qanastek/EMEA-V3 huggingface dataset:
Because of the potential risk of thrombotic complications, clinical surveillance for early signs of thrombotic and consumptive coagulopathy should be initiated with appropriate biological testing when administering this product to patients with liver disease, to patients post-operatively, to neonates, or to patients at risk of thrombotic phenomena or DIC.
Minħabba r- riskju ta ’ kumplikazzjonijiet trombotiċi, huwa mportanti li jsir monitoraġġ kliniku għal sinjali bikrija tal- koagulopatija trombotika u konsumattiva u għandha ssir eżaminazzjoni bijoloġika xierqa meta jingħata dan il- prodott lil pazjenti b’ mard tal- fwied, pazjenti wara li jkunu għamlu xi operazzjoni, trabi tat- twelied, jew pazjenti li qiegħdin f’ riskju ta ’ fenomeni trombotiċi jew DIC.
To minimize the possibility of agglutination, it is important to limit the amount of blood entering the tubing.
Biex il - possibbiltà ta ’ agglutinazzjoni tkun imminimizzata, hu importanti li tillimita l- ammont ta ’ demm li jidħol fit- tubi.
If agglutination of red blood cells in the tubing/ syringe is observed, discard all this material (tubing, syringe and BeneFIX solution) and resume administration with a new package.
Jekk tkun osservata agglutinazzjoni taċ- ċelluli l - ħomor tad- demm fit- tubu/ siringa, armi l- apparat kollu (tubi, siringa u s- soluzzjoni ta ’ BeneFIX) u kompli t- teħid minn pakkett ġdid.
Based on the rare occurrence of haemophilia B in women, experience regarding the use of factor IX during pregnancy and breast-feeding is not available.
Msejsa fuq in- numru ta ’ każijiet rari ta ’ emofilja B fin- nisa, l- esperjenza rigward l- użu tal- fattur IX waqt it- tqala u l- irdigħ mhix disponibbli.
Therefore, factor IX should be used during pregnancy and breast-feeding only if clearly indicated.
Għalhekk, il- fattur IX għandu jintuża matul it- tqala u l- irdigħ biss jekk ikun verament indikat.
The frequency of adverse reactions reported in association with BeneFIX would be categorized as uncommon (≥ 1/ 1000 to ≤ 1/ 100) or rare (≥ 1/ 10,000 to ≤ 1/ 1000).
Il- frekwenza ta 'reazzjonijiet avverbħala mhux komuni (≥ 1/ 1000 sa ≤ 1/ 100) jew rari (≥ 1/ 10, 000 sa ≤ 1/ 1000).
Adverse reactions based on experience from clinical trials and postmarketing experience are presented below by system organ class and frequency of occurrence.
17 Reazzjonijiet avversi bbażati fuq esperjenza minn provi kliniċi u esperjenza ta 'wara t- tqegħid fis- suq huma ppreżentati hawn taħt skond il- klassi ta' l- organu tas- sistema u l- frekwenza ta 'l- okkorrenza.
17 Nervous system disorders
Disturbi tas- sistema nervuża
General disorders and administration site conditions
kondizzjonijiet fis- sit tat- teħid
Neutralising antibodies (factor IX inhibition)* Hypersensitivity/ allergic reactions; such reactions may include anaphylaxis*, bronchospasm/ respiratory distress, hypotension, angioedema, tachycardia, chest tightness, generalised urticarial, hives, rash, burning sensation in jaw and skull, chills (rigors), tingling, flushing, lethargy, restlessness, dry cough/ sneezing
Anti- korpi newtralizzanti (inibizzjoni ta ’ fattur IX) * Sensittività eċċessiva/ reazzjonijiet allerġiċi; dawn ir- reazzjonijiet jistgħu jinkludu anafilassi *, spażmi fil- bronki/ diffikultà biex tieħu n- nifs, pressjoni baxxa, anġjodema, takikardja, tagħfis tas- sider, urtikarja ġeneralizzata, urtikarja, raxx, sensazzjoni ta ’ ħruq fix- xedaq u l- kranju, reżħiet (rogħda), tingiż, fwawar fil- wiċċ, telqa, irrikwitezza, sogħla xotta/ għatis
Hypersensitivity responses can occur.
Jista ’ jkun hemm l - effett ta ’ sensittività eċċessiva.
18 Renal
18 M’ hemmx biżżejjed informazzjoni sabiex jiġi fornut tagħrif fuq l- inċidenza ta ’ l- impeditur fil- pazjenti li ma kienux ikkurati qabel.
Pharmacotherapeutic group: antihaemorrhagic Blood Coagulation Factor IX; ATC code:
Fattur IX tal- Koagulazzjoni tad- Demm kontra l- emorraġiji; Kodiċi ATC:
Infusion of BeneFIX into 56 PTP patients (baseline data) with haemophilia B has shown an in vivo recovery ranging from 15 to 62% (mean 33.7 +/ - 10.3%).
Unità Internazzjonali waħda
One International Unit of BeneFIX showed a mean 0.75 IU/ dl (range 0.3 to 1.4 IU/ dl) increase in the circulating level of factor IX.
19 ta ’ BeneFIX uriet medja ta ’ 0. 75 IU/ dl (bejn 0. 3 sa 1. 4 IU/ dl) żjieda fil- livell ta ’ ċirkulazzjoni tal- fattur IX.
For a subset of the 56 patients, data are available from baseline to 24 months.
Għal proporzjon minn dawn is- 56 pazjent, l- informazzjoni hi disponibbli mill- linja bażi ta ’ referenza sa 24 xahar.
19 Table 1.
0. 19
Recombinant Factor IX Summary of Pharmacokinetic Parameters for Activity Data by Month in Previously Treated Patients
0. 64, 0. 75
Parameter Recovery (%)
IU/ kg)
Month n Mean Median SD Range 95% CI 0 56 33.7 31.5 10.31 15.3– 62.2 30.9, 36.4 6 53 31.8 31.0 9.04 15.3– 56.7 29.4, 34.3 12 50 31.3 30.5 8.75 16.2 – 53.1 28.8, 33.7 18 47 30.7 28.9 9.24 12.6– 62.1 28.0, 33.5 24 47 31.0 30.6 8.80 16.2– 59.4 28.4, 33.6
0. 21 0. 20 4. 97
FIX increase (IU/ dl per IU/ kg)
0. 28– 1. 38 0. 36– 1. 32 11. 1– 36. 4
0 56 0.75 0.70 0.23 0.34– 1.38 0.69, 0.81 6 53 0.71 0.69 0.20 0.34– 1.26 0.65, 0.76 12 50 0.70 0.68 0.19 0.36 – 1.18 0.64, 0.75 18 47 0.68 0.64 0.21 0.28– 1.38 0.62, 0.74 24 47 0.69 0.68 0.20 0.36– 1.32 0.63, 0.75
0. 62, 0. 74 0. 63, 0. 75 18. 0, 20. 7
Elimination half-life (hrs)
Half- life ta ’ l -
AUC0- ∞ (IU × hr/ dl)
(sigħat) AUC0- ∞ (IU x hr/ dl)
0 56 619.8 605.2 155.7 366.5– 1072.6 578.1, 661.5 6 53 579.8 562.2 146.1 330.9– 900.1 539.5, 620.1 12 49 575.7 566.0 151.0 290.3 – 1080.8 532.4, 619.1 18 46 561.8 560.9 155.6 254.5– 940.8 515.7, 608.0 24 45 577.6 551.7 154.7 284.1– 1045.4 531.1, 624.1
16. 8, 21. 0 16. 8, 20. 9 578. 1, 661. 5 539. 5, 620. 1 532. 4, 619. 1 515. 7, 608. 0 531. 1, 624. 1 1. 6, 2. 5
Half-life
Half- life
0 54 2.0 1.5 1.60 0.07-5.73 1.6,2.5
1. 0
6 12 18 24
12
52 48 44 43
44 43
2.3 2.2 2.0 1.8
2. 07 2. 01
1.0 1.2 1.3 0.78
0. 11- 7. 43 4. 66- 13. 64
2.62 2.70 1.94 2.07
1. 1, 2. 4 7. 86, 8. 94
0.12-9.98 0.13-14.34 0.13-6.21 0.11-7.43
Ir- rata ta ’ kemm
1.5,3.0 1.5,3.0 1.4,2.6 1.1,2.4
idum biex jiġi
Clearance (ml/ hr/ kg)
(ml/ siegħa/ kg)
0 6 12 18 24
18 24
56 53 49 46 45
46 45
8.4 9.2 9.3 9.6 9.2
9. 2
8.2 8.9 8.8 8.9 9.1
9. 1
2.01 2.48 2.53 2.85 2.40
2. 40
4.66-13.64 5.55-15.11 4.63-17.22 5.31-19.65 4.78-17.60
4. 78- 17. 60
7.86,8.94 8.53,9.89 8.56,10.01 8.78,10.47 8.52,9.96
8. 52, 9. 96
56 53 49 46 45
56 26. 0 53 25. 6 49 24. 6 46 24. 7 45 25. 1
6.07 5.68 6.47 7.40 6.94
25. 8 25. 3 22. 2 22. 7 23. 9
15.81-46.09 13.44-42.26 14.83-38.75 15.30-50.75 15.65-47.52
6. 07 15. 81- 46. 09 5. 68 13. 44- 42. 26 6. 47 14. 83- 38. 75 7. 40 15. 30- 50. 75 6. 94 15. 65- 47. 52
24.35,27.60 24.01,27.15 22.75,26.47 22.55,26.94 23.00,27.17
24. 35, 27. 60 24. 01, 27. 15 22. 75, 26. 47 22. 55, 26. 94 23. 00, 27. 17
Data exclude those collected from one patient after evidence of inhibitor development was observed at 9 months.
L- informazzjoni teskludi dik miġbura minn pazjent wieħed wara evidenza li żviluppa impeditur wara 9 xhur.
20 A 28% lower recovery of recombinant Factor IX in comparison to plasma derived Factor IX was shown.
20 Intwera li kien hemm tnaqqis ta ’ 28% fl- irkupru ta ’ Fattur IX rikombinanti meta mqabbel ma ’ Fattur IX derivat mill- plażma.
The pharmacokinetic parameters obtained in studies comparing recombinant Factor IX to plasma derived Factor IX were similar to those obtained in human studies.
Il- parametri farmakokinetiċi miksuba fi studji fejn ġew imqabbla Fattur IX rikombinanti u Fattur IX derivat mill- plażma kienu bħal dawk miksuba fl- istudji li saru fuq il- bniedem.
Non-clinical data reveal no special hazard for humans based on conventional studies of genotoxicity.
Informazzjoni li mhix klinika, magħmula fuq studji konvenzjonali ta ’ l- effett tossiku fuq il- ġeni, ma ’ turi l- ebda periklu speċjali għall- bnedmin.
The reconstituted product should be used immediately, but no longer than 3 hours after reconstitution.
Preferibbilment, is- soluzzjoni rikostitwita għandha tintuża immedjatament, iżda mhux aktar tard minn 3 sigħat wara r- rikostituzzjoni.
For the purpose of ambulatory use the product may be removed from refrigerated storage for one single period of maximum 1 month at room temperature (up to 25 ºC).
Għall- għan ta ’ użu ambulatorju, il- prodott jista ’ jinħareġ mill- ħażna fil- friġġ għall- perijodu wieħed sa massimu ta ’ xahar fit- temperatura tal- kamra (sa 25 ºC).
500 IU of powder in a vial (type 1 glass) with a stopper (chlorobutyl) and a flip-off seal (aluminium).
500 ml ta ’ trab f’ kunjett (ħġieġ ta ’ Tip I) b’ tapp (chlorobutyl) u siġill flip- off (aluminju).
A tip-cap (bromobutyl) and a sterile filter spike, a sterile infusion set, two alcohol swabs, two plasters.
Għatu tat- tarf (bromobutyl) u ponta tal- filtru sterili, sett sterili ta ’ l- infużjoni, żewġ biċċiet bl- alkoħol biex tnaddaf u żewġ stikek.
21 6.6 Special precautions for disposal and other handling
21 6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema u għal immaniġġar ieħor
27 August 1997 Date of last renewal:
27 ta’ Awissu 1997 Data ta ’ l- aħħar tiġdid:
27 August 2007
27 ta’ Awissu 2007
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/
22 Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropea dwar il - Mediċini (EMEA) http: // www. emea. europa. eu /.
BeneFIX 1000 IU powder and solvent for solution for injection
BeneFIX 1000 IU trab u solvent għal soluzzjoni għall- injezzjoni
Each vial contains nominally 1000 IU nonacog alfa (recombinant coagulation factor IX).
Kull kunjett nominalment fih 1000 IU nonacog alfa (fattur IX tal- koagulazzjoni rikombinanti).
After reconstitution with the accompanying 10 ml water for injection, each ml of the solution contains approximately 100 IU/ ml nonacog alfa.
Wara r - rikostituzzjoni b’ 10 ml ta ’ ilma għall- injezzjonijiet li hu pprovdut miegħu, kull 1 ml tas- soluzzjoni jkun fih madwar 100 IU nonacog alfa.
Each vial contains 100 mg sucrose.
Kull kunjett fih 100 mg ta ’ sucrose.
24 parameters such as half-life and recovery, as well as the clinical situation into consideration in order to adjust the dose as appropriate.
24 L- ammont li għandu jingħata u kull kemm għandu jingħata għandhom dejjem jitqiesu skond l - effettività klinika fil- każ individwali.
Degree of haemorrhage/ Type of surgical procedure Haemorrhage
25 Grad ta ’ emorraġija/ Tip ta ’ proċedura kirurġika Emorraġija
See also section 4.4.
Dawn il- pazjenti għandhom ikunu qegħdin taħt is- sorveljanza ta ’ tobba b’ esperjenza fil- kura ta ’ pazjenti bl- emofilja.
In most of the cases, an infusion rate of up to 4 ml per minute has been used.
Ara wkoll sezzjoni 4. 4.
26 4.3 Contraindications
26 Metodu ta ’ kif għandu jingħata
Hypersensitivity to the active substance or to any of the excipients.
BeneFIX għandu jingħata b’ rata ta ’ infużjoni baxxa.
Because of the risk of allergic reactions with factor IX concentrates, the initial administrations of factor IX should, according to the treating physician’ s judgement, be performed under medical observation where proper medical care for allergic reactions could be provided.
27 Minħabba r- riskju ta ’ reazzjonijiet allerġiċi għall- konċentrati ta ’ fattur IX, l- għoti inizjali ta ’ fattur IX għandu, skond il- parir tat- tabib li qiegħed jikkura, isir taħt sorveljanza medika fejn tkun tista ’ tingħata kura medika xierqa għal reazzjonijiet allerġiċi.
These frequencies have been estimated on a per- infusion basis and are described using the following categories: uncommon (≥ 1/ 1000 to ≤ 1/ 100); rare (≥ 1/ 10,000 to ≤ 1/ 1000).
28 Dawn il- frekwenzi ġew stmati fuq bażi ta ’ kull infużjoni u huma deskritti billi jintużaw il- kategoriji li ġejjin: mhux komuni (≥1/ 1000 sa ≤1/ 100); rari (≥1/ 10, 000 sa ≤1/ 1000).
28 Nervous system disorders
Disturbi tas- sistema nervuża
Nephrotic syndrome has been reported following high doses of plasma derived Factor IX to induce immune tolerance in haemophilia B patients with factor IX inhibitors and a history of allergic reactions.
M’ hemmx biżżejjed informazzjoni sabiex jiġi fornut tagħrif fuq l- inċidenza ta ’ l- impeditur fil- pazjenti li ma kienux ikkurati qabel.
29 Renal
29 Is- sindromu nefrotiku kien rappurtat, wara dożi qawwija ta ’ Fattur IX derivat mill- plażma, biex jikkaġuna tolleranza immuni f’ pazjenti ta ’ l- emofilja B li għandhom l- impedituri għall- fattur IX u li kellhom reazzjonijiet allerġiċi fil- passat.
For a subset of the 56 patients, data are available from baseline to 24 months.
30 Għal proporzjon minn dawn is- 56 pazjent, l- informazzjoni hi disponibbli mill- linja bażi ta ’ referenza sa 24 xahar.
30 Table 1.
Medja 33. 7
Recombinant Factor IX Summary of Pharmacokinetic Parameters for Activity Data by Month in Previously Treated Patients
95% CI 30. 9, 36. 4
Parameter Recovery (%)
Irkupru (%)
Month n Mean Median SD Range 95% CI 0 56 33.7 31.5 10.31 15.3– 62.2 30.9, 36.4 6 53 31.8 31.0 9.04 15.3– 56.7 29.4, 34.3 12 50 31.3 30.5 8.75 16.2 – 53.1 28.8, 33.7 18 47 30.7 28.9 9.24 12.6– 62.1 28.0, 33.5 24 47 31.0 30.6 8.80 16.2– 59.4 28.4, 33.6
29. 4, 34. 3 28. 8, 33. 7 28. 0, 33. 5 28. 4, 33. 6
FIX increase (IU/ dl per IU/ kg)
Żjieda FIX (IU/ dl għal kull IU/ kg)
0 56 0.75 0.70 0.23 0.34– 1.38 0.69, 0.81 6 53 0.71 0.69 0.20 0.34– 1.26 0.65, 0.76 12 50 0.70 0.68 0.19 0.36 – 1.18 0.64, 0.75 18 47 0.68 0.64 0.21 0.28– 1.38 0.62, 0.74 24 47 0.69 0.68 0.20 0.36– 1.32 0.63, 0.75
0. 70 0. 69 0. 68 0. 64 0. 68 19. 1
Elimination half-life (hrs)
0. 23 0. 20 0. 19 0. 21 0. 20 4. 97
0 56 19.3 19.1 4.97 11.1– 36.4 18.0, 20.7 6 53 19.8 18.2 6.26 9.6– 38.2 18.1, 21.6 12 49 18.5 16.6 5.89 10.6 – 33.7 16.8, 20.2 18 46 18.9 16.3 7.02 10.7– 38.3 16.8, 21.0 24 45 18.9 17.3 6.84 10.9– 42.2 16.8, 20.9
0. 69, 0. 81 0. 65, 0. 76 0. 64, 0. 75 0. 62, 0. 74 0. 63, 0. 75 18. 0, 20. 7
Pharmacokinetic parameters of recombinant Factor IX have also been determined after single and
Il- parametri farmakokinetiċi
31 multiple intravenous doses in different species.
31 miksuba fi studji fejn ġew imqabbla Fattur IX rikombinanti u Fattur IX derivat mill- plażma kienu bħal dawk miksuba fl- istudji li saru fuq il- bniedem.
The pharmacokinetic parameters obtained in studies comparing recombinant Factor IX to plasma derived Factor IX were similar to those obtained in human studies.
Jidher li d- differenzi strutturali fil- molekula ta ’ Fattur IX rikombinanti meta mqabbla ma ’ Fattur IX derivat mill- plażma jikkontibwixxu għad- differenza fl - irkupru.
1000 IU of powder in a vial (type 1 glass) with a stopper (chlorobutyl) and a flip-off seal (aluminium).
1000 ml ta ’ trab f’ kunjett (ħġieġ ta ’ Tip I) b’ tapp (chlorobutyl) u siġill flip- off (aluminju).
A tip-cap (bromobutyl) and a sterile filter spike, a sterile infusion set, two alcohol swabs, two plasters.
Għatu tat - tarf (bromobutyl) u ponta tal- filtru sterili, sett sterili ta ’ l- infużjoni, żewġ biċċiet bl- alkoħol biex tnaddaf u żewġ stikek.
32 6.6 Special precautions for disposal and other handling
32 6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema u għal immaniġġar ieħor
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/
33 Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropea dwar il - Mediċini (EMEA) http: // www. emea. europa. eu /.
Each vial contains nominally 250 IU nonacog alfa (recombinant coagulation factor IX).
Kull kunjett nominalment fih 250 IU ta 'nonacog alfa (fattur IX tal- koagulazzjoni rikombinanti).
After reconstitution with the accompanying 5 ml (0.234%) sodium chloride solution for injection, each ml of the solution contains approximately 50 IU nonacog alfa.
Wara r- rikostituzzjoni bis- soluzzjoni għall- injezzjoni ta '5 ml (0. 234%) sodium chloride li hi pprovduta miegħu, kull 1 ml ta' soluzzjoni jkun fih madwar 50 IU nonacog alfa.
The potency (IU) is determined using the European Pharmacopoeia one-stage clotting assay.
Il- qawwa (IU) hi stabbilita bl- użu ta 'l- assay ta ’ t- tagħqid tad- demm fi stadju wieħed kif deskritt skond il- Farmakopea Ewropea.
The specific activity of BeneFIX is not less than 200 IU/ mg protein.
L- attività speċifika ta ’ BeneFIX hija ta 'mhux anqas minn 200 IU/ mg ta ’ proteina.
Recombinant coagulation factor IX is a glycoprotein that is secreted by genetically engineered mammalian cells derived from a Chinese hamster ovary (CHO) cell line.
Il- fattur IX rikombinanti tal- koagulazzjoni huwa glikoproteina, miksub permezz ta ’ l- inġinerija ġenetika ta ’ ċelluli mammiferi derivat mir- razza ta 'ċelluli ta ’ l- ovarji ta ’ ħamster ċiniż (CHO).
Each vial contains 40 mg sucrose.
Kull kunjett fih 40 mg ta ’ sucrose.
The dosage and duration of the substitution therapy depends on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition.
Id- doża u t- tul tat- terapija ta’ sostituzzjoni jiddependu fuq is- severità tad- defiċjenza tal- fattur IX, il- lok u l- ammont ta 'fsada, u l- kondizzjoni klinika tal- pazjent.
35 parameters such as half-life and recovery, as well as the clinical situation into consideration in order to adjust the dose as appropriate.
35 L- ammont li għandu jingħata u kull kemm għandu jingħata għandhom dejjem jitqiesu skond l - effettività klinika fil- każ individwali.
The number of units of factor IX administered is expressed in International Units (IU), which are related to the current WHO standard for factor IX products.
In- numru ta ’ unitajiet tal- fattur IX mogħtija jitfissru f’ Unitajiet Internazzjonali (IU), li huma marbuta ma 'l- istandard attwali ta ’ l- Organiżżazzjoni Dinjina tas- Saħħa għall- prodotti tal- fattur IX.
Factor IX activity in plasma is expressed either as a percentage (relative to normal human plasma) or in International Units (relative to an international standard for factor IX in plasma).
L- attività tal- fattur IX fil- plażma jitfisser bħala persentaġġ (relattiv mal- plażma tal- bniedem) jew bħala Unitajiet Internazzjonali (marbuta ma 'l- istandard internazzjonali għall- fattur IX fil- plażma).
