Hydrocortisone: Difference between revisions

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<!-- Definition and medical uses -->
<!-- Definition and medical uses -->
'''Hydrocortisone''' is the name for the hormone [[cortisol]] when supplied as a medication.<ref>{{cite book | vauthors = Becker KL |title=Principles and Practice of Endocrinology and Metabolism|date=2001|publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-1750-2 |page=762 |url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA762|language=en|url-status=live|archive-url=https://web.archive.org/web/20160914013845/https://books.google.ca/books?id=FVfzRvaucq8C&pg=PA762|archive-date=14 September 2016}}</ref> It is a [[corticosteroid]] and works as an [[anti-inflammatory]] and by [[immunosuppressant|immune suppression]].<ref name="AHFS2016" /> Uses include conditions such as [[adrenocortical insufficiency]], [[adrenogenital syndrome]], [[hypercalcemia|high blood calcium]], [[thyroiditis]], [[rheumatoid arthritis]], [[dermatitis]], [[asthma]], and [[COPD]].<ref name="AHFS2016">{{cite web|title=Hydrocortisone|url=https://www.drugs.com/monograph/hydrocortisone.html|website=Drugs.com|publisher=American Society of Health-System Pharmacists|access-date=30 August 2016|date=9 February 2015|url-status=live|archive-url=https://web.archive.org/web/20160920063137/https://www.drugs.com/monograph/hydrocortisone.html|archive-date=20 September 2016}}</ref> It is the treatment of choice for adrenocortical insufficiency.<ref name="Ric2015">{{cite book | vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=978-1-284-05756-0|page=202}}</ref> It can be given [[by mouth]], [[topically]], or by [[Injection (medicine)|injection]].<ref name="AHFS2016" /> Stopping treatment after long-term use should be done slowly.<ref name="AHFS2016" />
'''Hydrocortisone''' is the name for the hormone [[cortisol]] when supplied as a medication.<ref>{{cite book | vauthors = Becker KL |title=Principles and Practice of Endocrinology and Metabolism|date=2001|publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-1750-2 |page=762 |url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA762|language=en|url-status=live|archive-url=https://web.archive.org/web/20160914013845/https://books.google.ca/books?id=FVfzRvaucq8C&pg=PA762|archive-date=14 September 2016}}</ref> It is a [[corticosteroid]] and works as an [[anti-inflammatory]] and by [[immunosuppressant|immune suppression]].<ref name="AHFS2016" /> Uses include conditions such as [[adrenocortical insufficiency]], [[adrenogenital syndrome]], [[hypercalcemia|high blood calcium]], [[thyroiditis]], [[rheumatoid arthritis]], [[dermatitis]], [[asthma]], and [[COPD]].<ref name="AHFS2016">{{cite web|title=Hydrocortisone|url=https://www.drugs.com/monograph/hydrocortisone.html|website=Drugs.com|publisher=American Society of Health-System Pharmacists|access-date=30 August 2016|date=9 February 2015|url-status=live|archive-url=https://web.archive.org/web/20160920063137/https://www.drugs.com/monograph/hydrocortisone.html|archive-date=20 September 2016}}</ref> It is the treatment of choice for adrenocortical insufficiency.<ref name="Ric2015">{{cite book | vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=978-1-284-05756-0|page=202}}</ref> It can be given [[by mouth]], [[topically]], [[Rectal administration|rectally]] or by [[Injection (medicine)|injection]].<ref name="AHFS2016" /> Stopping treatment after long-term use should be done slowly.<ref name="AHFS2016" />


