natgillin/translations-raw huggingface dataset:
Busilvex må ikke gives som hurtig intravenøs injektion, bolusinjektion eller perifer injektion.
Busilvex should not be given by rapid intravenous, bolus or peripheral injection.
Da der er indberettet krampeanfald ved anvendelse af Busilvex i høje doser, skal alle patienter have præmedicin i form af krampestillende midler.
All patients should be pre-medicated with anticonvulsant medicinal products to prevent seizures reported with the use of high dose busulfan.
Det anbefales at administrere krampestillende midler fra 12 timer inden Busilvex til 24 timer efter sidste dosis Busilvex.
It is recommended to administer anticonvulsants 12 h prior to Busilvex to 24 h after the last dose of Busilvex.
Alle voksne patienter i studierne fik phenytoin.
In adults all studied patients received phenytoin.
4. 4 og 4. 5).
There is no experience with other anticonvulsant agents such as benzodiazepines (see sections 4.4 and 4.5).
Pædiatriske patienter i studierne fik enten phenytoin eller benzodiazepiner.
In children studied patients received either phenytoin or benzodiazepines.
Der skal gives antiemetika før første dosis Busilvex og fortsættes dermed i et fast regime under behandlingen i overensstemmelse med lokal praksis.
Antiemetics should be administered prior to the first dose of Busilvex and continued on a fixed schedule according to local practice through its administration.
Voksne For adipøse patienter skal det overvejes, om doseringen bør baseres på en justeret idealvægt (AIBW).
In adults For obese patients, dosing based on adjusted ideal body weight (AIBW) should be considered.
Idealvægten (IBW) beregnes som følger:
Ideal body weight (IBW) is calculated as follows:
IBW kvinder (kg) =45+0, 91x( højde i cm- 152).
IBW men (kg)=50 + 0.91x (height in cm-152); IBW women (kg)= 45 + 0.91x (height in cm-152).
Justeret idealvægt (AIBW) beregnes som følger:
Adjusted ideal body weight (AIBW) is calculated as follows:
AIBW = IBW+0, 25x( faktisk legemsvægt - IBW).
AIBW= IBW+0.25x (actual body weight - IBW).
Pædiatriske patienter Lægemidlet bør ikke anvendes til adipøse børn og unge med en BMI- vægt (kg) / højde (m²) > 30 kg/ m² før yderligere data foreligger.
In paediatric patients The medicinal product is not recommended in obese children and adolescents with body mass index Weight (kg)/ (m)² > 30 kg/ m² until further data become available.
Patienter med nedsat nyrefunktion:
Renally impaired patient:
Der er ikke udført forsøg omfattende patienter med nedsat nyrefunktion, men da busulfan udskilles i moderat omfang med urinen, anbefales dosisjustering ikke hos disse patienter.
Studies in renally impaired patients have not been conducted, however, as busulfan is moderately excreted in the urine, dose modification is not recommended in these patients.
Det anbefales dog at udvise forsigtighed (se pkt 4. 8 og 5. 2).
However, caution is recommended (see sections 4.8 and 5.2).
Patienter med nedsat leverfunktion:
Hepatically impaired patient:
4. 4).
Caution is recommended, particularly in those patients with severe hepatic impairment (see section 4.4).
Ældre patienter:
3 Elderly patient:
Der er dog kun begrænset information om sikker anvendelse af Busilvex til patienter over 60 år.
However, for the safe use of Busilvex in patients older than 60 years only limited information is available.
5. 2) til ældre som til voksne (< 50 år).
Same dose (see section 5.2) for elderly as for adults (< 50 years old) should be used.
4. 6).
Hypersensitivity to the active substance or to any of the excipients Pregnancy (see section 4.6)
Der bør anvendes midler til understøttelse af trombocyt - og erytrocyttallet samt vækstfaktorer såsom granulocytkolonistimulerende middel (G- CSF) efter medicinsk behov.
