qanastek/EMEA-V3 huggingface dataset:
It is recommended that increased caution should be exercised in titrating the dose of Effentora in elderly patients.
Huwa rakkomandat li għandha tingħata aktar attenzjoni fit- titrazzjoni tad - doża ta ’ Effentora f’ pazjenti anzjani.
3 Hepatic or renal impairment:
Indeboliment tal- fwied u renali
Effentora should be administered with caution to patients with moderate or severe hepatic or renal impairment (see section 4.4).
Effentora għandu jingħata b’ attenzjoni lill- pazjenti b’ indeboliment moderat jew sever tal- fwied jew renali (ara sezzjoni 4. 4).
Patients with xerostomia:
Pazjenti b’ kserostomija:
Patients experiencing xerostomia are advised to drink water to moisten the buccal cavity prior to administration of Effentora.
Pazjenti b’ esperjenza ta ’ kserostomija huma avżati biex jixorbu l- ilma biex ixarbu l- kavità tal- ħalq qabel għoti ta ’ Effentora.
If this recommendation does not result in an appropriate effervescence, then a switch of therapy may be advised.
Jekk din ir- rakkomandazzjoni ma tirriżultax f’ effervexxenza xierqa, bidla tat- terapija tista ’ tiġi rakkomandata.
Method of administration:
Metodu ta ’ l- għoti:
Effentora tablet once exposed to moisture utilises an effervescent reaction to deliver the active substance.
Ladarba pillola Effentora tiġi esposta għall- umdità, din tutilizza reazzjoni effervexxenti biex twassal is- sustanza attiva.
Therefore patients should be instructed not to open the blister until ready to place the tablet in the buccal cavity.
Għalhekk, il- pazjenti għandhom jiġi rakkomandati biex ma jiftħux il- folja qabel ikunu lesti biex ipoġġu l- pillola ġol- kavità tal- ħalq.
Opening the blister package Patients should be instructed NOT to attempt to push the tablet through the blister because this could damage the buccal tablet.
Kif jinfetaħ il- pakkett tal- folja Il- pazjenti għandhom jiġu mgħallma biex MA JIPPRUVAWX jimbuttaw il- pillola minn ġol- folja minħabba li dan jista ’ jagħmel ħsara lill- pillola għall- ħalq.
The correct method of releasing the tablet from the blister is:
Il- metodu korrett ta ’ kif tinħeles pillola mill- folja hija:
One of the blister units should be separated from the blister card by tearing it apart at the perforations.
Waħda mill- unitajiet tal- folja għandha tiġi separata mill- kartuna tal- folja billi tiċċarrat ’ l barra fil - perforazzjonijiet.
The blister unit should then be flexed along the line printed on the backing foil where indicated.
L- unità tal- folja għandha tintlewa tul il- linja stampata fuq il- folja ta ’ wara fejn indikat.
The backing foil should be peeled back to expose the tablet.
Il- folja ta ’ wara għandha titqaxxar biex tiġi esposta l- pillola.
Patients should be instructed not to attempt to crush or split the tablet.
Il- pazjenti għandhom jiġu mgħallma biex ma jippruvawx ifarku jew jaqsmu l- pillola.
The tablet should not be stored once removed from the blister package as the tablet integrity can not be guaranteed and a risk of accidental exposure to a tablet can occur.
Il- pillola m’ għandhiex tinħażen ladarba titneħħa mill- pakkett tal- folja minħabba li l- integrità tal- pillola ma tistax tiġi garantita u jista ’ jkun hemm riskju ta ’ esponiment aċċidentali għall- pillola.
Tablet administration Patients should remove the tablet from the blister unit and immediately place the entire Effentora tablet in the upper portion of the buccal cavity (above an upper rear molar between the cheek and gum).
Għoti tal- pillola Il- pazjenti għandhom ineħħu l- pillola minn ġol- folja u minnufiħ ipoġġu l- pillola sħiħa ta ’ Effentora fil- parti ta ’ fuq tal- kavità tal- ħalq (’ l fuq minn darsa ta ’ wara ta ’ fuq, bejn il- ħadd u l- ħanek).
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 għandu jitpoġġa u jinżamm fil- kavità tal- ħalq għall- perjodu suffiċjenti biex issir id - disintegrazzjoni tal- pillola li s- soltu tieħu madwar 14- 25 minuta.
The Effentora tablet should not be sucked, chewed or swallowed, as this will result in lower plasma concentrations than when taken as directed.
Il- pillola ta ’ Effentora m’ għandiex tintreda ’, tintmagħad jew tinbela ’, għax dan iwassal għall - konċentrazzjonijiet fil- plażma aktar baxxi minn dawk meta tittieħed kif rakkomandat.
After 30 minutes, if remnants from the Effentora tablet remain, they may be swallowed with a glass of water.
Wara 30 minuta, jekk jibqa ’ xi fdalijiet tal- pillola ta ’ Effentora, dawn jistgħu jinbelgħu ma tazza ilma.
The length of time that the tablet takes to fully disintegrate following oromucosal administration does not appear to affect early systemic exposure to fentanyl.
It- tul ta ’ żmien li l- pillola tieħu biex tiddisintegra għal kollox wara għoti oromukużali ma jidhirx li jaffettwa l- esponiment sistemiku bikri għal fentanyl.
Patients should not consume any food and drink when a tablet is in the buccal cavity.
I- pazjenti m’ għandhomx jieħdu ikel u xorb waqt li l- pillola tkun fil- kavità tal- ħalq.
In case of buccal mucosa irritation, a change in tablet placement within the buccal cavity should be recommended.
F’ każ ta ’ irritazzjoni tal- mukuża tal- ħalq, bidla tal- post fejn titpoġġa l- pillola fil- kavità tal- ħalq għandha tiġi rakkomandata.
Patients without maintenance opioid therapy (see section 4.1) as there is an increased risk of respiratory depression.
4 Pazjenti mingħajr terapija ta ’ manteniment b’ opioid (ara sezzjoni 4. 1) minħabba li hemm riskju miżjud ta ’ depressjoni respiratorja.
Severe respiratory depression or severe obstructive lung conditions.
Depressjoni respiratorja severa jew kondizzjonijiet severi ta ’ ostruzzjoni tal- pulmun.
4 4.4 Special warnings and precautions for use
4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu
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.
