Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, 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.
|Trade names||Dextenza, Ozurdex, Cortidex, Neofordex, others|
|By mouth, intravenous therapy (IV), intramuscular injection (IM), subcutaneous injection (SC), intraosseous (IO), eye drop|
|Elimination half-life||biological half-life: 36 to 54 hours; plasma half-life: 4 to 5 hours|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||392.467 g·mol−1|
|3D model (JSmol)|
|Melting point||262 °C (504 °F)|
|(what is this?)|
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. 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. 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 1961. It is on the World Health Organization's List of Essential Medicines. In 2017, it was the 321st most commonly prescribed medication in the United States, with more than one million prescriptions.
Dexamethasone is used to treat many inflammatory and autoimmune disorders, such as rheumatoid arthritis and bronchospasm. 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.
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 which often causes puffy, swollen cheeks.[medical citation needed]
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 FDA to treat ocular conditions such as diabetic macular edema, central retinal vein occlusion, and uveitis. Dexamethasone has also been used with antibiotics to treat acute endophthalmitis.
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.[medical citation needed]
Dexamethasone may be administered before antibiotics in cases of bacterial meningitis. It acts to reduce the inflammatory response of the body to the bacteria killed by the antibiotics (bacterial death releases proinflammatory mediators that can cause a response which is harmful), thus reducing hearing loss and neurological damage.
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. 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.
In brain tumors (primary or metastatic), dexamethasone is used to counteract the development of edema, which could eventually compress other brain structures. It is also given in cord 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.
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), or a combination of doxorubicin (Adriamycin) and vincristine or bortezomib/lenalidomide/dexamethasone.[medical citation needed]
Dexamethasone is recommended by the National Health Service in the UK and the National Institutes of Health (NIH) in the US for patients with COVID-19 who need either mechanical ventilation or supplemental oxygen (without ventilation).
The Infectious Diseases Society of America (IDSA) guideline panel suggests the use of glucocorticoids for patients with severe COVID-19, defined as patients with SpO2 ≤94% on room air, and those who require supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). 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).
A meta-analysis of seven clinical trials of critically ill COVID-19 patients, 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).
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 40 kg) who require supplemental oxygen therapy. Dexamethasone can be taken by mouth or given as an injection or infusion (drip) into a vein.
Therapy with dexamethasone at a dose of 6 mg once daily for up to 10 days has decreased 28-day mortality in patients with COVID-19 on respiratory support. There is no evidence supporting the long-term use of steroids in patients with COVID-19 to prevent potential adverse sequelae such as pulmonary fibrosis. On the contrary, such an extended course of steroids could be detrimental. It is plausible for exogenous glucocorticoids to precipitate clinical thrombosis in the prothrombotic environment of Covid-19. In addition, prolonged corticosteroid therapy might contribute to the so-called long COVID syndrome that manifests with fatigue and psychological symptoms, in which steroid-related adverse drug reactions such as myopathy, neuromuscular weakness, and psychiatric symptoms might have a part to play. Thus corticosteroids seem to be a double-edged sword in the fight against COVID-19 and need to be used judiciously, considering the risk-benefit ratio, as a short-course (e.g., up to 10 days) therapeutic agent in a select group of patients with COVID-19 for whom survival benefit has been reported.
Dexamethasone may be given to women at risk of delivering prematurely to promote maturation of the fetus' 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.
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. Experimental use of dexamethasone in pregnancy for fetal CAH treatment was discontinued in Sweden when one in five cases suffered adverse events.
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.
Dexamethasone is used in the treatment of high-altitude cerebral edema (HACE), as well as high-altitude pulmonary edema (HAPE). It is commonly carried on mountain-climbing expeditions to help climbers deal with complications of altitude sickness.
Nausea and vomitingEdit
Intravenous dexamethasone is effective for 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.
The exact incidence of the adverse effects of dexamethasone are 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.
- Increased appetite
- Weight gain
- Impaired skin healing
- Increased risk of infection
- Raised intraocular pressure
- Cataract (in cases of long-term treatment it occurs in about 10% of patients)
- Adrenal suppression
- Growth stunting (in children)
- Cushing's syndrome
- Peptic ulcer
- Diabetes mellitus type 2
- Pancreatitis (inflammation of the pancreas)
- Sodium and water retention
- Abdominal distension
- Corneal or scleral thinning
- Skin atrophy
- Psychological dependence
- Vertebral collapse
- Oesophageal ulcer
- Intracranial hypertension (long-term treatment)
- Facial plethora
- Muscular atrophy
- Nitrogen depletion due to protein catabolism
- Allergic reactions including anaphylaxis
Sudden withdrawal after long-term treatment with corticosteroids can lead to:
Known drug interactions include:
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. The molecular and crystal structure of dexamethasone has been determined by X-ray crystallography. 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).
To synthesize dexamethasone, 16β-methylprednisolone acetate is dehydrated to the 9,11-dehydro derivative. 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.
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. A preprint containing the full dataset was published on 22 June 2020 and demand for dexamethasone surged after publication of the preprint. The preliminary report was published in The New England Journal of Medicine on 18 July 2020.
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, 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." In July 2020, the WHO stated they are in the process of updating treatment guidelines to include dexamethasone or other steroids. In September 2020, the WHO released updated guidance on using corticosteroids for COVID‑19.
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. In September 2020, the EMA received an application for marketing authorization of dexamethasone for COVID‑19.
Society and cultureEdit
Dexamethasone is inexpensive. 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.
Dexamethasone is given in legal Bangladesh brothels to prostitutes not yet of legal age, causing weight gain aimed at making them appear older and healthier to customers and police.
Combined with marbofloxacin and clotrimazole, dexamethasone is available under the name Aurizon, CAS number 115550-35-1, 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.
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Dexamethasone is only recommended for use during pregnancy when there are no alternatives and benefit outweighs risk.
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Recommendation 4. Among hospitalized patients 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 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 patients 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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