Approach to hepatotoxicity caused by first-line antituberculous drugs in adults*

* First-line antituberculous drugs include isoniazid, rifampin, pyrazinamide, and ethambutol. Isoniazid, rifampin, and pyrazinamide are potentially hepatotoxic; ethambutol is not hepatotoxic.

¶ Liver function tests include measurement of serum bilirubin, alkaline phosphatase, and hepatocellular enzymes (alanine aminotransferase and aspartate aminotransferase).

Δ Alternative causes of elevated liver function tests include alcohol, acetaminophen, viral hepatitis, gallstones, biliary obstruction, and others.

◊ Signs and symptoms of hepatotoxicity include nausea, vomiting, malaise, low-grade fever, and anorexia. Refer to the UpToDate topic on drug-induced liver injury for further discussion.

§ The approach to subsequent monitoring depends on clinical circumstances; some favor checking liver function tests weekly until on a stable regimen, then every two to four weeks thereafter.

¥ There is overlap in the pattern of liver injury caused by rifampin, isoniazid, and pyrazinamide; all individually or in combination may contribute to hepatotoxicity.

‡ Intervals of treatment interruption warranting resumption of therapy from the beginning vary between initiation and continuation phases; refer to UpToDate text for further discussion.