natgillin/translations-raw huggingface dataset:
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.
Nelarabin se z adenozin- deaminazo (ADA) hitro demetilira v ara- G, v celici pa se nato z deoksigvanozin- kinazo in deoksicitidin- kinazo fosforilira v 5 ’ - monofosfatni presnovek.
The monophosphate metabolite is subsequently converted to the active 5’ -triphosphate form, ara-GTP.
Monofosfatni presnovek nato preide v aktivno 5 ’ - trifosfatno obliko, ara- GTP.
Accumulation of ara-GTP in leukaemic blasts allows for preferential incorporation of ara-GTP into deoxyribonucleic acid (DNA) leading to inhibition of DNA synthesis.
Kopičenje ara- GTP v levkemičnih blastnih celicah omogoča želeno vgraditev ara- GTP v deoksiribonukleinsko kislino (DNA), kar vodi v zavrtje sinteze DNA.
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).
V odprti študiji, ki sta jo izvedli raziskovalni skupini “ Cancer and Leukaemia Group B ” in “ Southwest Oncology Group ”, so varnost in učinkovitost nelarabina vrednotili pri 39 odraslih bolnikih z akutno limfoblastno levkemijo celic T (T- ALL) ali limfoblastnim limfomom celic T (T- LBL).
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).
Bolniki so bili stari od 16 do 65 let (srednja starost 34 let).
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.
Bolniki so prejemali nelarabin v odmerku 1. 500 mg/ m2/ dan v obliki dvourne intravenske infuzije na 1., 3. in 5. dan 21- dnevnega cikla.
Five of the 28 patients (18%) [95% CI:
Popolni odziv (delež blastov v kostnem mozgu ≤ 5%, brez drugih znakov bolezni in izboljšanje periferne krvne slike v celoti) je bil dosežen pri petih od 28 bolnikov (18%) [95% interval zaupanja:
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).
6% — 37%], ki so se zdravili z nelarabinom.
A total of 6 patients (21%) [95% CI:
Popolni odziv s hematološkim izboljšanjem ali brez njega je bil dosežen pri skupno 6 bolnikih (21%) [95% interval zaupanja:
8 %– 41%] achieved a complete response with or without haematological recovery.
8% – 41%].
Time to complete response in both classifications of response ranged from 2.9 to 11.7 weeks.
Po obeh definicijah odziva je bil popolni odziv dosežen po 2, 9 do 11, 7 tednih.
Median overall survival was 20.6 weeks [95% CI:
Srednja celotna doba preživetja je bila 20, 6 tednov [95% interval zaupanja:
Survival at one year was 29% [95% CI:
Enoletno preživetje je bilo 29- odstotno [95% interval zaupanja:
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).
Pri 149 bolnikih je prišlo do ponovitve akutne limfoblastne levkemije celic T (T- ALL) ali limfoblastnega limfoma celic T (T- LBL) ali pa se na predhodno zdravljenje niso odzvali.
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.
Zdravljenje se je ponavljalo vsakih 21 dni.
Of the 39 patients who had received two or more prior induction regimens, 5 (13%) [95% CI:
Od 39 bolnikov, ki so se predhodno zdravili z dvema ali več indukcijskimi režimi zdravljenja, je bil pri 5 (13%) [95% interval zaupanja:
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:
4% – 27%] dosežen popolni odziv (delež blastov v kostnem mozgu ≤ 5%, brez drugih znakov bolezni in izboljšanje periferne krvne slike v celoti), pri 9 (23%) [95% interval zaupanja:
11 %– 39%] achieved complete responses with or without full haematological recovery.
11% – 39%] pa popolni odziv s hematološkim izboljšanjem ali brez njega.
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:
Enoletno preživetje je bilo 14- odstotno [95% interval zaupanja:
9 Thirteen (42%) of the 31 patients treated with one prior induction regimen achieved a complete response overall.
Pri trinajstih (42%) od 31 bolnikov, ki so se predhodno zdravili z enim indukcijskim režimom zdravljenja, je bil dosežen popolni odziv v celoti.
Four (44%) of the nine refractory patients experienced a complete response to nelarabine.
Popolni odziv na nelarabin je bil dosežen pri štirih (44%) od teh devetih neodzivnih bolnikov.
