natgillin/translations-raw huggingface dataset:
Effentora- tabletten bør placeres og forblive inde i mundhulen indtil, den er helt opløst, hvilket normalt tager cirka 14- 25 minutter.
Effentora should be placed and retained within the buccal cavity for a period sufficient to allow disintegration of the tablet which usually takes approximately 14-25 minutes.
Effentora- tabletten må ikke suges/ suttes på, tygges eller synkes, da dette vil resultere i lavere plasmakoncentrationer, end når tabletten tages som anvist.
The Effentora tablet should not be sucked, chewed or swallowed, as this will result in lower plasma concentrations than when taken as directed.
Hvis der efter 30 minutter stadig er rester af Effentora- tabletten tilbage, kan de synkes sammen med et glas vand.
After 30 minutes, if remnants from the Effentora tablet remain, they may be swallowed with a glass of water.
Hvis der optræder irritation i gummen/ kinden, anbefales det at finde en ny placering til tabletten.
In case of buccal mucosa irritation, a change in tablet placement within the buccal cavity should be recommended.
4. 1), da der er øget risiko for respirationsdepression.
Patients without maintenance opioid therapy (see section 4.1) as there is an increased risk of respiratory depression.
4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen
4 4.4 Special warnings and precautions for use
Patienter og deres plejere/ hjælpere skal informeres om, at Effentora indeholder et aktivt stof i en mængde, der kan være dødelig for børn, og at de derfor skal opbevare alle tabletterne utilgængeligt for børn.
Patients and their carers must be instructed that Effentora contains an active substance in an amount that can be fatal to a child, and therefore to keep all tablets out of the reach and sight of children.
Det er vigtigt, at behandlingen mod vedvarende smerter med langtidsvirkende opioid er stabiliseret, inden behandlingen med Effentora indledes.
It is important that the long acting opioid treatment used to treat the patient’ s persistent pain has been stabilised before Effentora therapy begins.
Effentora bør kun administreres med yderste forsigtighed til patienter, der kan være specielt følsomme over for de intrakranielle virkninger af CO2 retention, såsom patienter med tegn på forhøjet intrakranielt tryk eller svækket bevidsthed.
Effentora should only be administered with extreme caution in patients who may be particularly susceptible to the intracranial effects of CO2 retention, such as those with evidence of increased intracranial pressure or impaired consciousness.
Intravenøs fentanyl kan forårsage bradykardi.
Intravenous fentanyl may produce bradycardia.
I kliniske forsøg med Effentora blev der ikke observeret klare tegn på bradykardi.
In clinical trials with Effentora, no clear evidence for bradycardia was observed.
Effentora bør dog anvendes med forsigtighed til patienter med allerede eksisterende bradyarytmier.
However, Effentora should be used with caution in patients with pre- existing bradyarrhythmias.
Effentora bør desuden administreres med forsigtighed til patienter med nedsat lever - eller nyrefunktion.
In addition, Effentora should be administered with caution to patients with hepatic or renal impairment.
Ved intravenøs administration er det dog påvist, at clearance af fentanyl ændres på grund af ændringer i den metaboliske clearance og i plasma proteiner hos patienter med nedsat lever - eller nyrefunktion.
The influence of hepatic and renal impairment on the pharmacokinetics of the medicinal product has not been evaluated, however, when administered intravenously the clearance of fentanyl has been shown to be altered in hepatic and renal impairment due to alterations in metabolic clearance and plasma proteins.
Dette kan medføre øgede og forlængede opioide virkninger.
After administration of Effentora, impaired hepatic and renal function may both increase the bioavailability of swallowed fentanyl and decrease its systemic clearance, which could lead to increased and prolonged opioid effects.
Der bør derfor udvises særlig forsigtighed under titreringen hos patienter med moderat eller svær lever - eller nyresygdom.
Therefore, special care should be taken during the titration process in patients with moderate or severe hepatic or renal impairment.
Der kan udvikles tolerance og fysisk og/ eller psykisk afhængighed efter gentagen administration af opioider såsom fentanyl.
Tolerance and physical and/ or psychological dependence may develop upon repeated administration of opioids such as fentanyl.
Dette lægemiddel indeholder 8 mg natrium pr. tablet.
This medicinal product contains 8 mg sodium per tablet.
Der kan derfor optræde potentielle interaktioner, når Effentora gives samtidig med stoffer, der påvirker CYP3A4- aktivitet.
Fentanyl is metabolised mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4), therefore potential interactions may occur when Effentora is given concurrently with agents that affect CYP3A4 activity.
Samtidig administration med stoffer, der inducerer CYP3A4- aktivitet, kan reducere effekten af Effentora.
Coadministration with agents that induce 3A4 activity may reduce the efficacy of Effentora.
5 ritonavir, ketoconazol, itraconazol, troleandomycin, clarithromycin og nelfinavir) eller moderate CYP3A4- hæmmere (f. eks. amprenavir, aprepitant, diltiazem, erythromycin, fluconazol, fosamprenavir, grapefrugtjuice og verapamil) kan resultere i forhøjede plasmakoncentrationer af fentanyl, hvilket potentielt kan forårsage alvorlige bivirkninger herunder fatal respirationsdepression.
The concomitant use of Effentora with strong CYP3A4 inhibitors (e. g., ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, and nelfinavir) or moderate CYP3A4 inhibitors (e. g., amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, and verapamil) may result in increased fentanyl plasma concentrations, potentially causing serious adverse drug reactions including fatal respiratory depression.
Patienter, der behandles med Effentora samtidig med moderate eller stærke CYP3A4- hæmmere bør monitoreres omhyggeligt i længere tid.
Patients receiving Effentora concomitantly with moderate or strong CYP3A4 inhibitors should be carefully monitored for an extended period of time.
Samtidig brug af CNS- depressiva, herunder andre opioider, sedativa eller hypnotika, medikamenter til generel anæstesi, fenotiaziner, beroligende midler, skeletmuskel- relaxantia, sederende antihistaminer og alkohol kan medføre yderligere hæmmende virkning.
5 The concomitant use of other central nervous system depressants, including other opioids, sedatives or hypnotics, general anaesthetics, phenothiazines, tranquillisers, skeletal muscle relaxants, sedating antihistamines and alcohol may produce additive depressant effects.
Effentora bør ikke anvendes til patienter, som er blevet behandlet med monoaminooxidasehæmmere (MAO- hæmmere) inden for de sidste 14 dage, da der er indberettet alvorlig og uforudsigelig øget virkning af MAO- hæmmere i forbindelse med opioide analgetika.
Effentora is not recommended for use in patients who have received monoamine oxidase (MAO) inhibitors within 14 days because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.
Samtidig brug af partielle opioide agonister/ antagonister (f. eks. buprenorfin, nalbufin, pentazocin) frarådes.
The concomitant use of partial opioid agonists/ antagonists (e. g. buprenorphine, nalbuphine, pentazocine) is not recommended.
Der foreligger ikke tilstrækkelige data om brugen af fentanyl hos gravide.
There are no adequate data from the use of fentanyl in pregnant women.
Effentora bør ikke anvendes under graviditet, medmindre det er klart nødvendigt.
Effentora should not be used in pregnancy unless clearly necessary.
Fentanyl bør kun anvendes af ammende kvinder, hvis fordelene mere end opvejer de potentielle risici for både moder og barn.
Fentanyl should only be used by breastfeeding women if the benefits outweigh the potential risks for both mother and child.
Imidlertid nedsætter opioide analgetika den mentale og/ eller fysiske evne, der kræves til at udføre farlige opgaver (f. eks. at køre bil eller betjene maskiner).
However, opioid analgesics impair the mental and/ or physical ability required for the performance of potentially dangerous tasks (e. g., driving a car or operating machinery).
Der kan forventes typiske opioide bivirkninger fra Effentora- behandlingen.
Typical opioid undesirable effects are to be expected with Effentora.
