Rifampin, isoniazid, and pyrazinamide (Oral)

Severe and sometimes fatal hepatitis associated with isoniazid, a component of rifampin, isoniazid and pyrazinamide, therapy may occur and may develop even after many months of treatment. The risk of developing hepatitis is age related. Approximate case rates by age are: 0 per 1000 for persons under 20 years of age, 3 per 1000 for persons in the 20 to 34 year age group, 12 per 1000 for persons in the 35 to 49 year age group, 23 per 1000 for persons in the 50 to 64 year age group, and 8 per 1000 for persons over 65 years of age. The risk of hepatitis is increased with daily consumption of alcohol. Precise data to provide a fatality rate for isoniazid-related hepatitis is not available; however, in a US Public Health Service Surveillance Study of 13,838 persons taking isoniazid, there were 8 deaths among 174 cases of hepatitis.Therefore, patients given rifampin, isoniazid and pyrazinamide, which contains isoniazid, should be carefully monitored and interviewed at monthly intervals. Serum transaminase concentration becomes elevated in about 10% to 20% of patients, usually during the first few months of therapy, but it can occur at any time. Usually enzyme levels return to normal despite continuance of drug, but in some cases progressive liver dysfunction occurs. Patients should be instructed to report immediately any of the prodromal symptoms of hepatitis, such as fatigue, weakness, malaise, anorexia, nausea, or vomiting. If these symptoms appear or if signs suggestive of hepatic damage are detected, rifampin, isoniazid and pyrazinamide should be discontinued promptly since continued use of the drug in these cases has been reported to cause a more severe form of liver damage.Patients with tuberculosis should be given appropriate treatment with alternative drugs. If isoniazid, a component of rifampin, isoniazid and pyrazinamide, must be reinstituted, it should be reinstituted only after symptoms and laboratory abnormalities have cleared. Rifampin, isoniazid and pyrazinamide should not be restarted, instead, isoniazid ,should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of recurrent liver involvement. Treatment should be deferred in persons with acute hepatic diseases .