Il- pazjenti u dawk li jieħdu ħsiebhom għandhom jiġi mgħallma li Effentora fih sustanza attiva fi kwantità li tista ’ tkun fatali għat- tfal, u għalhekk biex iżommu l- pilloli kollha fejn ma jintlaħqux u ma jidrhux mit- tfal.
In order to minimise the risks of opioid-related undesirable effects and to identify the effective dose, it is imperative that patients be monitored closely by health professionals during the titration process.
Sabiex jitnaqqsu r- riskji ta ’ effetti mhux mixtieqa relatati mal- opioids u tiġi identifikata d- doża effettiva, huwa vitali li l- pazjenti jiġu sorveljati mill- viċin minn professjonisti fil- qasam mediku waqt il- proċess ta ’ titrazzjoni.
It is important that the long acting opioid treatment used to treat the patient’ s persistent pain has been stabilised before Effentora therapy begins.
Huwa importanti li l- kura b’ opioid li jaħdem fit- tul użata għall- kura tal- uġigħ persistenti tal- pazjenti tkun ġiet stabilizzata qabel tinbeda terapija b’ Effentora.
As with all opioids, there is a risk of clinically significant respiratory depression associated with the use of fentanyl.
Bħal bl- opioids kollha, hemm riskju ta ’ depressjoni respiratorja ta ’ sinifikanza klinika assoċjata ma ’ l - użu ta ’ fentanyl.
Particular caution should be used when titrating Effentora in patients with non-severe chronic obstructive pulmonary disease or other medical conditions predisposing them to respiratory depression, as even normally therapeutic doses of Effentora may further decrease respiratory drive to the point of respiratory failure.
Għandha tintuża attenzjoni partikulari meta jiġi ttitrat Effentora f’ pazjenti b’ marda pulmonari ostruttiva kronika mhux severa jew b’ kundizzjonijiet mediċi oħra li jippredisponu għal depressjoni respisratorja, minħabba li anki dożi terapewtiċi normali ta ’ Effentora jistgħu jnaqqsu aktar l- ħidma respiratorja sal- punt ta ’ insuffiċjenza respiratorja.
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.
Effentora għandu jingħata biss b’ attenzjoni estrema f’ pazjenti li jistgħu jkunu partikolarment suxxettibli għall- effetti intrakranjali ta ’ żamma ta ’ CO2, bħal dawk b’ evidenza ta ’ żjieda fil- pressjoni intrakranjali jew b’ koxjenza mnaqqsa.
Opioids may obscure the clinical course of a patient with a head injury and should be used only if clinically warranted.
Opioids jistgħu jaħbu l- progressjoni klinika ta ’ pazjent b’ ferita fir- ras u għandhom jintużaw biss jekk iġġustifikat klinikament.
Intravenous fentanyl may produce bradycardia.
Fentanyl ġol- vini jista ’ jipproduċi bradikardja.
In clinical trials with Effentora, no clear evidence for bradycardia was observed.
Fi provi kliniċi b’ Effentora, ma kienet osservata l- ebda evidenza ċara ta ’ bradikardja.
However, Effentora should be used with caution in patients with pre- existing bradyarrhythmias.
Iżda, Effentora għandu jintuża b’ attenzjoni f’ pazjenti bi bradiarritmija eżistenti minn qabel.
In addition, Effentora should be administered with caution to patients with hepatic or renal impairment.
Barra dan, Effentora għandu jingħata b’ attenzjoni lill- pazjenti b’ indeboliment tal- fwied jew renali.
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.
L - influwenza ta ’ indeboliment tal- fwied u renali fuq il- farmakokinetika tal- prodott mediċinali ma ġietx ivvalutata, iżda, intwera li meta mogħti ġol- vini it- tneħħija ta ’ fentanyl tiġi mibdula f’ indeboliment tal - fwied u renali minħabba bidliet fit- tneħħija metabolika u fil- proteini fil- plażma.
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.
Wara l- għoti ta ’ Effentora, kemm funzjoni mnaqqsa tal- fwied, kif ukoll dik renali tista ’ żżid il- biodisponibiltà ta ’ fentanyl li jinbela ’ u tnaqqas it- tneħħija sistemika tiegħu, li jistgħu jwasslu għall- effetti tal- opioid miżjuda u mtawwla.
Therefore, special care should be taken during the titration process in patients with moderate or severe hepatic or renal impairment.
Għalhekk, għandha tittieħed attenzjoni speċjali waqt il- proċess ta ’ titrazzjoni f’ pazjenti b’ indeboliment tal- fwied jew renali, moderat jew sever.
Careful consideration should be given to patients with hypovolaemia and hypotension.
Għandha tingħata kunsiderazzjoni b’ attenzjoni lill- pazjenti b’ ipovolimja u pressjoni baxxa.
Tolerance and physical and/ or psychological dependence may develop upon repeated administration of opioids such as fentanyl.
Tolleranza u dipendenza fiżika u/ jew psikoloġika jistgħu jiżviluppaw wara għoti ripetut ta ’ opioids bħal fentanyl.
However, iatrogenic addiction following therapeutic use of opioids is rare.
Madankollu, dipendenza atroġenika wara użu terapewtiku ta ’ opioids hija rari.
This medicinal product contains 8 mg sodium per tablet.
Dan il- prodott mediċinali fih 8 mg sodium kull pillola.
To be taken into consideration by patients on a controlled sodium diet.
Dan għandu jittieħed f’ kunsiderazzjoni minn pazjenti fuq dieta b’ sodium ikkontrollat.
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.
5 Fentanyl huwa metabolizzat primarjament permezz tas- sistema ta ’ isoenzima taċ- ċitokromju uman P450 3A4 (CYP3A4), għalhekk jistgħu jseħħu interazzjonijiet potenzjali meta Effentora jingħata flimkien ma ’ sustanzi li jaffettwaw l- attività ta ’ CYP3A4.
Coadministration with agents that induce 3A4 activity may reduce the efficacy of Effentora.
L- għoti flimkien ma ’ sustanzi li jinduċu l - attività ta ’ 3A4 tista ’ tnaqqas l- effikaċja ta ’ Effentora.
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.
