qanastek/EMEA-V3 huggingface dataset:
is or In controlled clinical studies, use of Nespo and other erythropoiesis-stimulating agents (ESAs) have shown:
• tnaqqis fil- ħin għal progress ta ’ tumur f’ pazjenti b’ kanċer avvanzat fir- ras u fl- għonq li qed jirċievu kura bir- raġġi meta mogħti biex tintlaħaq emoglobina ta ’ aktar minn 14 g/ dl (8. 7 mmol/ l), l- użu ta ’ ESAs mhux indikat f ’ din il- popolazzjoni ta ’ pazjenti. il
th •
• tnaqqis fit- tul ta ’ ħajja u żjieda fl- imwiet attribwiti ma ’ progressjoni tal- mard f ’ 4 xhur f ’ al
au shortened time to tumour progression in patients with advanced head and neck cancer receiving radiation therapy when administered to target a haemoglobin of greater than 14 g/ dl (8.7 mmol/ l), ESAs are not indicated for use in this patient population.
pazjenti b ’ kanċer metastastiku fis- sider, li qed jirċievu l- kimoterapija, meta ngħatalhom biex in
• er shortened overall survival and increased deaths attributed to disease progression at 4 months in ng patients with metastatic breast cancer receiving chemotherapy when administered to target a haemoglobin of 12-14 g/ dl (7.5-8.7 mmol/ l) lo
jintlaħaq targit ta ’ emoglobina ta ’ 12- 14 g/ dl (7. 5 – 8. 7 mmol/ l) iċ
• increased risk of death when administered to target a haemoglobin of 12 g/ dl (7.5 mmol/ l) in no
• żjieda fir- riskju ta ’ mewt meta ngħatalhom biex jintlaħaq targit ta ’ emoglobina ta ’ 12 g/ dl (7. 5mmol/ l) f ’ pazjenti b ’ tumur mallinn attiv li mhux qed jirċievu la kimoterapija u l- anqas ed
patients with active malignant disease receiving neither chemotherapy nor radiation therapy. ESAs are not indicated for use in this patient population. ct
ESAs mhux indikata għall- użu f ’ din il- popolazzjoni ta ’ pazjenti. m
The decision to administer recombinant du
Id- deċiżjoni li jingħataw eritropojetins rikombinanti għandha tkun ibbażata fuq evalwazzjoni tal- benefiċju- riskju bil- parteċipazzjoni tal- pazjent, li għandha tikkunsidra l - t ot
Factors that should be considered ro
kuntest kliniku speċifiku.
in this assessment should include the type of tumour and its stage; the degree of anaemia; life- lp
Fatturi li għandhom jitqiesu f’ din l- evalwazzjoni għandhom jinkludu t- tip ta ’ tumur u l- stadju tiegħu; il- gravità tal- anemija; it- tul tal- għejxien, l- ambjent li fih il- pazjent qed jiġi od
In patients with solid tumours or lymphoproliferative malignancies, if the haemoglobin value exceeds in
Jekk il- livell ta 'l- emoglobina jaqbeż it- 12 g/ dl (7. 5 mmol/ l), f ’ pazjenti b’ tumuri solidi jew limfoproliferattivi, l- addattament tad- doża kif deskritt f’ sezzjoni 4. 2 għandu jiġi rispettat b’ attenzjoni, sabiex jitnaqqas ir- riskju potenzjali ta ’ episodji tromboemboliċi.
Platelet counts and haemoglobin level should also be monitored at regular intervals. ed
L- għadd tal- plejtlits u l- livell ta ’ l - emoglobina għandhom jiġu mmonitorjati b 'intervalli regolari.
However, there is potential for an interaction with drugs that are highly bound to red blood cells e. g. cyclosporin, tacrolimus.
Madankollu, jista ’ jkun hemm potenzjal għal interazzjoni ma ’ mediċini li jeħlu b’ mod qawwi maċ - 176 ċelluli ħomor tad- demm eżempju, cyclosporin, tacrolimus.
For Nespo no clinical data on exposed pregnancies are available.
M ’ hemm l- ebda tagħrif kliniku disponibbli dwar l- effett ta ’ Nespo fuq it- tqala.
163 Animal studies do not indicate direct harmful effects with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development.
Studji fuq l- annimali ma jindikawx effetti ta ’ ħsara diretta f’ dak li għandu x ’ jaqsam mat- tqala, l - iżvilupp ta ’ l- embriju u tal- fetu, il- ħlas jew l- iżvilupp ta ’ wara t- twelid.
Caution should be exercised when prescribing to pregnant women.
t za Nespo għandu jingħata b’ attenzjoni lill- nisa tqal.
As there is no clinical experience with lactating women Nespo should not be administered to women who are breast-feeding.
riz Billi m’ hemm l- ebda esperjenza klinika relatata ma ’ nisa li qed ireddgħu, Nespo m’ għandux jingħata lil dawn in- nisa.
4.7 Effects on ability to drive and use machines
to treddiegħ.
There have been no observed effects with Nespo on the ability to drive and use machines.
aw 4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
ed 4.8 Undesirable effects
Ma ġewx osservati effetti b 'Nespo fuq il- ħila biex issuq jew tħaddem magni.
or There have been reports of serious allergic reactions including anaphylactic reaction, angioedema, dyspnoea, skin rash and urticaria associated with darbepoetin alfa.
x du 4. 8 Effetti mhux mixtieqa ħa Ġenerali ’ g Kien hemm rapporti ta ’ reazzjonijiet ta ’ sensittività eċċessiva serji li jinkludu reazzjonijiet anafilattiċi, anġioedema, qtugħ ta 'nifs, raxx tal- ġilda u urtikarja, assoċjati ma ’ darbapoetin alfa. im
th au Clinical Trial Experience
Espenjenza fi prova klinika il
er Data presented from controlled studies included 1357 patients, 766 who received Nespo and 591 ng patients who received r-HuEPO.
Tagħrif ippreżentat minn studji kkontrollati inkludew 1357 pazjenti, 766 li ngħataw Nespo u 591 in
In the Nespo group, 83% were receiving dialysis and 17% were not receiving dialysis. lo
Fil- grupp ta ’ Nespo, 83% kienu fuq dijaliżi u 17% ma kienux fuq dijaliżi. iċ
Injection site pain was reported as attributable to treatment in studies where Nespo was administered no
Fi studji fl ’ liema Nespo ingħata bħala injezzjoni taħt il- ġilda, l- uġigħ fis- sit ta 'l- injezzjoni ġie ed
via subcutaneous injection.
attribwit għall- kura.
The injection site discomfort was generally mild and transient in nature and occurred predominantly after the first injection. ct
L- iskumdità fis- sit ta 'l- injezzjoni kienet ġeneralment moderata u temporanja u nħasset l- aktar wara l- ewwel injezzjoni. m
Incidence of undesirable effects considered related to treatment with Nespo from controlled clinical du
L- inċidenza ta ’ effetti mhux mixtieqa meqjusa bħala relatati mal- kura b’ Nespo fi studji kliniċi kontrollati huma dawn: t ot
studies are: ro
Effetti mhux mixtieqa
MedDRA system organ class Cardiac Disorders lp
Disturbi fil- qalb
Subject Incidence Very Common (≥ 1/ 10)
Komuni ħafna (≥1/ 10)
Adverse Drug Reaction Hypertension
Pressjoni għolja
Skin and Subcutaneous Tissue Disorders a
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
Vascular disorders in
Disturbi vaskulari
Uncommon (≥ 1/ 1,000 to
Mhux komuni (≥1/ 1, 000 sa ≤1/ 100)
General Disorders and Administration Site Conditions ed
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata
Adverse reactions were determined based on pooled data from seven randomised, double-blind, M
Pazjenti bil- kanċer
placebo-controlled studies of Nespo with a total of 2112 patients (Nespo 1200, placebo 912).
177 Reazzjonijiet avversi ġew determinati fuq l- informazzjoni li nġabret minn sebgħa studji, randomised, double- blind, kkontrollati bi plaċebo ta ’ Nespo b ’ total ta ’ 2112- il pazjent (Nespo 1200, plaċebo 912).
Patients with solid tumours (e. g., lung, breast, colon, ovarian cancers) and lymphoid malignancies (e. g., lymphoma, multiple myeloma) were enrolled in the clinical studies.
Pazjenti b ’ tumuri solidi (eż. tumuri fil- pulmun, fis- sider, fil- kolon, fl- ovarji) u tumuri limfojdi malinni (eż, limfoma, mijeloma multipla) ħadu sehem fl- istudji kliniċi.
164 Incidence of undesirable effects considered related to treatment with Nespo from controlled clinical studies are:
L- inċidenza ta ’ effetti mhux mixtieqa meqjusa bħala relatati ma ’ kura b’ Nespo fi studji kliniċi kontrollati huma dawn:
Subject Incidence Common (≥ 1/ 100 to < 1/ 10)
Inċidenza fis- suġġett
Thromboembolic events, including pulmonary embolism
Avvenimenti tromboemboliċi,
ed Postmarketing Experience
aw Esperjenza wara t- tqegħid fuq is- suq
is The following adverse reactions have been identified during postmarketing use of Nespo:
x Ir- reazzjonijiet avversi li ġejjin ġew identifikati waqt l- użu wara t- tqegħid fuq is- suq ta ’ Nespo:
or th • Pure Red Cell Aplasia.
du • Aplażja pura ta ’ ċelluli ħomor (PRCA).
In isolated cases, neutralising anti-erythropoietin antibody mediated pure red cell aplasia (PRCA) associated with Nespo therapy have been reported predominantly in
F’ każijiet iżolati, aplażja pura ta ’ ċelluli ħomor ikkawżata minn anitkorpi anti- eritropojetin newtraliżanti ġiet irrappurtata b’ assoċazzjoni ma ’ kura ħa b’ Aranaesp l- aktar f’ pazjenti b’ insuffiċjenza renali kronika (CRF) ikkurati minn taħt il- ġilda.
In case PRCA is diagnosed, therapy with Nespo must be discontinued and patients should not be switched to another recombinant erythropoietic protein (see section 4.4).
F’ każ li aplażja pura ta ’ ċelluli ħomor (PRCA) tiġi djanjostikata, il- kura, b’ Nespo għandha ’ g titwaqqaf u l- pazjenti m’ għandhiex tinbidlilhom il- kura għal proteina rikombinanti eritropojetika oħra (ara sezzjoni 4. 4). im
• er Allergic reactions, including anaphylactic reaction, angioedema, skin rash and urticaria. ng • Convulsions. lo
• Reazzjonijiet allerġiċi, inklużi reazzjonijiet anafilattiċi, anġioedema, raxx tal- ġilda u urtikarja. il
4.9 Overdose no
• Aċċessjonijiet. al
Even at very high serum levels, no symptoms of overdose have been observed. ct du
sintomi ta ’ doża eċċessiva ma ġew osservati. ed
If clinically indicated, phlebotomy may be performed. ro lp
Jekk klinikament indikat, tista ’ ssir flebotomija. m t
PHARMACOLOGICAL PROPERTIES a
TAGĦRIF FARMAKOLOĠIKU ot
5.1 Pharmacodynamic properties in
5. 1 Tagħrif farmakodinamiku od
B03XA02. ic ed
Pr
The production of erythropoietin primarily occurs in and is regulated by the M
Il- produzzjoni ta ’ l- eritropojetina sseħħ primarjament u tiġi rregolata fil- kilwa b’ rispons għal bidliet fl- ossiġenazzjoni tat- tessuti.
Production of endogenous erythropoietin is impaired in patients with chronic renal failure and the primary cause of their anaemia is due to erythropoietin deficiency.
Il- produzzjoni ta ’ l- eritropojetina endoġena hija mnaqqsa f’ pazjenti b 'insuffiċjenza renali kronika u l- kawża ewlenija ta ’ l- anemija tagħhom hija minħabba nuqqas f' eritropojetina.
In patients with cancer receiving chemotherapy the etiology of anaemia is multifactorial.
F’ pazjenti bil- kanċer li qed jirċievu kimoterapija, l- kawża ta ’ l- anemija għandha ħafna fatturi.
In these patients, erythropoietin deficiency and a reduced response of erythroid progenitor cells to endogenous erythropoietin both contribute significantly towards their anaemia.
F’ dawn il- pazjenti, kemm in- nuqqas fl- eritropojetina kif ukoll ir- rispons imnaqqas taċ- ċelluli eritrojdi proġenituri jikkontribwixxu b’ mod sinifikattiv għall- anemija.
Darbepoetin alfa stimulates erythropoiesis by the same mechanism as the endogenous hormone.
178 Darbepoetin alfa tistimola l- eritropojeżi bl- istess mekkaniżmu ta ’ l- ormon endoġenu.
Darbepoetin alfa has five N-linked carbohydrate chains whereas the endogenous hormone and recombinant human erythropoietins (r-HuEPO) have three.
Darbepoetin alfa għandha ħames ktajjen ta ’ karboidrati N- linked, filwaqt li l- ormon endoġenu u l- eritropojetina umana rikombinanti (r- HuEPO) għandhom tlieta.
Due to its increased carbohydrate content darbepoetin alfa has a longer terminal half-life than r-HuEPO and consequently a greater
Minħabba l- kontenut akbar ta ’ karboidrati, darbepoetin alfa għandha half- life terminali itwal minn r- HuEPO, u għalhekk għandha attività in vivo akbar.
Despite these molecular changes, darbepoetin alfa retains a very narrow specificity for the erythropoietin receptor.
Minkejja dawn il- bidliet molekolari, darbepoetin alfa għandha speċifiċità dejqa ħafna għar- riċettur ta ’ l - eritropojetina.
Cancer patients receiving chemotherapy
Pazjenti bil- kanċer li jirċievu l- kimoterapija
In a prospective, randomised double-blind, placebo-controlled study conducted in 314 lung cancer patients receiving platinum containing chemotherapy there was a significant reduction in transfusion requirements (p < 0.001).
t za Fi studju prospettiv, randomised double- blind, ikkontrollat bil- plaċebo, li sar fuq 314- il pazjent b’ kanċer fil- pulmun li kienu qed jirċievu kimoterapija li fiha l- platinum, kien hemm tnaqqis
Clinical studies have demonstrated that darbepoetin alfa had similar effectiveness when administered as a single injection either once every three weeks, once every two weeks, or weekly without any increase in total dose requirements.
to Studji kliniċi wrew li darbepoetin alfa kellha effikaċja simili meta ngħatat bħala injezzjoni waħda darba kull tliet ġimgħat, darba kull ġimgħatejn, jew darba fil- ġimgħa mingħajr l- ebda żieda fil- ħtiġijiet
ed The safety and effectiveness of once every three weeks dosing of Nespo therapy in reducing the requirement for red blood cell transfusions in patients undergoing chemotherapy was assessed in a
x trasfużjonijiet ta 'ċelluli ħomor tad- demm f' pazjenti li kienu qed jirċievu l- kimoterapija ġew assessjati
is randomised, double-blind, multinational study.
du fi studju randomized, double- blind, multi- nazzjonali.
This study was conducted in 705 anaemic patients with
Dan l- istudju sar f '705 pazjent anemiku b' tumuri malinni mhux majelojdi li kienu qed jirċievu kimoterapija ta 'bosta ċikli.
In both groups, the dose was
Il- pazjenti ġew randomised biex jirċievu Nespo b 'doża ta' 500 μg darba kull tliet ġimgħat jew 2. 25 μg / kg darba fil - ħa ġimgħa.
th reduced by 40% of the previous dose (e. g., for first dose reduction, to 300 μ g in the once every three weeks group and 1.35 μ g / kg in the once weekly group) if haemoglobin increased by more than 1 g/ dl
Fiż- żewġ gruppi, id- doża ġiet mnaqqsa b '40% mid- doża ta' qabel (eżempju, l- ewwel tnaqqis fid- doża, tnaqqis għal 300 μg fil- grupp ta 'darba kull tliet ġimgħat u tnaqqis għal 1. 35 μg / kg fil- grupp ’ g ta' darba fil- ġimgħa) jekk l- emoglobin żdiedet b 'aktar minn 1 g/ dl f' perijodu ta '14- il ġurnata.
In the once every three weeks group, 72% of patients required dose reductions.
Fil- grupp ta 'darba im
In the once weekly group, 75% of patients required dose reductions.
fil- ġimgħa, 75% tal- pazjenti kellhom bżonn tnaqqis fid- doża.
er every three weeks being comparable to once weekly administration with respect to the incidence of subjects receiving at least one red blood cell transfusion from week 5 to the end of treatment phase. ng In a prospective, randomised double-blind, placebo-controlled study conducted in 344 anaemic lo patients with lymphoproliferative malignancies receiving chemotherapy there was a significant reduction in transfusion requirements and an improvement in haemoglobin response (p < 0.001). no
Dan l- istudju jsostni li 500 μg darba kull tliet ġimgħat huwa komparabbli għal għoti ta 'darba fil- ġimgħa, fl- aspett li l- inċidenza ta' individwi li rċevew mill- anqas trasfużjoni ta 'ċelluli ħomor tad- demm waħda mill- ħames ġimgħa sa l- aħħar fażi il
Improvement in fatigue, as measured by the Functional Assessment of Cancer Therapy-fatigue (FACT-fatigue) scale, was also observed. ct
Fi studju prospettiv, randomised double- blind, ikkontrollat bil- plaċebo, li sar fuq 344 pazjent anemiku in
Erythropoetin is a growth factor that primarily stimulates red blood cell production.
Ġie osservat ukoll titjib fl- għeja iċ
Erythropoietin receptors may be expressed on the surface of a variety of tumour cells. du
li ġie mkejjel bil- kejl Functional Assessment of Cancer Therapy- fatigue (FACT- fatigue). ed
The lp
L- għejxien u l- progressjoni tat- tumur ġew eżaminati f ’ ħames studji kkontrollati kbar li involvew total ta ’ 2833 pazjent, liema minnhom erba ’ studji kieku studji double blind kkontrollati bil- placebo u l - t ot
target haemoglobin concentration in two studies was > 13 g/ dl; in the remaining three studies it was 12-14 g/ dl.
istudju l- ieħor kien studju open- label.
In the four placebo-controlled studies the hazard in
Il- konċentrazzjoni targit ta ’ l- emoglobina f ’ żewġ studji kienet > 13 g/ dl; fit- tlitt od
ratios for overall survival ranged between 1.25 and 2.47 in favour of controls.
studji l- oħra kienet 12- 14 g/ dl.
These studies have shown a consistent unexplained statistically significant excess mortality in patients who have anaemia ic
F’ erba ’ studji Pr
associated with various common cancers who received recombinant human erythropoietin compared ed
kkontrollati bil- placebo r- ratio ta ’ periklu ta ’ l- għejxien kien bejn 1. 25 u 2. 47 favur dawk li rċevew il - kontroll.
Overall survival outcome in the trials could not be satisfactorily explained by differences in the incidence of thrombosis and related complications between those given recombinant human M
Dawn l- istudji wrew eċċess ta ’ mortalità statistikament sinnifikanti mhux spejgat f ’ pazjenti li għandhom anemija assoċjata ma ’ varji tipi ta ’ kanċer komuni li rċevew eritropoeitin rikombinanti uman meta mqabbla mal- kontrolli.
erythropoietin and those in the control group.
Ir- riżultat ta ’ l- għejxien fl- istudji ma setgħax jiġi spejgat b ’ suddisfazzjoni bid- differenzi ta ’ l- inċidenza tat- trombożi u kumplikazzjonijiet relatati bejn dawk li rċevew l- eritropoeitin rikombinanti uman u dawk fil- grupp ta ’ kontroll.
A systematic review has also been performed involving more than 9000 cancer patients participating in 57 clinical trials.
179 Analażi sistematika saret fuq 9000 pazjent bil- kancer li pparteċipaw f ’ 57 studji kliniċi.
0.99, 1.18; 42 trials and 8167 patients).
Meta- analiżi tat- tgħarif ta ’ l- għejxien pproduċa ratio tar- riskju ta ’ 1. 08 favur il- kontrolli (95% CI: 0. 99, 1. 18; 42 studji u 8167 pazjenti).
An increased relative risk of thromboembolic events (RR 1.67, 95% CI:
Riskju relattiv għola ta ’ avveniment thromboemboliċi (RR 1. 67, 95% CI:
1.35, 2.06, 35 trials and 6769 patients) was observed in patients treated with recombinant human erythropoietin.
1. 35, 2. 06, 35 studju u 6769 pazjent) ġew osservati f ’ pazjenti kkurati b ’ eritropoetin uman rikombinanti.
166 chemotherapy to achieve haemoglobin concentrations less than 13 g/ dl, is unclear because few patients with these characteristics were included in the data reviewed.
t jilħqu konċentrazzjoni ta ’ l- emoglobin ta ’ anqas minn 13 g/ dl, mhux ċar minħabba li ftit pazjenti b ’
Due to its increased carbohydrate content the level of darbepoetin alfa in the circulation remains above the minimum stimulatory concentration for erythropoiesis for longer than the equivalent molar dose of r-HuEPO, allowing darbepoetin alfa to be administered less frequently to achieve the same biological response.
B’ hekk darbepoetin alfa tkun tista ’ tingħata inqas ta ’ spiss
ed The pharmacokinetics of darbepoetin alfa has been studied clinically in chronic renal failure patients following intravenous and subcutaneous administration.
x du Il- farmakokinetika ta ’ darbepoetin alfa ġiet studjata klinikament f’ pazjenti b 'insuffiċjenza renali kronika wara l- għoti ġol vina u taħt il- ġilda.
The terminal half-life of darbepoetin alfa is 21 hours (SD 7.5) when administered intravenously.
Il- half life terminali ta ’ darbepoetin alfa hija 21 siegħa (SD 7. 5) meta mogħti ġol- vina.
is 0.56) and the volume of distribution (Vss) is approximately equal to plasma volume (50 ml/ kg).
Il- clearance ta ’ darbepoetin alfa hija ta ’ 1. 9 ml/ siegħa/ kg (SD 0. 56) u ħa l- volum ta ’ distribuzzjoni (Vss) huwa bejn wieħed u ieħor l- istess bħall- volum tal- plażma (50 ml/ kg).
Following monthly administration of darbepoetin alfa, at subcutaneous doses ranging from 0.6 to 2.1 µg/ kg, the terminal half-life was 73
Wara l- għoti ta 'darbepoetin alfa darba ’ g fix- xahar, b' dożi taħt il- ġilda li jvarjaw bejn 0. 6 u 2. 1 µg/ kg, il- half- life terminali kienet ta '73 siegħa (SD 24).
In clinical studies, minimal
Il- half- life terminali ta 'darbepoetin alfa hija itwal meta mogħti taħt il- ġilda milli meta mogħti im
au accumulation was observed with either route of administration.
Fl- istudji kliniċi, akkumulazzjoni minima ġiet osservata fiż- żewġ modi ta ’ teħid.
In preclinical studies it has been shown that renal clearance is minimal (up to 2% of total clearance), and does not affect the serum half-life.
Fi studji qabel l- użu kliniku, intwera li l- clearance renali hija minima (sa 2% il- clearance totali), u ma teffettwax il- half life fis- serum. il al
er Data from 809 patients receiving Nespo in European clinical studies were analysed to assess the dose ng required to maintain haemoglobin; no difference was observed between the average weekly dose administered via the intravenous or subcutaneous routes of injection. lo
Tagħrif miġbur minn 809 pazjenti li ngħataw Nespo fi studji kliniċi Ewropej ġie analizzat sabiex tinstab id- doża meħtieġa biex l- emoglobina tinżamm f’ livell stabbli; l- ebda differenza ma ġiet in
Assessment of the pharmacokinetics of darbepoetin alfa in paediatric patients (3 to 16 years) with CRF no
osservata bejn id- doża medja ta 'darba fil- ġimgħa mogħtija b' injezzjoni taħt il- ġilda u bejn dik mogħtija b 'injezzjoni ġol- vina. iċ ed
who were either receiving or not receiving dialysis determined pharmacokinetic profiles for sampling periods up to 1 week (168 hours) after a single subcutaneous or intravenous dose.
Meta m
Compared with pharmacokinetic data from adults with CRF where the same sampling duration was used, the ct
mqabbla ma 'tagħrif farmakokinetiku f' adulti li għandhom CRF fl- liema l- istess dewmien ta' sampling intuża, it- tqabbil wera li l- farmakokinetika ta 'darbepoetin alfa hija simili f' pazjenti adulti u f 'pazjenti t
comparison showed that the pharmacokinetics of darbepoetin alfa were similar for paediatric and adult patients with CRF.
tfal li għandhom CRF.
Following intravenous administration, an approximate 25% difference between du
Wara għoti ġol- vina, ġiet osservata differenza ta '25% fl- erja taħt il- kurva minn ot
paediatric and adult patients in the area under the curve from time 0 to infinity (AUC[0-∞]) was observed; however, this difference was less than the 2-fold range in AUC(0- ∞) observed for the ro
ħin 0 sa l- infinità (AUC[ 0- ∞]) bejn pazjenti tfal u pazjenti adulti; madankollu, din id- differenza kienet anqas minn darbtejn il- medda f 'AUC[ 0- ∞] osservata f' pazjenti tfal.
pediatricpatients.
AUC[ 0- ∞] kienet simili f 'od
CRF following both intravenous and subcutaneous administration. a
pazjenti adulti u f 'pazjenti tfal li għandhom CRF wara għoti taħt il- ġilda. Il- Half- life kienet ukoll simili f' pazjenti adulti u f 'pazjenti tfal li għandhom CRF kemm wara għoti ġol- vina kif ukoll wara Pr
Cancer patients receiving chemotherapy in
għoti taħt il- ġilda.
Following subcutaneous administration of 2.25 µg/ kg to adult cancer patients a mean peak ic
Pazjenti bil- kanċer li jirċievu l- kimoterapija
concentration of 10.6 ng/ ml (SD 5.9) of darbepoetin alfa was reached at a mean time of 91 hours ed
Wara l- għoti taħt il- ġilda ta ’ 2. 25 μg/ kg lil pazjenti adulti bil- kanċer, l- ogħla konċentrazzjoni medja ta ’ 10. 6 ng/ ml (SD 5. 9) ta 'darbepoetin alfa ntlaħqet f ’ ħin medju ta ’ 91 siegħa (SD 19. 7).
Pharmacokinetic parameters did not M
Kien
There was an expected moderate (< 2 fold) increase in serum concentration as steady state was approached, but no unexpected accumulation upon repeated administration.
180 hemm żjieda moderata mistennija (< darbtejn) fil- konċentrazzjoni fis- serum hekk kif qagħda stabbli kienet avviċinata, iżda l- ebda akkumulazzjoni mhux mistennija ma seħħet meta ngħataw aktar dożi.
A pharmacokinetic study in patients with chemotherapy-induced anaemia treated with 6.75 µg/ kg darbepoetin alfa administered SC every 3 weeks in combination with chemotherapy was conducted which allowed for full characterisation of the terminal half-life.
Sar studju farmakokinetiku f 'pazjenti b' anemija kkawżata mill- kimoterapija, dawn ngħataw 6. 75 µg/ kg darbepoetin alfa taħt il- ġilda darba kull tliet ġimgħat flimkien mal- kimoterapija, b 'hekk saret karatterizazzjoni kompleta tal- half- life terminali.
In all studies in rats and dogs Nespo produced marked increases in haemoglobin, haematocrits, red blood cell counts and reticulocytes, which correspond to the expected pharmacological effects.
Fl- istudji kollha li saru fuq klieb u firien, Nespo wassal għal żjidiet sostanzjali fl- emoglobina, l -
167 effect (decreased tissue perfusion due to increased blood viscosity).
t za ematokriti, l- għadd ta ’ ċelluli ħomor u r- retikuloċiti, li jikkorrispondu għall- effetti farmakoloġiċi mistennija.
These included myelofibrosis and splenic hypertrophy as well as broadening of the ECG-QRS complex in dogs but no dysrhythmia and no effect on the QT interval were observed.
riz Dawn kienu jinkludu majelofibrożi u ipertrofija tal- marrara kif ukoll twessigħ tal- kumpless ECG- QRS fil- klieb, imma ma kienux osservati la tibdil fir- rata ta ’ tħabbit tal- qalb u lanqas effett fuq l- intervall
Nespo did not reveal any genotoxic potential nor did it have any effect on the proliferation of non- haematological cells in vitro or in vivo.
aw Nespo ma wera l- ebda potenzjal ġenotossiku u ma kellu l- ebda effett fuq il- proliferazzjoni ta ’ ċelluli mhux ematoloġiċi in vitro jew in vivo.
The carcinogenic potential of darbepoetin alfa has not been evaluated in long-term animal studies.
x darbepoetin alfa ma ġiex evalwat fi studji fit- tul fuq l- annimali.
In studies performed in rats and rabbits no clinically relevant evidence of harmful effects with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development was observed.
du Fi studji li saru fuq fniek u firien, l- ebda evidenza ta ’ relevanza klinika ma wriet ħsara f’ dak li għandu x ’ jaqsam ma ’ tqala, żvilupp ta ’ l- embriju jew tal- fetu, il- ħlas jew l- iżvilupp wara t- twelid.
Placental transfer was minimal.
It - ħa trasferiment mill- plaċenta kien minimu.
No alteration of fertility was detected.
L- ebda bidla fil- fertilità ma ġiet osservata. ’ g
PHARMACEUTICAL PARTICULARS
TAGĦRIF FARMAĊEWTIKU im
or 6.1 List of excipients
6. 1 Lista ta ’ sustanzi mhux attivi il
th Sodium phosphate monobasic Sodium phosphate dibasic
Sodium phosphate monobasic Sodium phosphate dibasic al
au Sodium chloride Polysorbate 80
Polysorbate 80 Ilma għall- injezzjoni iċ
er Water 6.2
6. 2 Inkompatibilitajiet ed
for injections Incompatibilities
Minħabba li ma sarux studji li juru liema huma l- prodotti li ma jaqblux ma 'Nespo, dan il- prodott m
In the absence of incompatibility studies, Nespo should not be mixed or administered as an infusion with other medicinal products. no
mediċinali m’ għandux jitħallat jew jingħata bħala infużjoni ma ’ prodotti mediċinali oħrajn.
6.3 Shelf life ct
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali t ot
2 years. du
Sentejn od
6.4 Special precautions for storage ro
6. 4 Prekawzjonijiet speċjali għall- ħażna Pr
Store in a refrigerator (2°C – 8°C) Do not freeze. lp
Tagħmlux fil- friża.
refrigerator and has reached room temperature (up to 25°C) it must either be used within 7 days or disposed of. ed
La darba kunjett jkun tneħħa millfriġġ u jkun laħaq temperatura ambjentali (sa 25°C) dan għandu jintuża fi żmien sebgħat ijiem jew jintrema.
6.5 Nature and contents of container M
181 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
Package containing one or four clear glass vial(s) with rubber stopper(s) of 15 µg Nespo solution for injection in 1 ml (15 µg/ ml).
Pakkett li fih kunjett wieħed jew erba 'kunjetti ta' ħġieġ ċar b 'tapp( ijiet) tal- lastiku b' soluzzjoni għall - injezzjoni ta 'Nespo ta' 15 µg f '1 ml (15 µg/ ml).
The vials are made from type 1 glass with fluoropolymer coated rubber stoppers.
Il- kunjetti huma magħmula minn ħġieġ Tip I b 'tappijiet tal- lastiku b' rita ta 'fluoropolymer.
168 6.6 Special precautions for disposal
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
Nespo is a sterile but unpreserved product.
t za Nespo hija soluzzjoni sterili iżda mhux ppreservata.
Do not administer more than one dose per vial.
Tagħtix aktar minn doża waħda minn kunjett wieħed.
Any medicinal product remaining in the vial should be disposed of.
Il- prodott mediċinali li jifdal ġewwa l- kunjett għandu jintrema.
Before administration the Nespo solution should be inspected for visible particles.
riz Qabel l- għoti s- soluzzjoni ta 'Nespo għandha tiġi ispezzjonata għal frak viżibbli.
Only solutions which are colourless, clear or slightly opalescent, should be injected.
to injezzjonijiet b 'soluzzjoni mingħajr kulur, ċara jew kemm kemm tiddi b' ħafna lwien.
Rotate the injection sites and inject slowly to avoid discomfort at the site of injection.
aw Biddel is- sit ta 'l - injezzjoni u injetta bil- mod sabiex tevita l- iskumdità fis- sit ta' l- injezzjoni.
Any unused product or waste material should be disposed of in accordance with local requirements.
x Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa wara l- użu tal- prodott għandu jintrema kif
MARKETING AUTHORISATION HOLDER
du jitolbu l- liġijiet lokali. ħa 7.
or Dompé Biotec S. p. A.
ID- DETENTUR TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ ’ g Dompé Biotec S. p. A.
Via San Martino 12
Via San Martino 12 im
th I-20122 Milan Italy
I- 20122 Milan Italja il
au er 8.
NUMRU( I) TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ 8. al in
EU/ 1/ 01/ 184/ 023 1 Pack EU/ 1/ 01/ 184/ 024 4 pack lo no
EU/ 1/ 01/ 184/ 023 Pakkett ta '1 EU/ 1/ 01/ 184/ 024 Pakkett ta' 4 iċ
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION
DATA TA ’ L- EWWEL AWTORIZZAZZJONI/ TIĠDID TA ’ L- AWTORIZZAZZJONI ed
8 June 2001 ct
8 Ġunju 2001 m
Date of last renewal:
Data ta 'l- aħħar tiġdid:
19 May 2006 du
19 Mejju 2006 t ot
DATE OF REVISION OF THE TEXT ro lp
DATA TA ’ META ĠIET RIVEDUTA L- KITBA od Pr
Detailed information on this medicinal product is available on the website of the European Medicines a
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il- Mediċini (EMEA) http: // www. emea. europa. eu /.
169 1.
182 1.
Nespo 25 micrograms solution for injection in a vial.
Nespo 25 mikrogramma soluzzjoni għall- injezzjoni ġo kunjett
Each vial contains 25 micrograms of darbepoetin alfa in 1 ml (25 µg/ ml).
Kull kunjett fih 25 mikrogramma ta 'darbepoetin alfa f' 1 ml (25 µg/ ml).
170 Adult patients with chronic renal failure
183 Pazjenti adulti li għandhom insuffiċjenza renali kronika
Clinical studies have demonstrated that adult patients receiving r-HuEPO one, two or three times weekly may be converted to once weekly or once every other week Nespo.
184 Studji kliniċi wrew li pazjenti adulti li jirċievu r- HuEPO darba, darbtejn jew tliet darbiet fil- ġimgħa jistgħu jibdlu għal Nespo darba fil- ġimgħa jew darba kull ġimgħatejn.
171 individual variability, titration to optimal therapeutic doses is expected for individual patients.
Minħabba varjazzjonijiet minn pazjent għall- ieħor, l- aħjar doża terapewtika għandha tiġi mkejla għal kull pazjent individwali.
