Bedaquiline

Tuberculosis management - Bedaquiline

1. Bedaquiline

2. -Chemical structure of bedaquiline-Formula C36H35BrN2O6

3. Structure of ATP synthase 1)F1 complex (Catalytic) 2)F0 complex(Proton pump)

4. F1 complex 3 alpha and 3 beta chains form complex that catalyses ATP synthesis. Gamma epsilon forms central stalk Delta hold structure

5. F0 complex Proton pump 10-14 C subunits and A subunit interact to form a channel

6. Mycobacterium ATP synthase complex

7. Mechanism of action Diaryl quinoline. It inhibits mycobacterial ATP synthase,an enzyme necessary for energy production in tuberculous bacilli.

8. History of the drug It was discovered by a team lead by Koen Andries at Janssen pharmaceutica. It is manufactured by Johnson and Johnson who sought approval of the drug. In 2016 the WHO came under criticism for recommending it as an essential medicine.

9. Brand name-Sirturo Metabolism-Liver,CYP3A4
Half life-5.5 months Route of administration-Oral
Excretion-Faecal Cost in India-Earlier it was 400 US dollars for 6 months therapy,now Johnson and Johnson company has reduced it by 32 percent to 340 US dollars for 6 months.

10. Use-MDR TB
Bedaquiline+Moxifloxacin+Pretomanid+Pyrazinamide Dose-400 mg daily for 2 weeks followed by 200 mg thrice weekly for 22 weeks

11. Side effects 1)Anorexia 2)Nausea
3) Hepatotoxicity 4) Arthralgia Very important-Black box warning as it may cause QTC prolongation,arrythmias which may even lead to death.

12. Normal Qtc interval-0.4-0.44 seconds Bedaquiline->0.48 seconds

13. Bedaquiline monitoring ECG monitoring at baseline,2,12 and 24 weeks after starting treatment. K,Ca,Mg Monitored Avoid rifampicin-Enzyme inducer Ketoconacole-Enzyme inhibitor

14. Thank you