qanastek/EMEA-V3 huggingface dataset:
*Nausea and vomiting were efficacy parameters in the first 5 days of post-chemotherapy treatment and were reported as adverse reactions only thereafter.
* In- nawseja u r- rimettar kienu parametri ta ’ l- effikaċja fl- ewwel 5 ijiem wara t- trattament bil - kimoterapija u ġew irrapportati biss bħala esperjenzi avversi wara.
The adverse reactions profiles in the Multiple-Cycle extension for up to 5 additional cycles of chemotherapy were generally similar to those observed in Cycle 1.
Il- profili tar- reazzjonijiet avversi fl- estensjoni Multiple- Cycle sa 5 ċikli addizzjonali ta 'kimoterapija kienu ġeneralment simili għal dawk osservati f' Ċiklu 1.
Additional adverse reactions were observed in patients treated with aprepitant (40 mg) for postoperative nausea and vomiting and a greater incidence than with ondansetron: abdominal pain upper, bowel sounds abnormal, dysarthria, dyspnoea, hypoaesthesia, insomnia, miosis, nausea, sensory disturbance, stomach discomfort, visual acuity reduced, wheezing.
Reazzjonijiet avversi addizzjonali ġew osservati f' pazjenti ttrattati b' aprepitant (40 mg) għal nawseja u remettar ta 'wara l- operazzjoni u f' inċidenza akbar milli b' ondansetron: uġigħ fil- parti ta' fuq ta 'l - addome, ħsejjes anormali fil- musrana, disartrija, dispneja, ipoestesja, insomnja, mijożi, nawseja, disturbi fis- seni, skonfort fl- istonku, tnaqqis fl- akutezza tal- vista, tħarħir.
In addition, two serious adverse reactions were reported in clinical studies in postoperative nausea and vomiting (PONV) in patients taking a higher dose of aprepitant: one case of constipation, and one case of sub-ileus.
Barra minn hekk, ġew irrapportati żewġ każijiet avversi serji fi studji kliniċi rigward n- nawseja u rimettar ta 'wara l- operazzjoni (PONV) f' pazjenti li kienu qed jingħataw doża ogħla ta' aprepitant: każ wieħed ta 'stitikezza, u każ ieħor ta' sub- ileus.
17 One case of angioedema and urticaria was reported as a serious adverse event in a patient receiving aprepitant in a non-CINV/ non-PONV study.
Każ ta ’ anġjoedema u urtikarja ġie rrapportat bħala reazzjoni avversa serja f’ pazjent li ngħata aprepitant fi stħarriġ non- CINV/ non- PONV.
In 2 randomised, double-blind studies encompassing a total of 1,094 patients receiving chemotherapy that included cisplatin ≥ 70 mg/ m2, aprepitant in combination with an ondansetron/ dexamethasone regimen (see section 4.2) was compared with a standard regimen (placebo plus ondansetron 32 mg intravenously administered on Day 1 plus dexamethasone 20 mg orally on Day 1 and 8 mg orally twice daily on Days 2 to 4).
18 32 mg ondansetron ġol- vina li ngħata f' Jum 1 flimkien ma 'dexamethasone 20 mg mogħti mill- ħalq f' Jum 1 u 8 mg mogħtija darbtejn kuljum fil- Jiem 2 sa 4).
Efficacy was based on evaluation of the following composite measure: complete response (defined as no emetic episodes and no use of rescue therapy) primarily during Cycle 1.
L- effikaċja kienet ibbażata fuq evalwazzjoni tal- miżura komposta li ġejja: rispons sħiħ (imfisser bħala mingħajr episodji emetiċi u l- ebda użu ta 'terapija ta' salvataġġ) prinċipalment waqt Ċiklu 1.
The results were evaluated for each individual study and for the 2 studies combined.
Ir- riżultati ġew evalwati għal kull studju individwali u għaż- żewġ studji kkombinati.
A summary of the key study results from the combined analysis is shown in Table 1.
Sommarju tar- riżultati ewlenin ta 'l- istudju mill- analiżi kombinata hija murija fit- Tabella 1.
18 Table 1 Percent of Patients Receiving Highly Emetogenic Chemotherapy Responding by Treatment Group and Phase — Cycle 1
Tabella 1 Perċentwal ta 'Pazjenti li Kienu qed Jirċievu Kimoterapija Ferm Emetoġenika li Jirrispondu skond il- Grupp u Fażi ta' Trattament — Ċiklu 1
Aprepitant Regimen
Kors ta '
Standard Therapy
Terapija
Differences*
Differenzi *
COMPOSITE MEASURES
Aprepitant
(N=
Standard
Complete Response (no emesis and no
Rispons Sħiħ (l- ebda emesi u l- ebda terapija ta 'salvataġġ) (14. 0, 25. 8) 19. 9 47. 8 67. 7 Globali (0- 120 siegħa) (7. 9, 17. 6) 12. 7 73. 2 86. 0 0- 24 siegħa (14. 5, 26. 1) 20. 3 51. 2 71. 5 25- 120 siegħa
INDIVIDUAL MEASURES No Emesis (no emetic episodes regardless of use of rescue therapy)
MIŻURI INDIVIDWALI L- ebda emesi (l- ebda każ ta 'emesi minkejja l- użu ta' terapija ta 'salvataġġ) (16. 4, 28. 0) 22. 2 49. 7 71. 9 Globali (0- 120 siegħa) (8. 0, 17. 5) 12. 7 74. 0 86. 8 0- 24 siegħa (17. 0, 28. 2) 22. 6 53. 5 76. 2 25- 120 siegħa L- Ebda Nawseja Sinifikanti (Massimu ta' VAS < 25 mm fuq skala ta '0 - 100 mm)
Overall (0-120 hours) 25-120 hours
Globali (0- 120 siegħa) 25- 120 siegħa
* The confidence intervals were calculated with no adjustment for gender and concomitant chemotherapy, which were included in the primary analysis of odds ratios and logistic models. † One patient in the Aprepitant Regimen only had data in the acute phase and was excluded from the overall and delayed phase analyses; one patient in the Standard Regimen only had data in the delayed phase and was excluded from the overall and acute phase analyses.
* L- intervalli ta 'kunfidenza ġew ikkalkulati mingħajr ebda aġġustament għall- ġeneru tal - persuna u għal kimoterapija li kienet qed tingħata fl- istess ħin, li kienu inklużi fl- analiżi primarja ta ’ l- odds ratios u mudelli loġistiċi.
The estimated time to first emesis in the combined analysis is depicted by the Kaplan-Meier plot in Figure 1.
19 Il- ħin stmat għall- ewwel emesi fl- analiżi kkombinata hu muri bil- Kaplan- Meier plot f' Figura 1.
Figure 1 Percent of Patients Receiving Highly Emetogenic Chemotherapy Who Remain Emesis Free Over Time – Cycle 1
Figura 1 Perċentwal ta 'Pazjenti li Kienu qed Jirċievu Kimoterapija Ferm Emetoġenika Li Jibqgħu Mingħajr Emesi Maż- Żmien – Ċiklu 1
Percent of Patients
Percentwal ta ’ Pazjenti
Aprepitant Regimen (N=520) Standard Therapy (N=523)
Kors ta ’ Aprepitant (N=520) Terapija standard (N=523)
Time (hours)
Hin (sighat)
Statistically significant differences in efficacy were also observed in each of the 2 individual studies.
Statistikament, ġew osservati differenzi sinifikanti fl- effikaċja f' kull wieħed miż- żewġ studji.
