natgillin/translations-raw huggingface dataset:
I fase 3-studiet (C16010) havde 10 patienter (5 i hver behandlingsgruppe) svært nedsat nyrefunktion ved baseline.
In the Phase 3 study (C16010), 10 patients (5 in each treatment regimen) had severe renal impairment at baseline.
• manglende lyst til at spise (appetitløshed)
• not feeling like eating (decreased appetite)
† Standardiserede MedDRA-retningslinjer (SMQ'er)
† Standardised MedDRA Queries (SMQs)
• lavt blodtryk (hypotension)
• lowered blood pressure (hypotension)
Før en ny behandlingscyklus påbegyndes:
Prior to initiating a new cycle of therapy:
• Tag NINLARO mindst én time før eller mindst to timer efter indtagelse af føde.
• Take NINLARO at least one hour before or at least two hours after food.
Af de 5 patienter i ixazomib-gruppen havde én patient bekræftet delvis respons og 3 bekræftet stabil sygdom (2 havde dog ikke-bekræftet delvis respons, og 1 havde ikke-bekræftet meget god delvis respons).
Of the 5 patients in the ixazomib regimen, one patient had a confirmed partial response and 3 confirmed stable disease (however 2 were unconfirmed partial response and 1 was an unconfirmed very good partial response).
*p-værdien er baseret på den stratificerede log rank test. †Hazard ratio er baseret på den stratificerede Cox-regressionsmodel.
*P-value is based on the stratified log-rank test. †Hazard ratio is based on a stratified Cox's proportional hazard regression model.
Patienterne skal informeres om ikke at føre motorkøretøj og betjene maskiner, hvis de oplever nogen af disse -bivirkninger.
Patients should be advised not to drive or operate machines if they experience any of these symptoms.
Der anvendes følgende konventioner til klassificering af hyppigheden af bivirkninger (ADR): meget almindelig (≥ 1/10), almindelig (≥ 1/100 til < 1/10), ikke almindelig (≥ 1/1.000 til < 1/100), sjælden (≥ 1/10.000 til < 1/1.000), meget sjælden (< 1/10.000), ikke kendt (kan ikke estimeres ud fra forhåndenværende data).
The following convention is used for the classification of the frequency of an adverse drug reaction (ADR): 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); very rare (< 1/10,000); not known (cannot be estimated from the available data).
DATO FOR FØRSTE MARKEDSFØRINGSTILLADELSE/FORNYELSE AF TILLADELSEN Dato for første markedsføringstilladelse: 21. november 2016 Dato for seneste fornyelse: 16. september 2019
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 21 November 2016
57% af patienterne var mænd.
Fifty seven percent of patients were male.
Den terminale halveringstid (t1/2) for ixazomib er 9,5 dage.
The terminal half-life (t1/2) of ixazomib was 9.5 days.
Hyppigere monitorering skal overvejes i de første tre cyklusser i henhold til produktresuméet for lenalidomid.
More frequent monitoring should be considered during the first three cycles as per the lenalidomide SmPC.
Hver pakning indeholder 3 hårde kapsler (tre enkeltpakninger, som hver indeholder et blisterkort forseglet i en mappe.
Each pack contains 3 hard capsules (three single cartons, each containing a blister sealed inside a wallet.
Ved disse bivirkninger er første dosisjustering at pausere/reducere lenalidomid.
For these toxicities, the first dose modification step is to withhold/reduce lenalidomide.
PVC-aluminiums-/aluminiumsblisterkort forseglet i en mappe, der indeholder én kapsel.
PVC-Aluminium /Aluminium blister sealed inside a wallet pack containing one capsule.
Der er ingen data fra anvendelse af ixazomib til gravide kvinder.
There are no data for the use of ixazomib in pregnant women.
Ixazomib er en oral, meget selektiv og reversibel proteasomhæmmer.
Ixazomib is an oral, highly selective and reversible proteasome inhibitor.
Der er observeret træthed og svimmelhed i kliniske studier.
Fatigue and dizziness have been observed in clinical trials.
Brug ikke lægemidlet, hvis du bemærker eventuelle skader eller tegn på, at emballagen har været åbnet.
Do not use this medicine if you notice any damage or signs of tampering to medicine packaging.
