natgillin/translations-raw huggingface dataset:
Intrakraniel blødning, retroperitoneal blødning, blodtab som udløser transfusion af mindst to portioner fuldblod eller pakkede røde blodceller eller blødning, som resulterer i et fald i hæmoglobin på mere end 3 g/ dl eller et fald i hæmoglobin på mere end 4g/ dl (eller 12% i hæmatokrit) uden at der er identificeret en blødningskilde.
Major bleeding was defined as the occurrence of any of the following: intracranial haemorrhage, retroperitoneal haemorrhage, blood loss leading to a transfusion of at least two units of whole blood or packed red blood cells, or bleeding resulting in a haemoglobin drop of more than 3 g/ dl, or a fall in haemoglobin greater than 4 g/ dl (or 12% of haematocrit) with no bleeding site identified.
Minor blødning er defineret som en hvilken som helst blødning, som ikke opfylder kriterier for en major blødning.
Minor haemorrhage was defined as any observed bleeding event that did not meet the criteria for a major haemorrhage.
Både minor blødning og major blødning var signifikant mindre hyppig i bivalirudingruppen end i heparin - + GPIIb/ IIIa- inhibitor- gruppen.
Both minor and major bleeds were significantly less frequent with bivalirudin than the heparin plus GPIIb/ IIIa inhibitor comparator group.
Major blødning opstod hyppigst ved punkturstedet (se Tabel 5).
Major bleeding occurred most frequently at the sheath puncture site (see Table 5).
8 Tabel 5.
8 Table 5.
REPLACE- 2- studiet; frekvensdata for blødningskilde (bivalirudin vs. heparin + GPIIb/ IIIa- inhibitor).
REPLACE-2; bleeding site frequency data (bivalirudin versus heparin + GPIIb/ IIIa inhibitor).
GPIIb/ IIIa
heparin bivalirudin +GPIIb/ IIIa
Blødningskilde
Bleeding site
(N=2994)%
(N=2994)%
inhibitor (N=3008)%
inhibitor (N=3008)%
Arteriepunktur indstikssted Andet indstikssted Retroperitonealt Gastrointestinalt Øre, næse eller hals
Sheath puncture site Other puncture site Retroperitoneal Gastrointestinal Ear, Nose or Throat
0, 8 0, 2 0, 2 0, 1 0, 1
0.8 0.2 0.2 0.1 0.1
2, 5 0, 2 0, 5 0, 6 0, 3
2.5 0.2 0.5 0.6 0.3
0, 001 1, 000 0, 062 0, 003 0, 085
0.001 1.000 0.062 0.003 0.085
Urogenitialt Intrakranielt
Genitourinary Intracranial Cardio/ pulmonary Other
0, 1 0, 1
< 0.1 < 0.1 0.1 0.4
0, 2 0, 1
0.2 0.1 0.3 0.5
Cardio/ pulmonært
0.125 1.000 0.035 0.556
Post- marketing erfaring
Post-marketing experience
Bivirkninger som har været rapporteret fra omfattende post- marketing erfaring, og som ikke er rapporteret ovenfor, er opdelt efter organklasse i Tabel 6.
Adverse reactions that have been reported from extensive post-marketing experience and that have not been reported above are summarised by system organ class in Table 6.
Der er rapporteret alvorlig blødning, herunder blødning med dødelig udgang, fra post- marketing erfaring med bivalirudin.
Serious bleeding, including bleeding with a fatal outcome has been reported in post-marketing experience for bivalirudin.
Post- marketing- bivirkninger indrapporteret for bivalirudin
Post-marketing adverse reactions reported for bivalirudin
Organklasse Immunsystemet
Immune system disorders
Ukendt hyppighed Anafylaktisk reaktion/ shock, inklusive fatalt shock, hypersensitivitet, urticaria
Anaphylactic reaction, anaphylactic shock including fatal shock, hypersensitivity, urticaria
Hjertet
Vascular disorders
Trombose inklusive fatal trombose, hæmatom
Thrombus including fatal thrombus, haematoma
Bolusdoser op til 7, 5 mg/ kg med bivalirudin som enkeltdosis er også rapporteret.
Single bolus doses of bivalirudin up to 7.5mg/ kg have also been reported.
Ingen af tilfældene var associeret med blødning eller andre bivirkninger.
None of these cases were associated with bleeding or other adverse events.
B01AE06
Direct thrombin inhibitors ATC code B01AE06.
9 Angiox indeholder bivalirudin, som er en direkte og specifik trombininhibitor, som bindes både til det katalytiske site og det anionbindende exosite for både det frie trombin i opløsning og det fibrinbundne trombin i tromben.
Angiox contains bivalirudin, a direct and specific thrombin inhibitor that binds both to the catalytic site and the anion-binding exosite of fluid-phase and clot-bound thrombin.
Bivalirudin hæmmer alle disse trombineffekter.
Bivalirudin inhibits each of these thrombin effects.
Bindingen af bivalirudin til trombin – og dermed dets aktivitet – er reversibel, idet trombin langsomt spalter bivalirudin, Arg3- Pro4- bindingen, hvilket medfører en genetablering af trombins funktion som aktiv site.
The binding of bivalirudin to thrombin, and therefore its activity, is reversible as thrombin slowly cleaves the bivalirudin, Arg3-Pro4, bond, resulting in recovery of thrombin active site function.
Dermed virker bivalirudin initialt som en komplet non- kompetitiv inhibitor af trombin, men ændrer sig over tid til at blive en kompetetiv inhibitor, som muliggør, at initialt inhiberede trombinmolekyler kan interagere med andre koagulationsubstrater og medvirke til koagulation om nødvendigt.
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.
In vitro undersøgelser har også vist, at bivalirudin forlænger den aktiverede partielle tromboplastintid (aPTT), trombintiden (TT) og pro- trombintiden (PT) i normal human plasma på en koncentrationsafhængig måde og at bivalirudin ikke inducerer blodpladeaggregationsrespons mod sera fra patienter med kendt tidligere Heparin- Induceret- Trombocytopeni/ Trombose Syndrom (HIT/ HITTS).
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).
Hos raske frivillige og patienter udviser bivalirudin en dosis - og koncentrationsafhængig antikoagulationsaktivitet påvist ved forlængelse af ACT, aPTT, PT, INR og TT.
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.
Den farmakodynamiske effekt af bivalirudin kan vurderes ved måling af antikoagulationsaktivitet, herunder ACT.
The pharmacodynamic effects of bivalirudin may be assessed using measures of anticoagulation including the ACT.
ACT- værdien er positivt korreleret med dosis og plasmakoncentrationen af den indgivne mængde bivalirudin.
The ACT value is positively correlated with the dose and plasma concentration of bivalirudin administered.
Data fra 366 patienter viser, at ACT ikke påvirkes af samtidig behandling med en GPIIb/ IIIa- inhibitor.
Data from 366 patients indicates that the ACT is unaffected by concomitant treatment with a GPIIb/ IIIa inhibitor.
I kliniske undersøgelser har bivalirudin vist sig at give tilstrækkelig antikoagulation under PCI - procedurer.
In clinical studies bivalirudin has been shown to provide adequate anticoagulation during PCI procedures.
ACUITY- studiet
ACUITY Trial
Det inkluderede 13. 819 patienter med høj risiko for AKS.
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.
I ACUITY- studiets arm B og C var den rekommanderede bivalirudindosis en initialt postrandomiseret IV bolus på 0, 1 mg/ kg legemsvægt efterfulgt af en kontinuerlig IV- infusion med 0, 25 mg/ kg legemsvægt/ time under angiografi eller som klinisk påkrævet.
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.
Patienter der gik videre til en PCI fik en ekstra IV- bolus af bivalirudin på 0, 5 mg/ kg legemsvægt efterfulgt af en øget IV- infusion op til 1, 75 mg/ kg legemsvægt/ time.
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.
