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Hepatotoxicity from isoniazid and rifampin among children treated for tuberculosis
Abstract:
To estimate rates of hepatotoxicity in the United States among children treated for tuberculosis, we conducted a retrospective survey of health departments and individual practitioners. We received 874 reports suitable for analysis of children treated during 1977 to 1979. A total of 16 hepatotoxic reactions were reported; 14/430 (3.3%) children receiving isoniazid and rifampin had a hepatotoxic reaction, which approximates the rate seen in adults taking these drugs. Half of the reactions occurred during the first month of therapy, and all of the well-documented reactions were noted during the first 10 weeks. Because the likelihood of hepatotoxicity may be increased with higher drug doses, limiting the dose of isoniazid to 10 mg/kg and that of rifampin to 15 mg/kg may help minimize hepatotoxic reactions. Because more serious disease, especially disseminated tuberculosis, may further increase the risk of hepatotoxicity, close monitoring of such children receiving isoniazid and rifampin should help minimize serious hepatotoxicity. Routine biochemical monitoring may not be necessary for all children, eg, those with mild forms of disease and those with normal pretreatment liver function who are treated with lower drug doses.
Insights
Hepatotoxicity from tuberculosis drugs isoniazid and rifampin in children occurred at a rate similar to adults. Limiting drug doses and close monitoring, especially for severe disease, can minimize risks.
Area of Science:
- Pediatric Infectious Diseases
- Hepatology
- Pharmacovigilance
Background:
- Tuberculosis (TB) treatment in children requires careful consideration of potential side effects.
- Hepatotoxicity is a known risk associated with anti-tuberculosis medications.
Purpose of the Study:
- To estimate the incidence of drug-induced liver injury (hepatotoxicity) in children treated for tuberculosis in the U.S.
- To identify risk factors and timing of hepatotoxicity during TB treatment in pediatric patients.
Main Methods:
- A retrospective survey of U.S. health departments and practitioners was conducted.
- Data from 874 children treated for tuberculosis between 1977 and 1979 were analyzed.
Main Results:
- Sixteen hepatotoxic reactions were reported among the analyzed cases.
- The rate of hepatotoxicity for children receiving isoniazid and rifampin was 3.3% (14/430), comparable to adult rates.
- Most reactions occurred within the first 10 weeks of therapy, with half within the first month.
Conclusions:
- Hepatotoxicity from isoniazid and rifampin in children is a significant concern, mirroring adult responses.
- Lowering drug dosages (isoniazid to 10 mg/kg, rifampin to 15 mg/kg) and close monitoring, particularly for disseminated TB, may reduce risks.
- Routine biochemical monitoring may not be essential for all children, especially those with mild disease or normal baseline liver function receiving lower doses.