|Other names||Pretomanid FGK, PA-824|
|Main uses||Multi-drug-resistant tuberculosis|
|Side effects||Nerve damage, acne, vomiting, headache, low blood sugar, diarrhea, liver inflammation|
|Typical dose||200 mg OD|
|Chemical and physical data|
|Molar mass||359.261 g·mol−1|
|3D model (JSmol)|
Pretomanid, sold under the brand name Dovprela, is an antibiotic used to treat multi-drug-resistant tuberculosis affecting the lungs. It is generally used together with bedaquiline and linezolid. It is taken by mouth.
Common side effects include nerve damage, acne, vomiting, headache, low blood sugar, diarrhea, and liver inflammation. Other side effects may include bone marrow suppression, optic neuropathy, and QT prolongation. Safety in pregnancy is unclear. It is in the nitroimidazole class of medications.
Pretomanid was approved for medical use in the United States in 2019 and Europe in 2020. In the developing world it cost 364 USD for 6 months in 2019. In the United States this amount costs about 3,800 USD as of 2021. It was developed by the TB Alliance.
Pretomanid is indicated in combination with bedaquiline and linezolid, in adults, for the treatment of pulmonary extensively drug resistant (XDR), or treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB).
It is generally take at a dose of 200 mg per day for at least 6 months.
Pretomanid is the generic, nonproprietary name for the novel anti-bacterial drug compound formerly called PA-824. Pretomanid is referred to as "Pa" in regimen abbreviations, such as BPaL. The "preto" prefix of the compound's name honors Pretoria, South Africa, the home of a TB Alliance clinical development office where much of the drug's development took place. The "manid" suffix is used to group compounds with similar chemical structures. This class of drug is variously referred to as nitroimidazoles, nitroimidazooxazines or nitroimidazopyrans. Development of this compound was initiated because of the urgent need for new antibacterial drugs effective against resistant strains of tuberculosis. Also, current anti-TB drugs are mainly effective against replicating and metabolically active bacteria, creating a need for drugs effective against persisting or latent bacterial infections as often occur in patients with tuberculosis.
Pretomanid was first identified in 2000, in a series of 100 nitroimidazopyran derivatives synthesized and tested for antitubercular activity, by PathoGenesis (now a subsidiary of Novartis). Importantly, pretomanid has activity against static M. tuberculosis isolates that survive under anaerobic conditions, with bactericidal activity comparable to that of the existing drug metronidazole. Pretomanid requires metabolic activation by Mycobacterium for antibacterial activity. Pretomanid was not the most potent compound in the series against cultures of M. tuberculosis, but it was the most active in infected mice after oral administration. Oral pretomanid was active against tuberculosis in mice and guinea pigs at safely tolerated dosages for up to 28 days.
The U.S. Food and Drug Administration (FDA) approved pretomanid only in combination with bedaquiline and linezolid for treatment of a limited and specific population of adults with extensively drug resistant, treatment-intolerant or nonresponsive multidrug resistant pulmonary tuberculosis. Pretomanid was approved under the Limited Population Pathway (LPAD pathway) for antibacterial and antifungal drugs. The LPAD Pathway was established by Congress under the 21st Century Cures Act to expedite development and approval of antibacterial and antifungal drugs to treat serious or life-threatening infections in a limited population of patients with unmet need. Pretomanid is only the third tuberculosis drug to receive FDA approval in more than 40 years.
The FDA granted Pretomanid priority review and orphan drug designation. The FDA granted The Global Alliance for TB Drug Development (TB Alliance) the approval of Pretomanid and a Tropical Disease Priority Review Voucher.
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