qanastek/EMEA-V3 huggingface dataset:
The safety and efficacy of Neupopeg have not been investigated in patients with myelodysplastic syndrome, chronic myelogenous leukaemia, and in patients with secondary Acute Myeloid Leukaemia (AML); therefore, it should not be used in such patients.
Is- sigurta 'u l- effikaċja ta' Neupopeg għad ma ġewx investigati f 'pazjenti b' sindromu majelodisplastiku, lewkimja mjeloġenika kronika, u f 'pazjenti b' Lewkimja Majelojde Akuta sekondarja; għalhekk, Neupopeg m 'għandux jintuża f' pazjenti bħal dawn.
ed The safety and efficacy of Neupopeg administration in de novo AML patients aged < 55 years with cytogenetics t(15; 17) have not been established.
t za Is- sigurtà u l- effikaċja ta 'l- għoti ta' Neupopeg ma 'ċitoġenetiċi t( 15; 17) f' pazjenti taħt il- 55 sena li
is or The safety and efficacy of Neupopeg have not been investigated in patients receiving high dose
to Is- sigurta` u l- effikaċja ta ’ Neupopeg ma ġewx investigati f’ pazjenti li qed jirċievu doża għolja ta ’
th chemotherapy.
aw kimoterapija.
au Rare (≥ 1/ 10,000 to < 1/ 1,000) pulmonary adverse effects, in particular interstitial pneumonia, have been reported after G-CSF administration.
x Effeti mhux mixtieqa rari (≥ 1/ 10, 000 u < 1/ 1, 000) tal- pulmun, b 'mod partikulari pulmonite du interstizjali, ġew rrappurtati wara l- għoti tal- fattur li jistimola l- kolonji ta ’ granuloċiti.
Patients with a recent history of pulmonary infiltrates or er pneumonia may be at higher risk. ng
Pazjenti b' każ reċenti ta 'infiltrati pulmonari jew pulmonite jista' jkollhom riskju għola. ħa ’ g
The onset of pulmonary signs such as cough, fever, and dyspnoea in association with radiological lo
Bidu ta ’ sinjali pulmonari bħal sogħla, deni u qtugħ ta ’ nifs flimkien ma ’ sinjali radjuloġiċi ta ’ m
In such o
infiltrati pulmonari, u deterjorazzjoni tal- funzjoni tal- pulmun flimkien ma ’ żjieda fl- għadd ta ’ newtrofili jistgħu jkunu sinjali tal- bidu tas- sindromu tat- tbatija respiratorja fl- adulti (ARDS). li
circumstances Neupopeg should be discontinued at the discretion of the physician and the appropriate tn
F’ ċirkostanzi bħal dawn Neupopeg għandu jitwaqqaf skond il- parir tat- tabib u għandha tingħata l- kura i
treatment given. uc
addattata. al in
Common (≥ 1/ 100 to < 1/ 10) but generally asymptomatic cases of splenomegaly and very rare od
Ġew rrappurtati wara l- għoti ta 'pegfilgrastim, każijiet ta' tkabbir tal- milza, dawn kienu komuni iċ
(< 1/ 10,000) cases of splenic rupture, including some fatal cases, have been reported following administration of pegfilgrastim.
(≥ 1/ 100 u < 1/ 10) iżda ġeneralment mingħajr sintomi, u każijiet rari ħafna (< 1/ 10, 000) ta 'milza ed
examination, ultrasound).
mifqugħha, fosthom ftit każijiet fatali.
A diagnosis of splenic rupture should be considered in patients reporting left al
Għalhekk, id- daqs tal- milza għandu jiġi monitorjat b' attenzjoni (per eżempju b 'eżaminazzjoni klinika, b' eżami ultrasoniku).
upper abdominal pain or shoulder tip pain. in
Dijanjożi ta ’ milza mifqugħha għandha tm
Treatment with Neupopeg alone does not preclude thrombocytopenia and anaemia because full dose ic
tkun ikkunsidrata f’ pazjenti b ’ uġigħ addominali fin- naħa ta ’ fuq tax- xellug jew fit- tarf ta ’ l- ispalla. ot
Regular monitoring of ed
Kura b’ Neupopeg waħdu ma jeskludix tromboċitopenija u anemija minħabba li tinżamm id- doża sħiħa od
platelet count and haematocrit is recommended.
Huwa rakkommandat li isir immonitorjar regolari ta ’ l- għadd ta ’ plejtlits u l- ematokrit.
Neupopeg should not be used to increase the dose of cytotoxic chemotherapy beyond established dosage regimens.
Neupopeg m’ għandux jintuża biex tiżdied id- doża ta ’ kimoterapija ċitotossika għal aktar mill- limiti stabiliti tad- dożaġġ.
Therefore, physicians should exercise caution when administering Neupopeg in patients with sickle cell disease, should monitor appropriate clinical parameters and laboratory status and be attentive to the possible association of Neupopeg with splenic enlargement and vaso-occlusive crisis.
Għalhekk, it- tobba għandhom joqgħodu attenti meta jagħtu Neupopeg lil pazjenti b’ mard taċ- ċellula b’ forma ta ’ minġel, għandhom jikkontrollaw il- parametri kliniċi xierqa u l- qagħda tal- parametri tal- laboratorju u joqgħodu attenti għall- assoċjazzjoni possibbli bejn Neupopeg u t- tkabbir tal- milza u kriżi vaso- okklusiva.
White blood cell counts of 100 x 109/ l or greater have been observed in less than 1% of patients receiving Neupopeg.
Għadd taċ- ċelluli bojod ta ’ 100 x 109 / l jew aktar ġew osservati f’ inqas minn 1% tal- pazjenti li ngħataw Neupopeg.
Such elevation in white blood cells is transient, typically seen 24 to 48 hours after administration and is consistent with the pharmacodynamic effects of Neupopeg.
Din iż- żjieda taċ- ċelluli bojod hija temporanja, tipikament osservata 24 sa 48 siegħa wara l- għoti u hija konsistenti ma ’ l- effetti farmakodinamiċi ta ’ Neupopeg.
The safety and efficacy of Neupopeg for the mobilisation of blood progenitor cells in patients or healthy donors has not been adequately evaluated.
3 Ma ġewx evalwati b’ mod xieraq is- sigurta` u l- effikaċja ta ’ Neupopeg għall- mobiliżazzjoni taċ- ċelluli proġenitriċi tad- demm f ’ pazjenti jew f 'donaturi b’ saħħithom.
The needle cover of the pre-filled syringe contains dry natural rubber (a derivative of latex), which may cause allergic reactions.
L- għatu tal- labra tas- siringa mimlija għal- lest fih lastiku naturali niexef (mnissel mill- latex), li jista 'jikkawza reazzjonijiet allerġiċi.
Neupopeg contains sorbitol.
Neupopeg fih sorbitol.
Neupopeg contains less than 1 mmol (23 mg) sodium per 6 mg dose, i. e. essentially ‘ sodium-free’.
Neupopeg fih anqas minn 1 mmol (23 mg) sodium għal kull doża ta ’ 6 mg, għalhekk huwa essenzjalment ‘ mingħajr sodium ’.
4.5 Interaction with other medicinal products and other forms of interaction
t za 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
Due to the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy‚ Neupopeg
riz to Minħabba s- sensittivita` potenzjali għal kimoterapija ċitotossika ta ’ ċelluli majelojdi li qed jiddividu malajr, Neupopeg għandu jingħata bejn wieħed u ieħor 24 siegħa wara l- għoti ta ’ kimoterapija
ed should be administered approximately 24 hours after administration of cytotoxic chemotherapy.
aw ċitotossika.
Concomitant
Fl- istudji kliniċi, Neupopeg ingħata mingħajr problemi 14- il jum qabel il- kimoterapija.
is use of Neupopeg with any chemotherapy agent has not been evaluated in patients.
Ma ġiex evalwat f’ pazjenti l- użu ta ’ Neupopeg flimkien ma ’ kwalunkwe aġent kimoterapewtiku.
In animal models
Fi
or concomitant administration of Neupopeg and 5-fluorouracil (5-FU) or other antimetabolites has been shown to potentiate myelosuppression.
x studji fuq annimali, l- għoti ta ’ Neupopeg ma ’ 5- fluorouracil (5 - FU) jew anti- metaboliti oħra wriet du żjieda fil- majelosoppressjoni. ħa
th au Possible interactions with other haematopoietic growth factors and cytokines have not been specifically investigated in clinical studies.
Ma ġewx investigati speċifikament fi studji kliniċi l- interazzjonijiet possibbli ma ’ fatturi ta ’ tkabbir ’ g
er
ematopojetiċi u ċitokini. m
ng The potential for interaction with lithium, which also promotes the release of neutrophils, has not been specifically investigated.
Il- potenzjal ta ’ interazzjoni ma ’ lithium, li wkoll jippromovi il- ħelisen ta ’ newtrofili, ma ġiex li
There is no evidence that such an interaction would be harmful. lo
M’ hemm l- ebda evidenza li interazzjoni bħal din tista ’ tkun ta ’ ħsara. i al
The safety and efficacy of Neupopeg have not been evaluated in patients receiving chemotherapy o
Is- sigurta` u l- effikaċja ta ’ Neupopeg ma ġewx evalwati f’ pazjenti li qed jirċievu kimoterapija in
associated with delayed myelosuppression e. g., nitrosoureas. tn uc
assoċjata ma ’ majelosoppressjoni ittardjata eż, nitrosureja. iċ ed
Specific interaction or metabolism studies have not been performed, however, clinical studies have not indicated an interaction of Neupopeg with any other medicinal products. od
Ma sarux studji speċifiċi dwar l- interazzjonijiet u l- metaboliżmu, madanakollu, studji kliniċi ma indikawx interazzjoni ta ’ Neupopeg ma ’ prodotti mediċinali oħra. tm
4.6 Pregnancy and lactation pr
4. 6 Tqala u Treddigħ ot
Studies in animals have al
M’ hemmx tgħarif biżżejjed dwar l- użu ta’ pegfilgrastim waqt it- tqala. Studji fuq bhejjem urew ħsara od
shown reproductive toxicity (see section 5.3).
fuq is- sistema riproduttiva (ara 5. 3).
The potential risk for humans is unknown. in ic
Pr
Neupopeg should not be used during pregnancy unless clearly necessary. ed
Neupopeg m’ għandux jintuża waqt it- tqala jekk mhux assolutament meħtieġ.
There is no clinical experience with breast-feeding women, therefore Neupopeg should not be M
M’ hemm l- ebda esperjenza klinika f’ nisa li qed ireddgħu, għalhekk Neupopeg m’ għandux jingħata lil nisa li qed irreddgħu.
In randomised clinical studies in patients with malignancy receiving Neupopeg after cytotoxic chemotherapy, most adverse events were caused by the underlying malignancy or cytotoxic chemotherapy.
Fi studji kliniċi randomised li saru fuq pazjenti b’ tumur malinn li kienu qed jingħataw Neupopeg wara l- kimoterapija ċitotossika, ħafna mill- effetti mhux mixtieqa kienu kkawżati mit- tumur jew mill - kimoterapija ċitotossika.
Allergic-type reactions, including anaphylaxis, skin rash, urticaria, angioedema, dyspnoea, hypotension, injection site reactions, erythaema and flushing, occurring on initial or subsequent treatment have been reported with Neupopeg.
Reazzjonijiet ta ’ allerġija, inklużi anafilassi, raxx tal- ġilda, urtikarja, anġjoedema, qtugħ ta 'nifs, pressjoni baxxa, reazzjonijiet fil- post ta ’ l- injezzjoni, eritema u fwawar, li seħħew ma ’ l- ewwel trattament jew ma ’ trattament ta ’ wara, ġew rrappurtati b’ Neupopeg.
Reversible, mild to moderate elevations in uric acid and alkaline phosphatase, with no associated clinical effects, were common (≥ 1/ 100 to < 1/ 10); reversible, mild to moderate elevations in lactate dehydrogenase, with no associated clinical effects, were very common (≥ 1/ 10) in patients receiving Neupopeg following cytotoxic chemotherapy.
Żjidiet ħfief għal moderati li jerġgħu għan- normal, u mingħajr effetti kliniċi assoċjati, f’ uric acid u f ’ alkaline phosphatase kienu komuni (≥ 1/ 100 u < 1/ 10); żjidiet ħfief għal moderati li jerġgħu għan - normal, u mingħajr effetti kliniċi assoċjati, f’ lactate dehydrogenase, kienu komuni ħafna (≥ 1/ 10)
Nausea was observed in healthy volunteers and patients receiving chemotherapy.
t za f’ pazjenti li ngħataw Neupopeg wara l- kimoterapija ċitotossika.
Common (≥ 1/ 100 to < 1/ 10) but generally asymptomatic cases of splenomegaly and very rare cases of splenic rupture, including some fatal cases, have been reported following administration of
riz to Ġew rrappurtati wara l- għoti ta 'pegfilgrastim, każijiet ta' tkabbir tal- milza, dawn kienu komuni (≥ 1/ 100 u < 1/ 10) iżda ġeneralment mingħajr sintomi, u każijiet rari ħafna ta 'milza mifqugħha, fosthom
ed pegfilgrastim (see section 4.4).
aw ftit każijiet fatali (ara sezzjoni 4. 4).
Other commonly reported undesirable effects include pain, injection site pain; chest pain (non-cardiac); headache; arthralgia; myalgia; back, limb, musculo-skeletal and
Effetti mhux mixtieqa oħra rrappurtati b’ mod komuni jinkludu uġigħ, uġigħ fis- sitfil- post ta ’ l- injezzjoni; uġigħ fis- sider (mhx kardijaku); uġigħ ta ’ ras; artralġja;
or Rare (≥ 1/ 10,000 to < 1/ 1,000) pulmonary adverse effects including interstitial pneumonia, pulmonary
x mijalġja; uġigħ fid- dahar, riġlejn u dirgħajn, muskoloskeletali u fl- għonq. du Effeti mhux mixtieqa rari (≥ 1/ 10, 000 u < 1/ 1, 000) tal- pulmun fosthom pulmonite interstizjali, nefħa ħa
Some of the reported cases
minn akkumulazzjoni ta 'ilma fil- pulmun, infiltrati pulmonari, jew fibrożi pulmonari ġew rrappurtati. ’ g
au have resulted in respiratory failure or Adult Respiratory Distress Syndrome (ARDS), which may be fatal (see section 4.4)
Ftit mill- każijiet rrappurtati rriżultaw f 'inkapaċità respiratorja jew sindromu tat- tbatija respiratorja fl - adulti (ARDS), li jistgħu jkunu fatali (ara sezzjoni 4. 4) m li
er
Każijiet rari (≥ 1/ 10, 000 u < 1/ 1, 000) ta 'tromboċitopenija u lewkoċitożi ġew rrappurtati. i al
ng Rare (≥ 1/ 10,000 to < 1/ 1,000) cases of thrombocytopenia and leukocytosis have been reported. lo
Ġew rrappurtati każijiet rari (≥ 1/ 10, 000 sa < 1/ 1, 000) tas- sindromu Sweet, għalkemm f' ċertu każijiet in
Rare (≥ 1/ 10,000 to < 1/ 1,000) cases of Sweet ’ s syndrome have been reported, although in some cases underlying haematological malignancies may play a role. o tn
it- tumur malinn ematoloġiku li hemm minn taħt jista 'jkollu sehem f' dan. iċ ed
Very rare (< 1/ 10,000) events of cutaneous vasculitis have been reported in patients treated with uc
Każijiet rari ħafna (< 1/ 10, 000) ta 'infjammazzjoni vaskulari fil- ġilda ġew osservati f' pazjenti li ngħataw Neulasta.
Neupopeg.
mhux magħruf. ot
Very rare (< 1/ 10,000) elevations in liver function tests (LFTs) for ALT (alanine aminotransferase) or AST (aspartate aminotransferase), have been observed in patients after receiving pegfilgrastim pr
Każijiet rari ħafna (< 1/ 10, 000) ta 'żjidiet f’ ALT (alanine aminotransferase) jew f’ AST (aspartate aminotransferase), fit- testijiet tal- funzjoni tal- fwied (LFTs), ġew osservati f’ pazjenti wara li ngħataw od
following cytotoxic chemotherapy.
pegfilgrastim wara kimoterapija ċitotossika.
These elevations are transient and return to baseline. al
Dawn iż- żjidiet kienu temporanji u jerġgħu lura għal linja Pr
Isolated cases of sickle cell crises have been reported in patients with sickle cell disease (see section in
bażi.
4.4). ic ed
Każijiet iżolati tal- marda taċ- ċellula b’ forma ta ’ minġel ġew rrappurtati f 'pazjenti bil- marda taċ - ċellula b’ forma ta ’ minġel (ara sezzjoni 4. 4).
4.9 Overdose M
4. 9 Doża eċċessiva
There is no experience with overdose of Neupopeg in humans.
M’ hemm l- ebda esperjenza b’ doża eċċessiva ta ’ Neupopeg fil- bnedmin.
Human granulocyte colony stimulating factor (G-CSF) is a glycoprotein, which regulates the production and release of neutrophils from the bone marrow.
5 Il- fattur uman li jistimola l- kolonji ta ’ granuloċiti (G- CSF) huwa glikoproteina li tirregola il - produzzjoni u l- ħelsien ta ’ newtrofili mill- mudullun.
Similarly to filgrastim, neutrophils produced in response to pegfilgrastim show normal or enhanced function as demonstrated by tests of chemotactic and phagocytic function.
Bħal fil- każ ta ’ filgrastim, in- newtrofili li jiġu prodotti b’ rispons għal pegfilgrastim juru funzjonijiet normali jew miżjuda kif intwera f’ testijiet dwar il- funzjoni kimotattika u fagoċitika.
In two randomised, double-blind, pivotal studies in patients with high risk stage II-IV breast cancer undergoing myelosuppressive chemotherapy consisting of doxorubicin and docetaxel, use of pegfilgrastim, as a single once per cycle dose, reduced the duration of neutropenia and the incidence of febrile neutropenia similarly to that observed with daily administrations of filgrastim (a median of 11 daily administrations).
F’ żewġ studji randomised, double- blind, ta ’ importanza kbira, f’ pazjenti b' kankru tas- sider ta 'riskju għoli stat I- IV li kienu qed jingħataw kimoterapija majelosopressiva li tikkonsisti f ’ doxorubicin u
In the absence of growth factor support, this regimen has been reported to result in a mean duration of grade 4 neutropenia of 5 to7 days, and a 30-40% incidence of febrile neutropenia.
t za docetaxel, l- użu ta ’ pegfilgrastim, bħala doża waħda kull ċiklu, naqqset id- dewmien tan- newtropenja u l- inċidenza ta ’ newtropenja bid- deni b’ mod simili għal dak osservat bl- għoti ta ’ kuljum ta ’ filgrastim
In one study (n=157), which used a 6mg fixed dose of pegfilgrastim the mean duration of grade 4 neutropenia for the pegfilgrastim group was 1.8 days compared with 1.6 days in the filgrastim group (difference 0.23 days, 95% CI -0.15, 0.63).
Fi studju wieħed (n=157), fejn intużat doża fissa ta ’ 6 mg ta ’
Over the entire study, the rate of febrile neutropenia was 13% of pegfilgrastim-treated patients compared with 20% of filgrastim-treated patients
aw pegfilgrastim id- dewmien medju tan- newtropenja grad 4 għall- grupp b’ pegfilgrastim kien ta ’ 1. 8 jiem meta mqabbel ma '1. 6 jiem tal- grupp b’ filgrastim (differenza ta ’ 0. 23 jiem, 95% CI - 0. 15, 0. 63).
ed (difference 7%, 95% CI of -19%, 5%).
x Matul l- istudju kollu, ir- rata ta ’ newtropenja bid- deni kienet ta ’ 13% tal- pazjenti kkurati du b’ pegfilgrastim mqabbla ma ’ 20% tal- pazjenti kkurati b’ filgrastim (differenza ta ’ 7%, 95% CI ta ’ - 19%, 5%).
In a second study (n=310), which used a weight-adjusted dose (100 micrograms/ kg), the mean duration of grade 4 neutropenia for the pegfilgrastim group was 1.7
Fi studju ieħor (n=310), fejn intużat doża maħduma skond il- piż (100 mikrogrammi/ kg), ħa
is days, compared with 1.8 days in the filgrastim group (difference 0.03 days, 95% CI -0.36, 0.30).
ma ’ 1. 8 jiem tal- grupp b’ filgrastim (differenza ta ’ 0. 03 jiem, 95% CI - 0. 36, 0. 30).
The
Ir- rata totali ta ’ newtropenja bid- deni kienet ta ’ 9% tal- pazjenti kkurati b’ pegfilgrastim u 18% tal- pazjenti kkurati m
or overall rate of febrile neutropenia was 9% of patients treated with pegfilgrastim and 18% of patients treated with filgrastim (difference 9%, 95% CI of -16.8%, -1.1%).
b’ filgrastim (differenza ta ’ 9%, 95% CI ta ’ - 16. 8%, - 1. 1%). li i
th au In a placebo-controlled, double blind study in patients with breast cancer the effect of pegfilgrastim on the incidence of febrile neutropenia was evaluated following administration of a chemotherapy er regimen associated with a febrile neutropenia rate of 10-20% (docetaxel 100 mg/ m2 every 3 weeks for ng 4 cycles).
