qanastek/EMEA-V3 huggingface dataset:
ReFacto AF was first authorised as ReFacto in April 1999, for use in previously treated and untreated patients with haemophilia A, based on the results of three main studies.
Għall- ewwel, ReFacto AF kien awtorizzat bħala ReFacto f’ April 1999, għal użu fuq pazjenti bl - emofilija A li diġà kienu qed jirċievu trattament kif ukoll fuq pazjenti li ma kinux qed jirċievu trattament, abbażi tar- riżultati ta ’ tliet studji ewlenin.
In February 2009, a number of changes to the way ReFacto is made were introduced.
Fi Frar 2009, ġew introdotti għadd ta ’ bidliet fil- mod kif inhu magħmul ReFacto.
These included removal of the use of a protein called albumin, which is produced from human blood, from the manufacturing process.
Dawn inkludew it - tneħħija tal- użu ta ’ proteina msejħa albumina, li hija prodotta mid- demm uman, mill- proċess tal - manifatturar.
The name of the medicine was also changed from ReFacto to ReFacto AF.
L- isem tal- mediċina wkoll inbidel minn ReFacto għal ReFacto AF.
Following these changes, the company carried out a study to show that ReFacto and ReFacto AF were treated by the body in the same way.
Wara dawn il- bidliet, il- kumpanija wettqet studju biex turi li ReFacto u ReFacto AF ġew ittrattati mill - ġisem bl- istess mod.
It also carried out two main studies looking at the effectiveness of ReFacto AF: the first looked at the prevention and treatment of bleeding episodes in 94 previously treated patients and the second looked at the prevention of bleeding in 22 patients having surgery.
Hija wettqet ukoll żewġ studji ewlenin li ffukaw fuq l- effikaċja ta ’ ReFacto AF: l- ewwel wieħed iffoka fuq il- prevenzjoni u l- trattament ta ’ każijiet ta ’ fsada f’ 94 pazjent ikkurati minn qabel u t- tieni ffoka fuq il- prevenzjoni ta ’ fsada fi 22 pazjent li kellhom intervent kirurġiku.
What benefit has ReFacto AF shown during the studies?
Liema benefiċċju wera ReFacto AF waqt l- istudji mwettqa?
The studies showed that ReFacto AF was as safe and effective as ReFacto in preventing and treating bleeding episodes in patients with haemophilia A.
L- istudji wrew li ReFacto AF kien sigur u effettiv daqs ReFacto fil- prevenzjoni u fit- trattament ta ’ każijiet ta ’ fsada f’ pazjenti bl- emofilija A.
What is the risk associated with ReFacto AF?
X’ inhu r- riskju assoċjat ma ’ ReFacto AF?
Haemophilia A patients may develop antibodies (inhibitors) to factor VIII.
Il- pazjenti bl- emofilija A jistgħu jiżviluppaw antikorpi (inibituri) għall- fattur VIII.
If this happens, ReFacto AF will not work effectively, which may result in a loss of bleeding control.
Jekk iseħħ dan, ReFacto AF ma jaħdimx b’ mod effikaċi u jista ’ jirriżulta f’ nuqqas ta ’ kontroll ta ’ fsada.
The most common side effect with ReFacto AF (seen in more than 1 patient in 10) is vomiting.
L- iktar effett sekondarju komuni b’ ReFacto AF (li deher f' iktar minn pazjent 1 minn kull 10) huwa remettar.
For the full list of all side effects reported with ReFacto AF, see the Package Leaflet.
Għal - lista sħiħa tal- effetti sekondarji kollha rrappurtata b’ ReFacto AF, ara l- Fuljett ta ’ Tagħrif.
ReFacto AF should not be used in people who may be hypersensitive (allergic) to human coagulation factor VIII, to any of the other ingredients or to hamster proteins.
ReFacto AF ma għandux jintuża f’ nies li jistgħu jkunu ipersensittivi (allerġiċi) għall- fattur VIII uman tal- għaqid tad- demm, għal xi sustanza oħra tiegħu jew għall- proteini tal- ħamsters.
Why has ReFacto AF been approved?
Għaliex ġie approvat ReFacto AF?
The Committee for Medicinal Products for Human Use (CHMP) noted that ReFacto AF was comparable to ReFacto, the original form of the medicine.
Il- Kumitat għall- Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) innota li ReFacto AF kien komparabbli għal ReFacto, il- forma oriġinali tal- mediċina.
Therefore, the Committee decided that ReFacto AF’ s benefits are greater than its risks for the treatment and prevention of bleeding in patients with haemophilia A (congenital factor VIII deficiency).
Għaldaqstant, il- Kumitat iddeċieda li l - benefiċċji ta ’ ReFacto AF huma ikbar mir- riskji tiegħu għat- trattament u l- prevenzjoni ta ’ fsada f’ pazjenti bl- emofilija A (nuqqas konġenitu tal- fattur VIII).
The Committee recommended that ReFacto AF be given marketing authorisation.
Il- Kumitat irrakkomanda li ReFacto AF jingħata awtorizzazzjoni għat- tqegħid fis- suq.
Which measures are being taken to ensure the safe use of ReFacto AF?
Liema miżuri qed jittieħdu biex jiġi żgurat l- użu sigur ta ’ ReFacto AF?
To prepare for the gradual replacement of ReFacto with ReFacto AF on the market, the company that makes the medicine will provide educational packs for healthcare workers who will prescribe or use ReFacto AF, for all associations of haemophilia patients in the European Union (EU), for patients receiving ReFacto AF and for laboratories that will monitor patients receiving ReFacto AF.
Biex tħejji għas- sostituzzjoni bil- mod il- mod ta ’ ReFacto b’ ReFacto AF fis- suq, il- kumpanja li tipproduċi l- mediċina sejra tipprovdi pakketti edukattivi għall- ħaddiema tal- kura tas- saħħa li sejrin jippreskrivu jew jużaw ReFacto AF, għall- assoċjazzjonijiet kollha tal- pazjenti li jbatu bl- emofilija fl - Unjoni Ewropea (UE), għall- pazjenti li qed jirċievu ReFacto AF u għal- laboratorji li sejrin jimmonitorjaw pazjenti li sejrin jirċievu ReFacto AF.
These packs will include information on the differences between ReFacto and ReFacto AF, how to use ReFacto AF safely, how to report side effects, information on similar medicines available outside the EU, and a reminder that patients should carry enough ReFacto AF with them if they are travelling.
Dawn il- pakketti sejrin jinkludu tagħrif fuq id - differenzi bejn ReFacto u ReFacto AF, fuq kif tuża ReFacto AF b’ mod sigur, fuq kif tirrapporta effetti sekondarji, tagħrif fuq mediċini simili disponibbli barra l- UE, u nota ta ’ tfakkir li l- pazjenti għandhom iġorru biżżejjed ReFacto AF magħhom jekk sejrin jivvjaġġaw.
Other information about ReFacto AF:
Aktar tagħrif dwar ReFacto AF:
The European Commission granted a marketing authorisation valid throughout the EU for ReFacto on 13 April 1999.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fuq is- suq valida fl- Unjoni Ewropea kollha, għal ReFacto fit- 13 ta ’ April 1999.
The marketing authorisation holder is Wyeth Europa Ltd.
Id- detentur tal- awtorizzazzjoni għat- tqegħid fis- suq huwa Wyeth Europa Ltd.
The marketing authorisation was renewed on 13 April 2004 and on 13 April 2009.
L- awtorizzazzjoni għat- tqegħid fis- suq ġiet imġedda fit- 13 ta ’ April 2004 fit- 13 ta ’ April 2009.
The name of the medicine was changed to ReFacto AF on 18 December 2008.
L- isem tal- mediċina nbidel għal ReFacto AF fit- 18 ta ’ Diċembru 2008.
The full EPAR for ReFacto AF is available here.
L- EPAR sħiħ għal ReFacto AF jista ’ jiġi kkonsultat hawn.
This summary was last updated in 04-2009.
Dan is- sommarju ġie aġġornat l- aħħar fi:
ReFacto AF 250 IU powder and solvent for solution for injection.
ReFacto AF 250 IU trab u solvent għas- soluzzjoni għall- injezzjoni.
Each vial contains nominally 250 IU* moroctocog alfa**.
Kull kunjett nominalment fih 250 IU * ta ’ moroctocog alfa **.
After reconstitution, each ml of solution contains approximately 62.5 IU moroctocog alfa.
Wara r- rikostituzzjoni, kull ml ta ’ soluzzjoni fih madwar 62. 5 IU ta ’ moroctocog alfa.
* The potency (International Units) is determined using the European Pharmacopoeia chromogenic assay.
* Il- qawwa (Unitajiet Internazzjonali) hi stabbilita fuq it- testijiet kromoġeniċi tal- Farmakopoea Ewropea.
The specific activity of ReFacto AF is 7,600-13,800 IU/ mg protein.
L- attività speċifika ta ’ ReFacto AF hi ta ’ 7, 600- 13, 800 IU/ mg proteina.
** Human coagulation factor VIII produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells.
** Fattur VIII tal- koagulazzjoni umana, magħmul minn teknoloġija tad- DNA rikombinanti f’ ċelluli tal- ovarju tal- ħamster Ċiniż (CHO).
Moroctocog alfa is a glycoprotein with 1438 amino acids with a sequence that is comparable to the 90 + 80 kDa form of factor VIII (i. e.
Moroctocog alfa hu glikoproteina b’ 1438 aċidi amminiċi b’ sekwenza ta ’ aċidi amminiċi li hi komparabbli mal- għamla ta ’ 90+ 80 kDa tal- fattur VIII (i. e.
B-domain deleted) and similar post-translational modifications to those of the plasma-derived molecule.
B - domain mħassar), u modifikazzjoniet ta ’ wara l- bidla, simili għal molekula derivata mill- plażma.
The manufacturing process for ReFacto has been modified to eliminate any exogenous human- or animal-derived protein in the cell culture process, purification, or final formulation; and at the same time the invented name has been changed to ReFacto AF.
Il- proċess tal- manifattura għal ReFacto kien modifikat biex tiġi eliminata kwalunkwe proteina esoġenika umana jew li hi derivata mill- annimali fil- proċess tal- koltura taċ- ċelluli, purifikazzjoni, jew il- formulazzjoni finali; u fl- istess ħin l- isem inventat inbidel għal ReFacto AF.
After reconstitution, 1.23 mmol (29 mg) sodium per vial.
Wara r- rikostituzzjoni, 1. 23 mmol (29 mg) ta ’ sodium f’ kull kunjett.
Powder and solvent for solution for injection.
Trab u solvent għas- soluzzjoni għall- injezzjoni.
White to off-white cake/ powder.
Kejk/ trab abjad sa offwajt.
Clear, colourless solvent.
Solvent ċar u bla kulur.
Treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency).
Kura u prevenzjoni ta ’ emorraġija ta ’ demm f’ pazjenti li għandhom emofilja A (nuqqas konġenitali tal- fattur VIII).
ReFacto AF is appropriate for use in adults and children of all ages, including newborns.
ReFacto AF hu adattat għall- użu fl- adulti u t- tfal ta ’ kull età, li jinkludu trabi tat- twelid.
ReFacto AF does not contain von Willebrand factor, and hence is not indicated in von Willebrand’ s disease.
ReFacto AF m’ għandux il- fattur von Willebrand u għalhekk m’ huwiex użat għall- marda von Willebrand.
Treatment should be initiated under the supervision of a physician experienced in the treatment of haemophilia A.
Il- kura għandha tinbeda taħt is- superviżjoni ta ’ tabib li għandu esperjenza fil- kura ta ’ l- emofilja A.
2 The labelled potency of ReFacto AF is based on the European Pharmacopoeial chromogenic substrate assay, in which the manufacturing potency standard has been calibrated to the WHO International Standard using the chromogenic substrate assay.
2 Il- qawwa tikkettata ta ’ ReFacto AF hi bbażata fuq l- assaġġ tas- substrat kromoġeniku tal - Pharmacopoeia Ewropea, li fih il- qawwa standard tal- manifattura kien ikkalibrat mal- Istandard Internazzjonali tal- WHO billi ntuża l- assaġġ tas- substrat kromoġeniku.
When monitoring patients' factor VIII activity levels during treatment with ReFacto AF, use of the European Pharmacopoeial chromogenic substrate assay is strongly recommended.
Meta jsir monitoraġġ tal- livelli tal- attività ta ’ fattur VIII fil- pazjenti waqt il- kura b’ ReFacto AF, l- użu tal- assaġġ tas- substrat kromoġeniku tal- Pharmacopoeia Ewropea hu rakkomandat bil- qawwi.
The chromogenic assay yields results which are higher than those observed with use of the one-stage clotting assay.
L- assaġġ kromoġeniku jagħti riżultati li huma ogħla minn dawk osservati bl- użu tal- assaġġ tat- tagħqid tad- demm ta ’ stadju wieħed.
Typically, one-stage clotting assay results are 20-50% lower than the chromogenic substrate assay results.
Tipikament, ir- riżultati tal- assaġġ tat- tagħqid tad- demm ta ’ stadju wieħed huma 20- 50% iktar baxxi mir- riżultati tal- assaġġ tas- substrat kromoġeniku.
The ReFacto AF laboratory standard can be used to correct for this discrepancy (see section 5.2).
L- istandard tal- laboratorju ta ’ ReFacto AF jista ’ jintuża biex jikkoreġi din id- diskrepanza (ara sezzjoni 5. 2).
Another moroctocog alfa product approved for use outside Europe has a different potency assigned using a manufacturing potency standard that has been calibrated to the WHO International Standard using a one-stage clotting assay; this product is identified by the tradename XYNTHA.
Prodott ieħor ta ’ moroctocog alfa approvat għall- użu barra mill- Ewropa għandu qawwa differenti assenjata bl- użu ta ’ standard tal- qawwa tal- manifattura li kien ikkalibrat għall- Istandard Internazzjonali tal- WHO billi ntuża l- assaġġ tat- tagħqid tad- demm ta ’ stadju wieħed; dan il- prodott hu identifikat mill- isem kummerċjali XYNTHA.
Due to the difference in methods used to assign product potency of XYNTHA and ReFacto AF, 1 IU of the XYNTHA product (one-stage assay calibrated) is approximately equivalent to 1.38 IU of the ReFacto AF product (chromogenic assay calibrated).
Minħabba d- differenza fil- metodi użati biex jassenjaw il- qawwa tal- prodott ta ’ XYNTHA u ReFacto AF, 1 IU tal- prodott XYNTHA (assaġġ ikkalibrat ta ’ stadju wieħed) hi ekwivalenti għal madwar 1. 38 IU tal- prodott ReFacto AF (assaġġ ikkalibrat kromoġeniku).
If a patient normally treated with XYNTHA is prescribed ReFacto AF, the treating physician may consider adjustment of dosing recommendations based on factor VIII recovery values.
Jekk pazjent normalment ikkurat b’ XYNTHA jingħata riċetta għal ReFacto AF, it - tabib li jkun qed jikkurah jista ’ jikkunsidra aġġustament tar- rakkomandazzjonijiet tad- dożaġġ ibbażata fuq il- valuri tal- irkupru ta ’ fattur VIII.
Based on their current regimen, individuals with haemophilia A should be advised to bring an adequate supply of factor VIII product for anticipated treatment when travelling.
Ibbażat fuq il- kors attwali tagħhom, individwi li jkollhom l- emofilja A għandhom jingħataw parir biex jieħdu magħhom provvista adegwata ta ’ prodott ta ’ fattur VIII għall- kura antiċipata meta jkunu qed jivvjaġġaw.
Patients should be advised to consult with their healthcare provider prior to travel.
Il- pazjenti għandhom jingħataw parir biex ikellmu lill- fornitur tal- kura tas- saħħa tagħhom qabel ma jivvjaġġaw.
The dosage and duration of the substitution therapy depend on the severity of the factor VIII deficiency, on the location and extent of bleeding, and on the patient’ s clinical condition.
Id- dożaġġ u l- perjodu ta ’ l- użu tat- terapija ta ’ sostituzzjoni jiddependu minn kemm hi qawwija d - defiċjenza tal- fattur VIII, minn fejn issir u kemm iddum l- emorraġija, u mill- kundizzjoni klinika tal - pazjent.
Doses administered should be titrated to the patient's clinical response.
Id- dożi mogħtija għandhom ikunu ttitrati eżatt skond ir- rispons kliniku tal- pazjent.
In the presence of an inhibitor, higher doses or appropriate specific treatment may be required.
Dożi aktar għoljin jew kura speċifika jistgħu jkunu bżonjużi fil- preżenza ta ’ inibitur.
The number of units of factor VIII administered is expressed in International Units (IUs), which are related to the current WHO standard for factor VIII products.
Il- kwantità mkejla tal- fattur VIII mogħtija hija dik espressa f’ Unitajiet Internazzjonali (IU), li hija relatata ma ’ l- istandard użati mill- WHO għall- prodotti ta ’ fattur VIII.
Factor VIII 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 VIII in plasma).
L- attività ta ’ fattur VIII fil - plażma hi espressa jew bħala perċentwali (ir- relazzjoni mal- plażma normali tal- bniedem) jew f’ Unitajiet Internazzjonali (ir- relazzjoni ma ’ l- Istandard Internazzjonali għall- fattur VIII fil- plażma).
One International Unit (IU) of factor VIII activity is equivalent to the quantity of factor VIII in one ml of normal human plasma.
Unità Internazzjonali (IU) waħda tal- attività tal- fattur VIII hi ekwivalenti għall- kwantità tal- fattur VIII f’ ml wieħed tal- plażma normali tal- bniedem.
The calculation of the required dosage of factor VIII is based upon the empirical finding that 1 International Unit (IU) of factor VIII per kg body weight raises the plasma factor VIII activity by 2 IU/ dl.
Il- kalkulazzjoni tad- doża meħtieġa tal- fattur VIII hi bbażata fuq sejbiet esperimentali li juru li Unità Internazzjonali (IU) waħda tal- fattur VIII għal kull kilogramm ta ’ piż tal- ġisem tgħolli l- attività tal- plażma tal- fattur VIII b’ 2 IU/ dl.
The required dosage is determined using the following formula:
Id- doża meħtieġa hi determinata bl- użu tal- kalkulazzjoni li ġejja:
Required units (IU) = body weight (kg) x desired factor VIII rise (% or IU/ dl) x 0.5 (IU/ kg per IU/ dl), where 0.5 IU/ kg per IU/ dl represents the reciprocal of the incremental recovery generally observed following infusions of factor VIII.
Unitajiet meħtieġa (IU) = il- piż tal- ġisem (kg) x kemm irid jogħla l- fattur VIII (% jew IU/ dl) x 0. 5 (IU/ kg għal kull IU/ dl) fejn 0. 5 IU/ kg kull IU/ dl jirrappreżenta r- reċiproku tal- irkupru inkrementali ġeneralment osservat wara l- infużjonijiet ta ’ fattur VIII.
The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness in the individual case.
L- ammont li għandu jiġi mogħti u l- frekwenza ta ’ l- għoti ta ’ ReFacto għandhom ikunu bbażati ma ’ l- effiċjenza klinika tal- każ individwali.
In the case of the following haemorrhagic events, the factor VIII activity should not fall below the given plasma levels (in% of normal or in IU/ dl) in the corresponding period.
F’ dawn il- każijiet ta ’ emorraġija ta ’ demm, l- attività tal- fattur VIII m’ għandhiex taqa ’ taħt il- livelli tal- plażma mogħtija (f ’% tan- normali jew f’ IU/ dl) fil- perjodu respettiv.
The following table can be used to guide dosing in bleeding episodes and surgery:
It- tabella li ġejja tista ’ tintuża bħala gwida għad- dożi f’ każijiet ta ’ emorraġija ta ’ demm jew f’ operazzjonijiet.
3 Degree of haemorrhage/ Type of surgical procedure
Grad ta ’ telf ta ’ demm /
Factor VIII level required (% or IU/ dl)
Fattur VIII (% jew
Frequency of doses (hours)/ Duration of therapy (days)
(sigħat) / Id- dewmien tat- terapija
Haemorrhage
Telf ta ’ demm
Early haemarthrosis, muscle bleeding or oral bleeding
3 Emartrosi bikrija, muskolu jnixxi d- demm jew demm ħiereġ mill- ħalq.
Repeat every 12-24 hours.
Irrepeti kull 12- 24 siegħa.
At least 1 day until the bleeding episode as indicated by pain is resolved or healing is achieved.
Għall- anqas għal ġurnata waħda sakemm l- episodju tat- tnixxija tad- demm, kif indikat bl - uġigħ, hu riżolt, jew il- fejqan hu miksub.
More extensive haemarthrosis, muscle bleeding or haematoma
Emartrosi aktar estensiva, muskolu jnixxi d- demm jew tumur tad- demm.
30-60
60- 100
Repeat infusion every 12-24 hours for 3-4 days or more until pain and acute disability are resolved.
Irrepeti l- infużjoni kull 8- 24 siegħa sakemm il- periklu hu riżolt.
Life-threatening haemorrhages
Operazzjonijiet
Minor, including tooth extraction
Minuri inkluż qlugħ ta ’ snien
30-60
30- 60 80- 100
Every 24 hours, at least 1 day, until healing is achieved.
Kull 24 siegħa għall- inqas għal ġurnata waħda sakemm il- fejqan iseħħ.
80-100 (pre- and post-operative)
(qabel u wara l- operazzjoni)
Repeat infusion every 8-24 hours until adequate wound healing, then therapy for at least another 7 days to maintain a factor VIII activity of 30% to 60% (IU/ dl).
sakemm tfiq il- ġerħa, u agħti aktar terapija mill- anqas għall- 7 ijiem oħra sabiex tinżamm l- attività tal- fattur VIII minn 30% sa 60% (IU/ dl).
During the course of treatment, appropriate determination of factor VIII levels is advised to guide the dose to be administered and the frequency of repeated infusions.
Matul il- kors tal- kura, hu rakkomandat li d- doża li għandha tiġi mogħtija, u l- frekwenza ta ’ infużjonijiet ripetuti, skond riżultati tat- testijiet tal- livelli ta ’ fattur VIII.
In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor VIII activity) is indispensable.
Hu indispensabbli li fil- każ ta ’ interventi kirurġiċi maġġuri, ikun hemm osservazzjoni preċiża tat- terapija mibdula, permezz ta ’ l - analiżi ta ’ koagulazzjoni (l- attivà tal- fattur VIII fil- plażma).
Individual patients may vary in their response to factor VIII, achieving different levels of in vivo recovery and demonstrating different half-lives.
Pazjenti individwali jistgħu jvarjaw fir - rispons tagħhom għall- fattur VIII, u jiksbu livelli differenti fil- fejqan tagħhom in vivo, u juru half- lives differenti.
For long-term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses are 20 to 40 IU of factor VIII per kg body weight at intervals of 2 to 3 days.
Id- dożi frekwenti li jingħataw f’ każ ta ’ prevenzjoni għall- żmien fit- tul kontra l- emorraġija ta ’ demm f’ pazjenti li għandhom emofilja A severa, huma bejn 20 sa 40 IU ta ’ fattur VIII għal kull kg piż tal - ġisem f’ intervalli ta ’ bejn 2 sa 3 ijiem.
In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary.
F’ xi kazijiet, speċjalment f’ pazjenti iżgħar, l- intervall ta ’ bejn doża u oħra għandu jonqos, jew dożi ogħla jistgħu jkunu neċessarji.
Patients using factor-VIII replacement therapy are to be monitored for the development of factor VIII inhibitors.
Il- pazjenti li jużaw it- terapija tas- sostituzzjoni ta ’ fattur VIII għandhom ikunu taħt osservazzjoni għall - iżvilupp ta ’ inibituri ta ’ fattur VIII.
If expected factor VIII activity plasma levels are not attained, or if bleeding is not controlled with an appropriate dose, an assay should be performed to determine if factor VIII inhibitors are present.
Jekk il- livelli ta ’ l- attività tal- fattur VIII fil- plażma mistennija ma jintlaħqux, jew jekk l- emorraġija ta ’ demm ma tkunx ikkontrollata b’ doża adegwata, għandha ssir analiżi sabiex jiġi stabbilit jekk hemmx preżenti xi inibituri ta ’ fattur VIII.
Data from clinical trials indicated that if inhibitors are present at levels less than 10 Bethesda Units (BUs), administration of additional antihaemophilic factor may neutralise the inhibitors.
Id- dejta minn provi kliniċi indikat li jekk l- inibituri jinsabu f’ livelli ta ’ inqas minn 10 Unitajiet Bethesda (BU), l- għoti ta ’ fattur addizzjonali antiemofiliku jista ’ jinnewtralizza l- inibituri.
In patients with levels of inhibitor above 10 BU, factor VIII therapy may not be effective and other therapeutic options should be considered.
F’ pazjenti b’ livelli għoljin ta ’ inibitur ta ’ iktar minn 10 BU, it- terapija ta ’ fattur VIII tista ’ ma tkunx effettiva u għandhom jiġu kkunsidrati għażliet terapewtiċi oħra.
Management of such patients should be directed by physicians with experience in the care of patients with haemophilia (see section 4.4).
Dawn il- pazjenti għandhom ikunu taħt superviżjoni ta ’ tobba b’ esperjenza fil- kura ta ’ pazjenti b’ emofilja (ara sezzjoni 4. 4).
Renal or hepatic impairment Dosage adjustment for patients with renal or hepatic impairment has not been studied in clinical trials.
Indeboliment renali jew epatiku Aġġustament fid- dożaġġ għal pazjenti b’ indeboliment renali jew epatiku ma kienx studjat fi provi kliniċi.
4 Paediatric patients Safety and efficacy studies with ReFacto have been performed both in previously treated children and adolescents (n=31, ages 8-18 years) and in previously untreated neonates, infants and children (n=101, ages < 1-52 months).
Pazjenti pedjatriċi Studji dwar is- sigurtà u effikaċja b’ ReFacto twettqu kemm fi tfal u adolexxenti li kienu kkurati qabel (n=31, età 8- 18- il sena), kif ukoll fi trabi tat- twelid, trabi u tfal li ma kinux ikkurati qabel (n=101, età < 1- 52 xahar).
The need for an increased dose relative to that used for adults and older children should be anticipated when treating younger children with ReFacto AF.
Il- ħtieġa għal żieda fid- doża meta mqabbla ma ’ dik użata għall- adulti u tfal li għandhom iktar żmien, għandha tiġi antiċipata meta tikkura tfal iżgħar b’ ReFacto AF.
In a study of ReFacto in children less than 6 years of age, pharmacokinetic analysis revealed half-life and recovery less than that observed in older children and adults (see section 5.2).
Fi studju ta ’ ReFacto fit- tfal ta ’ inqas 4 minn 6 snin, l- analiżi farmakokinetika żvelat half- life u rkuprar li kien inqas minn dak osservat fit- tfal li kellhom iktar żmien u fl- adulti (ara sezzjoni 5. 2).
During the clinical trials, children less than 6 years of age on a prophylaxis regimen used an average dose of 50 IU/ kg of ReFacto and experienced an average of 6.1 bleeding episodes per year.
Matul il- provi kliniċi, it- tfal ta ’ inqas minn 6 snin fuq kors ta ’ profilassi użaw doża medja ta ’ 50 IU/ kg ta ’ ReFacto u kellhom medja ta ’ 6. 1 episodji ta ’ emorraġija kull sena.
Older children and adults on a prophylaxis regimen used an average dose of 27 IU/ kg and experienced an average of 10 bleeding episodes per year.
Tfal akbar u adulti fuq kors ta ’ profilassi użaw doża medja ta ’ 27 IU/ kg u kellhom medja ta ’ 10 episodji ta ’ emorraġiji kull sena.
In a clinical trial setting the mean dose per infusion of ReFacto for bleeding episodes in children less than 6 years of age was higher than the mean dose administered to older children and adults (51.3 IU/ kg and 29.3 IU/ kg, respectively).
Fi sfond ta ’ prova klinika, id- doża medja ta ’ kull infużjoni ta ’ ReFacto għal episodji ta ’ ħruġ tad- demm fi tfal ta ’ inqas minn 6 snin kienet ogħla mid- doża medja mogħtija lil tfal li kellhom iktar żmien u adulti (51. 3 IU/ kg u 29. 3 IU/ kg, rispettivament).
ReFacto AF is administered by intravenous injection over several minutes after reconstitution of the lyophilised powder for injection with sodium chloride 9 mg/ ml (0.9%) solution for injection (provided).
ReFacto AF jingħata b’ injezzjoni ġol- vina fuq perjodu ta ’ diversi minuti wara li t- trab lajofilizzat għall- injezzjoni jiġi rikostitwit f’ 9 mg/ ml (0. 9%) ta ’ sodium chloride, soluzzjoni għall- injezzjoni (pprovdut).
The rate of administration should be determined by the patient’ s comfort level.
Ir- rata ta ’ l- għoti ta ’ ReFacto għandha tkun determinata skond il- livell ta ’ kumdità tal - pazjent.
Appropriate training is recommended for non-healthcare professionals administering the product.
Taħriġ adattat hu rakkomandat għal persuni professjonisti li mhumiex fil- qasam tal- kura tas- saħħa li jagħtu l- prodott.
In the interest of patients, it is recommended that every time ReFacto AF is administered, the name and batch number of the product should be recorded.
Fl- interess tal- pazjenti, hu rakkomandat li kull darba li jingħata ReFacto AF, l- isem u n- numru tal- lott tal- prodott għandhom jiġu rreġistrati.
For reconstitution instructions prior to administration, see section 6.6.
Għal istruzzjonijiet dwar ir- rikostituzzjoni qabel l- għoti, ara sezzjoni 6. 6.
Hypersensitivity to the active substance or to any of the excipients.
Sensittività eċċessiva għas- sustanzi attivi jew għal sustanzi mhux attivi.
Hypersensitivity to hamster proteins.
Sensittività eċċessiva għall- proteini tal- ħamster.
As with any intravenous protein product, allergic-type hypersensitivity reactions are possible.
Kull prodott li ġej minn proteina u li jingħata ġol- vina, jista ’ jikkaġuna reazzjonijiet ta ’ sensittivà eċċessiva minħabba allerġija.
The product contains traces of hamster proteins.
Il- prodott għandu traċċi ta ’ proteini tal- ħamster.
Patients should be informed of the early signs of hypersensitivity reactions (including hives, generalised urticaria, tightness of the chest, wheezing, hypotension) and anaphylaxis.
Il- pazjenti għandhom ikunu avżati bl- ewwel sinjali ta ’ reazzjonijiet ta ’ sensittività eċċessiva (li jinkludu ħorriqija, urtikarja ġenerali, rass fis- sider, tisfir fis- sider, pressjoni baxxa) u anafilassi.
If allergic or anaphylactic reactions occur, administration of ReFacto AF is to be discontinued immediately, and an appropriate treatment must be initiated.
Jekk ir- reazzjonijiet allerġiċi jew anafilattiċi jitfaċċaw, l- għoti ta ’ ReFacto AF għandu jitwaqqaf immedjatament, u tinbeda kura adegwata.
In case of shock, the current medical standards for treatment of shock are to be observed.
Fil- każ ta ’ xokk, għandhom jiġu osservati l- istandards kurrenti tal- kura għax- xokk.
Patients are to be advised to discontinue use of the product and contact their physician or seek immediate emergency care, depending on the type and severity of the reaction, if any of these symptoms occur.
Jekk x’ uħud minn dawn is- sintomi jseħħu, l- pazjenti għandhom ikunu avżati biex jieqfu jużaw il- prodott u sabiex jikkuntattjaw it- tabib jew ifittxu immedjatament kura ta ’ emerġenza, skond it- tip u s- severità tar- reazzjoni.
The formation of neutralising antibodies (inhibitors) to factor VIII is a known complication in the management of individuals with haemophilia A.
Il- formazzjoni ta ’ antikorpi li jinnewtralizzaw (inibituri) għal Fattur VIII hi komplikazzjoni magħrufa fl- immaniġġjar ta ’ individwi b’ emofilja A.
These inhibitors are usually IgG immunoglobulins directed against the factor VIII procoagulant activity, which are quantified in Bethesda Units (BUs) per ml of plasma using the Nijmegen modification of the Bethesda assay.
Dawn l- inibituri x’ aktarx huma immunoglobulini IgG immirati kontra l- attività prokoagulanti tal- Fattur VIII, li huma kkwantifikati f’ Unitajiet Bethesda (BU) għal kull ml ta ’ plażma meta tintuża l- modifikazzjoni ta ’ Nijmegen tal- assaġġ ta ’ Bethesda.
The risk of developing inhibitors is correlated to the exposure to factor VIII, this risk being highest within the first 20 exposure days.
Dan ir- riskju hu l- ogħla fl - ewwel 20 jum ta ’ espożizzjoni.
Inhibitors have been observed in previously treated patients receiving factor VIII products, including ReFacto AF.
L- inibituri kienu osservati f’ pazjenti li kienu kkurati qabel u li jkunu qed jirċievu prodotti ta ’ fattur VIII, li jinkludu ReFacto AF.
Cases of recurrence of inhibitors (low titre) have been observed after switching from one recombinant factor VIII product to another in previously treated patients with more than 100 exposure days who have a history of inhibitor development.
Każijiet ta ’ rikorrenza ta ’ inibituri (tajter baxx) kienu osservati wara l- bidla minn prodott ta ’ fattur rikombinanti VIII għal ieħor f’ pazjenti li kienu kkurati qabel b’ aktar minn 100 jum ta ’ espożizzjoni, li kellhom passat mediku ta ’ żvilupp ta ’ inibitur.
Patients treated with
Rapporti ta ’ nuqqas ta ’ effett, primarjament f’ pazjenti tal- profilassi, kienu riċevuti fil- provi kliniċi u fl -
5 recombinant coagulation factor VIII should be carefully monitored for the development of inhibitors by appropriate clinical observations and laboratory tests (see also section 4.8).
5 isfond ta ’ wara t- tqegħid fis- suq ta ’ ReFacto.
The reported lack of effect with ReFacto has been described as bleeding into target joints, bleeding into new joints or a subjective feeling by the patient of new onset bleeding.
In- nuqqas ta ’ effett irrappurtat b’ ReFacto kien deskritt bħala ħruġ ta ’ demm ġol- ġogi fil- mira, ħruġ ta ’ demm ġo ġogi ġodda jew sensazzjoni suġġettiva mill - pazjent ta ’ episodju ġdid ta ’ ħruġ ta ’ demm.
When prescribing ReFacto AF it is important to individually titrate and monitor each patient's factor level in order to ensure an adequate therapeutic response.
Meta tingħata riċetta għal ReFacto AF hu importanti li tagħmel titrazzjoni individwali u jsir monitoraġġ tal- livell tal- fattur ta ’ kull pazjent biex jiġi żgurat rispons terapewtiku adegwat.
In the interest of patient safety, it is recommended that every time ReFacto AF is administered, the name on the carton and batch number of the product are recorded.
Fl- interess tas- sigurtà tal- pazjent, hu rakkomandat li kull darba li ReFacto AF jingħata, l- isem fuq il - kartuna u n- numru tal- lott tal- prodott jiġu rrekordjati.
Patients can affix one of the peel- off labels found on the vial to document the batch number in their diary or for reporting any side effects.
Il- pazjenti jistgħu jwaħħlu waħda mit- tikketti li jistgħu jinqalgħu li hemm fuq il- kunjett biex jiktbu n- numru tal- lott fid- djarju tagħhom jew biex jirrappurtaw xi effetti sekondarji.
After reconstitution this medicinal product contains 1.23 mmol (29 mg) sodium per vial, to be taken into consideration by patients on a controlled sodium diet.
Wara r- rikostituzzjoni, dan il- prodott mediċinali fih 1. 23 mmol (29 mg) ta ’ sodium f’ kull kunjett, u dan il- fatt irid jiġi kkunsidrat minn pazjenti li qegħdin fuq dieta kkontrollata tas- sodium.
Animal reproduction studies have not been conducted with factor VIII.
Ma sarux studji tar- riproduzzjoni ta ’ l- annimali għal Fattur VIII.
Because of the rare occurrence of haemophilia A in women, experience regarding the use of factor VIII during pregnancy and breast- feeding is not available.
Minħabba l- okkorrenza rari tal - emofilja A fin- nisa, m’ hemmx l- esperjenza rigward l- użu ta ’ fattur VIII matul it- tqala u t- treddigħ.
Therefore, factor VIII should be used during pregnancy and lactation only if clearly indicated.
Għalhekk, fattur VIII għandu jintuża matul it- tqala u t- treddigħ meta dan hu biss indikat b’ mod ċar.
Factor VIII inhibition
Inibizzjoni għall- Fattur VIII
The occurrence of neutralising antibodies (inhibitors) to factor VIII is well known in the treatment of patients with haemophilia A.
L- okkorrenza ta ’ antikorpi li jinnewtralizzaw (inibituri) il- fattur VIII hu fatt magħruf sewwa fil- kura ta ’ pazjenti b’ emofilja A.
As with all coagulation factor VIII products, patients are to be monitored for the development of inhibitors that are to be titrated in Bethesda Units (BUs) using the Nijmegen modification of the Bethesda assay.
Bħal fil- każ tal- prodotti kollha ta ’ fattur VIII tal- koagulazzjoni, il- pazjenti għandhom ikunu mmonitorjati għall- iżvilupp ta ’ inibituri li jridu jkunu ttitrati f’ Unitajiet Bethesda (BUs) bl- użu tal- modifikazzjoni ta ’ Nijmegen tal- assaġġ ta ’ Bethesda.
If such inhibitors occur, the condition may manifest itself as an insufficient clinical response.
Jekk jiżviluppaw dawn l - inibituri, il- kundizzjoni tista ’ tidher bħala rispons kliniku insuffiċjenti.
In such cases, it is recommended that a specialised haemophilia centre be contacted.
F’ każijiet bħal dawn, hu rakkomandat li ċentru speċjalizzat ta ’ l- emofilja jiġi kkuntattjat.
In a clinical study with ReFacto AF in previously treated patients (PTPs), the incidence of factor VIII inhibitors was the primary safety endpoint.
Fi studju kliniku b’ ReFacto AF f’ pazjenti li kienu kkurati qabel (PTPs), l- inċidenza ta ’ inibituri ta ’ fattur VIII kienet il- punt aħħari tas- sigurtà primarja.
Two clinically silent, low-titre, transient inhibitors were observed in 94 patients with a median exposure of 76 exposure days (ED, range 1-92), corresponding to 2.2% of the 89 patients with at least 50 ED.
Żewġ inibituri temporanji, klinikament silenzjużi, u b’ tajter baxx, kienu osservati f’ 94 pazjent b’ medjan ta ’ espożizzjoni ta ’ 76 jum ta ’ espożizzjoni (ED, medda 1- 92), li jikkorrispondu għal 2. 2% tad- 89 pazjent b’ mill- inqas 50 ED.
In a supporting study of ReFacto AF, 1 de novo and 2 recurrent inhibitors (all low-titre, central laboratory determination) were observed in 110 patients; median exposure of 58 ED (range 5-140) and 98 patients had at least 50 ED to ReFacto AF.
Fi studju ta ’ appoġġ ta ’ ReFacto AF, inibitur 1 de novo u 2 inibituri rikorrenti (kollha b’ tajter baxx, determinazzjoni ta ’ laboratorju ċentrali) kienu osservati f’ 110 pazjenti; medjan ta ’ espożizzjoni ta ’ 58 ED (medda 5- 140) u 98 pazjent kellhom mill- inqas 50 ED għal ReFacto AF.
Ninety-eight (98) of the original 110 patients continued treatment in a second supportive study and had subsequent extended exposure to ReFacto AF with a median of 169 additional ED (range 9-425).
Tmienja u disgħin (98) mill- 110 pazjenti oriġinali komplew il- kura fit- tieni studju ta ’ appoġġ u kellhom espożizzjoni estiża sussegwenti għal ReFacto AF b’ medjan ta ’ 169 ED addizzjonali (medda 9- 425).
One (1) additional low-titre de novo inhibitor was observed.
Inibitur wieħed (1) addizzjonali de novo b’ tajter baxx kien osservat.
The frequency of inhibitors observed in these studies is within the expected range.
Il- frekwenza tal- inibituri osservati f’ dawn l- istudji hi fil- medda mistennija.
In a clinical study with ReFacto in PTPs, 1 inhibitor was observed in 113 patients.
Fi studju kliniku b’ ReFacto f’ PTPs, inibitur 1 kien osservat f’ 113- il pazjent.
Also, there have been spontaneous post-marketing reports of high-titre inhibitors involving previously treated patients.
Kien hemm ukoll rapporti spontanji wara t- tqegħid fis- suq ta ’ inibituri b’ tajters għoljin li kienu jinvolvu pazjenti li kienu kkurati qabel.
6 There are no clinical data on previously untreated patients (PUPs) with ReFacto AF.
6 M’ hemm l- ebda dejta klinika dwar pazjenti li ma kinux ikkurati qabel (PUPs) b’ ReFacto AF.
However, clinical trials are planned in previously untreated patients (PUPs) with ReFacto AF.
Madankollu, provi kliniċi huma ppjanati f’ pazjenti li ma kinux ikkurati qabel (PUPs) b’ ReFacto AF.
In a clinical trial, 32 out of 101 (32%) previously untreated patients (PUPs) treated with ReFacto developed inhibitors:
Fi prova klinika, 32 minn 101 (32%) pazjenti li ma kinux ikkurati qabel (PUPs) u ġew ikkurati b’ ReFacto, żviluppaw inibituri:
16 out of 101 (16%) with a titre > 5 BU and 16 out of 101 (16%) with a titre ≤ 5 BU.
16 minn 101 (16%) b’ tajter ta ’ > 5 BU u 16 minn 101 (16%) b’ tajter ta ’ ≤ 5 BU.
The median number of exposure days up to inhibitor development in these patients was 12 (range 3-49).
In- numru medjan ta ’ jiem ta ’ espożizzjoni sal- iżvilupp tal- inibitur f’ dawn il- pazjenti kien ta ’ 12 (medda 3- 49).
Of the 16 patients with high titres, 15 received immune tolerance (IT) treatment.
Mis- 16- il pazjent b’ tajters għoljin, 15 irċivew kura ta ’ tolleranza immuni (IT).
Of the 16 patients with low titres, IT treatment was started in 10.
Mis- 16- il pazjent b’ tajters baxxi, il- kura IT inbdiet f’ 10 minnhom.
IT had an efficacy of 73% for patients with high titres and 90% for those with low titres.
L- IT kellha effikaċja ta ’ 73% għal pazjenti b’ tajters għoljin u 90% għal dawk b’ tajters baxxi.
For all 101 treated PUPs, regardless of inhibitor development, the median number of exposure days is 197 (range 1-1299).
Għall- 101 pazjenti kollha PUPs li kienu kkurati, irrispettivament mill- iżvilupp tal- inibitur, in- numru medjan ta ’ jiem ta ’ espożizzjoni hu ta ’ 197 (medda 1- 1299).
Adverse reactions based on experience from clinical trials with ReFacto or ReFacto AF are presented in the table below by system organ class.
Reazzjonijiet avversi bbażati fuq esperjenza minn provi kliniċi b’ ReFacto jew ReFacto AF huma ppreżentati fit- tabella hawn taħt skond il- klassi ta ’ l- organu tas- sistema.
These frequencies have been estimated on a per-patient basis and are described using the following categories: very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); and uncommon (≥ 1/ 1,000 to < 1/ 100).
Dawn il- frekwenzi ġew stmati fuq bażi ta ’ kull pazjent u huma deskritti billi jintużaw il- kategoriji li ġejjin: komuni ħafna (≥1/ 10); komuni (≥1/ 100 sa < 1/ 10); u mhux komuni (≥1/ 1, 000 sa < 1/ 100).
Frequency of Occurrence per Patient with ReFacto or ReFacto AF
Frekwenza ta ’ Okkorrenza għal kull Pazjent b’ ReFacto jew ReFacto AF
System Organ Class
Sistema tal- Klassi tal -
Uncommon
Organi
(≥ 1/ 1,000 to < 1/ 100)
(≥1/ 1, 000 sa < 1/ 100)
Blood and lymphatic disorders Metabolism and nutrition disorders
Inibituri ta ’ Fattur VIII Disturbi tad- demm u
Factor VIII inhibitors - PUPs
Fattur VIII - PUPs
Factor VIII inhibitors - PTPs
Disturbi fil - metaboliżmu u n - nutrizzjoni
Nervous system disorders Cardiac disorders
Disturbi fis- sistema nervuża
Neuropathy, dizziness, somnolence, dysgeusia Angina pectoris, tachycardia, palpitations
Anġina pectoris, takikardija, palpitazzjonijiet
Haemorrhage/ Haematoma
Emorraġija / Ematoma
Hypotension, thrombophlebitis, vasodilatation, flushing
Pressjoni baxxa, tromboflebite, vażodilatazzjoni, fwawar
Nausea
Nawseja
Abdominal pain, diarrhoea
Uġigħ addominali, dijarea
Urticaria, pruritis, rash, hyperhidrosis
Urtikarja, ħakk, raxx, iperidrosi
Musculoskeletal, connective tissue and bone disorders
Disturbi muskolu - skeltrali u tal - connective tissue u tal - għadam
Myalgia
Mijalġja
General disorders and administration site conditions Investigations
Disturbi ġenerali u kundizzjonijiet ta ’ mnejn jingħata
Asthenia, pyrexia
Astenja, deni
Chills/ feeling cold, injection site inflammation, injection site reaction, injection site pain Aspartate aminotransferase increased, alanine aminotransferase increased, blood bilirubin increased, blood creatine phosphokinase increased
Żieda f’ aspartate aminotransferase, żieda f’ alanine aminotransferase, żieda fil- bilirubina fid- demm, żieda fil- creatine phosphokinase fid- demm
Surgical and medical procedures
Proċeduri kirurġiċi u mediċi
Vascular access complication
Komplikazzjoni fl - aċċess vaskulari
One event of cyst in an 11-year old patient and one event described as confusion in a 13-year old patient have been reported as possibly related to ReFacto AF treatment.
Avveniment wieħed ta ’ ċesta f’ pazjent ta ’ 11- il sena u avveniment wieħed deskritt bħala konfużjoni f’ pazjent ta ’ 13- il sena, kienu rrappurtati bħala li kienu possibbilment marbuta mal- kura b’ ReFacto AF.
7 Safety of ReFacto AF was evaluated in previously treated children and adolescents (n=18, age 12-16 in a study and n=49, age 7-16 in a supporting study).
Is- sigurtà ta ’ ReFacto AF kienet evalwata fi tfal u adolexxenti li kienu kkurati qabel (n=18, età 12- 16 fi studju, u n=49, età 7- 16 fi studju ta ’ appoġġ).
Although a limited number of children have been studied, there is a tendency for higher frequencies of adverse events in children aged 7-16 as compared to adults.
Għalkemm numru limitat ta ’ tfal kienu studjati, hemm tendenza għal frekwenzi ogħla ta ’ avvenimenti avversi fit- tfal ta ’ bejn 7 u 16- il sena meta mqabbel mal- adulti.
A clinical trial evaluating use of moroctocog alfa (AF-CC) in children less than 6 years of age is on going.
Prova klinika li evalwat l- użu ta ’ moroctocog alfa (AF- CC) fi tfal ta ’ inqas minn 6 snin għadha għaddejja.
The following adverse events have also been reported for ReFacto: paraesthesia, fatigue, blurred vision, acne, gastritis, gastroenteritis, and pain.
L- avvenimenti avversi li ġejjin kienu rrappurtati wkoll għal ReFacto: parestesija, għeja kbira, vista mċajpra, akne, gastrite, gastroenterite, u wġigħ.
Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the infusion site, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed infrequently for ReFacto, and may in some cases progress to severe anaphylaxis including shock (see section 4.4).
Sensittività eċċessiva u reazzjonijiet allerġiċi (li jistgħu jinkludu anġjodema, ħruq u tingiż fil- post ta ’ l- infużjoni, reżħat, sħanat żejda, urtikarja ġenerali, uġigħ ta ’ ras, ħorriqija, pressjoni baxxa, telqa, nawsja, nuqqas ta ’ sabar, takikardija, għafis fis- sider, tingiż, rimettar, tisfir fis- sider) dehru mhux ta ’ spiss għal ReFacto u jistgħu f’ xi każijiet jaggravaw għal anafilassi severa inkluż xokk (ara sezzjoni 4. 4).
Trace amounts of hamster protein may be present in ReFacto AF.
Traċċi tal- proteini tal- ħamsters jistgħu jkunu preżenti f’ ReFacto AF.
Very rarely, development of antibodies to hamster protein has been observed, but there were no clinical sequelae.
L- iżvilupp ta ’ antikorpi għall - proteini tal- ħamsters kien osservat b’ mod rari ħafna, iżda ma kien hemm l- ebda konsegwenzi kliniċi.
In a study of ReFacto, twenty of 113 (18%) PTPs had an increase in anti-CHO antibody titre, without any apparent clinical effect.
Fi studju dwar ReFacto, għoxrin mill- 113 (18%) tal- PTPs kellhom żieda fit- tajter ta ’ l- antikorpi anti - CHO, mingħajr l- ebda effett kliniku apparenti.
If any reaction takes place that is thought to be related to the administration of ReFacto AF, the rate of infusion is to be decreased or the infusion stopped, as dictated by the response of the patient (see section 4.4).
Jekk ikun hemm xi reazzjoni li hi maħsuba li hi relatata ma ’ l- amministrazzjoni ta ’ ReFacto AF, ir- rata ta ’ l- infużjoni għandha titnaqqas jew l- infużjoni għandha titwaqqaf, skond ir- rispons tal- pazjent (ara sezzjoni 4. 4).
Pharmacotherapeutic group: antihaemorrhagics, blood coagulation factor VIII; ATC code:
Kategorija farmakoterapewtika: mediċini kontra l- emoraġġija, fattur VIII tal- koagulazzjoni tad- demm; Kodiċi ATC:
ReFacto AF contains B-domain deleted recombinant coagulation factor VIII (moroctocog alfa).
ReFacto AF fih il- fattur tal- koagulazzjoni rikombinanti VIII (moroctocog alfa) bid- dominju B imħassar.
It is a glycoprotein with an approximate molecular mass of 170,000 Da consisting of 1438 amino acids.
Hu glikoproteina b’ massa molekulari ta ’ bejn wieħed u ieħor ta ’ 170, 000 Da magħmula
ReFacto AF has functional characteristics comparable to those of endogenous factor VIII.
ReFacto AF għandu karatteristiċi funzjonali komparabbli ma ’ dawk ta ’ fattur VIII endoġeniku.
Factor VIII activity is greatly reduced in patients with haemophilia A, and, therefore, replacement therapy is necessary.
L- attività ta ’ fattur VIII hi mnaqqsa ħafna f’ pazjenti bl- emofilja A, u, għalhekk, hemm bżonn ta ’ terapija biex tagħmel tajjeb għal dan in- nuqqas.
When infused into a haemophiliac patient, factor VIII binds to the von Willebrand factor present in the patient’ s circulation.
Meta l- prodott jingħata f’ pazjenti bl- emofilja, il- fattur VIII jingħaqad mal- fattur von Willebrand preżenti fiċ- ċirkulazzjoni tal- pazjent.
Activated factor VIII acts as a cofactor for activated factor IX, accelerating the conversion of factor X to activated factor X.
Il- fattur attivat VIII jaħdem bħala kofattur attiv għal fattur attiv IX u jaċċelera l- konverżjoni minn fattur X għal fattur X attivat.
Activated factor X converts prothrombin into thrombin.
Il- fattur X attivat jibdel prothrombin fi thrombin.
Thrombin then converts fibrinogen into fibrin, and a clot is formed.
Thrombin imbagħad tbiddel il- fibrinoġen f’ fibrin u tifforma embolu tad- demm.
Haemophilia A is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor VIII: C and results in profuse bleeding into joints, muscles or internal organs, either spontaneously or as a result of accidental or surgical trauma.
Din tirriżulta f’ emorraġija qawwija ta ’ demm fil- ġogi, muskoli, jew organi interni, spontanjament jew bħala riżultat ta ’ trawma aċċidentali jew ta ’ l- operazzjonijiet.
By replacement therapy, the plasma levels of factor VIII are increased, thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies.
Bit- terapija tas- sostituzzjoni, il- livelli tal- fattur VIII fil- plażma jiżdiedu, u b’ hekk dan jikkoreġi temporanjament id- defiċjenza tal- fattur u jikkoreġi t- tendenzi tat- tnixxija tad- demm.
Pharmacokinetic properties of ReFacto, derived from a cross-over study of ReFacto and a plasma- derived FVIII concentrate, using the chromogenic substrate assay (see section 4.2), in 18 previously treated patients are listed in the table below.
Il- proprjetajiet farmakokinetiċi ta ’ ReFacto, miskuba minn studju cross- over ta ’ ReFacto u ta ’ konċentrat FVIII derivat mill- plażma, bl- użu tal- assaġġ ta ’ substrat kromoġeniku (ara sezzjoni 4. 2), fi 18- il pazjent li kienu kkurati qabel, huma elenkati fit- tabella hawn taħt.
Pharmacokinetic parameter estimates for ReFacto in previously treated patients with haemophilia A PK parameter
Stimi tal- parametri farmakokinetiċi għal ReFacto f’ pazjenti li kienu kkurati qabel u li għandhom l - emofilja A.
Mean
Medja
AUCt (IU· h/ ml)
AUCt (IU: siegħa/ ml) t1/ 2 (sigħat)
19.9
19. 9 14. 8
4.9
4. 9 5. 6
19.9
19. 9 12. 7
t1/ 2 (h) CL (ml/ h· kg) MRT (h) K-value
CL (ml/ siegħa: kg) MRT (siegħa) Valur K
14.8 2.4 20.2
0. 75 7. 4
5.6 0.75 7.4
2. 3 18. 0
(IU/ dl increase in FVIII: C per IU/ kg FVIII given)
(IU/ dl żieda fi FVIII: C kull IU/ kg FVIII mogħti)
Abbreviations:
Taqsiriet:
AUCt = area under the plasma concentration-time curve from zero to the last measurable concentration; t½ = half-life; CL = clearance; MRT = mean residence time; K-value = incremental recovery; SD = standard deviation
AUCt = żona taħt il- kurva konċentrazzjoni- ħin minn żero sal- aħħar konċentrazzjoni li tista ’ titkejjel; t½ = half- life; CL = tneħħija; MRT = ħin medju tar- residenza; valur K = irkuprar inkrementali; SD = devjazzjoni standard