natgillin/translations-raw huggingface dataset:
Ansøgeren redegjorde også for forskellen mellem de frivillige (opioid- naive) og målpatientpopulationen (kroniske opioidbrugere) og bemærkede, at mønstret for relaterede hændelser stemte overens med den foreliggende litteratur om sikkerhedsprofilen for fentanyl- produkter og udeblivelsen af dosisrelaterede tendenser i forekomsten af uønskede hændelser.
The Applicant also discussed the difference between the volunteers (opioid-naïve) and the target patient population (chronic opioid users), noting that the pattern of related events was consistent with available literature on the safety profile of fentanyl products and the absence of dose-related trends in the incidence of adverse events.
Et stort antal Rapinyl- doser er blevet indgivet i disse fase III- forsøg, og høje doser af Rapinyl er anvendt under lange indgiftsperioder uden grund til bekymring over arten og hyppigheden af rapporterede alvorlige uønskede hændelser.
A large number of Rapinyl doses have been administered during these Phase III studies and high doses of Rapinyl have been used for long periods of administration without any cause for concern over the nature and frequency of reported SAEs.
CHMP blev forsikret i kraft af rapporteringen af de udeblevne sikkerhedssignaler med relation til alvorlige uønskede hændelser, men anmodede ansøgeren om at fremsende en komplet sikkerhedsanalyse som en betingelse for markedsføringstilladelserne.
The CHMP was reassured by the 13 absence of safety signals related to SAEs were reported but requested the Applicant to submit a full safety analysis as conditions to the Marketing Authorisations.
Ansøgeren leverede case- beretninger for alle de dødsfald, der var meddelt til ansøgeren, og gennemgik de uønskede hændelser, der var resulteret i dødsfald, og konkluderede, at investigatorerne ikke anså disse dødsfald for at være relateret til forsøgslægemidlet.
The Applicant provided the case narratives for all the deaths notified to the Applicant and reviewed the adverse events with an outcome of death, and concluded that these deaths not considered as related to the study drug by the study investigators.
Én patient havde et vellykket selvmordsforsøg, men selv om selvmordstanker er kendt for at være mere almindelige hos patienter med cancer end i befolkningen som helhed, har hverken selvmord eller selvmordstanker været rapporteret som en uønsket hændelse forbundet med Actiq eller Fentora/ Effentora, og på baggrund af at den farmakokinetiske profil for Rapinyl ligner profilen for Actiq, mener ansøgeren, at dette var et sporadisk tilfælde, hvilket stemmer overens med investigators vurdering af, at hændelsen ikke er relateret.
One patient had a successful suicide attempt but while suicidal ideation is known to be more common in patients with cancer than in the general population, neither suicide nor suicidal ideation has been reported as an adverse event associated with Actiq nor with Fentora/ Effentora and based on the similar pharmacokinetic profile of Rapinyl and Actiq, the Applicant believes that this was a sporadic case, consistent with the investigator’ s assessment as being unrelated.
Det vellykkede selvmordsforsøg kræver imidlertid opmærksomhed, og da depression og humørsvingninger er uønskede hændelser, der er angivet i produktresuméet for Actiq, vurderede CHMP, at den type hændelser skulle monitoreres tæt, og anmodede om, at der bliver fulgt op på problemet i bivirkningsobservationerne post- marketing.
However, the successful suicidal attempt requires attention, and because depression and mood liability are adverse events listed in the SPC of Actiq, the CHMP considered that these kinds of events should be closely monitored and requested the issue to be followed up in post-marketing Pharmacovigilance.
Selv om antallet af analyserede patienter er temmelig lavt, er der nu tilgængelige oplysninger om behandlingen af BTP hos cancerpatienter i et dosisområde fra 100- 800 µg, og der var ingen nye sikkerhedssignaler.
Even though the number of patients analysed is rather low, information is now available on the treatment of BTP in cancer patients at a dose range from 100 µg up to 800 µg and there were no new safety signals.
På grund af det lille antal patienter, der er blevet eksponeret i længere i tid, skal de endelige resultater af forsøg EN3267- 005 og EN3267- 007 fremsendes som betingelse for markedsføringstilladelserne.
Due to the low number of patients exposed for a long time, the final results of the studies EN3267-005 and EN3267-007 should be provided as conditions to the Marketing Authorisations.
14 På grund af det temmelig lille antal patienter, der er blevet eksponeret i længere i tid, skal de endelige resultater fra forsøg EN3267- 005 og EN3267- 007 samt data fra den komplette sikkerhedsanalyse om alvorlige uønskede hændelser imidlertid fremsendes som betingelse for markedsføringstilladelserne.
However, due to the quite low number of patients exposed for a long time, the Applicant was asked to provide the final results of the studies EN3267-005 and EN3267-007 and the full safety analysis data on SAEs as conditions to the Marketing Authorisations.
På baggrund af gennemgangen af dataene og ansøgerens svar på spørgsmålene på listen med uafklarede spørgsmål og på de resterende spørgsmål anså CHMP risk/ benefit- forholdet for Rapinyl for at være positivt, og anvendelsen af Rapinyl sublingual tablet 50, 100, 200, 300, 400, 600 og 800 µg kan godkendes, forudsat at ansøgeren indarbejder ændringerne til teksten i produktinformationen og opfylder betingelserne for markedsføringstilladelsen som beskrevet i bilag IV.
Based on the review of the data and on the Applicant responses to list of outstanding issues and to the remaining issues, the CHMP considered the benefit/ risk ratio of Rapinyl to be positive and the application for Rapinyl sublingual tablet 50, 100, 200, 300, 400, 600 and 800 μ g to be approvable, provided that the Applicant implements the amendments made to the text of the Product Information and fulfills the conditions to the Marketing Authorisation as described in Annex IV.
- Svarene fremsendt af ansøgeren, i særlig grad de yderligere kliniske data fremsendt under CHMP' s
- the responses provided by the Applicant, in particular the additional clinical data submitted during
indbringelsesprocedure, besvarer CHMP' s spørgsmål tilfredsstillende,
the CHMP referral procedure, successfully addressed the CHMP concerns,
- Dosisområdet for Rapinyl og dosisproportionaliteten mellem Actiq og Rapinyl blev anset som
- the dose range of Rapinyl and the dose proportionalilty between Actiq and Rapinyl was considered
værende underbygget,
as established
- Og under forudsætning af, at ansøgeren opfylder betingelserne for markedsføringstilladelsen som
- and provided that the Applicant fulfils the conditions to the Marketing Authorisation as listed in
angivet i bilag IV,
Annex IV
- CHMP anså risk/ benefit- forholdet for Rapinyl for at være positivt,
- the CHMP considered the benefit/ risk of Rapinyl to be positive
anbefaler CHMP ændring af produktresuméerne og godkendelse af de markedsføringstilladelser, for hvilke produktresumé, etikettering og indlægsseddel fremgår af bilag III for Rapinyl og tilknyttede navne (se bilag I).
the CHMP has recommended the amendment of the Summaries of Product Characteristics and the granting of the Marketing Authorisations for which the Summary of Product Characteristics, labelling and package leaflet are set out in Annex III for Rapinyl and associated names (see Annex I).
Rapinyl og tilhørende navne (se bilag I) 50 mikrogram sublinguale resoribletter [Se bilag I – udfyldes nationalt]
Rapinyl and associated names (see Annex I) 50 microgram sublingual tablets [See Annex I - To be completed nationally]
Hver sublingual resoriblet indeholder 50 mikrogram fentanyl (som citrat) 100 mikrogram fentanyl (som citrat) 200 mikrogram fentanyl (som citrat) 300 mikrogram fentanyl (som citrat) 400 mikrogram fentanyl (som citrat) 600 mikrogram fentanyl (som citrat) 800 mikrogram fentanyl (som citrat)
Each sublingual tablet contains 50 micrograms fentanyl (as citrate) 100 micrograms fentanyl (as citrate) 200 micrograms fentanyl (as citrate) 300 micrograms fentanyl (as citrate) 400 micrograms fentanyl (as citrate) 600 micrograms fentanyl (as citrate) 800 micrograms fentanyl (as citrate)
50 mikrogram subingual resoriblet er en hvid femkantet tablet 100 mikrogram sublingual resoriblet er en hvid, rund tablet 200 mikrogram sublingual resoriblet er en hvid, oval tablet 300 mikrogram sublingual resoriblet er en hvid, trekantet tablet 400 mikrogram sublingual resoriblet er en hvid, diamantformet tablet 600 mikrogram sublingual resoriblet er en hvid ” D ” - formet tablet 800 mikrogram sublingual resoriblet er en hvid, kapselformet tablet
50 microgram sublingual tablet is a white pentagon-shaped tablet 100 microgram sublingual tablet is a white round tablet 200 microgram sublingual tablet is a white oval-shaped tablet 300 microgram sublingual tablet is a white triangle-shaped tablet 400 microgram sublingual tablet is a white diamond-shaped tablet 600 microgram sublingual tablet is a white “ D” -shaped tablet 800 microgram sublingual tablet is a white capsule-shaped tablet
Rapinyl sublinguale resoribletter skal administreres direkte under tungen på det dybeste sted.
Rapinyl sublingual tablets should be administered directly under the tongue at the deepest part.
18 hulrum uden at tygges eller suges.
Rapinyl sublingual tablets should not be swallowed, but allowed to completely dissolve in the 18 sublingual cavity without chewing or sucking.
Patienterne skal kontrolleres omhyggeligt, indtil en passende dosis er opnået, dvs. en dosis som giver tilstrækkelig analgesi med acceptable bivirkninger for hver periode med gennembrudssmerter.
Patients should be carefully monitored until an appropriate dose is reached, i. e. that provides adequate analgesia with acceptable adverse reactions for each episode of breakthrough pain.
Et skift fra andre fentanylholdige produkter til Rapinyl må ikke ske i forholdet 1: 1 på grund af forskellige absorptionsprofiler.
Switching from other fentanyl containing products to Rapinyl must not occur at a 1:1 ratio because of different absorption profiles.
Hvis der ikke opnås tilstrækkelig analgesi inden for 15- 30 minutter efter indtagelse af en enkelt sublingualresoriblet, kan der gives en 100 mikrogram sublingual resoriblet mere.
If adequate analgesia is not obtained within 15-30 minutes of administration of a single sublingual tablet, a second 100 microgram sublingual tablet may be administered.
Denne titrering skal foregå ved at administrere en enkelt sublingual resoriblet efterfulgt af administration af en supplerende sublingual resoriblet efter 15- 30 minutter, hvis der ikke er opnået tilstrækkelig smertelindring.
This titration should follow the course of administering a single sublingual tablet, with administration of a supplemental second sublingual tablet after 15-30 minutes, if inadequate pain relief is obtained.
Styrke (mikrogram) af første sublinguale resoriblet pr. periode med gennembrudssmerter
Strength (micrograms) of first sublingual
Styrke (mikrogram) af supplerende (anden) sublinguale resoriblet, der om nødvendigt skal tages 15- 30 minutter efter første resoriblet
(second) sublingual tablet to be taken 15-30 minutes after first tablet, if required
For at minimere risikoen for opioidrelaterede bivirkninger og for at identificere den passende dosis, er det bydende nødvendigt, at patienterne kontrolleres nøje af sundhedspersonale under titreringsprocessen.
In order to minimise the risk of opioid– related adverse reactions and to identify the appropriate dose, it is imperative that patients be monitored closely by health professionals during the titration process.
19 Vedligeholdelsesbehandling:
19 Maintenance therapy:
Hvis der opleves mere end fire perioder af gennembrudssmerter om dagen i mere end fire på hinanden følgende dage, skal dosis af det anvendte langtidsvirkende opioid mod persisterende smerter revurderes.
If more than four episodes of breakthrough pain are experienced per day over a period of more than four consecutive days, then the dose of the long acting opioid used for persistent pain should be re- evaluated.
4. 4).
Use in elderly patients Dose titration needs to be approached with particular care and patients observed carefully for signs of fentanyl toxicity (see section 4.4).
4. 4).
Use in patients with renal and hepatic impairment Patients with kidney or liver dysfunction should be carefully observed for signs of fentanyl toxicity during the Rapinyl titration phase (see section 4.4).
4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen Patienter og deres plejere skal instrueres i, at Rapinyl indeholder et aktivt stof i en mænge, der kan være fatalt for et barn, og at alle tabletter derfor skal opbevares utilgængeligt for børn.
Patients and their carers must be instructed that Rapinyl 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.
Rapinyl, skal patienter og deres plejere gøres fuldt opmærksomme på betydningen af at tage Rapinyl korrekt, og hvad de skal gøre, hvis der opstår symptomer på overdosis.
Due to the potentially serious undesirable effects that can occur when taking an opioid therapy such as Rapinyl, patients and their carers should be made fully aware of the importance of taking Rapinyl correctly and what action to take should symptoms of overdose occur.
Før behandlingen med Rapinyl initieres, er det vigtigt, at patientens langtidsvirkende opioidbehandling, der anvendes til at kontrollere deres persisterende smerter, er blevet stabiliseret.
Before Rapinyl therapy is initiated, it is important that the patient’ s long-acting opioid treatment used to control their persistent pain has been stabilised.
Ved gentagen indtagelse af opioider såsom fentanyl kan der udvikles tolerans og fysisk og/ eller psykologisk afhængighed.
Upon repeated administration of opioids such as fentanyl, tolerance and physical and/ or psychological dependence may develop.
20 Fælles for alle opioider er der en risiko for klinisk signifikant respirationsdepression forbundet med brugen af Rapinyl.
20 In common with all opioids, there is a risk of clinically significant respiratory depression associated with the use of Rapinyl.
Der skal udvises særlig forsigtighed under dosistitrering med Rapinyl hos patienter med kronisk obstruktiv lungesygdom eller andre medicinske tilstande, der prædisponerer dem for respirationsdepression (f. eks. myasthenia gravis), på grund af risikoen for yderligere respirationsdepression, der ville kunne medføre respirationssvigt.
Particular caution should be exercised during dose titration with Rapinyl in patients with chronic obstructive pulmonary disease or other medical conditions predisposing them to respiratory depression (e. g. myasthenia gravis) because of the risk of further respiratory depression, which could lead to respiratory failure.
Rapinyl må kun administreres med yderste forsigtighed til patienter, der kan være særligt følsomme over for de intrakranielle virkninger af hyperkapni som f. eks. de patienter, der viser tegn på forhøjet intrakranielt tryk, nedsat bevidsthedsniveau, coma eller hjernetumorer.
Rapinyl should only be administered with extreme caution in patients who may be particularly susceptible to the intracranial effects of hyperkapnia, such as those showing evidence of raised intracranial pressure, reduced consciousness, coma or brain tumours.
Rapinyl skal administreres med forsigtighed til patienter med nedsat lever - eller nyrefunktion, især under titreringsfasen.
Rapinyl should be administered with caution to patients with liver or kidney dysfunction, especially during the titration phase.
Anvendelsen af Rapinyl til patienter med nedsat lever - eller nyrefunktion kan øge biotilgængeligheden af fentanyl og nedsætte dets systemiske clearance, hvilket kunne føre til akkumulation og øgede og forlængede opioidvirkninger.
The use of Rapinyl in patients with hepatic or renal impairment may increase the bioavailability of fentanyl and decrease its systemic clearance, which could lead to accumulation and increased and prolonged opioid effects.
Lægemidler, der hæmmer CYP3A4- aktivitet såsom makrolidantibiotika (f. eks. erythromycin), azolsvampemidler (f. eks. ketoconazol, itraconazol) eller visse proteasehæmmere (f. eks. ritonavir), kan øge fenatyls biotilgængelighed ved at nedsætte dets systemiske clearance og potentielt forstærke eller forlænge opioidvirkningerne.
Active substances that inhibit CYP3A4 activity such as macrolide antibiotics (e. g. erythromycin), azole antifungal agents (e. g. ketoconazole, itraconazole) or certain protease inhibitors (e. g. ritonavir) may increase the bioavailability of fentanyl by decreasing its systemic clearance, potentially enhancing or prolonging opioid effects.
Fentanyl skal derfor administreres med forsigtighed til patienter, hvis det indtages samtidigt med CYP3A4- hæmmere.
Fentanyl should therefore be given to patients with caution if administered concomitantly with CYP3A4 inhibitors.
Samtidig anvendelse af andre CNS- depressiva såsom andre morfinderivater (analgetika og antitussiva), universel anæstesi, skeletmuskelrelaksantia, sedative antidepressiva, sedative H1 - antihistaminer, barbiturater, anxiolytika (dvs. benzodiazepiner), hypnotika, antipsykotika, clonidin og beslægtede stoffer kan fremkalde øgede CNS dæmpende virkninger.
Concomitant use of other CNS depressants, such as other morphine derivatives (analgesics and antitussives), general anaesthetics, skeletal muscle relaxants, sedative antidepressants, sedative H1 antihistamines, barbiturates, anxiolytics (ie benzodiazepines), hypnotics, antipsychotics, clonidine and related substances may produce increased CNS depressant effects.
Anvendelse af Rapinyl frarådes til patienter, der har fået monoaminooxidase (MAO) - hæmmere inden for 14 dage, fordi alvorlig og uforudsigelig potensering af MAO- hæmmere er rapporteret i forbindelse med opioide analgetika.
Rapinyl 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.
21 Samtidig anvendelse af partielle opioidagonister / - antagonister (f. eks. buprenorphin, nalbuphin, pentazocin) frarådes.
21 The concomitant use of partial opioid agonists/ antagonists (e. g. buprenorphine, nalbuphine, pentazocine) is not recommended.
Fentanyl udskilles i modermælk og kan medføre sedation og respirationsdepression hos det ammede barn.
Fentanyl is excreted into breast milk and may cause sedation and respiratory depression in the breast- fed child.
Fentanyl bør kun administreres til ammende kvinder, hvis fordelene helt klart opvejer de potentielle risici for både moder og barn.
Fentanyl should only be used by breast-feeding women if the benefits clearly outweigh the potential risks for both mother and child.
Patienter skal rådes til ikke at føre motorkøretøj eller betjene maskiner, hvis de bliver svimle eller døsige eller oplever tåge - eller dobbeltsyn, mens de tager Rapinyl.
Patients should be advised not to drive or operate machinery if they become dizzy or drowsy or experience blurred or double vision while taking Rapinyl.
Kvalme, opkastning, obstipation, hovedpine, somnolens/ træthed og svimmelhed.
Other very commonly reported adverse reactions include: nausea, vomiting, constipation, headache, somnolence/ fatigue and dizziness.
Bivirkninger set i kliniske undersøgelser med Rapinyl hos patienter og frivillige forsøgspersoner med et formodet forhold til behandling er anført herunder efter systemorganklasse og hyppighed (meget almindelig ≥1/ 10; almindelig ≥1/ 100 til < 1/ 10).
Adverse reactions from clinical studies with Rapinyl in patients and volunteers, with a suspected relationship to treatment, are listed below by system organ class and frequency (very common ≥ 1/ 10; common ≥ 1/ 100 to < 1/ 10).
Svimmelhed, somnolens, hovedpine Almindelig:
Dizziness, somnolence, headache Common:
Vasovagal reaktion, hypoæstesi, paræstesi, hyperakusis
Vasovagal reaction, hypoaesthesia, paraesthesia, hyperacusis
Abnormt syn
Vision abnormal
Respirationsdepression, rhinitis, pharyngitis
Respiratory depression, rhinitis, pharyngitis
Kvalme Almindelig:
Nausea Common:
22 Hud og subkutane væv Almindelig:
Vomiting, abdominal pain, diarrhoea, constipation, stomach discomfort, dyspepsia, dry mouth 22 Skin and subcutaneous tissue disorders Common:
Ortostatisk hypotension, rødme, hedeture
Orthostatic hypotension, flushing, hot flush
Almene sygdomme og reaktioner på administrationsstedet Meget almindelig:
General disorders and administration site conditions Very common:
Træthed Almindelig:
Fatigue Common:
Asteni, irritation på applikationsstedet
Asthenia, application site irritation
Depression, anoreksi, nedsat koncentration, eufori
Depression, anorexia, concentration impaired, euphoria
Alle ovenstående bivirkninger er rapporteret hos opioidnaive forsøgspersoner, der fik Rapinyl.
All the above adverse reactions were reported in opioid naïve volunteers administered with Rapinyl.
Følgende bivirkninger forbundet med andre fentanylprodukter er ligeledes rapporteret (meget almindelig ≥1/ 10; almindelig ≥1/ 100 til < 1/ 10; ikke almindelig ≥ 1/ 1. 000 til < 1/ 100; sjælden ≥1/ 10 000; meget sjælden < 1/ 10. 000; ikke kendte (kan ikke estimeres ud fra forhåndenværende data)).
The following adverse reactions associated with other medicinal products containing fentanyl have also been reported (very common ≥ 1/ 10; common ≥ 1/ 100 to < 1/ 10; uncommon ≥ 1/ 1000 to < 1/ 100; rare ≥ 1/ 10,000 to < 1/ 1000; very rare < 1/ 10,000; not known (cannot be estimated from available data)):
Bradykardi, takykardi, hypertension Meget sjælden:
Bradycardia, tachycardia, hypertension Very rare:
Myoclonus, insomni, smagsforstyrrelser Ikke almindelig:
Myoclonus, insomnia, taste disorders Uncommon:
Unormal gang/ koordination, vertigo, amnesi, taleforstyrrelser, tremor
Abnormal gait/ coordination, vertigo, amnesia, speech disorders, tremor
Luftveje, thorax og mediastinum Ikke almindelig:
Respiratory thoracic and mediastinal disorders Uncommon:
Hypoventilation, astma, dyspnø Meget sjælden:
Hypoventilation, asthma, dyspnoea, Very rare:
Apnø, hæmoptyse
Apnoea, haemoptysis
Gastrointestinal okklusion, dysfagi, mundsår/ stomatitis, tungelidelse Ikke almindelig:
Gastro-intestinal occlusion, dysphagia, mouth ulcers/ stomatitis, tongue disorder Uncommon:
Forstørret abdomen, flatulens, tørst Sjælden:
Enlarged abdomen, flatulence, thirst Rare:
Blærespasmer, oliguri
Urinary retention, change in urinary frequency Very rare: bladder spasm, oliguria
Svedudbrud
Sweating
Tilskadekomster
Accidental injuries
Hallucinationer, konfusion, angst, nervøsitet, unormal tankegang, unormale drømme Ikke almindelig:
Hallucinations, confusion, anxiety, nervousness, abnormal thinking, abnormal dreams Uncommon:
Uro, depersonalisation, emotionel labilitet
Agitation, depersonalisation, emotional lability 23 4.9 Overdose
Der skal udvises forsigtighed ved anvendelese af naloxon eller andre opioidantagonister til behandling af overdosering hos patienter, der får vedligeholdelsesdoser af opioid, på grund af risikoen for at fremkalde et akut abstinenssyndrom.
Care should be taken when using naloxone or other opioid antagonists to treat overdose in opioid- maintained patients, due to the risk of precipitating an acute withdrawal syndrome.
ATC- kode:
Phenylpiperidine derivatives, ATC code:
Fentanyl er et potent µ- opioid analgetikum med hurtig analgetisk virkning og kort virkningsvarighed.
Fentanyl is a potent µ-opioid analgesic with rapid onset of analgesia and short duration of action.
100 gange mere potent end morfin som analgetikum.
Fentanyl is approximately 100-fold more potent than morphine as an analgesic.