Hepatitis on high dose isoniazid: reintroduction of the drug in severe tuberculous meningitis.

Hepatitis developed in two patients treated with high doses (1000 mg/day) of isoniazid for severe tuberculous meningitis. Isoniazid was discontinued and later readministered in gradually increasing intrathecal and subsequently oral doses, up to the final dose of 400 mg/day. Transaminases remained normal, during 12 months on this dose, suggesting dose dependence of hepatotoxicity or a metabolic adaptation to the injury. Continued isoniazid treatment can be important in similar cases and it may become possible, if oral or intrathecal doses significantly lower than the initial hepatotoxic ones, are used.