Prothionamide
Prothionamide (Pto)
Prothionamide is taken as part of a treatment regimen, usually involving 5 medicines, to treat MDR TB. It has the same active substances and cross resistance with ethionamide. Prothionamide is part of a group of drugs thioamides.
Dosage:
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Adults: |
Adults with liver damage - creatine clearance < 30 ml/min: |
Children: |
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15 – 20 mg/kg daily (max 1000 mg) |
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N/A |
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Prothionamide is taken twice daily, generally one tablet (250 mg) in the daytime and 2 tablets (500 mg) at night. Prothionamide is taken during the intensive and continuation phases of treatment. |
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How it works:
Prothionamide is clinically effective in the treatment of TB; the precise mechanisms of action remain unknown, but a cell-based activation method causes an inhibiting complex.
Side effects:
The side effects of prothionamide are similar to ethionamide. Prothionamide is most commonly associated with nausea and vomiting. It may cause depression and hallucinations. Rarely, prothionamide will cause jaundice, menstrual disturbances and peripheral neuropathy.
Prothionamide should not be used in patients with severe liver disease. Blood sugar levels must be monitored in diabetic patients. Prothionamide is not recommended for pregnant women as it has been shown to be teratogenic in animal studies.
Clinical evidence and approval:
Prothionamide has received approval in Germany for the treatment of TB and drug resistant TB.
Prothionamide and ethionamide are clinically interchangeable, there is complete cross resistance between the two medicines.1
While prothionamide is widely used to treat MDR TB, there is little published evidence demonstrating safety and efficacy.
Pricing (per lowest unit, i.e. single tablet or injection):
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SA Private sector |
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N/A |
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250 mg |
R0.95 US$0.14 |
* 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:
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Further research is needed to establish the safety and efficacy of paediatric use. No paediatric formulations are available. [MSF]
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Further research is needed to establish interactions with antiretrovirals, particularly those associated with hepatoxicity. [MSF]
Manufacturers and suppliers:
Today there is only one prothionamide product approved by a stringent regulatory authority (Fatol in Germany) and none is prequalified by WHO. 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 manufacturer (Lupin) has submitted a dossier to WHO Prequalification and has been accepted for evaluation, and an additional producer (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
1 JA Caminero et al. Best drug treatment for multidrug-resistant and extensively drug-resistant tuberculosis. Lancet Infect Dis. 2010 Sep;10(9):621-9.
