natgillin/translations-raw huggingface dataset:
Thus, bivalirudin initially acts as a complete non-competitive inhibitor of thrombin, but transitions over time to become a competitive inhibitor enabling initially inhibited thrombin molecules to interact with other clotting substrates and to coagulation if required.
Zato bivalirudin sprva deluje kot popolni nekompetativni inhibitor trombina, sčasoma pa postane kompetativni inhibitor s čimer omogoči sprva inhibiranim molekulam trombina, da medsebojno delujejo z drugimi substancami strjevanja in omogočijo koagulacijo, če je potrebno.
In vitro studies have also shown that bivalirudin prolongs the activated partial thromboplastin time (aPTT) thrombin time (TT) and pro-thrombin time (PT) of normal human plasma in a concentration- dependent manner and that bivalirudin does not induce a platelet aggregation response against sera from patients with a history of Heparin-Induced Thrombocytopenia/ Thrombosis Syndrome (HIT/ HITTS).
Študije in vitro kažejo tudi, da bivalirudin podaljša čas aktiviranega parcialnega tromboplastinskega časa (aTPČ), trombinskega časa (TČ) in protrombinskega časa (PČ) normalne človeške plazme na od koncentracije odvisen način in da bivalirudin ne povzroča agregacije krvnih ploščic kot odziv na serum pri bolnikih s heparinsko povzročenim sindromom trombocitopenije/ tromboze (HIT/ HITTS – » Heparin- Induced Thrombocytopenia/ Thrombosis Syndrom «) v anamnezi.
In healthy volunteers and patients, bivalirudin exhibits dose- and concentration dependent anticoagulant activity as evidenced as prolongation of the ACT, aPTT, PT, INR and TT.
Pri zdravih prostovoljcih in bolnikih bivalirudin kaže od odmerka in koncentracije odvisno antikoagulacijsko aktivnost, kar dokazuje podaljšanje ACT, aTČP, PČ, INR in TČ.
Data from 366 patients indicates that the ACT is unaffected by concomitant treatment with a GPIIb/ IIIa inhibitor.
Podatki 366 bolnikov kažejo, da sočasno zdravljenje z inhibitorjem GPIIb/ IIIa ne vpliva na ATC.
ACUITY Trial
Študija ACUITY
The ACUITY trial was a prospective, randomised open-label, trial of bivalirudin with or without GPIIb/ IIIa inhibitor (Arms B and C respectively) versus unfractionated heparin or enoxaparin with GPIIb/ IIIa inhibitor (Arm A) in 13,819 high risk ACS patients.
Študija ACUITY je bila prospektivna, odprta, randomizirana študija bivalirudina z ali brez inhibitorja GPIIb/ IIIa (krak B in krak C v istem vrstnem redu) v primerjavi z nefrakcioniranim heparinom ali enoksaparinom z inhibitorjem GPIIb/ IIIa (krak A) pri 13. 819 bolniki z visokim tveganjem za AKS.
In Arms B and C of the ACUITY trial, the recommended dose of bivalirudin was an initial post- randomisation IV bolus of 0.1mg/ kg followed by a continuous IV infusion of 0.25 mg/ kg/ h during angiography or as clinically warranted.
V krakih B in C študije ACUITY je bil priporočeni odmerek bivalirudina začetni post randomizacijski i. v. bolus 0, 1 mg/ kg, ki mu je sledila neprekinjena i. v. infuzija 0, 25 mg/ kg/ h med angiografijo ali kot je bilo klinično zagotovljeno.
For patients undergoing PCI, an additional IV bolus of 0.5mg/ kg bivalirudin was administered and the rate of IV infusion increased to 1.75 mg/ kg/ h.
Bolniki, ki so prestajali PCI, so prejeli dodaten i. v. bolus 0, 5 mg/ kg bivalirudina, hitrost i. v. infuzije pa se je povečala na 1, 75 mg/ kg/ h.
10 In Arm A of the ACUITY trial, UFH or enoxaparin was administered in accordance with the relevant guidelines for the management of ACS in patients with UA and NSTEMI.
10 (pred angiografijo) ali v času PCI.
A total of 356 (7.7%) of patients randomised to Arm C also received a GPIIb/ IIIa inhibitor.
