The long-term use of dexamethasone may result inthrush, bone loss,cataracts, easy bruising, or muscle weakness.[10] It is inpregnancy category C in the United States, meaning that it should only be used when the benefits are predicted to be greater than the risks.[12] 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.[13] It should not be taken whenbreastfeeding.[10] Dexamethasone hasanti-inflammatory andimmunosuppressant effects.[10]
Dexamethasone was first synthesized in 1957 byPhilip Showalter Hench and was approved for medical use in 1958.[14][15][16] It is on theWorld Health Organization's List of Essential Medicines.[17] In 2023, it was the 246th most commonly prescribed medication in the United States, with more than 1million prescriptions.[18][19] It is available as ageneric medication.[20] In 2023, the combination of dexamethasone withneomycin andpolymyxin B was the 260th most commonly prescribed medication in the United States, with more than 1million prescriptions;[18][21] and the combination of dexamethasone withciprofloxacin was the 283rd most commonly prescribed medication in the United States, with more than 700,000 prescriptions;[18][22]
It is also given in small amounts before and/or after some forms ofdental surgery, such as the extraction of thewisdom teeth, an operation that often causes puffy, swollen cheeks.[25]
Dexamethasone is commonly given as a treatment forcroup in children.[26] A single dose can reduce the swelling of the airway to improve breathing and reduce discomfort.[26]
Dexamethasone is sometimes injected into the heel when treatingplantar fasciitis or heel pain, sometimes in conjunction withtriamcinolone acetonide. There is no evidence that this treatment helps in the long term, however, dexamethasone may provide short-term pain relief.[27]
It may be useful to counteractallergic anaphylactic shock, however this is not usually recommended by clinical guidelines.[28]
It is present in certaineye drops – particularly aftereye surgery – and as anasal spray, and certain ear drops (can be combined with an antibiotic and an antifungal). Dexamethasone intravitreal steroid implants have been approved by the USFood and Drug Administration (FDA) to treat ocular conditions such asdiabetic macular edema,central retinal vein occlusion, anduveitis. However, the evidence is poor quality relating to the treatment of uveitis, with the potential side effects (cataract progression and raisedintraocular pressure) being significant, and the benefits not certainly greater than standard treatment.[29] Dexamethasone has also been used with antibiotics to treat acuteendophthalmitis.[30]
Dexamethasone is used in transvenous screw-incardiac pacing leads to minimize the inflammatory response of themyocardium. 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.[medical citation needed]
Dexamethasone may be administered before antibiotics in cases ofbacterial meningitis.Gram-negative bacteria — to which the causative agent of bacterial meningitis,neisseria meningitidis, belongs — have highly immunogeniclipopolysaccharides 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.[31]
A single ampoule of dexamethasone phosphate for injection
Inbrain tumors (primary or metastatic), dexamethasone is used to counteract the development ofedema, which could eventually compress other brain structures.[34] It is also given incord compression, where a tumor is compressing the spinal cord.[medical citation needed] Evidence on the safety and efficacy of using dexamethasone to treat malignant brain tumors is not clear.[35]
TheInfectious Diseases Society of America (IDSA) guideline panel suggests the use of glucocorticoids for people with severe COVID-19, defined as people withSpO2 ≤94% on room air, and those who require supplemental oxygen, mechanical ventilation, orextracorporeal membrane oxygenation (ECMO).[39] The IDSA recommends against the use of glucocorticoids for those with COVID-19 without hypoxemia requiring supplemental oxygen.[39]
TheWorld 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).[40] The WHO suggests not to use corticosteroids in the treatment of people with non-severe COVID-19 (conditional recommendation, based on low certainty evidence).[40]
TheOxford UniversityRECOVERY Trial issued a press release announcing preliminary results that the drug could reduce deaths by about a third in participants onventilators and by about a fifth in participants on oxygen; it did not benefit people who did not require respiratory support.[41] Ameta-analysis of seven clinical trials of critically ill COVID-19 participants, each treated with one of three differentcorticosteroids found a statistically significant reduction in death.[42] The largest reduction was obtained with dexamethasone (36% compared to placebo).[42][43]
