In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Approximately 0.7% of the patients from the multiple-dose clinical trials discontinued ZITHROMAX ® (azithromycin) therapy because of treatment-related side effects. Most of the side effects leading to discontinuation were related to the gastrointestinal tract, e. g., nausea, vomiting, diarrhea, or abdominal pain. Rarely but potentially serious side effects were angioedema and cholestatic jaundice.
Significant abnormalities (irrespective of drug relationship) occurring during the clinical trials were reported as follows: With an incidence of 1-2%, elevated serum creatine phosphokinase, potassium, ALT (SGPT), GGT, and AST (SGOT).
With an incidence of less than 1%, leukopenia, neutropenia, decreased platelet count, elevated serum alkaline phosphatase, bilirubin, BUN, creatinine, blood glucose, LDH, and phosphate.
When follow-up was provided, changes in laboratory tests appeared to be reversible. In multiple-dose clinical trials involving more than 3000 patients, 3 patients discontinued therapy because of treatment-related liver enzyme abnormalities and 1 because of a renal function abnormality. In a phase I drug interaction study performed in normal volunteers, 1 of 6 subjects given the combination of azithromycin and rifabutin, 1 of 7 given rifabutin alone and 0 of 6 given azithromycin alone developed a clinically significant neutropenia (< 500 cells/ mm 3 ).
Laboratory abnormalities seen in clinical trials for the prevention of disseminated Mycobacterium avium disease in severely immunocompromised HIV-infected patients are presented in the CLINICAL STUDIES section.
Chronic therapy (median duration: 87.5 days, range: 1-229 days) that resulted in laboratory abnormalities in >5% subjects with normal baseline values in the pivotal trial for treatment of disseminated MAC in severely immunocompromised HIV infected patients treated with azithromycin 600 mg daily in combination with ethambutol include: a reduction in absolute neutrophils to <50% of the lower limit of normal (10/ 52, 19%) and an increase to five times the upper limit of normal in alkaline phosphatase (3/ 35, 9%). These findings in subjects with normal baseline values are similar when compared to all subjects for analyses of neutrophil reductions (22/ 75 [29%]) and elevated alkaline phosphatase (16/ 80 [20%]). Causality of these laboratory abnormalities due to the use of study drug has not been established.