Dosisjustering af ixazomib er ikke nødvendig for patienter over 65 år.
No dose adjustment of ixazomib is required for patients over 65 years of age.
NINLARO anbefales ikke under graviditet, da det kan skade dit ufødte barn.
NINLARO is not recommended during pregnancy as it may harm your unborn baby.
Dag 1 Dag 2 til 7
Day 1 Days 2 to 7
3 pakker af 1 hård kapsel.
3 packs of 1 hard capsule.
Det primære endepunkt var progressionsfri overlevelse (PFS) i henhold til de standardiserede responskriterier fra IMWG (International Myeloma Working Group) fra 2011 efter vurdering af et uafhængigt bedømmelsesudvalg (IRC) baseret på centrallaboratorie-resultater.
The primary endpoint was progression-free survival (PFS) according to the 2011 International Myeloma Working Group (IMWG) Consensus Uniform Response Criteria as assessed by a blinded independent review committee (IRC) based on central laboratory results.
Tag den næste dosis som planlagt, når det er tid.
Take the next dose, as normal, when it is due.
Farmakoterapeutisk klassifikation: Antineoplastiske midler, andre antineoplastiske midler, ATC-kode: L01XX50
Pharmacotherapeutic group: Antineoplastic agents, other antineoplastic agents, ATC code: L01XX50
Ixazomib-Cmax blev reduceret med 4%, og AUC blev øget med 11%.
Ixazomib Cmax was decreased by 4% and AUC was increased by 11%.
Baseret på en populationsfarmakokinetisk analyse er den systemiske clearance (CL) ca. 1,86 l/time med en inter-individuel variation på 44%.
Based on a population PK analysis, systemic clearance (CL) was approximately 1.86 L/hr with inter-individual variability of 44%.
Ixazomib-AUC øges proportionalt med dosis i et dosisområde på 0,2-10,6 mg.
Ixazomib AUC increases in a dose proportional manner over a dose range of 0.2-10.6 mg.
Tag hver NINLARO-kapsel hel sammen med vand på samme tidspunkt hver uge, mindst én time før eller mindst to timer efter indtagelse af føde.
Take each NINLARO capsule whole with water at the same time each week, at least one hour before or no sooner than two hours after any food.
Fase 3-studiet udelukkede patienter, der var refraktære over for lenalidomid eller proteasomhæmmere, og patienter, der havde fået mere end tre tidligere behandlinger.
The Phase 3 study excluded patients who were refractory to lenalidomide or proteasome inhibitors and patients who received more than three prior therapies.
Behandlingen fortsatte indtil sygdomsprogression eller uacceptabel toksicitet.
Treatment continued until disease progression or unacceptable toxicities.
23% af patienterne havde light chain disease, og 12% havde kun målbar sygdom ved free light chain assay.
Twenty three percent of patients had light chain disease and 12% of patients had measurable disease by free light chain assay only.
Da NINLARO anvendes i kombination med lenalidomid, skal du overholde programmet for forebyggelse af graviditet, der gælder for lenalidomid, fordi lenalidomid kan være skadeligt for det ufødte barn.
As NINLARO is given in combination with lenalidomide, you should adhere to the pregnancy prevention programme of lenalidomide because lenalidomide can be harmful to the unborn child.
Ixazomib er til oral anvendelse.
Ixazomib is for oral use.
Det gennemsnitlige AUC var 35% højere hos asiatiske patienter, men der var overlap i AUC for ixazomib på tværs af hvide og asiatiske patienter.
The mean AUC was 35% higher in Asian patients; however, there was overlap in the AUC of ixazomib across White and Asian patients.
25% af patienterne havde kreatininclearance på < 60 ml/min.
Twenty five percent of patients had a creatinine clearance of < 60 mL/min.
Hvis du har taget for meget NINLARO, skal du tale med en læge eller tage direkte på hospitalet.
If you take more NINLARO than you should, talk to a doctor or go to a hospital straight away.
77% af patienterne recidiverede efter tidligere behandlinger, og 11% var refraktære over for tidligere behandlinger.
Seventy seven percent of patients relapsed after prior therapies and 11% were refractory to prior therapies.
