Rifampicin was frequently implicated by the treating physicians, and was considered responsible for almost two-thirds of adverse events.

When compared with HIV-negative patients with TB, a higher rate of serious (grade III/IV) toxicities was found in TB/HIV coinfected patients, but there was no difference in the discontinuation rate of TB medication between the groups [65]. Hepatotoxicity is a common and potentially serious adverse event. It is defined as: serum AST or ALT >3 × upper limit of normal in the presence of symptoms, or Other causes of hepatitis, such as concomitant drugs and viral hepatitis, http://www.selleckchem.com/products/VX-765.html should be investigated. Hepatotoxicity

may be caused by many drugs used in the treatment of HIV-positive patients, for instance azoles and macrolides, and not all hepatotoxic reactions are always caused by anti-tuberculosis therapy. Hepatotoxicity caused by isoniazid in the general population increases with age, occurring in <0.3% of those under 35 years old and in 2.3% of those >50 years old. It is also more likely in those with heavy alcohol intake or hepatitis C virus coinfection and in those also on rifampicin. High rates of adverse reactions requiring changes in therapy have been reported in HIV-infected patients who are likely to have some or all of selleck chemicals the other risk factors mentioned Erlotinib concentration above. The rates of adverse reaction were 26% in one HIV-infected cohort compared with 3% in the HIV-uninfected group, and other studies have shown similar results [120,121]. Another study showed little increase in hepatotoxicity in HIV-positive patients with TB although only 16.3% were receiving antiretrovirals and the study included children [122]. Management of hepatitis: I.  Stop all potentially hepatotoxic drugs immediately,

including isoniazid, rifampicin, pyrazinamide, antiretrovirals and cotrimoxazole. All patients should be screened for active hepatitis B and C. The risk of hepatotoxicity with pre-existing liver disease is greatest with pyrazinamide, then isoniazid, and then rifampicin. Isoniazid and rifampicin are essential drugs in short-course TB treatment regimens and should be used whenever possible, even in the presence of pre-existing liver disease. In patients with baseline abnormal hepatic transaminases, a rise of two-to-three times this abnormal baseline should be used as the threshold for hepatotoxicity [119]. If hepatotoxicity occurs then other regimens can be used, for instance: I.  Avoid pyrazinamide and treat with isoniazid and rifampicin for 9 months, adding ethambutol for the first 8 weeks or until isoniazid and rifampicin susceptibility is demonstrated.