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The use of direct oral anticoagulants (DOACs) has quadrupled in Dutch clinical practice over a 5-year period in the late 2010s.
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There is considerable regional variation in which specific DOAC is preferred.
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The number of patients who take interacting medications has also quadrupled.
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The profile of interacting medications has changed over time from cardiovascular to medications affecting other organ systems, suggesting DOAC use is expanded to more diverse patient populations.
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This manuscript includes a chart with common DOAC-drug interactions and refers to easy-to-use drug interaction tools.
Introduction
Methods
Study design and setting
Participants and prescription data
Outcomes of interest
Statistical analyses
Results
Participants
Trends among new DOAC users
Trends in use of concomitant interacting medications
2014 (n = 8,345) | 2015 (n = 10,292) | 2016 (n = 17,249) | 2017 (n = 27,857) | 2018 (n = 35,468) | P-value | |
---|---|---|---|---|---|---|
Amiodarone | 12.6% (1,052) | 11.6% (1,197) | 10.4% (1,802) | 9.2% (2,565) | 8.5% (3,023) | < 0.001 |
Digoxin | 41.7% (3,481) | 40.3% (4,146) | 38.9% (6,704) | 38.0% (10,585) | 35.5% (12,606) | < 0.001 |
Diltiazem | 4.7% (395) | 4.3% (439) | 3.4% (584) | 3.6% (990) | 3.1% (1,107) | < 0.001 |
Quinidine | 0.0% (1) | 0.0% (0) | 0.0% (2) | 0.0% (5) | 0.0% (5) | 0.75 |
Verapamil | 20.5% (1,712) | 18.0% (1,857) | 15.4% (2,652) | 12.7% (3,532) | 10.8% (3,822) | < 0.001 |
Atorvastatin | 29.2% (2,438) | 30.8% (3,169) | 31.6% (5,446) | 32.0% (8,913) | 31.9% (11,305) | < 0.001 |
Clarithromycin | 0.9% (75) | 1.6% (161) | 1.7% (291) | 2.0% (547) | 2.1% (738) | < 0.001 |
Erythromycin | 0.3% (21) | 0.2% (18) | 0.1% (25) | 0.2% (46) | 0.3% (58) | 0.40 |
Rifampicin (rifampin) | 0.1% (7) | 0.1% (8) | 0.1% (21) | 0.1% (24) | 0.1% (50) | 0.19 |
Protease inhibitors | 0.0% (1) | 0.0% (0) | 0.0% (0) | 0.0% (4) | 0.0% (17) | 0.001 |
Fluconazole | 0.7% (58) | 0.8% (79) | 1.3% (227) | 1.4% (399) | 1.8% (642) | < 0.001 |
Keto/itraconazole | 0.2% (18) | 0.3% (32) | 0.3% (41) | 0.2% (65) | 0.3% (88) | 0.68 |
Carbamazepine | 0.7% (55) | 0.4% (45) | 0.4% (72) | 0.5% (145) | 0.4% (155) | 0.04 |
Antiepileptic drugs | 2.5% (205) | 2.6% (268) | 3.0% (526) | 3.4% (958) | 3.8% (1,334) | < 0.001 |
Antimitotic drugs | 0.0% (0) | 0.0% (0) | 0.0% (0) | 0.0% (3) | 0.1% (30) | < 0.001 |
Doxorubicin | 0.0% (0) | 0.0% (0) | 0.0% (1) | 0.0% (3) | 0.1% (18) | < 0.001 |
Tyrosine kinase inhibitors | 0.0% (0) | 0.1% (12) | 0.1% (11) | 0.1% (38) | 0.2% (73) | < 0.001 |
Antihormonal drugs | 0.8% (66) | 1.1% (114) | 1.2% (199) | 1.4% (383) | 1.7% (589) | < 0.001 |
Calcineurin inhibitors | 0.1% (7) | 0.2% (19) | 0.3% (60) | 0.7% (193) | 0.9% (334) | < 0.001 |
