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Screening for clinically relevant drug-drug interactions between direct oral anticoagulants and antineoplastic
Bang Truong1, Lori Hornsby2, Brent I Fox1
1Department of Health Outcomes Research and Policy, Auburn University Harrison College of Pharmacy, 4306D Walker Building, Auburn, AL, 36849, USA.
Background:
Use of direct oral anticoagulants (DOACs) in patients with cancer remains suboptimal due to the concern regarding potential drug-drug interactions (DDIs) with antineoplastic treatments. However, the clinical relevance of these DDIs is unknown.
Methods:
We conducted a pharmacovigilance study of adverse event (AE) reports from the US Food and Drug Administration Adverse Event Reporting System from 1/1/2004 to 12/31/2021. AE reports containing DOACs and antineoplastic agents with CYP3A4/P-gp inhibitory or inducing activity suggested by published pharmacokinetic studies were included (n = 36,066). The outcomes of interest were bleeding or stroke, identified by MedDRA dictionary version 25.0. We used disproportionality analyses (DPA), logistic regression models (LR), and Multi-item Gamma-Poisson Shrinker (MGPS) (Empirical Bayes Geometric Means (EBGM) and 90% credible intervals (90% CIs)) algorithms to identify the safety signal of DDIs.
Results:
The highest bleeding reporting rates for each drug class were the combination of DOACs with neratinib (39.08%, n = 34), tamoxifen (21.22%, n = 104), irinotecan (20.54%, n = 83), and cyclosporine (19.17%, n = 227). The highest rate of stroke was found for prednisolone (2.43%, n = 113). In the primary analysis, no signal of DDIs by the antineoplastic therapeutic class was detected by MGPS, DPA, and LR approaches. By individual antineoplastic drug, DOACs-neratinib was the only signal detected [EBGM (EB05-EB95) = 2.71 (2.03-3.54)].
Conclusion:
No signal of DDIs between DOACs and antineoplastic agents was detected, except for DOAC-neratinib. Most DDIs between DOACs and antineoplastic agents may not be clinically relevant. The DDIs between DOACs and neratinib should be further examined in future research.
Insights
Direct oral anticoagulants (DOACs) use in cancer patients is limited by drug-drug interaction (DDI) concerns. This study found no significant DDIs between DOACs and most antineoplastic agents, except for neratinib.
Area of Science:
- Pharmacology
- Oncology
- Drug Safety
Background:
- Direct oral anticoagulants (DOACs) use in cancer patients is suboptimal due to concerns about drug-drug interactions (DDIs) with antineoplastic treatments.
- The clinical significance of these potential DDIs remains largely unknown, impacting treatment decisions.
Purpose of the Study:
- To investigate the clinical relevance and safety signals of DDIs between DOACs and antineoplastic agents.
- To identify specific antineoplastic drugs that may pose a risk when co-administered with DOACs.
Main Methods:
- A pharmacovigilance study analyzing 36,066 adverse event reports from the FDA Adverse Event Reporting System (2004-2021).
- Included DOACs and antineoplastic agents with known CYP3A4/P-gp interactions.
- Utilized disproportionality analyses (DPA), logistic regression (LR), and Multi-item Gamma-Poisson Shrinker (MGPS) to detect safety signals for bleeding or stroke.
Main Results:
- No significant DDI safety signals were detected between DOACs and most antineoplastic agents across MGPS, DPA, and LR analyses.
- The combination of DOACs with neratinib showed the highest bleeding reporting rate (39.08%) and was the only DDI signal detected by MGPS.
- Prednisolone showed the highest stroke reporting rate (2.43%) when combined with DOACs.
Conclusions:
- Generally, DDIs between DOACs and antineoplastic agents appear to have limited clinical relevance.
- A potential DDI signal exists specifically between DOACs and neratinib, warranting further investigation.
- These findings may help optimize anticoagulant use in cancer patients by clarifying DDI risks.
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