4.3 Review

Anti-infectives - Adverse reactions to first-line antituberculosis drugs

Journal

EXPERT OPINION ON DRUG SAFETY
Volume 5, Issue 2, Pages 231-249

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1517/14740338.5.2.231

Keywords

drug-induced hepatitis; ethambutol; isoniazid; pyrazinamide; rifampin; streptomycin; tuberculosis (TB)

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Introduction: Tuberculosis continues to be a major cause of morbidity and mortality worldwide. Currently available drugs are effective for treatment of the disease or latent infection, but may cause serious adverse effects. Methods: The authors reviewed the literature for side effects of five first-line antituberculous medications (isoniazid, rifampin, pyrazinamide, ethambutol and streptomycin). Incidence of the major side effects were compiled with particular attention to the incidence of isoniazid hepatotoxicity. Results: Hepatotoxicity to isoniazid is a serious problem. Although overall incidence may be decreasing, incidence averaged 9.2 per 1000 patients who were compliant, in multiple studies, with a case fatality rate of 4.7%. The incidence is higher with increasing age. Other serious adverse effects include dermatological, gastrointestinal, hypersensitivity, neurological, haematological and renal reactions. They can lead to drug discontinuation (in up to 10% of patients) or even more serious morbidity or mortality. Conclusions: Side effects to antituberculosis drugs are common, and include hepatitis, cutaneous reactions, gastrointestinal intolerance, haematological reactions and renal failure. These adverse effects must be recognised early, to reduce associated morbidity and mortality.

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