qanastek/EMEA-V3 huggingface dataset:
Co-administration with pimozide, terfenadine, astemizole or cisapride (see section 4.5).
Amministrazzjoni flimkien ma ’ pimozide, terfenadine, astemizole jew cisapride (ara sezzjoni 4. 5).
There are limited data in patients with moderate hepatic insufficiency and no data in patients with severe hepatic insufficiency.
Hemm dejta limitata f’ pazjenti b’ indeboliment epatiku moderat u l- ebda dejta f’ pazjenti b’ indeboliment epatiku sever.
IVEMEND should be used with caution in these patients (see section 5.2).
IVEMEND għandu jintuża b’ kawtela f’ dawn il- pazjenti (ara sezzjoni 5. 2).
IVEMEND and oral aprepitant should be used with caution in patients receiving concomitant orally administered medicinal products that are metabolised primarily through CYP3A4 (see section 4.5).
IVEMEND u aprepitant orali għandhom jintużaw b’ kawtela f’ pazjenti li qed jirċievu prodotti mediċinali amministrati fl- istess ħin oralment li huma metabolizzati primarjament permezz ta ’ 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, amministrazzjoni fl- istess ħin ma ’ irinotecan għandha ssir b ’ kawtela partikolari għaliex il- kombinazzjoni tista ’ tirriżulta f’ żieda fit- tossiċità.
Co-administration of fosaprepitant with ergot alkaloid derivatives, which are CYP3A4 substrates, may result in elevated plasma concentrations of these medicinal products.
Amministrazzjoni flimkien ta ’ fosaprepitant ma ’ derivattivi ergot alkalojde, li huma sottostratti ta ’ CYP3A4, tista ’ tirriżulta f’ konċentrazzjonijiet għoljin fil- plażma ta ’ dawn il- prodotti mediċinali.
Therefore, caution is advised due to the potential risk of ergot-related toxicity.
Għaldaqstant għandha tingħata kawtela minħabba r- riskju potenzjali ta ’ tossiċità relatata ma ’ ergot.
Co-administration of oral aprepitant with warfarin results in decreased prothrombin time, reported as International Normalised Ratio (INR).
Amministrazzjoni flimkien ta ’ aprepitant orali ma ’ warfarin jirriżulta fi prothrombin time imnaqqas, irrapportat bħala Proporzjon Normalizzat Internazzjonali (INR).
In patients on chronic warfarin therapy, the INR should be monitored closely during treatment with oral aprepitant and for 2 weeks following each 3-day regimen of fosaprepitant followed by oral aprepitant for chemotherapy induced nausea and vomiting (see section 4.5).
F’ pazjenti fuq terapija kronika bil - warfarin, l- INR għandu jiġi sorveljat mill- qrib waqt trattament b’ aprepitant orali u għal ġimagħtejn wara kull reġimen ta ’ 3 ijiem b’ fosaprepitant segwit b’ aprepitant orali għal nawsja u rimettar imqanqla mill- kimoterapija (ara sezzjoni 4. 5).
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration of aprepitant.
L- effikaċja ta ’ kontraċettivi ormonali tista ’ tkun imnaqqsa matul u għal 28 jum wara l - amministrazzjoni ta ’ aprepitant.
Alternative or back-up methods of contraception should be used during treatment with fosaprepitant or aprepitant and for 2 months following the last dose of aprepitant (see section 4.5).
Waqt trattament b’ fosaprepitant jew aprepitant u għal xahrejn wara l - aħħar doża ta ’ aprepitant għandhom jintużaw metodi ta ’ kontraċezzjoni alternattivi jew ta ’ riserva (ara sezzjoni 4. 5).
Concomitant administration of fosaprepitant with medicinal products 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).
Amministrazzjoni konkomittanti ta ’ fosaprepitant ma ’ prodotti mediċinali li jinduċu bil- qawwa l - attività ta ’ CYP3A4 (eż. rifampicin, phenytoin, carbamazepine, phenobarbital) għandha tiġi evitata għaliex il- kombinazzjoni tirriżulta fi tnaqqis ta ’ konċentrazzjonijiet ta ’ aprepitant fil- plażma (ara sezzjoni 4. 5).
John’ s Wort is not recommended.
Amministrazzjoni ta ’ fosaprepitant ma ’ St John’ s Wort m’ hijiex irrikmandata.
Concomitant administration of fosaprepitant with medicinal products 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).
Amministrazzjoni konkomittanti ta ’ fosaprepitant ma ’ prodotti mediċinali oħra li jimpedixxu l- attività CYP3A4 (eż. ritonavir, ketoconazole, clarithromycin, telithromycin) għandha ssir b’ kawtela minħabba li l- kombinazzjoni tirriżulta f’ żieda fil- konċentrazzjonijiet tal- plasma ta ’ aprepitant (ara sezzjoni 4. 5).
IVEMEND should not be given as a bolus injection, but should always be diluted and given as a slow intravenous infusion (see section 4.2).
IVEMEND m’ għandux jingħata bħala injezzjoni bolus, iżda għandu dejjem jiġi dilwit u mogħti bil - mod bħala infużjoni fil- vina (ara sezzjoni 4. 2).
IVEMEND should not be administered intramuscularly or subcutaneously.
IVEMEND m’ għandux jingħata fil- muskoli jew taħt il - ġilda.
Mild injection site thrombosis has been observed at higher doses (see section 4.9).
F’ dożi aktar għoljin ġiet osservata trombożi ħafifa fis- sit ta ’ l- injezzjoni (ara sezzjoni 4. 9).
If signs or symptoms of local irritation occur, the injection or infusion should be terminated and restarted in another vein.
Jekk iseħħu sinjali u sintomi ta ’ irritazzjoni lokali, l- injezzjoni jew l- infużjoni għandha titwaqqaf u terġa ’ tinbeda f’ vina oħra.
When administered intravenously fosaprepitant is rapidly converted to aprepitant.
Fosaprepitant, jinbidel rapidament f’ aprepitant meta mogħti fil- vina.
Drug interactions following administration of fosaprepitant are likely to occur with medicinal products that interact with oral aprepitant.
Wara l- amministazzjoni ta ’ fosaprepitant x’ aktarx iseħħu bosta interazzjonijiet ma ’ prodotti mediċinali li jaħdmu fuq aprepitant orali.