Fi studju double- blind, kontrollat bil- plaċebo, fuq pazjenti bil- kankru tas- sider ġie evalwat l- effett ta 'al
The lo
pegfilgrastim fuq l- inċidenza tan- newtropenja bid- deni wara l- għoti ta 'ċiklu ta' kimoterapija assoċjat in
incidence of febrile neutropenia was lower for patients randomised to receive pegfilgrastim compared with placebo (1% versus 17%, p < 0.001).
Disa 'iċ
The incidence of hospitalisations and IV anti-infective use o
mija u tmienja u għoxrin pazjent ġew mqassma b' mod randomised biex jirċievu jew doża waħda ta 'ed
associated with a clinical diagnosis of febrile neutropenia was lower in the pegfilgrastim group tn
pegfilgrastim jew plaċebo bejn wieħed u ieħor 24 siegħa (Tieni ġurnata) wara l- kimoterapija f' kull ċiklu.
compared with placebo (1% versus 14%, p < 0.001; and 2% versus 10%, p < 0.001) uc
mqabbla ma 'dawk li reċevew il- plaċebo (1% versus 17%, p < 0. 001).
A small (n=83), Phase II, randomised, double-blind study in patients receiving chemotherapy for od
grupp ta 'pegfilgrastim meta mqabbla mal- grupp tal- plaċebo (1% versus 14%, p < 0. 001; u 2% versus od
Median time to recovery from severe neutropenia was pr
Fi studju żgħir (n=83), Fażi II, randomised, double- blind f 'pazjenti li reġgħet qabdithom lewkimja majelojde akuta u li qed jirċievu il- kimoterapija għaliha, ġie mqabbel pegfilgrastim (doża waħda ta' 6 mg) ma 'filgrastim waqt il- kimoterapija tal- bidu.
estimated as 22 days in both treatment groups.
Il- ħin medju biex tirkupra minn newtropenja severa ġie stmat għal 22 ġurnata fiż- żewġ ġruppi.
Long term outcome was not studied (see section 4.4). al
L- effett fit- tul ma ġiex studjat (ara sezzjoni 4. 4).
5.2 Pharmacokinetic properties in ic
5. 2 Tagħrif farmakokinetiku
The elimination of pegfilgrastim is M
Wara doża waħda ta ’ pegfilgrastim taħt il- ġilda, l- ogħla konċentrazzjoni fis- serum ta ’ pegfilgrastim tintlaħaq minn 16 sa 120 siegħa wara d- dożaġġ u l- konċentrazzjonijiet fis- serum ta ’ pegfilgrastim jinżammu tul il- perjodu ta ’ newtropenja wara l- kimoterapija majelosoppressiva.
Pegfilgrastim appears to be mainly eliminated by neutrophil mediated clearance, which becomes saturated at higher doses.
L- eliminazzjoni ta ’ pegfilgrastim m’ hiex lineari meta relatata mad- doża; u r- rata ta ’ tneħħija mis- serum ta ’ pegfilgrastim tonqos hekk kif tiżdied id- doża.
Consistent with a self-regulating clearance mechanism, the serum concentration of pegfilgrastim declines rapidly at the onset of neutrophil recovery (see Figure 1).
Jidher li pegfilgrastim jiġi mneħħi l- biċċa l- kbira permezz ta ’ tneħħija medjata minn newtrofili, din tiġi saturata f’ dożi ogħla.
Figure 1.
Fi qbil ma ’ mekkaniżmu ta ’ tneħħija li jirregola lilu nnifsu, il- konċentrazzjoni fis- serum ta ’ pegfilgrastim tonqos b’ ħeffa kbira malli jibdew jirpiljaw in- newtrofili (ara Figura 1).
Profile of Median Pegfilgrastim Serum Concentration and Absolute Neutrophil Count (ANC) in Chemotherapy Treated Patients after a Single 6 mg Injection
6 Figura 1 Profil tal- Medja tal- Konċentrazzjoni fis- serum ta ’ Pegfilgrastim u l- Għadd Assolut ta ’ Newtrofili (ANC) f ’ Pazjenti Kkurati b ’ kimoterapija wara Injezzjoni Waħda ta’ 6 mg
Median Absolute Neutrophil Count (cells x 109/ l)
Fi studju open label ta ’ doża waħda (n=31), varji stadji ta ’ indeboliment renali, inkluż mard renal ta ’ l- aħħar stadju, ma ’ g
1000
kellhom l- ebda impatt fuq il- farmakokinetika ta ’ pegfilgrastim. m
ANC
Tagħrif limitat jindika li l- farmakokinetika ta ’ pegfilgrastim fl- anzjani (> 65 sena) hija simili għal dik li
100 10
fl- adulti. i al
3
Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurta` tal- mediċina 5. 3 in iċ
th Due to the neutrophil-mediated clearance mechanism, the pharmacokinetics of pegfilgrastim is not
Tagħrif ta ’ qabel l- użu kliniku miġbur minn studji konvenzjonali fuq l- effett tossiku minn dożi ed
In a open label, single dose study (n=31) various stages of renal impairment, including end-stage renal disease, had no impact on the pharmacokinetics of pegfilgrastim. er ng Limited data indicate that the pharmacokinetics of pegfilgrastim in elderly subjects (> 65 years) is similar to that in adults. lo o
riptetuti, wera l- effetti farmakoloġiċi mistennija fosthom żjidiet fl- għadd ta ’ lewkoċiti, iperplasija majelojde fil- mudullun, ematopojesi ekstramedullari u tkabbir tal- milza. tm
Preclinical data from conventional studies of repeated dose toxicity revealed the expected uc
Ma kien hemm l- ebda effett mhux mixtieq osservat fil- frieħ ta ’ firien tqal li ngħataw pegfilgrastim taħt ot
pharmacological effects including increases in leukocyte count, myeloid hyperplasia in bone marrow, od
il- ġilda, iżda fil- fniek pegfilgrastim ikkawża tossiċita` fl- embriju/ fetu (telfien ta’ l- embriju) f’ dożi od
loss) at low subcutaneous doses.
baxxi taħt il- ġilda.
In rat studies, it was shown that pegfilgrastim may cross the placenta. in
Fi studji fil- firien, intwera li pegfilgrastim għandu mnejn jgħaddi mis- sekonda.
The relevance of these findings for humans is not known. ic ed
Pr
PHARMACEUTICAL PARTICULARS M
TAGĦRIF FARMAĊEWTIKU
Neupopeg may be exposed to room temperature (not above 30°C) for a maximum single period of up to 72 hours.
Neupopeg jista ’ jiġi espost għal temperatura ambjentali (mhux aktar minn 30°C) għal perijodu wieħed ta’ massimu ta ’ 72 siegħa.
Neupopeg left at room temperature for more than 72 hours should be discarded.
Neupopeg li tħalla f’ temperatura ambjentali għal aktar minn 72 siegħa
Do not freeze.
riz Tagħmlux fil- friża.
Accidental exposure to freezing temperatures for a single period of less than 24 hours does not adversely affect the stability of Neupopeg.
to minn 24 siegħa ma jeffettwax ħażin l- istabilita` ta ’ Neupopeg.
Keep the container in the outer carton, in order to protect from light.
aw Żomm il- kontenitur fil- pakkett ta ’ barra, sabiex tilqa 'mid- dawl.
ed 6.5 Nature and contents of container
In- natura tal- kontenitur u ta ’ dak li hemm ġo fiħ
is 0.6 ml of solution for injection in a pre-filled syringe (Type I glass), with a rubber stopper, and with a
0. 6 ml ta ’ soluzzjoni għall- injezzjoni ġo siringa mimlija għall- lest (Ħġieġ Tip I), b ’ tapp tal- lastiku, u ħa
or stainless steel needle.
b ’ labra ta ’ l- azzar li ma jissaddadx.
Pack size of one, in either blistered or non-blistered packaging.
Għall - ’ g
Single use only.
użu ta ’ darba. m
th The needle cover of the pre-filled syringe contains dry natural rubber (a derivative of latex) (see
L- għatu tal- labra tas- siringa mimlija għal- lest fih lastiku naturali niexef (mnissel mill- latex) (ara li
au section 4.4).
sezzjoni 4. 4). i al
Not all pack sizes may be marketed. er ng
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali. in iċ
6.6 Special precautions for disposal and other handling lo
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema u għal immaniġġar ieħor ed
Before administration, Neupopeg solution should be inspected visually for particulate matter.
Qabel l- għoti, is- soluzzjoni Neupopeg trid tiġi spezzjonata viżwalment għallfrak.
Only a o
Għandhom jsiru tm
solution that is clear and colourless should be injected. tn uc
injezzjonijiet biss b’ soluzzjoni li tkun ċara u bla kulur. ot
Excessive shaking may aggregate pegfilgrastim, rendering it biologically inactive. od
Taħwid żejjed għandu mnejn jgħaqqad pegfilgrastim u jagħmlu bijoloġikament inattiv. od
Allow the pre-filled syringe to reach room temperature before injecting. pr
Pr
Any unused product or waste material should be disposed of in accordance with local requirements. al in
Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali.
MARKETING AUTHORISATION HOLDER ic ed
ID- DETENTUR TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
Via San Martino 12 M
Via San Martino 12 I- 20122 Milan Italja
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/
t za Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il - Mediċini (EMEA) http: // www. emea. europa. eu /.
ed is or th au er ng lo o tn uc od pr al in ic ed M 1.
riz to aw x du ħa ’ g m li i al in iċ ed tm ot od Pr
Neupopeg 6 mg solution for injection in a pre-filled pen.
Neupopeg 6 mg soluzzjoni għall- injezzjoni ġo pinna mimlija għal- lest.
*Produced in Escherichia coli cells by recombinant DNA technology followed by conjugation with polyethylene glycol (PEG). ** The concentration is 20 mg/ ml if the PEG moiety is included
* Magħmul f ’ ċellui ta ’ Escherichia coli b ’ teknoloġija rikombinanti- DNA u wara b ’ konjugazzjoni ma ’ polyethylene glycol (PEG). ** Il- konċentrazzjoni hija ta ’ 20 mg/ ml jekk tiġi inkluża l- porzjoni PEG.
The potency of this product should not be compared to the potency of another pegylated or non- pegylated protein of the same therapeutic class.
Il- qawwa ta ’ dan il- prodott m’ għandix tiġi mqabbla mal- qawwa ta ’ proteina pegylated jew mhux
For more information, see section 5.1
Għal aktar informazzjoni, are sezzjoni 5. 1.
ed Excipients:
riz Sustanzi mhux attivi:
is or Excipients known to have a recognised action: sorbitol E420, sodium acetate (see section 4.4).
to Sustanzi mhux attivi li għandhom azzjoni magħrufa: sorbitol E- 420, sodium acetate (ara sezzjoni 4. 4).
PHARMACEUTICAL FORM er ng
GĦAMLA FARMAĊEWTIKA ħa ’ g
Solution for injection in a pre-filled pen (SureClick). lo
Soluzzjoni għall- injezzjoni ġo pinna mimlija għal- lest (SureClick). m
Clear, colourless solution for injection. o tn uc
Soluzzjoni għall- injezzjoni ċara u mingħajr kulur. li i al
CLINICAL PARTICULARS od
TAGĦRIF KLINIKU in iċ
4.1 Therapeutic indications pr
4. 1 Indikazzjonijiet terapewtiċi ed
Reduction in the duration of neutropenia and the incidence of febrile neutropenia in patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and al
Tnaqqis fid- dewmien tan- newtropenja u ta’ l- inċidenza ta ’ newtropenja bid- deni f’ pazjenti kkurati tm
myelodysplastic syndromes). in ic
b’ kimoterapija ċitotossika għal tumur malinn (bl- eċċezzjoni ta ’ lewkimja majelojde kronika u sindromi majelodisplastiċi). ot
4.2 Posology and method of administration ed
4. 2 Pożoloġija u metodu ta ’ kif għandu jingħata od Pr
Neupopeg therapy should be initiated and supervised by physicians experienced in oncology and/ or M
Il- kura b’ Neupopeg għandha tinbeda u tiġi segwita minn tobba b’ esperjenza fl- onkoloġija u/ jew l - ematoloġija.
One 6 mg dose (a single pre-filled pen) of Neupopeg (SureClick) is recommended for each chemotherapy cycle, administered as a subcutaneous injection approximately 24 hours following cytotoxic chemotherapy.
Doża waħda ta ’ 6mg (pinna waħda mimlija għal- lest) ta ’ Neupopeg (SureClick) hija rrakkomandata għal kull ċiklu ta ’ kimoterapija, mogħtija bħala injezzjoni taħt il- ġilda bejn wieħed u ieħor 24 siegħa wara l- kimoterapija ċitotossika.
Limited clinical data suggest a similar effect on time to recovery of severe neutropenia for pegfilgrastim to filgrastim in patients with de novo acute myeloid leukaemia (see section 5.1).
Tagħrif kliniku limitat jissuġerixxi li l- effett fuq il- ħin biex tirkupra minn newtropenja severa f' pazjenti li reġgħet qabdithom lewkimja majelojde mill- ġdid, hija komparabbli bejn dawk li ngħataw pegfilgrastim u dawk li ngħataw filgrastim (ara sezzjoni 5. 1).
However, the long-term effects of Neupopeg have not been established in acute myeloid leukaemia; therefore, it should be used with caution in this patient population.
Madanakollu, l- effett fit- tul ta 'Neupopeg għad ma ġiex stabbilit f' lewkimja majelojde akuta, għalhekk Neupopeg għandu jintuża b 'kawzjoni f' dawn il- pazjenti.
The safety and efficacy of Neupopeg have not been investigated in patients with myelodysplastic syndrome, chronic myelogenous leukaemia, and in patients with secondary Acute Myeloid Leukaemia (AML); therefore, it should not be used in such patients.
Is- sigurtà u l- effikaċja ta 'Neupopeg għad ma ġewx investigati f' pazjenti b 'sindromu majelodisplastiku, lewkimja mjeloġenika kronika, u f' pazjenti b 'Lewkimja Majelojde Akuta sekondarja; għalhekk, Neupopeg m' għandux jintuża f 'pazjenti bħal dawn.
Particular care should be taken to distinguish the diagnosis of blast transformation of chronic myeloid leukaemia from acute myeloid leukaemia.
