Safety of fluoroquinolone use in patients with hepatotoxicity induced by anti-tuberculosis regimens

Clin Infect Dis. 2009 Jun 1;48(11):1526-33. doi: 10.1086/598929.

Abstract

Background: Fluoroquinolones are frequently used to replace agents in first-line anti-tuberculosis (anti-TB) regimens in patients with TB who have drug-induced hepatic dysfunction. We investigated the safety of using fluoroquinolone in an area where TB is endemic and where there is a high incidence of drug-induced liver injury.

Methods: From September 2003 through August 2006, patients who had aspartate aminotransferase and/or alanine aminotransferase levels >3 times the upper limit of normal in the presence of hepatitis symptoms or who had aspartate aminotransferase and/or alanine aminotransferase levels >5 times the upper limit of normal after receipt of anti-TB treatment were enrolled. The control group received ethambutol, with or without streptomycin; study groups received either (1) ethambutol plus levofloxacin, with or without streptomycin; or (2) ethambutol plus moxifloxacin, with or without streptomycin. The outcome measurement was the time from onset of hepatitis to normalization of liver functions.

Results: One hundred thirty-four (11.3%) of 1191 patients received a diagnosis of hepatotoxicity and needed to stop anti-TB treatment. The risk factor was abnormal baseline transaminase levels. Twenty-two of the 134 patients received the control medication, 40 received levofloxacin, and 45 received moxifloxacin; the remaining patients were excluded from the study. There were no significant prestudy differences between groups. Time to liver function normalization was almost the same for all groups (mean +/- standard deviation, 29.1+/-21.4, 25.5+/-17.6, and 29.7+/-14.3 days, respectively).

Conclusions: Abnormal baseline transaminase levels are the independent risk factors for anti-TB therapy-induced hepatitis. Levofloxacin and moxifloxacin caused no additional hepatotoxicity when they were used by patients with hepatitis induced by first-line anti-TB drugs.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / blood
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / therapeutic use
  • Antitubercular Agents / adverse effects*
  • Antitubercular Agents / therapeutic use
  • Aspartate Aminotransferases / blood
  • Aza Compounds / adverse effects
  • Aza Compounds / therapeutic use
  • Ethambutol / adverse effects
  • Ethambutol / therapeutic use
  • Female
  • Fluoroquinolones / adverse effects*
  • Fluoroquinolones / therapeutic use
  • Hepatic Insufficiency / chemically induced*
  • Humans
  • Levofloxacin
  • Male
  • Middle Aged
  • Moxifloxacin
  • Ofloxacin / adverse effects
  • Ofloxacin / therapeutic use
  • Quinolines / adverse effects
  • Quinolines / therapeutic use
  • Streptomycin / adverse effects
  • Streptomycin / therapeutic use
  • Treatment Outcome
  • Tuberculosis / complications*
  • Tuberculosis / drug therapy*
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Antitubercular Agents
  • Aza Compounds
  • Fluoroquinolones
  • Quinolines
  • Levofloxacin
  • Ethambutol
  • Ofloxacin
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Moxifloxacin
  • Streptomycin