Antituberculosis Agents and Carbamazepine

Ms. A, a 44-year-old woman, was admitted to the psychiatric ward with symptoms of hypomania. She had a 10-year history of bipolar affective disorder that had been adequately controlled with carbamazepine, 200 mg b.i.d., and trifluoperazine, 5 mg b.i.d. Before admission, because of suspected tuberculosis, Ms. A had been given 600 mg/day of rifampin, 300 mg/day of isoniazid, and 50 mg/day of pyridoxine. Her serum carbamazepine level 2 weeks after admission was 3.1 mg/liter (therapeutic range=4–10); thus, her dose was increased to 200 mg t.i.d. Subsequent serum measurements (1 week apart) provided the following readings: 2.8, 2.5, and 2.3 mg/liter. The results of liver and renal function tests were normal.

Although our literature search retrieved no evidence of a drug interaction involving antituberculosis agents and a decrease in serum carbamazepine levels, the most likely cause of the continued low levels was a combination of carbamazepine auto-induced metabolism and the concomitant antituberculosis agents Ms. A was taking. The antituberculosis drugs were discontinued, and 5 days later, Ms. A’s serum carbamazepine level was 4.9 mg/liter. Ms. A was discharged with a carbamazepine dose of 400 mg b.i.d., having fully recovered from her hypomanic episode. Two months after discharge, her carbamazepine level was found to be 4.6 mg/liter, and her mood was euthymic.