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Drug Interactions between Androgen Receptor Axis-Targeted Therapies and Antithrombotic Therapies in Prostate Cancer: Delphi Consensus
by
, , ,
Kori Leblanc
1,2,*
,
Scott J. Edwards
3,4,
George Dranitsaris
5, 
Darryl P. Leong
6,7,
Marc Carrier
8,9,
Shawn Malone
10,11,
Ricardo A. Rendon
12,13,
Alison M. Bond
14,
Troy D. Sitland
13,15,
Pawel Zalewski
16,
Michelle Wang
17 and
Urban Emmenegger
18,19
1
Department of Pharmacy, University Health Network, Toronto, ON M5G 2C4, Canada
2
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada
3
Cancer Care Program, Eastern Health, St. John’s, NL A1B 3V6, Canada
4
School of Pharmacy, Memorial University of Newfoundland, St John’s, NL A1B 3V6, Canada
5
Department of Public Health, Falk College, Syracuse University, Syracuse, NY 13244, USA
6
Hamilton Health Sciences, Population Health Research Institute, Hamilton, ON L8L 2X2, Canada
7
Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada
8
The Ottawa Hospital Research Institute, Ottawa, ON K1Y 4E9, Canada
9
Department of Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada
10
The Ottawa Hospital Cancer Centre, Ottawa, ON K1H 8L6, Canada
11
Department of Radiology, University of Ottawa, Ottawa, ON K1N 6N5, Canada
12
Queen Elizabeth II Health Sciences Centre, Halifax, NS B3H 3A7, Canada
13
Department of Urology, Dalhousie University, Halifax, NS B3H 1Y6, Canada
14
Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada
15
The Moncton Hospital, Moncton, NB E1C 4B7, Canada
16
Durham Regional Cancer Centre, Oshawa, ON L1G 2B9, Canada
17
Bayer Inc., Mississauga, ON L4W 5R6, Canada
18
Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada
19
Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
*
Author to whom correspondence should be addressed.
Cancers 2024, 16(19), 3336; https://doi.org/10.3390/cancers16193336 (registering DOI)
Submission received: 8 August 2024
/
Accepted: 24 September 2024
/
Published: 29 September 2024
(This article belongs to the Special Issue Clinical Pharmacology in Cancer)
Simple Summary
Prostate cancer is most commonly diagnosed in males after the age of 55 years. These patients are also at risk for cardiovascular disease and venous thromboembolism requiring antithrombotic therapy. Prostate cancer treatments, such as androgen receptor axis-targeted therapies (ARATs, i.e., abiraterone acetate, apalutamide, darolutamide, and enzalutamide), may interact with common antithrombotic medications like warfarin, clopidogrel, and the direct oral anticoagulants. However, the data detailing the clinical outcomes of patients treated with these combinations are limited. We undertook a comprehensive review of the literature and modified Delphi process to enable development of an evidence-based consensus document for the co-prescribing of ARATs with antithrombotic medications. Our assessments relied heavily on pharmacokinetic data and extrapolation from drug interaction studies of similarly metabolized drugs, highlighting the need for more research into the clinical impact of drug interactions in prostate cancer patients. Nonetheless, we provide a practical framework to support clinicians in day-to-day therapeutic decision making.
Abstract
Background/Objectives: Abiraterone acetate, apalutamide, darolutamide, and enzalutamide, which make up the androgen receptor axis-targeted therapies (ARATs) drug class, are commonly used in the management of prostate cancer. Many patients on ARATs also receive oral antithrombotic therapy (i.e., anticoagulants or antiplatelets). The concomitant use of ARATs and antithrombotic therapies creates the potential for clinically relevant drug–drug interactions, but the literature regarding the actual consequences of these interactions, and guidance for co-prescribing, is limited. We assembled a multidisciplinary panel of experts and provided them with clinical information derived from a comprehensive literature review regarding the drug–drug interactions between ARATs and antithrombotic therapies. Methods: A three-stage modified electronic Delphi process was used to gather and consolidate opinions from the panel. Each stage consisted of up to three rounds of voting to achieve consensus on which ARAT/antithrombotic therapy drug pairs warrant attention, the possible clinical consequences of drug–drug interactions, and suggested actions for management. Results: The panel achieved consensus to avoid 11 ARAT/antithrombotic therapy drug pairs and modify therapy for eight pairs. Assessments relied heavily on pharmacokinetic data and extrapolation from drug–drug interaction studies of similarly metabolized drugs. Conclusions: This e-Delphi process highlights the need for further research into the clinical impact of ARAT/antithrombotic drug interactions. Nonetheless, the suggested actions aim to provide clinicians with a practical framework for therapeutic decision making.
