natgillin/translations-raw huggingface dataset:
Der er ingen eller utilstrækkelige data fra anvendelse af busulfan eller DMA til gravide kvinder.
There are no or limited amount of data from the use of busulfan or DMA in pregnant women.
FB-kombinationen muliggjorde tilstrækkelig myeloablation moduleret via intensiteten af det konditionerende regime ved variation af antallet af dage med busulfaninfusion.
The FB combination allowed sufficient myeloablation modulated by the intensity of conditioning regimen through the variation of number of days of busulfan infusion.
Kronisk GVHD blev kun indberettet, hvis sygdommen førte til dødsfald: En patient døde 13 måneder efter transplantation.
Chronic GVHD was reported only if it is the cause of death: one patient died 13 months post-transplant.
I vandige medier bevirker frigørelse af methansulphonatgrupperne produktion af carbonioner, som kan alkylere DNA, hvilket menes at være en vigtig biologisk mekanisme bag den cytotoksiske effekt.
In aqueous media, release of the methanesulphonate groups produces carbonium ions which can alkylate DNA, thought to be an important biological mechanism for its cytotoxic effect.
De inter- og intra-individuelle variationer i plasmaeksponering var lavere end henholdsvis 20 % og 10
Inter and intra patient variabilities in plasma exposure were lower than 20% and 10%, respectively.
Der skal iagttages særlig forsigtighed, hvis De anvender itraconazol og metronidazol (anvendes til visse infektioner) eller ketobemidon (anvendes til at behandle smerter), fordi det kan forøge bivirkningerne.
Particular caution should be taken if you use itraconazole and metronidazole (used for certain types of infections) or ketobemidone (used to treat pain), because this may increase the side-effects.
Virusinfektion CMV-reaktivering EBV-reaktivering Bakterieinfektion
Viral infection CMV reactivation EBV reactivation Bacterial infection
NAVN OG ADRESSE PÅ INDEHAVEREN AF MARKEDSFØRINGSTILLADELSEN 12.
NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 12.
Solvensen dimethylacetamid (DMA) kan også nedsætte fertiliteten.
The solvent dimethylacetamide (DMA) may also impair fertility.
Denne indlægsseddel blev senest ændret{MM/ÅÅÅÅ}
This leaflet was last revised in {MM/YYYY}
Størstedelen af publikationerne rapporterede om komplet donorkimærisme efter dag +30 hos 90-100 % af patienterne.
A majority of publications reported a complete donor chimerism at day+30 for 90-100% of patients.
5.2) til ældre som til voksne (< 50 år).
Same dose (see section 5.2) for elderly patients as for adults (< 50 years old) should be used.
Forekomsten af TMA er multifaktoriel, og intravenøs busulfan i sig selv vurderes ikke at være en primær faktor for udvikling af denne reaktion.
The occurrence of TMA is multifactorial and busulfan IV by itself cannot be considered as a main factor in the development of this reaction.
Akut GVHD blev anset for alvorlig hos 3 patienter.
Acute GVHD was rated as serious in 3 patients.
En dosis DMA på 400 mg/kg/dag administreret under organogenese gav signifikante udviklingsmæssige anomalier.
Doses of 400 mg/kg/day DMA administered during organogenesis caused significant developmental anomalies.
Omtrent 30 % af den indgivne dosis udskilles med urinen i løbet af 48 timer med 1 % som uomdannet busulfan.
Approximately 30% of the administered dose is excreted into the urine over 48 hours with 1% as unchanged busulfan.
Den vellykkede optagelse af cellerne hos alle patienter i fase II-studier indikerede, at mål-AUC'erne var korrekte.
The successful engraftment achieved in all patients during phase II trials suggests the appropriateness of the targeted AUCs.
Der var ingen primær eller sekundær transplantationsafstødning.
There is no primary or secondary graft rejection.
Den totale busulfandosis pr. patient var mellem 6,4 mg/kg og 9,6 mg/kg.
Total dose of busulfan per patient was between 6.4 mg/kg and 9.6 mg/kg.
HVOD indtraf hos: 8,2 % (5/61) af de allogene patienter (fatal hos 2 patienter) og 2,5 % (1/42) af de autologe patienter.
HVOD occurred in: 8.2% (5/61) allogeneic patients (fatal in 2 patients) and 2.5% (1/42) of autologous patients.
93 % af de allogene patienter udviste fuldstændig kimærisme.
93% of allogeneic patients showed complete chimerism.
Læger og sundhedspersonale anmodes om at indberette alle formodede bivirkninger via det det nationale rapporteringssystem anført i Appendiks V.
Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V
Forekomsten af infektiøse episoder eller reaktivering af opportunistiske patogener afspejler primært immunstatus hos den patient, der får konditionerende behandling.
The occurrence of infectious episodes or reactivation of opportunistic infectious agents mainly reflects the immune status of the patient receiving a conditioning regimen.
Gentagne doser af DMA medførte tegn på levertoksicitet, hvoraf det første var stigninger i enzymer i klinisk-kemiske serumprøver efterfulgt af histopatologiske forandringer i hepatocytterne.
Repeated doses of DMA produced signs of liver toxicity, the first being increases in serum clinical enzymes followed by histopatological changes in the hepatocytes.
De omfattede infektion og graft-versushost-disease (GVHD), som, også selv om der ikke var en direkte årsagssammenhæng, var hovedårsagerne til morbiditet og mortalitet, især ved allogen HPCT.
These include infection and Graft-versus host disease (GVHD) which although not directly related, were the major causes of morbidity and mortality, especially in allogeneic HPCT.
Smerter eller betændelse ved injektionsstedet Mucosit
Pain or inflammation at injection site Mucositis
Veneokklusiv sygdom (VOD) blev indberettet for 15 % (4/27) og 7 % (2/28) efter henholdsvis autolog og allogen transplantation.
Veno occlusive disease (VOD) was reported in 15% (4/27) and 7% (2/28) of the autologous and allogenic transplant respectively.
Venookklusiv sygdom blev indberettet hos mellem 3,9 % og 15,4 %.
VOD was reported with a range between 3.9% and 15.4%.
Busilvex kan reagere med andre lægemidler.
Busilvex may interact with other medicines.
Ovariesuppression og amenoré med menopausale symptomer forekommer hyppigt hos præmenopausale patienter.
Ovarian suppression and amenorrhoea with menopausal symptoms commonly occur in pre-menopausal patients.
En kontinuerlig variation i clearance inden for området 2,49 til 3,92 ml/min/kg er fastlagt hos børn i alderen < 6 måneder og op til 17 år.
A continuous variation of clearance ranging from 2.49 to 3.92 ml/minute/kg has been established in children from < 6 months up to 17 years old.
Skal fortyndes før brug
Must be diluted before use
I dette studie fik 24 voksne patienter clonazepam (0,025-0,03 mg/kg/dag som kontinuerlig intravenøs infusion) som antikonvulsiv behandling, og farmakokinetiske data for disse patienter blev sammenlignet med historiske data indsamlet hos patienter behandlet med phenytoin.
In this study, 24 adult patients received clonazepam (0.025-0.03 mg/kg/day as IV continuous infusions) as anticonvulsant therapy and the PK data of these patients were compared to historical data collected in patients treated with phenytoin.
I begge studier fik alle patienter 16 ud af 16 doser Busilvex.
In both studies, all patients received a 16/16 dose regimen of Busilvex.
En farmakokinetisk populationsanalyse er blevet udført i en kohorte af 205 børn fordelt på passende vis med hensyn til legemsvægt (3,5 til 62,5 kg) samt biologiske og sygdomsrelaterede (maligne og non-maligne) karakteristika, således at de var repræsentative for den høje grad af heterogenitet blandt børn, der gennemgår HPCT.
A population pharmacokinetic analysis has been performed in a cohort of 205 children adequately distributed with respect to bodyweight (3.5 to 62.5 kg), biological and diseases (malignant and nonmalignant) characteristics, thus representative of the high heterogeneity of children undergoing HPCT.
Den væsentligste toksiske virkning er omfattende myeloablation og pancytopeni, men centralnervesystemet, lever, lunger og gastrointestinalkanalen kan også blive påvirket.
The principal toxic effect is profound myeloablation and pancytopenia but the central nervous system, liver, lungs, and gastrointestinal tract may also be affected.
Hvis De spekulerer på at få børn, skal De tale med Deres læge før behandlingen.
If you are concerned about having children, you should discuss this with your doctor before treatment.
Dette studie viste, at legemsvægt var den fremherskende covariat til at forklare busulfans farmakokinetiske variabilitet hos børn versus legemsoverflade eller alder.
This study demonstrated that bodyweight was the predominant covariate to explain the busulfan pharmacokinetic variability in children over body surface area or age.
Busulfan anses for at være leukæmogent.
Busulfan is thought to be leukemogenic.
Hos mennesker var de vigtigste toksiske virkninger hepatotoksicitet og virkninger på centralnervesystemet.
In human the principal toxic effects were hepatotoxicity and central nervous system (CNS) effects.
Der er desuden rapporteret om tilfælde af øgede plasmaniveauer af busulfan efter administration af metronidazol.
Also, there are published case reports of increased plasma levels of busulfan after administration of metronidazole.
Under hensyntagen til PRAC's vurderingsrapport om PSUR'en/PSUR'erne for busulfan er CHMP nået frem til følgende videnskabelige konklusioner:
Taking into account the PRAC Assessment Report on the PSUR(s) for busulfan, the scientific conclusions of CHMP are as follows:
GENEREL KLASSIFIKATION FOR UDLEVERING Receptpligtigt lægemiddel med begrænset rekvirering.
GENERAL CLASSIFICATION FOR SUPPLY Medicinal product subject to restricted medical prescription.
Opmærksomheden bør derfor rettes mod dette pulmonale problem hos patienter, der tidligere har fået mediastinal eller pulmonal stråleterapi (se pkt.
Therefore, attention should be paid to this pulmonary issue in patients with prior history of mediastinal or pulmonary radiation (see section 4.8).
Justeret idealvægt (AIBW) beregnes som følger: AIBW = IBW+0,25x(faktisk legemsvægt - IBW).
Adjusted ideal body weight (AIBW) is calculated as follows: AIBW= IBW+0.25x (actual body weight - IBW).
I disse studier fik i alt 1.574 patienter FB som konditionering med reduceret intensitet (RIC) inden transplantation af hæmatopoietiske progenitorceller.
In these studies, a total of 1574 patients received FB as a reduced intensity conditioning (RIC) regimen prior to haematopoietic progenitor cell transplantation.
Hæmoragisk cystitis, inklusive hæmoragisk cystitis forårsaget af virusinfektion, blev indberettet hos mellem 16 % og 18,1 %.
Haemorrhagic cystitis including haemorrhagic cystitis induced by viral infection was reported in a range between 16% and 18.1%.
Hos rotter medførte en døgndosis DMA på 450 mg/kg hos rotter i 9 dage inaktiv spermatogenese.
In rats, a DMA daily dose of 450 mg/kg given to rats for nine days caused inactive spermatogenesis.
HVOD er en kendt potentiel komplikation til konditionerende behandling efter transplantation.
HVOD is a recognized potential complication of conditioning therapy post-transplant.
Bivirkninger, der er indrapporteret i forbindelse med overvågningen efter markedsføring, er indført i tabellerne med hyppigheden ”ikke kendt”.
Undesirable effects coming from post-marketing survey have been implemented in the tables with the incidence “not known”.
Busulfan er teratogent hos rotter, mus og kaniner.
Busulfan is a teratogen in rats, mice and rabbits.
Impotens, sterilitet, azoospermi og testikulær atrofi er indberettet hos mandlige patienter.
Impotence, sterility, azoospermia, and testicular atrophy have been reported in male patients.
Hvis De er gravid eller ammer, har mistanke om, at De er gravid, eller planlægger at blive gravid, skal De spørge Deres læge til råds, før De bruger dette lægemiddel.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor before you receive treatment with Busilvex.