<!-- Side effects and mechanism -->
<!-- Side effects and mechanism -->
Side effects may include mood changes, increased risk of [[infection]], and [[edema]] (swelling).<ref name="AHFS2016" /> With long-term use, common side effects include [[osteoporosis]], [[upset stomach]], [[physical weakness]], easy [[bruising]], and [[candidiasis]] (yeast infections).<ref name="AHFS2016" /> It is unclear if it is safe for use during [[pregnancy]].<ref>{{cite web|title=Hydrocortisone Pregnancy and Breastfeeding Warnings|url=https://www.drugs.com/pregnancy/hydrocortisone.html|website=Drugs.com|access-date=1 September 2016|url-status=live|archive-url=https://web.archive.org/web/20160920090158/https://www.drugs.com/pregnancy/hydrocortisone.html|archive-date=20 September 2016}}</ref>
Common side effects may include mood changes, [[Polyphagia|increased appetite]], [[hyperglycemia]], [[hypertension]], and [[edema]] (swelling).<ref name=":0">{{Cite web |title=Hydrocortisone: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD |url=https://www.webmd.com/drugs/2/drug-6731-581/hydrocortisone-oral/hydrocortisone-oral/details |access-date=2025-06-10 |website=www.webmd.com |language=en}}</ref> With long-term use, common side effects include [[osteoporosis]], adrenal insufficiency, [[upset stomach]], [[physical weakness]], easy [[bruising]], and [[candidiasis]] (yeast infections).<ref name="AHFS2016" /><ref name=":0" /> It is unclear if it is safe for use during [[pregnancy]].<ref>{{cite web|title=Hydrocortisone Pregnancy and Breastfeeding Warnings|url=https://www.drugs.com/pregnancy/hydrocortisone.html|website=Drugs.com|access-date=1 September 2016|url-status=live|archive-url=https://web.archive.org/web/20160920090158/https://www.drugs.com/pregnancy/hydrocortisone.html|archive-date=20 September 2016}}</ref>


<!-- History and society -->
<!-- History and society -->
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In the UK, the [[Competition and Markets Authority]] (CMA) concluded an investigation into the supply of hydrocortisone tablets, finding that from October 2008 onwards, drug suppliers Auden McKenzie and [[Actavis plc]] had charged "excessive and unfair prices" for 10mg and 20mg tablets and entered into agreements with potential competitors, paying companies who agreed not to enter the hydrocortisone market and enabling Auden McKenzie and Actavis to supply the drugs as "[[generic drug|generic]]" rather than branded products and thereby escape price controls until eventually other companies entered the market.  Auden and Actavis overcharged the UK's [[National Health Service]] for over ten years. Fines totalling over £255m were levied against the companies involved in this breach of [[competition law]].<ref>{{OGL-attribution|Competition and Markets Authority, [https://assets.publishing.service.gov.uk/media/624597bbe90e075f0b5a3da4/Case_50277_Decision.pdf Decision: Hydrocortisone tablets. Excessive and unfair pricing and Anti-competitive agreements], published 31 March 2022, accessed 1 June 2023}}</ref>
In the UK, the [[Competition and Markets Authority]] (CMA) concluded an investigation into the supply of hydrocortisone tablets, finding that from October 2008 onwards, drug suppliers Auden McKenzie and [[Actavis plc]] had charged "excessive and unfair prices" for 10mg and 20mg tablets and entered into agreements with potential competitors, paying companies who agreed not to enter the hydrocortisone market and enabling Auden McKenzie and Actavis to supply the drugs as "[[generic drug|generic]]" rather than branded products and thereby escape price controls until eventually other companies entered the market.  Auden and Actavis overcharged the UK's [[National Health Service]] for over ten years. Fines totalling over £255m were levied against the companies involved in this breach of [[competition law]].<ref>{{OGL-attribution|Competition and Markets Authority, [https://assets.publishing.service.gov.uk/media/624597bbe90e075f0b5a3da4/Case_50277_Decision.pdf Decision: Hydrocortisone tablets. Excessive and unfair pricing and Anti-competitive agreements], published 31 March 2022, accessed 1 June 2023}}</ref>


