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Bedaquiline: a novel diarylquinoline for multidrug-resistant tuberculosis.
Ann Pharmacother 2014; 48(1):107-15AP

Abstract

OBJECTIVE

To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, dosage, and administration of bedaquiline, a novel oral diarylquinoline antimycobacterial agent approved by the Food and Drug Administration for the treatment of adults with pulmonary multidrug-resistant tuberculosis (MDR-TB).

DATA SOURCES

A search of PubMed (January 2004-May 2013) and International Pharmaceutical Abstracts (January 2004-May 2013) using the search terms bedaquiline, diarylquinoline, R207910, and TMC207 was performed. Supplementary sources included proceedings of the Union World Conference on Lung Health.

STUDY SELECTION AND DATA EXTRACTION

Preclinical data as well as Phase 1 and 2 studies published in English were evaluated.

DATA SYNTHESIS

Bedaquiline possesses a unique mechanism of action that disrupts the activity of the mycobacterial adenosine triphosphate synthase. Clinical trials have been conducted evaluating the use of bedaquiline in combination with a background regimen for the treatment of adults with pulmonary MDR-TB. Bedaquiline has an excellent in vitro activity against Mycobacterium tuberculosis, including multidrug resistant M tuberculosis; however, its side effect profile limits its use against MDR-TB when no other effective regimen can be provided. Bedaquiline carries Black Box warnings for increased risk of unexplained mortality and QT prolongation. Bedaquiline is metabolized via the CYP3A4 isoenzyme and thus interacts with rifamycins and several antiretrovirals.

CONCLUSIONS

In an era of emerging resistance and given the suboptimal efficacy and toxicity of currently available regimens for MDR-TB, bedaquiline represents a great addition to the existing armamentarium of anti-TB agents particularly in areas of the world where the disease is endemic.

Authors+Show Affiliations

Palm Beach Atlantic University, West Palm Beach, FL, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

24259600

Citation

Chahine, Elias B., et al. "Bedaquiline: a Novel Diarylquinoline for Multidrug-resistant Tuberculosis." The Annals of Pharmacotherapy, vol. 48, no. 1, 2014, pp. 107-15.
Chahine EB, Karaoui LR, Mansour H. Bedaquiline: a novel diarylquinoline for multidrug-resistant tuberculosis. Ann Pharmacother. 2014;48(1):107-15.
Chahine, E. B., Karaoui, L. R., & Mansour, H. (2014). Bedaquiline: a novel diarylquinoline for multidrug-resistant tuberculosis. The Annals of Pharmacotherapy, 48(1), pp. 107-15. doi:10.1177/1060028013504087.
Chahine EB, Karaoui LR, Mansour H. Bedaquiline: a Novel Diarylquinoline for Multidrug-resistant Tuberculosis. Ann Pharmacother. 2014;48(1):107-15. PubMed PMID: 24259600.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bedaquiline: a novel diarylquinoline for multidrug-resistant tuberculosis. AU - Chahine,Elias B, AU - Karaoui,Lamis R, AU - Mansour,Hanine, Y1 - 2013/11/01/ PY - 2013/11/22/entrez PY - 2013/11/22/pubmed PY - 2014/9/10/medline KW - MDR-TB KW - antimycobacterial KW - bedaquiline KW - diarylquinoline KW - multi-drug resistant tuberculosis SP - 107 EP - 15 JF - The Annals of pharmacotherapy JO - Ann Pharmacother VL - 48 IS - 1 N2 - OBJECTIVE: To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, dosage, and administration of bedaquiline, a novel oral diarylquinoline antimycobacterial agent approved by the Food and Drug Administration for the treatment of adults with pulmonary multidrug-resistant tuberculosis (MDR-TB). DATA SOURCES: A search of PubMed (January 2004-May 2013) and International Pharmaceutical Abstracts (January 2004-May 2013) using the search terms bedaquiline, diarylquinoline, R207910, and TMC207 was performed. Supplementary sources included proceedings of the Union World Conference on Lung Health. STUDY SELECTION AND DATA EXTRACTION: Preclinical data as well as Phase 1 and 2 studies published in English were evaluated. DATA SYNTHESIS: Bedaquiline possesses a unique mechanism of action that disrupts the activity of the mycobacterial adenosine triphosphate synthase. Clinical trials have been conducted evaluating the use of bedaquiline in combination with a background regimen for the treatment of adults with pulmonary MDR-TB. Bedaquiline has an excellent in vitro activity against Mycobacterium tuberculosis, including multidrug resistant M tuberculosis; however, its side effect profile limits its use against MDR-TB when no other effective regimen can be provided. Bedaquiline carries Black Box warnings for increased risk of unexplained mortality and QT prolongation. Bedaquiline is metabolized via the CYP3A4 isoenzyme and thus interacts with rifamycins and several antiretrovirals. CONCLUSIONS: In an era of emerging resistance and given the suboptimal efficacy and toxicity of currently available regimens for MDR-TB, bedaquiline represents a great addition to the existing armamentarium of anti-TB agents particularly in areas of the world where the disease is endemic. SN - 1542-6270 UR - https://www.unboundmedicine.com/medline/citation/24259600/Bedaquiline:_a_novel_diarylquinoline_for_multidrug_resistant_tuberculosis_ L2 - http://journals.sagepub.com/doi/full/10.1177/1060028013504087?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -