natgillin/translations-raw huggingface dataset:
Hvis neutropeni og/eller trombocytopeni fortsætter, og den næste behandlingsserie udsættes yderligere 7 dage, skal der udføres en knoglemarvsundersøgelse for at vurdere cellularitet og procentdel af blaster.
If neutropaenia and/or thrombocytopaenia persist and the next block of treatment is delayed another 7 days, a bone marrow assessment should be performed to assess cellularity and percentage of blasts.
Efter rekonstitution indeholder én flaske 99 ml oral suspension.
After constitution, one bottle contains 99 mL of oral suspension.
Hos disse patienter blev grad 3 eller 4 lungeødem og pulmonal hypertension hver især indberettet hos 1% af patienterne.
In these patients grade 3 or 4 pulmonary oedema and pulmonary hypertension were each reported in 1% of patients.
Dasatinib og dets metabolitter udskilles minimalt via nyrerne.
Dasatinib and its metabolites are minimally excreted via the kidney.
Resultaterne er angivet i Tabel 15.
Results are shown in Table 15.
I et understøttende studie fik 35 ud af 55 pædiatriske patienter SPRYCEL i kombination med kemoterapi i et diskontinuerligt dosisregime (to uger i behandling efterfulgt af en til to uger uden behandling), og 20 fik SPRYCEL i kombination med kemoterapi i et kontinuerligt dosisregime.
In a supportive study, of 55 paediatric patients, 35 received SPRYCEL in combination with chemotherapy on a discontinuous dosing regimen (two weeks on treatment followed by one to two weeks off) and 20 received SPRYCEL in combination with chemotherapy on a continuous dosing regimen.
Til patienter med behov for rifampicin eller andre CYP3A4-induktorer bør der anvendes alternative lægemidler med mindre enzyminduktionspotentiale.
In patients in whom rifampicin or other CYP3A4 inducers are indicated, alternative medicinal products with less enzyme induction potential should be used.
Pleuraeffusion grad 3 eller 4 kan kræve thoracocentese og iltbehandling.
Grade 3 or 4 pleural effusion may require thoracocentesis and oxygen therapy.
Ca. 5% af de SPRYCEL behandlede patienter, som havde normale baseline-niveauer, oplevede grad 3 eller 4 forbigående hypokalcæmi på et tidspunkt under forløbet.
Approximately 5% of the SPRYCEL-treated patients who had normal baseline levels experienced grade 3 or 4 transient hypocalcaemia at some time during the course of the study.
Pædiatrisk population (Ph+ CML-CP og Ph+ ALL)
Paediatric population (Ph+ CML-CP and Ph+ ALL)
Træk langsomt den ordinerede mængde SPRYCEL oral suspension ud af flasken ved at trække sprøjtens stempel nedad, indtil markeringen, der svarer til den ordinerede dosis, nås.
Slowly withdraw the amount of SPRYCEL oral suspension prescribed by pulling the syringe plunger until it reaches the marking of the dose prescribed.
Der er ingen erfaring med SPRYCEL behandling til børn under 1 år.
There is no experience with SPRYCEL treatment in children under 1 year of age.
Den højeste dosis medførte plasmaniveauer (AUC), der generelt svarer til niveauet hos mennesker ved den anbefalede startdosis på mellem 100 mg og 140 mg dagligt.
The highest dose resulted in a plasma exposure (AUC) level generally equivalent to the human exposure at the recommended range of starting doses from 100 mg to 140 mg daily.
Baseret på resultaterne fra et enkeltdosis farmakokinetisk studie, kan patienter med let, moderat eller alvorlig leverinsufficiens få den anbefalede startdosis (se pkt.
Based on the findings from a single-dose pharmacokinetic study, patients with mild, moderate or severe hepatic impairment may receive the recommended starting dose (see section 5.2).
Uomdannet dasatinib stod for henholdsvis 0,1% og 19% af dosis i urin og fæces, mens resten af dosis var metabolitter.
Unchanged dasatinib accounted for 0.1% and 19% of the dose in urine and faeces, respectively, with the remainder of the dose as metabolites.
Det anbefales derfor, at patienten er forsigtig, når der føres motorkøretøj eller betjenes maskiner.
