Ethionamide dosing

Ethionamide Adults 15-20 mg/kg per day, usually 500-750 mg/day in a single daily dose or two divided doses Children 15-20 mg/kg per day Gastrointestinal effects, hepatotoxicity, neurotoxicity, endocrine effects Baseline FFTs Monthly FFTs if underlying liver disease is present TSH at baseline and monthly intervals... 

Metabolism/Excretion - Ethionamide is extensively metabolized to active and inactive metabolites with less than 1% excreted as the free form in urine. Ethionamide has a plasma elimination half-life of approximately 2 hours after oral dosing. 

Ethionamide is administered at an initial dose of 250 mg once daily, which is increased in 250-mg increments to the recommended dosage of 1 g/d (or 15 mg/kg/d), if possible. The 1 g/d dosage, though theoretically desirable, is poorly tolerated because of the intense gastric irritation and neurologic symptoms that commonly occur, and one often must settle for a total daily dose of 500-750 mg. Ethionamide is also hepatotoxic. Neurologic symptoms may be alleviated by pyridoxine. 

Disposition in the Body. Readily absorbed after oral administration and widely distributed throughout the body. Peak plasma concentrations are attained 2 to 3 hours after a dose. It is extensively metabolised and is excreted in the urine mainly as metabolites with little unchanged drug. The metabolites include ethionamide sulphoxide, 2-ethylisonicotinic acid, and 2-ethyl-isonicotinamide. 

Ethionamide is considered a secondary drug for the treatment of tuberculosis. It is used in the treatment of i.soniazid-resistant tuberculosis or when the patient i.s intolerant to Iso-niazid and other drugs. Because of its low potency, the highest tolerated dose of ethionamide i.s usually recommended. Ga.strointestinal intolerance is the most common side effect associated with its use. Visual disturbances and hcpatotoxic-iiy have also been reported. 

Ethionamide and its sulfoxide metabolite are cleared hepati-cally, so dosing is unchanged. °p-Aminosalicylic acid is converted largely to metabolites prior to renal elimination these metabolites may accumulate in renal failure. For patients on hemodialysis, the usual 12-hour dosing interval for p-aminosalicylic acid granules seems to be safe. Dialysis will remove the metabolites. Serum concentration monitoring must be performed for cycloserine to avoid dose-related toxicities in renal failure patients... 

Ethionamide, which has bacteriostatic actions against M. tuberculosis (0.5 to 1 g/day in divided doses) is indicated in the treatment of tuberculosis where first-line drugs such as isoniazid and rifampin have failed. The side effects of ethionamide may include nausea and vomiting, diarrhea, metallic taste, hepatitis, jaundice, stomatitis, depression, drowsiness, asthenia, peripheral neuritis, olfactory disturbances, diplopia, blurred vision, optic neuritis, convulsions, postural hypotension, thrombocytopenia, gynecomastia, impotence, menorrhagia, or diabetes mellitus. 

Ethionamide is a secondary agent, to be used concurrently with other drugs only when therapy with primary agents is ineffective or contraindicated. The initial dose of ethionamide for adults is 250 mg twice daily given orally it is increased by 125 mg/day every 5 days until a dose of 15-20 mg/kg/day is achieved. The maximal dose is 1 g daily. The drug is taken with meals in divided doses to minimize gastric irritation. Children should receive 15-20 mg/kg/day in two divided doses, not to exceed 1 g daily. 

Ethionamide is a congener of INH, but cross-resistance does not occur. The major disadvantage of ethionamide is severe gastrointestinal irritation and adverse neurologic effects at doses needed to achieve effective plasma levels. 

A study in 12 healthy subjects found that the bioavailability of a single SOO-mg dose of ethionamide was not significantly affected by food, orange juice or antacids, when compared with ethiona-... 

Established Drugs - The oxidative degradation of ethionamide to sulfoxide and other products vitro was studied with relation to activity in tuberculosis. A test for ethionamide sulfoxide in urine was devised so that clinicians could check that patients were ingesting the drug. Clinical and laboratory experience with ethambutol was reported in I5 papers and was summarized by Herman. The pro and con of the isoniazid prophylaxis of tuberculosis was discussed, and the production of hepatic carcinoma in mice with this agent was disclosed.The metabolism of doubly labeled thiocarlide XIII was studied in humans. Blood levels were 10-12 mcg/ml from doses 6 g per day, twice the level seen in rabbits. 

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