Deflazacort (original) (raw)

From Wikipedia, the free encyclopedia

Pharmaceutical drug

Pharmaceutical compound

Deflazacort
Clinical data
Trade names Emflaza, Calcort, others
AHFS/Drugs.com Monograph
Routes of administration By mouth
ATC code H02AB13 (WHO)
Legal status
Legal status UK: POM (Prescription only) US: ℞-only[1]
Pharmacokinetic data
Protein binding 40%
Metabolism By plasma esterases, to active metabolite
Elimination half-life 1.1–1.9 hours (metabolite)
Excretion Kidney (70%) and fecal (30%)
Identifiers
IUPAC name (11β,16β)-21-(Acetyloxy)-11-hydroxy-2′-methyl-5′_H_-pregna-1,4-dieno[17,16-_d_]oxazole-3,20-dione
CAS Number 14484-47-0 checkY
PubChem CID 189821
DrugBank DB11921 ☒N
ChemSpider 164861 ☒N
UNII KR5YZ6AE4B
KEGG D03671 checkY
ChEMBL ChEMBL1201891 ☒N
CompTox Dashboard (EPA) DTXSID9020378 Edit this at Wikidata
ECHA InfoCard 100.034.969 Edit this at Wikidata
Chemical and physical data
Formula C25H31NO6
Molar mass 441.524 g·mol−1
3D model (JSmol) Interactive image
SMILES O=C(OCC(=O)[C@]25/N=C(\O[C@@H]5C[C@H]1[C@H]4[C@H]([C@@H](O)C[C@@]12C)[C@]/3(/C=C\C(=O)\C=C\3CC4)C)C)C
InChI InChI=1S/C25H31NO6/c1-13-26-25(20(30)12-31-14(2)27)21(32-13)10-18-17-6-5-15-9-16(28)7-8-23(15,3)22(17)19(29)11-24(18,25)4/h7-9,17-19,21-22,29H,5-6,10-12H2,1-4H3/t17-,18-,19-,21+,22+,23-,24-,25+/m0/s1 ☒NKey:FBHSPRKOSMHSIF-GRMWVWQJSA-N ☒N
☒NcheckY (what is this?) (verify)

Deflazacort, sold under the brand name Calcort among others, is a glucocorticoid belonging to acetonides or O-isopropylidene derivative.[2] It is used as an anti-inflammatory and was patented in 1969[2] and approved for medical use in 1985.[3] The US Food and Drug Administration considers it to be a first-in-class medication for Duchenne Muscular Dystrophy.[4]

The manufacturer lists the following uses for deflazacort:[5]

In the United States, deflazacort is approved for the treatment of duchenne muscular dystrophy in people over the age of two.[6]

Deflazacort carries the risks common to all corticosteroids, including immune suppression, decreased bone density, steroid induced muscle atrophy, myopathy and endocrine insufficiency. In clinical trials, the most common side effects (>10% above placebo) were Cushing's-like appearance, weight gain, and increased appetite.[1]

Mechanism of action

[edit]

Deflazacort is an inactive prodrug which is metabolized rapidly to the active drug 21-desacetyldeflazacort.[7]

Deflazacort's potency is around 70–90% that of prednisone.[8] A 2017 review found its activity of 7.5 mg of deflazacort is approximately equivalent to 25 mg cortisone, 20 mg hydrocortisone, 5 mg of prednisolone or prednisone, 4 mg of methylprednisolone or triamcinolone, or 0.75 mg of betamethasone or dexamethasone. The review noted that the drug has a high therapeutic index, being used at initial oral doses ranging from 6 to 90 mg, and probably requires a 50% higher dose to induce the same demineralizing effect as prednisolone. Thus it has "a smaller impact on calcium metabolism than any other synthetic corticosteroid, and therefore shows a lower risk of growth rate retardation in children and of osteoporosis" in the elderly, and comparatively small effects on carbohydrate metabolism, sodium retention, and hypokalemia.[9]

Deflazacort was first introduced in 1969 to treat rheumatoid arthritis, nephritic syndrome, SLE, transplantation, polymyalgia rheumatica, sarcoidosis and juvenile chronic arthritis.[2]

In January 2015, the US Food and Drug Administration (FDA) granted fast track status to Marathon Pharmaceuticals to pursue approval of deflazacort as a potential treatment for Duchenne muscular dystrophy, a rare, "progressive and fatal disease" that affects boys.[10] Although deflazacort was approved by the FDA for use in treatment of Duchenne muscular dystrophy on February 9, 2017,[6][11] Marathon CEO announced on February 13, 2017, that the launch of deflazacort (Emflaza) would be delayed amidst controversy over the steep price Marathon was asking for the drug in the United States - $89,000 per year, which is "roughly 70 times" more than it would cost overseas.[12]

Society and culture

[edit]

The US Food and Drug Administration approved deflazacort to treat people aged five years of age and older with Duchenne muscular dystrophy, a rare genetic disorder that causes progressive muscle deterioration and weakness. Emflaza is a corticosteroid that works by decreasing inflammation and reducing the activity of the immune system.[6] NDA 208684 was approved in February 2017, as a Type 1- new molecular entity with orphan status.[13]

Deflazacort is available as an inexpensive generic. For example, in Canada, deflazacort can be purchased for around $1 per tablet.[14]

Deflazacort is sold in the United States under the brand name Emflaza after PTC Therapeutics, Inc. acquired all rights to Emflaza in March 2017.[15] Deflazacort is sold in the United Kingdom under the trade name Calcort;[8] in Brazil as Cortax, Decortil, Defcort and Deflanil; in India as Moaid, Zenflav, Defolet, DFZ, Decotaz, and DefZot; in Bangladesh as Xalcort; in Panama as Zamen; Spain as Zamene; and in Honduras as Flezacor.

  1. ^ a b "Emflaza- deflazacort tablet; Emflaza- deflazacort suspension". DailyMed. 18 June 2024. Retrieved 10 April 2025.
  2. ^ a b c Nayak S, Acharjya B (19 December 2008). "Deflazacort versus other glucocorticoids: a comparison". Indian Journal of Dermatology. 53 (4): 167–170. doi:10.4103/0019-5154.44786. PMC 2763756. PMID 19882026.
  3. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 486. ISBN 9783527607495.
  4. ^ New Drug Therapy Approvals 2017. U.S. Food and Drug Administration (FDA) (Report). January 2018. Archived from the original (PDF) on 14 September 2019. Retrieved 16 September 2020.
  5. ^ "Refla: deflazacort" (PDF).
  6. ^ a b c "FDA approves drug to treat Duchenne muscular dystrophy". U.S. Food and Drug Administration (FDA) (Press release). Archived from the original on 30 May 2019. Retrieved 18 February 2017. Public Domain This article incorporates text from this source, which is in the public domain.
  7. ^ Möllmann H, Hochhaus G, Rohatagi S, Barth J, Derendorf H (July 1995). "Pharmacokinetic/pharmacodynamic evaluation of deflazacort in comparison to methylprednisolone and prednisolone". Pharmaceutical Research. 12 (7): 1096–100. doi:10.1023/a:1016287104656. PMID 7494809. S2CID 9920545.
  8. ^ a b "Calcort". electronic Medicines Compendium. 11 June 2008. Archived from the original on 24 December 2012. Retrieved on October 28, 2008.
  9. ^ Parente L (January 2017). "Deflazacort: therapeutic index, relative potency and equivalent doses versus other corticosteroids". BMC Pharmacology & Toxicology. 18 (1): 1. doi:10.1186/s40360-016-0111-8. PMC 5216559. PMID 28057083.
  10. ^ Hirst EJ (19 January 2015), Duchenne muscular dystrophy drug could get OK for U.S. sales in 2016, The Chicago Tribune, retrieved 13 February 2017, has been shown to prolong lives ... a progressive and fatal disease that has no drug treatment available in the US
  11. ^ "Marathon Pharmaceuticals to Charge $89,000 for Muscular Dystrophy Drug". The Wall Street Journal. 10 February 2017. Archived from the original on 10 February 2017. Retrieved 10 February 2017.
  12. ^ Walker J, Pulliam S (13 February 2017), "Marathon Pharmaceuticals to Charge $89,000 for Muscular Dystrophy Drug After 70-Fold Increase", The Wall Street Journal, retrieved 13 February 2017, FDA-approved deflazacort treats rare type of disease affecting boys
  13. ^ "Drugs@FDA: FDA Approved Drug Products". U.S. Food and Drug Administration (FDA).
  14. ^ Mukherjee CS (10 February 2017). "Brainstorm Health Daily". Retrieved 13 February 2017.
  15. ^ "PTC Therapeutics Completes Acquisition of Emflaza for the Treatment of Duchenne Muscular Dystrophy in the U.S." PTC Therapeutics, Inc.