Platelet and red blood cell support, as well as the use of growth factors such as granulocyte colony stimulating agent (G-CSF), should be employed as medically indicated.
Absolut neutrofiltal < 0, 5x109/ l ved en median på 4 dage efter transplantationen optrådte hos 100% af de voksne patienter og var normaliseret ved en median på 10 og 13 dage efter henholdsvis autolog og allogen transplantation (median for neutropeniperiode henholdsvis 6 og 9 dage).
In adults, absolute neutrophil counts < 0.5x109/ l at a median of 4 days post transplant occurred in 100% of patients and recovered at median day 10 and 13 days following autologous and allogeneic transplant respectively (median neutropenic period of 6 and 9 days respectively).
Trombocytopeni (< 25x109/ l eller behov for trombocyttransfusion) forekom ved median 5- 6 dage hos 98% af patienterne.
Thrombocytopenia (< 25x109/ l or requiring platelet transfusion) occurred at a median of 5-6 days in 98% of patients.
Anæmi (hæmoglobin < 8, 0 g/ dl) forekom hos 69% af patienterne.
Anaemia (haemoglobin < 8.0 g/ dl) occurred in 69% of patients.
Absolut neutrofiltal < 0, 5x109/ l ved en median på 3 dage efter transplantationen optrådte hos 100% af de pædiatriske patienter og varede 5 og 18, 5 dage efter henholdsvis autolog og allogen transplantation.
In paediatric patients, absolute neutrophil counts < 0.5x109/ l at a median of 3 days post transplant occurred in 100% of patients and lasted 5 and 18.5 days in autologous and allogeneic transplant respectively.
Trombocytopeni (< 25x109/ l eller behov for trombocyttransfusion) forekom hos 100% af de pædiatriske patienter.
In children, thrombocytopenia (< 25x109/ l or requiring platelet transfusion) occurred in 100% of patients.
Anæmi (hæmoglobin < 8, 0 g/ dl) forekom hos 100% af patienterne.
Anaemia (haemoglobin < 8.0 g/ dl) occurred in 100% of patients.
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.
Busulfan metaboliseres hovedsageligt via leveren, og der skal derfor udvises forsigtighed, når Busilvex anvendes til patienter med eksisterende leverfunktionsnedsættelse, specielt patienter med svær nedsættelse.
Since busulfan is mainly metabolized through the liver, caution should be observed when Busilvex is used in patients with pre-existing impairment of liver function, especially in those with severe hepatic impairment.
Det anbefales at monitorere serumtransaminase, alkalisk fosfatase og bilirubin regelmæssigt hos denne patientgruppe i 28 dage efter transplantationen til påvisning af evt. hepatotoksicitet.
It is recommended when treating these patients that serum transaminase, alkaline phosphatase, and bilirubin should be monitored regularly 28 days following transplant for early detection of hepatotoxicity.
4. 8).
Patients who have received prior radiation therapy, greater than or equal to three cycles of chemotherapy, or prior progenitor cell transplant may be at an increased risk (see section 4.8).
4. 5).
Caution should be exercised when using paracetamol prior to (less than 72 hours) or concurrently with Busilvex due to a possible decrease in the metabolism of busulfan (See section 4.5).
Som dokumenteret i kliniske forsøg, oplevede ingen af de behandlede patienter hjertetamponade eller særlig kardiotoksicitet med forbindelse til Busilvex.
As documented in clinical studies, no treated patients experienced cardiac tamponade or other specific cardiac toxicities related to Busilvex.
4. 8).
However cardiac function should be monitored regularly in patients receiving Busilvex (see section 4.8).
I kliniske Busilvex- forsøg er der forekommet shocklunge - acute respiratory distress syndrome fulgt af respirationssvigt forbundet med interstitiel lungefibrose hos en patient, som afgik ved døden, om end det ikke var muligt at påvise en klar ætiologi.
4 Occurrence of acute respiratory distress syndrome with subsequent respiratory failure associated with interstitial pulmonary fibrosis was reported in Busilvex studies in one patient who died, although, no clear aetiology was identified.
