Features of drug-drug interactions rivaroxaban and calcium channel blockers depending on the ABCB1 genotype (rs1045642 and rs4148738) in patients 80 years of age and older with non-valvular atrial fibrillation
Background. The use of P-glycoprotein (P-gp) inhibitors and carriage of certain ABCB1 polymorphisms can lead to increased concentrations of rivaroxaban and the development of bleeding.The aim of the study. To study the features of drug-drug interactions (DDI) of rivaroxaban in patients over 80 years...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | Russian |
| Published: |
Scientific Сentre for Family Health and Human Reproduction Problems
2024-01-01
|
| Series: | Acta Biomedica Scientifica |
| Subjects: | |
| Online Access: | https://www.actabiomedica.ru/jour/article/view/4493 |
| _version_ | 1797237142639869952 |
|---|---|
| author | D. A. Sychev K. B. Mirzaev M. S. Cherniaeva N. V. Shakhgildyan Sh. P. Abdullaev N. P. Denisenko Zh. A. Sozaeva A. A. Kachanova V. R. Shastina S. V. Gorbatenkova |
| author_facet | D. A. Sychev K. B. Mirzaev M. S. Cherniaeva N. V. Shakhgildyan Sh. P. Abdullaev N. P. Denisenko Zh. A. Sozaeva A. A. Kachanova V. R. Shastina S. V. Gorbatenkova |
| author_sort | D. A. Sychev |
| collection | DOAJ |
| description | Background. The use of P-glycoprotein (P-gp) inhibitors and carriage of certain ABCB1 polymorphisms can lead to increased concentrations of rivaroxaban and the development of bleeding.The aim of the study. To study the features of drug-drug interactions (DDI) of rivaroxaban in patients over 80 years of age with non-valvular atrial fibrillation depending on the ABCB1 genotype (rs1045642 and rs4148738) using the example of verapamil (P-gp inhibitor) and amlodipine.Materials and methods. One hundred and twenty-eight patients were examined (median age – 87.5 [83–90] years). Genotyping, determination of the minimum equilibrium concentration of rivaroxaban (Cmin, ss), with standardization for the daily dose (Cmin, ss/D), coagulogram and analysis of medical documentation for the presence of clinically relevant non-major bleeding (CRNM) were carried out. Analysis of CRNM was performed depending on the ABCB1 genotype.Results. The use of rivaroxaban with verapamil in comparison with patients not taking calcium channel blockers (CCBs) leads to high Cmin, ss values in the CC genotype (rs1045642, rs4148738); Сmin, ss and Сmin, ss/D in the CT genotype (rs1045642); prothrombin time in the CC genotype (rs1045642), more frequent occurrence of CRNM in the TT genotype (rs1045642, rs4148738). In comparison with patients taking amlodipine, it leads to high Cmin, ss values in the CT genotype (rs1045642), a more frequent occurrence of CRNM in the TT genotype (rs1045642, rs4148738). The use of rivaroxaban with amlodipine in comparison with patients not taking CCBs leads to high Cmin, ss and Cmin, ss/D values in the CC genotype (rs1045642) (p < 0.017).Conclusion. The use of verapamil with rivaroxaban in ABCB1 TT carriers (rs4148738 and rs4148738) leads to the development of CRNM in 75 and 78 % of cases, respectively. In patients taking rivaroxaban, it is advisable to test the ABCB1 genotype (rs4148738 and rs4148738) before adding a P-gp inhibitor to therapy. |
| first_indexed | 2024-03-08T12:15:02Z |
| format | Article |
| id | doaj.art-80ceb717f6c74d60a892134e49db667e |
| institution | Directory Open Access Journal |
| issn | 2541-9420 2587-9596 |
| language | Russian |
| last_indexed | 2024-04-24T17:15:03Z |
| publishDate | 2024-01-01 |
| publisher | Scientific Сentre for Family Health and Human Reproduction Problems |
| record_format | Article |
| series | Acta Biomedica Scientifica |
