FrancophonIA/ELRC3.0 huggingface dataset:
English: Neurologic reactions including dizziness, gait disturbance and paraesthesia were reported in patients receiving larotrectinib (see section 4.8).
Danish: Neurologiske reaktioner, herunder svimmelhed, gangbesvær og paræstesi blev rapporteret hos patienter, der fik larotrectinib (se pkt.
English: In particular, tell your doctor, pharmacist or nurse if you are taking any of the following medicines: - medicines used to treat fungal or bacterial infections called itraconazole, voriconazole,
Danish: Fortæl det især til lægen, apotekspersonalet eller sygeplejersken, hvis du tager nogle af de følgende lægemidler: - lægemidler, der anvendes til at behandle svampe- eller bakterieinfektioner, kaldet itraconazol,
English: Table 1: Recommended dose modifications for VITRAKVI for adverse reactions Dose modification
Danish: Tabel 1: Anbefalede dosismodifikationer for VITRAKVI for bivirkninger Dosismodifikation
English: In a 1-month repeat-dose study in rats, fewer corpora lutea, increased incidence of anestrus and decreased uterine weight with uterine atrophy were observed and these effects were reversible.
Danish: I et 1-måned langt forsøg med gentagne doser hos rotter blev der observeret færre corpora lutea, en øget forekomst af anøstrus og en nedsat livmodervægt med livmoderatrofi, og disse virkninger var reversible.
English: Effect of larotrectinib on substrates of PXR regulated enzymes In vitro studies indicate that larotrectinib may induce PXR regulated enzymes (e.g. CYP2C family and UGT).
Danish: Virkningen af larotrectinib på substrater af PXR regulerede enzymer In vitro studier indikerer, at larotrectinib kan inducere PXR regulerede enzymer (f.eks. CYP2C familien og UGT).
English: Overall response rate (ORR) % (n)
Danish: Samlet responsrate (ORR)a % (n)
English: Pull the plunger down to the mark equal to the dose in mL prescribed by your doctor.
Danish: - Træk stemplet ned til mærkningen, som svarer til dosen i ml, som lægen har ordineret.
English: The target for larotrectinib is the TRK family of proteins inclusive of TRKA, TRKB, and TRKC that are encoded by NTRK1, NTRK2 and NTRK3 genes, respectively.
Danish: Målet for larotrectinib er TRK-proteinfamilien, herunder TRKA, TRKB og TRKC, der kodes af hhv. NTRK1-, NTRK2- og NTRK3-generne.
English: Pharmacotherapeutic group: Antineoplastic and immunomodulating agents, antineoplastic agents, protein kinase inhibitors, ATC code: L01XE53.
Danish: Farmakoterapeutisk klassifikation: Antineoplastiske og immunmodulerende stoffer, antineoplastiske stoffer, proteinkinaseinhibitor, ATC-kode: L01XE53
English: Adult and paediatric patients with body surface area of at least 1.0 m2
Danish: Voksne og pædiatriske patienter med et legemsoverfladeareal på mindst 1,0 m2
English: Larotrectinib is an adenosine triphosphate (ATP)-competitive and selective tropomyosin receptor kinase (TRK) inhibitor that was rationally designed to avoid activity with off-target kinases.
Danish: Larotrectinib er en adenosintriphosphat (ATP)-kompetitiv og selektiv tropomyosinreceptorkinase (TRK)-inhibitor, der er blevet rationelt designet til at undgå aktivitet med off-target kinaser.
English: VITRAKVI can increase the amount of the liver enzymes ALT and AST in your blood.
Danish: VITRAKVI kan øge mængden af leverenzymerne ALAT og ASAT i dit blod.
English: Typical tube diameter, tube lengths and derived prime volumes are presented in Table 7.
Danish: Typiske sondediametre, sondelængder og afledte primevolumener vises i tabel 7.
English: Children
Danish: Barn
English: Patients should be advised not to drive and use machines, until they are reasonably certain VITRAKVI therapy does not affect them adversely (see section 4.4).
Danish: Patienterne skal rådes til ikke at føre motorkøretøj og betjene maskiner, indtil de er rimeligt sikre på, at behandlingen med VITRAKVI ikke påvirker dem negativt (se pkt.
English: Talk to your doctor, pharmacist or nurse or go to a hospital straight away.
Danish: Kontakt lægen, apotekspersonalet eller sygeplejersken, eller tag straks på hospitalet.
English: No clinical studies have been performed to investigate interactions with OATP1B1 substrates.
Danish: Der er ikke udført kliniske interaktionsstudier med OATP1B1-substrater.
English: - feeling dizzy, tingling, feeling numb, or a burning feeling in your hands and feet (very common side effect, may affect more than 1 in 10 people), difficulty walking normally (common side effect, may affect up to 1 in 10 people).
Danish: - Svimmelhed, prikkende, følelsesløs fornemmelse eller en brændende fornemmelse i hænder og fødder (meget almindelig bivirkning, kan forekomme hos flere end 1 ud af 10 personer), gangbesvær (almindelig bivirkning, kan forekomme hos op til 1 ud af 10 personer).
English: Co-administration with CYP3A4/P-gp inducers
Danish: Samtidig administration med CYP3A4/P-gp induktorer
English: Patients (n=102)
Danish: Patienter (n = 102)
English: In all cases, patients with evidence of anti-tumour activity who required a dose reduction were able to continue dosing at a reduced dose and/or schedule (see section 4.4).
Danish: I alle tilfældene var patienterne med evidens for anti-tumoraktivitet, hvor en dosisreduktion var nødvendig, i stand til at fortsætte doseringen med nedsat dosis og/ eller skema (se pkt.
English: If withheld, the VITRAKVI dose should be modified when resumed (see section 4.2).
Danish: Hvis VITRAKVI-dosen tilbageholdes, skal den modificeres, når den genoptages (se pkt.
English: Adult
Danish: Voksen
English: In in vitro and in vivo tumour models, larotrectinib demonstrated anti-tumour activity in cells with constitutive activation of TRK proteins resulting from gene fusions, deletion of a protein regulatory domain, or in cells with TRK protein overexpression.
Danish: I in vitro- og in vivo-tumormodeller viste larotrectinib antitumoraktivitet i celler med konstitutiv aktivering af TRK-proteiner som resultat af genfusioner, deletion af et regulatorisk proteindomæne, eller i celler med overekspression af TRK-protein.
English: There are no clinical data on the effect of larotrectinib on fertility.
Danish: Der foreligger ingen kliniske data om larotrectinibs virkning på fertilitet.
English: Women of childbearing potential should have a pregnancy test prior to starting treatment with VITRAKVI.
Danish: Kvinder i den fertile alder bør få taget en graviditetstest, før de påbegynder behandlingen med VITRAKVI.
English: The pooled efficacy results for overall response rate, duration of response and time to first response, in the primary analysis population (n=93) and with post-hoc addition of primary CNS tumours (n=9) resulting in the pooled population (n=102), are presented in Table 5 and Table 6.
Danish: De poolede effektresultater for samlet responsrate, varighed af respons og tid til første respons, i den primære analysepopulation (n = 93), og med post-hoc tilføjelse af primære CNS tumorer (n = 9), hvilket resulterede i den poolede population (n = 102), er vist i tabel 5 og tabel 6.
English: What you need to know before you take VITRAKVI Do not take VITRAKVI if
Danish: Det skal du vide, før du begynder at tage VITRAKVI Tag ikke VITRAKVI
English: The oral solution should be administered by mouth using an oral syringe of 1 mL or 5 mL volume or enterally by using a nasogastric feeding tube.
Danish: Den orale opløsning bør administreres via munden med en oral sprøjte på 1 ml eller 5 ml eller enteralt med en nasogastrisk sonde.
English: Adolescents (n=8)c
Danish: Unge (n=8)c
English: Larotrectinib had minimal activity in cell lines with point mutations in the TRKA kinase domain, including the clinically identified acquired resistance mutation, G595R.
Danish: Larotrectinib havde minimal aktivitet i cellelinjer med punktmutationer i TRKA-kinasedomænet, inklusive den klinisk identificerede resistensmutation, G595R.
English: Common (may affect up to 1 in 10 people): - change in how things taste (dysgeusia) - increased amount of “alkaline phosphatase” in blood tests (very common in children).
Danish: Almindelig (kan forekomme hos op til 1 ud af 10 personer): - ændret smagssans (dysgeusi) - forøget mængde af ”basisk fosfatase” i blodprøver (meget almindeligt hos børn).
English: Of 125 patients in the overall safety population who received VITRAKVI, 28 (22%) patients were 65 years or older and 8 (6%) patients were 75 years or older.
Danish: Ud af de 125 patienter i den samlede sikkerhedspopulation, som fik VITRAKVI, var 28 (22 %) patienter 65 år eller ældre, og 8 (6 %) patienter var i alderen 75 år eller ældre.
English: Tube prime volume (mL)
Danish: Sondeprimevolumen (ml)
English: The safety of VITRAKVI was evaluated in 125 patients with TRK fusion-positive cancer in one of three clinical trials, Studies 1, 2 (“NAVIGATE”), and 3 (“SCOUT”).
Danish: VITRAKVIs sikkerhedsprofil blev evalueret hos 125 patienter med TRK-fusionspositiv cancer i et af de tre kliniske studier, studie 1, 2 (”NAVIGATE”) og 3 (”SCOUT”).
English: • Phase 1/2 multinational, open-label, dose escalation and expansion study; Phase 2 expansion cohort required advanced solid tumours with an NTRK gene fusion, including locally advanced infantile fibrosarcoma
Danish: • Fase 1/2 multinationalt, åbent, dosisoptrapnings- og forlængelsesstudie, fase 2 forlængelseskohorte krævede fremskredne solide tumorer med en NTRK-genfusion, herunder lokalt fremskreden infantil fibrosarkom
English: Breast-feeding should be discontinued during treatment with VITRAKVI and for 3 days following the final dose.
Danish: Amning skal ophøre under behandling med VITRAKVI og i 3 dage efter den sidste dosis.
English: Package leaflet: Information for the patient VITRAKVI 20 mg/mL oral solution larotrectinib This medicine is subject to additional monitoring.
Danish: Indlægsseddel: Information til patienten VITRAKVI 20 mg/ml oral opløsning larotrectinib Dette lægemiddel er underlagt supplerende overvågning.
English: All primary CNS tumour patients had received prior cancer treatment (surgery, radiotherapy and/or previous systemic therapy).
Danish: Alle patienter med primære CNS-tumorer havde tidligere fået cancerbehandling (kirurgi, strålebehandling og/eller tidligere systemisk behandling).
English: In order to further investigate the long-term toxicity and developmental effects of larotrectinib in paediatric patients, with particular focus on neurodevelopment including cognitive function, the MAH should submit the final report of study LOXO-TRK-15003 (SCOUT) including 5 year follow up data.
Danish: For yderligere at undersøge den langvarige toksicitet og de udviklingsmæssige virkninger af larotrectinib hos pædiatriske patienter, med særligt fokus på neurologisk udvikling herunder kognitiv funktion, skal indehaveren af markedsføringstilladelsen indsende den færdige rapport af LOXO-TRK-15003 (SCOUT)-studiet herunder data fra de 5 års opfølgning.
English: Skin lesions were not seen in monkeys.
Danish: Hudlæsionerne blev ikke observeret hos aber.
English: It is therefore not known if the presence of a concomitant oncogenic driver in addition to an NTRK gene fusion affects the efficacy of TRK inhibition.
Danish: Det vides derfor ikke, om samtidig tilstedeværelse af onkogene faktorer, ud over en NTRK-genfusion, påvirker effekten af TRKinhibering.
English: Congenital mesoblastic nephromaa
Danish: Medfødt mesoblastisk nefroma
English: The safety population characteristics were comprised of patients with a median age of 45 years (range: 0.1, 80) with 30% of patients being paediatric patients.
Danish: Sikkerhedspopulationens karakteristik bestod af patienter med en medianalder på 45 år (interval: 0,1; 80), hvoraf 30 % var pædiatriske patienter.
English: Ask your pharmacist how to throw away medicines you no longer use.
Danish: - Spørg apotekspersonalet, hvordan du skal bortskaffe medicinrester.
