natgillin/translations-raw huggingface dataset:
Den kemiske og fysiske stabilitet efter åbning og efter rekonstitution og fortynding er blevet påvist i 24 timer ved at 2 °C til 8 °C eller 6 timer ved stuetemperatur.
Chemical and physical in-use stability after reconstitution and dilution has been demonstrated for 24 hours at 2 °C to 8 °C, or 6 hours at room temperature.
Anvendelse til disse patienter anbefales ikke, medmindre den potentielle fordel opvejer risikoen.
Use in these patients is not recommended unless the potential benefit is considered to outweigh the risks.
Tabel 3Farmakokinetiske parametre ved steady state for isavuconazol efter oral administration af CRESEMBA Parameter Statistik
Table 3Steady state pharmacokinetic parameters of isavuconazole following oral administration of CRESEMBA Parameter Statistic
Kapslerne må ikke tygges, knuses, opløses eller åbnes.
Do not chew, crush, dissolve or open the capsules.
All-cause-mortaliteten på dag 42 i denne population var 18,7% for isavuconazol og 22,2% for voriconazol.
The all-cause mortality at Day 42 in this population was 18.7% for isavuconazole and 22.2% for voriconazole.
Som vist i nedenstående Tabel 4 er den absolutte biotilgængelighed af isavuconazol 98% efter oral administration af en enkelt dosis CRESEMBA.
As shown in table 4 below, the absolute bioavailability of isavuconazole following oral administration of a single dose of CRESEMBA is 98%.
Serumkoncentrationerne af digoxin bør monitoreres og bruges til titrering af digoxindosis.
Digoxin: serum digoxin concentrations should be monitored and used for titration of the digoxin dose.
Studier med raske personer har vist, at isavuconazols farmakokinetik er proportionel op til 600 mg pr. dag.
Studies in healthy subjects have demonstrated that the pharmacokinetics of isavuconazole are proportional up to 600 mg per day.
Hvis De ønsker yderligere oplysninger om Cresemba, skal De henvende Dem til den lokale repræsentant for indehaveren af markedsføringstilladelsen:
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Bupropion: om nødvendigt forhøjelse af dosis.
Bupropion: dose increase if required.
I dyremodeller af dissemineret og pulmonal aspergillose er det farmakodynamiske indeks, som er vigtigt for effekten, eksponering divideret med minimum inhibitory concentration (MIC) (AUC/MIC).
In animal models of disseminated and pulmonary aspergillosis, the pharmacodynamic (PD) index important in efficacy is exposure divided by minimum inhibitory concentration (MIC) (AUC/MIC).
14 hårde kapsler (i to aluminiumblisterkort), hvor hver kapsellomme er forbundet med en lomme med tørremiddel.
14 hard capsules (in two aluminum blisters), with each capsule pocket connected to a pocket with desiccant.
Det inaktive spaltningsprodukt elimineres fortrinsvis gennem metabolisme og efterfølgende udskillelse af metabolitterne via nyrerne.
The inactive cleavage product is primarily eliminated by metabolism and subsequent renal excretion of the metabolites.
Forhøjede levertransaminaser eller hepatitis
Elevated liver transaminases or hepatitis
AUCinf = area under the plasma concentration time-profiler ekstrapoleret til uendelighed; AUCtau = area under the plasma concentration time-profiler i det 24 timers interval ved steady-state; Cmax = højeste plasmakoncentration; Cmin,ss = laveste niveauer ved steady-state.
AUCinf = area under the plasma concentration-time profiles extrapolated to infinity; AUCtau = area under the plasma concentration-time profiles during the 24 h interval at steady state; Cmax = peak plasma concentration; Cmin,ss = trough levels at steady state.
CRESEMBA skal rekonstitueres og derefter yderligere fortyndes til en koncentration på cirka 0,8 mg/ml isavuconazol inden administration som en intravenøs infusion i mindst 1 time for at reducere risikoen for infusionsrelaterede reaktioner.
CRESEMBA must be reconstituted and then further diluted to a concentration corresponding to approximately 0.8 mg/mL isavuconazole prior to administration by intravenous infusion over a minimum of 1 hour to reduce the risk of infusion-related reactions.
