Deflazacort: Difference between revisions

{{short description|Pharmaceutical drug}}

{{Infobox drug

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 447631837

| IUPAC_name = (11β,16β)-21-(Acetyloxy)-11-hydroxy-2′-methyl-5′''H''-pregna-1,4-dieno[17,16-''d'']oxazole-3,20-dione

| image = Deflazacort structure.svg

| tradename = Emflaza, Calcort, others

| Drugs.com = {{drugs.com|monograph|deflazacort}}

| pregnancy_US = N

| legal_UK = POM

| legal_US = Rx-only

| routes_of_administration = [[Oral administration|By mouth]]

| excretion = [[Kidney]] (70%) and fecal (30%)

| CAS_number_Ref = {{cascite|correct|??}}

| PubChem = 189821

| DrugBank_Ref = {{drugbankcite|changed|drugbank}}

| DrugBank = DB11921

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 1201891

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 164861

| 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

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 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

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = FBHSPRKOSMHSIF-GRMWVWQJSA-N

| C=25 | H=31 | N=1 | O=6

'''Deflazacort''' (trade name '''Calcort''' among others) is a [[glucocorticoid]] belonging to acetonides or O-isopropylidene derivative.<ref name="ReferenceA">{{Cite journal|title=Deflazacort versus other glucocorticoids: A comparison|first1=Surajit|last1=Nayak|first2=Basanti|last2=Acharjya|date=December 19, 2008|journal=Indian Journal of Dermatology|volume=53|issue=4|pages=167–170|doi=10.4103/0019-5154.44786|pmid=19882026|pmc=2763756 |doi-access=free }}</ref> It is used as an [[anti-inflammatory]] and was patented in 1969<ref name="ReferenceA"/> and approved for medical use in 1985.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR | name-list-style = vanc |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=486 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA486 |language=en}}</ref> The U.S. [[Food and Drug Administration]] (FDA) considers it to be a [[first-in-class medication]] for [[Duchenne Muscular Dystrophy]].<ref>{{cite report | title=New Drug Therapy Approvals 2017 | website=U.S. [[Food and Drug Administration]] (FDA) | date=January 2018 | url=https://www.fda.gov/media/110526/download | format=PDF | access-date=16 September 2020}}</ref>

== Medical uses ==

The manufacturer lists the following uses for deflazacort:<ref>{{cite web | url = http://julpharbd.com/products/pdf/1502065105738588954.pdf| title = Refla: deflazacort }}</ref>

{{columns-list|colwidth=30em|

* [[Acute interstitial nephritis]]

* [[Anaphylaxis]]

* [[Asthma]]

* [[Autoimmune haemolytic anaemia]]

* [[Bullous pemphigoid]]

* Mixed [[connective tissue disease]] (other than systemic sclerosis)

* [[Crohn's disease]]

* [[Dermatomyositis]]

* [[Idiopathic thrombocytopenic purpura]]

* [[Juvenile chronic arthritis]]

* Severe [[hypersensitivity]] reactions

* [[Immunosuppression]] in transplantation

* Acute and [[lymphatic leukaemia]]

* Malignant [[lymphoma]]

* [[Multiple myeloma]]

* [[Muscular dystrophy]]

* [[Rheumatoid arthritis]]

* [[Polymyalgia rheumatica]]

* [[Nephrotic syndrome]]

* [[Pemphigus]]

* [[Polyarteritis nodosa]]

* [[Pyoderma gangrenosum]]

* [[Sarcoidosis]]

* [[Systemic lupus erythematosus]]

* [[Ulcerative colitis]]

}}

In the United States, deflazacort is approved for the treatment of [[duchenne muscular dystrophy]] in people over the age of two.<ref name="FDA PR">{{cite press release |title=FDA approves drug to treat Duchenne muscular dystrophy|url=https://www.fda.gov/news-events/press-announcements/fda-approves-drug-treat-duchenne-muscular-dystrophy |website=U.S. Food and Drug Administration |access-date=18 February 2017 }} {{PD-notice}}</ref>

== Adverse effects ==

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.<ref>{{cite web | title=Emflaza- deflazacort tablet Emflaza- deflazacort suspension | website=DailyMed | date=29 January 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31b347d2-f156-4055-9d8f-7cf0df420296 | access-date=17 September 2020}}</ref>

== Pharmacology ==

{{main|Glucocorticoid#Pharmacology}}

=== Mechanism of action ===

{{further|Glucocorticoid#Mechanism of action}}

Deflazacort is an inactive [[prodrug]] which is [[drug metabolism|metabolized]] rapidly to the active drug 21-desacetyldeflazacort.<ref>{{cite journal | vauthors = Möllmann H, Hochhaus G, Rohatagi S, Barth J, Derendorf H | title = Pharmacokinetic/pharmacodynamic evaluation of deflazacort in comparison to methylprednisolone and prednisolone | journal = Pharmaceutical Research | volume = 12 | issue = 7 | pages = 1096–100 | date = July 1995 | pmid = 7494809 | doi = 10.1023/a:1016287104656 | s2cid = 9920545 }}</ref>