Hvis en patient kaster op efter at have taget en dosis, skal patienten ikke tage en ny dosis, men genoptage doseringen på tidspunktet for den næste planlagte dosis.
If a patient vomits after taking a dose, the patient should not repeat the dose but should resume dosing at the time of the next scheduled dose.
NINLARO kan påvirke din evne til at køre motorkøretøj og betjene maskiner.
NINLARO may affect your ability to drive or use machines.
• kvalme, opkastning og diarré
• nausea, vomiting and diarrhoea
Ved den primære analyse (median opfølgning på 14,7 måneder og et mediant antal cyklusser på 13) var PFS statistisk signifikant forskellig mellem de to behandlingsarme.
At the primary analysis (median follow up of 14.7 months and a median of 13 cycles), PFS was statistically significantly different between the treatment arms.
Der er ikke udført studier af fertilitet og tidlig fosterudvikling eller præ- og postnatal toksikologiske studier med ixazomib, men reproduktionsvæv blev evalueret i de generelle toksicitetsstudier.
Studies of fertility and early embryonic development and pre- and post-natal toxicology were not conducted with ixazomib, but evaluation of reproductive tissues was conducted in the general toxicity studies.
Andre bivirkninger Fortæl det til din læge eller apotekspersonalet, hvis nogen af nedenstående bivirkninger bliver svære.
Other possible side effects Tell your doctor or pharmacist if any of the side effects below become severe.
Der er ingen kendt specifik antidot mod overdosering af ixazomib.
There is no known specific antidote for ixazomib overdose.
Efter oral indgivelse viste et studie af vævsfordelingen af ixazomib hos rotter, at hjernen og rygmarven var blandt de væv, der havde de laveste niveauer, hvilket tyder på, at penetrationen af ixazomib gennem blod-hjerne-barrieren synes at være begrænset.
Following oral administration, a tissue distribution study in rats revealed that the brain and spinal cord were amongst the tissues with the lowest levels, suggesting that the penetration of ixazomib through the blood-brain barrier appears to be limited.
PRES er en sjælden, reversibel neurologisk lidelse, som kan vise sig med krampeanfald, hypertension, hovedpine, ændret bevidsthedsniveau og synsforstyrrelser.
PRES is a rare, reversible, neurological disorder which can present with seizure, hypertension, headache, altered consciousness, and visual disturbances.
Thalidomid er et aktivt stof, som er teratogent hos mennesker, og som forårsager alvorlige livstruende medfødte misdannelser.
Thalidomide is a known human teratogenic active substance that causes severe life-threatening birth defects.
Patienter, der skiftede behandling før sygdomsprogression, var kvalificerede til at deltage, ligesom patienter med kontrolleret kardiovaskulær sygdom var det.
Patients that changed therapies prior to disease progression were eligible for enrolment, as well as those with controlled cardiovascular conditions.
Hvis ixazomib anvendes under graviditet, eller hvis patienten bliver gravid, mens hun tager ixazomib, skal patienten informeres om den potentielle risiko for fostret.
If ixazomib is used during pregnancy or if the patient becomes pregnant while taking ixazomib, the patient should be apprised of the potential hazard to the foetus.
Ixazomib forårsagede kun embryo-føtal toksicitet hos drægtige rotter og kaniner ved maternelt toksiske doser og ved eksponeringer, som var lidt højere end observeret hos patienter, der fik den anbefalede dosis.
Ixazomib caused embryo-foetal toxicity in pregnant rats and rabbits only at maternally toxic doses and at exposures that were slightly higher than those observed in patients receiving the recommended dose.
Da myelomatose er en heterogen sygdom, kan fordelene variere i de forskellige undergrupper i fase 3-studiet (se Figur 2).
As multiple myeloma is a heterogeneous disease, benefit may vary across subgroups in the Phase 3 study (C16010) (see Figure 2).
Figur 1: Kaplan-Meier kurver over progressionsfri overlevelse i ITT-populationen
Figure 1: Kaplan-Meier plot of progression-free survival in the intent-to-treat population
Ixazomibcitrat er et pro-drug, der under fysiologiske betingelser hurtigt hydrolyseres til dets biologisk aktive form, ixazomib.
Ixazomib citrate, a prodrug, is a substance that rapidly hydrolyses under physiological conditions to its biologically active form, ixazomib.
