OTTAWA, CANADA -- December 21, 2005 -- Bristol-Myers Squibb (BMS) Canada, following discussions with Health Canada, is informing health care professionals of important safety information regarding the use of Tequin* (gatifloxacin).

Serious cases of both hypoglycemia and hyperglycemia have been reported postmarketing in association with the administration of Tequin regimen.

Very rare events of hyperglycemia and hypoglycemia were life-threatening. In the majority of cases, patients had other underlying medical problems and were receiving concomitant medications that may have contributed to the glucose abnormality. A few of these cases resulted in fatal outcome.

Diabetics and elderly patients (>75 years of age) who may have unrecognized diabetes, age-related decrease in renal function, underlying medical problems, and/or are taking concomitant medications associated with dysglycemia may be at particular risk for serious hyperglycemia or hypoglycemia. However, hypoglycemia and particularly hyperglycemia have occurred in a number of patients with no prior history of diabetes

When Tequin is used in diabetic patients, blood glucose should be closely monitored. Signs and symptoms of hypoglycemia should be monitored, especially during the first 3 days of therapy, and signs and symptoms of hyperglycemia should be monitored in diabetics and patients who may be at risk for hyperglycemia, especially following the third day of therapy (mostly between 4 and 10 days following initiation of therapy). If signs and symptoms of either hypoglycemia or hyperglycemia occur in any patient being treated with Tequin, appropriate therapy must be initiated immediately and Tequin should be discontinued.

Changes in Blood Glucose

Disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported with Tequin, usually but not always in diabetic patients. Therefore, careful monitoring of blood glucose is recommended when Tequin is administered to diabetic patients.

Studies conducted in patients with type II diabetes mellitus controlled on oral hypoglycemic agents have demonstrated that Tequin is associated with transient disturbances in glucose homeostasis, including an increase in serum insulin and decrease in serum glucose following administration of initial doses (i.e. first two days of treatment), sometimes associated with symptomatic hypoglycemia. Increases in fasting serum glucose were also observed, usually after the third day of Tequin administration and continuing throughout the duration of treatment, but returning to pre-dose values by 14 days after the completion of treatment.

In a postmarketing study involving over 15 000 patients, the occurrence of hyperglycemic events related to Tequin was 0.007% in nondiabetic patients and 1.3% in diabetic patients. The incidence of hypoglycemic events was 0.03% in nondiabetic patients and 0.64% in diabetic patients. The incidence of serious hyperglycemia and hypoglycemia was 0.03% of the total population, all reversible with appropriate management, which included discontinuation of Tequin therapy.

During the postmarketing period, there have been reports of serious disturbances of glucose homeostasis in patients treated with Tequin. Hypoglycemic episodes, in some cases severe, have been reported in patients with diabetes mellitus treated with either sulfonylurea or non-sulfonylurea oral hypoglycemic medications. These events frequently occurred on the first day of therapy and usually within 3 days following the initiation of Tequin. Hyperglycemic episodes, in some cases severe and associated with hyperosmolar non-ketotic hyperglycemic coma, were reported in diabetic patients, mostly between 4 and 10 days following the initiation of Tequin therapy. Some of the hyperglycemic and hypoglycemic events were life-threatening. These reports were extremely rare, and many of these patients had other underlying medical problems and were receiving concomitant medications that may have contributed to the glucose abnormality. These events were reversible when appropriately managed.

Episodes of hyperglycemia, including extremely rare hyperosmolar non-ketotic hyperglycemic coma, occurred in patients not previously diagnosed with diabetes mellitus. Very elderly patients (>75 years of age) who may have unrecognized diabetes, age-related decrease in renal function, underlying medical problems, and/or are taking concomitant medications associated with hyperglycemia may be at particular risk for serious hyperglycemia.

The dose of Tequin should be adjusted based on underlying renal function.

When Tequin is used in diabetic patients, blood glucose should be closely monitored. Signs and symptoms of hypoglycemia should be monitored, especially during the first 3 days of therapy, and signs and symptoms of hyperglycemia should be monitored in diabetics and patients who may be at risk for hyperglycemia, especially following the third day of therapy. If signs and symptoms of either hypoglycemia or hyperglycemia occur in any patient being treated with Tequin, appropriate therapy must be initiated immediately and Tequin should be discontinued."

Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments.

The identification, characterization and management of marketed health product-related adverse reactions are dependent on the active participation of health care professionals in adverse reaction reporting programmes. Any occurrences of hypoglycaemia or hyperglycemia or other serious or unexpected adverse reactions in patients receiving Tequin should be reported to Bristol-Myers Squibb or Health Canada at the following addresses:

Bristol-Myers Squibb Canada

2365 Côte-de-Liesse

Montréal, Québec

H4N 2M7

Tel : 866-463-6267

Any suspected adverse reaction can also be reported to:

Canadian Adverse Drug Reaction Monitoring Program (CADRMP)

Marketed Health Products Directorate

HEALTH CANADA

Address Locator: 0701C

OTTAWA, Ontario, K1A 0K9

Tel: (613) 957-0337 or Fax: (613) 957-0335

To report an Adverse Reaction, consumers and health professionals may call toll free:

Tel: 866 234-2345

Fax: 866 678-6789

cadrmp@hc-sc.gc.ca

The AR Reporting Form and the AR Guidelines can be found on the Health Canada web site or in The Canadian Compendium of Pharmaceuticals and Specialties.

For other inquiries related to this communication, please contact Health Canada at:

Marketed Health Products Directorate

E-mail: mhpd_dpsc@hc-sc.gc.ca

Tel: (613) 954-6522

Fax: (613) 952-7738

SOURCE: Health Canada