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Drug–drug interaction of rivaroxaban and calcium channel blockers in patients aged 80 years and older with nonvalvular atrial fibrillation

  • Dmitry Sychev ORCID logo , Karin Mirzaev ORCID logo , Marina Cherniaeva ORCID logo EMAIL logo , Maria Kulikova ORCID logo , Pavel Bochkov ORCID logo , Roman Shevchenko ORCID logo , Svetlana Gorbatenkova , Olga Golovina ORCID logo , Olga Ostroumova ORCID logo , Damirya Bahteeva ORCID logo and Eric Rytkin ORCID logo
Published/Copyright: September 4, 2020
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Drug Metabolism and Personalized Therapy
From the journal Drug Metabolism and Personalized Therapy Volume 35 Issue 3

Abstract

Objectives

For revealing the peculiarities of the drug–drug interaction of rivaroxaban (substrate CYP3A4 and P-gp) and calcium channel blockers (CCBs) (verapamil – inhibitor CYP3A4 and P-gp and amlodipine – substrate CYP3A4) in patients 80 years and older with nonvalvular atrial fibrillation (NAF) we studied 128 patients.

Methods

All patients were divided into groups depending on the therapy taken: the 1st – rivaroxaban + amlodipine (n=51), the 2nd – rivaroxaban + verapamil (n=30), the control group – rivaroxaban without CCBs (n=47). A trough steady-state plasma concentration (Cmin,ss) of rivaroxaban, prothrombin time (PT) in the blood plasma and the event of clinically relevant non-major (CRNM) bleeding were assessed for each patient.

Results

Patient in group 2 had higher Cmin,ss of rivaroxaban, PT and CRNM than subjects in the control group (Me 73.8 [50.6–108.8] ng/mL vs. 40.5 [25.6–74.3] ng/mL; Me 14.8 [13.4–17.3] s vs. 13.8 [12.6–14.4] s; 34% vs. 13%, respectively, p<0.05 for all). When compared, the PT and complication rate in group 1 with the control group Cmin,ss of rivaroxaban were practically the same (p>0.05 for all).

Conclusions

In patients ≥80 years with NAF, the use of rivaroxaban in combination with verapamil may not be safe and can lead to CRNM bleeding.

Keywords: amlodipine; drug–drug interaction; elderly patients; nonvalvular atrial fibrillation; pharmacokinetics; rivaroxaban; therapeutic drug monitoring; verapamil
Corresponding author: Marina Cherniaeva, MD, PhD, Associate Professor of the Department of Internal and Preventive Medicine of Federal State Budgetary Institution of Higher Professional Education “Central State Medical Academy of the Presidential Administration of the Russian Federation”, Marshal Timoshenko Street, 19, Building 1A, 121359Moscow, Russia; and Geriatrician, General Practitioner State Budgetary Institution of Health “Hospital for War Veterans No. 2” of the Department of Health of Moscow, Russia, 109472, Moscow, Volgogradsky prospect, 168. Phone: +7-964-587-3003, E-mail:

Funding source: Russian Science Foundation

Award Identifier / Grant number: 16-15-00227

  1. Research funding: This study has been supported by the Russian Science Foundation under Project No. 16-15-00227.

  2. Author contributions: DS – Conceptualization, Methodology, Resources, Investigation, Writing – Review & Editing, Project administration, Funding acquisition. KM – Resources, Investigation, Writing: Review & Editing, Funding acquisition. MC – Conceptualization, Methodology, Validation, Formal analysis, Investigation, Data Curation, Writing: Original Draft, Project administration. MK – Investigation, Formal analysis, Writing: Original Draft. PB – Resources, Investigation, Writing: Original Draft. RS – Resources, Investigation, Writing: Original Draft. SG – Investigation, Resources, Writing: Original Draft. OG – Investigation, Formal analysis, Writing: Original Draft. OO – Conceptualization, Methodology, Writing: Review & Editing. DB – Investigation, Formal analysis, Writing: Original Draft. ER – Investigation, Writing: Review & Editing. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The study was approved by the Ethics Committee of the Russian Medical Academy of Continuous Professional Education (Protocol No. 1 from 22.01.2019), and it was conducted in accordance with the Declaration of Helsinki in compliance with Good Clinical Practice.

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Received: 2020-05-31
Accepted: 2020-06-22
Published Online: 2020-09-04

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/dmpt-2020-0127
Keywords for this article
amlodipine; drug–drug interaction; elderly patients; nonvalvular atrial fibrillation; pharmacokinetics; rivaroxaban; therapeutic drug monitoring; verapamil

Articles in the same Issue

  1. Editorial
  2. Clinical implementation of pharmacogenetics and personalized drug prescription based on e-health: the MedeA initiative
  3. Review
  4. Pain pharmacogenetics
  5. Herbal preparations in the management of hypothyroidism in Unani medicine
  6. Mini Review
  7. Dapsone for Pneumocystis jirovecii pneumonia prophylaxis – applying theory to clinical practice with a focus on drug interactions
  8. Original Articles
  9. No effect of lipoic acid on catalytic activity of cytochrome P450 3A4
  10. Exploring the potential of pyrazoline containing molecules as Aβ aggregation inhibitors in Alzheimer’s disease
  11. Potential drug-drug interactions in ICU patients: a retrospective study
  12. Drug–drug interaction of rivaroxaban and calcium channel blockers in patients aged 80 years and older with nonvalvular atrial fibrillation
  13. Silver sulfadiazine loaded breathable hydrogel sponge for wound healing
  14. Protective effect of Cyperus esculentus (tiger nut) extract against scopolamine-induced memory loss and oxidative stress in mouse brain
  15. Role of purinergic signaling pathways in the adaptogenic-like activity of methyl jasmonate in rats exposed to unpredictable chronic mild stress
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