1. 7. Anti-TB regimen in special situations of liver disease, renal impairment, and pregnancy.

2. Liver disease Patients with pre-existing liver disease can receive the usual TB regimens provided that there is no clinical evidence of chronic liver disease, hepatitis virus carriage, a past history of acute hepatitis, current excessive alcohol consumption. However, hepatotoxic reactions to anti-TB drugs may be more common among these patients and should therefore be anticipated The first-line drugs HRZ are all associated with hepatotoxicity. – Pyrazinamide is the most hepatotoxic Treatment of tuberculosis: guidelines - 4 th ed. WHO http://whqlibdoc.who.int/publications/2010/9789241547833_eng.pdf

3. The more unstable or severe the liver disease is, the fewer hepatotoxic drugs should be used. In general, patients with chronic liver disease should not receive pyrazinamide. All other drugs can be used, but close monitoring of liver enzymes is advised. If the serum AST level is more than 3 times normal before the initiation of treatment, the following regimens should be considered. Two hepatotoxic drugs (rather than the three in the standard regimen): 9 months of HRE 2 months of HRSE followed by 6 months of HR 6–9 months of RZE. One hepatotoxic drug: 2 months of HES, followed by 10 months of HE No hepatotoxic drugs: 18–24 months of streptomycin, ethambutol and a fluoroquinolone.

4. Renal impairment The recommended initial TB treatment regimen for patients with renal failure or severe renal insufficiency is 2 months of HRZE, followed by 4 months of HR. Isoniazid and rifampicin are eliminated by biliary excretion, so no change in dosing is necessary. There is significant renal excretion of ethambutol and metabolites of pyrazinamide and doses should therefore be adjusted. Three times per week administration of these two drugs at the following doses is recommended: pyrazinamide (25 mg/kg), and ethambutol (15 mg/kg) Treatment of tuberculosis: guidelines - 4 th ed. WHO http://whqlibdoc.who.int/publications/2010/9789241547833_eng.pdf

5. Renal impairment While receiving isoniazid, patients with severe renal insufficiency or failure should also be given pyridoxine in order to prevent peripheral neuropathy. Streptomycin should be avoided in patients with renal failure because of an increased risk of nephrotoxicity and ototoxicity. If streptomycin must be used, the dosage is 15 mg/kg, two or three times per week, to a maximum of 1 gram per dose, and serum levels of the drug should be monitored.

6. Pregnancy Women of childbearing age should be asked about current or planned pregnancy before starting TB treatment. A pregnant woman should be advised that successful treatment of TB with the standard regimen is important for successful outcome of pregnancy. With the exception of streptomycin, the first line anti-TB drugs are safe for use in pregnancy – streptomycin is ototoxic to the fetus and should not be used during pregnancy. Pyridoxine supplementation is recommended for all pregnant women taking isoniazid Treatment of tuberculosis: guidelines - 4 th ed. WHO http://whqlibdoc.who.int/publications/2010/9789241547833_eng.pdf