Clinically significant drug interactions with antituberculosis agents

Abstract

Tuberculosis (TB) has, until recently, been considered to be primarily of historical importance in the United States, but in the past 10 years the number of reported cases has increased. As a result of mismanaged patients and poor treatment outcomes, a strain of Mycobacterium tuberculosis resistant to both of the most effective antitubercular agents, isoniazid (INH) and rifampin has emerged and necessitates the use of more toxic and less effective drugs for longer periods of time. Compounding the problem is the treatment of HIV/ AIDS patients with TB, which also requires several medications during treatment (1,2). Psychiatric populations are at greater risk for developing TB, and are often treated with multiple medications that have the potential to interact adversely with antitubercular agents. Rifampin is a well-known potent inducer of both cytochrome P450 (CYP) 2C and CYP3A and has the majority of clinically significant drug interactions. INH inhibits the metabolism of many drugs due to a mechanism other than CYP enzyme involvement. Drug interactions involving these and other antitubercular drugs can result in either therapeutic failure or toxicity of antitubercular and/or psychoactive agents. Additionally psychosis has occurred, although rarely, as a direct result of the use of antitubercular treatment in TB patients with no history of psychiatric symptoms (3). Prevention of these drug-induced adverse events as well as education and medication compliance are essential factors in the optimal treatment of psychiatric patients with comorbid TB.