ETHIONAMIDE
| ETHIONAMIDE (e-thye-on-am'ide) Trecator Classifications: antituberculosis agent; antileprosy (sulfone) agent; Therapeutic:antitubercular; antileprosy Prototype: Isoniazid Pregnancy Category: D |
Availability
250 mg tablets
Action
Ethionamide appears to inhibit mycolic acid synthesis, which disrupts the formation of the mycobacterial cell wall. Bacteriostatic or bactericidal depending on concentration used and susceptibility of organism. Emergence of resistant strains may be delayed or prevented when administered concurrently with other antituberculosis drugs.
Therapeutic Effect
Effective against human and bovine strains of Mycobacterium tuberculosis and M. kansasii and some strains of Mycobacterium avium-intracellulare complex. Also active against M. leprae.
Uses
Any form of active tuberculosis when treatment with primary antituberculosis drugs (e.g., isoniazid, streptomycin, ethambutol, rifampin) has failed. Must be given with at least one other effective antituberculosis agent.
Unlabeled Uses
Atypical mycobacterial infections and tuberculous meningitis.
Contraindications
Hypersensitivity to ethionamide and chemically related drugs [e.g., isoniazid, niacin (nicotinamide)]; severe liver damage; hepatic encephalopathy; pregnancy (category C), in children <12 y.
Cautious Use
Diabetes mellitus, liver dysfunction, history of psychiatric illnesses including depression; history of thyroid disease; lactation.
Route & Dosage
| Tuberculosis Adult: PO 0.5–1 g/d divided q8–12h Child: PO 15–20 mg/kg/d in 2–3 equally divided doses (max: 1 g/d) |
Administration
Oral- Give with or after meals to minimize GI adverse effects. Some patients tolerate ethionamide best when it is taken as a single dose after the evening meal or as a single dose at bedtime. GI symptoms appear to increase with divided doses, although serum concentrations may be higher.
- About 50% of patients cannot tolerate a single dose larger than 500 mg because of GI adverse effects. An antiemetic may be prescribed, but if symptoms persist, drug should be discontinued.
- Physician may prescribe pyridoxine (vitamin B6) concurrently to prevent or relieve peripheral neuritis and other neurotoxic effects.
- Store in a cool, dry place at 8°–15° C (46°–59° F) in a tightly closed container unless otherwise directed.
Adverse Effects (≥1%)
CNS: Headache, restlessness, mental depression, drowsiness, dizziness, ataxia, hallucinations, paresthesias, convulsions. GI: Dose related and frequent; symptoms may be due to CNS stimulation rather than to GI irritation: anorexia, epigastric distress, nausea, vomiting, metallic taste, diarrhea, stomatitis, sialorrhea. Metabolic: Elevated ALT, AST; hepatitis (with jaundice), hypothyroidism. Urogenital: Menorrhagia, impotence. Body as a Whole: Postural hypotension.Interactions
Drug: Cycloserine, isoniazid may increase neurotoxic effects.Pharmacokinetics
Absorption: 80% absorbed from GI tract. Peak: 3 h. Duration: 9 h. Distribution: Widely distributed including CSF; crosses placenta; distribution into breast milk unknown. Metabolism: In liver. Elimination: In urine. Half-Life: 3 h.Nursing Implications
Assessment & Drug Effects
- Lab tests: Perform C&S prior to start of therapy. Baseline liver function tests (AST and ALT), CBC, and kidney function tests including urinalysis and every 2–4 wk during therapy.
- Report onset of skin rash. Progression to exfoliative dermatitis can occur if drug is not promptly discontinued.
- Monitor blood glucose & HbA1C closely in the diabetic until response to drug is established. These patients appear to be especially prone to hepatotoxicity (see Appendix F).
Patient & Family Education
- Avoid alcohol or use in moderation because ethionamide may increase potential for liver dysfunction.
- Notify physician of S&S of hepatotoxicity (see Appendix F); generally reversible if drug is promptly withdrawn.
- Make position changes slowly and in stages, particularly from lying to upright posture if experiencing hypotension.
Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; 
Canadian drug name; 
Prototype drug