English: Table 4: Clinical studies contributing to the efficacy analyses in solid and primary CNS tumours Study name, design and patient population
Danish: Tabel 4: Kliniske studier, der bidrog til virkningsanalyser af solide og primære CNS-tumorer Studienavn, design og patientpopulation
English: For Grade 3 or 4 adverse reactions: - VITRAKVI should be withheld until the adverse reaction resolves or improves to baseline or
Danish: For grad 3- eller 4-bivirkninger: - VITRAKVI bør pauseres, indtil bivirkningen går væk eller vender tilbage til niveauet ved baseline eller grad 1.
English: Permanent discontinuation of VITRAKVI for treatment emergent adverse reactions, regardless of attribution occurred in 3% of patients (one case each of ALT increase, AST increase, intestinal perforation, jaundice, small intestinal obstruction).
Danish: Permanent seponering af VITRAKVI for behandlingsrelaterede bivirkninger, uanset tilskrivning, forekom hos 3 % af patienterne (ét tilfælde ved hver ALAT-forhøjelse, ASAT-forhøjelse, perforering af tarmen, gulsot, tyndtarm obstruktion).
English: If concomitant use of these CYP3A substrates with narrow therapeutic range is required in patients taking VITRAKVI, dose reductions of the CYP3A substrates may be required due to adverse reactions.
Danish: Hvis det er nødvendigt at bruge disse CYP3Asubstrater med snævert terapeutisk interval til patienter, der samtidigt tager VITRAKVI, kan det være nødvendigt at reducere dosis af CYP3A-substrater som følge af bivirkninger.
English: Mixing with the feeding formulas could lead to tube blockages.
Danish: Blandes det med ernæringsformuleringer, kan det føre til blokering af sonden.
English: Due to the rarity of TRK fusion-positive cancer, patients were studied across multiple tumour types with a limited number of patients in some tumour types, causing uncertainty in the ORR estimate per tumour type.
Danish: På grund af den TRK fusionspositive cancers sjældenhed blev patienter undersøgt på tværs af flere tumortyper med et begrænset antal patienter i nogle tumortyper, hvilket giver forårsager usikkerhed i ORR-estimatet pr. tumortype.
English: - For instructions for use of oral syringes and feeding tubes see section 6.6.
Danish: - For instruktioner i anvendelse af orale sprøjter og ernæringssonder, se pkt.
English: VITRAKVI is available as a capsule or oral solution with equivalent oral bioavailability and may be used interchangeably.
Danish: VITRAKVI fås som en kapsel eller oral opløsning med tilsvarende oral biotilgængelighed og der kan skiftes mellem de to formuleringer.
English: Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.
Danish: Yderligere opløsninger om dette lægemiddel findes på Det Europæiske Lægemiddelagenturs hjemmeside http://www.ema.europa.eu.
English: - Take the oral syringe and ensure that the plunger is fully depressed.
Danish: - Tag den orale sprøjte og sørg for, at stemplet er trykket helt ned.
English: There are no data from the use of larotrectinib in pregnant women.
Danish: Der er ingen data fra anvendelse af larotrectinib til gravide kvinder.
English: No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A) (see section 5.2).
Danish: Ingen dosisjustering anbefales hos patienter med let nedsat leverfunktion (Child-Pugh A) (se pkt.
English: The recommended dose modifications for VITRAKVI for adverse reactions are provided in Table 1.
Danish: De anbefalede dosismodifikationer for VITRAKVI for bivirkninger kan ses i tabel 1.
English: In patients whose cancer is due to an altered NTRK gene, the change in the gene causes the body to make an abnormal protein called TRK fusion protein, which can lead to uncontrolled cell growth and cancer.
Danish: Hos patienter, hvis kræft skyldes et ændret NTRK-gen, vil ændringen i dette gen, få kroppen til at danne et unormalt protein, som kaldes TRK-fusionsprotein, der kan medføre ukontrolleret celledeling og kræft.
English: No clinical data is available on the effect of a moderate inducer, but a decrease in larotrectinib exposure is expected.
Danish: Der foreligger ingen kliniske data vedrørende virkningen af en moderat induktor, men der forventes et fald i eksponeringen for larotrectinib.
English: - Pull the plunger down to the graduation mark equal to the quantity in mL as prescribed.
Danish: - Træk stemplet ned til gradueringsmærket, der svarer til den ordinerede mængde i ml.
English: The effect may be quantitatively different depending on tumour type, as well as on concomitant genetic alterations (see section 5.1).
Danish: Virkningen kan være kvantitativt forskellig afhængig af tumortype, såvel som af samtidige genetiske ændringer (se pkt.
English: The calculated dose volume should be rounded to the nearest 0.1 mL.
Danish: Den beregnede dosisvolumen bør afrundes til den nærmeste 0,1 ml.
English: Patients with primary CNS tumours
Danish: Patienter med primære CNS-tumorer
English: Each carton contains one bottle of 100 mL oral solution.
Danish: Hver karton indeholder en flaske med 100 ml oral opløsning.
English: Cmax was observed to increase slightly by 1.1, 1.1 and 1.5-fold respectively.
Danish: Der blev observeret en let øget Cmax med hhv. 1,1; 1,1 og 1,5 gange.
English: The majority of adverse reactions were Grade 1 or 2 in severity (see Table 3) and were resolved without VITRAKVI dose modification or discontinuation.
Danish: Hovedparten af bivirkninger var grad 1 eller grad 2 i sværhedsgrad (se tabel 3), og de gik væk uden dosismodifikationer eller seponering af VITRAKVI.
English: Study 3 “SCOUT” NCT02637687
Danish: Studie 3“SCOUT” NCT02637687
English: Sodium dihydrogen phosphate dihydrate (E 339) Citric acid (E 330)
Danish: Natriumdihydrogenphosphatdihydrat (E 339) Citronsyre (E 330)
English: If the patient vomits after taking a dose, the patient should not take an additional dose to make up for vomiting.
Danish: Hvis patienten kaster op efter indtagelse af en dosis, må patienten ikke tage en til dosis som erstatning for den dosis, der blev kastet op.
English: Put the bottle cap on and tightly close the bottle - leave the adapter in the bottle.
Danish: - Sæt låget på flasken og luk flasken grundigt - lad adapteren blive i flasken.
English: Effect of gastric pH-elevating agents on larotrectinib Larotrectinib has pH-dependent solubility.
Danish: Virkning af stoffer, der forhøjer gastrisk pH på larotrectinib Larotrectinib har en pH-afhængig opløselighed.
English: The measured impact of any concomitant genomic alterations on larotrectinib efficacy is provided below (see clinical efficacy).
Danish: Den målte virkning af eventuelle samtidige genomiske ændringer på larotrectinib er angivet nedenfor (se klinisk virkning).
English: In 85 patients with wide molecular characterisation before larotrectinib treatment, the ORR in 48 patients who had other genomic alterations in addition to NTRK gene fusion was 58%, and in 37 patients without other genomic alterations ORR was 84%.
Danish: Hos 85 patienter med bred molekylær karakterisering før behandling med larotrectinib, var ORR 58 % hos 48 patienter, som havde andre genomiske forandringer ud over NTRK-genfusionen, og ORR var 84 % hos 37 patienter uden andre genomiske forandringer.
English: Effect of larotrectinib on other transporter substrates In vitro studies indicate that larotrectinib is an inhibitor of OATP1B1.
Danish: Virkning af larotrectinib på andre transportersubstrater In vitro studier indikerer, at larotrectinib er en inhibitor af OATP1B1.
English: The adverse reactions gait disturbance (17% versus 3% in under 65 years), and blood alkaline phosphatase increased (4% versus 2% in under 65 years) were more frequent in patients of 65 years or older.
Danish: Bivirkningerne gangbesvær (17 % versus 3 % hos patienter under 65 år) og forhøjet basisk fosfatase i blodet (4 % versus 2 % hos patienter under 65 år) var hyppigere hos patienter i alderen 65 år eller ældre.
English: reactions included two cases Neutrophil count decreased (Neutropenia) and one case of anaemia.
Danish: Grad 3 bivirkninger omfattede to tilfælde med nedsat neutrofiltal (neutropeni) og ét tilfælde af anæmi.
English: If you have any questions on how VITRAKVI works or why it has been prescribed for you, ask your doctor, pharmacist or nurse.
Danish: Hvis du har spørgsmål om, hvordan VITRAKVI virker, eller hvorfor du har fået det ordineret, skal du spørge lægen, apotekspersonalet eller sygeplejersken.
English: VITRAKVI has a moderate influence on the ability to drive and use machines.
Danish: VITRAKVI påvirker i moderat grad evnen til at føre motorkøretøj og betjene maskiner.
English: In vitro studies indicate that larotrectinib is not a substrate for either OATP1B1 or OATP1B3.
Danish: In vitro studier indikerer, at larotrectinib ikke er substrat for OATP1B1 eller OATP1B3.
English: At the time of analysis, the median duration of response had not been reached, 75% patients had responses which were ongoing with an estimated 88% of responses lasting 6 months or longer and 75% of responses lasting 12 months or longer.
Danish: På analysetidspunktet var den mediane varighed af responset ikke nået, 75 % af patienterne havde et igangværende respons, hvoraf det blev estimeret, at 88 % af dette respons ville vare i 6 måneder eller længere, og 75 % af responset ville vare i 12 måneder eller længere.
English: For the majority of neurologic reactions, onset occurred within the first three months of treatment.
Danish: For de fleste neurologiske reaktioner opstod disse i løbet af de første 3 måneders behandling.
English: Each carton contains 1 child-resistant plastic bottle containing 56 hard gelatine capsules.
Danish: Hver karton indeholder 1 børnesikret plastbeholder indeholdende 56 hårde gelatinekapsler.
English: In cancer patients given VITRAKVI capsules, peak plasma levels (Cmax) of larotrectinib were achieved at approximately 1 hour after dosing.
Danish: Hos cancerpatienter, der får VITRAKVI-kapsler, opnås maksimale plasmaniveauer (Cmax) af larotrectinib ca. 1 time efter dosering.
English: Push the plunger fully into the syringe and then put the syringe in the adapter opening.
Danish: - Skub stemplet helt ind i sprøjten, og sæt dernæst sprøjten på adapterens åbning.
English: Carcinogenicity studies have not been performed with larotrectinib.
Danish: Der er ikke udført carcinogenicitetsstudier med larotrectinib.
English: Larotrectinib was not mutagenic in bacterial reverse mutation (Ames) assays and in in vitro mammalian mutagenesis assays.
Danish: Larotrectinib var ikke mutagent i bakterielle revers mutationsanalyser (Ames) og i in vitro mutageneseanalyser hos pattedyr.
English: - parahydroxybenzoate: it may cause allergic reactions (possibly delayed).
Danish: - parahydroxybenzoat: det kan give allergiske reaktioner (kan optræde efter behandlingen)
English: In-frame gene fusion events resulting from chromosomal rearrangements of the human genes NTRK1, NTRK2, and NTRK3 lead to the formation of oncogenic TRK fusion proteins.
Danish: In-frame genfusionshændelser, som resultat af kromosomal omarrangering af de humane gener NTRK1, NTRK2 og NTRK3, fører til dannelsen af onkogene TRK-fusionsproteiner.
English: The pooled primary analysis set of efficacy includes 93 patients with TRK fusion-positive cancer enrolled across the three studies that had measurable disease assessed by RECIST v1.1, a non-CNS primary tumour and received at least one dose of larotrectinib.
Danish: Det poolede primære analysesæt for virkning omfattede 93 patienter med TRKfusionspositiv cancer inkluderet fra de 3 studier, der havde målbar sygdom vurderet ved RECIST v1.1, en ikke-CNS primær tumor og hvor de fik mindst en dosis larotrectinib.
English: Clinical signs of gastrointestinal toxicity were dose limiting in monkeys.
Danish: De kliniske tegn på mave-tarm-toksicitet var dosisbegrænsende hos aber.
English: SD: stable disease + denotes ongoing response a independent review committee analysis by RECIST v1.1 b patients with a primary CNS tumour were evaluated per investigator assessment using either RANO or RECIST v1.1
Danish: SD: stabil sygdom + benævner igangværende respons a analyse foretaget af uafhængig bedømmelseskomité med RECIST 1.1 b patienter med en primær CNS-tumor blev evalueret ifølge vurdering af investigator ved hjælp af enten RANO eller
English: Effect of larotrectinib on CYP3A substrates
Danish: Virkning af larotrectinib på CYP3A-substrater
English: Effect of larotrectinib on CYP2B6 substrates
Danish: Virkning af larotrectinib på CYP2B6-substrater