Abstract

Clarithromycin is an orally active, advanced-generation macrolide that has been reformulated as an extended-release tablet (Biaxin) XL Filmtab allowing convenient once-daily administration. The reformulation is intended to improve patient compliance and the tolerability of the drug. Although maximum plasma clarithromycin concentrations are lower and reached later with the extended-release tablets than with the immediate-release tablets, the two formulations are bioequivalent with respect to the area under the plasma concentration-time curve. Bioequivalence is also achieved between the formulations for the microbiologically active metabolite, 14-hydroxy-clarithromycin. Two randomized trials in patients with acute exacerbations of chronic bronchitis (AECB) showed that a 7-day course of clarithromycin extended-release 1000 mg once daily produced clinical cure rates of 83% and 85% and bacteriologic cure rates of 86% and 92% at the test-of-cure study visit. Similar rates of cure were achieved with a 7-day course of twice-daily clarithromycin immediate-release and with a 10-day course of twice-daily amoxicillin/clavulanic acid.A 7-day course of clarithromycin extended-release 1000 mg once daily produced clinical and bacteriologic cure rates of 88% and 86%, respectively, in patients with community-acquired pneumonia (CAP). Similar cure rates were achieved in recipients of once-daily levofloxacin in the same trial. In patients with acute maxillary sinusitis, a 14-day course of either once-daily clarithromycin extended-release or twice-daily clarithromycin immediate-release produced statistically equivalent clinical cure rates of 85% and 79%, respectively. Both treatment groups achieved similar rates of radiographic success and resolution of sinusitis. Recent results indicate that clarithromycin extended-release 500 mg once daily for 5 days is also effective in the treatment of patients with streptococcal pharyngitis/tonsillitis and in the treatment of AECB. The most frequently reported drug-related events with clarithromycin extended-release were abnormal taste (7% incidence), diarrhea (6%) and nausea (3%). Most adverse drug reactions were of a mild and transient nature. In comparative clinical trials, clarithromycin extended-release had an improved gastrointestinal tolerability profile compared with the immediate-release formulation. In addition, clarithromycin extended-release was better tolerated than amoxicillin/clavulanic acid and as well tolerated as levofloxacin. Further studies are required to assess the cost-effectiveness ratio of clarithromycin relative to comparator antibacterial agents. CONCLUSION: Clarithromycin extended-release is an effective treatment for AECB, CAP, acute maxillary sinusitis, and pharyngitis (although not approved for the latter in the US), and is administered in a convenient dosage regimen that has the potential to encourage good compliance. The reformulation modulates clarithromycin absorption kinetics thereby improving tolerability. Therefore, clarithromycin extended-release provides a useful option for the treatment of specific respiratory tract infections.