In the same 2 clinical studies, 851 patients continued into the Multiple-Cycle extension for up to 5 additional cycles of chemotherapy.
Fl- istess 2 studji kliniċi, 851 pazjenti komplew fl- estensjoni taċ- Ċiklu- Multiplu għal sa 5 ċikli ta ’ kimoterapija addizzjonali.
The efficacy of the aprepitant regimen was apparently maintained during all cycles.
Apparentament, l- effikaċja tal- kors ta ’ aprepitant inżammet matul iċ- ċikli kollha.
19 In a randomised, double-blind study in a total of 866 patients (864 females, 2 males) receiving chemotherapy that included cyclophosphamide 750-1500 mg/ m2; or cyclophosphamide 500- 1500 mg/ m2 and doxorubicin (< 60 mg/ m2) or epirubicin (< 100 mg/ m2), aprepitant in combination with an ondansetron/ dexamethasone regimen (see section 4.2) was compared with standard therapy (placebo plus ondansetron 8 mg orally (twice on Day 1, and every 12 hours on Days 2 and 3) plus dexamethasone 20 mg orally on Day 1).
Fi stħarriġ double- blind, b' mod każwali, f’ total ta ’ 866 pazjent (864 mara, 2 irġiel) li kienu qed jingħataw il- kimoterapija li nkludiet cyclophosphamide 750- 1500 mg/ m2; jew cyclophosphamide 500 - 1500 mg/ m2 u doxorubicin (60 mg/ m2) jew epirubicin (100 mg/ m2), aprepitant flimkien ma ’ kors ta ’ ondansetron/ dexamethasone (ara sezzjoni 4. 2) tqabbel ma ’ terapija standard (plaċebo u 8 mg ondansetron oralment (darbtejn f’ Jum 1, u kull 12- il siegħa f’ Jiem 2 u 3) flimkien ma ’ 20 mg dexamethasone oralment f’ Jum 1).
Efficacy was based on evaluation of the composite measure: complete response (defined as no emetic episodes and no use of rescue therapy) primarily during Cycle 1.
L- effikaċja kienet ibbażata fuq evalwazzjoni tal- miżura komposta li ġejja: rispons sħiħ (imfisser bħala mingħajr episodji emetiċi u l- ebda użu ta 'terapija ta' salvataġġ) prinċipalment waqt Ċiklu 1.
A summary of the key study results is shown in Table 2.
Sommarju tar- riżultati ewlenin ta 'l- istudju hija murija fit- Tabella 2.
Table 2 Percent of Patients Responding by Treatment Group and Phase — Cycle 1 Moderately Emetogenic Chemotherapy
20 Tabella 2 Perċentwali ta 'Pazjenti li Jirrispondu skond il- Grupp u Fażi ta' Trattament — Ċiklu 1 Kimoterapija Moderatament Emetoġenika
COMPOSITE MEASURES
MIŻURI KOMPOSTI
Complete Response (no emesis and no rescue therapy)
Rispons Sħiħ (l- ebda emesi u l- ebda terapija ta 'salvataġġ)
Overall (0-120 hours) 0-24 hours 25-120 hours
Globali (0- 120 siegħa) 0- 24 siegħa 25- 120 siegħa
50.8 75.7 55.4
50. 8 75. 7 55. 4
42.5 69.0 49.1
42. 5 69. 0 49. 1
8.3 6.7 6.3
8. 3 6. 7 6. 3
(1.6, 15.0) (0.7, 12.7) (-0.4, 13.0)
(1. 6, 15. 0) (0. 7, 12. 7) (- 0. 4, 13. 0)
INDIVIDUAL MEASURES No Emesis (no emetic episodes regardless of use of rescue therapy)
MIŻURI INDIVIDWALI L- ebda emesi (l- ebda każ ta 'emesi minkejja l- użu ta' terapija ta 'salvataġġ)
75.7 87.5 80.8
75. 7 87. 5 80. 8
58.7 77.3 69.1
58. 7 77. 3 69. 1
17.0 10.2 11.7
17. 0 10. 2 11. 7
(10.8, 23.2) (5.1, 15.3) (5.9, 17.5)
(10. 8, 23. 2) (5. 1, 15. 3) (5. 9, 17. 5)
No Significant Nausea (maximum VAS < 25 mm on a scale of 0-100 mm)
L- Ebda Nawseja Sinifikanti (Massimu ta 'VAS < 25 mm fuq skala ta' 0 - 100 mm)
60.9 79.5 65.3
60. 9 79. 5 65. 3
55.7 78.3 61.5
55. 7 78. 3 61. 5
5.3 1.3 3.9
5. 3 1. 3 3. 9
(-1.3, 11.9) (-4.2, 6.8) (-2.6, 10.3)
(- 1. 3, 11. 9) (- 4. 2, 6. 8) (- 2. 6, 10. 3)
* The confidence intervals were calculated with no adjustment for age category (< 55 years, ≥ 55 years) and investigator group, which were included in the primary analysis of odds ratios and logistic models. † One patient in the Aprepitant Regimen only had data in the acute phase and was excluded from the overall and delayed phase analyses.
* L- intervalli ta 'kunfidenza ġew ikkalkulati bla ebda aġġustament għall- kategorija t' età (< 55 sena, ≥55 sena) u għall- grupp ta ’ l- investigatur, li kienu inklużi fl- analiżi primarja ta ’ l- odds ratios u mudelli loġistiċi.
20 The estimated time to first emesis in the study is depicted by the Kaplan-Meier plot in Figure 2.
Il- ħin stmat għall- ewwel emesi fl- analiżi hu muri bil- Kaplan- Meier plot f' Figura 2.
Figure 2 Percent of Patients Receiving Moderately Emetogenic Chemotherapy Who Remain Emesis Free Over Time – Cycle 1
Figura 2 Perċentwal ta 'Pazjenti li Jkunu qed Jirċievu Kimoterapija Moderatament Emetoġenika Li Jibqgħu Mingħajr Emesi Maż- Żmien – Ċiklu 1
Aprepitant Regimen (N=432) Standard Therapy (N=424) 90%
Kors ta ’ Aprepitant (N=432) Terapija Standard (N=424) 90% Perċentwal ta ’ Pazjenti
Time (hours)
Ħin (sigħat)
In the same clinical study, 744 patients continued into the Multiple-Cycle extension for up to 3 additional cycles of chemotherapy.
21 Fl- istess studju kliniku, 744 pazjent komplew fl- estensjoni taċ- Ċiklu- Multiplu għal sa 3 ċikli ta ’ kimoterapija addizzjonali.
The efficacy of the aprepitant regimen was apparently maintained during all cycles.
Apparentament, l- effikaċja tal- kors inżammet matul iċ- ċikli kollha.
Oral administration of the capsule with an approximately 800 Kcal standard breakfast resulted in an up to 40% increase in AUC of aprepitant.
Amministrazzjoni orali tal- kapsula b' kolazzjon standard ta 'madwar 800 Kcal irriżulta f' żieda ta' 40% fl- AUC ta 'aprepitant.
This increase is not considered clinically relevant.
Din iż- żieda m' hiex meqjusa klinikament rilevanti.
The pharmacokinetics of aprepitant is non-linear across the clinical dose range.
Il- farmakokinetiċi ta 'aprepitant m' humiex lineari fil- firxa kollha tad- doża klinika.
In healthy young adults, the increase in AUC0-∞ was 26% greater than dose proportional between 80 mg and 125 mg single doses administered in the fed state.
F' adulti żgħar b' saħħithom, iż- żieda fl- AUC0- ∞ kienet ta '26% ogħla mid- doża proporzjonali ta' bejn 80 mg u 125 mg ta 'dożi waħdenin mogħtija wara li jkunu kielu.
Following oral administration of a single 125 mg dose of EMEND on Day 1 and 80 mg once daily on Days 2 and 3, the AUC0-24hr (mean±SD) was 19.6±2.5 microgram x h/ ml and 21.2±6.3 microgram x h/ ml on Days 1 and 3, respectively.
Wara l- għoti mill- ħalq ta 'doża waħda ta' 125 mg ta 'EMEND f' Jum 1u 80 mg darba kuljum fil- Jiem 2 u 3, l- AUC0- 24hr (medja±SD) kienet ta' 19. 6±2. 5 mikrogrammi x siegħa/ ml u 21. 2±6. 3 mikrogrammi x siegħa/ ml fil- Jiem 1 u 3, rispettivament.
Cmax was 1.6±0.36 microgram/ ml and 1.4±0.22 microgram/ ml on Days 1 and 3, respectively.
Cmax kien 1. 6±0. 36 mikrogrammi/ ml u 1. 4±0. 22 mikrogrammi/ ml f' Jiem 1 u 3, rispettivament.
The geometric mean apparent volume of distribution at steady state (Vdss) is approximately 66 l in humans.
Kif jiġi Distribwit Aprepitant jintrabat b’ mod qawwi mal- proteini, b’ medja ta ’ 97% Fil- bnedmin, il- medja ġeometrika tal- volum apparenti tad- distribuzzjoni fi stat fiss (Vdss) huwa bejn wieħed u ieħor 66 l.
21 Metabolism Aprepitant undergoes extensive metabolism.
Metaboliżmu Aprepitant jgħaddi minn metaboliżmu estensiv.
In vitro studies using human liver microsomes indicate that aprepitant is metabolised primarily by CYP3A4 and potentially with minor contribution by CYP1A2 and CYP2C19.
Studji in vitro bl- użu ta ’ mikrosomi tal- fwied umani ndikaw li aprepitant huwa metabolizzat primarjament permezz ta ’ CYP3A4 u potenzjalment b’ kontribuzzjoni minuri permezz ta ’ CYP1A2 u CYP2C19.
Following a single intravenously administered 100 mg dose of [14C]- fosaprepitant, a prodrug for aprepitant, to healthy subjects, 57% of the radioactivity was recovered in urine and 45% in faeces.
Wara l- għoti mill- vina ta ’ doża waħda ta ’ 100 - mg ta ’ [14C] - fosaprepitant, promediċina għal aprepitant f’ individwi b’ saħħithom, 57% tar- radjoattività ġiet irkuprata fl- awrina u 45% fl- ippurgar.
The plasma clearance of aprepitant is dose-dependent, decreasing with increased dose and ranged from approximately 60 to 72 ml/ min in the therapeutic dose range.
Ir- rata ta 'l- eliminazzjoni ta ’ aprepitant fil- plażma hija dipendenti fuq id- doża, tonqos maż- żieda fid - doża u tvarja minn bejn wieħed u ieħor 60 sa 72ml/ min fil- limiti tad- doża terapewtika.
The terminal half-life ranged from approximately 9 to 13 hours.
Il- half- life terminali kienet bejn 9 sa 13- il siegħa, bejn wieħed u ieħor.
Gender:
22 Ġeneru:
Mild hepatic impairment (Child-Pugh class A) does not affect the pharmacokinetics of aprepitant to a clinically relevant extent.
Indeboliment epatiku ħafif (Punteġġ ta ’ bejn 5 sa 6 f’ Child- Pugh) ma jaffettwax il- farmakokinetika ta ’ aprepitant sa punt klinikament rilevanti.
Conclusions regarding the influence of moderate hepatic impairment (Child-Pugh class B) on aprepitant pharmacokinetics cannot be drawn from available data.
Ma jistgħux isiru konklużjonijiet dwar l- influwenza ta ’ indeboliment epatiku moderat (Child Pugh klassi B) fuq il- farmakokinetiċi ta ’ aprepitant mid- data disponibbli.
22 Relationship between concentration and effect Using a highly specific NK1-receptor tracer, positron emission tomography (PET) studies in healthy young men have shown that aprepitant penetrates into the brain and occupies NK1 receptors in a dose- and plasma- concentration-dependent manner.
Relazzjoni bejn il- konċentrazzjoni u l- effett (PK/ PD) Bl- użu ta ’ traċċatur speċifiku ħafna għar- riċettur NK1, studji positron emission tomography (PET) f’ irġiel għadhom żgħar u b’ saħħithom urew li aprepitant jippenetra fil- moħħ u jokkupa r- riċetturi- NK1 b' mod li jiddipendi fuq id- doża u l- konċentrazzjoni fil- plażma.
5.3 Pre-clinical safety data
5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina
Pre-clinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to reproduction.
Data ta ’ qabel il- provi kliniċi, ibbażata fuq studji konvenzjonali dwar tossiċita kkawżata minn doża waħda jew dożi miltipli, ma turi l- ebda riskju specjali għall- bniedem, ta ’ tossicità, ġenotossiċità, potenzjal karċinoġeniku u tossiċità għar- riproduzzjoni.
However, it should be noted that systemic exposure in rodents was similar or even lower than therapeutic exposure in humans at the 125 mg/ 80 mg dose.
Madankollu, għandu jiġi nnotat li espożizzjoni sistematika f' annimali gerriema kienet simili jew saħansita inqas minn espożizzjoni terapewtika fil - bnedmin fid- doża ta '125 mg/ 80 mg.
In particular, although no adverse effects were noted in reproduction studies at human exposure levels, the animal exposures are not sufficient to make an adequate risk assessment in man.
B' mod partikolari, għalkemm l- ebda effetti avversi ma ġew innotati fl- istudju dwar ir- riproduzzjoni f' livelli ta 'espożizzjoni għall- bniedem, l- espożizzjonijiet għall- annimali m' humiex biżżejjed sabiex issir stima adegwata dwar ir- riskju fil- bniedem.
Capsule content Sucrose Microcrystalline cellulose (E 460) Hydroxypropyl cellulose (E 463) Sodium laurilsulfate
Kontenut tal- kapsula sucrose microcrystalline cellulose (E 460) hydroxypropyl cellulose (E 463) sodium laurilsulfate 23 Il- qoxra tal- kapsula gelatin jistgħu jintużaw sodium laurilsulfate u silica colloidal anhydrous titanium dioxide (E 171)
Printing ink Shellac Potassium hydroxide Black iron oxide (E 172)
Linka ta 'l- istampar shellac potassium hydroxide black iron oxide (E 172)
Store in the original package in order to protect from moisture.
Żommhom fil- pakkett oriġinali sabiex tipproteġi mill- umdità.
Different pack sizes including different strengths are available.
Daqsijiet differenti tal- pakketti li jinkludu dożi differenti huma disponibbli.
Aluminium blister containing one 80 mg capsule.
Folja ta 'l- aluminju li fiha kapsula waħda ta' 80 mg.
Aluminium blister containing two 80 mg capsules.
Folja ta 'l- aluminju li fiha żewġ kapsuli ta' 80 mg.
5 Aluminium blisters each containing one 80 mg capsule.
5 folji ta 'l- aluminju li kull waħda minnhom fiha kapsula waħda ta' 80 mg.
