natgillin/translations-raw huggingface dataset:
Under overvågningen efter markedføring er der blevet rapporteret tilfælde med interferens mellem daptomycin og særlige reagenser, som bruges i visse analyser af protombintid/ International Normalised Ratio (PT/ INR).
During post– marketing surveillance, cases of interference between daptomycin and particular reagents used in some assays of Prothrombin Time/ International Normalised Ratio (PT/ INR) have been reported.
Denne interferens førte til en tilsyneladende forlængelse af PT og øget INR.
This interference led to an apparent prolongation of PT and elevation of INR.
Hvis der fremkommer uforklarlige abnormaliteter af PT/ INR hos patienter, der behandles med daptomycin, bør en mulig in vitro- interaktion med laboratorieundersøgelsen tages i betragtning.
If unexplained abnormalities of PT/ INR are observed in patients taking daptomycin, consideration should be given to a possible in vitro interaction with the laboratory test.
Muligheden for fejlagtige resultater kan minimeres ved at tage prøverne til PT - eller INR- analysen nær tidspunktet for laveste daptomycin- plasmakoncentration.
The possibility of erroneous results may be minimised by drawing samples for PT or INR testing near the time of trough plasma concentrations of daptomycin.
5. 3).
Animal studies do not indicate direct or indirect harmful effects with respect to fertility, pregnancy, embryonal/ fetal development, parturition or postnatal development (see section 5.3).
Cubicin bør ikke anvendes under graviditet, medmindre det er klart nødvendigt, dvs. kun hvis den potentielle fordel opvejer den mulige risiko.
Cubicin should not be used during pregnancy unless clearly necessary i. e., only if the potential benefit outweighs the possible risk.
Det vides ikke om daptomycin udskilles i human modermælk.
It is not known whether daptomycin is excreted in human milk.
Amning bør derfor afbrydes under behandlingen med Cubicin.
Therefore, breastfeeding should be discontinued during treatment with Cubicin.
Kliniske undersøgelser I kliniske undersøgelser er 2. 011 individer blevet behandlet med Cubicin.
Clinical Studies In clinical studies, 2,011 subjects received Cubicin.
460 individer fik en daglig dosis på 6 mg/ kg, heraf var 304 patienter og 156 raske frivillige.
Within these trials, 1,221 subjects received a daily dose of 4 mg/ kg, of whom 1,108 were patients and 113 were healthy volunteers; 460 subjects received a daily dose of 6 mg/ kg, of whom 304 were patients and 156 were healthy volunteers.
Bivirkninger (dvs. af investigator antaget at være muligvis, sandsynligvis eller definitivt relateret til lægemidlet) blev rapporteret med sammenlignelige frekvenser for Cubicin og komparative regimer.
Adverse reactions (i. e. considered by the investigator to be possibly, probably, or definitely related to the medicinal product) were reported at similar frequencies for Cubicin and comparator regimens.
Hos de patienter, der blev behandlet med Cubicin, blev de efterfølgende bivirkninger nævnt oftest under behandlingen samt ved follow- up: hovedpine, kvalme, opkastning, diarré, svampeinfektioner, udslæt, reaktioner på infusionsstedet, forhøjet kreatinfosfokinase (CPK) og abnorme leverenzymer, alanin- amino- transferase (ALAT), aspartat- amino- stransferase (ASAT), alkalinfosfatase.
For subjects who received Cubicin, the adverse reactions that were most frequently reported during therapy plus follow-up were: headache, nausea, vomiting, diarrhoea, fungal infections, rash, infusion site reaction, increased Creatine phosphokinase (CPK) and abnormal liver enzymes; Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase.
Hyppigheden svarer til almindelig = ≥ 1/ 100, < 1/ 10; ikke almindelig = > 1/ 1. 000, < 1/ 100; sjælden = > 1/ 10. 000, < 1/ 1. 000; Meget sjælden = ≤ 1/ 10. 000.
The following adverse reactions were reported during therapy and during follow-up with frequencies corresponding to Common = ≥ 1/ 100 ,< 1/10; Uncommon = > 1/1 ,000, < 1/100; Rare = > 1/10,000, < 1/ 1,000, Very rare = ≤ 1/10 ,000:
De alvorligeste skal anføres først.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
6 Infektioner og parasitære sygdomme Almindelig: svampeinfektioner Ikke almindelig: urinvejsinfektion
Urinary tract infection
Blod - og lymfesystem Ikke almindelig: trombocytæmi, anæmi, eosinofili
Thrombocythaemia, anaemia, eosinophilia
Metabolisme og ernæring Ikke almindelig: anoreksi, hyperglykæmi
Anorexia, hyperglycaemia
Angst, insomnia
Anxiety, insomnia
Nervesystemet Almindelig: hovedpine Ikke almindelig: svimmelhed, paræstesi, smagsforstyrrelser
Dizziness, paraesthesiae, taste disorder
Hjerte Ikke almindelig: supraventriculær takykardi, ekstrasystole
Supraventricular tachycardia, extrasystole
Vaskulære sygdomme Ikke almindelig: hedeture, hypertension, hypotension
Flushes, hypertension, hypotension
Mave- tarmkanalen Almindelig: kvalme, opkastning, diarré Ikke almindelig: forstoppelse, abdominalsmerter, dyspepsi, glossitis
Constipation, abdominal pain, dyspepsia, glossitis
Lever og galdeveje Ikke almindelig: hepatitis
Jaundice
Hud og subkutane væv Almindelig: udslæt Ikke almindelig: pruritis, urticaria
Pruritis, urticaria
Knogler, led, muskler og bindevæv Ikke almindelig: myositis, muskelsvaghed, muskelsmerter, artralgi
Myositis, muscle weakness, muscle pain, arthralgia
Nyrer og urinveje Ikke almindelig: nyreinsufficiens, inklusiv nyrebeskadigelse og nyresvigt
Renal insufficiency, including renal impairment and renal failure
Det reproduktive system og mammae Ikke almindelig: vaginitis
Vaginitis
Almene symptomer og reaktioner på administrationsstedet Almindelig: reaktion på infusionsstedet Ikke almindelig: pyreksi, svaghed, træthed, smerte
Pyrexia, weakness, fatigue, pain
Undersøgelser Almindelig: abnorme leverfunktionstest (forhøjet ASAT, ALAT og alkalinfosfatase), forhøjet CPK Ikke almindelig: elektrolytforstyrrelser, forhøjet serumkreatinin, forhøjet myoglobin, forhøjet lactatdehydrogenase (LDH)
Electrolyte imbalance, increased serum creatinine, increased myoglobin, Lactic dehydrogenase (LDH) increased
Efter markedsføring Bivirkninger, som er blevet rapporteret efter markedsføring og som ikke er nævnt ovenfor:
7 Post-Marketing Adverse reactions that have been reported Post-Marketing that are not listed above are:
7 Immunsystemet Overfølsomhed, som viste sig som enkeltstående, spontane rapporter, inklusive men ikke begrænset til, pulmonær eosinofili, vesicobulløst udslæt med involvering af slimhinder og fornemmelsen af hævelse i mund og svælg.
Immune system disorders Hypersensitivity, manifested by isolated spontaneous reports including, but not limited to; pulmonary eosinophilia, vesicobullous rash with mucous membrane involvement and sensation of oropharyngeal swelling.
Anafylaksi Infusionsrelaterede reaktioner herunder følgende symptomer: takykardi, hvæsende vejrtrækning, pyreksi, rigor, systemiske hedeture, vertigo, synkope og metalsmag
Anaphylaxis Infusion reactions including the following symptoms: tachycardia, wheezing, pyrexia, rigors, systemic flushing, vertigo, syncope and metallic taste.
50% af tilfældene hos patienter med allerede eksisterende nyreinsufficiens eller hos patienter, som samtidig blev behandlet med andre lægemidler, kendt for at forårsage rhabdomyolyse.
Musculoskeletal, connective tissue and bone disorders Rhabdomyolysis When clinical information on the patients was available to make a judgement, approximately 50% of the cases occurred in patients with pre-existing renal insufficiency, or in those receiving concomitant medications known to cause rhabdomyolysis.