Estimation of the required dose of BeneFIX can be based on the finding that one unit of factor IX activity per kg body weight is expected to increase the circulating level of factor IX, an average of 0.8 IU/ dl (range from 0.4 to 1.4 IU/ dl) in adult patients (≥ 15 years).
Stima tad- doża meħtieġa ta ’ BeneFIX tista ’ tkun ibbażata fuq il- fatt li unità waħda ta ’ attività ta ’ fattur IX għal kull kg tal- piż tal- ġisem hi mistennija li żżid il - livell ta ’ ċirkolazzjoni tal- fattur IX, b' medja ta '0. 8 IU/ dl (minn 0. 4 sa 1. 4 IU/ dl) f’ pazjenti adulti (≥ 15- il sena).
For a recovery 0.8 IU/ dl (average increase of factor IX), then:
Għal irkupru 0. 8 IU/ dl (żjieda medja ta ’ fattur IX), imbagħad:
Degree of haemorrhage/ Type of surgical procedure Haemorrhage
Grad ta ’ emorraġija/ Tip ta ’ proċedura kirurġika Emorraġija
Repeat infusion every 24 hours for 3- 4 days or more until pain and acute disability are resolved.
Irrepeti l- infużjoni kull 24 siegħa għal 3 - 4 ijiem jew aktar sakemm l- uġigħ u d- diżabilità akuta jgħaddi.
Repeat infusion every 8 to 24 hours until threat is resolved.
Irrepeti l- infużjoni kull 8 - 24 siegħa sakemm ma tibqax fil- periklu.
Every 24 hours, at least 1 day, until healing is achieved.
Kull 24 siegħa, mill- anqas għal 30- 60 Minuri: ġurnata, sakemm tfiq.
Repeat infusion every 8-24 hours
Inkluż qlugħ tas- snien
therapy for at least another 7 days to maintain a factor IX activity of 30% to 60% (IU/ dl)
Irrepeti l- infużjoni kull 8 - 24 siegħa 80- 100 Maġġuri: sakemm jinkiseb fejqan adegwat tal - (qabel u wara l - ferita, imbagħad t- terapija titkompla operazzjoni) għal mill- anqas 7 ijiem oħra sabiex tinżamm l- attività tal- fattur IX ta ’ 30% sa ’ 60% (IU/ dl)
During the course of treatment, appropriate determination of factor IX levels is advised to guide the dose to be administered and the frequency of repeated infusions.
36 Waqt il- kors tal- kura, hu rakkomandat li jiġu stabbiliti l- livelli tal- fattur IX bħala gwida tad- doża li għandha tingħata u l- frekwenza ta ’ l- infużjonijiet ripetuti.
In clinical studies, 57% of the paediatric patients increased their doses due to lower than expected recovery or to obtain sufficient therapeutic response or both, some to an average dose of > 50 IU/ kg.
Fi studji kliniċi, 57% tal- pazjenti pedjatriċi pedjatriċi żiedu d- dożi tagħhom għax kellhom rkupru anqas minn dak li kien mistenni jew sabiex jiksbu effett terapewtiku suffiċjenti jew minħabba t- tnejn li huma.
Therefore, close monitoring of factor IX plasma activity should be performed, as well as calculation of pharmacokinetic parameters such as recovery and half-life, as clinically indicated, in order to adjust doses as appropriate.
Għalhekk, wieħed għandu jeżamina mill- qrib l- attività tal- fattur IX, fil- plażma u jridu jsiru kalkoli tal- parametri farmakokinetiċi bħal ma huma l- irkupru u l- half- life, hekk kif inhu indikat klinikament, sabiex id- dożi jiġu mibdula kif meħtieġ.
BeneFIX is administered by intravenous infusion after reconstitution of the lyophilised powder for solution for injection with sterile 0.234% sodium chloride solution (see section 6.6).
BeneFIX jingħata permezz għall- injezzjoni fil- vina wara r- rikostituzzjoni tat- trab lijofilizzat għas - soluzzjoni ta ’ l- injezzjoni b’ soluzzjoni ta ’ 0. 234% sodium chloride sterilizzat (ara sezzjoni 6. 6).
In most of the cases, an infusion rate of up to 4 ml per minute has been used.
Fil- maġġoranza tal- każi, intużat rata ta ’ infużjoni sa 4 ml kull minuta.
The rate of administration should be determined by the patient’ s comfort level.
Ir- rata ta ’ l- għoti għandha tkun stabbilita skond il- livell ta ’ komfort tal- pazjent.
37 4.3 Contraindications
4. 3 Kontra- indikazzjonijiet
Known allergic reaction to hamster proteins.
Reazzjoni allerġika magħrufa għall- proteini tal- ħamsters.
Activity-neutralizing antibodies (inhibitors) are an uncommon event in previously treated patients (PTPs) receiving factor IX-containing products.
Il- preżenza ta ’ anti- korpi li jinnewtralizzaw l- attività (impedituri) hu avveniment mhux komuni f’ pazjenti li kienu ġew ikkurati qabel (PTP’ s) li qed jirċievu prodotti li fihom il- fattur IX.
Since during clinical studies one PTP treated with BeneFIX developed a clinically relevant low responding inhibitor and experience on antigenicity with recombinant factor IX is still limited, patients treated with BeneFIX should be carefully monitored for the development of factor IX inhibitors that should be titrated in Bethesda Units using appropriate biological testing.
Billi matul l - istudji kliniċi pazjent PTP wieħed li kien qed jieħu BeneFIX żviluppa impeditur klinikament relevanti ta rispons baxx u l- esperjenza dwar l- antiġeniċità mal- fattur IX rikombinanti għadha ristretta, il - pazjenti li jiġu kkurati b’ BeneFIX għandhom ikunu sorveljati b' mod partikolari għall- iżvilupp ta ’ impedituri tal- fattur IX li għandhom ikunu ttitrati f’ Unitajiet Bethesda permezz ta 'ttestjar bijoloġiku xieraq.
Additional safety and efficacy studies in paediatric patients are ongoing in previously treated, minimally treated, and previously untreated paediatric patients.
37 pedjatriċi huma għaddejjin kontinwament fuq pazjenti pedjatriċi trattati qabel, trattati minimament u dawk li mhux trattati qabel.
There have been reports in the literature showing a correlation between the occurrence of a factor IX inhibitor and allergic reactions.
Kien hemm rapporti li wrew korrelazzjoni bejn l- frekwenza ta 'każijiet ta ’ impeditur għall- fattur IX u reazzjonijiet allerġiċi.
Posology has to be adjusted according to the pharmacokinetics of each patient.
Il- pożoloġija għandha tkun aġġustata skond il- farmakokinetiċi ta 'kull pazjent.
So far, no clinical sequelae have been reported in association with this observation.
S’ issa, ma ġewx irrappurtati kumplikazzjonijiet assoċjati ma ’ din l- osservazzjoni.
In the interest of patients, it is recommended that, whenever possible, every time that BeneFIX is administered to them, the name and batch number of the product is registered.
38 Fl- interess tal- pazjenti, hu rakkomandat, li kull meta jkun possibli, kull darba li jingħatalhom BeneFIX, l- isem u n- numru tal- lott tal- prodott għandhom jiġu rreġistrati.
Based on the rare occurrence of haemophilia B in women, experience regarding the use of factor IX during pregnancy and breastfeeding is not available.
Msejsa fuq in- numru ta 'każijiet rari ta ’ emofilja B fin- nisa, l- esperjenza rigward l- użu tal- fattur IX waqt it- tqala u t- treddigħ mhix disponibbli.
Therefore, factor IX should be used during pregnancy and breast-feeding only if clearly indicated.
