Canadian Adverse Reaction Newsletter
Volume 13, Number 3, July 2003

Gatifloxacin (Tequin™) is a broad-spectrum antibacterial fluoroquinolone with activity against gram-negative and gram-positive aerobic and anaerobic microorganisms and is also effective against clinically important atypical microorganisms.¹ Health Canada's database of spontaneous reports of adverse reactions indicates that hypoglycemia and hyperglycemia have been reported more frequently with gatifloxacin than with other quinolone antibiotics. Case reports of hypoglycemia associated with gatifloxacin have also been published.^2-5 The Canadian product monograph for Tequin™ was recently updated in response to reported cases of serious, and in some cases life-threatening, disturbances of glucose homeostasis.¹

Health Canada received 28 reports of abnormal glucose metabolism associated with gatifloxacin (44% of total reports received for the drug) from Feb. 21, 2001 (the date marketed in Canada), to Feb. 28, 2003: 19 were of hypoglycemia, 7 were of hyperglycemia and 2 were of both hypoglycemia and hyperglycemia (Table 1). Twenty-five of the cases involved patients with type 2 diabetes (determined from the patient's history or use of concomitant medications), 2 involved nondiabetic patients, and in 1 case the diabetic status was unknown. The 28 cases were serious, and 19 of the patients were admitted to hospital or had a prolonged hospital stay because of the reaction. The 2 patients who died (86 and 102 years of age) had hyperglycemia, no prior history of diabetes and decreased renal function at the time of the reaction.

Concomitant use of hypoglycemic agents was noted in 18 of the 19 cases in which a hypoglycemic reaction was reported. The exact mechanism of hypoglycemia is unknown, but some hypotheses include a possible increase in the serum insulin level following the administration of gatifloxacin or the existence of a possible interaction between glyburide and gatifloxacin.^2-5

A postmarketing study of gatifloxacin involving more than 15 000 patients reported an incidence of hypoglycemic events of 0.3 per 1000 among nondiabetic patients and 6.4 per 1000 among diabetic patients.¹ The corresponding rates for hyperglycemia were 0.07 per 1000 and 13 per 1000. All of these cases were reversible with appropriate treatment, which included the discontinuation of gatifloxacin.¹

Key points¹

• Hypoglycemia and hyperglycemia have been reported following the use of gatifloxacin, usually but not always in diabetic patients.
• Hypoglycemic reactions frequently occurred within the first day of therapy and usually within 3 days. These reactions were reported in diabetic patients receiving either sulfonylurea or non-sulfonylurea oral hypoglycemic medications.
• Most hyperglycemic reactions occurred 4 to 10 days after the start of therapy; very elderly patients (> 75 years of age) who may have unrecognized diabetes, age-related decrease in renal function or underlying medical problems or are taking concomitant medications associated with hyperglycemia may be at particular risk.
• Blood glucose levels should be monitored carefully when gatifloxacin is used in diabetic patients.
• Gatifloxacin therapy should be stopped and appropriate treatment started immediately if any signs or symptoms of hypoglycemia or hyperglycemia appear.
• Gatifloxacin is mainly eliminated by the kidneys; therefore, a reduced dosage is recommended in patients with a creatinine clearance of less than 0.67 mL/s (40 mL/min).
• Patients should be educated about these possible adverse reactions with gatifloxacin.