Oral antibiotics lower mycophenolate mofetil drug exposure, possibly by interfering with the enterohepatic recirculation: A case series

Mycophenolate mofetil has an important role as immunosuppressive agent in solid organ transplant recipients. Exposure to the active mycophenolic acid (MPA) can be monitored using therapeutic drug monitoring. We present three cases in which MPA exposure severely decreased after oral antibiotic coadministration. By diminishing gut bacteria beta-glucuronidase activity, oral antibiotics can prevent deglucuronidation of the inactive MPA-7-O-glucuronide metabolite to MPA and thereby possibly prevent its enterohepatic recirculation. This pharmacokinetic interaction could result in rejection, which makes it clinically relevant in solid organ transplant recipients, especially when therapeutic drug monitoring frequency is low. Routine screening for this interaction, preferably supported by clinical decision support systems, and pragmatic close monitoring of the MPA exposure in cases is advised.

Automated summary

Oral antibiotics coadministration can decrease the exposure to mycophenolic acid (MPA) by reducing enzyme activity, which could result in rejection in solid organ transplant recipients. This interaction is clinically significant, especially when therapeutic drug monitoring frequency is low.