Delamanid

Delamanid
Names
Trade namesDeltyba
Other namesOPC-67683
IUPAC name
  • (2R)-2-Methyl-6-nitro-2-[(4-{4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl}phenoxy)methyl]-2,3-dihydroimidazo[2,1-b][1,3]oxazole
Clinical data
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Routes of
use		by mouth (film-coated tablets)
Defined daily dose0.2 gram[1]
External links
AHFS/Drugs.comInternational Drug Names
Legal
License data
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetics
Protein binding≥99.5%
Metabolismin plasma by albumin, in liver
by CYP3A4 (to a lesser extent)
Elimination half-life30–38 hours
Excretionnot excreted in urine[2]
Chemical and physical data
FormulaC25H25F3N4O6
Molar mass534.492 g·mol−1
3D model (JSmol)
SMILES
  • FC(F)(F)Oc5ccc(OC4CCN(c3ccc(OC[C@@]2(Oc1nc(cn1C2)[N+]([O-])=O)C)cc3)CC4)cc5
InChI
  • InChI=1S/C25H25F3N4O6/c1-24(15-31-14-22(32(33)34)29-23(31)38-24)16-35-18-4-2-17(3-5-18)30-12-10-20(11-13-30)36-19-6-8-21(9-7-19)37-25(26,27)28/h2-9,14,20H,10-13,15-16H2,1H3/t24-/m1/s1
  • Key:XDAOLTSRNUSPPH-XMMPIXPASA-N

Delamanid, sold under the brand name Deltyba, is a medication used to treat tuberculosis.[3] Specifically it is used, along with other antituberculosis medications, for active multidrug-resistant tuberculosis.[3] It is taken by mouth.[3]

Common side effects include headache, dizziness, and nausea.[4] Other side effects include QT prolongation.[3] It has not been studied in pregnancy as of 2016.[5] Delamanid works by blocking the manufacture of mycolic acids thus destabilising the bacterial cell wall.[6] It is in the nitroimidazole class of medications.[7]

Delamanid was approved for medical use in 2014 in Europe, Japan, and South Korea.[8] It is on the World Health Organization's List of Essential Medicines.[9] As of 2016 the Stop TB Partnership had an agreement to get the medication for US$1,700 per six month for use in more than 100 countries.[10]

Medical uses

Delamanid is used, along with other antituberculosis medications, for active multidrug-resistant tuberculosis.[3]

Dosage

The defined daily dose is 0.2 gram (by mouth).[1]

Side effects

Common side effects include headache, dizziness, and nausea.[4] Other side effects include QT prolongation.[3] It has not been studied in pregnancy as of 2016.[5]

Interactions

Delamanid is metabolised by the liver enzyme CYP3A4; therefore strong inducers of this enzyme can reduce its effectiveness.[11]

History

In phase II clinical trials, the drug was used in combination with standard treatments, such as four or five of the drugs ethambutol, isoniazid, pyrazinamide, rifampicin, aminoglycoside antibiotics, and quinolones. Healing rates (measured as sputum culture conversion) were significantly better in patients who additionally took delamanid.[12][13]

The European Medicines Agency (EMA) recommended conditional marketing authorization for delamanid in adults with multidrug-resistant pulmonary tuberculosis without other treatment options because of resistance or tolerability. The EMA considered the data show that the benefits of delamanid outweigh the risks, but that additional studies were needed on the long-term effectiveness.[14]

Society and culture

The medication was not readily available globally as of 2015.[3] It was believed that pricing will be similar to bedaquiline, which for six months is approximately US$900 in low income countries, US$3,000 in middle income countries, and US$30,000 in high income countries.[3] As of 2016 the Stop TB Partnership had an agreement to get the medication for US$1,700 per six month.[10]

See also

References

  1. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 31 October 2020. Retrieved 20 September 2020.
  2. ↑ "Deltyba (delamanid): Summary of Product Characteristics. 5.2. Pharmacokinetic Properties" (PDF). Otsuka Novel Products GmbH. p. 10. Archived (PDF) from the original on 17 August 2016. Retrieved 9 July 2016.
  3. 1 2 3 4 5 6 7 8 World Health Organization (2015). The selection and use of essential medicines. Twentieth report of the WHO Expert Committee 2015 (including 19th WHO Model List of Essential Medicines and 5th WHO Model List of Essential Medicines for Children). Geneva: World Health Organization. pp. 30–1. hdl:10665/189763. ISBN 9789241209946. ISSN 0512-3054. WHO technical report series;994.
  4. 1 2 Side Effects of Drugs Annual: A Worldwide Yearly Survey of New Data in Adverse Drug Reactions. Elsevier. 2016. p. 284. ISBN 9780444638892. Archived from the original on 2016-12-20.
  5. 1 2 Cohen, Jonathan; Powderly, William G.; Opal, Steven M. (2016). Infectious Diseases. Elsevier Health Sciences. p. 284. ISBN 9780702063381. Archived from the original on 2016-12-20.
  6. ↑ Blair, HA; Scott, LJ (January 2015). "Delamanid: a review of its use in patients with multidrug-resistant tuberculosis". Drugs. 75 (1): 91–100. doi:10.1007/s40265-014-0331-4. PMID 25404020.
  7. ↑ Cavalcanti, Milena de Paiva; Pereira, Valeria Rego Alves; Dessein, Alain Joseph Jacques (2017). Tropical Diseases: An Overview of Major Diseases Occurring in the Americas. Bentham Science Publishers. p. 461. ISBN 9781681085876. Archived from the original on 2018-04-14. Retrieved 2018-04-14.
  8. ↑ Fischer, Janos (2016). Successful Drug Discovery. John Wiley & Sons. p. 139. ISBN 9783527341153. Archived from the original on 2016-12-20.
  9. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  10. 1 2 "Stop TB Partnership | "Stop TB Partnership's Global Drug Facility jumpstarts access to new drugs for MDR-TB with innovative public-private partnerships". www.stoptb.org. Archived from the original on 16 January 2017. Retrieved 15 January 2017.
  11. ↑ Pharmazeutische Zeitung: Delamanid: Neuer Wirkstoff gegen multiresistente TB Archived 2015-09-24 at the Wayback Machine, 9 May 2014. (in German)
  12. ↑ H. Spreitzer (18 February 2013). "Neue Wirkstoffe – Bedaquilin und Delamanid". Österreichische Apothekerzeitung (in German) (4/2013): 22.{{cite journal}}: CS1 maint: unrecognized language (link)
  13. ↑ Gler, M. T.; Skripconoka, V.; Sanchez-Garavito, E.; Xiao, H.; Cabrera-Rivero, J. L.; Vargas-Vasquez, D. E.; Gao, M.; Awad, M.; Park, S. K.; Shim, T. S.; Suh, G. Y.; Danilovits, M.; Ogata, H.; Kurve, A.; Chang, J.; Suzuki, K.; Tupasi, T.; Koh, W. J.; Seaworth, B.; Geiter, L. J.; Wells, C. D. (2012). "Delamanid for Multidrug-Resistant Pulmonary Tuberculosis". New England Journal of Medicine. 366 (23): 2151–2160. doi:10.1056/NEJMoa1112433. PMID 22670901.
  14. ↑ Drug Discovery & Development. EMA Recommends Two New Tuberculosis Treatments. Archived 2013-12-03 at the Wayback Machine November 22, 2013.
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