Acute hepatitis associated with levofloxacin in a patient with renal insufficiency

Jon-David Schwalm and Christine Lee1 reported a case of acute hepatitis in a hemodialysis patient taking oral levofloxacin. We observed profuse epistaxis and an acute rise in hepatic enzyme levels, particularly alkaline phosphatase, with levofloxacin therapy in a 63-year-old patient with mitral valve disease, coronary artery disease and chronic renal insufficiency, which resolved with discontinuation of the drug. The hepatic enzyme levels rose again when another drug in the same class, ciprofloxacin, was initiated. A full description of this case is available as an eletter on eCMAJ (www.cmaj.ca/cgi/eletters/168/7/847).

Coagulopathy associated with use of a fluoroquinolone and warfarin, as observed in this patient, is relatively well established.2 An increase in hepatic enzymes is less well established, although it has been observed with other drugs in the same class.3 Delayed hepatotoxicity can occur with accumulation of amiodarone (used to manage atrial fibrillation in this patient) but is usually heralded by a rise in alanine aminotransferase months after initiation of therapy, unless the reaction is idiosyncratic and occurs within the first 4 weeks.4 The initial rise in hepatic enzymes in this patient occurred within days of initiation of levofloxacin and of the rechallenge with the second fluoroquinolone (ciprofloxacin). This patient had acute-on-chronic renal failure, as did the patient described by Schwalm and Lee.1 The creatinine level was 212 mol/L on initiation of levofloxacin, peaking at 407 mol/L at the time of presentation with epistaxis and decreasing to 177 mol/L 4 days after discontinuation of levofloxacin. Nephrotoxicity and allergic nephritis have been linked to levofloxacin.5 Renal dysfunction might have been the underlying problem, with altered renal clearance increasing the potential for hepatoxicity. The creatinine level did not increase with the ciprofloxacin rechallenge.

Physicians should be alert to the possibility of fluoroquinolone-associated hepatotoxicity. Comorbidities such as renal failure may increase the potential for such toxic effects.

Kelly Airey Elizabeth Koller University of Nebraska Medical Center Nebraska–Western Iowa Veterans Administration Health Care Center Omaha, Neb.