19% havde højrisiko cytogenetiske abnormiteter (del[17], t[4;14], t[14;16]) N = 137), 10% havde del(17) (N = 69), og 34% havde 1q amplifikation (1q21) (N = 247).
Nineteen percent had high-risk cytogenetic abnormalities (del[17], t[4;14], t[14;16]) (N=137), 10% had del(17) (N=69) and 34% had 1q amplification (1q21) (N=247).
Ikke-kliniske farmakologiske sikkerhedsstudier, både in vitro (på hERG-kanaler) og in vivo (på telemetriovervågede hunde efter en enkelt oral indgivelse) viste ingen indvirkning af ixazomib på kardiovaskulære og respiratoriske funktioner ved AUC på mere end 8 gange den kliniske værdi.
Non-clinical safety pharmacology studies both in vitro (on hERG channels) and in vivo (in telemetered dogs following single oral administration) demonstrated no effects of ixazomib on cardiovascular or respiratory functions at AUC more than 8-fold higher than the clinical value.
Hvis kapslen går i stykker, skal du tørre pulveret op og passe på, at det ikke hvirvles op i luften.
If the capsule breaks, clean up the powder, taking care that it does not cause dust in the air.
Hvis du glemmer at tage NINLARO
If you forget to take NINLARO
Gastrointestinal toksicitet
Gastrointestinal toxicities
Andre ikke-hæmatologiske toksiciteter Andre grad 3 eller 4 ikke-hæmatologiske toksiciteter
Other Grade 3 or 4 non-haematological toxicities
Behandling af myelomatose skal slå myelomcellerne ihjel og reducere sygdommens symptomer.
Treatment for multiple myeloma involves killing myeloma cells and reducing the symptoms of the disease.
Responsvarighed§, måneder Median
Duration of Response§, months Median
Fortæl det også straks til en læge, hvis du bemærker nogen af følgende s jældne bivirkninger, som kan forekomme hos op til 1 ud af 1.000 personer:
Additionally, tell a doctor immediately if you notice any of these following rare side effects which may affect up to 1 in 1,000 people:
Toksikologiske og/eller farmakologiske studier hos dyr
Animal toxicology and/or pharmacology
Metabolisering via flere CYP-enzymer og ikke-CYP-proteiner forventes at være den vigtigste clearancemekanisme for ixazomib.
Metabolism by multiple CYP enzymes and non-CYP proteins is expected to be the major clearance mechanism for ixazomib.
Et randomiseret, dobbeltblindet, placebokontrolleret fase 3-studie blev gennemførtudført i Kina (N = 115) med samme studiedesign og egnethedskriterier.
A randomised, double-blind, placebo-controlled Phase 3 study was conducted in China (N=115) with a similar study design and eligibility criteria.
Ixazomib var positiv i en in vitro klastogenicitetstest i humane perifere blodlymfocytter.
Ixazomib was positive in an in vitro clastogenicity test in human peripheral blood lymphocytes.
Uomdannet ixazomib udgjorde < 3,5% af den indgivne dosis, der blev genfundet i urinen.
Unchanged ixazomib accounted for < 3.5% of the administered dose recovered in urine.
Evidensen vurderes følgelig at indikere, at ixazomib ikke repræsenterer en genotoksisk risiko.
Therefore, the weight of evidence indicates that ixazomib is not considered to present a genotoxic risk.
Posteriort reversibelt encefalopati-syndrom (PRES) er forekommet hos patienter, der fik ixazomib.
Posterior reversible encephalopathy syndrome (PRES) has occurred in patients receiving ixazomib.
 = Indtagelse af lægemidlet
= intake of medicinal product
• Trombocyttal skal være ≥ 75.000/mm3
• Platelet count should be ≥ 75,000/mm3
Ixazomibbehandling havde ingen indvirkning på hanlige eller hunlige forplantningsorganer i studier af op til 6 måneders varighed hos rotter og af op til 9 måneders varighed hos hunde.
There were no effects due to ixazomib treatment on male or female reproductive organs in studies up to 6-months duration in rats and up to 9-months duration in dogs.
Ixazomib forventes ikke at forårsage lægemiddelinteraktioner via CYP-hæmning eller -induktion.
