157
Views
0
CrossRef citations to date
0
Altmetric
Review

Interactions between antiepileptic drugs and direct oral anticoagulants for primary and secondary stroke prevention

, &
Pages 359-376 | Received 30 Jan 2024, Accepted 03 May 2024, Published online: 09 May 2024

References

  • Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. New Engl J Med. 2009;361(12):1139–1151. doi: 10.1056/NEJMoa0905561
  • Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. New Engl J Med. 2011;365(10):883–891. doi: 10.1056/NEJMoa1009638
  • Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. New Engl J Med. 2011;365(11):981–992. doi: 10.1056/NEJMoa1107039
  • Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093–2104. doi: 10.1056/NEJMoa1310907
  • van der Hulle T, Kooiman J, den Exter PL, et al. Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost. 2014;12(3):320–328. doi: 10.1111/jth.12485
  • Rosovsky RP, Kline-Rogers E, Lake L, et al. Direct oral anticoagulants in obese patients with venous thromboembolism: results of an expert consensus panel. Am J Med. 2023;136(6):523–533. doi: 10.1016/j.amjmed.2023.01.010
  • Moret C, Acosta-Isaac R, Mojal S, et al. Clinical outcomes in patients with atrial fibrillation treated with DOACs in a specialized anticoagulation center: critical appraisal of real-world data. PLOS ONE. 2023;18(2):e0279297. doi: 10.1371/journal.pone.0279297
  • Haymart B, Barnes GD, Kong X, et al. Comparison of patient outcomes before and after switching from warfarin to a direct oral anticoagulant based on time in therapeutic range guideline recommendations. JAMA Netw Open. 2022;5(7):e2222089. doi: 10.1001/jamanetworkopen.2022.22089
  • Hindricks G, Potpara T, Dagres N, et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021;42:373–498. doi: 10.1093/eurheartj/ehaa612
  • Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543–603. doi: 10.1093/eurheartj/ehz405
  • Vazquez SR. Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Blood. 2018;132(21):2230–2239. doi: 10.1182/blood-2018-06-848747
  • Rizzo A, Donzelli S, Girgenti V, et al. In vitro antineoplastic effects of brivaracetam and lacosamide on human glioma cells. J Exp Clin Cancer Res. 2017;36(1):76. doi: 10.1186/s13046-017-0546-9
  • Stockis A, Watanabe S, Scheen AJ. Effect of brivaracetam on CYP3A activity, measured by oral midazolam. J Clin Pharmacol. 2015;55(5):543–548. doi: 10.1002/jcph.446
  • Rolan P, Sargentini-Maier ML, Pigeolet E, et al. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after multiple increasing oral doses in healthy men. Br J Clin Pharmacol. 2008;66(1):71–75. doi: 10.1111/j.1365-2125.2008.03158.x
  • Zhu HJ, Wang JS, Markowitz JS, et al. Characterization of P-glycoprotein inhibition by major cannabinoids from marijuana. J Pharmacol Exp Ther. 2006;317(2):850–857. doi: 10.1124/jpet.105.098541
  • Auzmendi J, Palestro P, Blachman A, et al. Cannabidiol (CBD) Inhibited Rhodamine-123 Efflux in Cultured Vascular Endothelial Cells and astrocytes under hypoxic conditions. Front Behav Neurosci. 2020;14:32. doi: 10.3389/fnbeh.2020.00032
  • Nasrin S, Watson CJW, Perez-Paramo YX, et al. Cannabinoid metabolites as inhibitors of Major Hepatic CYP450 Enzymes, with implications for Cannabis-Drug Interactions. Drug Metab Dispos. 2021;49(12):1070–1080. doi: 10.1124/dmd.121.000442
  • Teichmann E, Blessing E, Hinz B. Non-psychoactive phytocannabinoids inhibit inflammation-related changes of human coronary artery smooth muscle and endothelial cells. Cells. 2023;12(19):2389. doi: 10.3390/cells12192389
  • Formukong EA, Evans AT, Evans FJ. The inhibitory effects of cannabinoids, the active constituents of cannabis sativa L. on human and rabbit platelet aggregation. J Pharm Pharmacol. 1989;41(10):705–709. doi: 10.1111/j.2042-7158.1989.tb06345.x