L- użu ta ’ Effentora flimkien ma ’ inibituri qawwija ta ’ CYP3A4 (e. ż., ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, u nelfinavir) jew inibituri moderati ta ’ CYP3A4 (e. ż., amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, meraq tal- grejpfrut, u verapamil) jista ’ jwassal għal żjieda fil - konċentrazzjonijiet ta ’ fentanyl fil- plażma, u potenzjalment jikkawżaw reazzjonijiet avversi tal - mediċina serji inkluż depressjoni respiratorja fatali.
Patients receiving Effentora concomitantly with moderate or strong CYP3A4 inhibitors should be carefully monitored for an extended period of time.
Pazjenti li qed jirċeivu Effentora flimkien ma ’ inibituri moderati jew qawwija ta ’ CYP3A4 għandhom jiġu sorveljati b’ attenzjoni għal perjodu mtawwal ta ’ żmien.
Dosage increase should be done with caution.
Żjieda fid- doża għandha ssir b’ attenzjoni.
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.
L- użu fl- istess waqt ta ’ depressanti tas- sistema nervuża ċentrali oħra, inkluż opioids oħra, sedattivi jew ipnotiċi, anestetiċi ġenerali, phenothiazines, kalmanti, rilassanti tal- muskoli skeltrali, antistamini sedattivi u alkoħol, jista ’ jipproduċi effetti dipressanti miżjuda.
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.
Effentora mhux irrakkomandat għall- użu f’ pazjenti li rċevew inibituri ta ’ monoamine oxidase (MAO) fi żmien 14- il ġurnata, minħabba li b’ analġeżiċi opioid kien irrapportat żjieda severa fil- qawwa, li ma tistax titbassar minn inibituri ta ’ MAO.
The concomitant use of partial opioid agonists/ antagonists (e. g. buprenorphine, nalbuphine, pentazocine) is not recommended.
L- użu fl- istess waqt ta ’ agonisti/ antagonisti parzjali ta ’ opioid (e. ż. buprenorphine, nalbuphine, pentazocine) mhux irrakkomandat.
They have high affinity to opioid receptors with relatively low intrinsic activity and therefore partially antagonise the analgesic effect of fentanyl and may induce withdrawal symptoms in opioid dependant patients.
Dawn għandhom affinità għolja għar- riċetturi ta ’ opioid, b’ attività ntrinsika relattivament baxxa, u għalhekk parzjalment inaqqsu l- effett analġeżiku ta ’ fentanyl u jistgħu jikkawżaw sintomi ta ’ rtirar f’ pazjenti dipendenti fuq l- opioids.
There are no adequate data from the use of fentanyl in pregnant women.
M’ hemmx tgħarif biżżejjed dwar l- użu ta ’ fentanyl waqt it- tqala.
Studies in animals have shown reproductive toxicity (see section 5.3).
Studji fuq bhejjem urew ħsara fuq is - sistema riproduttiva (ara sezzjoni 5. 3).
Effentora should not be used in pregnancy unless clearly necessary.
Effentora m’ għandux jintuża waqt it- tqala ħlief meta hemm bżonn speċifiku.
Following long-term treatment, fentanyl may cause withdrawal in the new-born infant.
Wara kura fit- tul, fentanyl jista ’ jikkawża sintomi ta ’ rtirar fit- tarbija li għadha titwieled.
It is advised not to use fentanyl during labour and delivery (including caesarean section) because fentanyl passes through the placenta and may cause respiratory depression in the foetus.
Huwa rakkomandat li fentanyl ma jintużax waqt il- ħlas u t- twelid (inkluż ċesarja) minħabba li fentanyl jgħaddi minn ġol- plaċenta u jista ’ jikkawża depressjoni respiratorja fil- fetu.
If Effentora is administered, an antidote for the child should be readily available.
Jekk Effentora jingħata, antidotu għat- tarbija għandu jkun disponibbli malajr.
Fentanyl passes into breast milk and may cause sedation and respiratory depression in the breast-fed child.
Fentanyl jgħaddi għal ġol- ħalib tas- sider u jista ’ jikkawża sedazzjoni u depressjoni respiratorja fit - tarbija li qed tiġi mredda ’.
Fentanyl should only be used by breastfeeding women if the benefits outweigh the potential risks for both mother and child.
Fentanyl għandu jintuża minn nisa li qed ireddgħu biss jekk il- benefiċċji huma akbar mir- riskji potenzjali kemm għall- omm kif ukoll għat- tarbija.
No studies of the effects on the ability to drive and use machines have been performed.
Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni.
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).
Madankollu, analġeżiċi opioid inaqqsu l- ħila mentali u/ jew fiżika meħtieġa biex jitwettaq xogħol potenzjalment perikoluż (e. ż., sewqan ta ’ karozza jew tħaddim ta ’ magni).
Patients should be advised not to drive or operate machinery if they experience somnolence, dizziness, or visual disturbance while taking Effentora and not to drive or operate machinery until they know how they react.
Pazjenti għandhom jiġu avżati biex ma jsuqux jew iħaddmu magni jekk ikollhom esperjenza ta ’ nagħas, sturdament, jew disturbi fil- vista waqt li qed jieħdu Effentora u biex ma jsuqux jew iħaddmu magni qabel ikunu jafu kif ser jirreaġixxu.
Typical opioid undesirable effects are to be expected with Effentora.
Effetti mhux mixtieqa tipikament konnessi ma ’ opioids huma mistennija b’ Effentora.
Frequently, these will cease or decrease in intensity with continued use of the medicinal product, as the patient is titrated to the most appropriate dose.
Frekwentement, dawn jiefqu jew jonqsu fl- intensità b’ użu kontinwu tal- prodott mediċinali, minħabba li l- pazjent huwa ttitrat għad- doża l- aktar xierqa.
However, the most serious adverse reactions are respiratory depression (potentially leading to apnoea or respiratory arrest), circulatory depression, hypotension and shock and all patients should be closely monitored for these.
Madankollu, l- aktar reazzjonijiet avversi serji huma depressjoni respiratorja (potenzjalment twassal għall- apneja jew waqfien respiratorju), depressjoni ċirkolatorja, pressjoni baxxa u xokk u l- pazjenti kollha għandhom jiġu sorveljati mill- viċin għal dawn.
The clinical studies of Effentora were designed to evaluate safety and efficacy in treating BTP and all patients were also taking concomitant opioids, such as sustained-release morphine or transdermal fentanyl, for their persistent pain.