The following information was derived from data with oral aprepitant and studies conducted with fosaprepitant and midazolam or diltiazem.
It- tagħrif li ġej kien maħruġ minn dejta b’ aprepitant orali u minn studji magħmula b’ fosaprepitant u midazolam jew diltiazem.
4 Aprepitant is a substrate, a moderate inhibitor, and an inducer of CYP3A4.
Aprepitant huwa sottostrat, inibitur moderat u induttur ta ’ CYP3A4.
Aprepitant is also an inducer of CYP2C9.
Aprepitant huwa wkoll induttur ta ’ CYP2C9.
During treatment with oral aprepitant, CYP3A4 is inhibited.
Waqt trattament b’ aprepitant orali, CYP3A4 huwa impedut.
After the end of treatment, oral aprepitant causes a transient moderate induction of CYP2C9 and a transient mild induction of CYP3A4 and glucuronidation.
Wara t- tmiem tat- trattament, aprepitant orali jikkaġuna induzzjoni moderata ta ’ CYP2C9 ta ’ qasir żmien u induzzjoni moderata ta ’ CYP3A4 ta ’ qasir żmien u glukuronidazzjoni.
Effect of aprepitant on the pharmacokinetics of other agents CYP3A4 inhibition As a moderate inhibitor of CYP3A4, aprepitant can increase plasma concentrations of orally co-administered medicinal products that are metabolised through CYP3A4.
Effett ta ’ aprepitant fuq il- farmakokinetika ta ’ mediċini oħra Inibizzjoni ta ’ CYP3A4 Bħala inibitur moderat ta ’ CYP3A4, aprepitant jista ’ jikkaġuna żieda fil- konċentrazzjonijiet fil- plażma ta ’ prodotti mediċinali oħra amministrati flimkien li huma metabolizzati permezz ta ’ CYP3A4.
The AUC of orally administered CYP3A4 substrates may increase up to approximately 3-fold during the 3-day treatment with fosaprepitant followed by oral aprepitant; the effect of aprepitant on the plasma concentrations of intravenously administered CYP3A4 substrates is expected to be smaller.
L- AUC ta ’ sottostrati ta ’ CYP3A4 amministrati oralment jistgħu jiżdiedu b’ madwar 3- drabi matul it- tlett ijiem trattament b’ fosaprepitant segwit minn aprepitant orali; l- effetti ta ’ aprepitant fuq konċentrazzjonijiet tal- plażma ta ’ sottostrati ta ’ CYP3A4 amministrati fil- vina huma mistennija li jkunu iżgħar.
Caution is advised during concomitant administration of fosaprepitant and CYP3A4 substrates.
Hija irrikmandata l- kawtela waqt amministrazzjoni fl- istess ħin ta ’ fosaprepitant u sottostrati ta ’ CYP3A4.
Fosaprepitant must not be used concurrently with pimozide, terfenadine, astemizole, or cisapride.
Fosaprepitant m’ għandux jintuża fl- istess waqt ma ’ pimozide, terfenadine, astemizole, jew cisapride.
Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these medicinal products, potentially causing serious or life-threatening reactions.
Impediment ta ’ CYP3A4 permezz ta ’ aprepitant jista ’ jirriżulta f’ konċentrazzjonijiet għoljin ta ’ dawn il- prodotti mediċinali u potenzjalment jista ’ jikkaġuna reazzjonijiet serji jew ta ’ theddid għall- ħajja.
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 within two weeks following initiation of dosing regimen.
Induzzjoni Bħala induttur moderat ta ’ CYP2C9 u induttur ħafif ta ’ CYP3A4 u glukuronidazzjoni, aprepitant jista ’ jnaqqas il- konċentrazzjonijiet fil- plażma ta ’ sottostrati eliminati permezz ta ’ dawn ir- rotot fi żmien ġimagħtejn wara l- bidu tar- reġimen tad- dożaġġ.
This effect may become apparent only after the end of a 3 day regimen of fosaprepitant followed by aprepitant.
Dan l- effett jista ’ jibda jidher biss wara tmiem ta ’ reġimen ta ’ 3 ijiem ta ’ fosaprepitant segwit b’ aprepitant.
For CYP2C9 and CYP3A4 substrates, the induction is transient with a maximum effect reached 3-5 days after end of the oral aprepitant 3-day treatment.
Għal sottostrati ta ’ CYP2C9 u CYP3A4, l - induzzjoni hija ta ’ qasir żmien b’ effett massimu milħuq 3- 5 ijiem wara tmiem ta ’ 3 ijiem trattament b’ aprepitant orali.
The effect is maintained for a few days, thereafter slowly declines and is clinically insignificant by two weeks after end of oral aprepitant treatment.
L- effett huwa miżmum għal ftit jiem, għaldaqstant jonqos bil- mod u huwa klinikament mhux sinjifikanti sa ġimagħtejn wara tmiem trattament orali b’ aprepitant.
Mild induction of glucuronidation is also seen with 80 mg oral aprepitant given for 7 days.
Induzzjoni ta ’ glukuronidazzjoni tidher ukoll bi 80 mg ta ’ aprepitant orali mogħti għal 7 ijiem.
Data are lacking regarding effects on CYP2C8 and CYP2C19.
M’ hemmx biżżejjed tagħrif dwar l- effetti fuq CYP2C8 u CYP2C19.
Caution is advised when warfarin, acenocoumarol, tolbutamide, phenytoin or other medicinal products that are known to be metabolised by CYP2C9 are administered during this time period.
Hija irrikmandata l- kawtela meta warfarin, acenocoumarol, tolbutamide, phenytoin jew prodotti mediċinali li huma magħrufa li huma metabolizzati permezz ta ’ CYP2C9 jiġu amministrati matul dan il- perijodu.
Fosaprepitant or aprepitant does not seem to interact with the P-glycoprotein transporter, as demonstrated by the lack of interaction of oral aprepitant with digoxin.
Fosaprepitant jew aprepitant ma jidhrux li jaġixxu flimkien mat- trasportatur P- glycoprotein, kif muri permezz tan- nuqqas ta ’ interazzjoni ta ’ aprepitant orali ma ’ digoxin.
