Purpose: Direct oral anticoagulants (DOACs) pose a challenge when given with potent CYP3A4 and P-gp inhibitors, such as the commonly prescribed pharmacokinetic booster ritonavir. As per the manufacturer, apixaban offers a dose reduction when administered concurrently with ritonavir; thus, we explore the clinical indication and safety of apixaban when given with ritonavir-boosted highly active antiretroviral therapy (HAART) in an HIV patient. Summary: We describe a 73-year-old male with extensive cardiac history, including a past medical history of resolved left ventricular thrombus, newly diagnosed non-valvular atrial fibrillation treated with warfarin, and HIV infection treated with ritonavir-boosted HAART. The patient presented to the emergency department with bleeding from multiple sites, necessitating the use of vitamin K. Consequently, his hospital course was complicated by episodes of minor bleeding and labile INR. Due to the complicated nature of his condition and the potential for drug-drug interactions (DDIs), he was transitioned from warfarin to apixaban. Since there is little readily available data to support the use of rivaroxaban and dabigatran with ritonavir, our patient was safely started on dose-reduced apixaban for stroke prophylaxis in atrial fibrillation due to the predictable nature of apixaban pharmacokinetics and proven superiority regarding adverse effects, as compared to other DOACs. Conclusion: Dose-reduced apixaban is a safe and viable choice in patients with atrial fibrillation warranting stroke prophylaxis while concurrently receiving ritonavir-boosted HAART.
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Department of Health and Human Services; 2011:1-167.
2.
HsuJCLiYMarcusGM, et al. Atrial fibrillation and atrial flutter in human immunodeficiency virus-infected persons. J Am Coll Cardiol. 2013;61(22):2288-2295.
3.
SicoJJChangCHSo-ArmahK, et al. HIV status and the risk of ischemic stroke among men. Neurology. 2015;84(19):1933-1940.
4.
SterneJABodaliaPNBrydenPA, et al. Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis. Health Technol Assess. 2017;21(9):1-386.
ParasrampuriaDATruittKE. Pharmacokinetics and pharmacodynamics of edoxaban, a non-vitamin K antagonist oral nticoagulant that inhibits clotting factor xa. Clin Pharmacokinet. 2016;55:641-655.
7.
SevrioukovaIFPoulosTL. Structure and mechanism of the complex between cytochrome P4503A4 and ritonavir. Proc Natl Acad Sci USA. 2010;107(43):18422-18427.
8.
LipGYHBanerjeeABorianiG, et al. Antithrombotic therapy for atrial fibrillation. Chest. 2018;154(5):1121-1201.
9.
RayWAChungCPMurrayKT, et al. Association of oral anticoagulants and proton pump inhibitor cotherapy with hospitalization for upper gastrointestinal tract bleeding. JAMA. 2018;320(21):2221-2230.
10.
NislySAStevensBN. Ritonavir- or cobicistat-boosted antiretroviral therapy and direct oral anticoagulants: A case for apixaban. Int J STD AIDS. 2019;30(7):718-722.
11.
GaronzikSByonWMyersELiXMarchisinDMurthyB. The effects of clarithromycin on the pharmacokinetics of apixaban in healthy volunteers: A single-sequence crossover study. Am J Cardiovasc Drugs. 2019;19(6):561-567.
12.
ZhangDHeKHerbstJJ, et al. Characterization of efflux transporters involved in distribution and disposition of apixaban. Drug Metabol Dispos. 2013; 4(4):827-835.
13.
WangLLZhangDRaghavanN, et al. In vitro assessment of metabolic drug-drug interaction potential of apixaban through cytochrome P450 phenotyping, inhibition, and induction studies. Drug Metab Dispos. 2010;38(3):448-458.
