Tolerability of azithromycin as malaria prophylaxis in adults in northeast papua, indonesia

Abstract

Drug tolerability affects compliance. We evaluated the tolerability levels of azithromycin (750-mg loading dose plus 250 mg/day; n = 148 subjects), doxycycline (100 mg/day; n = 75), and placebo (n = 77) as prophylaxis against malaria in Indonesian adults over 20 weeks. Self-reported and elicited symptoms, health perception, hearing, hematology, and biochemistry were assessed. The loading dose was well tolerated. The frequencies (number per person-years [p-yr]) of all daily reported symptoms were similar in the three arms of the study: 40.2/p-yr for azithromycin, 39.7/p-yr for doxycycline, and 38.2/p-yr for placebo. Relative to those who received placebo, azithromycin recipients complained more often of heartburn (rate ratio = 10.5 [95% confidence interval, 2.8 to 88.1]), paresthesia (2.03 [1.08 to 4.24]), and mild (1.55 [1.01 to 2.48]) and severe (11.2 [1.34 to infinity ]) itching but less often of fever (0.21 [0.09 to 0.49]) and tinnitus (0.09 [0.04 to 0.21]). Azithromycin recipients showed no evidence of clinical hearing loss or hematologic, hepatic, or renal toxicity. One azithromycin recipient developed an erythematous rash. Daily azithromycin was well tolerated by these Indonesian adults during 20 weeks of treatment.

FIG. 1.

Trends in selected symptoms as reported by azithromycin, doxycycline, and placebo recipients on a symptom questionnaire on days 0 and 1 (D0 and D1) and at monthly intervals (M1 through M4) during a malaria prophylaxis study in Papua. These elicited symptoms represent an alternative data set to that of the daily volunteered symptoms presented in Table 1. m, moderate; m&s, mild and severe.