Għalhekk, il- fattur IX għandu jintuża matul it- tqala u t- treddigħ biss jekk ikun verament indikat.
General disorders and administration site conditions
Disturbi ġenerali u kondizzjonijiet fis- sit tat- teħid
information below.
* Ara informazzjoni oħra aktar `l isfel.
Hypersensitivity/ allergic reactions
39 Sensittività eċċessiva / reazzjonijiet allerġiċi
Due to the production process BeneFIX contains trace amounts of hamster cell proteins.
Minħabba l- proċess ta ’ produzzjoni BeneFIX jista ’ jkun fih traċċi ta ’ proteini tal- ħamsters.
There are insufficient data to provide information on inhibitor incidence in PUPs.
M’ hemmx biżżejjed informazzjoni sabiex jiġi fornut tagħrif fuq l- inċidenza ta ’ l- impeditur fil- pazjenti li ma kienux ikkurati qabel.
Nephrotic syndrome has been reported following high doses of plasma derived Factor IX to induce immune tolerance in haemophilia B patients with factor IX inhibitors and a history of allergic reactions.
Is- sindromu nefrotiku kien rappurtat, wara dożi qawwija ta ’ Fattur IX derivat mill- plażma, biex jikkaġuna tolleranza immuni f’ pazjenti ta ’ l- emofilja B li għandhom l- impedituri għall- fattur IX u li kellhom reazzjonijiet allerġiċi fil- passat.
Renal
Kliewi
The relationship of the infarct to prior administration of BeneFIX is uncertain.
Ir- relazzjoni ta ’ l- infart ma ’ l- għoti ta ’ BeneFIX mhix ċerta.
Haemophilia B is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor IX and results in profuse bleeding into joints, muscles or internal organs, either spontaneously or as a result of accidental or surgical trauma.
40 L- emofilja B hi marda ereditarja tal- koagulazzjoni tad- demm minħabba livelli mnaqqsa ta ’ fattur IX u tirriżulta fi fsada fil- ġogi, fil- muskoli u fl- organi interni, li tkun spontaneja jew bħala riżultat ta ’ trawma aċċidentali jew kirurġika.
The medicinal product has been authorised under “ Exceptional Circumstances”
Din il- mediċina kienet awtorizzata taħt ‘ Ċirkustanzi ta ’ Eċċezzjoni ’.
For a subset of the 56 patients, data are available from baseline to 24 months.
Għal proporzjon minn dawn is- 56 pazjent, l- informazzjoni hi disponibbli mill- linja bażi ta 'referenza sa 24 xahar.
Table 1.
41 Tabella 1.
Recombinant Factor IX Parameters for Activity Data by Month in Previously Treated Patients
Ġabra fil- qosor tal- Fattur IX Rikombinanti tal- Parametri Farmakokinetiċi għall - Informazzjoni fix- xahar dwar l- Attività f’ Pazjenti li kienu kkurati qabel
Parameter Recovery (%)
Parametru
Month n Mean Median SD Range 0 56 33.7 31.5 10.31 15.3– 62.2
Xahar n Medja Medjan SD Medda 95% CI 30. 9, 36. 4 15. 3 – 62. 2 10. 31 31. 5 33. 7 56
95% CI 30.9, 36.4
Irkupru (%)
Month n Mean Median SD Range 95% CI 6 53 31.8 31.0 9.04 15.3– 56.7 29.4, 34.3 12 50 31.3 30.5 8.75 16.2– 53.1 28.8, 33.7 18 47 30.7 28.9 9.24 12.6 – 62.1 28.0, 33.5 24 47 31.0 30.6 8.80 16.2– 59.4 28.4, 33.6
0 29. 4, 34. 3 15. 3 – 56. 7 9. 04 31. 0 31. 8 53 6 28. 8, 33. 7 16. 2 – 53. 1 8. 75 30. 5 31. 3 50 12 28. 0, 33. 5 12. 6 – 62. 1 9. 24 28. 9 30. 7 47 18 28. 4, 33. 6 16. 2 – 59. 4 8. 80 30. 6 31. 0 47 24 0. 69, 0. 81 0. 34 – 1. 38 0. 23 0. 70 0. 75 56
FIX increase (IU/ dl per IU/ kg)
Żjieda FIX
Elimination half-life (hrs)
0 0. 65, 0. 76 0. 34 – 1. 26 0. 20 0. 69 0. 71 53
AUC0- ∞ (IU × hr/ dl) Half-life
(IU/ dl għal kull
6 12 18 24
6 0. 64, 0. 75 0. 36 – 1. 18 0. 19 0. 68 0. 70 50
52 48 44 43
IU/ kg)
2.3 2.2 2.0 1.8
12 0. 62, 0. 74 0. 28 – 1. 38 0. 21 0. 64 0. 68 47 18 0. 63, 0. 75 0. 36 – 1. 32 0. 20 0. 68 0. 69 47 24 18. 0, 20. 7 11. 1 – 36. 4 4. 97 19. 1 19. 3
1.0 1.2 1.3 0.78
Half- life ta 'l -
2.62 2.70 1.94 2.07
0 56 18. 1, 21. 6 9. 6 – 38. 2 6. 26 18. 2 19. 8
0.12-9.98 0.13-14.34 0.13-6.21 0.11-7.43
eliminazzjoni
1.5,3.0 1.5,3.0 1.4,2.6 1.1,2.4
6 53 16. 8, 20. 2 10. 6 – 33. 7 5. 89 16. 6 18. 5
Clearance (ml/ hr/ kg)
(sigħat) AUC0- ∞ (IU x hr/ dl)
0 6 12 18 24
12 49 16. 8, 21. 0 10. 7 – 38. 3 7. 02 16. 3 18. 9 18 46 16. 8, 20. 9 10. 9 – 42. 2 6. 84 17. 3 18. 9 45 24 619. 8 605. 2 155. 7 366. 5 – 1072. 6 578. 1, 661. 5 56 0 579. 8 562. 2 146. 1 330. 9 – 900. 1 539. 5, 620. 1 53 6 575. 7 566. 0 151. 0 290. 3 – 1080. 8 532. 4, 619. 1 49 12 561. 8 560. 9 155. 6 254. 5 – 940. 8 515. 7, 608. 0 46 18 45 577. 6 551. 7 154. 7 284. 1 – 1045. 4 531. 1, 624. 1 24 1. 6, 2. 5 0. 07 - 5. 73 1. 60 1. 5 2. 0
56 53 49 46 45
Half- life
8.4 9.2 9.3 9.6 9.2
0 54 1. 5, 3. 0 0. 12 - 9. 98 2. 62 1. 0 2. 3
8.2 8.9 8.8 8.9 9.1
Inizzjali (sigħat)
2.01 2.48 2.53 2.85 2.40
6 52 1. 5, 3. 0 0. 13 - 14. 34 2. 70 1. 2 2. 2 12 48 1. 4, 2. 6 0. 13 - 6. 21 1. 94 1. 3 2. 0 18 44 1. 1, 2. 4 0. 11 - 7. 43 2. 07 0. 78 1. 8 43 24
4.66-13.64 5.55-15.11 4.63-17.22 5.31-19.65 4.78-17.60
Ir- rata ta 'kemm idum biex jiġi eliminat (ml/ siegħa/ kg)
7.86,8.94 8.53,9.89 8.56,10.01 8.78,10.47 8.52,9.96
0 56 8. 4 8. 2 2. 01 4. 66 - 13. 64 7. 86, 8. 94 6 53 9. 2 8. 9 2. 48 5. 55 - 15. 11 8. 53, 9. 89 12 49 9. 3 8. 8 2. 53 4. 63 - 17. 22 8. 56, 10. 01 18 46 9. 6 8. 9 2. 85 5. 31 - 19. 65 8. 78, 10. 47 24 45 9. 2 9. 1 2. 40 4. 78 - 17. 60 8. 52, 9. 96
25.8 25.3 22.2 22.7 23.9
25. 8 25. 3 22. 2 22. 7 23. 9
6.07 5.68 6.47 7.40 6.94
6. 07 5. 68 6. 47 7. 40 6. 94
15.81-46.09 13.44-42.26 14.83-38.75 15.30-50.75 15.65-47.52
15. 81 - 46. 09 13. 44 - 42. 26 14. 83 - 38. 75 15. 30 - 50. 75 15. 65 - 47. 52
A 28% lower recovery of recombinant Factor IX in comparison to plasma derived Factor IX was shown.
Intwera li kien hemm tnaqqis ta '28% fl- irkupru ta' Fattur IX rikombinanti meta mqabbel ma 'Fattur IX derivat mill- plażma.
42 Structural differences of the recombinant Factor IX molecule compared with plasma derived Factor IX appear to contribute to the different recovery compared to plasma derived Factor IX.
Jidher li d- differenzi strutturali fil- molekula ta ’ Fattur IX rikombinanti meta mqabbla ma ’ Fattur IX derivat mill- plażma jikkontibwixxu għad- differenza fl - irkupru.
5.3 Preclinical safety data
42 5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurtà tal- mediċina
Non-clinical data reveal no special hazard for humans based on conventional studies of genotoxicity.
Informazzjoni li mhix klinika ma turi l- ebda periklu speċjali għall- bnedmin, ibbażata fuq studji konvenzjonali dwar l- effett tossiku fuq il- ġeni.
Solvent Sodium chloride solution
Solvent Soluzzjoni ta ’ sodium chloride
Treatment failure can occur as a consequence of human coagulation factor IX adsorption to the internal surfaces of some infusion equipment.
Falliment tal- kura jista ’ jseħħ bħala konsegwenza ta ’ assorbiment tal- fattur IX ta 'koagulazzjoni tal- bniedem fl- uċuh interni ta ’ xi tagħmir ta ’ l- infużjoni.
Store and transport refrigerated (2°C - 8°C).
Żommu kiesaħ waqt il- ħażna u l- ġarr (2ºC – 8ºC).
Do not freeze, in order to prevent damage to the prefilled syringe.
Biex ma ssirx ħsara lis- siringa mimlija għal- lest, tagħmilhiex fil- friża.
250 IU of powder in a 10 ml vial (type 1 glass) with a stopper (chlorobutyl) and a flip-off seal (aluminium) and 5 ml of solvent in a prefilled syringe (type 1 glass) with a plunger stopper (bromobutyl), a tip-cap (bromobutyl) and a sterile vial adapter reconstitution device, a sterile infusion set, two alcohol swabs, a plaster, and a gauze pad.
250 IU ta 'trab f’ kunjett ta' 10 ml (ħġieġ ta 'tip 1) b' tapp (chlorobutyl) u siġill flip- off (aluminju) u 5 ml ta' solvent f' siringa mimlija għal- lest (ħġieġ ta 'tip 1) b' tapp- planġer (bromobutyl), għatu tat- tarf (bromobutyl) u adapter sterili tal- kunjett tat- tagħmir tar- rikostituzzjoni, sett sterili ta' l- infużjoni, żewġ biċċiet bl- alkoħol biex tnaddaf, stikka, u pad tal- garża.
43 6.6 Special precautions for disposal and other handling
43 6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema u għal immaniġġar ieħor
BeneFIX is administered by intravenous (IV) injection after reconstitution of the lyophilised powder for injection with the supplied solvent (0.234% w/ v sodium chloride solution) in the pre-filled syringe.
BeneFIX jingħata permezz ta ’ injezzjoni fil- vina (ġol- vina) wara r- rikostituzzjoni tat- trab lijofilizzat għall- injezzjoni bis- solvent fornut (0. 234% soluzzjoni ta 'w/ v sodium chloride) fis- siringa mimlija għal- lest.
This should be considered during the preparation and administration of BeneFIX.
Dan għandu jiġi kkunsidrat waqt il- preparazzjoni u l- għoti ta ’ BeneFIX.
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta 'l- Aġenzija Ewropea dwar il - Mediċini (EMEA) http: // www. emea. europa. eu /.
Each vial contains nominally 500 IU nonacog alfa (recombinant coagulation factor IX).
Kull kunjett nominalment fih 500 IU ta 'nonacog alfa (fattur IX tal- koagulazzjoni rikombinanti).
After reconstitution with the accompanying 5 ml (0.234%) sodium chloride solution for injection, each ml of the solution contains approximately 100 IU nonacog alfa
Wara r- rikostituzzjoni bis- soluzzjoni għall- injezzjoni ta '5 ml (0. 234%) sodium chloride li hi pprovduta miegħu, kull 1 ml ta' soluzzjoni jkun fih madwar 100 IU ta 'nonacog alfa.
45 parameters such as half-life and recovery, as well as the clinical situation into consideration in order to adjust the dose as appropriate.
45 L- ammont li għandu jingħata u kull kemm għandu jingħata għandhom dejjem jitqiesu skond l - effettività klinika fil- każ individwali.
During the course of treatment, appropriate determination of factor IX levels is advised to guide the dose to be administered and the frequency of repeated infusions.
46 Waqt il- kors tal- kura, hu rakkomandat li jiġu stabbiliti l- livelli tal- fattur IX bħala gwida tad- doża li għandha tingħata u l- frekwenza ta ’ l- infużjonijiet ripetuti.
47 4.3 Contraindications
4. 3 Kontra- indikazzjonijiet
Additional safety and efficacy studies in paediatric patients are ongoing in previously treated, minimally treated, and previously untreated paediatric patients.
47 pedjatriċi huma għaddejjin kontinwament fuq pazjenti pedjatriċi trattati qabel, trattati minimament u dawk li mhux trattati qabel.
Posology has to be adjusted according to the pharmacokinetics of each patient.
Il- pożoloġija għandha tkun agġġustata skond il- farmakokinetiċi ta ’ kull pazjent.
In the interest of patients, it is recommended that, whenever possible, every time that BeneFIX is administered to them, the name and batch number of the product is registered.
48 Fl- interess tal- pazjenti, hu rakkomandat, li kull meta jkun possibli, kull darba li jingħatalhom BeneFIX, l- isem u n- numru tal- lott tal- prodott għandhom jiġu rreġistrati.
No interaction studies have been performed.
Ma sarux studji dwar l- effett ta ’ mediċini jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku tal- prodott
49 Nervous system disorders
Disturbi tas- sistema nervuża
Hypersensitivity/ allergic reactions
49 Sensittività eċċessiva / reazzjonijiet allerġiċi
50 Renal
Kliewi
Recombinant coagulation factor IX is a recombinant DNA-based protein therapeutic which has structural and functional characteristics comparable to endogenous factor IX.
Il -
Factor IX is activated by factor VII/ tissue factor complex in the extrinsic pathway as well as factor XIa in the intrinsic coagulation pathway.
50 fattur IX hu attivat permezz tal- kumpless tal- fattur VII/ fattur tat- tessut fil- passaġġ estrinsiku, kif ukoll permezz tal- fattur XIa fil- passaġġ intrinsiku tal- koagulazzjoni.
