Bedaquiline as part of combination therapy in adults with pulmonary multi-drug resistant tuberculosis

Expert Rev Clin Pharmacol. 2016 Aug;9(8):1025-37. doi: 10.1080/17512433.2016.1200462. Epub 2016 Jun 27.

Abstract

Introduction: Few innovative anti-microbial products have been brought to market in recent years to combat the global multidrug resistant-tuberculosis (MDR-TB) epidemic. Bedaquiline, a novel oral diarylquinoline, was approved by the US FDA as a part of combination therapy in adults with pulmonary MDR-TB based on phase II trials.

Area covered: Pubmed searches were conducted using search terms bedaquiline, diarylquinoline, R207910, and TMC207 was performed. Supplementary sources included World Health Organization, Clinicaltrial.gov, US Food and Drug Administration. Bedaquiline is an ATP synthase inhibitor specific for M. tuberculosis and some nontuberculous mycobacteria. It is metabolized by CYP3A4 and it's drug exposure can be influenced by inducers and inhibitors of this enzyme. Phase II studies showed promising results on efficacy of bedaquiline when being used in combination with a background regimen for MDR-TB. Main safety concerns include QTc prolongation and hepatotoxicity. Phase III trials are ongoing to confirm efficacy findings from phase II studies and provide additional evidence of safety and efficacy. Expert commentary: Critical data for long-term efficacy and safety are incomplete and scarce, supporting the cautious use of bedaquiline.

Keywords: Bedaquiline; Mycobacterium tuberculosis; anti-tuberculosis drugs; multidrug-resistant tuberculosis; pharmacodynamics; pharmacokinetics.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Adult
  • Animals
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / adverse effects
  • Antitubercular Agents / therapeutic use
  • Cytochrome P-450 CYP3A / drug effects
  • Cytochrome P-450 CYP3A / metabolism
  • Diarylquinolines / administration & dosage
  • Diarylquinolines / adverse effects
  • Diarylquinolines / therapeutic use*
  • Drug Interactions
  • Drug Therapy, Combination
  • Humans
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / isolation & purification
  • Tuberculosis, Multidrug-Resistant / drug therapy*
  • Tuberculosis, Multidrug-Resistant / microbiology
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / microbiology

Substances

  • Antitubercular Agents
  • Diarylquinolines
  • bedaquiline
  • Cytochrome P-450 CYP3A