The usual oral dexamethasone dose should be reduced by approximately 50% when co-administered with a regimen of fosaprepitant followed by aprepitant.
Id- doża tas- soltu ta ’ dexamethasone orali għandha titnaqqas b’ madwar 50% meta amministrata flimkien ma ’ reġimen ta ’ fosaprepitant segwit b’ aprepitant.
The dose of dexamethasone in clinical chemotherapy induced nausea and vomiting trials was chosen to account for medicinal product interactions (see section 4.2).
Id- doża ta ’ dexamethasone f’ nawsja u rimettar imqanqla b’ kimoterapija klinika kienet magħżula biex tqis l- interazzjonijiet ta ’ prodotti mediċinali (ara sezzjoni 4. 2).
Oral aprepitant, when given as a regimen of 125 mg with dexamethasone co-administered orally as 20 mg on Day 1, and oral aprepitant 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.
Aprepitant orali, meta mogħti bħala reġimen ta '125 mg amministrat flimkien ma' dexamethasone oralment bħala 20 mg f' Jum 1, u aprepitant orali meta mogħti bħala 80 mg/ kuljum ma 'dexamethasone amministrat flimkien oralment bħala 8 mg f' Jiem 2 sa 5, żied l- AUC ta' dexamethasone, sottostrat ta 'CYP3A4, 2. 2 drabi f' 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 a regimen of fosaprepitant followed by aprepitant.
Id- doża tas- soltu ta ’ methylprednisolone amministrata fil- vina għandha tiġi mnaqqsa b’ madwar 25%, u d- doża tas- soltu ta ’ methylprednisolone orali għandha tiġi mnaqqsa b’ madwar 50% meta amministrata flimkien ma ’ reġimen ta ’ fosaprepitant segwit b’ aprepitant.
Oral aprepitant, 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.
Aprepitant orali, meta mogħti ma ’ reġimen ta ’ 125 mg f’ Jum 1 u 80 mg/ kuljum f’ Jiem 2 u 3, żied l - AUC ta ’ methylprednisolone, sottostrat ta ’ CYP3A4, segwit b’ 1. 3- drabi f’ Jum 1 u b ’ 2. 5- drabi f’ Jum
During continuous treatment with methylprednisolone, the AUC of methylprednisolone may decrease at later time points within 2 weeks following initiation of dosing with oral aprepitant, due to the inducing effect of aprepitant on CYP3A4.
Waqt trattament kontinwu b’ methyprednisolone, l- AUC ta ’ methylprednisolone jista ’ jonqos f’ punti ta ’ ħin aktar tard fi żmien ħmistax wara l- bidu ta ’ dożaġġ b’ aprepitant orali, minħabba l- effett ta ’ induzzjoni ta ’ aprepitant fuq CYP3A4.
This effect may be expected to be more pronounced for orally administered methylprednisolone.
Dan l- effett jista ’ jkun mistenni li jkun aktar qawwi għal methylprednisolone amministrat oralment.
Chemotherapeutic agents:
Sustanzi kimoterapewtiċi:
In pharmacokinetic studies, oral aprepitant, 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
Fi studji farmakokinetiċi, aprepitant orali, meta mogħti bħala reġimen ta ’ 125 mg f’ Jum 1 u 80 mg/ kuljum f’ Jiem 2 u 3, ma influwenzax il- farmakokinetiċi ta ’ docetaxel mogħti fil- vina f’ Jum 1 jew vinorelbine mogħti fil- vina f’ Jum 1 jew Jum 8.
Because the effect of aprepitant on the pharmacokinetics of orally administered CYP3A4 substrates is greater than the effect of aprepitant 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 ’ aprepitant fuq il- farmakokinetiċi ta ’ sottostrati CYP3A4 mogħtija oralment huwa akbar mill- effett ta ’ aprepitant fuq il- farmakokinetiċi ta ’ sottostrati CYP3A4 mogħtija fil- vina, interazzjoni ma ’ mediċini kimoterapewtiċi metabolizzati primarjament jew f’ parti minnhom permezz ta ’ CYP3A4 (eż., etoposide, vinorelbine) ma tistax tiġi eżkluża.
Caution is advised and additional monitoring may be appropriate in patients receiving such agents (see section 4.4).
Huwa rrikmandat li tintuża l- kawtela u tista ’ tkun xierqa sorveljanza addizjonali f’ pazjenti li qed jirċievu sustanzi bħal dawn (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 a 3-day regimen of fosaprepitant followed by aprepitant.
L- effetti potenzjali ta ’ żieda fil- konċentrazzjonijiet fil- plażma ta ’ midazolam jew benzodiazepines oħra metabolizzati permezz ta ’ CYP3A4 (alprazolam, triazolam) għandhom jiġu ikkunsidrati meta dawn il- mediċini jingħataw flimkien ma ’ reġimen ta ’ 3 ijiem ta ’ fosaprepitant segwit b’ aprepitant.
Fosaprepitant given at a dose of 100 mg over 15 minutes with a single dose of midazolam 2 mg increased the AUC of midazolam 1.6-fold.
Fosaprepitant mogħti f’ doża ta ’ 100 mg fuq 15- il minuta ma ’ doża waħda ta ’ 2 mg midazolam - żied l - AUC ta ’ midazolam b’ 1. 6- drabi.
This effect was not considered clinically important.
Dan l- effett ma kienx ikkunsidrat klinikament importanti.
Oral aprepitant increased the AUC of midazolam 2.3-fold on Day 1 and 3.3-fold on Day 5, when a single oral dose of midazolam 2 mg was co-administered on Days 1 and 5 of a regimen of oral aprepitant 125 mg on Day 1 and 80 mg/ day on Days 2 to 5.
Aprepitant orali żied l- AUC ta ’ midazolam 2. 3- drabi f’ Jum 1 u 3. 3- drabi f’ Jum 5, meta doża orali waħda ta ’ 2 mg midazolam ngħatat ma ’ sustanzi oħra f’ Jiem 1 u 5 ta ’ reġimen ta ’ 125 mg ta ’ aprepitant orali f’ Jum 1 u 80 mg/ kuljum f’ Jiem 2 sa 5.
