Safety of fluoroquinolone use in patients with hepatotoxicity induced by anti-tuberculosis regimens.
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.
Ho
Chao-Chi
CC
Departments of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Chen
Yee-Chun
YC
Hu
Fu-Chang
FC
Yu
Chong-Jen
CJ
Yang
Pan-Chyr
PC
Luh
Kwen-Tay
KT
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D001372:Aza Compounds / Q000009:adverse effects / Q000627:therapeutic use; D004977:Ethambutol / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects* / Q000627:therapeutic use; D048550:Hepatic Insufficiency / Q000139:chemically induced*; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000009:adverse effects / Q000627:therapeutic use; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use; D013307:Streptomycin / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D014376:Tuberculosis / Q000150:complications* / Q000188:drug therapy*; D055815:Young Adult
D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D064704:Levofloxacin; D004977:Ethambutol; D015242:Ofloxacin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000077266:Moxifloxacin; D013307:Streptomycin