23 6.6 Special precautions for disposal
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
EMEND 125 mg hard capsules
EMEND 125 mg kapsuli iebsin
Each capsule contains 125 mg of aprepitant.
Kull kapsula fiha 125 mg ta 'aprepitant.
125 mg sucrose.
125 mg sucrose.
Capsules are opaque with a white body and pink cap with “ 462” and “ 125 mg” printed radially in black ink on the body.
Il- kapsuli huma opaki b' parti bajda u b' kappa roża b '“ 462 ” u “ 125 mg ” stampati b' mod radjali b' linka sewda fuq il- parti l- bajda
Prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy in adults.
Prevenzjoni ta 'nawseja u rimettar assoċjati ma' kimoterapija tal- kanċer ferm emetoġenika bbażata fuq cisplatin fl- adulti.
EMEND 125 mg is given as part of combination therapy (see section 4.2).
EMEND 125 mg jingħata bħala parti minn terapija ta 'kombinazzjoni (ara sezzjoni 4. 2).
Posology EMEND is given for 3 days as part of a regimen that includes a corticosteroid and a 5-HT3 antagonist.
Pożoloġija EMEND jingħata għal tlett ijiem bħala parti minn kors li jinkludi kortikosterojd u antagonista ta ’ 5 - HT3.
In clinical studies with EMEND, the following regimens were used for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy:
26 Fi studji kliniċi b’ EMEND, il- korsijiet li ġejjin intużaw għall- prevenzjoni ta 'nawseja u rimettar assoċjati ma' kimoterapija tal- kanċer emetoġenika:
25 Highly Emetogenic Chemotherapy Regimen
Kors ta 'Kimoterapija Ferm Emetoġenika
80 mg PO
80 mg
12 mg PO
12 mg orali
x 8 mg PO
2 x 8 mg orali
For additional information on the co-administration with corticosteroids, see section 4.5.
Għal aktar tagħrif dwar l- għoti ta 'EMEND ma' kortikosterojdi, ara s- sezzjoni 4. 5.
Please refer to the Summary of Product Characteristics of co-administered antiemetic agents.
Jekk jogħġbok irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott ta ’ anti- emetiċi li jingħataw flimkien.
EMEND may be taken with or without food.
27 EMEND jista ’ jittieħed ma ’ l- ikel kif ukoll mhux ma ’ l- ikel.
26 Co-administration with pimozide, terfenadine, astemizole or cisapride.
EMEND ma għandux jingħata flimkien ma 'pimozide, terfenadine, astemizole jew cisapride.
(see section 4.5).
L - inibizzjoni ta 'cytochrome P450 isoenżim 3A4 (CYP3A4) minħabba aprepitant tista' tirriżulta f' konċentrazzjonijiet ogħla fil- plażma ta 'dawn is- sustanzi attivi, li jistgħu jikkawżaw reazzjonijiet serji jew li jipperikolaw il- ħajja (ara sezzjoni 4. 5).
After the end of treatment, EMEND causes a transient moderate induction of CYP2C9 and a transient mild induction of CYP3A4 and glucuronidation.
Wara t- tmiem tat- trattament, EMEND jikkawża induzzjoni moderata li mhiex permanenti ta ’ CYP2C9 u induzzjoni ħafifa li mhiex permanenti ta ’ CYP3A4 u glukorinidazzjoni.
Effect of CYP3A4 inhibition by aprepitant on the pharmacokinetics of other active substances As a moderate inhibitor of CYP3A4, aprepitant (125 mg/ 80 mg) can increase plasma concentrations of co-administered active substances that are metabolised through CYP3A4.
28 L- effett ta ’ inibizzjoni CYP3A4 b’ aprepitant fuq il- farmakokinetiċi ta 'sustanzi attivi oħrajn Bħala inibitur moderat ta ’ CYP3A4, aprepitant (125 mg/ 80 mg) jista ’ jżid l- konċenterazzjonijiet fil - plażma ta ’ sustanzi attivi oħra mogħtija flimkien, mill- ħalq li huma metabolizzati permezz ta ’ CYP3A4.
27 Induction As a moderate inducer of CYP2C9 and a mild inducer of CYP3A4 and glucuronidation, aprepitant can decrease plasma concentrations of substrates eliminated by these routes.
Induzzjoni Bħala induttur moderat ta 'CYP2C9 u induttur ħafif tas- CYP3A4 u glucoronidazzjoni, aprepitant jista' jnaqqas il- konċentrazzjonijiet tal- plażma ta 'sottostrati eliminati b' dawn il- modi.
For CYP2C9 and CYP3A4 substrates, the induction is transient with a maximum effect reached 3-5 days after end of the EMEND 3-day treatment.
Għal sottostrati ta 'CYP2C9 u CYP3A4, l - induzzjoni mhiex permanenti b' effett massimu milħuq 3- 5 t' ijiem wara tmiem it- tlett ijiem trattament b' EMEND.
Mild induction of glucuronidation is also seen with 80 mg oral aprepitant given for 7 days.
Tidher ukoll induzzjoni ħafifa ta 'glucoronidazzjoni permezz ta ’ 80 mg' aprepitant orali għal 7 ijiem.
Caution is advised when warfarin, acenocoumarol, tolbutamide, phenytoin or other active substance that are known to be metabolised by CYP2C9 are administered during this time period.
Huwa rrakkomandat li tingħata attenzjoni meta warfarin, acenocoumarol, tolbutamide, phenytoin jew sustanzi attivi oħrajn li huma magħrufin li huma metabolizzati permezz ta ’ 'CYP2C9 jingħataw matul dan il- perijodu.
The dose of dexamethasone in chemotherapy induced nausea and vomiting clinical trials was chosen to account foractive substance interactions (see section 4.2).
Id- doża ta 'dexamethasone fi provi kliniċi ta' nawseja u rimettar ikkaġunati minn kimoterapija klinika ntagħżlet sabiex tagħmel tajjeb għall - interazzjonijiet tas- sustanzi attivi (ara sezzjoni 4. 2).
EMEND, when given as a regimen of 125 mg with dexamethasone co-administered orally as 20 mg on Day 1, and EMEND when given as 80 mg/ day with dexamethasone co- administered orally as 8 mg on Days 2 through 5, increased the AUC of dexamethasone, a CYP3A4 substrate, 2.2-fold on Days 1 and 5.
EMEND, meta mogħti bħala kors ta '125 mg flimkien ma' dexamethasone orali f' doża ta '20 mg f' Jum 1, u EMEND meta mogħti bħala 80 mg kuljum flimkien ma' 8 mg dexamethasone oralifil- Jiem 2 sa 5, żied l- AUC ta 'dexamethasone, sottostrat ta' CYP3A4, bi 2. 2 drabi fil- Jiem 1 u 5.
During continuous treatment with methylprednisolone, the AUC of methylprednisolone may decrease at later time points within 2 weeks following initiation of dosing with EMEND, due to the inducing effect of aprepitant on CYP3A4.
Waqt trattament kontinwu b' methylprednisolone, l- AUC ta 'methylprednisolone tista' tonqos aktar tard fi żmien ġimagħtejn minn wara l- bidu tad- dożaġġ b' EMEND, minħabba l- effett induttiv ta 'aprepitant fuq CYP3A4.
Chemotherapeutic agents:
Mediċini kimoterapewtiċi:
In pharmacokinetic studies, EMEND, when given as a regimen of 125 mg on Day 1 and 80 mg/ day on Days 2 and 3, did not influence the pharmacokinetics of docetaxel administered intravenously on Day 1 or vinorelbine administered intravenously on Day 1 or Day 8.
Fi studji farmakokinetiċi, EMEND, meta mogħti bħala reġimen ta ’ 125 mg f’ Jum 1 u 80 mg/ kuljum f’ Jiem 2 u 3, ma nfluwenzax il- farmakokinetiċi ta ’ docetaxel mogħti fil- vina (b' mod intravenuż) f’ Jum 1 jew ta ’ vinorelbine mogħti ġol- vina f’ Jum 1 u Jum 8.
Because the effect of EMEND on the pharmacokinetics of orally administered CYP3A4 substrates is greater than the effect of EMEND on the pharmacokinetics of intravenously administered CYP3A4 substrates, an interaction with orally administered chemotherapeutic agents metabolised primarily or in part by CYP3A4 (e. g. etoposide, vinorelbine) cannot be excluded.
Minħabba li l- effett ta ’ EMEND fuq il- farmakokinetiċi ta ’ sottostrati ta ’ CYP3A4 mogħtija mill- ħalq huwa ikbar mill - effett ta ’ EMEND fuq il- farmakokinetiċi ta ’ sottostrati ta ’ CYP3A4 mogħtija ġol- vini, interazzjoni ma ’ aġenti kemjoterapewtiċi metabolizzati prinċipalment jew parzjalment bis- sistema CYP3A4 (eż. etoposide, vinorelbine) ma tistax tiġi eskluża.
The potential effects of increased plasma concentrations of midazolam or other benzodiazepines metabolised via CYP3A4 (alprazolam, triazolam) should be considered when co- administering these agents with EMEND (125 mg/ 80 mg).
L- effetti potenzjali ta ’ żidiet fil- konċentrazzjonijiet ta ’ midazolam fil- plażma jew benzodiazepines oħra metabolizzati permezz ta ’ CYP3A4 (alprazolam, triazolam) għandhom jiġu kkunsiderati meta dawn il- mediċini jingħataw flimkienma ’ EMEND (125 mg/ 80 mg).
EMEND increased the AUC of midazolam 25% on Day 4 and decreased the AUC of midazolam 19% on Day 8 and 4% on Day 15.
EMEND żied l- AUC ta ’ midazolam b’ 25% f’ Jum 4 u naqqas l- AUC ta ’ midazolam b '19% f’ Jum 8 u b’ 4% f’ Jum 15.
28 In a third study with intravenous and oral administration of midazolam, EMEND was given as 125 mg on Day 1 and 80 mg/ day on Days 2 and 3, together with ondansetron 32 mg Day 1, dexamethasone 12 mg Day 1 and 8 mg Days 2-4.
Fit- tielet stħarriġ fejn midazolam ingħatamil- vina / kuljum fil- Jiem 2 u 3, flimkien ma’ 32 mg ondansetron f’ Jum 1, 12 mg dexamethasone f’ Jum 1 u 8 mg fil- Jiem 2- 4.
An additional study was completed with intravenous administration of midazolam and EMEND.
Sar studju addizzjonali fejn midazolam ingħata mill - vina flimkien ma ’ EMEND.
Intravenous 2 mg midazolam was given 1 hour after oral administration of a single dose of EMEND 125 mg.
2 mg Midazolam ġol- vini ingħataw siegħa wara doża waħda orali ta '125 mg EMEND.
In patients on chronic warfarin therapy, the prothrombin time (INR) should be monitored closely during treatment with EMEND and for 2 weeks following each 3-day course of EMEND for chemotherapy induced nausea and vomiting (see section 4.4).
F' pazjenti li qegħdin fuq terapija kronika tal- warfarina, il- prothrombin time (INR) għandu jiġi sorveljat mill- qrib waqt it- trattament b' EMEND u għal ġimagħtejn wara kull kors ta 'tlett ijiem ta' EMEND għal nawseja u rimettar ikkawżati mill - - kimoterapija (ara sezzjoni 4. 4).
EMEND, when given as 125 mg on Day 1 and 80 mg/ day on Days 2 and 3, decreased the AUC of tolbutamide (a CYP2C9 substrate) by 23% on Day 4, 28% on Day 8, and 15% on Day 15, when a single dose of tolbutamide 500 mg was administered orally prior to the administration of the 3-day regimen of EMEND and on Days 4, 8, and 15.
Meta EMEND ngħata bħala 125 mg f’ Jum 1 u 80 mg kuljum f’ Jiem 2 u 3, naqqas l - AUC ta ’ tolbutamide (sottostrat ta ’ CYP2C9) bi 23% f’ Jum 4, 28% f’ Jum 8, u 15% f’ Jum 15, meta doża waħda ta ’ 500 mg tolbutamide ingħatat oralment qabel l- għoti ta ’ kors ta ’ tlett ijiem ta ’ EMEND u fil- Jiem 4, 8 u 15.
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration of EMEND.
L- effikaċja tal- kontraċettivi ormonali tista ’ titnaqqaswaqt u għal 28 jum wara l - għoti ta 'EMEND.
Aprepitant, when given once daily for 14 days as a 100 mg capsule with an oral contraceptive containing 35 μ g of ethinyl estradiol and 1 mg of norethindrone, decreased the AUC of ethinyl estradiol by 43%, and decreased the AUC of norethindrone by 8%.
Meta Aprepitant ingħata, darba kuljum għal 14- il jum bħala kapsula ta '100 mg flimkien ma ’' kontraċettiv orali li fih 35 μg ta 'ethinyl estradiol u 1 mg ta' norethindrone, naqqas l- AUC ta 'ethinyl estradiol bi 43%, u naqqas l- AUC ta' norethindrone bi 8%.
During days 9 through 21 in this study, there was as much as a 64% decrease in ethinyl estradiol trough concentrations and as much as a 60% decrease in norethindrone trough concentrations.
F’ dan l- istudju matul il- jiem 9 sa 21, kien hemm saħansitra sa 64% tnaqqis fil- konċentrazzjonijiet aktar baxxi ta ’ ethinyl estradiol u a sa 60% tnaqqis fil - konċentrazzjonijiet l- aktar baxxi ta ’ norethindrone.
In clinical interaction studies, aprepitant did not have clinically important effects on the pharmacokinetics of ondansetron, granisetron, or hydrodolasetron (the active metabolite of dolasetron).
30 Antagonisti ta '5- HT3 Fi studji ta ’ interazzjonijiet kliniċi, aprepitant ma kellux effetti klinikament importanti fuq il- farmakokinetiċi ta ’ ondansetron, granisetron, jew hydrodolasetron (il- metabolit attiv ta ’ dolasetron).
Aprepitant does not seem to interact with the P-glycoprotein transporter, as suggested by the lack of interaction of EMEND with digoxin.
Aprepitant ma jidhirx li jinteraġġixxi mat- traportatur P- glycoprotein, kif issuġġerit min- nuqqas ta ’ interazzjoni ta ’ aprepitant ma ’ digoxin.
Effect of other agents on the pharmacokinetics of aprepitant Concomitant administration of EMEND with active substances that inhibit CYP3A4 activity (e. g., ritonavir, ketoconazole, clarithromycin, telithromycin) should be approached cautiously, as the combination results in increased plasma concentrations of aprepitant.
Effett ta 'mediċini oħra fuq il- farmakokinetiċi ta' aprepitant L- għoti fl- istess ħin ta 'EMEND ma' sustanzi attivi li jimpedixxu l- attività ta ’ CYP3A4 (eż. ritonavir, ketoconazole, clarithromycin, telithromycin) għandu jsir b' kawtela billi flimkien jirriżultaw f' konċentrazzjonijiet ogħla ta 'aprepitant fil- plażma.
