qanastek/EMEA-V3 huggingface dataset:
Distribution Aprepitant is highly protein bound, with a mean of 97%.
Kif jiġi Distribwit Aprepitant jintrabat b’ mod qawwi mal- proteini, b’ medja ta ’ 97%.
The geometric mean apparent volume of distribution at steady state (Vdss) is approximately 66 l in humans.
Fil- bnedmin, il- medja ġeometrika tal- volum apparenti tad- distribuzzjoni fi stat fiss (Vdss) huwa bejn wieħed u ieħor 66 l.
Metabolism Aprepitant undergoes extensive metabolism.
Metaboliżmu Aprepitant jgħaddi minn metaboliżmu estensiv.
In healthy young adults, aprepitant accounts for approximately 19% of the radioactivity in plasma over 72 hours following a single intravenous administration 100 mg dose of [14C]-fosaprepitant, a prodrug for aprepitant, indicating a substantial presence of metabolites in the plasma.
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.
Twelve metabolites of aprepitant have been identified in human plasma.
Tnax- il metabolit ta ’ aprepitant ġew identifikati fil- plażma umana.
The metabolism of aprepitant occurs largely via oxidation at the morpholine ring and its side chains and the resultant metabolites were only weakly active.
Il- metaboliżmu ta ’ aprepitant iseħħ fil- parti l- kbira permezz ta ’ ossidazzjoni fiċ - ċirku morpholine u s- side chains tiegħu u l- metaboliti li rriżultaw kienu biss ta ’ attività dgħajfa.
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 7 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.
Elimination Aprepitant is not excreted unchanged in urine.
Eliminazzjoni Aprepitant ma jiġix eliminat mhux mibdul fl- awrina.
Metabolites are excreted in urine and via biliary excretion in faeces.
Il- metaboliti jiġu eliminati fl- 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- 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.
7 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 is approximately 9 hours after administration of a single 40 mg dose.
Il- half- life terminali hija bejn wieħed u ieħor 9 sigħat wara l- għoti ta ’ doża waħda ta ’ 40 mg.
Pharmacokinetics in special populations Elderly:
Farmakokinetiċi f' popolazzjonijiet speċjali L- Anzjani:
Following oral administration of a single 125 mg dose of aprepitant on Day 1 and 80 mg once daily on Days 2 through 5, the AUC0-24hr of aprepitant was 21% higher on Day 1 and 36% higher on Day 5 in elderly (≥ 65 years) relative to younger adults.
Wara l- għoti mill- ħalq ta ’ doża waħda ta ’ 125 mg ta ’ aprepitant f’ Jum 1 u 80 mg darba kuljum fil- Jiem 2 sa 5, l- AUC0- 24hr ta ’ aprepitant kienet 21% ogħla f’ Jum 1 u 36% ogħla f’ Jum 5 fl - anzjani (≥ 65 sena) meta mqabbla ma ’ adulti iżgħar fl- età.
The Cmax was 10% higher on Day 1 and 24% higher on Day 5 in elderly relative to younger adults.
Is- Cmax kien 10% ogħla f' Jum 1 u 24% ogħla f' Jum 5 fl- anzjani meta mqabbel ma 'adulti iżgħar fl- età.
These differences are not considered clinically meaningful.
Dawn id- differenzi m' humiex meqjusin klinikament sinifikattivi.
No dosage adjustment for EMEND is necessary in elderly patients.
L- ebda aġġustament fid- doża ta ’ EMEND m’ huwiex meħtieġ fl- anzjani.
Gender:
Ġeneru:
Following oral administration of a single 125 mg dose of aprepitant, 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.
These differences are not considered clinically meaningful.
Il- half- life ta ’ aprepitant hija 25% aktar baxxa fin- nisa meta mqabbel ma ’ l- irġiel u t- tmax tiegħu jseħħ bejn wieħed u ieħor fl- istess ħin Dawn id- differenzi m' humiex meqjusin klinikament sinifikattivi.
No dosage adjustment for EMEND is necessary based on gender.
L- ebda aġġustament fid- doża ta ’ EMEND ma huwa meħtieġ fuq il- bażi tal- ġeneru.
Mild hepatic impairment (Child-Pugh class A) does not affect the pharmacokinetics of aprepitant to a clinically relevant extent.
Indeboliment epatiku ħafif Child- Pugh Klassi A) ma jaffettwax il - farmakokinetika ta ’ aprepitant sa punt klinikament rilevanti.
No dose adjustment is necessary for patients with mild hepatic impairment.
L- ebda aġġustament m' huwa meħtieġ għal pazjenti li għandhom indeboliment epatiku ħafif.
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.
There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh class C).
Ma hemm l- ebda data klinika jew farmakokinetika f’ pazjenti b’ indeboliment epatiku serju (Child- Pugh klassi C).
A single 240 mg dose of aprepitant was administered to patients with severe renal impairment (CrCl < 30 ml/ min) and to patients with end stage renal disease (ESRD) requiring haemodialysis.