6 L- istudji kliniċi ta ’ Effentora kienu maħsuba biex jivvalutaw is- sigurtà u l- effikaċja fil- kura ta ’ BTP u l- pazjenti kollha kienu qed jieħdu wkoll opioids fl- istess waqt, bħal morfina li tintreħa bil- mod jew fentanyl minn ġol- ġilda, għall- uġigħ persistenti tagħhom.
Therefore it is not possible to definitively separate the effects of Effentora alone.
Għalhekk mhux possibli li jiġu separati b’ mod definittiv l- effetti ta ’ Effentora waħdu.
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):
Ir- reazzjonijiet avversi kkunsidrati bħala ta ’ l- inqas possibilment relatati mal- kura mill- istudji kliniċi kienu kif ġej (frekwenza definita bħala: komuni ħafna ≥1/ 10, komuni ≥1/ 100 sa < 1/ 10, mhux komuni ≥ 1/ 1, 000 sa < 1/ 100; f’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa għandhom jitniżżlu skond is- serjetà tagħhom.
6 Investigations
Investigazzjonijiet
Uncommon Platelet count decreased Heart rate increased Haematocrit decreased Haemoglobin decreased
Mhux Komuni Għadd tal- plejtlits imnaqqas Rata tal- qalb miżjuda Ematokrita mnaqqsa Emoglobina mnaqqsa
Cardiac disorders Blood and lymphatic system disorders
Disturbi fil- qalb Disturbi tad- demm u tas- sistema limfatika
Tachycardia, Bradycardia Anaemia Neutropenia Thrombocytopenia
Takikardja, Bradikardja Anemija Newtropenja Tromboċitopenja
Dysgeusia Somnolence Lethargy Headache Tremor Sedation
Disġewsja Ngħas Letarġija Uġigħ ta ’ ras Tregħid Sedazzjoni
Depressed level of consciousness Disturbance in attention Cognitive disorder Hypoaesthesia Balance disorder Migraine Motor dysfunction Dysarthria
Livell ta ’ koxjenza mnaqqas Disturbi fl- attenzjoni Disturb konoxxittiv Ipoestesija Disturb fil- bilanċ Emigranja Funzjoni motorja mhux normali Disartrija
Visual disturbance Ocular hyperaemia Abnormal sensation in eye Photopsia Blurred vision Visual acuity reduced
Disturbi fil- vista Iperimja ta 'l- għajn Sensazzjoni mhux normali fl- għajn Fotopsja Vista mċajpra Akutezza fil- vista mnaqqsa
Ear and labyrinth disorders
Disturbi fil- widnejn u fis- sistema labirintika Disturbi respiratorji, toraċiċi u medjastinali
Vertigo Tinnitus Ear discomfort
Vertigo Tinnitus Skomdu fil- widna Qtugħ ta ’ nifs Uġigħ faringolarinġali
Respiratory, thoracic and mediastinal disorders
Komuni ħafna
Dyspnoea Pharyngolaryngeal pain
Mhux Komuni
Nausea
Tqalligħ
Vomiting Constipation Stomatitis Dry mouth Diarrhoea
Rimettar Stitikezza Stomatite Ħalq xott Dijarea
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
Ulċerazzjoni fil- ħalq Ipoestesija orali Skomdu orali Nfafet fil- mukuża orali Telf tal- kulur tal- mukuża orali Disturb fit- tessut artab orali Glossodinja Nfafet fl- ilsien Uġigħ fil- ħanek Skomdu fl- istonku Ulċerazzjoni fl- ilsien Disturbi fl- ilsien Dispepsja Uġigħ addominali Esofaġite Marda ta ’ rifluss gastro - esofagali Xuftejn maqsuma Xoffa xotta Disturbi fis- snien Uġigħ fis- snien
Urinary retention
Żamma ta ’ l- awrina
7 Skin and subcutaneous tissue disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il - ġilda
Very common
Ħakk Iperidrożi
Uncommon Cold sweat Facial swelling Rash Generalised pruritus Alopecia Onychorrhexis
Għaraq kiesaħ Nefħa fil- wiċċ Raxx Ħakk ġeneralizzat Alopeċja Onikorreksis
Musculoskeletal and connective tissue disorders
Disturbi muskolu - skeltrali u tal - connective tissue
Myalgia Muscle twitching Muscular weakness Back pain
Majalġja Tiġbid tal- muskoli Debulizza muskolari Uġigħ fid- dahar
Oral candidiasis Pharyngitis Oral pustule
Kandidajasi orali Farinġite Nuffata orali
Injury, poisoning and procedural complications
Korriment, avvelena ment u komplikazzjonijiet ta ’ xi proċedura
Fall
Waqa ’
Multiple myeloma
Majloma multipla
Flushing Hypertension Hot flush
Fwawar Pressjoni għolja Fawra
Application site reactions including pain, ulcer, irritation, paraesthesia, anaesthesia, erythema, oedema, swelling and vesicles
Reazzjonijiet fis- sit tal- injezzjoni inkluż uġigħ, ulċera, irritazzjoni, parestesija, anestesija, eritima, edima, nefħa u nfafet żgħar
Asthenia Malaise Sluggishness Chest discomfort Feeling abnormal Feeling jittery Thirst Feeling cold Chills Feeling hot Drug withdrawal syndrome
Astenja Tħossok ma tiflaħx Letarġija Skomdu fis- sider Tħossok mhux normali Tħossok bla paċenzja Għatx Tħoss il- bard Kesħa Tħoss is- sħana Sindrome ta ’ rtirar tal - mediċina
Disorientation Euphoric mood
Disorjenament Burdata ewforika
Anxiety Nervousness Hallucination Visual hallucination Insomnia Confusional state
Ansjetà Nervi Alluċinazzjonijiet Alluċinazzjonijiet viżwali Nuqqas ta ’ rqad Stat konfuż
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.
Is- sintomi ta ’ doża eċċessiva ta ’ fentanyl huma mistennija li jkunu ta ’ natura simili bħal dawk ta ’ fentanyl ġol- vini u ta ’ opioids oħra, u huma estensjoni ta ’ l- azzjonijiet farmakoloġiċi tiegħu, b ’ depressjoni respiratorja bħala l- aktar effett sinnifikanti serju.
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.
