Hepatotoxicity of rifampin-pyrazinamide and isoniazid preventive therapy and tuberculosis treatment.
BACKGROUND
Severe liver injury has been attributed to preventive treatment of latent tuberculosis infection with a 2-month course of rifampin-pyrazinamide.


METHODS
A retrospective cohort study in The Netherlands compared the hepatotoxicity of preventive treatment with rifampin-pyrazinamide with that of preventive treatment with isoniazid, and also with that of treatment for active tuberculosis containing at least isoniazid, rifampin, and pyrazinamide.


RESULTS
Preventive treatment with rifampin-pyrazinamide caused severe hepatotoxicity more often than did preventive treatment with isoniazid (odds ratio [OR], 2.61; 95% confidence interval [CI], 1.26-5.39; P=.012), especially in patients <25 years old. It also caused severe hepatotoxicity more often than triple- or quadruple-drug tuberculosis treatment (OR, 2.61; 95% CI, 1.21-5.59; P=.016), especially if the pyrazinamide dose was > or =30 mg/kg. Preventive treatment with rifampin-pyrazinamide was more hepatotoxic even when the advised pyrazinamide dose of up to 20 mg/kg for preventive treatment was compared with the pyrazinamide dose of 30 mg/kg for tuberculosis treatment.


CONCLUSIONS
Preventive treatment with rifampin-pyrazinamide causes severe hepatotoxicity more often than does preventive treatment with isoniazid or curative treatment for tuberculosis.
van Hest
Rob
R
Department of Tuberculosis Control, Municipal Health Service, Rotterdam, The Netherlands. vanhestr@ggd.rotterdam.nl
Baars
Hennie
H
Kik
Sandra
S
van Gerven
Paul
P
Trompenaars
Marie-Christine
MC
Kalisvaart
Nico
N
Keizer
Sytze
S
Borgdorff
Martien
M
Mensen
Marlies
M
Cobelens
Frank
F
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular / Q000009:adverse effects / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D015331:Cohort Studies; D004359:Drug Therapy, Combination / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011446:Prospective Studies; D011718:Pyrazinamide / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D012293:Rifampin / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy* / Q000517:prevention & control*
D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin