natgillin/translations-raw huggingface dataset:
Derfor skal der tages højde for risikoen for blødning, når tilstanden hos en patient, der får antikoagulantia, evalueres.
Therefore, the possibility of haemorrhage is to be considered in evaluating the condition in any anticoagulated patient.
6 Bivirkningerne i de tre fase III- studier, er anført i tabel 1 nedenfor efter systemorganklasse (i henhold til MedDRA) og hyppighed.
Adverse reactions in the three phase III studies are listed in table 1 below by system organ class (in MedDRA) and by frequency.
Almindelig:
Table 1:
Ikke almindelig:
Treatment-emergent adverse reactions
Sjælden:
Common
Meget sjælden:
Uncommon
Ikke kendt:
Rare
≥ 1/ 100 til < 1/ 10 ≥ 1/ 1. 000 til < 1/ 100 ≥ 1/ 10. 000 til < 1/ 1. 000 < 1/ 10. 000 kan ikke beregnes ud fra de foreliggende data.
Not known*
Tabel 1:
Investigations
Bivirkninger,
Increased GGT, increase in
der er opstået under behandling
transaminases (incl.
Almindelig Undersøgelser
increased (with or without concomitant increase of ALT)
Øget GGT, stigning i transaminaser (herunder stigning i ALAT, stigning i ASAT) Hjerte Blod og lymfesystem
Cardiac disorders Tachycardia Blood and lymphatic system disorders
Øget lipase, øget amylase, øget bilirubin i blodet, øget LDH, øget alkalisk fosfatase Takykardi
Anaemia (incl. respective laboratory parameter)
Stigning i konjungeret bilirubin (med eller uden samtidig stigning i ALAT)
Thrombocythaemia (incl. platelet count increased)
Anæmi (herunder de respektive laboratorieparametre) Nervesystemet Mave- tarm- kanalen
Nervous system disorders Syncope (incl. loss of consciousness), dizziness, headache Gastrointestinal disorders
Trombocytæmi (herunder øget trombocyttal) Synkope (herunder bevidsthedstab), svimmelhed, hovedpine
Nausea
Obstipation, diaré, abdominalsmerter og gastrointestinale smerter (herunder smerter i den øvre del af abdomen og mavegener), dyspepsi (herunder gener i epigastrium), mundtørhed, opkastning Nedsat nyrefunktion (herunder øget kreatinin i blodet, øget urinstof i blodet)
Constipation, diarrhoea, abdominal and gastrointestinal pain (incl. upper abdominal pain, stomach discomfort), dyspepsia (incl. epigastric discomfort), dry mouth, vomiting
Pruritus (herunder sjældne tilfælde af generaliseret pruritus), udslæt, urticaria (herunder sjældne tilfælde af generaliseret urticaria), kontusion Knogler, led, muskler og bindevæv Smerter i ekstremitet Traumer, forgiftninger og behandlingskomplikationer Sårsekretion
Renal and urinary disorders Renal impairment (incl. blood creatinine increased, blood urea increased) Skin and subcutaneous tissue disorders Pruritus (incl. rare cases of generalised pruritus), rash, urticaria (incl. rare cases of generalised urticaria), contusion Musculoskeletal and connective tissue disorders Pain in extremity Injury, poisoning and procedural complications Wound secretion Vascular disorders
Vaskulære sygdomme
Post-procedural
Ikke almindelig
Haemorrhage (incl. haematoma and rare
Ikke kendt *
Bleeding into a
Blødning (herunder hæmatom og sjældne tilfælde af muskelblødning), gastrointestinal blødning (herunder gingival blødning, rektal blødning, hematemese), hæmaturi (herunder blod i urinen), blødning i genitalkanalen (herunder menorrhagi), hypotension (herunder fald i blodtryk, hypotension under proceduren), næseblod
haemorrhage (incl. cases of muscle haemorrhage), post-operative gastrointestinal tract haemorrhage (incl. anaemia, and gingival bleeding, rectal haemorrhage, wound haememesis), haematuria (incl. blood haemorrhage) urine present), genital tract haemorrhage (incl. menorrhagia), hypotension (incl. blood pressure decreased, procedural hypotension), nose bleed General disorders and administration site conditions Localised oedema, peripheral oedema, feeling unwell (incl. fatigue, asthenia), fever Immune system disorders
Blødning i et kritisk organ (f. eks. hjernen), adrenal blødning, konjunktival blødning, hæmoptyse
critical organ (e. g. brain), adrenal haemorrhage, conjunctival haemorrhage, haemoptysis
Almene symptomer og reaktioner på administrationsstedet Lokalt ødem, perifert ødem, utilpashed (herunder træthed og asteni), feber Immunsystemet Lever og galdeveje
Hepatobiliary disorders
Hypersensitivitet
Hypersensi- tivity
* Bivirkninger, der er rapporteret i andre kliniske studier end de tre fase III- studier, hvor patienterne gennemgik et omfattende ortopædkirurgisk indgreb på underekstremiteterne.
