Ethionamide

Ethionamide (Eto)

Ethionamide is part of a group of drugs used in the treatment of drug resistant TB called thioamides. It is used as part of treatment regimens, generally involving 5 medicines, to treat MDR and XDR TB. It was discovered in 1956.

Ethionamide is used as part of a South Africa’s standard regimen to treat MDR TB.

Dosage:

How it works:

Ethionamide is an antibiotic used in the treatment of tuberculosis. The action may be through disruption of mycolic acid.

Side effects:

Ethionamide can cause persistent nausea and vomiting. Decreasing the dosage will decrease the symptoms, which is why ethionamide is taken twice a day. Ethionamide may also cause dizziness and fatigue. Occasionally ethionamide may cause jaundice (yellowing of the skin and eyes) or changes in mood (depression) and allergic reactions. Rarely, ethionamide will cause peripheral neuritis (tingling in the hands and feet) as well as vision disturbances.

It is recommended that ethionamide is avoided during pregnancy as it may increase nausea and vomiting. Ethionamide was shown to be teratogenic  in animal studies.

Ethionamide should not be used in patients with severe liver disease or porphyria (a rare, inherited disease affecting the skin and nervous system). Blood sugar levels should be monitored in diabetic patients.

Clinical evidence and approval:

Ethionamide has received FDA approval for the treatment of tuberculosis in patients resistant or intolerant to other medications.

A prospective uncontrolled study of 39 patients published in 2006, found that regimens containing ethionamide appear to be safe and effective.¹

Ethionamide is part of a group of second line agents used to treat drug resistant TB. The use of thioamides, including ethionamide and protionamide, is recommended before other second line agents (cycloserine or terizidone). There is complete cross resistance between ethionamide and protionamide.²

Evidence shows that strains that are resistant to low concentrations of isoniazid are probably susceptible to ethionamide and prothionamide. However, strains that are susceptible to high concentrations of isoniazid are usually resistant to ethionamide. The use of high-dose isoniazid and ethionamide increases the chance of successful treatment.³

Pricing (per lowest unit, i.e. single tablet or injection):

* Private sector prices sourced on 26/07/11. Global Drug Facility prices converted to rands on 26/07/11.

* Private and public sector prices may vary between suppliers. The lowest available prices are shown here.

Advocacy issues:

• Further research is needed on safety and efficacy for paediatric treatment. Paediatric formulations are not available. Further research is needed on potential interactions with antiretrovirals, including the potential increased risk of liver damage when combined with nevirapine and efavirenz. [MSF]

• The SA public sector price is 2.8 x higher than available international prices.

Manufacturers and suppliers:

Today only two ethionamide products are quality-assured; one is prequalified by WHO (Macleods) and Pfizer has the marketing license for ethionamide in the US and Canada. Such a limited number of quality-approved sources means this product is relatively vulnerable to supply disruption.

The situation is likely to improve as a further two manufacturers (Lupin, Cipla) have submitted dossiers to WHO Prequalification and have been accepted for evaluation. The Cipla product has already been assessed by the Expert Review Panel for the GDF and the Global Fund and is currently listed as purchasable in 2011 with Global Fund money. An additional manufacturer (Micro Labs) is expected to submit during the course of 2011.

Additional manufacturers may exist in China, India, the former Soviet Union and other countries, but whether they comply with WHO quality standards is unknown.⁵

 

Source: MSF