I ACUITY- studiets arm A blev UFH eller enoxaparin administreret i henhold til relevante retningslinier for AKS- patienter med UA og NSTEMI.
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.
Patienter i arm A og B blev også randomiseret til behandling med GPIIb/ IIIa- inhibitor enten på randomiseringstidspunktet (før angiografi) eller ved
Patients in Arms A and B were also randomised to receive a GPIIb/ IIIa inhibitor either upfront at the time of randomization (prior to angiography) or at the time of PCI.
I alt 356 patienter (7, 7%) som var randomiseret til arm C blev også behandlet med en GPIIb/ IIIa - inhibitor.
A total of 356 (7.7%) of patients randomised to Arm C also received a GPIIb/ IIIa inhibitor.
Højrisiko- patienter i ACUITY- populationen som havde brug for en angiografi indenfor 72 timer blev ligeligt fordelt ud på de tre behandlingsarme.
High risk patient characteristics of the ACUITY population that mandated angiography within 72 hours were balanced across the three treatment arms.
Cirka 77% af patienterne havde tilbagevendende iskæmi, cirka 70% havde dynamiske EKG- forandringer eller forhøjede kardiale biomarkører, cirka 28% havde diabetes og cirka 99% af alle patienter undergik en angiografi indenfor 72 timer.
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.
Efter angiografi blev patienterne enten henvist til medicinsk behandling (33%), PCI (56%) eller CABG (11%).
Following angiographic assessment, patients were triaged to either medical management (33%), PCI (56%) or CABG (11%).
Patienter fra studiet, der fik blodfortyndende behandling fik det i form af acetylsalicylsyre og clopidogrel.
Additional anti-platelet therapy utilised in the study included aspirin and clopidogrel.
De primære analyser og resultater af ACUITY ved 30 dage og 1 år er vist i tabel 7 og 8 for den samlede population (ITT) og for patienter, der fik acetylsalicylsyre og clopidogrel som foreskrevet i protokollen (før angiografi eller før PCI).
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.
Tabel 7.
11 Table 7.
30- dages endepunktsdata og 1 årsdata og forskelle mellem sammensatte iskæmiske endepunkt og dens bestanddele overfor den samlede population (ITT)
ACUITY trial; 30-day and 1-year risk differences for the composite endpoint and its components for the overall population (ITT)
det
ischaemic
Samlede population (ITT) Arm A Arm B
Overall population (ITT) Arm A Arm B UFH/ e bival nox +GPII Arm C
B– A UFH/ enox bival Arm C
+GPII b/ IIIa B– A bival
30- dage
inhibit
+GPIIb/ IIIa - +GPIIb/ IIIa - inhibitor inhibitor (N=4603) (N=4604)%%
or
Forskel i risiko (95% CI)
(95% CI)
Bival alene (N=4612)%
(N=4612)
Sammensat
(N=46 03)%
7, 3 7, 7
Composite
iskæmi
ischae mia
(- 0, 60; 1, 55)
(-0.60, 1.55)
(- 0, 53; 1, 63)
(-0.53, 1.63)
0, 17 (- 0, 31; 0, 66)
0.17
0, 26 (- 0, 23; 0, 75)
(-0.31, 0.66)
Myokardie - infarkt
(-0.23, 0.75)
0, 04 (- 0, 84; 0, 93)
0.04 (-0.84, 0.93)
0, 45 (- 0, 46; 1, 35)
0.45 (-0.46, 1.35)
0, 39 (- 0, 24; 1, 03)
0.39 (-0.24, 1.03)
0, 10 (- 0, 51; 0, 72)
0.10 (-0.51, 0.72)
Sammensat iskæmi
Composite
15, 3
16.0
15, 9
0.71
0, 65 (- 0, 83; 2, 13)
ischae mia
16, 0
(-0.83, 2.13)
0, 71 (- 0, 77; 2, 19)
(-0.77, 2.19)
0, 04 (- 0, 83; 0, 74)
0.04
- 0, 18 (- 0, 96; 0, 60)
(-0.83, 0.74)
Myokardie - infarkt
(-0.96, 0.60)
0, 19 (- 0, 84; 1, 23)
0.19 (-0.84, 1.23)
0, 83 (- 0, 22; 1, 89)
0.83 (-0.22, 1.89)
0, 78 (- 0, 36; 1, 92)
0.78 (-0.36, 1.92)
0, 37 (- 0, 75, 1, 50)
0.37 (-0.75, 1.50)
