Newer anti tb drugs

INTRODUCTION OF NEWER ANTI-TB DRUGS, WITH BRIEF INTRODUCTION OF BEDAQUILINE AND DELAMANID USED IN INDIA

1. NEWER ANTI-TB DRUGS IN DRUG RESISTANT TB Dr Ankur Gupta

2. Complexity and toxicity of the current TB drug regimes. Problem of TB drug resistance. Interactions of the current  TB drugs  . Why are new TB drugs needed?

3. WORLD

4. INDIA WORLD

5. New TB drugs need to provide Shorter and simpler, but still affordable, multi drug regimes for drug sensitive  TB Shorter, more effective , less toxic, and less expensive regimes for  drug resistant TB Short, simple, easily tolerable and safe regimes for  latent TB Drugs with few drug drug interactions.

6. NAMES

7. RNTCP

8. PRETREATMENT EVALUATION

9. BEDAQUILINE (BDQ) Diarylquinoline class MOA-Binds to subunit c of mycobacterial ATP synthase and inhibits its activity. Terminal half-life approximately 4-5 months. Recommended dose is 400 mg once daily for 2 weeks followed by 200 mg thrice weekly for 22 weeks.

10. BEDAQUILINE (BDQ) Inclusion criteria - adults aged > 18 years having pulmonary MDR-TB. Additional requirements non-pregnant females or females not on hormonal birth control methods (continue practicing birth control methods throughout the treatment period or have been post-menopausal for past 2 years patients with controlled stable arrhythmia can be considered after obtaining cardiac consultation.

11. BEDAQUILINE - INDICATION MDR/RR-TB patients with resistance to any/all FQ OR to any/all SLI. XDR-TB patients. Mixed pattern resistant TB patients. Treatment failures of MDR-TB + FQ/SLI resistance OR XDR-TB. MDR/RR-TB patients with extensive pulmonary lesions, advanced disease and others deemed at higher baseline risk for poor outcomes.

12. STUDY DESIGN

13. Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis . Lancet 2018; 392: 821–34 12030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Treatment outcomes were significantly better with use of linezolid , later generation fluoroquinolones , bedaquiline , clofazimine , and carbapenems for treatment of multidrug-resistant tuberculosis.

14. DST guided regimen

15. ADVERSE DRUG REACTION - BDQ AST and/or ALT elevations Amylase and/or lipase elevations, Musculoskeletal system abnormalities Cardiac rhythm disturbances - QT interval monitoring Gastrointestinal disorders.

16. DELAMANID Nitroimidazole class. MOA- Blocks synthesis of mycolic acids and release nitric oxide (bactericidal). Half life – approx 36 hours. Recommended dose – 100 mg twice a day for 24 weeks

17. DELAMANID Inclusion criteria - adults aged > 18 years having pulmonary MDR-TB. Additional requirements non-pregnant females or females not on hormonal birth control methods (continue practicing birth control methods throughout the treatment period or have been post-menopausal for past 2 years patients with controlled stable arrhythmia can be considered after obtaining cardiac consultation.

18. DELAMANID - INDICATION MDR/RR-TB patients with resistance to any/all FQ OR to any/all SLI. XDR-TB patients. Mixed pattern resistant TB patients. Treatment failures of MDR-TB + FQ/SLI resistance OR XDR-TB. MDR/RR-TB patients with extensive pulmonary lesions, advanced disease and others deemed at higher baseline risk for poor outcomes.

19. DST guided regimen

20. ADVERSE DRUG REACTION - DLM QTc interval prolongation. Gastrointestinal system disorders.

21. DLM v/s BDQ No absolute contraindication for use in EP MDR-TB patients. WHO has issued an interim guideline in 2016 for the use of Delamanid in 6-17 years age group with a dosage of 50 mg BID (6-11 years) and 100 mg BID (12-17 years) for 6 months

22. THANK YOU