qanastek/EMEA-V3 huggingface dataset:
Only a clear and colourless solution should be used.
Għandha tintuża biss soluzzjoni ċara u bla kulur.
Remove the blue cap from BAXJECT II.
Neħħi t- tapp il- blu minn BAXJECT II.
DO NOT DRAW AIR INTO THE SYRINGE.
TIĠBIDX ARJA GĦAL ĠOS- SIRINGA.
Connect the syringe to BAXJECT II (Fig. d).
Qabbad is- siringa ma 'BAXJECT II (Fig. d).
Invert the system (the vial with the reconstituted solution has to be on top).
Aqleb is- sistema (bil- kunjett bis- soluzzjoni rikostitwita ’ l fuq).
Disconnect the syringe.
Aqla ’ s- siringa.
Attach a butterfly needle to the syringe.
Waħħal labra farfett mas- siringa.
Inject intravenously.
Injetta għal ġol- vina.
The solution should be administered slowly, at a rate as determined by the patient’ s comfort level, not to exceed 10 ml per minute.
Is- soluzzjoni għandha tkun amministrata bil- mod, b’ rata kif ikun komdu l- pazjent biha imma li ma taqbiżx 10 ml kull minuta.
The pulse rate should be determined before and during administration of ADVATE.
Ir- rata tal- polz għandha titkejjel qabel u waqt l- amministrazzjoni ta ’ ADVATE.
Should a significant increase occur, reducing the rate of administration or temporarily interrupting the injection usually allows the symptoms to disappear promptly (see sections 4.4 and 4.8).
Jekk isseħħ żieda sinifikanti, it- tnaqqis tar- rata tal- amministrazzjoni jew l- interruzzjoni temporanja tal- injezzjoni normalment jippermettu li s- sintomi jisparixxu minnufih (ara sezzjonijiet 4. 4 u 4. 8).
02 March 2004 Date of last renewal:
02 ta 'Marzu 2004 Data tal- aħħar tiġdid:
04 March 2009
04 ta 'Marzu 2009
Detailed information on this product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/
Tagħrif dettaljat dwar dan il- prodott mediċinali huwa disponibbli fuq il- website tal- Aġenzija Ewropea dwar il- Mediċini (EMEA) http: // www. emea. europa. eu /
ADVATE 500 IU powder and solvent for solution for injection.
ADVATE 500 IU trab u solvent għal soluzzjoni għall- injezzjoni.
Each vial contains nominally 500 IU* human coagulation factor VIII (rDNA), octocog alfa**.
Ġeneralment kull kunjett fih 500 IU * ta ’ fattur VIII tal- koagulazzjoni tal- bniedem (rDNA), octocog alfa **.
After reconstitution, each ml solution for injection contains approximately 100 IU octocog alfa. * The potency (International Units) is determined using the chromogenic assay against an in-house standard that is referenced to the WHO standard.
Wara r- rikostituzzjoni, kull ml ta ’ soluzzjoni għall- injezzjoni fih madwar 100 IU octocog alfa. * Il- qawwa (Unitajiet Internazzjonali) hi stabbilita permezz ta ’ assaġġ kromoġeniku li jitqabbel mal- istandard intern li għandu bħala referenza l- istandard ta ’ WHO.
0.45 mmol sodium (10 mg) per vial.
0. 45 mmol sodium (10 mg) kull kunjett Għal- lista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
ADVATE does not contain von Willebrand Factor in pharmacologically effective quantities and is therefore not indicated in von Willebrand disease.
ADVATE ma fihx il- fattur von Willebrand fi kwantitajiet farmakoloġiċi effettivi u għaldaqstant mhuwiex indikat fil- mard ta ’ von Willebrand.
12 One IU of factor VIII activity is equivalent to that quantity of factor VIII in one ml of normal human plasma.
IU waħda tal- attività ta ’ fattur VIII hija ekwivalenti għal dik il- kwantità ta ’ fattur VIII f’ ml ta ’ plażma uman normali.
The calculation of the required dose of factor VIII is based on the empirical finding that 1 IU factor VIII per kg body weight raises the plasma factor VIII activity by 2 IU/ dl.
13 waħda ta ’ fattur VIII għal kull kg ta ’ piż tal- ġisem ittella ’ l- attività tal- fattur VIII fil- plażma b’ 2 IU/ dl.
Life threatening haemorrhages.
għall- ħajja.
Under certain circumstances (e. g. presence of a low titre inhibitor) doses larger than those calculated using the formula may be necessary.
F’ ċerti ċirkostanzi (eż. il- preżenza ta ’ impeditur tat- tajter baxx) jistgħu jkunu neċessarji dożi akbar minn dawk ikkalkolati meta tintuża l- formula.
In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of plasma 13 factor VIII activity assay is indispensable.
F’ każ ta ’ interventi kirurġiċi maġġuri b’ mod partikolari, is- sorveljanza preċiża tat- terapija ta ’ sostituzzjoni permezz ta ’ analiżi fuq l- attività tal- fattur VIII fil- plażma hija indispensabbli.
Prophylaxis For long-term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses are 20 to 40 IU of factor VIIIper kg body weight at intervals of 2 to 3 days.
14 Profilassi Għal profilassi fit- tul kontra l- emorraġija f’ pazjenti b’ emofilja A severa, id- dożi li ġeneralment jingħataw huma 20 sa 40 IU ta ’ fattur VIII għal kull kg ta ’ piż tal- ġisem f’ intervalli ta ’ 2 jew 3 ijiem.
4.5 Interaction with other medicinal products and other forms of interaction
15 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarijiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
14 No interaction studies have been performed with ADVATE.
Ma sarux studji dwar l- effett ta ’ ADVATE jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku tal- prodott.
Based on the rare occurrence of haemophilia A in women, experience regarding the use of factor VIII during pregnancy and breast- feeding is not available.
Minħabba każijiet rari ta 'emofilja A fin- nisa, esperjenza li tirrigwarda l- użu ta ’ fattur VIII waqt it- tqala u t- treddigħ mhix disponibbli.
3 Neonates (age 0 – 1 month), infants (age 1 month – 2 years), children (age 2 - 12 years), adolescents (age 12 - 16 years) and adults (age over 16 years)
3 Trabi għadhom jitwieldu (0 - xahar), trabi (xahar - sentejn), tfal (2 - 12- il sena), adoloxxenti (12 - 16- il sena) u adulti (aktar minn 16- il sena)
15 Table 2 Frequency of adverse drug reactions (ADRs) in clinical trials
16 Tabella 2 Frekwenza ta ’ reazzjonijiet avversi għal mediċina (ADRs) fi provi kliniċi
Frequency
pazjenti) a
(% patients)a Eye disorders Vascular disorders
Disturbi fl- għajnejn
Eye inflammation Haematoma Hot flush Pallor
Infjammazzjoni tal- għajnejn
0.43 0.43 0.43 0.43
Mhux komuni
Uncommon Uncommon Uncommon Uncommon
Disturbi vaskulari
Respiratory, thoracic and Dyspnoea mediastinal disorders
Ematoma Fawra tal- menopawsa Sfurija
0.43
0. 43 0. 43 0. 43
Uncommon
Mhux komuni Mhux komuni Mhux komuni
16 Inhibitor Development The immunogenicity of ADVATE was evaluated in previously treated patients.
Żvilupp ta ’ Impeditur L- immunoġeniċità ta 'ADVATE ġiet evalwata f' pazjenti kkurati qabel.