Endvidere kan busulfan muligvis inducere
In addition, busulfan might induce pulmonary toxicity that may be additive to the effects produced by other cytotoxic agents.
4. 8).
Therefore, attention should be paid to this pulmonary issue in patients with prior history of mediastinal or pulmonary radiation (see section 4.8).
4. 8).
Periodic monitoring of renal function should be considered during therapy with Busilvex (see section 4.8).
Der er indberettet krampeanfald ved behandling med høje doser af busulfan.
Seizures have been reported with high dose busulfan treatment.
Der bør udvises forsigtighed, når den anbefalede dosis Busilvex gives til patienter, som tidligere har haft krampeanfald.
Special caution should be exercised when administering the recommended dose of Busilvex to patients with a history of seizures.
Patienterne skal have passende profylakse i form af antiepileptika Alle data med Busilvex til voksne blev indhentet under anvendelse af phenytoin.
In adults, all data with Busilvex were obtained using phenytoin.
Der findes ingen data, hvor der anvendt andre antiepileptika som f. eks benzodiazepiner.
There are no data available on the use of other anticonvulsant agents such as benzodiazepines.
Effekten af andre antiepileptika (bortset fra phenytoin) på busulfans farmakokinetik kendes således ikke (se 4. 2 og 4. 5).
Thus, the effect of anticonvulsant agents (other than phenytoin) on busulfan pharmacokinetics is not known.
Data med Busilvex til pædiatriske patienter blev indhentet med anvendelse af benzodiazepiner eller phenytoin.
In paediatric patients, data with Busilvex were obtained using benzodiazepines or phenytoin.
Verdenssundhedsorganisationen har konkluderet, at der er en kausal sammenhæng mellem eksponering for busulfan og cancer.
The World Health Association has concluded that there is a causal relationship between busulfan exposure and cancer.
Busulfan kan nedsætte fertiliteten.
Fertility: busulfan can impair fertility.
Det anbefales, at mænd behandlet med Busilvex undgår at avle børn under og op til 6 måneder efter behandlingen, og at de rådgives om nedfrysning af sæd før behandlingen på grund af muligheden for irreversible infertilitet på grund af behandling med Busilvex.
Therefore, men treated with Busilvex are advised not to father a child during and up to 6 months after treatment and to seek advice on cryo-conservation of sperm prior to treatment because of the possibility of irreversible infertility due to therapy with Busilvex.
Busulfan- behandling hos præpubertær pige forhindrede pubertetsstart på grund af ovariesvigt.
Busulfan treatment in a pre-adolescent girl prevented the onset of puberty due to ovarian failure.
4. 6 og 5. 3).
DMA decreases fertility in male and female rodents (see sections 4.6 and 5.3)
Der er ikke udført særlige kliniske forsøg med henblik på at vurdere lægemiddelinteraktion mellem intravenøs busulfan og itraconazol.
No specific clinical trial was carried out to assess drug-drug interaction between intravenous busulfan and itraconazole.
Ifølge publicerede studier med deltagelse af voksne kan administration af itraconazol til patienter, der får højdosis busulfan nedsætte clearance af busulfan.
From published studies, in adults administration of itraconazole to patients receiving high-dose busulfan may result in reduced busulfan clearance.
Patienterne skal monitoreres for tegn på toksiske reaktioner på busulfan, når itraconazol gives som profylaktisk svampemiddel sammen med intravenøs busulfan.
Patients should be monitored for signs of busulfan toxicity when itraconazole is used as an antifungal prophylaxis with intravenous busulfan.
For et behandlingsregime med BuCy2 til voksne er der indberettet, at tidsintervallet mellem sidste perorale administration af busulfan og første administration af cyclophosphamid kan påvirke udvikling af toksicitet.
In adults, for the BuCy2 regimen it has been reported that the time interval between the last oral busulfan administration and the first cyclophosphamide administration may influence the development of toxicities.
Der er observeret nedsat forekomst af hepatisk veneoklussion (HVOD) og anden behandlingsrelateret toksicitet hos patienter, hvor tidsrummet mellem sidste dosis busulfan og første dosis cyclophosphamid er > 24 timer.
A reduced incidence of Hepatic Veino Occlusive Disease (HVOD) and other regimen- related toxicity have been observed in patients when the lag time between the last dose of oral busulfan and the first dose of cyclophosphamide is > 24hours.
For et behandlingsregimen med BuMel til pædiatriske patienter er det indberettet, at administration af melphalan mindre end 24 timer efter den sidste orale administration af busulfan kan påvirke udviklingen af toksiciteter.
In paediatric patients, for the BuMel regimen it has been reported that the administration of melphalan less than 24 hours after the last oral busulfan administration may influence the development of toxicities.
4. 4).
Paracetamol is described to decrease glutathione levels in blood and tissues, and may therefore decrease busulfan clearance when used in combination (see section 4.4).
5 der får højdosis busulfan, har vist sig at øge busulfan- clearance på grund af induktion af glutathion- S - transferase.
5 Phenytoin or benzodiazepines were administered for seizure prophylaxis in all patients in the clinical trials conducted with intravenous busulfan.
4. 4).
The concomitant systemic administration of phenytoin to patients receiving high-dose busulfan has been reported to increase busulfan clearance, due to induction of glutathion-S-transferase.
4. 2 og 4. 4).
However no evidence of this effect has been seen in intravenous data. (see section 4.4) No interaction has been reported when benzodiazepines such as diazepam, clonazepam or lorazepam have been used to prevent seizures with high-dose busulfan (see sections 4.2 and 4.4).
Interaktion blev ikke observeret ved kombination af busulfan og fluconazol (antimykotikum) eller 5- HT3- antiemetika såsom ondansetron og granisetron.
No interaction was observed when busulfan was combined with fluconazole (antifungal agent) or 5 HT3 antiemetics such as ondansetron or granisetron.
Graviditet HPCT er kontraindiceret hos gravide kvinder, hvorfor Busilvex er kontraindiceret under graviditet.
Pregnancy HPCT is contraindicated in pregnant women; therefore, Busilvex is contraindicated during pregnancy.
I prækliniske forsøg har busulfan medført embryoføtale dødsfald og misdannelser (se pkt 5. 3).
Busulfan has caused embryofoetal lethality and malformations in pre-clinical studies. (see section 5.3)
Der foreligger ikke tilstrækkelige data fra anvendelse af enten busulfan eller DMA til gravide kvinder.
There are no adequate data from the use of either busulfan or DMA in pregnant woman.
Der er indberettet enkelte tilfælde af medfødte anomalier med lavdosis peroralt 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.
Amning Det vides ikke, om busulfan og DMA udskilles i modermælk.
Lactation It is not known whether busulfan and DMA are excreted in human milk.
Eftersom busulfan har udvist potentiale for tumorgenicitet i forsøg hos mennesker og dyr, skal amning indstilles før behandlingens start.
Because of the potential for tumorigenicity shown for busulfan in human and animal studies, breast-feeding should be discontinued at the start of therapy.
Fertilitet Busulfan og DMA kan nedsætte fertilitet hos mænd eller kvinder.
Fertility Busulfan and DMA can impair fertility in man or woman.
4. 4).
Therefore it is advised not to father child during the treament and up to 6 months after treatment and to seek advice on cryo-conservation of sperm prior to treatment because of the possibility of irreversible infertility (see section 4.4).
Bivirkninger hos voksne Informationerne om bivirkninger stammer fra to kliniske forsøg (n=103) med Busilvex.
Averse events in adults Adverse events information is derived from two clinical trials (n=103) of Busilvex.
De omfattede infektion og graft- versus - host- 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.
Blod og lymfesystem:
Blood and the lymphatic system disorders:
Derfor fik alle patienter omfattende cytopeni: leukopeni 96%, trombocytopeni 94% og anæmi 88%.
Therefore all patients experienced profound cytopenia: leukopenia 96%, thrombocytopenia 94%, and anemia 88%.
Data vedrørende forekomsten af akut graft- versus- host- disease (a- GVHD) blev indsamlet i OMC - BUS- 4 studiet (under allogeneic) (n=61).
6 The incidence of acute graft versus host disease (a-GVHD) data was collected in OMC-BUS-4 study(allogeneic)(n=61).
11 patienter i alt (18%) fik a- GVHD.
A total of 11 patients (18%) experienced a-GVHD.
Akut GVHD blev
The incidence of a- GVHD grades I-II was 13% (8/ 61), while the incidence of grade III-IV was 5% (3/ 61).
6 anset for alvorlig hos 3 patienter.
Acute GVHD was rated as serious in 3 patients.
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.
39% af patienterne (40/ 103) oplevede en eller flere episoder med infektion, hvoraf 83% (33/ 40) blev klassificeret som mild eller moderat.
39% of patients (40/ 103) experienced one or more episodes of infection, of which 83% (33/ 40) were rated as mild or moderate.
Pneumoni var dødelig hos 1% (1/ 103) og livstruende hos 3% af patienterne.
Pneumonia was fatal in 1% (1/ 103) and life-threatening in 3% of patients.
Andre infektioner blev anset for alvorlige hos 3% af patienterne.
Other infections were considered severe in 3% of patients.
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%.
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%.
15% af de alvorlige uønskede hændelser (SAEs) omfattede levertoksicitet.
15% of SAEs involved liver toxicity.
HVOD indtraf hos:
HVOD occurred in:
8, 2% (5/ 61) af de allogene patienter (fatal hos 2 patienter) og 2, 5% (1/ 42) af de autologe patienter.
8.2% (5/ 61) allogeneic patients (fatal in 2 patients) and 2.5% (1/ 42) of autologous patients.
Der blev også set forhøjet bilirubin (n=3) og forhøjet ASAT (n=1).
Elevated bilirubine (n=3) and elevated AST (n=1) were also observed.
To af de ovenfor nævnte fire patienter med alvorlig serum- hepatotoksicitet var blandt patienterne med diagnosticeret HVOD.
Two of the above four patients with serious serum hepatotoxicity were among patients with diagnosed HVOD.
I Busilvex- forsøgene afgik en patient ved døden på grund af shocklunge - acute respiratory distress syndrome - fulgt af respirationssvigt forbundet med interstitiel lungefibrose.
One patient experienced a fatal case of acute respiratory distress syndrome with subsequent respiratory failure associated with interstitial pulmonary fibrosis in the Busilvex studies.
Endvidere nævner litteraturen ændringer i cornea og øjets linse med peroral busulfan.
In addition the literature review reports alterations of cornea and lens of the eye with oral busulfan.
Bivirkninger hos pædiatriske patienter Informationerne om uønskede hændelser stammer fra det kliniske forsøg på børn (n=55).
Adverse events in paediatric patients Adverse events information are derived from the clinical study in paediatrics (n=55).
Data vedrørende forekomsten af akut graft- versus- host- disease (a- GVHD) blev indsamlet for allogene patienter (n=28).
The incidence of acute graft versus host disease (a-GVHD) data was collected in allogeneic patients (n=28).
14 patienter i alt (50%) fik a- GVHD.
A total of 14 patients (50%) experienced a-GVHD.
Forekomsten af a- GVHD grad I- II var 46, 4% (13/ 28), mens forekomsten af grad III- IV var 3, 6% (1/ 28).
The incidence of a-GVHD grades I-II was 46.4% (13/ 28), while the incidence of grade III-IV was 3.6% (1/ 28).
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.
89% af patienterne (49/ 55) oplevede infektioner (dokumenteret og udokumenteret febril neutropeni).
