Health Canada warns of liver disorders in patients taking levofloxacin.

Health Canada reported that from Jan. 1, 1997, through June 30, 2006, it received 22 domestic reports of dysglycemia suspected of being associated with levofloxacin. Marketed in Canada since 1997, levofloxacin is a broad-spectrum fluoroquinolone antibiotic that is indicated for the treatment of certain respiratory tract, skin and urinary tract bacterial infections in adults.

Dysglycemia and liver disorders in association with levofloxacin have been reported in the literature. The adverse reactions reported to Health Canada included one report of diabetes mellitus, two reports of hyperglycemia alone, 16 of hypoglycemia alone and three of hyperglycemia and hypoglycemia combined. The majority of reported cases of dysglycemia involved patients with diabetes and the median age was 71 years.

One of the mechanisms behind the development of hypoglycemia with levofloxacin may involve the inhibition of pancreatic [beta]-cell potassium channels, resulting in the release of insulin, which in turn could result in hypoglycemia. Disturbances of blood glucose levels are labeled in the product monograph.

During the same period, Health Canada received 44 domestic reports of liver and biliary disorders suspected of being associated with levofloxacin, including five cases of hepatic failure, nine of hepatitis and one of hepatorenal syndrome; five of these 15 cases of liver disorders were fatal. The remaining 29 reports included increased liver enzyme levels, cholestatic hepatitis and jaundice. The median time to onset of adverse reactions was five days.

The mechanisms leading to the development of liver disorders with levofloxacin are not well defined. Although drug-induced liver diseases can mimic all forms of acute and chronic hepatobiliary diseases, a particular drug generally has a characteristic clinical and pathological signature and latency period when liver injury occurs. Most drug-induced liver disorders are similar to acute hepatitis, cholestasis or mixed presentation. In the 44 cases reported to Health Canada, where sufficient information was provided, cases of hepatocellular, cholestatic and mixed liver injuries were observed. Drug-induced toxic effects are a common cause of liver injury.