Approach to stepwise resumption of tuberculosis treatment in adults with hepatotoxicity caused by first-line antituberculous drugs*

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

¶ Rifampin is an uncommon cause of hepatotoxicity. If initiation of rifampin and ethambutol is not tolerated, we discontinue rifampin and sequentially add other antituberculous agents. Treatment may be completed with a 3-drug regimen. If isoniazid is tolerated, it can be given with ethambutol and a fluoroquinolone; if isoniazid is not tolerated, ethambutol, pyrazinamide, and a fluoroquinolone may be given. If neither isoniazid nor pyrazinamide is tolerated, a regimen for multidrug-resistant tuberculosis may be used.

Δ 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.