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Dysglycemia Associated With The Use Of Fluoroquinolones- Focus On Gatifloxacin
Correspondence Address :
Dr Jimmy Jose,Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences,
Manipal University, Karnataka, India 576 104.
Ph no. 91-820-2922403 , Fax no: 91-820-2571998, Jimmy_jose2001@yahoo.com
Fluoroquinolones are generally regarded as safe antimicrobial agents with relatively few adverse effects or drug interactions. Dysglycemia (hypo or hyperglycemia) has been reported rarely with many of the fluoroquinolones. The latest data suggests that gatifloxacin is one of the newer fluoroquinolones and is associated with a higher incidence of dysglycemic effects. The exact mechanism behind this effect is not known. The risk factors for the development of this effect are identified as diabetes mellitus, older age, renal insufficiency, and patients taking medications for diabetics (especially hypoglycemic agents). Potential for this increased risk of serious glucose abnormalities should be considered especially while using gatifoxacin in the identified risk groups.
Gatifloxacin, fluoroquinolone, dysglycemia, hypoglycemia, hyperglycemia
Fluoroquinolones are among the most widely prescribed antibiotics especially for respiratory and urinary tract infections. They are generally regarded as safe drugs associated with mild gastrointestinal and CNS symptoms (1),(2),(3). Recent events have brought new attention to quinolone safety. Four quinolones have been withdrawn from the US market: temafloxacin, as a result of hemolysis, renal failure and hypoglycemia; trovafloxacin, as a result of hepatotoxicity; grepafloxacin, as a result of torsades de pointes; and sparfloxacin as a result of phototoxicity and torsades de pointes (4).
The latest safety concern regarding the use of quinolones includes associated dysglycemic effects. Dysglycemia (hypo or hyperglycemia) has been reported rarely with many of the fluoroquinolones (5). However, published case reports and databases of adverse drug reactions (ADRs) and certain studies recently conducted suggest that dysglycemia is more common with gatifloxacin than with other fluoroquinolones (4),(5),(6),(7).
Gatifloxacin is one of the newer broad spectrum fluoroquinolones available and was approved by the US food and drug administration in December 1999 (8). Ever since its release in the market, there have been numerous reports implicating gatifloxacin as a cause of hypoglycemia and hyperglycemia. This prompted Bristol-Meyer Squibb Co. to list diabetes mellitus as a contraindication to gatifloxacin use in the US product labeling (9) and Health Canada to issue an advisory against the use of gatifloxacin in patients with diabetes (10).
Mechanism
Even though it is not yet well established how fluoroquinolones cause hyperglycemia, investigations have identified a possible mechanism of fluoroquinolone induced hypoglycemia. In vitro experiments have revealed that fluoroquinolones can stimulate insulin release and subsequently hypoglycemia by blocking the ATP-sensitive potassium channels of pancreatic cells (11),(12). It can trigger the vacuolation of pancreatic beta cells and subsequently lead to reduced insulin levels and hyperglycemia (6),(7),(11),(12),(13).
Evidence
Evidence that gatifloxacin causes dysglycemia effects in humans includes case reports and small studies in healthy volunteers or hospital inpatients (6). Further, recently there is evidence from more systematically conducted studies in larger population (4),(6),(7). Two population-based case control studies were conducted by Park-Wyllie et al (6) in a population of approximately 1.4 million. In Ontario in Canada, residents 66 years of age or older were studied to examine dysglycemia including the related health outcomes associated with various antibiotics received on an outpatient basis (macrolide, a second-generation cephalosporin or respiratory quinolone; gatifloxacin, levofloxacin, moxifloxacin, or ciprofloxacin). Based on the results, the authors concluded that compared to other antibiotics analyzed in the study, the use of gatifloxacin among outpatients is associated with an increased risk of in-hospital treatment for hypoglycemia and hyperglycemia. The risk was similar regardless of the presence or absence of diabetes. With the exception of a slight increase in the risk of hypoglycemia with levofloxacin, these risks were not shared by other fluoroquinolones.
Frothingham compared the rates of glucose homeostasis<
Based on the available evidence, a strong association between the use of gatifloxacin and the occurrence of dysglycemia is noted. Potential for this increased risk of serious glucose abnormalities should be considered especially while using gatifloxacin in the identified risk groups.
Conflict of Interest: None declared
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