qanastek/EMEA-V3 huggingface dataset:
In addition, the sponsor provided a number of independent overwhelmingly positive benefit/ risk judgements from experts in palliative care.
Barra minn hekk, l- isponsor ipprovda numru ta 'opinjonijiet indipendenti pożittivi ħafna dwar il- benefiċċju/ riskju minn esperti fil- kura palljattiva.
The CHMP not endorse the Applicant claims of dose-relationship between Rapinyl and Actiq and therefore could not conclude on the comparability of systemic exposure obtained with Rapinyl and 10 Actiq.
11 Is- CHMP ma aċċettax l- argumenti ta 'l- Applikant dwar ir- relazzjoni tad- dożi bejn Rapinyl u Actiq u għalhekk ma setax jikkonkludi dwar il- komparabilità ta' l- esponiment sistemiku miksub b' Rapinyl u Actiq.
The CHMP also considered it necessary to assess the full report of the analysis on the comparability of Rapinyl and Actiq, as the available PK data could not support the similarity of both products.
Is- CHMP ħass ukoll li kien meħtieġ li jevalwa r- rapport sħiħ ta 'l- analiżi dwar il- komparabilità ta' Rapinyl u Actiq, billi l- informazzjoni farmakokinetika disponibbli ma kinitx issostni x- xebh taż - żewġ prodotti.
Therefore the efficacy/ safety profile of Rapinyl could be established.
Għaldaqstant, l- effikaċja/ profil tas- sigurtà ta 'Rapinyl ma setgħux jiġu stabbiliti.
The CHMP agreed that the pharmacodynamic properties and the effectiveness of fentanyl are well established and noted the pain model in BTP.
Is- CHMP qabel li l- karatteristiċi farmakodinamiċi u l- effikaċja ta 'fentanyl huma stabbiliti sewwa u nnota l- mudell ta' wġigħ fil- BTP.
Considering the narrow therapeutic margin of fentanyl, the efficacy/ safety profile is tightly dependant on systemic exposure to this drug and as a consequence the comparability of systemic exposure is pivotal.
Minħabba l- marġinu terapewtiku dejjaq ta 'fentanyl, il- profil ta' l - effikaċja/ sigurtà huwa dipendenti ħafna fuq l- esponiment sistemiku għal din il- mediċina u għalhekk il - komparabilità ta 'l- esponiment sistemiku hija ta' importanza fundamentali.
Furthermore, the CHMP was not convinced by the Applicant claim of bioavailability of fentanyl comparison between Rapinyl and Actiq, requesting a robust demonstration of similarity in systemic exposure.
Barra minn hekk, is- CHMP ma kienx konvint mill- affermazzjoni ta 'bijodisponibilità li għamel l- applikant dwar il- paragun ta' fentanyl bejn Rapinyl u Actiq, u talab dimostrazzjoni b' saħħitha tax- xebh f' esponiment sistemiku.
The CHMP considered the low adverse spectrum incidence in opioid-tolerant patients reassuring and noted the statement in the SPC on dose titration.
Is - CHMP ikkunsidra l- inċidenza baxxa ta 'l- ispettru avvers f' pazjenti li jittolleraw l- oppjojdi bħala rassikuranti u nnota d- dikjarazzjoni fl- SPC dwar it- titrazzjoni tad- doża.
The reasonably low intra-individual variation in fentanyl plasma concentrations was also noted, including variation related to fluid intake, mouth wounds, xerostomia (dry mouth) and mucositis.
Ġiet innotata wkoll il - varjazzjoni raġonevolment baxxa fil- konċentrazzjonijiet ta 'fentanyl fil- plażma ta' l- istess individwu, fosthom varjazzjoni relatata mat- teħid tal- fluwidi, feriti fil- ħalq, kserostomija (ħalq xott) u mukożite.
However, the CHMP still considers that the safety of Rapinyl needs further clarification, in particular with regards to repeated administration, the 800 µg dose and the dose titration.
Madankollu, is- CHMP xorta jħoss li s- sigurtà ta 'Rapinyl teħtieġ iżjed kjarifika, b' mod partikolari fir - rigward ta' l- għoti ripetut, id- doża ta '800 µg u t- titrazzjoni tad- doża.
In conclusion, the CHMP considered that the Applicant provided limited information on the patient treatment (titration towards an efficient dose, multiple administrations, administration up to the highest dosage) which prevented an evaluation of efficacy and safety of Rapinyl in the clinical setting and characterisation of the full clinically relevant time effect profile of the drug.
Fl- aħħar nett, is- CHMP ħass li l- applikant ipprovda informazzjoni limitata dwar it- trattament tal - pazjent (titrazzjoni lejn doża effiċjenti, iżjed minn għoti wieħed, għoti sa l- akbar doża) li impediet evalwazzjoni ta 'l- effikaċja u s- sigurtà ta' Rapinyl fl- ambjent kliniku u karatterizzazzjoni tal- profil kliniku rilevanti sħiħ ta 'l- effett tal- mediċina mal- ħin.
Therefore, although the CHMP considers that Rapinyl could be used for the treatment of breakthrough pain in cancer patients the combined available pharmacokinetic, pharmacological and clinical data were considered insufficient and the CHMP requested the Applicant to provide clinical demonstration of the efficacy and safety of Rapinyl at the proposed dosages, including the highest one.
Għaldaqstant, għalkemm is- CHMP iqis li Rapinyl jista 'jintuża għat- trattament ta' wġigħ qawwi f' pazjenti morda bil- kanċer, l- informazzjoni farmakokinetika, farmakoloġika u klinika disponibbli ma kinitx meqjusa bħala suffiċjenti u s- CHMP talab lill- Applikant sabiex jipprovdi dimostrazzjoni klinika ta 'l- effikaċja u s- sigurtà ta' Rapinyl bid - dożi proposti, inkluża l- akbar waħda.
The Applicant provided data from a study investigating the pharmacokinetics of Rapinyl in 8 opioid tolerant cancer patients, which demonstrated that the pharmacokinetic parameters in patients were not different from those in healthy volunteers, with a similar pharmacokinetic variability.
L- applikant ipprovda informazzjoni minn studju li investiga l- farmakokinetika ta 'Rapinyl fi 8 pazjenti morda bil- kanċer tolleranti għall- oppjojdi, li wera li l- parametri farmakokinetiċi fil- pazjenti ma kinux differenti minn dawk f' voluntiera b' saħħithom, b' varjabilità farmakokinetika simili.
The Applicant also discussed xerostomia and mucositis and was of the opinion that neither was expected to significantly affect the dissolution or absorption of sublingual Rapinyl, although noting that Rapinyl was not expected to be used in patients with severe mucositis.
L- applikant iddiskuta wkoll il- kserostomija u l- mukożite u kien ta 'l- opinjoni li l- ebda waħda ma kienet mistennija li taffettwa b' mod sinifikanti t- taħlil jew l- assorbiment ta' Rapinyl taħt l- ilsien, għalkemm innota li Rapinyl ma kienx mistenni li ser jintuża f' pazjenti li jkollhom mukożite akuta.
The CHMP considered that while there are no reasons to suspect that individualised dose titration would not work for the majority of the patients, the CHMP noted that the highest dose was not studied and considered the study size (n=8) to be too small to draw any reliable conclusions due to the limited number of observations and the absence of statistical analysis of the available data.
Is- CHMP ħass li filwaqt li ma kien hemm ebda raġuni biex wieħed jissuspetta li t- titrazzjoni personalizzata tad- doża ma kinitx ser taħdem għall- maġġoranza tal- pazjenti, huwa nnota li l- akbar doża ma kinitx ġiet studjata u qies id- daqs ta 'l- istudju (n=8) bħala żgħir wisq biex wieħed ikun jista' joħroġ xi konklużjonijiet affidabbli minħabba n- numru limitat ta 'osservazzjonijiet u n- nuqqas ta' analiżi statistika mill- informazzjoni disponibbli.
The CHMP therefore concluded that the comparability of patients to healthy volunteers was not demonstrated.
Is- CHMP għalhekk ikkonkluda li l- komparabilità tal - pazjenti mal- voluntiera b' saħħithom ma ġietx murija.
Conclusion on LoQ In conclusion, the CHMP noted that no new data was provided by the Applicant during the procedure but disagreed with the Applicant point of view that further clinical efficacy and safety data are not needed, indeed the justification relies entirely on a bridging strategy that assumes that the bioavailability obtained with Rapinyl is twice higher than that obtained with Actiq at the same molar dose.
Konklużjoni dwar il- LoQ Bħala konklużjoni, is- CHMP innota li ma ngħatat ebda informazzjoni ġdida mill- applikant waqt il - proċedura iżda ma qabilx mal- pożizzjoni ta 'l- applikant li ma kinitx meħtieġa iżjed informazzjoni dwar l- effikaċja u s- sigurtà klinika, fil- fatt il- ġustifikazzjoni tibbaża kompletament fuq strateġija ta' bridging li tassumi li l- bijodisponibilità miksuba b' Rapinyl hija darbtejn ogħla minn dik miksuba b' Actiq bl - istess doża molari.
The CHMP considered that this was not demonstrated by the data provided due to the questionability of the reliability of study EN3267-001, because the data does not allow the evaluation of the bioavailability of the two formulations, and because the pooled analysis cannot be endorsed.
Is- CHMP ħass li dan ma ntweriex mill- informazzjoni pprovduta minħabba d- dubju ta 'l- affidabilità ta' l- istudju EN3267- 001, minħabba li l- informazzjoni ma tippermettix l- evalwazzjoni tal- bijodisponibilità taż- żewġ formulazzjonijiet, u minħabba li l- analiżi miġbura ma tistax tiġi aċċettata.
Furthermore, the CHMP considered that the provided clinical data on the efficacy and safety of Rapinyl in the treatment of BTP under normal conditions are scarce and that no conclusion could be drawn from the clinical study provided.
Barra minn hekk, is- CHMP ħass li l- informazzjoni klinika pprovduta dwar l- effikaċja u s - sigurtà ta 'Rapinyl fit- trattament ta' BTP taħt kundizzjonijiet normali kienet skarsa u li ma setgħet tinħareġ l- ebda konklużjoni mill- istudju kliniku pprovdut.
In addition, because limited PK data are available in patients, these data cannot be compared to the ones obtained in healthy volunteers.
Barra dan, minħabba li teżisti informazzjoni farmakokinetika limitata fil- pazjenti, din l- informazzjoni ma tistax titqabbel ma 'dik miksuba minn voluntiera b' saħħithom.
Therefore, the CHMP was unable to agree that the safety and efficacy profile of Rapinyl could be anticipated from the provided documentation.
Għalhekk, is- CHMP ma setax jaqbel li l- profil tas- sigurtà u l- effikaċja ta '
In conclusion, the CHMP requested additional data supporting the efficacy and safety of Rapinyl (independently of Actiq) in the treatment of BTP and adopted a List of Outstanding Issues.
Fl- aħħarnett, is- CHMP talab iżjed informazzjoni li ssostni l- effikaċja u s- sigurtà ta 'Rapinyl (indipendentement minn Actiq) fit- trattament tal- BTP u adotta Lista ta' Kwistjonijiet Pendenti (LoI).
11 Responses to the LoOI and CHMP assessment
Tweġibiet għal- LoI u għall- valutazzjoni tas- CHMP
The Applicant was able to provide in the response to the LoOI the interim analyses from 2 ongoing Phase III safety and efficacy clinical studies (EN3267-005 and EN3267-007), performed in the US by Endo.
Fit- tweġiba għal- LoI, l- applikant seta 'jipprovdi l- analiżijiet provviżorji minn 2 studji kliniċi ta' Fażi III li għaddejjin dwar is- sigurtà u l- effikaċja (EN3267- 005 u EN3267- 007), imwettqa fl- Istati Uniti minn Endo.
The data submitted builds on clinical data from 221 volunteers and 41 patients.
L- informazzjoni sottomessa tibni fuq tagħrif kliniku minn 221 voluntier u 41 pazjent.
The Applicant also provided data demonstrating that Rapinyl met the primary efficacy endpoint (Sum of Pain Intensity Difference from baseline to 30 minutes (SPID30)) and that the results were highly statistically significant (p=0.0004).
L- applikant ipprovda wkoll informazzjoni li turi li Rapinyl laħaq l- endpoint primarju ta 'l - effikaċja (Total tad- Differenza fil- Qawwa ta' l- Uġigħ mil- linja bażi sa 30 minuta (SPID30)) u li r - riżultati kienu statistikament sinifikanti ferm (p=0. 0004).
In addition, a clinically relevant time-effect profile appropriate for an episode of breakthrough painl and meaningful clinical benefits for the patients were shown; patients could identify an effective dose of Rapinyl and use it successfully to control multiple episodes of breakthrough pain.
Barra minn hekk, intwerew profil klinikament sinifikanti ta 'l- effett mal- ħin għal episodju ta' wġigħ qawwi u benefiċċji kliniċi sinifikanti għall- pazjenti; il- pazjenti setgħu jidentifikaw doża effikaċi ta 'Rapinyl u jużawha b' suċċess biex jikkontrollaw diversi episodji ta' wġigħ qawwi.
The Applicant concluded that an optimal dose of Rapinyl provides a rapid onset of analgesia which mirrors the profile of cancer breakthrough pain.
L- applikant ikkonkluda li doża ottimali ta 'Rapinyl tipprovdi bidu malajr ta' serħan mill- uġigħ li jirrifletti l- profil ta 'l- uġigħ qawwi tal- kanċer.
The Applicant considered the rate and extent of absorption to be similar for Rapinyl and Actiq and that the similarity in the PK profiles during the first 30-minute rapid absorption phase is established.
L- applikant ikkunsidra r- rata u l- livell ta 'assorbiment bħala simili għal Rapinyl u Actiq u li x- xebh fil- profili farmakokinetiċi matul l- ewwel fażi ta' 30 minuta ta 'assorbiment rapidu hija stabbilita.
Furthermore, the data generated for Rapinyl and the substantial additional cancer patient exposure data demonstrate that volunteers and patients have similar pharmacokinetics, negating the need for additional studies in healthy volunteers.
Barra minn hekk, l- informazzjoni ġġenerata għal Rapinyl u l- informazzjoni addizzjonali konsiderevoli dwar l - esponiment tal- pazjenti morda bil- kanċer turi li l- voluntiera u l- pazjenti għandhom farmakokinetika simili, u hekk xejnet il- ħtieġa għal iżjed studji fuq voluntiera b' saħħithom.
The Applicant considered that Rapinyl can be successfully titrated and repeatedly administered effectively and safely to treat patients with multiple episodes of breakthrough pain.
L- applikant ikkunsidra li Rapinyl jista 'jiġi titrat b' suċċess u jingħata ripetutament b' mod effikaċi u mingħajr periklu biex jiġu ttrattati pazjenti b' episodji multipli ta' wġigħ episodiku qawwi.
Safety data from EN3267-005 and EN3267-007 have also been provided based on an interim cut of the safety database in January 2008, comprising only serious adverse events (SAEs).
Kienet ipprovduta wkoll informazzjoni dwar is- sigurtà minn EN3267- 005 u EN3267- 007 li kienet ibbażata fuq qtugħ provviżorju tad- dejtabejż dwar is- sigurtà f' Jannar 2008, li kienet tinkludi biss episodji avversi gravi (SAEs).
Up to this date there were no reports of any SAEs assessed as being related to Rapinyl in either study.
Sal- lum ma kien hemm ebda rapport ta 'xi SAEs valutati bħala relatati ma' Rapinyl xi wieħed mill- istudji.
As the safety of transmucosal fentanyl is well described, any relevant safety issues would have been observed as serious events.
Billi s- sigurtà ta 'fentanyl minn ġol- mukuża hija deskritta tajjeb, kwalunkwe kwistjoni rilevanti tas- sigurtà kienet tiġi osservata bħala episodju gravi.
The Applicant also defended the 800ug dose and discussed the safety of Rapinyl when superimposed on a continuous fentanyl or non-fentanyl opioid pain therapy and considered that the transmucosal delivery of fentanyl produces consistent results, independent of the type of baseline therapy.
L- applikant iddefenda wkoll id- doża ta '800ug u ddiskuta s- sigurtà ta' Rapinyl meta jingħata fuq terapija analġeżika kontinwa abbażi ta 'fentanyl jew ta' oppjojdi ieħor u qies li t- twassil ta 'fentanyl minn ġol - mukuża jipproduċi riżultati konsistenti, indipendentement mit- tip ta' terapija bażi.
In conclusion, the Applicant considered that the results from studies EN3267-005 and EN3267-007 confirm the conclusions based on the original bridging strategy and demonstrate that Rapinyl can be safely and effectively used to treat multiple episodes of cancer breakthrough pain in opioid-tolerant patients.
Fl- aħħar nett, l- applikant ikkunsidra li r- riżultati mill- istudji EN3267- 005 u EN3267- 007 jikkonfermaw ir- riżultati bbażati fuq l- istrateġija oriġinali ta 'bridging u juru li Rapinyl jista' jintuża b' mod effikaċi u mingħajr periklu biex jittratta episodji multipli ta 'wġigħ episodiku tal- kanċer f' pazjenti li jittolleraw l- oppjojdi.
The Applicant believes that the original bridging strategy plus the significant body of confirmatory efficacy and safety data in cancer patients provided demonstrate that Rapinyl does indeed have a positive benefit-risk profile.
L- applikant jemmen li l- istrateġija oriġinali ta 'bridging flimkien mal- korp sinifikanti ta' informazzjoni ta 'konferma li ġiet ipprovduta dwar is- sigurtà u l- effikaċja f' pazjenti morda bil- kanċer juru li Rapinyl tassew għandu profil ta' benefiċċju- riskju pożittiv.
Notwithstanding this, the Applicant remains committed to the proposed comprehensive risk management plan that will be put in place.
Minkejja dan, l- applikant jisħaq fuq l- impenn għall- pjan komprensiv propost għall- ġestjoni tar- riskju li għandu jiġi implimentat.
The CHMP acknowledged the data submitted, noting and assessing the data from the clinical studies EN3267-005 and EN3267-007.
Is- CHMP irrikonoxxa l- informazzjoni ppreżentata, billi nnota u vvaluta l- informazzjoni mill- istudji kliniċi EN3267- 005 u EN3267- 007.
The main use of the referred interim analyses is in the detection of any new safety signals and as a comparison of the efficacy in relation to earlier findings.
L- użu prinċipali ta 'l- analiżijiet provviżorji riferuti huwa fir - rilevament ta' kwalunkwe sinjal ġdid tas- sigurtà u bħala tqabbil ta 'l- effikaċja ma' riżultati preċedenti.
The CHMP considered that the information provided was sufficient for concluding that repeat dose data following Actiq and Rapinyl are similar, and the dose proportionalilty between Actiq and Rapinyl was considered as established through the single dose data, pending further clinical safety and efficacy data.
Is- CHMP ikkunsidra li l- informazzjoni pprovduta kienet suffiċjenti biex wieħed jikkonkludi li t - tagħrif dwar dożi ripetuti ta 'Actiq u Rapinyl kien simili, u li l- proporzjonalità tad- doża bejn Actiq u Rapinyl kienet ikkunsidrata bħala stabbilita mill- informazzjoni dwar doża waħda, sakemm toħroġ aktar informazzjoni dwar l- effikaċja u s- sigurtà klinika.
The CHMP also agreed that the proposed dose range for Rapinyl is sufficiently documented and that further efficacy and safety data on dose titration is not necessary.
Is- CHMP qabel ukoll li l- medda ta 'dożaġġi proposta għal Rapinyl hija dokumentata b' mod suffiċjenti u li m' hemmx bżonn ta' iżjed informazzjoni dwar is- sigurtà u l- effikaċja fir- rigward tat- titrazzjoni tad- doża.
In addition, there is solid experience in treating BTP in patients with chronic cancer already receiving a stable dose of background analgesia with strong opioids.
Barra minn hekk, teżisti esperjenza konsiderevoli fit- trattament tal- BTP fil- pazjenti b' kanċer kroniku li diġà jkunu qegħdin jirċievu livell stabbli ta 'analġeżija kontinwa permezz ta' oppjojdi b' azzjoni qawwija.
However, although the interim data support the proposed dose range for Rapinyl, the CHMP requested additional clinical data clearly demonstrating the efficacy/ safety of Rapinyl.
Madankollu, għalkemm l - informazzjoni provviżorja ssostni l- medda ta 'dożaġġi proposta għal Rapinyl, is- CHMP talab informazzjoni klinika addizzjonali li turi b' mod ċar l- effikaċja/ sigurtà ta' Rapinyl.
The CHMP considered the pharmacokinetic data in healthy volunteers vs. patients to be limited; however it agreed that the available data do not indicate alarming differences.
Is- CHMP ikkunsidra li l- informazzjoni farmakokinetika minn voluntiera b' saħħithom vs. il- pazjenti hija limitata; madankollu huwa qabel li l- informazzjoni disponibbli ma tindikax differenzi allarmanti.
The CHMP considered that while the efficacy data showed statistically significant difference in favour of Rapinyl versus placebo on SPID 30, the CHMP considered that the primary endpoints should include the assessment of pain intensity difference by simple scale and to define responder.
13 Is- CHMP ikkunsidra li filwaqt li l- informazzjoni dwar l- effikaċja wriet differenza statistika sinifikanti favur Rapinyl meta mqabbel mal- plaċebo fuq SPID 30, huwa ħass li l- endpoints primarji għandhom jinkludu l- valutazzjoni tad- differenza fil- qawwa ta 'l- wġigħ permezz ta' skala sempliċi u li jiġi identifikat min iwieġeb.
In this study, the primary criteria chosen (SPID) and the time chosen for assessment of efficacy (30 min) do not seem appropriate to evaluate the efficacy of a treatment on BTP episodes, which are known to present a median duration of 30 min.
F' dan l- istudju, il- kriterji prinċipali magħżula (SPID) u l- ħin magħżul għall - valutazzjoni ta 'l- effikaċja (30 minuta) ma jidhrux adegwati biex tiġi valutata l- effikaċja ta' trattament fuq episodji ta 'BTP, li huma magħrufa li jippreżentaw tul medju ta' 30 minuta.
Furthermore, while the reasons given by the
Is- CHMP kien ta 'l - opinjoni li l- applikant għandu jipprovdi analiżi tal- perċentwali ta' dawk li rrispondew 30% u 50% wara 10 u 15- il minuta sabiex ikun ivvalutat aħjar il- profil kliniku sinifikanti ta 'l- effett mal- ħin.
12 Applicant for analyzing only SAEs at this stage are endorsed, and the absence of new important safety issues was considered re-assuring by the CHMP, a full safety analysis should be provided by the Applicant.
Barra minn hekk, filwaqt li r- raġunijiet mogħtija mill- applikant biex f' dan l- istadju jiġu analizzati biss is- SAEs huma aċċettati, u n- nuqqas ta 'kwistjonijiet importanti ġodda tas- sigurtà kien ikkunsidrat bħala rassikuranti mils- CHMP, l- applikant għandu jipprovdi analiżi sħiħa dwar is- sigurtà.
Finally, the CHMP considered that the database on efficacy and safety of Rapinyl in the treatment of cancer patients with BTP is rather poor and requested further safety analyses to be provided: detailed exposition of patients to Rapinyl, full safety analysis, narratives of the deaths.
Fl- aħħar nett, is - CHMP ħass li d- dejtabejż dwar is- sigurtà u l- effikaċja ta 'Rapinyl fil- trattament ta' pazjenti morda bil - kanċer b' BTP hija pjuttost fqira u talab biex jiġu pprovduti aktar analiżijiet dwar is- sigurtà: esponiment dettaljat tal- pazjenti għal Rapinyl, analiżi sħiħa tas- sigurtà, deskrizzjoni ta 'l- imwiet.
Based on the review of the data and the responses, the CHMP considered the application for Rapinyl to be approvable, provided that the Applicant addressed the List of Remaining Issues satisfactorily.
Fuq il- bażi ta 'l- eżami mill- ġdid ta' l- informazzjoni u t- tweġibiet, is- CHMP ikkunsidra li l - applikazzjoni għal Rapinyl tista 'tiġi approvata, bil- kundizzjoni li l- applikant jindirizza l- Lista tal - Kwistjonijiet li Fadal b' mod sodisfaċenti.
Responses to the Remaining Issues and CHMP assessment
Tweġibiet għall- Kwistjonijiet li Fadal u għall- valutazzjoni tas- CHMP
The Applicant confirmed that the tablets used in the Endo Phase III studies, EN3267-005 and EN3267-007, are qualitatively and quantitatively identical to the tablets currently under review in Europe and that the manufacturing process is the same using fentanyl citrate from the same supplier, with identical specifications.
L- applikant ikkonferma li l- pilloli użati fl- istudji ta 'Fażi III ta' Endo, EN3267- 005 u EN3267- 007, huma kwalitattivament u kwantitattivament identiċi għall- pilloli li attwalment qegħdin jiġu eżaminati fl- Ewropa u li l- proċess tal- produzzjoni huwa l- istess billi juża fentanyl ċitrat mill- istess fornitur, bi speċifikazzjonijiet identiċi.
This allows the extrapolation of the conclusions from these studies to Rapinyl.
Dan jippermetti li l- konklużjonijiet minn dawn l- istudji jiġu estrapolati għal Rapinyl.
The CHMP agreed and considered the issue to be resolved.
Is- CHMP qabel u kkunsidra l- kwistjoni bħala solvuta.
The Applicant provided further reassurances on the use of Rapinyl in patiens with mucositis, based on publications and guidelines, concluding that patients with mild/ moderate mucositis can use oral medication, while transmucosal forms of fentanyl are not suitable for use in patients with severe mucositis where other routes of analgesia administration are preferable.
L- applikant ipprovda iżjed assigurazzjonijiet dwar l- użu ta 'Rapinyl f' pazjenti li jkollhom mukożite, ibbażati fuq pubblikazzjonijiet u linji gwida, li kkonkludew li pazjenti li jkollhom mukożite ħafifa/ moderata jistgħu jużaw medikazzjoni orali, filwaqt li forom transmukożali ta' fentanyl mhumiex adatti biex jintużaw f' pazjenti li jkollhom mukożite akuta fejn huwa preferibbli li jintużaw metodi oħra għall- għoti ta 'l- analġeżiċi.
The Applicant implemented a revised a cautionary statement in section 4.4 of the SPC, recommending extra caution during the titration of patients with mouth wounds or mucositis.
L- applikant aġġorna s- sezzjoni 4. 4 ta 'l- SPC bi twissija ta' kawtela, li fiha rrakkomanda iżjed kawtela waqt it- titrazzjoni ta 'pazjenti li jkollhom feriti f' ħalqhom jew mukożite.
The Applicant further described data from the time of the safety cut-off (Jan-08) and considered that the derived information compared favourably to values quoted for Effentora and Actiq, although the reason for patient drop-out was not provided by the sponsor.
L - applikant spjega iżjed fid- dettall informazzjoni dwar il- ħin tal- qtugħ il- linja tas- sigurtà (Jannar 08) u kkunsidra li l- informazzjoni derivata kienet tikkumpara sewwa mal- valuri kkwotati għal Effentora u Actiq, għalkemm ir- raġuni għat- tluq tal- pazjenti ma ngħatatx mill- isponsor.
In addition, the oral cavity was inspected by the clinician or nurse 15-20 minutes after treatment to check for local irritation, no abnormal results were identified and the tablets were well tolerated after both single and repeat doses.
Barra minn hekk, il- kavità orali ġiet eżaminata mit- tabib jew l- infermier 15- 20 minuta wara t- trattament biex jikkontrollow jekk hemmx irritazzjoni orali, ma kien identifikat ebda riżutat anomalu u l- pilloli kienu tollerati sewwa kemm wara doża waħda kif ukoll wara dożi ripetuti.
The CHMP considered that the number of patients successfully titrating to an effective dose is close to the one observed for both Actiq and Effentora and observed that as 97% of the patients successfully titrating to an effective dose were able to complete the randomisation phase of the study, no particular safety issues were identified.
Is- CHMP ikkunsidra li n- numru ta 'pazjenti li kienu qegħdin jittitraw b' suċċess għal doża effikaċi kien qrib dak osservat kemm għal Actiq kif ukoll għal Effentora u osserva li billi 97% tal- pazjenti li kienu qegħdin jittitraw b' suċċess għal doża effikaċi kienu kapaċi jtemmu l- fażi ta' randomizzazzjoni ta 'l- istudju, ma kienu identifikati l- ebda kwistjoni partikolari ta' sigurtà.
The Applicant referred to the provided analysis of Pain Intensity Difference (PID) for Rapinyl compared to placebo from the 10 minute time point in the EN3267-005 study.
L- applikant irrefera għall- analiżi pprovduta dwar is- Differenza fl- Intensità ta 'l- Uġigħ (PID) għal Rapinyl imqabbel ma' plaċebo mill- punt temporali ta '10 minuti fl- istudju EN3267- 005.
While no analysis of 30% and 50% responders at 10 and 15 minutes was conducted in the interim analysis, this analysis was requested from the sponsor in the final clinical study report.
Filwaqt li ma saret l- ebda analiżi ta 'dawk li rrispondew 30% u 50% wara 10 u 15- il minuta fl- analiżi provviżorja, din l- analiżi ntalbet mill- isponsor fir- rapport finali ta' l- istudju kliniku.
In the absence of the data, the Applicant provided data demonstrating a direct correlation between 33% responder analysis and PID, and used the current available pain data and the PID values to estimate the responder rates between active and placebo treatment at earlier time points.
Fl- assenza ta 'l- informazzjoni, l- applikant ipprovda informazzjoni li turi korrelazzjoni diretta bejn l- analiżi ta' 33% ta 'dawk li rrispondew u l- PID, u uża l- informazzjoni attwalment disponibbli dwar l- uġigħ u l- valuri PID biex jikkalkula r- rati ta' dawk li wieġbu bejn it- trattament attiv u plaċebo f' punti temporali aktar kmieni.
While not validated, the results obtained from the extrapolations compared favourably to Effentora and Actiq.
Filwaqt li ma kinux ivvalidati, ir- riżultati miksuba mill- estrapolazzjonijiet ikkomparaw sewwa ma 'Effentora u Actiq.
In conclusion, the Applicant believes that the demonstration of a statistically significant improvement in PID at 10 and 15 minutes in EN3267- 005 is the appropriate, clinically relevant measure of the early effectiveness of Rapinyl, and that an improvement in PID is directly reflected in an increase in responder rate.
L- applikant ippreżenta wkoll u ddiskuta b' mod estensiv informazzjoni dwar l- esponiment għall- 131 pazjent li
The Applicant also presented and extensively discussed exposure data for the 131 patients that successfully titrated in studies EN3267-005 and 007 and for the patients completing the 3 and 12-month follow-up periods.
14 ddożaw b' suċċess fl- istudji EN3267- 005 u 007 u għall- pazjenti li temmew il- perjodi ta 'segwitu ta' 3 u 12- il xahar.
The Applicant discussed the previously provided SAE dataset up to the 18th January 2008 safety cut- off and considered that the new safety data supplemented the bridging strategy and was in line with a further review of SAE data up to the 15th May-08.
L- applikant iddiskuta d- dataset ipprovdut qabel ta 'SAE sal- qtugħ il- linja tas- sigurtà tat- 18 ta' Jannar 2008 u ħass li l- informazzjoni ġdida dwar is- sigurtà ssuplimentat l- istrateġija ta 'bridging u kienet konformi ma' eżami mill- ġdid ieħor ta 'l- informazzjoni dwar is- SAE sal- 15 ta' Mejju 2008.
The Applicant described the observed SAE signals and noted that only one case was evaluated as related to the study drug by the investigator..
L- applikant iddeskriva s- sinjali osservati ta 'SAE u nnota li każ wieħed biss kien evalwat bħala marbut mal - mediċina ta' l- istudju mill- investigatur.
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.
L- applikant iddiskuta wkoll id- differenza bejn il- voluntiera (qatt ma ħadu oppjojdi qabel) u l- popolazzjoni tal- pazjenti fil- mira (utenti kroniċi ta 'l- oppjojdi), fejn innota li l- mudell ta' l- episodji relatati kien konsistenti mal- letteratura disponibbli dwar il- profil tas - sigurtà tal- prodotti li fihom fentanyl u n- nuqqas ta 'xejriet relatati mad- doża fl- inċidenza ta' episodji avversi.
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.
Matul dawn l- istudji ta 'Fażi III ngħataw numru kbir ta' dożi ta 'Rapinyl u ntużaw dożi għoljin ta' Rapinyl għal perjodi twal ta 'għoti mingħajr ebda raġuni għal tħassib dwar in- natura u l- frekwenza tas- SAEs irrappurtati.
Thus the Applicant considered the safety-profile of Rapinyl to be appropriate for this indication.
Għaldaqstant l- applikant ikkunsidra l- profil tas- sigurtà ta 'Rapinyl bħala adatt għal din l- indikazzjoni.
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.
Is- CHMP kien rassigurat min- nuqqas ta 'sinjali tas- sigurtà relatati mas- SAEs iżda talab lill- Applikant sabiex jissottometti analiżi sħiħa tas- sigurtà bħala kundizzjonijiet għall - Awtorizzazzjonijiet għat- Tqegħid fis- Suq.
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.
L- applikant ipprovda d- deskrizzjonijiet tal- każ għall- imwiet kollha nnotifikati lill- applikant u eżamina mill- ġdid l- episodji avversi b' eżitu ta 'mewt, u kkonkluda li dawn l- imwiet ma kinux ikkunsidrati bħala relatati mal- mediċina ta' l- istudju mill- investigaturi ta 'l- istudju.
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.
Pazjent wieħed kellu attentat ta 'suwiċidju li rnexxa iżda filwaqt li l- ħsibijiet dwar suwiċidju huma magħrufa li huma iżjed komuni fil - pazjenti morda bil- kanċer milli fil- popolazzjoni ġenerali, la s- suwiċidju u lanqas il- ħsibijiet dwar suwiċidju ma ġew irrappurtati bħala episodji avversi assoċjati ma' Actiq jew ma 'Fentora/ Effentora u fuq il- bażi tal- profil farmakokinetiku simili ta' Rapinyl u Actiq, l- applikant jemmen li dan kien każ sporadiku, konsistenti mal- valutazzjoni ta 'l- investigatur bħala li mhuwiex relatat.
The CHMP reviewed the death narratives and agreed with the Applicant conclusions.
Is- CHMP eżamina mill- ġdid id- deskrizzjonijiet ta 'l- imwiet u qabel mal- konklużjonijiet ta' l- applikant.
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.
Madankollu, l - attentat ta 'suwiċidju li rnexxa jeħtieġ jingħata attenzjoni, u minħabba li d- depressjoni u t- tibdil fil - burdata huma episodji avversi elenkati fl- SPC ta' Actiq, is- CHMP ħass li dawn it- tipi ta 'episodji għandhom jiġu mmonitorjati mill- qrib u talab sabiex il- kwistjoni tiġi segwita fil- Farmakoviġilanza ta' wara t- tqegħid tal- prodott fis- suq.
GROUNDS FOR AMENDMENT OF THE SUMMARIES OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET
RAĠUNIJIET GĦALL- EMENDA TAS- SOMMARJI TAL- KARATTERISTIĊI TAL - PRODOTT, IT- TIKKETTI U L- FULJETT TA 'TAGĦRIF
The CHMP welcomed the new interim analyses of efficacy and safety data for Rapinyl, but considered that the new data must be regarded as preliminary data, as the complete trial results are not yet available for assessment.
Is- CHMP laqa 'b' sodisfazzjon l- analiżijiet provviżorji ġodda ta' l- informazzjoni dwar l- effikaċja u s - sigurtà ta 'Rapinyl, iżda ħass li l- informazzjoni ġdida trid titqies bħala informazzjoni preliminari, billi r- riżultati sħaħ tal- provi għadhom mhumiex disponibbli għall- valutazzjoni.
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.
Minkejja li n- numru ta 'pazjenti analizzati huwa pjuttost baxx, issa teżisti informazzjoni dwar it- trattament tal- BTP f' pazjenti morda bil- kanċer f' medda ta' dożaġġi minn 100 µg sa 800 µg u ma kien hemm ebda sinjal ġdid tas - sigurtà.
This was supported by the known properties of fentanyl, the submitted clinical data, the revised SPC version recommending strict individual dose titration, and the proposed Risk Management Plan.
Dan kien sostnut mill- karatteristiċi magħrufa ta 'fentanyl, l- informazzjoni klinika sottomessa, il- verżjoni riveduta ta' l- SPC li tirrakkomanda titrazzjoni strettament individwali tad- doża, u l- Pjan propost għall- Ġestjoni tar- Riskju.
The efficacy data show that Rapinyl is statistically different from placebo in the treatment of BTP and these results seem clinically relevant.
L- informazzjoni dwar l- effikaċja turi li Rapinyl huwa statistikament differenti mill- plaċebo fit - trattament tal- BTP u dawn ir- riżultati jidhru klinikament rilevanti.
An extrapolation of the PID at 10 and 15 minutes to responder rates has been provided by the Applicant.
