Monograph: |
Thiacetazone
Adverse Effects
Gastro-intestinal disorders, hypersensitivity reactions includ-
ing skin rashes, conjunctivitis, and vertigo arc the side-
effects
most frequently reported with thiacetazone although the inci-
dence appears to vary from country to country. Toxic epider-
mal necrolysis, exfoliative dermatitis, which has sometimes
been fatal, and the Stevens-Johnson syndrome have been re-
ported, Thiacetazone may cause bone-marrow depression
with leucopenia. agranulocytosis. and thrombocytopenia.
Acute haemolytic anaemia may occur and a large percentage
of patients will have some minor degree of anaemia. Hepato-
toxicity with jaundice may also develop. Cerebral oedema has
been reported.
In a IO-year series of 1212 patients with tuberculosis who
were treated with a regimen of streptomycin, isoniazid, and
thiacetazone. 171 (14%) had adverse reactions associated
with thiacetazone. The most common side-effects were giddi-
ness (10%). occurring mainly in association with streptomy-
cin. and skin rashes (39%) including exfoliation and the
Stevens-Johnson syndrome.
Effects on the nervous system. Acute peripheral neurop-
athy which occurred in a 50-year-old man on 2 separate occa-
sions within 15 minutes of administration of thiacetazone
may have been due to an allergic reaction.
Effects on the skin. A high incidence of severe and some-
times fatal cutaneous hypersensitivity reactions to thiaceta-
zone has been reported in patients with HIV infection being
treated for tuberculosis. WHO advised that thiacetazone
should be avoided in such patients Unfortunately, thiaceta-
zone has been one of the mainstays of tuberculosis treatment
in the developing world because of its relatively low cost.
Some have supported a change to rifampicin-based regimens
in. for example, parts of Africa with a high incidence of HIV
infection. Others have found a lower frequency of fatalities
from adverse cutaneous reactions to thiacetazone than report-
ed previously and have suggested that improved management
might allow retention of thiacetazone in tuberculosis pro-
grammes. This was rejected by other workers who consid-
ered that better and more cost-effective regimens were
available than those containing thiacetazone. A pragmatic
approach may be to adopt a strategy depending upon the pre-
vailing incidence of HIV infection in the population. Thus.
where the incidence of HIV infection is high, ethambutol
should be substituted for thiacetazone: where the incidence is
moderate, routine HIV testing could be used to identify pa-
tients at risk; and where the incidence is low. education of
patients on the risks of skin reaction would be adequate.
Hypertrichosis. Hypertrichosis occurred in 2 children and
was associated with the use of thiacetazone.
Precautions
The efficacy and toxicity of a regimen of treatment which in-
cludes thiacetazone should be determined in a community be-
fore it is used widely since there appear to be geographical
differences.
Thiacetazone should not be given to patients with liver im-
pairment. It has also been suggested that because thiaceta-
zone has a low therapeutic index and is excreted mainly in the
urine, it should not be given to patients with renal
impairment,
It should probably be avoided in HIV-positive patients be-
cause they are at increased risk of severe adverse effects
(see
Effects on the Skin, above).
Interactions
Thiacetazone may enhance the ototoxicity of streptomycin.
Antimicrobial Action
Thiacetazone is bacteriostatic. It is effective against most
strains of Mycobacterium tuberculosis, although sensitivity
varies in different parts of the world. The MIC for sensitive
strains is I ug per mL.
Thiacetazone is also bacteriostatic against Micobacterium le-
prae. Resistance to thiacetazone develops when used alone.
Cross-resistance can develop between thiacetazone and
ethionamide, or prothionamide.
Pharmacokinetics
Thiacetazone is absorbed from the gastro-intestinal tract and
peak plasma concentrations of I to 2 ug per mL have been
obtained about 4 to 5 hours after a 150-mg dose. About 20%
of a dose is excreted unchanged in the urine. A half-life of
about 12 hours has been reported.
Uses and Administration
Thiacetazone has been used in association with other antimy-
cobacterials in the initial and continuation treatment phases
of
tuberculosis, Thiacetazone-containing regimens are
less effective than the short-course regimens recommended
by WHO and are used in long-term regimens combined with
isoniazid in some developing countries to reduce drug costs,
However, thiacetazone is not generally recommended for use
in HIV-positive patients because of the risk of severe adverse
reactions (but see Effects on the Skin. above).
Thiacelazone has been used in the treatment of leprosy,
but WHO now considers that such use is no longer
justified.
In the treatment of tuberculosis thiacetazone has been given
orally in doses of 150 mg daily or 2.5 mg per kg body-weight
daily. Thiacetazone may be used with isoniazid usually in the
continuation phase of some longer treatment regimens to pre-
vent emergence of isoniazid resistance. Thiacetazone has also
been used in the initial phase in association with streptomycin
and isoniazid. Daily administration is recommended as the
drug is less effective when given intermittently.
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