  • Walsh SK, Hepburn CY, Kane KA, et al. Acute administration of cannabidiol in vivo suppresses ischaemia-induced cardiac arrhythmias and reduces infarct size when given at reperfusion. Br J Pharmacol. 2010;160(5):1234–1242. doi: 10.1111/j.1476-5381.2010.00755.x
  • Brueck S, Bruckmueller H, Wegner D, et al. Transcriptional and Post-transcriptional Regulation of Duodenal P-Glycoprotein and MRP2 in healthy human subjects after chronic treatment with rifampin and Carbamazepine. Mol Pharm. 2019;16(9):3823–3830. doi: 10.1021/acs.molpharmaceut.9b00458
  • Lombardo L, Pellitteri R, Balazy M, et al. Induction of nuclear receptors and drug resistance in the brain microvascular endothelial cells treated with antiepileptic drugs. Curr Neurovasc Res. 2008;5(2):82–92. doi: 10.2174/156720208784310196
  • Yang HW, Liu HY, Liu X, et al. Increased P-glycoprotein function and level after long-term exposure of four antiepileptic drugs to rat brain microvascular endothelial cells in vitro. Neurosci Lett. 2008;434(3):299–303. doi: 10.1016/j.neulet.2008.01.071
  • Järvinen E, Hammer HS, Pötz O, et al. 3D spheroid primary human hepatocytes for prediction of cytochrome P450 and drug transporter induction. Clin Pharmacol Ther. 2023;113(6):1284–1294. doi: 10.1002/cpt.2887
  • Hole K, Wollmann BM, Nguyen C, et al. Comparison of CYP3A4-inducing capacity of enzyme-inducing antiepileptic drugs using 4β-hydroxycholesterol as biomarker. Ther Drug Monit. 2018;40(4):463–468. doi: 10.1097/FTD.0000000000000518
  • Grimm SW, Richtand NM, Winter HR, et al. Effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics. Br J Clin Pharmacol. 2006;61(1):58–69. doi: 10.1111/j.1365-2125.2005.02507.x
  • Lutz JD, Kirby BJ, Wang L, et al. Cytochrome P450 3A induction predicts P-glycoprotein Induction; part 2: prediction of decreased substrate exposure after Rifabutin or carbamazepine. Clin Pharmacol Ther. 2018;104(6):1191–1198. doi: 10.1002/cpt.1072
  • Vlase L, Neag M, Popa A, et al. Pharmacokinetic interaction between ivabradine and carbamazepine in healthy volunteers. J Clin Pharm Ther. 2011;36(2):225–229. doi: 10.1111/j.1365-2710.2010.01170.x
  • Gjestad C, Huynh DK, Haslemo T, et al. 4β-hydroxycholesterol correlates with dose but not steady-state concentration of carbamazepine: indication of intestinal CYP3A in biomarker formation? Br J Clin Pharmacol. 2016;81(2):269–276. doi: 10.1111/bcp.12833
  • Xiao W, Zhou K, Yang M, et al. Carbamazepine induces platelet apoptosis and thrombocytopenia through protein kinase a. Front Pharmacol. 2021;12:749930. doi: 10.3389/fphar.2021.749930
  • Rajtar G, Zółkowska D, Czechowska G, et al. Effects of antiepileptic drugs on rat platelet aggregation: ex vivo and in vitro study. Epilepsy Res. 2001;43(1):59–66. doi: 10.1016/S0920-1211(00)00176-5
  • Kobayashi T, Hirai H, Iino M, et al. Inhibitory effects of the antiepileptic drug ethosuximide on G protein-activated inwardly rectifying K+ channels. Neuropharmacology. 2009;56(2):499–506. doi: 10.1016/j.neuropharm.2008.10.003
  • Greene SA, Kwak C, Kamin M, et al. Effect of cenobamate on the single-dose pharmacokinetics of multiple cytochrome P450 probes using a cocktail approach in healthy subjects. Clin Transl Sci. 2022;15(4):899–911. doi: 10.1111/cts.13204
  • Walzer M, Bekersky I, Blum RA, et al. Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Pharmacotherapy. 2012;32(4):340–353. doi: 10.1002/j.1875-9114.2012.01028.x
  • Vrzal R, Kubesova K, Pavek P, et al. Benzodiazepines medazepam and midazolam are activators of pregnane X receptor and weak inducers of CYP3A4: investigation in primary cultures of human hepatocytes and hepatocarcinoma cell lines. Toxicol Lett. 2010;193(2):183–188. doi: 10.1016/j.toxlet.2010.01.004
  • Rajtar G, Zółkowska D, Kleinrok Z. Effect of diazepam and clonazepam on the function of isolated rat platelet and neutrophil. Med Sci Monit. 2002;8:I37–44.
  • Falcão A, Pinto R, Nunes T, et al. Effect of repeated administration of eslicarbazepine acetate on the pharmacokinetics of simvastatin in healthy subjects. Epilepsy Res. 2013;106(1–2):244–249. doi: 10.1016/j.eplepsyres.2013.04.009
  • Egnell AC, Houston B, Boyer S. In vivo CYP3A4 heteroactivation is a possible mechanism for the drug interaction between felbamate and carbamazepine. J Pharmacol Exp Ther. 2003;305(3):1251–1262. doi: 10.1124/jpet.102.047530
  • Martin P, Czerwiński M, Limaye PB, et al. In vitro evaluation suggests fenfluramine and norfenfluramine are unlikely to act as perpetrators of drug interactions. Pharmacol Res Perspect. 2022;10(3):e00959. doi: 10.1002/prp2.959
  • Barradas MA, Mikhailidis DP, Dandona P. The effect of fenfluramine on collagen-induced platelet aggregation in vitro. Br J Clin Pharmacol. 1983;16(4):459. doi: 10.1111/j.1365-2125.1983.tb02198.x
  • Russell GR, Phelps SJ, Shelton CM, et al. Impact of Drug Interactions on Clobazam and N-Desmethylclobazam concentrations in pediatric patients with epilepsy. Ther Drug Monit. 2018;40(4):452–462. doi: 10.1097/FTD.0000000000000530
  • Ranzino AM, Sorrells KR, Manor SM. Possible acute thrombocytopenia post esomeprazole and hydantoin coadministration. J Pharm Pract. 2010;23(2):140–143. doi: 10.1177/0897190009341308
  • Benedetti MS. Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies. Fundamemntal Clinical Pharma. 2000;14(4):301–319. doi: 10.1111/j.1472-8206.2000.tb00411.x
  • Pan CF, Shen MY, Wu CJ, et al. Inhibitory mechanisms of gabapentin, an antiseizure drug, on platelet aggregation. J Pharm Pharmacol. 2007;59(9):1255–1261. doi: 10.1211/jpp.59.9.0010
  • Cawello W. Clinical pharmacokinetic and pharmacodynamic profile of lacosamide. Clin Pharmacokinet. 2015;54(9):901–914. doi: 10.1007/s40262-015-0276-0
  • Wang-Tilz Y, Tilz C, Wang B, et al. Influence of lamotrigine and topiramate on MDR1 expression in difficult-to-treat temporal lobe epilepsy. Epilepsia. 2006;47(2):233–239. doi: 10.1111/j.1528-1167.2006.00414.x
  • Perucca E. Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol. 2006;61(3):246–255. doi: 10.1111/j.1365-2125.2005.02529.x
  • Siniscalchi A, Gallelli L, Calabrò G, et al. Phenobarbital/Lamotrigine coadministration–induced blood dyscrasia in a patient with epilepsy. Ann Pharmacother. 2010;44(12):2031–2034. doi: 10.1345/aph.1P335
  • Moerman L, Wyffels L, Slaets D, et al. Antiepileptic drugs modulate P-glycoproteins in the brain: a mice study with (11)C-desmethylloperamide. Epilepsy Res. 2011;94(1–2):18–25. doi: 10.1016/j.eplepsyres.2010.12.013
  • Ucar HK, Sarigecili E, Bilen S, et al. Short-term and long-term effects of Levetiracetam Monotherapy on Hematological Parameters in children with idiopathic epilepsy. Sisli Etfal Hastan Tip Bul. 2023;57(1):46–53. doi: 10.14744/SEMB.2022.98523
  • Sato M, Hirakata H, Ikeda M, et al. Effects of barbiturates on human platelet aggregation differ depending on their chemical structures. Can J Physiol Pharmacol. 2003;81(8):806–814. doi: 10.1139/y03-075
  • Murayama N, Shimada M, Yamazoe Y, et al. Distinct effects of phenobarbital and its N-methylated derivative on liver cytochrome P450 induction. Arch Biochem Biophys. 1996;328(1):184–192. doi: 10.1006/abbi.1996.0159
  • Ji J, Li G, Ma Y, et al. Expression of multidrug resistance genes in peripheral blood of patients with refractory epilepsy and the reverse effect of Oxcarbazepine on its expression. Iran J Public Health. 2018;47(1):40–48.
