationer på 8 – 15 ng/ ml på 5. dagen og 5 – 10 ng/ ml efter 6. måned.
The initial oral per protocol dose of tacrolimus was 0.2 mg/ kg/ day with subsequent dose adjustments to target trough levels of 8 to 15 ng/ ml by Day 5 and 5 to 10 ng/ mL after Month 6.
Pancreas overlevelse var efter 1 år signifikant bedre med tacrolimus end med ciclosporin:
Pancreas survival at 1 year was significantly superior with tacrolimus:
91, 3% versus 74, 5% (p < 0, 0005) medens overlevelsen af nyretransplantater var ens i de 2 grupper.
91.3% versus 74.5% with ciclosporin (p < 0.0005), whereas renal graft survival was similar in both groups.
I alt 34 patienter skiftede behandling fra ciclosporin til tacrolimus, medens kun 6 tacrolimuspatienter havde behov for a alternativ behandling (Bechstein et al., Transplantation 2004; 77: 1221) Intestinal transplantation Publicerede kliniske resultater fra et enkelt center om brug af tacrolimus som primær behandling efter intestinale transplantationer viste at overlevelsesraten af 155 patienter (65 intestinal alene, 75 lever og tarm og 25 multivicerale) der fik tacrolimus og prednisolon var 75% efter 1 år, 54% efter 5år og 42% efter 10 år.
Intestinal transplantation Published clinical experience from a single centre on the use of tacrolimus for primary treatment following intestinal transplantation showed that the actuarial survival rate of 155 patients (65 intestine alone, 75 liver and intestine, and 25 multivisceral) receiving tacrolimus and prednisone was 75% at 1 year, 54% at 5 years, and 42% at 10 years.
Forskellige innovationer som teknik til tidlig diagnose af Epstein- Bar (EBV) og CMV infektioner, knoglemarvs forøgelse, samtidig brug af interleukin- 2 antagonisten daclizumab, lavere initiale doser af tacrolimus med dalkoncentrationer på 10- 15 ng/ ml og senest allotransplantat bestråling, har bidraget til at forbedre resultaterne ved denne indikation (Abu- Elmagd et al., Ann Surg 2001; 234: 404).
27 A variety of innovations, such as techniques for early detection of Epstein-Barr (EBV) and CMV infections, bone marrow augmentation, the adjunct use of the interleukin-2 antagonist daclizumab, lower initial tacrolimus doses with target trough levels of 10 to 15 ng/ ml, and most recently allograft irradiation were considered to have contributed to improved results in this indication over time (Abu- Elmagd et al., Ann Surg 2001; 234:404).
Absorption I mennesker er det vist, at tacrolimus kan absorberes i hele mave- tarmkanalen.
Absorption In man tacrolimus has been shown to be able to be absorbed throughout the gastrointestinal tract.
Efter peroral administrering af < [(Sær) navn] > kapsler ses peak blodkoncentrationer (Cmax) af tacrolimus efter omkring 1- 3 timer.
Following oral administration of< Invented name > capsules peak concentrations (Cmax) of tacrolimus in blood are achieved in approximately 1 - 3 hours.
I nogle patienter synes tacrolimus dog at blive kontinuerligt absorberet over en
In some patients, tacrolimus appears to be continuously absorbed over a prolonged period yielding a relatively flat absorption profile.
Efter peroral administrering (0, 30 mg/ kg/ dag) til levertransplanterede patienter opnåede flertallet steady- state koncentrationer of < [(Sær) navn] > i løbet af 3 dage.
After oral administration (0.30 mg/ kg/ day) to liver transplant patients, steady-state concentrations of< Invented name > were achieved within 3 days in the majority of patients.
Hos raske forsøgspersoner er kapsler hårde à < [(Sær) navn] > 0, 5 mg, < [(Sær) navn] > 1 mg og < [(Sær) navn] > 5 mg bio- ækvivalente når de administreres i ækvivalente doser.
In healthy subjects ,< Invented name > 0.5 mg ,< Invented name > 1 mg and < Invented name > 5 mg Capsules, hard have been shown to be bioequivalent, when administered as equivalent dose.