11 Table 8.
12 Table 8.
ACUITY studiet; 30- dages endepunkt og 1 årsdata og forskelle mellem det sammensatte iskæmiske endepunkt og dets bestanddele overfor patienter der blev behandlet med acetylsalicylsyre og clopidogrel per protokolgruppe *
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*
Patienter behandlet med acetylsalicylsyre & clopidogrel per protokolgruppe Arm A Arm B B– A Arm C C– A UFH/ enox bival Forskel i bival Forskel i +GPIIb/ IIIa - +GPIIb/ IIIa - risiko alene risiko inhibitor inhibitor (95% CI) (N=2911) (95% CI) (N=2842) (N=2924)%%%
Risk diff. alone inhibit or (95% CI) (95% CI) (N=2911) or (N=29% (N=28 24) 42)%%
Sammensat iskæmi Død
Composite ischae mia
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)
1.4 1.4 -0.00 1.2 -0.14 (-0.60, 0.60) (-0.72, 0.45)
Myokardie - infarkt Uplanlagt revask.
Unplanned revasc.
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 (- 0, 61; 1, 08) (- 1, 20; 0, 39)
2.6 2.8 0.23 2.2 -0.41 (-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) 3, 7 3, 9 0, 20 3, 3 - 0, 36 (- 0, 78; 1, 19) (- 1, 31; 0, 59)
16.1 16.8 0.68 15.8 -0.35 (-1.24, 2.59) (-2.24, 1.54)
Myokardie - infarkt Uplanlagt revask. * clopidogrel
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) 9, 4 10, 0 0, 59 8, 9 - 0, 53 (- 0, 94; 2, 12) (- 2, 02; 0, 96) præ- angiografi eller præ- PCI
9.4 10.0 0.59 8.9 -0.53 (-0.94, 2.12) (-2.02, 0.96)
Hyppigheden af blødningstilfælde ved både ACUITY- skala og TIMI- skala frem til dag 30 er vist i Tabel 9 for den samlede population (ITT) og for patienter der fik acetylsalicylsyre og clopidogrel per protokolgruppe.
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.
12 Table 9.
13 Table 9.
ACUITY- studiet; blødningstilfælde frem til dag 30 for den samlede population (ITT) overfor den gruppe patienter der fik acetylsalicylsyre og clopidogrel per protokolgruppe *
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*
Patienter der fik acetylsalicylsyre & Samlede population (ITT) clopidogrel per protokolgruppe UFH/ enox bival bival UFH/ enox bival bival + + alene + + alene GPIIb/ IIIa GPIIb/ IIIa (N=4612) GPIIb/ IIIa - GPIIb/ IIIa - (N=2911) - inhibitor - inhibitor% inhibitor inhibitor% (N=4603) (N=4604) (N=2842) (N=2924)%%%%
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)%%%%
ACUITY - skala major blødning1
ACUITY
5, 7 5, 3 3, 0 5, 9 5, 4 3, 1
5.7 5.3 3.0 5.9 5.4 3.1
TIMI- skala major blødning2
1 scale major TIMI scale major2
1, 9 1, 7 0, 9 1, 9 1, 9 0, 8
0.9 1.9 1.9
* clopidogrel præ- angiografi eller præ- PCI 1 ACUITY major blødning defineres som en af følgende: intrakraniel, retroperitonal, intraokulær, hæmoragi ved indstikssted, hvor radiologi eller kirurgisk indgreb er nødvendigt, hæmatom ≥ 5 cm i diameter ved indstikssted, reduktion i hæmoglobinkoncentrationen på ≥ 4g/ dL uden synlig blødningskilde, reduktion i hæmoglobinkoncentration på > / = 3g/ dL med en synlig blødningskilde, reoperation pga. blødning, brug af enhver form for blodprodukt til transfusion.
