Pretomanid can significantly increase plasma rivaroxaban concentrations-a case report

Area of Science:

• Pharmacology
• Drug Interactions
• Clinical Pharmacy

Background:

• Rivaroxaban, a direct factor Xa inhibitor, is cleared renally via P-glycoprotein (P-gp) and organic anion transporter 3 (OAT3).
• Pretomanid, an antibiotic for multidrug-resistant tuberculosis (MDR-TB), is an in vitro OAT3 inhibitor.
• This report details a pharmacokinetic interaction between rivaroxaban and pretomanid in an MDR-TB patient.

Observation:

• Initiation of pretomanid therapy led to a twofold increase in rivaroxaban trough plasma concentration.
• The rivaroxaban dose was halved in response to the elevated concentration.
• Subsequent dose reduction restored rivaroxaban trough concentration to baseline levels.

Findings:

• The observed interaction is attributed to pretomanid's inhibition of OAT3, reducing rivaroxaban's renal clearance.
• Other MDR-TB medications and concurrent drugs were deemed unlikely contributors to the interaction.

Implications:

• Pretomanid may significantly alter the pharmacokinetics of rivaroxaban and other OAT3 substrates, especially those with a narrow therapeutic index.
• Further investigation into pretomanid's role as a drug interaction perpetrator is crucial, given the increasing prevalence of MDR-TB.
• Clinical monitoring for drug interactions involving pretomanid is recommended for patients on OAT3 substrates.