Immaniġġjar immedjat ta ’ doża eċċessiva ta ’ opioid tinkludi t- tneħħija tal- pillola għall- ħalq Effentora, jekk għada fil- ħalq, il- konferma ta ’ passaġġ għall- arja, stimulazzjoni fiżika u verbali tal- pazjent, valutazzjoni tal- livell ta ’ koxjenza, stat ta ’ ventilazzjoni u ċirkolazzjoni, u ventilazzjoni assistita (appoġġ b’ ventilazzjoni) jekk hemm bżonn.
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.
Għall- kura ta ’ doża eċċessiva (teħid bi żball) f’ persuna li qatt ma tkun ħadet opioids qabel, għandu jinkiseb aċċess ġol- vini u naloxone jew antagonisti tal- opioids oħra għandhom jiġu ntużati kif indikat klinikament.
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.
Id- dewmien tad- depressjoni respiratorja wara doża eċċessiva jista ’ jkun itwal mill- effetti ta ’ l- azzjoni ta ’ l- antagonist tal- opioids (e. ż., il- half- life ta ’ naloxone tvarja minn 30 sa 81 minuta) u jista ’ jkun hemm bżonn ta ’ għotja ripetuta.
Consult the Summary of Product Characteristics of the individual opioid antagonist for details about such use.
Ikkonsulta is- Sommarju tal- Karatteristiċi tal- Prodott ta ’ l - antagonist tal- opioids individwali għall dettalji dwar dan l- użu.
For treatment of overdose in opioid-maintained patients, intravenous access should be obtained.
Għall- kura ta ’ doża eċċessiva f’ pazjenti miżmuma fuq opioids, għandu jinkiseb aċċess ġol- vini.
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.
F’ xi każijiet huwa ġġustifikat l- użu bil- għaqal ta ’ naloxone jew ta ’ antagonist ta ’ l- opioids ieħor, iżda dan huwa assoċjat mar- riskju li jippreċipita sindrome akuta ta ’ rtirar tal- mediċina.
Although muscle rigidity interfering with respiration has not been seen following the use of Effentora, this is possible with fentanyl and other opioids.
Għalkemm ma kienitx osservata riġidità fil- muskoli li tinterferixxi mar- respirazzjoni wara l- użu ta ’ Effentora, din hija possibli b’ fentanyl u b’ opioids oħra.
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.
Jekk din iseħħ, għandha tiġi mmaniġġjata bl - użu ta ’ ventilazzjoni assistita, b’ anatagonist ta ’ l- opioids, u bħala alternattiva finali, b’ sustanza li timblokka in- newromuskolatura.
Fentanyl is an opioid analgesic, interacting predominantly with the opioid µ-receptor.
9 Fentanyl huwa analġeżiku opioid, li jinteraġixxi l- aktar mar- riċettur µ tal- opioids.
Its primary therapeutic actions are analgesia and sedation.
L- azzjonijiet terapewtiċi primarji tiegħu huma analġeżija u sedazzjoni.
Secondary pharmacological effects are respiratory depression, bradycardia, hypothermia, constipation, miosis, physical dependence and euphoria.
L- effetti farmakoloġiċi sekondarji huma depressjoni respiratorja, bradikardja, ipotermja, stitikezza, mijosi, dipendenza fiżika u ewforja.
The analgesic effects of fentanyl are related to its plasma level.
L- effetti analġeżiċi ta ’ fentanyl huma relatati mal- livell tiegħu fil- plażma.
In general, the effective concentration and the concentration at which toxicity occurs increase with increasing tolerance to opioids.
Ġeneralment, il - konċentrazzjoni effettiva u l- konċentrazzjoni li fiha sseħħ it- tossiċità jiżdiedu hekk kif tiżdied it - tolleranza għal opioids.
The rate of development of tolerance varies widely among individuals.
Ir- rata ta ’ żvilupp ta ’ tolleranza tvarja ħafna fost individwi.
As a result, the dose of Effentora should be individually titrated to achieve the desired effect (see section 4.2).
Bħala riżultat, id - doża ta ’ Effentora għandha tiġi ttitrata individwalment biex jinkiseb l- effet mixtieq (ara sezzjoni 4. 2).
All opioid µ-receptor agonists, including fentanyl, produce dose dependent respiratory depression.
L- antagonisti tar- riċettur µ tal- opioids kollha, inkluż fentanyl, jipproduċu depressjoni respiratorja dipendenti mid- doża.
The risk of respiratory depression is less in patients receiving chronic opioid therapy as these patients will develop tolerance to respiratory depressant effects.
Ir- riskju ta ’ depressjoni respiratorja hija inqas f’ pazjenti li qed jirċievu terapija kronika b’ opioid peress li dawn il- pazjenti ser jiżviluppaw tolleranza għall- effetti ta ’ depressjoni respiratorja.
The safety and efficacy of Effentora have been evaluated in patients taking the drug at the onset of the breakthrough pain episode.
Is- sigurtà u l- effikaċja ta ’ Effentora ġew ivvalutati f’ pazjenti li jieħdu il- mediċina mal- bidu tal - episodju ta ’ uġigħ li jinħass.
Pre-emptive use of Effentora for predictable pain episodes was not investigated in the clinical trials.
L- użu minn qabel ta ’ Effentora għall- episodji mistennija ta ’ uġigħ ma kienx investigat fil- provi kliniċi.
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.
Twettqgħu żewġ studji crossover, double- blind, randomised, ikkontrollati bil- plaċebo li nvolvew 248 pazjent b’ BTP u kanċer li kellhom esperjenza ta ’ medja ta ’ episodju wieħed sa 4 episodji ta ’ BTP kuljum waqt li qed jieħdu terapija ta ’ manteniment b’ opioid.
During an initial open-label phase, patients were titrated to an effective dose of Effentora.
Waqt fażi open- label tal- bidu, l- pazjenti kienu ttitrati għall- doża effettiva ta ’ Effentora.
Patients who identified an effective dose entered the double-blind phase of the study.
Pazjenti li identifikaw doża effettiva daħlu fil- fażi double- blind ta ’ l- istudju.
The primary efficacy variable was the patient’ s assessment of pain intensity.
L- varjabbli primarja ta ’ l- effikaċja kienet il- valutazzjoni tal- pazjent ta ’ l- intensità ta ’ l- uġigħ.
Patients assessed pain intensity on a 11-point scale.
