Potential Dexamethasone–Direct Oral Anticoagulant Drug Interaction: Is This a Concern in COVID?

Smythe, Maureen A.; Burns, Carly; Liu, Qianyue; Garwood, Candice L.

doi:10.1177/10600280211025042

Cited by 9 publications

(8 citation statements)

References 69 publications

(135 reference statements)

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“…Moreover, it is plausible that CYPs metabolic activity is downregulated during ARDS and other severely inflammatory states, resulting in an altered pharmacokinetic clearance and interaction. Therefore, one may recommend the avoidance of DOACs (especially apixaban and rivaroxaban) in admitted patients on dexamethasone until high-quality evidence is becoming available [ 122 ]. A small study in patients showed that peak DOAC levels on dexamethasone were below the expected range in 33.3%, of whom about two-thirds had also low levels without dexamethasone [ 123 ].…”

Section: Challenges With Current Antithrombotic Treatmentmentioning

confidence: 99%

COVID-19 Coagulopathy: From Pathogenesis to Treatment

et al. 2022

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Coronavirus disease 2019 (COVID-19) has emerged as a pandemic at the end of 2019 and continues to exert an unfavourable worldwide health impact on a large proportion of the population. A remarkable feature of COVID-19 disease is the precipitation of a hypercoagulable state, mainly in severe cases, leading to micro- and macrothrombosis, respiratory failure and death. Despite the implementation of various therapeutic regimes, including anticoagulants, a large number of patients suffer from such serious complications. This review aims to describe the current knowledge on the pathophysiology of the coagulation mechanism in COVID-19. We describe the interplay between three important mediators of the disease and how this may lead to a hyperinflammatory and pro-thrombotic state that affects outcome; namely, the endothelium, the immune system and the coagulation system. In line with the hypercoagulability state during COVID-19, we further review on the rare but severe vaccine-induced thrombotic thrombocytopenia. We also summarize and comment on available anticoagulant treatment options and include suggestions for some future treatment considerations for COVID-19 anti-coagulation therapy.

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Section: Challenges With Current Antithrombotic Treatmentmentioning

confidence: 99%

COVID-19 Coagulopathy: From Pathogenesis to Treatment

et al. 2022

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“…Drugs employed for COVID-19, particularly those interacting with CYP3A4 and P-gp metabolic pathways, may affect the pharmacokinetic and pharmacodynamic profiles of DOACs, thereby altering their anticoagulant activity [6][7][8]. Dexamethasone, an inducer of both CYP3A4 and P-gp, may reduce bioavailability and increase clearance of DOACs, potentially leading to reduced plasma concentrations [9][10][11]. Although it remains possible that a longer exposure or higher doses of dexamethasone would result in clinically relevant effects, our data, which confirm and expand previous preliminary findings, seem to be reassuring as they suggest that relevant systematic interactions, if any, are unlikely [13].…”

Section: Discussionmentioning

confidence: 99%

“…Of note, dexamethasone, administered intravenously at a dose of 6 mg, has become standard-of-care for the treatment of hypoxemic COVID-19 patients [4]. Whether concomitant administration of DOACs and dexamethasone, a well-known inducer of both CYP3A4 and P-gp [9,10], results in lower DOAC concentrations that may be clinically relevant is currently uncertain [6,7,11].…”

Section: Introductionmentioning

confidence: 99%

Direct oral anticoagulant plasma levels in hospitalized COVID-19 patients treated with dexamethasone

Potere

Candeloro

Porreca

et al. 2021

J Thromb Thrombolysis

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Direct oral anticoagulants (DOACs) are not recommended in COVID-19 patients receiving dexamethasone because of potential drug-drug and drug-disease interactions affecting anticoagulant concentration and activity. To evaluate short- and long-term pharmacokinetic interactions, serial through and peak DOAC plasma levels were prospectively measured during and after dexamethasone therapy, as well as during the acute phase and after recovery from COVID-19 in hospitalized, non-critically ill patients undergoing treatment with DOACs. Thirty-three (18 males, mean age 79 years) consecutive patients received DOACs (17 apixaban, 12 rivaroxaban, 4 edoxaban) for atrial fibrillation (n = 22), venous thromboembolism (n = 10), and acute myocardial infarction (n = 1). Twenty-six patients also received dexamethasone at a dose of 6 mg once daily for a median of 14 days. Trough DOAC levels on dexamethasone were within and below expected reference ranges respectively in 87.5 and 8.3% of patients, with no statistically significant differences at 48–72 h and 14–21 days after dexamethasone discontinuation. Peak DOAC levels on dexamethasone were within expected reference ranges in 58.3% of patients, and below ranges in 33.3%, of whom over two thirds had low values also off dexamethasone. No significant differences in DOAC levels were found during hospitalization and after resolution of COVID-19. Overall, 28 patients were discharged alive, and none experienced thrombotic or bleeding events. In this study, dexamethasone administration or acute COVID-19 seemed not to affect DOAC levels in hospitalized, non-critically ill COVID-19 patients.

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“…Dexamethasone, prednisone, and other corticosteroids may increase the bleeding risk at upper GI level; thus, a potential PD interaction is predicted (Table 10). In addition, dexamethasone may induce P-gp and partially affect the anticoagulant action of DOACs, although clinical data suggesting that dexamethasone is a P-gp inducer are limited and indirect [113,114].…”

Section: Potential Drug-drug Interaction With Antineoplastic and Immu...mentioning

confidence: 99%

Drug-Drug Interactions of Direct Oral Anticoagulants (DOACs): From Pharmacological to Clinical Practice

Ferri

Colombo

Tenconi³

et al. 2022

Pharmaceutics

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The direct oral anticoagulants (DOACs), dabigatran, rivaroxaban, apixaban, and edoxaban, are becoming the most commonly prescribed drugs for preventing ischemic stroke in patients with non-valvular atrial fibrillation (NVAF) and for the treatment and prevention of venous thromboembolism (VTE). Rivaroxaban was also recently approved for the treatment of patients with a recent acute coronary syndrome (ACS). Their use demonstrated to have a favorable risk-benefit profile, with significant reductions in stroke, intracranial hemorrhage, and mortality compared to warfarin, but with increased gastrointestinal bleeding. Nevertheless, their safety profile is compromised in multimorbidity patients requiring contemporary administration of several drugs. Comorbidity and polypharmacy have a high prevalence in elderly patients, who are also more susceptible to bleeding events. The combination of multiple treatments can cause relevant drug–drug interactions (DDIs) by affecting the exposure or the pharmacological activities of DOACs. Although important differences of the pharmacokinetic (PK) properties can be observed between DOACs, all of them are substrate of P-glycoprotein (P-gp) and thus may interact with strong inducers or inhibitors of this drug transporter. On the contrary, rivaroxaban and, to a lower extent, apixaban, are also susceptible to drugs altering the cytochrome P450 isoenzyme (CYP) activities. In the present review, we summarize the potential DDI of DOACs with several classes of drugs that have been reported or have characteristics that may predict clinically significant DDIs when administered together with DOACs. Possible strategies, including dosage reduction, avoiding concomitant administration, or different time of treatment, will be also discussed to reduce the incidence of DDI with DOACs. Considering the available data from specific clinical trials or registries analysis, the use of DOACs is associated with fewer clinically relevant DDIs than warfarin, and their use represents an acceptable clinical choice. Nevertheless, DDIs can be significant in certain patient conditions so a careful evaluation should be made before prescribing a specific DOAC.

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Potential Dexamethasone–Direct Oral Anticoagulant Drug Interaction: Is This a Concern in COVID?

Cited by 9 publications

References 69 publications

COVID-19 Coagulopathy: From Pathogenesis to Treatment

COVID-19 Coagulopathy: From Pathogenesis to Treatment

Direct oral anticoagulant plasma levels in hospitalized COVID-19 patients treated with dexamethasone

Drug-Drug Interactions of Direct Oral Anticoagulants (DOACs): From Pharmacological to Clinical Practice

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