Ethionamide

Antibiotic Class:

Nicotinamide derivative (thioamide)

Antimicrobial Spectrum:

Narrow spectrum of activity - chiefly M. tuberculosis and M. leprae

Mechanism of Action:

Ethionamide disrupts mycolic acid synthesis.

Pharmacodynamics:

Ethionamide is generally bacteriostatic at the doses that can be achieved in humans.  Since its action is somewhat similar to isoniazid's, and the latter appears to have AUC/MIC as the primary pharmacodynamically linked variable, perhaps that also is true of ethionamide.

Pharmacokinetics:

Cmax: 2-5 mg/L; Tmax: about 2 hours; Bioavailability: not known, but likely is high; Protein binding: estimated at 10-30%

Adverse Effects:

Gastrointestinal intolerance is by far the major problem with ethionamide - nausea is common and vomiting may occur.  Hepatocellular injury is possible with ethionamide but is not common.  Various CNS effects have been reported.  Hypothyroidism, gynecomastia, alopecia, impotence also have been reported.

Dosage:

PO: 250 mg tablets

Usual dose: 250-500 mg once or twice daily, rarely exceeding 1000 mg.

Disease state based dosing:

Hepatic failures: No specific recommendations, but ethionamide is hepatically cleared, so caution is required.

Renal failures: Adjustment not required.

Contraindications/Warnings/Precautions:

Do not give to pregnant women

Drug Interactions:

No known interactions based on clearance. May be cleared by cytochrome P450 system, although this is not known with certainty.

Pregnancy:

Category X: Do not give to pregnant women

Monitoring Requirements:

Toxic:  baseline liver enzymes

Brand names/Manufacturer:

Trecator