natgillin/translations-raw huggingface dataset:
· Allergiske reaktioner kan forekomme, og de fleste patienter vil få lette symptomer såsom kløe eller trykken for brystet.
· Allergic reactions can occur and most patients will have mild symptoms such as itching or tightness in the chest.
Som med alle terapeutiske proteiner er der med trastuzumabemtansin risiko for immunrespons.
As with all therapeutic proteins, there is the potential for an immune response to trastuzumab emtansine.
Nodulær regenerativ hyperplasi (NRH)
Nodular Regenerative Hyperplasia (NRH)
Overordnet var størstedelen af overfølsomhedsreaktionerne lette eller moderate i sværhedsgrad og forsvandt ved behandling.
Overall, the majority of hypersensitivity reactions were mild or moderate in severity and resolved upon treatment.
Der er ingen data fra anvendelse af trastuzumabemtansin til gravide kvinder.
There are no data from the use of trastuzumab emtansine in pregnant women.
In vitro var DM1 substrat for P-glykoprotein (P-gp).
In vitro, DM1 was a substrate of P-glycoprotein (P-gp).
Rekonstitueret Kadcyla-koncentrat skal fortyndes i polyvinylchlorid (PVC) eller latex-fri, PVC-fri polyolefin-infusionsposer.
The reconstituted Kadcyla solution should be diluted in polyvinyl chloride (PVC) or latex-free PVC-free polyolefin infusion bags.
Du får Kadcyla af en læge eller sygeplejerske på hospitalet: · Det gives i en vene via et drop (intravenøs infusion).
Kadcyla will be given to you by a doctor or nurse in a hospital or clinic: · It is given by a drip into a vein (intravenous infusion).
Infusionsvæsken må ikke fryses eller rystes under opbevaring.
Do not freeze or shake the infusion during storage.
· Kadcyla fås i pakker med 1 hætteglas.
· Kadcyla is available in packs containing 1 vial.
Der sås ingen dosissammenhæng i de kliniske studier.
No dose relationship was observed in clinical studies.
· Hvis du bliver gravid under behandling med Kadcyla, skal du straks kontakte lægen.
· If you do become pregnant during treatment with Kadcyla, tell your doctor straight away.
Patienterne fik strålebehandling og/eller hormonterapi samtidig med forsøgsbehandlingen i overensstemmelse med lokale retningslinjer.
Patients received radiotherapy and/or hormonal therapy concurrent with study treatment as per local guidelines.
I størstedelen af tilfældene var bivirkningen asymptomatisk grad 1 eller 2 fald i LVEF.
The majority of events were asymptomatic Grade 1 or 2 decrease in LVEF.
· Øvrige indholdsstoffer: ravsyre, natriumhydroxid (se afsnit 2 under ”Vigtig information om nogle af indholdsstofferne i Kadcyla”), saccharose og polysorbat 20
· The other ingredients are succinic acid, sodium hydroxide (see section 2 under ‘Important information about some of the ingredients of Kadcyla'), sucrose, and polysorbate 20.
Dato for første markedsføringstilladelse: 15. november 2013 Dato for seneste fornyelse: 17. september 2018
Date of latest renewal: 17 September 2018
Da mange lægemidler udskilles i humanmælk, og da der er risiko for alvorlige bivirkninger hos det ammede barn, bør kvinder holde op med at amme, inden behandling med trastuzumabemtansin påbegyndes.
Since many medicinal products are excreted in human milk and because of the potential for serious adverse reactions in breast-feeding infants, women should discontinue breast-feeding prior to initiating treatment with trastuzumab emtansine.
Hvis du udvikler en af disse reaktioner, vil de nedsætte infusionshastigheden eller stoppe infusionen, og de kan give dig behandling, som modvirker bivirkningerne.
If you develop a reaction, they will slow down or stop the infusion and may give you treatment to counteract the side effects.
(angivet i afsnit 6).
(see section 4.2).
For at bedre sporbarheden af biologiske lægemidler skal det administrerede lægemiddels handelsnavn og batchnummer altid registreres (eller angives) tydeligt i patientjournalen.
In order to improve traceability of biological medicinal products, the tradename and the batch number of the administered product should be clearly recorded (or stated) in the patient file.