Il- pazjenti vvalutaw l- intensità ta ’ l- uġigħ fuq skala ta ’ 11- il punt.
For each BTP episode, pain intensity was assessed prior to and at several time points after treatment.
Għal kull episodju ta ’ BTP, l- intensità ta ’ l- uġigħ kienet ivvalutata qabel u f’ bosta punti ta ’ ħin wara l- kura.
Sixty-seven percent of the patients were able to be titrated to an effective dose.
Sebgħa u sittin fil- mija tal- pazjenti setgħu jiġu ttitrati għal doża effettiva.
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).
Fl- istudji kliniku pivitali (studju 1), l- mira primarja kienet l- medja ta ’ l- għadd tad- differenza fil - punteġġi ta ’ l- intensità ta ’ l- uġigħ mill- iddożar sa 60 minuta, inkluża (SPID60), li kienet statistikament sinnifikanti meta mqabbla mal- plaċebo (p < 0. 0001).
9 Study 1:
Studju 1:
Mean (+/ - SEM) Pain Intensity Difference at Each Time Point (Full Analysis Set) Mean (SEM) Pain Intensity Differences
Medja (+ / - SEM) tad- Differenzi fl- Intensità tal- Ugigh f’ Kull Punt ta ’ Hin (Sett ta ’ Analizi Kompluta) Medja (SEM) tad- Differenza fl- Intensità tal- Ugigh
SPID60 mean (+/ - SD) EFFENTORA=9.7(5.58) p < 0.0001 Placebo=4.9(4.38)
Medja SPID60 (+ / - SD) EFFENTORA=9. 7( 5. 58) p < 0. 0001 Placebo=4. 9( 4. 38)
Time from Administration of Study Drug (Minutes)
Hin mill- Ghoti tal- Medicina taht Studju (Minuti)
Treatment Group
Grupp ta ’ Kura
+ 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
+ p < 0. 0001 EFFENTORA kontra placebo, favur EFFENTORA, permezz ta ’ analizi ta ’ varjanza PID=differenza fl- intensità ta ’ l- ugigh; SEM=zball stàndard tal- medja
Study 2:
Studju 2:
Mean (+/ - SEM) Pain Intensity Difference at Each Time Point (Full Analysis Set)
Medja (+ / - SEM) tad- Differenza fl- Intensità tal- Ugigh f’ Kull Punt ta ’ Hin (Sett ta ’ Analizi Kompluta) Medja (SEM) tad- Differenza fl- Intensità tal- Ugigh
SPID30 mean (+/ - SD) EFFENTORA=3.2(2.60) p < 0.0001 Mean (SEM) Pain Intensity Differences
Medja SPID30 (+ / - SD) EFFENTORA=3. 2( 2. 60) p < 0. 0001 Placebo=2. 0( 2. 21) Placebo=4. 9( 4. 38)
* 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
* p < 0. 01 EFFENTORA kontra placebo, favur EFFENTORA, permezz ta ’ analizi rank b’ kampjun wiehed iffirmat Wilcoxon + p < 0. 0001 EFFENTORA kontra placebo, favur EFFENTORA, permezz ta ’ analizi rank b’ kampjun wiehed iffirmat Wilcoxon PID=differenza fl- intensità ta ’ l- ugigh; SEM=zball stàndard tal- medja
In the second pivotal study (study 2), the primary endpoint was SPID30, which was also statistically significant compared to placebo (p < 0.0001).
11 Fit- tieni studju pivitali (studju 2), l- mira primarja kienet SPID30, li kienet ukoll statistikament sinnifikanti meta mqabbla mal- plaċebo (p < 0. 0001).
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.
Deher titjib statistikament sinnifikanti fid- differenza fl- intensità tal- uġigħ b’ Effentora kontra plaċebo minn wara 10 minuti fi Studju 1 u minn wara 15- il minuta (l- aktar punt ta ’ ħin bikri mkejjel) fi Studju 2.
These differences continued to be significant at each subsequent time point in each individual study.
Dawn id- differenzi baqgħu sinnifikanti f’ kull punt ta ’ ħin sussegwenti f’ kull studju individwali.
General introduction Fentanyl is highly lipophilic and can be absorbed very rapidly through the oral mucosa and more slowly by the conventional gastrointestinal route.
Introduzzjoni Ġenerali Fentanyl huwa lipofiliku ħafna u jista ’ jiġi assorbit malajr ħafna minn ġol- mukuża orali u aktar bil - mod mir- rotta gastro- intestinali konvenzjonali.
It is subject to first-pass hepatic and intestinal metabolism and the metabolites do not contribute to fentanyl’ s therapeutic effects.
Huwa suġġett għall- metaboliżmu tal- fwied u tal - musrana ta ’ l- ewwel passaġġ u l- metaboliti ma jikkontribwixxux għall- effetti terapewtiċi ta ’ fentanyl.
Effentora employs a delivery technology which utilises an effervescent reaction which enhances the rate and extent of fentanyl absorbed through the buccal mucosa.
Effentora juża teknoloġija ta ’ tqassim li tutilizza reazzjoni effervexxenti li ttejjeb ir- rata u l- kwantità ta ’ assorbiment ta ’ fentanyl minn ġol- mukuża tal- ħalq.
Transient pH changes accompanying the effervescent reaction may optimise dissolution (at a lower pH) and membrane permeation (at a higher pH).
Bidliet temporanji tal- pH li jseħħu mar - reazzjoni effervexxenti jistgħu jtejbu d- dissoluzzjoni (f’ pH aktar baxxa) u l- porożita tal- membrana (f’ pH aktar għoli).
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.
Ħin ta ’ żamma (iddefinit bħala it- tul ta ’ żmien li l- pillola tieħu biex tiddisintegra għal kollox wara għoti mill- ħalq), ma jaffettwax l- esponiment sistemiku bikri għal fentanyl.
The effect of renal or hepatic impairment on the pharmacokinetics of Effentora has not been studied.
L- effett ta ’ indeboliment renali jew tal- fwied fuq il- farmakokinetika ta ’ Effentora ma ġiex studjat.
Absorption:
Assorbmient:
Following oromucosal administration of Effentora, fentanyl is readily absorbed with an absolute bioavailability of 65%.
Wara għoti oromukużali ta ’ Effentora, fentanyl huwa assorbit malajr b’ biodisponibiltà assoluta ta ’ 65%.
