Ritonavir- or cobicistat-boosted antiretroviral therapy and direct oral anticoagulants: A case for apixaban

Nisly, Sarah A.; Stevens, Brooke

doi:10.1177/0956462419832099

Cited by 16 publications

(9 citation statements)

References 13 publications

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“…If the patient is already on a 2.5 mg dose, concurrent use should be avoided. In a case series of 6 patients, reduced dose apixaban was used successfully with RTV or cobicistat-boosted regimens [ 47 ]. Dabigatran is not metabolized by CYP450 and is primarily cleared through renal elimination, so significant interactions are not anticipated.…”

Section: Discussionmentioning

confidence: 99%

Lopinavir-Ritonavir in SARS-CoV-2 Infection and Drug-Drug Interactions with Cardioactive Medications

Agarwal

2020

Cardiovasc Drugs Ther

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Lopinavir-ritonavir combination is being used for the treatment of SARS-CoV-2 infection. A low dose of ritonavir is added to other protease inhibitors to take advantage of potent inhibition of cytochrome (CYP) P450 3A4, thereby significantly increasing the plasma concentration of coadministered lopinavir. Ritonavir also inhibits CYP2D6 and induces CYP2B6, CYP2C19, CYP2C9, and CYP1A2. This potent, time-dependent interference of major hepatic drug-metabolizing enzymes by ritonavir leads to several clinically important drug-drug interactions. A number of patients presenting with acute coronary syndrome and acute heart failure may have SARS-CoV-2 infection simultaneously. Lopinavir-ritonavir is added to their prescription of multiple cardiac medications leading to potential drug-drug interactions. Many cardiology, pulmonology, and intensivist physicians have never been exposed to clinical scenarios requiring co-prescription of cardiac and antiviral therapies. Therefore, it is essential to enumerate these drug-drug interactions, to avoid any serious drug toxicity, to consider alternate and safer drugs, and to ensure better patient care.

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Section: Discussionmentioning

confidence: 99%

Lopinavir-Ritonavir in SARS-CoV-2 Infection and Drug-Drug Interactions with Cardioactive Medications

Agarwal

2020

Cardiovasc Drugs Ther

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“…Notably, although several studies and case reports [40][41][42][43][44][45][46][47] investigated the impact of ritonavir or tocilizumab on DOAC exposure, none of these was performed in the context of COVID-19. Particularly, the degree of COVID-19 severity and associated renal and/or hepatic injury may increase the likelihood and clinical relevance of DDIs.…”

Section: Direct Oral Anticoagulants In the Setting Of Covid-19 And Camentioning

confidence: 99%

The Complex Management of Atrial Fibrillation and Cancer in the COVID-19 Era: Drug Interactions, Thromboembolic Risk, and Proarrhythmia

Gatti

Raschi

Poluzzi

et al. 2020

Curr Heart Fail Rep

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Purpose of Review Cardiotoxicity by anticancer agents has emerged as a multifaceted issue and is expected to affect both mortality and morbidity. This review summarizes clinical challenges in the management of oncological patients requiring anticoagulants for atrial fibrillation (AF) also considering the current outbreak of the COVID-19 (coronavirus disease 2019) pandemic, since this infection can add challenges to the management of both conditions. Specifically, the aims are manyfold: (1) describe the evolving use of direct oral anticoagulants (DOACs) in AF patients with cancer; (2) critically appraise the risk of clinically important drug-drug interactions (DDIs) between DOACs and oral targeted anticancer agents; (3) address expected DDIs between DOACs and candidate anti-COVID drugs, with implications on management of the underlying thrombotic risk; and (4) characterize the proarrhythmic liability in cardio-oncology in the setting of COVID-19, focusing on QT prolongation. Recent Findings AF in cardio-oncology poses diagnostic and management challenges, also due to the number of anticancer drugs recently associated with AF onset/worsening. Oral targeted drugs can potentially interact with DOACs, with increased bleeding risk mainly due to pharmacokinetic DDIs. Moreover, the vast majority of oral anticancer agents cause QT prolongation with direct and indirect mechanisms, potentially resulting in the occurrence of torsade de pointes, especially in susceptible patients with COVID-19 receiving additional drugs with QT liability. Summary Oncologists and cardiologists must be aware of the increased bleeding risk and arrhythmic susceptibility of patients with AF and cancer due to DDIs. High-risk individuals with COVID-19 should be prioritized to target preventive strategies, including optimal antithrombotic management, medication review, and stringent monitoring.

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“…6 The oral factor Xa inhibitors, apixaban, rivaroxaban, and edoxaban, are substrates of P-gp transporters and to varying degrees, CYP3A4. [6][7][8][9][10] Dabigatran circumvents many CYP interactions; however, it is still implicated in P-gp drug interactions. The use of DOACs in PLWH has been limited to small cohorts.…”

Section: Introductionmentioning

confidence: 99%

Direct oral anticoagulants versus warfarin in people living with human immunodeficiency virus

et al. 2021

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Human immunodeficiency virus (HIV) is associated with increased rates of cardiovascular disease and vascular events, and people living with HIV (PLWH) may often have indications for therapeutic anticoagulation. However, the ideal anticoagulant in PLWH remains unknown. This retrospective cohort evaluated the tolerability and effectiveness of oral anticoagulants in PLWH. The primary outcome was tolerability, defined as a composite of bleeding and/or discontinuation rates. The secondary outcomes included recurrent thromboembolism, bleeding, and discontinuations, independently. There were 92 patients included for analysis, 48 in the direct oral anticoagulant (DOAC) arm and 44 in the warfarin arm. There were 35 (38%) PLWH that did not tolerate oral anticoagulation therapy in the total cohort. Among these, 19 received a DOAC and 16 received warfarin. There were 16 (17%) PLWH that experienced a bleeding event: six in the DOAC arm and 10 in the warfarin arm. There were 15 (16%) PLWH that experienced recurrent thromboembolism, with similar rates between DOAC versus warfarin (10, 21% vs 5, 11%, respectively; p = 0.11). The most commonly prescribed HIV regimens were protease inhibitor and integrase inhibitor-based regimens. Overall, anticoagulation-related outcomes with either a DOAC or warfarin were poor in our cohort of PLWH, with high rates of bleeding, discontinuations, and recurrent thromboembolism. Further studies are necessary to validate and assess reasons for poor tolerability.

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Ritonavir- or cobicistat-boosted antiretroviral therapy and direct oral anticoagulants: A case for apixaban

Cited by 16 publications

References 13 publications

Lopinavir-Ritonavir in SARS-CoV-2 Infection and Drug-Drug Interactions with Cardioactive Medications

Lopinavir-Ritonavir in SARS-CoV-2 Infection and Drug-Drug Interactions with Cardioactive Medications

The Complex Management of Atrial Fibrillation and Cancer in the COVID-19 Era: Drug Interactions, Thromboembolic Risk, and Proarrhythmia

Direct oral anticoagulants versus warfarin in people living with human immunodeficiency virus

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