*) Adverse events have been reported in other clinical studies than the three phase III studies in patients undergoing major orthopaedic surgery of the lower limbs
Overdosering efter indtagelse af rivaroxaban kan medføre hæmoragiske komplikationer på grund af de farmakodynamiske egenskaber.
Overdose following administration of rivaroxaban may lead to haemorrhagic complications due to its pharmacodynamic properties.
Der findes ikke en specifik antidot, som antagoniserer rivaroxabans farmakodynamiske virkning.
A specific antidote antagonising the pharmacodynamic effect of rivaroxaban is not available.
Hvis der forekommer blødning, kan behandlingen heraf omfatte følgende trin: • Udskydelse af den næste indtagelse af rivaroxaban eller seponering af behandlingen, alt efter hvad der er relevant.
Should bleeding occur, management of the haemorrhage may include the following steps: • delay of next rivaroxaban administration or discontinuation of treatment as appropriate.
5. 2). • Der skal overvejes passende symptomatisk behandling, f. eks. mekanisk kompression, kirurgisk intervention, væskesubstitution og hæmodynamisk understøttelse samt transfusion af blodprodukter eller - komponenter.
Rivaroxaban has mean terminal half-lives between 7 and 11 hours (see section 5.2). • appropriate symptomatic treatment, e. g. mechanical compression, surgical interventions, fluid replacement and haemodynamic support, blood product or component transfusion should be considered.
Hvis en livstruende blødningen ikke kan reguleres ved ovenstående tiltag, kan det overvejes at give rekombinant faktor VIIa.
If life-threatening bleeding cannot be controlled by the above measures, administration of recombinant factor VIIa may be considered.
Der er dog på nuværende tidspunkt ingen erfaring med brug af rekombinant faktor VIIa hos personer, der får rivaroxaban.
However, there is currently no experience with the use of recombinant factor VIIa in individuals receiving rivaroxaban.
Anbefalingen er baseret på begrænsede, ikke- kliniske data.
The recommendation is based on limited non-clinical data.
Der er hverken videnskabeligt rationale for fordele ved eller erfaring med anvendelse af systemiske hæmostatika (f. eks. desmopressin, aprotinin, traneksamsyre eller aminokapronsyre) hos personer, som får rivaroxaban.
There is neither scientific rationale for benefit nor experience with the use of systemic haemostatics (e. g. desmopressin, aprotinin, tranexamic acid, aminocaproic acid) in individuals receiving rivaroxaban.
Andre antitrombotiske midler, ATC- kode:
Other antithrombotic agents, ATC code:
Virkningsmekanisme Rivaroxaban er en yderst selektiv, direkte faktor Xa- hæmmer med oral biotilgængelighed.
Mechanism of Action Rivaroxaban is a highly selective direct factor Xa inhibitor with oral bioavailability.
Hæmning af faktor Xa afbryder blodkoagulationskaskadens intrinsiske og ekstrinsiske bane, og hæmmer både dannelsen af trombin og tromber.
Inhibition of Factor Xa interrupts the intrinsic and extrinsic pathway of the blood coagulation cascade, inhibiting both thrombin formation and development of thrombi.
Rivaroxaban hæmmer ikke trombin (aktiveret faktor II), og der er ikke vist nogen effekt på blodpladerne.
Rivaroxaban does not inhibit thrombin (activated Factor II) and no effects on platelets have been demonstrated.
Farmakodynamiske effekter Der er set dosiafhængig hæmning af faktor Xa- aktivitet hos mennesker.
Pharmacodynamic effects Dose-dependent inhibition of Factor Xa activity was observed in humans.
Protrombintiden (PT) påvirkes af rivaroxaban i forhold til dosis og i tæt sammenhæng med plasmakoncentrationerne (r- værdi lig med 0, 98), hvis der anvendes Neoplastin til analysen.