De alvorligste bivirkninger angives først):
The adverse reactions considered to be at least possibly-related to treatment from clinical studies were as follows (frequencies defined as: very common ≥ 1/ 10, common ≥ 1/ 100 to < 1/ 10, uncommon ≥ 1/ 1,000 to < 1/ 100; within each frequency grouping, undesirable effects are presented in order of decreasing seriousness):
Undersøgelser
Very common
Meget almindelig
6 Investigations
Ikke almindelig Nedsat blodpladetal, øget hjertefrekvens, nedsat hæmatokrit, nedsat hæmoglobin
Uncommon Platelet count decreased Heart rate increased Haematocrit decreased Haemoglobin decreased
Takykardi, bradykardi Anæmi, neutropeni, trombocytopeni
Tachycardia, Bradycardia Anaemia Neutropenia Thrombocytopenia
Dysgeusi, somnolens, letargi, hovedpine, tremor, sedation
Dysgeusia Somnolence Lethargy Headache Tremor Sedation
Nedsat bevidsthedsniveau, opmærksomhedsforstyrrelse, kognitiv forstyrrelse, hypoæstesi, balanceforstyrrelse, migræne, motorisk dysfunktion, dysartri
Depressed level of consciousness Disturbance in attention Cognitive disorder Hypoaesthesia Balance disorder Migraine Motor dysfunction Dysarthria
Synsforstyrrelse, okular hyperæmi, unormal fornemmelse i øjet, fotopsi, sløret syn, nedsat synsskarphed
Visual disturbance Ocular hyperaemia Abnormal sensation in eye Photopsia Blurred vision Visual acuity reduced
Vertigo, tinnitus, øreproblemer
Vertigo Tinnitus Ear discomfort
Dyspnø, pharyngolaryngeal smerte
Dyspnoea Pharyngolaryngeal pain
Opkastning, forstoppelse, stomatitis, mundtørhed, diare
Vomiting Constipation Stomatitis Dry mouth Diarrhoea
Mundsår, oral hypoæstesi, ubehag i munden, blister i mundslimhinden, misfarvning af mundslimhinden, lidelse i det bløde væv i munden, glossodyni, vabler på tungen, smerte i gummen, maveubehag, sår på tungen, lidelse i tungen, dyspepsi, mavesmerte, oesophagitis, gastroøsofageal reflukssygdom, sprukne læber, tørre læber, tandlidelse, tandpine
Mouth ulceration Oral hypoaesthesia Oral discomfort Oral mucosal blistering Oral mucosal discolouration Oral soft tissue disorder Glossodynia Tongue blistering Gingival pain Stomach discomfort Tongue ulceration Tongue disorder Dyspepsia Abdominal pain Oesophagitis Gastrooesophagal reflux disease Chapped lips Dry lip Tooth disorder Toothache
Hud og subkutane væv
Very common
Pruritus, hyperhydrose
Common Pruritis Hyperhydrosis
Koldsved, ansigtssved, udslæt, generel pruritus, alopeci, onychorrhexis
Uncommon Cold sweat Facial swelling Rash Generalised pruritus Alopecia Onychorrhexis
Myalgi, muskeltrækninger, muskelsvaghed, rygsmerte
Myalgia Muscle twitching Muscular weakness Back pain
Anoreksi Oral candidiasis, faryngitis, pustel i munden
Oral candidiasis Pharyngitis Oral pustule
7 Traumer, forgiftninger og behandlingskomplika - tioner
Injury, poisoning and procedural complications
Almindelig
Fall
Multiple myelomer
Multiple myeloma
Rødme, hypertension, hedeture
Flushing Hypertension Hot flush
Reaktioner ved applikationsstedet herunder smerte, sår, irritation, paræstesi, anæstesi, erytem, ødem, hævelse og blærer
Application site reactions including pain, ulcer, irritation, paraesthesia, anaesthesia, erythema, oedema, swelling and vesicles
Asteni, ubehag, sløvhed, ubehag i brystet, unormal fornemmelse, anspændt følelse, tørst, frysende fornemmelse, kulderystelser, varmefølelse, abstinenssyndrom
Asthenia Malaise Sluggishness Chest discomfort Feeling abnormal Feeling jittery Thirst Feeling cold Chills Feeling hot Drug withdrawal syndrome
Disorientering, euforisk stemning
Disorientation Euphoric mood
Ængstelse, nervøsitet, hallucinationer, synshallucination, insomni, konfusion
Anxiety Nervousness Hallucination Visual hallucination Insomnia Confusional state
Symptomerne på fentanyl- overdosering forventes at svare til de symptomer, der forbindes med intravenøs fentanyl og andre opioider, og er en udvidelse af stoffets farmakologiske virkning, hvor den mest alvorlig signifikante virkning er respirationsdepression.