Therefore, caution should be recommended when driving a car or operating machines.
Hyppigheden af major molekylært respons ved 24 måneder var 45% (35% for imatinib resistente patienter og 74% for imatinib intolerante patienter).
The rate of major molecular response at 24 months was 45% (35% for imatinib-resistant patients and 74% for imatinib-intolerant patients).
Dasatinib var clastogent in vitro med deling af CHO-celler (Chinese Hamster Ovary celler).
Dasatinib was clastogenic in vitro to dividing Chinese Hamster Ovary (CHO) cells.
Rekonstitueret oral suspension blandet med mælk, yoghurt, æblejuice eller æblemos kan opbevares ved 25°C eller derunder i op til 1 time.
Constituted oral suspension mixed with milk, yogurt, apple juice, or applesauce may be stored at or below 25°C for up to 1 hour.
Der opnåedes fuldstændigt hæmatologisk respons eller MCyR hos patienter med en række BCR-ABL-mutationer forbundet med imatinib resistens bortset fra T315I.
Complete haematologic response or MCyR was achieved in patients harbouring a variety of BCR-ABL mutations associated with imatinib resistance except T315I.
Mediantid fra diagnose til randomisering var 64 måneder i dasatinib gruppen og 52 måneder i imatinib gruppen.
The median time from diagnosis to randomisation was 64 months in the dasatinib group and 52 months in the imatinib group.
Respons var varige i alle faser af CML og Ph+ ALL.
Responses were durable across all phases of CML and Ph+ ALL.
Disse virkninger forekom ved doser, der ikke gav maternel toksicitet, hvilket tyder på, at dasatinib er et selektivt reproduktionstoksin fra implantationstidspunktet til organogenesen er afsluttet.
These effects occurred at doses that did not produce maternal toxicity, indicating that dasatinib is a selective reproductive toxicant from implantation through the completion of organogenesis.
Dasatinib var ikke mutagent i in vitro bakterielle celle-assay (Ames test) og var ikke genotoksisk i et in vivo mikronukleus-studie med rotter.
Dasatinib was not mutagenic in in vitro bacterial cell assays (Ames test) and was not genotoxic in an in vivo rat micronucleus study.
Efter rekonstitution indeholder flasken 99 ml oral suspension, heraf er 90 ml tiltænkt dosering og administration.
Once constituted, the bottle contains 99 mL of oral suspension, of which 90 mL is intended for dosing and administration.
Dasatinib er blevet undersøgt i et randomiseret klinisk studie med 519 patienter med nyligt diagnosticeret CML i kronisk fase, som inkluderede patienter med tidligere hjertesygdom.
Dasatinib was studied in a randomised clinical study of 519 patients with newly diagnosed CML in chronic phase which included patients with prior cardiac disease.
Variabiliteten i dasatinibeksponering er højere i fastende tilstand (47% CV) sammenlignet med et fedtfattigt måltid (39% CV) og et måltid med højt fedtindhold (32% CV).
Dasatinib exposure variability is higher under fasted conditions (47% CV) compared to light-fat meal (39% CV) and high-fat meal (32% CV) conditions.
Ni patienter (12%) gennemgik terapeutisk torakocentese.
Nine (12%) patients underwent therapeutic thoracentesis.
Accelereret (n= 174)
Accelerated (n= 174)
Opbevaringsforhold efter rekonstitution af lægemidlet, se pkt.
For storage conditions after constitution of the medicinal product, see section 6.3.
Dasatinib er et substrat og en hæmmer af cytochrom P450 (CYP)3A4.
Dasatinib is a substrate and an inhibitor of cytochrome P450 (CYP) 3A4.
Dasatinib metaboliseres i omfattende grad hos mennesker, og mange enzymer er involverede i metaboliseringen.
Dasatinib is extensively metabolised in humans with multiple enzymes involved in the generation of the metabolites.
Imatinib resistente patienter n=124
Imatinib-resistant patients n=124
Behandling skal initieres af en læge med erfaring i diagnosticering og behandling af patienter med leukæmi.
Therapy should be initiated by a physician experienced in the diagnosis and treatment of patients with leukaemia.
Sekundære endepunkter omfattede tid i cCCyR (måling af responsvarighed), tid til cCCyR, major molekylært respons (MMR), tid til MMR, progressionsfri overlevelse (PFS) og samlet overlevelse (OS).
Secondary endpoints included time in cCCyR (measure of durability of response), time to cCCyR, major molecular response (MMR) rate, time to MMR, progression free survival (PFS) and overall survival (OS).
• Omryst grundigt før hver brug.
• Shake well before each use.
CYP3A4 er i høj grad ansvarlig for metabolismen af dasatinib.
CYP3A4 is a major enzyme responsible for the metabolism of dasatinib.
Hos dasatinib behandlede patienter var de observerede mutationer T315I, F317I/L og V299L.
The mutations detected among the dasatinib-treated patients were T315I, F317I/L and V299L.
Resultater for patienter med knoglemarvstransplantation efter behandling med dasatinib er endnu ikke fuldt evalueret.
The outcome of patients with bone marrow transplantation after dasatinib treatment has not been fully evaluated.
SPRYCEL kan tages med eller uden mad og bør tages konsekvent enten om morgenen eller om aftenen (se pkt.
SPRYCEL can be taken with or without a meal and should be taken consistently either in the morning or in the evening (see section 5.2).
Tid-til cCCyR Tid-til MMR Varighed af cCCyR
Time-to cCCyR Time-to MMR Durability of cCCyR
I et in vivo enkeltdosisstudie med telemetri-monitorerede aber, der var ved bevidsthed, er der dog ikke set ændringer i QT-interval eller formen af ekg-takker.
However, in an in vivo single-dose study in conscious telemetered monkeys, there were no changes in QT interval or ECG wave form.
Sjælden dyb venetrombose, emboli, livedo reticularis
Rare deep vein thrombosis, embolism, livedo reticularis
Myelosuppression er almindeligvis reversibel og kan oftest håndteres ved midlertidigt at afbryde dasatinib eller ved dosisreduktion.
Myelosuppression is generally reversible and usually managed by withholding dasatinib temporarily or by dose reduction.
Lactosemonohydrat Mikrokrystallinsk cellulose Croscarmellosenatrium Hydroxypropylcellulose Magnesiumstearat
Lactose monohydrate Microcrystalline cellulose Croscarmellose sodium Hydroxypropylcellulose Magnesium stearate
Dasatinibs ikke-kliniske sikkerhedsprofil er vurderet i mange in vitro og in vivo-studier med mus, rotter, aber og kaniner.
The non-clinical safety profile of dasatinib was assessed in a battery of in vitro and in vivo studies in mice, rats, monkeys, and rabbits.
Antacida kan derfor administreres i op til 2 timer inden eller 2 timer efter SPRYCEL (se pkt.
Thus, antacids may be administered up to 2 hours prior to or 2 hours following SPRYCEL (see section 4.4).
Apotekspersonalet eller en kvalificeret sundhedsperson vil rekonstituere (blande for at få en væske) SPRYCEL pulver til oral suspension for at få en SPRYCEL oral suspension, før den bliver udleveret til dig.
Your pharmacist or qualified healthcare professional will constitute (mix to form a liquid) SPRYCEL powder for oral suspension to form SPRYCEL oral suspension before dispensing to you.
Ekkokardiografi bør foretages ved behandlingsstart hos alle patienter med symptomer på hjertesygdom og bør overvejes hos patienter med risikofaktorer for hjerte- eller lungesygdom.
An echocardiography should be performed at treatment initiation in every patient presenting symptoms of cardiac disease and considered in patients with risk factors for cardiac or pulmonary disease.
I studiet med CML i kronisk fase, var det primære endepunkt MCyR hos imatinib resistente patienter.
In the study in chronic phase CML, the primary endpoint was MCyR in imatinib-resistant patients.
Forandringer i de gastrointestinale, hæmatopoietiske og lymfoide systemer var reversible efter behandlingsophør.
Changes in the gastrointestinal, haematopoietic and lymphoid systems were reversible following cessation of treatment.
Blandt dasatinib behandlede CML-CP pædiatriske patienter tidligere eksponeret over for imatinib blev følgende mutationer påvist ved behandlingens afslutning: T315A, E255K og F317L.
