Rivaroxaban Precision Dosing Strategy for Real‐World Atrial Fibrillation Patients

Konicki, Robyn; Weiner, Daniel; Patterson, J. Herbert; González, Daniel; Kashuba, Angela D. M.; Cao, Yanguang; Gehi, Anil K.; Watkins, Paul B.; Powell, J. Robert

doi:10.1111/cts.12766

Cited by 14 publications

(20 citation statements)

References 42 publications

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“…Similar thresholds (i.e. 20% change in AUC) have been selected in recent studies investigating precision dosing strategies for rivaroxaban using a population pharmacokinetic model 48 . However, wider thresholds have been used to guide decisions regarding dose adjustments by the Food and Drug Administration and the marketing authorisation holder, with no dose adjustment recommended in case of mild renal impairment, despite a 44% increase in AUC 22 .…”

Section: Discussionmentioning

confidence: 99%

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Effects of Hypericum perforatum (St John's wort) on the pharmacokinetics and pharmacodynamics of rivaroxaban in humans

Scholz

Liakoni

Hammann

et al. 2020

Brit J Clinical Pharma

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Aims To investigate the influence of a cytochrome P450 CYP3A4 and efflux transporter P‐glycoprotein (P‐gp) inducing Hypericum perforatum extract on the pharmacokinetics and pharmacodynamics of rivaroxaban. Methods Open‐label, nonrandomized, sequential treatment interaction study. Following CYP3A4 and P‐gp phenotyping using low‐dose midazolam and fexofenadine, 12 healthy volunteers received a single oral dose of 20 mg rivaroxaban and rivaroxaban plasma concentrations and inhibition of the activated coagulation factor X (factor Xa) activity were measured prior to and up to 48 h postdosing. The procedures were repeated after 2 weeks’ treatment with the H. perforatum extract. Results The geometric mean ratios for the area under the concentration–time curve and Cmax of rivaroxaban after/before induction with the H. perforatum extract were 0.76 (90% confidence interval [CI] 0.70, 0.82) and 0.86 (90% CI 0.76, 0.97), respectively. Inhibition of factor Xa activity was reduced with a geometric mean area under the effect–time curve ratio after/before induction of 0.80 (90% CI 0.71, 0.89). No clinically significant differences were found regarding Tmax (median 1.5 vs 1 h, P = .26) and terminal elimination half‐life (mean 10.6 vs 10.8 h, P = .93) of rivaroxaban. The H. perforatum extract significantly induced CYP3A4 and P‐gp activity, as evidenced by phenotyping. Conclusion The CYP3A4/P‐gp inducing H. perforatum extract caused a decrease of rivaroxaban exposure with a proportional decrease of the pharmacodynamic effect. Although the data do not justify a contraindication for the combination or a systematic adjustment of rivaroxaban dosage, avoidance of the combination or laboratory monitoring should be considered in patients taking hyperforin‐containing H. perforatum extracts with rivaroxaban.

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Section: Discussionmentioning

confidence: 99%

“…In patients with concomitant use of strong CYP3A4/P‐gp inducers, higher rivaroxaban doses (e.g. 30 mg daily, as proposed by others for patients with a creatinine clearance ≥160 mL/min 48 ) should be evaluated in future studies to provide better guidance for dose adjustment.…”

Section: Discussionmentioning

confidence: 99%

Effects of Hypericum perforatum (St John's wort) on the pharmacokinetics and pharmacodynamics of rivaroxaban in humans

Scholz

Liakoni

Hammann

et al. 2020

Brit J Clinical Pharma

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“…Udruženost genskog polimorfizma i hemoragijskih događaja će svakako biti predmet daljih istraživanja. Danas su u toku ispitivanja koja testiraju bolje dozne režime za rivaroksaban kako bi se osigurala maksimalna efikasnost leka uz smanjenje rizika od krvarenja 23,24,25 .…”

Section: šTa Kažu Studije Iz Realnog žIvota?unclassified

“…Rivaroksaban se ne daje u terminalnoj bubrežnoj slabosti kod klirensa kreatinina < 15 mL/minuti. Kako bi bili sigurni da je lečenje rivaroksabanom započeto i nastavljeno sa korektnom dozom, bubrežna funkcija bi trebalo da se proveri pri uvođenju leka u terapiju, godišnje nakon toga i u uslovima kada se može javiti pogoršanje bubrežne funkcije, kao što su infekcija, dehidratacija, operativni zahvat 7,25 . Iako je terminalna bubrežna slabost kontraindikacija za upotrebu rivaroksabana, njegova bezbednost i efikasnost u blagom do umerenom renalnom oštećenju je pokazana u metaanalizama gde su NOAK lekovi bili upoređivani sa varfarinom.…”

Section: Renoprotektivni Efekat Rivaroksabana?unclassified

New oral anticoagulants in nonvalvular atrial fibrillation

Apostolović¹,

Stanojević²,

Kostić³

2022

Galenika Med J

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Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and its incidence is 1-2% of the world's population. Atrial fibrillation is associated with an increased risk of morbidity and mortality, primarily due to an increased risk of stroke that is five times higher than in the general population. Therefore, life-long anticoagulant therapy is indicated in patients with atrial fibrillation in the prevention of stroke when CHA2DS2-VASc [congestive heart failure, hypertension, age > 75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, gender (female)] score > 2 in men and > 3 in women. For last ten years, anticoagulant therapy involved the use of vitamin K antagonists, primarily warfarin. Until the appearance of non-vitamin K oral anticoagulants (NOACs), that do not require routine efficacy monitoring and have more favorable pharmacological profile, warfarin use is significantly reduced in non-valvular AF. By the year 2017. the percentage of patients on NOAC-s exceeded the number of those on warfarin worldwide. Four NOAC-s are approved for use in patients with AF of nonvalvular origin in Europe: apixaban, dabigatran, edoxaban and rivaroxaban. Evidence from phase III studies suggests that NOAC-s are more effective and safer than warfarin. The most prescribed NOAC in almost all "real life" studies from the USA was rivaroxaban. For rivaroxaban "real life data" such as the XANTUS study show that the incidence of stroke and major bleeding is low (0.7 and 2.1 events per 100 patients / year). The efficacy of rivaroxaban in nonvalvular AF was first demonstrated in the ROCKET-AF large, multicenter, randomized, double-blind study in 14,264 patients. Rivaroxaban was non-inferior to warfarin in the prevention of ischemic stroke and systemic embolism. The overall percentages of major and clinically relevant non-major haemorrhages did not differ between rivaroxaban and warfarin, but there were fewer intracranial or fatal haemorrhages in the rivaroxaban group (0,5% vs 0,7% per year, HR 0,67, 95% CI 0,47-0,93, p = 0,02).

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“…When dose titration is feasible, starting with a dose based on population characteristics (e.g., age or kidney function) would likely save time rather than when only one dose is provided for all patients. For indications like stroke prevention with direct‐acting oral anticoagulants, underdosing is associated with potentially catastrophic outcomes 3,4 . In that drug dosing usually directly influences each patient’s eventual efficacy and safety experience, we believe improvement in initial optimal dosing based on prior knowledge is achievable based on technologies available now.…”

mentioning

confidence: 99%