The symptoms of fentanyl overdose are expected to be similar in nature to those of intravenous fentanyl and other opioids, and are an extension of its pharmacological actions, with the most serious significant effect being respiratory depression.
Umiddelbar behandling af opioidoverdosering omfatter fjernelse af Effentora- bukkaltabletten, hvis den stadig er i munden, at sikre frie luftveje, fysisk og verbal stimulering af patienten, vurdering af bevidsthedsniveau, åndedræts - og kredsløbsstatus samt om nødvendigt assisteret ventilation (åndedrætshjælp).
Immediate management of opioid overdose includes removal of the Effentora buccal tablet, if still in the mouth, ensuring a patent airway, physical and verbal stimulation of the patient, assessment of the level of consciousness, ventilatory and circulatory status, and assisted ventilation (ventilatory support) if necessary.
Ved behandling af overdosering (utilsigtet indtagelse) hos en person, som ikke tidligere har fået opioider, skal der sørges for intravenøs adgang, og naloxon eller en anden opioid- antagonist bør anvendes, alt efter hvad der er klinisk indiceret.
8 For treatment of overdose (accidental ingestion) in the opioid-naive person, intravenous access should be obtained and naloxone or other opioid antagonists should be employed as clinically indicated.
Respirationsdepression efter overdosering kan vare længere end effekten af opioid– antagonisten (f. eks. er halveringstiden af naloxon mellem 30 og 81 minutter), og gentagen indgivelse kan være nødvendig.
The duration of respiratory depression following overdose may be longer than the effects of the opioid antagonist’ s action (e. g., the half-life of naloxone ranges from 30 to 81 minutes) and repeated administration may be necessary.
Der henvises til produktresumeet for den enkelte opioid- antagonist for nærmere oplysninger om sådan anvendelse.
Consult the Summary of Product Characteristics of the individual opioid antagonist for details about such use.
Til behandling af overdosering hos patienter i opioid- vedligeholdelsesbehandling bør der sørges for intravenøs adgang.
For treatment of overdose in opioid-maintained patients, intravenous access should be obtained.
Velovervejet anvendelse af naloxon eller anden opioid- antagonist kan være berettiget i visse tilfælde, men er forbundet med risiko for akut abstinenssyndrom.
The judicious use of naloxone or another opioid antagonist may be warranted in some instances, but it is associated with the risk of precipitating an acute withdrawal syndrome.
Skulle dette forekomme, bør det behandles ved brug af assisteret ventilation, med en opioid- antagonist og som det sidste alternativ med et neuromuskulært blokerende middel.
If it occurs, it should be managed by the use of assisted ventilation, by an opioid antagonist, and as a final alternative, by a neuromuscular blocking agent.
Fentanyl er et opioidanalgetikum, der overvejende interagerer med opioid- µ- receptoren.
Fentanyl is an opioid analgesic, interacting predominantly with the opioid µ-receptor.
4. 2).
As a result, the dose of Effentora should be individually titrated to achieve the desired effect (see section 4.2).
Alle opioid- µ- receptor- agonister, inklusive fentanyl, medfører dosisafhængig respirationsdepression.
All opioid µ-receptor agonists, including fentanyl, produce dose dependent respiratory depression.
Der er udført to dobbeltblinde, randomiserede, placebokontrollerede, crossover- undersøgelser med i alt 248 cancerpatienter med gennembrudssmerter, som oplevede i gennemsnit 1 til 4 anfald af gennembrudssmerter om dagen, mens de modtog opioid- vedligeholdelsesbehandling.
Two double-blind, randomized, placebo-controlled crossover studies have been conducted involving a total of 248 patients with BTP and cancer who experienced on average 1 to 4 episodes of BTP per day while taking maintenance opioid therapy.
