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Pretomanid can significantly increase plasma rivaroxaban concentrations—a case report

Home Pretomanid can significantly increase plasma rivaroxaban concentrations—a case report

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Abstract

Background

Rivaroxaban, a direct factor Xa inhibitor, is an oral anticoagulant used in the prevention and treatment of thromboembolic disease. The clearance of rivaroxaban involves excretion unchanged via the kidneys where it is subject to active secretion into the renal tubules, involving P-glycoprotein (P-gp) and organic anion transporter 3 (OAT3). Pretomanid, a nitroimidazole antibiotic used for multidrug-resistant tuberculosis (MDR-TB), is an OAT3 inhibitor based on in vitro data. This case report describes a “natural experiment” involving rivaroxaban concentration monitoring. It entails a novel pharmacokinetic interaction between rivaroxaban and pretomanid in a 61-year-old male undergoing MDR-TB treatment.

Result

Following pretomanid initiation, rivaroxaban trough plasma concentration increased more than two-fold, prompting a halving of rivaroxaban dose, and subsequent restoration of trough concentration to pre-pretomanid value.

Discussion

This interaction appears to be mediated by pretomanid inhibition of OAT3, which reduces renal clearance of rivaroxaban. Other components of MDR-TB regimen and pre-existing medications are unlikely to be contributory based on their pharmacokinetic profiles.

Conclusion

This case highlights the potential impact of drug interactions involving pretomanid and known OAT3 perpetrators on the pharmacokinetics of rivaroxaban and other OAT3 substrates, particularly those of low therapeutic index, such as methotrexate. Given the global rise in MDR-TB, further research into pretomanid as a perpetrator of drug interactions is warranted.

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Data availability

No datasets were generated or analysed during the current study.

References

  1. Nyang’wa BT, Berry C, Kazounis E, Motta I, Parpieva N, Tigay Z, Solodovnikova V, Liverko I, Moodliar R, Dodd M, Ngubane N, Rassool M, McHugh TD, Spigelman M, Moore DAJ, Ritmeijer K, du Cros P, Fielding K; TB-PRACTECAL Study Collaborators (2022 ) A 24-Week, all-oral regimen for rifampin-resistant tuberculosis. N Engl J Med 387(25):2331–2343

  2. Otsuka Y, Choules MP, Bonate PL, Komatsu K (2020) Physiologically-based pharmacokinetic modelling for the prediction of a drug-drug interaction of combined effects on P-glycoprotein and cytochrome P450 3A. CPT Pharmacometrics Syst Pharmacol 9(11):659–669

    Article CAS PubMed PubMed Central Google Scholar

  3. Cheong EJY, Teo DWX, Chua DXY, Chan ECY (2019) Systematic development and verification of a physiologically based pharmacokinetic model of rivaroxaban. Drug Metab Dispos 47(11):1291–1306

    Article CAS PubMed Google Scholar

  4. US Food and Drug Administration. PRETOMANID label information.https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/212862s008lbl.pdf. Accessed 13 June 2025.

  5. Zhang M, Moore GA, Chin PKL (2020) Simultaneous determination of dabigatran, rivaroxaban, and apixaban in human plasma by liquid chromatography/tandem mass spectrometry. Ther Drug Monit 42(3):473–480

    Article CAS PubMed Google Scholar

  6. Douxfils J, Adcock DM, Bates SM, Favaloro EJ, Gouin-Thibault I, Guillermo C, Kawai Y, Lindhoff-Last E, Kitchen S, Gosselin RC (2021) Update of the International Council for Standardization in Haematology recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost 121(8):1008–1020

    Article PubMed Google Scholar

  7. Cavaillez T, Weinmann L, Mouton C, Delassasseigne C, Sesay M, Biais M et al (2021) A retrospective study of indications and consequences of monitoring direct oral anticoagulant plasma concentrations on patient care in a university hospital: The Retro-AOD study. Thromb Res 206:76–83

    Article CAS PubMed Google Scholar

  8. Vonk SEM, Terheggen-Lagro SWJ, Mouissie LM, Mathôt RAA, Kemper EM (2022Jan) Amsterdam Mucociliary Clearance Disease (AMCD) research group. No drug-drug interaction between tezacaftor-ivacaftor and clofazimine: A case report. J Cyst Fibros 21(1):e5–e7

    Article CAS PubMed Google Scholar

  9. van Heeswijk RP, Dannemann B, Hoetelmans RM (2014) Bedaquiline: a review of human pharmacokinetics and drug-drug interactions. J Antimicrob Chemother 69(9):2310–2318

    Article PubMed Google Scholar

  10. Stalker DJ, Jungbluth GL (2003) Clinical pharmacokinetics of linezolid, a novel oxazolidinone antibacterial. Clin Pharmacokinet 42(13):1129–1140

    Article CAS PubMed Google Scholar

  11. Stass H, Kubitza D (2001) Profile of moxifloxacin drug interactions. Clin Infect Dis 15(32 Suppl 1):S47-50

    Article Google Scholar

  12. Chen Y, Li H, Wang K, Wang Y (2023) Recent advances in synthetic drugs and natural actives interacting with OAT3. Molecules 28(12):4740

    Article CAS PubMed PubMed Central Google Scholar

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Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology, Christchurch Hospital, Te Whatu Ora Waitaha Canterbury, Christchurch, New Zealand

    Dali Fan & Paul Ken Leong Chin

  2. Department of Respiratory Medicine, Christchurch Hospital, Te Whatu Ora Waitaha Canterbury, Christchurch, New Zealand

    Teurai Chikura & Sarah McCrostie

  3. Department of Medicine, University of Otago, Christchurch, New Zealand

    Paul Ken Leong Chin

Contributions

D.F and P.C wrote the main manuscript text. T.C and S.M helped with data collection. All authors reviewed the manuscript.

Corresponding author

Correspondence to Dali Fan.

Ethics declarations

Ethics approval

An ethics committee was not consulted, as this is a case report, and, therapeutic drug monitoring is a routine service provided within our health system.

Consent to participate

Informed consent was obtained in writing from the patient to investigate this drug-drug interaction and to publish any findings in an academic journal.

Conflict of interest

The authors have no conflicts of interest relevant to this manuscript to disclose.

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Fan, D., Chikura, T., McCrostie, S. et al. Pretomanid can significantly increase plasma rivaroxaban concentrations—a case report. Eur J Clin Pharmacol (2025). https://doi.org/10.1007/s00228-025-03871-1

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  • DOI  https://doi.org/10.1007/s00228-025-03871-1

Keywords

  • Rivaroxaban
  • Pretomanid
  • Organic anion transporter 3 (OAT3)
  • Drug interaction
  • Therapeutic drug monitoring

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