qanastek/EMEA-V3 huggingface dataset:
Long term treatment with Filgrastim ratiopharm may be required to maintain a normal number of white cells in your blood.
Jista ’ jkun hemm bżonn ta ’ kura b’ Filgrastim ratiopharm fit- tul sabiex jinżammu livelli normali ta ’ l- għadd ta ’ ċelluli bojod f’ demmek.
Filgrastim ratiopharm and peripheral blood stem cell mobilisation If you are donating stem cells for yourself, the usual dose is 0.5 million to 1 million international units (MIU) per kilogram bodyweight each day.
Filgrastim ratiopharm u mobilizzazzjoni ta ’ ċelluli proġenitriċi tad- demm periferali Jekk inti donatur ta ’ PBPC għalik innifsek, id- doża li tintuża komunement hija 0. 5 miljun sa 1 miljun international units (MIU) għal kull kilogramm ta ’ piż tal- ġisem, kuljum.
Filgrastim ratiopharm treatment will last for up to 2 weeks and in exceptional cases longer.
Kura b’ Filgrastim ratiopharm ser idum sa ġimgħatejn jew, f’ każijiet eċċezzjonali, anki iktar.
Filgrastim ratiopharm treatment will last for 4 to 5 days.
Kura b’ Filgrastim ratiopharm ser jieħu minn 4 sa 5 ijiem.
If you use more Filgrastim ratiopharm than you should If you use more Filgrastim ratiopharm than you should, contact your doctor or pharmacist as soon as possible.
Jekk tuża Filgrastim ratiopharm aktar milli suppost Jekk tuża Filgrastim ratiopharm aktar milli suppost, għandek tgħarraf lit- tabib jew l- ispiżjar tiegħek mill- iktar fis possibbli.
If you forget to use Filgrastim ratiopharm Do not use a double dose to make up for a forgotten injection.
Jekk tinsa tuża Filgrastim ratiopharm M’ għandekx tieħu doża doppja biex tpatti għal kull doża li tkun insejt tieħu.
If you stop using Filgrastim ratiopharm Before you stop using Filgrastim ratiopharm, talk to your doctor.
Jekk tieqaf tuża Filgrastim ratiopharm Qabel ma tieqaf tuża Filgrastim ratiopharm, tkellem mat- tabib tiegħek.
Like all medicines, Filgrastim ratiopharm can cause side effects, although not everybody gets them.
Bħal kull mediċina oħra, Filgrastim ratiopharm jista ’ jkollu effetti sekondarji, għalkemm ma jidhrux fuq kulħadd.
more than 1 user in 10 1 to 10 users in 100 1 to 10 users in 1,000 1 to 10 users in 10,000 less than 1 user in 10,000 frequency cannot be estimated from the available data.
anqas minn 1 minn kull 10, 000 pazjent ma tistax tittieħed stima mid- data disponibbli
If you think you are having this type of reaction, stop your Filgrastim ratiopharm injection and get medical help immediately.
Jekk taħseb li qed ikollok xi reazzjoni minn dawn, waqqaf l- injezzjoni ta ’ Filgrastim ratiopharm u fittex għajnuna medika immedjatament.
It is important that you contact your doctor immediately if you experience pain in the upper left side of the abdomen or left shoulder pain since this may relate to a problem with your spleen.
Huwa importanti li tgħarraf lit- tabib tiegħek immedjatament jekk jkollok uġigħ fin- naħa ta 'fuq fix- xellug ta' l- addome jew ikollok uġigħ fl- ispalla xellugija, peress li dan jista 'jkun relatat ma' problema fil- milza tiegħek.
If you have Sickle Cell Disease, make sure that you tell your doctor before you start taking Filgrastim ratiopharm.
Jekk tbati mill- marda ta ’ Sickle Cell, kun żgur li tgħarraf it- tabib tiegħek qabel ma tibda kura b’ Filgrastim ratiopharm.
HOW TO STORE Filgrastim ratiopharm
KIF TAĦŻEN Filgrastim ratiopharm
Do not use Filgrastim ratiopharm after the expiry date which is stated on the outer carton and on the pre-filled syringe after EXP.
Tużax Filgrastim ratiopharm wara d- data ta ’ skadenza li tidher fuq il- kartuna u fuq is- siringa mimlija għal- lest wara “ JIS ”.
Do not use Filgrastim ratiopharm if you notice it is cloudy or there are particles in it.
Tużax Filgrastim ratiopharm jekk tinnota li s- soluzzjoni mhix ċara jew jekk hemm xi frak fiha.
56 Medicines should not be disposed of via wastewater or household waste.
Il- mediċini m’ għandhomx jintremew ma ’ l- ilma tad- dranaġġ jew ma ’ l- iskart domestiku.
What Filgrastim ratiopharm contains
X’ fih Filgrastim ratiopharm:
Filgrastim ratiopharm 30 MIU/ 0.5 ml:
Filgrastim ratiopharm 30 MIU/ 0. 5ml:
Filgrastim ratiopharm 48 MIU/ 0.8 ml:
Filgrastim ratiopharm 48 MIU:
You will find detailed information about the ingredient sorbitol (a sugar) in section 2. under the heading “ Important information about some of the ingredients of Filgrastim ratiopharm”.
Tista ’ ssib informazzjoni dettaljata dwar l- ingredjent sorbitol (tip ta ’ zokkor) f’ sezzjoni 2 taħt it - titlu “ Tagħrif importanti dwar xi wħud mis- sustanzi ta ’ Filgrastim ratiopharm ”.
What Filgrastim ratiopharm looks like and contents of the pack Filgrastim ratiopharm is a solution for injection or infusion in a pre-filled syringe.
Filgrastim ratiopharm huwa soluzzjoni għall- injezzjoni jew infużjoni ġo siringa mimlija għal- lest.
Filgrastim ratiopharm is a clear and colourless solution.
Filgrastim ratiopharm huwa soluzzjoni ċar u mingħajr kulur.
Filgrastim ratiopharm are supplied in packs of 1, 5 or 10 pre-filled syringes or multipacks of 10 (2 packs of 5) pre-filled syringes.
Filgrastim ratiopharm jiġi f’ pakketti ta ’ 1, 5 jew 10 siringi mimlijin għal- lest jew f’ pakkett multiplu ta’ 10 (2 pakketti ta ’ 5).
Marketing Authorisation Holder ratiopharm GmbH Graf-Arco-Straße 3 D-89079 Ulm Germany info@ratiopharm. de
Id- Detentur ta ’ l- Awtorizzazzjoni għat- tqegħid fis- Suq: ratiopharm GmbH Graf- Arco- Straße 3 D- 89079 Ulm Il- Ġermanja info@ ratiopharm. de
Κύπρος ratiopharm GmbH, Γερμανία Τηλ: +49 731 402 02
Sverige Κύπρος ratiopharm AB ratiopharm GmbH, Γερμανία Τηλ: +49 731 402 02
Sverige ratiopharm AB Tel: +46 42 37 0740
Tel: +46 42 37 0740
This section contains information on how to give yourself an injection of Filgrastim ratiopharm.
Din il- parti tal- fuljett fiha tagħrif dwar kif tagħti injezzjoni ta ’ Filgrastim ratiopharm lilek innifsek.