På grundlag af humane data er busulfan klassificeret af International Agency for Research on Cancer (IARC) som et humant karcinogen.
On the basis of human data, busulfan has been classified by the International Agency for Research on Cancer (IARC) as a human carcinogen.
Inden for hver hyppighedsgruppe er bivirkningerne angivet efter faldende alvorlighedsgrad.
Within each frequency grouping, adverse events are presented in order of decreasing seriousness.
- Øvrige indholdsstoffer: Dimethylacetamid og macrogol 400.
The other ingredients are dimethylacetamide and macrogol 400.
Hjerneabsces Cellulitis Sepsis
Brain abscess Cellulitis Sepsis
Seks af 103 patienter fik HVOD.
Six of 103 patients (6%) experienced HVOD.
* Indrapporteret efter markedsføringen ** Inkluderer hæmoragisk cystitis forårsaget af virusinfektion
* reported in post marketing experience ** include haemorrhagic cystitis induced by viral infection
De hyppigste infektiøse bivirkninger var: Cytomegalovirus (CMV)-reaktivering [30,7 % - 80,0 %], Epstein-Barr-virus (EBV)-reaktivering [2,3 % - 61 %], bakterieinfektioner [32,0 % - 38,9 %] og virusinfektioner [1,3 % - 17,2 %].
The most frequent infectious adverse reactions were Cytomegalovirus (CMV) reactivation [range: 30.7% - 80.0%], Epstein-Barr Virus (EBV) reactivation [range: 2.3% - 61%], bacterial infections [range: 32.0% - 38.9%] and viral infections [range: 1.3% - 17.2%].
Hvis De ønsker yderligere oplysninger om dette lægemiddel, skal De henvende Dem til indehaveren af markedsføringstilladelsen.
For any information about this medicine, please contact the Marketing Authorisation Holder
Leversygdom med veneokklusion er en alvorlig komplikation, som kan forekomme under behandling med Busilvex.
Hepatic veno-occlusive disease is a major complication that can occur during treatment with Busilvex.
Busilvex fås i multipakninger med 2 pakninger, der hver indeholder 4 hætteglas.
Busilvex is available in multipacks comprising 2 packs, each containing 4 vials.
Gennemgang af litteraturen muliggør en sammenligning af farmakokinetiske serier udført enten inden for samme studie eller mellem studier og viste uændrede, dosisuafhængige farmakokinetiske parametre uanset dosering og behandlingsplan.
The review of the literature allows a comparison of PK series performed either within the same study or between studies and demonstrated unchanged dose-independent PK parameters regardless the dosage or the schedule of administration.
Dosis og indgivelse: Dosen af Busilvex beregnes ud fra Deres legemsvægt.
Dose and administration: The dose of Busilvex will be calculated according to your body weight.
Profylaktisk eller empirisk brug af midler mod infektionssygdomme (antibiotika, antimykotika, antivirale midler) bør overvejes til profylakse og behandling af infektioner i løbet af perioden med neutropeni.
Prophylactic or empiric use of anti-infectives (bacterial, fungal, viral) should be considered for the prevention and management of infections during the neutropenic period.
Lægemidlet bør ikke anvendes til adipøse børn og unge med en BMI (kg/m²) > 30 kg/m², før yderligere data foreligger.
The medicinal product is not recommended in obese children and adolescents with body mass index Weight (kg)/(m²) > 30 kg/m² until further data become available.
Busilvex må ikke gives som hurtig intravenøs injektion, bolus eller perifer injektion.
Busilvex should not be given by rapid intravenous, bolus or peripheral injection.
Angst Depression Insomni
Anxiety Depression Insomnia
Feber blev indberettet for 87 % af patienterne og klassificeret som mild til moderat hos 84 % og alvorlig hos 3 %.
Fever was reported in 87% of patients and graded as mild/moderate in 84% and severe in 3%.
Ifølge to rapporter kan busulfan fjernes ved dialyse, og det bør derfor overvejes at sætte patienten i dialyse i tilfælde af en overdosis.
There have been two reports that busulfan is dialyzable, thus dialysis should be considered in the case of an overdose.
Heraf følger, at kontrollen af AUC efter intravenøs busulfan inden for det terapeutiske vindue ikke ændres, og der blev påvist samme target-performance med de to behandlingsplaner.
As a result, the control of intravenous busulfan AUC within the therapeutic windows is not modified and a similar targeting performance between the two schedules was illustrated.
Busulfan hører til en gruppe substanser, som er potentielt karcinogene på grund af deres virkemåde.
Busulfan belongs to a class of substances which are potentially carcinogenic based on their mechanism of action.
Kvinder skal stoppe med at amme, inden behandlingen med Busilvex påbegyndes.
Women must stop breast-feeding before starting their treatment with Busilvex.
Der bør fastlægges procedurer for korrekt håndtering og bortskaffelse af cytotoksiske lægemidler.
Procedures for proper handling and disposal of anticancer medicinal products should be considered.
Generel mortalitet og mortalitet uden recidiv mere end 100 dage efter transplantationen var henholdsvis (8/61) 13 % og (6/61) 10 % hos allotransplanterede patienter.
Overall mortality and non- relapse mortality at more than 100 days post-transplant was (8/61) 13% and (6/61) 10% in allotransplanted patients, respectively.
Der er kun begrænset klinisk erfaring med anvendelse af busulfan som en del af et konditionerende regimen inden HPCT hos børn med Fanconis anæmi.
There is limited clinical experience of the use of busulfan as a component of a conditioning regimen prior to HSCT in children with Fanconi's anaemia.
Terminalhalveringstiden lå i intervallet 2,8 til 3,9 timer.
The terminal half-life ranged from 2.8 to 3.9 hours.
Sammenlignet med regimet med fire daglige administrationer er regimet med én daglig administration karakteriseret af en højere maksimal koncentration, ingen lægemiddelakkumulation og en udvaskningsperiode (uden cirkulerende busulfan) mellem administrationerne.
Compared to the four times a day regimen, the once-daily regimen is characterized by a higher peak concentration, no drug accumulation and a wash out period (without circulating busulfan concentration) between consecutive administrations.
Forekomsten af hver af de bivirkninger, der er angivet i nedenstående tabel, er defineret i henhold til den højeste forekomst, der er set i publicerede kliniske studier med RIC-regimet, i hvilke den population, der blev behandlet med FB, var tydeligt identificeret, uanset behandlingsplan for busulfan og endepunkter.
The incidence of each adverse reactions presented in the following table has been defined according to the highest incidence observed in published clinical trials in RIC regimen for which the population treated with FB was clearly identified, whatever the schedules of busulfan administrations and endpoints.
Som dokumenteret i kliniske studier oplevede ingen af de behandlede patienter hjertetamponade eller anden specifik kardiotoksicitet med forbindelse til Busilvex.
As documented in clinical studies, no treated patients experienced cardiac tamponade or other specific cardiac toxicities related to Busilvex.
Farmakokinetik hos voksne
Pharmacokinetics in adults
Det er af særlig interesse, at der i studiet af denne interaktion i tre patientgrupper blev set højere plasmaniveauer af busulfan i den gruppe, der fik metronidazolprofylakse under behandlingen med busulfan, end hos de patienter, der ikke fik metronidazol.
It is of particular interest the study of this interaction in three groups of patients in which higher plasma levels of busulfan were observed in the group receiving metronidazol prophylaxis during busulfan treatment than in those without metronidazoles.
De omfattede sygdomme var akut leukæmi efter første remission, under første eller senere recidiv, under første remission (højrisiko) eller ved induktionssvigt; kronisk myeloid leukæmi i den kroniske eller fremskredne fase; primær refraktær eller resistent recidiverende Hodgkins sygdom eller nonHodgkin lymfom samt myelodysplastisk syndrom.
Diseases included were acute leukaemia past first remission, in first or subsequent relapse, in first remission (high risk), or induction failures; chronic melogenous leukaemia in chronic or advanced phase; primary refractory or resistant relapsed Hodgkin's disease or non-Hodgkin's lymphoma, and myelodysplastic syndrome.