Patienter, som identificerede en effektiv dosis, gik videre i undersøgelsens dobbeltblinde fase.
Patients who identified an effective dose entered the double-blind phase of the study.
Den primære effektvariabel var patientens vurdering af smerteintensitet.
The primary efficacy variable was the patient’ s assessment of pain intensity.
Patienterne vurderede smerteintensiteten på en 11 punkts- skala.
Patients assessed pain intensity on a 11-point scale.
67% af patienterne kunne titreres til en effektiv dosis.
Sixty-seven percent of the patients were able to be titrated to an effective dose.
I den pivotale, kliniske undersøgelse (forsøg 1) var det primære endepunkt den gennemsnitlige sum af forskellene i smerteintensitet fra doseringen til 60 minutter efter, inklusive (SPID60), som var statistisk signifikant sammenlignet med placebo (p < 0, 0001).
In the pivotal clinical study (study 1), the primary endpoint was the average sum of differences in pain intensity scores from dosing to 60 minutes, inclusive (SPID60), which was statistically significant compared to placebo (p < 0.0001).
9 Forsøg 1:
9 Study 1:
Middel (+ / - SEM) forskel i smerteintensitet ved hvert tidspunkt (komplet analysesæt) Middel (SEM) forskelle i smerteintensitet
Mean (+/ - SEM) Pain Intensity Difference at Each Time Point (Full Analysis Set) Mean (SEM) Pain Intensity Differences
SPID60 Middel (+ / - SD) EFFENTORA=9, 7( 5, 58) p < 0, 0001 Placebo=4, 9( 4, 38)
SPID60 mean (+/ - SD) EFFENTORA=9.7(5.58) p < 0.0001 Placebo=4.9(4.38)
Tid fra administration af forsøgsmedicin (minutter)
Time from Administration of Study Drug (Minutes)
+ p < 0, 0001 EFFENTORA versus placebo, til EFFENTORAS fordel, ved variansanalyse PID=forskel i smerteintensitet; SEM=standard error of the mean
+ p < 0.0001 EFFENTORA versus placebo, in favor of EFFENTORA, by an analysis of variance PID=pain intensity difference; SEM=standard error of the mean
Forsøg 2:
Study 2:
Middel (+ / - SEM) forskel i smerteintensitet ved hvert tidspunkt (komplet analysesæt)
Mean (+/ - SEM) Pain Intensity Difference at Each Time Point (Full Analysis Set)
SPID30 middel (+ / - SD) EFFENTORA=3, 2( 2, 60) p < 0, 0001 Middel (SEM) forskelle i smerteintensitet
SPID30 mean (+/ - SD) EFFENTORA=3.2(2.60) p < 0.0001 Mean (SEM) Pain Intensity Differences
Placebo=2, 0( 2, 21)
Placebo=2.0(2.21)
* p < 0, 01 EFFENTORA versus placebo, til EFFENTORAS, fordel, ved one- sample Wilcoxon signed rank test + p < 0, 0001 EFFENTORA versus placebo, til EFFENTORAS fordel, ved one- sample Wilcoxon signed rank test PID=forskel i smerteintensitet; SEM=standard error of the mean
* p < 0.01 EFFENTORA versus placebo, in favor of EFFENTORA, by one-sample Wilcoxon signed rank test + p < 0.0001 EFFENTORA versus placebo, in favor of EFFENTORA, by one-sample Wilcoxon signed rank test PID=pain intensity difference; SEM=standard error of the mean
I den anden pivotale undersøgelse (forsøg 2) var det primære endepunkt SPID30, som ligeledes var statistisk signifikant sammenlignet med placebo (p < 0, 0001).
In the second pivotal study (study 2), the primary endpoint was SPID30, which was also statistically significant compared to placebo (p < 0.0001).
10 Der blev observeret en statistisk signifikant forbedring i forskellen i smerteintensitet med Effentora versus placebo så tidligt som ved 10 minutter i forsøg 1 og så tidligt som ved 15 minutter (det tidligst målte tidspunkt) i forsøg 2.