=== Relative potency ===

Deflazacort's potency is around 70–90% that of [[prednisone]].<ref name="eMC"/> A 2017 review found its activity of 7.5&nbsp;mg of deflazacort is approximately equivalent to 25&nbsp;mg [[cortisone]], 20&nbsp;mg [[hydrocortisone]], 5&nbsp;mg of [[prednisolone]] or [[prednisone]], 4&nbsp;mg of [[methylprednisolone]] or [[triamcinolone]], or 0.75&nbsp;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&nbsp;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.<ref>{{cite journal | vauthors = Parente L | title = Deflazacort: therapeutic index, relative potency and equivalent doses versus other corticosteroids | journal = BMC Pharmacology & Toxicology | volume = 18 | issue = 1 | pages = 1 | date = January 2017 | pmid = 28057083 | pmc = 5216559 | doi = 10.1186/s40360-016-0111-8 | doi-access = free }}</ref>

== History ==

Deflazacort was first introduced in 1969 to treat rheumatoid arthritis, nephritic syndrome, SLE, transplantation, polymyalgia rheumatica, sarcoidosis and juvenile chronic arthritis.<ref name="ReferenceA"/>

In January 2015, the FDA granted [[fast track (FDA)|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.<ref name="chicagotribune_marathon_2015">

{{citation|quote= has been shown to prolong lives ... a progressive and fatal disease that has no drug treatment available in the US|title=Duchenne muscular dystrophy drug could get OK for U.S. sales in 2016

|url=http://www.chicagotribune.com/business/ct-marathon-muscular-dystrophy-drug-0119-biz-20150119-story.html#page=1|publisher=The Chicago Tribune| vauthors = Hirst EJ |date= January 19, 2015|access-date=February 13, 2017 }}</ref> Although deflazacort was approved by the FDA for use in treatment of Duchenne muscular dystrophy on February 9, 2017,<ref>{{cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm540945.htm|title=FDA approves drug to treat Duchenne muscular dystrophy |date=2017-02-09|website=www.fda.gov|language=en|access-date=2017-02-10}}</ref><ref>{{cite web|url=https://www.wsj.com/articles/marathon-pharmaceuticals-to-charge-89-000-for-muscular-dystrophy-drug-1486738267|title=Marathon Pharmaceuticals to Charge $89,000 for Muscular Dystrophy Drug|date=2017-02-10|website=www.wsj.com|language=en|archive-url=https://web.archive.org/web/20170210155321/https://www.wsj.com/articles/marathon-pharmaceuticals-to-charge-89-000-for-muscular-dystrophy-drug-1486738267|archive-date=2017-02-10|url-status=dead|access-date=2017-02-10}}</ref> 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.<ref name="WSJ_Marathon_deflazacort_2017a">{{citation |quote=FDA-approved deflazacort treats rare type of disease affecting boys |title=Marathon Pharmaceuticals to Charge $89,000 for Muscular Dystrophy Drug After 70-Fold Increase |url=https://www.wsj.com/articles/marathon-pharmaceuticals-to-charge-89-000-for-muscular-dystrophy-drug-1486738267|publisher=The Wall Street Journal| vauthors = Walker J, Pulliam S |date= February 13, 2017 |access-date=February 13, 2017 }}</ref> 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.<ref>{{cite web | url = http://fortune.com/2017/02/10/brainstorm-health-daily-02-10/ | title = Brainstorm Health Daily | date = February 10, 2017 |access-date= February 13, 2017 | vauthors = Mukherjee CS }}</ref>

Deflazacort is sold in the United States under the brand name Emflaza after PTC Therapeutics, Inc. acquired all rights to Emflaza on March 16, 2017.<ref>{{cite web|url=http://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-completes-acquisition-emflazatm-treatment|title=PTC Therapeutics Completes Acquisition of Emflaza for the Treatment of Duchenne Muscular Dystrophy in the U.S.|website=PTC Therapeutics, Inc.}}</ref> Deflazacort is sold in the United Kingdom under the trade name Calcort;<ref name="eMC">{{cite web | url = http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?documentid=20915 | archive-url = https://archive.today/20121224012214/http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?documentid=20915 | url-status = dead | archive-date = December 24, 2012 | title = Calcort | date = June 11, 2008 | publisher = electronic Medicines Compendium }} Retrieved on October 28, 2008.</ref> 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.<ref name=Centralx>{{cite web | url = http://www.bulas.med.br/index.pl?C=A&V=66506F737449443D39333933266163743D73686F7752656164436F6D6D656E7473<!--convenience link--> | title = Substâncias: DEFLAZACORT | year = 2008 | publisher = Centralx|language=pt}} Retrieved on October 28, 2008.</ref>

The U.S. Food and Drug Administration approved deflazacort to treat people age five 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.<ref name="FDA PR" /> NDA 208684 was approved on February 9, 2017, as a Type 1- new molecular entity with orphan status.<ref>{{cite web|url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=208684|title=Drugs@FDA: FDA Approved Drug Products|website=U.S. [[Food and Drug Administration]] (FDA)}}</ref>

== References ==

{{Reflist}}

== External links ==

* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/deflazacort | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Deflazacort }}

{{Other drugs for disorders of the musculo-skeletal system}}

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