Nervesystemet Perifer neuropati
Nervous system disorders Peripheral neuropathy
Undersøgelser I nogle tilfælde med myopati med forhøjede CPK- værdier og muskelsymptomer havde patienterne ligeledes forhøjede transaminaser.
Investigations In some cases of myopathy involving raised CPK and muscle symptoms, the patients also presented with elevated transaminases.
Disse forhøjede transaminaser blev formodet at være relateret til effekten på skeletmuskulaturen.
These transaminase increases were likely to be related to the skeletal muscle effects.
Størstedelen af de forhøjede transaminaser havde en toksicitetsgrad på 1- 3 og forsvandt efter seponering af behandlingen.
The majority of transaminase elevations were of Grade 1-3 toxicity and resolved upon discontinuation of treatment.
11% af den administrerede dosis fjernes i løbet af 48 timer).
Daptomycin is slowly cleared from the body by haemodialysis (approximately 15% of the administered dose is removed over 4 hours) or by peritoneal dialysis (approximately 11% of the administered dose is removed over 48 hours).
Antibakterielle midler til systemisk brug, Andre Antibakterielle, ATC- kode:
Antibacterials for systemic use, Other antibacterials, ATC code:
Virkemåde Daptomycin er et naturligt cyklisk lipopeptid, som kun er aktiv imod Gram- positive bakterier.
Mode of action Daptomycin is a cyclic lipopeptide natural product that is active against Gram positive bacteria only.
Virkemekanismen involverer binding (under tilstedeværelse af kalciumioner) til bakteriemembraner på celler både i vækst - og i stationærfase, hvilket forårsager en depolarisering og fører til hurtig hæmning af protein, DNA, og RNA- syntese.
The mechanism of action involves binding (in the presence of calcium ions) to bacterial membranes of both growing and stationary phase cells causing depolarisation and leading to a rapid inhibition of protein, DNA, and RNA synthesis.
PK/ PD forhold Daptomycin udviser in vitro hurtig, koncentrationsafhængig bakteriedræbende aktivitet mod Gram - positive organismer.
PK/ PD relationship Daptomycin exhibits rapid, concentration dependent bactericidal activity against sensitive Gram positive organisms in vitro.
I dyreforsøg korrelerer AUC/ MIC og Cmax/ MIC med effekt og forudsagt bakteriedrab in vivo ved enkeltdoser, der er ækvivalente til humandoser på 4 mg/ kg og 6 mg/ kg én gang dagligt.
In animal models AUC/ MIC and Cmax/ MIC correlate with efficacy and predicted bacterial kill in vivo at single doses equivalent to human doses of 4 mg/ kg and 6 mg/ kg once daily.
Resistensmekanisme Der er rapporteret om stammer med nedsat følsomhed over for daptomycin specielt under behandlingen af patienter med infektioner, der er vanskelige at behandle, og/ eller efter administration i forlængede perioder.
8 Mechanisms of resistance Strains with decreased susceptibility to daptomycin have been reported especially during the treatment of patients with difficult-to-treat infections and/ or following administration for prolonged periods.
Der er i særdeleshed blevet rapporteret om manglende effekt af behandling hos patienter, der er inficeret med Staphylococcus aureus, Enterococcus faecalis eller Enterococcus
In particular, there have been reports of treatment failures in patients infected with Staphylococcus aureus, Enterococcus faecalis or Enterococcus faecium, including bacteraemic patients, that have been associated with the selection of organisms with reduced susceptibility or frank resistance to daptomycin during therapy.
Der er endnu ikke identificeret nogen resistensmekanisme over for daptomycin.
The mechanism of resistance to daptomycin has not yet been identified.
Følsomhedsgrænser Mindste hæmmede koncentration (MIC), følsomhedsgrænser, fastlagt af EUCAST (European Committee on Antimicrobial Susceptibility Testing) for stafylokokker og streptokokker (undtagen S. pneumoniae) er: følsom ≤ 1 mg/ l og resistent > 1 mg/ l.
Breakpoints Minimum inhibitory concentration (MIC) breakpoint established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for Staphylococci and Streptococci (except S. pneumoniae) are Susceptible ≤ 1 mg/ l and Resistant > 1 mg/ l.
Følsomhed Resistensprævalensen kan variere geografisk og tidsmæssigt for udvalgte arter og lokal information om resistens er ønskelig, især når svære infektioner behandles.
