Rivaroxaban and macitentan can be coadministered without dose adjustment but the combination of rivaroxaban and St John's wort should be avoided

Huppertz, Andrea; Werntz, Lars; Meid, Andreas D.; Foerster, Kathrin I.; Burhenne, Jürgen; Czock, David; Mikus, Gerd; Haefeli, Walter E.

doi:10.1111/bcp.13757

Cited by 18 publications

(15 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Still, the impact on DOAC exposure can vary substantially between the inducing agents, making dose adjustment complicated. For example, St. John's wort reduced rivaroxaban exposure by 26% and thus had only a minimal impact on rivaroxaban exposure compared with rifampicin (50%) [74].…”

Section: Drug-drug Interactions Affecting Doac Therapymentioning

confidence: 99%

“…6 Area under the concentration–time curve ratios (AUCR) and maximum (peak) concentration ratios ( C max R) of rivaroxaban with and without concomitantly taken drugs. Results of drug–drug interaction trials that have been conducted and published up to January 2020 are depicted [ 62 , 63 , 69 , 74 , 81 – 83 , 98 , 104 , 118 – 122 ]. A ratio equals 1 if the co-administered drug statistically insignificantly influenced direct oral anticoagulant (DOAC) pharmacokinetics.…”

Section: Basics Of Doac Pharmacokineticsmentioning

confidence: 99%

See 1 more Smart Citation

Drug–Drug Interactions with Direct Oral Anticoagulants

et al. 2020

Self Cite

View full text Add to dashboard Cite

A large body of evidence suggests that not only direct anticoagulant effects but also major bleeding events and stroke prevention depend on plasma concentrations of direct oral anticoagulants (DOACs). Concomitant drugs that cause drug-drug interactions (DDIs) alter DOAC exposure by increasing or decreasing DOAC bioavailability and/or clearance; hence, they might affect the efficacy and safety of DOAC therapy. Patients with renal impairment already receive smaller DOAC maintenance doses because avoidance of elevated DOAC exposure might prevent serious bleeding events. For other causes of increased exposure such as DDIs, management is often less well-defined. Considering that DOAC patients are often older and have multiple co-morbidities, polypharmacy is highly prevalent. However, the effect of multiple drugs on DOAC exposure, and especially the impact of DDIs when concurring with drug-disease interactions as observed in renal impairment, has not been thoroughly elucidated. In order to provide effective and safe anticoagulation with DOACs, understanding the mechanisms and magnitude of DDIs appears relevant. Instead of avoiding drug combinations with DOACs, more DDI trials should be conducted and new strategies such as dose adjustments based on therapeutic drug monitoring should be investigated. However, dose adjustments based on concentration measurements cannot currently be recommended because evidence-based data are missing.

show abstract

Section: Drug-drug Interactions Affecting Doac Therapymentioning

confidence: 99%

Section: Basics Of Doac Pharmacokineticsmentioning

confidence: 99%

Drug–Drug Interactions with Direct Oral Anticoagulants

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Third, rivaroxaban was administered in all phases and might have affected the pharmacokinetics of the other drugs. However, rivaroxaban has never acted as a perpetrator in drug–drug interactions and did not affect midazolam clearance . Fourth, sequence effects cannot be excluded, because of the fixed‐sequence design.…”

Section: Discussionmentioning

confidence: 99%

“…Rivaroxaban, fluconazole and midazolam concentrations in plasma were analysed with ultra‐performance liquid chromatography coupled to tandem mass spectrometry (UHPLC–MS/MS) according to previously described assays or as described below. The lower limits of quantification were 1 μg L −1 for rivaroxaban, 0.025 mg L −1 for fluconazole and 93.0 fg mL −1 for midazolam.…”

Section: Methodsmentioning

confidence: 99%

“…For example, the antifungal ketoconazole increased rivaroxaban exposure 2.58‐fold . In contrast, inducers, such as rifampicin and St John's Wort, can lead to clinically relevant decreases in rivaroxaban exposure . Thus, in patients treated with rivaroxaban, cotreatment with drugs that are combined P‐gp and strong CYP3A4 inhibitors and drugs that are P‐gp and strong CYP3A inducers should be avoided …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Perpetrator effects of ciclosporin (P‐glycoprotein inhibitor) and its combination with fluconazole (CYP3A inhibitor) on the pharmacokinetics of rivaroxaban in healthy volunteers

Brings

Lehmann

Foerster

et al. 2019

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

Aims: Rivaroxaban exposure is considerably increased by drugs that are combined P-glycoprotein (P-gp) and strong cytochrome P450 (CYP) 3A inhibitors (e.g. ketoconazole). The aim of the present study was to investigate the effects of the potent P-gp inhibitor ciclosporin and its combination with the moderate CYP3A inhibitor fluconazole on rivaroxaban pharmacokinetics and on CYP3A activity.Methods: Twelve healthy volunteers received 20 mg rivaroxaban orally alone, in combination with ciclosporin (dose-individualized oral regimen), and in combination with ciclosporin and fluconazole (400 mg day −1 orally). CYP3A4 activity was estimated using a midazolam microdose. Pharmacokinetics was analysed using noncompartmental and compartmental methods.Results: Compared to baseline, ciclosporin increased rivaroxaban average exposure by 47% (90% confidence interval 28-68%), maximum concentration by 104% (70-146%), and decreased CYP3A4 activity by 34% (25-42%). Ciclosporin combined with fluconazole increased rivaroxaban average exposure by 86% (58-119%) and maximum concentration by 115% (83-153%), which was considerably stronger than observed in historical controls receiving rivaroxaban with fluconazole alone, and decreased CYP3A4 activity by 79% (76-82%).Conclusion: Patients treated with rivaroxaban in combination with single modulators of multiple elimination pathways or multiple modulators of single elimination pathways (CYP3A, P-gp) require particular care. KEYWORDS ciclosporin, cytochrome P450 CYP3A, drug-drug interaction, fluconazole, midazolam, pharmacokinetics, rivaroxabanThe authors confirm that the PI for this paper is David Czock and that he had direct clinical responsibility for patients. Trial register: German clinical trials register.

show abstract

Investigating Intestinal Transporter Involvement in Rivaroxaban Disposition through Examination of Changes in Absorption

Kou

Sodhi

et al. 2021

Pharm Res

View full text Add to dashboard Cite

Background-Interactions between antiretrovirals (ARVs) and transplant immunosuppressant agents (IS) among HIV-infected transplant recipients may lead to lack of efficacy or toxicity. In transplant recipients not infected with HIV, cyclosporine (CsA) and tacrolimus (TAC) trough levels (C0) or those drawn two hours after dosing (C2) correlate with drug exposure (AUC/dose) and outcomes. Due to ARV-IS interactions in HIV-infected individuals, and the high rate of rejection in these subjects, we investigated the correlations between IS concentrations and exposure to determine the best method to monitor immunosuppressant levels.Methods-We prospectively studied 50 HIV-infected transplant recipients undergoing kidney or liver transplantation evaluating the pharmacokinetics of the IS over time after transplantation

show abstract

Rivaroxaban and macitentan can be coadministered without dose adjustment but the combination of rivaroxaban and St John's wort should be avoided

Cited by 18 publications

References 52 publications

Drug–Drug Interactions with Direct Oral Anticoagulants

Drug–Drug Interactions with Direct Oral Anticoagulants

Perpetrator effects of ciclosporin (P‐glycoprotein inhibitor) and its combination with fluconazole (CYP3A inhibitor) on the pharmacokinetics of rivaroxaban in healthy volunteers

Investigating Intestinal Transporter Involvement in Rivaroxaban Disposition through Examination of Changes in Absorption

Contact Info

Product

Resources

About