Farmakoterapeutisk klassifikation: Antimykotika til systemisk anvendelse, triazolderivater, ATCkode: J02AC05
Pharmacotherapeutic group: Antimycotics for systemic use, triazole derivatives, ATC code: J02AC05
Den anbefalede dosis er to kapsler én gang om dagen.
The recommended dose is two capsules once a day.
Den samlede respons i denne population var n = 43 (35%) for isavuconazol og n = 42 (38,9%) for voriconazol.
The overall response in this population was n = 43 (35%) for isavuconazole and n = 42 (38.9%) for voriconazole.
Andre lægemidlers potentiale for at påvirke isavuconazols farmakokinetik
Potential of medicinal products to affect the pharmacokinetics of isavuconazole
Effekter på lægemiddelkoncentrationer / Geometrisk gennemsnitsændring (%) i AUC, Cmax (Virkemåde)
Effects on drug concentrations / Geometric Mean Change (%) in AUC, Cmax (Mode of action)
Interaktionerne mellem isavuconazol og samtidigt administrerede lægemidler vises i Tabel 1 (stigninger er vist som “↑”, fald som “↓”), inddelt efter terapeutisk klasse.
Interactions between isavuconazole and co-administered medicinal products are listed in Table 1 (increase is indicated as “↑”, decrease as “↓”), ordered by therapeutic class.
CRESEMBA kapsler skal synkes hele.
CRESEMBA capsules should be swallowed whole.
Den samlede respons ved EOT (end-of-treatment) i myITT-populationen (patienter med påvist og sandsynlig invasiv aspergillose baseret på cytologi, histolog, dyrkning eller galactomannan-test) blev vurderet af en uafhængig, blindet Data Review Committee.
The overall response at end-of-treatment (EOT) in the myITT population (patients with proven and probable invasive aspergillosis based on cytology, histology, culture or galactomannan testing) was assessed by an independent blinded Data Review Committee.
NNRTI'er, nonnukleoside reverse transkriptasehæmmere; P-gp, P-glycoprotein.
NNRTI, non-nucleoside reverse-transcriptase inhibitor; P-gp, P-glycoprotein.
Isavuconazol har intet registrerbart mutagent eller genotoksisk potentiale.
Isavuconazole has no discernible mutagenic or genotoxic potential.
Udskillelse via nyrerne af uændret isavuconazol var mindre end 1% af den administrerede dosis.
Renal excretion of intact isavuconazole was less than 1% of the dose administered.
Hver pakning indeholder 2 aluminiumblisterkort med 7 kapsler i hver.
Each carton contains 2 aluminium blisters pack, with 7 capsules each.
Dette lægemiddel er kun beregnet til engangsbrug.
This medicinal product is for single use only.
For instruktioner om rekonstitution og fortynding af CRESEMBA før administration, se pkt.
For detailed instructions on the reconstitution and dilution of CRESEMBA before administration, see section 6.6.
Isavuconazoniumsulfat er et vandopløseligt prodrug, der kan administreres som en intravenøs infusion eller oralt som hårde kapsler.
Isavuconazonium sulfate is a water-soluble prodrug that can be administered as an intravenous infusion or orally as hard capsules.
I et QT-studie med raske personer forkortede isavuconazol QTc-intervallet på en måde, der var forbundet med koncentrationen.
In a QT study in healthy human subjects, isavuconazole shortened the QTc interval in a concentration-related manner.
Tabel 4Farmakokinetisk sammenligning af oral og intravenøs dosis (gennemsnit) ISA 400 mg oral
Table 4Pharmacokinetic comparison for oral and intravenous dose (Mean) ISA 400 mg oral
Efter oral administration af radioaktivt mærket isavuconazoniumsulfat til raske personer blev gennemsnitligt 46,1% af den radioaktive dosis udskilt i fæces, og 45,5% blev udskilt i urin.
Following oral administration of radio-labelled isavuconazonium sulfate to healthy subjects, a mean of 46.1% of the radioactive dose was recovered in faeces, and 45.5% was recovered in urine.
CRESEMBA må ikke anvendes under graviditet, medmindre det er til patienter med alvorlige eller potentielt livstruende svampeinfektioner, hvor isavuconazol kan anvendes, hvis de forventede fordele for moderen opvejer den mulige risiko for fostret.