Skupaj 356 (7, 7%) bolnikov, ki so bili randomizirani v krak C, je prav tako prejelo inhibitor GPIIb/ IIIa.
High risk patient characteristics of the ACUITY population that mandated angiography within 72 hours were balanced across the three treatment arms.
Bolniki z visokim tveganjem, ki je bilo značilno za populacijo ACUITY, in zaradi česar je bila potrebna angiografija v 72 urah, so bili proporcionalno razdeljeni v vse tri krake zdravljenja.
Approximately 77% of patients had recurrent ischaemia, approximately 70% had dynamic ECG changes or elevated cardiac biomarkers, approximately 28% had diabetes and approximately 99% of patients underwent angiography within 72 hours.
Približno 77% bolnikov je imelo ponavljajočo ishemijo, približno 70% je imelo dinamične spremembe EKG ali povišane srčne biološke označevalce, približno 28% jih je imelo diabetes in približno 99% bolnikov je prestalo angiografijo v 72 urah.
Following angiographic assessment, patients were triaged to either medical management (33%), PCI (56%) or CABG (11%).
Po angiografskem ocenjevanju so bolnike triažirali v medicinsko vodenje (33%), v skupino za PCI (56%) ali CABG (11%).
Additional anti-platelet therapy utilised in the study included aspirin and clopidogrel.
Dodatna antitrombocitna terapija, ki so jo uporabljali v študiji je vključevala uporabo acetilsalicilne kisline in klopidogrela.
The primary analysis and results for ACUITY at 30-days and 1 year for the overall (ITT) population and for the patients that received aspirin and clopidogrel as per protocol (pre-angiography or pre-PCI) are shown in Tables 7 and 8.
Primarna analiza in rezultati študije ACUITY po 30 dneh in 1 letu za celotno vključeno populacijo (ITT) in za bolnike, ki so prejemali acetilsalicilno kislino ter klopidogrel v skladu s protokolom (pred angiografijo ali pred PCI), so prikazani v tabelah 7 in 8.
11 Table 7.
Tabela 7.
ACUITY trial; 30-day and 1-year risk differences for the composite endpoint and its components for the overall population (ITT)
30- dnevne in 1- letne študije razlike tveganj pri ishemiji kot opazovanem dogodku pri celotni vključeni populaciji
Overall population (ITT) Arm A Arm B UFH/ e bival nox +GPII Arm C
Celotna populacija (ITT) C– A Krak B Krak A B– A razlika Krak C bival + UFH/ enoks razlika tveganj samo bival inhibitor + inhibitor tveganj (N=4. 612) GPIIb/ IIIa GPIIb/ IIIa (95% CI) (95% CI)% (N=4. 604) (N=4. 603)%% 30 dni Kompozitna
+GPII b/ IIIa B– A bival
7, 3
C– A
7, 7
b/ IIIa
0, 48
inhibit
7, 8
Risk diff.
0, 55
alone
ishemija
Risk diff.
(- 0, 60; 1, 55)
inhibit
(- 0, 53; 1, 63)
or
Smrt
(95% CI)
1, 3
(N=4612)
1, 5
(95% CI)
0, 17 (- 0, 31; 0, 66)
(N=46
0, 26 (- 0, 23; 0, 75)
30-day
4, 9
04)
0. 04
7.8
5, 4
0.55
0, 45
(-0.60, 1.55)
(- 0, 84; 0, 93)
(-0.53, 1.63)
(- 0, 46; 1, 35)
Death
1 leto
1.3
2, 3
1.5
2, 7
0.17
0. 39 (- 0, 24; 1, 03)
1.6
2, 4
(-0.31, 0.66)
0, 10 (- 0, 51; 0, 72)
(-0.23, 0.75)
Kompozitna
4.9
15, 3
5.0
15, 9
0.04 (-0.84, 0.93)
0, 65
5.4
16, 0
0.45 (-0.46, 1.35)
0, 71
1-year
ishemija
0.39 (-0.24, 1.03)
(- 0, 83; 2, 13)
0.10 (-0.51, 0.72)
(- 0, 77; 2, 19)
0.65
Smrt
16.0
3, 9
0.71
3, 8
(-0.83, 2.13)
0, 04 (- 0, 83; 0, 74)
(-0.77, 2.19)
- 0, 18 (- 0, 96; 0, 60)
Death
MI
3.9
6, 8
3.8
7, 0
0.04
0. 19
3.7
7, 6
(-0.83, 0.74)
0, 83
(-0.96, 0.60)
(- 0, 84; 1, 23)
0.83 (-0.22, 1.89)
(- 0, 22; 1, 89)
Unplanned revasc.
Nenačrtovana revaskulariza cija.
0.78 (-0.36, 1.92)
0, 78 (- 0, 36; 1, 92)
0.37 (-0.75, 1.50)
0, 37 (- 0, 75; 1, 50)
12 Table 8.
11 Tabela 8.
ACUITY trial; 30-day and 1-year risk differences for the composite ischaemic endpoint and its components for patients that received aspirin and clopidogrel as per protocol*
Študija ACUITY; 30- dnevne in 1- letne študije razlike tveganj pri kompozitni ishemiji in njenih komponentah kot opazovanih dogodkov pri bolnikih, ki so prejemali acetilsalicilno kislino in klopidogrel v skladu s protokolom *
30-day
30- day
Risk diff. alone inhibit or (95% CI) (95% CI) (N=2911) or (N=29% (N=28 24) 42)%%
Bolniki, ki so prejemali aspirin & klopidogrel v skladu s protokolom Krak B Krak A C– A B– A Krak C bival + UFH/ enoks Razlika Razlika Samo bival inhibitor + inhibitor tveganj tveganj (N=2. 911) GPIIb/ IIIa GPIIb/ IIIa (95% CI) (95% CI)% (N=2. 924) (N=2. 842)%%
Composite ischae mia
Kompozitna ishemija Smrt
1.4 1.4 -0.00 1.2 -0.14 (-0.60, 0.60) (-0.72, 0.45)
7, 4 7, 4 0, 03 7, 0 - 0, 35 (- 1, 32; 1, 38) (- 1, 68; 0, 99) 1, 4 1, 4 - 0, 00 1, 2 - 0, 14 (- 0, 60; 0, 60) (- 0, 72; 0, 45)
4.8 4.9 0.04 4.7 -0.08 (-1.07, 1.14) (-1.18, 1.02)
4, 8 4, 9 0, 04 4, 7 - 0, 08 (- 1, 07; 1, 14) (- 1, 18; 1, 02) 2, 6 2, 8 0, 23 2, 2 - 0, 41
1-year
Nenačrtovana revaskulariza cija 1 leto
2.6 2.8 0.23 2.2 -0.41 (-0.61, 1.08) (-1.20, 0.39)
(- 0, 61; 1, 08) (- 1, 20; 0, 39)
16.1 16.8 0.68 15.8 -0.35 (-1.24, 2.59) (-2.24, 1.54)
16, 1 16,. 8 0, 68 15, 8 - 0, 35 (- 1, 24; 2, 59) (- 2, 24; 1, 54) 3, 7 3, 9 0, 20 3, 3 - 0, 36 (- 0, 78; 1, 19) (- 1, 31; 0, 59)
6.7 7.3 0.60 6.8 0.19 (-0.71, 1.91) (-1.11, 1.48)
6, 7 7, 3 0, 60 6, 8 0, 19 (- 0, 71; 1, 91) (- 1, 11; 1, 48) 9, 4 10, 0 0, 59 8, 9 - 0, 53
9.4 10.0 0.59 8.9 -0.53 (-0.94, 2.12) (-2.02, 0.96)
(- 0, 94; 2, 12) (- 2, 02; 0, 96)
*clopidogrel pre-angiography or pre-PCI
* klopidogrel pred angiografijo ali pred PCI
The incidence of both ACUITY-scale and TIMI-scale bleeding events up to day 30 is presented in Table 9 for the overall (ITT) population and for patients that received aspirin and clopidogrel as per protocol.
Incidenca na lestvici ACUITY in na lestvici TIMI krvavitev do 30. dne je predstavljena v tabeli 9 za celotno vključeno populacijo (ITT) in za bolnike, ki so prejemali acetilsalicilno kislino in klopidogrel v skladu s protokolom.
13 Table 9.
Tabela 9.
ACUITY trial; bleeding events up to day 30 for the overall (ITT) population and the population of patients who received aspirin and clopidogrel as per protocol*
Študija ACUITY; krvavitve do dne 30 za celotno vključeno populacijo (ITT) in populacijo bolnikov, ki so prejemali acetilsalicilno kislino in klopidogrel v skladu s protokolom *
Patients receiving aspirin & clopidogrel Overall population (ITT) as per protocol UFH/ enox bival bival UFH/ enox bival bival + + alone + + GPIIb/ IIIa alone GPIIb/ IIIa GPIIb/ IIIa (N=4612) GPIIb/ IIIa inhibitor (N=2911) inhibitor inhibitor% inhibitor (N=2924)% (N=4603) (N=4604) (N=2842)%%%%
Bolniki, ki so prejemali acetilsalicilno Celotna vključena populacija (ITT) kislino in klopidogrel v skladu s protokolom Samo bival UFH/ enoks Samo UFH/ enoks bival bival + inhibitor + inhibitor bival + inhibitor + inhibitor (N=2. 911) GPIIb/ IIIa GPIIb/ IIIa (N=4. 612) GPIIb/ IIIa GPIIb/ IIIa% (N=2. 924) (N=2. 842)% (N=4. 603) (N=4. 604)%%%%
5.7 5.3 3.0 5.9 5.4 3.1
Večja po lestvici ACUITY1
1 scale major TIMI scale major2
5. 3 3. 0 5. 9 5. 4 3. 1 5. 7
1.9
Večja po lestvici TIMI2
0.9 1.9 1.9
1. 9 1. 9 0. 8 1. 7 0. 9 1. 9
0.8
2 Večja krvavitev je v študiji TIMI opredeljena kot intrakranialna krvavitev ali znižanje koncentracije hemoglobina za 5 g/ dl ali več Prednost bivalirudina pred UHF/ enoksaparinom plus inhibitorjem GP // b/ IIIa z vidika krvavitev je bila opažena le v kraku, ki je prejemal samo bivalirudin.
*clopidogrel pre-angiography or pre-PCI1 ACUITY major bleeding defined as any one of the following: intracranial, retroperitoneal, intraocular, access site haemorrhage requiring radiological or surgical intervention, ≥ 5cm diameter haematoma at puncture site, reduction in haemoglobin concentration of ≥ 4g/ dL without an overt source of bleeding, reduction in haemaglobin concentration of ≥ 3g/ dL with an overt source of bleeding, re-operation for bleeding, use of any blood product transfusion.
Večje krvavitve med REPLACE- 2 so bile opredeljene z ne- TIMI kriteriji.
2 TIMI major bleeding defined as intracranial bleeding or a decrease in haemoglobin concentration ≥ 5g/ dL
Rezultati študije REPLACE- 2:
The advantage of bivalirudin over UFH/ enoxaparin plus GPIIb/ IIIa inhibitor in terms of bleeding events was only observed in the bivalirudin monotherapy arm.
30- dnevne končne točke (vključena populacija ("intent- to- treat") in populacija po protokolu)
Major bleeding in REPLACE-2 was defined by non-TIMI criteria.
Vključeni bolniki ("intent- to - treat")
Table 10.
Po protokolu
REPLACE-2 study populations
heparin bivalirudin
results:
heparin
30-day endpoints (intent-to-treat and per-protocol
(N=2. 994)
Intent-to-treat Per-protocol heparin heparin
+ inhibitor
Endpoint
(N=2. 902)
bivalirudin + GPIIb/ IIIa bivalirudin + GPIIb/ IIIa (N=2994) inhibitor (N=2902) inhibitor% (N=3008)% (N=2882)%%
GPIIb/ IIIa
Quadruple
GPIIb/ IIIa
endpoint
(N=3. 008)%
9.2 10.0 9.2 10.0
(N=2. 882)%
Triple endpoint* Components:
Četvorna končna točka Trojna končna točka * Komponente:
Death Myocardial Infarction Major bleeding**
Nujna revaskularizacija
0.2 7.0 2.4
1, 2
0.4 6.2 4.1
1, 4
0.2 7.1 2.2
1, 2
revascularization * excludes major bleeding component.
* izključuje komponento večje krvavitve.
Clinical trials in a small number of patients have provided limited information about the use of Angiox in patients with HIT/ HITTS.
Heparinsko povzročena trombocitopenija (HIT – »» Heparin- Induced Thrombocytopenia «) in heparinsko povzročeni sindrom trombocitopenije/ tromboze (HIT/ HITTS - » Heparin- Induced Thrombocytopenia/ Thrombosis Syndrom «): klinična preskušanja na majhni skupini bolnikov nudijo omejene podatke o uporabi Angioxa pri bolnikih s HIT/ HITTS.
The bioavailability of bivalirudin for intravenous use is complete and immediate.
Biološka uporabnost bivalirudina danega intravensko je popolna in takojšnja.
The mean steady-state concentration of bivalirudin following a constant intravenous infusion of 2.5 mg/ kg/ h is 12.4 µg/ ml.
Povprečna koncentracija bivalirudina v stanju dinamičnega ravnovesja po konstantni intravenski infuziji 2, 5 mg/ kg/ h je 12, 4 µg/ ml.
The steady-state volume of distribution is 0.1 litre/ kg.
Volumen porazdelitve v stanju dinamičnega ravnovesja je 0, 1 litra/ kg.
Biotransformation:
13 Biotransformacija:
As a peptide, bivalirudin is expected to undergo catabolism to its constituent amino acids, with subsequent recycling of the amino acid in the body pool.
Bivalirudin je kot peptid podvržen katabolizmu na aminokisline, ki ga sestavljajo s posledično ponovno uporabo aminokislin v telesu.
The primary metabolite resulting from the cleavage of Arg3-Pro4 bond of the N-terminal sequence by thrombin is not active because of the loss of affinity to the catalytic active site of thrombin.
Osnovni presnovek, ki nastane kot posledica cepitve vezi Arg3- Pro4 N- terminalnega zaporedja s trombinom ni aktiven zaradi izgube afinitete do katalitično aktivnega mesta trombina.
About 20% of bivalirudin is excreted unchanged in the urine.
Približno 20% bivalirudina se nespremenjenega izloči z urinom.
The concentration-time profile following intravenous administration is well described by a two-compartment model.
Profil koncentracija- čas po intravenskem dajanju je dobro opisan z dvokomponentnim modelom.
Elimination follows a first order process with a terminal half-life of 25 ± 12 minutes in patients with normal renal function.
Izločanje sledi procesu prve stopnje s končno razpolovno dobo 25 ± 12 minut pri bolnikih z normalno ledvično funkcijo.
The corresponding clearance is about 3.4 ± 0.5 ml/ min/ kg.
Ustrezen očistek je približno 3, 4 ± 0, 5 ml/ min/ kg.
Hepatic Insufficiency:
Jetrna insuficienca:
The pharmacokinetics of bivalirudin have not been studied in patients with hepatic impairment but are not expected to be altered because bivalirudin is not metabolized by liver enzymes such as cytochrome P-450 isozymes.
Farmakokinetika bivalirudina ni bila preučena pri bolnikih z okvarjenimi jetri, vendar se verjetno ne bo spremenila, ker bivalirudina ne presnavljajo jetrni encimi, kot so izoencimi citokroma P- 450.
Renal Insufficiency:
Ledvična insuficienca:
The systemic clearance of bivalirudin decreases with glomerular filtration rate (GFR).
Telesni očistek bivalirudina se zmanjša s stopnjo glomerularne filtracije (GFR – » glomerular filtration rate «).
Clearance is reduced by approximately 20% in patients with moderate or severe renal impairment, and 80% in dialysis-dependent patients (Table 11).
Očistek se pri bolnikih z zmerno ali hudo ledvično okvaro zmanjša za približno 20%, pri dializnih bolnikih pa za 80% (tabela 11).
Table 11.
Tabela 11.
Pharmacokinetic parameters for bivalirudin in patients with normal and impaired renal function.
Farmakokinetični parametri za bivalirudin pri bolnikih z normalno in okvarjeno ledvično funkcijo.
Clearance
Očistek
Half-life (minutes)
(minut)
(ml/ min/ kg) Normal renal function (≥ 90ml/ min) Mild renal impairment (60-89 ml/ min) Moderate renal impairment (30-59 ml/ min) Severe renal impairment (10-29 ml/ min)
Normalna ledvična funkcija (≥90 ml/ min) Blaga ledvična okvara (60 - 89 ml/ min) Zmerna ledvična okvara (30 - 59 ml/ min) Huda ledvična okvara (10 - 29 ml/ min) Dializni bolniki (ne med dializo)
3.4 3.4 2.7 2.8
3, 4 3, 4 2, 7 2, 8 1, 0
25 22 34 57
25 22 34 57 3, 5 ur
In patients with renal insufficiency, coagulation parameters such as the ACT should be monitored during Angiox therapy.
Pri bolnikih z ledvično insuficienco morate med terapijo z zdravilom Angiox nadzorovati parametre strjevanja, kot je ACT.
Dose adjustments for this age group should be on the basis of renal function, see section 4.2.
Prilagoditev odmerkov za to starostno skupino mora biti odvisna od ledvične funkcije; glejte poglavje 4. 2.
15 Weight:
Telesna masa:
Bivalirudin dose is body weight adjusted in mg/ kg.
Odmerek bivalirudina je prilagojen telesni masi v mg/ kg.
5.3 Pre-clinical safety data
5. 3 Predklinični podatki o varnosti
Toxicity in animals upon repeated or continuous exposure (1 day to 4 weeks at exposure levels of up to 10 times the clinical steady state plasma concentration) was limited to exaggerated pharmacological effects.
Toksičnost pri živalih po večkratni ali neprekinjeni izpostavljenosti (1 dan do 4 tedne pri stopnji izpostavljenosti do 10- kratne plazemske koncentracije v kliničnem stanju dinamičnega ravnovesja) je bila omejena na povečane farmakološke učinke.
Bivalirudin is intended for short-term administration and therefore no data on the long-term carcinogenic potential of bivalirudin are available.
14 Bivalirudin je namenjen kratkotrajnemu dajanju in zato ni podatkov o dolgotrajnem karcinogenem potencialu bivalirudina.
Mannitol Sodium hydroxide solution 2% (for pH adjustment).
6. 2 Inkompatibilnosti
The following medicinal products should not be administered in the same intravenous line as bivalirudin since they result in haze formation, micro-particulate formation or gross precipitation; alteplase, amiodarone HCl, amphotericin B, chlorpromazine HCl, diazepam, prochlorperazine edisylate, reteplase, streptokinase and vancomycin HCl.
Naslednjih zdravil ne dajajte po isti intravenski poti kot bivalirudin, ker ima to lahko za posledico tvorbo razpršenih kapljic, mikrodelcev ali močno precipitacijo; alteplas, amiodaronijev klorid, amfotericin B, klorpromazinijev klorid, diazepam, proklorperazin edisilat, reteplas, streptokinaza in vankomicinijev klorid.
Chemical and physical in-use stability has been demonstrated for 24 hours at 2-8oC.
Rekonstituirana raztopina: kemična in fizikalna stabilnost ob uporabi je bila dokazana za 24 ur pri temperaturi 2 oC - 8 oC.
Chemical and physical in-use stability has been demonstrated for 24 hours at 25oC.
Razredčena raztopina: kemična in fizikalna stabilnost ob uporabi je bila dokazana za 24 ur pri temperaturi 25 oC.
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 – 8 oC, unless reconstitution/ dilution has taken place in controlled and validated aseptic conditions.
Ne shranjujte dlje kot 24 ur pri temperaturi med 2 oC in 8 °C, razen če rekonstitucija in redčenje nista bila opravljena v nadzorovanih in preverjeno aseptičnih pogojih.
Lyophilised powder:
Liofiliziran prašek:
Store in a refrigerator (2 – 8oC).
Shranjujte v hladilniku (2 oC - 8 oC).
16 Diluted solution:
Razredčena raztopina:
Angiox is supplied as a lyophilised powder in 10 ml single use glass vials (Type 1) closed with a butyl rubber stopper and sealed with a crimped aluminum seal.
Angiox je dobavljen kot liofiliziran prašek v 10 ml steklenih vialah (Tip 1) za enkratno uporabo, zaprtih z butilnim gumijastim zamaškom in nabranim aluminijastim zamaškom.
Angiox is available in packs of 2 and 10 vials.
Angiox je pakiran v škatlah po 2 in 10 vial.
Instructions for administration
Navodila za dajanje zdravila.
Withdraw 5ml from the vial, and further dilute in a total volume of 50ml of glucose solution for injection 5%, or sodium chloride 9mg/ ml (0.9%) solution for injection to give a final bivalirudin concentration of 5mg/ ml.
Dodajte 5 ml vode za injekcije v eno vialo Angioxa.
The reconstituted/ diluted solution should be inspected visually for particulate matter and discolouration.
Preglejte, ali rekonstituirana/ razredčena raztopina vsebuje delce in ali je barva spremenjena.
The reconstituted/ diluted solution will be a clear to slightly opalescent, colourless to slightly yellow solution.
Rekonstituirana/ razredčena raztopina bo bistra do rahlo opalescentna, brezbarvna do rahlo rumene barve.
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17 ANNEX II
16 DODATEK II
Hälsa Pharma GmbH, Immermannstraße 9, 33619 Bielefeld, GERMANY
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• OTHER CONDITIONS
Navedba smiselno ni potrebna..
Risk Management Plan
• DRUGI POGOJI
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 4 of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation and any subsequent updates of the RMP agreed by the CHMP.
Načrt upravljanja tveganja MAH se zavezuje, da bo izvedel študije in dodatne dejavnosti farmakovigilance, ki so navedene v načrtu farmakovigilance, kot je bilo dogovorjeno v različici 4 Načrta upravljanja tveganja (RMP – » Risk Management Plan «), ki je bil predstavljen v Modulu 1. 8. 2. dovoljenja za promet z zdravilom in vseh morebitnih dodatnih posodobitvah RMP, kot je bilo dogovorjeno s CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
Sočasno z naslednjim periodičnim poročilom o varnosti zdravila (PSUR) je treba predložiti dopolnjen Načrt upravljanja tveganja v skladu s Smernicami za sisteme upravljanja tveganja pri zdravilih za uporabo v humani medicini Odbora za zdravila za uporabo v humani medicini (CHMP).
In addition, an updated RMP should be submitted;
Poleg tega je treba predložiti posodobljen RMP:
• When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities •
kadar so prejete nove informacije, ki lahko vplivajo na trenutno specifikacijo varnosti, Farmakovigilančni načrt ali dejavnosti zmanjševanja tveganja;
Within 60 days of an important (pharmacovigilance or risk minimisation) milestone reached
v 60 dneh od pomembne ugotovitve (farmakovigilanca ali zmanjševanje tveganja); na zahtevo Evropske agencije za zdravila (EMEA).
being
18 DODATEK III
At the request of the EMEA.
OZNAČEVANJE IN NAVODILO ZA UPORABO
LABELLING AND PACKAGE LEAFLET
OZNAČEVANJE
LABELLING
20 PODATKI NA ZUNANJI OVOJNINI ALI STIČNI OZ.
21 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
PRIMARNI OVOJNINI, KADAR ZUNANJE NI
Outer carton (pack of 2 vials).
Škatla (pakiranje z 2 vialama).
Angiox 250 mg powder for concentrate for solution for injection or infusion. bivalirudin
Angiox 250 mg prašek za koncentrat za raztopino za injiciranje ali infundiranje. bivalirudin
Mannitol, sodium hydroxide 2%.
Manitol, 2% natrijev hidroksid.
2 vials.
2 viali.
EXP {MM/YYYY}
Uporabno do ali EXP (MM/ LLLL)
BATCH NUMBER
ŠTEVILKA SERIJE 13.
23 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
22 PODATKI NA ZUNANJI OVOJNINI ALI STIČNI OZ.
Outer carton (pack of 10 vials).
Škatla (pakiranje z 10 vialami).
10 vials.
10 vial.
Justification for not including Braille accepted.
Sprejeta je utemeljitev, da Braillova pisava ni potrebna..
25 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
24 PODATKI, KI MORAJO BITI NAJMANJ NAVEDENI NA MANJŠIH STIČNIH OVOJNINAH
Angiox 250 mg powder for concentrate for solution for injection or infusion Intravenous use bivalirudin
Intravenozna uporaba bivalirudin