Concomitant administration of EMEND with herbal preparations containing St.
L- għoti ta 'EMEND flimkien ma' St.
29 Ketoconazole:
Ketoconazole:
In a clinical study of patients receiving moderately emetogenic chemotherapy, clinical adverse reactions were reported in approximately 21% of patients treated with the aprepitant regimen compared with approximately 20% of patients treated with standard therapy.
Fi studju kliniku ta 'pazjenti li kienu qed jirċievu kimoterapija moderatament emetoġenika, ġew irrapportati reazzjonijiet avversi kliniċi f' madwar 21% tal- pazjenti ttrattati bil- kors ta' aprepitant meta mqabbla ma 'madwar 20% tal- pazjenti ttrattati bit- terapija 31 standard.
The most common adverse reactions reported at a greater incidence in patients treated with the aprepitant regimen than with standard therapy in patients receiving highly emetogenic chemotherapy were: hiccups (4.6% versus 2.9%), asthenia/ fatigue (2.9% versus 1.6%), alanine aminotransferase (ALT) increased (2.8% versus 1.5%), constipation (2.2% versus 2.0%), headache (2.2% versus 1.8%), and anorexia (2.0% versus 0.5%).
Ir- reazzjonijiet avversi l- aktar komuni rrapportati f' inċidenza akbar f' pazjenti trattati bil- kors ta 'aprepitant milli bit- terapija standard, f' pazjenti li kienu qed jirċievu kimoterapija ferm emetoġenika kienu: sulluzzu (4. 6% kontra 2. 9%), astenja/ għejja (2. 9% kontra 1. 6%), żieda fl- alanine aminotransferase (ALT) (2. 8% kontra 1. 5%), stitikezza (2. 2% kontra 2. 0%), uġigħ ta' ras (2. 2% kontra 1. 8%), u anoreksja (2. 0% kontra 0. 5%).
The following adverse reactions were observed in patients treated with the aprepitant regimen and at a greater incidence than with standard therapy:
Ir- reazzjonijiet avversi li ġejjin ġew osservati f' pazjenti ttrattati bil- kors ta '' aprepitant u f' inċidenza akbar milli b' terapija standard:
Bradycardia febrile neutropenia, anaemia
bradikardja newtropenja bid- deni, anemija
uncommon uncommon
mhux komuni mhux komuni komuni
Conjunctivitis
konġuntivite
Ear and labyrinth disorders Respiratory, thoracic and mediastinal disorders
Disturbi fil- widnejn u fis- sistema tinnite labirintika Disturbi respiratorji, toraċiċi u sulluzzu medjastinali farinġite, għatis, sogħla, taqtir min- naħa ta ’ wara ta ’ l- imnieħer, irritazzjoni fil- griżmejn Disturbi gastro- intestinali stitikezza, dijarrea, dispepsja, tifwiq
uncommon common
mhux komuni komuni mhux komuni komuni
pharyngitis, sneezing, cough, postnasal drip, throat irritation
ulċera duwodenali pperforata, nawseja *, rimetter *, rifluss ta 'l- aċidu, diżgewżja, skumdità epigastrika, stitikezza esaġerata, mard ta' rifluss gastroesofagu, uġigħ addominali, ħalq niexef, enterocolite, gass, stomatite
Gastrointestinal disorders
Disturbi fil- kliewi u fis- sistema polijurja, disurja, pollakjurja urinaria
polyuria, dysuria, pollakiuria rash, acne, photosensitivity, hyperhidrosis, oily skin, pruritus, skin lesion
Disturbi fil- ġilda u fit- tessuti ta ’ raxx, akne, fotosensittività, iperidrożi, ġilda taħt il- ġilda żejtnija, prurite, feriti fil- ġilda
uncommon uncommon
mhux komuni
Musculoskeletal and connective tissue disorders
Disturbi muskolu- skeltrali u tal - bugħawwieġ, mijalġja connective tissue
Metabolism and nutrition disorders
Disturbi fil- metaboliżmu u n - anoreksja nutrizzjoni
weight gain, polydipsia
żieda fil- piż, polidipsja Infezzjonijiet u infestazzjonijiet kandidajiżi, infezzjoni ta 'l- istaphylococcus
uncommon
mhux komuni mhux komuni
Infection and infestations Vascular disorders General disorders and administration site conditions
32 Disturbi vaskulari Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata
candidiasis, staphylococcal infection flushing/ hot flush asthaenia/ fatigue
fwawar astenja/ għejja
uncommon uncommon common
mhux komuni komuni
Additional adverse reactions were observed in patients treated with aprepitant (40 mg) for postoperative nausea and vomiting and a greater incidence than with ondansetron: abdominal pain upper, bowel sounds abnormal, dysarthria, dyspnoea, hypoaesthesia, insomnia, miosis, nausea, sensory disturbance, stomach discomfort, visual acuity reduced, wheezing.
Reazzjonijiet avversi addizzjonali ġew osservati f' pazjenti ttrattati b' aprepitant (40 mg) għal nawseja u remettar ta 'wara l- operazzjoni u f' inċidenza akbar milli b' ondansetron: uġigħ fil- parti ta' fuq ta 'l - addome, ħsejjes anormali fil- musrana, disartrija, dispnea, ipoestesja, insomnija, mijożi, nawseja, disturb i fis- seni, skonfort fl- istonku, tnaqqis fl- akutezza tal- vista, tħarħir.
31 One case of angioedema and urticaria was reported as a serious adverse event in a patient receiving aprepitant in a non-CINV/ non-PONV study.
Każ ta ’ anġjoedema u urtikarja ġie rrapportat bħala reazzjoni avversa serja f’ pazjent li ngħata aprepitant fi stħarriġ non- CINV/ non- PONV.
In the event of overdose, EMEND should be discontinued and general supportive treatment and monitoring should be provided.
F’ każ ta ’ doża eċċessiva, EMEND għandu jitwaqqafu għandu jiġi pprovdut trattament ġenerali ta ’ appoġġ u monitoraġġ.
Aprepitant is a selective high-affinity antagonist at human substance P neurokinin 1 (NK1) receptors.
Aprepitant huwa antagonist selettiv b’ affinità għolja għar - riċetturi tas- sustanza P newrokinina 1 (NK1) tal- bniedem.
In 2 randomised, double-blind studies encompassing a total of 1,094 patients receiving chemotherapy that included cisplatin ≥ 70 mg/ m2, aprepitant in combination with an ondansetron/ dexamethasone regimen (see section 4.2) was compared with a standard regimen (placebo plus ondansetron 32 mg intravenously administered on Day 1 plus dexamethasone 20 mg orally on Day 1 and 8 mg orally twice daily on Days 2 to 4).
33 F' żewġ studji b' mod każwali u double- blind li kienu jkopru total ta '1, 094 pazjent li kienu qed jirċievu l- kimoterapija li kienet tinkludi cisplatin ≥ 70 mg/ m2, aprepitant flimkien ma' kors ta 'ondansetron/ dexamethasone (ara sezzjoni 4. 2) ġie mqabbel ma' kors standard (plaċebo flimkien ma '32 mg ondansetron ġol- vina li ingħata f' Jum 1 flimkien ma' dexamethasone 20 mg mogħti mill- ħalq f' Jum 1 u 8 mg mogħtija darbtejn kuljum fil- Jiem 2 sa 4).
32 Table 1 Percent of Patients Receiving Highly Emetogenic Chemotherapy Responding by Treatment Group and Phase — Cycle 1
Tabella 1 Perċentwal ta 'Pazjenti li Jirċievu Kienu qed Jirċievu Kimoterapija Ferm Emetoġenika li Jirrispondu skond il- Grupp u Fażi ta' Trattament — Ċiklu 1
Aprepitant Regimen
Terapija
Standard Therapy
Kors ta '
Differences*
Standard
COMPOSITE MEASURES
Differenzi *
(N=
Aprepitant (N= 524)
521) †%
(N= 521)
Complete Response (no emesis and no
Rispons Sħiħ (l- ebda emesi u l- ebda terapija ta 'salvataġġ)
67.7 47.8 86.0 73.2 71.5 51.2
47. 8 73. 2 51. 2
19.9 12.7 20.3
19. 9 12. 7 20. 3
(14.0, 25.8) (7.9, 17.6) (14.5, 26.1)
(14. 0, 25. 8) (7. 9, 17. 6) (14. 5, 26. 1)
INDIVIDUAL MEASURES No Emesis (no emetic episodes regardless of use of rescue therapy)
MIŻURI INDIVIDWALI L- ebda emesi (l- ebda każ ta 'emesi minkejja l- użu m ta' terapija ta 'salvataġġ)
71.9 86.8 76.2
71. 9 86. 8 76. 2
49.7 74.0 53.5
49. 7 74. 0 53. 5
22.2 12.7 22.6
22. 2 12. 7 22. 6
(16.4, 28.0) (8.0, 17.5) (17.0, 28.2)
(16. 4, 28. 0) (8. 0, 17. 5) (17. 0, 28. 2)
The estimated time to first emesis in the combined analysis is depicted by the Kaplan-Meier plot in Figure 1.
34 Il- ħin stmat għall- ewwel emesi fl- analiżi kkombinata hu muri bil- Kaplan- Meier plot f' Figura 1.
Aprepitant Regimen (N=520) Standard Therapy (N=523)
Regimen ta ’ Aprepitant( N=520) Terapija Standard (N=523)
33 In a randomised, double-blind study in a total of 866 patients (864 females, 2 males) receiving chemotherapy that included cyclophosphamide 750-1500 mg/ m2; or cyclophosphamide 500- 1500 mg/ m2 and doxorubicin (< 60 mg/ m2) or epirubicin (< 100 mg/ m2), aprepitant in combination with an ondansetron/ dexamethasone regimen (see section 4.2) was compared with standard therapy (placebo plus ondansetron 8 mg orally (twice on Day 1, and every 12 hours on Days 2 and 3) plus dexamethasone 20 mg orally on Day 1).
Fi stħarriġ double- blind, b' mod każwali, f’ total ta ’ 866 pazjent (864 mara, 2 irġiel) li kienu qed jingħataw il- kimoterapija li nkludiet cyclophosphamide 750- 1500 mg/ m2; jew cyclophosphamide 500 - 1500 mg/ m2 u doxorubicin (60 mg/ m2) jew epirubicin (100 mg/ m2), aprepitant flimkien ma ’ kors ta ’ ondansetron/ dexamethasone (ara sezzjoni 4. 2) tqabbel ma ’ terapija standard (plaċebo u 8 mg ondansetron oralment (darbtejn f’ Jum 1, u kull 12- il siegħa f’ Jiem 2 u 3) flimkien ma ’ 20 mg dexamethasone oralment f’ Jum 1).
A summary of the key study results is shown in Table 2.
Sommarju a tar- riżultati ewlenin ta 'l- istudju hija murija fit- Tabella 2.
Table 2 Percent of Patients Responding by Treatment Group and Phase — Cycle 1 Moderately Emetogenic Chemotherapy
35 Tabella 2 Perċentwali ta 'Pazjenti li Jirrispondu skond il- Grupp u Fażi ta' Trattament — Ċiklu 1 Kimoterapija Moderatament Emetoġenika
INDIVIDUAL MEASURES No Emesis (no emetic episodes regardless of use of rescue therapy)
L- ebda emesi (l- ebda każ ta 'emesi minkejja l- użu ta' terapija ta 'salvataġġ)
* The confidence intervals were calculated with no adjustment for age category (< 55 years, ≥ 55 years) and investigator group, which were included in the primary analysis of odds ratios and logistic models. † One patient in the Aprepitant Regimen only had data in the acute phase and was excluded from the overall and delayed phase analyses.
* L- intervalli ta 'kunfidenza ġew ikkalkulati bla ebda aġġustament għall- kategorija t' età (< 55 sena, ≥ 55 sena) u għall- grupp ta ’ l- investigatur, li kienu inklużi fl- analiżi primarja ta ’ l- odds ratios u mudelli loġistiċi.
34 The estimated time to first emesis in the study is depicted by the Kaplan-Meier plot in Figure 2.
Il- ħin stmat għall- ewwel emesi fl- analiżi hu muri bil- Kaplan- Meier plot f' Figura 2.
100%
100% Kors ta ’ Aprepitant (N=432) Terapija Standard (N=424) 90% Perċentwal ta ’ Pazjenti
In the same clinical study, 744 patients continued into the Multiple-Cycle extension for up to 3 additional cycles of chemotherapy.
36 Fl- istess studju kliniku, 744 pazjent komplew fl- estensjoni taċ- Ċiklu- Multiplu sgħal sa 3 ċikli ta ’ kimoterapija addizzjonali.
The pharmacokinetics of aprepitant is non-linear across the clinical dose range.
Il- farmakokinetiċi ta 'aprepitant m' h lineari fil- firxa kollha tad- doża klinika.
In healthy young adults, aprepitant accounts for approximately 19% of the radioactivity in plasma over 72 hours following a single intravenous
F' adulti żgħar b' saħħithom aprepitant huwa responsabbli għal bejn wieħed u ieħor 19% tar- radjoattività fil- plażma fuq perijodu ta ’ 72 siegħa wara l- għoti mill- vina ta ’ doża waħda ta ’ 100 mg ta ’ [14C] - fosaprepitant, promediċina għal aprepitant, li tindika l- preżenza sostanzjali ta ’ metaboliti fil- plażma.
Metabolites are excreted in urine and via biliary excretion in faeces.
Il- metaboliti jiġu eliminatfl- awrina u permezz ta ’ eliminazzjoni biljarja fl- ippurgar.
Following a single intravenously administered 100 mg dose of [14C]- fosaprepitant, a prodrug for aprepitant, to healthy subjects, 57% of the radioactivity was recovered in urine and 45% in faeces.
Wara l- għoti mill- vinata ’ doża waħda ta ’ 100 mg ta ’ [14C] - fosaprepitant, promediċina għal aprepitant f’ individwi b’ saħħithom, 57% tar- radjoattività ġiet irkuprata fl- awrina u 45% fl- ippurgar.
The plasma clearance of aprepitant is dose-dependent, decreasing with increased dose and ranged from approximately 60 to 72 ml/ min in the therapeutic dose range.
Ir- rata ta 'l- eliminazzjoni ta ’ aprepitant fil- plażma hija dipendenti fuq id- doża, tonqos maż- żieda fid - doża u tvarja minn bejn wieħed u ieħor 60 sa 72 ml/ min fil- limiti tad- doża terapewtika.
The terminal half-life ranged from approximately 9 to 13 hours.
Il- half- life terminali varja minn 9 sa 13- il siegħa.
Gender:
37 Ġeneru:
Following oral administration of a single 125 mg dose ofaprepitant, the Cmax for aprepitant is 16% higher in females as compared with males.