== Research ==
==Research==
===Chronic fatigue syndrome===
[[Cortisol]] levels have been found to be altered in people with [[myalgic encephalomyelitis/chronic fatigue syndrome]] (ME/CFS).<ref name="TaccoriMaksoudEaton-Fitch2023">{{cite journal | vauthors = Taccori A, Maksoud R, Eaton-Fitch N, Patel M, Marshall-Gradisnik S | title = A systematic review and meta-analysis of urinary biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) | journal = J Transl Med | volume = 21 | issue = 1 | pages = 440 | date = July 2023 | pmid = 37408028 | pmc = 10320942 | doi = 10.1186/s12967-023-04295-0 | doi-access = free | url = }}</ref><ref name="TakCleareOrmel2011">{{cite journal | vauthors = Tak LM, Cleare AJ, Ormel J, Manoharan A, Kok IC, Wessely S, Rosmalen JG | title = Meta-analysis and meta-regression of hypothalamic-pituitary-adrenal axis activity in functional somatic disorders | journal = Biol Psychol | volume = 87 | issue = 2 | pages = 183–194 | date = May 2011 | pmid = 21315796 | doi = 10.1016/j.biopsycho.2011.02.002 | url = }}</ref><ref name="PowellLiossiMoss-Morris2013">{{cite journal | vauthors = Powell DJ, Liossi C, Moss-Morris R, Schlotz W | title = Unstimulated cortisol secretory activity in everyday life and its relationship with fatigue and chronic fatigue syndrome: a systematic review and subset meta-analysis | journal = Psychoneuroendocrinology | volume = 38 | issue = 11 | pages = 2405–2422 | date = November 2013 | pmid = 23916911 | doi = 10.1016/j.psyneuen.2013.07.004 | url = | doi-access = free }}</ref> Hydrocortisone has been clinically studied in the treatment of ME/CFS.<ref name="CollatzJohnstonStaines2016">{{cite journal | vauthors = Collatz A, Johnston SC, Staines DR, Marshall-Gradisnik SM | title = A Systematic Review of Drug Therapies for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis | journal = Clin Ther | volume = 38 | issue = 6 | pages = 1263–1271.e9 | date = June 2016 | pmid = 27229907 | doi = 10.1016/j.clinthera.2016.04.038 | url = }}</ref><ref name="CleareHeapMalhi1999">{{cite journal | vauthors = Cleare AJ, Heap E, Malhi GS, Wessely S, O'Keane V, Miell J | title = Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial | journal = Lancet | volume = 353 | issue = 9151 | pages = 455–458 | date = February 1999 | pmid = 9989716 | doi = 10.1016/S0140-6736(98)04074-4 | url = }}</ref><ref name="McKenzieO'FallonDale1998">{{cite journal | vauthors = McKenzie R, O'Fallon A, Dale J, Demitrack M, Sharma G, Deloria M, Garcia-Borreguero D, Blackwelder W, Straus SE | title = Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial | journal = JAMA | volume = 280 | issue = 12 | pages = 1061–1066 | date = 1998 | pmid = 9757853 | doi = 10.1001/jama.280.12.1061 | url = }}</ref> A 2016 [[systematic review]] found that it had been assessed for this purpose in six clinical studies.<ref name="CollatzJohnstonStaines2016" /> Its clinical effectiveness was conflicting in the studies, ranging from not effective, to slightly or mildly effective, to moderately effective.<ref name="CollatzJohnstonStaines2016" /> Four of the studies came from one research group.<ref name="CollatzJohnstonStaines2016" /> The systematic review called for higher-quality trials.<ref name="CollatzJohnstonStaines2016" /> A 2015 systematic review found that the clinical data on hydrocortisone for ME/CFS was inconclusive.<ref name="SmithHaneyMcDonagh2015">{{cite journal | vauthors = Smith ME, Haney E, McDonagh M, Pappas M, Daeges M, Wasson N, Fu R, Nelson HD | title = Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop | journal = Ann Intern Med | volume = 162 | issue = 12 | pages = 841–850 | date = June 2015 | pmid = 26075755 | doi = 10.7326/M15-0114 | url = }}</ref>


===COVID-19===
===COVID-19===

Latest revision as of 22:45, 10 June 2025

Template:Short description Template:Use dmy dates Template:Cs1 config Template:Drugbox

Hydrocortisone is the name for the hormone cortisol when supplied as a medication.[1] It is a corticosteroid and works as an anti-inflammatory and by immune suppression.[2] Uses include conditions such as adrenocortical insufficiency, adrenogenital syndrome, high blood calcium, thyroiditis, rheumatoid arthritis, dermatitis, asthma, and COPD.[2] It is the treatment of choice for adrenocortical insufficiency.[3] It can be given by mouth, topically, rectally or by injection.[2] Stopping treatment after long-term use should be done slowly.[2]

Common side effects may include mood changes, increased appetite, hyperglycemia, hypertension, and edema (swelling).[4] With long-term use, common side effects include osteoporosis, adrenal insufficiency, upset stomach, physical weakness, easy bruising, and candidiasis (yeast infections).[2][4] It is unclear if it is safe for use during pregnancy.[5]

Hydrocortisone was patented in 1936 and approved for medical use in 1941.[6][7] It is on the World Health Organization's List of Essential Medicines.[8] It is available as a generic medication.[2] In 2022, it was the 202nd most commonly prescribed medication in the United States, with more than 2Template:Nbspmillion prescriptions.[9][10]

Medical uses

Hydrocortisone is the pharmaceutical term for cortisol used in oral administration, intravenous injection, or topical application. It is used as an immunosuppressive drug, given by injection in the treatment of severe allergic reactions such as anaphylaxis and angioedema, in place of prednisolone in patients needing steroid treatment but unable to take oral medication, and perioperatively in patients on long-term steroid treatment to prevent an adrenal crisis. It may also be injected into inflamed joints resulting from diseases such as gout.Script error: No such module "Unsubst".