Among dasatinib-treated CML-CP paediatric patients previously exposed to imatinib, the mutations detected at the end of treatment were: T315A, E255K and F317L.
Effekten af dasatinib er baseret på hæmatologiske og cytogenetiske responsrater.
The efficacy of dasatinib is based on haematological and cytogenetic response rates.
I et pædiatrisk farmakokinetisk studie er den dosisnormaliserede eksponering af dasatinib (Cavg, Cmin og Cmax) sammenlignelig mellem 21 patienter med CP-CML og 16 patienter med Ph+ ALL.
In a paediatric pharmacokinetics study, dose-normalized dasatinib exposure (Cavg, Cmin and Cmax) appears similar between 21 patients with CP-CML and 16 patients with Ph+ ALL.
Gravide eller ammende kvinder bør undgå eksponering for SPRYCEL pulver til oral suspension.
Pregnant or breast-feeding women should avoid exposure to SPRYCEL powder for oral suspension.
Gastrointestinal toksicitet var dosisbegrænsende hos rotter og aber, da tarmen vedvarende var et målorgan.
Gastrointestinal toxicity was dose-limiting in rats and monkeys, as the intestine was a consistent target organ.
Kongestivt hjertesvigt/hjerteinsufficiens og lungeødem blev rapporteret hos < 2% af patienterne.
Congestive heart failure/cardiac dysfunction and pulmonary oedema were reported in < 2% of patients.
Hos patienter med CML er de hvide blodlegemer, der kaldes granulocytter, begyndt at vokse uden kontrol.
In people with CML, white cells called granulocytes start growing out of control.
Dasatinib anses for at være ikke-fototoksisk in vivo efter en enkelt oral administration til hårløse hunmus ved eksponeringer op til 3 gange større end de humane eksponeringer efter administration af den anbefalede terapeutiske dosis (baseret på AUC).
Dasatinib was considered to be non-phototoxic in vivo after a single oral administration to female hairless mice at exposures up to 3-fold the human exposure following administration of the recommended therapeutic dose (based on AUC).
Patienter, som udvikler dyspnø og træthed efter initiering af behandlingen, bør undersøges for almindelig ætiologi inklusive pleuraeffusion, pulmonal ødem, anæmi eller lungeinfiltration.
Patients who develop dyspnoea and fatigue after initiation of therapy should be evaluated for common etiologies including pleural effusion, pulmonary oedema, anaemia, or lung infiltration.
Patienter bør undersøges for tegn og symptomer på underliggende kardiopulmonal sygdom før initiering af dasatinib behandling.
Patients should be evaluated for signs and symptoms of underlying cardiopulmonary disease prior to initiating dasatinib therapy.
Andre relevante virkningsresultater omfattede CCyR og samlet molekylært respons (CMR).
Other relevant efficacy results included CCyR and complete molecular response (CMR) rates.
• 12 ml oral sprøjte der fulgte med flasken.
• 12-mL oral syringe provided with the bottle.
Efter opklaring af en alvorlig (grad 3 eller 4) episode kan behandlingen genoptages efter behov ved en reduceret dosis afhængig af bivirkningens initiale sværhedsgrad.
Following resolution of a severe (grade 3 or 4) episode, treatment can be resumed as appropriate at a reduced dose depending on the initial severity of the adverse reaction.
Tid til MMR er vist grafisk i Figur 1.
The time to MMR is displayed graphically in Figure 1.
Baseline-karakteristika var ligeligt fordelt mellem de to behandlingsgrupper med hensyn til alder (gennemsnitslader var 46 år for SPRYCEL gruppen og 49 år for imatinib gruppen med henholdsvis 10% og 11% af patienterne på 65 år eller derover), køn (henholdsvis 44% og 37% kvinder) og race (kaukasisk 51% og 55%, asiatisk 42% og 37%).
Baseline characteristics were well balanced between the two treatment groups with respect to age (median age was 46 years for the SPRYCEL group and 49 years for the imatinib group with 10% and 11% of patients 65 years of age or older, respectively), gender (women 44% and 37%, respectively), and race (Caucasian 51% and 55%; Asian 42% and 37%, respectively).
I alt 46 dasatinib behandlede patienter havde recidiverende pleuraeffusion.