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.
Il- profil ta ’ assorbiment ta ’ Effentora huwa l- biċċa l- kbira r- riżultat ta ’ assorbiment tal- bidu malajr mill- mukuża tal- ħalq, b’ konċentrazzjonijiet massimi fil- plażma wara li jittieħed kampjun minn ġol- vina ġeneralment jintlaħqu fi żmien siegħa wara l- għoti fil- mukuża tal- ħalq.
Approximately 50% of the total dose administered is rapidly absorbed transmucosally and becomes systemically available.
Madwar 50% tad - doża totali mogħtija hija assorbita malajr minn ġol- mukuża u ssir disponibbli b’ mod sistemiku.
The remaining half of the total dose is swallowed and slowly absorbed from the gastrointestinal tract.
In- nofs tad- doża totali li jibqa ’, jinbela ’ u jiġi assorbit bil- mod mill- apparat gastro- intestinali.
About 30% of the amount swallowed (50% of the total dose) escapes hepatic and intestinal first-pass elimination and becomes systemically available.
Madwar 30% ta ’ l- ammont li jinbela ’ (50% tad- doża totali) jeħles mill- eliminazzjoni tal- fwied u tal- musrana ta ’ l - ewwel passaġġ u jsir disponibbli b’ mod sistemiku.
The main pharmacokinetic parameters are shown in the following table.
Il- parametri farmakokinetiċi maġġuri huma mniżżla fit- tabella li ġejja.
Pharmacokinetic Parameters* in Adult Subjects Receiving Effentora
Parametri Farmakokinetiċi * f’ Individwi Adulti li Rċevew Effentora
Pharmacokinetic parameter (mean)
Parametru farmakokinetiku (medja)
Effentora 400 micrograms
Effentora 400 mikrogramma
Absolute bioavailability
Biodisponibiltà assoluta
Fraction absorbed transmucosally
Porzjon assorbit minn ġol - mukuża
46.8 (20-240)
46. 8 (20- 240)
1.02 (± 0.42)
1. 02 (± 0. 42)
0.40 (± 0.18)
0. 40 (± 0. 18)
6.48 (± 2.98)
6. 48 (± 2. 98)
* Based on venous blood samples (plasma).
* Ibbażat fuq kampjuni tad- demm minn ġol- vina (plażma).
Fentanyl citrate concentrations obtained in serum were higher than in plasma:
Konċentrazzjonijiet ta ’ fentanyl citrate miksuba fis- serum kienu ogħla minn dawk fil- plażma:
Serum AUC and Cmax were approximately 20% and 30% higher than plasma AUC and Cmax, respectively.
12 30% ogħla mill- AUC u Cmax tal- plażma, rispettivament.
The reason of this difference is unknown. ** Data for Tmax presented as median (range).
Ir- raġuni ta ’ din id- differenza mhix magħrufa. ** Tagħrif għal Tmax ippreżentat bħala medjan (firxa).
11 In pharmacokinetic studies that compared the absolute and relative bioavailability of Effentora and oral transmucosal fentanyl citrate (OTFC), the rate and extent of fentanyl absorption in Effentora demonstrated exposure that was between 30% to 50% greater than that for oral transmucosal fentanyl citrate.
Fi studji farkokinetiċi li qabblu il- biodisponibiltà assoluta u relattiva ta ’ Effentora u ta ’ fentanyl citrate orali minn ġol- mukuża (OTFC), ir- rata u l- kwantità ta ’ assorbiment ta ’ fentanyl f’ Effentora wrew esponiment li kien bejn 30% sa 50% akbar minn dak għal fentanyl citrate orali minn ġol- mukuża.
However, in these patients, a starting dose higher than 100 micrograms may be considered.
Madankollu, f’ dawn il - pazjenti, tista ’ tiġi kkunsidrata doża tal- bidu ogħla minn 100 mikrogramma.
Mean Plasma Concentration Versus Time Profiles Following Singles Doses of EFFENTORA and OTFC in Healthy Subjects
Koncentrazzjonijiet Medji fil- Plazma Kontra Hin Profili Wara Dozi Singoli ta ’ EFFENTORA u OTFC f’ Individwi f’ Sahhithom
OTFC (normalized to 400 mcg)
OTFC (normalizzat ghal 400 mcg)
Time after Dose Administration (hours) OTFC data was done adjusted (800 mcg to 400 mcg)
Hin wara l- Ghotja tad- Doza (sighat) Taghrif OTFC sar aggustat (800 mcg sa 400 mcg)
Differences in exposure with Effentora were observed in a clinical study with patients with grade 1 mucositis.
Differenzi fl- esponiment b’ Effentora kienu osservati fi studju kliniku b’ pazjenti b’ mukożite ta ’ grad 1.
Cmax and AUC0-8 were 1% and 25% higher in patients with mucositis compared to those without mucositis, respectively.
Cmax u AUC0- 8 kienu 1% u 25% ogħla rispettivament, f’ pazjenti b’ mukożite meta mqabbel ma ’ dawk mingħajr mukożite.
The differences observed were not clinically significant.
Id- differenza osservata ma kienitx ta ’ sinifikanza klinika.
Distribution Fentanyl is highly lipophilic and is well distributed beyond the vascular system, with a large apparent volume of distribution.
Distribuzzjoni Fentanyl huwa lipofiliku ħafna u huwa distribwit sew barra mis- sistema vaskulari, b’ volum ta ’ distribuzzjoni apparenti kbir.
After buccal administration of Effentora, fentanyl undergoes initial rapid distribution that represents an equilibration of fentanyl between plasma and the highly perfused tissues (brain, heart and lungs).
Wara l- għoti mill- ħalq ta ’ Effentora, fentanyl jgħaddi minn distribuzzjoni rapida tal- bidu li tirrappreżenta ekwilibriju ta ’ fentanyl bejn il- plażma u t- tessuti perfużi ħafna (moħħ, qalb u pulmun).
Subsequently, fentanyl is redistributed between the deep tissue compartment (muscle and fat) and the plasma.
Wara, fentanyl jiġi ridistribwit bejn il- kompartiment tat- tessut fond (muskolu u xaħam) u l- plażma.
The plasma protein binding of fentanyl is 80% to 85%.
It- twaħħil mal- proteini fil- plażma ta ’ fentanyl huwa 80% sa 85%.
The main binding protein is alpha-1-acid glycoprotein, but both albumin and lipoproteins contribute to some extent.
Il- proteina ta ’ twaħħil maġġuri hija alpha- 1- acid glycoprotein, iżda albumin u lipoproteini t- tnejn jikkontribwixxu xi ftit.
The free fraction of fentanyl increases with acidosis.
Il- parti ħielsa ta ’ fentanyl tiżdied bl- aċidożi.
12 Biotransformation The metabolic pathways following buccal administration of Effentora have not been characterised in clinical studies.
13 Biotrasformazzjoni Ir- rotot metaboliċi wara l- għoti mill- ħalq ta ’ Effentora ma ġewx ikkaratterizzati fi studji kliniċi.
Fentanyl is metabolised in the liver and in the intestinal mucosa to norfentanyl by CYP3A4 isoform.
Fentanyl huwa metabolizzat fil- fwied u fil- mukuża tal- musrana għal norfentanyl permezz ta ’ isoforma ta ’ CYP3A4.
Norfentanyl is not pharmacologically active in animal studies.
Norfentanyl mhux farmakoloġikament attiv fi studji fl- annimali.
More than 90% of the administered dose of fentanyl is eliminated by biotransformation to N-dealkylated and hydroxylated inactive metabolites.
Aktar minn 90% tad - doża mogħtija ta ’ fentanyl hija eliminata permezz ta ’ biotrasformazzjoni għall- metaboliti mhux attivi N- dealkylated u hydroxylated.
Elimination Following the intravenous administration of fentanyl, less than 7% of the administered dose is excreted unchanged in the urine, and only about 1% is excreted unchanged in the faeces.
Eliminazzjoni Wara għoti ġol- vini ta ’ fentanyl, inqas minn 7% tad- doża mogħtija hija mneħħija mhux mibdula fl - awrina, u madwar 1% biss hija mneħħija mhux mibdula fl- ippurgar.
The metabolites are mainly excreted in the urine, while faecal excretion is less important.
Il- biċċa l- kbira tal- metaboliti jitneħħew fl- awrina, filwaqt li tneħħija fl- ippurgar hija inqas importanti.
Following the administration of Effentora, the terminal elimination phase of fentanyl is the result of the redistribution between plasma and a deep tissue compartment.
Wara għoti ta ’ Effentora, il- fażi ta ’ tneħħija terminali ta ’ fentanyl hija r- riżultat tar- ridistribuzzjoni bejn il- plażma u l- kumpartiment tat- tessut fond.
This phase of elimination is slow, resulting in a median terminal elimination half-life t1/ 2 of approximately 22 hours following buccal administration of the effervescent formulation and approximately 18 hours following intravenous administration.
Din il- fażi ta ’ eliminazzjoni hija bil- mod, u twassal għall- half- life t1/ 2 ta ’ eliminazzjoni terminali medjana ta ’ madwar 22 siegħa wara għoti mill- ħalq tal - formulazzjoni effervexxenti u ta ’ madwar 18- il siegħa wara għoti ġol- vini.
The total plasma clearance of fentanyl following intravenous administration is approximately 42 L/ h.
It- tneħħija totali mill - plażma ta ’ fentanyl wara għoti ġol- vini hija madwar 42 l/ h.
Linearity/ non-linearity Dose proportionality from 100 micrograms to 1000 micrograms has been demonstrated.
Linearità/ nuqqas ta ’ linearità Ġiet murija proporzjonalità mad- doża minn 100 mikrogramma sa 1000 mikrogramma.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.
Informazzjoni li mhiex klinika, magħmula fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku minn dożi ripetuti u effett tossiku fuq il- ġeni, ma turi l- ebda periklu speċjali għall- bnedmin.
Studies with female rats revealed reduced fertility and enhanced embryonal mortality.
Studji b’ firien femminili wrew fertilità mnaqqsa u mortalità miżjuda tal- embriju.
More recent studies showed that effects on the embryo were due to maternal toxicity and not to direct effects of the substance on the developing embryo.
Studji aktar reċenti wrew li l- effetti fuq l- embriju kienu minħabba t- tossiċità fl- omm u mhux minħabba effetti diretti tas - sustanza fuq l- embriju li qed jiżviluppa.
In a study on pre- and postnatal development the survival rate of offspring was significantly reduced at doses which slightly reduced maternal weight.
Fi studju fuq l- iżvilupp ta ’ qabel u ta ’ wara t- twelid ir- rata ta ’ sopravivenza tal- wild kienet mnaqqsa b’ mod sinnifikanti f’ dożi li naqqsu kemmxejn il- piż ta ’ l- omm.
This effect could either be due to altered maternal care or a direct effect of fentanyl on the pups.
Dan l- effett jista ’ jkun jew minħabba kura ta ’ l- omm mibdula jew effett dirett ta ’ fentanyl fuq il - ġriewi.
Effects on somatic development and behaviour of the offspring were not observed.
Effetti fuq l- iżvilupp somatiku u l- imġiebgħa tal- wild ma kienux osservati.
Teratogenic effects have not been demonstrated.
Ma ġewx murija effetti teratoġeniċi.
Long term carcinogenicity studies have not been performed.
Ma twettqux studji fit- tul fuq il- karċinoġeniċità.
Mannitol Sodium starch glycolate type A Sodium hydrogen carbonate Sodium carbonate anhydrous Citric acid anhydrous Magnesium stearate
Mannitol Sodium starch glycolate tip A Sodium hydrogen carbonate Sodium carbonate anhydrous Citric acid anhydrous Magnesium stearate
13 6.4 Special precautions for storage
6. 4 Prekawzjonijiet speċjali għall- ħażna
Store in the original package in order to protect from moisture.
14 Aħżen fil- pakkett oriġinali sabiex tilqa ’ mill- umdita ’.
Aluminium laminated blister of PVC/ Al foil/ Polyamide/ PVC with paper/ polyester lidding.
Folja laminata tal- aluminju ta ’ PVC/ folja ta ’ Al/ Polyamide/ PVC b’ għatu tal- karta/ polyester.
Blister packs are supplied in cartons of 4 or 28 tablets.
Pakketti tal- folja huma fornuti f’ kartuna ta ’ 4 jew 28 pillola.
Not all pack-sizes may be marketed.
Jista jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.