Drug-Drug Interactions of ERLEADA and Other Androgen Receptor Pathway Inhibitors With Cardiovascular Risk-Lowering Medications

SUMMARY

• Pharmacokinetic profiles of androgen receptor pathway inhibitors (ARPIs) and potential for drug-drug interactions in patients taking ARPIs with select concomitant cardiovascular risk-lowering medications is summarized in Tables: Overview of Select Metabolic and Transporter-Based Interactions for ARPIs and Summary of Potential DDIs Between ARPIs and Select Cardiovascular Risk-Lowering Medications. Clinical significance has not been fully established.
• Oral Anticoagulants
  • The impact of concomitant use of ERLEADA with oral anticoagulants on the incidence of treatment-emergent thrombotic and embolic adverse events (AEs) was evaluated in descriptive post-hoc analyses of the phase 3 registrational SPARTAN and TITAN studies. There was a total of 75 patients taking concomitant direct factor Xa inhibitors, 21 patients taking direct thrombin inhibitors, and 125 patients taking vitamin K antagonists in the ERLEADA or placebo groups. The occurrence of thrombotic and embolic AEs was similar between the ERLEADA and placebo groups in the overall safety population and in the subgroups that did or did not receive anticoagulants in both the TITAN and SPARTAN studies. Among patients receiving concomitant oral anticoagulants, rates of thrombotic and thromboembolic events were similar in the ERLEADA plus androgen deprivation therapy (ADT) group vs placebo plus ADT group, respectively (SPARTAN: 11.6% vs 12.5%; TITAN: 19.4% vs 21.4%).¹ 
  •  In a retrospective real‑world study, concurrent use of ARPIs, including ERLEADA, with oral anticoagulants was not associated with an increased risk of thrombotic or embolic events in patients with prostate cancer.² 
• Antiplatelet
  • Pharmacokinetic properties and potential drug interactions of ARPIs with antithrombotic therapies have been published in literature.^3,4 
• Statins
  • In posthoc analyses of the SPARTAN and TITAN studies, statin exposure was associated with improved overall survival (OS) in the ERLEADA treatment groups and was also linked to a higher risk of grade ≥3 cardiac AEs in both the ERLEADA and placebo groups.^5,6
  •  In a secondary propensitymatched analysis of SPARTAN, metastasisfree survival (MFS) did not differ overall between statin users and nonusers; however, a treatmentbystatin interaction was reported, with worse MFS among statin users in the placebo group and no statistically significant difference among patients receiving ERLEADA.⁷ 
• Review articles on pharmacokinetic properties and/or drug-drug interactions that include the ARPI drug class and cardiovascular risk-lowering medications are available in the literature. Results have been limited to 2025-onwards.^8-12 
• This summary is not inclusive of all cardiovascular risk-lowering medications. For additional information, please refer to local product labeling and/or contact the respective medication manufacturers.

BACKGROUND

The pharmacokinetic profiles of ARPIs are influenced by CYP450 enzymes and drug transporters. Details are summarized in Table: Overview of Select Metabolic and Transporter-Based Interactions for ARPIs.

DRUG-DRUG iNTERACTIONS SUMMARY

In patients taking ARPIs along with concomitant cardiovascular risk-lowering medications, there is potential for drug-drug interactions (Table: Summary of Potential DDIs Between ARPIs and Select Cardiovascular Risk-Lowering Medications). Clinical significance has not been fully established.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 17 March 2026.