Interventions for Tuberculosis Control and Elimination 2002

number of cases, the health care provider, based on the assumption that the
treatment was causing adverse drug events, discontinued the treatment.
When the code indicating what the patient was taking was broken and
the results analyzed, it became apparent that 20% of all episodes considered
to have been adverse drug events to the “medication” were, in fact,
“placebo” effects. 641 This indicates that the “adverse events” were, indeed,
intercurrent illnesses or events unrelated to the treatment itself, although
they had every appearance of having been due to the medications.
This has important implications for the evaluation of “adverse events”
in patients on treatment for tuberculosis. If one or other of the essential
medications used in the treatment of tuberculosis (such as isoniazid or
rifampicin) is stopped due to what is (incorrectly) perceived as an adverse
drug event, the outcome of the treatment can be seriously affected.
Discontinuation of an essential medication in the treatment of a tuberculosis
patient for what is perceived as an adverse drug event must be carefully
considered and correctly undertaken if the patient’s chances of successful
treatment are not to be seriously affected.
The patient with hepatitis
Clinical hepatitis is to be suspected in a patient presenting with a syndrome
of malaise, nausea, vomiting, anorexia, fever, abdominal pain, hepatomegaly,
jaundice or dark urine. 642
Hepatic disease during anti-tuberculosis chemotherapy is not necessarily
caused by the drugs, but may be attributable to other causes, such
as alcohol abuse, cirrhosis, infectious hepatitis or indeed the tuberculosis
itself. Nevertheless, appropriate management of the patient requires an
approach as if one or more of the drugs were responsible.
The key suspect drugs are isoniazid, pyrazinamide, and rifampicin, if
the patient is on any of these. In that case, such as in the intensive phase
of chemotherapy, all three drugs should be stopped immediately if the symptoms
are severe and/or if there is jaundice. The patient should temporarily
be placed on ethambutol plus streptomycin in such a case. This combination
is unlikely to be hepatotoxic and, while a relatively weak combination,
still ensures temporary adequate treatment without a high risk of emerging
drug resistance. In the presence of malaise and nausea only (without
jaundice), rifampicin might in addition be kept in the regimen as it is rarely
a cause of hepatitis.
87