ArticleBritish journal of clinical pharmacology2018
Rivaroxaban and macitentan can be coadministered without dose adjustment but the combination of rivaroxaban and St John's wort should be avoided.
Article in British journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.
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Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 21 citations in OpenAlex.
- Use of direct oral anticoagulants in chronic thromboembolic pulmonary hypertension: a systematic review.Journal of thrombosis and thrombolysis · 2022Pooled it
- Investigating Intestinal Transporter Involvement in Rivaroxaban Disposition through Examination of Changes in Absorption.Pharmaceutical research · 2021Pooled it
- Perpetrator effects of ciclosporin (P-glycoprotein inhibitor) and its combination with fluconazole (CYP3A inhibitor) on the pharmacokinetics of rivaroxaban in healthy volunteers.British journal of clinical pharmacology · 2019Trial
- Pharmacokinetic Variability of Direct Oral Anticoagulants and Calcium Channel Blockers: A Comparative Analysis of Exposure Data from Clinical Studies.Pharmaceutics · 2026Article
- Herbal Medicines and Drugs Interactions: Cytochrome P450 Responsibility.Current medicinal chemistry · 2026Review
- Dose-dependent induction of CYP3A activity by St. John's wort alone and in combination with rifampin.Clinical and translational science · 2024Article
- Extracellular Vesicles as Surrogates for the Regulation of the Drug Transporters ABCC2 (MRP2) and ABCG2 (BCRP).International journal of molecular sciences · 2024Article
- Effects of bergapten on the pharmacokinetics of macitentan in rats bothFrontiers in pharmacology · 2023Article
- Review
- Sensitive UHPLC-MS/MS quantification method for 4β- and 4α-hydroxycholesterol in plasma for accurate CYP3A phenotyping.Journal of lipid research · 2022Article
- Application of a microdosed cocktail of 3 oral factor Xa inhibitors to study drug-drug interactions with different perpetrator drugs.British journal of clinical pharmacology · 2020Article
- Drug-Drug Interactions with Direct Oral Anticoagulants.Clinical pharmacokinetics · 2020Review
- Rivaroxaban and macitentan can be coadministered without dose adjustment but the combination of rivaroxaban and St John's wort should be avoided.British journal of clinical pharmacology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsWe assessed the potential mutual interaction of oral macitentan (cytochrome P450 (CYP) 3A4 substrate) at steady-state with single-dose oral rivaroxaban (CYP3A4 and P-glycoprotein substrate) and evaluated the effect of the CYP3A and P-glycoprotein inducer St John's wort (SJW) on the pharmacokinetics of these drugs in healthy volunteers.
methodsTwelve healthy volunteers completed this open-label, monocentre, two-period, one-sequence phase I clinical trial. The pharmacokinetics of macitentan (10 mg) was assessed on study days 3 (single dose), 15 (steady-state), 16 (impact of rivaroxaban) and 29 (after induction by oral SJW), and of rivaroxaban on days 2 (single dose), 16 (impact of macitentan at steady-state) and 29 (after induction by SJW). Concurrently, we quantified changes of CYP3A activity using oral microdoses of midazolam (30 μg).
resultsRivaroxaban and macitentan did not significantly change the pharmacokinetics of each other. After induction with SJW, CYP3A activity increased by 272% and geometric mean ratios of macitentan AUC decreased by 48% and of C
conclusionsThere is no evidence for a relevant pharmacokinetic interaction between macitentan and rivaroxaban suggesting that these two drugs can be combined without dose adjustment. SJW strongly increased CYP3A activity and substantially reduced rivaroxaban and macitentan exposure while estimated net endothelin antagonism only decreased by 20%, which is considered clinically irrelevant. The combination of SJW with rivaroxaban should be avoided.
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