It is important that you do not try to give yourself the injection unless you have received special training
Huwa importanti li ma tippruvax tagħti l- injezzjoni lilek innifsek jekk ma tkunx irċevejt taħriġ speċjali mingħand it- tabib jew infermiera tiegħek.
How do I inject Filgrastim ratiopharm myself?
Kif ninjetta Filgrastim ratiopharm lili innifsi?
- a pre-filled syringe of Filgrastim ratiopharm,
- siringa mimlija għal- lest b’ Filgrastim ratiopharm;
What should I do before I give myself a subcutaneous injection of Filgrastim ratiopharm?
X’ għandi nagħmel qabel ma ninjetta lili nnifsi taħt il- ġilda b’ Filgrastim ratiopharm?
Take your Filgrastim ratiopharm pre-filled syringe out of the refrigerator.
Oħroġ s- siringa mimlija għal- lest b’ Filgrastim ratiopharm mill- friġġ.
Check the appearance of Filgrastim ratiopharm.
Iċċekkja d- dehra ta ’ Filgrastim ratiopharm.
Do not warm Filgrastim ratiopharm in any other way (for example, do not warm it in a microwave or in hot water).
Issaħħanx Filgrastim ratiopharm bl’ ebda mod ieħor (eżempju: issaħħanx fil- forn majkrowejv jew f’ ilma jaħraq).
Find a comfortable, well-lit place and put everything you need where you can reach them (the Filgrastim ratiopharm pre-filled syringe, alcohol wipes and the puncture-proof container).
(is- siringa mimlija għal- lest b’ Filgrastim ratiopharm, msielaħ ta ’ l- alkoħol u r- reċipjent li ma jitaqqabx).
How do I prepare my Filgrastim ratiopharm injection?
Kif nipprepara l- injezzjoni ta ’ Filgrastim ratiopharm?
Before you inject Filgrastim ratiopharm you must do the following:
Qabel ma tinjetta ratiogratim trid tagħmel dan li ġej:
59 2.
2
Push the plunger up to the number (ml) on the syringe that matches the dose of Filgrastim ratiopharm that your doctor prescribed.
Imbotta l- planġer san- numru (ml) fuq it- tubu tas- siringa li jikkorispondi mad- doża ta ’ Filgrastim ratiopharm preskritta mit- tabib tiegħek.
Check again to make sure the correct dose of Filgrastim ratiopharm is in the syringe.
Erġa iċċekkja li hemm id- doża preskritta ta’ Filgrastim ratiopharm fis- siringa.
It is better to change the injection site every day to avoid the risk of soreness at any one site.
60 Tajjeb li kuljum tibdel is- sit fejn tingħata l- injezzjoni sabiex tnaqqas ir- riskju ta ’ uġigħ f’ xi sit partikolari.
Do not use any Filgrastim ratiopharm that is left in the syringe.
M’ għandekx tuża xi Filgrastim ratiopharm li jkun baqa ’ fis- siringa.
Filgrastim ratiopharm does not contain any preservative.
Filgrastim ratiopharm ma fihx l- ebda preservattiv.
In view of the possible risk of microbial contamination, Filgrastim ratiopharm syringes are for single use only.
Minħabba r- riskju potenzjali ta ’ kontaminazzjoni bil- mikrobi, is- siringi ta ’ Filgrastim ratiopharm iridu jintużaw darba biss.
Accidental exposure to freezing temperatures does not adversely affect the stability of Filgrastim ratiopharm.
61 L- esposizzjoni bi żball għal temperatura ta ’ friża ma jeffettwax ħażin l- istabilita` ta ’ Filgrastim ratiopharm.
Filgrastim ratiopharm should not be diluted with sodium chloride solution.
Filgrastim ratiopharm m’ għandux jiġi dilwit ma ’ soluzzjoni ta ’ sodium chloride.
If required, Filgrastim ratiopharm may be diluted in glucose 50 mg/ ml (5%) solution for infusion.
Jekk ikun hemm bżonn, Filgrastim ratiopharm jista ’ jiġi dilwit f’ soluzzjoni għal infużjoni ta ’ glucose 50 mg/ ml (5%).
Only clear solutions without particles should be used.
Is - soluzzjoni għanha tintuża biss jekk tkun ċara u mingħajr frak.
61 After dilution:
Wara d- dilwit:
Chemical and physical in-use stability of the diluted solution for infusion has been demonstrated for 24 hours at 2 °C to 8 °C.
Stabilità kimika u fiżika waqt l- użu tas- soluzzjoni rikostitwita kienet demostrata għal 24 siegħa f’ temperatura ta ’ 2°C - 8°C.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 °C to 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.
Jekk ma jintużax immedjatament, il- perjodu u l- kundizzjonijiet tal- ħażna qabel l- użu huma r- responsabilità ta ’ min jużah u normalment ma jkunx ta ’ iktar minn 24 siegħa f’ temperatura ta ’ bejn 2 °C – 8 °C, sa kemm rrikostituzzjoni ma sseħħx f’ kundizzjonijiet kontrollati u validati asettiċitament.
What is Firazyr?
X’ inhu Firazyr?
Firazyr is a solution for injection that contains the active substance icatibant.
Firazyr hu soluzzjoni għall- injezzjoni li fiha s- sustanza attiva icatibant.
What is Firazyr used for?
Għal x' hiex jintuża Firazyr?
Firazyr is used to treat the symptoms of attacks of hereditary angioedema in adults.
Firazyr huwa wżat sabiex jittratta s- sintomi ta ’ attakki ta ’ anġjodemija ereditarja f’ adulti.
Patients with angioedema have attacks of swelling that can occur anywhere in the body, such as in the face or limbs, or around the gut, causing discomfort and pain. ‘ Hereditary ’ means that the disease is caused by the patient ’ s genes.
Pazjenti b’ anġjodemija jkollhom attakki ta ’ nefħiet li jistgħu jitilgħu f’ kull part ital- ġisem, bħal fil- wiċċ jew fir - riġlejn u fid- dirgħajn, jew madwar il- musrana, li jikkawwżaw skumdità u uġiegħ. ‘ Ereditarja ’ tfisser li l- marda hija kkawwżata mill- ġene tal- pazjenti.
Firazyr is used in patients whose angioedema is linked to naturally low levels of a protein called ‘ C1 esterase inhibitor’.
Firazyr huwa wżat f’ pazjenti li l- enġjodemija hija marbuta ma ’ livelli baxxi naturali ta ’ proteina msejħa ‘ inibitur esterażi C1 ’.
Because the number of patients who have hereditary angioedema is low, the disease is considered ‘ rare’, and Firazyr was designated an ‘ orphan medicine ’ (a medicine used in rare diseases) on 17 February 2003.
Billi l- għadd ta 'pazjenti li jbatu minn anġjodemija ereditarja huwa wieħed baxx, il- marda hija meqjusa' rari ', u Firazyr ġie ikkategorizzat bħala' mediċina orfni '(mediċina użata fil- mardiet rari) fis- 17 ta' Frar 2003.
How is Firazyr used?
Kif jintuża Firazyr?
Firazyr is given as a slow injection under the skin by a doctor or nurse, preferably in the abdomen (tummy).
Firazyr jingħata bħala injezzjoni taħt il- ġilda minn tabib jew infermier, preferibbilment fil- parti addominali (fiż- żaqq).