Susceptibility The prevalence of resistance may vary geographically and over time for selected species and local information on resistance is desirable, particularly when treating severe infections.
Sædvanligvis følsomme arter Staphylococcus aureus * Staphylococcus haemolyticus Coagulase negative stafylokokker Streptococcus agalactiae * Streptococcus dysgalactiae subsp equisimilis * Streptococcus pyogenes * Gruppe G streptokokker Clostridium perfringens Peptostreptococcus spp Naturligt resistente organismer Gram- negative organismer * betegner arter, hvor aktivitet anses for at være påvist på tilfredsstillende måde i kliniske undersøgelser.
Commonly Susceptible Species Staphylococcus aureus * Staphylococcus haemolyticus Coagulase negative staphylococci Streptococcus agalactiae* Streptococcus dysgalactiae subsp equisimilis* Streptococcus pyogenes* Group G streptococci Clostridium perfringens Peptostreptococcus spp Inherently resistant organisms Gram negative organisms * denotes species against which it is considered that activity has been satisfactorily demonstrated in clinical studies.
Information fra kliniske undersøgelser I to kliniske undersøgelser med komplicerede hud - og bløddelsinfektioner opfyldte 36% af patienterne behandlet med Cubicin kriteriet for systemisk inflammatorisk responssyndrom (SIRS).
Information from clinical trials In two clinical trials in complicated skin and soft tissues infections, 36% of patients treated with Cubicin met the criteria for systemic inflammatory response syndrome (SIRS).
I et randomiseret, kontrolleret, åbent studie med 235 patienter med Staphylococcus aureus bakteriæmi (dvs. mindst én positiv blodkultur af Staphylococcus aureus før modtagelsen af første dosis), opfyldte 19 ud af 120 patienter behandlet med Cubicin kriteriet for RIE.
In a randomised controlled open-label study in 235 patients with Staphylococcus aureus bacteraemia (i. e, at least one positive blood culture of Staphylococcus aureus prior to receiving the first dose) 19 of 120 patients treated with Cubicin met the criteria for RIE.
Af disse 19 patienter var 11 inficerede med methicillin- følsom og 8 med methicillin- resistent Staphylococcus aureus.
Of these 19 patients 11 were infected with methicillin-susceptible and 8 with methicillin-resistant Staphylococcus aureus.
Succesraten for RIE - patienterne er vist i nedenstående tabel.
The success rates in RIE patients are shown in the table below.
Population ITT - (intention to treat) Population
9 Differences in Population
Daptomycin n/ N (%)
Daptomycin
Komparator n/ N (%)
n/ N (%) n/ N (%)
Forskel i Succesrate (95% KI)
Rates (95% CI)
RIE PP - (per protocol) Population
RIE PP (per protocol) Population
Blandt disse fejlslagne behandlinger var 6 Cubicin -
Failure of treatment due to persisting or relapsing Staphylococcus aureus infections was observed in 19/ 120 (15.8%) patients treated with Cubicin, 9/ 53 (16.7%) patients treated with vancomycin and 2/ 62 (3.2%) patients treated with an anti-staphylococcal semi-synthetic penicillin.
9 behandlede patienter og 1 vancomycin- behandlet patient, som udviklede tiltagende MICer på eller efter behandling (se ” Resistensmekanisme ” ovenfor).
Among these failures six patients treated with Cubicin and one patient treated with vancomycin were infected with Staphylococcus aureus that developed increasing MICs of daptomycin on or following therapy (see “ Mechanisms of resistance” above).
Daptomycins farmakokinetik er generelt lineær og uafhængig af tid ved doser på 4 til 12 mg/ kg administreret som enkeltdosis én gang daglig i op til 14 dage i raske frivillige.
Daptomycin pharmacokinetics are generally linear and time-independent at doses of 4 to 12 mg/ kg administered as a single daily dose for up to 14 days in healthy volunteers.
Steady- state - koncentrationer opnås ved den tredje daglige dosis.
Steady-state concentrations are achieved by the third daily dose.
0, 1 l/ kg hos voksne frivillige probander, hvilket er overensstemmende med fordeling hovedsageligt i det ekstracellulære rum.
Distribution The steady state volume of distribution of daptomycin was approximately 0.1 l/ kg in healthy adult volunteers, consistent with distribution primarily within the extracellular space.
Dyreforsøg angående fordelingen i væv hat vist at daptomycin hovedsageligt fordeles i meget vaskulariseret væv og i mindre grad passerer blod- hjernebarrieren og placentabarrieren efter enkelt - og multiple doser.
Tissue distribution studies in animals have shown that daptomycin preferentially distributes into highly vascularised tissues and to a lesser degree penetrates the blood-brain barrier and the placental barrier following single and multiple doses.
90% inklusive patienter med nyreinsufficiens.
In healthy volunteers and patients treated with daptomycin, protein binding averaged about 90% including subjects with renal insufficiency.
Metabolisme In vitro- forsøg har vist, at der kun er begrænset eller ingen mikrosomal- medieret levermetabolisme af daptomycin hos mennesker, og at CYP450- systemet kun er minimalt involveret i daptomycins metabolisme.
Metabolism In vitro studies have demonstrated that there is no or limited liver microsomal mediated metabolism of daptomycin in humans and that CYP450 involvement in daptomycin metabolism is minimal.
Analyse af plasmaprøver fra patienter, som fik en dosis på 6 mg/ kg daptomycin viste ingen metabolisme, hvilket tyder på meget lille til slet ingen systemisk metabolisme.
Analysis of plasma samples from subjects who received a 6 mg/ kg dose of daptomycin did not show any trace of metabolism, suggesting little to no systemic metabolism.
Endvidere blev der ikke observeret metabolitter i plasma efter administration af radioaktivt mærket stof til mennesker, baseret på samlet radioaktiv mærkning og mikrobiologisk aktive koncentrationer.
Furthermore, no metabolites have been observed in plasma following administration of radiolabeled drug to humans based on total radiolabel and microbiologically active concentrations.
To af de fire metabolitter, der blev fundet i urin, er fase 1 oxiderede metabolitter, som er til stede i lav koncentration.
Of the four minor metabolites detected in urine, two are Phase I oxidative metabolites present in low concentrations.
Elimination Daptomycin udskilles primært via nyrerne.
Elimination Daptomycin is excreted primarily by the kidneys.
7 til 9 ml/ t/ kg og renal clearance er 4 til 7 ml/ t/ kg.
10 Following intravenous administration, plasma clearance of daptomycin is approximately 7 to 9 ml/ h/ kg and its renal clearance is 4 to 7 ml/ h/ kg.
50% af dosis blev genfundet i urin som uomdannet daptomycin.
In a mass balance study using radiolabelled material, 78% of the administered dose was recovered from the urine based on total radioactivity, whilst urinary recovery of unchanged daptomycin was approximately 50% of the dose.
Ældre En dosisjustering baseret på alder er ikke nødvendig.
Elderly No dose adjustment is necessary based on age alone.
Nyrefunktionen bør dog bestemmes og dosis bør reduceres, hvis der er tegn på svær nyreinsufficiens.
However, renal function should be assessed and the dose should be reduced if there is evidence of severe renal insufficiency.
Børn og unge (< 18 år) Farmakokinetiske profiler for 3 aldersgrupper (2- 6 år, 7- 11 år og 12- 17 år) blev opnået efter en enkelt intravenøs administration af daptomycin 4 mg/ kg hos pædiatriske patienter med vist eller mistænkt Gram- positiv infektion.
Children and adolescents (< 18 years of age) Pharmacokinetic profiles were obtained following single intravenous administration of daptomycin 4 mg/ kg in paediatric patients with proven or suspected Gram-positive infection, divided into three age groups (2-6 years, 7-11 years and 12-17 years).
Daptomycins farmakokinetik efter en enkelt 4 mg/ kg dosis hos unge på
The pharmacokinetics of daptomycin following a single 4 mg/ kg dose in adolescents aged 12-17 years are generally similar to those of healthy adult subjects with normal renal function with trends towards lower AUC and Cmax in adolescents.
I de yngre aldersgrupper (2- 6 år og 7- 11 år) var eksponering (Cmax og AUC) og eliminationshalveringstid for den samme mg/ kg dosis nedsat i forhold til de unge.
In the younger age groups (2-6 years and 7-11 years), exposure (Cmax and AUC) and elimination half-life for the same mg/ kg dose were reduced compared with adolescents.
28% hos moderat adipøse patienter (Body Mass Index på 25- 40 kg/ m2) og med 42% hos ekstremt adipøse patienter (Body Mass Index på > 40 kg/ m2).
Obesity Relative to non-obese subjects daptomycin systemic exposure measured by AUC is increased by about 28% in moderately obese subjects (Body Mass Index of 25-40 kg/ m2) and by 42% in extremely obese subjects (Body Mass Index of > 40 kg/ m2).
Køn Der er ikke observeret forskelle med hensyn til køn i daptomycins farmakokinetik.
Gender No clinically significant gender-related differences in daptomycin pharmacokinetics have been observed.
Nyreinsufficiens Efter administration af en enkeltdosis på 4 mg/ kg eller 6 mg/ kg daptomycin til patienter med forskellige grader af nyreinsufficiens, var daptomycins clearance (CL) nedsat og systemisk eksposition (AUC) forhøjet.
Renal insufficiency Following administration of a single 4 mg/ kg or 6 mg/ kg dose of daptomycin to subjects with various degrees of renal insufficiency, daptomycin clearance (CL) was reduced and systemic exposure (AUC) was increased.
Se pkt.
In subjects with severe renal insufficiency (CLcr < 30 ml/ min) and end-stage renal disease, exposure (AUC) and elimination half life were increased between 2-3-fold relative to healthy subjects.
4. 2 angående nødvendigheden af dosisjustering.
See section 4.2 regarding the need for dose adjustment.
Leverinsufficiens Daptomycins farmakokinetik ændres ikke hos patienter med moderat leverinsufficiens (Child- Pugh leverinsufficiens klasse B) sammenlignet med sunde frivillige probander, matchede mht. køn, alder og vægt, efter administration af en enkeltdosis på 4 mg/ kg.
Hepatic insufficiency The pharmacokinetics of daptomycin is not altered in subjects with moderate hepatic insufficiency (Child-Pugh B classification of hepatic insufficiency) compared with healthy volunteers matched for gender, age and weight following a single 4 mg/ kg dose.
En dosisjustering er ikke nødvendig, når daptomycin administreres til patienter med moderat leverinsufficiens.
No dosage adjustment is necessary when administering daptomycin in patients with moderate hepatic insufficiency.
Daptomycins farmakokinetik hos patienter med svær leverinsufficiens (Child- Pugh klasse C) er ikke evalueret.
The pharmacokinetics of daptomycin in patients with severe hepatic insufficiency (Child-Pugh C classification) have not been evaluated.
I studier af klinisk relevant længde (14 til 28 dage) blev administration af daptomycin associeret med minimale til lette degenerative/ regenerative forandringer i skeletmuskulaturen hos rotter og hunde.
In studies of clinically-relevant duration (14-28 days), daptomycin administration was associated with minimal to mild degenerative/ regenerative changes in skeletal muscle in the rat and dog.
0, 05% af myofibre blev påvirket) og var ved højere doser ledsaget af stigninger i CPK.
Microscopic changes in skeletal muscle were minimal (approximately 0.05% of myofibres affected) and at the higher doses were accompanied by elevations in CPK.
Der blev ikke observeret fibrose eller rhabdomyolyse.
No fibrosis or rhabdomyolysis was observed.
LOEL- niveauet (lowest observable effect level) for myopati i rotter og hunde fremkom ved eksponeringsværdier på 0, 8 til 2, 3 gange det humanterapeutiske niveau på 6 mg/ kg for patienter med normal nyrefunktion.
11 The lowest observable effect level (LOEL) for myopathy in rats and dogs occurred at exposure levels of 0.8 to 2.3-fold the human therapeutic levels at 6 mg/ kg for patients with normal renal function.
Denne påvirkning blev primært relateret til plasma Cmax.
Effects on peripheral nerves were observed at higher doses than those associated with skeletal muscle effects in adult rats and dogs, and were primarily related to plasma Cmax.