Hos stabile levertransplanterede patienter, er den perorale biotilgængelighed reduceret når < [(Sær) navn] > administreres efter et måltid med moderat fedtindhold (34% af kalorierne).
In stable liver transplant patients, the oral bioavailability of< Invented name > was reduced when it was administered after a meal of moderate fat (34% of calories) content.
I en undersøgelse med stabile nyretransplanterede patienter er virkningen på peroral biotilgængelighed mindre udtalt ved indgift af < [(Sær) navn] > umiddelbart efter en normal kontinental morgenmad.
In a study of stable renal transplant patients who were administered< Invented name > immediately after a standard continental breakfast the effect on oral bioavailability was less pronounced.
Der var et fald i AUC (2- 12%) og Cmax (15- 38%) og en øgning af tmax (38- 80%) i fuldblod.
Decreases in AUC (2 to 12%) and Cmax (15 to 38%), and an increase in tmax (38 to 80%) in whole blood were evident.
Galdeflow påvirker ikke absorption af < [(Sær) navn] >.
Bile flow does not influence the absorption of< Invented name >.
Der er god korrelation mellem AUC og fuldblodskoncentrationerne ved steady- state.
A strong correlation exists between AUC and whole blood trough levels at steady-state.
Fordeling og elimination Tacrolimus farmakokinetik efter intravenøs infusion kan bedst beskrives med en to- compartment model.
Distribution and elimination In man, the disposition of tacrolimus after intravenous infusion may be described as biphasic.
I plasma er tacrolimus stærkt bundet (> 98, 8%) til plasmaprotein, hovedsagelig til serumalbumin og surt alfa- 1- glykoprotein.
In plasma, tacrolimus is highly bound (> 98.8%) to plasma proteins, mainly to serum albumin and α -1-acid glycoprotein.
Hos raske forsøgspersoner var den gennemsnitlige totale body clearance (TBC) beregnet fra fuldblodskoncentrationer 2, 25 l/ time.
In healthy subjects, the average total body clearance (TBC) estimated from whole blood concentrations was 2.25 l/ h.
Hos voksne lever -, nyre - og hjertetransplanterede har man set værdier på henholdsvis 4, 1 l/ time, 6, 7 l/ time og 3, 9 l/ time.
In adult liver, kidney and heart transplant patients, values of 4.1 l/ h, 6.7 l/ h and 3.9 l/ h, respectively, have been observed.
Hos levertransplanterede voksne og børn var værdien henholdsvis 11, 7 timer og 12, 4 timer og hos voksne nyretransplanterede fandt man en værdi på 15, 6 timer.
In adult and paediatric liver transplant patients, it averaged 11.7 hours and 12.4 hours, respectively, compared with 15.6 hours in adult kidney transplant recipients.
I den systemiske cirkulation findes kun en af de inaktive metabolitter i lave koncentrationer.
28 of the inactive metabolites is present at low concentrations.
Udskillelse Efter peroral og efter intravenøs administrering af 14C- mærket tacrolimus blev størstedelen af radioaktiviteten elimineret i fæces.
Excretion Following intravenous and oral administration of 14C-labelled tacrolimus, most of the radioactivity was eliminated in the faeces.
28 Nyrer og pankreas var de primære organer, der blev påvirket i toksicitetsstudier på rotter og bavianer.
The kidneys and the pancreas were the primary organs affected in toxicity studies performed in rats and baboons.
[Udfyldes nationalt]
6.1 List of excipients [To be completed nationally]
MARKEDSFØRINGSTILLADELSESNUMMER (NUMRE)
MARKETING AUTHORISATION HOLDER
DATO FOR FØRSTE TILLADELSE/ FORNYELSE AF TILLADELSEN
MARKETING AUTHORISATION NUMBER(S) [To be completed nationally]
DATO FOR ÆNDRING AF TEKSTEN
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION
29 1.
29 [To be completed nationally]
Prograf og tilknyttede særnavne (se bilag I) 5 mg/ ml koncentrat till infusionsvæske, opløsning
Prograf and associated names (see Annex I) 5 mg/ ml concentrate for solution for infusion
[Se bilag I - Udfyldes nationalt]
[see Annex I - to be completed nationally]
Administrationsmåde Koncentratet må kun benyttes til intravenøs infusion efter fortynding med passende infusionsvæske (se afsnit 6. 6).
