natgillin/translations-raw huggingface dataset:
Virksomheden fremlagde også data som dokumentation for anvendelsen af EMEND til støtte for 7 Westferry Circus, Canary Wharf, London E14 4HB, UK Tel.
There were two studies in highly emetogenic chemotherapy, involving a total of 1,094 patients, where EMEND combined with dexamethasone (a 7 Westferry Circus, Canary Wharf, London E14 4HB, UK Tel.
(44- 20) 74 18 84 00 Fax (44- 20) 74 18 84 16 E- mail: mail@ emea. europa. eu http: // www. emea. europa. eu ©EMEA 2008 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged anvendelsen af IVEMEND, da 125- mg- kapslerne blev anvendt på kemoterapidagen i alle EMEND - undersøgelserne.
(44-20) 74 18 84 00 Fax (44-20) 74 18 84 16 E-mail: mail@emea. europa. eu http: / /www. emea. europa. eu ©EMEA 2008 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged corticosteroid) and ondansetron was compared with a standard treatment of only dexamethasone and ondansetron.
I en undersøgelse af mindre emetogen kemoterapi blev EMEND sammenlignet på samme måde hos 866 patienter med brystkræft, som fik cyclophosphamid med eller uden doxorubicin eller epirubicin.
One study in less emetogenic chemotherapy compared EMEND in the same way in 866 patients with breast cancer who were receiving cyclophosphamide with or without doxorubicin or epirubicin.
Behandlingens virkning blev bedømt på andelen af patienter, der oplevede kvalme og opkastning i de første fem dage efter at have fået kemoterapi.
The measure of effectiveness was the proportion of patients who had nausea and vomiting over the five days after receiving the chemotherapy.
Hvilken fordel viser undersøgelserne, at der er ved IVEMEND?
What benefit has IVEMEND shown during the studies?
I undersøgelserne af højemetogen kemoterapi udgjorde andelen af patienter, som ikke oplevede kvalme eller opkastning i løbet af fem dage, 67, 7% i EMEND- gruppen og 47, 8% i sammenligningsgruppen.
In the studies in highly emetogenic chemotherapy, the proportion of patients who had no nausea or vomiting over five days was 67.7% in the EMEND group and 47.8% in the comparator group.
I undersøgelsen af patienter, der fik mindre emetogen kemoterapibehandling, var procentandelen 50, 8% (EMEND- gruppen) og 42, 5% (sammenligningsgruppen).
In the study in patients receiving less emetogenic chemotherapy, the percentages were 50.8% (EMEND group) and 42.5% (comparator group).
Den påviste virkning af EMEND 125 mg kapsler ved indgivelse på kemoterapibehandlingens første dag gælder også for IVEMEND, da de to lægemidler viste sig at producere det samme indhold af aprepitant i kroppen.
This benefit shown by EMEND 125 mg capsules given on the first day of chemotherapy can be applied to IVEMEND as the two medicines were shown to produce equivalent levels of aprepitant in the body.
Hvilken risiko er der forbundet med IVEMEND?
What is the risk associated with IVEMEND?
Den fuldstændige liste over indberettede bivirkninger ved IVEMEND fremgår af indlægssedlen.
The most common side effects with IVEMEND (seen in between 1 and 10 patients in 100) are increased liver enzymes, headache, dizziness, hiccups, constipation, diarrhoea, dyspepsia (indigestion), eructation (burping), anorexia (loss of appetite) and asthenia or fatigue (weakness or tiredness). For the full list of all side effects reported with IVEMEND, see the Package Leaflet.
IVEMEND bør ikke anvendes hos personer, som kan være overfølsomme (allergiske) over for aprepitant, polysorbat 80 eller et af de øvrige indholdsstoffer.
IVEMEND should not be used in people who may be hypersensitive (allergic) to aprepitant, to polysorbate 80 or any of the other ingredients.
IVEMEND kan ikke gives samtidigt med følgende lægemidler: • pimozid (anvendes til behandling af psykiske sygdomme) • astemizol og terfenadin (anvendes til behandling af allergisymptomer – disse lægemidler kan eventuelt udleveres uden recept) • cisaprid (anvendes til lindring af visse maveproblemer).
IVEMEND cannot be given at the same time as the following medicines: • pimozide (used to treat mental illness), • astemizole, terfenadine (commonly used to treat allergy symptoms - these medicines may be available without prescription), • cisapride (used to relieve certain stomach problems).
Hvorfor blev IVEMEND godkendt?
Why has IVEMEND been approved?
Udvalget for Humanmedicinske Lægemidler (CHMP) konkluderede, at IVEMEND er virksomt til at forebygge akut og forsinket kvalme og opkastning i forbindelse med højemetogen cisplatinbaseret kræftkemoterapi og kvalme og opkastning i forbindelse med moderat emetogen kræftkemoterapi.
The Committee for Medicinal products for Human Use (CHMP) decided that IVEMEND is effective in the prevention of acute and delayed nausea and vomiting associated with highly emetogenic cisplatin-based cancer chemotherapy and of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.
Udvalget fandt, at fordelene ved IVEMEND opvejer risiciene, og anbefalede udstedelse af markedsføringstilladelse for IVEMEND.
The Committee decided that IVEMEND’ s benefits are greater than its risks and recommended that IVEMEND be given marketing authorisation.
Andre oplysninger om IVEMEND:
Other information about IVEMEND:
Europa- Kommissionen udstedte en markedsføringstilladelse med gyldighed i hele Den Europæiske Union for IVEMEND til Merck Sharp & Dohme Ltd den 11. januar 2008.
The European Commission granted a marketing authorisation valid throughout the European Union for IVEMEND to Merck Sharp & Dohme Ltd on 11 January 2008.
Den fuldstændige EPAR for IVEMEND findes her.
The full EPAR for IVEMEND can be found here.
EU/ 1/ 07/ 437/ 001 EU/ 1/ 07/ 437/ 002
EU/ 1/ 07/ 437/ 001
IVEMEND IVEMEND
IVEMEND
115 mg 115 mg
115 mg
Pulver til infusionsvæske, opløsning Pulver til infusionsvæske, opløsning
Powder for solution for infusion
Intravenøs anvendelse Intravenøs anvendelse
Powder for solution for infusion
Hætteglas (glas) Hætteglas (glas)
vial (glass)
1 hætteglas 10 hætteglas
10 vials
IVEMEND 115 mg pulver til infusionsvæske, opløsning.
IVEMEND 115 mg powder for solution for infusion.
Hvert hætteglas indeholder fosaprepitant dimeglumin svarende til 115 mg fosaprepitant.
Each vial contains fosaprepitant dimeglumine equivalent to 115 mg fosaprepitant.
6. 6).
After reconstitution and dilution 1 ml of solution contains 1 mg fosaprepitant (see section 6.6).
Hvidt til off- white pulver i amorf form.
White to off-white amorphous powder.
Forebyggelse af akut og sen kvalme og opkastning i forbindelse med højemetogen cisplatinbaseret cancerkemoterapi.
Prevention of acute and delayed nausea and vomiting associated with highly emetogenic cisplatin-based cancer chemotherapy.
Forebyggelse af kvalme og opkastning i forbindelse med moderat emetogen cancerkemoterapi.
Prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy.
4. 2).
IVEMEND is given as part of a combination therapy (see section 4.2).
IVEMEND er et frysetørret aprepitant- prodrug, som indeholder polysorbat 80 (PS80), til intravenøs administration.
IVEMEND is a lyophilized prodrug of aprepitant containing polysorbate 80 (PS80) for intravenous administration.
Aprepitant findes som kapsler til peroral administration.
Aprepitant is available as capsules for oral administration.
6. 6).
Posology IVEMEND (115 mg) may be substituted for aprepitant (125 mg) prior to chemotherapy, on Day 1 only of the chemotherapy induced nausea and vomiting (CINV) regimen as an infusion administered over 15 minutes (see section 6.6).
IVEMEND (115 mg) 30 minutter før kemoterapibehandling eller aprepitant (125 mg) en time før kemoterapibehandling på dag 1 og aprepitant (80 mg) på dag 2 og 3 som tillæg til kortikosteroid og 5- HT3- antagonist.
The 3-day CINV regimen includes IVEMEND (115 mg) 30 minutes prior to chemotherapy treatment or aprepitant (125 mg) one hour prior to chemotherapy treatment on Day 1; aprepitant (80 mg) on Days 2 and 3; in addition to a corticosteroid and a 5-HT3 antagonist.
På grundlag af kliniske undersøgelser med aprepitant anbefales følgende regime til forebyggelse af kvalme og opkastning i forbindelse med emetogen cancerkemoterapi:
2 The following regimen is recommended, based on clinical studies with aprepitant, for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy.
2 Højemetogen kemoterapi- behandlingsregime
Highly Emetogenic Chemotherapy Regimen
ingen ingen
none
intravenøst
none
80 mg peroralt 80 mg peroralt
80 mg orally 80 mg orally
Dexamethason Ondansetron
Dexamethasone
12 mg peroralt 32 mg intravenøst
12 mg orally
8 mg peroralt 8 mg peroralt ingen ingen
8 mg orally 8 mg orally
8 mg peroralt ingen
8 mg orally
I kliniske undersøgelser blev:
In clinical studies:
Aprepitant givet peroralt 1 time før kemoterapibehandling på dag 1 og om morgenen på dag 2 og 3.
Aprepitant was administered orally 1 hour prior to chemotherapy treatment on Day 1 and in the morning on Days 2 and 3.
Dexamethason givet 30 minutter før kemoterapibehandling på dag 1 og om morgenen på dag 2- 4.
Dexamethasone was administered 30 minutes prior to chemotherapy treatment on Day 1 and in the morning on Days 2 to 4.
Dosis af dexamethason blev valgt for at tage højde for lægemiddelinteraktioner.
The dose of dexamethasone was chosen to account for medicinal product interactions.
Ondansetron givet intravenøst 30 minutter før kemoterapibehandling på dag 1.
Ondansetron was administered intravenously 30 minutes prior to chemotherapy treatment on Day 1.
80 mg peroralt
80 mg orally
12 mg peroralt
12 mg orally
2 x 8 mg peroralt
2 x 8 mg orally
Dexamethason givet 30 minutter før kemoterapibehandling på dag 1.
Dexamethasone was administered 30 minutes prior to chemotherapy treatment on Day 1.
Ondansetron, en 8 mg kapsel, givet 30- 60 minutter før kemoterapibehandling og 8 timer efter den første dosis på dag 1.
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.
Data vedrørende effekten af kombination med andre kortikosteroider og 5- HT3 antagonister er begrænsede.
Efficacy data on combination with other corticosteroids and 5-HT3 antagonists are limited.
Der henvises til den fulde produktinformation for samtidigt administrerede antiemetika.
Refer to the full product information of co-administered antiemetic agents.
Ældre Dosisjustering er ikke nødvendig hos ældre patienter.
Elderly No dose adjustment is necessary for the elderly.
5. 2).
Renal Impairment No dose adjustment is necessary for patients with renal insufficiency or for patients with end stage renal disease undergoing haemodialysis (see section 5.2).
Leverinsufficiens Dosisjustering er ikke nødvendig hos patienter med mild leverinsufficiens.
Hepatic Impairment No dose adjustment is necessary for patients with mild hepatic insufficiency.
4. 4 og 5. 2).
There are limited data in patients with moderate hepatic insufficiency and no data in patients with severe hepatic insufficiency (see sections 4.4 and 5.2).
Børn og unge IVEMEND bør ikke anvendes til børn under 18 år p. g. a. utilstrækkelig dokumentation for sikkerhed og virkning (se pkt.
Children and adolescents IVEMEND is not recommended for use in children below the age of 18 years of age due to insufficient data on safety and efficacy (see section 5.2).
5. 2).
Method of Administration
6. 6).
Intravenous administration occurs preferably through a running intravenous infusion over 15 minutes (see section 6.6).
IVEMEND må ikke gives som bolusinjektion eller ufortyndet opløsning, og bør ikke gives intramuskulært eller subkutant
Do not administer IVEMEND as a bolus injection or undiluted solution.
Overfølsomhed over for det aktive stof, aprepitant, eller over for polysorbat 80 eller et eller flere af de andre hjælpestoffer.
Hypersensitivity to the active substance, aprepitant, or to polysorbate 80 or any of the other excipients.
Der foreligger begrænsede data for patienter med moderat leverinsufficiens og ingen data for patienter med svær leverinsufficiens.
There are limited data in patients with moderate hepatic insufficiency and no data in patients with severe hepatic insufficiency.
5. 2).
IVEMEND should be used with caution in these patients (see section 5.2).
IVEMEND og peroral aprepitant bør anvendes med forsigtighed til patienter, som er i samtidig peroral behandling med lægemidler, der primært metaboliseres gennem CYP3A4 (se pkt.
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).
Samtidig administration af fosaprepitant og ergotalkaloidderivater, der er CYP3A4- substrater, kan medføre forhøjede plasmakoncentrationer af disse lægemidler.
Co-administration of fosaprepitant with ergot alkaloid derivatives, which are CYP3A4 substrates, may result in elevated plasma concentrations of these medicinal products.
Der bør derfor udvises forsigtighed p. g. a. den mulige risiko for ergotrelateret toksicitet.
Therefore, caution is advised due to the potential risk of ergot-related toxicity.
Samtidig administration af peroral aprepitant og warfarin medfører nedsat prothrombintid, målt ved International Normaliseret Ratio (INR).
Co-administration of oral aprepitant with warfarin results in decreased prothrombin time, reported as International Normalised Ratio (INR).
4. 5).
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).
Effekten af hormonel antikonception kan være nedsat under og i 28 dage efter behandling med aprepitant.
The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration of aprepitant.
4. 5).
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).
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).
Samtidig administration af fosaprepitant og perikon frarådes.
John’ s Wort is not recommended.
4. 5).
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).
IVEMEND bør ikke gives intramuskulært eller subkutant.
IVEMEND should not be administered intramuscularly or subcutaneously.
4. 9).
Mild injection site thrombosis has been observed at higher doses (see section 4.9).
Udvikles tegn eller symptomer på lokal irritation, bør infusionen afbrydes og startes påny i en anden vene.
If signs or symptoms of local irritation occur, the injection or infusion should be terminated and restarted in another vein.
Der må forventes de samme lægemiddelinteraktioner ved administration af fosaprepitant som ved aprepitant.
Drug interactions following administration of fosaprepitant are likely to occur with medicinal products that interact with oral aprepitant.
Følgende information stammer fra data for peroral aprepitant samt undersøgelser, der er udført med fosaprepitant og midazolam eller diltiazem.
The following information was derived from data with oral aprepitant and studies conducted with fosaprepitant and midazolam or diltiazem.
4 Aprepitant har en tofaset effekt på CYP3A4.
4 Aprepitant is a substrate, a moderate inhibitor, and an inducer of CYP3A4.
Pågående behandling med peroral aprepitant hæmmer CYP3A4, mens der efter afsluttet behandling ses en forbigående moderat induktion af CYP3A4 og en let induktion af CYP2C9 og glukuronidering.
After the end of treatment, oral aprepitant causes a transient moderate induction of CYP2C9 and a transient mild induction of CYP3A4 and glucuronidation.
Aprepitants effekt på andre lægemidlers farmakokinetik CYP3A4- hæmning Som en moderat hæmmer af CYP3A4 kan aprepitant øge plasmakoncentrationen af samtidigt administrerede perorale lægemidler, som metaboliseres gennem CYP3A4.
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.
Virkningen af aprepitant på plasmakoncentrationen af intravenøst administrerede CYP3A4- substrater forventes at være mindre.
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.
Det tilrådes at udvise forsigtighed ved samtidig administration af fosaprepitant og CYP3A4- substrater.
Caution is advised during concomitant administration of fosaprepitant and CYP3A4 substrates.
Aprepitants hæmning af CYP3A4 kan resultere i forhøjede plasmakoncentrationer af disse lægemidler, hvilket kan medføre potentielt alvorlige eller livstruende reaktioner.
Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these medicinal products, potentially causing serious or life-threatening reactions.
Induktion Som moderat inducer af CYP2C9 og let inducer af CYP3A4 og glukuronidering kan aprepitant i op til 2 uger efter initiering af dosisregimet nedsætte plasmakoncentrationen af substrater, der elimineres af disse.
