Levaquin® (levofloxacin)-Induced Hypoglycemia
Last updated: 01/31/2006
Effects of the quinolones on glucose metabolism are well documented. Both hypoglycemia and hyperglycemia have been reported after initiation of quinolone therapy. Of the currently marketed quinolones, gatifloxacin (Tequin®) is more commonly recognized as having the possibility of a hypoglycemic adverse event. However, fatal hypoglycemia (glucose=6) has been reported in an elderly type 2 diabetic patient without a history of hypoglycemia within 6 hours after receiving intravenous levofloxacin 250mg. Levofloxacin, moxifloxacin and ciprofloxacin are currently on formulary at CHH, but gatifloxacin is not.
Two large-scale retrospective studies were recently published on hypoglycemia with quinolones. One study found that the incidence of hypoglycemia with levofloxacin was one percent, whereas it was two percent for gatifloxacin. In the other study, a hypoglycemic rate of 0.1% was found for levofloxacin and a 0.5% for gatifloxacin. In this study, ciprofloxacin and the control drug ceftriaxone were not associated with hypoglycemia. Despite the large numbers of patients evaluated, these studies are limited by the few hospitals involved in data collection.
In post-marketing surveillance studies on the quinolones, hypoglycemia was reported in 0.04% of patients receiving ciprofloxacin, 0.1% of patients re-ceiving levofloxacin, and 0.08% in patients receiving gatifloxacin. Despite these reported rates of hypoglycemia, the FDA voluntary Adverse Event Reporting system, in which Cabell Huntington Hospital participates, has greater than fifty times more dysglycemic adverse reports for gatifloxacin than for other quinolones. Reasons for the great discrepancy in what is reported to the FDA compared to what has been published in studies are unknown but may be due in part to severity of the hypoglycemia, or due to clinician awareness of the adverse effect for gatifloxacin but not other quinolones.
Valuable information that has come from these trials is a very consistent picture of the patients that are likely to develop hypoglycemia with levofloxacin (or gatifloxacin). The greatest risk factor for developing levofloxacin-hypoglycemia is concurrent administration of oral hypoglycemic agents; of these, the insulin-producing sulfonylureas are the most implicated. The mechanism for this potentiation of effects is unknown, but is not due to a direct drug-drug interaction that results in elevated levels of any oral hypoglycemic agent. Another major risk factor is age; hypoglycemia was more likely to occur if the patient was older than sixty-five years of age. This may explain the lower incidence of hypoglycemia in post-marketing studies compared to the hospital studies. Other risk factors for hypoglycemia include renal failure, hypoalbuminemia, liver disease, malignancy, and heart failure.
Clinicians need to report incidents of suspected quinolone-induced hypoglycemia through our Adverse Drug Reaction system, either by dialing 'ADRS' from a Cabell Huntington Hospital phone or by using the online reporting system via a link on the left side of the CHH Intranet homepage under the clinicians header. Also as a reminder, another well-established significant adverse effect, albeit a very low incidence, is Torsades de Pointes. As higher dosages of quinolones are being used to treat serious infections, more adverse effects are likely, and it is important to recognize and report these adverse effects.