Co-administration with ketoconazole, a strong CYP3A4 inhibitor, results in a 22% increase in the AUC, and potentially an increase in the rate of adverse effects experiencedSince bedaquiline can also prolong the QT interval, use of other QT prolonging drugs should be avoided. Other medications for tuberculosis that can prolong the QT interval include fluoroquinolones and clofazimine. Mechanism of action
Bedaquiline blocks the proton pump for ATP synthase of mycobacteria. It is the first member of a new class of drugs called the diarylquinolines. Bedaquiline is bactericidal. ATP production is required for cellular energy production and its loss leads inhibition of mycobacterial growth within hours of the addition of bedaquiline. The onset of bedaquiline-induced mycobacterial cell death does not occur until several days after treatment, but nonetheless kills consistently thereafter. Resistance
The specific part of ATP synthase affected by bedaquiline is subunit c which is encoded by the gene atpE. Mutations in atpE can lead to resistance. Mutations in drug efflux pumps have also been linked to resistance. Ongoing research
In vitro experiments have indicated that Bedaquiline may also target the mitochondrial ATP synthase of malignant mammalian cells and reduce the rate of metastasis. History
Bedaquiline was described for the first time in 2004 at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting, after the drug had been in development for over seven years.
Bedaquiline, sold under the brand name Sirturo, is a medication used to treat active tuberculosis. Specifically, it is used to treat multi-drug-resistant tuberculosis (MDR-TB) along with other medications for tuberculosis. It is used by mouth.Common side effects include nausea, joint pains, headaches, and chest pain. Serious side effects include QT prolongation, liver dysfunction, and an increased risk of death. While harm during pregnancy has not been found, it has not been well studied in this population. It is in the diarylquinoline antimycobacterial class of medications. It works by blocking the ability of M. tuberculosis to make adenosine 5-triphosphate (ATP).Bedaquiline was approved for medical use in the United States in 2012. It is on the World Health Organizations List of Essential Medicines. The cost for six months is approximately US$900 in low-income countries, US$3,000 in middle-income countries, and US$30,000 in high-income countries.The public sector invested US$455–747 million in developing bedaquiline. This is thought to be 1.6× to 5.1× what the owner, Janssen Biotech, invested (estimated at US$90–240 million). If capitalized and risk-adjusted, these costs become US$647–1,201 million and US$292–772 million, respectively.