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Real-World Analysis of Potential Pharmacokinetic and Pharmacodynamic Drug Interactions with Apixaban in Patients with Non-Valvular Atrial Fibrillation

Authors Badreldin HA, Alghamdi J, Alshaya O, Alshehri A, Alreshoud L, Altoukhi R, Vasudevan S, Ismail WW, Mohamed MSA

Received 3 May 2020

Accepted for publication 1 July 2020

Published 22 July 2020 Volume 2020:13 Pages 419—427

DOI https://doi.org/10.2147/IJGM.S260813

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Scott Fraser


Hisham A Badreldin,1 Jahad Alghamdi,2 Omar Alshaya,1 Abdulmajeed Alshehri,1 Lamya Alreshoud,1 Renad Altoukhi,1 Senthilvel Vasudevan,1 Wesam W Ismail,1,3 Mohamed Salih Aziz Mohamed4

1Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia; 2The Saudi Biobank, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia; 3Department of Pharmacy Practice and Science, College of Pharmacy, The University of Iowa, Iowa City, IA, United States; 4Adult Cardiology Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia

Correspondence: Hisham A Badreldin
King Saud bin Abdulaziz University for Health Sciences, PO Box 3660, Riyadh 11481, Saudi Arabia
Tel +966 11 4299999 ext. 95103
Fax +966 11 4299999 Ext 95058
Email aldeenh@ksau-hs.edu.sa

Purpose: We conducted this study to assess the real-world prevalence, nature, predictors, and clinical necessity of apixaban pharmacokinetic (PK) and pharmacodynamic (PD) drug interactions in patients with non-valvular atrial fibrillation (NVAF) at a tertiary medical institution in Saudi Arabia.
Patients and Methods: An observational retrospective cohort analysis was conducted in adult patients diagnosed with NVAF receiving apixaban for stroke prevention from the period of June 2015 to May 2019.
Results: Of the 1271 patients included in the analysis, 611 (48.1%) patients had potential PD– or PK–drug interactions with apixaban. Of those, 490 (38.6%) patients had potential PD drug–drug interactions (DDIs) and 121 (9.5%) patients had potential PK-DDIs. PD-DDIs with apixaban were mainly with antiplatelet therapy followed by non-steroidal anti-inflammatory drugs and antidepressants. PK-DDIs with apixaban were mainly with combined P-gp/CYP3A4 inhibitors or inducers. History of minor bleeding was positively correlated with PD-DDIs with apixaban, ß coefficient = 0.455 (OR 1.58; 95% CI 1.01– 2.45); p< 0.05. History of acute coronary syndrome was positively correlated with PD-DDIs with apixaban, ß coefficient = 0.515 (OR 1.60; 95% CI 1.36– 1.99); p< 0.05. History of heart failure was positively correlated with PK-DDIs with apixaban, ß coefficient = 0.459 (OR 1.58; 95% CI 1.07– 2.35); p< 0.05. Almost 15% of the included patients had no clinical indication to receive the potential interacting drug with apixaban and about 20% of them were assuming an inappropriate apixaban dose according to the product package insert.
Conclusion: Pharmacodynamics and pharmacokinetics interactions are common in more than half of the patients with NVAF receiving apixaban for stroke prevention in this real-world analysis. Some of these interacting medications are not indicated. Drug–drug interactions should always be considered and monitored with apixaban with a regular assessment of the need for any interacting medication.

Keywords: apixaban, drug interaction, pharmacokinetic, pharmacodynamic, atrial fibrillation

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