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.
Denne virkning viser sig eventuelt først efter afslutning af et 3- dages regime med (fos) aprepitant.
This effect may become apparent only after the end of a 3 day regimen of fosaprepitant followed by aprepitant.
For CYP2C9 - og CYP3A4- substrater er induktionen forbigående, og maksimal effekt opnås 3- 5 dage efter afslutning af 3- dages behandling med peroral 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.
Virkningen opretholdes i nogle få dage, aftager derefter langsomt og er uden klinisk signifikans to uger efter afslutning af peroral aprepitantbehandling.
The effect is maintained for a few days, thereafter slowly declines and is clinically insignificant by two weeks after end of oral aprepitant treatment.
Mild induktion af glukuronidering ses også med 80 mg peroral aprepitant givet i 7 dage.
Mild induction of glucuronidation is also seen with 80 mg oral aprepitant given for 7 days.
Der bør udvises forsigtighed når warfarin, acenocoumarol, tolbutamid, phenytoin eller andre lægemidler, der vides at blive metaboliseret af CYP2C9, administreres i denne periode.
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.
Fosaprepitant eller aprepitant synes ikke at interagere med P- glycoproteintransportøren, hvilket ses af manglen på interaktion mellem peroral aprepitant og digoxin.
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.
50%, når det administreres samtidigt med et fosaprepitantregime efterfulgt af aprepitant.
The usual oral dexamethasone dose should be reduced by approximately 50% when co-administered with a regimen of fosaprepitant followed by aprepitant.
I kliniske undersøgelser af kvalme og opkastning forårsaget af kemoterapi blev Dexamethasondosis valgt for at tage højde for lægemiddelinteraktioner (se pkt.
The dose of dexamethasone in clinical chemotherapy induced nausea and vomiting trials was chosen to account for medicinal product interactions (see section 4.2).
Når peroral aprepitant blev administreret som et behandlingsregime med 125 mg givet samtidig med 20 mg dexamethason peroralt på dag 1, og aprepitant blev givet peroralt 80 mg/ dag samtidig med dexamethason 8 mg peroralt på dag 2 til og med dag 5, øgedes AUC for dexamethason 2, 2 gange på dag 1 og 5.
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.
50%, når de administreres samtidigt med et fosaprepitantregime efterfulgt af aprepitant.
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.
Når peroral aprepitant blev administreret som et behandlingsregime med 125 mg på dag 1 og 80 mg/ dag på dag 2 og 3 samtidig med at methylprednisolon 125 mg blev givet intravenøst på dag 1 og 40 mg peroralt på dag 2 og 3, øgedes AUC for methylprednisolon 1, 3 gange på dag 1 og 2, 5 gange på dag 3.
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.
Ved kontinuerlig behandling med methylprednisolon kan AUC for methylprednisolonforbigående blive nedsat i op til 2 uger efter behandlingsstart med peroral aprepitant, hvilket skyldes aprepitants sene inducerende virkning på CYP3A4.
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.
Denne virkning kan forventes at være mere udtalt for peroralt administreret methylprednisolon.
This effect may be expected to be more pronounced for orally administered methylprednisolone.
5 Kemoterapeutika:
Chemotherapeutic agents:
I farmakokinetiske undersøgelser, hvor peroral aprepitant blev givet som et behandlingsregime med 125 mg på dag 1 og 80 mg/ dag på dag 2 og 3, påvirkede det ikke docetaxels farmakokinetik, når docetaxel blev administreret intravenøst på dag 1 eller vinorelbin farmakokinetik, når vinorelbin blev administreret intravenøst på dag 1 og 8.
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
Aprepitants indvirkning på CYP3A4 - substraters farmakokinetik er større, når disse administreres peroralt end intravenøst.
5 intravenously on Day 1 or vinorelbine administered intravenously on Day 1 or Day 8.
Derfor kan interaktion med peroralt administrerede lægemidler til kemoterapibehandling, som primært eller delvist metaboliseres ved hjælp af CYP3A4 (fx etoposid, vinorelbin), ikke udelukkes.
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.
4. 4).
Caution is advised and additional monitoring may be appropriate in patients receiving such agents (see section 4.4).