The monophosphate metabolite is subsequently converted to the active 5’ -triphosphate from, ara-GTP.
Monofosfatni presnovek nato preide v aktivno 5 ’ - trifosfatno obliko, ara- GTP.
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.
Farmakokinetiko nelarabina in ara- G pri bolnikih, mlajših od 18 let, in odraslih bolnikih z neodzivno levkemijo ali limfomom, so ovrednotili z analizo presečne študije, kjer so uporabili podatke iz štirih študij I. faze.
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.
Običajno so bile večje od Cmax vrednosti nelarabina, kar kaže na hitro in obsežno konverzijo nelarabina v ara- G.
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.
Po dvourni infuziji nelarabina v odmerku 1. 500 mg/ m2 je bila pri odraslih bolnikih srednja plazemska koncentracija Cmax (% KV) nelarabina 13, 9 µM (81%), srednja vrednost AUCinf nelarabina (% KV) pa 13, 5 µM. h (56%).
Mean plasma ara-G Cmax and AUCinf values were 115 µM (16%) and 571 µM. h (30%), respectively.
Srednja plazemska vrednost Cmax ara- G je bila 115 µM (16%), srednja plazemska vrednost AUCinf ara- G pa 571 µM. h (30%).
Intracellular Cmax for ara-GTP appeared within 3 to 25 hours on day 1.
10 Znotrajcelične Cmax koncentracije ara- GTP so bile dosežene v 3 do 25 urah na 1. dan.
Mean (%CV) intracellular ara-GTP Cmax and AUC values were 95.6 µM (139%) and 2214 µM. h (263%) at this dose.
Pri tem odmerku je bila srednja znotrajcelična vrednost Cmax (% KV) ara- GTP 95, 6 µM (139%), srednja vrednost AUC pa 2. 214 µM. h (263%).
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.
Cmax 45, 0 µM (40%), AUCinf pa 38, 0 µM. h (39%).
Mean plasma ara-G Cmax and AUCinf values were 60.1 µM (17%) and 212 µM. h (18%), respectively.
Srednja plazemska vrednost Cmax ara- G je bila 60. 1 µM (17%), srednja plazemska vrednost AUCinf ara- G pa 212 µM. h (18%).
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.
Na osnovi kombiniranih farmakokinetičnih podatkov iz študij I. faze z odmerki nelarabina od 104 do 2. 900 mg/ m2 je porazdelitev nelarabina in ara- G v telesu obsežna.
Specifically, for nelarabine, mean (%CV) VSS values were 115 l/ m2 (159%) and 89.4 l/ m2 (278%) in adult and paediatric patients, respectively.
Pri odraslih bolnikih je bila srednja vrednost (% KV) VSS nelarabina 115 l/ m2 (159%), pri pediatričnih pa 89, 4 l/ m2 (278%).
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.
Srednje vrednost VSS/ F ara- G je bila pri odraslih 44, 8 l/ m2 (32%), pri pediatričnih bolnikih pa 32, 1 l/ m2 (25%).
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.
Pri koncentracijah do 600 µM nelarabina ali ara- G vezava ni odvisna od koncentracije.
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.
Pri uporabi nelarabina na dnevni osnovi ali po shemi na 1., 3. in 5. dan niso opazili kopičenja nelarabina ali ara- G v plazmi.
Intracellular ara-GTP concentrations in leukaemic blasts were quantifiable for a prolonged period after nelarabine administration.
Znotrajcelične koncentracije ara- GTP v levkemičnih blastnih celicah so bile merljive daljši čas po aplikaciji nelarabina.
Intracellular ara-GTP accumulated with repeated administration of nelarabine.
Pri ponavljajočih se aplikacijah se je ara- GTP kopičil v celicah.
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.
Po shemi na 1., 3. in 5. dan so bile vrednosti Cmax na 3. dan za približno 50% večje od vrednosti Cmax na 1. dan, vrednosti AUC( 0- t) pa so bile na 3. dan za približno 30% večje od vrednosti AUC( 0- t) na 1. dan.
The principal route of metabolism for nelarabine is O-demethylation by adenosine deaminase to form ara-G, which undergoes hydrolysis to form guanine.
Glavni način presnove nelarabina je O- demetilacija z adenozin- deaminazo, pri čemer nastane ara- G, ki se nato hidrolizira do gvanina.
In addition, some nelarabine is hydrolysed to form methylguanine, which is O-demethylated to form guanine.
Razen tega se nekaj nelarabina hidrolizira tudi do metilgvanina, ki nato z O- demetilacijo preide v gvanin.
Guanine is N-deaminated to form xanthine, which is further oxidized to yield uric acid.
Gvanin z N- deaminacijo preide v ksantin, ki se nato nadalje oksidira do sečne kisline.
Nelarabine and ara-G are rapidly eliminated from plasma with a half-life of approximately 30 minutes and 3 hours, respectively.
Nelarabin in ara- G se hitro izločita iz plazme, pri čemer je razpolovni čas nelarabina približno 30 minut, razpolovni čas ara- G pa približno 3 ure.
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).
Ti podatki so bili pridobljeni pri bolnikih z neodzivno levkemijo ali limfomom, ki so prejemali nelarabin v odmerku 1. 500 mg/ m2 (odrasli) ali 650 mg/ m2 (otroci).
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).
Kombinirani farmakokinetični podatki iz študij I. faze z odmerki nelarabina od 104 do 2. 900 mg/ m2 kažejo, da je pri odraslih bolnikih na 1. dan srednja vrednost (% KV) očistka (Cl) nelarabina 138 l/ h/ m2 (104%), pri pediatričnih bolnikih pa 125 l/ h/ m2 (214%) (n = 65 odrasli bolniki, n = 21 otroci).
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.
Na 1. dan je navidezni očistek ara- G (Cl/ F) primerljiv med obema starostnima skupinama (9, 5 l/ h/ m2 (35%) pri odraslih bolnikih in 10, 8 l/ h/ m2 (36%) pri otrocih).
Nelarabine and ara-G are partially eliminated by the kidneys.
11 Nelarabin in ara- G se deloma izločata skozi ledvice.
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.
Pri 28 odraslih bolnikih se je v 24 urah po prejemu infuzije nelarabina na 1. dan z urinom v povprečju izločilo 5, 3% nelarabina in 23, 2% ara- G glede na prejeti odmerek.
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.
Pri 21 odraslih bolnikih je bil povprečni ledvični očistek nelarabina 9, 0 l/ h/ m2 (151%), povprečni ledvični očistek ara- G pa 2, 6 l/ h/ m2 (83%).
Because the timecourse of intracellular ara-GTP was prolonged, its elimination half-life could not be accurately estimated.
Ker so bile vrednosti znotrajceličnega ara- GTP določene v daljšem časovnem okviru, njegovega razpolovnega časa izločanja ni bilo možno zanesljivo določiti.
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.
Kombinirani farmakokinetični podatki iz študij I. faze z odmerki nelarabina od 104 do 2. 900 mg/ m2 kažejo, da so vrednosti očistka (Cl) in Vss za nelarabin in ara- G med obema starostnima skupinama primerljive.
Further data with respect to nelarabine and ara-G pharmacokinetics in the paediatric population are provided in other subsections.
Drugi podatki o farmakokinetiki nelarabina in ara- G pri otrocih so navedeni v drugih podpoglavjih.
Gender has no effect on nelarabine or ara-G plasma pharmacokinetics.
Spol ne vpliva na farmakokinetiko nelarabina ali ara- G.
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.
Pri istem odmerku so bile znotrajcelične vrednosti Cmax in AUC( 0– t) ara- GTP pri odraslih bolnicah v povprečju za 2 - do 3- krat večje kot pri odraslih bolnikih.
The effect of race on nelarabine and ara-G pharmacokinetics has not been specifically studied.
Vpliva rase na farmakokinetiko nelarabina ali ara- G niso posebej proučevali.
In a pharmacokinetic/ pharmacodynamic cross study analysis, race had no apparent effect on nelarabine, ara-G, or intracellular ara-GTP pharmacokinetics.
Analiza presečne farmakokinetične/ farmakodinamične študije ne kaže, da bi rasa očitneje vplivala na farmakokinetiko nelarabina, ara- G ali znotrajceličnega ara- GTP.
The pharmacokinetics of nelarabine and ara-G have not been specifically studied in renally impaired or haemodialysed patients.
Pri bolnikih z ledvično okvaro ali bolnikih na hemodializi farmakokinetike nelarabina in ara- G niso posebej proučevali.
Nelarabine is excreted by the kidney to a small extent (5 to 10% of the administered dose).
Nelarabin se skozi ledvice izloča v majhnem obsegu (5 do 10% prejetega odmerka).
Ara-G is excreted by the kidney to a greater extent (20 to 30% of the administered nelarabine dose).
Ara- G pa se skozi ledvice izloča v večjem obsegu (20 do 30% prejetega odmerka nelarabina).
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).
V kliničnih študijah so bili odrasli in otroci razvrščeni v tri skupine glede na okvaro ledvic: z normalnim delovanjem ledvic (Clcr večji od 80 ml/ min (n = 56)), z blago ledvično okvaro (Clcr enak 50 do 80 ml/ min (n = 12)) in z zmerno ledvično okvaro (Clcr manjši od 50 ml/ min (n = 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).
Pri bolnikih z blago ledvično okvaro je bil navidezni srednji očistek (Cl/ F) ara- G za približno 7% manjši kot pri bolnikih z normalnim delovanjem ledvic (glejte poglavje 4. 2).
No data are available to provide a dose advice for patients with Clcr less than 50 ml/ min.
Pri bolnikih s Clcr manjšim od 50 ml/ min zaradi pomanjkanja podatkov priporočil za prilagoditev odmerka ne moremo podati.
Age has no effect on the pharmacokinetics of nelarabine or ara-G.
Starost ne vpliva na farmakokinetiko nelarabina ali ara- G.
Decreased renal function, which is more common in the elderly, may reduce ara-G clearance (see section 4.2).
Zaradi zmanjšanega delovanje ledvic, ki je pri starostnikih pogostejše, se lahko zmanjša očistek ara- G (glejte poglavje 4. 2).
5.3 Preclinical safety data
12 5. 3 Predklinični podatki o varnosti
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.
Možen pomen za klinično uporabo je naslednji: pri dnevnem zdravljenju z nelarabinom, ki je trajalo 23 dni, je nelarabin pri izpostavljenosti, ki je bila manjša od terapevtske izpostavljenosti človeka, pri opicah povzročil histopatološke spremembe v centralnem živčnem sistemu (vakuolizacija bele substance ter degenerativne spremembe v velikih možganih, malih možganih in hrbtnem mozgu).
Nelarabine was mutagenic to L5178Y/ TK mouse lymphoma cells with and without metabolic activation.
Nelarabin je na celicah mišjega limfoma L5178Y/ TK deloval mutageno, in sicer s presnovno aktivacijo ali brez nje.
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.
V primerjavi s kontrolnimi učinkovinami je nelarabin pri plodovih kuncev povzročil večjo pojavnost malformacij, anomalij in variacij pri dajanju med obdobjem organogeneze v odmerkih, ki so na osnovi mg/ m2 predstavljali približno 24% odmerka za odrasle bolnike.
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.
Pri vseh odmerkih so opazili odsotnost žolčnika, dodatne pljučne režnje, zraščenost posameznih segmentov prsnice (sternebrae) ali dodatne segmente prsnice in zakasnelo zakostenevanje.
Maternal body weight gain and fetal body weights were reduced in rabbits given a dose approximately 2-fold the adult human dose.
Pri odmerku, ki je bil približno 2- krat večji od odmerka za odrasle bolnike, so pri kuncih opazili počasnejše povečevanje telesne mase pri materah ter manjšo telesno maso plodov.
12 No studies have been conducted in animals to assess the effects of nelarabine on fertility.
Študij o vplivu nelarabina na plodnost pri živalih niso izvedli.
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.
Pri opicah, ki so 30 zaporednih dni prejemale nelarabin intravensko v odmerkih, ki so na osnovi mg/ m2 predstavljali približno do 32% odmerka za odrasle bolnike, niso opazili neželenih učinkov na moda ali jajčnike.
Not applicable.
6. 1 Seznam pomožnih snovi
6.3 Shelf life
13 6. 3 Rok uporabnosti
Clear glass (Type I) vials with a non-latex bromobutyl rubber stopper, sealed with an aluminium cap.
Prozorne steklene viale (steklo tipa I), zaprte z gumijastim zamaškom iz bromobutila, ki ne vsebuje lateksa, in zapečatene z aluminijasto zaporko.
— Staff should be trained in how to handle and transfer the medicinal product.
— Osebje mora biti ustrezno usposobljeno za rokovanje z zdravilom in njegovo aplikacijo.
— Pregnant staff should be excluded from working with this medicinal product.
— Nosečnice ne smejo rokovati z zdravilom.
— Personnel handling this medicinal product during handling/ transfer should wear protective clothing including mask, goggles and gloves.
— Osebje, ki rokuje z zdravilom, mora med pripravo in aplikacijo zdravila nositi zaščitna oblačila, vključno z masko, zaščitnimi očali in rokavicami.
— All items for administration or cleaning, including gloves, should be placed in high-risk, waste disposal bags for high-temperature incineration.
— Vse pripomočke, ki jih potrebujete pri aplikaciji zdravila ali čiščenju, tudi rokavice, morate odvreči v vreče za odstranjevanje nevarnih odpadkov, ki so namenjene sežigu pri visokih temperaturah.
Liquid waste may be flushed with large amounts of water.
Odpadno tekočino lahko sperete z velikimi količinami vode.
— Accidental contact with the skin or eyes should be treated immediately with copious amounts of water.
— Ob naključnem stiku zdravila s kožo ali z očmi, morate površino, ki je bila v stiku, takoj sprati z velikimi količinami vode.
13 Any unused product or waste material should be disposed of in accordance with local requirements.
Neuporabljeno zdravilo ali odpadni material zavrzite v skladu z lokalnimi predpisi.
Glaxo Group Limited, Berkeley Avenue, Greenford, Middlesex UB6 0NN, United Kingdom
Glaxo Group Limited, Berkeley Avenue, Greenford, Middlesex UB6 0NN, Velika Britanija
14 ANNEX II
15 DODATEK II
Harmire Road Barnard Castle Durham, DL12 8DT United Kingdom
Harmire Road Barnard Castle Durham, DL12 8DT Velika Britanija
• CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON THE MARKETING AUTHORISATION HOLDER
POGOJI ALI OMEJITVE GLEDE OSKRBE IN UPORABE, PREDPISANI IMETNIKU • DOVOLJENJA ZA PROMET Z ZDRAVILOM
• OTHER CONDITIONS
DRUGI POGOJI •
The MAH must ensure that the system of pharmacovigilance, as described in version 6.2 presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
Imetnik dovoljenja za promet z zdravilom mora zagotoviti, da je sistem farmakovigilance, kot je opisan v različici 6. 2, predstavljen v modulu 1. 8. 1 vloge za pridobitev dovoljenja za promet z zdravilom, vzpostavljen in deluje, preden da zdravilo v promet in toliko časa, kolikor bo zdravilo v uporabi.
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 4 of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by the CHMP.
Imetnik dovoljenja za promet z zdravilom se zavezuje, da bo izvajal vse študije in dodatne farmakovigilančne aktivnosti, podrobno opisane v načrtu farmakovigilance, sprejetem v različici 4 načrta za obvladovanje tveganja (RMP - "Risk Management Plan"), predstavljenem v modulu 1. 8. 2 vloge za pridobitev dovoljenja za promet z zdravilom in vseh nadaljnjih posodobitvah RMP, s katerimi soglaša Odbor za zdravila za uporabo v humani medicini (CHMP).
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
V skladu s smernicami CHMP o sistemih upravljanja tveganja za zdravila za humano uporabo mora imetnik dovoljenja za promet predložiti posodobljen načrt RMP hkrati z naslednjim periodičnim poročilom o varnosti zdravila (PSUR).
• When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities • Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached • At the request of the EMEA
• kadar imetnik dovoljenja za promet z zdravilom prejema nove informacije, ki bi lahko vplivale na trenutne varnostne specifikacije zdravila, načrt farmakovigilance ali na dejavnosti za zmanjševanje tveganja. • v 60 dneh, potem ko je dosežen pomemben mejnik (pri farmakovigilanci ali dejavnostih za zmanjševanje tveganja). • na zahtevo Evropske agencije za zdravila (EMEA).