It may be used topically for allergic rashes, eczema, psoriasis, itching, and other inflammatory skin conditions. Topical hydrocortisone creams and ointments are available in most countries without prescription in strengths ranging from 0.05% to 2.5% (depending on local regulations) with stronger forms available by prescription only.Script error: No such module "Unsubst".

It may also be used rectally in suppositories to relieve the swelling, itch, and irritation in hemorrhoids.[11]

It may be used as an acetate form (hydrocortisone acetate), which has slightly different pharmacokinetics and pharmacodynamics.[11][12]

Pharmacology

Pharmacodynamics

Hydrocortisone is a corticosteroid, acting specifically as both a glucocorticoid and as a mineralocorticoid. That is, it is an agonist of the glucocorticoid and mineralocorticoid receptors.Script error: No such module "Unsubst".

Hydrocortisone has low potency relative to synthetic corticosteroids.[13] Compared to hydrocortisone, prednisolone is about 4Template:Nbsptimes as potent and dexamethasone about 40Template:Nbsptimes as potent in terms of anti-inflammatory effect.[14] Prednisolone can also be used as cortisol replacement, and at replacement dose levels (rather than anti-inflammatory levels), prednisolone is about 8Template:Nbsptimes more potent than cortisol.[15] The equivalent doses and relative potencies of hydrocortisone compared to various other synthetic corticosteroids have also been reviewed and summarized.[13]

The endogenous production rate of cortisol is approximately 5.7 to 9.9Template:Nbspmg/m2 per day, which corresponds to an oral hydrocortisone dose of approximately 15 to 20Template:Nbspmg/day (for a 70-kg person).[16][17] One review described daily cortisol production of 10Template:Nbspmg in healthy volunteers and reported that daily cortisol production could increase up to 400Template:Nbspmg in conditions of severe stress (e.g., surgery).[18]

The total and/or free concentrations of cortisol/hydrocortisone required for various glucocorticoid effects have been determined.[18]

Pharmacokinetics

Absorption

The bioavailability of oral hydrocortisone is about 96% ± 20% (SD).[18][19] The pharmacokinetics of hydrocortisone are non-linear.[18] The peak level of oral hydrocortisone is 15.3 ± 2.9 (SD) μg/L per 1Template:Nbspmg dose.[18] The time to peak concentrations of oral hydrocortisone is 1.2 ± 0.4 (SD) hours.[18]

The topical percutaneous absorption of hydrocortisone varies widely depending on experimental circumstances and has been reported to range from 0.5 to 14.9% in different studies.[20] Some skin application sites, like the scrotum and vulva, absorb hydrocortisone much more efficiently than other application sites, like the forearm.[20][21][22] In one study, the amount of hydrocortisone absorbed ranged from 0.2% to 36.2% depending on the application site, with the ball of the foot having the lowest absorption and the scrotum having the highest absorption.[22] The absorption of hydrocortisone by the vulva has ranged from 4.4 to 8.1%, relative to 1.3 to 2.8% for the arm, in different studies and subjects.[22][23][24]

Distribution

Most cortisol in the blood (all but about 4%) is bound to proteins, including corticosteroid binding globulin (CBG) and serum albumin. A pharmacokinetic review stated that 92% ± 2% (SD) (92–93%) of hydrocortisone is plasma protein-bound.[18] Free cortisol passes easily through cellular membranes.[25] Inside cells it interacts with corticosteroid receptors.[26]

Metabolism

Hydrocortisone is metabolized by 11β-hydroxysteroid dehydrogenases (11β-HSDs) into cortisone, an inactive metabolite.[19][18] It is additionally 5α-, 5β-, and 3α-reduced into dihydrocortisols, dihydrocortisones, tetrahydrocortisols, and tetrahydrocortisones.[27][18][19]

Elimination

The elimination half-life of hydrocortisone ranges from about 1.2 to 2.0 (SD) hours, with an average of around 1.5Template:Nbsphours, regardless of oral versus parenteral administration.[18][19] The duration of action of systemic hydrocortisone has been listed as 8 to 12Template:Nbsphours.[13]

