Interventions for Tuberculosis Control and Elimination 2002

Adverse drug events similar to those associated with the use of
rifampicin have been reported. 1099
Interactions that are expected most likely resemble those with
rifampicin.
The pattern and mechanism of resistance to rifapentine is identical to
that of rifampicin.
Thioamides
Following on from the discovery of the pyridine-containing isoniazid, numerous
pyridine derivatives were tested, and the activity of thio-isonicotinamide
against M. tuberculosis was found by several groups, 1106,1107 ethionamide,
one of these thioamides, was introduced by the group of Liberman, Rist,
and Grumbach. 1106-1108
Thioamides are active against M. tuberculosis and to a lesser extent
against other mycobacteria. 1109
The mechanism of action of ethionamide is, like isoniazid, at the level
of synthesis of mycolic acids. 46
Prothionamide is rapidly absorbed and rapidly excreted. 1110 Therefore,
the daily dosage is usually divided into two doses. Ethionamide has excellent
penetration into cerebrospinal fluid. 570
The usual dosage of both ethionamide and prothionamide is 500 to
1,000 mg per day, divided into two doses. 1111
The most important adverse drug event from thioamides are gastrointestinal
disturbances and hepatotoxicity. 1112-1119 It also appears to potentiate
the hypothyroid effect of para-aminosalicylic acid. Comparisons between
ethionamide and prothionamide seem to indicate that the latter might be less
toxic than the former, 1111,1120 though the difference might not be important.
Although isoniazid and thioamide have the same parent compound,
isonicotinic acid, isoniazid-resistant bacilli are often susceptible to ethionamide.
1108
Drugs and drug classes with potential activity against
M. tuberculosis under investigation and development
There can be little doubt about the necessity for the development of new
anti-tuberculosis medications, given the limited amount of available
choices. 1121 The Global Alliance for Tuberculosis Drug Development has
161