På grund af den lave forekomst af ADA, kan der ikke konkluderes på antitrastuzumabemtansin-antistoffernes betydning for trastuzumabemtansins farmakokinetik, sikkerhed eller virkning.
Due to the low incidence of ADA, conclusions cannot be made on the impact of anti- trastuzumab emtansine antibodies on the pharmacokinetics, safety, and efficacy of trastuzumab emtansine.
· Gulfarvning af huden og det hvide i øjnene (gulsot) - dette kan være tegn på svær leverskade.
· Your skin and whites of your eyes get yellow (jaundice) - these could be signs of severe liver damage.
Hvis du glemmer eller udebliver fra en behandling med Kadcyla, skal du lave en ny aftale så hurtigt som muligt.
If you forget or miss your Kadcyla appointment, make another appointment as soon as possible.
Patienterne skal observeres under infusionen og i mindst 30 minutter efter infusionen.
Patients should be observed during the infusion and for at least 30 minutes after infusion.
Herefter justeres behandlingsskemaet, så det igen passer med et 3-ugers interval mellem doserne.
The schedule of administration should be adjusted to maintain a 3-week interval between doses.
I KATHERINE sås vedvarende behandlingsgavn af trastuzumabemtansin på IDFS i alle de præspecificerede subgrupper, der blev evalueret, hvilket understøtter det overordnede resultat.
In KATHERINE, consistent treatment benefit of trastuzumab emtansine for IDFS was seen in all the pre-specified subgroups evaluated, supporting the overall result.
Hvis en patient har behov for 2 udsættelser på grund af trombocytopeni, kan det overvejes at nedsætte dosis med 1 dosisniveau
If a patient requires 2 delays due to thrombocytopenia, consider reducing dose by one level.
Kadcyla opbevares på hospitalet af sundhedspersonalet.
Kadcyla will be stored by the health professionals at the hospital or clinic.
I tilfælde af en reel allergisk reaktion (hvor reaktionen bliver alvorligere ved efterfølgende infusioner), skal trastuzumabemtansin seponeres permanent.
In the event of a true hypersensitivity reaction (in which severity of reaction increases with subsequent infusions), trastuzumab emtansine treatment must be permanently discontinued.
● MCC-linkeren er designet til at begrænse systemisk frigørelse og øger målrettet afgivelse af DM1, hvilket er påvist ved meget lave niveauer af frit DM1 i plasma.
· The MCC linker is designed to limit systemic release and increase targeted delivery of DM1, as demonstrated by detection of very low levels of free DM1 in plasma.
Tal med lægen om, hvilken type prævention der vil være bedst for dig.
Talk to your doctor about the best contraception for you.
Patienterne blev randomiseret (1:1) til trastuzumab eller trastuzumabemtansin.
Patients were randomized (1:1) to receive trastuzumab or trastuzumab emtansine.
I alt 991 patienter randomiseredes til trastuzumabemtansin eller lapatinib plus capecitabin:
A total of 991 patients were randomised to trastuzumab emtansine or lapatinib plus capecitabine as follows:
ADMINISTRATIONSMETODE Til intravenøs anvendelse efter rekonstitution og fortynding
METHOD OF ADMINISTRATION For intravenous use after reconstitution and dilution
● medicin mod depression, såsom nefazodon
· medicine for depression called nefazodone
Patienter behandlet med trastuzumabemtansin har øget risiko for at udvikle dysfunktion af venstre ventrikel.
Patients treated with trastuzumab emtansine are at increased risk of developing left ventricular dysfunction.
Reaktionerne forekommer hyppigst inden for 24 timer efter infusionen.
These reactions have been observed more frequently within 24 hours of infusion.
Dosis af trastuzumabemtansin bør ikke titreres op igen, når den først er reduceret.
Trastuzumab emtansine dose should not be re-escalated after a dose reduction is made.
Infusionsstedet skal overvåges omhyggeligt for eventuel subkutan infiltration under administrationen (se pkt.
The infusion site should be closely monitored for possible subcutaneous infiltration during administration (see section 4.8).
· du tidligere har haft leverproblemer.
· you have any history of liver problems.
· Uventede blå mærker og blødning (fx næseblod).
· Unexpected bruising and bleeding (such as nose bleeds).