Chemistry

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Hydrocortisone, also known as 11β,17α,21-trihydroxypregn-4-ene-3,20-dione, is a naturally occurring pregnane steroid.[28][29] A variety of hydrocortisone esters exist and have been marketed for medical use.[28][29]

Society and culture

Legal status

In March 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Efmody, intended for the treatment of congenital adrenal hyperplasia (CAH) in people aged twelve years and older.[30] The applicant for this medicinal product is Diurnal Europe BV.[30] Hydrocortisone (Efmody) was approved for medical use in the European Union, in May 2021, for the treatment of congenital adrenal hyperplasia (CAH) in people aged twelve years and older.[31]

Anti-competitive practices

In the UK, the Competition and Markets Authority (CMA) concluded an investigation into the supply of hydrocortisone tablets, finding that from October 2008 onwards, drug suppliers Auden McKenzie and Actavis plc had charged "excessive and unfair prices" for 10mg and 20mg tablets and entered into agreements with potential competitors, paying companies who agreed not to enter the hydrocortisone market and enabling Auden McKenzie and Actavis to supply the drugs as "generic" rather than branded products and thereby escape price controls until eventually other companies entered the market. Auden and Actavis overcharged the UK's National Health Service for over ten years. Fines totalling over £255m were levied against the companies involved in this breach of competition law.[32]

Research

Chronic fatigue syndrome

Cortisol levels have been found to be altered in people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).[33][34][35] Hydrocortisone has been clinically studied in the treatment of ME/CFS.[36][37][38] A 2016 systematic review found that it had been assessed for this purpose in six clinical studies.[36] Its clinical effectiveness was conflicting in the studies, ranging from not effective, to slightly or mildly effective, to moderately effective.[36] Four of the studies came from one research group.[36] The systematic review called for higher-quality trials.[36] A 2015 systematic review found that the clinical data on hydrocortisone for ME/CFS was inconclusive.[39]

COVID-19

Hydrocortisone was found to be effective in reducing mortality rate of critically ill COVID-19 patients when compared to other usual care or a placebo.[40]

References

Template:Reflist

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  1. ↑ Script error: No such module "citation/CS1".
  2. ↑ a b c d e f Script error: No such module "citation/CS1".
  3. ↑ Script error: No such module "citation/CS1".
  4. ↑ a b Script error: No such module "citation/CS1".
  5. ↑ Script error: No such module "citation/CS1".
  6. ↑ U.S. patent 2183589
  7. ↑ Script error: No such module "citation/CS1".
  8. ↑ Script error: No such module "citation/CS1".
  9. ↑ Script error: No such module "citation/CS1".
  10. ↑ Script error: No such module "citation/CS1".
  11. ↑ a b Cite error: Invalid <ref> tag; no text was provided for refs named anusol-acetate
  12. ↑ Script error: No such module "Citation/CS1".
  13. ↑ a b c Script error: No such module "Citation/CS1".
  14. ↑ Script error: No such module "citation/CS1".
  15. ↑ Script error: No such module "Citation/CS1".
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  18. ↑ a b c d e f g h i j Cite error: Invalid <ref> tag; no text was provided for refs named pmid15634032
  19. ↑ a b c d Cite error: Invalid <ref> tag; no text was provided for refs named pmid18611115
  20. ↑ a b Script error: No such module "Citation/CS1".
  21. ↑ Script error: No such module "Citation/CS1".
  22. ↑ a b c Script error: No such module "citation/CS1".
  23. ↑ Script error: No such module "Citation/CS1".
  24. ↑ Script error: No such module "Citation/CS1".
  25. ↑ Script error: No such module "Citation/CS1".
  26. ↑ Script error: No such module "citation/CS1".
  27. ↑ Script error: No such module "Citation/CS1".
  28. ↑ a b Script error: No such module "citation/CS1".
  29. ↑ a b Script error: No such module "citation/CS1".
  30. ↑ a b Script error: No such module "citation/CS1". Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  31. ↑ Script error: No such module "citation/CS1". Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  32. ↑ Template:OGL-attribution
  33. ↑ Script error: No such module "Citation/CS1".
  34. ↑ Script error: No such module "Citation/CS1".
  35. ↑ Script error: No such module "Citation/CS1".
  36. ↑ a b c d e Script error: No such module "Citation/CS1".
  37. ↑ Script error: No such module "Citation/CS1".
  38. ↑ Script error: No such module "Citation/CS1".
  39. ↑ Script error: No such module "Citation/CS1".
  40. ↑ Script error: No such module "Citation/CS1".
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