Monitoring tuberculosis therapy
A number of tests are recommended before starting treatment for tuberculosis (TB)—see Before starting therapy.
If tuberculosis therapy is not being administered under supervision (eg directly observed therapy), check adherence with the patient, and by other measures such as pill counting, and urine testing if available1. If possible, collect a sputum sample for culture on a monthly basis until it is culture-negative; thereafter, collect a sputum sample for culture when clinically indicated, and at the end of treatment.
Ask patients who are taking ethambutol about visual adverse effects at each visit. Check visual acuity and colour vision before starting treatment and then at monthly intervals, especially if therapy is continued for longer than 2 months. Checking for visual adverse effects is particularly important in people with kidney impairment because ethambutol accumulates (due to decreased clearance). If signs of ocular toxicity develop, discontinue ethambutol immediately and refer to an ophthalmologist.
Educate patients about the risk and symptoms of hepatitis and monitor liver function (eg in adults, at baseline, 2, 4 and 8 weeks, then monthly or second monthly while on treatment). Liver function monitoring is particularly important for older patients; patients with abnormal baseline liver biochemistry, pre-existing liver disease, chronic viral hepatitis or a history of hazardous alcohol consumption; and women who are pregnant. Minor elevation of serum transaminases is common and usually does not require discontinuation of therapy. Withdraw all drugs immediately if clinical jaundice develops or if the patient has elevated serum transaminases (five times the upper limit of normal if asymptomatic, or three times the upper limit of normal if symptomatic [eg nausea, vomiting]).
TB therapy can be reintroduced once the alanine aminotransferase (ALT) concentration has returned to below 2 times the upper limit of normal, or, in patients with elevated baseline ALT (from pre-existing liver disease), drugs are restarted when the ALT returns to near-baseline levels. There are two approaches to reintroduce TB therapy when all drugs have been stopped due to drug-related liver injury. One is to reintroduce rifampicin plus ethambutol, followed by isoniazid a week later, and pyrazinamide a week after that, while monitoring liver function. Alternatively, depending on the degree of liver injury and the presence of other risk factors for liver disease, it may be reasonable to reintroduce all three drugs simultaneously, at the full doses. Both approaches carry a risk of recurrence of hepatotoxicity of approximately 12%.