Prothrombin time (PT) is influenced by rivaroxaban in a dose dependent way with a close correlation to plasma concentrations (r value equals 0.98) if Neoplastin is used for the assay.
PT skal måles i sekunder, da INR (international normalised ratio) kun kalibreres og valideres for coumariner og ikke kan anvendes i forbindelse med andre antikoagulantia.
The readout for PT is to be done in seconds, because the INR (International Normalized Ratio) is only calibrated and validated for coumarins and cannot be used for any other anticoagulant.
Hos patienter, som gennemgik større ortopædkirurgiske indgreb, lå 5/ 95- percentilerne for PT (Neoplastin) 2- 4 timer efter indtagelse af tabletterne (dvs. da der var opnået maksimal effekt) på mellem 13 og 25 sekunder (baselineværdier før kirurgi 12 til 15 sek.).
In patients undergoing major orthopaedic surgery, the 5/ 95 percentiles for PT (Neoplastin) 2 - 4 hours after tablet intake (i. e. at the time of maximum effect) ranged from 13 to 25 s (baseline values before surgery 12 to 15s).
Anti- faktor Xa- aktiviteten påvirkes også af rivaroxaban, men der er ingen kalibreringsstandard.
Anti- Factor Xa activity is also influenced by rivaroxaban; however, no standard for calibration is available.
Klinisk effekt og sikkerhed Det kliniske program for rivaroxaban har til formål at påvise rivaroxabans effekt på forebyggelsen af venøs tromboemboli (VTE), dvs. proksimal og distal dyb venetrombose (DVT) og lungeemboli (PE) hos patienter, der gennemgår større ortopædkirurgiske indgreb i underekstremiteterne.
Clinical efficacy and safety The rivaroxaban clinical programme was designed to demonstrate the efficacy of rivaroxaban for the prevention of VTE, i. e. proximal and distal deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients undergoing major orthopaedic surgery of the lower limbs.
Over 9. 500 patienter (7. 050, der fik foretaget hofteledsalloplastik, og 2. 531, der fik foretaget knæalloplastik) deltog i kontrollerede, randomiserede, dobbeltblindede kliniske fase III- studier, også kaldet RECORD - programmet.
Over 9,500 patients (7,050 in total hip replacement surgery and 2,531 in total knee replacement surgery) were studied in controlled randomised double-blind phase III clinical studies, the RECORD-programme.
Der blev foretaget en sammenligning mellem indtagelse af 10 mg rivaroxaban én gang dagligt tidligst 6 timer efter operationen og 40 mg enoxaparin givet én gang dagligt, startende 12 timer før operationen.
8 Rivaroxaban 10 mg once daily (od) started no sooner than 6 hours post-operatively was compared with enoxaparin 40 mg once daily started 12 hours pre-operatively.
I alle tre fase III- studier (se tabel 2) medførte indtagelsen af rivaroxaban en signifikant reduktion i den samlede forekomst af VTE (alle former for venografisk detekteret eller symptomatisk DVT, ikke- fatal PE og dødsfald) og alvorlig VTE (proksimal DVT, ikke- fatal PE og VTE- relateret dødsfald), som var de på forhånd specificerede primære og væsentligste sekundære effekt- endepunkter.
In all three phase III studies (see table 2), rivaroxaban significantly reduced the rate of total VTE (any venographically detected or symptomatic DVT, non fatal PE and death) and major VTE (proximal DVT, non fatal PE and VTE-related death), the pre-specified primary and major secondary efficacy endpoints.
Desuden var forekomsten af symptomatisk VTE (symptomatisk DVT, ikke- fatal PE og VTE- relateret dødsfald) i alle tre studier lavere hos patienter, der blev behandlet med rivaroxaban, end hos patienter, der blev behandlet med enoxaparin.
Furthermore, in all three studies the rate of symptomatic VTE (symptomatic DVT, non- fatal PE, VTE-related death) was lower in rivaroxaban treated patients compared to patients treated with enoxaparin.
9 Tabel 2:
Table 2:
Effekt - og sikkerhedsresultater fra kliniske fase III- studier
Efficacy and safety results from phase III clinical studies
Forsøgs - population
Study Population
patienter, der fik foretaget hofteledsalloplastik
4,541 patients undergoing total hip replacement surgery
2. 509 patienter, der fik foretaget hofteledsalloplastik
2,509 patients undergoing total hip replacement surgery
2. 531 patienter, der fik foretaget knæalloplastik
2,531 patients undergoing total replacement surgery
Behandlings -
knee
10 mg rivaro -
Treatment dose and duration after surgery
p 10 mg 40 mg p
Rivaroxaban Enoxaparin p 10 mg od 40 mg od 35 ± 4 days 35 ± 4 days
p 10 mg 40 mg p
Rivaroxaban Enoxaparin p 10 mg od 40 mg od 35 ± 4 days 12 ± 2 days
40 mg enox - p 10 mg 40 mg p 10 mg 40 mg
Rivaroxaban Enoxaparin 10 mg od 40 mg od 12 ± 2 days 12 ± 2 days
dosis og - varighed efter operationen
Total VTE Major VTE
enoxa- parin én gang dagligt 12 ± 2 dage
18 (1.1%) 4 (0.2%)
18 (1, 1%) 58 (3, 7%)
58 (3.7%) 33 (2.0%)
17 (2, 0%)
17 (2.0%) 6 (0.6%)
81 (9, 3%) < 0, 001
81 (9.3%) < 0.001 49 (5.1%) < 0.001
79 (9, 6%) 166 (18, 9%) < 0, 001
79 (9.6%) 9 (1.0%)
< 0, 001
166 (18.9%) < 0.001 24 (2.6%) 0.01
49 (5, 1%) < 0, 001
Sympto- matic VTE
9 (1, 0%) 24 (2, 6%) 0, 01
6 (0.4%)
6 (0, 4%) 11 (0, 7%)
11 (0.7%)
8 (1, 0%) 24 (2, 7%)
24 (2.7%)
6 (0, 3%) 2 (0, 1%)
1 (0.1%)
1 (0, 1%)
7 (0.6%)
7 (0, 6%) 6 (0, 5%)
6 (0.5%)
Analysen af de samlede resultater fra fase III- studierne understøttede de data, der blev indsamlet i de enkelte studier vedrørende en reduktion i det samlede antal VTE’ er, alvorlige VTE’ er og symptomatiske VTE’ er med 10 mg rivaroxaban én gang dagligt, sammenlignet med 40 mg enoxaparin én gang dagligt.
The analysis of the pooled results of the phase III trials corroborated the data obtained in the individual studies regarding reduction of total VTE, major VTE and symptomatic VTE with rivaroxaban 10 mg once daily compared to enoxaparin 40 mg once daily.
Absorption Den absolutte biotilgængelighed for rivaroxaban er høj (80% - 100%) ved en dosis på 10 mg.
Absorption The absolute bioavailability of rivaroxaban is high (80% - 100%) for the 10 mg dose.
Rivaroxaban absorberes hurtigt, og den maksimale koncentration (Cmax) opnås 2- 4 timer efter indtagelsen af tabletten.
Rivaroxaban is rapidly absorbed with maximum concentrations (Cmax) appearing 2 - 4 hours after tablet intake.
Indtagelse af mad påvirker ikke rivaroxabans AUC eller Cmax efter en 10 mg dosis.
Intake with food does not affect rivaroxaban AUC or Cmax at the 10 mg dose.
En dosis rivaroxaban på 10 mg kan tages sammen med eller uden mad.
Rivaroxaban 10 mg dose can be taken with or without food.
Variabiliteten i rivaroxabans farmakokinetik er moderat med en inter- individuel variabilitet (CV%), der ligger mellem 30% og 40%, bortset fra på operationsdagen og dagen efter, hvor variabiliteten i eksponering er høj (70%).
Variability in rivaroxaban pharmacokinetics is moderate with inter-individual variability (CV%) ranging from 30% to 40%, apart from the day of surgery and the following day when variability in exposure is high (70%).
Serumalbumin er hovedkomponenten i denne binding.
Distribution Plasma protein binding in humans is high at approximately 92% to 95%, with serum albumin being the main binding component.
2/ 3 af den administrede rivaroxabandosis nedbrydes ved metabolisering, hvoraf halvdelen udskilles med urinen og den anden halvdel med fæces.
Metabolism and Elimination Of the administered rivaroxaban dose, approximately 2/ 3 undergoes metabolic degradation, with half then being eliminated renally and the other half eliminated by the faecal route.
Den sidste tredjedel af den administrerede dosis udskilles uændret i urinen, fortrinsvis via aktiv renal sekretion.
The final 1/ 3 of the administered dose undergoes direct renal excretion as unchanged active substance in the urine, mainly via active renal secretion.
Rivaroxaban metaboliseres via CYP3A4, CYP2J2 og CYP- uafhængige mekanismer.