Ixazomib is not expected to produce drug-drug interactions via CYP inhibition or induction.
Ixazomibs sikkerhed og virkning hos børn under 18 år er ikke klarlagt.
The safety and efficacy of ixazomib in children below 18 years of age have not been established.
Kvinder skal undgå at blive gravide, mens de er i behandling med ixazomib.
Women should avoid becoming pregnant while being treated with ixazomib.
Ved ugentlig oral dosering blev der dag 15 observeret ca. 2-fold akkumulering i AUC.
Approximately 2-fold accumulation in AUC was observed with weekly oral dosing on Day 15.
Ixazomib skal tages på omtrent samme tidspunkt dag 1, 8 og 15 i hver behandlingscyklus og mindst 1 time før eller 2 timer efter indtagelse af føde (se pkt.
Ixazomib should be taken at approximately the same time on days 1, 8, and 15 of each treatment cycle at least 1 hour before or at least 2 hours after food (see section 5.2).
Livskvaliteten, vurderet på grundlag af score for overordnet helbredsstatus (EORTC QLQ-C30 og MY-20), blev bevaret under behandlingen og var sammenlignelig i de to grupper i fase 3-studiet (C16010).
Quality of life as assessed by global health scores (EORTC QLQ-C30 and MY-20) was maintained during treatment and was similar in both treatment regimens in the Phase 3 study (C16010).
Undgå at køre motorkøretøj og betjene maskiner, hvis du får disse bivirkninger.
Do not drive or operate machines if you have these side effects.
Fortæl det straks til din læge eller på apoteket, hvis du får nogen af følgende alvorlige meget almindelige bivirkninger, som kan forekomme hos flere end 1 ud af 10 personer:
Tell your doctor or pharmacist straight away if you notice any of these following very common serious side effects which may affect more than 1 in 10 people:
Ixazomib Lenalidomid
Ixazomib Lenalidomide
Proteasomer er strukturer inde i cellen, der nedbryder proteiner, og er vigtige for cellens overlevelse.
These are structures inside the cell that digest proteins and are important for cell survival.
Medbring emballagen til lægemidlet.
Take the medicine pack with you.
Den hyppigst rapporterede bivirkning var perifer sensorisk neuropati (16% og 12% i henholdsvis ixazomib- og placebogruppen).
The most commonly reported reaction was peripheral sensory neuropathy (16% and 12% in the ixazomib and placebo regimen, respectively).
 Dagligt  Dagligt  Dagligt Dexamethason 
 Daily  Daily  Daily Dexamethasone 
Hvis du er en kvinde i den fødedygtige alder eller en mand, der kan blive far til et barn, skal du benytte sikker prævention under behandlingen og i mindst 90 dage efter, behandlingen er afsluttet.
If you are a woman of childbearing potential or a man who can father a child, you must use effective contraception during and for 90 days after treatment.
I begge grupper havde under 1% af patienterne trombocyttal ≤ 5.000/mm3 under behandlingen.
Less than 1% of patients in both regimens had a platelet count ≤ 5,000/mm3 during treatment.
• Det absolutte neutrofiltal skal være ≥ 1.000/mm3
• Absolute neutrophil count should be ≥ 1,000/mm3
MINDSTEKRAV TIL MÆRKNING PÅ BLISTER ELLER STRIP BLISTER TIL MAPPE
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS BLISTER FOR WALLET
93% af patienterne havde ECOG-performancestatus 0-1, og 12% havde ISS-stadie III ved baseline (N = 90).
Ninety three percent of patients had an ECOG performance status of 0-1 and 12% had baseline ISS stage III disease (N=90).
Mange af de patienter, der var inkluderet i forsøget, havde fremskreden sygdom med Durie-Salmon stadie III (69%) ved den initialt stillede diagnose og en behandlingshistorik med mindst to foregående behandlinger (60%) samt status som thalidomidrefraktær (63%).
Many of the patients enrolled in the study had advanced disease with Durie-Salmon Stage III (69%) at initial diagnosis and a treatment history of receiving at least 2 prior therapies (60%) and being thalidomide refractory (63%).