A total of 46 dasatinib-treated patients had recurrent pleural effusions.
Følgende bivirkninger, eksklusive unormale laboratorieprøver, indberettedes hos patienter behandlet med SPRYCEL brugt som enkeltstofbehandling i kliniske studier og efter markedsføring (Tabel 5).
The following adverse reactions, excluding laboratory abnormalities, were reported in patients treated with SPRYCEL used as single-agent therapy in clinical studies and post-marketing experience (Table 5).
På grund af begrænsningerne ved dette studie bør der udvises forsigtighed ved administration af dasatinib til patienter med leverinsufficiens.
Due to the limitations of this clinical study, caution is recommended when administering dasatinib to patients with hepatic impairment.
Den kumulative rate for dasatanib relateret pleuraeffusion (alle grader) over tid var 10% ved 12 måneder, 14% ved 24 måneder, 19% ved 36 måneder, 24% ved 48 måneder og 28% ved 60 måneder.
The cumulative rate of dasatinib-related pleural effusion (all grades) over time was 10% at 12 months, 14% at 24 months, 19% at 36 months, 24% at 48 months and 28% at 60 months.
Hyppigheden af MCyR efter to år var ens for patienter med BCR-ABL-mutation, P-loop-mutation eller ingen mutation ved baseline (henholdsvis 63%, 61% og 62%).
The rates of MCyR at 2 years were similar whether patients had any baseline BCR-ABL mutation, P-loop mutation, or no mutation (63%, 61% and 62%, respectively).
Fysisk-kemiske og tilgængelige farmakodynamiske/toksikologiske data vedrørende dasatinib peger mod, at stoffet udskilles i modermælk, og det kan ikke udelukkes, at der er en risiko for det ammende barn.
Physico-chemical and available pharmacodynamic/toxicological data on dasatinib point to excretion in breast milk and a risk to the suckling child cannot be excluded.
Der er udført 2 kliniske studier med patienter, der er resistente eller intolerante over for imatinib; det primære effektendepunkt i disse studier var MCyR (Major Cytogenetic Response).
Two clinical studies were conducted in patients resistant or intolerant to imatinib; the primary efficacy endpoint in these studies was Major Cytogenetic Response (MCyR).
Dosisjustering ved bivirkninger Myelosuppression
Dose adjustment for adverse reactions Myelosuppression
Ved tredje episode reduceres dosis til 50 mg én gang dagligt (hos nyligt diagnosticerede patienter) eller seponeres (hos patienter, der har været resistente eller intolerante over for tidligere behandling, inklusive imatinib).
For third episode, further reduce dose to 50 mg once daily (for newly diagnosed patients) or discontinue (for patients resistant or intolerant to prior therapy including imatinib).
Sjælden spontan abort
Rare abortion
Hvis der opstår laboratoriefund eller kliniske fund associeret med TMA hos patienter, som modtager SPRYCEL, skal behandling med SPRYCEL seponeres, og der skal udføres en grundig evaluering for TMA, inklusive ADAMTS13aktivitet og anti-ADAMTS13-antistoffer.
If laboratory or clinical findings associated with TMA occur in a patient receiving SPRYCEL, treatment with SPRYCEL should be discontinued and thorough evaluation for TMA, including ADAMTS13 activity and antiADAMTS13-antibody determination, should be completed.
Efter mindst 60 måneders opfølgning var den kumulative rate 2,3% for permanent seponering på grund af myelosuppression grad 3 eller 4.
After a minimum of 60 months follow-up the cumulative rate of permanent discontinuation due to grade 3 or 4 myelosuppression was 2.3%.
Forbered omhyggeligt SPRYCEL oral suspension til administration, afmål dosen og fyld sprøjten som vist:
Carefully prepare the SPRYCEL oral suspension for administration, measure the dose, and fill the syringe, like this:
n/a = ikke relevant; CI = konfidensinterval; ULN = øvre normalgrænse.
n/a = not applicable; CI = confidence interval; ULN = upper limit of normal range.
Medianvarigheden af dasatinib relateret pleuraeffusion (alle grader) var 283 dage (~40 uger).
The median duration of dasatinib-related pleural effusion (all grades) was 283 days (~40 weeks).