During clinical trials with ADVATE in 145 paediatric and adult patients 4 diagnosed with severe to moderately severe haemophilia A (FVIII ≤ 2%), with previous exposure to factor VIII concentrates ≥ 150 days, one patient developed a low-titre inhibitor (2.4 BU in the modified Bethesda assay) after 26 exposure days to ADVATE.
Waqt provi kliniċi b' ADVATE f' 145 pazjent 4 pedjatriku u adult, iddijanjostikati b' emofilja A severa għal severa moderatament (FVIII ≤ 2%), b' espożizzjoni preċedenti għal konċentrati tal- fattur VIII ≥ 150 jum, pazjent wieħed żviluppa tajter baxx għal impeditur (2. 4 BU fl- analiżi Bethesda modifikata) wara 26 jum ta 'espożizzjoni għal ADVATE.
4.9 Overdose
18 4. 9 Doża eċċessiva
The factor VIII/ von Willebrand Factor complex consists of two molecules (factor VIII and von Willebrand factor) with different physiological functions.
Il- fattur VIII/ kumpless tal- Fattur von Willebrand jikkonsisti f’ żewġ molekuli (fattur VIII u l- fattur von Willebrand) b’ funzjonijiet fiżjoloġiċi differenti.
ADVATE contains recombinant coagulation factor VIII (octocog alfa), a glycoprotein that is biologically equivalent to the factor VIII glycoprotein found in human plasma.
ADVATE fih il- fattur VIII tal- koagulazzjoni rikombinanti (octocog alfa), glikoproteina li hi bijoloġikament ekwivalenti għal glikoproteina ta ’ fattur VIII li tinsab fil- plażma tal- bniedem.
Haemophilia A is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor VIII activity and results in profuse bleeding into joints, muscles or internal organs, either
L- emofilja A hija marda ereditarja fil- koagulazzjoni tad- demm marbuta mas- sess li hija kkawżata minn livelli mnaqqsin fl- attività tal- fattur VIII u tirriżulta f’ emorraġija abbondanti għal ġol- ġogi, il- muskoli jew organi interni, jew b’ mod naturali jew bħala riżultat ta ’ trawma aċċidentali jew kirurġika.
The plasma levels of factor VIII are increased by replacement therapy, thereby enabling a temporary correction of the factor VIII deficiency and correction of the bleeding tendency.
Il- livelli tal- fattur VIII fil- plażma jiżdiedu bit- terapija ta ’ sostituzzjoni, u b’ hekk jippermettu korrezzjoni temporanja għan- nuqqas tal- fattur u l- korrezzjoni tat- tendenza għal fsada.
Table 3 Summary of pharmacokinetic parameters for ADVATE in 100 patients with severe to moderately severe haemophilia A (factor VIII ≤ 2%) Interquartile PK Parameter
Tabella 3 Ġabra fil- qosor tal- parametri farmakokinetiċi għal ADVATE f’ 100 pazjent b’ emofilja A severa jew moderatament severa (fattur VIII ≤ 2%) Medda Parametru PK
Mean
Medja 1527 *
Median
Medjan
Range
Interkwartili
AUC0-∞ (IU· h/ dl) t1/ 2 (h) Adjusted Recovery
AUC0- ∞ (IU· h/ dl)
Data from single-dose administrations of ADVATE in 53 paediatric patients less than 6 years of age were used to obtain this table.
19 Intużat informazzjoni minn amministrazzjonijiet ta 'doża waħda ta' ADVATE fi 53 pazjent pedjatriku ta 'anqas minn 6 snin biex tinkiseb din it- tabella.
18 Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, acute toxicology, repeated dose toxicity, local toxicity and genotoxicity.
Informazzjoni mhux klinika ma turi l- ebda periklu speċjali għall- bniedem fuq il- bażi ta 'studji ta' sigurtà farmakoloġika, tossikoloġija akuta, tossiċità b' doża ripetuta, tossiċità lokali u ġenotossiċità.
19 6.6 Special precautions for disposal and other handling
6. 6 Prekawzjonijiet speċjali għar- rimi ta 'prodotti mediċinali u għal immaniġġar ieħor
ADVATE is to be administered intravenously after reconstitution of the lyophilized product with the provided sterilised water for injections.
ADVATE għandu jiġi amministrat ġol- vina wara rikostituzzjoni tal- prodott lijofilizzat bl- ilma sterilizzat ipprovdut għall- injezzjonijiet.
ADVATE 1000 IU powder and solvent for solution for injection.
ADVATE 1000 IU trab u solvent għal soluzzjoni għall- injezzjoni.
Each vial contains nominally 1000 IU* human coagulation factor VIII (rDNA), octocog alfa**.
Ġeneralment kull kunjett fih 1000 IU * ta ’ fattur VIII tal- koagulazzjoni tal- bniedem (rDNA), octocog alfa **.
After reconstitution, each ml solution for injection contains approximately 200 IU octocog alfa. * The potency (International Units) is determined using the chromogenic assay against an in-house standard that is referenced to the WHO standard.
Wara r- rikostituzzjoni, kull ml ta ’ soluzzjoni għall- injezzjoni fih madwar 200 IU octocog alfa. * Il- qawwa (Unitajiet Internazzjonali) hi stabbilita permezz ta ’ assaġġ kromoġeniku li jitqabbel mal- istandard intern li għandu bħala referenza l- istandard ta ’ WHO.
22 One IU of factor VIII activity is equivalent to that quantity of factor VIII in one ml of normal human plasma.
IU waħda tal- attività ta ’ fattur VIII hija ekwivalenti għal dik il- kwantità ta ’ fattur VIII f’ ml ta ’ plażma uman normali.
The calculation of the required dose of factor VIII is based on the empirical finding that 1 IU factor VIII per kg body weight raises the plasma factor VIII activity by 2 IU/ dl.
24 waħda ta ’ fattur VIII għal kull kg ta ’ piż tal- ġisem ittella ’ l- attività tal- fattur VIII fil- plażma b’ 2 IU/ dl.
In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of plasma 23 factor VIII activity assay is indispensable.
F’ każ ta ’ interventi kirurġiċi maġġuri b’ mod partikolari, is- sorveljanza preċiża tat- terapija ta ’ sostituzzjoni permezz ta ’ analiżi fuq l- attività tal- fattur VIII fil- plażma hija indispensabbli.
Prophylaxis For long-term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses are 20 to 40 IU of factor VIIIper kg body weight at intervals of 2 to 3 days.
25 Profilassi Għal profilassi fit- tul kontra l- emorraġija f’ pazjenti b’ emofilja A severa, id- dożi li ġeneralment jingħataw huma 20 sa 40 IU ta ’ fattur VIII għal kull kg ta ’ piż tal- ġisem f’ intervalli ta ’ 2 jew 3 ijiem.
4.5 Interaction with other medicinal products and other forms of interaction
26 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarijiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
24 No interaction studies have been performed with ADVATE.
Ma sarux studji dwar l- effett ta ’ ADVATE jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku tal- prodott.
5 Neonates (age 0 – 1 month), infants (age 1 month – 2 years), children (age 2 - 12 years), adolescents (age 12 - 16 years) and adults (age over 16 years)
5 Trabi għadhom jitwieldu (0 - xahar), trabi (xahar - sentejn), tfal (2 - 12- il sena), adoloxxenti (12 - 16- il sena) u adulti (aktar minn 16- il sena)
25 Table 2 Frequency of adverse drug reactions (ADRs) in clinical trials
27 Tabella 2 Frekwenza ta ’ reazzjonijiet avversi għal mediċina (ADRs) fi provi kliniċi
26 Inhibitor Development The immunogenicity of ADVATE was evaluated in previously treated patients.
Żvilupp ta ’ Impeditur L- immunoġeniċità ta 'ADVATE ġiet evalwata f' pazjenti kkurati qabel.
During clinical trials with ADVATE in 145 paediatric and adult patients 6 diagnosed with severe to moderately severe haemophilia A (FVIII ≤ 2%), with previous exposure to factor VIII concentrates ≥ 150 days, one patient developed a low-titre inhibitor (2.4 BU in the modified Bethesda assay) after 26 exposure days to ADVATE.
Waqt provi kliniċi b' ADVATE f' 145 pazjent 6 pedjatriku u adult, iddijanjostikati b' emofilja A severa għal severa moderatament (FVIII ≤ 2%), b' espożizzjoni preċedenti għal konċentrati tal- fattur VIII ≥ 150 jum, pazjent wieħed żviluppa tajter baxx għal impeditur (2. 4 BU fl- analiżi Bethesda modifikata) wara 26 jum ta 'espożizzjoni għal ADVATE.
4.9 Overdose
29 4. 9 Doża eċċessiva
Data from single-dose administrations of ADVATE in 53 paediatric patients less than 6 years of age were used to obtain this table.
30 Intużat informazzjoni minn amministrazzjonijiet ta 'doża waħda ta' ADVATE fi 53 pazjent pedjatriku ta 'anqas minn 6 snin biex tinkiseb din it- tabella.
28 Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, acute toxicology, repeated dose toxicity, local toxicity and genotoxicity.
Informazzjoni mhux klinika ma turi l- ebda periklu speċjali għall- bniedem fuq il- bażi ta 'studji ta' sigurtà farmakoloġika, tossikoloġija akuta, tossiċità b' doża ripetuta, tossiċità lokali u ġenotossiċità.
29 6.6 Special precautions for disposal and other handling
6. 6 Prekawzjonijiet speċjali għar- rimi ta 'prodotti mediċinali u għal immaniġġar ieħor
ADVATE 1500 IU powder and solvent for solution for injection.
ADVATE 1500 IU trab u solvent għal soluzzjoni għall- injezzjoni.
Each vial contains nominally 1500 IU* human coagulation factor VIII (rDNA), octocog alfa**.
Ġeneralment kull kunjett fih 1500 IU * ta ’ fattur VIII tal- koagulazzjoni tal- bniedem (rDNA), octocog alfa **.
After reconstitution, each ml solution for injection contains approximately 300 IU octocog alfa. * The potency (International Units) is determined using the chromogenic assay against an in-house standard that is referenced to the WHO standard.
Wara r- rikostituzzjoni, kull ml ta ’ soluzzjoni għall- injezzjoni fih madwar 300 IU octocog alfa. * Il- qawwa (Unitajiet Internazzjonali) hi stabbilita permezz ta ’ assaġġ kromoġeniku li jitqabbel mal- istandard intern li għandu bħala referenza l- istandard ta ’ WHO.
32 One IU of factor VIII activity is equivalent to that quantity of factor VIII in one ml of normal human plasma.
IU waħda tal- attività ta ’ fattur VIII hija ekwivalenti għal dik il- kwantità ta ’ fattur VIII f’ ml ta ’ plażma uman normali.
The calculation of the required dose of factor VIII is based on the empirical finding that 1 IU factor VIII per kg body weight raises the plasma factor VIII activity by 2 IU/ dl.
35 waħda ta ’ fattur VIII għal kull kg ta ’ piż tal- ġisem ittella ’ l- attività tal- fattur VIII fil- plażma b’ 2 IU/ dl.
Under certain circumstances (e. g. presence of a low-titre inhibitor) doses larger than those calculated using the formula may be necessary.
F’ ċerti ċirkostanzi (eż. il- preżenza ta ’ impeditur tat- tajter baxx) jistgħu jkunu neċessarji dożi akbar minn dawk ikkalkolati meta tintuża l- formula.
In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of plasma 33 factor VIII activity assay is indispensable.
F’ każ ta ’ interventi kirurġiċi maġġuri b’ mod partikolari, is- sorveljanza preċiża tat- terapija ta ’ sostituzzjoni permezz ta ’ analiżi fuq l- attività tal- fattur VIII fil- plażma hija indispensabbli.
Prophylaxis For long-term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses are 20 to 40 IU of factor VIIIper kg body weight at intervals of 2 to 3 days.
36 Profilassi Għal profilassi fit- tul kontra l- emorraġija f’ pazjenti b’ emofilja A severa, id- dożi li ġeneralment jingħataw huma 20 sa 40 IU ta ’ fattur VIII għal kull kg ta ’ piż tal- ġisem f’ intervalli ta ’ 2 jew 3 ijiem.
4.5 Interaction with other medicinal products and other forms of interaction
37 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarijiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
34 No interaction studies have been performed with ADVATE.
Ma sarux studji dwar l- effett ta ’ ADVATE jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku tal- prodott.
7 Neonates (age 0 – 1 month), infants (age 1 month – 2 years), children (age 2 - 12 years), adolescents (age 12 - 16 years) and adults (age over 16 years)
7 Trabi għadhom jitwieldu (0 - xahar), trabi (xahar - sentejn), tfal (2 - 12- il sena), adoloxxenti (12 - 16- il sena) u adulti (aktar minn 16- il sena)
35 Table 2 Frequency of adverse drug reactions (ADRs) in clinical trials
38 Tabella 2 Frekwenza ta ’ reazzjonijiet avversi għal mediċina (ADRs) fi provi kliniċi
36 Inhibitor Development The immunogenicity of ADVATE was evaluated in previously treated patients.
Żvilupp ta ’ Impeditur L- immunoġeniċità ta 'ADVATE ġiet evalwata f' pazjenti kkurati qabel.
During clinical trials with ADVATE in 145 paediatric and adult patients 8 diagnosed with severe to moderately severe haemophilia A (FVIII ≤ 2%), with previous exposure to factor VIII concentrates ≥ 150 days, one patient developed a low-titre inhibitor (2.4 BU in the modified Bethesda assay) after 26 exposure days to ADVATE.
Waqt provi kliniċi b' ADVATE f' 145 pazjent 8 pedjatriku u adult, iddijanjostikati b' emofilja A severa għal severa moderatament (FVIII ≤ 2%), b' espożizzjoni preċedenti għal konċentrati tal- fattur VIII ≥ 150 jum, pazjent wieħed żviluppa tajter baxx għal impeditur (2. 4 BU fl- analiżi Bethesda modifikata) wara 26 jum ta 'espożizzjoni għal ADVATE.
4.9 Overdose
40 4. 9 Doża eċċessiva
Data from single-dose administrations of ADVATE in 53 paediatric patients less than 6 years of age were used to obtain this table.
41 Intużat informazzjoni minn amministrazzjonijiet ta 'doża waħda ta' ADVATE fi 53 pazjent pedjatriku ta 'anqas minn 6 snin biex tinkiseb din it- tabella.
38 Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, acute toxicology, repeated dose toxicity, local toxicity and genotoxicity.
Informazzjoni mhux klinika ma turi l- ebda periklu speċjali għall- bniedem fuq il- bażi ta 'studji ta' sigurtà farmakoloġika, tossikoloġija akuta, tossiċità b' doża ripetuta, tossiċità lokali u ġenotossiċità.
39 6.6 Special precautions for disposal and other handling
6. 6 Prekawzjonijiet speċjali għar- rimi ta 'prodotti mediċinali u għal immaniġġar ieħor
ADVATE 2000 IU powder and solvent for solution for injection.
ADVATE 2000 IU trab u solvent għal soluzzjoni għall- injezzjoni.
Each vial contains nominally 2000 IU* human coagulation factor VIII (rDNA), octocog alfa**.
Ġeneralment kull kunjett fih 2000 IU * ta ’ fattur VIII tal- koagulazzjoni tal- bniedem (rDNA), octocog alfa **.
After reconstitution, each ml solution for injection contains approximately 400 IU octocog alfa. * The potency (International Units) is determined using the chromogenic assay against an in-house standard that is referenced to the WHO standard.
Wara r- rikostituzzjoni, kull ml ta ’ soluzzjoni għall- injezzjoni fih madwar 400 IU octocog alfa. * Il- qawwa (Unitajiet Internazzjonali) hi stabbilita permezz ta ’ assaġġ kromoġeniku li jitqabbel mal- istandard intern li għandu bħala referenza l- istandard ta ’ WHO.
42 One IU of factor VIII activity is equivalent to that quantity of factor VIII in one ml of normal human plasma.
IU waħda tal- attività ta ’ fattur VIII hija ekwivalenti għal dik il- kwantità ta ’ fattur VIII f’ ml ta ’ plażma uman normali.
The calculation of the required dose of factor VIII is based on the empirical finding that 1 IU factor VIII per kg body weight raises the plasma factor VIII activity by 2 IU/ dl.
46 waħda ta ’ fattur VIII għal kull kg ta ’ piż tal- ġisem ittella ’ l- attività tal- fattur VIII fil- plażma b’ 2 IU/ dl.
In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of plasma 43 factor VIII activity assay is indispensable.
F’ każ ta ’ interventi kirurġiċi maġġuri b’ mod partikolari, is- sorveljanza preċiża tat- terapija ta ’ sostituzzjoni permezz ta ’ analiżi fuq l- attività tal- fattur VIII fil- plażma hija indispensabbli.
Prophylaxis For long-term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses are 20 to 40 IU of factor VIIIper kg body weight at intervals of 2 to 3 days.
47 Profilassi Għal profilassi fit- tul kontra l- emorraġija f’ pazjenti b’ emofilja A severa, id- dożi li ġeneralment jingħataw huma 20 sa 40 IU ta ’ fattur VIII għal kull kg ta ’ piż tal- ġisem f’ intervalli ta ’ 2 jew 3 ijiem.
4.5 Interaction with other medicinal products and other forms of interaction
48 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarijiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
44 No interaction studies have been performed with ADVATE.
Ma sarux studji dwar l- effett ta ’ ADVATE jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku tal- prodott.
9 Neonates (age 0 – 1 month), infants (age 1 month – 2 years), children (age 2 - 12 years), adolescents (age 12 - 16 years) and adults (age over 16 years)
9 Trabi għadhom jitwieldu (0 - xahar), trabi (xahar - sentejn), tfal (2 - 12- il sena), adoloxxenti (12 - 16- il sena) u adulti (aktar minn 16- il sena)
45 Table 2 Frequency of adverse drug reactions (ADRs) in clinical trials
49 Tabella 2 Frekwenza ta ’ reazzjonijiet avversi għal mediċina (ADRs) fi provi kliniċi
46 Inhibitor Development The immunogenicity of ADVATE was evaluated in previously treated patients.
Żvilupp ta ’ Impeditur L- immunoġeniċità ta 'ADVATE ġiet evalwata f' pazjenti kkurati qabel.
During clinical trials with ADVATE in 145 paediatric and adult patients 10 diagnosed with severe to moderately severe haemophilia A (FVIII ≤ 2%), with previous exposure to factor VIII concentrates ≥ 150 days, one patient developed a low-titre inhibitor (2.4 BU in the modified Bethesda assay) after 26 exposure days to ADVATE.
Waqt provi kliniċi b' ADVATE f' 145 pazjent 10 pedjatriku u adult, iddijanjostikati b' emofilja A severa għal severa moderatament (FVIII ≤ 2%), b' espożizzjoni preċedenti għal konċentrati tal- fattur VIII ≥ 150 jum, pazjent wieħed żviluppa tajter baxx għal impeditur (2. 4 BU fl- analiżi Bethesda modifikata) wara 26 jum ta 'espożizzjoni għal ADVATE.
4.9 Overdose
51 4. 9 Doża eċċessiva
Data from single-dose administrations of ADVATE in 53 paediatric patients less than 6 years of age were used to obtain this table.
52 Intużat informazzjoni minn amministrazzjonijiet ta 'doża waħda ta' ADVATE fi 53 pazjent pedjatriku ta 'anqas minn 6 snin biex tinkiseb din it- tabella.
48 Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, acute toxicology, repeated dose toxicity, local toxicity and genotoxicity.