Attenzjoni speċjali għandha tingħata biex tiġi distinta id- djanjożi ta 'tibdil taċ- ċelluli blastiċi ta' lewkimja majelojde kronika minn
ed The safety and efficacy of Neupopeg administration in de novo AML patients aged < 55 years with cytogenetics t(15; 17) have not been established.
riz Is- sigurtà u l- effikaċja ta 'l- għoti ta' Neupopeg ma 'ċitoġenetiċi t( 15; 17) f' pazjenti taħt il- 55 sena li
is or The safety and efficacy of Neupopeg have not been investigated in patients receiving high dose
to reġgħet qabdithom lewkimja majelojde akuta mill- ġdid, għad ma ġewx stabiliti.
th chemotherapy.
aw Is- sigurta` u l- effikaċja ta ’ Neupopeg ma ġewx investigati f’ pazjenti li qed jirċievu doża għolja ta ’ kimoterapija.
au Rare (≥ 1/ 10,000 to < 1/ 1,000) pulmonary adverse effects, in particular interstitial pneumonia, have been reported after G-CSF administration.
Pazjenti b' każ ħa
Patients with a recent history of pulmonary infiltrates or er pneumonia may be at higher risk. ng
reċenti ta 'infiltrati pulmonari jew pulmonite jista' jkollhom riskju għola. ’ g m
The onset of pulmonary signs such as cough, fever, and dyspnoea in association with radiological lo
Bidu ta ’ sinjali pulmonari bħal sogħla, deni u qtugħ ta ’ nifs flimkien ma ’ sinjali radjuloġiċi ta ’ infiltrati pulmonari, u deterjorazzjoni tal- funzjoni tal- pulmun flimkien ma ’ żjieda fl- għadd ta ’ li
signs of pulmonary infiltrates, and deterioration in pulmonary function along with increased neutrophil count may be preliminary signs of Adult Respiratory Distress Syndrome (ARDS).
newtrofili jistgħu jkunu sinjali tal- bidu tas- sindromi tat- tbatija respiratorja fl- adulti (ARDS).
In such o
F ’ i
circumstances Neupopeg should be discontinued at the discretion of the physician and the appropriate tn
ċirkostanzi bħal dawn Neupopeg għandu jitwaqqaf skond il- parir tat- tabib u għandha tingħata l- kura al
treatment given. uc
addattata. in iċ
Common (≥ 1/ 100 to < 1/ 10) but generally asymptomatic cases of splenomegaly and very rare od
Ġew rrappurtati wara l- għoti ta 'pegfilgrastim, każijiet ta' tkabbir tal- milza, dawn kienu komuni ed
(< 1/ 10,000) cases of splenic rupture, including some fatal cases, have been reported following administration of pegfilgrastim.
(≥ 1/ 100 u < 1/ 10) iżda ġeneralment mingħajr sintomi, u każijiet rari ħafna (< 1/ 10, 000) ta 'milza mifqugħha, fosthom ftit każijiet fatali.
Therefore, spleen size should be carefully monitored (e. g. clinical pr
Għalhekk, id- daqs tal- milza għandu jiġi monitorjat b' attenzjoni tm
A diagnosis of splenic rupture should be considered in patients reporting left al
(per eżempju b 'eżaminazzjoni klinika, b' eżami ultrasoniku).
Treatment with Neupopeg alone does not preclude thrombocytopenia and anaemia because full dose ic
Dijanjożi ta ’ milza mifqugħha għandha tkun ikkunsidrata f’ pazjenti b ’ uġigħ addominali fin- naħa ta ’ fuq tax- xellug jew fit- tarf ta ’ l- ispalla. ot od
myelosuppressive chemotherapy is maintained on the prescribed schedule.
Kura b’ Neupopeg waħdu ma jeskludix tromboċitopenija u anemija minħabba li tinżamm id- doża sħiħa ta 'kimoterapija majelosoppressiva fl- iskeda preskritta.
Regular monitoring of ed
Huwa rakkommandat li isir immonitorjar Pr
M
regolari ta ’ l- għadd ta ’ plejtlits u l- ematokrit.
Neupopeg should not be used to increase the dose of cytotoxic chemotherapy beyond established dosage regimens.
Neupopeg m’ għandux jintuża biex tiżdied id- doża ta ’ kimoterapija ċitotossika għal aktar mil- limiti stabiliti tad- dożaġġ.
Therefore, physicians should exercise caution when administering Neupopeg in patients with sickle cell disease, should monitor appropriate clinical parameters and laboratory status and be attentive to the possible association of Neupopeg with splenic enlargement and vaso-occlusive crisis.
Għalhekk, it- tobba għandhom joqgħodu attenti meta jagħtu Neupopeg lil pazjenti b ’ mard taċ- ċellula b’ forma ta ’ minġel, għandhom jikkontrollaw il- parametri kliniċi xierqa u l- qagħda tal- parametri tal- laboratorju u joqgħodu attenti għall- assoċjazzjoni possibbli bejn Neupopeg u t- tkabbir tal- milza u kriżi vaso- okklusiva.
The safety and efficacy of Neupopeg for the mobilisation of blood progenitor cells in patients or healthy donors has not been adequately evaluated.
11 Ma ġewx evalwati b’ mod xieraq is- sigurta` u l- effikaċja ta ’ Neupopeg għall- mobiliżazzjoni taċ- ċelluli proġenitriċi tad- demm f ’ pazjenti jew f 'donaturi b’ saħħithom
The needle cover of the pre-filled pen contains dry natural rubber (a derivative of latex), which may cause allergic reactions.
L- għatu tal- labra tal- pinna mimlija għal- lest fih lastiku naturali niexef (mnissel mill- latex), dan jista 'jikkawża reazzjonijiet allerġiċi.
4.5 Interaction with other medicinal products and other forms of interaction
t za 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu
Due to the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy‚ Neupopeg
to Minħabba s- sensittivita` potenzjali għal kimoterapija ċitotossika ta ’ ċelluli majelojdi li qed jiddividu
ed should be administered approximately 24 hours after administration of cytotoxic chemotherapy.
aw malajr, Neupopeg għandu jingħata bejn wieħed u ieħor 24 siegħa wara l- għoti ta ’ kimoterapija ċitotossika.
In animal models
x Ma ġiex evalwat f’ pazjenti l- użu ta ’ Neupopeg flimkien ma ’ kwalunkwe aġenti kimoterapewtiku.
or concomitant administration of Neupopeg and 5-fluorouracil (5-FU) or other antimetabolites has been shown to potentiate myelosuppression.
Fi du studji fuq annimali, l- għoti ta ’ Neupopeg u 5- fluorouracil (5 - FU) jew anti- metaboliti oħra wriet żjieda fil- majelosoppressjoni. ħa ’ g
th au Possible interactions with other haematopoietic growth factors and cytokines have not been specifically investigated in clinical studies.
Ma ġewx investigati speċifikament fi studji kliniċi l- interazzjonijiet possibbli ma ’ fatturi ta ’ tkabbir ematopojetiċi u ċitokini. m li
er
Il- potenzjal ta ’ interazzjoni ma ’ lithium, li wkoll jippromovi il- ħelisen ta ’ newtrofili, ma ġiex i
ng The potential for interaction with lithium, which also promotes the release of neutrophils, has not been specifically investigated.
M’ hemm l- ebda evidenza li interazzjoni bħal din tista ’ tkun ta ’ ħsara. al in
The safety and efficacy of Neupopeg have not been evaluated in patients receiving chemotherapy o
Is- sigurta` u l- effikaċja ta ’ Neupopeg ma ġietx evalwata f’ pazjenti li qed jirċievu kimoterapija iċ
associated with delayed myelosuppression e. g., nitrosoureas. tn uc
assoċjata ma ’ majelosoppressjoni ittardjata eż, nitrosureja. ed
Specific interaction or metabolism studies have not been performed, however, clinical studies have not indicated an interaction of Neupopeg with any other medicinal products. od
indikawx interazzjoni ta ’ Neupopeg ma ’ prodotti mediċinali oħra. ot
4.6 Pregnancy and lactation pr
4. 6 Tqala u Treddigħ od
Studies in animals have al
Studji fl- annimali wrew Pr
shown reproductive toxicity (see section 5.3).
tossiċita` riproduttiva (ara sezzjoni 5. 3).
The potential risk for humans is unknown. in ic
Mhux magħruf ir- riskju potenzjali fuq il- bnedmin.
There is no clinical experience with breast-feeding women, therefore Neupopeg should not be M
M’ hemm l- ebda esperjenza klinika f’ nisa li qed ireddgħu, u għalhekk Neupopeg m’ għandux jingħata lil nisa li qed irreddgħu.
4.7 Effects on ability to drive and use machines
12 4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
Allergic-type reactions, including anaphylaxis, skin rash, urticaria, angioedema, dyspnoea, hypotension, injection site reactions, erythaema and flushing, occurring on initial or subsequent treatment have been reported with Neupopeg.
Reazzjonijiet ta ’ allerġija, inklużi anafilassi, raxx tal- ġilda, urtikarja, anġjoedema, qtugħ ta 'nifs, pressjoni baxxa, reazzjonijiet fl- post ta ’ l- injezzjoni, eritema u fwawar, li seħħew mal- bidu jew wara l -
In some cases, symptoms have recurred with rechallenge, suggesting a causal relationship.
to addattata, flimkien ma 'osservazzjoni mill- qrib tal- pazjent fuq bosta ġranet.
If a serious allergic reaction occurs, appropriate therapy should be administered, with close patient follow-up over several days.
Pegfilgrastim għandu jiġi mwaqqaf għal dejjem f' pazjenti li jkollhom reazzjoni allerġika serja.
Pegfilgrastim should be permanently discontinued in patients who experience a serious allergic reaction.
aw Żjidiet ħfief għal moderati li jerġgħu għan- normal, u mingħajr effetti kliniċi assoċjati, f’ uric acid u f ’
Reversible, mild to moderate elevations in uric acid and alkaline phosphatase, with no associated clinical effects, were common (≥ 1/ 100 to < 1/ 10); reversible, mild to moderate elevations in lactate dehydrogenase, with no associated clinical effects, were very common (≥ 1/ 10) in patients receiving Neupopeg following cytotoxic chemotherapy.
Dardir ġie osservat f’ voluntiera ħa
Nausea was observed in healthy volunteers and patients receiving chemotherapy.
b’ saħħithom u f’ pazjenti li ngħataw il- kimoterapija. ’ g
Common (≥ 1/ 100 to < 1/ 10) but generally asymptomatic cases of splenomegaly and very rare cases of splenic rupture, including some fatal cases, have been reported following administration of
Ġew rrappurtati wara l- għoti ta 'pegfilgrastim, każijiet ta' tkabbir tal- milza, dawn kienu komuni (≥ m
ed pegfilgrastim (see section 4.4).
ftit każijiet fatali (ara sezzjoni 4. 4).
Other commonly reported undesirable effects include pain, injection site pain; chest pain (non-cardiac); headache; arthralgia; myalgia; back, limb, musculo-skeletal and
uġigħ, uġigħ fis- sitfil- post ta ’ l- injezzjoni; uġigħ fis- sider (mhx kardijaku); uġigħ ta ’ ras; artralġja; al
is neck pain.
mijalġja; uġigħ fid- dahar, riġlejn u dirgħajn, muskoloskeletali u fl- għonq. in iċ
or Rare (≥ 1/ 10,000 to < 1/ 1,000) pulmonary adverse effects including interstitial pneumonia, pulmonary
Effeti mhux mixtieqa rari (≥ 1/ 10, 000 u < 1/ 1, 000) tal- pulmun fosthom pulmonite interstizjali, nefħa ed
Some of the reported cases
minn akkumulazzjoni ta 'ilma fil- pulmun, infiltrati pulmonari, jew fibrożi pulmonari ġew rrappurtati.
au have resulted in respiratory failure or Adult Respiratory Distress Syndrome (ARDS), which may be fatal (see section 4.4)
adulti (ARDS), li jistgħu jkunu fatali (ara sezzjoni 4. 4) ot
er
Każijiet rari (≥ 1/ 10, 000 u < 1/ 1, 000) ta 'tromboċitopenija u lewkoċitożi ġew rrappurtati. od
ng Rare (≥ 1/ 10,000 to < 1/ 1,000) cases of thrombocytopenia and leukocytosis have been reported. lo
Ġew rrappurtati każijiet rari (≥ 1/ 10, 000 sa < 1/ 1, 000) tas- sindromu Sweet, għalkemm f' ċertu każijiet Pr
Rare (≥ 1/ 10,000 to < 1/ 1,000) cases of Sweet ’ s syndrome have been reported, although in some cases underlying haematological malignancies may play a role. o tn
it- tumur malinn ematoloġiku li hemm minn taħt jista 'jkollu sehem f' dan.
The mechanism of vasculitis in patients receiving Neupopeg is unknown. od
Il- mekkaniżmu ta 'l- infjammazzjoni vaskulari f' pazjenti li qed jirċievu Neulasta mhux magħruf.
Very rare (< 1/ 10,000) elevations in liver function tests (LFTs) for ALT (alanine aminotransferase) or AST (aspartate aminotransferase), have been observed in patients after receiving pegfilgrastim pr
Każijiet rari ħafna (< 1/ 10, 000) ta 'żjidiet f’ ALT (alanine aminotransferase) jew f’ AST (aspartate aminotransferase), fit- testijiet tal- funzjoni tal- fwied (LFTs), ġew osservati f’ pazjenti wara li ngħataw pegfilgrastim wara kimoterapija ċitotossika.
These elevations are transient and return to baseline. al
Dawn iż- żjidiet kienu temporanji u jerġgħu lura għal linja bażi.
4.9 Overdose M
13 4. 9 Doża eċċessiva
Pegfilgrastim and filgrastim have been shown to have identical modes of action, causing a marked increase in peripheral blood neutrophil counts within 24 hours, with minor increases in monocytes and/ or lymphocytes.
Bħal fil- każ ta ’
Similarly to filgrastim, neutrophils produced in response to pegfilgrastim show normal or enhanced function as demonstrated by tests of chemotactic and phagocytic function.
riz filgrastim, in- newtrofili li jiġu prodotti b’ rispons għal pegfilgrastim juru funzjonijiet normali jew
G-CSF can promote growth of myeloid cells, including malignant cells, in vitro and similar effects may be seen on some non-myeloid cells in vitro.
aw G- CSF jista ’ jippromovi t- tkabbir in vitro ta ’ ċelluli majelojdi, inklużi ċelluli malinni, u effetti simili jistgħu jidhru wkoll fuq xi ċelluli mhux majelojdi in vitro.
In two randomised, double-blind, pivotal studies in patients with high risk stage II-IV breast cancer undergoing myelosuppressive chemotherapy consisting of doxorubicin and docetaxel, use of pegfilgrastim, as a single once per cycle dose, reduced the duration of neutropenia and the incidence of febrile neutropenia similarly to that observed with daily administrations of filgrastim (a median of 11 daily administrations).
x du F’ żewġ studji randomised, double- blind, ta ’ importanza kbira, f’ pazjenti b' kankru tas- sider ta 'riskju għoli stat I- IV li kienu qed jingħataw kimoterapija majelosopressiva li tikkonsisti f ’ doxorubicin u ħa
In the absence of growth factor support, this regimen has been reported to result in a mean duration of grade 4 neutropenia of 5 to7 days, and a 30-40% incidence of febrile neutropenia.
docetaxel, l- użu ta ’ pegfilgrastim, bħala doża waħda kull ċiklu, naqqset id- dewmien tan- newtropenja u ’ g
In one study (n=157), which used a 6mg fixed dose of pegfilgrastim the mean duration of grade 4 neutropenia for the pegfilgrastim group was 1.8 days compared with 1.6 days in the filgrastim group (difference 0.23 days, 95% CI -0.15, 0.63).
Fin- nuqqas ta ’ appoġġ ta ’ fattur ta ’ tkabbir, ġie rrappurtat li din l - m
Over the entire study, the rate of febrile neutropenia was 13% of pegfilgrastim-treated patients compared with 20% of filgrastim-treated patients
iskema ta’ dożaġġ tirriżulta f’ newtropenja ta ’ grad 4 li ddum medja ta ’ 5 sa 7 ijiem, u inċidenza ta ’ 30 - li
ed (difference 7%, 95% CI of -19%, 5%).
40% ta ’ newtropenja bid- deni.
In a second study (n=310), which used a weight-adjusted dose (100 microgramsg/ kg), the mean duration of grade 4 neutropenia for the pegfilgrastim group was 1.7
Fi studju wieħed (n=157), fejn intużat doża fissa ta ’ 6 mg ta ’ i
The
pegfilgrastim id- dewmien medju tan- newtropenja grad 4 għall- grupp b’ pegfilgrastim kien ta ’ 1. 8 jiem al
or overall rate of febrile neutropenia was 9% of patients treated with pegfilgrastim and 18% of patients treated with filgrastim (difference 9%, 95% CI of -16.8%, -1.1%).
meta mqabbel ma '1. 6 jiem tal- grupp b’ filgrastim (differenza ta ’ 0. 23 jiem, 95% CI - 0. 15, 0. 63). in
th au In a placebo-controlled, double blind study in patients with breast cancer the effect of pegfilgrastim on the incidence of febrile neutropenia was evaluated following administration of a chemotherapy er regimen associated with a febrile neutropenia rate of 10-20% (docetaxel 100 mg/ m2 every 3 weeks for ng 4 cycles).
Matul l- istudju kollu, ir- rata ta ’ newtropenja bid- deni kienet ta ’ 13% tal- pazjenti kkurati iċ
Nine hundred and twenty eight patients were randomised to receive either a single dose of pegfilgrastim or placebo approximately 24 hours (Day 2) after chemotherapy in each cycle.
b’ pegfilgrastim mqabbla ma ’ 20% tal- pazjenti kkurati b’ filgrastim (differenza ta ’ 7%, 95% CI ta ’ - ed
The lo
19%, 5%).
incidence of febrile neutropenia was lower for patients randomised to receive pegfilgrastim compared with placebo (1% versus 17%, p < 0.001).
ma ’ 1. 8 jiem tal- grupp b’ filgrastim (differenza ta ’ 0. 03 jiem, 95% CI - 0. 36, 0. 30).
The incidence of hospitalisations and IV anti-infective use o
Ir- rata totali ta ’ newtropenja bid- deni kienet ta ’ 9% tal- pazjenti kkurati b’ pegfilgrastim u 18% tal- pazjenti kkurati ot
associated with a clinical diagnosis of febrile neutropenia was lower in the pegfilgrastim group tn
b’ filgrastim (differenza ta ’ 9%, 95% CI ta ’ - 16. 8%, - 1. 1%). od
compared with placebo (1% versus 14%, p < 0.001; and 2% versus 10%, p < 0.001) uc
Fi studju double- blind, kontrollat bil- plaċebo, fuq pazjenti bil- kankru tas- sider ġie evalwat l- effett ta 'Pr
A small (n=83), Phase II, randomised, double-blind study in patients receiving chemotherapy for od
L- inċidenza tan- newtropenja bid- deni kienet aktar baxxa f' pazjenti li rċevew pegfilgrastim meta mqabbla ma 'dawk li reċevew il- plaċebo (1% versus 17%, p < 0. 001).
5.2 Pharmacokinetic properties in ic
14 5. 2 Tagħrif farmakokinetiku
Median Absolute Neutrophil Count (cells x 109/ l)
t za riz to aw x du ħa ’ g m li i al in iċ
1000
Minħabba l- mekkaniżmu ta ’ tneħħija medjata minn newtrofili, il- farmakokinetika ta ’ pegfilgrastim ed
Median Serum Pegfilgrastim Conc.
mhix mistennija li tiġi effettwata minn indeboliment fil- kliewi jew fil- fwied.
ANC
Fi studju open label ta ’ doża waħda (n=31), varji stadji ta ’ indeboliment renali, inkluż mard renal ta ’ l- aħħar stadju, ma tm
100 10
kellhom l- ebda impatt fuq il- farmakokinetika ta ’ pegfilgrastim. ot od
10
Tagħrif limitat jindika li l- farmakokinetika ta ’ pegfilgrastim fl- anzjani (> 65 sena) hija simili għal dik fl- adulti.
is
Pr
6
Tagħrif ta ’ qabel l- użu kliniku miġbur minn studji konvenzjonali fuq l- effett tossiku minn dożi riptetuti, wera l- effetti farmakoloġiċi mistennija fosthom żjidiet fl- għadd ta ’ lewkoċiti, iperplasija majelojde fil- mudullun, ematopojesi ekstramedullari u tkabbir tal- milza.
9
Ir - rilevanza ta ’ dawn is- sejbiet għall- bnedmin mhix magħrufa.
15
15 6.
5.3 Preclinical safety data tn
TAGĦRIF FARMAĊEWTIKU
The relevance of these findings for humans is not known. ic ed
6. 1 Lista ta ’ sustanzi mhux attivi
6.3 Shelf life
t za 6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
30 months.
riz to 30 xahar.
6.4 Special precautions for storage
aw 6. 4 Prekawzjonijiet speċjali għall- ħażna
Store in a refrigerator (2°C – 8°C).
x Aħżen fi friġġ (2°C – 8°C).
Neupopeg may be exposed to room temperature (not above 30°C) for a maximum single period of up to 72 hours.
Neupopeg jista ’ jiġi espost għal temperatura ambjentali (mhux aktar minn 30°C) darba waħda għal massimu ta ’ 72 siegħa.