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

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Canadian Adverse Reaction Newsletter
Volume 13, Number 3, July 2003
Marketed Health Products Directorate, Health Products and Foods Branch

In This Issue
Gatifloxacin (Tequin™): hypoglycemia and hyperglycemia
Serotonin syndrome
Summary of advisories
Case presentation: red yeast rice and rhabdomyolysis

Scope

This quarterly publication alerts health professionals to potential signals detected through the review of case reports submitted to Health Canada. It is a useful mechanism to disseminate information on suspected adverse reactions to health products occurring in humans before comprehensive risk-benefit evaluations and regulatory decisions are undertaken. The continuous evaluation of health product safety profiles depends on the quality of your reports.

Reporting Adverse Reactions
Contact Health Canada
or a Regional AR Centre
free of charge
Phone: 866 234-2345
Fax: 866 678-6789
Email: cadrmp@hc-sc.gc.ca

Click here for the Adverse Reaction Reporting Form

Caveat: Adverse reactions (ARs) to health products are considered to be suspicions, as a definite causal association often cannot be determined. Spontaneous reports of ARs cannot be used to estimate the incidence of ARs because ARs remain underreported and patient exposure is unknown.

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Gatifloxacin (Tequin™): hypoglycemia and hyperglycemia

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.
Geneviève Létourneau, BPharm, Québec Regional AR Centre; Heather Morrison, BSc, MLIS; Marielle McMorran, BSc, BSc(Pharm), Health Canada

References

1. Tequin™, gatifloxacin tablets [product monograph]. Montreal: Bristol-Myers Squibb Canada Inc.; 2002 Dec 24.
2. Parilo MA. Gatifloxacin-associated hypoglycemia. J Pharm Technol 2002;18:319-20.
3. Hussein G, Perkins LT, Sternberg M, Bland C. Gatifloxacin-induced hypoglycemia: a case report and review of the literature. Clin Res Regul Aff 2002;19(4):333-9.
4. Baker SE, Hangii MC. Possible gatifloxacin-induced hypoglycemia. Ann Pharmacother 2002;36:1722-6.
5. Menzies DJ, Dorsainvil PA, Cunha BA, Johnson DH. Severe and persistent hypoglycemia due to gatifloxacin interaction with oral hypoglycemia agents. Am J Med 2002;113(3):232-4.
6. Meltzer S, Leiter L, Daneman D, Gerstein HC, Lau D, Ludwig S, et al. 1998 clinical practice guidelines for the management of diabetes in Canada. CMAJ 1998;159(8 Suppl):S1-29.

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