dexamethasone

{{Short description|Corticosteroid medication}}

{{Use dmy dates|date=December 2023}}

{{Use American English|date=July 2020}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Infobox drug

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 443584169

| image = Dexamethasone structure.svg

| image_class = skin-invert-image

| width =

| alt = Skeletal formula of dexamethasone

| image2 = Dexamethasone ball-and-stick model from xtal 2007.png

| width2 =

| alt2 = Ball-and-stick model of the dexamethasone molecule

| caption =

| pronounce =

| tradename = Decadron, Ozurdex, Dexycu, others

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

| MedlinePlus = a682792

| DailyMedID = Dexamethasone

| pregnancy_AU = A

| pregnancy_AU_comment = {{cite web | title=Prescribing medicines in pregnancy database | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/products/medicines/find-information-about-medicine/prescribing-medicines-pregnancy-database | access-date=17 April 2025}}

| pregnancy_category =

| routes_of_administration = By mouth, intravenous, intramuscular, subcutaneous, intraosseous, intravitreal, eye drop

| class =

| ATC_prefix = A01

| ATC_suffix = AC02

| ATC_supplemental = {{ATC|C05|AA09}}, {{ATC|D07|AB19}}, {{ATC|D10|AA03}}, {{ATC|H02|AB02}}, {{ATC|R01|AD03}}, {{ATC|S01|BA01}}, {{ATC|S02|BA06}}, {{ATC|S03|BA01}}

| legal_AU = S4

| legal_AU_comment = {{cite web |title=Dexamethasone Juno (Juno Pharmaceuticals Pty Ltd) |url=https://www.tga.gov.au/resources/prescription-medicines-registrations/dexamethasone-juno-juno-pharmaceuticals-pty-ltd |website=Department of Health and Aged Care |archive-url=https://web.archive.org/web/20230318025927/https://www.tga.gov.au/resources/prescription-medicines-registrations/dexamethasone-juno-juno-pharmaceuticals-pty-ltd |archive-date=18 March 2023 |url-status=live}}

| legal_BR =

| legal_BR_comment =

| legal_CA = Rx-only

| legal_CA_comment =

| legal_DE =

| legal_DE_comment =

| legal_NZ =

| legal_NZ_comment =

| legal_UK = POM

| legal_UK_comment =

| legal_US = Rx-only

| legal_US_comment = {{cite web | title=Ozurdex- dexamethasone implant | website=DailyMed | date=30 October 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4b204f44-6e8a-4d17-803c-268f0b04679f | access-date=27 March 2022 | archive-date=27 March 2022 | archive-url=https://web.archive.org/web/20220327232705/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4b204f44-6e8a-4d17-803c-268f0b04679f | url-status=live }}{{cite web | title=Dexamethasone sodium phosphate solution/ drops | website=DailyMed | date=31 July 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6bdcefbe-51e3-4ca4-afda-5aeca7b6fa73 | access-date=27 March 2022 | archive-date=27 January 2022 | archive-url=https://web.archive.org/web/20220127213839/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6bdcefbe-51e3-4ca4-afda-5aeca7b6fa73 | url-status=live }}{{cite web | title=Dexycu- dexamethasone injection, suspension | website=DailyMed | date=20 December 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=583d70ed-bc42-465b-983d-c770db58406f | access-date=27 March 2022 | archive-date=27 March 2022 | archive-url=https://web.archive.org/web/20220327234559/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=583d70ed-bc42-465b-983d-c770db58406f | url-status=live }}

| legal_EU = Rx-only

| legal_EU_comment = {{cite web | title=Ozurdex EPAR | website=European Medicines Agency (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/ozurdex | access-date=24 October 2020 | archive-date=27 October 2020 | archive-url=https://web.archive.org/web/20201027062744/https://www.ema.europa.eu/en/medicines/human/EPAR/ozurdex | url-status=live }}{{cite web | title=Neofordex EPAR | website=European Medicines Agency (EMA) | date=25 July 2014 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/neofordex | archive-url=https://web.archive.org/web/20241007224603/https://www.ema.europa.eu/en/medicines/human/EPAR/neofordex | url-status=dead | archive-date=7 October 2024 | access-date=24 October 2020 }}

| legal_UN =

| legal_UN_comment =

| legal_status = Rx-only

| bioavailability = 80–90%

| protein_bound = 77%

| metabolism = Liver

| metabolites =

| onset =

| elimination_half-life = biological half-life: 36 to 54 hours; plasma half-life: 4 to 5 hours{{cite journal | vauthors = Dogra P, Vijayashankar NP | title = Dexamethasone Suppression Test | journal = StatPearls | issue = 14 September 2020 | date = 14 September 2020 | pmid = 31194457}}{{cite journal | vauthors = Jobe AH, Milad MA, Peppard T, Jusko WJ | title = Pharmacokinetics and Pharmacodynamics of Intramuscular and Oral Betamethasone and Dexamethasone in Reproductive Age Women in India | journal = Clinical and Translational Science | volume = 13 | issue = 2 | pages = 391–99 | date = March 2020 | pmid = 31808984 | pmc = 7070803 | doi = 10.1111/cts.12724}}

| duration_of_action =

| excretion = Urine (65%)

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 50-02-2

| CAS_supplemental =

| PubChem = 5743

| IUPHAR_ligand = 2768

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

| DrugBank = DB01234

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 5541

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 7S5I7G3JQL

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D00292

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 41879

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 384467

| NIAID_ChemDB =

| PDB_ligand = DEX

| synonyms =

| IUPAC_name = (8S,9R,10S,11S,13S,14S,16R,17R)-9-Fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one

| C=22 | H=29 | F=1 | O=5

| SMILES = O=C(CO)[C@]3(O)[C@]2(C[C@H](O)[C@]4(F)[C@@]1(C(=CC(=O)C=C1)CC[C@H]4[C@@H]2C[C@H]3C)C)C

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C22H29FO5/c1-12-8-16-15-5-4-13-9-14(25)6-7-19(13,2)21(15,23)17(26)10-20(16,3)22(12,28)18(27)11-24/h6-7,9,12,15-17,24,26,28H,4-5,8,10-11H2,1-3H3/t12-,15+,16+,17+,19+,20+,21+,22+/m1/s1

| StdInChI_comment =

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = UREBDLICKHMUKA-CXSFZGCWSA-N

| density =

| density_notes =

| melting_point = 262

| melting_high =

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

}}

Dexamethasone is a fluorinated glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive pulmonary disease (COPD), croup, brain swelling, eye pain following eye surgery, superior vena cava syndrome (a complication of some forms of cancer),{{cite book| vauthors = Wilkinson IB |date = 13 July 2017 |title= Oxford Handbook of Clinical Medicine |page = 176 |publisher = OUP Oxford |isbn=978-0-19-968990-3 }} and along with antibiotics in tuberculosis. In adrenocortical insufficiency, it may be used in combination with a mineralocorticoid medication such as fludrocortisone. In preterm labor, it may be used to improve outcomes in the baby. It may be given by mouth, as an injection into a muscle, as an injection into a vein, as a topical cream or ointment for the skin or as a topical ophthalmic solution to the eye. The effects of dexamethasone are frequently seen within a day and last for about three days.{{cite web|title=Dexamethasone|url=https://www.drugs.com/monograph/dexamethasone.html|publisher=The American Society of Health-System Pharmacists|access-date=29 July 2015|url-status=live|archive-url=https://web.archive.org/web/20170831175940/https://www.drugs.com/monograph/dexamethasone.html|archive-date=31 August 2017}}

The long-term use of dexamethasone may result in thrush, bone loss, cataracts, easy bruising, or muscle weakness. It is in pregnancy category C in the United States, meaning that it should only be used when the benefits are predicted to be greater than the risks.{{cite web|title=Dexamethasone Use During Pregnancy|url=https://www.drugs.com/pregnancy/dexamethasone.html|website=Drugs.com|access-date=9 June 2016|quote=Dexamethasone is only recommended for use during pregnancy when there are no alternatives and benefit outweighs risk.|url-status=live|archive-url=https://web.archive.org/web/20160517153059/http://www.drugs.com/pregnancy/dexamethasone.html|archive-date=17 May 2016}} In Australia, the oral use is category A, meaning it has been frequently used in pregnancy and not been found to cause problems to the baby.{{cite web|title=Prescribing medicines in pregnancy database|url=http://www.tga.gov.au/hp/medicines-pregnancy.htm|work=Australian Government|access-date=22 April 2014|date=3 March 2014|quote=Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.|url-status=live|archive-url=https://web.archive.org/web/20140408040902/http://www.tga.gov.au/hp/medicines-pregnancy.htm|archive-date=8 April 2014}} It should not be taken when breastfeeding. Dexamethasone has anti-inflammatory and immunosuppressant effects.

Dexamethasone was first synthesized in 1957 by Philip Showalter Hench and was approved for medical use in 1958.{{cite web | title=Drugs@FDA: Dexamethasone | website=U.S. Food and Drug Administration (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=011664 | access-date=27 March 2022 | archive-date=30 November 2017 | archive-url=https://web.archive.org/web/20171130231459/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=011664 | url-status=dead }}{{cite book | vauthors = Rankovic Z, Hargreaves R, Bingham M |title=Drug discovery and medicinal chemistry for psychiatric disorders|date=2012|publisher=Royal Society of Chemistry|location=Cambridge|isbn=9781849733656|page=286|url=https://books.google.com/books?id=J4Mq3Lm1R7kC&pg=PA286|url-status=live|archive-url=https://web.archive.org/web/20160305022353/https://books.google.ca/books?id=J4Mq3Lm1R7kC&pg=PA286|archive-date=5 March 2016}}{{cite book |vauthors=Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=485 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA485 |access-date=17 June 2020 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110032815/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA485 |url-status=live }} It is on the World Health Organization's List of Essential Medicines.{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }} In 2022, it was the 234th most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}{{cite web | title = Dexamethasone Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Dexamethasone | access-date = 30 August 2024 }} It is available as a generic medication.{{cite web | title=Competitive Generic Therapy Approvals | website=U.S. Food and Drug Administration (FDA) | date=29 June 2023 | url=https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | access-date=29 June 2023 | archive-date=29 June 2023 | archive-url=https://web.archive.org/web/20230629233651/https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | url-status=dead }} In 2022, the combination of dexamethasone with neomycin and polymyxin B was the 274th most commonly prescribed medication in the United States, with more than 800,000 prescriptions.{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}{{cite web | title = Dexamethasone; Neomycin; Polymyxin B Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/DexamethasoneNeomycinPolymyxinB | access-date = 30 August 2024 }}

Medical uses

=Anti-inflammatory=

File:Dexamethasone tablets.jpg

Dexamethasone is used to treat many inflammatory and autoimmune disorders, such as rheumatoid arthritis and bronchospasm.{{cite web | vauthors = Till J |title=Paramedic Clinical Training Aid |url= http://paramedic-info.com/PDA/index.html |access-date=30 August 2011 |url-status=dead |archive-url=https://web.archive.org/web/20120331110331/http://paramedic-info.com/PDA/index.html |archive-date=31 March 2012 }} Idiopathic thrombocytopenic purpura, a decrease in numbers of platelets due to an immune problem, responds to 40 mg daily for four days; it may be administered in 14-day cycles. It is unclear whether dexamethasone in this condition is significantly better than other glucocorticoids.{{cite journal | vauthors = Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B, Grainger J, Greer I, Hunt BJ, Imbach PA, Lyons G, McMillan R, Rodeghiero F, Sanz MA, Tarantino M, Watson S, Young J, Kuter DJ | title = International consensus report on the investigation and management of primary immune thrombocytopenia | journal = Blood | volume = 115 | issue = 2 | pages = 168–86 | date = January 2010 | pmid = 19846889 | doi = 10.1182/blood-2009-06-225565 | doi-access = free }}

It is also given in small amounts before and/or after some forms of dental surgery, such as the extraction of the wisdom teeth, an operation that often causes puffy, swollen cheeks.{{cite journal |vauthors=Schmelzeisen R, Frölich JC |year=1993 |title=Prevention of postoperative swelling and pain by dexamethasone after operative removal of impacted third molar teeth |journal=European Journal of Clinical Pharmacology |volume=44 |issue=3 |pages=275–77 |doi=10.1007/BF00271371 |pmid=8491244 |s2cid=12528750}}

Dexamethasone is commonly given as a treatment for croup in children. A single dose can reduce the swelling of the airway to improve breathing and reduce discomfort.{{cite web |url=https://www.mayoclinic.org/diseases-conditions/croup/diagnosis-treatment/drc-20350354 |title=Croup – Diagnosis & Treatment |website=Mayo Clinic |access-date=13 October 2017 |quote=Dexamethasone is usually recommended because of its long-lasting effects (up to 72 hours). |archive-date=10 October 2017 |archive-url=https://web.archive.org/web/20171010063045/http://www.mayoclinic.org/diseases-conditions/croup/diagnosis-treatment/drc-20350354 |url-status=live }}

Dexamethasone is sometimes injected into the heel when treating plantar fasciitis or heel pain, sometimes in conjunction with triamcinolone acetonide. There is no evidence that this treatment helps in the long term, however, dexamethasone may provide short-term pain relief.{{cite journal | vauthors = Arnold MJ, Gruber J | title = Injected Corticosteroids for Plantar Heel Pain | language = en-US | journal = American Family Physician | volume = 97 | issue = 3 | pages = 169–170 | date = February 2018 | pmid = 29431981 | url = https://www.aafp.org/pubs/afp/issues/2018/0201/p169.html }}

It may be useful to counteract allergic anaphylactic shock, however this is not usually recommended by clinical guidelines.{{cite journal | vauthors = Dodd A, Hughes A, Sargant N, Whyte AF, Soar J, Turner PJ | title = Evidence update for the treatment of anaphylaxis | journal = Resuscitation | volume = 163 | pages = 86–96 | date = April 2021 | pmid = 33895231 | doi = 10.1016/j.resuscitation.2021.04.010 | pmc = 8139870 | hdl = 1983/82ab8f32-67a9-4277-8750-2246aabf5d96 | hdl-access = free }}

It is present in certain eye drops – particularly after eye surgery – and as a nasal spray, and certain ear drops (can be combined with an antibiotic and an antifungal). Dexamethasone intravitreal steroid implants have been approved by the US Food and Drug Administration (FDA) to treat ocular conditions such as diabetic macular edema, central retinal vein occlusion, and uveitis. However, the evidence is poor quality relating to the treatment of uveitis, with the potential side effects (cataract progression and raised intraocular pressure) being significant, and the benefits not certainly greater than standard treatment.{{cite journal | vauthors = Reddy A, Liu SH, Brady CJ, Sieving PC, Palestine AG | title = Corticosteroid implants for chronic non-infectious uveitis | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 8 | pages = CD010469 | date = August 2023 | pmid = 37642198 | pmc = 10464657 | doi = 10.1002/14651858.CD010469.pub4 }} Dexamethasone has also been used with antibiotics to treat acute endophthalmitis.{{cite journal | vauthors = Emami S, Kitayama K, Coleman AL | title = Adjunctive steroid therapy versus antibiotics alone for acute endophthalmitis after intraocular procedure | journal = The Cochrane Database of Systematic Reviews | volume = 2022 | issue = 6 | pages = CD012131 | date = June 2022 | pmid = 35665485 | pmc = 9169535 | doi = 10.1002/14651858.CD012131.pub3 }}