The recommended dose of Firazyr is one injection.
Id- doża rakkomandata ta ’ Firazyr hija injezzjoni waħda.
If symptoms continue or come back, a second injection can be given after six hours.
Jekk is- sintomi jippersistu jew jerġgħu jitfaċċaw, it- tieni injezzjoni tista ’ tingħata wara sitt sigħat.
If needed, treatment can be repeated for a third time after an additional six hours.
Jekk meħtieġ it - trattament jista ’ jiġi repetut għat- tielet darba wara sitt sigħat addizzjonali.
No more than three injections should be given in any 24-hour period.
Ma għandhomx jingħataw aktar minn tliet injezzjonijiet f’ perjodu ta ’ 24 siegħa.
Firazyr has not been tested in children.
Firazyr ma ġiex ittestjat fit- tfal.
How does Firazyr work?
Kif jaħdem Firazyr?
Patients with hereditary angioedema have high levels of a substance called ‘ bradykinin’, which is involved in causing inflammation and swelling.
Pazjenti b’ anġjodemija ereditarja jkollhom livelli għoljin ta ’ sustanza msejjħa ‘ bradykinin ’, li tikkawwża infjammazzjoni u nefħa.
The active substance in Firazyr, icatibant, blocks the receptors that bradykinin normally attaches itself to.
Is- sustanza attiva icatibant f’ Firazyr timblokka r- riċetturi li normalment bradykinin jeħel magħhom.
This blocks the activity of bradykinin, helping to relieve the symptoms of the disease.
Dan jimblokka l- attività ta ’ bradykinin billi jgħin sabiex jittaffew is- sintomi tal- marda.
How has Firazyr been studied?
Kif ġie studjat Firazyr?
The effects of Firazyr were first tested in experimental models before being studied in humans.
L- effetti ta ’ Firazyr għall- ewwel ġew ittestjati f’ mudelli esperimentali qabel ma ’ ġew studjati fil - bniedem.
Firazyr has been studied in two main studies in patients with angioedema of the skin or the abdomen.
Firazyr ġie studjat f’ żewġ studji prinċipali f’ pazjenti b’ anġjodemija tal- ġilda jew addominali.
The first study compared Firazyr with tranexamic acid (another medicine used for this disease) in 74
L- ewwel studju qabbel Firazyr ma ’ l- aċidu traneksamiku (mediċina oħra użata għal din il- marda) f’ 74 pazjent, u
Reproduction is authorised provided the source is acknowledged. patients, and the second study compared Firazyr with placebo (a dummy treatment) in 56 patients.
Reproduction is authorised provided the source is acknowledged. t- tieni studju qabbel Firazyr ma ’ plaċebo (trattament finta) f’ 56 pazjent.
The main measure of effectiveness was how long it took until the patient’ s symptoms were relieved.
Il- kejl prinċipali ta ’ effikaċja kien ibbażat fuq kemm żmien huwa meħtieġ sabiex jittaffew is- sintomi tal- pazjent.
What benefit has Firazyr shown during the studies?
Liema benefiċċju wera Firazyr waqt l- istudji li ġew mwettqa?
Firazyr was more effective than tranexamic acid and placebo in controlling the symptoms of the disease.
Firazyr kien aktar effettiv mill- aċidu traneksemiku u l- plaċebo fil- kontroll ta ’ sintomi tal- marda.
In both studies, the time it took for the patient ’ s symptoms to improve was shorter for patients taking Firazyr than for those taking tranexamic acid or placebo.
Fiż - żewġ studji, iż- żmien li dam il- pazjent sabiex is- sintomi jameljoraw kien aqsar għal pazjenti li jieħdu Firazyr milli f’ dawk li jieħdu l- aċidu traneksamiku jew plaċebo.
Patients experienced relief an average of 2.0 to 2.5 hours after receiving Firazyr, compared with 12.0 hours after receiving tranexamic acid and 4.6 hours after receiving placebo.
Pazjenti esperjenzaw serħan u tafija ma ’ sagħtejn sa sagħtejn u nofs wara li jirċievu Firazyr, imqabbel ma ’ 12 – il siegħa wara li rċieva l - aċidu traneksemiku u 4. 6 sigħat wara li jirċievi placebo.
What is the risk associated with Firazyr?
X’ inhu r- riskju assoċjat ma ’ Firazyr?
The most common side effects with Firazyr (seen in more than 1 patient in 10) are erythema (redness), swelling, a warm sensation, burning, itching and pain.
L- aktar effetti sekondarji komuni b’ Firazyr (murija f’ aktar minn pazjent wieħed minn 10) huma eritema (ħmura), nefħiet, sensazzjoni ta ’ sħana, ħruq, ħakk u uġiegħ.
For the full list of all side effects reported with Firazyr, see the Package Leaflet.
Għal- lista sħiħa ta 'l- effetti sekondarji rrappurtati ma' Firazyr, ara l- Fuljett ta 'Tagħrif.
Firazyr should not be used in people who may be hypersensitive (allergic) to icatibant or to any of the other ingredients.
Firazyr m' għandux jintuża minn persuni li jkunu ipersensittivi allerġiċi għal icatibant jew għal xi sustanza oħra tiegħu.
Why has Firazyr been approved?
Għaliex ġie approvata Firazyr?
The Committee for Medicinal Products for Human Use (CHMP) decided that Firazyr’ s benefits are greater than its risks for the symptomatic treatment of acute attacks of hereditary angioedema in adults.
Il- Kumitat għall- Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) iddeċieda li Firazyr għandu iktar benefiċċji milli riskji fit- trattament ta ’ attakki akuti ta ’ anġjodemija ereditarja f’ adulti.
The Committee recommended that Firazyr be given marketing authorisation.
Il- Kumitat irrakkomanda li Firazyr jingħata awtorizzazzjoni għat- tqegħid fis- suq.
Other information about Firazyr:
Informazzjoni oħra dwar Firazyr:
The European Commission granted a marketing authorisation valid throughout the European Union for Firazyr to Jerini AG on 11 July 2008.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida madwar l- Unjoni Ewropea kollha għal Firazyr lil Jerini AG fl- 11 ta ’ Lulju 2008.
The summary of opinion of the Committee for Orphan Medicinal Products for Firazyr is available here.
Is- sommarju ta ’ l- opinjoni tal- Kumitat għal Prodotti Mediċinali Orfni għal Firazyr huwa disponibbli minn hawnhekk.
The full EPAR for Firazyr can be found here.
L- EPAR sħiħ għal CRIXIVAN jista ’ jiġi kkonsultat hawnhekk
EMEA Number
Numru ta ’ l- EMEA
Subcutaneous use
Taħt il- ġilda
pre-filled syringe (glass)
Siringa mimlija minn qabel (ħġieġ)
1 pre-filled syringe + 1 needle
Siringa mimlija minn qabel + labra
Firazyr 30 mg solution for injection in pre-filled syringe
Firazyr 30 mg soluzzjoni għal injezzjoni f’ siringa mimlija għal- lest
Each pre-filled syringe of 3 ml contains icatibant acetate equivalent to 30 mg icatibant.
Kull siringa mimlija għal- lest ta ’ 3 ml fiha icatibant acetate ekwivalenti għal 30 mg icatibant.
Each ml of the solution contains 10 mg of icatibant.
Kull 1 ml tas- soluzzjoni fih 10 mg ta ’ icatibant.
For a full list of excipients see section 6.1.
Għal- lista sħiħa ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
Solution for injection.
Soluzzjoni għal injezzjoni.
The solution is a clear and colourless liquid.
Is- soluzzjoni hija likwidu ċar u mingħajr lewn.
Firazyr is indicated for symptomatic treatment of acute attacks of hereditary angioedema (HAE) in adults (with C1-esterase-inhibitor deficiency).
Firazyr huwa indikat għat- trattament sintomatiku ta ’ attakki akuti ta ’ anġjoedema ereditarja (HAE) fl - adulti b’ defiċjenza fl- inibitur C1 esterażi..
The recommended dose of Firazyr is one subcutaneous injection of 30 mg administered by a health care professional, preferably in the abdominal area, for the treatment of a hereditary angioedema attack.
Id- doża rakkomandata ta ’ Firazyr hija injezzjoni waħda ta ’ 30 mg taħt il- ġilda mogħtija minn professjonist tal- kura tas- saħħa, preferibbilment fiż- żona addominali, għat- trattament ta ’ anġjoedema ereditarja.
Firazyr is not for self-administration.
Finazyr m’ huwiex maħsub sabiex il- pazjent jinjetta lilu nnifsu
For single use only.
Firazyr huwa maħsub għal użu taħt il- ġilda. Għal użu singolu biss.
Patients with laryngeal attacks need to be carefully managed in an appropriate medical institution after injection until the physician considers discharge to be safe.
Pazjenti b’ attakki tal- larinġi jridu jiġu kkurati b’ attenzjoni f’ istituzzjoni medika xierqa wara l - injezzjoni sakemm it- tabib jikkunsidra r- rilaxx tagħhom bħala mingħajr periklu.
Injection should be given slowly due to the large volume to be administered (3 ml).
L- injezzjoni għandha tingħata bil- mod minħabba l- volum kbir li jrid jingħata (3 ml).
In the majority of cases a single injection of Firazyr is sufficient to treat an attack.
Fil- maġġoranza tal- każijiet, injezzjoni waħda ta ’ Firazyr hija biżżejjed biex tikkura attakk.
In case of insufficient relief or recurrence of symptoms, a second injection of Firazyr can be administered after 6 hours.
F’ każ ta ’ solljev insuffiċjenti jew rikorrenza tas- sintomi, tista ’ tingħata injezzjoni oħra ta ’ Firazyr wara sitt sigħat.
If the second injection produces insufficient relief or a recurrence of symptoms is observed, a third injection of Firazyr can be administered after a further 6 hours.
Jekk it- tieni injezzjoni tipproduċi solljev insuffiċjenti jew tiġi osservata rikorrenza tas- sintomi, tista ’ tingħata t- tielet injezzjoni ta ’ Firazyr wara 6 sigħat oħra.
No more than 3 injections of Firazyr should be administered in a 24 hour period.
M’ għandhomx jingħataw aktar minn 3 injezzjonijiet ta ’ Firazyr f’ perjodu ta ’ 24 siegħa.
In the clinical trials, not more than 8 injections of Firazyr per month have been administered.
Fil- provi kliniċi, ma ngħatawx aktar minn 8 injezzjonijiet ta ’ Firazyr fix- xahar.
Children and adolescents There is no experience in children.
Tfal u adoloxxenti M’ hemmx esperjenza dwar l- użu fit- tfal.
Elderly patients Limited information is available on patients older than 65 years of age.
Pazjenti anzjani Hemm informazzjoni limitata dwar pazjenti ta ’ ’ l fuq minn 65 sena.
Elderly patients have been shown to have increased systemic exposure to icatibant.
Pazjenti anzjani wrew li għandhom esponiment sistemiku akbar għal icatibant.
The relevance of this to the safety of Firazyr is unknown (see section 5.2).
Mhix magħrufa r - rilevanza ta ’ dan għas- sigurtà ta ’ Firazyr (ara sezzjoni 5. 2).
2 Hepatic impairment No dosage adjustment is required in patients with hepatic impairment.
2 Indeboliment epatiku M’ hemmx bżonn ta ’ aġġustament fid- doża f’ pazjenti b’ indeboliment epatiku.
Renal impairment No dosage adjustment is required in patients with renal impairment.
Indeboliment tal- fwied M’ hemmx bżonn ta ’ aġġustament fid- doża f’ pazjenti b’ indeboliment tal- fwied.
Hypersensitivity to the active substance or to any of the excipients.
Ipersensittività għas- sustanza attiva jew għal xi sustanzi mhux attivi.
Ischemic heart disease Under ischemic conditions, a deterioration of cardiac function and a decrease in coronary blood flow could theoretically arise from antagonism of bradykinin receptor type 2.
Mard tal- qalb iskemiku Taħt kundizzjonijiet iskemiċi, jista ’ teoretikament ikun hemm deterjorament tal- funzjoni tal- qalb u tnaqqis fil- fluss tad- demm koronarju minn antagoniżmu tar- riċettur tal- bradykinin ta ’ tip 2.
Caution should therefore be observed in the administration of Firazyr to patients with acute ischemic heart disease or unstable angina pectoris (see section 5.3).
Għalhekk għandha tiġi osservata kawtela fl- għoti ta ’ Firazyr lil pazjenti b’ mard tal- qalb iskemiku akut jew angina pectoris instabbli (ara sezzjoni 5. 3).
Stroke Although there is evidence to support a beneficial effect of B2 receptor blockade immediately following a stroke, there is a theoretical possibility that icatibant may attenuate the positive late phase neuroprotective effects of bradykinin.
Puplesija Għalkemm hemm evidenza li ssostni effett benefiku ta ’ mblokk tar- riċettur B2 immedjatament wara puplesija, hemm possibilità teoretika li icatibant jista ’ jnaqqas l- effetti newroprotettivi pożittivi fi stadju tardiv ta ’ bradykinin.
Accordingly, caution should be observed in the administration of icatibant to patients in the weeks following a stroke.
Għalhekk, għandha tiġi osservata attenzjoni fl- għoti ta ’ icatibant lill - pazjenti fil- ġimgħat wara puplesija.
Pharmacokinetic drug interactions involving CYP450 are not expected (see section 5.2)
Mhumiex mistennija interazzjonijiet farmakokinetiċi tal- mediċina li jinvolvu CYP450 (ara sezzjoni 5. 2)
Co-administration of Firazyr with ACE inhibitors has not been studied.
L- għoti fl- istess ħin ta ’ Firazyr ma ’ inibituri ACE ma ġiex studjat.
ACE inhibitors are contraindicated in HAE patients due to possible enhancement of bradykinin levels.
L- inibituri ACE huma kontraindikati f’ pazjenti HAE minħabba żieda possibbli fil- livelli ta ’ bradykinin.
For icatibant, no clinical data on exposed pregnancies are available.
Għal icatibant, m’ hemmx tagħrif kliniku dwar l- użu waqt it- tqala.
Animal studies showed effects on uterine implantation and parturition (see section 5.3), but the potential risk for humans is unknown.
Studji fuq bhejjem urew effetti fuq l- uterine implantation u t- twelid (ara sezzjoni 5. 3), iżda mhux magħruf ir- riskju potenzjali fuq in- nies.
Firazyr should be used during pregnancy only, if the potential benefit justifies the potential risk for the foetus, (e. g for treatment of potentially life threatening laryngeal attacks).
Firazyr għandu jintuża waqt it- tqala biss jekk il- benefiċċju potenzjali jiġġustifika r- riskju li jista ’ jkun hemm għall- fetu (eż. għat- trattament ta ’ attakki fil- larinġi li jistgħu jkunu ta ’ periklu għall- ħajja).
Icatibant is excreted in the milk of lactating rats at concentrations similar to those in maternal blood.
Icatibant jitneħħa fil- ħalib ta ’ firien li jreddgħu f’ konċentrazzjonijiet simili għal dawk li jinstabu fil - ħalib ta ’ l- omm.
No effects were detected in the post-natal development of rat pups.
Ma nstabu ebda effetti fl- iżvilupp ta ’ wara t- twelid ta ’ frieħ tal- firien.
It is unknown whether icatibant is excreted in human breast milk but it is recommended that breastfeeding women, who wish to take Firazyr, should not breastfeed for 12 hours after treatment.
Mhux magħruf jekk icatibant jitneħħiex fil- ħalib tas- sider uman iżda huwa rakkomandat li nisa jreddgħu, li jkunu jixtiequ jieħdu Firazyr, m’ għandhomx ireddgħu għal 12- il siegħa wara t- trattament.
5.3).
F’ annimali żgħar, l- użu ripetut ta ’ icatibant ittardja b’ mod riversibbli l- maturità sesswali (ara sezzjoni 5. 3).
Firazyr has minor or moderate influence on the ability to drive and use machines.
Firazyr għandu effett żgħir jew moderat fuq il- ħila biex issuq u tħaddem magni.
Fatigue, lethargy, tiredeness, somnolence, and dizziness have been reported uncommonly following the use of Firazyr.
Għeja, letarġija, ngħas, u sturdament ġew irrappurtati b’ mod mhux komuni wara l- użu ta ’ Firazyr.
These symptoms may occur as a result of an attack of HAE.
Dawn is- sintomi jistgħu jseħħu b’ riżultat ta ’ attakk ta ’ HAE.
However, a causal relationship to the use of Firazyr cannot be excluded.
Madankollu, ma tistax tiġi eskluża relazzjoni kawżali ma ’ l- użu ta ’ Firazyr.
Patients should be advised not to drive and use machines if they feel tired or dizzy.
Il- pazjenti għandhom jiġu avżati biex ma jsuqux u jħaddmu magni jekk iħossuhom għajjenin jew storduti.
3 4.8 Undesirable effects
3 4. 8 Effetti mhux mixtieqa
The safety of icatibant has been established in 1022 subjects treated with various doses, regimens and routes of administration during Phase I-III studies in various indications.
Is- sigurtà ta ’ icatibant ġiet stabbilita f’ 1022 individwu trattati b’ diversi dożi, reġimi u rotot ta ’ amministrazzjoni waqt studji ta ’ Fażi I- III f’ diversi indikazzjonijiet.
Sixty three (HAE) patients received icatibant in two Phase III trials for treatment of an attack in the controlled phase and 118 patients were treated in the open label phase.
Tlieta u sittin pazjent (HAE) ingħataw icatibant f’ żewġ provi ta ’ Fażi III għat- trattament ta ’ attakk fil - fażi kontrollata u 118- il pazjent ġew ittrattati fil- fażi open label.
Almost all subjects who were treated with subcutaneous icatibant in clinical trials developed reactions at the site of injection including erythema, swelling, warm sensation, burning, itching and/ or cutaneous pain.
Kważi l- persuni kollha li ġew ittrattati b’ icatibant taħt il- ġilda fi provi kliniċi żviluppaw reazzjonijiet fis- sit ta ’ l- injezzjoni fosthom eritema, nefħa, sensazzjoni ta ’ sħana, ħruq, ħakk u/ jew uġigħ fil- ġilda.
These reactions were generally mild in severity, transient, and resolved without further intervention.
Ġeneralment dawn ir- reazzjonijiet kienu ħfief, għaddiena, u marru mingħajr aktar intervent.
The frequency of adverse reactions listed in Table 1 is defined using the following convention:
Il- frekwenza tar- reazzjonijiet avversi elenkati f’ Tabella 1 hija definita bl- użu tal- konvenzjoni segwenti:
Very common (≥ 1/ 10); common (≥ 1/ 100, < 1/ 10); uncommon (≥ 1/ 1,000, < 1/ 100); rare (≥ 1/ 10,000, < 1/ 1,000); very rare (< 1/ 10,000).
Komuni ħafna (≥1/ 10); komuni (≥ 1/ 100, < 1/ 10); mhux komuni (≥1/ 1, 000, < 1/ 100); rari (≥1/ 10, 000, < 1/ 1, 000); rari ħafna (< 1/ 10, 000).
Due to the low number of patients, each of the uncommon events has only been reported in a single patient.
Minħabba n- numru baxx ta ’ pazjenti, kull wieħed mill- effetti mhux komuni ġew irrapurtati biss f’ pazjenti singoli.
Adverse reactions reported with icatibant in the phase III clinical trials.
Reazzjonijiet avversi rrappurtati b’ icatibant fil- provi kliniċi ta ’ fażi III.
Adverse reactions
Reazzjonijiet avversi Disturbi konġeniti, familjali u ġenetiċi
Common
Komuni Anġjodema ereditarja *
Congenital, familial and genetic disorders
Disturbi gastrointestinali Disturbi ġenerali u kundizzjonijiet tal- post fejn tingħata l -
Hereditary angioedema*
Eritema, nefħa, sensazzjoni ta ’ sħana, ħruq, ħakk u wġigħ fil -
Gastrointestinal disorders
Nawżea, uġigħ addominali Asteijna
Nausea, abdominal pain
Remettar Għejja, piressija
General disorders and administration site conditions
injezzjoni Infezzjonijiet u infestazzjonijiet
Asthenia
ġilda
Injury, poisoning and procedural complications
Kumplikazzjonijiet proċedurali, korrimenti u vvelenar
Contusion
Kontużjoni
Blood creatinine phosphokinase increased, liver function test abnormal
Żieda ta ’ kreatin fosfokinażi fid- demm, test anomalu tal - funzjoni tal- fwied
Weight increased, prothrombin time prolonged
Żieda fil- piż, żieda fil - ħin għall- koagulazzjoni tad- demm
Metabolism and nutrition disorders
Metaboliżmu u problemi nutrizzjonali
Hyperuricaemia
Iperuriċemja
Nervous system disorders
Disturbi tas- sistema nervuża Disturbi renali u urinarji
Renal and urinary disorders
Sturdament, uġigħ ta ’ ras
Proteinuria
Proteinurja
Respiratory, thoracic and mediastinal disorders
Disturbi respiratorji, fis- sider u medjastinali
Nasal congestion
Konġestjoni nażali
Asthma, cough
Ażma, sogħla
Skin and subcutaneous tissue disorders
Disturbi fil- ġilda u fit - tessut taħt il- ġilda
Pruritus, erythema,
Prurite, eritema,
* HAE attacks were reported as adverse reactions, however based on time of occurrence, the majority were recurrent attacks and not related to treatment with Firazyr.
* L- attakki ta ’ HAE ġew irrappurtati bħala reazzjonijiet avversi, madankollu fuq il- bażi tal- ħin li seħħu, il- biċċa l- kbira kienu attakki rikorrenti u mhux relatati mat- trattament b’ Firazyr.
4 4.9 Overdose
4 4. 9 Doża eċċessiva
No clinical information on overdose is available.
M’ hemmx informazzjoni klinika disponibbli dwar doża eċċessiva.
A dose of 3.2 mg/ kg intravenously (approximately 8 times the therapeutic dose) caused transient erythema, itching or hypotension in healthy subjects.
Doża ta ’ 3. 2 mg/ kg fil- vina (madwar 8 darbiet id- doża terapewtika) kkawżat eritema għaddiena, ħakk jew pressjoni baxxa f’ individwi b’ saħħithom.
No therapeutic intervention was necessary.
Ma kien meħtieġ ebda intervent terapewtiku.
[to be decided] ATC code:
[għad trid tiġi deċiża] Kodiċi ATC:
[not yet assigned].
[għadu mhux assenjat].
HAE (an autosomal dominant disease) is caused by an absence or dysfunction of C1-esterase- inhibitor.
L- HAE (marda awtosomali dominanti) hija kkawżata minn nuqqas jew disfunzjoni ta ’ l- inibitur esterase C1.
HAE attacks are accompanied by an increased release of bradykinin, which is the key mediator in the development of the clinical symptoms.
L- attakki ta ’ HAE huma akkumpanjati minn rilaxx akbar ta ’ bradykinin, li huwa l - medjatur prinċipali fl- iżvilupp tas- sintomi kliniċi.
HAE manifests as intermittent attacks of subcutaneous and/ or sub mucosal oedema involving the upper respiratory tract, the skin and the gastrointestinal tract.
HAE tidher bħala attakki intermittenti ta ’ edema taħt il- ġilda u/ jew taħt il- mukuża li jinvolvu l- parti ta ’ fuq ta ’ l- apparat respiratorju, il- ġilda u l- apparat gastrointestinali.
An attack usually lasts between 2 to 5 days.
Attakk ġeneralment idum bejn 2 u 5 tijiem.
Icatibant is a selective competitive antagonist at the bradykinin type 2 (B2) receptor.
Icatibant huwa antagonist selettiv kompetittiv fir- riċettur tal- bradykinin ta ’ tip 2 (B2).
It is a synthetic decapeptide with a structure similar to bradykinin, but with 5 non-proteinogenic amino acids.
Huwa decapeptide sintetiku bi struttura simili għal bradykinin, iżda b’ ħames aċidi amminiċi mhux proteinoġeniċi.
In HAE increased bradykinin concentrations are the key mediator in the development of the clinical symptoms.
F’ HAE, konċentrazzjonijiet akbar ta ’ bradykinin huma l- medjatur prinċipali fl - iżvilupp tas- sintomi kliniċi.
In healthy young subjects, icatibant administered in doses of 0.8 mg/ kg over 4 hours; 1.5 mg/ kg/ day or 0.15 mg/ kg/ day for 3 days, development of bradykinin-induced hypotension, vasodilatation and reflex tachycardia was prevented.
F’ individwi żgħażagħ b’ saħħithom, icatibant mogħti f’ dożi ta ’ 0. 8 mg/ kg fuq 4 sigħat; 1. 5 mg/ kg/ kuljum jew 0. 15 mg/ kg/ kuljum għal 3 ijiem, ġiet evitata pressjoni baxxa, vażodilazzjoni u takikardja ta ’ rifless indotti minn bradykinin.
Icatibant was shown to be a competitive antagonist when the bradykinin challenge dose was increased 4-fold.
Icatibant intwera li huwa antagonist kompetittiv meta c - challenge dose ta ’ bradykinin żdiedet b’ erba ’ darbiet.
Efficacy data were obtained from an initial open-label Phase II study and from two randomised, double blind controlled multi centre Phase III studies (one with oral tranexamic acid as the comparator and one placebo controlled).
L- informazzjoni dwar l- effikaċja nkisbet minn studju open- label inizjali ta ’ Fażi II u minn żewġ studji double blind, multi- ċentri, randomizzati u kkontrollati ta ’ Fażi III (wieħed b’ aċidu traneżamiku orali bħala l- komparatur u wieħed ikkontrollat l- plaċebo).
The pivotal Phase III studies were otherwise identical in design.
Mill- bqija l- istudji pivitali ta ’ Fażi III kienu identiċi fid- disinn tagħhom.
A total of 130 patients were randomized to receive either a 30 mg dose of icatibant (63 patients) or comparator (either tranexamic acid, - 38 or placebo - 29 patients).
Total ta ’ 130 pazjent ġew magħżula b’ mod każwali biex jirċievu jew doża ta ’ 30 mg icatibant (63 pazjent) jew komparatur (jew aċidu traneksamiku, 38 jew plaċebo 29 pazjent).
Subsequent episodes of HAE were treated in an open label extension.
Episodji suċċessivi ta ’ HAE ġew trattati f’ estensjoni open label.
Patients with symptoms of laryngeal angioedema received open label treatment with icatibant.
Il- pazjenti b’ sintomi ta ’ anġjoedema larinġali rċevew trattament open label b’ icatibant.
In the Phase III trials, the primary efficacy endpoint was time to onset of symptom relief using a visual analogue scale (VAS).
Fil- provi ta ’ Fażi III, l- endpoint primarju ta ’ l- effikaċja kien il- ħin sal- bidu tas- solljiev mis- sintomi bl - użu ta ’ visual analogue scale (VAS).
In both studies, patients on icatibant had a faster median time to onset of symptom relief (2.0 and 2.5 hours, respectively) compared to tranexamic acid (12.0 hours) and placebo (4.6 hours).
Fiż- żewġ studji, il- pazjenti fuq icatibant kellhom ħin medjan aktar mgħaġġel għall- bidu tas- solljiev mis- sintomi (sagħtejn u sagħtejn u nofs rispettivament) meta mqabbel ma l- aċidu traneksamiku (12. 0- il siegħa) u l- plaċebo (4. 6 sigħat).
The treatment effect of icatibant was confirmed by secondary efficacy endpoints.
L- effett tat- trattament b’ icatibant kien ikkonfermat b’ endpoints sekondarji ta ’ l- effikaċja.
The following table shows the results for the two pivotal trials
It- tabella li ġejja turi r- riżultati għaż- żewġ provi pivitali
Controlled Clinical Study of FIRAZYR vs Tranexamic acid or Placebo:
5 Studju Kliniku Ikkontrollat ta ’ FIRAZYR vs Aċidu traneżamiku/ Plaċebo:
Efficacy Results
Riżultati ta ’ l- effikaċja
STUDY 1
STUDJU 1
Tranexamic
Aċidu
STUDY 2
STUDJU 2
Number of subjects
traneżamiku Numru ta ’
Number of subjects
Numru ta ’
in ITT Population
individwi fil - Popolazzjoni ITT Linja ta ’ bażi
in ITT Population
individwi fil - Popolazzjoni ITT Linja ta ’ Bażi
5 Controlled Clinical Study of FIRAZYR vs Tranexamic acid or Placebo:
61. 5
STUDY 1
VAS (mm)
Tranexamic
69. 3
STUDY 2
67. 7
Icatibant
Bidla mil- linja
Placebo
ta ’ bażi għal 4
Baseline
- 41. 6
Baseline
- 14. 6 ta ’ ba
VAS(mm) Change from
ta ’ bażi għal 4 - 41. 6 - 14. 6 ta ’ bażi għal 4
63.7
- 44. 6
61.5
- 23. 5
VAS(mm) Change from
sigħat Differenza bejn
69.3
- 27. 8 (- 39. 4, - 16. 2)
67.7
sigħat Differenza bejn
baseline to 4 hours Difference
it- trattamenti
-41.6
p < 0. 001
-14.6
it- trattamenti
baseline to 4 hours Difference
- 22. 3 (- 36. 1, - 9. 3) p = 0. 002
between treatments -27.8 (-39.4, -16.2) p < 0.001 between treatments -22.3 (-36.1, -9.3) p = 0.002 (95% CI, p-value) Change from
(95% CI, valur - p) Bidla mil- linja
(95% CI, p-value) Change from
(95% CI, valur - p) Bidla mil- linja
baseline to 12 hours Difference
ta ’ bażi għal 12 - il siegħa Differenza bejn
between treatments -24.1 (-33.6, -14.6) p < 0.001 between treatments -14.0 (-27.7, -0.3) p = 0.046 (95% CI, p-value) Median time to onset of symptom relief (hours) All episodes
it- trattamenti
(95% CI, p-value) Median time to onset of symptom relief (hours) All episodes
- 14. 0 (- 27. 7, - 0. 3) p = 0. 046 (95% CI, valur - (95% CI, valur - p) Ħin medjan għall- bidu tas - solljev mis - sintomi (sigħat)
(N = 74) Response rate (%, CI) at 4 hours after start of treatment
(N = 74) Rata ta ’ rispons (%, CI) 4 sigħat wara l- bidu tat - trattament
12.0
12. 0
(N = 56) Response rate (%, CI) at 4 hours after start of treatment
(N = 56) Rata ta ’ rispons (%, CI) 4 sigħat wara l- bidu tat - trattament
All episodes
L- episodji kollha
80.0
80. 0
30.6 Al
30. 6 L- ep
All episodes 80.0 30.6 All episodes
L- episodji kollha 80. 0 30. 6 L- episodji kollha
46.4
46. 4
(N = 74) Median time to onset of symptom relief: all symptoms (hours):
(N = 74) Ħin medjan għall- bidu tas - solljiev mis - sintomi: is - sintomi kollha (sigħat):
(63.1, 91.6)
(63. 1, 91. 6) (16. 3,
(16.3, 48.1)
48. 1) (N =
(N = 56) Median time to onset of symptom relief: all symptoms (hours):
56) Ħin medjan għall- bidu tas - soljliev mis - sintomi: is - sintomi kollha (sigħat):
(46.0, 83.5)
(46. 0, 83. 5)
(27.5, 66.1)
(27. 5, 66. 1)
Abdominal pain Skin swelling Skin pain Median time to almost complete symptom relief (hours) All episodes
Nefħa fil- ġilda Uġigħ fil- ġilda Ħin medjan għal solljiev kważi komplet mis - sintomi (sigħat) L- episodji kollha
1.6 2.6 1.5
2. 6 1. 5
3.5 18.1 12.0
18. 1 12. 0
2.0 3.1 1.6
3. 1 1. 6
3.3 10.2 9.0
10. 2 9. 0
(N = 74) Median time to regression of symptoms, by patient (hours) All episodes
(N = 74)
51.0
51. 0
(N = 56) Median time to regression of symptoms, by patient (hours) All episodes
(N = 56)
23.3
23. 3
(N = 74) Median time to overall patient improvement, by physician (hours) All episodes
(N = 74) Ħin medjan għal titjib globali tal - pazjent, mit - tabib (sigħat)
(N = 56) Median time to overall patient improvement, by physician (hours) All episodes
(N = 56) Ħin medjan għal titjib globali tal - pazjent, mit- tabib (sigħat)
6 One hundred and eighteen patients were treated in the open label extension (OLE) phase for a total of 597 separate attacks.
Mija u tmintax- il pazjent ġew trattati fil- fażi ta ’ l- estensjoni open label (OLE) għal total ta ’ 597 attakk separat.
The efficacy results were similar to those seen in the controlled phase of the studies.
Ir- riżultati ta ’ l- effikaċja kienu simili għal dawk li dehru fil- fażi kkontrollata ta ’ l- istudji.
The majority of attacks (89.3% and 90.9%, respectively) in both studies required only a single dose of icatibant.
Il - maġġoranza ta ’ l- attakki (89. 3% u 90. 9%, rispettivament) fiż- żewġ studji kienu jeħtieġu biss doża waħda ta ’ icatibant.
A total of 36 patients were treated for a total of 61 attacks of HAE affecting the larynx.
Total ta ’ 36 pazjent ġew trattati għal total ta ’ 61 attakk ta ’ HAE li affettwa l- larinġi.
The results were again similar to patients with non-laryngeal attacks of HAE with a median time to start of regression of symptoms of 0.6 - 1.0 hours (controlled phase).
Għal darba oħra, ir- riżultati kienu simili għal dawk ta ’ pazjenti b’ attakki ta ’ HAE mhux larinġali b’ ħin medju għall- bidu tar- regressjoni tas- sintomi ta ’ 0. 6 – 1. 0 sigħat (fażi kkontrollata).
The pharmacokinetics of icatibant has been extensively characterized by studies using both intravenous and subcutaneous administration to healthy volunteers and patients.
Il- farmakokinetika ta ’ icatibant ġiet ikkaratterizzata b’ mod estensiv bi studji li użaw kemm għoti fil - vina kif ukoll taħt il- ġilda lil voluntiera b’ saħħithom u pazjenti.
The pharmacokinetic profile of icatibant in patients with HAE is similar to that in healthy volunteers.
Il- profil farmakokinetiku ta ’ icatibant f’ pazjenti b’ HAE huwa simili għal dak f’ voluntiera b’ saħħithom.
Absorption Following subcutaneous administration, the absolute bioavailability of icatibant is 97%.
Assorbiment Wara għoti taħt il- ġilda, il- bijodisponibilità assoluta ta ’ icatibant hija 97%.
The time to maximum concentration is approximately 0.5 hours.
Il- ħin għall - konċentrazzjoni massima huwa ta ’ madwar 0. 5 sigħat.
Distribution Icatibant volume of distribution (Vss) is about 20-25 L.
Distribuzzjoni Il- volum ta ’ distribuzzjoni ta ’ icatibant (Vss) huwa madwar 20- 25 L.
Plasma protein binding is 44%.
It- twaħħil mal- proteini tal - plasma huwa ta ’ 44%.
Elimination Icatibant is mainly eliminated by metabolism with less than 10% of the dose eliminated in the urine as unchanged drug.
Eliminazzjoni Icatibant jitneħħa prinċipalment bil- metaboliżmu b’ anqas minn 10% tad- doża tiġi mneħħija fl- awrina bħala mediċina mhux mibdula.
Clearance is about 15-20 l/ h and independent of dose.
It- tneħħija hija madwar 15- 20 litru/ siegħa u hija indipendenti mid - doża.
The terminal half-life is about 1-2 hours.
Il- half- life terminali hija ta ’ madwar siegħa sa sagħtejn..
Metabolism Icatibant is extensively metabolized by proteolytic enzymes to inactive metabolites that are primarily excreted in the urine.
Metaboliżmu Icatibant huwa metabolizzat b’ mod estensiv minn enzimi proteolitiċi għal metaboliti inattivi li jitneħħew primarjament fl- awrina.
In vitro studies have confirmed that icatibant is not degraded by oxidative metabolic pathways and is not an inhibitor of major cytochrome P450 (CYP) isoenzymes (CYP 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4) and is not an inducer of CYP 1A2 and 3A4.
Studji in vitro kkonfermaw li icatibant ma jiġix degradat minn passaġġi metaboliċi ossidattivi u mhuwiex inibitur ta ’ isoenzimi (CYP) maġġuri taċ- ċitokromu P450 (CYP 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, u 3A4) u mhuwiex induttur ta ’ CYP 1A2 u 3A4.
Special populations Data suggest an age-related decline in clearance resulting in about 50-60% higher exposure in the elderly (75-80 years) compared to a patient aged 40 years.
7 Id- dejta turi tnaqqis fit- tneħħija relatata ma ’ l- età li tirriżulta f’ madwar 50- 60% iktar esponiment fl - anzjani (bejn 75 u 80 sena) meta pparagunat ma ’ pazjent ta ’ 40 sena.
Data suggests that gender and weight do not have a significant influence on icatibant pharmacokinetics.
Id- dejta tgħid li s- sess u l- piż m’ għandhomx influwenza sinifikattiva fuq il- farmakokinetika ta ’ icabitant.
Limited data suggest that icatibant exposure is not influenced by hepatic or renal impairment.
Id- dejta limitata turi li l- esponiment għal icatibant mhuwiex influwenzat minn indeboliment epatiku jew tal- kliewi.
The influence of race on icatibant pharmacokinetics has not been evaluated.
L- influwenza tar- razza fuq il- farmakokinetika ta ’ icatibant ma ġietx evalwata.
There are no pharmacokinetic data in children.
M’ hemmx informazzjoni farmakokinetika fit- tfal.
Repeated-dose studies of up to 3-months duration have been conducted in rat and dog.
Saru studji b’ dożi ripetuti fuq il- far u l- kelb li damu sejrin sa tliet xhur.
Maximum daily exposures (AUC) at the No Observed Adverse Effect Levels in the 3-month study in rat were 3.6 times and in the 4 week study in dog were 9.4 times the AUC in humans after a subcutaneous dose of 30 mg.
L- esponimenti massimi tal - ġurnata (AUC) fil- Livelli fejn Ma Kienu Osservati Ebda Effetti Avversi fl- istudju ta ’ tliet xhur fuq il - far kienu 3. 6 darbiet u fl- istudju ta ’ erba ’ ġimgħat fuq il- kelb kienu 9. 4 darbiet l- AUC fil- bniedem wara doża taħt il- ġilda ta ’ 30 mg.
Long-term studies to determine the carcinogenic potential of icatibant have not been conducted to date.
Sa llum għadhom ma sarux studji fit- tul biex jiġi stabbilit il- potenzjal karċinoġeniku ta ’ icatibant.
In a standard battery of in vitro and in vivo tests icatibant was not genotoxic.
F’ batterija standard ta ’ testijiet in vitro u in vivo, icatibant ma kellux effett tossiku fuq il- ġeni.
Icatibant is a potent
Icatibant ma kienx teratoġeniku meta ngħata b’ injezzjoni taħt il- ġilda waqt l- iżvilupp bikri ta ’ l - embriju u tal- fetu fil- far (doża massima 25 mg/ kg/ kuljum) u l- fenek (doża massima 10 mg/ kg/ kuljum).
7 antagonist of bradykinin and therefore, at high dose levels, treatment can have effects on the uterine implantation process and subsequent uterine stability in early pregnancy.
Icatibant huwa antagonist qawwi ta ’ bradykinin u għalhekk, f’ livelli ta ’ dożi għoljin, it- trattament jista ’ jkollu effetti fuq il- proċess ta ’ l- uterine implantation u l- istabilità suċċessiva ta ’ l- utru fil- bidu tat- tqala.
These uterine effects also manifest in late stage pregnancy where icatibant exhibits a tocolytic effect resulting in delayed parturition in the rat, with increased fetal distress and perinatal death at high doses (10 mg/ kg/ day).
Dawn l- effetti fuq l- utru jidhru wkoll fl- aħħar fażi tat- tqala meta icatibant juri effett tokolitiku li jirriżulta fl- ittardjar tat- twelid fil- far, tbatija akbar tal- fetu u mewt perinatali b’ dożi għoljin (10 mg/ kg/ kuljum).
In immature rats and dogs, repeated use of icatibant reversibly delayed sexual maturation.
Fi ġrieden u klieb li għadhom żgħar, l- użu ripetut ta ’ icatibant ittardja b’ mod riversibbli l- maturità sesswali.
The effects appeared to be secondary to icatibant-induced changes in gonadotrophin levels, and were reversible.
L- effetti dehru li kienu sekondarji għat- tibdiliet indotti minn icabitant fil- livelli ta ’ gonadotrofina, u kienu riversibbli.
Similar effects of icatibant on gonadotrophins also occurred in sexually mature dogs.
Effetti simili ta ’ icatibant jew gonadotrofina seħħew ukoll fi klieb li kienu sesswalment maturi..
Icatibant had no effect on the fertility of male mice and rats.
Icatibant ma kellux effett fuq il- fertilità tal- ġrieden u l- firien irġiel.
Icatibant did not elicit any cardiac conduction change in vitro (hERG channel) or in vivo in normal dogs or in various dog models (ventricular pacing, physical exertion and coronary ligation) where no associated hemodynamic changes were observed.
Icatibant ma ġab ebda tibdil fil- konduzzjoni kardijaka in vitro (kanal hERG) jew in vivo fi klieb normali jew f’ diversi mudelli ta ’ klieb (pass ventrikolari, sforz fiżiku u rabta koronarja) meta ma ġie osservat l- ebda tibdil ħemodinamiku relatat.
Icatibant has been shown to aggravate induced cardiac ischemia in several non-clinical models, although a detrimental effect has not consistently been shown in acute ischemia.
Icatibant intwera li jiggrava l- iskemija indotta tal- qalb f’ diversi mudelli mhux kliniċi, għalkemm effett detrimentali ma ntweriex b’ mod konsistenti f’ iskemija akuta.
Sodium chloride Acetic acid, glacial (for pH adjustment) Sodium hydroxide (for pH adjustment) Water for injections
Sodium chloride Acetic acid, glacial (għal aġġustament tal- pH) Sodium hydroxide (għal aġġustament tal- pH) Ilma għall- injezzjonijiet
24 months.
24- il xahar.
6.4 Special precautions for storage
8 6. 4 Prekawzjonijiet speċjali għall- ħażna
Do not store above 25○ C.
Taħżinx f’ temperatura ’ l fuq minn 25○C.
6.5 Nature and content of container
L- għamla tal- kontenitur u ta ’ dak li hemm ġo fih 6. 5