  • Zaccara G, Gangemi PF, Bendoni L, et al. Influence of single and repeated doses of oxcarbazepine on the pharmacokinetic profile of felodipine. Ther Drug Monit. 1993;15(1):39–42. doi: 10.1097/00007691-199302000-00007
  • Ogbebor O, Agrawal A, Yegneswaran B. Lesson of the month 1: to stop a fit, but swinging low. Clin Med. 2018;18(3):256–258. doi: 10.7861/clinmedicine.18-3-256
  • Majid O, Laurenza A, Ferry J, et al. Impact of perampanel on pharmacokinetics of concomitant antiepileptics in patients with partial-onset seizures: pooled analysis of clinical trials. Br J Clin Pharmacol. 2016;82(2):422–430. doi: 10.1111/bcp.12951
  • Goldstein R, Jacobs AR, Zighan L, et al. Interactions between direct oral anticoagulants (DOACs) and Antiseizure Medications: potential implications on DOAC treatment. CNS Drugs. 2023;37(3):203–214. doi: 10.1007/s40263-023-00990-0
  • Almuhanna RA, Muddassir R, Almaghrabi M, et al. Perampanel-induced, new-onset thrombocytopenia in a patient with refractory seizures: a case report. Cureus. 2023;15:e37781. doi: 10.7759/cureus.37781
  • Alvariza S, Fagiolino P, Vázquez M, et al. Chronic administration of phenytoin induces efflux transporter overexpression in rats. Pharmacol Rep. 2014;66(6):946–951. doi: 10.1016/j.pharep.2014.06.007
  • Ben-Menachem E. Pregabalin pharmacology and its relevance to clinical practice. Epilepsia. 2004;45(Suppl 6):13–18. doi: 10.1111/j.0013-9580.2004.455003.x
  • Qu C, Xie Y, Qin F, et al. Neuropsychiatric symptoms accompanying thrombocytopenia following pregabalin treatment for neuralgia: a case report. Int J Clin Pharm. 2014;36(6):1138–1140. doi: 10.1007/s11096-014-0026-7
  • Patsalos PN, Fröscher W, Pisani F, et al. The importance of drug interactions in epilepsy therapy. Epilepsia. 2002;43(4):365–385. doi: 10.1046/j.1528-1157.2002.13001.x
  • Tompson DJ, Crean CS, Buraglio M, et al. Lack of effect of ezogabine/retigabine on the pharmacokinetics of digoxin in healthy individuals: results from a drug-drug interaction study. Clin Pharmacol. 2014;6:149–159. doi: 10.2147/CPAA.S64131
  • Ekiciler A, Chen WLK, Bo Y, et al. Quantitative cytochrome P450 3A4 induction risk assessment using human hepatocytes complemented with pregnane X receptor-activating profiles. Drug Metab Dispos. 2023;51(3):276–284. doi: 10.1124/dmd.122.001132
  • Tran A, Rey E, Pons G, et al. Influence of stiripentol on cytochrome P450-mediated metabolic pathways in humans: in vitro and in vivo comparison and calculation of in vivo inhibition constants. Clin Pharmacol Ther. 1997;62(5):490–504. doi: 10.1016/S0009-9236(97)90044-8
  • Chen Q, Xin M, Wang L, et al. Inhibition of LDHA to induce eEF2 release enhances thrombocytopoiesis. Blood. 2022;139(19):2958–2971. doi: 10.1182/blood.2022015620
  • Pita-Calandre E. Implicaciones clínicas de la farmacología y la farmacocinética de la tiagabina. RevNeurol. 1999;28(3):337–339. doi: 10.33588/rn.2803.98523
  • Nallani SC, Glauser TA, Hariparsad N, et al. Dose-dependent induction of cytochrome P450 (CYP) 3A4 and activation of pregnane X receptor by topiramate. Epilepsia. 2003;44(12):1521–1528. doi: 10.1111/j.0013-9580.2003.06203.x
  • Polimeni G, Grugno R, Vitetta A, et al. A case of topiramate-induced epistaxis. Curr Drug Saf. 2009;4(3):207–208. doi: 10.2174/157488609789007001
  • Eyal S, Lamb JG, Smith-Yockman M, et al. The antiepileptic and anticancer agent, valproic acid, induces P-glycoprotein in human tumour cell lines and in rat liver. Br J Pharmacol. 2006;149(3):250–260. doi: 10.1038/sj.bjp.0706830
  • Cerveny L, Svecova L, Anzenbacherova E, et al. Valproic acid induces CYP3A4 and MDR1 gene expression by activation of constitutive androstane receptor and pregnane X receptor pathways. Drug Metab Dispos. 2007;35(7):1032–1041. doi: 10.1124/dmd.106.014456
  • Wen X, Wang JS, Kivistö KT, et al. In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: preferential inhibition of cytochrome P450 2C9 (CYP2C9). Br J Clin Pharmacol. 2001;52(5):547–553. doi: 10.1046/j.0306-5251.2001.01474.x
  • Bartels M, Govers A, Polak R, et al. Megakaryocyte lineage development is controlled by modulation of protein acetylation. PLOS ONE. 2018;13(4):e0196400. doi: 10.1371/journal.pone.0196400
  • Davidson DC, Hirschman MP, Spinelli SL, et al. Antiplatelet activity of valproic acid contributes to decreased soluble CD40 ligand production in HIV type 1-infected individuals. J Immunol. 2011;186(1):584–591. doi: 10.4049/jimmunol.1001911
  • Kis B, Szupera Z, Mezei Z, et al. Valproate treatment and platelet function: the role of arachidonate metabolites. Epilepsia. 1999;40(3):307–310. doi: 10.1111/j.1528-1157.1999.tb00709.x
  • Raza M, Al-Shabanah OA. Effect of vigabatrin on contractile response to arachidonic acid and prostaglandins in smooth muscle preparations and platelet aggregation in experimental laboratory animals. Pharmacol Res. 2003;47:477–483. doi: 10.1016/S1043-6618(03)00045-8
  • Baulac M, Leppik IE. Efficacy and safety of adjunctive zonisamide therapy for refractory partial seizures. Epilepsy Res. 2007;75(2–3):75–83. doi: 10.1016/j.eplepsyres.2007.04.007
  • Vlase L, Popa A, Neag M, et al. Pharmacokinetic interaction between ivabradine and phenytoin in healthy subjects. Clin Drug Invest. 2012;32(8):533–538. doi: 10.1007/BF03261904
  • Wong Y, Yeh C, Thyrum P. The effects of concomitant phenytoin administration on the steady-state pharmacokinetics of quetiapine. J Clin Psychopharmacol. 2001;21(1):89–93. doi: 10.1097/00004714-200102000-00016
  • Jaspers Focks J, Brouwer MA, Wojdyla DM, et al. Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial. BMJ. 2016;353:i2868. doi: 10.1136/bmj.i2868
  • Wang CL, Wu VC, Chang KH, et al. Assessing major bleeding risk in atrial fibrillation patients concurrently taking non-vitamin K antagonist oral anticoagulants and antiepileptic drugs. Eur Heart J Cardiovasc Pharmacother. 2020;6(3):147–154. doi: 10.1093/ehjcvp/pvz035
  • Forbes HL, Polasek TM. Potential drug–drug interactions with direct oral anticoagulants in elderly hospitalized patients. Therapeutic Advances In Drug Safety. 2017;8(10):319–328. doi: 10.1177/2042098617719815
  • Harskamp RE, Himmelreich JCL, Wong GWM, et al. Prescription patterns of direct oral anticoagulants and concomitant use of interacting medications in the Netherlands. Neth Heart J. 2021;29(9):451–459. doi: 10.1007/s12471-021-01612-4
  • Giustozzi M, Mazzetti M, Paciaroni M, et al. Concomitant use of direct oral anticoagulants and antiepileptic drugs: a prospective cohort study in patients with atrial fibrillation. Clin Drug Investig. 2021;41(1):43–51. doi: 10.1007/s40261-020-00982-8
  • Ip BY, Ko H, Wong GL, et al. Thromboembolic risks with concurrent direct oral anticoagulants and antiseizure medications: a population-based analysis. CNS Drugs. 2022;36(12):1313–1324. doi: 10.1007/s40263-022-00971-9
  • Perlman A, Hochberg-Klein S, Choshen Cohen L, et al. Management strategies of the interaction between direct oral anticoagulant and drug-metabolizing enzyme inducers. J Thromb Thrombolysis. 2019;47(4):590–595. doi: 10.1007/s11239-018-01804-7
  • World Health Organization Collaborating Centre for Drug Statistics Methodology (WHOCC). Oslo: Norwegian Institute of Public Health; 2015 [cited 2023 Nov 21]. Available from: https://www.whocc.no/atc_ddd_index
  • Acton EK, Gelfand MA, Hennessy S, et al. Trends in oral anticoagulant co-prescription with antiepileptic drugs among adults with epilepsy, 2010-2018. Epilepsy Behav. 2020;113:107550. doi: 10.1016/j.yebeh.2020.107550
  • Taha M, Li W, Schmidt CM, et al. The interactions between anticonvulsants and non-vitamin K antagonist oral anticoagulant agents: a systematic review. Epilepsy Res. 2020;162:106304. doi: 10.1016/j.eplepsyres.2020.106304
  • Galgani A, Palleria C, Iannone LF, et al. Pharmacokinetic interactions of clinical interest between direct oral anticoagulants and antiepileptic drugs. Front Neurol. 2018;9:1067. doi: 10.3389/fneur.2018.01067
  • Candeloro M, Carlin S, Shapiro MJ, et al. Drug-drug interactions between direct oral anticoagulants and anticonvulsants and clinical outcomes: a systematic review. Res Pract Thromb Haemost. 2023;7(3):100137. doi: 10.1016/j.rpth.2023.100137
  • Steffel J, Collins R, Antz M, et al. 2021 European heart rhythm association practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in patients with atrial fibrillation. Europace. 2021;23(10):1612–1676. doi: 10.1093/europace/euab065
  • Perlman A, Wanounou M, Goldstein R, et al. Ischemic and thrombotic events associated with concomitant xa-inhibiting direct oral anticoagulants and antiepileptic drugs: analysis of the FDA adverse event reporting system (FAERS). CNS Drugs. 2019;33(12):1223–1228. doi: 10.1007/s40263-019-00677-5
  • Perlman A, Goldstein R, Choshen Cohen L, et al. Effect of Enzyme-Inducing Antiseizure Medications on the risk of sub-therapeutic concentrations of direct oral anticoagulants: a retrospective cohort study. CNS Drugs. 2021;35(3):305–316. doi: 10.1007/s40263-021-00795-z