L- applikant ipprovda estrapolazzjoni tal- PID wara 10 u 15- il minuta għar- rati ta 'dawk li rrispondew.
This calculation seems reasonable, however, responder analysis should be provided when available.
Dan il- kalkolu jidher raġonevoli, madankollu, għandha tiġi pprovduta analiżi ta 'dawk li rrispondew meta tkun disponibbli.
The available data on exposition was provided as requested and even if the data are not the definitive ones, the CHMP considered that exposure to Rapinyl is sufficient at this point in time.
L- informazzjoni disponibbli dwar l- esponiment ingħatat kif mitlub u anki jekk l- informazzjoni mhijiex dik definittiva, is- CHMP ħass li l- esponiment għal Rapinyl huwa suffiċjenti f' dan il- ħin.
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.
Minħabba n - numru baxx ta 'pazjenti esposti għal ħin twil, ir- riżultati finali ta' l- istudji EN3267- 005 u EN3267- 007 għandhom jiġu pprovduti bħala kundizzjonijiet għall- Awtorizzazzjonijiet tat- Tqegħid tal- prodott fis - Suq.
From the efficacy and safety data provided, Rapinyl seems to be comparable to other fentanyl containing products (Actiq and Effentora) for the treatment of BTP in cancer patients.
Mill- informazzjoni pprovduta dwar is- sigurtà u l- effikaċja, Rapinyl jidher li huwa komparabbli ma 'prodotti oħra li fihom fentanyl (Actiq u Effentora) għat- trattament tal- BTP f' pazjenti morda bil - kanċer.
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.
15 Madankollu, minħabba n- numru pjuttost baxx ta 'pazjenti esposti għal ħin twil, l- applikant intalab jipprovdi r- riżultati finali ta' l- istudji EN3267- 005 u EN3267- 007 u l- informazzjoni sħiħa dwar l - analiżi tas- sigurtà fir- rigward tas- SAEs bħala kundizzjonijiet għall- Awtorizzazzjonijiet għat- Tqegħid tal- prodott fis- Suq.
In addition, the suicidality should be monitored, as depression and mood liability are part of the reported AEs for Actiq.
Barra minn hekk, għandha tiġi mmonitorjata l- possibilità ta 'suwiċidju, billi d - depressjoni u t- tibdil fil- burdata huma parti mill- episodji avversi rrappurtati għal Actiq.
In conclusion, the CHMP considered that the Applicant had answered the questions adequately.
Fl- aħħar nett, is- CHMP ħass li l- applikant kien wieġeb il- mistoqsijiet b' mod adegwat.
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.
Fuq il- bażi ta 'l - eżami mill- ġdid ta' l- informazzjoni u fuq it- tweġibiet ta 'l- applikant għal- lista ta' kwistjonijiet pendenti u għall- kwistjonijiet li fadal, is- CHMP ikkunsidra r- relazzjoni tal- benefiċċju/ riskju ta 'Rapinyl bħala waħda pożittiva u li l- applikazzjoni għal Rapinyl pillola għal taħt l- ilsien 50, 100, 200, 300, 400, 600 u 800 µg tista' tiġi approvata, bil- kundizzjoni li l- applikant jimplimenta l- emendi magħmula fit- test ta 'l - Informazzjoni dwar il- Prodott u jissodisfa l- kundizzjonijiet għall- Awtorizzazzjoni għat- Tqegħid tal - prodott fis- Suq kif deskritt fl- Anness IV.
- the responses provided by the Applicant, in particular the additional clinical data submitted during
- ir- risposti pprovduti mill- applikant, b' mod partikolari l- informazzjoni klinika addizzjonali
the CHMP referral procedure, successfully addressed the CHMP concerns,
ppreżentata waqt il- proċedura ta 'referenza tas- CHMP, indirizzaw b' suċċess it- tħassib tas- CHMP,
- the dose range of Rapinyl and the dose proportionalilty between Actiq and Rapinyl was considered
- il- medda tad- dożi ta 'Rapinyl u l- proporzjonalità tad- dożi bejn Actiq u Rapinyl kienet ikkunsidrata
as established
bħala stabbilita
- and provided that the Applicant fulfils the conditions to the Marketing Authorisation as listed in
- u bil- kundizzjoni li l- applikant jissodisfa l- kundizzjonijiet għall- Awtorizzazzjoni tat- Tqegħid tal -
Annex IV
prodott fis- Suq kif elenkati fl- Anness IV
- the CHMP considered the benefit/ risk of Rapinyl to be positive
- is- CHMP ikkunsidra l- benefiċċju/ riskju ta 'Rapinyl bħala pożittiv
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).
is- CHMP irrakkomanda l- emenda tas- Sommarji tal- Karatteristiċi tal- Prodott u l- għoti ta 'l - Awtorizzazzjonijiet għat- Tqegħid fis- Suq li għalihom is- Sommarju tal- Karatteristiċi tal- Prodott, it - tikketti u l- fuljett ta' tagħrif huma ppreżentati fl- Anness III għal Rapinyl u l- ismijiet assoċjati (ara Anness I).
The conditions to the Marketing Authorisation as listed in Annex IV.
Il- kundizzjonijiet għall- Awtorizzazzjoni tat- Tqegħid tal- prodott fis- Suq huma elenkati fl - Anness IV.
16 SUMMARY OF PRODUCT CHARACTERISTICS
16 ANNESS III
Rapinyl and associated names (see Annex I) 50 microgram sublingual tablets [See Annex I - To be completed nationally]
Rapinyl u ismijiet assoċjati (ara Anness I) 50 mikrogramma pilloli għal taħt l- ilsien [Ara Anness I - biex jimtela mill- pajjiż partikolari]
Rapinyl 100 microgram sublingual tablets Rapinyl 200 microgram sublingual tablets Rapinyl 300 microgram sublingual tablets Rapinyl 400 microgram sublingual tablets Rapinyl 600 microgram sublingual tablets Rapinyl 800 microgram sublingual tablets
Rapinyl 100 mikrogramma pilloli għal taħt l- ilsien Rapinyl 200 mikrogramma pilloli għal taħt l- ilsien Rapinyl 300 mikrogramma pilloli għal taħt l- ilsien Rapinyl 400 mikrogramma pilloli għal taħt l- ilsien Rapinyl 600 mikrogramma pilloli għal taħt l- ilsien Rapinyl 800 mikrogramma pilloli għal taħt l- ilsien
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)
Kull pillola għal taħt l- ilsien fiha 50 mikrogrammma fentanyl (bħala citrate) 100 mikrogramma fentanyl (bħala citrate) 200 mikrogramma fentanyl (bħala citrate) 300 mikrogramma fentanyl (bħala citrate) 400 mikrogramma fentanyl (bħala citrate) 600 mikrogramma fentanyl (bħala citrate) 800 mikrogramma fentanyl (bħala citrate)
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
Il- pillola għal taħt l- ilsien ta ’ 200 mikrogramma hi pillola bajda f’ forma ovali Il- pillola għal taħt l- ilsien ta ’ 300 mikrogramma hi pillola bajda f’ forma triangolari Il- pillola għal taħt l- ilsien ta ’ 400 mikrogramma hi pillola bajda f’ forma ta ’ djamant Il- pillola għal taħt l- ilsien ta ’ 600 mikrogramma hi pillola bajda f’ forma ta ’ D Il- pillola għal taħt l- ilsien ta ’ 800 mikrogramm hi pillola bajda f’ forma ta ’ kapsula
Management of breakthrough pain in adult patients using opioid therapy for chronic cancer pain.
It- treġija ta ’ uġigħ li jisfonda f’ pazjenti adulti li jużaw terapija opjojdi għal uġigħ minn kanċer kroniku.
Breakthrough pain is a transient exacerbation of otherwise controlled chronic background pain.
L- uġigħ sfondat huwa tħarriex għaddien ta ’ uġigħ kroniku li ġeneralment ikun fl- isfond.
Rapinyl should only be administered to patients who are considered tolerant to their opioid therapy for persistent cancer pain.
Rapinyl għandu jingħata biss lil pazjenti li huma kkonsidrati tolleranti għat- terapija tagħhom ta ’ opjojdi għal uġigħ persistenti mill- kanċer.
Patients can be considered opioid tolerant if they take at least 60 mg oral morphine per day, 25 micrograms transdermal fentanyl per hour, or an equianalgesic dose of another opioid for a week or longer.
Il- pazjenti għandhom ikunu kkonsidrati li huma tolleranti jekk jieħdu ta ’ lanqas 60 mg ta ’ morfina orali kuljum, 25 mikrogramm fentanyl minn ġol- ġilda kull siegħa, jew doża analġeżika ekwivalenti oħra ta ’ opjojdi għal ġimgħa jew aktar.
Rapinyl sublingual tablets should be administered directly under the tongue at the deepest part.
Il- pilloli għal taħt l- ilsien Rapinyl għandhom jingħataw direttament taħt l- ilsien fl- aktar parti profonda.
Rapinyl sublingual tablets should not be swallowed, but allowed to completely dissolve in the 18 sublingual cavity without chewing or sucking.
Il- pilloli għal taħt l- ilsien Rapinyl m’ għandhomx jinbelgħu, imma għandhom jitħallew jinħallu fil- kavità ta ’ taħt l- ilsien mingħajr ma jimtagħdu jew jintreddgħu.
Patients should be advised not to eat or drink anything until the sublingual tablet is completely dissolved.
Il- pazjenti għandhom jingħataw parir biex la jieklu u lanqas jixorbu sakemm il- pillola għal taħt l- ilsien tkun inħallet kollha.
In patients who have a dry mouth water may be used to moisten the buccal mucosa before taking Rapinyl.
19 Pazjenti li għandhom ħalqhom xott jistgħu jieħdu l- ilma biex isir niedi il- mukosa tal- ħalq qabel ma jieħdu Rapinyl.
Dose titration:
Tittrazzjoni tad- doża:
The optimal dose of Rapinyl will be determined by upward titration, on an individual patient basis.
L- aħjar doża ta ’ Rapinyl għandha tiġi stabilità b’ tittrazzjoni ’ l fuq, fuq bażi individwali għal kull pazjent.
Several doses are available for use during the dose titration phase.
Diversi dożi huma disponibbli għal użu waqt il- fażi ta ’ tittrazzjoni tad- doża.
The initial dose of Rapinyl used should be 100 micrograms, titrating upwards as necessary through the range of available dosage strengths.
Id- doża inizjali ta ’ Rapinyl użata għandha tkun ta ’ 100 mikrogramma, b’ tittrazzjoni ’ l fuq kif meħtieġ permezz tal - meded ta ’ qawwiet ta ’ dożi disponibbli.
The 50 microgram strength sublingual tablet may be used for an intermediate dose-titration step.
Il- qawwa tal- pillola ta ’ taħt l- ilsien ta ’ 50 mikrrogramma tista ’ tintuża bħala pass intermedju ta ’ tittrazzjoni tad- doża.
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.
Il- pazjenti għandhom jiġu monitorati bir- reqqa sakemm id- doża xierqa tintlaħaq, i. e. dik li tipprovdi analġesja adattat b’ reazzjonijiet avversi aċċettabbli għal kull episodju ta ’ uġigħ li jisfonda.
Switching from other fentanyl containing products to Rapinyl must not occur at a 1:1 ratio because of different absorption profiles.
It- taqlib minn prodotti oħra li fihom fentanyl għal Rapinyl m’ għandux iseħħ fuq proporzjon ta ’ 1: 1 minħabba l- profili ta ’ assorbiment differenti.
If patients are switched from another fentanyl containing product, a new dose titration with Rapinyl is required.
Jekk pazjenti jinqelbu minn prodott ieħor li fih fentanyl huwa meħtieġ li għal Rapinyl ikun hemm tittrazzjoni għal doża ġdida.
The following dose regimen is recommended for titration, although in all cases the physician should take into account the clinical need of the patient, age and concomitant illness.
Ir- reġimen għad- doża li ġej huwa rakkomandat għal tittrazzjoni, għalkemm it- tabib għandu jqies il - ħtiġijiet kliniċi tal- pazjent, l- età u l- mard konkomittanti f’ kull każ.
All patients must start therapy with a single 100 microgram sublingual tablet.
Il- pazjenti kollha għandhom jibdew b’ terapija ta ’ pillola waħda għal taħt l- ilsien ta ’ 100 mikrogramma.
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.
Jekk analġesja adegwata ma tintlaħaqx fi żmien 15- 30 minuta wara l- għoti ta ’ pillola waħda għal taħt l- ilsien, tista ’ tingħata t- tieni pillola għal taħt l- ilsien ta ’ 100 mikrogramma.