Method of administration The concentrate should be used for intravenous infusion only after it is diluted with suitable carrier media (see section 6.6).
Varighed af dosering Patienter skal overgå fra intravenøs til oral behandling så snart tilstanden tillader det.
Duration of dosing Patients should be converted from intravenous to oral medication as soon as individual circumstances permit.
Intravenøs behandling bør ikke strække sig over mere end 7 dage.
Intravenous therapy should not be continued for more than 7 days.
Doseringsvejledning - Lever transplantation Profylakse af transplantatafstødning - voksne Initialt benyttes en peroral dosering på 0, 10 - 0, 20 mg/ kg/ dag, fordelt på to doser (f. eks. morgen og aften).
31 Prophylaxis of transplant rejection - adults Oral< Invented name > therapy should commence at 0.10 - 0.20 mg/kg/day administered as two divided doses (e.g. morning and evening).
12 timer efter indgrebet.
Administration should commence approximately 12 hours after the completion of surgery.
30 Hvis den kliniske tilstand ikke tillader peroral behandling gives en intravenøs dosis på 0, 01 - 0, 05 mg/ kg/ dag som kontinuerlig infusion over 24 timer.
If the dose cannot be administered orally as a result of the clinical condition of the patient, intravenous therapy of 0.01 - 0.05 mg/ kg/ day should be initiated as a continuous 24-hour infusion.
Doseringsvejledning – Hjertetransplantationer Profylakse af transplantatafstødning – voksne < [(Sær) navn] > kan anvendes med antistofinduktion (hvilket muliggør forsinket start af < [(Sær) navn] > behandling), alternativt hos klinisk stabile patienter uden antistofinduktion.
Dosage recommendations - Heart transplantation Prophylaxis of transplant rejection – adults< Invented name > can be used with antibody induction (allowing for delayed start of < Invented name > therapy) or alternatively in clinically stable patients without antibody induction.
Efter antistofinduktion bør peroral < [(Sær) navn] > behandling begynde med en dosis på 0, 075 mg/ kg/ dag fordelt på 2 doser (f. eks. morgen og aften).
Administration
Administrationen bør begynde inden 5 dage efter operationen så snart patienten er stabil.
32 should commence within 5 days after the completion of surgery as soon as the patient's clinical condition is stabilised.
I dette tilfælde er
This approach was reserved for patients without organ dysfunction (e. g. renal dysfunction).
31 en initial oral tacrolimusdosis på 2- 4 mg/ dag givet sammen med mycophenolat mofetil og kortikosteroider eller sammen med sirolimus og kortikosteroider.
In that case, an initial oral tacrolimus dose of 2 to 4 mg per day was used in combination with mycophenolate mofetil and corticosteroids or in combination with sirolimus and corticosteroids.
Ciclosporin blodkoncentrationerne og patientens tilstand skal tages i betragtning før behandling med < [(Sær) navn] > indledes.
Conversion from ciclosporin Care should be taken when converting patients from ciclosporin-based to< Invented name > -based therapy (see sections 4.4 and 4.5). < Invented name > therapy should be initiated after considering ciclosporin blood concentrations and the clinical condition of the patient.
I praksis kan behandling med < [(Sær) navn] > starte 12 – 24 timer efter ophør af ciclosporinbehandlingen.
In practice ,< Invented name > therapy has been
Anbefalede fuldblodskoncentrationer
33 initiated 12 - 24 hours after discontinuation of ciclosporin.
32 Dosering skal baseres primært på kliniske vurderinger af afstødning og tolerabilitet hos den enkelte patient.
Target whole blood trough concentration recommendations Dosing should primarily be based on clinical assessments of rejection and tolerability in each individual patient.