51 Table 1.
51 Tabella 1.
Recombinant Factor IX Summary of Pharmacokinetic Parameters for Activity Data by Month in Previously Treated Patients
Ġabra fil- qosor tal- Fattur IX Rikombinanti tal- Parametri Farmakokinetiċi għall - Informazzjoni fix- xahar dwar l- Attività f’ Pazjenti li kienu kkurati qabel Parametru
6 12 18 24
Xahar
52 48 44 43
n 56
2.3 2.2 2.0 1.8
Medja 33. 7
1.0 1.2 1.3 0.78
Medjan 31. 5
0 6 12 18 24
SD 10. 31
8.4 9.2 9.3 9.6 9.2
Medda 15. 3 – 62. 2
8.2 8.9 8.8 8.9 9.1
95% CI 30. 9, 36. 4
MRT (hrs)
Irkupru (%)
56 53 49 46 45
53 50 47 47 56
26.0 25.6 24.6 24.7 25.1
31. 8 31. 3 30. 7 31. 0 0. 75
25.8 25.3 22.2 22.7 23.9
31. 0 30. 5 28. 9 30. 6 0. 70
6.07 5.68 6.47 7.40 6.94
9. 04 8. 75 9. 24 8. 80 0. 23
24.35,27.60 24.01,27.15 22.75,26.47 22.55,26.94 23.00,27.17
15. 3 – 56. 7 16. 2 – 53. 1 12. 6 – 62. 1 16. 2 – 59. 4 0. 34 – 1. 38
Powder Sucrose Glycine L-Histidine Polysorbate 80
29. 4, 34. 3 28. 8, 33. 7 28. 0, 33. 5 28. 4, 33. 6 0. 69, 0. 81
6.3 Shelf life
Żjieda FIX
53 6.5 Nature and contents of container
53
6.6 Special precautions for disposal and other handling
0. 71
BeneFIX is administered by intravenous (IV) injection after reconstitution of the lyophilised powder for injection with the supplied solvent (0.234% w/ v sodium chloride solution) in the pre-filled syringe.
0. 69
7.
0. 20
Wyeth Europa Ltd.
0. 34 – 1. 26
MARKETING AUTHORISATION NUMBER(S)
0. 65, 0. 76
EU/ 1/ 97/ 047/ 005
(IU/ dl għal kull
9.
6
Date of first authorisation:
50
10.
0. 70
{MM/ YYYY}
0. 68
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/
0. 19
54 1.
0. 36 – 1. 18
BeneFIX 1000 IU powder and solvent for solution for injection
0. 64, 0. 75
2.
IU/ kg)
Each vial contains nominally 1000 IU nonacog alfa (recombinant coagulation factor IX).
12 18 24
Excipients:
47 47
Each vial contains 40 mg sucrose.
0. 68 0. 69 19. 3
PHARMACEUTICAL FORM
0. 64 0. 68 19. 1
CLINICAL PARTICULARS
0. 21 0. 20 4. 97
4.1 Therapeutic indications
0. 28 – 1. 38 0. 36 – 1. 32 11. 1 – 36. 4
4.2 Posology and method of administration
0. 62, 0. 74 0. 63, 0. 75 18. 0, 20. 7
Posology
Half- life ta 'l -
The dosage and duration of the substitution therapy depends on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition.
56
To ensure that the desired factor IX activity level has been achieved, precise monitoring using the factor IX activity assay is advised and doses should be calculated taking the factor IX activity, pharmacokinetic
19. 8
55 parameters such as half-life and recovery, as well as the clinical situation into consideration in order to adjust the dose as appropriate.
18. 2
The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness in the individual case.
6. 26
The number of units of factor IX administered is expressed in International Units (IU), which are related to the current WHO standard for factor IX products.
9. 6 – 38. 2
One International Unit (IU) of factor IX activity is equivalent to that quantity of factor IX in one ml of normal human plasma.
18. 1, 21. 6
Number of factor IX IU required
eliminazzjoni
=
6
X
53
desired factor IX X increase (%) or (IU/ dl)
18. 5
reciprocal of observed recovery
16. 6
For a recovery 0.8 IU/ dl (average increase of factor IX), then:
5. 89
Number of factor IX IU required
10. 6 – 33. 7
=
16. 8, 20. 2
body weight (in kg)
(sigħat)
X
12
desired factor IX X increase (%) or (IU/ dl)
49
1.3 IU/ kg
18. 9
In the case of the following haemorrhagic events, the factor IX activity should not fall below the given plasma activity levels (in% of normal or in IU/ dl) in the corresponding period.
16. 3
Degree of haemorrhage/ Type of surgical procedure Haemorrhage
7. 02
Factor IX level required (%) or (IU/ dl)
10. 7 – 38. 3
Early haemarthrosis, muscle bleeding or oral bleeding
16. 8, 21. 0
20-40
18 24
Repeat every 24 hours.
46 45
More extensive haemarthrosis, muscle bleeding or haematoma
18. 9
30-60
17. 3
Repeat infusion every 24 hours for 3- 4 days or more until pain and acute disability are resolved.
6. 84
Life-threatening haemorrhages
10. 9 – 42. 2
60-100
16. 8, 20. 9
Repeat infusion every 8 to 24 hours until threat is resolved.
AUC0- ∞
56 Degree of haemorrhage/ Type of surgical procedure Surgery
56
30-60
619. 8
Major
605. 2
80-100
155. 7
(pre- and
366. 5 – 1072. 6
until adequate wound healing, then
578. 1, 661. 5
postoperative)
(IU x hr/ dl)
There are insufficient data to recommend the use of BeneFIX in children less than 6 years of age.
6
Patients should be monitored for the development of factor IX inhibitors.
53
See also section 4.4.
579. 8
Uncommon:
562. 2
Rare:
146. 1
Nausea Vomiting
330. 9 – 900. 1
Uncommon:
539. 5, 620. 1
Cellulitis, phlebitis, injection site reaction (including burning infusion site and injection site stinging), injection site discomfort
12
Pyrexia
575. 7
Rare:
566. 0
* See additional
151. 0
information below.
290. 3 – 1080. 8
Inhibitor development
532. 4, 619. 1
60 Renal
18
5.
46
5.1 Pharmacodynamic properties
561. 8
B02BD09
560. 9
There are insufficient data to recommend the use of BeneFIX in children less than 6 years of age.
155. 6
5.2 Pharmacokinetic properties
254. 5 – 940. 8
Infusion of BeneFIX into 56 PTP patients (baseline data) with haemophilia B has shown an in vivo recovery ranging from 15 to 62% (mean 33.7 +/ - 10.3%).
515. 7, 608. 0
For a subset of the 56 patients, data are available from baseline to 24 months.
24
The pharmacokinetic data for these patients at various time points are shown in the following table:
577. 6 2. 0
61 Table 1.
551. 7 1. 5
Recombinant Factor IX Summary of Pharmacokinetic Parameters for Activity Data by Month in Previously Treated Patients
154. 7 1. 60
Parameter Recovery (%)
284. 1 – 1045. 4 0. 07 - 5. 73
Month n Mean Median SD Range 95% CI 0 56 33.7 31.5 10.31 15.3– 62.2 30.9, 36.4 6 53 31.8 31.0 9.04 15.3– 56.7 29.4, 34.3 12 50 31.3 30.5 8.75 16.2 – 53.1 28.8, 33.7 18 47 30.7 28.9 9.24 12.6– 62.1 28.0, 33.5 24 47 31.0 30.6 8.80 16.2– 59.4 28.4, 33.6
531. 1, 624. 1 1. 6, 2. 5
FIX increase (IU/ dl per IU/ kg)
Half- life
0 56 0.75 0.70 0.23 0.34– 1.38 0.69, 0.81 6 53 0.71 0.69 0.20 0.34– 1.26 0.65, 0.76 12 50 0.70 0.68 0.19 0.36 – 1.18 0.64, 0.75 18 47 0.68 0.64 0.21 0.28– 1.38 0.62, 0.74 24 47 0.69 0.68 0.20 0.36– 1.32 0.63, 0.75
2. 62
Elimination half-life (hrs)
0. 12 - 9. 98
0 56 19.3 19.1 4.97 11.1– 36.4 18.0, 20.7 6 53 19.8 18.2 6.26 9.6– 38.2 18.1, 21.6 12 49 18.5 16.6 5.89 10.6 – 33.7 16.8, 20.2 18 46 18.9 16.3 7.02 10.7– 38.3 16.8, 21.0 24 45 18.9 17.3 6.84 10.9– 42.2 16.8, 20.9
1. 5, 3. 0
AUC0- ∞ (IU × hr/ dl) Half-life
Inizzjali (sigħat)
0 56 619.8 605.2 155.7 366.5– 1072.6 578.1, 661.5 6 53 579.8 562.2 146.1 330.9– 900.1 539.5, 620.1 12 49 575.7 566.0 151.0 290.3 – 1080.8 532.4, 619.1 18 46 561.8 560.9 155.6 254.5– 940.8 515.7, 608.0 24 45 577.6 551.7 154.7 284.1– 1045.4 531.1, 624.1 0 54 2.0 1.5 1.60 0.07-5.73 1.6,2.5
2. 70
Initial Phase (hrs)
0. 13 - 14. 34
2.3 2.2 2.0 1.8
1. 8
1.0 1.2 1.3 0.78
0. 78
2.62 2.70 1.94 2.07
2. 07
0.12-9.98 0.13-14.34 0.13-6.21 0.11-7.43
0. 11 - 7. 43
1.5,3.0 1.5,3.0 1.4,2.6 1.1,2.4
1. 1, 2. 4
Clearance (ml/ hr/ kg)
Ir- rata ta 'kemm idum biex jiġi eliminat (ml/ siegħa/ kg)
8.4 9.2 9.3 9.6 9.2
8. 4 9. 2 9. 3 9. 6 9. 2
8.2 8.9 8.8 8.9 9.1
8. 2 8. 9 8. 8 8. 9 9. 1
2.01 2.48 2.53 2.85 2.40
2. 01 2. 48 2. 53 2. 85 2. 40
4.66-13.64 5.55-15.11 4.63-17.22 5.31-19.65 4.78-17.60
4. 66 - 13. 64 5. 55 - 15. 11 4. 63 - 17. 22 5. 31 - 19. 65 4. 78 - 17. 60
7.86,8.94 8.53,9.89 8.56,10.01 8.78,10.47 8.52,9.96
7. 86, 8. 94 8. 53, 9. 89 8. 56, 10. 01 8. 78, 10. 47 8. 52, 9. 96
A 28% lower recovery of recombinant BeneFIX in comparison to plasma derived Factor IX was shown.
Intwera li kien hemm tnaqqis ta '28% fl- irkupru ta' Fattur IX rikombinanti meta mqabbel ma 'Fattur IX derivat mill- plażma.
Pharmacokinetic parameters of recombinant Factor IX have also been determined after single and multiple
Il- parametri farmakokinetiċi ta ’ Fattur IX rikombinanti kienu stabbiliti wkoll wara li ngħataw dożi ġol- vina mogħtija darba u aktar fi speċi differenti.
The reconstituted product should be used immediately, but no longer than 3 hours after reconstitution.
Is- soluzzjoni rikostitwita għandha tintuża immedjatament, iżda mhux iktar tard minn 3 sigħat wara r - rikostituzzjoni.
63 6.5 Nature and contents of container
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
1000 IU of powder in a 10 ml vial (type 1 glass) with a stopper (chlorobutyl) and a flip-off seal (aluminium) and 5 ml of solvent in a prefilled syringe (type 1 glass) with a plunger stopper (bromobutyl), a tip-cap (bromobutyl) and a sterile vial adapter reconstitution device, a sterile infusion set, two alcohol swabs, a plaster, and a gauze pad.
500 IU ta 'trab f’ kunjett ta' 10 ml (ħġieġ ta 'tip 1) b' tapp (chlorobutyl) u siġill flip- off (aluminju) u 5 ml ta' solvent f' siringa mimlija għal- lest (ħġieġ ta 'tip 1) b' tapp- planġer (bromobutyl), għatu tat- tarf (bromobutyl) u adapter sterili tal- kunjett tat- tagħmir tar- rikostituzzjoni, sett sterili ta' l- infużjoni, żewġ biċċiet bl- alkoħol biex tnaddaf, stikka, u pad tal- garża.
6.6 Special precautions for disposal and other handling
53 6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema u għal immaniġġar ieħor
EU/ 1/ 97/ 047/ 006
EU/ 1/ 97/ 047/ 005
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. eu. int/
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta 'l- Aġenzija Ewropea dwar il - Mediċini (EMEA) http: // www. emea. europa. eu /.
65 1.
54 1.
BeneFIX 2000 IU powder and solvent for solution for injection.
BeneFIX 1000 IU trab u solvent għal soluzzjoni għall- injezzjoni
Each vial contains nominally 2000 IU nonacog alfa (recombinant coagulation factor IX).
Kull kunjett nominalment fih 1000 IU ta 'nonacog alfa (fattur IX tal- koagulazzjoni rikombinanti).
After reconstitution with the accompanying 5 ml (0.234%) sodium chloride solution for injection, each ml of the solution contains approximately 400 IU nonacog alfa.
Wara r- rikostituzzjoni bis- soluzzjoni għall- injezzjoni ta '5 ml (0. 234%) sodium chloride li hi pprovduta miegħu, kull 1 ml ta' soluzzjoni jkun fih madwar 200 IU ta 'nonacog alfa.
The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness in the individual case.
55 L- ammont li għandu jingħata u kull kemm għandu jingħata għandhom dejjem jitqiesu skond l - effettività klinika fil- każ individwali.
During the course of treatment, appropriate determination of factor IX levels is advised to guide the dose to be administered and the frequency of repeated infusions.
56 Waqt il- kors tal- kura, hu rakkomandat li jiġu stabbiliti l- livelli tal- fattur IX bħala gwida tad- doża li għandha tingħata u l- frekwenza ta ’ l- infużjonijiet ripetuti.
Additional safety and efficacy studies in paediatric patients are ongoing in previously treated, minimally treated, and previously untreated paediatric patients.
57 pedjatriċi huma għaddejjin kontinwament fuq pazjenti pedjatriċi trattati qabel, trattati minimament u dawk li mhux trattati qabel.
Posology has to be adjusted according to the pharmacokinetics of each patient.
Il- pożoloġija għandha tkun aġġustata skond il- farmakokinetiċi ta ’ kull pazjent.
In the interest of patients, it is recommended that, whenever possible, every time that BeneFIX is administered to them, the name and batch number of the product is registered.
58 Fl- interess tal- pazjenti, hu rakkomandat, li kull meta jkun possibli, kull darba li jingħatalhom BeneFIX, l- isem u n- numru tal- lott tal- prodott għandhom jiġu rreġistrati.
70 Nervous system disorders
Disturbi tas- sistema nervuża
information below.
59 * Ara informazzjoni oħra aktar `l isfel.
71 Renal
Kliewi
Recombinant coagulation factor IX is a single chain glycoprotein with an approximate molecular mass of 55,000 Daltons that is a member of the serine protease family of vitamin K-dependent coagulation factors.
Il- fattur IX tal- koagulazzjoni rikombinanti li huwa glikoproteina ta ’ katina waħda b’ piż molekulari ta ’ madwar 55, 000 Daltons, jagħmel parti mill- grupp ta ’ serine protease tal- fatturi ta ’ koagulazzjoni dipendenti fuq il- vitamina K tal- fattur IX tal- koagulazzjoni rikombinanti li hi proteina terapewtika bbażata fuq id- DNA