Bedaquiline: a novel antitubercular agent for the treatment of multidrug-resistant tuberculosis

Pharmacotherapy. 2014 Nov;34(11):1187-97. doi: 10.1002/phar.1482. Epub 2014 Sep 9.


Bedaquiline is a diarylquinoline antitubercular drug with a novel mechanism of action against Mycobacterium tuberculosis. Bedaquiline works by inhibiting bacterial adenosine triphosphate (ATP) synthase and represents the first novel class of antituberculosis agents in more than 40 years. Bedaquiline is indicated for the treatment of multidrug-resistant tuberculosis (MDR TB) in combination with at least three other antitubercular drugs when no other effective regimen is available. The recommended bedaquiline dosage is 400 mg orally once/day for 2 weeks followed by 200 mg orally 3 times/week for 22 weeks. Bedaquiline should be administered with food, which increases the bioavailability 2-fold. Bedaquiline is metabolized by cytochrome P450 isoenzyme 3A4 and is impacted by both inducers and inhibitors of this isoenzyme. Concentration-dependent bactericidal activity was observed in laboratory and murine studies. Accelerated approval was granted in the United States and European Union based on the results of two phase IIb clinical studies that used sputum culture clearance as a surrogate end point for clinical efficacy. These studies showed greater sputum culture clearance up to week 24 for the bedaquiline group compared with placebo. Common adverse events in clinical trials included nausea, arthralgia, and headache. Serious adverse events included elevated serum transaminase levels and rate-corrected QT-interval prolongation. Unexplained higher mortality was seen in patients receiving bedaquiline versus those receiving placebo. Bedaquiline is a novel agent with a unique mechanism of action and has the potential to meet a great need in patients with MDR TB who have no other treatment options. Due to safety concerns and limited clinical information, phase III trials are needed to fully determine its place in therapy.

Keywords: ATP synthase; MDR TB; R207910; TMC207; bedaquiline; diarylquinoline; multidrug-resistant tuberculosis; tuberculosis.

Publication types

  • Review

MeSH terms

  • ATP Synthetase Complexes / antagonists & inhibitors*
  • Animals
  • Antitubercular Agents / adverse effects
  • Antitubercular Agents / pharmacokinetics
  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use*
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proton-Translocating ATPases
  • Diarylquinolines / adverse effects
  • Diarylquinolines / pharmacokinetics
  • Diarylquinolines / pharmacology
  • Diarylquinolines / therapeutic use*
  • Drug Interactions
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / pharmacokinetics
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / enzymology
  • Mycobacterium tuberculosis / growth & development
  • Practice Guidelines as Topic
  • Tuberculosis, Multidrug-Resistant / drug therapy*
  • Tuberculosis, Multidrug-Resistant / metabolism


  • Antitubercular Agents
  • Bacterial Proteins
  • Diarylquinolines
  • Drugs, Investigational
  • Enzyme Inhibitors
  • bedaquiline
  • ATP Synthetase Complexes
  • ATP synthase subunit C, Mycobacterium tuberculosis
  • Bacterial Proton-Translocating ATPases