Indeboliment renali Doża waħda ta ’ 240 mg ta ’ aprepitant ingħatat lill- pazjenti b’ indeboliment renali serju (CrCl < 30ml/ min) u lil pazjenti b’ mard tal- kliewi fl- aħħar stadju (ESRD) li jeħtieġu l - emodijaliżi.
In patients with severe renal impairment, the AUC0-∞ of total aprepitant (unbound and protein bound) decreased by 21% and Cmax decreased by 32%, relative to healthy subjects.
F’ pazjenti b’ indeboliment renali serju, l- AUC0- ∞ ta ’ aprepitant totali (dak mhux marbut u dak marbut mal- proteina) naqset b ’ 21% u Cmax naqset bi 32%, meta mqabbla ma ’ individwi b’ saħħithom.
In patients with ESRD undergoing haemodialysis, the AUC0-∞ of total aprepitant decreased by 42% and Cmax decreased by 32%.
F’ pazjenti b’ ESRD li jkunu qegħdin taħt emodijaliżi, l - AUC0- ∞ ta ’ aprepitant totali naqset b’ 42% u Cmax naqset bi 32%.
Haemodialysis conducted 4 or 48 hours after dosing had no significant effect on the pharmacokinetics of aprepitant; less than 0.2% of the dose was recovered in the dialysate.
Minħabba tnaqqis moderat fl- irbit ta ’ aprepitant mal- proteini f’ pazjenti b’ mard renali, l- AUC tal- mediċina farmakoloġikament attiva mhux marbuta ma ġietx affettwata b’ mod sinifikanti f’ pazjenti b’ indeboliment renali meta mqabbel ma ’ individwi b’ saħħithom Emodijaliżi magħmula minn 4 sa 48 siegħa wara d- dożaġġ, ma kellha l- ebda effett sinifikattiv fuq il - farmakokinetika ta ’ aprepitant; inqas minn 0. 2% tad- doża ġiet irkuprata fid- dijażilat.
No dose adjustment for EMEND is necessary for patients with renal impairment or for patients with ESRD undergoing haemodialysis.
L- ebda aġġustament fid- doża ta ’ EMEND ma huwa meħtieġ f’ pazjenti b’ indeboliment renali u f’ pazjenti b’ ESRD li tkun qed issirilhom ħemodijaliżi.
Relationship between concentration and effect (PK/ PD) 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.
Aprepitant plasma concentrations achieved with the 3- day regimen of EMEND are predicted to provide greater than 95% occupancy of brain NK1 receptors.
Huwa maħsub li konċentrazzjonijiet ta ’ aprepitant fil- plażma milħuqin bil- kors ta ’ tlett- ijiem ta ’ EMEND jokkupaw aktar minn 95% tar - riċetturi- NK1 tal- moħħ.
5.3 Pre-clinical safety data
8 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 riskji speċjali għall- bniedem,, ġenotossiċità, potenzjal karċinoġeniku u tossicità għar- riproduzzjoni.
It should be noted that systemic exposure in male rats was lower than the therapeutic exposure in humans at 40 mg.
Għandu jigi nnotat li espożizzjoni sistemika fil- firien irġiel kinet aktar baxxa mill- espożizzjoni fil- bnedmin b’ doża ta ’ 40 mg.
Consequently, no adequate assessment of potential effects on male fertility in rats can be made.
Konsegwentement, ma tista 'ssir ebda stima adegwata ta ’ effetti potenzjali fuq il- fertilità fil- firien irġiel.
However, in a 9 month study in dogs, no organ weight changes nor gross or histomorphologic findings were present in male reproductive organs at systemic exposures 35-fold above the therapeutic exposure in humans at 40 mg.
Madankollu, fi studju ta ’ 9 xhur, li sar fuq il- klieb, ma ġiet osservata l- ebda bidla fil- piż ta ’ l- organi, lanqas tisjib gross jew ħistomorfoloġiku fl- organi riproduttivi ta 'l- irġiel wara espożizzjoni sistematika ta' 35 darba aktar mill - espożizzjoni terapewtika fil- bnedmin b ’ doża ta ’ 40 mg.
Although no adverse effects were noted in reproduction studies when female animals were exposed 3.5- to 4-fold above the therapeutic exposure in humans at 40 mg, the potential effects on reproduction of alterations in neurokinin regulation are unknown.
Għalkemm ma ġie nnotat l- ebda effett avvers fi stħarriġ fuq ir- riproduzzjoni meta annimali nisa ġew esposti għal 3. 5 sa 4 darbiet aktar mill - espożizzjoni terapewtika fil- bnedmin b’ doża ta ’ 40 mg, l- effetti potenzjali fuq ir- riproduzzjoni ta ’ alterazzjonijiet fir- regolazzjoni ta ’ newrokinina mhumiex magħrufin.