CRESEMBA must not be used during pregnancy except in patients with severe or potentially lifethreatening fungal infections, in whom isavuconazole may be used if the anticipated benefits outweigh the possible risks to the foetus.
Den intravenøse administration af isavuconazol skal om muligt gennemføres inden for 6 timer efter rekonstitution og fortynding ved stuetemperatur.
If possible, the intravenous administration of isavuconazole should be completed within 6 hours after reconstitution and dilution at room temperature.
Lopinavir/ritonavir: Justering af dosis af lopinavir 400 mg / ritonavir 100 mg hver 12. time ikke nødvendig, men nøje monitorering for eventuel mangel på antiviral effekt.
Lopinavir/ritonavir: no dose adjustment for lopinavir 400 mg / ritonavir 100 mg every 12 hours required, but careful monitoring for any occurrence of lack of anti-viral efficacy.
Koffein:
Caffeine:
Der er rapporteret om svampestammer med nedsat følsomhed over for isavuconazol in vitro, og krydsresistens med voriconazol og andre triazol-antimykotika kan ikke udelukkes.
Fungal strains with reduced in vitro susceptibility to isavuconazole have been reported, and cross-resistance with voriconazole and other triazole antifungal agents cannot be excluded.
Til intravenøs anvendelse efter rekonstitution og fortynding Brug et rækkefilter ved infusionen.
For intravenous use after reconstitution and dilution Use an in-line filter for infusion.
Tag ikke Cresemba, hvis du er gravid, medmindre din læge har sagt, at du skal.
Do not take Cresemba if you are pregnant, unless your doctor tells you otherwise.
CRESEMBA bør ikke anvendes til kvinder i den fertile alder, som ikke anvender kontraception.
CRESEMBA is not recommended for women of childbearing potential who are not using contraception.
Udtalte forhøjelse af levertransaminaser på > 10 × ULN opstod hos 1,2% af de patienter, der fik isavuconazol.
Marked elevations of liver transaminases > 10 × ULN developed in 1.2% of patients on isavuconazole.
Der bør udvises forsigtighed, hvis CRESEMBA ordineres til patienter, der tager andre lægemidler, som vides at reducere QT-intervallet, for eksempel rufinamid.
Caution is warranted when prescribing CRESEMBA to patients taking other medicinal products known to decrease the QT interval, such as rufinamide.
Relevant lægemiddelmonitorering og justering af dosis kan være nødvendig i forbindelse med samtidig administration (se pkt.
Appropriate therapeutic drug monitoring and dose adjustment may be necessary during co-administration (see section 4.5).
Blisterkortet indeholder også tørremiddel.
The blister card also contains desiccant.
Isavuconazol distribueres i omfattende grad med en gennemsnitlig steady state-distributionsvolumen (Vss) på cirka 450 l. Isavuconazol er kraftigt proteinbundet (> 99%) til humane plasmaproteiner, fortrinsvis til albumin.
Isavuconazole is extensively distributed, with a mean steady state volume of distribution (Vss) of approximately 450 L. Isavuconazole is highly bound (> 99%) to human plasma proteins, predominantly to albumin.
Behandlingens varighed bør fastlægges på baggrund af den kliniske respons (se pkt.
Duration of therapy should be determined by the clinical response (see section 5.1).
Der tilrådes til forsigtighed, hvis CRESEMBA administreres samtidig med substrater af BCRP.
Caution is advised when CRESEMBA is given concomitantly with substrates of BCRP.
Isavuconazol kan forhøje eksponeringen af lægemidler, som er P-gp-substrater.
Isavuconazole may increase the exposure of medicinal products that are P-gp substrates.
Tabel 2 Oversigt over bivirkninger inddelt efter MedDRA systemorganklasse og hyppighed
Table 2 Summary of adverse reactions by MedDRA System Organ Class and frequency
Indinavir blev kun undersøgt efter en enkelt dosis isavuconazol på 400 mg.
Indinavir was only studied after a single dose of 400 mg isavuconazole.
Der blev ikke observeret nogen klinisk relevante ændringer i total Cmax og AUC for isavuconazol hos personer med mild, moderat eller stærkt nedsat nyrefunktion sammenlignet med personer med normal nyrefunktion.
No clinically relevant changes were observed in the total Cmax and AUC of isavuconazole in subjects with mild, moderate or severe renal impairment compared to subjects with normal renal function.
Monitorering af leverenzymer bør overvejes som klinisk indiceret.
Monitoring of hepatic enzymes should be considered, as clinically indicated.
Isavuconazol virker ved at dræbe eller standse væksten af den svamp, der forårsager infektionen.
How Cresemba works Isavuconazole works by killing or stopping the growth of the fungus, which causes the infection.
Eksponering in utero til den aktive del, isavuconazol, havde ingen virkning på de overlevende ungers fertilitet.
In utero exposure to the active moiety isavuconazole had no effect on the fertility of the surviving pups.
Hver kapsellomme er forbundet med en lomme, der indeholder et tørremiddel, som beskytter kapslen mod fugt.
Each capsule pocket is connected to a pocket that contains ‘desiccant' to protect the capsule from moisture.
Ud af de 403 patienter, der fik CRESEMBA i fase 3-studierne, havde 79 (20%) en estimeret glomerulær filtrationsrate (GFR) på under 60 ml/min./1,73 m2 Der er ikke behov for justering af dosis til patienter med nedsat nyrefunktion, herunder patienter med nyresygdom i slutstadiet.
Of the 403 patients who received CRESEMBA in the Phase 3 studies, 79 (20%) of patients had an estimated glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2. No dose adjustment is required in patients with renal impairment, including those patients with end-stage renal disease.
Hos rotter og kaniner var isavuconazol ved systemiske eksponeringer under det terapeutiske niveau forbundet med dosisrelaterede stigninger i forekomsten af knogleanomalier (rudimentære ribben) hos afkommet.
In rats and rabbits, isavuconazole at systemic exposures below the therapeutic level were associated with dose-related increases in the incidence of skeletal anomalies (rudimentary supernumerary ribs) in offspring.
Fortynding og administration
Dilution and administration
Isavuconazol må ikke infunderes i samme slange eller kanyle som andre intravenøse produkter.
Isavuconazole should not be infused into the same line or cannula concomitantly with other intravenous products.
Mycophenolsyre (MPA, aktiv metabolit) :
Mycophenolic acid (MPA, active metabolite) :
Den kliniske effekt er påvist for følgende Aspergillus-arter: Aspergillus fumigatus, A. flavus, A. niger og A. terreus (se yderligere herunder).
Clinical efficacy has been demonstrated for the following Aspergillus species: Aspergillus fumigatus, A. flavus, A. niger, and A. terreus(see further below).
Skift til oral isavuconazol
Switch to oral isavuconazole
Der er indberettet tilfælde af hepatitis ved behandling med antifungale azoler inklusive CRESEMBA.
Hepatitis has been reported with azole antifungal agents including CRESEMBA.
AUC (t•ng/ml) CV %
AUC (h•ng/mL) CV %
For andre potente CYP3A4-hæmmere, for eksempel clarithromycin, indinavir og saquinavir, kan der forventes en mindre udtalt effekt, baseret på deres relative styrke.
For other strong CYP3A4 inhibitors, such as clarithromycin, indinavir and saquinavir, a less pronounced effect can be expected, based on their relative potency.
Hvis disse reaktioner opstår, skal infusionen afbrydes.
The infusion should be stopped if these reactions occur.
MyITT-populationen omfattede 123 patienter, der fik isavuconazol, og 108 patienter, der fik voriconazol.
The myITT population comprised 123 patients receiving isavuconazole and 108 patients receiving voriconazole.
En forhøjelse af dosis til 600 mg medførte en forskel i LSM i forhold til placebo på 24,6 ms 2 timer efter dosering [90% CI: 28,7; 20,4 ms].
Increasing the dose to 600 mg resulted in an LSM difference from placebo of 24.6 ms at 2 hours post dose [90% CI: 28.7, 20.4 ms].
I intent-to-treatpopulationen (ITT-populationen) fik 258 patienter isavuconazol, og 258 patienter fik voriconazol.
In the intent-to-treat (ITT) population, 258 patients received isavuconazole and 258 patients received voriconazole.