If the rise in haemoglobin is greater than 2 g/ dl (1.25 mmol/ l) in four weeks reduce the dose by approximately 25%, depending on the rate of increase.
185 Jekk iż- żjieda fl- emoglobina tkun ta ’ aktar minn 2 g/ dl (1. 25 mmol/ l) f’ erba ’ ġimgħat, id- doża trid titnaqqas b 'bejn wieħed u ieħor 25%, skond ir- rata taż- żjieda.
172 increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at approximately 25% lower than the previous dose.
Il- pazjenti għandhom jiġu mmonitorjati mill- qrib sa biex jiġi assigurat li tintuża l- anqas doża ta ’ Nespo approvata biex jiġi pprovdut kontroll fuq is- sintomi ta ’ l- anemija.
Patients should be monitored closely to ensure that the lowest approved dose of Nespo is used to provide adequate control of the symptoms of anaemia.
Wara kull aġġustament fid- doża jew fl- iskeda l- emoglobina trid tiġi mmonitorjata kull ġimgħa jew
After any dose or schedule adjustment the haemoglobin should be monitored every one or two weeks.
t za ġimgħatejn.
When changing the route of administration the same dose must be used and the haemoglobin monitored every one or two weeks so that the appropriate dose adjustments can be made to keep the
riz Meta tibdel ir- rotta tal- amministrazzjoni, l- istess doża trid tiġi wżata u l- emoglobina trid tiġi mmonitorjata kull ġimgħa jew ġimagħtejn ħalli l- aġġustamenti xierqa fid- doża jkunu jistgħu jsiru
ed haemoglobin at the desired level.
to sabiex l- emoglobina tinżamm fil- livell mixtieq.
is Treatment of symptomatic chemotherapy induced anaemia in cancer patients
aw Kura ta ’ l- anemija sintomatika minħabba l- kimoterapija f’ pazjenti bil- kanċer
or Nespo should be administered by the subcutaneous route to patients with anaemia (e. g. haemoglobin concentration ≤ 10 g/ dl (6.2 mmol/ l)) in order to increase haemoglobin to not greater than 12 g/ dl
Nespo għandu jingħata taħt il- ġilda lil pazjenti b 'anemija (eżempju: konċentrazzjoni ta ’ emoglobina
th (7.5 mmol/ l).
Is- sintomi
au Due to intra-patient variability, occasional individual haemoglobin values for a patient above and
du u kumplikazzjonijiet ta ’ l- anemija jvarjaw bl- eta, is- sess, u l- piz ta ’ mard fuq kollox; evalwazzjoni minn tabib ta ’ l- istat kliniku u l- kundizzjoni tal- pazjent hija neċessarja. ħa Minħabba varjazzjonijiet bejn pazjent u ieħor, jistgħu okkażjonalment jiġu osservati f’ pazjenti valuri ta ’ l- emoglobina ‘ l fuq jew taħt il- livelli ta ’ emoglobina mixtieqa.
er below the desired haemoglobin level may be observed.
Varjazzjoni fl- emoglobina għandha ’ g tiġi ndirizzata permezz ta ’ immaniġjar tad- doża, b ’ kunsiderazzjoni għat- targit ta ’ l- emoglobina ta ’ 10g/ dl (6. 2 mmol/ l) għal 12 g/ dl (7. 5mmol/ l).
Haemoglobin variability should be addressed through dose management, with consideration for the haemoglobin target range of 10 g/ dl ng (6.2 mmol/ l) to 12 g/ dl (7.5 mmol/ l).
Livell ta ’ l- emoglobina miżmum fit- tul għal aktar minn im
A sustained haemoglobin level of greater than 12 g/ dl (7.5 mmol/ l) should be avoided; guidance for appropriate dose adjustments for when haemoglobin lo values exceeding 12 g/ dl (7.5 mmol/ l) are observed are described below. no
12 g/ dl (7. 5 mmol/ l) għandu jiġi evitat; tmexxija għall- aġġustament fid- doża xieraq għal meta l- valuri ta ’ l- emoglobina jaqbżu it- 12 g/ dl (7. 5 mmol/ l) huma murija hawn taħt. il
If the clinical response of the patient (fatigue, haemoglobin response) is inadequate after nine weeks, further therapy may not be effective. ct du
emoglobina) mhux adegwat wara disa 'ġimgħat, aktar kura tista' ma tkunx effettiva. in
Nespo therapy should be discontinued approximately four weeks after the end of chemotherapy. ro
Il- kura b 'Nespo għandha titwaqqaf bejn wieħed u ieħor erba' ġimgħat wara tmiem il- kimoterapija. iċ
Once the therapeutic objective for an individual patient has been achieved, the dose should be reduced by 25 to 50% in order to ensure that the lowest approved dose of Nespo is used to maintain lp
La darba li l- għan tal- kura għal pazjent individwali jkun ntlaħaq, id- doża trid titnaqqas għal bejn 25% ed
haemoglobin at a level that controls the symptoms of anaemia.
u 50% tintuża l- anqas doża approvata ta ’ Nespo sabiex tinżamm l- emoglobina fl- livell li jikkontrolla s - sintomi ta ’ l- anemija.
Appropriate dose titration between 500 μ g, 300 μ g, and 150 μ g should be considered. a in
Aġġustament xieraq fid- doża ta ’ bejn 500 μg, 300 μg, u 150 μg għandu jiġi m
Patients should be monitored closely, if the haemoglobin exceeds 12 g/ dl (7.5 mmol/ l), the dose should be reduced by approximately 25 to 50%.
Il- pazjenti għandhom jiġu mmonitorjati mill- qrib, jekk l- emoglobina taqbeż it- 12g/ dl (7. 5mmol/ l), id - t ot
discontinued if haemoglobin levels exceed 13 g/ dl (8.1 mmol/ l).
doża għandha titnaqqas b’ bejn wieħed u ieħor 25 u 50%.
Therapy should be reinitiated at ed
Il- kura għandha terġa od
approximately 25% lower than the previous dose after haemoglobin levels fall to 12 g/ dl (7.5 mmol/ l) or below.
tinbeda b’ doża ta ’ bejn wieħed u ieħor 25% anqas mid- doża ta ’ qabel wara li l- emoglobina tkun waqgħet għal 12 g/ dl (7. 5 mmol/ l) jew anqas.
173 4.4 Special warnings and precautions for use
186 4. 4 Avviżi speċjali u prekawzjonijiet speċjali għall- użu
Blood pressure should be monitored in all patients, particularly during initiation of Nespo therapy.
Il- pressjoni tad- demm għandha tiġi mmonitorjata fil- pazjenti kollha, speċjalment fil- bidu tal- kura b’ Nespo.
In order to ensure effective erythropoiesis, iron status should be evaluated for all patients prior to and during treatment and supplementary iron therapy may be necessary.
Sabiex tiġi assigurata eritropojeżi effettiva, il- qagħda tal- ħadid trid tiġi evalwata għal pazjenti kollha qabel u waqt il- kura u jista ’ jkun hemm l- bżonn ta ’ kura supplementari bil- ħadid.