Kendt overfølsomhed overfor andre indholdstoffer < Udfyldes nationalt - især polyoxyethylen - hydrogeniseret ricinusolie eller strukturrelaterede stoffer. >
Hypersensitivity to any of the excipients< To be implemented nationally - in particular polyoxyethylene hydrogenated castor oil or structurally related compounds. >
Urtemedicin indeholdende prikbladet hyperikum eller anden urtemedicin bør undgås ved behandling med < [(Sær) navn] > pga. risikoen for inetraktioner, som kan medføre fald i blodkoncentrationen af tacrolimus og nedsat klinisk effekt (se afsnit 4. 5 Interaktion med andre lægemidler og andre former for interaktion).
John’ s wort (Hypericum perforatum) or other herbal preparations should be avoided when taking< Invented name > due to the risk of interactions that lead to decrease in blood concentrations of tacrolimus and reduced clinical effect of tacrolimus (see section 4.5 Interactions with other medicinal products and other forms of interactions).
De fleste tilfælde har været reversible og er primært set hos børn, der har haft langt højere bloddalkoncentrationer af < [(Sær) navn] > end den anbefalede maksimale koncentration.
Most cases have been reversible, occurring primarily in children with tacrolimus blood trough concentrations much higher than the recommended maximum levels.
Andre faktorer, der kan øge risikoen for disse kliniske tilstande, er tidligere eller bestående hjertelidelse, behandling med kortikosteroider, hypertension, nedsat nyre - eller leverfunktion, infektion, væskeretention og ødem.
Other factors observed to increase the risk of these clinical conditions included pre-existing heart disease, corticosteroid usage, hypertension, renal or hepatic dysfunction, infections, fluid overload, and
Derfor skal patienter i risikogruppen, specielt små børn og patienter i intensiv immunosuppression kontrolleres med f. eks. ekkokardiografi eller EKG før og efter transplantation (f. eks. initialt, efter 3 måneder og igen efter 9- 12 måneder).
Accordingly, high-risk patients, particularly young children and those receiving substantial immunosuppression should be monitored, using such procedures as echocardiography or ECG pre- and post-transplant (e. g. initially at three months and then at 9-12 months).
Tacrolimus kan forlænge QT intervallet men der
If abnormalities develop, dose reduction of< Invented name > therapy, or change of treatment to another immunosuppressive agent should be considered.
33 mangler væsentligt bevis for at det forårsager Torsades de Pointes.
Tacrolimus may prolong the QT interval but at this time lacks substantial evidence for causing Torsades de Pointes.
Infusionsvæsken kan give irritation på injektionsstedet, hvis det rekonstituerede < [(Sær) navn] > 5 mg/ ml koncentrat till infusionsvæske, opløsning fejlagtigt gives intraarterielt eller perivasalt.
If administered accidentally either arterially or perivasally, the reconstituted< Invented name > 5 mg/ml Concentrate for Solution for Infusion may cause irritation at the injection site.
[Udfyldes nationalt] < [(Sær) navn] > 5 mg/ ml koncentrat till infusionsvæske, opløsning indeholder polyoxyethylen - hydrogeniseret ricinusolie, der kan give anafylaktiske reaktioner.
[To be implemented nationally] < < Invented name > 5 mg/ ml Concentrate for Solution for Infusion contains polyoxyethylene hydrogenated castor oil, which has been reported to cause anaphylactoid reactions.
Man bør derfor udvise forsigtighed ved patienter, der tidligere er blevet behandlet med i. v. injektion eller infusion af lægemidler indeholdende polyoxyethylenhydrogeniseret ricinusolie og patienter med allergi.
Caution is therefore necessary in patients who have previously received preparations containing polyoxyethylene castor oil derivatives either by intravenous injection or infusion, and in patients with an allergenic predisposition.
Risikoen for anafylaktiske reaktioner kan reduceres ved langsom infusion af < [(Sær) navn] > 5 mg/ ml koncentrat till infusionsvæske, opløsning eller ved forudgående administrering af antihistamin.
The risk of anaphylaxis may be reduced by slow infusion of reconstituted< Invented name > 5 mg/ml Concentrate for Solution for Infusion or by the prior administration of an antihistamine.
Ethanolindholdet (638 mg/ ml) i < [(Sær) navn] > 5 mg/ ml koncentrat till infusionsvæske, opløsning bør tages i betragtning.
The ethanol content (638 mg per ml) of< Invented name > 5mg/ml Concentrate for Solution for Infusion should be taken into account. >