| spelling | doaj.art-80ceb717f6c74d60a892134e49db667e2024-03-28T07:49:29ZrusScientific Сentre for Family Health and Human Reproduction ProblemsActa Biomedica Scientifica2541-94202587-95962024-01-0186518010.29413/ABS.2023-8.6.62657Features of drug-drug interactions rivaroxaban and calcium channel blockers depending on the ABCB1 genotype (rs1045642 and rs4148738) in patients 80 years of age and older with non-valvular atrial fibrillationD. A. Sychev0K. B. Mirzaev1M. S. Cherniaeva2N. V. Shakhgildyan3Sh. P. Abdullaev4N. P. Denisenko5Zh. A. Sozaeva6A. A. Kachanova7V. R. Shastina8S. V. Gorbatenkova9Russian Medical Academy of Continuous Professional EducationRussian Medical Academy of Continuous Professional EducationCentral State Medical Academy of the Administrative Directorate of the President of the Russian Federation; War Veterans Hospital No. 2 of the Department of Health Services of MoscowLomonosov Moscow State UniversityRussian Medical Academy of Continuous Professional EducationRussian Medical Academy of Continuous Professional EducationRussian Medical Academy of Continuous Professional EducationRussian Medical Academy of Continuous Professional EducationWar Veterans Hospital No. 2 of the Department of Health Services of Moscow; I.M. Sechenov First Moscow State Medical University (Sechenov University)War Veterans Hospital No. 2 of the Department of Health Services of MoscowBackground. The use of P-glycoprotein (P-gp) inhibitors and carriage of certain ABCB1 polymorphisms can lead to increased concentrations of rivaroxaban and the development of bleeding.The aim of the study. To study the features of drug-drug interactions (DDI) of rivaroxaban in patients over 80 years of age with non-valvular atrial fibrillation depending on the ABCB1 genotype (rs1045642 and rs4148738) using the example of verapamil (P-gp inhibitor) and amlodipine.Materials and methods. One hundred and twenty-eight patients were examined (median age – 87.5 [83–90] years). Genotyping, determination of the minimum equilibrium concentration of rivaroxaban (Cmin, ss), with standardization for the daily dose (Cmin, ss/D), coagulogram and analysis of medical documentation for the presence of clinically relevant non-major bleeding (CRNM) were carried out. Analysis of CRNM was performed depending on the ABCB1 genotype.Results. The use of rivaroxaban with verapamil in comparison with patients not taking calcium channel blockers (CCBs) leads to high Cmin, ss values in the CC genotype (rs1045642, rs4148738); Сmin, ss and Сmin, ss/D in the CT genotype (rs1045642); prothrombin time in the CC genotype (rs1045642), more frequent occurrence of CRNM in the TT genotype (rs1045642, rs4148738). In comparison with patients taking amlodipine, it leads to high Cmin, ss values in the CT genotype (rs1045642), a more frequent occurrence of CRNM in the TT genotype (rs1045642, rs4148738). The use of rivaroxaban with amlodipine in comparison with patients not taking CCBs leads to high Cmin, ss and Cmin, ss/D values in the CC genotype (rs1045642) (p < 0.017).Conclusion. The use of verapamil with rivaroxaban in ABCB1 TT carriers (rs4148738 and rs4148738) leads to the development of CRNM in 75 and 78 % of cases, respectively. In patients taking rivaroxaban, it is advisable to test the ABCB1 genotype (rs4148738 and rs4148738) before adding a P-gp inhibitor to therapy.https://www.actabiomedica.ru/jour/article/view/4493drug-drug interactionsrivaroxabanverapamilabcb1 (rs1045642 and rs4148738)therapeutic drug monitoringolder patients |
| spellingShingle | D. A. Sychev K. B. Mirzaev M. S. Cherniaeva N. V. Shakhgildyan Sh. P. Abdullaev N. P. Denisenko Zh. A. Sozaeva A. A. Kachanova V. R. Shastina S. V. Gorbatenkova Features of drug-drug interactions rivaroxaban and calcium channel blockers depending on the ABCB1 genotype (rs1045642 and rs4148738) in patients 80 years of age and older with non-valvular atrial fibrillation Acta Biomedica Scientifica drug-drug interactions rivaroxaban verapamil abcb1 (rs1045642 and rs4148738) therapeutic drug monitoring older patients |
| title | Features of drug-drug interactions rivaroxaban and calcium channel blockers depending on the ABCB1 genotype (rs1045642 and rs4148738) in patients 80 years of age and older with non-valvular atrial fibrillation |
| title_full | Features of drug-drug interactions rivaroxaban and calcium channel blockers depending on the ABCB1 genotype (rs1045642 and rs4148738) in patients 80 years of age and older with non-valvular atrial fibrillation |
| title_fullStr | Features of drug-drug interactions rivaroxaban and calcium channel blockers depending on the ABCB1 genotype (rs1045642 and rs4148738) in patients 80 years of age and older with non-valvular atrial fibrillation |
| title_full_unstemmed | Features of drug-drug interactions rivaroxaban and calcium channel blockers depending on the ABCB1 genotype (rs1045642 and rs4148738) in patients 80 years of age and older with non-valvular atrial fibrillation |
| title_short | Features of drug-drug interactions rivaroxaban and calcium channel blockers depending on the ABCB1 genotype (rs1045642 and rs4148738) in patients 80 years of age and older with non-valvular atrial fibrillation |
| title_sort | features of drug drug interactions rivaroxaban and calcium channel blockers depending on the abcb1 genotype rs1045642 and rs4148738 in patients 80 years of age and older with non valvular atrial fibrillation |
| topic | drug-drug interactions rivaroxaban verapamil abcb1 (rs1045642 and rs4148738) therapeutic drug monitoring older patients |
| url | https://www.actabiomedica.ru/jour/article/view/4493 |
| work_keys_str_mv | AT dasychev featuresofdrugdruginteractionsrivaroxabanandcalciumchannelblockersdependingontheabcb1genotypers1045642andrs4148738inpatients80yearsofageandolderwithnonvalvularatrialfibrillation AT kbmirzaev featuresofdrugdruginteractionsrivaroxabanandcalciumchannelblockersdependingontheabcb1genotypers1045642andrs4148738inpatients80yearsofageandolderwithnonvalvularatrialfibrillation AT mscherniaeva featuresofdrugdruginteractionsrivaroxabanandcalciumchannelblockersdependingontheabcb1genotypers1045642andrs4148738inpatients80yearsofageandolderwithnonvalvularatrialfibrillation AT nvshakhgildyan featuresofdrugdruginteractionsrivaroxabanandcalciumchannelblockersdependingontheabcb1genotypers1045642andrs4148738inpatients80yearsofageandolderwithnonvalvularatrialfibrillation AT shpabdullaev featuresofdrugdruginteractionsrivaroxabanandcalciumchannelblockersdependingontheabcb1genotypers1045642andrs4148738inpatients80yearsofageandolderwithnonvalvularatrialfibrillation AT npdenisenko featuresofdrugdruginteractionsrivaroxabanandcalciumchannelblockersdependingontheabcb1genotypers1045642andrs4148738inpatients80yearsofageandolderwithnonvalvularatrialfibrillation AT zhasozaeva featuresofdrugdruginteractionsrivaroxabanandcalciumchannelblockersdependingontheabcb1genotypers1045642andrs4148738inpatients80yearsofageandolderwithnonvalvularatrialfibrillation AT aakachanova featuresofdrugdruginteractionsrivaroxabanandcalciumchannelblockersdependingontheabcb1genotypers1045642andrs4148738inpatients80yearsofageandolderwithnonvalvularatrialfibrillation AT vrshastina featuresofdrugdruginteractionsrivaroxabanandcalciumchannelblockersdependingontheabcb1genotypers1045642andrs4148738inpatients80yearsofageandolderwithnonvalvularatrialfibrillation AT svgorbatenkova featuresofdrugdruginteractionsrivaroxabanandcalciumchannelblockersdependingontheabcb1genotypers1045642andrs4148738inpatients80yearsofageandolderwithnonvalvularatrialfibrillation |