Clinafloxacin-Theophylline Drug Interaction

Abstract

To report an apparent pharmacokinetic interaction between clinafloxacin and theophylline in a patient with chronic obstructive pulmonary disease (COPD). A patient with a history of COPD was admitted for a fracture of the right femoral neck. Admission medications included extended-release theophylline 400 mg bid. The initial serum theophylline concentration was 81.03 mumol/L (normal 55-110). A subsequent concentration was subtherapeutic (46.62 mumol/L) and the theophylline dosage was increased to 300 mg tid. Therapeutic steady-state concentrations were achieved. The patient later developed pneumonia and was enrolled in a study of nosocomial acquired pneumonia involving clinafloxacin versus ceftazidime. He was randomized to receive clinafloxacin 200 mg iv q12h. After clinafloxacin therapy was initiated, the serum theophylline concentration increased into the toxic range (155.96 mumol/L). Theophylline administration was held for 2 doses and the dosage then reduced to 200 mg tid. Serum concentrations decreased to within the therapeutic range. The fluoroquinolones have been shown to interact with the hepatic metabolism of theophylline and increase serum theophylline concentrations. The quinolone metabolite, 4-oxoquinolone, inhibits the N-demethylation of theophylline, leading to a decrease in the clearance of theophylline. The resultant rise in theophylline concentrations corresponds with the decrease in clearance and possible toxicity. In our patient, careful monitoring of theophylline concentrations and dosage adjustments resulted in the restoration of therapeutic serum concentrations. The observation of this drug interaction between clinafloxacin and theophylline suggests a need for prudent monitoring of theophylline concentrations. Dosage adjustments may be warranted when this combination of medications is used. Such action may prevent significant toxicities and prolonged hospitalization. Further controlled clinical trials in healthy volunteers are needed to substantiate the interaction between clinafloxacin and theophylline.