natgillin/translations-raw huggingface dataset:
Psykiske forstyrrelser
Psychiatric disorders Confusional state
Nervesystemet Anfald (inkl. kramper, grand mal kramper, status epilepticus)
Nervous system disorders
Almindelig:
Seizures (including convulsions, Common:
Almindelig:
Amnesia Common:
3 (3) Meget almindelig:
3 (3) Somnolence Very common:
24 (23) Meget almindelig:
24 (23) Peripheral neurological Very common:
6 (7) Meget almindelig:
6 (7) Very common:
Meget almindelig:
Hypoesthesia Very common:
18 (17) Meget almindelig:
18 (17) Paresthesia Very common:
15 (15) Almindelig:
15 (15)
3 (4) Almindelig:
5 (6) Common:
2 (2)
3 (4)
6 Systemorganklasser MedDRA
6 MedDRA Preferred Term(s)
Balanceforstyrrelser Tremor Svimmelhed Hovedpine Dysgeusi
Ataxia Balance disorder Tremor Dizziness Headache Dysgeusia
Almindelig:
9 (9) Common:
2 (2) Almindelig:
2 (2) Common:
5 (5) Meget almindelig:
5 (5) Very common:
22 (21) Meget almindelig:
22 (21) Very common:
15 (15) Almindelig:
15 (15) Common:
- Almindelig:
2 (2) N/ A Common:
3 (4) - Meget almindelig:
3 (4) N/ A Very common:
14 (17) -
14 (17) N/ A
Der er også rapporteret om hændelser med demyelinisation og ascenderende perifer neuropati, der ligner Guillain- Barré syndrom En person i den pædiatriske gruppe havde en fatal neurologisk hændelse af status epilepticus.
One subject in the paediatric group had a fatal neurological event of status epilepticus.
Hypotension
Hypotension
Luftveje, thorax og mediastinum Pleural effusion Pibende åndedrætslyd Dyspnø Hoste
Respiratory, thoracic, and mediastinal disorders Pleural effusion Wheezing Dyspnea Cough
10 (10) Almindelig:
10 (10) Common:
21 (20) Meget almindelig:
21 (20) Very common:
- - - -
N/ A N/ A N/ A N/ A
Diarré Stomatitis Opkastning Mavesmerter Obstipation Kvalme
Diarrhoea Stomatitis Vomiting Abdominal pain Constipation Nausea
23 (22) Almindelig:
23 (22) Common:
8 (8) Meget almindelig:
8 (8) Very common:
9 (9) Meget almindelig:
9(9) Very common:
1 (1) Almindelig:
1 (1) Common:
8 (10) - Almindelig:
8 (10) N/ A Common:
Lever og galdeveje Hyperbilirubinæmi Øget transaminase Øget aspartataminotransferase
Hepatobiliary disorders Hyperbilirubinaemia Transaminases increased Aspartate aminotransferase increased
3 (3) - Almindelig:
3 (3) N/ A Common:
8 (10) Meget almindelig:
8 (10) Very common:
10 (12) -
10(12) N/ A
Knogler, led, muskler og bindevæv
Musculoskeletal and connective tissue disorders Muscle weakness Myalgia
13 (13) Almindelig:
13 (13)
- - Almindelig:
N/ A N/ A
7 Systemorganklasser MedDRA
7 MedDRA Preferred Term(s)
Rygsmerter Smerter i ekstremitet
Arthralgia Back pain Pain in extremity
8 (8) Almindelig:
8 (8) Common:
- Almindelig:
1 (1) N/ A Common:
Øget blodkreatinin
Blood creatinine increased
Almene symptomer og reaktioner på administrationsstedet Ødem Abnormal gangart Perifert ødem Feber Smerter Træthed Asteni
General disorders and administrative site conditions Oedema Gait abnormal Oedema peripheral Pyrexia Pain Fatigue Asthenia
11 (11) Almindelig:
11 (11) Common:
6 (6) Meget almindelig:
6 (6) Very common:
15 (15) Meget almindelig:
15 (15) Very common:
24 (23) Meget almindelig:
24 (23) Very common:
11 (11) Meget almindelig:
11 (11) Very common:
51 (50) Meget almindelig:
51 (50) Very common:
- - - Almindelig:
N/ A N/ A N/ A Common:
2 (2) - Almindelig:
2 (2) N/ A Common:
Data fra forsøg fra National Cancer Institute/ programmet for udleveringstilladelse og fase I- forsøg
Data from NCI studies/ compassionate use programme and phase I studies
Ud over de bivirkninger, der er observeret i de pivotale kliniske forsøg, er der også data fra 875 patienter fra NCI forsøg/ program for udleveringstilladelse (694 patienter) og fase I- forsøg (181 patienter) med nelarabin.
In addition to the adverse reactions seen in the pivotal clinical trials, there are also data from 875 patients from NCI studies/ compassionate use programme (694 patients) and Phase I (181 patients) studies of nelarabine.
4. 2 og 4. 4)
Tumour lysis syndrome – 7 cases (see sections 4.2 and 4.4)
2400 mg/ m2) daglig i 5 dage til 5 voksne patienter og op til 2900 mg/ m2 til yderligere 2 voksne på dag 1, 3 og 5.
Nelarabine has been administered in clinical trials up to a dose of 75 mg/ kg (approximately 2,250 mg/ m2) daily for 5 days to a paediatric patient, up to a dose of 60 mg/ kg (approximately 2,400 mg/ m2) daily for 5 days to 5 adult patients and up to 2,900 mg/ m2 in a further 2 adults on days 1, 3 and 5.
Det er sandsynligt, at en overdosis af nelarabin vil resultere i svær neurotoksicitet (muligvis inkl. paralyse, coma), myelosuppression og potentielt død.
It is likely that nelarabine overdose would result in severe neurotoxicity (possibly including paralysis, coma), myelosuppression and potentially death.
Ved en dosis på 2200 mg/ m2 givet på dag 1, 3 og 5 hver 21. dag, udviklede 2 patienter en signifikant grad 3 ascenderende sensorisk neuropati.
At a dose of 2200 mg/ m2 given on days 1, 3 and 5 every 21 days, 2 patients developed a significant grade 3 ascending sensory neuropathy.
8 Der findes ingen kendt antidot i tilfælde af overdosering med nelarabin.
8 There is no known antidote for nelarabine overdose.
Antineoplastiske midler, antimetabolitter, purinanaloger, ATC- kode:
Antineoplastic agents, antimetabolites, purine analogues, ATC code:
Nelarabin er et pro- drug af deoxyguanosin analog ara- G.
Nelarabine is a pro-drug of the deoxyguanosine analogue ara-G.
Nelarabin demethyleres hurtigt af adenosindeaminase (ADA) til ara- G, som derefter phosphoryleres intracellulært af deoxyguanosinkinase og deoxycytidinkinase til dets 5 ’ - monophosphatmetabolit.
Nelarabine is rapidly demethylated by adenosine deaminase (ADA) to ara-G and then phosphorylated intracellularly by deoxyguanosine kinase and deoxycytidine kinase to its 5’ -monophosphate metabolite.
Monophosphatmetabolitten omdannes derefter til den aktive 5 ’ - triphosphat fra ara- GTP.
The monophosphate metabolite is subsequently converted to the active 5’ -triphosphate form, ara-GTP.
Akkumulering af ara- GTP i leukæmiske stamceller giver mulighed for selektiv indarbejdning af ara- GTP i deoxyribonukleinsyre (DNA), som fører til hæmning af DNA- syntesen.
Accumulation of ara-GTP in leukaemic blasts allows for preferential incorporation of ara-GTP into deoxyribonucleic acid (DNA) leading to inhibition of DNA synthesis.
In- vitro er T- celler mere sensitive end B- celler over for nelarabins cytotoksiske virkning.
In vitro, T-cells are more sensitive than B-cells to the cytotoxic effects of nelarabine.
Voksenforsøg
Adult studies
I et åbent forsøg udført af Cancer and Leukaemia Group B og Southwest Oncology Group blev nelarabins sikkerhed og effekt undersøgt hos 39 voksne med T- celle akut lymfoblastær leukæmi (T- ALL) eller lymfoblastær lymfom (T- LBL).
In an open-label study carried out by the Cancer and Leukaemia Group B and the Southwest Oncology Group, the safety and efficacy of nelarabine were evaluated in 39 adults with T-cell acute lymphoblastic leukaemia (T-ALL) or lymphoblastic lymphoma (T-LBL).
28 ud af de 39 voksne, i alderen 16 - 65 år (i gennemsnit 34 år), var recidiverede eller refraktære i mindst to tidligere induktionsregimer.
Twenty– eight of the 39 adults had relapsed or were refractory to at least two prior induction regimens and aged between 16 to 65 years of age (mean 34 years).
Nelarabin i doser på 1500 mg/ m2/ døgn blev givet intravenøst over 2 timer på dag 1, 3 og 5 i en cyklus på 21 dage.
Nelarabine at a dose of 1500 mg/ m2/ day was administered intravenously over two hours on days 1, 3 and 5 of a 21 day cycle.
5 af de 28 patienter (18%) [95% CI:
Five of the 28 patients (18%) [95% CI:
6% — 37%], som blev behandlet med nelarabin, opnåede komplet respons (knoglemarvscelletal ≤ 5%, ingen andre tegn på sygdom og fuld restitution af perifere blodtal).
6 %— 37%] treated with nelarabine achieved a complete response (bone marrow blast counts ≤ 5%, no other evidence of disease, and full recovery of peripheral blood counts).
I alt 6 patienter (21%) [95% CI:
A total of 6 patients (21%) [95% CI:
8% – 41%] opnåede komplet respons med eller uden hæmatologisk restitution.
8 %– 41%] achieved a complete response with or without haematological recovery.
Tid til komplet respons i begge responsgrupper varierede mellem 2, 9 og 11, 7 uger.
Time to complete response in both classifications of response ranged from 2.9 to 11.7 weeks.
Median af samlet overlevelse var 20, 6 uger [95% Cl:
Median overall survival was 20.6 weeks [95% CI:
10, 4 – 36, 4].
10.4– 36.4].
Overlevelse efter 1 år var 29% [95% CI:
Survival at one year was 29% [95% CI:
Pædiatriske forsøg
Paediatric studies
I et åbent multicenterforsøg udført af Childrens Oncology Group, blev nelarabin givet intravenøst over 1 time i 5 dage til 151 patienter ≤ 21 år, hvoraf 149 havde fået recidiv eller havde refraktær T- celle akut lymfoblastær leukæmi (T- ALL) eller T- celle lymfoblastær lymfom (T- LBL).
In an open-label, multicenter study carried out by Childrens Oncology Group, nelarabine was administered intravenously over 1 hour for 5 days to 151 patients ≤ 21 years of age, 149 of whom had relapsed or refractory T-cell acute lymphoblastic leukaemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL).
84 patienter, hvoraf 39 havde fået 2 eller flere tidligere induktionsbehandlinger, og hvoraf 31 havde fået 1 tidligere induktionsbehandling, blev behandlet med 650 mg/ m2/ døgn nelarabin givet intravenøst over 1 time daglig i 5 på hinanden følgende dage gentaget hver 21. dag.
Eighty-four (84) patients, 39 of whom had received two or more prior induction regimens and 31 whom had received one prior induction regimen, were treated with 650 mg/ m2/ day of nelarabine administered intravenously over 1 hour daily for 5 consecutive days repeated every 21 days.
Af de 39 patienter, der havde fået 2 eller flere tidligere induktionsbehandlinger, oplevede 5 (13%) [95% CI:
Of the 39 patients who had received two or more prior induction regimens, 5 (13%) [95% CI:
4% – 27%] et komplet respons (knoglemarvscelletal ≤ 5%, ingen andre tegn på sygdom, og fuldstændig restitution af perifere blodtal) og 9 (23%) [95% CI:
4 %– 27%] achieved a complete response (bone marrow blast counts ≤ 5%, no other evidence of disease, and full recovery of peripheral blood counts) and 9 (23%) [95% CI:
11% – 39%] opnåede komplet respons med eller uden fuldstændig hæmatologisk restitution.
11 %– 39%] achieved complete responses with or without full haematological recovery.
Varighed af respons i begge responsgrupper varierede mellem 4, 7 og 36, 4 uger, samlet median overlevelse var 13, 1 uger [95% CI:
Duration of response in both classifications of response ranged between 4.7 and 36.4 weeks and median overall survival was 13.1 weeks [95% CI:
8. 7 – 17. 4], og overlevelse efter 1 år var 14% [95% CI:
8.7– 17.4] and survival at one year was 14% [95% CI:
9 13 (42%) af de 31 patienter, der tidligere havde modtaget 1 induktionsbehandling, opnåede et komplet respons.
9 Thirteen (42%) of the 31 patients treated with one prior induction regimen achieved a complete response overall.
4 (44%) af disse 9 refraktære patienter opnåede et komplet respons på nelarabin.
Four (44%) of the nine refractory patients experienced a complete response to nelarabine.
Det betyder at det ikke har været muligt at opnå fuldstændig dokumentation for dette lægemiddel fordi det drejer sig om en sjælden sygdom.
This means that due to the rarity of the disease it has not been possible to obtain complete information on this medicinal product.
Monophosphatmetabolitten omdannes derefter til den aktive 5 ’ - triphosphat fra ara- GTP.
The monophosphate metabolite is subsequently converted to the active 5’ -triphosphate from, ara-GTP.
I en krydsforsøgsanalyse med data fra 4 fase I- forsøg blev farmakokinetikken af nelarabin og ara- G undersøgt hos patienter under 18 år og voksne patienter med refraktær leukæmi eller lymfom.
In a cross-study analysis using data from four Phase I studies, the pharmacokinetics of nelarabine and ara-G were characterized in patients aged less than 18 years and adult patients with refractory leukaemia or lymphoma.
Plasma ara- G Cmax- værdier sås generelt ved afslutningen af nelarabin- infusionen og var generelt højere end nelarabin Cmax- værdier, hvilket tyder på hurtig og ekstensiv omdannelse af nelarabin til ara- G.
Plasma ara-G Cmax values generally occurred at the end of the nelarabine infusion and were generally higher than nelarabine Cmax values, suggesting rapid and extensive conversion of nelarabine to ara-G.
Efter infusion af 1500 mg/ m2 nelarabin over 2 timer til voksne patienter, var middelplasma for nelarabin Cmax og AUCinf hhv 13, 9 µmol/ l (81%) og 13, 5 µmol/ l time (56%).
After infusion of 1,500 mg/ m2 nelarabine over two hours in adult patients, mean (%CV) plasma nelarabine Cmax and AUCinf values were 13.9 µM (81%) and 13.5 µM. h (56%) respectively.
115 µmol/ l (16%) og 571 µmol/ l time (30%).
Mean plasma ara-G Cmax and AUCinf values were 115 µM (16%) and 571 µM. h (30%), respectively.
Intracellulær Cmax for ara- GTP blev set i løbet af 3 - 25 timer på dag 1.
Intracellular Cmax for ara-GTP appeared within 3 to 25 hours on day 1.
Middel intracellulær ara- GTP Cmax og AUC- var 95, 6 µmol/ l (139%) og 2214 µmol/ l time (263%) efter denne dosis.
Mean (%CV) intracellular ara-GTP Cmax and AUC values were 95.6 µM (139%) and 2214 µM. h (263%) at this dose.
45, 0 µmol/ l (40%) og 38, 0 µmol/ l time (39%).
After infusion of 400 or 650 mg/ m2 nelarabine over one hour in 6 paediatric patients, mean (%CV) plasma nelarabine Cmax and AUCinf values, adjusted to a 650 mg/ m2 dose, were 45.0 µM (40%) and 38.0 µM. h (39%), respectively.
60, 1 µmol/ l (17%) og 212 µmol/ l time (18%).
Mean plasma ara-G Cmax and AUCinf values were 60.1 µM (17%) and 212 µM. h (18%), respectively.
Nelarabin og ara- G fordeles i vid udstrækning i hele kroppen, baseret på kombinerede fase I farmakokinetiske data for nelarabindoser på 104 - 2900 mg/ m2.
Nelarabine and ara-G are extensively distributed throughout the body based on combined Phase I pharmacokinetic data at nelarabine doses of 104 to 2,900 mg/ m2.
115 l/ m2 (159%) og 89, 4 l/ m2 (278%) for voksne og pædiatriske patienter.
Specifically, for nelarabine, mean (%CV) VSS values were 115 l/ m2 (159%) and 89.4 l/ m2 (278%) in adult and paediatric patients, respectively.
44, 8 l/ m2 (32%) og 32, 1 l/ m2 (25%) for voksne og pædiatriske patienter.
For ara-G, mean VSS/ F values were 44.8 l/ m2 (32%) and 32.1 l/ m2 (25%) in adult and paediatric patients, respectively.
Nelarabin og ara- G er ikke overvejende bundet til humane plasmaproteiner (mindre end 25%) in vitro, og bindingen er uafhængig af nelarabin eller ara- G i koncentrationer op til 600 µmol/ l.
10 Nelarabine and ara-G are not substantially bound to human plasma proteins (less than 25%) in vitro, and binding is independent of nelarabine or ara-G concentrations up to 600 µM.
10 Der blev ikke set nogen akkumulering af nelarabin eller ara- G i plasma efter administration af nelarabin daglig eller efter administration på dag 1, 3, 5.
No accumulation of nelarabine or ara-G was observed in plasma after nelarabine administration on either a daily or a day 1, 3, 5 schedule.
Intracellulær ara- GTP koncentationer i leukæmiske stamceller kunne kvantificeres i en længere periode efter administration af nelarabin.
Intracellular ara-GTP concentrations in leukaemic blasts were quantifiable for a prolonged period after nelarabine administration.
Intracellulær ara- GTP ophobes efter gentagen administration af nelarabin.
Intracellular ara-GTP accumulated with repeated administration of nelarabine.
50% og 30% større end Cmax og AUC( 0- t) - værdier på dag 1.
On the day 1, 3, and 5 schedule, Cmax and AUC(0-t) values on day 3 were approximately 50% and 30%, respectively, greater than Cmax and AUC(0-t) values on day 1.
Den primære metabolisering af nelarabin er O- demethylering vha. adenosindeaminase til dannelse af ara- G, som undergår hydrolyse og danner guanin.
The principal route of metabolism for nelarabine is O-demethylation by adenosine deaminase to form ara-G, which undergoes hydrolysis to form guanine.
Desuden hydrolyseres noget nelarabin og danner methylguanin, som O- demethyleres og danner guanin.
In addition, some nelarabine is hydrolysed to form methylguanine, which is O-demethylated to form guanine.
Guanin N- deamineres og danner xantin, som yderligere oxideres for at give urinsyre.
Guanine is N-deaminated to form xanthine, which is further oxidized to yield uric acid.
30 minutter og 3 timer.
Nelarabine and ara-G are rapidly eliminated from plasma with a half-life of approximately 30 minutes and 3 hours, respectively.
Disse resultater blev vist hos patienter med refraktær leukæmi eller lymfom efter en dosis på 1500 mg/ m2 nelarabin (voksen) eller 650 mg/ m2 (børn).
These findings were demonstrated in patients with refractory leukaemia or lymphoma given a dose of 1,500 mg/ m2 nelarabine (adults) or a 650 mg/ m2 (paediatrics).
138 l/ time/ m2 (104%) og 125 l/ time/ m2 (214%) hos voksne og pædiatriske patienter, på dag 1 (n = 65 voksne, n = 21 pædiatriske patienter).
Combined Phase 1 pharmacokinetic data at nelarabine doses of 104 to 2,900 mg/ m2 indicate that mean (%CV) clearance (Cl) values for nelarabine are 138 l/ h/ m2 (104%) and 125 l/ h/ m2 (214%) in adult and paediatric patients, respectively, on day 1 (n = 65 adults, n = 21 paediatric patients).
Den umiddelbare clearance for ara- G er sammenlignelig i de to grupper [9, 5 l/ time/ m2 (35%) hos voksne patienter og 10, 8 l/ time/ m2 (36%) i pædiatriske patienter] på dag 1.
The apparent clearance of ara-G (Cl/ F) is comparable between the two groups [9.5 l/ h/ m2 (35%) in adult patients and 10.8 l/ h/ m2 (36%) in paediatric patients] on day 1.
Nelarabin og ara- G udskilles delvis via nyrerne.
Nelarabine and ara-G are partially eliminated by the kidneys.
5, 3% og 23, 2% af den administrerede dosis.
In 28 adult patients, 24 hours after nelarabine infusion on day 1, mean urinary excretion of nelarabine and ara-G was 5.3% and 23.2% of the administered dose, respectively.
Den renale clearance var i gennemsnit hos 21 voksne patienter 9, 0 l/ time/ m2 (151%) for nelarabin og 2, 6 l/ time/ m2 (83%) for ara- G.
Renal clearance averaged 9.0 l/ h/ m2 (151%) for nelarabine and 2.6 l/ h/ m2 (83%) for ara-G in 21 adult patients.
Da tidsforløbet for intracellulær ara- GTP var forlænget, kunne dets halveringstid ikke fastsættes nøjagtigt.
Because the timecourse of intracellular ara-GTP was prolonged, its elimination half-life could not be accurately estimated.
Kombinerede fase I farmakokinetiske data ved nelarabindoser på 104 - 2900 mg/ m2 tyder på, at clearance og Vss- værdier for nelarabin og ara- G er sammenlignelige mellem de to grupper.
Combined Phase 1 pharmacokinetic data at nelarabine doses of 104 to 2,900 mg/ m2 indicate that the clearance (Cl) and Vss values for nelarabine and ara-G are comparable between the two groups.
Yderligere data, hvad angår nelarabin og ara- G farmakokinetik i den pædiatriske population findes i andre afsnit.
Further data with respect to nelarabine and ara-G pharmacokinetics in the paediatric population are provided in other subsections.
Køn har ingen indflydelse på farmakokinetikken af nelarabin og ara- G i plasma.
Gender has no effect on nelarabine or ara-G plasma pharmacokinetics.
Intracellulær ara- GTP Cmax og AUC (0- t) - værdier på samme dosisniveau var 2 – 3 gange større i gennemsnit hos voksne kvindelige patienter end hos voksne mandlige patienter.
Intracellular ara-GTP Cmax and AUC(0– t) values at the same dose level were 2– to 3– fold greater on average in adult female than in adult male patients.
11 Indflydelsen af race på farmakokinetikken af nelarabin og ara- G er ikke undersøgt specifikt.
11 Race
I en farmakokinetisk/ farmakodynamisk krydsanalyse havde race ikke nogen tydelig virkning på farmakokinetikken af nelarabin, ara- G eller intracellulær ara- GTP.
In a pharmacokinetic/ pharmacodynamic cross study analysis, race had no apparent effect on nelarabine, ara-G, or intracellular ara-GTP pharmacokinetics.
Farmakokinetikken af nelarabin og ara- G er ikke undersøgt specifikt hos patienter med nedsat nyrefunktion eller hos patienter i hæmodialyse.
The pharmacokinetics of nelarabine and ara-G have not been specifically studied in renally impaired or haemodialysed patients.
Nelarabin udskilles kun i ringe grad via nyrerne (5 - 10% af den indgivne dosis).
Nelarabine is excreted by the kidney to a small extent (5 to 10% of the administered dose).
Ara- G udskilles i højere grad via nyrerne (20 - 30% af den indgivne nelarabindosis).
Ara-G is excreted by the kidney to a greater extent (20 to 30% of the administered nelarabine dose).
Voksne og børn i kliniske forsøg blev delt op i 3 grupper efter nedsat nyrefunktion: normal nedsat nyrefunktion med clearance større end 80 ml/ min (n = 56), let nedsat nyrefunktion med clearance på 50 - 80 ml/ min (n = 12), og moderat nedsat nyrefunktion med clearance under 50 ml/ min (n = 2).
Adults and children in clinical studies were categorized into the three groups according to renal impairment: normal with Clcr greater than 80 ml/ min (n = 56), mild with Clcr equalling 50 to 80 ml/ min (n = 12), and moderate with Clcr less than 50 ml/ min (n = 2).
4. 2).
The mean apparent clearance (Cl/ F) of ara-G was about 7% lower in patients with mild renal impairment than in patients with normal renal function (see section 4.2).
Der findes ingen data til støtte for dosisvejledning til patienter med clearance mindre end 50 ml/ min.
No data are available to provide a dose advice for patients with Clcr less than 50 ml/ min.
Alder har ingen indvirkning på farmakokinetikken for nelarabin eller ara- G.
Age has no effect on the pharmacokinetics of nelarabine or ara-G.
4. 2)
Decreased renal function, which is more common in the elderly, may reduce ara-G clearance (see section 4.2).
Nelarabin forårsagede histopatologiske ændringer i centralnervesystemet (den hvide substans), vakuolisering og degenerative ændringer i cerebrum, cerebellum og rygmarv hos aber efter behandling med nelarabin daglig i 23 dage ved eksponering under den humane, terapeutiske eksponering.
Adverse reactions not observed in clinical studies, but seen in animals at exposure levels similar to clinical exposure levels and with possible relevance to clinical use were as follows: nelarabine caused histopathological changes to the central nervous system (white matter) vacuolation and degenerative changes in cerebrum, cerebellum and spinal cord of monkeys after treatment with nelarabine daily during 23 days, at exposures below the human therapeutic exposure.
Nelarabin var mutagen for L5178Y/ TK muselymfomceller med og uden metabolisk aktivering.
Nelarabine was mutagenic to L5178Y/ TK mouse lymphoma cells with and without metabolic activation.
Der blev set ganespalte hos kaniner efter doser på ca.
Compared to controls, nelarabine caused increased incidences of fetal malformations, anomalies, and variations in rabbits when given at doses approximately 24% of the adult human dose on a mg/ m2 basis during the period of organogenesis.
79% af humane voksendosis, mens manglende galdeblære, accessoriske lungelapper, sammensmeltede eller ekstra sternebrae og forsinket knogledannelse blev set for alle doser.
Cleft palate was seen in rabbits given a dose approximately 2-fold the adult human dose, absent pollices in rabbits given a dose approximately 79% of the adult human dose while absent gall bladder, accessory lung lobes, fused or extra sternebrae and delayed ossification was seen at all doses.
2 gange den human voksne dosis.
Maternal body weight gain and fetal body weights were reduced in rabbits given a dose approximately 2-fold the adult human dose.
Der er ikke udført forsøg med dyr til vurdering af effekten af nelarabin på fertilitet.
12 No studies have been conducted in animals to assess the effects of nelarabine on fertility.
32% af den humane voksne dosis baseret på mg/ m2 i 30 på hinanden følgende dage.
However, no undesirable effects were seen in the testes or ovaries of monkeys given nelarabine intravenously at doses up to approximately 32% of the adult human dose on a mg/ m2 basis for 30 consecutive days.
Natiumchlorid Vand til injektionsvæsker Saltsyre (til pH justering) Natriumhydroxid (til pH justering)
Sodium chloride Water for injections Hydrochloric acid (to adjust the pH) Sodium hydroxide (to adjust the pH)