Probable Drug Interaction Between Intravenous Ciprofloxacin and Mycophenolate Mofetil in a Bone Marrow Transplant Recipient

Abstract

Several studies have reported that oral antibacterials, including ciprofloxacin, administered during mycophenolate mofetil therapy may reduce mycophenolic acid (the active drug moiety) exposure. To our knowledge, however, this effect has never been described with antibiotics administered by the parenteral route. We describe a 17‐year‐old female who received intravenous mycophenolate mofetil after bone marrow transplantation, with therapeutic drug monitoring performed during therapy. On day 2 of mycophenolate mofetil therapy, the mycophenolic acid area under the plasma concentration‐time curve was 30.3 mg•hour/L. On day 8, although her mycophenolate mofetil dosage had remained unchanged, the mycophenolic acid area under the plasma concentration‐time curve was unexpectedly lower at 10.7 mg•hour/L. A drug interaction was suspected. Three intravenous antiinfective drugs had been introduced after initial therapeutic drug monitoring had been performed—ciprofloxacin, trimethoprim‐sulfamethoxazole, and caspofungin. The patient subsequently developed severe graft‐versus‐host disease during mycophenolate mofetil therapy and died. Use of the Horn drug interaction probability scale indicated a probable interaction between intravenous mycophenolate mofetil and intravenous ciprofloxacin in this patient. The available literature does not support the role of either trimethoprim‐sulfamethoxazole or caspofungin in a drug interaction with mycophenolate mofetil. Published studies have shown that ciprofloxacin is partially excreted by transintestinal elimination after intravenous administration and that it may greatly reduce the levels of enterobacteria of gastrointestinal flora, which are responsible for mycophenolic acid enterohepatic recirculation. Clinicians should be aware that ciprofloxacin, even administered intravenously, may modify the pharmacokinetics of mycophenolate mofetil. Ciprofloxacin should be used with caution in patients receiving mycophenolate mofetil; if this antiinfective must be used, therapeutic drug monitoring should be performed to guide dosage adjustments.