Ethionamide: Difference between revisions

Latest revision as of 13:03, 21 March 2025

Ethionamide is a second-line antibiotic used in the treatment of tuberculosis (TB), particularly in cases of multidrug-resistant tuberculosis (MDR-TB). It is not used as monotherapy but rather in combination with other antituberculosis agents to prevent the development of resistance.

Ethionamide has been associated with transient, asymptomatic elevations in serum aminotransferase levels and, in rare cases, can cause acute hepatotoxicity. Liver injury, although uncommon, can be severe.

Mechanism of Action[edit]

Ethionamide (pronounced eth-eye-on'-uh-mide) is classified as a thio-isonicotinamide compound and is structurally related to isoniazid. Like isoniazid, ethionamide is a prodrug—it must undergo activation within the mycobacterial cell to become pharmacologically active.

The activated form of ethionamide inhibits the enzyme enoyl-acyl carrier protein reductase (InhA), which is essential for mycolic acid synthesis, a key component of the mycobacterial cell wall.
Despite structural similarity to isoniazid, ethionamide is activated by different mycobacterial enzymes, resulting in minimal cross-resistance between the two drugs.
Because of this, ethionamide and isoniazid can be used together in combination regimens for MDR-TB.

Indications[edit]

Ethionamide is used in:

Multidrug-resistant tuberculosis (MDR-TB): Typically administered in combination with agents such as isoniazid, rifampin, ethambutol, and pyrazinamide
Cases where first-line agents are contraindicated or ineffective
Lepromatous leprosy: As an adjunctive treatment due to its antimycobacterial properties

Dosage and Administration[edit]

Ethionamide is available in 250 mg oral tablets, marketed under various generic names and the brand name Trecator.

Initial dose: 250 mg twice daily
Maintenance dose: Gradually increased to 15–20 mg/kg/day, divided into two or three doses
Maximum daily dose: 1 gram
Adjunctive therapy: Pyridoxine (Vitamin B6, 50 mg/day) is often co-administered to reduce the risk of neurotoxicity

Adverse Effects[edit]

Common side effects include:

Gastrointestinal upset
Nausea, diarrhea, anorexia
Metallic taste, stomatitis
Depression, drowsiness, and fatigue

Less common but serious side effects:

Hepatotoxicity
Peripheral neuropathy (more likely without pyridoxine supplementation)
Hypothyroidism (especially in patients with co-administration of PAS)

Pharmacology[edit]

Absorption: Well absorbed orally
Metabolism: Primarily hepatic
Elimination: Metabolites excreted via urine
Half-life: Approximately 2–3 hours

Precautions and Monitoring[edit]

Liver function tests (LFTs) should be monitored regularly during treatment
Neurological monitoring is important due to risk of neurotoxicity
Caution in patients with hepatic impairment or history of mental illness

Availability[edit]

Ethionamide is listed by the World Health Organization as an essential medicine for the treatment of tuberculosis. It is distributed globally through national TB programs and specialized infectious disease centers.

@@ Line 1: / Line 1: @@
-{{intro}}
+[[File:Ethionamide.svg|thumb|Chemical structure of Ethionamide]]
-Ethionamide is a second line drug in the therapy of [[tuberculosis]] used only in combination with other agents and for drug-resistance [[tuberculosis]]. Ethionamide has been linked to transient, asymptomatic elevations in serum [[aminotransferase]] levels and in uncommon instances of acute [[liver injury]], which can be severe.
+[[File:Ethionamide 3D spacefill.png|thumb|3D space-filling model of Ethionamide]]
-{{moa}}
+'''Ethionamide''' is a second-line [[antibiotic]] used in the treatment of [[tuberculosis]] (TB), particularly in cases of multidrug-resistant tuberculosis (MDR-TB). It is not used as monotherapy but rather in combination with other antituberculosis agents to prevent the development of resistance.
-Ethionamide (eth" eye on' a mide) is a thio-isonicotinamide somewhat similar in structure to isoniazid. Ethionamide is a prodrug and, like isoniazid, requires activation whereupon it inhibits mycobacterial fatty acid synthesis (enoyl-ACP reductase) that is necessary for cell wall synthesis and repair. Interestingly, there is little cross resistance between isoniazid and ethionamide, probably because they are activated by different mycobacterial enzymes, and therefore can be used together. Ethionamide is currently used only as a secondary agent in the treatment of active [[tuberculosis]], always in combination with other [[antituberculosis]] agents such as isoniazid, ethambutol, pyrazinamide and/or rifampin and usually for multidrug resistant mycobacterial [[infections]] or in situations where first agents are contraindicated. Ethionamide also has activity against lepromatous leprosy. Ethionamide is available as 250 mg tablets in generic forms and under the brand name Trecator. The typical dose in adults is 250 mg twice daily, but can then be increased gradually to a total dose of 15 to 20 mg/kg per day to a maximum of 1 gram daily. Pyridoxine (vitamin B6: 50 mg daily) is usually administered with ethionamide. Common side effects include [[gastrointestinal upset]], [[nausea]], anorexia, [[diarrhea]], metallic taste, stomatitis, depression, drowsiness and fatigue.
+Ethionamide has been associated with transient, asymptomatic elevations in serum [[aminotransferase]] levels and, in rare cases, can cause acute [[hepatotoxicity]]. Liver injury, although uncommon, can be severe.
-{{tb drugs}}
+== Mechanism of Action ==
+Ethionamide (pronounced ''eth''-eye-on'-uh-mide) is classified as a '''thio-isonicotinamide''' compound and is structurally related to [[isoniazid]]. Like isoniazid, ethionamide is a '''prodrug'''—it must undergo activation within the mycobacterial cell to become pharmacologically active.
-{{coststubd}}
+* The activated form of ethionamide inhibits the enzyme '''enoyl-acyl carrier protein reductase''' (InhA), which is essential for mycolic acid synthesis, a key component of the [[mycobacterial cell wall]].
+* Despite structural similarity to isoniazid, ethionamide is activated by different mycobacterial enzymes, resulting in minimal cross-resistance between the two drugs.
+* Because of this, ethionamide and isoniazid can be used together in combination regimens for MDR-TB.
+== Indications ==
+Ethionamide is used in:
+* Multidrug-resistant tuberculosis (MDR-TB): Typically administered in combination with agents such as [[isoniazid]], [[rifampin]], [[ethambutol]], and [[pyrazinamide]]
+* Cases where first-line agents are contraindicated or ineffective
+* Lepromatous leprosy: As an adjunctive treatment due to its antimycobacterial properties
+== Dosage and Administration ==
+Ethionamide is available in 250 mg oral tablets, marketed under various generic names and the brand name '''Trecator'''.
+* Initial dose: 250 mg twice daily
+* Maintenance dose: Gradually increased to 15–20 mg/kg/day, divided into two or three doses
+* Maximum daily dose: 1 gram
+* Adjunctive therapy: Pyridoxine (Vitamin B6, 50 mg/day) is often co-administered to reduce the risk of neurotoxicity
+== Adverse Effects ==
+Common side effects include:
+* [[Gastrointestinal upset]]
+* [[Nausea]], [[diarrhea]], [[anorexia]]
+* Metallic taste, stomatitis
+* [[Depression]], drowsiness, and fatigue
+Less common but serious side effects:
+* [[Hepatotoxicity]]
+* [[Peripheral neuropathy]] (more likely without pyridoxine supplementation)
+* [[Hypothyroidism]] (especially in patients with co-administration of PAS)
+== Pharmacology ==
+* Absorption: Well absorbed orally
+* Metabolism: Primarily hepatic
+* Elimination: Metabolites excreted via urine
+* Half-life: Approximately 2–3 hours
+== Precautions and Monitoring ==
+* Liver function tests (LFTs) should be monitored regularly during treatment
+* Neurological monitoring is important due to risk of neurotoxicity
+* Caution in patients with hepatic impairment or history of mental illness
+== Availability ==
+Ethionamide is listed by the [[World Health Organization]] as an essential medicine for the treatment of tuberculosis. It is distributed globally through national TB programs and specialized infectious disease centers.
+== See Also ==
+* [[Tuberculosis]]
+* [[Multidrug-resistant tuberculosis]]
+* [[Isoniazid]]
+* [[Rifampin]]
+* [[Leprosy]]
+* [[Antituberculosis drugs]]
+* [[Mycolic acid]]
+{{Antimycobacterials}}
+{{portal bar|Medicine}}
+[[Category:Pyridines]]
+[[Category:Anti-tuberculosis drugs]]
+[[Category:Antileprotic drugs]]
+[[Category:Tuberculosis treatment]]
+[[Category:Antibiotics]]
+[[Category:Thioamides]]
+[[Category:World Health Organization essential medicines]]
+[[Category:Hepatotoxins]]
+{{stub}}