9 Rivaroxaban is metabolised via CYP3A4, CYP2J2 and CYP-independent mechanisms.
In vitro- undersøgelser har vist, at rivaroxaban er et substrat af transportproteinerne P- gp (P - glycoprotein) og Bcrp (brystcancer- resistensprotein).
Based on in vitro investigations rivaroxaban is a substrate of the transporter proteins P-gp (P-glycoprotein) and Bcrp (breast cancer resistance protein).
Rivaroxaban har en systemisk clearance på omkring 10 l/ t, og kan således klassificeres som et lægemiddel med lav clearance.
With a systemic clearance of about 10 l/ h, rivaroxaban can be classified as a low-clearance drug.
4, 5 timer.
After intravenous administration of a 1 mg dose the elimination half-life is about 4.5 hours.
Efter 10 mg indgivet oralt bliver elimineringen begrænset af absorptionshastigheden med gennemsnitlige terminale halveringstider på 7- 11 timer.
After oral administration of a 10 mg dose the elimination becomes absorption rate limited with mean terminal half-lives of 7 to 11 hours.
Dette skyldtes hovedsageligt en reduceret (tilsyneladende) total og renal clearance.
Special populations Gender/ Elderly (above 65 years) Elderly patients exhibited higher plasma concentrations than younger patients, with mean AUC values being approximately 1.5 fold higher, mainly due to reduced (apparent) total and renal clearance.
Forskellige vægtkategorier Ekstrem legemsvægt (< 50 kg eller > 120 kg) havde kun ringe indvirkning på rivaroxabans plasmakoncentrationer (under 25%).
Different weight categories Extremes in body weight (< 50 kg or > 120 kg) had only a small influence on rivaroxaban plasma concentrations (less than 25%).
Interetniske forskelle Der blev ikke observeret nogen klinisk relevante interetniske forskelle mellem kaukasiske (hvide), afroamerikanske, latinamerikanske, japanske og kinesiske patienter, hvad angår rivaroxabans farmakokinetik og farmakodynamik.
Inter-ethnic differences No clinically relevant inter-ethnic differences among Caucasian, African-American, Hispanic, Japanese or Chinese patients were observed regarding rivaroxaban pharmacokinetics and pharmacodynamics.
Nedsat leverfunktion Hos cirrosepatienter med svagt nedsat leverfunktion (klassificeret som Child Pugh A) sås der kun mindre ændringer i rivaroxabans farmakokinetik (gennemsnitlig stigning i AUC for rivaroxaban på 1, 2 gange), hvilket næsten er sammenligneligt med den tilsvarende raske kontrolgruppe.
Hepatic impairment Cirrhotic patients with mild hepatic impairment (classified as Child Pugh A) exhibited only minor changes in rivaroxaban pharmacokinetics (1.2 fold increase in rivaroxaban AUC on average), nearly comparable to their matched healthy control group.
Hos cirrosepatienter med moderat nedsat leverfunktion (klassificeret som Child Pugh B) steg det gennemsnitlige AUC for rivaroxaban signifikant med 2, 3 gange sammenlignet med raske frivillige.
In cirrhotic patients with moderate hepatic impairment (classified as Child Pugh B), rivaroxaban mean AUC was significantly increased by 2.3 fold compared to healthy volunteers.
Ubunden AUC var øget med en faktor 2, 6.
Unbound AUC was increased 2.6 fold.
PT- forlængelsen steg ligeledes med en faktor på 2, 1.
The inhibition of Factor Xa activity was increased by a factor of 2.6 in patients with moderate hepatic impairment as compared to healthy volunteers; prolongation of PT was similarly increased by a factor of 2.1.
Det resulterede i et stejlere PK/ PD- forhold mellem koncentration og PT.
Patients with moderate hepatic impairment were more sensitive to rivaroxaban resulting in a steeper PK/ PD relationship between concentration and PT.
Xarelto er kontraindiceret til patienter med leversygdom, der medfører koagulationsdefekt og en klinisk relevant blødningsrisiko.
Xarelto is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk.
4. 3 og 4. 4).
Xarelto may be used with caution in cirrhotic patients with moderate hepatic impairment (Child Pugh B) if it is not associated with coagulopathy (see sections 4.3 and 4.4).
Dette blev vurderet ved målinger af patienternes kreatininclearance.
Renal impairment There was an increase in rivaroxaban exposure correlated to decrease in renal function, as assessed via creatinine clearance measurements.
Hos personer med mildt (kreatininclearance 50- 80 ml/ min.), moderat (kreatininclearance 30- 49 ml/ min.) og svært (kreatininclearance 15- 29 ml/ min.) nedsat nyrefunktion sås der en stigning i plasmakoncentrationerne af rivaroxaban (AUC) på henholdsvis 1, 4, 1, 5 og 1, 6 gange.
In individuals with mild (creatinine clearance 50 - 80 ml/ min), moderate (creatinine clearance 30 - 49 ml/ min) and severe (creatinine clearance 15 - 29 ml/ min) renal impairment, rivaroxaban plasma concentrations (AUC) were increased 1.4, 1.5 and 1.6 fold respectively.
PT- forlængelsen steg ligeledes med en faktor på henholdsvis 1, 3, 2, 2 og 2, 4.
In individuals with mild, moderate and severe renal impairment the overall inhibition of factor Xa activity was increased by a factor of 1.5, 1.9 and 2.0 respectively as compared to healthy volunteers; prolongation of PT was similarly increased by a factor of 1.3, 2.2 and 2.4 respectively.
Der foreligger ingen data om patienter med kreatininclearance på < 15 ml/ min.
There are no data in patients with creatinine clearance < 15 ml/ min.
Xarelto bør ikke bruges til patienter med en kreatininclearance på < 15 ml/ min.
Use is not recommended in patients with creatinine clearance < 15 ml/ min.
4. 4).
Xarelto is to be used with caution in patients with creatinine clearance 15 - 29 ml/ min (see section 4.4).
Farmakokinetiske / farmakodynamiske forhold Det farmakokinetiske/ farmakodynamiske forhold (PK/ PD) mellem rivaroxaban plasmakoncentrationer og forskellige PD- endepunkter (faktor Xa- hæmning, PT, aPTT, Heptest) er blevet evalueret efter indgivelse i et bredt dosisinterval (5- 30 mg 2 gange dagligt).
10 Pharmacokinetic/ pharmacodynamic relationship The Pharmacokinetic/ pharmacodynamic (PK/ PD) relationship between rivaroxaban plasma concentration and several PD endpoints (Factor Xa inhibition, PT, aPTT, Heptest) has been evaluated after administration of a wide range of doses (5 - 30 mg bid).
Rivaroxaban 10 mg én gang dagligt resulterede i en steady- state Cmax på ca.
Rivaroxaban 10 mg od results in a steady state Cmax of about 125 µg/ l.
Forholdet mellem koncentrationen af rivaroxaban og faktor Xa- aktiviteten blev bedst beskrevet af en Emax- model.
The relationship between rivaroxaban concentration and Factor Xa activity was best described by an Emax model.
Hældningen varierede betydeligt afhængig af de forskellige anvendte PT - reagenser.
Depending on the different PT reagents used, the slope differed considerably.
Når der blev anvendt Neoplastin PT, var baseline PT omkring 13s og hældningen var
When Neoplastin PT was used, baseline PT was about 13 s and the slope was around 3 to 4 s/ (100 µg/ l).
Resultaterne af PK/ PD analyserne i fase II var konsistente med de data, der blev fundet hos raske forsøgspersoner.
The results of the PK/ PD analyses in Phase II were consistent with the data established in healthy subjects.
Hos patienter var basislinie - faktor Xa og - PT påvirket af det kirurgiske indgreb, hvilket resulterede i en ændring i koncentration- PT- hældningen mellem dagen efter det kirurgiske indgreb og steady- state.
In patients, baseline Factor Xa and PT were influenced by the surgery resulting in a difference in the concentration-PT slope between the day post-surgery and steady state.
Ikke- kliniske data baseret på konventionelle sikkerhedsfarmakologiske studier, toksicitetsstudier med enkeltdosis, fototoksicitet og genotoksicitet viste ingen speciel risiko for mennesker.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, single dose toxicity, phototoxicity and genotoxicity.
Hos rotter ansås de øgede IgG - og IgA - plasmaniveauer for at være klinisk relevante eksponeringsnuveauer.
In rats, increased IgG and IgA plasma levels were seen at clinically relevant exposure levels.
Dyreforsøg har vist reproduktionstoksicitet, som er relateret til rivaroxabans farmakologiske virkningsmekanisme (f. eks. blødningskomplikationer).
Animal studies have shown reproductive toxicity related to the pharmacological mode of action of rivaroxaban (e. g. haemorrhagic complications).