Dexamethasone | 0.9% (78) | 2.1% (215) | 3.3% (573) | 4.6% (1,285) | 7.1% (2,519) | < 0.001 |
Sertraline | 1.0% (84) | 1.0% (108) | 1.5% (255) | 1.6% (444) | 1.4% (496) | < 0.001 |
Venlafaxine | 2.1% (175) | 2.1% (217) | 2.2% (387) | 2.2% (618) | 2.1% (742) | 0.72 |
Amitriptyline | 4.0% (322) | 4.1% (418) | 5.0% (863) | 5.3% (1,479) | 5.3% (1,895) | < 0.001 |
Haloperidol | 0.5% (44) | 0.7% (76) | 1.0% (168) | 1.6% (441) | 2.2% (786) | < 0.001 |
Methotrexate | 2.8% (235) | 3.2% (333) | 3.3% (563) | 3.6% (996) | 3.3% (1,188) | 0.01 |
Dabigatran | Rivaroxaban | Apixaban | Edoxaban | |||||
---|---|---|---|---|---|---|---|---|
2014 (n = 4,324) | 2018 (n = 7,473) | 2014 (n = 3,103) | 2018 (n = 12,672) | 2014 (n = 866) | 2018 (n = 11,784) | 2014 (n = 0) | 2018 (n = 3,486) | |
Number of interacting drugs | 1.27 ± 0.53 | 1.23 ± 0.51 | 1.26 ± 0.54 | 1.21 ± 0.50 | 1.24 ± 0.49 | 1.23 ± 0.51 | – | 1.28 ± 0.56 |
Amiodarone | 12.8% (554) | 10.8% (1969) | 12.4% (385) | 8.9% (2,389) | 11.8% (102) | 9.9% (2,368) | – | 10.6% (591) |
Digoxin | 42.9% (1,855) | 38.9% (7,083) | 39.3% (1,221) | 35.5% (9,547) | 43.2% (374) | 40.3% (9,598) | – | 37.1% (2,063) |
Diltiazem | 4.9% (212) | 3.7% (683) | 4.8% (149) | 3.5% (937) | 3.9% (34) | 2.8% (655) | – | 4.0% (222) |
Verapamil | 19.2% (829) | 14.0% (2557) | 22.7% (704) | 13.7% (3676) | 19.7% (171) | 12.6% (3,009) | – | 12.2% (677) |
Atorvastatin | 29.8% (1,287) | 35.9% (6,534) | 28.9% (897) | 34.0% (9,125) | 28.1% (243) | 34.9% (8,307) | – | 32.8% (1,825) |
Clarithromycin | 1.1% (47) | 1.8% (324) | 0.6% (18) | 1.2% (313) | 0.9% (8) | 1.2% (294) | – | 1.3% (75) |
Protease inhibitors | 0.0% (1) | 0.0% (9) | 0.0% (0) | 0.0% (6) | 0.0% (0) | 0.0% (2) | – | 0.1% (4) |
Fluconazole | 0.9% (37) | 1.1% (204) | 0.5% (16) | 1.3% (341) | 0.5% (4) | 1.3% (306) | – | 1.6% (90) |
Antiepileptic drugs | 2.6% (114) | 3.6% (665) | 2.3% (70) | 3.9% (1,042) | 2.3% (20) | 3.8% (898) | – | 3.4% (188) |
Antimitotic drugs | 0.0% (0) | 0.0% (3) | 0.0% (0) | 0.1% (19) | 0.0% (0) | 0.0% (9) | – | 0.1% (4) |
Doxorubicin | 0.0% (0) | 0.0% (3) | 0.0% (0) | 0.1% (15) | 0.0% (0) | 0.0% (0) | – | 0.1% (3) |
Tyrosine kinase inhibitors | 0.0% (0) | 0.2% (29) | 0.0% (0) | 0.2% (45) | 0.0% (0) | 0.1% (26) | – | 0.2% (13) |
Antihormonal drugs | 0.7% (32) | 1.1% (197) | 1.0% (30) | 1.7% (462) | 0.3% (3) | 1.2% (276) | – | 2.1% (115) |
Calcineurin inhibitors | 0.1% (3) | 0.1% (22) | 0.1% (2) | 0.8% (215) | 0.2% (2) | 1.0% (242) | – | 0.8% (47) |
Dexamethasone | 0.9% (41) | 3.1% (566) | 1.0% (31) | 5.4% (1462) | 0.7% (6) | 3.8% (912) | – | 8.8% (491) |
Sertraline | 0.9% (41) | 1.3% (240) | 1.3% (40) | 1.7% (455) | 0.3% (3) | 1.5% (348) | – | 1.5% (79) |
Amitriptyline | 3.8% (163) | 4.6% (837) | 3.8% (118) | 5.9% (1,572) | 5.8 (50) | 5.0% (1,192) | – | 4.8% (266) |
Haloperidol | 0.6% (25) | 1.6% (299) | 0.5% (16) | 1.5% (391) | 0.3% (3) | 1.7% (395) | – | 1.6% (87) |
Methotrexate | 2.5% (108) | 3.2% (588) | 3.4% (105) | 3.9% (1,061) | 2.4% (21) | 3.5% (834) | – | 3.4% (187) |