[Hepatic toxicity of antitubercular agents. Role of different drugs. 199 cases].
One hundred and ninety-nine cases of hepatic injury related to antituberculous treatment were analysed in order to assess the role played by each drug and to look for predisposing factors. This is a retrospective study of 169 cases reported in the literature and 30 cases reported to the regional pharmacovigilance centre of Paris Saint-Antoine. The mortality rate was related to the dose of isoniazid: it was 43 percent with a daily dose higher than 300 mg, and 9 percent with a daily dose of 300 mg or less (P < 0.001). Hepatic injury appeared significantly earlier in the case of rifampicin combination: 11 weeks without rifampicin and 2 weeks with rifampicin (P < 0.01). The role of pyrazinamide was difficult to determine because isoniazid and pyrazinamide were always used in combination. The influence of a preexisting liver disease could not be evaluated because of the small number of cases reported (8 cases). Alcoholism did not increase the mortality rate. Our results confirm the dose-dependent toxicity of isoniazid. Because of the short time elapsed before the apparent onset of hepatitis observed with the rifampicin combination, a close supervision of the patients should be exerted during the first weeks of treatment.
Altman
C
C
Service d'Hépato-Gastroentérologie, Hôpital Tenon, Paris.
Biour
M
M
Grangé
J D
JD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000627:therapeutic use / Q000633:toxicity*; D005260:Female; D006801:Humans; D007223:Infant; D007538:Isoniazid / Q000627:therapeutic use / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D011718:Pyrazinamide / Q000627:therapeutic use / Q000633:toxicity*; D012189:Retrospective Studies; D012293:Rifampin / Q000627:therapeutic use / Q000633:toxicity*; D013307:Streptomycin / Q000627:therapeutic use / Q000633:toxicity*; D014376:Tuberculosis / Q000188:drug therapy
D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin
Toxicité hépatique des antituberculeux. Rôle des différents médicaments. 199 observations.