Comparative tolerability of intravenous azithromycin, clarithromycin and erythromycin in healthy volunteers - Results of a double-blind, double-dummy, four-way crossover study

Objective: To compare the tolerability of intravenous azithromycin, clarith romycin, erythromycin and placebo. Design: A double-blind, double-dummy, placebo-controlled, four-way crossove r study was conducted in 12 healthy male volunteers. The participants were randomised to receive I-hour intravenous infusions of azithromycin 500mg (2 mg/ml) once daily, erythromycin 500mg (1 mg/ml) three times daily, clarith romycin 500mg (2 mg/ml) twice daily, or placebo (normal saline, 500ml) thre e times daily, with each regimen administered for 3 days. There was a minim um 4-week washout period before participants switched to an alternative reg imen, in random sequence, until all four regimens had been completed. Parti cipants were monitored for infusion site reactions and gastrointestinal (GI ) adverse events. Results: Clarithromycin caused clinically significant infusion site pain in 92% of the 12 participants evaluated and was exclusively associated with p hlebitis and inflammation. Areas under score-time curves (AUSs) rating the intensity of inflammation and pain were significantly higher for clarithrom ycin compared with azithromycin (p < 0.0005). Erythromycin infusion caused clinically significant abdominal pain or nausea in 25% of participants. The AUSs for GI tolerability were significantly different for erythromycin com pared with azithromycin (p < 0.001). Discontinuation rates due to infusion site reactions were 0% for azithromycin, 50% for clarithromycin, and 8% eac h for erythromycin and placebo. Treatment with erythromycin was interrupted or discontinued as a result of abdominal pain in 17% of patients and as a result of nausea in 8% of patients. Conclusions: Intravenous azithromycin had better infusion site tolerability than clarithromycin and better GI tolerability than erythromycin. The supe rior tolerability of azithromycin may avoid the discontinuation of intraven ous antimicrobial therapy in seriously ill patients and assist in reducing the duration of hospitalisation and the cost of patient management.