Dexamethasone is used in transvenous screw-in cardiac pacing leads to minimize the inflammatory response of the myocardium. The steroid is released into the myocardium as soon as the screw is extended and can play a significant role in minimizing the acute pacing threshold due to the reduction of inflammatory response. The typical quantity present in a lead tip is less than 1.0 mg.{{medcn|date=June 2020}}

Dexamethasone may be administered before antibiotics in cases of bacterial meningitis. Gram-negative bacteria — to which the causative agent of bacterial meningitis, neisseria meningitidis, belongs — have highly immunogenic lipopolysaccharides as a component of their cell membrane and trigger a strong inflammatory response. Pre-administration of dexamethasone before the administration of antibiotics acts to reduce that response, thus reducing hearing loss and neurological damage.{{cite journal |vauthors=Brouwer MC, McIntyre P, Prasad K, van de Beek D |date=September 2015|title=Corticosteroids for acute bacterial meningitis |journal=Cochrane Database of Systematic Reviews |volume=2015 |issue=9 |pages=CD004405 |doi=10.1002/14651858.CD004405.pub5 |pmc=6491272 |pmid=26362566 |doi-access=free }}

File:Dexamethasone phosphate for injection.jpg

=Cancer=

People with cancer undergoing chemotherapy are often given dexamethasone to counteract certain side effects of their antitumor treatments. Dexamethasone can increase the antiemetic effect of 5-HT3 receptor antagonists, such as ondansetron.{{cite journal | vauthors = Roila F, Ballatori E, Ruggeri B, DeAngelis V | title = Dexamethasone alone or in combination with ondansetron for the prevention of delayed nausea and vomiting induced by chemotherapy | journal = The New England Journal of Medicine | volume = 342 | issue = 21 | pages = 1554–59 | date = May 2000 | pmid = 10824073 | doi = 10.1056/NEJM200005253422102 | doi-access = free }} The exact mechanism of this interaction is not well-defined, but it has been theorized that this effect may be due to, among many other causes, inhibition of prostaglandin synthesis, anti-inflammatory effects, immunosuppressive effects, decreased release of endogenous opioids, or a combination of the aforementioned.{{cite journal | vauthors = Holte K, Kehlet H | title = Perioperative single-dose glucocorticoid administration: pathophysiologic effects and clinical implications | journal = Journal of the American College of Surgeons | volume = 195 | issue = 5 | pages = 694–712 | date = November 2002 | pmid = 12437261 | doi = 10.1016/s1072-7515(02)01491-6 }}

In brain tumors (primary or metastatic), dexamethasone is used to counteract the development of edema, which could eventually compress other brain structures.{{cite journal | vauthors = Kostaras X, Cusano F, Kline GA, Roa W, Easaw J | title = Use of dexamethasone in patients with high-grade glioma: a clinical practice guideline | journal = Current Oncology | volume = 21 | issue = 3 | pages = e493–e503 | date = June 2014 | pmid = 24940109 | pmc = 4059813 | doi = 10.3747/co.21.1769 }} It is also given in cord compression, where a tumor is compressing the spinal cord.{{medcn|date=June 2020}} Evidence on the safety and efficacy of using dexamethasone to treat malignant brain tumors is not clear.{{cite journal | vauthors = Jessurun CA, Hulsbergen AF, Cho LD, Aglio LS, Nandoe Tewarie RD, Broekman ML | title = Evidence-based dexamethasone dosing in malignant brain tumors: what do we really know? | journal = Journal of Neuro-Oncology | volume = 144 | issue = 2 | pages = 249–264 | date = September 2019 | pmid = 31346902 | pmc = 6700052 | doi = 10.1007/s11060-019-03238-4 | title-link = doi | doi-access = free }}

Dexamethasone is also used as a direct chemotherapeutic agent in certain hematological malignancies, especially in the treatment of multiple myeloma, in which dexamethasone is given alone or in combination with other chemotherapeutic drugs, including most commonly with thalidomide (Thal-dex), lenalidomide, bortezomib (Velcade, Vel-dex),{{cite journal | vauthors = Harousseau JL, Attal M, Leleu X, Troncy J, Pegourie B, Stoppa AM, Hulin C, Benboubker L, Fuzibet JG, Renaud M, Moreau P, Avet-Loiseau H | title = Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of an IFM phase II study | journal = Haematologica | volume = 91 | issue = 11 | pages = 1498–505 | date = November 2006 | pmid = 17043025 }} {{free access}} or a combination of doxorubicin (Adriamycin) and vincristine or bortezomib/lenalidomide/dexamethasone.{{medcn|date=June 2020}}

=COVID-19=

{{Anchor|COVID-19}}

{{See also|COVID-19 drug repurposing research#Dexamethasone}}

Dexamethasone is recommended by the National Health Service in the UK and the National Institutes of Health (NIH) in the US for people with COVID-19 who need either mechanical ventilation or supplemental oxygen (without ventilation).{{Cite web|title=Dexamethasone and COVID-19|url=https://www.sps.nhs.uk/articles/dexamethasone-and-covid-19/|access-date=22 July 2020|website=SPS – Specialist Pharmacy Service|archive-date=22 July 2020|archive-url=https://web.archive.org/web/20200722082343/https://www.sps.nhs.uk/articles/dexamethasone-and-covid-19/|url-status=dead}}{{Cite web|title=Corticosteroids|url=https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/immunomodulators/corticosteroids/|access-date=12 July 2020|website=COVID-19 Treatment Guidelines|publisher=National Institutes of Health|archive-date=19 July 2020|archive-url=https://web.archive.org/web/20200719163110/https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/immunomodulators/corticosteroids/|url-status=live}}

The Infectious Diseases Society of America (IDSA) guideline panel suggests the use of glucocorticoids for people with severe COVID-19, defined as people with SpO2 ≤94% on room air, and those who require supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).{{cite web|title=COVID-19 Guideline, Part 1: Treatment and Management|url=https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/|access-date=22 July 2020|website=Infectious Diseases Society of America|quote=Recommendation 4. Among hospitalized people with severe* COVID-19, the IDSA guideline panel suggests glucocorticoids rather than no glucocorticoids. (Conditional recommendation, Moderate certainty of evidence)
Remark: Dexamethasone 6 mg IV or PO for 10 days (or until discharge if earlier) or equivalent glucocorticoid dose may be substituted if dexamethasone is unavailable. Equivalent total daily doses of alternative glucocorticoids to dexamethasone 6 mg daily are methylprednisolone 32 mg and prednisone 40 mg.
Recommendation 5. Among hospitalized people with COVID-19 without hypoxemia requiring supplemental oxygen, the IDSA guideline panel suggests against the use of glucocorticoids. (Conditional recommendation, Low certainty of evidence)|archive-date=6 October 2020|archive-url=https://web.archive.org/web/20201006214733/https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management//|url-status=live}}
The IDSA recommends against the use of glucocorticoids for those with COVID-19 without hypoxemia requiring supplemental oxygen.

The World Health Organization (WHO) recommends systemic corticosteroids rather than no systemic corticosteroids for the treatment of people with COVID-19 (strong recommendation, based on moderate certainty evidence). The WHO suggests not to use corticosteroids in the treatment of people with non-severe COVID-19 (conditional recommendation, based on low certainty evidence).