Informazzjoni mhux klinika ma turi l- ebda periklu speċjali għall- bniedem fuq il- bażi ta 'studji ta' sigurtà farmakoloġika, tossikoloġija akuta, tossiċità b' doża ripetuta, tossiċità lokali u ġenotossiċità.
The solution should be administered slowly, at a rate as determined by the patient’ s comfort level, not to exceed 10 ml
Is- soluzzjoni għandha tkun amministrata bil- mod, b’ rata kif ikun komdu l- pazjent biha imma li ma taqbiżx 10 ml kull minuta.
ADVATE 3000 IU powder and solvent for solution for injection.
ADVATE 3000 IU trab u solvent għal soluzzjoni għall- injezzjoni.
Each vial contains nominally 3000 IU* human coagulation factor VIII (rDNA), octocog alfa**.
Ġeneralment kull kunjett fih 3000 IU * ta ’ fattur VIII tal- koagulazzjoni tal- bniedem (rDNA), octocog alfa **.
After reconstitution, each ml solution for injection contains approximately 600 IU octocog alfa. * The potency (International Units) is determined using the chromogenic assay against an in-house standard that is referenced to the WHO standard.
Wara r- rikostituzzjoni, kull ml ta ’ soluzzjoni għall- injezzjoni fih madwar 600 IU octocog alfa. * Il- qawwa (Unitajiet Internazzjonali) hi stabbilita permezz ta ’ assaġġ kromoġeniku li jitqabbel mal- istandard intern li għandu bħala referenza l- istandard ta ’ WHO.
52 One IU of factor VIII activity is equivalent to that quantity of factor VIII in one ml of normal human plasma.
IU waħda tal- attività ta ’ fattur VIII hija ekwivalenti għal dik il- kwantità ta ’ fattur VIII f’ ml ta ’ plażma uman normali.
The calculation of the required dose of factor VIII is based on the empirical finding that 1 IU factor VIII per kg body weight raises the plasma factor VIII activity by 2 IU/ dl.
57 waħda ta ’ fattur VIII għal kull kg ta ’ piż tal- ġisem ittella ’ l- attività tal- fattur VIII fil- plażma b’ 2 IU/ dl.
In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of plasma 53 factor VIII activity assay is indispensable.
F’ każ ta ’ interventi kirurġiċi maġġuri b’ mod partikolari, is- sorveljanza preċiża tat- terapija ta ’ sostituzzjoni permezz ta ’ analiżi fuq l- attività tal- fattur VIII fil- plażma hija indispensabbli.
Prophylaxis For long-term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses are 20 to 40 IU of factor VIIIper kg body weight at intervals of 2 to 3 days.
58 Profilassi Għal profilassi fit- tul kontra l- emorraġija f’ pazjenti b’ emofilja A severa, id- dożi li ġeneralment jingħataw huma 20 sa 40 IU ta ’ fattur VIII għal kull kg ta ’ piż tal- ġisem f’ intervalli ta ’ 2 jew 3 ijiem.
4.5 Interaction with other medicinal products and other forms of interaction
59 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarijiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
54 No interaction studies have been performed with ADVATE.
Ma sarux studji dwar l- effett ta ’ ADVATE jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku tal- prodott.
(% patients)a Infections and infestations Blood and lymphatic system disorders
Infezzjonijiet u infestazzjonijiet Disturbi tad- demm u tas- sistema limfatika
11 Neonates (age 0 – 1 month), infants (age 1 month – 2 years), children (age 2 - 12 years), adolescents (age 12 - 16 years) and adults (age over 16 years)
11 Trabi għadhom jitwieldu (0 - xahar), trabi (xahar - sentejn), tfal (2 - 12- il sena), adoloxxenti (12 - 16- il sena) u adulti (aktar minn 16- il sena)
55 Table 2 Frequency of adverse drug reactions (ADRs) in clinical trials
60 Tabella 2 Frekwenza ta ’ reazzjonijiet avversi għal mediċina (ADRs) fi provi kliniċi
0.85 0.43 0.43 0.43 0.85 0.85 0.43 0.43 1.28 0.43
0. 43
Uncommon Uncommon Uncommon Uncommon Uncommon Uncommon Uncommon Uncommon Common Uncommon
Mhux komuni
Chest pain Chills Feeling abnormal Investigations Anti-factor VIII antibody positive
Disturbi gastrointestinali Dijarea Uġigħ fin- naħa ta ’ fuq tal- addome
1 1 1 5
2 1
0.43 0.43 0.43 2.14
0. 85 0. 43
Uncommon Uncommon Uncommon Common
Mhux komuni Mhux komuni
Alanine aminotransferase increased
Nawsja Rimettar Disturbi fil- ġilda u Ħakk fit- tessuti ta 'taħt il- ġilda Raxx Tagħriq żejjed Dermatitis diaper Disturbi ġenerali u Deni kondizzjonijiet ta' mnejn Edima periferika jingħata
1
1 1 2 2 1 1 3 1
0.43
0. 43 0. 43 0. 85 0. 85 0. 43 0. 43 1. 28 0. 43
Uncommon
Mhux komuni Mhux komuni Mhux komuni Mhux komuni Mhux komuni Mhux komuni Komuni Mhux komuni
Coagulation factor VIII level decreasedb
Uġigħ fis- sider Tertir Sensazzjoni ta 'anormalità Stħarriġ Antikorp kontra fattur VIII pożittiv
0.43
0. 43 0. 43 0. 43 2. 14
Uncommon
Mhux komuni Mhux komuni Mhux komuni Komuni
Haematocrit decreased Laboratory test abnormal Injury, poisoning and Post procedural procedural complications complication
Żieda fl- alanine aminotransferase
Post procedural haemorrhage
Tnaqqis fil- livell ta 'fattur VIII tal- koagulazzjonib
Procedural site reaction
Ematokrit imnaqqas Test tal- laboratorju abnormali
0.43
0. 43 0. 43
Factor VIII inhibitor assays performed after completion of continuous infusion and at study termination were negative.
61 Tabella 2 Frekwenza ta ’ reazzjonijiet avversi għal mediċina (ADRs) fi provi kliniċi
56 Inhibitor Development The immunogenicity of ADVATE was evaluated in previously treated patients.
l- Organi
During clinical trials with ADVATE in 145 paediatric and adult patients 12 diagnosed with severe to moderately severe haemophilia A (FVIII ≤ 2%), with previous exposure to factor VIII concentrates ≥ 150 days, one patient developed a low-titre inhibitor (2.4 BU in the modified Bethesda assay) after 26 exposure days to ADVATE.
(%
Follow-up inhibitor tests in this patient after withdrawal from the study were negative.
pazjenti) a
In previously untreated patients in an ongoing clinical study, 5 (20%) of 25 patients who received ADVATE developed inhibitors to factor VIII.
Korriment, avvelenament Kumplikazzjonijiet wara u kumplikazzjonijiet l- proċedura
The patient’ s immune response to trace amounts of contaminating proteins was analysed by examining titres of antibodies to these proteins, laboratory parameters and reported adverse events.
