Rifampin plus Isoniazid in Initial Therapy of Pulmonary Tuberculosis and Rifampin and Ethambutol in Retreatment Cases

Lees, A.W.; Allan, G.W.; Smith, J.; Tyrrell, W.F.; Fallon, R. J.

doi:10.1016/s0012-3692(15)39159-5

Cited by 14 publications

(5 citation statements)

References 8 publications

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“…53 Later the same group described 110 previously untreated pulmonary tuberculosis patients receiving INH and RMP and a transient rise in transaminase values occurred in 21 (23%) and a rise in serum bilirubin in 8 (11%). 54 An extensive review of RMP published in 1971 summarized experience with RMP hepatotoxicity following monotherapy and as part of multidrug therapy; amongst 1366 individuals receiving RMP montherapy 5 (0.37%) became jaundiced and 1 (0.07%) developed biochemical abnormalities; 55 amongst 4280 patients treated with RMP and other drugs, including INH, 80 (1.87%) developed jaundice and another 27 (0.6%) other biochemical abnormalities. The case report of Askgaard et al also provides an instructive window on the interplay of INH and RMP in ADIH.…”

Section: Resultsmentioning

confidence: 99%

Antituberculosis Drug-Induced Hepatotoxicity in Children

Donald

2011

Pediatric Reports

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Recent increases in the dosages of the essential antituberculosis agents isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA) for use in children recommended by World Health Organization have raised concerns regarding the risk of hepatotoxicity. Published data relating to the incidence and pathogenesis of antituberculosis drug-induced hepatotoxicity (ADIH), particularly in children, is reviewed. Amongst 12,708 children receiving chemoprophylaxis, mainly with INH, but also other combinations of INH, RMP and PZA only 1 case (0.06%) of jaundice was recorded and abnormal liver functions documented in 110 (8%) of the 1225 children studied. Excluding tuberculous meningitis (TBM) 8984 were children treated for tuberculosis disease and jaundice documented in 75 (0.83%) and abnormal liver function tests in 380 (9.9%) of the 3855 children evaluated. Amongst 717 children treated for TBM, however, jaundice occurred in 72 (10.8%) and abnormal LFT were recorded in 174 (52.9%) of those studied. Case reports document the occurrence of ADIH in at least 63 children. Signs and symptoms of ADIH were frequently ignored in the recorded cases. ADIH can occur in children at any age or at any dosage of INH, RMP or PZA, but the incidence of.ADIH is is considerably lower in children than in adults. Children with disseminated forms of disease are at greater risk of ADIH. The use of the higher dosages of INH, RMP and PZA recently recommended by WHO is unlikely to result in a greater risk of ADIH in children.

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Section: Resultsmentioning

confidence: 99%

Antituberculosis Drug-Induced Hepatotoxicity in Children

Donald

2011

Pediatric Reports

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“…It is difficult to say which drug was responsible for the liver dysfunction, as every patient received a combination of drugs. Although liver dysfunction caused by RFP alone has been reported (24), the incidence is very low, while INH with RFP has caused liver dysfunction more frequently (5)(6)(7)(8)(9)25). Thus, INH may be the agent most responsible for the liver dysfunction in these cases.…”

Section: Discussionmentioning

confidence: 99%

Elevated Serum Aminotransferase Induced by Isoniazid in Relation to Isoniazid Acetylator Phenotype

1986

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Of 143 patients with pulmonary tuberculosis receiving isoniazid therapy, 52 (36%) had a transient elevation in serum aminotransferases. Among 74 patients taking isoniazid, rifampicin and streptomycin, 35 (47%) had such an increase, while of 69 patients taking isoniazid, amino-salicylic acid and streptomycin, 17 (24%) did; this difference was significant. Isoniazid therapy could be continued in all patients with the abnormal test results. In 36 of the patients receiving isoniazid, rifampicin and streptomycin, isoniazid and its metabolites were studied in the serum and urine using high-performance liquid chromatography after the oral administration of 10 mg per kg of isoniazid. We had chosen for this test 18 patients with normal aminotransferase levels and 18 with abnormal levels. There were 14 rapid acetylators in the patients with abnormal aminotransferase levels and 7 rapid acetylators in the patients with normal levels; this difference was significant. These results indicate that liver dysfunction is more often caused by an isoniazid/rifampicin regimen, and patients who are rapid acetylators are more susceptible.

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“…ll However, interpretation of both these investigations is complicated by the fact that the patients were simultaneously being treated with another hepatotoxic drug, rifampin. 12 Examination of the urinary metabolites of isoniazid provides a possible explanation for the increased incidence of isoniazid hepatitis in patients who acetylate the drug rapidly. Rapid acetylators hydrolyze 44.4% of a dose of isoniazid to isonicotinic acid, whereas slow acetylators convert only 30.5% of a dose to isonicotinic acid (Table IV).…”

Section: Discussionmentioning

confidence: 99%

Increased incidence of isoniazid hepatitis in rapid acetylators: possible relation to hydrazine metabolites

Mitchell

Thorgeirsson

Black

et al. 1975

Clin Pharma and Therapeutics

281

135

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Approximately 10% to 20% of isoniazid recipients manifest biochemical evidence of liver injury. A smaller number of patients develop clinically overt hepatitis. Isoniazid is metabolized in man at extremely variable rates, and the rate is under genetic control. Two separate clinical studies have noted a possible relation between susceptibility of patients to isoniazid liver injury and rapid metabolism (acetylation) of the drug. For this reason, 21 patients who had recovered from probable isoniazid hepatitis and 5 patients who previously had manifested biochemical evidence of mild isoniazid liver injury were genetically phenotyped as rapid or slow isoniazid acetylators by the sulfamethazine method. The rapid phenotype was found in 86% of patients with probable hepatitis and in 60% of the possible ones, whereas the expected frequency was 45%. Eximination of isoniazid metabolites revealed that rapid acetylators hydrolze much more isoniazid to isonic otinic hydrazine moiety than do slow acetylators. The hydrazine moiety liberated from isoniazed is primarily acetylhydrazine, and studies in animals show this metabolite to be converted to a potent acylating agent that produces liver necrosis. We suggest that release of the hepatotoxic hydrazino moiety of isoniazid in man is responsible for isoniazid liver injury.

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Rifampin plus Isoniazid in Initial Therapy of Pulmonary Tuberculosis and Rifampin and Ethambutol in Retreatment Cases

Cited by 14 publications

References 8 publications

Antituberculosis Drug-Induced Hepatotoxicity in Children

Antituberculosis Drug-Induced Hepatotoxicity in Children

Elevated Serum Aminotransferase Induced by Isoniazid in Relation to Isoniazid Acetylator Phenotype

Increased incidence of isoniazid hepatitis in rapid acetylators: possible relation to hydrazine metabolites

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