Behandling af symptomgivende bivirkninger kan kræve midlertidig afbrydelse, dosisreduktion eller seponering af trastuzumabemtansin, som beskrevet i retningslinjerne i teksten samt i tabel 1 og 2.
Management of symptomatic adverse reactions may require temporary interruption, dose reduction, or treatment discontinuation of trastuzumab emtansine as per guidelines provided in text and Tables 1 and 2 .
Yderligere endepunkter omfattede IDFS inklusive anden primær kræft (ikke bryst), sygdomsfri overlevelse (DFS), samlet overlevelse (OS) samt interval uden fjernrecidiv (DRFI).
Additional endpoints included IDFS including second primary non-breast cancer, disease-free survival (DFS), overall survival (OS), and distant recurrence-free interval (DRFI).
Beskrivelse af de vigtigste forskelle mellem trastuzumabemtansin og trastuzumab i henhold til indikation, dosering og administration samt forskelle i pakninger.
Description of the key differences between trastuzumab emtansine and trastuzumab in relation to indication, dose, administration and packaging differences.
I tabel 3 præsenteres samlede data fra den overordnede behandlingsperiode i mBC-studierne (N= 1871; median for antal trastuzumabemtansin-serier var 10) og i KATHERINE (N=740; median for antal serier var 14).
Table 3 shows pooled data from the overall treatment period in the MBC studies (N= 1871; median number of cycles of trastuzumab emtansine was 10) and in KATHERINE (N=740; median number of cycles was 14).
Et hætteglas med Kadcyla, rekonstitueret med vand til injektionsvæske (medfølger ikke) er stabilt i 24 timer ved 2ºC - 8ºC efter rekonstitution og må ikke fryses.
A vial of Kadcyla reconstituted with water for injections (not supplied) is stable for 24 hours at 2ºC - 8 ºC after reconstitution and must not be frozen.
Dette lægemiddel indeholder mindre end 1 mmol natrium (23 mg) per dosis og er dermed i det væsentlige ‘natriumfrit'.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodiumfree'.
Leverfunktionen skal monitoreres inden behandlingsstart og inden hver enkelt dosis.
Liver function should be monitored prior to initiation of treatment and each dose.
Stigningen i aminotransferaser var generelt forbigående.
Transaminase elevations were generally transient.
· du får blodfortyndende medicin (fx warfarin eller heparin).
· you are receiving treatment with blood thinning medicines (e.g. warfarin, heparin).
Det vides ikke, om indholdsstofferne i Kadcyla udskilles i mælken.
It is not known whether the ingredients in Kadcyla pass into breast-milk.
Patienterne (n=110) fik 3,6 mg/kg trastuzumabemtansin intravenøst hver 3. uge indtil sygdomsprogression eller uacceptabel toksicitet.
Patients (n = 110) received 3.6 mg/kg of trastuzumab emtansine intravenously every 3 weeks until disease progression or unacceptable toxicity.
Hos de fleste patienter forsvandt disse reaktioner i løbet af adskillige timer til en dag efter, infusionen var afsluttet.
In most patients, these reactions resolved over the course of several hours to a day after the infusion was terminated.
Dette kan være tegn på en inflammation (betændelseslignende reaktion) i lungerne, som kan være alvorlig og i værste fald dødelig.
These may be signs of inflammation of your lung, which may be serious, and even fatal.
Trastuzumabemtansin (N=740) Alle grader % Grad 3 (%) Grad 4 (%)
Trastuzumab emtansine (N=740) All Grade % Grade 3 (%) Grade 4 (%)
Du skal straks fortælle det til lægen, hvis du uventet oplever blå mærker eller blødning.
You should tell your doctor immediately if you notice any unexpected bruising or bleeding.
Beslutningen om at administrere trastuzumabemtansin hos mBC patienter med lav LVEF bør kun foretages efter nøje risk/benefit-vurdering, og hjertefunktion hos disse patienter skal nøje overvåges (se pkt.
The decision to administer trastuzumab emtansine in MBC patients with low LVEF must be made only after careful benefit risk assessment and cardiac function should be closely monitored in these patients (see section 4.8).
Derudover har eksploratoriske analyser vist, at kovariaternes (dvs. nyrefunktion, etnicitet og alder) betydning for farmakokinetikken for totaltrastuzumab og -DM1 var begrænset og ikke klinisk relevant.
In addition, exploratory analysis showed that the impact of covariates (i.e., renal function, race and age) on the pharmacokinetics of total trastuzumab and DM1 was limited and was not clinically relevant.
Aminotransferasestigninger var generelt forbigående med maksimal stigning på dag 8 efter administration og efterfølgende bedring til grad 1 eller mindre inden næste cyklus.
Transaminase elevations were generally transient with peak elevation at day 8 after administration of therapy and subsequent recovery to Grade 1 or less prior to the next cycle.
Der er observeret dødelige blødningshændelser i såvel mBC- som eBC-gruppen.
Cases of bleeding events with a fatal outcome have been observed in both MBC and EBC.
Størrelsesordenen af disse kovariaters effekt på eksponeringen af trastuzumabemtansin antyder dog, at kovariaterne sandsynligvis ikke vil have klinisk relevant effekt på trastuzumabemtansin-eksponeringen.
However, the magnitude of effect of these covariates on trastuzumab emtansine exposure suggests that these covariates are unlikely to have any clinically meaningful effect on trastuzumab emtansine exposure.
● Du skal fortsætte med at bruge prævention i mindst 7 måneder efter din sidste dosis Kadcyla.
· You should continue to take your contraception for at least 7 months after your last dose of
Det primære endepunkt i studiet var overlevelse uden invasiv sygdom (IDFS).
The primary efficacy endpoint of the study was Invasive Disease-Free Survival (IDFS).
Lægen vil undersøge dig for eventuelle symptomer på neurologiske problemer.
Your doctor will monitor you for signs and symptoms of neurological problems.
Der sås ingen signifikant forskel i trastuzumabemtansins farmakokinetik hos patienter <65 år (n=577), patienter i aldersgruppen 65-75 år (n=78) eller patienter >75 år (n=16).
No significant difference was observed in the PK of trastuzumab emtansine among patients < 65 years (n = 577), patients between 65-75 years (n = 78) and patients > 75 years (n = 16).
IDFS defineres som tid fra randomiseringsdato til første recidiv af ipsilateral invasiv brysttumor, recidiv af ipsilateral lokal eller regional brystkræft, fjernrecidiv, kontralateral invasiv brystkræft eller død af enhver årsag.
IDFS was defined as the time from the date of randomization to first occurrence of ipsilateral invasive breast tumor recurrence, ipsilateral local or regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, or death from any cause.
Hos patienter med mBC var den samlede forekomst af perifer neuropati 29,0% og 8,6% for grad ≥2.
In patients with MBC, the overall incidence of peripheral neuropathy was 29.0% and 8.6% for Grade ≥ 2.
· Vend forsigtigt hætteglasset, indtil koncentratet er helt opløst.
· Swirl the vial gently until completely dissolved.
Sikkerhed af trastuzumabemtansin er evalueret hos 2.611 brystkræftpatienter i kliniske studier.
The safety of trastuzumab emtansine has been evaluated in 2,611 breast cancer patients in clinical studies.
Metastatisk brystkræft
Metastatic Breast Cancer
Nedsat fertilitet og teratogenicitet
Impairment of fertility and teratogenicity
intravenøst hver 3. uge (n=70).
3 weeks (n = 70).
Tid til symptomprogression, defineret ved et fald på 5 point i TOI-B-score (Trials Outcome Index-Breast), der er en del af FACT-B QoL-spørgeskemaet (Functional Assessment of Cancer Therapy-Breast Quality of Life), blev også vurderet i løbet af det kliniske studie.
Time to symptom progression, as defined by a 5-point decrease in the score derived from the Trials Outcome Index-Breast (TOI-B) subscale of the Functional Assessment of Cancer Therapy-Breast Quality of Life (FACT-B QoL) questionnaire was also assessed during the clinical study.
● DM1, den cytotoksiske komponent i trastuzumabemtansin, bindes til tubulin.
· DM1, the cytotoxic component of trastuzumab emtansine, binds to tubulin.
Tabel 6 Resumé af effekt fra Studie BO27938 (KATHERINE) Trastuzumab N = 743
Table 6 Summary of efficacy from study BO27938 (KATHERINE) Trastuzumab N = 743
DM1 hæmmede ikke major CYP-enzymer in vitro.
DM1 did not inhibit major CYP450 enzymes in vitro.
Reaktionerne var sædvanligvis lette eller moderate og omfattede erytem, ømhed, hudirritation, smerter eller hævelse på infusionsstedet.
These reactions were usually mild or moderate and comprised erythema, tenderness, skin irritation, pain, or swelling at the infusion site.
Hvis du holder op med Kadcyla-behandlingen Du må ikke stoppe behandlingen med Kadcyla uden at have snakket med lægen først.
If you stop Kadcyla treatment Do not stop treatment with this medicine without talking to your doctor first.
Farmakoterapeutisk klassifikation: Antineoplastiske stoffer, andre antineoplastiske stoffer, monoklonale antistoffer, ATC-kode: L01XC14
Pharmacotherapeutic group: Antineoplastic agents, other antineoplastic agents, monoclonal antibodies, ATC code: L01XC14
I gennemsnit konjugeres 3,5 DM1-molekyler til ét trastuzumabmolekyle.
An average of 3.5 DM1 molecules are conjugated to each molecule of trastuzumab.
Kemisk og fysisk holdbarhed af den rekonstituerede opløsning er dokumenteret at være op til 24 timer ved 2 °C til 8 °C.
Chemical and physical in-use stability of the reconstituted solution has been demonstrated for up to 24 hours at 2°C to 8°C.
Objektiv responsrate var 58,0% med trastuzumab plus docetaxel og 64,2% med trastuzumabemtansin.
The objective response rate (ORR) was 58.0% with trastuzumab plus docetaxel and 64.2% with trastuzumab emtansine.
● have udviklet sygdomsrecidiv under adjuverende behandling eller inden for seks måneder efter, den adjuverende behandling er afsluttet.
· Developed disease recurrence during or within six months of completing adjuvant therapy.
Medianalder for patienter randomiseret til trastuzumabemtansin var 53 år; de fleste patienter var kvinder (99,8%), størstedelen var kaukasere (72%), og 57% havde østrogen-receptor- og/eller progesteron-receptorpositiv sygdom.
For patients randomised to trastuzumab emtansine, the median age was 53 years, most patients were female (99.8%), the majority were Caucasian (72%), and 57% had oestrogen-receptor and/or progesterone-receptor positive disease.
Studiet sammenlignede trastuzumabemtansins sikkerhed og virkning med sikkerheden og virkningen af lapatinib plus capecitabin.
The study compared the safety and efficacy of trastuzumab emtansine with that of lapatinib plus capecitabine.
De fleste af de indberettede bivirkninger var af sværhedsgrad 1 eller 2.
The majority of ADRs reported were of Grade 1 or 2 severity.
Dette lægemiddel må ikke blandes med andre lægemidler end dem, der er anført under pkt.
This medicinal product must not be mixed or diluted with other medicinal products except those mentioned in section 6.6.
Figur 3 Kaplan-Meier-kurver for samlet overlevelse
Figure 3 Kaplan-meier curve of overall survival
Giv samme dosisniveau
Treat at the same dose level
Forhøjet alkalisk fosfatase i blodet, forhøjet bilirubin i blodet
Blood alkaline phosphatase increased, blood bilirubin increased
Opbevar altid lægemidlet i den lukkede originalpakke i køleskab, ved en temperatur på 2ºC - 8ºC.
Always keep this medicine in the closed original pack at a temperature of 2ºC - 8 ºC in a refrigerator.
Trastuzumabemtansin (N=490) Alle grader (%) Grad 3 (%)
Trastuzumab emtansine (N=490) All Grades (%) Grade 3 (%) Grade 4 (%)
Kadcyla (trastuzumabemtansin) og Herceptin (trastuzumab) er to meget forskellige lægemidler med forskellige aktive indholdsstoffer, og de må aldrig erstatte hinanden.
Kadcyla (trastuzumab emtansine) and Herceptin (trastuzumab) are two very different products with different active substances never to be used interchangeably.
Der er indberettet ASAT- og ALAT-forhøjelser grad 3 og 4 hos henholdsvis 4,2% og 2,7% af patienterne med mBC; disse forekom sædvanligvis i de første behandlingscyklusser (1-6).
Grade 3 or 4 increased AST and ALT were reported in 4.2% and 2.7% of patients with MBC respectively and usually occurred in the early treatment cycles (1-6).
Lægen eller sundhedspersonalet vil holde øje med, om du får disse bivirkninger.
Your doctor or nurse will check to see whether you are having any of these side effects.
DM1 var ikke mutagent i en in vitro bakteriel mutationstest (Ames).
DM1 was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay.
Medianværdi for varighed af respons, vurderet af en uafhængig komité, blev ikke nået (95% konfidensinterval 4,6 måneder til ikke estimérbar).
The median duration of response by IRC was not reached (95% CI, 4.6 months to not estimable).
Der er ikke udført fertilitetsstudier med dyr for at evaluere effekten af trastuzumabemtansin.
No fertility studies in animals have been performed to evaluate the effect of trastuzumab emtansine.
Tumorprognostiske karakteristika omfattede hormonreceptorstatus (positiv: 72,3%, negativ: 27,7%), klinisk stadie ved præsentation (inoperabel: 25,3%, operabel: 74,8%) og patologisk nodalstatus efter præ-operativ behandling (nodalpositiv: 46,4%, nodalnegativ eller ikke vurderet: 53,6%) var ensartet behandlingsarmene imellem.
Tumor prognostic characteristics including hormone receptor status (positive: 72.3%, negative: 27.7%), clinical stage at presentation (inoperable: 25.3%, operable: 74.8%) and pathological nodal status after preoperative therapy (node positive: 46.4%, node negative or not evaluated: 53.6%) were similar in the study arms.
Der er efter markedsføring indberettet tilfælde af oligohydramnios, nogle forbundet med dødelig lungehypoplasi, hos gravide kvinder behandlet med trastuzumab.
In the post-marketing setting, cases of oligohydramnios, some associated with fatal pulmonary hypoplasia, have been reported in pregnant women receiving trastuzumab.
Hvis det ikke anvendes straks, kan de rekonstituerede hætteglas opbevares i op til 24 timer ved 2°C til 8°C, forudsat at rekonstituering fandt sted under kontrollerede og validerede aseptiske forhold.
If not used immediately, the reconstituted vials can be stored for up to 24 hours at 2°C to 8°C, provided it was reconstituted under controlled and validated aseptic conditions, and must be discarded thereafter.
Kadcyla forsinkede patient-rapporteret tid til symptomprogression i 7,1 måned sammenlignet med 4,6 måned i kontrolarmen (hazard ratio 0,796 (0,667; 0,951); p-værdi 0,0121).
Kadcyla delayed patient-reported time to symptom progression for 7.1 months compared with 4.6 months for the control arm (Hazard Ratio 0.796 (0.667, 0.951); p-value 0.0121).
· Hvis du tåler den første infusion godt, kan næste infusion gives i løbet af 30 minutter.
· If the first infusion is well tolerated, the infusion on your next visit may be given over 30 minutes.
Indehaveren af markedsføringstilladelsen skal aftale indholdet og formen af uddannelsesmateriale for Kadcyla (trastuzumabemtansin) og en kommunikationsplan med den relevante nationale myndighed før lancering af Kadcyla (trastuzumabemtansin) i hvert enkelt medlemsland.
The MAH shall agree the content and format of the Kadcyla (trastuzumab emtansine) educational material and a communication plan with the National Competent Authority in the Member State before Kadcyla (trastuzumab emtansine) is launched in each Member State.
Det Europæiske Lægemiddelagentur har dispenseret fra kravet om at fremlægge resultaterne af studier med trastuzumabemtansin i alle undergrupper af den pædiatriske population ved indikationen brystkræft (se pkt.
The European Medicines Agency has waived the obligation to submit the results of studies with trastuzumab emtansine in all subsets of the paediatric population in breast cancer (see section 4.2 for information on paediatric use).
Der er ikke set akkumulering af trastuzumabemtansin efter gentagen dosering ved intravenøs infusion hver 3. uge.
No accumulation of trastuzumab emtansine was observed after repeated dosing of intravenous infusion every 3 weeks.