Isavuconazol var negativ i en bakteriel tilbagemutationstest, var svagt klastogen ved cytotoksiske koncentrationer i L5178Y tk+/muselymfom-kromosomaberrationsanalysen og viste ingen biologisk relevant eller statistisk signifikant stigning i hyppigheden af mikronuklei i en mikronukleustest in vivo på rotter.
Isavuconazole was negative in a bacterial reverse mutation assay, was weakly clastogenic at cytotoxic concentrations in the L5178Y tk+/- mouse lymphoma chromosome aberration assay, and showed no biologically relevant or statistically significant increase in the frequency of micronuclei in an in vivo rat micronucleus test.
Koncentrationerne af proteasehæmmeren kan falde (som det er set med lopinavir/ritonavir) eller stige.
Protease inhibitor concentrations may decrease (as observed with lopinavir/ritonavir) or increase.
Cresemba bruges til voksne til behandling af følgende svampeinfektioner: - invasiv aspergillose, der skyldes en svamp i gruppen ‘Aspergillus'; - mucormycose, der skyldes en svamp i gruppen ‘Mucorales', til patienter, hvis behandling med amphotericin B ikke er egnet.
Cresemba is used in adults to treat the following fungal infections: - invasive aspergillosis, caused by a fungus in the ‘Aspergillus' group; - mucormycosis, caused by a fungus beloning to the ‘Mucorales' group in patients for whom a treatment with amphotericin B is not appropriate.
Du må ikke holde op med at tage Cresemba, medmindre din læge har sagt, at du skal.
Do not stop taking Cresemba unless you doctor has told you to do so.
Dosisjustering om nødvendigt.
adjustment if required.
Det er vigtigt, at du bliver ved med at tage dette lægemiddel, så længe som din læge har sagt, at du skal gøre det.
It is important to keep taking this medicine as long as your doctor tells you.
svarende til 200 mg isavuconazol.
corresponding to 200 mg isavuconazole.
For patienter med sandsynlig eller påvist mucormycose, som det er defineret af den uafhængige Data Review Committee (DRC), var all-cause-mortaliteten på dag 84 43,2% (16/37) for den samlede patientpopulation, 42,9% (9/21) for mucormycose-patienter, der fik isavuconazol som primær behandling, og 43,8% (7/16) for mucormycose-patienter, der fik isavuconazol, og som var refraktære eller intolerante over for tidligere antimykotisk behandling (fortrinsvis amphotericin B-baserede behandlinger).
For patients with probable or proven mucormycosis as defined by the independent Data Review Committee (DRC), all-cause mortality at Day 84 was 43.2% (16/37) for the overall patient population, 42.9% (9/21) for mucormycosis patients receiving isavuconazole as primary treatment, and 43.8% (7/16) for mucormycosis patients receiving isavuconazole who were refractory to, or intolerant of, prior antifungal therapy (mainly amphotericin B-based treatments).
Den systemiske eksponering for lægemidler, der metaboliseres af CYP2B6, kan være reduceret, når de administreres samtidig med CRESEMBA.
Systemic exposure to medicinal products metabolised by CYP2B6 may be decreased when co-administered with CRESEMBA.
CRESEMBA kan tages med eller uden mad.
CRESEMBA can be taken with or without food.
De tilgængelige farmakodynamiske/toksikologiske data fra dyreforsøg viser, at isavuconazol/metabolitter udskilles i mælk (se pkt.
Available pharmacodynamic/toxicological data in animals have shown excretion of isavuconazole/metabolites in milk (see section 5.3).
Ét 10 ml type I-hætteglas med gummiprop og aluminiumshætte med plastforsegling.
One 10 mL Type I glass vial with rubber stopper and an aluminum cap with plastic seal.
Samtidig administration af CRESEMBA og høje doser ritonavir (>200 mg hver 12. time) er kontraindiceret.
The concomitant administration of CRESEMBA and high doses of ritonavir (>200 mg every 12 hours) is contraindicated.
Isavuconazol er en mild hæmmer af den organiske kationtransportør 2 (OCT2).
Isavuconazole is a mild inhibitor of the organic cation transporter 2 (OCT2).
Generelt er de koncentrationer af isavuconazol, der er nødvendige for at hæmme Mucorales, højere end dem, der er nødvendige for at hæmme størstedelen af Aspergillus-arterne.
