Objective: To report a case of decreased theophylline clearance by the addition of levofloxacin in a patient receiving theophylline and clarithromycin.
Case summary: A 59-year-old Japanese man who was receiving theophylline for emphysema experienced stimulation, insomnia, and tachycardia due to theophylline toxicity after clarithromycin and levofloxacin were added to the regimen. The combination of these agents resulted in a decrease in theophylline clearance to approximately 60% of the initial value obtained while the patient was receiving theophylline alone. The adverse effects disappeared after the dosage was reduced and the theophylline serum concentration decreased; however, there was no change in theophylline clearance. After discontinuation of levofloxacin, the theophylline serum concentration decreased, and theophylline clearance returned to the initial level even though clarithromycin was continued.
Discussion: Levofloxacin is believed not to influence the clearance of theophylline, although some new fluoroquinolones have been reported to do so. This case indicates that levofloxacin and clarithromycin inhibited theophylline metabolic pathways catalyzed by both CYP1A2 and CYP3A4 and resulted in the decrease in theophylline clearance. The clearance of theophylline, therefore, is not influenced by clarithromycin alone.
Conclusions: Careful monitoring is required when levofloxacin is prescribed for patients who are taking clarithromycin with theophylline.