Deflazacort

Deflazacort (trade name Calcort among others) is a glucocorticoid used as an anti-inflammatory and immunosuppressant.

Deflazacort
Clinical data
Trade namesEmflaza, Calcort, others
AHFS/Drugs.comInternational Drug Names
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding40%
MetabolismBy plasma esterases, to active metabolite
Elimination half-life1.1–1.9 hours (metabolite)
ExcretionRenal (70%) and fecal (30%)
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.034.969
Chemical and physical data
FormulaC25H31NO6
Molar mass441.517 g/mol g·mol−1
3D model (JSmol)
 NY (what is this?)  (verify)

It was patented in 1965 and approved for medical use in 1985.[1]

Medical uses

The manufacturer lists the following uses for deflazacort:[2]

In the United States, deflazacort is approved for the treatment of duchenne muscular dystrophy in people over the age of 5.[3]

Adverse effects

Deflazacort carries the risks common to all corticosteroids, including immune suppression, decreased bone density, and endocrine insufficiency. In clinical trials, the most common side effects (>10% above placebo) were Cushing's-like appearance, weight gain, and increased appetite.[4]

Pharmacology

Mechanism of action
Further information: Glucocorticoid § Mechanism of action

Deflazacort is an inactive prodrug which is metabolized rapidly to the active drug 21-desacetyldeflazacort.[5]

Relative potency

Deflazacort's potency is around 70–90% that of prednisone.[6] 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.[7]

History

In January 2015, the 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.[8] Although deflazacort was approved by the FDA for use in treatment of Duchenne muscular dystrophy on February 9, 2017,[9][10] 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.[11] Because deflazacort is an older drug which has been long-approved in some other countries, it is now available in many places as an inexpensive generic. For example, in Canada deflazacort can be purchased for around $1 per tablet.[12]

Deflazacort is sold in the United States under the trade name Emflaza after a company called PTC Therapeutics, Inc. acquired all rights to Emflaza on March 16, 2017.[13] Deflazacort is sold in the United Kingdom under the trade name Calcort;[6] 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.[14]

The U.S. Food and Drug Administration approved Emflaza (deflazacort) tablets and oral suspension to treat patients age 5 years and older with Duchenne muscular dystrophy (DMD), 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.[15] NDA 208684 was approved on February 9, 2017 as a Type 1- new molecular entity with orphan status.[16]

References
  1. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 486. ISBN 9783527607495.
  2. "Refla: deflazacort" (PDF).
  3. Commissioner, Office of the. "Press Announcements - FDA approves drug to treat Duchenne muscular dystrophy". www.fda.gov. Retrieved 18 February 2017.
  4. "Info" (PDF). www.accessdata.fda.gov. 2017.
  5. Möllmann, H; Hochhaus, G; Rohatagi, S; Barth, J; Derendorf, H (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.
  6. "Calcort". electronic Medicines Compendium. June 11, 2008. Retrieved on October 28, 2008.
  7. Luca Parente (2017). "Deflazacort: therapeutic index, relative potency and equivalent doses versus other corticosteroids". BMC Pharmacol Toxicol. doi:10.1186/s40360-016-0111-8. PMC 5216559. Missing or empty |url= (help)
  8. Ellen Jean Hirst (January 19, 2015), Duchenne muscular dystrophy drug could get OK for U.S. sales in 2016, The Chicago Tribune, retrieved February 13, 2017, has been shown to prolong lives ... a progressive and fatal disease that has no drug treatment available in the US
  9. "FDA approves drug to treat Duchenne muscular dystrophy". www.fda.gov. 2017-02-09. Retrieved 2017-02-10.
  10. "Marathon Pharmaceuticals to Charge $89,000 for Muscular Dystrophy Drug". www.wsj.com. 2017-02-10. Archived from the original on 2017-02-10. Retrieved 2017-02-10.
  11. Joseph Walker and Susan Pulliam (February 13, 2017), Marathon Pharmaceuticals to Charge $89,000 for Muscular Dystrophy Drug After 70-Fold Increase, The Wall Street Journal, retrieved February 13, 2017, FDA-approved deflazacort treats rare type of disease affecting boysCS1 maint: uses authors parameter (link)
  12. Clifton Sy Mukherjee (February 10, 2017). "Brainstorm Health Daily". Retrieved February 13, 2017.
  13. "PTC Therapeutics Completes Acquisition of Emflaza™ for the Treatment of Duchenne Muscular Dystrophy in the U.S." PTC Therapeutics, Inc.
  14. "Substâncias: DEFLAZACORT" (in Portuguese). Centralx. 2008. Retrieved on October 28, 2008.
  15. Commissioner, Office of the. "Press Announcements - FDA approves drug to treat Duchenne muscular dystrophy". www.fda.gov.
  16. "Drugs@FDA: FDA Approved Drug Products". www.accessdata.fda.gov.
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