The Oxford University RECOVERY Trial issued a press release announcing preliminary results that the drug could reduce deaths by about a third in participants on ventilators and by about a fifth in participants on oxygen; it did not benefit people who did not require respiratory support.{{cite news|date=16 June 2020|title=Dexamethasone reduces death in hospitalized people with severe respiratory complications of COVID-19|website=University of Oxford|url=http://www.ox.ac.uk/news/2020-06-16-dexamethasone-reduces-death-hospitalised-patients-severe-respiratory-complications|access-date=16 June 2020|archive-date=16 June 2020|archive-url=https://web.archive.org/web/20200616145052/http://www.ox.ac.uk/news/2020-06-16-dexamethasone-reduces-death-hospitalised-patients-severe-respiratory-complications/|url-status=live}} A meta-analysis of seven clinical trials of critically ill COVID-19 participants, each treated with one of three different corticosteroids found a statistically significant reduction in death. The largest reduction was obtained with dexamethasone (36% compared to placebo).{{cite journal | vauthors = Sterne JA, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, Annane D, Azevedo LC, Berwanger O, Cavalcanti AB, Dequin PF, Du B, Emberson J, Fisher D, Giraudeau B, Gordon AC, Granholm A, Green C, Haynes R, Heming N, Higgins JP, Horby P, Jüni P, Landray MJ, Le Gouge A, Leclerc M, Lim WS, Machado FR, McArthur C, Meziani F, Møller MH, Perner A, Petersen MW, Savovic J, Tomazini V, Veiga VC, Webb S, Marshall JC | collaboration = The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group | title = Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis | journal = JAMA | date = September 2020 | volume = 324 | issue = 13 | pages = 1330–1341 | doi = 10.1001/jama.2020.17023 | pmid = 32876694 | pmc = 7489434 | s2cid = 221467783 | doi-access = free }}{{cite journal | title = Corticosteroids in COVID-19 ARDS: Evidence and Hope During the Pandemic | vauthors = Prescott HC, Rice TW | journal = JAMA | date = September 2020 | volume = 324 | issue = 13 | pages = 1292–1295 | doi = 10.1001/jama.2020.16747 | pmid = 32876693 | s2cid = 221468015 | doi-access = free }}

In September 2020, the European Medicines Agency (EMA) endorsed the use of dexamethasone in adults and adolescents, from twelve years of age and weighing at least {{convert|40|kg|lb}}, who require supplemental oxygen therapy.{{cite press release | title=EMA endorses use of dexamethasone in COVID-19 patients on oxygen or mechanical ventilation | website=European Medicines Agency (EMA) | date=18 September 2020 | url=https://www.ema.europa.eu/en/news/ema-endorses-use-dexamethasone-covid-19-patients-oxygen-mechanical-ventilation | access-date=21 September 2020 | archive-date=14 February 2021 | archive-url=https://web.archive.org/web/20210214060918/https://www.ema.europa.eu/en/news/ema-endorses-use-dexamethasone-covid-19-patients-oxygen-mechanical-ventilation | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Dexamethasone can be taken by mouth or given as an injection or infusion (drip) into a vein.

In November 2020, the Public Health Agency of Canada's Clinical Pharmacology Task Group recommended dexamethasone for hospitalized patients requiring mechanical ventilation.{{Cite web |last=Public Health Agency of Canada |date=23 November 2020 |title=Ad-hoc COVID-19 Clinical Pharmacology Task Group: Statement on dexamethasone |url=https://www.canada.ca/en/public-health/corporate/mandate/about-agency/external-advisory-bodies/list/covid-19-clinical-pharmacology-task-group/statement-dexamethasone.html#a5 |url-status=dead |archive-url=https://archive.today/20201227053419/https://www.canada.ca/en/public-health/corporate/mandate/about-agency/external-advisory-bodies/list/covid-19-clinical-pharmacology-task-group/statement-dexamethasone.html%23a5 |archive-date=27 December 2020 |access-date=1 April 2022 |website=Government of Canada }} Although dexamethasone, and other glucocorticoids, reduce mortality in COVID-19 they have also been associated with an increased risk of secondary infections,{{cite journal | vauthors = Conway Morris A, Kohler K, De Corte T, Ercole A, De Grooth HJ, Elbers PW, Povoa P, Morais R, Koulenti D, Jog S, Nielsen N, Jubb A, Cecconi M, De Waele J | title = Co-infection and ICU-acquired infection in COIVD-19 ICU patients: a secondary analysis of the UNITE-COVID data set | journal = Critical Care | volume = 26 | issue = 1 | pages = 236 | date = August 2022 | pmid = 35922860 | pmc = 9347163 | doi = 10.1186/s13054-022-04108-8 | doi-access = free }}{{cite journal | vauthors = Meynaar IA, van Rijn S, Ottens TH, van Burgel ND, van Nieuwkoop C | title = Increased risk of central line-associated bloodstream infection in COVID-19 patients associated with dexamethasone but not with interleukin antagonists | journal = Intensive Care Medicine | volume = 48 | issue = 7 | pages = 954–957 | date = July 2022 | pmid = 35670819 | pmc = 9171741 | doi = 10.1007/s00134-022-06750-w }}{{cite journal | vauthors = Scaravilli V, Guzzardella A, Madotto F, Beltrama V, Muscatello A, Bellani G, Monti G, Greco M, Pesenti A, Bandera A, Grasselli G | title = Impact of dexamethasone on the incidence of ventilator-associated pneumonia in mechanically ventilated COVID-19 patients: a propensity-matched cohort study | journal = Critical Care | volume = 26 | issue = 1 | pages = 176 | date = June 2022 | pmid = 35698155 | pmc = 9191402 | doi = 10.1186/s13054-022-04049-2 | doi-access = free }} secondary infections being a significant issue in critically ill COVID-19 patients.{{cite journal | vauthors = Maes M, Higginson E, Pereira-Dias J, Curran MD, Parmar S, Khokhar F, Cuchet-Lourenço D, Lux J, Sharma-Hajela S, Ravenhill B, Hamed I, Heales L, Mahroof R, Soderholm A, Forrest S, Sridhar S, Brown NM, Baker S, Navapurkar V, Dougan G, Bartholdson Scott J, Conway Morris A | title = Ventilator-associated pneumonia in critically ill patients with COVID-19 | journal = Critical Care | volume = 25 | issue = 1 | pages = 25 | date = January 2021 | pmid = 33430915 | pmc = 7797892 | doi = 10.1186/s13054-021-03460-5 | doi-access = free }}

The mechanism of action of dexamethasone involves suppression of late-stage interferon type I programs in severe COVID-19 patients.{{cite journal | vauthors = Sinha S, Rosin NL, Arora R, Labit E, Jaffer A, Cao L, Farias R, Nguyen AP, de Almeida LG, Dufour A, Bromley A, McDonald B, Gillrie MR, Fritzler MJ, Yipp BG, Biernaskie J | title = Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19 | journal = Nature Medicine | volume = 28 | issue = 1 | pages = 201–211 | date = January 2022 | pmid = 34782790 | pmc = 8799469 | doi = 10.1038/s41591-021-01576-3 | s2cid = 244132637 }}

= Surgery =

Dexamethasone is used fairly regularly, often as a single intravenous dose, during surgery to prevent postoperative nausea and vomiting, manage pain, potentially reduce the amount of pain medication required, and help reduce post-surgery hospitalisation time. The adverse effects of taking steroids after surgery on wound healing, blood sugar levels, and in diabetics are not completely understood; however, dexamethasone likely does not increase the risk of postoperative infections.{{cite journal | vauthors = Polderman JA, Farhang-Razi V, Van Dieren S, Kranke P, DeVries JH, Hollmann MW, Preckel B, Hermanides J | title = Adverse side effects of dexamethasone in surgical patients | journal = The Cochrane Database of Systematic Reviews | volume = 11 | issue = 11 | pages = CD011940 | date = November 2018 | pmid = 30480776 | pmc = 6426282 | doi = 10.1002/14651858.CD011940.pub3 }}

=Endocrine=

Dexamethasone is the treatment for the very rare disorder of glucocorticoid resistance.{{cite journal | vauthors = Chrousos GP, Detera-Wadleigh SD, Karl M | title = Syndromes of glucocorticoid resistance | journal = Annals of Internal Medicine | volume = 119 | issue = 11 | pages = 1113–24 | date = December 1993 | pmid = 8239231 | doi = 10.7326/0003-4819-119-11-199312010-00009 | url = http://annals.org/pdfaccess.ashx?url=/data/journals/aim/19786/0000605-199312010-00009.pdf | access-date = 4 July 2020 | url-status = dead | s2cid = 26040431 | archive-url = https://web.archive.org/web/20170814034732/http://annals.org/pdfaccess.ashx?url=%2Fdata%2Fjournals%2Faim%2F19786%2F0000605-199312010-00009.pdf | archive-date = 14 August 2017 }}{{cite journal | vauthors = Charmandari E, Kino T, Ichijo T, Chrousos GP | title = Generalized glucocorticoid resistance: clinical aspects, molecular mechanisms, and implications of a rare genetic disorder | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 93 | issue = 5 | pages = 1563–72 | date = May 2008 | pmid = 18319312 | pmc = 2386273 | doi = 10.1210/jc.2008-0040 }}

In adrenal insufficiency and Addison's disease, dexamethasone is prescribed when the patient does not respond well to prednisone or methylprednisolone.{{medcn|date=June 2020}}

It can be used in congenital adrenal hyperplasia in older adolescents and adults to suppress adrenocorticotropic hormone (ACTH) production. It is typically given at night.Dan L. Longo, Anthony Fauci, Dennis Kasper, Stephen Hauser, J. Jerry Jameson and Joseph Loscalzo, [https://books.google.com/books?id=7gxjMV8hClsC&q=Harrison%27s+Principles+of+Internal+Medicine Harrison's Principles of Internal Medicine], 18th edition, p. 3055

=Pregnancy=

Dexamethasone may be given to women at risk of delivering prematurely to promote maturation of the fetus's lungs. This administration, given from one day to one week before delivery, has been associated with low birth weight, although not with increased rates of neonatal death.{{cite journal | vauthors = Bloom SL, Sheffield JS, McIntire DD, Leveno KJ | title = Antenatal dexamethasone and decreased birth weight | journal = Obstetrics and Gynecology | volume = 97 | issue = 4 | pages = 485–90 | date = April 2001 | pmid = 11275014 | doi = 10.1016/S0029-7844(00)01206-0 | s2cid = 33601749 }}

Dexamethasone has also been used during pregnancy as an off-label prenatal treatment for the symptoms of congenital adrenal hyperplasia (CAH) in female babies. CAH causes a variety of physical abnormalities, notably ambiguous genitalia. Early prenatal CAH treatment has been shown to reduce some CAH symptoms, but it does not treat the underlying congenital disorder. This use is controversial: it is inadequately studied, only around one in ten of the fetuses of women treated are at risk of the condition, and serious adverse events have been documented.{{Cite web|url=http://content.time.com/time/health/article/0,8599,1996453,00.html|archive-url=https://web.archive.org/web/20160831150342/http://content.time.com/time/health/article/0,8599,1996453,00.html|url-status=dead|title=A Prenatal Treatment Raises Questions of Medical Ethics| vauthors = Elton C |date=18 June 2010|archive-date=31 August 2016|via=content.time.com}} Experimental use of dexamethasone in pregnancy for fetal CAH treatment was discontinued in Sweden when one in five cases had adverse events.{{cite journal | vauthors = Hirvikoski T, Nordenström A, Wedell A, Ritzén M, Lajic S | title = Prenatal dexamethasone treatment of children at risk for congenital adrenal hyperplasia: the Swedish experience and standpoint | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 97 | issue = 6 | pages = 1881–83 | date = June 2012 | pmid = 22466333 | doi = 10.1210/jc.2012-1222 | doi-access = free }}

A small clinical trial found long-term effects on verbal working memory among the small group of children treated prenatally, but the small number of test subjects means the study cannot be considered definitive.{{cite journal | vauthors = Hirvikoski T, Nordenström A, Lindholm T, Lindblad F, Ritzén EM, Wedell A, Lajic S | title = Cognitive functions in children at risk for congenital adrenal hyperplasia treated prenatally with dexamethasone | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 92 | issue = 2 | pages = 542–48 | date = February 2007 | pmid = 17148562 | doi = 10.1210/jc.2006-1340 | doi-access = free }}{{cite journal | vauthors = Lajic S, Nordenström A, Hirvikoski T | journal = Endocrine Development| title = Long-term outcome of prenatal dexamethasone treatment of 21-hydroxylase deficiency | volume = 20 | pages = 96–105 | year = 2011 | pmid = 21164263 | doi = 10.1159/000321228 | isbn = 978-3-8055-9643-5 }}

=High-altitude illnesses=

Dexamethasone is used in the treatment of high-altitude cerebral edema (HACE), as well as high-altitude pulmonary edema (HAPE).{{cite journal |vauthors=Simancas-Racines D, Arevalo-Rodriguez I, Osorio D, Franco JV, Xu Y, Hidalgo R |title=Interventions for treating acute high altitude illness |journal=Cochrane Database Syst Rev |volume=6 |issue= 12|pages=CD009567 |date=June 2018 |pmid=29959871 |pmc=6513207 |doi=10.1002/14651858.CD009567.pub2 |url= }} It is commonly carried on mountain-climbing expeditions to help climbers deal with complications of altitude sickness.{{cite book | vauthors = Cymerman A, Rock PB | title = Medical Problems in High Mountain Environments. A Handbook for Medical Officers | publisher = US Army Research Inst. of Environmental Medicine Thermal and Mountain Medicine Division Technical Report | volume = USARIEM-TN94-2 | url = http://operationalmedicine.org/TextbookFiles/highmountain.pdf#page=19&zoom=auto,-76,314 | archive-url = https://web.archive.org/web/20170617133159/http://operationalmedicine.org/TextbookFiles/highmountain.pdf#page=19&zoom=auto,-76,314 | url-status = dead | archive-date = 17 June 2017 | access-date = 17 June 2020 | year = 1994 }}{{cite journal | vauthors = Eledrisi MS | title = First-line therapy for hypertension | journal = Annals of Internal Medicine | volume = 146 | issue = 8 | pages = 615 | date = April 2007 | pmid = 17438328 | doi = 10.7326/0003-4819-146-8-200704170-00021 }}

=Nausea and vomiting=

Intravenous dexamethasone is effective for the prevention of nausea and vomiting in people who had surgery and whose post-operative pain was treated with long-acting spinal or epidural spinal opioids.{{cite journal | vauthors = Grape S, Usmanova I, Kirkham KR, Albrecht E | title = Intravenous dexamethasone for prophylaxis of postoperative nausea and vomiting after administration of long-acting neuraxial opioids: a systematic review and meta-analysis | journal = Anaesthesia | volume = 73 | issue = 4 | pages = 480–89 | date = April 2018 | pmid = 29226971 | doi = 10.1111/anae.14166 | doi-access = free }}

The combination of dexamethasone and a 5-HT3 receptor antagonist such as ondansetron is more effective than a 5-HT3 receptor antagonist alone in preventing postoperative nausea and vomiting.{{cite journal | vauthors = Kovac AL | title = Meta-analysis of the use of rescue antiemetics following PONV prophylactic failure with 5-HT3 antagonist/dexamethasone versus single-agent therapies | journal = The Annals of Pharmacotherapy | volume = 40 | issue = 5 | pages = 873–87 | date = May 2006 | pmid = 16670361 | doi = 10.1345/aph.1G338 | s2cid = 32843029 }}

=Sore throat=

A single dose of dexamethasone or another steroid speeds the improvement of a sore throat.{{cite journal | vauthors = Sadeghirad B, Siemieniuk RA, Brignardello-Petersen R, Papola D, Lytvyn L, Vandvik PO, Merglen A, Guyatt GH, Agoritsas T | title = Corticosteroids for treatment of sore throat: systematic review and meta-analysis of randomised trials | journal = BMJ | volume = 358 | pages = j3887 | date = September 2017 | pmid = 28931508 | pmc = 5605780 | doi = 10.1136/bmj.j3887 }}

Contraindications

Contraindications of dexamethasone include,{{cite web|title=Decadron, Dexamethasone Intensol (dexamethasone) dosing, indications, interactions, adverse effects, and more|work=Medscape Reference|publisher=WebMD|access-date=11 December 2013|url=http://reference.medscape.com/drug/decadron-dexamethasone-intensol-dexamethasone-342741#showall|url-status=live|archive-url=https://web.archive.org/web/20131212220123/http://reference.medscape.com/drug/decadron-dexamethasone-intensol-dexamethasone-342741#showall|archive-date=12 December 2013}} but are not limited to:

Adverse effects

The exact incidence of the adverse effects of dexamethasone is not available, hence estimates have been made as to the incidence of the adverse effects below based on the adverse effects of related corticosteroids and on available documentation on dexamethasone.{{cite web|title=Product Information Dexamethsone (dexamethasone)|work=TGA eBusiness Services|publisher=Aspen Pharmacare Australia Pty Ltd|date=10 August 2010|access-date=11 December 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-06682-3|format=PDF|archive-date=28 January 2017|archive-url=https://web.archive.org/web/20170128131300/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-06682-3|url-status=live}} (Accept terms and conditions to open PDF, which doesn't work in archived version){{cite web|title=Product Information Dexmethsone Injection|work=TGA eBusiness ServicesAspen Pharmacare Australia Pty Ltd|publisher=Aspen Pharmacare Australia Pty Ltd|date=2 March 2011|access-date=11 December 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-02528-3|format=PDF|archive-date=29 January 2017|archive-url=https://web.archive.org/web/20170129093042/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-02528-3|url-status=live}} (Accept terms and conditions to open PDF, which doesn't work in archived version){{cite web|title=Dexamethasone tablet [ECR Pharmaceuticals]|work=DailyMed|publisher=ECR Pharmaceuticals|date=December 2010|access-date=11 December 2013|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=428cc7bb-e0f9-466c-b38f-11ac22cda752|url-status=live|archive-url=https://web.archive.org/web/20131213040029/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=428cc7bb-e0f9-466c-b38f-11ac22cda752|archive-date=13 December 2013}}{{cite web|title=Dexamethasone Tablet BP 2.0 mg – Summary of Product Characteristics (SPC)|work=electronic Medicines Compendium|publisher=Merck Sharp & Dohme Limited|date=26 January 2018|access-date=17 June 2020|url=https://www.medicines.org.uk/emc/product/5411/smpc|archive-date=17 June 2020|archive-url=https://web.archive.org/web/20200617215029/https://www.medicines.org.uk/emc/product/5411/smpc|url-status=live}}{{cite web|title=Dexamethasone 4.0 mg/ml injection – Summary of Product Characteristics (SPC)|work=electronic Medicines Compendium|publisher=Merck Sharp & Dohme Limited|date=4 December 2013|access-date=11 December 2013|url=http://www.medicines.org.uk/emc/medicine/8369/SPC/Dexamethasone+4.0mg+ml+injection/|url-status=dead|archive-url=https://web.archive.org/web/20150508054341/http://www.medicines.org.uk/emc/medicine/8369/SPC/Dexamethasone+4.0mg+ml+injection/|archive-date=8 May 2015}}

=Common=

{{Div col}}

{{Div col end}}

=Unknown frequency=

=Withdrawal=

Sudden withdrawal after long-term treatment with corticosteroids can lead to

{{Div col|colwidth=18em}}

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Interactions

Known drug interactions include:

Pharmacology

{{see also|Glucocorticoid#Pharmacology}}

=Pharmacodynamics=

As a glucocorticoid, dexamethasone is an agonist of the glucocorticoid receptor (GR).{{cite journal | vauthors = Cole TJ | title = Glucocorticoid action and the development of selective glucocorticoid receptor ligands | journal = Biotechnol Annu Rev | series = Biotechnology Annual Review | volume = 12 | issue = | pages = 269–300 | date = 2006 | pmid = 17045197 | doi = 10.1016/S1387-2656(06)12008-6 | isbn = 9780444527240 | url = }} It is highly selective for the GR over the mineralocorticoid receptor (MR),{{cite journal | vauthors = Meijer OC, de Kloet ER | title = A Refill for the Brain Mineralocorticoid Receptor: The Benefit of Cortisol Add-On to Dexamethasone Therapy | journal = Endocrinology | volume = 158 | issue = 3 | pages = 448–454 | date = March 2017 | pmid = 27967238 | doi = 10.1210/en.2016-1495 | s2cid = 7311584 | url = | doi-access = free }} and in relation to this, has minimal mineralocorticoid activity.{{cite book | vauthors = De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Nicolaides NC, Pavlaki AN, Maria Alexandra MA, Chrousos GP | title = Glucocorticoid Therapy and Adrenal Suppression | chapter = Endotext | year = 2000 | publisher = MDText.com | pmid = 25905379 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK279156/ | access-date = 17 June 2020 | archive-date = 1 July 2020 | archive-url = https://web.archive.org/web/20200701151045/https://www.ncbi.nlm.nih.gov/books/NBK279156/ | url-status = live }}{{cite journal | vauthors = Liu D, Ahmet A, Ward L, Krishnamoorthy P, Mandelcorn ED, Leigh R, Brown JP, Cohen A, Kim H | title = A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy | journal = Allergy, Asthma, and Clinical Immunology | volume = 9 | issue = 1 | pages = 30 | date = August 2013 | pmid = 23947590 | pmc = 3765115 | doi = 10.1186/1710-1492-9-30 | doi-access = free }} This is in contrast to endogenous corticosteroids like cortisol, which bind to and activate both the GR and the MR. Dexamethasone is 25 times more potent than hydrocortisone (cortisol) as a glucocorticoid. Its affinity (Ki) for the GR was about 1.2{{nbsp}}nM in one study.

The activation of the GR by dexamethasone results in dose-dependent suppression of the hypothalamic–pituitary–adrenal axis (HPA axis) and of production of endogenous corticosteroids by the adrenal glands, thereby reducing circulating endogenous concentrations of corticosteroids like cortisol and corticosterone.

Dexamethasone poorly penetrates the blood–brain barrier into the central nervous system due to binding to P-glycoprotein.{{cite journal | vauthors = De Kloet ER | title = Why Dexamethasone Poorly Penetrates in Brain | journal = Stress | volume = 2 | issue = 1 | pages = 13–20 | date = October 1997 | pmid = 9787252 | doi = 10.3109/10253899709014734 | url = }} However, higher doses of dexamethasone override the export capacity of P-glycoprotein and enter the brain to produce central activation of GRs. In conjunction with the suppression of endogenous corticosteroids by dexamethasone, this results in skewed ratios of activation of peripheral versus central GRs as well as skewed ratios of activation of GRs versus MRs when compared to non-synthetic corticosteroids. These differences can have significant clinical relevance.

Chemistry

Dexamethasone is a synthetic pregnane corticosteroid and derivative of cortisol (hydrocortisone) and is also known as 1-dehydro-9α-fluoro-16α-methylhydrocortisone or as 9α-fluoro-11β,17α,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione.{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA366|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=366–|url-status=live|archive-url=https://web.archive.org/web/20170215024945/https://books.google.com/books?id=0vXTBwAAQBAJ|archive-date=15 February 2017}}{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA310|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=310–|url-status=live|archive-url=https://web.archive.org/web/20170824142254/https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA310|archive-date=24 August 2017}} The molecular and crystal structure of dexamethasone has been determined by X-ray crystallography.{{ cite journal | vauthors = Raynor JW, Minor W, Chruszcz M | year = 2007 | title = Dexamethasone at 119 K | journal = Acta Crystallographica Section E | volume = 63 | issue = 6 | pages = o2791–93 | doi = 10.1107/S1600536807020806 | bibcode = 2007AcCrE..63o2791R }} It is a stereoisomer of betamethasone, the two compounds differing only in the spatial configuration of the methyl group at position 16 (see steroid nomenclature).{{cite journal | vauthors = Antignac JP, Le Bizec B, Monteau F, Andre F | title = Differentiation of betamethasone and dexamethasone using liquid chromatography/positive electrospray tandem mass spectrometry and multivariate statistical analysis | journal = Journal of Mass Spectrometry | volume = 37 | issue = 1 | pages = 69–75 | date = January 2002 | pmid = 11813313 | doi = 10.1002/jms.260 | bibcode = 2002JMSp...37...69A }}

=Synthesis=

To synthesize dexamethasone, 16β-methylprednisolone acetate is dehydrated to the 9,11-dehydro derivative.{{Cite journal | vauthors = Arth GE, Fried J, ((Johnston DBR)), Hoff DR, Sarett HL, Silber RH, Stoerk HC, Winter CA | journal = Journal of the American Chemical Society | year = 1958 | volume = 80 | pages = 3161–63 | issue = 12 | title = 16-Methylated steroids. II. 16α-Methyl analogs of cortisone, a new group of anti-inflammatory steroids. 9α-Halo derivatives | doi = 10.1021/ja01545a063 | bibcode = 1958JAChS..80.3161A }}{{Cite journal |vauthors=Taub D, Hoffsommer RD, Slates HL, lWendler NL | title = 16β-Methyl cortical steroids | journal = Journal of the American Chemical Society |year=1958 | volume = 80 | pages = 4435 | issue=16|doi=10.1021/ja01549a095| bibcode = 1958JAChS..80.4435T }} This is then reacted with a source of hypobromite, such as basic N-bromosuccinimide, to form the 9α-bromo-11β-hydrin derivative, which is then ring-closed to an epoxide. A ring-opening reaction with hydrogen fluoride in tetrahydrofuran gives dexamethasone.{{citation needed|date=June 2020}}

File:Dexamethasone synth.png

= Spectroscopy =

In chemistry, spectroscopy is used to analyze products of reactions. To understand if dexamethasone is synthesized from a reaction, spectroscopy must be taken and compared to the literature spectrum. There are multiple spectroscopy analyses that can be taken including 1H NMR, 13C NMR, IR, Mass spectrometry, and UV/vis spectroscopy.

File:1H NMR for Dexamethasone.png|1H NMR for Dexamethasone Speakman, N. M. A., Heard, A. W., & Nitschke, J. R. (2024). A CuI6L4 Cage Dynamically Reconfigures to Form Suit[4]anes and Selectively Bind Fluorinated Steroids. Journal of the American Chemical Society, 146(15), 10234–10239. https://doi.org/10.1021/jacs.4c00257

File:13C NMR for Dexamethasone.png|13C NMR for Dexamethasone

The NMR spectrum shown above can be used to compare to product synthesized through reactions to figure out if Dexamethasone was synthesized. 1H NMR, among other things, shows that there are 29 hydrogens and 13C NMR shows that there are 22 carbons.

File:Infrared spectroscopy of Dexamethasone.png|Infrared spectroscopy of Dexamethasone Shing, C. (2023). Novel cocrystals of dexamethasone. Hong Kong:

File:UV-vis spectroscopy of Dexamethasone.png|UV-vis spectroscopy of Dexamethasone Takegami, S., Kitamura, K., Funakoshi, T., & Kitade, T. (2008). Partitioning of anti-inflammatory steroid drugs into phosphatidylcholine and phosphatidylcholine-cholesterol small unilamellar vesicles as studied by second-derivative spectrophotometry. Chemical and Pharmaceutical Bulletin, 56(5), 663–667. {{doi|10.1248/cpb.56.663}}

Using IR spectroscopy, the peaks show the functional groups found in the molecule. You can see peaks at 3472, 1662, and 1618 representing alcohol, aldehyde, and alkene functional groups. UV-vis spectroscopy is another way to analyze a product to figure out what it is.

Finally, mass spectroscopy showed peaks at: 393.1, 355.2 147.1 m/z. The peak at 393.1 m/z is the peak for dexamethasone as its molecular weight is 392.46 m/z.Mulabagal, V., Wilson, C., & Hayworth, J. S. (2017). An ultrahigh-performance chromatography/tandem mass spectrometry quantitative method for trace analysis of potential endocrine disrupting steroid hormones in estuarine sediments. Rapid Communications in Mass Spectrometry, 31(5), 419–429. {{doi|10.1002/rcm.7807}}

History

Dexamethasone was first synthesized by Philip Showalter Hench in 1957.{{Cite web|url=https://targetcivils.in/1089/|title=Dexamethasone|date=17 June 2020|access-date=18 June 2020|archive-date=1 October 2020|archive-url=https://web.archive.org/web/20201001110933/https://targetcivils.in/1089/|url-status=dead}} It was introduced for medical use in 1958.{{cite journal | vauthors = Khan MO, Park KK, Lee HJ | title = Antedrugs: an approach to safer drugs | journal = Current Medicinal Chemistry | volume = 12 | issue = 19 | pages = 2227–39 | year = 2005 | pmid = 16178782 | doi = 10.2174/0929867054864840 }}

On 16 June 2020, the RECOVERY Trial announced preliminary results stating that dexamethasone improves survival rates of hospitalized patients with COVID-19 receiving oxygen or on a ventilator. Benefits were only observed in patients requiring respiratory support; those who did not require breathing support saw a worse survival rate than the control group, although the difference may have been due to chance.{{cite web|date=16 June 2020|title=Dexamethasone in COVID-19|url=https://www.gpni.co.uk/wp-content/uploads/2020/06/DEXAMETHASONE-IN-COVID-19.pdf|access-date=18 June 2020|website=www.gpni.co.uk|archive-date=17 June 2020|archive-url=https://web.archive.org/web/20200617192738/https://www.gpni.co.uk/wp-content/uploads/2020/06/DEXAMETHASONE-IN-COVID-19.pdf|url-status=live}}

A preprint containing the full dataset was published on 22 June 2020, and demand for dexamethasone surged after the publication of the preprint.{{cite journal|vauthors=Mahase E|date=June 2020|title=Covid-19: Demand for dexamethasone surges as RECOVERY trial publishes preprint|journal=BMJ|volume=369|pages=m2512|doi=10.1136/bmj.m2512|pmid=32576548|doi-access=free}} The preliminary report was published in The New England Journal of Medicine on 18 July 2020.{{cite journal | vauthors=Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ | date=July 2020 | title=Dexamethasone in Hospitalized Patients with Covid-19 – Preliminary Report | journal=New England Journal of Medicine | volume=384 | issue=8 | pages=693–704 | doi=10.1056/NEJMoa2021436 | pmid=32678530 | pmc=7383595 | doi-access=free | title-link=doi }} The final report was published in February 2021.{{cite journal | vauthors = Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ | title = Dexamethasone in Hospitalized Patients with Covid-19 | journal = N Engl J Med | volume = 384 | issue = 8 | pages = 693–704 | date = February 2021 | pmid = 32678530 | pmc = 7383595 | doi = 10.1056/NEJMoa2021436 | doi-access = free | title-link = doi }}

