Thiacetazone is active against many strains of M. tuberculosis.
It is not marketed in the United States.
However, because of its low cost, it is used as a first-line
agent in East Africa, especially in combination with
compounds such as isoniazid. The most common side
effects of thiacetazone include GI intolerance and development
of rashes. It causes significant ototoxicity, especially
when coadministered with streptomycin. Lifethreatening
hypersensitivity reactions, such as hepatitis,
transient marrow aplastic syndromes, neutropenia, and
thrombocytopenia, have been reported.
Pharmaceutical Applications
Thioacetazone (USAN amithiozone) is a synthetic compound
discovered during initial work on the sulfonamides, to which
it is structurally related. It is only slightly soluble in water. It
is a weak bacteristatic drug, with frequent serious side effects,
particularly in HIV-positive persons to whom it must never
knowingly be given. On the advice of the WHO it no longer
has a place in the treatment of tuberculosis, except as a last
resort in cases of extreme drug resistance.
In-vitro MICs vary considerably according to the medium
used and bear little relation to in-vivo efficacy. Many strains
of M. tuberculosis isolated in East Africa, India and Hong
Kong are naturally more resistant than strains from Europe.
Acquired resistance, as a result of monotherapy, is prevalent
in the developing countries.
Thioacetazone is well absorbed, achieving a plasma
concentration
of 1–4 mg/L 2–4 h after a 100 mg oral dose.
The plasma half-life is 8–12 h. Little is known about the
distribution
of the drug. Several metabolites are described.
About 20% is eliminated in the urine; the fate of the remainder
is unknown. Rashes are common, occurring in 2–4%
of patients in Africa but much more frequently in those of
Chinese ethnic origin. More severe skin reactions, exfoliative
dermatitis and Stevens–Johnson syndrome occur in less than
0.5% of HIV-negative patients, but there is a 10-fold increase
of these reactions in HIV-positive patients, proving fatal in up
to 3% of such patients. Other common side effects include
gastrointestinal reactions, vertigo and conjunctivitis. Less
common reactions include hepatitis, erythema multiforme,
hemolytic anemia and, rarely, agranulocytosis. Prolonged
therapy may rarely lead to hypertrichosis, gynecomastia and
osteoporosis. It is very rarely used, but may occasionally be
considered (with other antituberculosis drugs) in extremely
drug resistant tuberculosis.
