Antibiotics:
Comment:
Several studies in transplant patients and healthy subjects have shown that amoxicillin and ciprofloxacin can reduce plasma concentrations of mycophenolic acid (MPA, the active metabolite of mycophenolate). In one case a patient died of severe graft-versus-host disease after ciprofloxacin was added and the AUC of MPA fell to one-third of previous values. Metronidazole has also been reported to reduce MPA concentrations, but the effect may not be as large as with amoxicillin/clavulanate or ciprofloxacin. MPA is excreted in the bile as an inactive glucuronide metabolite, and glucuronidases in intestinal bacteria metabolize the glucuronide back to MPA, which can be reabsorbed. The interaction is thought to result from antibiotic-induced reduction in these bacteria, thus interrupting the enterohepatic recirculation and decreasing MPA plasma concentrations. In one case, intravenous ciprofloxacin appeared to reduce MPA plasma concentrations. Other fluoroquinolones (and perhaps some other antibiotics) may have a similar effect on mycophenolate. Norfloxacin appeared to have an additive effect with metronidazole in reducing MPA concentrations in one study but, norfloxacin given alone had little effect. A small study found reduced MPA concentrations following bowel decontamination with tobramycin plus cefuroxime. Available evidence suggests that co-trimoxazole (trimethoprim/sulfamethoxazole) does not interact with mycophenolate.
Class 3: Assess Risk & Take Action if Necessary