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
Capsule shell Gelatin Titanium dioxide (E 171) Yellow iron oxide (E 172) Sodium laurilsulfate and silica colloidal anhydrous may be used
Il- qoxra tal- kapsula gelatin titanium dioxide (E 171) yellow iron oxide (E 172) jistgħu jintużaw sodium laurilsulfate u silica colloidal anhydrous
Printing ink Shellac Potassium hydroxide Black iron oxide (E 172)
inka ta 'l- istampar shellac potassium hydroxide black iron oxide (E 172)
4 years
4 snin
Store in the original package in order to protect from moisture.
Żomm fil- pakkett oriġinali sabiex tipproteġi mill- umdità.
Aluminium blister containing one 40 mg capsule.
Folja ta 'l- aluminju li fiha kapsula waħda ta' 40 mg.
5 Aluminium blisters each containing one 40 mg capsule.
5 folji ta 'l- aluminju li kull waħda minnhom fiha kapsula waħda ta' 40 mg.
6.6 Special precautions for disposal
9 6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
Hertford Road, Hoddesdon Hertfordshire EN 11 9BU United Kingdom
Hertford Road, Hoddesdon Hertfordshire EN 11 9BU Ir- Renju Unit
DATE OF FIRST AUTHORISATION/ RENEWAL OF AUTHORISATION
DATA TA ’ L- EWWEL AWTORIZZAZZJONI/ TIĠDID TA ’ L- AWTORIZZAZZJONI
11 November 2003 Date of latest renewal:
11 ta 'Novembru 2003 Data ta ’ l- aħħar tiġdid:
11 November 2008
11 ta 'Novembru 2008
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/.
Informazzjoni dettaljati dwar dan il- prodott mediċinali hija disponibbli fuq il- website tal- Aġenzija Ewropea tal- Mediċini (EMEA) http: // www. emea. europa. eu /.
EMEND 80 mg hard capsules
EMEND 80 mg kapsuli iebsin
Each capsule contains 80 mg of aprepitant.
Kull kapsula fiha 80 mg ta 'aprepitant.
80 mg sucrose.
80 mg sucrose
Capsules are opaque with a white body and cap with “ 461” and “ 80 mg” printed radially in black ink on the body.
Il- kapsuli huma opaki bojod u b’ kappa ta ’ l- istess kulur b '“ 461 ” u “ 80 mg ” stampati b' mod radjali b' linka sewda fuqhom
Prevention of acute and delayed nausea and vomiting associated with highly emetogenic cisplatin- based cancer chemotherapy in adults.
Prevenzjoni ta 'nawseja akuta u ttardjata u rimettar assoċjat ma' kimoterapija tal- kanċer ferm emetoġenika bbażata fuq cisplatin fl- adulti.
Prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy in adults.
Prevenzjoni ta 'nawseja u rimettar assoċjati ma' kimoterapija tal- kanċer li hija moderatament emetoġenika fl- adulti.
EMEND 80 mg is given as part of combination therapy (see section 4.2).
EMEND 80 mg jingħata bħala parti minn terapija kombinata (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.
EMEND jingħata għal tlett ijiem bħala parti minn kors li jinkludi kortikosterojd u antagonista ta ’ 5 - HT3.
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.
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, 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.
Please refer to the Summary of Product Characteristics for fosaprepitant.
Jekk jogħġbok irreferi għas - Sommarju tal- Karatteristiċi tal- Prodott għal fosaprepitant.
11 Highly Emetogenic Chemotherapy Regimen
11 Fi studji kliniċi, il- korsijiet li ġejjin intużaw għall- prevenzjoni ta 'nawseja u rimettar assoċjati ma' kimoterapija tal- kanċer emetoġenika:
Day 1
Jum 1
Day 2
Jum 2
Day 3
Jum 3
Day 4
Jum 4
none
xejn
Dexamethasone Ondansetron
Dexamethasone Ondansetron
mg PO 8 mg PO none none
mg PO 8 mg PO xejn xejn
mg PO none
mg PO xejn
EMEND was 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.
Dexamethasone was administered 30 minutes prior to chemotherapy treatment on Day 1 and in the morning on Days 2 to 4.
Dexamethasone ngħata nofs siegħa qabel it- trattament kimoterapewtiku fl- 1 Jum u filgħodu ta 'Jiem 2 sa 4.
The dose of dexamethasone was chosen to account for active substance interactions.
Id- doża ta 'dexamethasone ntgħażlet sabiex tagħmel tajjeb għal interazzjonijiet ta' sustanzi attivi.
Ondansetron was administered intravenously 30 minutes prior to chemotherapy treatment on Day 1.
Jum 1
x 8 mg PO
2 x 8 mg PO
Dexamethasone was administered 30 minutes prior to chemotherapy treatment on Day 1.
Dexamethasone ingħata fil- vina 30 minuta qabel it- trattament ta 'kimoterapija fl- 1 Jum.
The dose of dexamethasone was chosen to account for active substance interactions.
Id- doża ta 'dexamethasone ntagħżlet sabiex tagħmel tajjeb għal interazzjonijiet ta' sustanzi attivi.
One 8 mg capsule of ondansetron was administered 30 to 60 minutes prior to chemotherapy treatment and one 8 mg capsule was administered 8 hours after first dose on Day 1.