Wara l- għoti mill- ħalq ta ’ doża waħda ta ’ 125 mg ta ’ aprepitant, is- Cmax għal aprepitant huwa 16% ogħla fin- nisa meta mqabbel ma ’ l- irġiel.
Mild hepatic impairment(Child-Pugh class A) does not affect the pharmacokinetics of aprepitant to a clinically relevant extent.
Indeboliment epatiku ħafif (Punteġġ ta ’ bejn 5 sa 6 f’ Child- Pugh) ma jaffettwax il- farmakokinetika ta ’ aprepitant sa punt klinikament rilevanti.
Relationship between concentration and effect Using a highly specific NK1-receptor tracer, positron emission tomography (PET) studies in healthy young men have shown that aprepitant penetrates into the brain and occupies NK1 receptors in a dose- and plasma- concentration-dependent manner.
Relazzjoni bejn il- konċentrazzjoni u l- effett (PK/ PD) Bl- użu ta ’ traċċatur speċifiku ħafna għar- riċettur NK1, studji positron emission tomography (PET) f’ irġiel għadhom żgħar u b’ saħħithom urew li aprepitant jippenetra fil- moħħ u jokkupa r- riċetturi- NK1 b' mod li jiddipendi fuq id- doża u l- konċentrazzjoni fil- plażma.
36 5.3 Pre-clinical safety data
5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina
Pre-clinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to reproduction.
Data ta ’ qabel il- provi kliniċi, ibbażata fuq studji konvenzjonali dwar tossiċita ’ kkawżata minn doża waħda jew dożi multipli ma turi l- ebda riskju specjali għall- bniedem ta ’ tossicità, ġenotossiċità, potenzjal karċinoġeniku u tossiċità għar- riproduzzjoni.
Capsule content Sucrose Microcrystalline cellulose (E 460) Hydroxypropyl cellulose (E 463) Sodium laurilsulfate
Kontenut tal- kapsula sucrosemicrocrystalline cellulose (E 460) hydroxypropyl cellulose (E 463) sodium laurilsulfate
Capsule shell Gelatin Sodium laurilsulfate and silica colloidal anhydrous may be used Titanium dioxide (E 171) Yellow iron oxide (E 172) Red iron oxide (E 172)
38 Il- qoxra tal- kapsula gelatin jistgħu jintużaw sodium laurilsulfate u silica colloidal anhydrous titanium dioxide (E 171) yellow iron oxide (E 172) red iron oxide (E 172)
Aluminium blister containing one 125 mg capsule.
Folja ta 'l- aluminju li fiha kapsula waħda ta' 125 mg.
5 Aluminium blisters each containing one 125 mg capsule.
5 folji ta 'l- aluminju li kull waħda minnhom fiha kapsula waħda ta' 125 mg.
11 November 2008
11 ta 'Novembru 2003 Data ta ’ l- aħħar tiġdid:
10.
11 ta 'Novembru 2008 39 10.
EMEND 125 mg hard capsules EMEND 80 mg hard capsules
EMEND 125 mg kapsuli iebsin EMEND 80 mg kapsuli iebsin
Each 125 mg capsule contains 125 mg of aprepitant.
Kull kapsula ta '125 mg fiha 125 mg ta' aprepitant.
Each 80 mg capsule contains 80 mg of aprepitant.
Kull kapsula ta '80 mg fiha 80 mg ta' aprepitant.
125 mg sucrose (in the 125 mg capsule).
125 mg sucrose (fil- kapsula ta ’ 125 mg).
80 mg sucrose (in the 80 mg capsule).
80 mg sucrose (fil- kapsula ta ’ 80 mg).
For a full list of excipients, see section 6.1.
Għal- lista sħiħa ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
The 125 mg capsule is opaque with a white body and pink cap with “ 462” and “ 125 mg” printed radially in black ink on the body.
Il- kapsuli ta '125 mg huma opaki b' parti bajda u b' kappa roża b' “ 462 ” u “ 125 mg ” stampati b' mod radjali b' linka sewda fuq il- parti l- bajda.
The 80 mg capsules are opaque with a white body and cap with “ 461” and “ 80 mg” printed radially in black ink on the body.
Il- kapsuli ta '80 mg huma opaki bojod u b' kappa ta ’ l- istess kulur b' “ 461 ” u “ 80 mg ” stampati b' mod radjali b' linka sewda fuqhom.
EMEND 125 mg/ 80 mg is given as part of combination therapy (see section 4.2).
EMEND 125 mg/ 80 mg jingħata bħala parti minn terapija ta 'kombinazzjoni (ara sezzjoni 4. 2).
The recommended posology of EMEND is 125 mg orally (PO) once daily one hour before start of chemotherapy on Day 1 and 80 mg PO once daily on Days 2 and 3.
Il- pożoloġija rakkomandata ta 'EMEND hija ta ’ 125 mg li tingħata mill- ħalq (PO) darba kuljum siegħa qabel il- bidu tal- kimoterapija fl- 1 Jum u 80 mg PO darba kuljum fil- Jiem 2 u 3.
Fosaprepitant 115 mg, a lyophilized prodrug of aprepitant, may be substituted for oral EMEND (125 mg), 30 minutes prior to chemotherapy, on Day 1 only of the chemotherapy-induced nausea and vomiting (CINV) regimen as an intravenous infusion administered over 15 minutes.
Fosaprepitant 115 mg, promediċina lijofilizzata ta ’ aprepitant, tista ’ tiġi sostitwita għal EMEND (125 mg) orali, 30 minuta qabel il- kimoterapija, f’ Jum 1 biss tar- reġimen għad- dardir u rimettar ikkawżat mill - kimoterapija (CINV) bħala infużjoni ġol- vini mogħtija fuq 15- il minuta.
In clinical studies with EMEND, the following regimens were used for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy:
41 Fi studji kliniċi b’ EMEND, il- korsijiet li ġejjin intużaw għall- prevenzjoni ta 'nawseja u rimettar assoċjati ma' kimoterapija tal- kanċer emetoġenika:
39 Highly Emetogenic Chemotherapy Regimen
Kors ta 'Kimoterapija Ferm Emetoġenika
EMENDwas administered orally 1 hour prior to chemotherapy treatment on Day 1 and in the morning on Days 2 and 3.
EMEND ingħata mill- ħalq siegħa qabel it- trattament kimoterapewtiku fl- 1 Jum u filgħodu ta 'Jiem 2 u 3.
For additional information on the co-administration with corticosteroids, see section 4.5.
Għal aktar tagħrif dwar l- għoti konġunt ta 'EMEND ma' kortikosterojdi, ara s- sezzjoni 4. 5.
Please refer to the Summary of Product Characteristics of co-administered antiemetics.
Jekk jogħġbok irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott ta ’ anti- emetiċi li jingħataw flimkien.
Children and adolescents EMEND is not recommended for use in children below 18 years due to insufficient data on safety and efficacy.
42 Tfal u adoloxxenti EMEND mhux irrakkomandat għall- użu fit- tfal ta ’ taħt it- 18- il sena peress li m’ hemmx biżżejjed informazzjoni dwar is- sigurtà u l- effikaċja.
Hypersensitivity to the active substance or to any of the excipients.
Sensittività eċċessiva għas- sustanzaattiva jew għal sustanzi mhux attivi.
40 Co-administration with pimozide, terfenadine, astemizole or cisapride.
EMEND ma għandux jingħata flimkien ma 'pimozide, terfenadine, astemizole jew cisapride.