Meta-Analysis of Quinolone—Theophylline Interactions

Abstract

Several fluoroquinolones currently under investigation or on the market potentially interact with theophylline. In this study, meta-analysis methodology was used to evaluate the significance of findings from quinolone-theophylline interaction studies. Two major databases were searched: Index Medicus (from 1986 to March 1990) and Current Content/Clinical Medicine (from 1985 to March 1990). A total of 32 studies were retrieved; 20 of these met the inclusion criteria. With a large effect size (ES) value of 2.26, enoxacin is the strongest inhibitor of theophylline metabolism of this family. The fail-safe N value was 135, indicating that 135 studies enrolling an average of 8 patients and showing no interaction (i.e., ES = 0) would be required to lower the ES to the threshold value of 0.1, which we considered a priori to render the results nonsignificant. Other fluoroquinolones showed a degree of interaction that can be considered significant: Ciprofloxacin (ES = 0.50, fail-safe N = 26), norfloxacin (ES = 0.31, fail-safe N = 10). Ofloxacin (ES = 0.13, fail-safe N = 4), lomefloxacin (ES = 0.12, fail-safe N = 2), and fleroxacin (ES = 0.06, fail-safe N = 2) provided the weakest evidence of interaction based on effect size and power. Among the fluoroquinolones studied, ofloxacin, lomefloxacin, and fleroxacin, when available, should be the fluoroquinolones of choice when the patient also is receiving theophylline.

Effect of combination therapy with ciprofloxacin and clarithromycin on theophylline pharmacokinetics in healthy volunteers

“…Consistent with previous investigations, we found that ciprofloxacin causes a significant increase in theophylline AUC (mean ϭ 45%); individual AUCs increased by 15 to 77% (10,17). Clarithromycin resulted in a mean increase in theophylline AUC of 8% (P Ͼ 0.05); the range was a 24% decrease to a 46% increase (Fig.…”

Pharmacokinetic Drug Interactions with Antimicrobial Agents

“…The magnitude of the interaction depends on the specific quinolone and the dosage. Lomefloxacin and fleroxacin do not appear to alter theophylline pharmacokinetics (Parent & LeBel 1991). Clinically significant interactions with the last two drugs are unusual.…”

Drug Interactions with Quinolone Antibacterials

“…A meta-analysis by Parent and LeBel (1991) determined the significance of the decreased theophylline clearance observed with individual quinolones. Enoxacin and ciprofloxacin gave the strongest evidence of an interaction with theophylline.…”