Deficiencies of
Nuqqas ta ’ ħadid, folic acid jew ta ’ vitamina B12 jnaqqsu l- effikaċja ta ’ l- aġenti li jistimolaw l -
ed iron, folic acid or vitamin B12 reduce the effectiveness of erythropoiesis stimulating agents and should therefore be corrected.
riz eritropojeżi u għalhekk għandhom jiġu kkoreġuti.
Intercurrent infections, inflammatory or traumatic episodes, occult blood loss, haemolysis, severe aluminium toxicity, underlying haematologic diseases, or bone marrow fibrosis
Infezzjonijiet li jitfaċċaw minn żmien għal ieħor, episodji ta ’ infjammazjoni jew trawma, telf ta ’ demm (li ma jidhirx waqt eżami mediku), emoliżi,
is may also compromise the erythropoietic response.
to tossiċità severa ta ’ aluminju, mard ematoloġiku moħbi, jew fibrożi fil- mudullun jistgħu wkoll jikkompromettu r- rispons eritropojetiku.
A reticulocyte count should be considered as part of
L- għadd tar- retikuloċiti għandu jiġi kkunsidrat bħala parti
or the evaluation.
aw mill- evalwazzjoni.
If the bone marrow is consistent with
Jekk il- kawżi tipiċi ta ’ nuqqas ta ’ rispons jiġu esklużi, u l- pazjent għandu retikuloċitopenija, eżami tal- mudullun għandu jiġi kkunsidrat.
th PRCA, testing for anti-erythropoietin antibodies should be performed.
Jekk il- mudullun hu konsistenti ma ’ aplażja pura ta ’ ċelluli ħomor (PRCA), għandhom jsiru testijiet għal anitkorpi anti- eritropojetiċi.
This has been
x du Aplażja pura ta ’ ċelluli ħomor ikkawżata minn anitkorpi anti- eritropojetin newtralizzanti ġiet irrappurtata b’ assoċazzjoni ma ’ kura bi proteini rikombinanti eritropojetiċi, inkluża darbepoetin alfa.
er predominantly reported in patients with CRF treated subcutaneously.
Din ġiet irrapurtata l- aktar f’ pazjenti b ’ insuffiċjenza renali kronika (CRF) li ngħataw il- kura taħt il - ħa ġilda.
Since the liver is thought to be the principal route of no
Dawn l- antikorpi ntwerew li jgħamlu cross- reaction mal- proteini eritropojetiċi kollha, u pażjenti b’ suspett jew b 'konferma li għandhom antikorpi newtralizzanti għal eritropojetin m’ għandiex ’ g tinbidlilhom il- kura għal darbapoetin alfa (ara sezzjoni 4. 8). im
elimination of Nespo and r-HuEPO, Nespo should be used with caution in patients with liver disease.
Mard attiv tal- fwied kien kriterju ta ’ esklużjoni fl- istudji kollha ta ’ Nespo, għalhekk m' hemm l- ebda tagħrif fuq pazjenti b 'indeboliment tal- funzjoni tal- fwied.
Nespo should also be used with caution in those patients with sickle cell anaemia or epilepsy. ct
Minħabba li huwa maħsub li l- fwied huwa r- rotta ewlenija ta ’ tneħħija ta ’ Nespo u r- HuEPO, Nespo għandu jintuża b’ attenzjoni f’ pazjenti il
This du
b’ mard tal- fwied. al
may be associated with life-threatening complications of the cardiovascular system. ro
Nespo għandu wkoll jintuża b’ attenzjoni f’ pazjenti b’ anemija tat- tip sickle cell jew epilessija. in
In clinical studies, an lp
Użu ħażin ta ’ Nespo minn persuni b’ saħħithom jista ’ jwassal għal żjieda eċċessiva fil- volum taċ - iċ
increased risk of death, serious cardiovascular events, and vascular access thrombosis was observed when erythropoiesis-stimulating agents (ESAs) were administered to target a haemoglobin of greater a
Dan jista ’ jkun assoċjat ma ’ kumplikazzjonijiet fis- sistema kardjovaskulari li jistgħu jpoġġu l- ħajja f’ periklu. ed
than 12 g/ dl (7.5 mmol/ l). in
F’ pazjenti b’ insuffiċjenza renali kronika, il- konċentrazzjoni ta ’ manutenzjoni ta ’ l- emoglobina m
Controlled clinical trials have not shown significant benefits attributable to the administration of ic
Fi studji kliniċi, riskju għola ta ’ mewt, avvenimenti kardjovaskulari serji u trombożi ta’ aċċess vaskulari ġew osservati meta aġenti li jistimolaw l- eritropojesi (ESAs) ġew mogħtija biex jintlaħaq targit ta ’ l - t ot
epoetins when haemoglobin concentration is increased beyond the level necessary to control ed
emoglobina ta ’ aktar minn 12g/ dl (7. 5 mmol/ l). od
symptoms of anaemia and to avoid blood transfusion.
Studji kliniċi kkontrollati ma ’ wrewx benefiċji sinnifikanti attribwiti għall- għoti ta ’ epoetins meta l - konċentrazzjoni ta ’ l- emoglobin tiżdied għal aktar mill- livell neċessarju biex tikkontrolla s- sintomi ta ’ l- anemija u biex tevita trasfużjoni tad- demm.
In patients with chronic renal failure and clinical evidence of ischaemic heart disease or congestive heart failure, the target haemoglobin should be determined individually.
187 F ’ pazjenti b 'insuffiċjenza renali kronika u b’ evidenza klinika ta ’ mard iskemiku tal- qalb jew ta' insuffiċjenza tal- qalb konġestiva, it- targit ta 'l- emoglobina jrid jiġi determinat individwalment.
174 Serum potassium levels should be monitored regularly during Nespo therapy.
Il- livelli ta ’ potassium fis- serum għandhom jiġu mmonitorjati b’ mod regolari waqt kura b’ Nespo.
Potassium elevation has been reported in a few patients receiving Nespo, though causality has not been established.
Żjieda fil- potassium ġiet irrappurtata f’ xi pazjenti li ngħataw Nespo, għalkemm il- kawża għadha ma ġietx stabbilita.
Cancer patients
t za Pazjenti bil- kanċer
Effect on tumour growth
Effett fuq it- tkabbir ta 'tumur
Erythropoietin receptors may be expressed on the surface of a variety of tumour cells.
to riċetturi ta 'eritropojetina jistgħu jiġu esprimati fuq il- wiċċ ta' varjetà ta 'ċelluli ta' tumur.
