Comparative efficacy of clarithromycin modified-release and clarithromycin immediate-release formulations in the treatment of lower respiratory tract infection

Background: A modified-release (MR) formulation of clarithromycin, distinct from the extended-release formulation, has recently been developed and has efficacy and tolerability similar to standard immediate-release (IR) clarithromycin, with the advantage of once-daily dosing. Objective: The purpose of this study was to compare the efficacy (as measured by relief of clinical symptoms and eradication of specific pathogens) and tolerability of clarithromycin MR 500 mg administered once daily versus clarithromycin IR 250 mg administered twice daily for 5 days. Methods: In this randomized, double-blind (with matching placebo), parallel-group. multicenter, controlled trial, patients with lower respiratory tract infection were randomized to 1 of 2 treatment regimens: clarithromycin MR 500 mg once daily plus clarithromycin IR 250 mg placebo twice daily or clarithromycin IR 250 mg BID plus clarithromycin MR 500 mg placebo once daily. Results: Statistically equivalent clinical cure and success rates, overall symptomatic improvement, and bacteriologic responses were achieved with both treatments. In the clarithromycin MR group. the clinical cure rate was 72.5% (87/120), and the clinical success rate (cure plus symptomatic improvement) was 97.5% (117/120). Of the 124 patients treated with clarithromycin IR 250 me BID. 98 (79.0%) achieved a clinical cure, and 120 (96.8%) achieved clinical success. There were no statistically significant between-group differences in clinical cure or success rates. More than 85% of patients in both study groups experienced improvement in dyspnea, cough, wheezing, chest discomfort, fatigue, and fever, and the visual appearance of sputum; these symptoms resolved completely in the majority of patients. Bacteriologic response (efficacy against specific pathogens), which was assessed as an objective efficacy criterion, was assessable for 40 patients treated with clarithromycin MR and 49 patients treated with clarithromycin IR. Bacteriologic eradication of the pretreatment target pathogen was achieved in 95.0% (38/40) of assessable patients treated with clarithromycin MR 500 mg once daily and 91.8% (45/49) of patients treated with clarithromycin IR 250 mg BID. Treatment-related adverse events were mild to moderate in all cases. Nausea (n = 9), diarrhea (n = 6), abdominal pain (n = 5), and gastric pain (n = 3) were the only study drug-related adverse events reported by greater than or equal to1 patient in each treatment arm. Diarrhea was reported only in the clarithromycin IR group (n = 6) (P = 0.029 vs clarithromycin MR). Conclusions: Clarithromycin MR 500 mg administered once daily for 5 days is as effective and well tolerated as the IR formulation, with the advantage of once-daily dosing and fewer episodes of diarrhea.