Kapsula waħda ta '8 mg ta' Ondansetron ngħatat minn 30 sa 60 minuta qabel it- trattament kimoterapewtiku u ngħatat kapsula ta '8 mg 8 sigħat wara l- ewwel doża fl- 1 Jum.
Efficacy data on combination with other corticosteroids and 5-HT3 antagonists are limited.
Id- data dwar l- effikaċja f' kombinazzjoni ma 'kortikosterojdi u antagonisti ta ’ 5- HT3 oħrajn hija limitata.
For additional information on the co-administration with corticosteroids, see section 4.5. Please refer to the Summary of Product Characteristics co-administered antiemetics.
Jekk jogħġbok irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott ta ’ anti- emetiċi li jingħataw flimkien.
Elderly (≥ 65 years) No dose adjustment is necessary for the elderly (see section 5.2).
Anzjani (≥ 65 sena) L- ebda aġġustament fid- doża m' huwa meħtieġ għall- anzjani.
Children and adolescents EMEND is not recommended for use in children below 18 years due to insufficient data on safety and efficacy.
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.
Method of administration The hard capsule should be swallowed whole.
Metodu ta ’ għoti Il- kapsula iebsa għandha timbela sħiħa.
EMEND may be taken with or without food.
12 EMEND jista ’ jittieħed ma ’ l- ikel kif ukoll mhux ma ’ l- ikel.
Hypersensitivity to the active substance or to any of the excipients.
Sensittività eċċessiva għas- sustanza( i) attiva( i) jew għal sustanzi mhux attivi.
Co-administration with pimozide, terfenadine, astemizole or cisapride (see section 4.5).
EMEND ma għandux jingħata flimkien ma 'pimozide, terfenadine, astemizole jew cisapride.
EMEND should be used with caution in patients receiving concomitant orally administered active substances that are metabolised primarily through CYP3A4 (see section 4.5).
EMEND għandu jintuża b' attenzjoni f' pazjenti li jieħdu, flimkien miegħu, sustanzi attivi li jittieħdu mill- ħalq li huma metabolizzati prinċipalment permezz tas- CYP3A4 (ara sezzjoni 4. 5).
Additionally, concomitant administration with irinotecan should be approached with particular caution as the combination might result in increased toxicity.
Barra minn hekk, l- għoti flimkien ma 'irinotecan għandu jsir b' attenzjoni partikolari billi l- kombinazzjoni tista' tirriżulta f' żieda fit- tossiċità.
Co-administration of EMEND with ergot alkaloid derivatives, which are CYP3A4 substrates, may result in elevated plasma concentrations of these active substances.
L- għoti ta 'EMEND flimkien ma' derivattivi ta ’ ergot alkaloid, li huma sottostrati tas- CYP3A4, jista 'jirriżulta f' konċentrazzjonijiet ogħla fil- plażma ta' dawn is- sustanzi attivi.
Therefore, caution is advised due to the potential risk of ergot-related toxicity.
Għalhekk, huwa rakkomandat li tingħata attenzjoni minħabba r- riskju potenzjali ta 'tossiċità relatata ma' l- ergot.
Co-administration of EMEND with warfarin results in decreased prothrombin time, reported as International Normalised Ratio (INR).
L- għoti fl- istess ħin ta 'EMEND ma' sustanzi attivi li jinduċu b' mod qawwi l- attività ta ’ CYP3A4 (eż. rifampicin, phenytoin, carbamazepine, phenobarbital) għandu jiġi evitat billi flimkien jirriżultaw fi tnaqqis fil- konċentrazzjonijiet ta 'aprepitant fil- plażma (ara sezzjoni 4. 5).
In patients on chronic warfarin therapy, the 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 4.5).
John’ s wort m' hijiex rakkomandata.
Alternative or back-up methods of contraception should be used during treatment with EMEND and for 2 months following the last dose of EMEND (see section 4.5).
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 minħabba li flimkien jirriżultaw f' konċentrazzjonijiet ogħla ta 'aprepitant fil- plażma (ara sezzjoni 4. 5).
Concomitant administration of EMEND with active substances that strongly induce CYP3A4 activity (e. g. rifampicin, phenytoin, carbamazepine, phenobarbital) should be avoided as the combination results in reductions of the plasma concentrations of aprepitant (see section 4.5).
L- għoti fl- istess ħin ta 'EMEND ma' sustanzi attivi li jinduċu l- attività b' mod qawwi CYP3A4 (eż. rifampicin, phenytoin, carbamazepine, phenobarbital) għandu jiġi evitat billi l- kombinazzjoni tirriżulta fi tnaqqis fil- konċentrazzjonijiet ta 'plażma ta' aprepitant (ara sezzjoni 4. 5).
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 (see section 4.5).
L- għoti fl- istess ħin ta 'EMEND ma' sustanzi attivi li jimpedixxu l- attività CYP3A4 (eż. ritonavir, ketoconazole, clarithromycin, telithromycin) għandu jsir b' mod kawt minħabba li t- taħlita tirriżulta f' konċentrazzjonijiet ogħla ta 'aprepitant fil- plażma (ara sezzjoni 4. 5).