The World Health Organization (WHO) states that dexamethasone should be reserved for seriously ill and critical patients receiving COVID-19 treatment in a hospital setting,{{cite news|date=17 June 2020|title=Important to use dexamethasone only for serious COVID cases – WHO|url=https://www.reuters.com/article/us-health-coronavirus-who-dexamethasone/important-to-use-dexamethasone-only-for-serious-covid-cases-who-idUSKBN23O2MT|access-date=18 June 2020|archive-date=17 June 2020|archive-url=https://web.archive.org/web/20200617200600/https://www.reuters.com/article/us-health-coronavirus-who-dexamethasone/important-to-use-dexamethasone-only-for-serious-covid-cases-who-idUSKBN23O2MT|url-status=live}} and the WHO Director-General stated that "WHO emphasizes that dexamethasone should only be used for patients with severe or critical disease, under close clinical supervision. There is no evidence this drug works for patients with mild disease or as a preventative measure, and it could cause harm."{{cite web|title=WHO Director-General's opening remarks at the media briefing on COVID-19|date=22 June 2020|url=https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---22-june-2020|access-date=26 June 2020|website=World Health Organization|archive-date=12 September 2020|archive-url=https://web.archive.org/web/20200912202605/https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---22-june-2020|url-status=live}} In July 2020, the WHO stated they were in the process of updating treatment guidelines to include dexamethasone or other steroids.{{Cite web|title=Q&A: Dexamethasone and COVID-19|url=https://www.who.int/news-room/q-a-detail/q-a-dexamethasone-and-covid-19|access-date=12 July 2020|website=World Health Organization (WHO)|archive-date=11 October 2020|archive-url=https://web.archive.org/web/20201011115730/https://www.who.int/news-room/q-a-detail/q-a-dexamethasone-and-covid-19/|url-status=live}} In September 2020, the WHO released updated guidance on using corticosteroids for COVID-19.{{cite report | vauthors=((World Health Organization)) | year=2020 | title=Corticosteroids for COVID-19: living guidance, 2 September 2020 | publisher=World Health Organization | hdl=10665/334125 | id=WHO/2019-nCoV/Corticosteroids/2020.1 | url=https://www.who.int/publications/i/item/WHO-2019-nCoV-Corticosteroids-2020.1 | access-date=2 September 2020 | archive-date=11 October 2020 | archive-url=https://web.archive.org/web/20201011091829/https://www.who.int/publications/i/item/WHO-2019-nCoV-Corticosteroids-2020.1 | url-status=live }}{{cite press release | title=WHO updates clinical care guidance with corticosteroid recommendations | website=World Health Organization (WHO) | date=2 September 2020 | url=https://www.who.int/news-room/feature-stories/detail/who-updates-clinical-care-guidance-with-corticosteroid-recommendations | access-date=27 March 2022 | archive-date=6 May 2021 | archive-url=https://web.archive.org/web/20210506094931/https://www.who.int/news-room/feature-stories/detail/who-updates-clinical-care-guidance-with-corticosteroid-recommendations | url-status=live }}

In July 2020, the European Medicines Agency (EMA) started reviewing results from the RECOVERY study arm that involved the use of dexamethasone in the treatment of patients with COVID-19 admitted to the hospital to provide an opinion on the results and in particular the potential use of dexamethasone for the treatment of adults with COVID-19.{{cite press release | title=EMA starts review of dexamethasone for treating adults with COVID-19 requiring respiratory support | website=European Medicines Agency (EMA) | date=24 July 2020 | url=https://www.ema.europa.eu/en/news/ema-starts-review-dexamethasone-treating-adults-covid-19-requiring-respiratory-support | access-date=27 July 2020 | archive-date=30 January 2021 | archive-url=https://web.archive.org/web/20210130205543/https://www.ema.europa.eu/en/news/ema-starts-review-dexamethasone-treating-adults-covid-19-requiring-respiratory-support | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.{{cite news | title=EMA to review results from study testing common steroid drug against COVID-19 | website=Reuters | date=24 July 2020 | url=https://www.reuters.com/article/us-health-coronavirus-ema-dexamethasone-idUSKCN24P1KH | access-date=27 July 2020 | archive-date=27 July 2020 | archive-url=https://web.archive.org/web/20200727203429/https://www.reuters.com/article/us-health-coronavirus-ema-dexamethasone-idUSKCN24P1KH | url-status=live }} In September 2020, the EMA received an application for marketing authorization of dexamethasone for COVID-19.{{cite web | title=EMA receives application for marketing authorisation of Dexamethasone Taw COVID-19 | website=European Medicines Agency (EMA) | date=2 September 2020 | url=https://www.ema.europa.eu/en/news/ema-receives-application-marketing-authorisation-dexamethasone-taw-covid-19 | access-date=2 September 2020 | archive-date=3 September 2020 | archive-url=https://web.archive.org/web/20200903082812/https://www.ema.europa.eu/en/news/ema-receives-application-marketing-authorisation-dexamethasone-taw-covid-19 | url-status=live }}

Society and culture

=Price=

Dexamethasone is inexpensive.{{cite web|title=Dexamethasone for Accelerating Lung Maturation in Preterm Babies |url=https://www.who.int/selection_medicines/committees/expert/19/applications/Dexamethasone_29_C_NI.pdf|access-date=29 July 2015|url-status=live|archive-url=https://web.archive.org/web/20151222111212/http://www.who.int/selection_medicines/committees/expert/19/applications/Dexamethasone_29_C_NI.pdf|archive-date=22 December 2015}} In the United States a month of medication is typically priced less than {{US$|25}}. In India, a course of treatment for preterm labor is about {{US$|0.50}}. The drug is available in most areas of the world.

=Nonmedical use=

Dexamethasone is given to prostituted Bangladeshi children, causing weight gain aimed at making them appear older and healthier to customers and police.{{cite web | vauthors = Dummett M |date=30 May 2010 |title=Bangladesh's dark brothel steroid secret |publisher=BBC News Online |url=https://www.bbc.co.uk/news/10173115 |url-status=live |archive-url=https://web.archive.org/web/20120222194217/http://www.bbc.co.uk/news/10173115 |archive-date=22 February 2012 }}

Dexamethasone and most glucocorticoids are banned by sporting bodies including the World Anti-Doping Agency.{{cite web | url = https://www.wada-ama.org/en/content/what-is-prohibited/prohibited-in-competition/glucocorticoids | title = Prohibited In-Competition: Glucocorticoids | publisher = World Anti-Doping Agency | access-date = 16 July 2018 | archive-date = 16 July 2018 | archive-url = https://web.archive.org/web/20180716170139/https://www.wada-ama.org/en/content/what-is-prohibited/prohibited-in-competition/glucocorticoids | url-status = dead }}

Veterinary use

Combined with marbofloxacin CAS number 115550-35-1and clotrimazole, dexamethasone is available under the name Aurizon, CAS number 50-02-2, and used to treat difficult ear infections, especially in dogs. It can also be combined with trichlormethiazide to treat horses with swelling of distal limbs and general bruising.{{cite web |url=http://www.wedgewoodpharmacy.com/monographs/trichlormethiazide.asp |title=Trichlormethiazide and Dexamethasone for veterinary use |publisher=Wedgewood Pharmacy |access-date=23 January 2008 |url-status=live |archive-url=https://web.archive.org/web/20071212125537/http://www.wedgewoodpharmacy.com/monographs/trichlormethiazide.asp |archive-date=12 December 2007 }} Dexamethasone is also used for emergency patients with hypoadrenocorticism as the drug does not interfere with adrenocorticotropic hormone stimulation testing.{{cite book | vauthors = Miller MD, Smarick SD | title=Advanced Monitoring and Procedures for Small Animal Emergency and Critical Care | chapter=The Small Animal Emergency Room | publisher=Wiley | date=2023-05-12 | isbn=978-1-119-58141-3 | doi=10.1002/9781119581154.ch2 | page=20}}

References

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