Interventions for Tuberculosis Control and Elimination 2002

pyrazinamide. Cutaneous adverse drug events are much more frequent
among patients with HIV infection than among non-HIV-infected patients.
If the patient is on thioacetazone, it is by far the most likely cause. It
should be stopped immediately, and never be given again.
In all instances of rash with or without fever, all drugs should be
stopped. When the symptoms subside, usually within a day or two, the
drug least likely to be the cause should be re-introduced in a test dose.
This drug is usually isoniazid and is given at a dose of 150 mg. If the
patient was hypersensitive to isoniazid, a rise in temperature, pruritus, or
rash will develop within two to three hours. 499 If there is no reaction to
the test dose, the next test dose might be tried. Over the following days,
the full dose is gradually introduced. Subsequently, rifampicin might be
similarly re-introduced, starting with a test dose of 75 mg (or less), and so
on. Under strict observation, it might be possible to desensitize with
rifampicin much more rapidly, i.e., within two days. 643 If there is pruritus
or rash only, desensitization to isoniazid might not be necessary, as
symptoms often subside spontaneously.
Very often desensitization is successful, and the full range of medications
can be reintroduced within one to two weeks. It should be reiterated
that such desensitization should never be attempted with thioacetazone.
The patient with hematologic abnormalities
Blood dyscrasias comprise only 10% of the total number of drug-induced
adverse events but account for approximately 40% of fatal reactions related
to drug administration. 93 They occur with all six essential anti-tuberculosis
medications. In symptomatic patients, the offending drug should be
withdrawn and never be given again.
Relative leukopenia and hemolytic anemia due to isoniazid require permanent
withdrawal of the drug and often treatment with corticosteroids to
reverse hemolysis. Sideroblastic anemia due to isoniazid is usually responsive
to treatment with pyridoxine. Rarely, other neutropenia, eosinophilia,
and thrombocytopenia may occur, which will respond to withdrawal of isoniazid.
Similarly, the rare pure red cell aplasia responds to withdrawal of
isoniazid. Complete recovery from agranulocytosis usually occurs following
withdrawal of isoniazid.
With the exception of thioacetazone, blood dyscrasias due to anti-tuberculosis
drugs are rare events. It is probably exceedingly difficult to identify
the offending drug in the field.
90