In another study with intravenous administration of midazolam, oral aprepitant was given as 125 mg on Day 1 and 80 mg/ day on Days 2 and 3, and midazolam 2 mg was given intravenously prior to the administration of the 3-day regimen of oral aprepitant and on Days 4, 8, and 15.
Fi studju ieħor bl- għoti ta ’ midazolam fil- vina, aprepitant orali ngħata bħala 125 mg f’ Jum 1 u 80 mg/ kuljum f’ Jiem 2 u 3, u 2 mg midazolam ngħataw fil- vina qabel l- amministrazzjoni ta ’ reġimen ta ’ 3 ijiem ta ’ aprepitant orali u f’ Jiem 4, 8, u 15.
Oral aprepitant increased the AUC of midazolam 25% on Day 4 and decreased the AUC of midazolam 19% on Day 8 and 4% on Day 15.
Aprepitant orali 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 kinux ikkunsidrati klinikament importanti.
In a third study with intravenous and oral administration of midazolam, oral aprepitant 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 studju b’ amministrazzjoni ta ’ midazolam orali u fil- vina, aprepitant orali ngħata bħala 125 mg f’ Jum 1 u 80 mg/ kuljum f’ Jiem 2 u 3, flimkien ma ’ 32 mg ondansetron f’ Jum 1, 12 mg dexamethasone f’ Jum 1 u 8 mg f’ Jiem 2- 4.
This combination (i. e. oral aprepitant, 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 il- kombinazzjoni (jiġifieri aprepitant orali, ondansetron u dexamethasone) naqqset l- AUC ta ’ midazolam orali b’ 16% f’ Jum 6, b’ 9% f’ Jum 8, b’ 7% f’ Jum 15 u bi 17% f’ Jum 22.
A fourth study was completed with intravenous administration of midazolam and oral aprepitant.
Sar raba ’ studju bl- għoti ta ’ midazolam fil- vina u aprepitant orali.
Intravenous midazolam 2 mg was given 1 hour after oral administration of a single dose of oral aprepitant 125 mg.
2mg midazolam fil- vina ngħataw siegħa wara għoti orali ta ’ doża waħda ta ’ 125 mg aprepitant orali.
The plasma AUC of midazolam was increased by 1.5-fold.
L- AUC ta ’ midazolam żdied b’ 1. 5- drabi.
This effect was not considered clinically important.
Dawn l- effetti ma kinux ikkunsidrati klinikament importanti.
In patients with mild to moderate hypertension, infusion of 100 mg fosaprepitant over 15 minutes with diltiazem 120 mg 3 times daily, resulted in a 1.4-fold increase in diltiazem AUC and a small but clinically meaningful decrease in blood pressure, but did not result in a clinically meaningful change in heart rate, or PR interval.
F’ pazjenti bi pressjoni għolja ħafifa għal moderata, infużjoni ta ’ 100 mg fosaprepitant fuq 15- il minuta ma ’ diltiazem 120 mg 3 drabi kuljum, tirriżulta f’ żieda ta ’ 1. 4- drabi fl- AUC ta ’ diltiazem u tnaqqis żgħir iżda klinikament sinjifikanti fil- pressjoni, iżda ma irriżultatx f’ bidla klinikament sinjifikanti fir- rata tal- qalb, jew fl- interval PR.
In patients on chronic warfarin therapy, the prothrombin time (INR) should be monitored closely during treatment with fosaprepitant or aprepitant and for 2 weeks following each 3-day regimen for chemotherapy induced nausea and vomiting (see section 4.4).
F’ pazjenti fuq terapija kronika b’ warfarin, il- prothrombin time (INR) għandu jiġi sorveljat bir- reqqa waqt trattament b’ fosaprepitant jew aprepitant u għal ġimagħtejn wara kull reġimen ta ’ 3 ijiem għal nawsja u rimettar imqanqla mill- kimoterapija (ara sezzjoni 4. 4).
When a single 125 mg dose of oral aprepitant 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 oral aprepitant 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 oral aprepitant.
Meta doża waħda ta ’ 125 mg aprepitant orali ngħatat f’ Jum 1 u 80 mg/ kuljum f’ Jiem 2 u 3 lil suġġetti b’ saħħithom li kienu stabilizzati fuq terapija kronika bil- warfarin, ma kien hemm l- ebda effett ta ’ aprepitant orali fuq l- AUC ta ’ warfarin R( +) jew S (-) fil- plasma stabbilita f’ Jum 3, kien hemm tnaqqis ta ’ 34% fil -
Oral aprepitant, 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 oral aprepitant and on Days 4, 8, and 15.
Aprepitant orali, meta mogħti bħala 125 mg f’ Jum 1 u 80 mg/ kuljum f’ Jiem 2 u 3, naqqas l- AUC ta ’ tolbutamide (sottostrat CYP2C9) bi 23% f’ Jum 4, bi 28% f’ Jum 8, u bi 15% f’ Jum 15, meta doża waħda ta ’ tolbutamide 500 mg ngħatat oralment qabel l- amministrazzjoni ta ’ reġimen ta ’ 3 ijiem ta ’ aprepitant orali u f’ Jiem 4, 8, u 15.
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration of oral aprepitant.
L- effikaċja ta ’ kontraċettivi orali tista ’ tkun imnaqqsa waqt u għal 28 jum wara l - amministrazzjoni ta ’ aprepitant orali.
Aprepitant, when given once daily for 14 days as a 100 mg capsule with an oral contraceptive containing
Metodi ta ’ kontraċezzjoni alternattivi jew ta ’ appoġġ għandhom jintużaw waqt trattament b’ fosaprepitant jew aprepitant orali u għal xahrejn wara l- aħħar doża ta ’ aprepitant.
6 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%.
Aprepitant, meta mogħti darba kuljum għal 14- il jum bħala kapsula ma ’ kontraċettiv orali li fih 35 μg ta ’ ethinyl estradiol u 1 mg ta ’ norethindrone, naqqas l- AUC ta ’ ethinyl estradiol b’ 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 withoral aprepitant, given as a regimen of 125 mg on Day 8 and 80 mg/ day on Days 9 and 10 with ondansetron 32 mg intravenously on 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, dożi waħdanin ta ’ kontraċettiv orali li fih ethinyl estradiol u norethindrone ngħataw f’ Jiem 1 sa 21 ma ’ aprepitant orali, mogħtija bħala reġimen ta ’ 125 mg f’ Jum 8 u 80 mg/ kuljum f’ Jiem 9 u 10 ma ’ 32 mg ondansetron ġol- vina f’ Jum 8 u dexamethasone orali mogħti bħala 12 mg f’ Jum 8 u 8 mg/ kuljum f’ 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.
Matul Jiem 9 sa 21 f’ dan l- istudju, kien hemm tnaqqis ta ’ mhux aktar minn 64% fil- konċentrazzjonijiet minimi ta ’ ethinyl estradiol u tnaqqis ta ’ mhux aktar minn 60% fil - konċentrazzjonijiet minimi 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).
Fi studji ta ’ interazzjoni klinika, aprepitant ma kellux effetti klinikament importanti fuq il- farmakokinetiċi ta ’ ondansetron, granisetron, jew hydrodolasetron (il- metabolit attiv ta ’ dolasetron).
Effect of other agents on the pharmacokinetics of aprepitant Concomitant administration of fosaprepitant or aprepitant with medicinal products that inhibit CYP3A4 activity (e. g., ritonavir, ketoconazole, clarithromycin, telithromycin) should be approached cautiously, as the combination results in increased plasma concentrations of aprepitant.
Effetti ta ’ mediċini oħra fuq il- farmakokinetika ta ’ aprepitant Amministrazzjoni konkomittanti ta ’ fosaprepitant jew aprepitant ma ’ prodotti mediċinali li jimpedixxu l- attività ta ’ CYP3A4 (eż., ritonavir, ketoconazole, clarithromycin, telithromycin) għandha ssir b’ kawtela, peress li l- kombinazzjoni tirriżulta f’ żieda fil- konċentrazzjonijiet ta ’ aprepitant fil- plażma.
Concomitant administration of fosaprepitant or aprepitant with medicinal products 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.
Amministrazzjoni konkomittanti ta ’ fosaprepitant jew aprepitant ma ’ prodotti mediċinali li jinduċu bil - qawwi l- attività ta ’ CYP3A4 (eż. rifampicin, phenytoin, carbamazepine, phenobarbital) għandha tiġi evitata peress li l- kombinazzjoni tirriżulta fi tnaqqis ta ’ konċentrazzjonijiet fil- plażma ta ’ aprepitant li jistgħu jirriżultaw f’ effikaċja mnaqqsa.
Concomitant administration of fosaprepitant with St.
Amministrazzjoni konkomitanti ta ’ fosaprepitant ma ’ St.
John’ s Wort is not recommended.
John’ s Wort m’ hijiex irrikmandata.
When a single 125 mg dose of oral aprepitant was administered on Day 5 of a 10-day regimen of 400 mg/ day of ketoconazole, a strong CYP3A4 inhibitor, the AUC of aprepitant increased approximately 5-fold and the mean terminal half-life of aprepitant increased approximately 3-fold.
Meta doża waħda ta ’ 125 mg aprepitant orali ngħatat f’ Jum 5 ta ’ reġimen ta ’ 10 ijiem ta ’ 400 mg/ kuljum ta ’ ketoconazole, inibitur qawwi ta ’ CYP3A4, l- AUC ta ’ aprepitant żdiedet b’ madwar 5 drabi u l- half- life terminali medja ta ’ aprepitant żdiedet b’ madwar 3 drabi.
Infusion of 100 mg fosaprepitant over 15 minutes with diltiazem 120 mg 3 times daily, resulted in a 1.5-fold increase of aprepitant AUC.
Infużjoni ta ’ 100 mg fosaprepitant fuq 15- il minuta b’ diltiazem 120 mg 3 drabi kuljum, irriżultat f’ żieda ta ’ 1. 5 drabi ta ’ l- AUC ta ’ aprepitant.
When a single 375 mg dose of oral 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 orali ngħatat f’ Jum 9 ta ’ reġimen ta ’ 14- il jum ta ’ 600 mg/ kuljum ta ’ rifampicin, induttur qawwi ta ’ CYP3A4, l- AUC ta ’ aprepitant naqas b’ 91% u l - half- life terminali medja naqas b’ 68%.
For fosaprepitant and aprepitant no clinical data on exposed pregnancies are available.
Ma jeżisti l- ebda tagħrif kliniku fuq tqaliet esposti għal fosaprepitant u aprepitant.
The potential for reproductive toxicities of fosaprepitant and aprepitant have not been fully characterized, since exposure levels above the therapeutic exposure in humans were not attained in animal studies.
Il- potenzjal għat- tossiċitajiet riproduttiva ta ’ fosaprepitant u aprepitant ma ġewx ikkaratterizzati bis - sħiħ, minħabba li livelli ta ’ espożizzjoni ogħla mill- espożizzjoni terapewtika fil- bnedmin ma nkisbux fi studji fl- 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 indikaw l- ebda effett dirett jew indirett fir- rigward tat- tqala, żvilupp embrijunali/ fetali, ħlas jew żvilupp ta ’ wara t- twelid (ara sezzjoni 5. 3).
The potential effects on reproduction of alterations in neurokinin regulation are unknown.
L- effetti potenzjali ta ’
It is not known whether aprepitant is excreted in human milk.
7 bidliet fir- regolament ta ’ newrokinin fuq ir- riproduzzjoni m’ humiex magħrufa.
Therefore, breast-feeding is not recommended during treatment with IVEMEND and oral aprepitant.
IVEMEND ma għandux jintuża waqt tqala sakemm dan ma jkunx neċessarjament meħtieġ.
4.7 Effects on ability to drive and use machines
Aprepitant huwa eliminat fil- ħalib ta ’ firien li qed irreddgħu wara amministrazzjoni fil- vina ta ’ fosaprepitant kif ukoll wara amministrazzjoni orali ta ’ aprepitant.
No studies on the effects of IVEMEND on the ability to drive and use machines have been performed.
Mhux magħruf jekk aprepitant huwiex eliminat fil- ħalib tal- bniedem.
However, when driving vehicles or operating machines, it should be taken into account that dizziness and fatigue have been reported after using IVEMEND (see section 4.8).
Għaldaqstant, it- treddigħ mhux irrikmandat waqt trattament b ’ IVEMEND jew b’ aprepitant orali.
7 4.8 Undesirable effects
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
Since fosaprepitant is converted to aprepitant, those adverse reactions associated with aprepitant are expected to occur with fosaprepitant.
Minħabba li fosaprepitant jinbidel f’ aprepitant, dawk ir- reazzjonijiet avversi assoċjati ma ’ aprepitant huma mistennija li jseħħu b’ fosaprepitant.
The safety profile of aprepitant was evaluated in approximately 4900 individuals.
Il- profil ta ’ sigurtà ta ’ aprepitant ġie evalwat fuq madwar 4900 individwu.
Various formulations of fosaprepitant have been administered to a total of 729 individuals including 347 healthy subjects and 149 patients with CINV.
Ġew amministrati formolazzjonijiet varji ta ’ fosaprepitant lil total ta ’ 729 individwu inkluż 347 suġġett b’ saħħtu u 149 pazjent b’ CINV.
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 ikkunsidrati li huma relatati mal- mediċina mill- investigatur kienu irrapportati f’ madwar 17% ta ’ pazjenti ittrattati bir- reġimen meta mqabbla ma ’ madwar 13% ta ’ pazjenti ittrattati b’ terapija standard f’ pazjenti li qed jirċievu kimoterapija emetoġenika ħafna.
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 avversi f’ 0. 6% ta ’ pazjenti ittrattati b’ reġimen ta ’ aprepitant meta mqabbla ma ’ 0. 4% ta ’ pazjenti ittrattati b’ 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 qed jirċievu kimoterapija moderatament emetoġenika, reazzjonijiet avversi kliniċi kienu irrapportati f’ madwar 21% ta ’ pazjenti irrapportati bir- reġimen ta ’ aprepitant meta mqabbla ma ’ madwar 20% ta ’ pazjenti ittrattati b’ 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 ittrattati b’ reġimen ta ’ aprepitant meta mqabbla ma ’ 0. 5% ta ’ pazjenti ittrattati b’ 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%), asthenia/ fatigue (2.9%), ALT increased (2.8%), constipation (2.2%), headache (2.2%), and anorexia (2.0%).
L- aktar reazzjonijiet avversi komuni irrapportati f’ inċidenza akbar f’ pazjenti ittrattati bir- reġimen ta ’ aprepitant milli b’ terapija standard f’ pazjenti li qed jirċievu kimoterapija emetoġenika ħafna kienu: sulluzzu (4. 6%), nuqqas ta ’ saħħa/ għeja kbira (2. 9%), żieda fl- ALT (2. 8%), stitikezza (2. 2%), uġigħ ta ’ ras (2. 2%), u anoressja (2. 0%).
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%).
L- aktar reazzjoni avversa komuni irrapportata f’ inċidenza akbar f’ pazjenti ittrattati bir- reġimen ta ’ aprepitant milli b’ terapija standard f’ pazjenti li qed jirċievu kimoterapija moderament emetoġenika kienet għeja kbira (2. 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 segwenti kienu osservati f’ pazjenti ittrattati bir- reġimen ta ’ aprepitant u f’ inċidenza akbar milli b’ terapija standard:
Frequencies are defined as: very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000) and very rare (< 1/ 10,000), not known (cannot be estimated from the available data).
Il- frekwenzi huma definiti bħala: komuni ħafna (≥1/ 10); komuni (≥1/ 100 sa < 1/ 10); mhux komuni (≥1/ 1, 000 sa < 1/ 100); rari (≥1/ 10, 000 sa < 1/ 1, 000) u rari ħafna (< 1/ 10, 000), mhux magħrufa (ma jistgħux jiġu stmati mit- tagħrif disponibbli).
Common:
Investigazzjonijiet:
ALT increased, AST increased.
Komuni: żieda fl- ALT, żieda fl- AST.
Uncommon: alkaline phosphatase increased, hyperglycaemia, microscopic haematuria, hyponatraemia, weight decreased.
Mhux komuni: żieda fl- alkaline phosphatase, ipergliċemija, ematurja mikroskopika, iponatraemija, tnaqqis fil- piż.
Cardiac disorders:
Disturbi tal- qalb:
Uncommon: bradycardia.
Mhux komuni: bradikardja.
Blood and the lymphatic system disorders:
Disturbi tad- demm u tas- sistema limfatika:
Uncommon: anaemia, febrile neutropenia.
Mhux komuni: anemija, newtropinja bid- deni.
Common: headache, dizziness.
8 Komuni: uġigħ ta ’ ras, sturdament.
Uncommon: dream abnormality, cognitive disorder.
Mhux komuni: anormalitajiet fil- ħolm, disturbi konjittivi.
Eye disorders:
Disturbi fl- għajnejn:
Uncommon: conjunctivitis.
Mhux komuni: konġuntivite.
Uncommon: tinnitus.
Mhux komuni: tinnitus.
Uncommon: pharyngitis, sneezing, cough, postnasal drip, throat irritation.
Komuni: sulluzzu Mhux komuni: farinġite, għatis, sogħla, taqtir min- naħa ta ’ wara ta ’ l- imnieħer, irritazzjoni fil - ġerżuma.
8 Common: constipation, diarrhoea, dyspepsia, eructation Uncommon: nausea*, vomiting*, acid reflux, dysgeusia, epigastric discomfort, obstipation, gastroesophageal reflux disease, perforating duodenal ulcer, abdominal pain, dry mouth, enterocolitis, flatulence, stomatitis.
Komuni: stitikezza, dijarea, dispepsja, tifwiq Mhux komuni: nawsja *, rimettar *, rifluss ta ’ l- aċidu, diżgwiżja, dwejjaq epigastriċi, obstipazzjoni, mard ta ’ rifluss gastroesofaġiku, ulċera duwodenali li tipperfora, uġigħ addominali, ħalq xott, enterokolite, gass, stomatite
Uncommon: polyuria, dysuria, pollakiuria.
Mhux komuni: polijurja, diżurja, pollakijurja
Uncommon: rash, acne, photosensitivity, hyperhidrosis, oily skin, pruritus, skin lesion.
Mhux komuni: raxx, akne, fotosensittività, iperidrożi, ġilda żejtnija, prurite, leżjoni tal- ġilda.
Uncommon: muscle cramp, myalgia.
Mhux komuni: bugħawwieġ, majalġja.
Metabolism and nutrition disorders:
Distrubi fil- metaboliżmu u fin- nutrizzjoni:
Common: anorexia.
Komuni: anoreksja.
Uncommon: weight gain, polydipsia.
Mhux komuni: żieda fil- piż, polidipsija.
Infection and infestations:
Infezzjoni u infestazzjonijiet:
Uncommon: candidiasis, staphylococcal infection.
Mhux komuni: kandidijażi, infezzjoni stafilokokkal.
Vascular disorders:
Distrubi vaskulari:
Uncommon: flushing/ hot flush.
Mhux komuni: ħmura/ fwawar.
Uncommon: oedema, chest discomfort, lethargy, thirst.
Mhux komuni: nuqqas ta ’ saħħa/ għeja kbira Mhux komuni: edema, skumdità fis- sider, telqa, għatx.
Psychiatric disorders:
Disturbi psikjattriċi:
Uncommon: disorientation, euphoria, anxiety.
Mhux komuni: disorjentazjzoni, ewforija, ansjetà.
*Nausea and vomiting were efficacy parameters in the first 5 days of post-chemotherapy treatment and were reported as adverse reactions only thereafter.
* Nawsja u rimettar kienu parametri ta ’ effikaċja fl- ewwel 5 ijiem wara trattament bil- kimoterapija u kienu irrapportati biss bħala reazzjonijiet avversi minn hemm ’ l quddiem.
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 ta ’ reazzjonijiet avversi fl- estensjoni taċ- Ċiklu Multiplu għal sa 5 ċikli ta ’ kimoterapija addizjonali kienu ġeneralment simili għal dawk osservati f’ Ċiklu 1.
One case of Stevens-Johnson syndrome was reported as a serious adverse event in a patient receiving aprepitant with cancer chemotherapy.
Każ tas- sindromu ta ’ Stevens- Johnson kien irrapportat bħala ġrajja avversa serja f’ pazjent li rċieva aprepitant waqt kimoterapija tal- kanċer.
In addition, infusion site induration and infusion site pain were common adverse reactions in a bioequivalence study in which 66 subjects were dosed with 115 mg of fosaprepitant intravenously.
9 Barra minn hekk, indurazzjoni fis- sit ta ’ l- infużjoni u uġigħ fis- sit ta ’ l- infużjoni kienu reazzjonijiet avversi komuni fi studju ta ’ bijoekwivalenza li fih 66 suġġett ingħataw doża b’ 115 mg ta ’ fosaprepitant ġol- vina.
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 addizjonali kienu osservati f’ pazjenti ittrattati b’ aprepitant (40 mg) għal nawsja u rimettar u f’ inċidenza akbar milli b’ ondansetron: uġigħ addominali, ħsejjes ta ’ l- imsaren anormali, diżartrija, dispneja (qtugħ ta ’ nifs), ipoestiżja, insomnja, mijożi, nawsja, disturb sensorili, dwejjaq fl - istonku, tnaqqis ta ’ l- akutezza viżwali, tħarħir.
In addition, two serious adverse reactions were reported in postoperative nausea and vomiting (PONV) clinical studies in patients taking a higher dose of aprepitant: one case of constipation, and one case of sub-ileus.
Barra minn hekk, żewġ reazzjonijiet avversi serji kienu irrapportati fi studji kliniċi ta ’ nawsja u rimettar ta ’ wara l- operazzjoni (PONV) f’ pazjenti li kienu qed jieħdu doża ogħla ta ’ aprepitant: każ ta ’ stitikezza, u każ wieħed ta ’ sotto- ileus (sub- ileus).
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 ’ anġjoedima u urtikarja kien irrapportat bħala reazzjoni avversa serja f’ pazjent li kien qed jirċievi aprepitant fi studju mhux- CINV/ mhux- PONV.
No specific information is available on the treatment of overdose.
L- ebda tagħrif speċifiku ma huwa disponibbli fuq it- trattament ta ’ doża eċċessiva.
Drowsiness and headache were reported in one patient who ingested 1,440 mg of aprepitant.
Ħedla u uġigħ ta ’ ras kienu irrapportati f’ pazjent li bela ’ 1, 440 mg ta ’ aprepitant.
Single doses up to 200 mg of fosaprepitant were generally well tolerated in healthy subjects.
Dożi waħdanin sa 200 mg ta ’ fosaprepitant kienu ġeneralment ittollerati sewwa f’ suġġetti b’ saħħithhom.
Three out of 33 subjects receiving 200 mg of fosaprepitant experienced mild injection site thrombosis.
Tlieta minn 33 suġġett li kienu qed jirċievu 200 mg ta ’ fosaprepitant esperjenzaw trombożi ħafifa fis - sit ta ’ l- injezzjoni.
In the event of overdose, fosaprepitant should be discontinued and general supportive treatment and monitoring should be provided.
Fil- każ ta ’ teħid eċċessiv, fosaprepitant għandu jitwaqqaf u għandu jiġi pprovdut trattament ta ’ appoġġ u ta ’ sorveljanza ġenerali.
Because of the antiemetic activity of aprepitant, drug-induced emesis may not be effective.
Minħabba l- attività antiemetika ta ’ aprepitant, emesi imqanqla mill - mediċina taf ma tkunx effettiva.
Aprepitant cannot be removed by haemodialysis.
Aprepitant ma jistax jitneħħa b’ emodijaliżi.
Pharmacotherapeutic group:
Kategorija farmakoterapetika:
Antiemetics and antinauseants, ATC code:
Antiemetiċi u antinawsjanti, Kodiċi ATC:
Fosaprepitant is the prodrug of aprepitant and when administered intravenously is converted rapidly to aprepitant (see section 5.2).
Fosaprepitant huwa promediċina ta ’ aprepitant u meta mogħti fil- vina jinqaleb rapidament f’ aprepitant (ara sezzjoni 5. 2).
The contribution of fosaprepitant to the overall antiemetic effect has not fully been characterized, but a transient contribution during the initial phase cannot be ruled out.
Il- kontribuzzjoni ta ’ fosaprepitant għall- effett antiemetiku ġenerali għadu ma ġiex ikkaratterizzat għal kollox, madankollu kontribuzzjoni temporanja matul il- fażi inizjali ma tistax tiġi eskluża.
Aprepitant is a selective high-affinity antagonist at human substance P neurokinin 1 (NK1) receptors.
Aprepitant huwa antagonista ta ’ affinità qawwija selettiv f’ riċetturi P neurokinin 1 (NK1) tas - sustanza umana.
The pharmacological effect of fosaprepitant is attributed to aprepitant.
L- effett farmakoloġiku ta ’ fosaprepitant huwa attribwit għal aprepitant.
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).
F’ żewġ studji mwettqin b’ mod każwali, double- blind li nkludew total ta ’ 1, 094 pazjent li rċievew kimoterapija li nkludiet cisplatin ≥70 mg/ m2, aprepitant f’ kombinazzjoni ma ’ reġimen ondansetron/ dexamethasone (ara sezzjoni 4. 2) tqabbel ma ’ reġimen standard (plaċebo flimkien ma ’ 32 mg ondansetron mogħtija fil- vina f’ Jum 1 flimkien ma ’ 20 mg dexamethasone oralment f’ Jum 1 u 8 mg oralment darbtejn kuljum f’ Jiem 2 u 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 segwenti: reazzjoni kompluta (definita bħala l- ebda episodju emetiku u l- ebda użu ta ’ terapija ta ’ salvataġġ) primarjament matul Ċiklu 1.
The results were evaluated for each individual study and for the 2 studies combined.
Ir- riżultati kienu evalwati għal kull studju individwali u għaż- żewġ studji ikkombinati.
10 A summary of the key study results from the combined analysis is shown in Table 1.
10 Sommarju tar- riżultati ewlenin ta ’ l- studji mill- analiżi ikkombinata jidhru f’ Tabella1.
Table 1 Percent of Patients Receiving Highly Emetogenic Chemotherapy Responding by Treatment Group and Phase — Cycle 1
Tabella 1 Perċentwal ta ’ Pazjenti li Qed Jirċievu Kimoterapija Emetoġenika Ħafna li Qed Jirrispondu skond il- Grupp ta ’ Trattament u Fażi – Ċiklu 1
Aprepitant Regimen
Reġimen
COMPOSITE MEASURES
ta ’
(N= 524 )†%%
524)%%
Complete Response (no emesis and no rescue therapy)
Reazzjoni Kompluta (l- ebda emesi u l- ebda terapija ta ’ salvataġġ)
Overall (0-120 hours) 0-24 hours 25-120 hours
Total (0- 120 sigħat) 0- 24 sigħat 25- 120 sigħat
67.7 86.0 71.5
67. 7 86. 0 71. 5
47.8 73.2 51.2
47. 8 73. 2 51. 2
INDIVIDUAL MEASURES No Emesis (no emetic episodes regardless of use of rescue therapy)
MIŻURI INDIVIDWALI L- Ebda Emesi (l- ebda episodju emetiku minkejja l- użu ta ’ terapija ta ’ salvataġġ)
No Significant Nausea (maximum VAS < 25 mm on a scale of 0-100 mm)
L- Ebda Nawsja Sinjifikanti (VAS massimu < 25 mm fuq skala ta ’ 0- 100 mm)
Overall (0-120 hours) 25-120 hours
Total (0- 120 sigħat) 25- 120 sigħat
* 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 kienu ikkalkulati mingħajr ebda aġġustament għas- sess u kimoterapija konkomittanti, li kienu inklużi fl- analiżi primarja ta ’ l- odds ratios u mudelli loġistiċi. † Pazjent wieħed b’ Reġimen ta ’ Aprepitant kellhom biss tagħrif fil- fażi akuta u kien eskluż mill- analiżi tal- fażi totali u mdewwma; pazjent wieħed fir- Reġimen Standard kellu biss tagħrif fil- fażi mdewma u ġie eskluż mill- analiżi tal- fażi totali u akuta.
The estimated time to first emesis in the combined analysis is depicted by the Kaplan-Meier plot in Figure 1.
Iż- żmien stmat għall- ewwel emesi fl- analiżi ikkombinata huwa deskrit permezz tad- dijagramma Kaplan- Meier 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 Qed Jirċievu Kimoterapija Emetoġenika Ħafna Li Jibqgħu Ħielsa mill- Emesi Maż- Żmien – Ċiklu 1
Aprepitant Regimen (N=520) Standard Therapy (N=523)
11 Reġimen ta ’ Aprepitant (N=520) Terapija Standard (N=523)
80%
Perċentwal ta ’ Pazjenti
Statistically significant differences in efficacy were also observed in each of the 2 individual studies.
Differenzi statistikament sinjifikanti fl- effikaċja kienu wkoll osservati f’ kull wieħed miż- żewġ studji individwali.
11 In the same 2 clinical studies, 851 patients continued into the Multiple-Cycle extension for up to 5 additional cycles of chemotherapy.
Fl- istess żewġ studji kliniċi, 851 pazjent komplew fl- estensjoni taċ- Ċiklu Multiplu għal sa 5 ċikli addizjonali ta ’ kimoterapija.
The efficacy of the aprepitant regimen was maintained during all cycles.
L- effikaċja tar- reġimen ta ’ aprepitant kienet miżmuma tul iċ- ċikli kollha.
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 studju mwettaq b’ mod każwali, double- blind f’ total ta ’ 866 pazjent (864 nisa, 2 irġiel) li rċievew kimoterapija li inkludiet cyclophosphamide 750- 1500 mg/ m2; jew cyclophosphamide 500- 1500 mg/ m2 u doxorubicin (≤60 mg/ m2) jew epirubicin (≤100 mg/ m2), aprepitant f’ kombinazzjoni ma ’ reġimen ondansetron/ dexamethasone (ara sezzjoni 4. 2) tqabbel ma ’ terapija standard (plaċebo flimkien ma ’ 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 segwenti: reazzjoni kompluta (definita bħala l- ebda episodju emetiku u l- ebda użu ta ’ terapija ta ’ salvataġġ) primarjament matul Ċiklu 1.
A summary of the key study results is shown in Table 2.
12 Sommarju tar- riżultati ewlenin ta ’ l- istudji mill- analiżi ikkombinata jidhru f’ Tabella 2.