• synsforstyrrelser, ændringer i mental tilstand eller krampeanfald (posteriort reversibelt encefalopati-syndrom)
• changes in vision, changes in mental status, or seizures (posterior reversible encephalopathy syndrome)
Dag 8 Dag 9 til 14
Day 8 Days 9 to 14
Brug ikke lægemidlet efter den udløbsdato, der står på blisteren, blistermappen og pakningen efter EXP. Udløbsdatoen er den sidste dag i den nævnte måned.
Do not use this medicine after the expiry date which is stated on the blister, wallet and carton after EXP.
Alvorlige bivirkninger er rapporteret hos ≥ 2% af patienterne og omfattede trombocytopeni (2%) og diarré (2%).
Serious adverse reactions reported in ≥ 2% of patients included thrombocytopenia (2%) and diarrhoea (2%).
ixazomib er ikke dialyserbart og kan derfor gives uden hensyntagen til tidsplanen for dialyse (se pkt.
Ixazomib is not dialyzable and, therefore, can be administered without regard to the timing of dialysis (see section 5.2).
Da myelomceller danner mange proteiner, kan blokering af proteasomers virkning slå kræftcellerne ihjel.
Because myeloma cells produce a lot of proteins, blocking the action of proteasomes can kill the cancerous cells.
De fleste fund for målorganerne viste delvis til fuld restitution efter seponering med undtagelse af neuronale fund i den lumbale dorsale rodganglie og rygsøjlen.
The majority of target organ findings demonstrated partial to full recovery following discontinuation of treatment, with the exception of neuronal findings in the lumbar dorsal root ganglion and dorsal column.
Husk især at fortælle lægen, apotekspersonalet eller sygeplejersken, hvis du tager et af følgende lægemidler: carbamazepin, phenytoin, rifampicin og perikon (Hypericum perforatum).
In particular, tell your doctor, pharmacist or nurse if you are taking any of the following medicines: carbamazepine, phenytoin, rifampicin and St. John's wort (Hypericum perforatum).
I 9-måneders studiet (10 cyklusser), hvor hunde fik lægemidlet oralt efter et doseringsskema, der efterlignede det kliniske regime (28-dages cyklus), var de mikroskopiske neuronale fund generelt minimale og blev kun observeret ved 0,2 mg/kg (4 mg/m2).
In the 9-month study (10 cycles) in dogs orally administered with a dosing schedule mimicking the clinical regimen (28-day cycle), microscopic neuronal effects were generally minimal in nature and only observed at 0.2 mg/kg (4 mg/m2).
Blod og lymfesystem Trombocytopeni*
Blood and lymphatic system disorders Thrombocytopenia*
Spørg apoteketspersonalet, hvordan du skal bortskaffe medicinrester.
Ask your pharmacist how to throw away medicines you no longer use.
Meget almindelige bivirkninger, som kan forekomme hos flere end 1 ud af 10 personer:
Very common side effects may affect more than 1 in 10 people:
Uden for fase 3-studiet blev følgende alvorlige bivirkninger rapporteret sjældent: akut febril neutrofil dermatose (Sweets syndrom), Stevens-Johnsons syndrom, transversel myelitis, posteriort reversibelt encefalopati-syndrom, tumorlysesyndrom og trombotisk trombocytopenisk purpura.
Outside of the Phase 3 study, the following serious adverse reactions were rarely reported: acute febrile neutrophilic dermatosis (Sweet's syndrome), Stevens-Johnson syndrome, transverse myelitis, posterior reversible encephalopathy syndrome, tumour lysis syndrome and thrombotic thrombocytopenic purpura.
Ixazomib er ikke substrat for BCRP, MRP2 eller hepatiske OATP'er.
Ixazomib is not a substrate of BCRP, MRP2 or hepatic OATPs.
Kombinationen af ixazomib og lenalidomid udviste synergistiske cytotoksiske virkninger i myelomatosecellelinjer.
The combination of ixazomib and lenalidomide demonstrated synergistic cytotoxic effects in multiple myeloma cell lines.
Antiviral profylakse skal overvejes hos patienter, der behandles med ixazomib, for at reducere risikoen for reaktivering af herpes zoster.
Antiviral prophylaxis should be considered in patients being treated with ixazomib to decrease the risk of herpes zoster reactivation.