*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.
2 TIMI major blødning defineres som intrakraniel blødning eller fald i hæmoglobinkoncentration ≥ 5g/ dL
2 TIMI major bleeding defined as intracranial bleeding or a decrease in haemoglobin concentration ≥ 5g/ dL
Fordelene ved bivalirudin overfor UFH/ enoxaparin plus GPIIb/ IIIa- inhibitor i forhold til tilfælde af blødninger er kun overvåget i bivalirudin- monotarapiarmen.
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 dages resultater baseret på baseret på firdobbelte og tredobbelte endepunkter fra en randomiseret, dobbelt- blind undersøgelse med over 6000 patienter, som fik foretaget PCI (REPLACE- 2), er vist i Tabel 10.
The 30-day results based on quadruple and triple endpoints from a randomized, double-blind trial of over 6,000 patients undergoing PCI (REPLACE-2), are shown in Table 10.
Major blødning blev i REPLACE- 2 defineret ud fra non- TIMI- kriterier.
Major bleeding in REPLACE-2 was defined by non-TIMI criteria.
REPLACE- 2- studieresultater:
results:
30- dages endepunkt (intent- to- treat og per- protokol - population)
30-day endpoints (intent-to-treat and per-protocol
Intent- to- treat Per- protokol heparin heparin bivalirudin + GPIIb/ IIIa - bivalirudin + GPIIb/ IIIa -
Intent-to-treat Per-protocol heparin heparin
(N=2994)%
bivalirudin + GPIIb/ IIIa bivalirudin + GPIIb/ IIIa (N=2994) inhibitor (N=2902) inhibitor% (N=3008)% (N=2882)%%
inhibitor (N=3008)%
Quadruple
(N=2902)%
endpoint
inhibitor (N=2882)%
9.2 10.0 9.2 10.0
Firdobbelt endepunkt Tredobbelt endepunkt * Delelementer:
Triple endpoint* Components:
9, 2 7, 6
7.6
10, 0 7, 1
7.1
9, 2 7, 8
7.8
Død Myokardieinfarkt Major blødning **
Death Myocardial Infarction Major bleeding**
0, 2 7, 0
0.2 7.0 2.4
0, 4 6, 2
0.4 6.2 4.1
0, 2 7, 1
0.2 7.1 2.2
0, 4 6, 4
0.4 6.4 4.0
(baseret på non- TIMI kriterier - se afsnit 4. 8)
(based on non-TIMI criteria - see section 4.8)
4, 1
Urgent
2, 2
1.2
4, 0
1.4
Tidlig revaskularisering
1.2 1.4 1.2
* undtaget delelementet alvorlige blødninger
revascularization * excludes major bleeding component.
13 Heparin- Induceret Trombocytopeni (HIT) og Heparin- Induceret Trombocytopeni- Trombose Syndrom (HIT/ HITTS):
14 Heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia-thrombosis syndrome (HIT/ HITTS):
Kliniske studier med et lille antal patienter har givet begrænset viden om brug af Angiox hos patienter med HIT/ HITTS.
Clinical trials in a small number of patients have provided limited information about the use of Angiox in patients with HIT/ HITTS.
Middel steady state koncentrationen af bivalirudin ved en konstant intravenøs infusion på 2, 5 mg/ kg legemsvægt/ time er 12, 4 μg/ ml.
The mean steady-state concentration of bivalirudin following a constant intravenous infusion of 2.5 mg/ kg/ h is 12.4 µg/ ml.
Distribution:
Distribution:
Steady state distributionsvolumen er 0, 1 liter/ kg.
The steady-state volume of distribution is 0.1 litre/ kg.
Bivalirudin binder sig ikke til plasmaproteiner (andre end trombin) eller til erythrocytter.
Bivalirudin does not bind to plasma proteins (other than thrombin) or to red blood cells.
Den primære metabolit, som fremkommer når Arg3- Pro4- bindingen af den N- terminale sekvens fraspaltes af trombin, er ikke aktiv på grund af tabet af affinitet til det katalytiske site på trombin.
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.
Cirka 20% af bivalirudin udskilles uforandret i urinen.
About 20% of bivalirudin is excreted unchanged in the urine.
Koncentration/ tids- profilen efter intravenøs administration er godt beskrevet ved en to - kompartment model.
The concentration-time profile following intravenous administration is well described by a two-compartment model.
Eliminationen følger en 1. ordens - proces med en terminal halveringstid på 25 ± 12 minutter hos patienter med normal nyrefunktion.
Elimination follows a first order process with a terminal half-life of 25 ± 12 minutes in patients with normal renal function.
Den relaterede clearance er cirka 3, 4 ± 0, 5 ml/ min/ kg.
The corresponding clearance is about 3.4 ± 0.5 ml/ min/ kg.
Nedsat leverfunktion:
Hepatic Insufficiency:
Bivalirudins farmakokinetik er ikke undersøgt hos patienter med nedsat leverfunktion, men forventes at være uændret, idet bivalirudin ikke metaboliseres af leverenzymer som cytokrom P- 450 isoenzymer.
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.
Nedsat nyrefunktion:
Renal Insufficiency:
Clearance er reduceret med cirka 20% hos patienter med moderat eller svært nedsat nyrefunktion, og med 80% hos dialyseafhængige patienter (Se Tabel 11).
Clearance is reduced by approximately 20% in patients with moderate or severe renal impairment, and 80% in dialysis-dependent patients (Table 11).
Farmakokinetiske parametre for bivalirudin hos patienter med normal og nedsat nyrefunktion.
Pharmacokinetic parameters for bivalirudin in patients with normal and impaired renal function.
Clearance Halveringstid Nyrefunktion (GFR) (ml/ min/ kg) (minutter)
Renal function (GFR)
Normal nyrefunktion (≥ 90ml/ min) Let nedsat nyrefunktion (60 - 89 ml/ min) Moderat nedsat nyrefunktion (30 - 59 ml/ min) Svært nedsat nyrefunktion (10 - 29 ml/ min)
(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)
3, 5 timer
3.5 hours
Koagulationsparametre, som for eksempel ACT, bør måles under Angioxbehandling af patienter med nedsat nyrefunktion.
In patients with renal insufficiency, coagulation parameters such as the ACT should be monitored during Angiox therapy.
Farmakokinetik er undersøgt hos ældre som en del af en nyrefarmakokinetik- undersøgelse.
Pharmacokinetics have been evaluated in elderly patients as part of a renal pharmacokinetic study.
Dosisjustering i denne aldersgruppe bør foretages på basis af den enkeltes nyrefunktion, se afsnit 4. 2.
Dose adjustments for this age group should be on the basis of renal function, see section 4.2.
14 Vægt:
15 Weight:
Dosis af bivalirudin justeres i mg pr. kg legemsvægt.
Bivalirudin dose is body weight adjusted in mg/ kg.
5. 3 Prækliniske sikkerhedsdata
5.3 Pre-clinical safety data
De prækliniske data viser ingen særlig risiko for mennesker vurderet ud fra konventionelle undersøgelser af sikkerhedsfarmakologi, toksicitet efter gentagne doser, genotoksicitet og reproduktionstoksicitet.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety, pharmacology, repeated dose toxicity, genotoxicity, or toxicity to reproduction.
Toksicitet hos dyr udsat for gentagen eller kontinuerlig eksponering (fra 1 dag til 4 ugers behandlingsniveau med op til 10 gange klinisk steady state plasmakoncentration) var begrænset til overdreven farmakologisk effekt.
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.
Sammenligning af enkeltdosis - og flerdosisundersøgelser viste, at toksiciteten primært var relateret til varigheden af behandlingen.
Comparison of the single and repeated dose studies revealed that toxicity was related primarily to duration of exposure.