0. 43
4.9 Overdose
Mhux komuni
No symptoms of overdose with recombinant coagulation factor VIII have been reported.
proċedurali Emorraġija wara l- proċedura
PHARMACOLOGICAL PROPERTIES
Mhux komuni
5.1 Pharmacodynamic properties
Reazzjoni fil- post tal- proċedura
ATC code:
0. 43
B02BD02.
Mhux komuni
The factor VIII/ von Willebrand Factor complex consists of two molecules (factor VIII and von Willebrand factor) with different physiological functions.
a) Perċentwali ta ’ pazjenti kkalkulati msejjes fuq in- numru totali ta 'pazjenti uniċi (234). b) It- tnaqqis mhux mistenni fil- livelli ta' fattur VIII tal- koagulazzjoni seħħ f' pazjent wieħed waqt infużjoni kontinwa ta 'ADVATE wara l- kirurġija (ġranet ta' wara l- operazzjoni 10- 14).
ADVATE contains recombinant coagulation factor VIII (octocog alfa), a glycoprotein that is biologically equivalent to the factor VIII glycoprotein found in human plasma.
L- analiżi fuq l- impeditur tal- fattur VIII li saru wara li tlestiet l- infużjoni kontinwa u meta ntemm l- istudju tat riżultat negattiv.
Octocog alfa is a glycoprotein consisting of 2332 amino acids with an approximate molecular mass of 280 kD.
Żvilupp ta ’ Impeditur L- immunoġeniċità ta 'ADVATE ġiet evalwata f' pazjenti kkurati qabel.
Activated factor VIII acts as a Cofactor for activated Factor IX, accelerating the conversion of Factor X to activated Factor X.
Waqt provi kliniċi b' ADVATE f' 145 pazjent 12 pedjatriku u adult, iddijanjostikati b' emofilja A severa għal severa moderatament (FVIII ≤ 2%), b' espożizzjoni preċedenti għal konċentrati tal- fattur VIII ≥ 150 jum, pazjent wieħed żviluppa tajter baxx għal impeditur (2. 4 BU fl- analiżi Bethesda modifikata) wara 26 jum ta 'espożizzjoni għal ADVATE.
Thrombin then converts fibrinogen into fibrin and a clot can be formed.
It- testijiet dwar l- impeditur li saru wara f' dan il- pazjent wara l- irtirar mill- istudju kienu negattivi.
Haemophilia A is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor VIII activity and results in profuse bleeding into joints, muscles or internal organs, either
Barra minn hekk, fi 53 pazjent pedjatriku taħt is- 6 snin, iddijanjostikati wkoll b' emofilja A severa għal severa moderatament (FVIII≤ 2%), b' espożizzjoni qabel għal konċentrati tal- fattur VIII ≥ 50 jum, ma nstab l- ebda impeditur ta 'FVIII.
12 paediatric patients (age 0 – 16 years) and adult patients (age over 16 years)
F' pazjenti mhux ikkurati qabel fi studju kliniku għadu sejjer, 5 (20%) minn 25 pazjent li rċevew ADVATE żviluppaw impedituri għal- fattur VIII.
57 spontaneously or as a result of accidental or surgical trauma.
Minn dawn, 4 kienu tajter għoli (≥5 BU) u 1 kien tajter baxx (< 5 BU).
The plasma levels of factor VIII are increased by replacement therapy, thereby enabling a temporary correction of the factor VIII deficiency and correction of the bleeding tendency.
Il- frekwenza tal- impedituri ta 'FVIII misjuba sa issa hija fil- medda mistennija u osservata qabel.
5.2 Pharmacokinetic properties
Pazjent wieħed kellu kemm xejra 'l fuq statistikament sinifikanti kif ukoll wera quċċata sostenuta fil- livell ta' antikorpi kontra l- proteini taċ- ċellula CHO, iżda l- ebda sinjali jew sintomi oħra li juru rispons allerġiku jew ta 'sensittività eċċessiva.
All pharmacokinetic studies with ADVATE were conducted in previously treated patients with severe to moderately severe haemophilia A (baseline factor VIII ≤ 2%).
Mill- 182 pazjent kkurat li ġew eżaminati għal antikorpi għall- IgG tal- ġrieden, 10 urew xejra 'l fuq statistikament sinifikanti b' analiżi ta' rigressjoni lineari u 2 urew quċċata sostnuta jew ponta għaddiena.
The analysis of plasma samples was conducted in a central laboratory using a one-stage clotting assay.
Pazjent wieħed kellu kemm xejra 'l fuq statistikament sinifikanti kif ukoll wera quċċata sostnuta fil- livell tal- antikorpi kontra l- IgG tal- ġrieden.
The pharmacokinetic parameters derived from a crossover study of ADVATE in 100 previously treated patients ≥ 10 years of age are listed in table 3 below.
Erbgħa minn dawn il- pazjenti rrapportaw episodji iżolati ta 'urtikarja, ħakk, raxx, u livelli daqsxejn għoljin ta' eosinofil fost bosta espożizzjonijiet ripetuti għall- prodott studjat.
Table 3 Summary of pharmacokinetic parameters for ADVATE in 100 patients with severe to moderately severe haemophilia A (factor VIII ≤ 2%) Interquartile PK Parameter
Bħal fil- każ ta 'prodotti oħra li jingħataw ġol- vina, reazzjonijiet allerġiċi ta' sensittività eċċessiva, fosthom anafilassi/ reazzjonijiet anafilattojdi, kienu rrapportati b' ADVATE (bi frekwenza mhux magħrufa).
AUC0-∞ (IU· h/ dl) t1/ 2 (h) Adjusted Recovery
12 pazjenti pedjatriċi (età ta ’ bejn 0- 16- il sena) u pazjenti adulti (’ il fuq minn 16- il sena)
1527* 11.8
62 4. 9 Doża eċċessiva
(IU/ dl/ IU/ kg) Cmax (IU/ dl) Clearance (dl/ kg· h) MRT (h) VSS (dl/ kg) * Geometric mean
L- ebda każ ta ’ doża eċċessiva bil- fattur VIII tal- koagulazzjoni rikombinanti uman ma ġie rrapportat.
2.38* 120* 0.037 15.2 0.52
TAGĦRIF FARMAKOLOĠIKU
0.50 26 0.030 4.8 0.39
5. 1 Tagħrif farmakodinamiku
2.42 119 0.033 14.1 0.48
Kodiċi ATC:
0.68 38 0.0147 4.2 0.13
B02BD02.
Data from single-dose administrations of ADVATE in 53 paediatric patients less than 6 years of age were used to obtain this table.
ADVATE fih il- fattur VIII tal- koagulazzjoni rikombinanti (octocog alfa), glikoproteina li hi bijoloġikament ekwivalenti għal glikoproteina ta ’ fattur VIII li tinsab fil- plażma tal- bniedem.
Table 4 Summary of pharmacokinetic parameters for ADVATE in 53 paediatric patients with severe to moderately severe haemophilia A
Il- fattur VIII attivat jaħdem bħala Ko- fattur għall- Fattur IX attivat, jaċċellera l- bdil ta 'Fattur X għal Fattur X attivat.
PK Parameter AUC0-∞ (IU· h/ dl) t1/ 2 (h) Adjusted Recovery
5. 2 Tagħrif farmakokinetiku
(IU/ dl/ IU/ kg) Cmax (IU/ dl) Clearance (dl/ kg· h) MRT (h) VSS (dl/ kg) * Geometric Mean
L- istudji farmakokinetiċi kollha b’ ADVATE saru f’ pazjenti li kienu trattati qabel għal emofilja A severa jew moderatament severa (linja bażi ta ’ riferiment ta ’ fattur VIII ≤ 2%).
Adjusted recovery and terminal half-life (t1/ 2) was approximately 20% lower in young children (less than 6 years of age) than in adults, which may be due in part to the known higher plasma volume per kilogram body weight in younger patients.
Il- parametri farmakokinetiċi li ħarġu minn studju inkroċjat ta ’ ADVATE f’ 100 pazjent li kienu ġew ikkurati qabel f’ età ≥10 snin huma elenkati f’ tabella 3 hawn taħt.
Pharmacokinetic data with ADVATE on previously untreated patients are currently not available.
Tabella 3 Ġabra fil- qosor tal- parametri farmakokinetiċi għal ADVATE f’ 100 pazjent b’ emofilja A severa jew moderatament severa (fattur VIII ≤ 2%) Medda Parametru PK
5.3 Preclinical safety data
Medja 1527 *
58 Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, acute toxicology, repeated dose toxicity, local toxicity and genotoxicity.
SD
6.
Medjan
6.1 List of excipients
Interkwartili
Solvent Sterilised water for injections
AUC0- ∞ (IU· h/ dl)
6.2 Incompatibilities
528
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products or solvents.
1549
6.3 Shelf life
668
Unopened powder vial 2 years.
t1/ 2 (h)
After reconstitution Chemical and physical in-use stability has been demonstrated for 3 hours at 25°C.
11. 1
6.4 Special precautions for storage
2. 8
Store in a refrigerator (2°C – 8°C).
Irkupru Aġġustat (IU/ dl/ IU/ kg)
During the shelf life, the product may be kept at room temperature (up to 25°C) for a single period not exceeding 2 months.
120 *
Keep the vial in the outer carton in order to protect from light.
0. 50
For storage conditions of the reconstituted medicinal product, see section 6.3.
2. 42
6.5 Nature and contents of container
0. 68
Each pack contains a powder vial, a vial containing 5 ml solvent (both type I glass closed with chlorobutyl rubber stoppers) and a device for reconstitution (BAXJECT II).
Cmax (IU/ dl)
6.6 Special precautions for disposal and other handling
26
ADVATE is to be administered intravenously after reconstitution of the lyophilized product with the provided sterilised water for injections.
119
59
38
- For reconstitution use only the sterilised water for injections and the reconstitution device
Rata ta ’ eliminazzjoni (dl/ kg· h) MRT (h) VSS (dl/ kg) * Medja ġeometrika
provided in the pack.
0. 037 15. 2 0. 52
For administration the use of a luer-lock syringe is required.
0. 030 4. 8 0. 39
- Use within three hours after reconstitution.
0. 033 14. 1 0. 48
- Do not refrigerate the preparation after reconstitution.
0. 0147 4. 2 0. 13
- Dispose any unused product or waste material in accordance with local requirements.
63 Intużat informazzjoni minn amministrazzjonijiet ta 'doża waħda ta' ADVATE fi 53 pazjent pedjatriku ta 'anqas minn 6 snin biex tinkiseb din it- tabella.
- Do not use if the BAXJECT II device, its sterile barrier system or its packaging is damaged or
Tabella 4 Parametri farmakokinetiċi fil- qosor għal ADVATE fi 53 pazjent pedjatriku b’ emofilja A severa għal moderatament severa
shows any sign of deterioration.
Parametru PK
Reconstitution Aseptic Technique should be used
Medja 1195 *
1.
SD
The vacuum will draw the solvent into the ADVATE vial (Fig. c).
AUC0- ∞ (IU· h/ dl)
The product dissolves rapidly (usually in less than 1 minute).
t1/ 2 (h) Irkupru Aġġustat
Fig. a
9. 7 1. 84 *
Fig. b
1. 9
Fig. c
(IU/ dl/ IU/ kg)
Administration Use Aseptic Technique
93 *
Parenteral medicinal products should be inspected for particulate matter prior to administration, whenever solution and container permit.
0. 42
Connect the syringe to BAXJECT II (Fig. d).
Cmax (IU/ dl) Rata ta ’ eliminazzjoni
Invert the system (the vial with the reconstituted solution has to be on top).
(dl/ kg· h) MRT (h) VSS (dl/ kg) * Medja Ġeometrika
Draw the reconstituted solution into the syringe by pulling the plunger back slowly (Fig. e).
0. 044 12. 2 0. 51
3.
0. 014 3. 1 0. 12
The solution should be administered slowly, at a rate as determined by the patient’ s comfort level, not to exceed 10 ml
L- irkupru aġġustat u l- half- life terminali (t1/ 2) kienu madwar 20% aktar baxxi fi tfal żgħar (ta ’ inqas minn 6 snin) milli fl- adulti, li jista ’ jkun dovut parti għal volum akbar magħruf tal- plażma għal kull kilogramm ta 'piż tal- ġisem f' pazjenti iżgħar.
The pulse rate should be determined before and during administration of ADVATE.
Attwalment m' hemmx tagħrif farmakokinetiku disponibbli dwar ADVATE fuq pazjenti li ma kinux ġew ikkurati qabel.
Should a significant increase occur, reducing the rate of administration or temporarily interrupting the injection usually allows the symptoms to disappear promptly (see sections 4.4 and 4.8).
5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina
Fig. d
Informazzjoni mhux klinika ma turi l- ebda periklu speċjali għall- bniedem fuq il- bażi ta 'studji ta' sigurtà farmakoloġika, tossikoloġija akuta, tossiċità b' doża ripetuta, tossiċità lokali u ġenotossiċità.
Fig. e
6.
MARKETING AUTHORISATION HOLDER
6. 1 Lista ta ’ sustanzi mhux attivi
Baxter AG Industriestrasse 67 A-1221 Vienna Austria
Trab Mannitol Sodium chloride Histidine Trehalose Calcium chloride Trometamol Polysorbate 80 Glutathione (ridott).
MARKETING AUTHORISATION NUMBER(S)
Solvent Ilma sterilizzat għall- injezzjonijiet.
EU/ 1/ 03/ 271/ 006
6. 2 Inkompatibilitajiet
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION
Fin- nuqqas ta 'studji dwar il- kompatibilità, dan il- prodott mediċinali m' għandux jiġi mħallat ma' prodotti mediċinali jew solventi oħrajn.
04 March 2009
64 6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
DATE OF REVISION OF THE TEXT
Kunjett ta ’ trab mhux miftuħ Sentejn.
Detailed information on this product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/
Wara r- rikostituzzjoni L- istabilità kimika u fiżika waqt l- użu ġiet murija għal 3 sigħat f’ temperatura ta ’ 25°C.
MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
Minn aspett mikrobijoloġiku, il- prodott għandu jintuża immedjatament wara r- rikostituzzjoni.
CONDITIONS OF THE MARKETING AUTHORISATION
6. 4 Prekawzjonijiet speċjali għall- ħażna
62 A MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
Tagħmlux fil- friża.
Name and address of the manufacturer of the biological active substance
Il- prodott ma jistax jerġa 'jinħażen fil- friġġ għal darb ’ oħra.
Baxter BioScience Manufacturing Sàrl Route de Pierre-à-Bot 111 CH-2000 Neuchâtel Switzerland
Żomm il- kunjett fil- kartuna biex tilqa 'mid- dawl.
Name and address of the manufacturer responsible for batch release
Dwar il- kondizzjonijiet għall- ħażna tal- prodott mediċinali rikostitwit, ara sezzjoni 6. 3.
Baxter SA Boulevard René Branquart 80 B-7860 Lessines Belgium
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
B CONDITIONS OF THE MARKETING AUTHORISATION
Kull pakkett fih kunjett tat- trab, kunjett li fih 5 ml solvent (it- tnejn magħmulin minn ħġieġ tat- tip I magħluqin b’ tapp tal- lastku chlorobutyl) u strument għar- rikostituzzjoni (BAXJECT II).
• CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON THE MARKETING AUTHORISATION HOLDER
6. 6 Prekawzjonijiet speċjali għar- rimi ta 'prodotti mediċinali u għal immaniġġar ieħor
Medicinal product subject to restricted medical prescription (See Annex I:
ADVATE għandu jiġi amministrat ġol- vina wara rikostituzzjoni tal- prodott lijofilizzat bl- ilma sterilizzat ipprovdut għall- injezzjonijiet.
Summary of Product Characteristics, section 4.2)
Wara r- rikostituzzjoni s- soluzzjoni għandha tkun ċara, bla kulur u ħielsa minn partikuli barranin.
• CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
- Għar- rikostituzzjoni uża biss l- ilma sterilizzat għall- injezzjonijiet u l- istrument
Not applicable.
għar- rikostituzzjoni pprovduti fil- pakkett.
• OTHER CONDITIONS
- Uża fi żmien tliet sigħat wara r- rikostituzzjoni.
Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance, as described in version 1.1 presented in Module 1.8.1. of the Marketing Authorisation, is in place and functioning before and whilst the product is on the market.
- Tpoġġix il- preparazzjoni fil- friġġ wara r- rikostituzzjoni.
Risk Management Plan The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 3.0 of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation and any subsequent updates of the RMP agreed by the CHMP.
- Armi kwalunkwe prodott mhux użat jew skart minn dawn il- prodotti skont ir- regolamenti lokali.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
- Tużax jekk l- istrument BAXJECT II, is- sistema ta 'barriera sterili tiegħu jew il- pakkett tiegħu
In addition, an updated RMP should be submitted • When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities • Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached • At the request of the EMEA
jkunu bil- ħsara jew juru xi sinjal ta 'taħsir
63 PSURs:
Rikostituzzjoni:
The holder of this marketing authorisation holder will submit PSURs every 6 months unless otherwise specified by the CHMP.
6.
64 ANNEX III
7.
LABELLING AND PACKAGE LEAFLET
B’ BAXJECT II imwaħħal mal- kunjett tas- solvent, aqleb
65 A.
65 is- sistema sabiex il- kunjett tas- solvent tkun fuq l- istrument.
LABELLING
Fig. a
66 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
Fig. b
OUTER CARTON
Fig. ċ
NAME OF THE MEDICINAL PRODUCT
Amministrazzjoni Uża Teknika Asettika
ADVATE 250 IU powder and solvent for solution for injection Octocog alfa (recombinant human coagulation factor VIII)
Il- prodotti tal- mediċina parenterali għandhom ikunu miflija għal xi frak qabel ma jingħataw, kull meta s- soluzzjoni u l- kontenitur jippermettu.
STATEMENT OF ACTIVE SUBSTANCE(S)
Għandha tintuża biss soluzzjoni ċara u bla kulur.
250 IU octocog alfa, approx.
Neħħi t- tapp il- blu minn BAXJECT II.
50 IU/ ml after reconstitution.
TIĠBIDX ARJA GĦAL ĠOS- SIRINGA.
Specific activity: approx.
Qabbad is- siringa ma 'BAXJECT II (Fig. d).
4,000 – 10,000 IU/ mg protein
Aqla ’ s- siringa.
LIST OF EXCIPIENTS
Injetta għal ġol- vina.
Excipients: mannitol, sodium chloride, histidine, trehalose, calcium chloride, trometamol, polysorbate 80, glutathione (reduced).
Jekk isseħħ żieda sinifikanti, it- tnaqqis tar- rata tal- amministrazzjoni jew l- interruzzjoni temporanja tal- injezzjoni normalment jippermettu li s- sintomi jisparixxu minnufih (ara sezzjonijiet 4. 4 u 4. 8).
Contents:
Fig. e
METHOD AND ROUTE(S) OF ADMINISTRATION
ID- DETENTUR TAL- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
Read the package leaflet before use.
Baxter AG Industriestrasse 67 A- 1221 Vienna L- Awstrija
6.
66 8.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE REACH AND SIGHT OF CHILDREN
NUMRU( I) TAL- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
Keep out of the reach and sight of children.
EU/ 1/ 03/ 271/ 006
OTHER SPECIAL WARNING(S), IF NECESSARY
DATA TAL- EWWEL AWTORIZZAZZJONI/ TIĠDID TAL- AWTORIZZAZZJONI
EXPIRY DATE
04 ta 'Marzu 2009
Do not use after the expiry date.
DATA TA ’ META ĠIET RIVEDUTA L- KITBA
67 9.
67 ANNESS II
SPECIAL STORAGE CONDITIONS
KUNDIZZJONIJIET TAL- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
Do not freeze.
Isem u indirizz tal- manifattur tas- sustanza bijoloġika attiva
Can be stored at room temperature (up to 25°C) for a single period up to 2 months.
Isem u indirizz tal- manifattur responsabbli għall- ħruġ tal- lott
Taken out of refrigerator on:
Prodott mediċinali jingħata b' riċetta ristretta tat- tabib (Ara Anness I: