Rivaroxaban With and Without Amiodarone in Renal Impairment

Cheong, Eleanor Jing Yi; Goh, Janice Jia Ni; Hong, Yanjun; Kojodjojo, Pipin; Chan, Eric Chun Yong

doi:10.1016/j.jacc.2018.01.044

Cited by 31 publications

(32 citation statements)

References 5 publications

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“…However, when combined with increasing age (65‐78 years) and mild renal impairment (creatinine clearance 50‐79 mL/min), the predicted increase in AUC was 2.4‐fold (95% CI: 2.15‐2.62). These changes were deemed clinically significant by the authors 10 …”

Section: Discussionmentioning

confidence: 99%

Supratheraputic rivaroxaban levels: A persistent drug‐drug interaction after discontinuation of amiodarone

Skov

Falskov

Jensen

et al. 2020

Basic Clin Pharma Tox

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We report the case of an 88‐year old woman referred for evaluation of increased INR. Surprisingly supratherapeutic levels of rivaroxaban was detected. Upon scrutiny of the patient's medical history, a drug‐drug interaction between amiodarone and rivaroxaban persisting 3 weeks after cessation of amiodaron remains the prime suspect causing the clinical picture. Both INR and rivaroxaban levels returned to normal within 3 days of cessation of rivaroxaban. The case highlights that rivaroxaban, although highly variably, does affect INR. Furthermore, it highlights that the potential for DDIs involving amiodarone may persists for weeks or months after discontinuation. Amiodarone is predicted to increase rivaroxaban exposure, through inhibition of rivaroxaban elimination via CYP3A4 and P‐gp. Elderly patients and patients with declining renal function are especially at risk of increased rivaroxaban exposure when a DDI with amiodarone occurs.

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Section: Discussionmentioning

confidence: 99%

Supratheraputic rivaroxaban levels: A persistent drug‐drug interaction after discontinuation of amiodarone

Skov

Falskov

Jensen

et al. 2020

Basic Clin Pharma Tox

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“…Simulations also indicated a significant 1.36-fold mean AUC increase [45]. Moreover, renal insufficiency had a synergistic effect, as the simulated mean AUC-fold change was 1.86-in patients with mild renal impairment and 1.61 in patients with moderate renal impairment where the rivaroxaban dosage was reduced to 15 mg [45].…”

Section: In Silico Studiesmentioning

confidence: 86%

“…The authors suggested that subjects with mild to severe renal dysfunction who are taking verapamil should receive a reduced dose of rivaroxaban to minimise synergistic drugdrug disease interactions and prevent further bleeding risks [44]. In another PBPK model, systemic exposure to 20 mg of rivaroxaban once daily for 20 days increased when coadministered with a loading dose of amiodarone 200 mg three times a day during the last fifteen days in healthy subjects [45]. Simulations also indicated a significant 1.36-fold mean AUC increase [45].…”

Section: In Silico Studiesmentioning

confidence: 99%

“…In another PBPK model, systemic exposure to 20 mg of rivaroxaban once daily for 20 days increased when coadministered with a loading dose of amiodarone 200 mg three times a day during the last fifteen days in healthy subjects [45]. Simulations also indicated a significant 1.36-fold mean AUC increase [45]. Moreover, renal insufficiency had a synergistic effect, as the simulated mean AUC-fold change was 1.86-in patients with mild renal impairment and 1.61 in patients with moderate renal impairment where the rivaroxaban dosage was reduced to 15 mg [45].…”

Section: In Silico Studiesmentioning

confidence: 99%

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Drug-Drug Interactions Leading to Adverse Drug Reactions with Rivaroxaban: A Systematic Review of the Literature and Analysis of VigiBase

Fernandez-Martinez

Lenoir

Samer

et al. 2021

JPM

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Rivaroxaban has become an alternative to vitamin K antagonists, which are considered to be at higher risk of drug-drug interactions (DDI) and more difficult to use. However, DDI do occur. We systematically reviewed studies that evaluated them and analysed DDI and subsequent adverse drug reactions (ADR) reported in spontaneous reports and VigiBase. We systematically searched articles that explored DDI with rivaroxaban up to 20 August 2018 via Medline, Embase and Google Scholar. Data from VigiBase came from spontaneous reports recovered up to 2 January 2018, where Omega was used to detect signals and identify potential interactions in terms of triplets with two drugs and one ADR. We identified 31 studies and 28 case reports. Studies showed significant variation in the pharmacokinetic for rivaroxaban, and an increased risk of haemorrhage or thromboembolic events due to DDI was highlighted in case reports. From VigiBase, a total of 21,261 triplets were analysed and the most reported was rivaroxaban–aspirin–gastrointestinal haemorrhage. In VigiBase, only 34.8% of the DDI reported were described or understood, and most were pharmacodynamic DDI. These data suggest that rivaroxaban should be considered to have significant potential for DDI, especially with CYP3A/P-gp modulators or with drugs that impair haemostasis.

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“…Many medications that are commonly prescribed in patients with atrial fibrillation (AF) can inhibit or induce ABCB1 activity and thereby influence DOAC pharmacokinetics 7 . For instance, it has been demonstrated that the concurrent use of moderate inhibitors of ABCB1 such as amiodarone or verapamil led to a nearly 40% increase in rivaroxaban exposure 8 , 9 . Combining this with renal impairment or older age, two common characteristics in AF patients, produced even stronger effect on rivaroxaban pharmacokinetics.…”

Section: Introductionmentioning

confidence: 99%

Effect of ABCB1 genetic polymorphisms on the transport of rivaroxaban in HEK293 recombinant cell lines

Sennesael

Panin²,

Vancraeynest

et al. 2018

Sci Rep

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Direct oral anticoagulants (DOAC) are substrates for the ABCB1 transporter (also called P-glycoprotein), an active efflux pump. ABCB1 polymorphisms have been previously reported to influence the pharmacokinetics of several drugs such as immunosuppressants and tyrosine kinase inhibitors. Recently, in vivo studies have suggested that genetic variants might contribute to the inter-individual variability in DOAC plasma concentrations. Therefore, we evaluated the in vitro effect of the most common coding ABCB1 single nucleotide polymorphisms (SNP), 1236 C > T-2677G > T-3435C > T, and the coding ABCB1 1199 G > A SNP on the transport activity towards rivaroxaban. HEK293 cells were transfected to overexpress the ABCB1 wild-type (1236C-2677G-3435C, 1199 G) or variant proteins (1236C-2677G-3435T, 1236T-2677T-3435T or 1199 A). ABCB1 expression decreased the intracellular accumulation of rivaroxaban, when compared to control cells. This confirms the involvement of ABCB1 in the active transport of rivaroxaban. However, the ABCB1 1236 C > T-2677G > T-3435C > T and 1199 G > A SNPs had no significant influence on the intracellular accumulation of rivaroxaban when compared to the wild-type protein. These results suggest that the ABCB1 coding SNPs investigated in the present study are unlikely to contribute to the inter-individual variability in rivaroxaban plasma concentrations.

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Rivaroxaban With and Without Amiodarone in Renal Impairment

Cited by 31 publications

References 5 publications

Supratheraputic rivaroxaban levels: A persistent drug‐drug interaction after discontinuation of amiodarone

Supratheraputic rivaroxaban levels: A persistent drug‐drug interaction after discontinuation of amiodarone

Drug-Drug Interactions Leading to Adverse Drug Reactions with Rivaroxaban: A Systematic Review of the Literature and Analysis of VigiBase

Effect of ABCB1 genetic polymorphisms on the transport of rivaroxaban in HEK293 recombinant cell lines

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