Glucose homeostasis abnormalities associated with use of gatifloxacin.
BACKGROUND
More than 20 published case reports have described an association between the use of gatifloxacin and hypoglycemia or hyperglycemia. We compare the rates of glucose homeostasis abnormality (GHA) adverse event reports (AERs) associated with the use of gatifloxacin and comparator quinolones.


METHODS
We obtained spontaneous AERs associated with the use of ciprofloxacin, gatifloxacin, levofloxacin, and moxifloxacin from the US Food and Drug Administration that were reported between November 1997 and September 2003. We removed duplicate and foreign cases. We used specific coding terms to identify GHA AERs. We calculated GHA AER rates, using either the total number of AERs or estimated retail prescriptions as denominators.


RESULTS
The use of ciprofloxacin, gatifloxacin, levofloxacin, and moxifloxacin was associated with 10,025 unique AERs in the United States, including 568 GHA AERs, 25 of which had fatality. Use of gatifloxacin was associated with 453 GHA AERs (80%) and 17 GHA AERs with fatality (68%). GHA AERs comprised 24% of all AERs associated with gatifloxacin, compared with ciprofloxacin (1.3%), levofloxacin (1.6%), and moxifloxacin (1.3%) (P<.0001 for each comparison). Use of gatifloxacin was associated with 477 GHA AERs per 10(7) retail prescriptions, compared with ciprofloxacin (4 GHA AERs), levofloxacin (11 GHA AERs), and moxifloxacin (39 GHA AERs) (P<.0001 for each comparison). Patients with GHA AERs were older and more likely to be receiving concomitant treatment for diabetes. Limitations of the study include the use of spontaneous adverse event reporting, which is incomplete and potentially biased. This analysis cannot be used alone to demonstrate causality.


CONCLUSIONS
Use of gatifloxacin is associated with a much higher rate of GHA AERs than are comparator quinolones. This analysis is consistent with the results of in vitro analyses, animal studies, human volunteer studies, case reports, and a large randomized trial. Alternatives to gatifloxacin should be used in patients with diabetes.
Frothingham
Richard
R
Veterans Affairs Medical Center, Durham, NC, USA. richard.frothingham@duke.edu
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000890:Anti-Infective Agents / Q000009:adverse effects; D001372:Aza Compounds / Q000009:adverse effects; D002648:Child; D002939:Ciprofloxacin / Q000009:adverse effects; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects*; D000077734:Gatifloxacin; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000009:adverse effects; D011804:Quinolines / Q000009:adverse effects
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin; D005947:Glucose; D000077734:Gatifloxacin; D000077266:Moxifloxacin