Safety and tolerability profile of second-line anti-tuberculosis medications

Tuberculosis (TB) remains a major public health problem, representing the second leading cause of death from infectious diseases globally, despite being nearly 100 % curable. Multidrug-resistant (MDR)-TB, a form of TB resistant to isoniazid and rifampicin (rifampin), two of the key first-line TB drugs, is becoming increasingly common. MDR-TB is treated with a combination of drugs that are less effective but more toxic than isoniazid and rifampicin. These drugs include fluoroquinolones, aminoglycosides, ethionamide, cycloserine, aminosalicyclic acid, linezolid and clofazimine among others. Minor adverse effects are quite common and they can be easily managed with symptomatic treatment. However, some adverse effects can be life-threatening, e.g. nephrotoxicity due to aminoglycosides, cardiotoxicity due to fluoroquinolones, gastrointestinal toxicity due to ethionamide or para-aminosalicylic acid, central nervous system toxicity due to cycloserine, etc. Baseline evaluation may help to identify patients who are at increased risk for adverse effects. Regular clinical and laboratory evaluation during treatment is very important to prevent adverse effects from becoming serious. Timely and intensive monitoring for, and management of adverse effects caused by, second-line drugs are essential components of drug-resistant TB control programmes; poor management of adverse effects increases the risk of non-adherence or irregular adherence to treatment, and may result in death or permanent morbidity. Treating physicians should have a thorough knowledge of the adverse effects associated with the use of second-line anti-TB drugs, and routinely monitor the occurrence of adverse drug reactions. In this review, we have compiled safety and tolerability information regarding second-line anti-TB drugs in both adults and children.