rifampin and Jaundice

Rifampin is a potent antituberculous drug. In the treatment of drug-resistant tuberculosis it is highly effective provided it is given in combination with other drugs to which the patient's organisms are sensitive. Rifampin and ethambutol is a particularly powerful combination and will achieve almost 100% sputum conversion. It seems likely that rifampin will replace streptomycin, and ethambutol will replace PAS in first-treatment cases. Optimum first-line treatment will thus consist of rifampin, INH and ethambutol, with the probability of almost 100% success and the possibility also that the total duration of treatment may be considerably reduced. Rifampin is well tolerated but it may give rise to liver dysfunction and thrombocytopenia in a small proportion of patients. Patients treated with rifampin must be kept under close supervision because of the risk of side effects and, more important, because irregular treatment may lead to the development of rifampin-resistant organisms.

Topics: Adult; Aged; Animals; Drug Combinations; Ethambutol; Female; Humans; Isoniazid; Jaundice; Male; Mice; Middle Aged; Mycobacterium tuberculosis; Pregnancy; Rifampin; Thrombocytopenia; Tuberculosis, Pulmonary

Prospective randomised clinical trial comparing the safety and efficacy of rifampicin- and thiacetazone-containing regimens in human immunodeficiency virus (HIV)-infected adults with pulmonary tuberculosis (TB) at the National Tuberculosis Treatment Centre, Kampala, Uganda.. To assess demographic, clinical and laboratory risk factors associated with toxicity during treatment with streptomycin, thiacetazone and isoniazid (STH) of HIV-1 infected adults with pulmonary TB.. Nested case-control study of all subjects randomized to the STH treatment arm. Baseline demographic, clinical, microbiological, hematological and radiographic characteristics were compared between subjects who developed and those who did not develop adverse drug reactions (ADR).. Of the 90 subjects randomized to STH, 13 developed ADR yielding an incidence rate of 19.6 events per 100 person years of observation (PYO). Eleven of the 13 ADR were cutaneous hypersensitivity reactions, including one fatal case of Stevens-Johnson syndrome. Eight of 13 patients who developed ADR were tuberculin anergic, compared to 12 of 77 patients who did not develop ADR (P < 0.001). An absolute lymphocyte count below 2000 cells/mm3 was also associated with ADR (P = 0.02).. Initial anergy to tuberculin and lymphocytopenia, markers of advanced HIV infection and immunosuppression, were associated with increased risk for adverse drug reactions during STH chemotherapy.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Case-Control Studies; Clonal Anergy; Confidence Intervals; Developing Countries; Drug Eruptions; Drug Therapy, Combination; Female; HIV-1; Humans; Incidence; Jaundice; Lymphopenia; Male; Middle Aged; Odds Ratio; Prospective Studies; Rifampin; Risk Factors; Stevens-Johnson Syndrome; Survival Rate; Thioacetazone; Tuberculosis, Pulmonary; Uganda

Topics: Adolescent; Adult; Antibodies; Clinical Trials as Topic; Drug Administration Schedule; Drug Eruptions; Drug Therapy, Combination; Dyspnea; Ethambutol; Female; Humans; Jaundice; Male; Middle Aged; Radiography; Rifampin; Sputum; Tuberculosis, Pulmonary

Topics: Clinical Trials as Topic; Drug Hypersensitivity; Drug Therapy, Combination; Ethambutol; Fever; Gastrointestinal Diseases; Humans; Jaundice; Purpura, Thrombocytopenic; Respiratory Insufficiency; Rifampin; Skin Manifestations; Time Factors; Tuberculosis, Pulmonary

Topics: Adult; Alanine Transaminase; Antibodies; Ethambutol; Female; Fever; Humans; Jaundice; Male; Middle Aged; Nausea; Pain; Placebos; Pyrazinamide; Respiratory Tract Diseases; Rifampin; Skin Manifestations; Tuberculosis, Pulmonary

This paper reports the nature, incidence, and severity of adverse reactions to regimens of rifampicin and ethambutol given once weekly, twice weekly, or daily and to a standard reserve regimen in a total of 330 Chinese failure patients who completed at least six months' chemotherapy in a therapeutic comparison in Hong Kong.The adverse reactions which occurred on the regimens of intermittent rifampicin were termed cutaneous, abdominal, "flu", and respiratory; in addition, purpura and abnormal liver function tests were encountered. There was an association of adverse reactions with the interval between doses and with the dose size of rifampicin, the highest incidence occurring with once-weekly rifampicin in high dosage. A procedure was developed for managing adverse reactions to intermittent rifampicin. Of 202 patients treated with intermittent rifampicin 60 developed adverse reactions, but in only 7 (3%) was it necessary to terminate the drug, though a further 10 (5%) were changed to daily rifampicin. On daily rifampicin, generalized hypersensitivity, cutaneous reactions, (one with purpura), and impaired liver function were encountered. Adverse reactions on the standard ethionamide, pyrazinamide, and cycloserine regimen were frequent and some were serious.