Generally, concentrations of isavuconazole required to inhibit Mucorales are higher than those required to inhibit the majority of Aspergillus species.
Der er indberettet alvorlige kutane bivirkninger, for eksempel Stevens-Johnsons syndrom, under behandling med azoler.
Severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, have been reported during treatment with azole antifungal agents.
Isavuconazols sikkerhed og virkning i behandlingen af patienter med invasiv aspergillose blev undersøgt i et dobbeltblindt, aktiv-kontrolleret klinisk studie med 516 patienter med invasiv svampesygdom, der skyldtes Aspergillus-arter eller andre filamentøse svampe.
The safety and efficacy of isavuconazole for the treatment of patients with invasive aspergillosis was evaluated in a double-blind, active-controlled clinical study in 516 patients with invasive fungal disease caused by Aspergillus species or other filamentous fungi.
Mannitol Svovlsyre (til pH-justering)
Mannitol Sulfuric acid (for pH-adjustment)
Ritonavir i høje doser kan reducere koncentrationerne af isavuconazol markant.
Ritonavir at high doses may significantly decrease isavuconazole concentrations.
Lægemidler, der transporteres af P-gp i tarmene
Medicinal products transported by P-gp in the intestine
Efter rekonstitution skal hele indholdet af det rekonstituerede koncentrat fjernes fra hætteglasset og tilsættes i en infusionspose, der indeholder mindst 250 ml enten natriumchlorid 9 mg/ml (0,9%) injektionsvæske eller 50 mg/ml (5%) dextroseopløsning.
After reconstitution, the entire content of the reconstituted concentrate should be removed from the vial and added to an infusion bag containing at least 250 mL of either sodium chloride 9 mg/mL (0.9%) solution for injection or 50 mg/mL (5%) dextrose solution.
C-mærket isavuconazoniumsulfat til diende rotter medførte udskillelse af radioaktivt mærket stof i mælken.
C-labelled isavuconazonium sulfate to lactating rats resulted in the recovery of radiolabel in the milk.
Det bør bemærkes, at der ikke var nogen dosisbestemmende undersøgelse af mucormycose, at patienterne fik samme dosis isavuconazol som ved behandling af invasiv aspergillose.
It should be noted that there was no dose-finding study in mucormycosis, and patients were administered the same dose of isavuconazole as was used for the treatment of invasive aspergillosis.
Amning skal ophøre under behandling med CRESEMBA.
Breast-feeding should be discontinued during treatment with CRESEMBA.
Isavuconazol er den aktive del, der dannes efter oral eller intravenøs administration af isavuconazoniumsulfat (se pkt.
Isavuconazole is the active moiety formed after oral or intravenous administration of isavuconazonium sulfate (see section 5.2).
Hætteglasset skal omrystes, så pulveret opløses helt.
The vial should be shaken to dissolve the powder completely.
I et dobbeltblindt, randomiseret, aktiv-kontrolleret klinisk studie med 516 patienter med invasiv svampesygdom, der skyldtes Aspergillus-arter eller andre filamentøse svampe, blev der indberettet forhøjede levertransaminaser (alaninaminotransferase eller aspartataminotransferase) > 3 × Upper Limit of Normal (ULN) efter afsluttet forsøgsbehandling hos 4,4% af de patienter, der fik CRESEMBA.
In a double-blind, randomized, active-controlled clinical study of 516 patients with invasive fungal disease caused by Aspergillus species or other filamentous fungi, elevated liver transaminases (alanine aminotransferase or aspartate aminotransferase) > 3 × Upper Limit of Normal (ULN) were reported at the end of study treatment in 4.4% of patients who received CRESEMBA.
Studier in vitro/in vivo viser, at CYP3A4, CYP3A5 og efterfølgende uridin-diphosphatglucuronosyltransferaser (UGT) er involveret i metabolismen for isavuconazol.
In vitro / in vivo studies indicate that CYP3A4, CYP3A5, and subsequently uridine diphosphateglucuronosyltransferases (UGT), are involved in the metabolism of isavuconazole.
Isavuconazol 200 mg (n = 37)
Isavuconazole 200 mg (n = 37)