Pharmacodynamics of Rivaroxaban and Dabigatran in Adults with Diffuse Large B-Cell Lymphoma Receiving R-CHOP Immunochemotherapy

<b>Background/Objectives</b>: Rivaroxaban and dabigatran are commonly used for thromboembolic disease management in active cancer patients. However, limited research explores the impact of concurrent chemotherapy on the pharmacodynamics of direct oral anticoagulants (DOAC). The aim of our study was to evaluate the impact of combined chemotherapy with rivaroxaban and dabigatran on the pharmacodynamics in patients with diffuse large B-cell lymphoma (DLBCL).; <b>Methods</b>: This was a prospective, pharmacodynamic study. Eligible subjects were ≥18 years old, diagnosed with DLBCL and initiating R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) immunochemotherapy. The enrolled adults received either rivaroxaban (10 mg once daily) or dabigatran etixalate (110 mg twice daily). Plasma anti-factor Xa (FXa) in participants on rivaroxaban and diluted thrombin time (dTT) in participants on dabigatran were assessed over the dosing interval before and after R-CHOP administration. Pharmacodynamic parameters of rivaroxaban and dabigatran were determined using a non-compartmental analysis.; <b>Results</b>: Twenty-six adults participated, with twelve in the rivaroxaban group and fourteen in the dabigatran group. The mean age was 59 ± 14.4 years. In the rivaroxaban group, the AUEC of FXa inhibition showed no significant change after R-CHOP (mean difference 3.8 ng·h/mL, 95% confidence interval (CI) -155.4 to 163.0, <i>p</i> = 0.96). Similarly, in the dabigatran group, the AUEC of dTT remained unchanged post R-CHOP (mean difference 54.41 ng·h/mL, 95% CI -99.09 to 207.9 ng/mL, <i>p</i> = 0.46). However, the median time-to-peak dTT was significantly faster with R-CHOP (3 h, [min-max, 1.5-8] compared to without it (4 h, [min-max, 3-8], <i>p</i> = 0.04); <b>Conclusions</b>: Concurrent R-CHOP chemotherapy did not significantly impact FXa inhibition by rivaroxaban or dTT by dabigatran. The time-to-peak dTT was faster when dabigatran was administered with R-CHOP.

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Journal
Pharmaceutics
Published
2024-10-11
DOI
https://doi.org/10.3390/pharmaceutics16101319
Primary Topic
Venous Thromboembolism Diagnosis and Management
Type
article
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article

Pharmacodynamics of Rivaroxaban and Dabigatran in Adults with Diffuse Large B-Cell Lymphoma Receiving R-CHOP Immunochemotherapy

Tim Roy Cressey, Lalita Norasetthada, Sasinee Hantrakool, Porntipa Apiwatnakorn et al.
Pharmaceutics
Venous Thromboembolism Diagnosis and Management
article

Pharmacodynamics of Rivaroxaban and Dabigatran in Adults with Diffuse Large B-Cell Lymphoma Receiving R-CHOP Immunochemotherapy

Tim Roy Cressey, Lalita Norasetthada, Sasinee Hantrakool, Porntipa Apiwatnakorn, Pokpong Piriyakhuntorn, Atisa Koonarat, Chatree Chai‐Adisaksopha, Teerachat Punnachet, Nonthakorn Hantrakun, Ekarat Rattarittamrong, Piangrawee Niprapan, Thanawat Rattanathammethee, Adisak Tantiworawit
article en

Abstract

<b>Background/Objectives</b>: Rivaroxaban and dabigatran are commonly used for thromboembolic disease management in active cancer patients. However, limited research explores the impact of concurrent chemotherapy on the pharmacodynamics of direct oral anticoagulants (DOAC). The aim of our study was to evaluate the impact of combined chemotherapy with rivaroxaban and dabigatran on the pharmacodynamics in patients with diffuse large B-cell lymphoma (DLBCL).; <b>Methods</b>: This was a prospective, pharmacodynamic study. Eligible subjects were ≥18 years old, diagnosed with DLBCL and initiating R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) immunochemotherapy. The enrolled adults received either rivaroxaban (10 mg once daily) or dabigatran etixalate (110 mg twice daily). Plasma anti-factor Xa (FXa) in participants on rivaroxaban and diluted thrombin time (dTT) in participants on dabigatran were assessed over the dosing interval before and after R-CHOP administration. Pharmacodynamic parameters of rivaroxaban and dabigatran were determined using a non-compartmental analysis.; <b>Results</b>: Twenty-six adults participated, with twelve in the rivaroxaban group and fourteen in the dabigatran group. The mean age was 59 ± 14.4 years. In the rivaroxaban group, the AUEC of FXa inhibition showed no significant change after R-CHOP (mean difference 3.8 ng·h/mL, 95% confidence interval (CI) -155.4 to 163.0, <i>p</i> = 0.96). Similarly, in the dabigatran group, the AUEC of dTT remained unchanged post R-CHOP (mean difference 54.41 ng·h/mL, 95% CI -99.09 to 207.9 ng/mL, <i>p</i> = 0.46). However, the median time-to-peak dTT was significantly faster with R-CHOP (3 h, [min-max, 1.5-8] compared to without it (4 h, [min-max, 3-8], <i>p</i> = 0.04); <b>Conclusions</b>: Concurrent R-CHOP chemotherapy did not significantly impact FXa inhibition by rivaroxaban or dTT by dabigatran. The time-to-peak dTT was faster when dabigatran was administered with R-CHOP.

PharmaceuticsVol. 16(10)
Lampang Hospital (TH), Nakornping Hospital (TH), Chiang Mai University (TH)
Chiang Mai University, Faculty of Medicine, Chiang Mai University
Good health and well-being
Openalex Percentile: Top 65%
Venous Thromboembolism Diagnosis and Management
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