Delamanid when other anti-tuberculosis-treatment regimens failed due to resistance or tolerability

Expert Opin Pharmacother. 2015 Feb;16(2):253-61. doi: 10.1517/14656566.2015.973853. Epub 2014 Oct 18.

Abstract

Introduction: The limited availability of effective drugs causes difficulties in the management of multidrug-resistant tuberculosis (MDR-TB) and novel therapeutic agents are needed. Delamanid , a new nitro-hydro-imidazooxazole derivative, inhibits mycolic acid synthesis. This review covers the efficacy and safety of delamanid for MDR-TB.

Area covered: This paper reviews the pharmacological profile of delamanid and the results of clinical trials evaluating its efficacy for treating MDR-TB in combination with other anti-TB drugs. The drug's safety and tolerability profiles are also considered.

Expert opinion: Delamanid showed potent activity against drug-susceptible and -resistant Mycobacterium tuberculosis in both in vitro and in vivo studies. In clinical trials, the drug showed significant early bactericidal activity in pulmonary TB patients, and increased culture conversion after 2 months of treatment in combination with an optimized background regimen in MDR-TB patients. In addition, decreased mortality was observed in MDR-TB patients who received > 6 months of delamanid treatment. The drug was generally tolerable, but QT prolongation should be monitored carefully using electrocardiograms and potassium levels. Therefore, delamanid could be used as part of an appropriate combination regimen for pulmonary MDR-TB in adult patients when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability.

Keywords: antitubercular agents; delamanid; multidrug-resistant tuberculosis; tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use*
  • Clinical Trials as Topic
  • Drug Resistance, Bacterial*
  • Drug Therapy, Combination
  • Humans
  • Mycobacterium tuberculosis / drug effects
  • Nitroimidazoles / pharmacology
  • Nitroimidazoles / therapeutic use*
  • Oxazoles / pharmacology
  • Oxazoles / therapeutic use*
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant / drug therapy*
  • Tuberculosis, Pulmonary / drug therapy*

Substances

  • Antitubercular Agents
  • Nitroimidazoles
  • OPC-67683
  • Oxazoles