DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20205541

Drug interactions of oral anticoagulants

Gayathri Anil, Pradhyumna Muraleedharan, Atiya Rehman Faruqui

Abstract


Background: Oral anticoagulants (OACs) are the drugs of choice where long-term anticoagulation is needed due to convenience of dosing. But their use has potential for several drug interactions. Monitoring for potential interactions with timely management will decrease the risk of complications of anticoagulation.

Methods: We aimed to assess the presence of potential drug-drug interactions in patients on oral anticoagulants for various indications. Prescriptions of a cohort of patients on oral anticoagulants were analyzed. Potential drug interactions were identified using free software available at www.drugs.com and classified into major, moderate and minor types.

Results: Of the 135 patients in the study, 83 were males and mean age was 52.9±17.3 years. Most commonly used OACs were vitamin K antagonists (VKAs) (80.0%) followed by direct oral anticoagulants (DOACs) (20.0%). Median number of concomitant medications per patient was 4 (IQR 3-6). A total of 307 potential interactions were identified in 121 patients with a median of 2 interactions per patient. Of the 56 patients who had potential for major drug interactions, 45 (41.6%) were on VKAs and 11 (40.7%) on DOACs had potential to develop major interactions. Using logistic regression model, significant predictors of major drug interactions were age>60 years (OR 2.50; 95% CI 1.05-5.95; p=0.04) and presence of venous thromboembolism VTE (OR 0.09; 95% CI 0.02-0.55; p=0.01).

Conclusions: This hospital-based study showed potential drug interactions with OACs. Age more than 60 years and presence of VTE were significant predictors of major interactions. Awareness of potential interactions and monitoring doses of OACs help to prevent complications of therapy.


Keywords


Oral Anticoagulants, Drug interactions, Warfarin

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References


Di Minno A, Frigerio B, Spadarella G, et al. Old and new oral anticoagulants: Food, herbal medicines and drug interactions. Blood Rev. 2017;31(4):193-203.

Jacobs LG. Warfarin pharmacology, clinical management, and evaluation of hemorrhagic risk for the elderly. Clin Geriatr Med. 2006;22(1):17-32.

Teklay G, Shiferaw N, Legesse B, Bekele ML. Drug-drug interactions and risk of bleeding among inpatients on warfarin therapy: A prospective observational study. Thromb J. 2014;12(1):1-8.

Vazquez SR. Drug-drug interactions in an era of multiple anticoagulants: A focus on clinically relevant drug interactions. Blood. 2018;132(21):2230-9.

Scaglione F. New oral anticoagulants: Comparative pharmacology with vitamin K antagonists. Clin Pharmacokinet. 2013;52(2):69-82.

Eriksson BI, Quinlan DJ, Weitz JI. Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor Xa inhibitors in development. Clin Pharmacokinet. 2009;48(1):1-22.

Gnoth MJ, Buetehorn U, Muenster U, Schwarz T. In Vitro and In Vivo P-Glycoprotein Transport Characteristics of Rivaroxaban. J Pharmacol Exp Ther. 2011;338(1):372-80.

Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: A summary of the evidence and biologic plausibility. Blood. 2011;118(24):6269-73.

Shalansky S, Pharm D, Lynd L, et al. Gingi Warfarine. 2007;27(9):1237-47.

Steinberg BA, Kim S, Piccini JP, Fonarow GC. Use and Associated Risks of Concomitant Aspirin Therapy with Oral Anticoagulation in Patients with Atrial Fibrillation: Insights from the ORBIT-AF Registry. Circulation. 2013;128(7):721-8.

Abdel-Aziz MI, Ali MAS, Hassan AKM, Elfaham TH. Warfarin-drug interactions: An emphasis on influence of polypharmacy and high doses of amoxicillin/clavulanate. J Clin Pharmacol. 2016;56(1):39-46.

Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017;17(1):1-10.

Kim JH, Kim GS, Kim EJ, Park S, Chung N, Chu SH. Factors affecting medication adherence and anticoagulation control in Korean patients taking warfarin. J Cardiovasc Nurs. 2011;26(6):466-74.

Kim BYB, Sharafoddini A, Tran N, Wen EY, Lee J. Consumer mobile apps for potential drug-drug interaction check: Systematic review and content analysis using the mobile app rating scale (MARS). JMIR mHealth uHealth. 2018;6(3):1-13.

Kheshti R, Aalipour M, Namazi S. A comparison of five common drug–drug interaction software programs regarding accuracy and comprehensiveness. J Res Pharm Pract. 2016;5(4):257.

Colet C de F, Amador TA, Heineck I. Drug Interactions and Adverse Events in a Cohort of Warfarin Users Attending Public Health Clinics. Int J Cardiovasc Sci. 2018;32(2):110-7.

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. Bio Med J. 2016;353:i2868.

Delaney JA, Opatrny L, Brophy JM, Suissa S. Drug-drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. Can Med Assoc J. 2007;177(4):347-51.

Kumar S, Danik SB, Altman RK, Barrett CD, Lip GY, Chatterjee S, et al. Non-Vitamin K Antagonist Oral Anticoagulants and Antiplatelet Therapy for Stroke Prevention in Patients With Atrial Fibrillation. Cardiol Rev. 2016;24(5):218-23.

Feng X, Sambamoorthi U, Innes K, Castelli G, LeMasters T, Xiong L, et al. Predictors of Major Bleeding Among Working-Age Adults with Atrial Fibrillation: Evaluating the Effects of Potential Drug-drug Interactions and Switching from Warfarin to Non-vitamin K Oral Anticoagulants. Cardiovasc Drugs Ther. 2018;32(6):591-600.

Jaakkola S, Nuotio I, Kiviniemi TO, Virtanen R, Issakoff M, Airaksinen KEJ. Incidence and predictors of excessive warfarin anticoagulation in patients with atrial fibrillation - The EWA study. PLoS One. 2017;12(4):1-11.