Possible Interaction of the Gut-selective Antibiotic Rifaximin with Carvedilol Associated with Transient Indirect Hyperbilirubinemia: A Case Report.

INTRODUCTION: Rifaximin is a gut-selective antimicrobial with poor bioavailability. One potential indication of rifaximin use is hepatic encephalopathy. The adverse effects are limited to the gastrointestinal system, and systemic disturbances are rare. We report a case of hyperbilirubinemia possibly associated with rifaximin-carvedilol co-administration. CASE PRESENTATION: A 58-year-old male with chronic liver disease (Child Pugh class B) of probable autoimmune etiology and associated chronic kidney disease developed transient indirect hyperbilirubinemia temporally associated with rifaximin-carvedilol co-administration. The hyperbilirubinemia improved with the discontinuation of both drugs. CONCLUSION: This appears to be the first report of new-onset indirect hyperbilirubinemia with rifaximin in the presence of carvedilol in a patient with chronic liver disease of autoimmune etiology. Carvedilol-mediated P-glycoprotein inhibition represents a biologically plausible but unproven mechanism for overexposure to rifaximin. Clinical studies are warranted to assess the potential consequences of P-glycoprotein-mediated modulation of rifaximin pharmacokinetics in patients with chronic liver and renal disease.