Layer 1

Clinical trial efficacy for dexamethasone and COVID-19

Dexamethasone identified as the first drug to improve survival rates in certain hospitalised COVID-19 patients

Unplanned learning

This article was correct at time of publishing (June 24). To keep up with the latest information please visit our coronavirus hub

Dexamethasone is a corticosteroid, otherwise known as a glucocorticoid, with primarily glucocorticoid effects. It has immunosuppressive, anti-inflammatory, antipyretic and anti-allergic effects like other glucocorticoids. When compared to prednisolone, its anti-inflammatory effects are thought to be seven times more potent. It has a long half-life of approximately 36–54 hours and has minimal water and salt-retaining effects (mineralocorticoid properties).(1)

How does dexamethasone work?

Corticosteroids are synthetic versions of the hormones produced by the adrenal glands. They have inhibitory effects on a broad range of immune responses and if they are taken in doses higher than what is produced by the body, glucocorticoids are efficacious in managing acute disease manifestations of inflammatory and autoimmune disorders.(2,3)

Glucocorticoids exert their effects by modulating gene expression. They bind to the intracellular glucocorticoid receptor, creating a complex that interacts with specific DNA sequences such as glucocorticoid-responsive elements and transcription factors. This results in; the blockage of proinflammatory genes, inhibiting the synthesis of inflammatory cytokines and the recruitment of transcription factors for genes coding for anti-inflammatory gene products. They also have effects on post-translational events inhibiting the secretion of inflammatory cytokines and reducing the production of cyclooxygenase-2 thereby reducing the production of prostaglandins.(3)

What is dexamethasone usually indicated for?

Dexamethasone is used in a wide variety of conditions including endocrine disorders, such as primary or secondary adrenocortical insufficiency and congenital adrenal hyperplasia, or for diagnostic testing of adrenocortical hyperfunction.(4)

It is also used in the management of non-endocrine disorders, such as allergy and anaphylaxis, blood disorders such as leukemia and myeloma, cardiovascular conditions, gastrointestinal disorders such as Crohn’s disease and ulcerative colitis, skin conditions, respiratory conditions such as asthma, ocular disorders and muscular conditions.(4)

What are the common side effects?

Short-term use with dexamethasone (less than three weeks) is not likely to result in significant side effects. Side effects are more likely at higher doses or when taken for a longer duration.(2)

Side effects experienced can be varied and include: increased appetite, indigestion or heartburn, changes in sleeping behaviour, diabetes, immunosuppression, increase in blood pressure, osteoporosis, glaucoma, mental health problems such as depression, and Cushing’s syndrome.(2)

Considerations with dexamethasone use

As dexamethasone suppresses the immune system, it increases the risk and severity of infections. It is therefore contraindicated in a systemic infection, unless targeted anti-infective therapy is being given. It should be used with caution in those who experience recurrent infections.(1)

Caution is also advised in patients with diabetes as it can affect sugar levels, hypertension or heart problems due to its water retaining effects, people with epilepsy, hypothyroidism, migraine, peptic ulceration, glaucoma and liver failure or renal insufficiency.(1)

What is the RECOVERY trial?

The RECOVERY Trial (Randomised Evaluation of COVid-19 thERapY), established in March 2020, is a randomised, controlled trial that has shown initial positive results for dexamethasone treatment in those with respiratory complications of COVID-19. This national clinical trial aims to identify treatments that may be beneficial for people hospitalised with suspected or confirmed COVID-19. Over 11,500 hospitalised patients with COVID-19 have been enrolled into the trial.(5)

Patients were randomised to receive the following treatment arms, or no additional treatment:(5)

  • tocilizumab
  • lopinavir-ritonavir
  • azithromycin
  • dexamethasone
  • convalescent plasma (collected from donors who have recovered from COVID-19 and contains antibodies against the SARS-CoV-2 virus).

Trials with a hydroxychloroquine treatment arm have now been stopped due to lack of efficacy.

Dexamethasone treatment resulted in a reduction in deaths – by a third in ventilated patients and by a fifth in those being given oxygen only. The trial did not show any benefit in patients who did not require respiratory support. The dose given was 6mg daily, administered by mouth or intravenous injection, for 10 days. These early results have caused a change in practice in the management of hospitalised patients with COVID-19.(5)

More information on the RECOVERY trial can be found on the RECOVERY trial website.

References
  1. Aspen Pharma Trading Limited (2018) Dexamethasone 2mg tablets.
  2. NHS Conditions (2020) Steroids.
  3. UpToDate (2019) Glucocorticoid effects on the immune system.
  4. Martindale Pharma (2018) Dexamethasone 2mg tablets.
  5. National Institute for Health Research (2020) First drug to reduce mortality in hospitalised patients with respiratory complications of COVID-19 found.
Complete your CPD logsheet
0 Comments
Login or register to post comments

Job of the week

Pharmacist (qualified Independent Prescriber)
London (Central), London (Greater)
Annual salary to start at £52,000 based on a 40 hour week.