  • Sennesael AL, Larock AS, Hainaut P, et al. The impact of strong inducers on direct oral anticoagulant levels. Am J Med. 2021;134(10):1295–1299. doi: 10.1016/j.amjmed.2021.06.003
  • Johannessen SI, Landmark CJ. Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol. 2010;8(3):254–267. doi: 10.2174/157015910792246254
  • Stöllberger C, Finsterer J. Interactions between non-vitamin K oral anticoagulants and antiepileptic drugs. Epilepsy Res. 2016;126:98–101. doi: 10.1016/j.eplepsyres.2016.06.003
  • Gronich N, Stein N, Muszkat M. Association between use of pharmacokinetic-interacting drugs and effectiveness and safety of direct acting oral anticoagulants: nested case-control study. Clin Pharmacol Ther. 2021;110(6):1526–1536. doi: 10.1002/cpt.2369
  • Chin PK, Wright DF, Zhang M, et al. Correlation between trough plasma dabigatran concentrations and estimates of glomerular filtration rate based on creatinine and cystatin C. Drugs R D. 2014;14(2):113–123. doi: 10.1007/s40268-014-0045-9
  • King PK, Stump TA, Walkama AM, et al. Management of phenobarbital and apixaban interaction in recurrent cardioembolic stroke. Ann Pharmacother. 2018;52(6):605–606. doi: 10.1177/1060028018759938
  • Zhou M, Leonard CE, Brensinger CM, et al. Pharmacoepidemiologic screening of potential oral anticoagulant drug interactions leading to thromboembolic events. Clin Pharmacol Ther. 2020;108(2):377–386. doi: 10.1002/cpt.1845
  • Ranzato F, Roberti R, Deluca C, et al. Pilot study on the probability of drug-drug interactions among direct oral anticoagulants (DOACs) and antiseizure medications (ASMs): a clinical perspective. Neurol Sci. 2024;45(1):277–288. doi: 10.1007/s10072-023-06992-6
  • Dagan G, Perlman A, Hochberg-Klein S, et al. Managing direct oral anticoagulants in patients with antiepileptic medication. Can J Cardiol. 2018;34(11):.e1534.1–.e1534.3. doi: 10.1016/j.cjca.2018.08.001
  • Caviness LA, Wassell KM, Howard-Thompson A. Acute elevation of liver function test values following concomitant administration of dabigatran and primidone. Am J Health Syst Pharm. 2022;79(15):1250–1254. doi: 10.1093/ajhp/zxac054
  • Sáez-Torres de Vicente M, Martínez Puig P, Valverde Toresano L. Ictus isquémico por posible interacción de rivaroxabán con primidona en paciente con fibrilación auricular. Medicina Clínica. 2021;156(5):255–256. doi: 10.1016/j.medcli.2019.12.024
  • Chang SH, Chou IJ, Yeh YH, et al. Association between use of non–vitamin K oral anticoagulants with and without concurrent medications and risk of Major bleeding in Nonvalvular Atrial Fibrillation. JAMA. 2017;318(13):1250–1259. doi: 10.1001/jama.2017.13883
  • Candeloro M, Eikelboom JW, Chan N, et al. Carbamazepine, phenytoin, and oral anticoagulants: drug-drug interaction and clinical events in a retrospective cohort. Res Pract Thromb Haemost. 2022;6(2):e12650. doi: 10.1002/rth2.12650
  • Wiggins BS, Northup A, Johnson D, et al. Reduced anticoagulant effect of dabigatran in a patient receiving concomitant phenytoin. Pharmacotherapy. 2016;36(2):e5–7. doi: 10.1002/phar.1698
  • Hager N, Bolt J, Albers L, et al. Development of left atrial thrombus after coadministration of dabigatran etexilate and phenytoin. Can J Cardiol. 2017;33(4):.e554.13–.e554.14. doi: 10.1016/j.cjca.2016.10.022
  • Becerra AF, Amuchastegui T, Tabares AH. Decreased rivaroxaban levels in a patient with cerebral vein thrombosis receiving phenytoin. Case Rep Hematol. 2017;2017:4760612. doi: 10.1155/2017/4760612
  • Laureano M, Crowther M, Eikelboom J, et al. Measurement of Dabigatran Drug Levels to manage patients taking interacting drugs: a case report. Am J Med. 2016;129(10):e247–8. doi: 10.1016/j.amjmed.2016.06.017
  • Bortz H, Corallo CE, Tran H. Increasing understanding regarding the risk of concomitant use of carbamazepine and direct oral anticoagulants. J Pharm Pract. 2019;32(2):123–125. doi: 10.1177/0897190018786837
  • Burden T, Thompson C, Bonanos E, et al. Lesson of the month 2: pulmonary embolism in a patient on rivaroxaban and concurrent carbamazepine. Clin Med. 2018;18(1):103–105. doi: 10.7861/clinmedicine.18-1-103
  • Risselada AJ, Visser MJ, van Roon E. Longembolie door interactie tussen rivaroxaban en carbamazepine [Pulmonary embolism due to interaction between rivaroxaban and carbamazepine]. Ned Tijdschr Geneeskd. 2013;157(52):A6568.
  • Stöllberger C, Finsterer J. Recurrent venous thrombosis under rivaroxaban and carbamazepine for symptomatic epilepsy. Neurol Neurochir Pol. 2017;51(2):194–196. doi: 10.1016/j.pjnns.2017.01.010
  • Abou Kaoud M, Nissan R, Segev A, et al. Levetiracetam interaction with direct oral anticoagulants: a pharmacovigilance study. CNS Drugs. 2023;37(12):1111–1121. doi: 10.1007/s40263-023-01052-1
  • Chadha A, Lopaschuk D, Ackman ML, et al. The problem with predictions: a cautionary tale of empirically adjusting apixaban dosing with carbamazepine. CJC Open. 2022;4(4):435–438. doi: 10.1016/j.cjco.2021.12.012
  • Bungard TJ, Roberts RN. Carbamazepine induction impacting apixaban concentrations: a case report. CJC Open. 2020;2:423–425. doi: 10.1016/j.cjco.2020.04.009
  • Evanger N, Szkotak A, Stang L, et al. Apixaban concentration with and without coadministration of carbamazepine: a case with No apparent interaction. Can J Hosp Pharm. 2017;70(6):463–467. doi: 10.4212/cjhp.v70i6.1714
  • Di Gennaro L, Lancellotti S, De Cristofaro R, et al. Carbamazepine interaction with direct oral anticoagulants: help from the laboratory for the personalized management of oral anticoagulant therapy. J Thromb Thrombolysis. 2019;48(3):528–531. doi: 10.1007/s11239-019-01866-1
  • Robinson ZS, Arvin JP, Madding KL. Rivaroxaban Failure in a Patient Taking Oxcarbazepine. Ann Pharmacother. 2021;55(10):1302–1303. doi: 10.1177/1060028021990374
  • Serra W, Li Calzi M, Coruzzi P. Left atrial appendage thrombosis during therapy with rivaroxaban in elective cardioversion for permanent atrial fibrillation. Clin Pract. 2015;5(3):788. doi: 10.4081/cp.2015.788
  • Langenbruch L, Meuth SG, Wiendl H, et al. Clinically relevant interaction of rivaroxaban and valproic acid - a case report. Seizure. 2020;80:46–47. doi: 10.1016/j.seizure.2020.05.024
  • Stöllberger C, Finsterer J. Prolonged anticoagulant activity of rivaroxaban in a polymorbid elderly female with non-convulsive epileptic state. Heart & Lung. 2014;43(3):262–263. doi: 10.1016/j.hrtlng.2014.03.004
  • Grymonprez M, Carnoy L, Capiau A, et al. Impact of P-glycoprotein and CYP3A4-interacting drugs on clinical outcomes in patients with atrial fibrillation using non-vitamin K antagonist oral anticoagulants: a nationwide cohort study. Eur Heart J Cardiovasc Pharmacother. 2023;9(8):722–730. doi: 10.1093/ehjcvp/pvad070
  • Mavri A, Ilc S. The efficacy of direct oral anticoagulants in patients on concomitant treatment with levetiracetam. Sci Rep. 2023;13(1):9257. doi: 10.1038/s41598-023-33876-8
  • Menichelli D, Pastori D, Pignatelli P, et al. Minimizing drug-drug interactions between dabigatran and levetiracetam through clinical management: a case report. Eur Heart J Case Rep. 2023;7(1):ytad006. doi: 10.1093/ehjcr/ytad006
  • Paciullo F, Costa C, Gresele P. Rivaroxaban plasma levels and Levetiracetam: a case report. Ann Intern Med. 2020;173(1):71–72. doi: 10.7326/L19-0712
  • Lin SY, Tang SC, Tsai LK, et al. Factors for recurrent stroke among Asian patients with non-valvular atrial fibrillation under non-vitamin K antagonist oral anticoagulant therapy. J Formos Med Assoc. 2020;119(12):1799–1806. doi: 10.1016/j.jfma.2020.02.003
  • Ho CJ, Chen SH, Lin CH, et al. Non-vitamin K oral anticoagulants and anti-seizure medications: a retrospective cohort study. Front Neurol. 2021;11:588053. doi: 10.3389/fneur.2020.588053
  • Manis MM, Petersen K, Roberts MZ, et al. Managing the drug-drug interaction with apixaban and Primidone: a case report. Hosp Pharm. 2023;58(4):345–349. doi: 10.1177/00185787221150928
  • Signorelli SS, Scuto S, Marino E, et al. Anticoagulants and osteoporosis. Int J Mol Sci. 2019;20(21):5275. doi: 10.3390/ijms20215275
  • Thompson LE, Davis BH, Narayan R, et al. Personalizing direct oral anticoagulant therapy for a diverse population: role of race, kidney function, drug interactions, and pharmacogenetics. Clin Pharmacol Ther. 2023;113(3):585–599. doi: 10.1002/cpt.2714
  • McGregor IS, Cairns EA, Abelev S, et al. Access to cannabidiol without a prescription: a cross-country comparison and analysis. Int J Drug Policy. 2020;85:102935. doi: 10.1016/j.drugpo.2020.102935
  • Goodman S, Wadsworth E, Schauer G, et al. Use and perceptions of Cannabidiol Products in Canada and in the United States. Cannabis Cannabinoid Res. 2022;7(3):355–364. doi: 10.1089/can.2020.0093
  • Guenoun M, Cohen S, Villaceque M, et al. Characteristics of patients with atrial fibrillation treated with direct oral anticoagulants and new insights into inappropriate dosing: results from the French National Prospective Registry: PAFF. Europace. 2023;25(10):euad302. doi: 10.1093/europace/euad302
  • Yamashita T, Suzuki S, Inoue H, et al. Two-year outcomes of more than 30 000 elderly patients with atrial fibrillation: results from the all Nippon AF in the elderly (ANAFIE) registry. Eur Heart J Qual Care Clin Outcomes. 2022;8(2):202–213. doi: 10.1093/ehjqcco/qcab025
  • Essien UR, Chiswell K, Kaltenbach LA, et al. Association of race and ethnicity with oral anticoagulation and associated outcomes in patients with atrial fibrillation: findings from the get with the guidelines-atrial fibrillation registry. JAMA Cardiol. 2022;7:1207–1217. doi: 10.1001/jamacardio.2022.3704
  • Bayer V, Kotalczyk A, Kea B, et al. Global oral anticoagulation use varies by region in patients with recent diagnosis of atrial fibrillation: the GLORIA-AF phase III registry. J Am Heart Assoc. 2022;11(6):e023907. doi: 10.1161/JAHA.121.023907
  • Platzbecker K, Müller-Fielitz H, Foraita R, et al. In atrial fibrillation epilepsy risk differs between oral anticoagulants: active comparator, nested case-control study. Europace. 2023;25(5):euad087. doi: 10.1093/europace/euad087
  • Carollo M, Crisafulli S, Ciccimarra F, et al. Exploring the level of agreement among different drug-drug interaction checkers: a comparative study on direct oral anticoagulants. Expert Opin Drug Metab Toxicol. 2024;20(3):157–164. doi: 10.1080/17425255.2024.2322134
  • Dimakos J, Douros A. Methodological considerations on the Use of Cohort Designs in drug-drug interaction studies in pharmacoepidemiology. Curr Epidemiol Rep. 2024. doi: 10.1007/s40471-024-00347-1
  • Hennessy S, Leonard CE, Gagne JJ, et al. Pharmacoepidemiologic Methods for Studying the Health effects of drug–drug interactions. Clin Pharma And Therapeutics. 2016;99(1):92–100. doi: 10.1002/cpt.277
  • Van der Linden L, Hias J, Vanassche T. The value and limitations of new oral anticoagulant plasma level assessments. Eur Heart J Suppl. 2022;24(Suppl A):A32–41. doi: 10.1093/eurheartj/suab153

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.