Det anbefales at administrere antikonvulsiva fra 12 timer før Busilvex til 24 timer efter sidste Busilvex-dosis.
It is recommended to administer anticonvulsants 12 h prior to Busilvex to 24 h after the last dose of Busilvex.
Farmakokinetikken for intravenøst busulfan blev undersøgt hos 124 evaluerbare patienter efter 2 timers intravenøs infusion af i alt 16 doser i løbet af 4 dage.
The pharmacokinetics of intravenous busulfan was studied in 124 evaluable patients following a 2hour intravenous infusion for a total of 16 doses over four days.
47 % af patienterne fik kuldegysninger, som var milde til moderate hos 46 % og svære hos 1 %.
47% of patients experienced chills which were mild/moderate in 46% and severe in 1%.
Kronisk GVHD (c-GVHD) blev indberettet, hvis sygdommen var alvorlig eller førte til dødsfald, og blev angivet som dødsårsag hos 3 patienter.
Chronic GVHD (c-GVHD) was reported if serious or the cause of death, and was reported as the cause of death in 3 patients.
Signalerne vedrørende orale formuleringer af busulfan og risiko for hepatisk veno-okklusiv sygdom hos patienter, der har fået tidligere strålebehandling/kemoterapi/HSCT, sterilitet og overdoseringsbehandling kan lukkes.
The signals concerning busulfan oral formulations and hepatic veno-oclusive disease risk in patients who have received prior radiation therapy /chemotherapy /HSCT, sterility, overdose treatment can be closed.
Busilvex kan også give symptomer på overgangsalder, og hos præ-teenagepiger kan det forhindre, at puberteten indtræder.
Busilvex can also produce symptoms of menopause and in pre-adolescent girls it can prevent the onset of puberty.
Forhøjede aminotransferaser grad 3 blev indberettet for 24 % af patienterne.
Grade 3 elevated transaminases were reported in 24% of patients.
Busulfan inducerede kromosomafvigelser in vitro (gnaver- og humane celler) og in vivo (gnavere og mennesker).
Busulfan induced chromosomal aberrations in vitro (rodent and human cell) and in vivo (rodents and humans).
Patienter, der får samtidig behandling med busulfan og itraconazol eller metronidazol, bør monitoreres tæt for tegn på busulfantoksicitet.
Patients who are concurrently treated with busulfan and itraconazole or metronidazole should be closely monitored for signs of busulfan toxicity.
Den terminale halveringstid var fra 2,26 til 2,52 timer.
The terminal half life ranged from 2.26 to 2.52 h.
I betragtning af de fremlagte data i den gennemgåede PSUR vurderede PRAC, at det er påkrævet at indføre ændringer i produktinformationen for lægemidler, der indeholder busulfan.
In view of the data presented in the reviewed PSUR, the PRAC considered that changes to the product information of medicinal products containing busulfan were warranted.
Leukæmipatienter, der fik busulfan, udviklede mange forskellige cytologiske anomalier, og nogle fik karcinomer.
Leukaemia patients treated with busulfan developed many different cytological abnormalities, and some developed carcinomas.
Opbevaringsforhold
Storage conditions
Der blev opnået busulfankoncentrationer i cerebrospinalvæske, som var sammenlignelige med koncentrationerne i plasma, om end disse koncentrationer formentlig er utilstrækkelige til at udvirke antineoplastisk aktivitet.
Busulfan concentrations in the cerebrospinal fluid are comparable to those in plasma although these concentrations are probably insufficient for anti-neoplastic activity.
Der er observeret forskellige kromosomafvigelser i celler fra patienter, der fik oralt busulfan.
Various chromosome aberrations have been observed in cells from patients receiving oral busulfan.
Der er indberettet enkelte tilfælde af medfødte anomalier med lavdosis oralt busulfan, men disse var ikke nødvendigvis relateret til den aktive substans, og eksponering i 3. trimester kan være forbundet med intrauterin væksthæmning.
A few cases of congenital abnormalities have been reported with low-dose oral busulfan, not necessarily attributable to the active substance, and third trimester exposure may be associated with impaired intrauterine growth.