As with all growth factors,
F ’ bosta studji
In several controlled studies, epoetins have not been shown to improve overall survival or decrease the risk of tumour progression in patients with anaemia associated with cancer.
aw kliniċi kkontrollati, epoetins wrew titjib fl- għejxien jew tnaqqis fir- riskju ta ’ progress ta ’ tumur f’ pazjenti b’ anemija assoċjata ma ’ kanċer.
is or In controlled clinical studies, use of Nespo and other erythropoiesis-stimulating agents (ESAs) have shown:
x Fi studji kliniċi kkontrollati, l- użu ta ’ Nespo u aġenti li jistimolaw l- eritropojesi (ESAs) wera:
au shortened time to tumour progression in patients with advanced head and neck cancer receiving radiation therapy when administered to target a haemoglobin of greater than 14 g/ dl (8.7 mmol/ l), ESAs are not indicated for use in this patient population.
du • tnaqqis fil- ħin għal progress ta ’ tumur f’ pazjenti b’ kanċer avvanzat fir- ras u fl- għonq li qed jirċievu kura bir- raġġi meta mogħti biex tintlaħaq emoglobina ta ’ aktar minn 14 g/ dl (8. 7 ħa mmol/ l), l- użu ta ’ ESAs mhux indikat f ’ din il- popolazzjoni ta ’ pazjenti. ’ g • tnaqqis fit- tul ta ’ ħajja u żjieda fl- imwiet attribwiti ma ’ progressjoni tal- mard f ’ 4 xhur f ’ pazjenti b ’ kanċer metastastiku fis- sider, li qed jirċievu l- kimoterapija, meta ngħatalhom biex im
• er shortened overall survival and increased deaths attributed to disease progression at 4 months in ng patients with metastatic breast cancer receiving chemotherapy when administered to target a haemoglobin of 12-14 g/ dl (7.5-8.7 mmol/ l) lo
jintlaħaq targit ta ’ emoglobina ta ’ 12- 14 g/ dl (7. 5 – 8. 7 mmol/ l)
• increased risk of death when administered to target a haemoglobin of 12 g/ dl (7.5 mmol/ l) in no
• żjieda fir- riskju ta ’ mewt meta ngħatalhom biex jintlaħaq targit ta ’ emoglobina ta ’ 12 g/ dl il
patients with active malignant disease receiving neither chemotherapy nor radiation therapy. ESAs are not indicated for use in this patient population. ct
ESAs mhux indikata għall- użu f ’ din il- popolazzjoni ta ’ pazjenti. al in
The decision to administer recombinant du
Id- deċiżjoni li jingħataw eritropojetins rikombinanti għandha tkun iċ
Factors that should be considered ro
ibbażata fuq evalwazzjoni tal- benefiċju- riskju bil- parteċipazzjoni tal- pazjent, li għandha tikkunsidra l - kuntest kliniku speċifiku.
in this assessment should include the type of tumour and its stage; the degree of anaemia; life- lp
Fatturi li għandhom jitqiesu f’ din l- evalwazzjoni għandhom jinkludu t- tip ta ’ ed
expectancy; the environment in which the patient is being treated; and patient preference (see section 5.1). a
tumur u l- stadju tiegħu; il- gravità tal- anemija; it- tul tal- għejxien, l- ambjent li fih il- pazjent qed jiġi kkurat; u l- preferenza tal- pazjent (ara sezzjoni 5. 1). m
In patients with solid tumours or lymphoproliferative malignancies, if the haemoglobin value exceeds in
Jekk il- livell ta 'l- emoglobina jaqbeż it- 12 g/ dl (7. 5 mmol/ l), f ’ pazjenti b’ tumuri solidi jew t
12 g/ dl (7.5 mmol/ l), the dosage adaptation described in section 4.2 should be closely respected, in ic
limfoproliferattivi, l- addattament tad- doża kif deskritt f’ sezzjoni 4. 2 għandu jiġi rispettat b’ attenzjoni, ot
order to minimise the potential risk of thromboembolic events.
sabiex jitnaqqas ir- riskju potenzjali ta ’ episodji tromboemboliċi.
Platelet counts and haemoglobin level should also be monitored at regular intervals. ed
L- għadd tal- plejtlits u l- livell ta ’ l - emoglobina għandhom jiġu mmonitorjati b 'intervalli regolari. od
4.5 Interaction with other medicinal products and other forms of interaction M
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu Pr
4.6 Pregnancy and lactation
188 4. 6 Tqala u treddigħ
175 Animal studies do not indicate direct harmful effects with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development.
Studji fuq l- annimali ma jindikawx effetti ta ’ ħsara diretta f’ dak li għandu x ’ jaqsam mat- tqala, l - iżvilupp ta ’ l- embriju u tal- fetu, il- ħlas jew l- iżvilupp ta ’ wara t- twelid.
Caution should be exercised when prescribing to pregnant women.
Nespo għandu jingħata b’ attenzjoni lill- nisa tqal.
As there is no clinical experience with lactating women Nespo should not be administered to women who are breast-feeding.
Billi m’ hemm l- ebda esperjenza klinika relatata ma ’ nisa li qed ireddgħu, Nespo m’ għandux jingħata
When Nespo therapy is absolutely indicated women must stop breast-feeding.
Meta l- kura b’ Nespo hija assolutament meħtieġa, il- mara għandha tieqaf mit - treddiegħ.
4.7 Effects on ability to drive and use machines
riz 4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
There have been no observed effects with Nespo on the ability to drive and use machines.
to Ma ġewx osservati effetti b 'Nespo fuq il- ħila biex issuq jew tħaddem magni.
ed 4.8 Undesirable effects
aw 4. 8 Effetti mhux mixtieqa
is General
Ġenerali
or There have been reports of serious allergic reactions including anaphylactic reaction, angioedema, dyspnoea, skin rash and urticaria associated with darbepoetin alfa.
x du Kien hemm rapporti ta ’ reazzjonijiet ta ’ sensittività eċċessiva serji li jinkludu reazzjonijiet anafilattiċi, anġioedema, qtugħ ta 'nifs, raxx tal- ġilda u urtikarja, assoċjati ma ’ darbapoetin alfa. ħa Espenjenza fi prova klinika ’ g Pazjenti b' insuffiċjenza renali kronika im
er Data presented from controlled studies included 1357 patients, 766 who received Nespo and 591 ng patients who received r-HuEPO.
Tagħrif ippreżentat minn studji kkontrollati inkludew 1357 pazjenti, 766 li ngħataw Nespo u 591 pazjent li ngħataw r- HuEPO.
In the Nespo group, 83% were receiving dialysis and 17% were not receiving dialysis. lo
Fil- grupp ta ’ Nespo, 83% kienu fuq dijaliżi u 17% ma kienux fuq dijaliżi. il
Injection site pain was reported as attributable to treatment in studies where Nespo was administered no
Fi studji fl ’ liema Nespo ingħata bħala injezzjoni taħt il- ġilda, l- uġigħ fis- sit ta 'l- injezzjoni ġie al
The injection site discomfort was generally mild and transient in nature and occurred predominantly after the first injection. ct
kienet ġeneralment moderata u temporanja u nħasset l- aktar wara l- ewwel injezzjoni. iċ
Incidence of undesirable effects considered related to treatment with Nespo from controlled clinical du
L- inċidenza ta ’ effetti mhux mixtieqa meqjusa bħala relatati mal- kura b’ Nespo fi studji kliniċi kontrollati huma dawn: ed
MedDRA system organ class Cardiac Disorders lp
Disturbi fil- qalb t
Skin and Subcutaneous Tissue Disorders a
Disturbi fil- ġilda u fit- tessuti ta ’
Rash/ Erythema
taħt il- ġilda
Uncommon (≥ 1/ 1,000 to
Mhux komuni (≥1/ 1, 000 sa
< 1/ 100) ic
≤1/ 100)