10 Statistically significant improvement in pain intensity difference was seen with Effentora versus placebo as early as 10 minutes in Study 1 and as early as 15 minutes (earliest time point measured) in Study 2.
Disse forskelle fortsatte med at være signifikante ved hvert efterfølgende tidspunkt i hvert enkelt forsøg.
These differences continued to be significant at each subsequent time point in each individual study.
Generel introduktion Fentanyl er meget lipofilt og absorberes meget hurtigt fra mundslimhinden og langsommere via den konventionelle gastrointestinale vej.
General introduction Fentanyl is highly lipophilic and can be absorbed very rapidly through the oral mucosa and more slowly by the conventional gastrointestinal route.
Det undergår “ førstepassage ” hepatisk og intestinal metabolisme, og metabolitterne bidrager ikke til fentanyls terapeutiske virkninger.
It is subject to first-pass hepatic and intestinal metabolism and the metabolites do not contribute to fentanyl’ s therapeutic effects.
Forbigående pH- ændringer i forbindelse med den brusende reaktion kan optimere opløsningen af tabletten (ved en lavere pH- værdi) samt gennemtrængningen af membranen (ved en højere pH- værdi).
Transient pH changes accompanying the effervescent reaction may optimise dissolution (at a lower pH) and membrane permeation (at a higher pH).
“ Dwell time ” (defineret som den tid det tager, til tabletten er fuldstændig opløst, efter at den er lagt op under kinden), har ikke indflydelse på, hvor tidligt den systemiske eksponering for fentanyl indtræder.
Dwell time (defined as the length of time that the tablet takes to fully disintegrate following buccal administration), does not affect early systemic exposure to fentanyl.
Indflydelsen af nedsat nyre - eller leverfunktion på Effentoras farmakokinetik er ikke blevet undersøgt.
The effect of renal or hepatic impairment on the pharmacokinetics of Effentora has not been studied.
Efter oromukosal administration af Effentora absorberes fentanyl hurtigt med en absolut biotilgængelighed på 65%.
Following oromucosal administration of Effentora, fentanyl is readily absorbed with an absolute bioavailability of 65%.
Peak plasma- koncentrationer, målt med venøse blodprøver, opnås sædvanligvis inden for en time efter oromukosal administration.
The absorption profile of Effentora is largely the result of an initial rapid absorption from the buccal mucosa, with peak plasma concentrations following venous sampling generally attained within an hour after oromucosal administration.
Cirka 50% af den totalt administrerede dosis absorberes hurtigt transmukosalt og bliver systemisk tilgængelig.
Approximately 50% of the total dose administered is rapidly absorbed transmucosally and becomes systemically available.
Den resterende halvdel af den totale dosis sluges og bliver langsomt absorberet fra mave- tarmkanalen.
The remaining half of the total dose is swallowed and slowly absorbed from the gastrointestinal tract.
Cirka 30% af den slugte mængde (50% af den totale dosis) undgår førstepassage- elimination i leveren og tarmene og bliver systemisk tilgængelig.
About 30% of the amount swallowed (50% of the total dose) escapes hepatic and intestinal first-pass elimination and becomes systemically available.
Farmakokinetiske parametre * hos voksne forsøgspersoner, der behandles med Effentora
Pharmacokinetic Parameters* in Adult Subjects Receiving Effentora
Tmax (minut) **
Tmax (minute) **
AUC0- tmax (ng. t/ ml)
AUC0-tmax (ng. hr/ ml)
AUC0- inf (ng. t/ ml)
AUC0-inf (ng. hr/ ml)
De koncentrationer af fentanylcitrat, der blev opnået i serum var højere end koncentrationerne i plasma:
Fentanyl citrate concentrations obtained in serum were higher than in plasma:
Serum AUC og Cmax var henholdsvis cirka 20% og 30% højere end plasma AUC og Cmax.
Serum AUC and Cmax were approximately 20% and 30% higher than plasma AUC and Cmax, respectively.
Grunden til denne forskel er ukendt. ** Data for Tmax vist som middel (område).
The reason of this difference is unknown. ** Data for Tmax presented as median (range).