Patients with rare hereditary problems of fructose intolerance, glucose- galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Pazjenti bi problemi ereditarji rari ta ’ intolleranza għal fructose, assorbiment ħażin ta ’ glucose- galactose jew insuffiċjenza ta ’ sucrose- isomaltase m’ għandhomx jieħdu din il - mediċina.
Aprepitant (125 mg/ 80 mg) is a substrate, a moderate inhibitor, and an inducer of CYP3A4.
Aprepitant (125 mg/ 80 mg) huwa substrat, inibitur moderat, u jinduċi CYP3A4.
Aprepitant is also an inducer of CYP2C9.
Aprepitant jinduċi wkoll CYP2C9.
During treatment with EMEND, CYP3A4 is inhibited.
Matul trattament b' EMEND, CYP3A4 huwa inibit.
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.
13 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.
The area under the curve (AUC) of orally administered CYP3A4 substrates may increase up to approximately 3-fold during the 3-day treatment with EMEND; the effect of aprepitant on the plasma concentrations of intravenously administered CYP3A4 substrates is expected to be smaller.
L- erja taħt il- kurva (AUC) ta ’ sottostrati ta ’ CYP3A4 mogħtija mill- ħalq tista ’ tiżdied sa bejn wieħed u ieħor 3 darbiet aktar waqt kors ta ’ 3 ijiem b’ EMEND; l- effett ta ’ aprepitant fuq konċentrazzjonijiet fil- plażma ta ’ sottostrati ta ’ CYP3A4 mogħtija fil- vina huwa mistenni li jkun iċken.
Caution is advised during concomitant administration of EMEND and CYP3A4 substrates.
Għandha tingħata attenzjoni meta EMEND u sottostrati ta 'CYP3A4 jingħataw flimkien.
EMEND must not be used concurrently with pimozide, terfenadine, astemizole, or cisapride (see section 4.3).
EMEND ma għandux jingħata flimkien ma 'pimozide, terfenadine, astemizole jew cisapride (ara sezzjoni 4. 3).
Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of theseactive substances, potentially causing serious or life-threatening reactions.
Inibizzjoni ta ’ CYP3A4 permezz ta ’ 'aprepitant tista ’ tirriżulta f’ konċentrazzjonijiet ogħla ta' dawn is- sustanzi attivi fil- plażma, li jistgħu jikkawżaw reazzjonijiet li jheddu l- ħajja.
13 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 glukoronidazzjoni, aprepitant jista' jnaqqas il- konċentrazzjonijiet tal- plażma ta 'sottostrati eliminati b' dawn il- modi.
This effect may become apparent only after the end of treatment with EMEND.
Dan l- effett jista 'biss jidher aktar ċar wara t- tmiem tat- trattament b' EMEND.
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 tijiem wara tmiem it- tlett ijiem trattament b' EMEND.
The effect is maintained for a few days, thereafter slowly declines and is clinically insignificant by two weeks after end of EMEND treatment.
L- effett jibqa 'għal ftit jiem, imbagħad jibda jnaqqas bil- mod u jsir klinikament insinifikanti fi żmiem ġimagħtejn minn tmiem it- 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 ’ 80mg' aprepitant orali għal 7 ijiem.
Data are lacking regarding effects on CYP2C8 and CYP2C19.
M' hemmx biżżejjed data dwar l - effetti fuq CYP2C8 u CYP2C19.
Caution is advised when warfarin, acenocoumarol, tolbutamide, phenytoin or other active substances 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 usual oral dexamethasone dose should be reduced by approximately 50% when co-administered with EMEND 125 mg/ 80 mg regimen.
Id- doża ta 'dexamethasone orali li ġeneralment tingħata għandha titnaqqas b' madwar 50% meta mogħtija flimkien ma' kors ta 'EMEND 125 mg/ 80 mg.
The dose of dexamethasone in chemotherapy induced nausea and vomiting clinical trials was chosen to account for active substance interactions (see section 4.2).
Id- doża ta 'dexamethasone fi provi kliniċi ta' nawseja u rimettar ikkaġunati minn kimoterapija 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 orali fil- Jiem 2 sa 5, żied l- AUC ta 'dexamethasone, sottostrat ta' CYP3A4, bi 2. 2 drabi fil- Jiem 1 u 5.
The usual intravenously administered methylprednisolone dose should be reduced approximately 25%, and the usual oral methylprednisolone dose should be reduced approximately 50% when co-administered with EMEND 125 mg/ 80 mg regimen.
Id- doża ta 'methylprednisolone li ġeneralment tingħata ġol- vina għandha titnaqqas b' madwar 25%, u d- doża ta' methylprednisolone li ġeneralment tingħata mill- ħalq għandha titnaqqas b' madwar 50% meta tingħata flimkien ma 'kors ta' EMEND 125 mg/ 80 mg.
EMEND, when given as a regimen of 125 mg on Day 1 and 80 mg/ day on Days 2 and 3, increased the AUC of methylprednisolone, a CYP3A4 substrate, by 1.3-fold on Day 1 and by 2.5-fold on Day 3, when methylprednisolone was co-administered intravenously as 125 mg on Day 1 and orally as 40 mg on Days 2 and 3.
EMEND, meta mogħti bħala kors ta '125 mg f' Jum 1 u 80 mg kuljum fil- Jiem 2 u 3, żied l- AUC ta' methylprednisolone, li hu sottostrat ta 'CYP3A4, b' 1. 3 drabi f' Jum 1 u b' 2. 5 drabi f' Jum 3, meta methylprednisolone ngħata flimkien miegħu, ġol- vina bħala 125 mg f' Jum 1 u oralment bħala 40 mg fil- Jiem 2 u 3.
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.
This effect may be expected to be more pronounced for orally administered methylprednisolone.
Dan l- effett mistenni jkun aktar qawwi fuq methylprednisolone mogħti mill - ħalq.
Chemotherapeutic agents:
Mediċini kemjoterapewtiċi::
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.
Caution is advised and additional monitoring may be appropriate in patients receiving such agents orally (see section 4.4).
Huwa rakkomandat li tingħata attenzjoni u jista 'jkun hemm bżonn ta' monitoraġġ addizzjonali f' pazjenti li jirċievu dawn is- sostanzi mill- ħalq (ara sezzjoni 4. 4).
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 flimkien ma ’ EMEND (125 mg/ 80 mg).
EMEND increased the AUC of midazolam, a sensitive CYP3A4 substrate, 2.3-fold on Day 1 and 3.3- fold on Day 5, when a single oral dose of 2 mg midazolam was co-administered on Days 1 and 5 of a regimen of EMEND 125 mg on Day 1 and 80 mg/ day on Days 2 to 5.
EMEND żied l- AUC ta ’ midazolam, sottostrat sensittiv ta ’ CYP3A4, bi 2. 3 drabi f’ Jum1 u bi 3. 3 drabi f’ Jum 5, meta ngħatat miegħu doża waħda ta ’ 2mg midazolam fil- Jiem 1 u 5 ta ’ kors ta ’ EMEND 125 mg f’ Jum 1 u 80 mg kuljum fil- Jiem 2 sa 5.
In another study with intravenous administration of midazolam, EMEND was given as 125 mg on Day 1 and 80 mg/ day on Days 2 and 3, and 2 mg midazolam was given intravenously prior to the administration of the 3-day regimen of EMEND and on Days 4, 8, and 15.
Fi studju ieħor fejn ingħata midazolam ġol- vina, EMEND ingħata bħala 125 mg f’ Jum 1 u 80 mg kuljum fil- Jiem 2 u 3, u 2 mg midazolam ingħataw ġol- vina qabel l- għoti ta ’ kors ta ’ tlett ijiem ta ’ EMEND u fil- Jiem 4, 8, u 15.
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.
These effects were not considered clinically important.
Dawn l- effetti ma tqiesux klinikament importanti.
14 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 ingħata mil- vina u mill- ħalq, EMEND ingħata bħala 125 mg f’ Jum 1 u 80 mg 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.
EMEND, ondansetron and dexamethasone) decreased the AUC of oral midazolam 16% on Day 6, 9% on Day 8, 7% on Day 15 and 17% on Day 22.
Din it- taħlita (jiġifieri EMEND, ondansetron u dexamethasone) naqqset l- AUC ta ’ midazolam mill- ħalq b’ 16% f’ Jum 6, b’ 9% f’ Jum 8, b’ 7% f’ Jum 15 u bi 17% f’ Jum 22.
These effects were not considered clinically important.
Dawn l - effetti ma tqiesux klinikament importanti.
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.
The plasma AUC of midazolam was increased by 1.5-fold.
L- AUC ta 'midazolam fil- plażma żdiedet b' darba u nofs.
This effect was not considered clinically important.
Dan l- effett ma tqiesx klinikament importanti.
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).
When a single 125 mg dose of EMEND was administered on Day 1 and 80 mg/ day on Days 2 and 3 to healthy subjects who were stabilised on chronic warfarin therapy, there was no effect of EMEND on the plasma AUC of R(+) or S(-) warfarin determined on Day 3; however, there was a 34% decrease in S(-) warfarin (a CYP2C9 substrate) trough concentration accompanied by a 14% decrease in INR 5 days after completion of dosing with EMEND.
Meta doża waħda ta '125 mg ta' EMEND ingħatat f' Jum 1 u 80 mg kuljum ingħataw fil- Jiem 2 u 3 f' individwi b' saħħithom li kienu stabbilizzati fuq terapija ta 'warfarina kronika, ma kien hemm l- ebda effett ta' EMEND fuq l - AUC fil- plażma ta 'warfarin R( +) jew S (-) stabbilita fil- Jum 3; madankollu, kien hemm tnaqqis ta' 34% fil- konċentrazzjoni l- aktar baxxa ta 'warfarin S (-) (sottostrat ta' CYP2C9) li kien akkumpanjat bi tnaqqis ta '14% f' INR 5 ijiem wara t- tmiem tad- dożaġġ b' EMEND.
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 ngħatat 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 ’ titnaqqas waqt u għal 28 jum wara l - għoti ta 'EMEND.
Alternative or back-up methods of contraception should be used during treatment with EMEND and for 2 months following the last dose of EMEND.
Waqt it- trattament b' EMEND u għal xahrejn wara l- aħħar doża ta 'EMEND għandhom jintużaw metodi alternattivi jew ta' back- up għal kontraċezzjoni.
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%.
In another study, single doses of an oral contraceptive containing ethinyl estradiol and norethindrone were administered on Days 1 through 21 with EMEND, given as a regimen of 125 mg on Day 8 and 80 mg/ day on Days 9 and 10 with ondansetron 32 mg intravenouslyon Day 8 and oral dexamethasone given as 12 mg on Day 8 and 8 mg/ day on Days 9, 10, and 11.
Fi studju ieħor, ingħataw dożi waħdanin ta ’ kontraċettiv orali li fih ethinyl estradiol u norethindrone, f’ Jiem 1 sa 21 flimkien ma ’ EMEND, mogħti bħala kors ta ’ 125 mg f’ Jum 8 u 80 mg kuljum f’ Jiem 9 u 10 ma 'ondansetron 32 mg IV f' Jum 8 u dexamthasome orali mogħti bħala 12 mg f' Jum 8 u 8 mg kuljum fil- Jiem 9, 10 u 11.
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 sa 64% tnaqqis fil - konċentrazzjonijiet l- aktar baxxi ta ’ ethinyl estradiol u 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).
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 aprepitant with digoxin.
15 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 'sustanzi attivi oħrajn 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 active substances that strongly induce CYP3A4 activity (e. g. rifampicin, phenytoin, carbamazepine, phenobarbital) should be avoided as the combination results in reductions of the plasma concentrations of aprepitant that may result in decreased efficacy of EMEND.
L- għoti fl- istess ħin ta 'EMEND ma' sustanzi attivi li jinduċu b' mod qawwi l- attività ta ’ CYP3A4 (eż. rifampicin, phenytoin, carbamazepine, phenobarbital) għandu jiġi evitat billi flimkien jirriżultaw fi tnaqqis fil- konċentrazzjonijiet ta 'aprepitant fil- plażma li jistgħu jirriżultaw fi tnaqqis fl- effikaċja ta ’ EMEND.
Concomitant administration of EMEND herbal preparations containing St.
L- għoti ta 'EMEND flimkien ma' St.
John’ s Wort (Hypericum perforatum) is not recommended.
John’ s wort m' huwiex rakkomandat.
15 Ketoconazole:
Ketoconazole:
When a single 375 mg dose of aprepitant was administered on Day 9 of a 14-day regimen of 600 mg/ day of rifampicin, a strong CYP3A4 inducer, the AUC of aprepitant decreased 91% and the mean terminal half-life decreased 68%.
Meta doża waħda ta ’ 375 mg ta ’ aprepitant ingħatat f’ Jum 9 ta ’ kors ta ’ 14- il jum ta ’ 600 mg kuljum ta ’ rifampicin, li jinduċi b’ mod qawwi CYP3A4, l- AUC ta ’ aprepitant naqset b’ 91% u l- half- life terminali medja naqset b' 68%.
The potential for reproductive toxicity of aprepitant has not been fully characterized, since exposure levels above the therapeutic exposure in humans at the 125 mg/ 80 mg dose were not attained in animal studies.
Il- potenzjal ta 'aprepitant għal tossiċità fis- sistema riproduttiva għadu ma ġiex ikkaratterizzat kompletament, minħabba li l- livelli ta' esponiment ogħla mil- livell ta 'esponiment terapewtiku fil- bniedem fid- doża ta' 125 mg/ 80 mg ma ntlaħqux fl- istudji bl- annimali.
These studies did not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development (see section 5.3).
Dawn l- istudji ma urew l- ebda indikazzjoni ta ’ effetti ta ’ ħsara diretta jew indiretta fir- rigward tat- tqala, żvilupp tal- embriju/ fetu, it- twelid u l- iżvilupp ta ’ wara t- twelid (ara sezzjoni 5. 3).
EMEND should not be used during pregnancy unless clearly necessary.
L- effetti potenzjali fuq ir- riproduzzjoni ta 'alterazzjonijiet fir - regolazzjoni ta' newrokinin m' humiex magħrufa.
Aprepitant is excreted in the milk of lactating rats.
Aprepitant joħroġ fil- ħalib ta 'firien li jreddgħu.
It is not known whether aprepitant is excreted in human milk; therefore, breast-feeding is not recommended during treatment with EMEND.
M' huwiex magħruf jekk aprepitantjoħroġx fil- ħalib uman; għalhekk, it- treddigħ m' huwiex rakkomandat waqt trattament b’ EMEND.
Adverse reactions considered as drug-related by the investigator were reported in approximately 17% of patients treated with the aprepitant regimen compared with approximately 13% of patients treated with standard therapy in patients receiving highly emetogenic chemotherapy.
Reazzjonijiet avversi meqjusin bħala relatati mal- mediċina mill- investigatur ġew irrapportati f' madwar 17% tal- pazjenti ttrattati bil- kors meta mqabbla ma 'madwar 13% tal- pazjenti ttrattati b' terapija standard f' pazjenti li jirċievu kimoterapija ferm emetoġenika.
Aprepitant was discontinued due to adverse reactions in 0.6% of patients treated with the aprepitant regimen compared with 0.4% of patients treated with standard therapy.
Aprepitant twaqqaf minħabba reazzjonijiet kontra f' 0. 6% ta 'pazjenti ttrattati bil- kors ta' aprepitant meta mqabbel ma '0. 4% ta' pazjenti ttrattati bit- terapija standard.
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 standard.
Aprepitant was discontinued due to adverse reactions in 1.1% of patients treated with the aprepitant regimen compared with 0.5% of patients treated with standard therapy.
Aprepitant twaqqaf minħabba reazzjonijiet avversi f' 1. 1% ta 'pazjenti ttrattati bil- kors ta' aprepitant meta mqabbel ma '0. 5% ta' pazjenti ttrattati bit- terapija 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%).
16 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 most common adverse reaction reported at a greater incidence in patients treated with the aprepitant regimen than with standard therapy in patients receiving moderately emetogenic chemotherapy was fatigue (2.5% versus 1.6%).
L- aktar reazzjoni avversa komuni rrapportata f' inċidenza akbar f' pazjenti ttrattati bil- kors ta 'aprepitant milli bit- terapija standard f' pazjenti li kienu qed jirċievu kimoterapija moderatament emetoġenika kienet l- għejja (2. 5% kontra 1. 6%).
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:
System Organ Class
Sistema ta ’ Klassifika ta ’ l - Organi
Frequency
Frekwenza komuni
ALT increased, AST increased
ALT ogħla, AST ogħla
Cardiac disorders Blood and lymphatic system disorders
alkaline phosphatase ogħla, ipergliċemija, ematurija mikroskopika, ipnotraemija, tnaqqis fil- piż Disturbi kardijaċi Disturbi tad- demm u tas- sistema limfatika
bradycardia febrile neutropenia, anaemia
bradikardja newtropenja bid- deni, anemija
Uncommon Uncommon
mhux komuni mhux komuni
headache, dizziness
uġigħ ta 'ras, sturdament
dream abnormality, cognitive disorder
anormalità fil- ħolm, disturbi konoxxittivi
conjunctivitis
konġuntivite
Uncommon
mhux komuni
Ear and labyrinth disorders Respiratory, thoracic and mediastinal disorders
Disturbi fil- widnejn u fis- sistema tinnite labirintika
Gastrointestinal disorders
Disturbi respiratorji, toraċiċi u sulluzzu medjastinali
perforating duodenal ulcer, nausea*, vomiting*, acid reflux, dysgeusia, epigastric discomfort, obstipation, gastroesophageal reflux disease, abdominal pain, dry mouth, enterocolitis, flatulence, stomatitis
farinġite, għatis, sogħla, taqtir min- naħa ta ’ wara ta ’ l- imnieħer, irritazzjoni fil- griżmejn Disturbi gastro- intestinali stitikezza, dijarrea, dispepsja, tifwiq
uncommon
mhux komuni komuni
Renal and urinary disorders Skin and subcutaneous tissue disorders
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
polyuria, dysuria, pollakiuria rash, acne, photosensitivity, hyperhidrosis, oily skin, pruritus, skin lesion
mhux komuni
Uncommon Uncommon
Disturbi fil- kliewi u fis- sistema polijurja, disurja, pollakjurja urinarja
Musculoskeletal and connective tissue disorders
Disturbi fil- ġilda u fit- tessuti ta ’ raxx, akne, fotosensittività, iperidrożi, ġilda taħt il- ġilda żejtnija, prurite, feriti fil- ġilda
Metabolism and nutrition disorders
Disturbi muskolu- skeltrali u tal - bugħawwieġ, mijalġja connective tissue
anorexia
mhux komuni
weight gain, polydipsia
Disturbi fil- metaboliżmu u n - anoreksja nutrizzjoni
uncommon
komuni
Infection and infestations Vascular disorders General disorders and administration site conditions
żieda fil- piż, polidipsja Infezzjonijiet u infestazzjonijiet kandidajiżi, infezzjoni ta 'l- istaphylococcus Disturbi vaskulari fwawar Disturbi ġenerali u astenja/ għejja kondizzjonijiet ta' mnejn jingħata
candidiasis, staphylococcal infection flushing/ hot flush asthaenia/ fatigue
mhux komuni mhux komuni mhux komuni komuni
Uncommon Uncommon common
17
oedema, chest discomfort, lethargy, thirst
edema, skumdità fis- sider, letarġija, għatx
disorientation, euphoria, anxiety
diżorjentazzjoni, ewforja, ansjetà