natgillin/translations-raw huggingface dataset:
De hyppigste bivirkninger ved Vidaza (som optræder hos mere end 60% af patienterne) er bivirkninger i blodet, herunder trombocytopeni (et lavt antal blodplader), neutropeni (lavt niveau af neutrofiler, en art hvide blodlegemer) og leukopeni (lavt niveau af hvide blodlegemer), bivirkninger i mave - og tarmregionen, herunder kvalme og opkastning, og reaktioner på injektionsstedet.
The most common side effects with Vidaza (seen in more than 60% of patients) are blood reactions including thrombocytopenia (low platelet counts), neutropenia (low levels of neutrophils, a type of white blood cell) and leucopenia (low white blood cell counts), side effects affecting the stomach and gut including nausea and vomiting, and injection site reactions.
Den fuldstændige liste over alle de indberettede bivirkninger ved Vidaza fremgår af indlægssedlen.
For the full list of all side effects reported with Vidaza, see the Package Leaflet.
Vidaza bør ikke anvendes hos patienter, der kan være overfølsomme (allergiske) over for azacitidin eller andre af indholdsstofferne.
Vidaza should not be used in people who may be hypersensitive (allergic) to azacitidine or any of the other ingredients.
Det må ikke anvendes hos patienter med fremskreden levercancer eller hos kvinder, som ammer.
It must not be used in patients with advanced liver cancer or in women who are breast-feeding.
Udvalget for Humanmedicinske Lægemidler (CHMP) konkluderede, at fordelene ved Vidaza er større end de risici, der er forbundet med stoffet, til behandling af voksne patienter, som ikke er egnede til hæmatopoietisk stamcelletransplantation, med intermediær- 2 og højrisiko myelodysplastiske syndromer, CMML med 10- 29% abnorme blaster uden myeloproliferativ sygdom eller AML med 20 - 30% blaster og multilinie dysplasi.
The Committee for Medicinal Products for Human Use (CHMP) decided that Vidaza’ s benefits are greater than its risks for the treatment of adult patients who are not eligible for haematopoietic stem cell transplantation with intermediate-2 and high-risk myelodysplastic syndromes, CMML with 10-29% abnormal blasts without myeloproliferative disorder or AML with 20-30% blasts and multilineage dysplasia.
Udvalget anbefalede udstedelse af markedsføringstilladelse for Vidaza.
The Committee recommended that Vidaza be given marketing authorisation.
Andre oplysninger om Vidaza:
Other information about Vidaza:
Europa- Kommissionen udstedte en markedsføringstilladelse med gyldighed i hele Den Europæiske Union for Vidaza til Celgene Europe Ltd. den 17. december 2008.
The European Commission granted a marketing authorisation valid throughout the European Union for Vidaza to Celgene Europe Ltd on 17 December 2008.
Registreringen af udpegelsen af Vidaza som lægemiddel til sjældne sygdomme kan ses her (myelodysplastiske syndromer) og her (AML).
The records of Vidaza’ s designations as an orphan medicine are available here (myelodysplastic syndromes) and here (AML).
2/ 3 Den fuldstændige EPAR for Vidaza findes her.
The full EPAR for Vidaza can be found here.
Paknings -
EU number
EU/ 1/ 08/ 488/ 001
EU/ 1/ 08/ 488/ 001
Vidaza
Vidaza
Subkutan anvendelse
subcutaneous use
Vidaza 25 mg/ ml pulver til injektionsvæske, suspension
Vidaza 25 mg/ ml powder for suspension for injection
Efter rekonstitution indeholder hver ml suspension 25 mg azacitidin.
After reconstitution, each ml suspension contains 25 mg azacitidine.
Pulver til injektionsvæske, suspension
Powder for suspension for injection.
Vidaza er indiceret til behandling af voksne patienter, som ikke er egnede til hæmatopoietisk stamcelletransplantation, og som lider af: • intermediær- 2 og højrisiko myelodysplastiske syndromer (MDS) i henhold til International Prognostic Scoring System (IPSS), • kronisk myelomonocytleukæmi (CMML) med 10- 29% blaster i marv uden myeloproliferativ sygdom, • akut myeloid leukæmi (AML) med 20- 30% blaster og multilinie dysplasi i henhold til klassifikationen fra World Health Organisation (WHO).
Vidaza is indicated for the treatment of adult patients who are not eligible for haematopoietic stem cell transplantation with: • intermediate-2 and high-risk myelodysplastic syndromes (MDS) according to the International Prognostic Scoring System (IPSS), • chronic myelomonocytic leukaemia (CMML) with 10-29% marrow blasts without myeloproliferative disorder, • acute myeloid leukaemia (AML) with 20-30% blasts and multi-lineage dysplasia, according to World Health Organisation (WHO) classification.
Behandling med Vidaza bør initieres og monitoreres under opsyn af en læge, der har erfaring i anvendelsen af kemoterapeutika.
Vidaza treatment should be initiated and monitored under the supervision of a physician experienced in the use of chemotherapeutic agents.
Patienter bør præmedicineres med antiemetika mod kvalme og opkastning.
Patients should be premedicated with anti-emetics for nausea and vomiting.
Behandlingen - injiceres subkutant dagligt i 7 dage, efterfulgt af en hvileperiode på 21 dage (28 dages behandlingscyklus).
Posology The recommended starting dose for the first treatment cycle, for all patients regardless of baseline haematology laboratory values, is 75 mg/ m2 of body surface area, injected subcutaneously, daily for 7 days, followed by a rest period of 21 days (28-day treatment cycle).
4. 4). Det kan være nødvendigt at udsætte starten af næste cyklus eller reducere dosis som beskrevet herunder.
Patients should be monitored for haematologic response/ toxicity and renal toxicities (see section 4.4); a delay in starting the next cycle or a dose reduction as described below may be necessary.
Hæmatologisk toksicitet defineres som den laveste hæmatologiske parameter i en given cyklus (nadirtal), såfremt trombocytterne falder til under 50, 0 x 109/ l, og/ eller det absolutte neutrofiltal (Absolute Neutrophil Count, ANC) falder under 1 x 109/ l.
Dose adjustment due to haematological toxicity Haematological toxicity is defined as the lowest count reached in a given cycle (nadir) if platelets fall below 50.0 x 109/ l and/ or absolute neutrophil count (ANC) below 1 x 109/ l.
2 Restituering defineres som en stigning i den/ de hæmatologiske parameter/ parametre, hvor hæmatologisk toksicitet blev observeret på mindst halvdelen af forskellen mellem nadirtallet og baselinetallet plus nadirtallet (dvs. den hæmatologiske parameter ved restituering ≥ nadirtallet + (0, 5 x [baselinetallet – nadirtallet]).
2 Recovery is defined as an increase of cell line(s) where haematological toxicity was observed of at least half of the difference of nadir and the baseline count plus the nadir count (i. e. blood count at recovery ≥ Nadir Count + (0.5 x [Baseline count – Nadir count]).
Patienter uden reducerede hæmatologiske parametre ved baseline (dvs. hvide blodlegemer (White Blood Cells, WBC) > 3, 0 x 109/ l, ANC > 1, 5 x 109/ l og trombocytter > 75, 0 x 109/ l) inden første behandling Hvis der observeres hæmatologisk toksicitet efter behandlingen med Vidaza, bør den næste behandlingscyklus med Vidaza udsættes, indtil trombocyttallet og ANC er restitueret.
White Blood Cells (WBC) > 3.0 x 109/ l and ANC > 1.5 x 109/ l, and platelets > 75.0 x 109/ l) prior to the first treatment If haematological toxicity is observed following Vidaza treatment, the next cycle of Vidaza therapy should be delayed until the platelet count and the ANC have recovered.
Trombocytter
Nadir counts 9 9
% dosis i den næste cyklus, hvis restituering *
% Dose in the next cycle, if recovery* is not
ANC (x 109/ l)
ANC (x 10 / l)
ikke opnås inden for 14 dage
achieved within 14 days
* Restituering = Givne hæmatologiske parametre ≥ nadirtal + (0, 5 x [baselinetal – Nadirtal])
*Recovery = counts ≥ Nadir count + (0.5 x [Baseline count – Nadir count])
Patienter med reducerede hæmatologiske parametre ved baseline (dvs.
Patients with reduced baseline blood counts (i. e.
Dette gælder også, hvis reduktionen er på mere end 50%, hvis der samtidigt konstateres stigning i cellelinjedifferentieringer i forhold til baseline.
WBC < 3.0 x 109/ l or ANC < 1.5 x 109/ l or platelets < 75.0 x 109/ l) prior to the first treatment Following Vidaza treatment, if the decrease in WBC or ANC or platelets from that prior to treatment is less than 50%, or greater than 50% but with an improvement in any cell line differentiation, the next cycle should not be delayed and no dose adjustment made.
Hvis reduktionen i WBC, ANC eller trombocytter er på mere end 50% i forhold til reduktionen før behandlingen, og uden forbedring i cellelinjedifferentieringen, bør den næste behandlingscyklus med Vidaza udsættes, indtil trombocyttallet og ANC er restitueret.
If the decrease in WBC or ANC or platelets is greater than 50% from that prior to treatment, with no improvement in cell line differentiation, the next cycle of Vidaza therapy should be delayed until the platelet count and the ANC have recovered.
Hvis knoglemarvscellulariteten er > 50%, bør der ikke foretages dosisjusteringer.
If the bone marrow cellularity is > 50%, no dose adjustments should be made.
Hvis knoglemarvscellulariteten er ≤ 50%, bør behandlingen udsættes, og dosis reduceres i overensstemmelse med følgende tabel:
If bone marrow cellularity is ≤ 50%, treatment should be delayed and the dose reduced according to the following table:
% dosis i næste cyklus, opnås inden for 14 dage
% Dose in the next cycle if recovery is not achieved within 14 days Recovery* ≤ 21 days Recovery* > 21 days
* Restituering = Givne hæmatologiske parametre ≥ Nadirtal+ (0, 5 x [baselinetal - – Nadirtal])
*Recovery = counts ≥ Nadir count + (0.5 x [Baseline count – Nadir count])
Særlige populationer Nedsat nyrefunktion:
Special populations Renal impairment:
Der er ikke foretaget regelrette undersøgelser af patienter med nedsat nyrefunktion.
No formal studies have been conducted in patients with decreased renal function.
Patienter med svært nedsat organfunktion bør monitoreres nøje for organpåvirkninger eller anden forværring i sygdomstilstanden.
Patients with severe organ impairment should be carefully monitored for adverse events.
Der foreligger ingen anbefalinger vedrørende justering af startdosis hos patienter med nedsat nyrefunktion (f. eks. baseline- serumkreatinin eller blodureanitrogen [BUN] ≥ 2- gange over den øvre grænse for normalværdien [ULN] eller serumbikarbonat mindre end 20 mmol/ l), inden behandlingen indledes; dosisjusteringer bør efterfølgende baseres på monitorering
No specific modification to the starting dose is recommended in patients with renal impairment (e. g. baseline serum creatinine or blood urea nitrogen [BUN] ≥ 2-fold above upper limit of normal [ULN] or serum bicarbonate less than 20 mmol/ l) prior to starting treatment; subsequent dose modifications should be based on haematology and renal laboratory values.
Hvis der forekommer uforklarlige fald i serumbikarbonat til mindre end 20 mmol/ l, bør dosis reduceres med 50% ved den næste behandlingscyklus.
If unexplained reductions in serum bicarbonate levels to less than 20 mmol/ l occur, the dose should be reduced by 50% on the next cycle.
4. 4).
If unexplained elevations in serum creatinine or BUN to ≥ 2-fold above baseline values and above ULN occur, the next cycle should be delayed until values return to normal or baseline and the dose should be reduced by 50% on the next treatment cycle (see section 4.4).
Patienter med svært nedsat leverfunktion bør monitoreres nøje for organpåvirkninger eller anden forværring i sygdomstilstanden.
Patients with severe hepatic organ impairment should be carefully monitored for adverse
4. 3 og 4. 4).
Vidaza is contraindicated in patients with advanced malignant hepatic tumours (see sections 4.3 and 4.4).
Vidaza bør ikke anvendes til børn under 18 år p. g. a. utilstrækkelig dokumentation for sikkerhed og virkning.
Vidaza is not recommended for use in children below 18 years due to insufficient data on safety and efficacy.
Laboratorieprøver Der skal gennemføres leverfunktionstest, og serumkreatinin skal bestemmes, inden behandlingen indledes, og analyserne bør gentages forud for hver ny behandlingscyklus.
Laboratory tests Liver function tests and serum creatinine should be determined prior to initiation of therapy and prior to each treatment cycle.
Analyserne bør gentages efter behov for at monitorere respons og toksicitet, men som et minimum bør en analyse foretages forud for hver behandlingscyklus.
Complete blood counts should be performed prior to initiation of therapy and as needed to monitor response and toxicity, but at a minimum, prior to each treatment cycle.
Indgivelsesmåde Efter rekonstitution skal Vidaza injiceres subkutant i overarmen, låret eller maven.
Method of administration Reconstituted Vidaza should be injected subcutaneously into the upper arm, thigh or abdomen.
Nye injektioner bør indgives mindst 2, 5 cm fra det forrige injektionssted og aldrig i områder, hvor vævet er ømt, blodunderløbent, rødt eller hårdt.
New injections should be given at least 2.5 cm from the previous site and never into areas where the site is tender, bruised, red, or hardened.
6. 6.
Detailed instructions for the reconstitution and administration procedure for Vidaza are provided in section 6.6.
Kendt overfølsomhed over for det aktive stof eller over for et eller flere af hjælpestofferne.
Known hypersensitivity to the active substance or to any of the excipients.
4. 4).
Advanced malignant hepatic tumours (see section 4.4).
4. 8).
Haematological toxicity Treatment with azacitidine is associated with anaemia, neutropenia and thrombocytopenia, particularly during the first 2 cycles (see section 4.8).
Den anbefalede dosis bør anvendes til den første behandlingscyklus.
Complete blood counts should be performed as needed to monitor response and toxicity, but at least prior to each treatment cycle.
4. 2).
After administration of the recommended dose for the first cycle, the dose for subsequent cycles should be reduced or its administration delayed based on nadir counts and haematological response (see section 4.2).
4 Nedsat leverfunktion Der er ikke foretaget nogen regelrette undersøgelser af patienter med nedsat leverfunktion.
Hepatic impairment No formal studies have been conducted in patients with hepatic impairment.
I sjældne tilfælde er det rapporteret, at patienter med omfattende tumorbyrde pga. metastatisk sygdom har fået progressiv leverkoma og er døde under behandlingen med azacitidin, især patienter med baseline - serumalbumin < 30 g/ l.
Patients with extensive tumour burden due to metastatic disease have been rarely reported to experience progressive hepatic coma and death during azacitidine treatment, especially in such patients with baseline serum albumin < 30 g/ l.
4. 3).
Azacitidine is contraindicated in patients with advanced malignant hepatic tumours (see section 4.3).
Nedsat nyrefunktion Nyrepåvirkning, der rækker fra forhøjet serumkreatinin til decideret nyresvigt og død, er blevet rapporteret i sjældne tilfælde hos patienter i kombinationsbehandling med intravenøs azacitidin og andre kemoterapeutika.
Renal impairment Renal abnormalities ranging from elevated serum creatinine to renal failure and death were reported rarely in patients treated with intravenous azacitidine in combination with other chemotherapeutic agents.
Derudover er der blevet konstateret renal tubulær acidose, der defineres som et fald i serumbikarbonat til < 20 mmol/ l ved samtidig forekomst af alkalisk urin og hypokalæmi (serumkalium < 3 mmol/ l) hos 5 personer med kronisk myeloid leukæmi (CML) i behandling med azacitidin og etoposid.
If
4. 2).
4 unexplained reductions in serum bicarbonate (< 20 mmol/ l) or elevations of serum creatinine or BUN occur, the dose should be reduced or administration delayed (see section 4.2).
4. 2).
Patients with renal impairment should be closely monitored for toxicity since azacitidine and/ or its metabolites are primarily excreted by the kidney (see section 4.2).
Hjerte - og lungesygdom Patienter med svært kongestivt hjertesvigt, klinisk ustabil hjertesygdom eller lungesygdom i anamnesen blev ekskluderet fra det pivotale kliniske studie, og Vidazas sikkerhed og virkning hos disse patienter er derfor ikke fastlagt.
Cardiac and pulmonary disease Patients with a history of severe congestive heart failure, clinically unstable cardiac disease or pulmonary disease were excluded from the pivotal clinical study and therefore the safety and efficacy of Vidaza in these patients has not been established.
Interaktioner i forbindelse med disse metaboliserende enzymer in vivo anses derfor for at være usandsynlige.
Based on in vitro data, azacitidine metabolism does not appear to be mediated by cytochrome P450 isoenzymes (CYPs), UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs), and glutathione transferases (GSTs); interactions related to these metabolizing enzymes in vivo are therefore considered unlikely.
5. 2).
Clinically significant inhibitory or inductive effects of azacitidine on cytochrome P450 enzymes are unlikely (see section 5.2).
Der er ikke foretaget nogen officiel klinisk undersøgelse af lægemiddelinteraktion med azacitidin.
No formal clinical drug interaction studies with azacitidine have been conducted.
Graviditet Foreliggende data for anvendelse af azacitidin til gravide er utilstrækkelige.
Pregnancy There are no adequate data on the use of azacitidine in pregnant women.
5. 3).
Studies in mice have shown reproductive toxicity (see section 5.3).
Mænd og fertile kvinder skal anvende sikker kontraception under behandlingen og indtil 3 måneder efter behandlingen.
Men and women of childbearing potential must use effective contraception during and up to 3 months after treatment.
Amning Det vides ikke, om azacitidin eller dets metabolitter udskilles i modermælken.
Lactation It is not known whether azacitidine or its metabolites are excreted in human milk.
Fertilitet Der er ingen data fra mennesker om azacitidins indvirkning på fertiliteten.
Fertility There are no human data on the effect of azacitidine on fertility.
I dyreforsøg er azacitidins skadelige virkning på fertiliteten hos hanner blevet dokumenteret (se pkt.
In animals, adverse effects of azacitidine on male fertility have been documented (see section 5.3).
5. 3) Mænd skal frarådes at blive far, mens de er i behandling, og de skal bruge sikker kontraception under behandlingen og indtil
Men should be advised not to father a child while receiving treatment and must use effective contraception during and up to 3 months after treatment.
Mandlige patienter tilrådes at søge rådgivning om opbevaring af sæd, inden behandlingen påbegyndes.
Before starting treatment, male patients should be advised to seek counselling on sperm storage.
Der er ikke foretaget undersøgelser af virkningen på evnen til at føre motorkøretøj eller betjene maskiner. Patienter bør underrettes om, at de kan få uønskede virkninger under behandlingen, f. eks. træthed.
Patients should be advised that they may experience undesirable effects such as fatigue, during treatment.
Der skal derfor rådes til forsigtighed, når der føres motorkøretøj eller betjenes maskiner.
Therefore, caution should be recommended when driving a car or operating machines.
Bivirkninger, der muligvis eller sandsynligvis kan relateres til administrationen af Vidaza, forekom hos 97% af patienterne.
Adverse reactions considered to be possibly or probably related to the administration of Vidaza have occurred in 97% of patients.
De oftest rapporterede bivirkninger ved behandlingen med azacitidin var hæmatologiske (71, 4%), herunder trombocytopeni, neutropeni og leukopeni (oftest grad 3- 4), symptomer fra mave- tarmkanalen (60, 6%), herunder kvalme og opkastning (oftest grad 1- 2) eller reaktioner på injektionsstedet (77, 1%; oftest grad 1- 2).
5 The most commonly reported adverse reactions with azacitidine treatment were haematological reactions (71.4%) including thrombocytopenia, neutropenia and leukopenia (usually Grade 3-4), gastrointestinal events (60.6%) including nausea, vomiting (usually Grade 1-2) or injection site reactions (77.1%; usually Grade 1-2).
De hyppigst rapporterede, alvorlige bivirkninger (> 2%), der blev observeret i det pivotale studie (AZA PH GL 2003 CL 001) samt i de understøttende studier (CALGB 9221 og CALGB 8921) omfattede febril neutropeni (8, 0%) og anæmi (2, 3%).
The most common serious adverse reactions (> 2%) noted from the pivotal study (AZA PH GL 2003 CL 001) and also reported in the supporting studies (CALGB 9221 and CALGB 8921) included febrile neutropenia (8.0%) and anaemia (2.3%).
Andre mindre hyppigt rapporterede, alvorlige bivirkninger (< 2%) omfattede neutropen sepsis, pneumoni, trombocytopeni og blødninger (f. eks hjerneblødning).
Other less frequently reported serious adverse reactions (< 2%) included neutropenic sepsis, pneumonia, thrombocytopenia and haemorrhagic events (e. g. cerebral haemorrhage).
Nedenstående tabel indeholder de bivirkninger, for hvilke et kausalt forhold til behandlingen med azacitidin anses for sandsynligt.
The table below contains the adverse reactions for which a causal relationship with azacitidine treatment could reasonably be established.
De oplyste hyppigheder er baseret på observationerne under det kliniske, pivotale studie eller de to understøttende, kliniske studier.
Frequencies given are based on the observations during the pivotal clinical study or two supporting clinical studies.
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).
Frequencies are defined as: 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).
pneumoni, nasopharyngitis
pneumonia, nasopharyngitis
neutropen sepsis, infektion i de øvre luftveje, urinvejsinfektion, sinusitis, pharyngitis, rhinitis, herpes simplex
neutropenic sepsis, upper respiratory tract infection, urinary tract infection, sinusitis, pharyngitis, rhinitis, herpes simplex
febril neutropeni, neutropeni, leukopeni, trombocytopeni, anæmi
febrile neutropenia, neutropenia, leukopenia, thrombocytopenia, anaemia
knoglemarvsvigt, pancytopeni
bone marrow failure, pancytopenia
overfølsomheds - reaktioner
hypersensitivity reactions
Anorexi
anorexia
hypokalæmi
hypokalemia
konfusionstilstand, angst, søvnløshed
confusional state, anxiety, insomnia
Nervesystemet Øjne
Nervous system disorders Eye disorders
svimmelhed, hovedpine
dizziness, headache
intrakraniel blødning, letargi øjenblødning, konjunktival blødning
intracranial haemorrhage, lethargy eye haemorrhage, conjunctival haemorrhage
6 Systemorgan - klasse
Vascular disorders
Meget almindelig
hypertension, hypotension, haematoma
Almindelig
Respiratory, thoracic and mediastinal disorders
Ikke almindelig
dyspnoea
Vaskulære sygdomme
dyspnoea exertional, pharyngolaryngeal pain
hypertension, hypotension, hæmatom
6 System Organ Class
Luftveje, thorax og mediastinum
Very common
dyspnø
Common
dyspnø ved anstrengelse, pharyngolaryngeal smerte
Uncommon
diarré, opkastning, konstipation, kvalme, mavesmerter
diarrhoea, vomiting, constipation, nausea, abdominal pain
gastrointestinal blødning, hæmorideblødning, stomatitis, gingival blødning, dyspepsi
gastrointestinal haemorrhage, haemorrhoidal haemorrhage, stomatitis, gingival bleeding, dyspepsia
petekkier, pruritus, udslæt, ecchymoser artralgi
petechiae, pruritus, rash, ecchymosis
purpura, alopeci, erytem, makulært udslæt myalgi, muskuloskeletale smerter
purpura, alopecia, erythema, rash macular
Nyrer og urinveje
arthralgia
Hæmaturi
haematuria
træthed, pyrexi, brystsmerter, erytem på injektionsstedet, smerte på injektionsstedet, reaktion på injektionsstedet (uspecificeret)
fatigue, pyrexia, chest pain, injection site erythema, injection site pain, injection site reaction (unspecified)
Utilpashed
injection site: bruising, haematoma, induration, rash, pruritus, inflammation, discoloration, nodule and haemorrhage. malaise
vægttab
weight decreased