Safety profile of oral and intravenous moxifloxacin: cumulative data from clinical trials and postmarketing studies.
BACKGROUND
The established safety profile of the fluoroquinolones has been disrupted in the past decade by the detection of low-frequency but potentially serious adverse events that have led to the license suspension, voluntary withdrawal, or restricted use of specific members of the class. Moxifloxacin is a broad-spectrum, advanced-generation fluoroquinolone that has potent activity against respiratory tract infections in adults in both oral and IV formulations.


OBJECTIVE
The goal of this article was to provide an overview of the cumulative safety data on both oral and IV moxifloxacin, including data from the most recent clinical trials and postmarketing studies.


METHODS
Data from clinical trials of moxifloxacin were captured from an electronic database maintained by the manufacturer. Safety data for oral moxifloxacin were obtained from 30 Phase II/III comparator studies (n = 7,368 moxifloxacin, n = 5,687 comparators), 1 Phase IV study (n = 18,374), and 4 postmarketing observational studies (n = 27,756). Safety data for IV moxifloxacin were obtained from 2 Phase III comparator studies (n = 550 maxifloxacin, n = 579 comparators). In addition, pharmacokinetic data were reviewed.


RESULTS
In Phase II/III comparator studies, gastrointestinal complaints were the most common adverse drug reactions (ADRs) associated with both formulations of moxifloxacin, with nausea occurring in 7.1% and 3.1% of patients receiving oral and IV moxifloxacin, respectively, and diarrhea occurring in 5.2% and 6.2% of patients. Discontinuation rates due to ADRs with oral and IV moxifloxacin were 2.7% and 6.0%, and mortality rates were 0.3% and 4.0%. Similar rates of withdrawal and mortality were observed in the comparator groups. There was no evidence that moxifloxacin caused disturbances in glucose metabolism in patients with or without diabetes mellitus, and there was no evidence of an increased risk for cardiovascular adverse events. Pharmacokinetic analyses indicated that dose adjustment of moxifloxacin does not appear to be necessary in elderly patients, those with renal dysfunction, or those with mild to moderate hepatic impairment. The pharmacokinetics of moxifloxacin have not been studied in patients with severe hepatic insufficiency. Moxifloxacin does not interact with a number of commonly prescribed drugs, although its absorption is decreased by concomitant administration of iron and cationic antacids.


CONCLUSIONS
Based on evidence from >7000 patients in clinical trials and >46,000 patients in postmarketing studies, moxifloxacin is generally well tolerated. Its lack of significant drug interactions in target groups makes it an option in diabetic patients or the elderly, as well as in those with renal impairment.
Ball
Peter
P
University of St. Andrews, Fife, Scotland.
Stahlmann
Ralf
R
Kubin
Rolf
R
Choudhri
Shurjeel
S
Owens
Robert
R
D000284:Administration, Oral; D000368:Aged; D001372:Aza Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D002986:Clinical Trials as Topic; D016208:Databases, Factual; D024841:Fluoroquinolones; D006801:Humans; D007275:Injections, Intravenous; D000077266:Moxifloxacin; D011358:Product Surveillance, Postmarketing / Q000706:statistics & numerical data*; D011804:Quinolines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin