New anti-TB drugs
Dr K K Aggarwal
As per Dr Soumya Swaminathan, DG ICMR, "The phase-3 clinical trials (on humans) of drug Bedaquilin has been successfully carried out in Africa, and the drug is likely to come to India next month." Another drug called Linezolid, which is in the final stages of human trials.
"The WHO attempts to make the world TB-free by 2035, while for India, it is 2050."
- Bedaquiline (Sirturo), the diarylquinoline TMC207, is a bactericidal antituberculous agent with a novel mechanism of mycobacterial adenosine triphosphate (ATP) synthase inhibition.
- Among 440 patients with MDR-TB in two phase II clinical trials, those who received bedaquiline in combination with optimized background regimens had faster and more frequent conversion to negative sputum culture than patients receiving the background regimens only (77.6 vs 57.6 percent) (N Engl J Med 2009;360:2397).
- Bedaquiline received accelerated approval by the US Food and Drug Administration (FDA) in December 2012 for use as part of combination therapy to treat adults with multidrug-resistant (MDR) pulmonary TB when other alternatives are not available. Dosing consists of 400 mg orally once daily for two weeks, followed by 200 mg orally three times weekly for a total treatment duration of 24 weeks.
- Bedaquiline is given with food and in combination with other TB drugs. Drug-drug interactions have been observed with CYP3A4 inducers (e.g., rifampin reduced bedaquiline exposure by approximately 50 percent) and CYP3A4 inhibitors (e.g., ketoconazole increased bedaquiline exposure by approximately 22 percent)
- The FDA approved bedaquiline with a boxed warning alerting that it can cause QT prolongation, which could lead to cardiac arrhythmia or death.
- In October 2013, provisional guidelines were issued by the United States Centers for Disease Control and Prevention (CDC) for use of bedaquiline that recommend clinical expert consultation and directly observed therapy (DOT) as part of a comprehensive case management strategy for cases where the drug is used.
- In children, pregnant women, individuals with extrapulmonary MDR-TB, and individuals with HIV or other comorbid conditions, CDC indicates that, although safety and effectiveness in these populations have not been determined, bedaquiline may be used on a case-by-case basis in these individuals when an effective treatment regimen cannot otherwise be provided.
Linezolid has modest bactericidal activity against TB. Its use is limited by adverse events (bone marrow suppression, neuropathy) and cost.