Treatment of tuberculosis in presence of hepatic and renal impairment

  Antituberculous drugs are potentially hepatotoxic and nephrotoxic, which may complicate the treatment course, increase treatment morbidity or even be potentially fatal if not recognized early. Prediction, prevention and precaution for early liver derangement are important to minimize antituberculosis drug hepatotoxicity (ATDH). Identification of hosts at risk can predict or prevent ATDH. Genetic polymorphism of drug metabolizing enzymes ( N ‐acetyltransferase 2, cytochrome P450 oxidase [CYP2E1], and glutathione S‐transferase) are suggested as one of the key factors in determining the risk of ATDH. Vigilant clinical and biochemical monitoring are mandatory to improve outcomes of patients with drug‐induced hepatotoxicity during antituberculosis chemotherapy. The clinical approach to ATDH depends on its phase of treatment and the severity of drug‐induced hepatitis. Current professional guidelines suggest withholding of antituberculosis drugs when alanine aminotransferase exceeds three‐ or five‐times the upper limit of normal. This can be followed by an interim nonhepatotoxic regime, or gradual introduction of one or two or three hepatotoxic drugs when liver function becomes normal. In the presence of renal impairment, antituberculosis drugs can be modified by manipulating the dosage or dose interval or both as follows: (1) no adjustment in dosage and dose interval; (2) increase of the dose interval without decreasing dose; (3) reduction of the dose without change in dose interval; and (4) reduction of the dose and increase of the dose interval.