Infections (documented and non documented febrile neutropenia) were experienced in 89% of patients (49/ 55).
Mild/ moderat feber blev indberettet for 76% af patienterne.
Mild/ moderate fever was reported in 76% of patients.
Forhøjede transaminaser grad 3 blev indberettet for 24% af patienterne.
Grade 3 elevated transaminases were reported in 24% of patients.
Veneokklusiv sygdom (VOD) blev indberettet for 15% (4/ 27) og 7% (2/ 28) efter henholdsvis autolog og allogen transplantation.
Veino occlusive disease (VOD) was reported in 15% (4/ 27) and 7% (2/ 28) of the autologous and allogenic transplant respectively.
Bivirkninger, som er indberettet for både voksne og børn i mere end et enkeltstående tilfælde, er anført nedenfor opdelt efter systemorganklasse og hyppighed.
Adverse reactions reported both in adults and paediatric patients as more than an isolated case are listed below, by system organ class and by frequency.
Inden for hver gruppering af hyppighed vises bivirkningerne i rækkefølge efter faldende alvorlighed.
Within each frequency grouping, adverse events are presented in order of decreasing seriousness.
Forekomsten defineres som følger: meget almindelig (> 1/ 10), almindelig (> 1/ 100, < 1/ 10), usædvanlig (> 1, 000, < 1/ 100).
Frequencies are defined as: very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10), uncommon (≥ 1/ 1,000, < 1/ 100).
Systemorganklasse Infektioner og parasitære sygdomme
System organ class
Meget almindelige Rhinit Pharyngit
Very common
Usædvanlige
Uncommon
7 Blod og lymfesystem
7 Infections and infestations
Anoreksi Hyperglykæmi Hypocalcæmi Hypokaliæmi Hypomagnesæmi Hypophosphatemi
Anorexia Hyperglycaemia Hypocalcaemia Hypokalaemia Hypomagnesaemia Hypophosphatemia
Angst Depression Insomnia
Anxiety Depression Insomnia
Arytmi Atrieflimren Kardiomegali Perikardial effusion Perikardit
Arrhythmia Atrial fibrillation Cardiomegaly Pericardial effusion Pericarditis
Trombose i a. femoralis Systemisk vaskulært lækage - syndrom
Femoral artery thrombosis Capillary leak syndrome
Hyperventilation Respirationssvigt Alveolær hæmoragi Astma Atelektase Pleural effusion
Hyperventilation Respiratory failure Alveolar haemorrhages Asthma Atelectasis Pleural effusion
Stomatit Diaré Abdominalsmerter Kvalme Opkastning Dyspepsi Ascites Forstoppelse Ubehag omkring anus
Stomatitis Diarrhoea Abdominal pain Nausea Vomiting Dyspepsia Ascites
Lever og galdeveje
Constipation
Hepatomegali Icterus
Anus discomfort
Hud og subkutane væv
8 Hepato-biliary disorders
Udslæt Pruritus
Hepatomegaly Jaundice
Hudafskalning Erytem
Rash Pruritis Alopecia
Knogler, led, muskler og bindevæv
Skin desquamation Erythema Pigmentation disorder
Alopeci Myalgi Rygsmerter Artralgi
Musculoskeletal and connective tissue disorders
Pigmenteringsdefekt
Myalgia Back pain
Nyrer og urinveje
Arthralgia Renal and urinary disorders
8
Asthenia Chills Fever Chest pain
Almene symptomer og
Oedema Oedema general
reaktioner på administrationsstedet
Pain or inflammation at injection site
Undersøgelser
Mucositis Investigations
Forhøjede transaminaser Forhøjet bilirubin Forhøjet GGT Forhøjet alkalisk fosfatase Vægtstigning Anormale vejrtrækningslyde Forhøjet kreatinin
Transaminases increased Bilirubin increased GGT increased Alkaline phosphatases increased Weight increased
Forhøjet BUN Nedsat uddrivningsfraktion
Abnormal breath sounds Creatinine elevated