In September 2020, theEuropean Medicines Agency (EMA) endorsed the use of dexamethasone in adults and adolescents, from twelve years of age and weighing at least 40 kilograms (88 lb), who require supplemental oxygen therapy.[44] Dexamethasone can be taken by mouth or given as an injection or infusion (drip) into a vein.[44]
In November 2020, thePublic Health Agency of Canada's Clinical Pharmacology Task Group recommended dexamethasone for hospitalized patients requiring mechanical ventilation.[45] Although dexamethasone, and other glucocorticoids, reduce mortality in COVID-19 they have also been associated with an increased risk of secondary infections,[46][47][48] secondary infections being a significant issue in critically ill COVID-19 patients.[49]
The mechanism of action of dexamethasone involves suppression of late-stageinterferon type I programs in severe COVID-19 patients.[50]
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.[51] 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.[51]
Dexamethasone may be given to women at risk of delivering prematurely to promotematuration of the fetus's lungs. This administration, given from one day to one week before delivery, has been associated withlow birth weight, although not with increased rates of neonatal death.[55]
Dexamethasone has also been used during pregnancy as anoff-label prenatal treatment for the symptoms ofcongenital adrenal hyperplasia (CAH) in female babies. CAH causes a variety of physical abnormalities, notablyambiguous genitalia. Early prenatal CAH treatment has been shown to reduce some CAH symptoms, but it does not treat the underlyingcongenital 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.[56] Experimental use of dexamethasone in pregnancy for fetal CAH treatment was discontinued in Sweden when one in five cases had adverse events.[57]
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.[58][59]
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.[63]
The combination of dexamethasone and a5-HT3 receptor antagonist such asondansetron is more effective than a 5-HT3 receptor antagonist alone in preventing postoperative nausea and vomiting.[64]
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.[67][68][69][70][71]
Dexamethasone poorly penetrates theblood–brain barrier into thecentral nervous system due to binding toP-glycoprotein.[74][78] However, higher doses of dexamethasone override the export capacity of P-glycoprotein and enter the brain to produce central activation of GRs.[74] 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.[74][78] These differences can have significant clinical relevance.[74][78]
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 including1H NMR,13C NMR,IR,Mass spectrometry, andUV/vis spectroscopy.
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.
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.[88]
On 16 June 2020, theRECOVERY Trial announced preliminary results stating that dexamethasone improves survival rates of hospitalized patients withCOVID-19 receiving oxygen or on aventilator. 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.[90]A preprint containing the full dataset was published on 22 June 2020, and demand for dexamethasone surged after the publication of the preprint.[91] The preliminary report was published inThe New England Journal of Medicine on 18 July 2020.[92] The final report was published in February 2021.[93]
TheWorld Health Organization (WHO) states that dexamethasone should be reserved for seriously ill and critical patients receiving COVID-19 treatment in a hospital setting,[94] 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."[95] In July 2020, the WHO stated they were in the process of updating treatment guidelines to include dexamethasone or other steroids.[96] In September 2020, the WHO released updated guidance on using corticosteroids for COVID-19.[40][97]
In July 2020, theEuropean 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.[98][99] In September 2020, the EMA received an application for marketing authorization of dexamethasone for COVID-19.[100]
Dexamethasone is inexpensive.[101] In the United States a month of medication is typically priced less thanUS$25.[10] In India, a course of treatment for preterm labor is aboutUS$0.50.[101] The drug is available in most areas of the world.[101]
Dexamethasone is given toprostituted Bangladeshi children, causing weight gain aimed at making them appear older and healthier to customers and police.[102]
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^ab"COVID-19 Guideline, Part 1: Treatment and Management".Infectious Diseases Society of America.Archived from the original on 6 October 2020. Retrieved22 July 2020.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)
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