Topics: Alanine Transaminase; Antitubercular Agents; Bone Diseases; Chemical and Drug Induced Liver Injury; Colic; Drug Eruptions; Dyspnea; Ethambutol; Fever; Hong Kong; Humans; Jaundice; Purpura; Rifampin; Time Factors; Tuberculosis, Pulmonary

Topics: Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; Clinical Trials as Topic; Eosinophilia; Humans; In Vitro Techniques; Intestinal Absorption; Isoniazid; Jaundice; L-Lactate Dehydrogenase; Liver; Liver Function Tests; Mycobacterium; Mycobacterium tuberculosis; Rifampin; Thrombocytopenia; Transaminases; Tuberculosis, Pulmonary

Topics: Child, Preschool; Cholestasis, Intrahepatic; Humans; Jaundice; Male; Pruritus; Recurrence; Rifampin; Time Factors

Bispebjerg Hospital, Department of Pulmonary Medicine, tuberculosis referral center for the Municipality of Copenhagen.. To evaluate routine procedure for the management of liver injury during antituberculosis treatment.. From 1983-1993, 765 patients for whom we could trace 752 files (98%) were treated at our ward with standard Danish treatment for tuberculosis. From 1983-1986 they received a three-drug (9-month) regimen and from 1986-1993 a four-drug (6-month) regimen consisting of isoniazid, rifampicin, ethambutol + pyrazinamide. Data from a retrospective chart review.. An increase in aspartate aminotransferase (AST) of more than twice the upper limit of normal (ULN) was recorded in 127 patients (16%). 66 had elevated AST before treatment; most of these were men with a daily alcohol consumption in excess of 60 g. In the remaining 61 patients (8%) AST increased during antituberculosis treatment. 30 of these patients were excessive alcohol consumers, and seven had alcoholic liver cirrhosis. Despite an increase in AST of median 6 x ULN (range 2-25 x ULN), it was possible to continue treatment in 31 (15 excessive alcohol consumers) or reintroduce it fully in 14 (12 excessive alcohol consumers). Only 16 patients (2%), including 11 women with no daily alcohol consumption, needed a modified regimen. These patients were older (P < 0.05), seven were jaundiced, and one had alcoholic liver cirrhosis. Hepatotoxicity was confirmed by challenge with pyrazinamide (n = 7), isoniazid (n = 6) and combined isoniazid/rifampicin (n = 1). No deaths were caused by hepatotoxicity.. In spite of an increase in AST levels to approximately 6 x ULN during antituberculosis treatment, the drugs can be continued or reintroduced in full in most cases. Risk factors of hepatotoxicity included old age, female sex and extensive tuberculosis, and not alcohol consumption. Overall, hepatotoxicity during antituberculosis treatment can be monitored and managed easily.

Topics: Adolescent; Adult; Aged; Alcohol Drinking; Antitubercular Agents; Aspartate Aminotransferases; Bilirubin; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Isoniazid; Jaundice; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Pyrazinamide; Retrospective Studies; Rifampin

Topics: Antitubercular Agents; Drug Therapy, Combination; Humans; Isoniazid; Jaundice; Pyrazinamide; Rifampin; Tuberculosis, Pulmonary

Results are presented of the incidence of hepatitis, nearly always with jaundice, among 1686 patients in clinical trials of the treatment of spinal tuberculosis, of tuberculosis meningitis and of pulmonary tuberculosis with short-course regimens containing rifampicin, isoniazid, streptomycin and pyrazinamide. The incidence was high in patients treated with daily regimens of isoniazid and rifampicin: 16-39% in children with tuberculous meningitis, 10% in patients with spinal tuberculosis (non-surgical cases), and 2-8% in those with pulmonary tuberculosis. Hepatitis, in those receiving rifampicin occurred more often in slow than in rapid acetylators of isoniazid, the proportions amongst those whose acetylator phenotype had been determined being 11% of 317 slow acetylators and 1% of 244 rapid acetylators. In children with tuberculous meningitis, the risk of hepatitis with isoniazid 20 mg/kg (39%) was higher than that with 12 mg/kg (16%), and appreciably lower in patients given rifampicin twice-weekly (5%) rather than daily (21%). There was no indication that pyrazinamide contributed to the hepatic toxicity.

Topics: Adolescent; Adult; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Humans; Infant; Isoniazid; Jaundice; Liver; Pyrazinamide; Rifampin; Tuberculosis; Tuberculosis, Meningeal; Tuberculosis, Pulmonary; Tuberculosis, Spinal

Topics: Adolescent; Adult; Aged; Child; Ethambutol; Female; Humans; Jaundice; Male; Middle Aged; Rifampin; Tuberculosis, Osteoarticular; Tuberculosis, Pulmonary

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Female; Humans; Jaundice; Male; Middle Aged; Rifampin; Sputum; Tuberculosis, Pulmonary

Topics: Aged; Drug Therapy, Combination; Female; Humans; Jaundice; Rifampin; Troleandomycin

Although short-course, largely twice weekly chemotherapy for treatment of tuberculosis has been shown to be effective in other countries, when given under closely controlled conditions, it has not been adopted in this country where most patients are older and are treated as outpatients. Since January, 1976, 315 patients (mean age 55.5 years) with proven pulmonary tuberculosis have been treated with rifampin (RIF) 600 mg and isoniazid (INH) 300 mg daily for one month, followed by RIF 600 mg and INH 900 mg twice-weekly for another eight months, self-administered except for a few patients. By three months, 95 percent had converted to negative culture. There were only ten failures among 185 patients in whom final results could be assessed. There has been only one relapse during 1-21 months of follow-up in 175 patients. Serious side effects were few: six instances of jaundice, two of "flu-like syndrome," and one of thrombocytopenia. This form of initial therapy for tuberculosis is safe, effective, and economical.

Topics: Adolescent; Adult; Aged; Drug Hypersensitivity; Humans; Isoniazid; Jaundice; Middle Aged; Rifampin; Thrombocytopenia; Time Factors; Tuberculosis, Pulmonary; Vomiting

Topics: Humans; Jaundice; Methods; Rifampin; Solvents; Spectrophotometry, Ultraviolet

Topics: Aged; Female; Hepatic Encephalopathy; Humans; Jaundice; Liver Cirrhosis; Male; Rifampin

Topics: Adult; Bilirubin; Chemical and Drug Induced Liver Injury; Clinical Enzyme Tests; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Isoenzymes; Isoniazid; Jaundice; L-Lactate Dehydrogenase; Male; Oxidoreductases; Rifampin; Transaminases; Tuberculosis

Topics: Anemia, Hemolytic; Coombs Test; Fever; Humans; Jaundice; Pain; Rifampin; Thrombocytopenia

Topics: Adult; Aged; Autopsy; Biopsy; Chemical and Drug Induced Liver Injury; Female; Humans; Isoniazid; Jaundice; Liver; Middle Aged; Rifampin

Topics: Alanine Transaminase; Antitubercular Agents; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Hepatitis A; Humans; Hyperbilirubinemia; Jaundice; Liver Diseases; Pruritus; Rifampin; Tuberculosis

Topics: Ethambutol; Humans; Isoniazid; Jaundice; Liver; Liver Diseases; Rifampin; Sulfobromophthalein; Tuberculosis, Pulmonary

Topics: Adult; Biopsy, Needle; Chemical and Drug Induced Liver Injury; Drug Hypersensitivity; Drug Tolerance; Female; Hepatitis A; Humans; Isoniazid; Jaundice; Liver; Male; Middle Aged; Rifampin; Tuberculosis

Topics: Chemical and Drug Induced Liver Injury; Ethambutol; Humans; Jaundice; Rifampin; Tuberculosis, Pulmonary

Topics: Chemical and Drug Induced Liver Injury; Humans; Jaundice; Liver; Rifampin; Tuberculosis

Topics: Adolescent; Adult; Aged; Bilirubin; Drug Resistance, Microbial; Ethambutol; Female; Follow-Up Studies; Humans; Isoniazid; Jaundice; Male; Middle Aged; Mycobacterium tuberculosis; Recurrence; Rifampin; Sputum; Tuberculosis, Pulmonary

Topics: Acute Kidney Injury; Adult; Drug Hypersensitivity; Humans; Jaundice; Male; Rifampin; Thrombocytopenia

Liver function and serum concentrations of rifampicin, a highly cholephilic antibiotic, have been studied after ingestion of a single dose of 600 mg of rifampicin in 12 patients, six of them having a normal liver and six a cirrhotic, and during treatment with 600 mg of rifampicin per day for 17 days in eight patients, four of them having a normal liver and four a cirrhotic. Rifampicin produced competition for the elimination of bilirubin and bromsulphalein by the liver. This competition, which seemed to involve mainly the uptake by the liver cell, was always rapidly reversible when treatment was discontinued. It makes it impossible, however, to interpret a bromsulphalein test during treatment with rifampicin. In the eight patients treated for 17 days, apart from the competition already mentioned, no clinical, biological, or morphological abnormalities of the liver were ascertained. But in this limited number of patients it is not possible to exclude the fact that rifampicin could provoke jaundice by idiosyncrasy in a small percentage of cases. The serum concentrations of rifampicin were higher in cirrhotic patients than in patients with normal livers, especially after one or two weeks of treatment. It is suggested that efficient blood concentrations of rifampicin would be achieved with small doses in case of previous hepatocellular insufficiency.

Topics: Adult; Aged; Bilirubin; Humans; Jaundice; Liver; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged; Rifampin; Sulfobromophthalein

Topics: Anuria; Diagnosis, Differential; Female; Humans; Hypothermia; Jaundice; Kidney Diseases; Liver Diseases; Necrosis; Rifampin; Tuberculosis, Pulmonary

Topics: Chemical and Drug Induced Liver Injury; Child, Preschool; Cholestasis; Humans; Isoniazid; Jaundice; Liver; Male; Rifampin; Tuberculosis, Miliary

Topics: Biopsy; Drug Tolerance; Ethionamide; Humans; Jaundice; Liver; Male; Middle Aged; Rifampin; Tuberculosis, Hepatic

Topics: Aged; Chemical and Drug Induced Liver Injury; Female; Humans; Imipramine; Isoniazid; Jaundice; Liver; Male; Middle Aged; Rifampin; Tuberculosis; Tuberculosis, Miliary

Topics: Acute Disease; Adolescent; Adult; Aged; Atrophy; Chemical and Drug Induced Liver Injury; Female; Hepatitis A; Humans; Jaundice; Liver; Male; Rifampin; Transaminases; Tuberculosis, Pulmonary

Topics: Humans; Isoniazid; Jaundice; Liver; Rifampin; Tuberculosis, Pulmonary

Topics: Aged; Biopsy; Chemical and Drug Induced Liver Injury; Ethionamide; Female; Humans; Isoniazid; Jaundice; Liver; Rifampin; Streptomycin; Tuberculosis, Pulmonary

Topics: Alanine Transaminase; Alcoholism; Aspartate Aminotransferases; Bilirubin; Biopsy; Chronic Disease; Drug Combinations; Follow-Up Studies; Humans; Jaundice; Liver; Liver Diseases; Liver Function Tests; Radiography; Rifampin; Time Factors; Tuberculosis, Pulmonary

Topics: Adult; Alkaline Phosphatase; Bilirubin; Female; Humans; Jaundice; Rifampin; Transaminases; Tuberculosis, Renal

Topics: Aged; Aspartate Aminotransferases; Humans; Isoniazid; Jaundice; Liver Function Tests; Male; Rifampin; Tuberculosis, Pulmonary

Topics: Drug Synergism; Humans; Isoniazid; Jaundice; Rifampin; Tuberculosis; Tuberculosis, Hepatic

Topics: Chemical and Drug Induced Liver Injury; Humans; Isoniazid; Jaundice; Liver; Rifampin; Transaminases

Topics: Adolescent; Adult; Aged; Chemical and Drug Induced Liver Injury; Female; Humans; Isoniazid; Jaundice; Liver; Male; Middle Aged; Rifampin

Topics: Ammonia; Animals; Bile; Hepatectomy; Humans; Hyperbilirubinemia; Jaundice; Liver; Liver Cirrhosis, Experimental; Liver Function Tests; Perfusion; Rifampin; Sulfobromophthalein; Swine

Topics: Humans; Jaundice; Rifampin; Spectrophotometry