CI = konfidensinterval; ULN = øvre normalgrænse.
CI = confidence interval; ULN = upper limit of normal range.
Medianbehandlingsvarigheden for alle patienter i fortsat behandling med en opfølgningsperiode på mindst 5 år (n=205) var 59 måneder (28-66 måneder).
The median duration of treatment for all patients still on therapy with a minimum of 5 years of follow-up (n=205) was 59 months (range 28-66 months).
Patienter, der rapporterede PAH under dasatinib behandling, tog ofte andre lægemidler eller havde komorbiditet i tillæg til den underliggende malignitet.
Patients with PAH reported during dasatinib treatment were often taking concomitant medicinal products or had co-morbidities in addition to the underlying malignancy.
* Se afsnittet ”Beskrivelse af udvalgte bivirkninger” for yderligere oplysninger.
* For additional details, see section "Description of selected adverse reactions"
Efter opklaring bør der foretages en funktionel vurdering, inden behandlingen med dasatinib genoptages.
After resolution, a functional assessment should be performed prior to resuming treatment with dasatinib.
3 Hvis cytopeni recidiverer, gentages trin 1, og behandlingen genoptages med reduceret dosis på 100 mg én gang dagligt (anden episode) eller 80 mg én gang dagligt (tredje episode).
3 If recurrence of cytopaenia, repeat step 1 and resume treatment at a reduced dose of 100 mg once daily (second episode) or 80 mg once daily (third episode).
Varighed af cCCyR
Durability of cCCyR
Sjælden lungeemboli, acute respiratory distress syndrome
Rare pulmonary embolism, acute respiratory distress syndrome
Dasatinib aktivitet in vitro i hERG- og Purkinje-fiberassays tydede på et potentiale for forlængelse af kardiel ventrikelrepolarisering (QT-interval).
Dasatinib activity in vitro in hERG and Purkinje fiber assays suggested a potential for prolongation of cardiac ventricular repolarisation (QT interval).
I separate eksperimenter med murine modeller af CML, forebyggede dasatinib in-vivo progression af kronisk CML til blastfase og forlængede overlevelsen hos mus med patient-deriverede CMLcellelinjer placeret forskellige steder, inklusive centralnervesystemet.
In vivo, in separate experiments using murine models of CML, dasatinib prevented the progression of chronic CML to blast phase and prolonged the survival of mice bearing patient-derived CML cell lines grown at various sites, including the central nervous system.
Oprindelig dosis
Original dose
Behandlingen genoptages med samme dosis, hvis det er første tilfælde og med reduceret dosis, hvis bivirkningen er tilbagevendende.
The same dose should be resumed if this is the first occurrence and the dose should be reduced if this is a recurrent adverse reaction.
Data beskrevet i tabellen er fra studier, hvor der blev anvendt en startdosis på 70 mg to gange dagligt.
Data described in this table are from studies using a starting dose of 70 mg twice daily.
Et dosisregime med 70 mg to gange dagligt blev ligeledes undersøgt.
A 70 mg twice daily regimen was also studied.
Hos patienter, der rapporterede sygdomsprogression eller som seponerede dasatinib eller imatinib behandling, blev der udført BCR-ABL sekventering af patienternes blodprøver, hvor disse er tilgængelige.
In patients who report disease progression or discontinue dasatinib or imatinib therapy, BCR-ABL sequencing was performed on blood samples from patients where these are available.
• Hvis mængden, der er behov for, overstiger 11 ml, skal den deles i 2 doser, som angivet i
• If the amount needed is greater than 11 mL, it must be split into 2 doses as indicated in Table 16.
Hvis du oplever bivirkninger, bør du tale med din læge eller apoteket.
If you get any side effects , talk to your doctor or pharmacist.
Disse data bør tages med i overvejelserne, hvis patienter skal skifte fra tabletter til pulver til oral suspension eller omvendt.
These data should be considered if patients are to switch from tablets to powder for oral suspension or vice versa.
Bruges med forsigtighed hos patienter med lever- eller nyreinsufficiens, da benzylalkohol kan akkumuleres over tid og forårsage metabolisk acidose.
Use with caution in patients with hepatic or renal impairment, as benzyl alcohol may accumulate over time and cause metabolic acidosis.