Published: 6 June 2024

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Dexamethasone: a highly potent and long-acting steroid

Published: 6 June 2024
Prescriber Update 45(2): 40–42
June 2024

Key messages

  • Dexamethasone is a highly potent and long-acting glucocorticoid. The risk of adverse effects is higher with dexamethasone than with other less-potent steroids.
  • Serious adverse effects include adrenal suppression, severe psychiatric reactions, osteonecrosis, and increased susceptibility to infections.
  • Prescribe dexamethasone at the lowest effective dose for the shortest possible duration. Withdrawal of dexamethasone should be gradual to reduce the risk of acute adrenal insufficiency.


This article is a reminder about the potential for serious adverse effects with dexamethasone.

Indications

Dexamethasone is a highly potent and long-acting corticosteroid with high glucocorticoid activity and minimal mineralocorticoid activity. Dexamethasone is approximately six times more potent than prednisone.1

Systemic dexamethasone is indicated for replacement therapy in adrenal insufficiency and to treat variety of severe autoimmune, inflammatory and allergic disorders.2,3 In addition, the tablets are indicated for treatment of severe COVID-19 disease and the solution for injection for the treatment of shock.2,3 Topical and intravitreal presentations are also available for the treatment of certain eye disorders.4,5

Serious adverse effects

Some of the more serious adverse effects from systemic administration of dexamethasone are described below. See the data sheets for more information.

Adrenal insufficiency2,3

Adrenal suppression may occur with the use of all glucocorticoids. Symptoms of adrenal suppression are non-specific and can include malaise, muscle weakness, mental changes, desquamation of the skin, nausea and vomiting, hypoglycaemia and dehydration.

The degree and duration of adrenal suppression is variable among patients and depends on the dose, frequency, and duration of therapy. Adrenal insufficiency may persist for several months after treatment discontinuation.

Abrupt withdrawal of glucocorticoids may result in life-threatening acute adrenal sufficiency.

Neuropsychiatric

Neuropsychiatric disturbances, including mood disturbances, insomnia, personality changes, irritability, anxiety, mania, depression, and suicidal ideation typically occur within a few days or weeks of starting treatment.2,3

Insomnia is considered to be a significant predictor for the onset of affective disorders including major depression,6 anxiety and psychotic disorders.7,8

Individuals with an existing or previous history of severe affective disorders may be at greater risk of neuropsychiatric adverse reactions.2,3

Musculoskeletal

Musculoskeletal complications include osteonecrosis, myopathy, osteoporosis and fractures.2,3

Approximately 30 to 50 percent of long-term glucocorticoid users develop secondary osteoporosis. Osteonecrosis can occur independently of osteoporosis, affecting 9 to 40 percent of patients on prolonged therapy or with short-term high doses.9,10

In infancy, childhood and adolescence, long-term treatment with glucocorticoids can cause growth retardation, which may be irreversible.2,3

Immunosuppression2,3

Suppression of the inflammatory response and immune function increases susceptibility to and the severity of infections. The typical signs and symptoms of serious infections may be masked. Latent infections, such as latent tuberculosis, can reactivate.

Live vaccines are contraindicated in individuals on high-dose corticosteroids.

New Zealand reports

Between January 1993 and March 2024, Medsafe and the Centre for Adverse Reactions Monitoring (CARM) received 87 reports where the suspect medicine was reported as dexamethasone (excluding combination products).

Of the 87 reports, there were:

  • 14 reports of osteonecrosis, with 3 of those occurring in children aged under 18 years
  • 8 reports of psychiatric disorders, including confusional state, mania, abnormal behaviour, aggression, anxiety, delusion, disorientation and insomnia.

Prescribing considerations

When prescribing dexamethasone:

  • use the lowest effective dose for the shortest possible period to manage the patient’s condition
  • consider risk factors that might make the patient more susceptible to adverse effects (eg, age, physical and psychiatric comorbidities)
  • regularly monitor the patient for adverse effects
  • avoid long-term use in children due to the risk of growth retardation
  • ensure gradual withdrawal to reduce the risk of acute adrenal insufficiency.

References

  1. New Zealand Formulary (NZF). 2024. NZF v141: Corticosteroids 1 March 2024. URL: nzf.org.nz/nzf_3802 (accessed 4 April 2024).
  2. Pharmacy Retailing (NZ) Limited t/a Healthcare Logistics. 2022. Dexmethsone New Zealand Data Sheet 19 October 2022. URL: www.medsafe.govt.nz/profs/Datasheet/d/dexmethsonetab.pdf (accessed 4 April 2024).
  3. Max Health Ltd. 2022. Dexamethasone Phosphate Solution for Injection New Zealand Data Sheet 29 August 2022. URL: www.medsafe.govt.nz/profs/Datasheet/d/dexamethasoneHamelninj.pdf (accessed 19 April 2024).
  4. Novartis New Zealand Limited. 2022. Maxidex New Zealand Data Sheet 29 September 2022. URL: www.medsafe.govt.nz/profs/Datasheet/m/Maxidexeyedropsoint.pdf (accessed 19 April 2024).
  5. AbbVie Limited. 2023. Ozurdex New Zealand Data Sheet 19 June 2023. URL: www.medsafe.govt.nz/profs/Datasheet/o/ozurdeximplant.pdf (accessed 19 April 2024).
  6. Mao B, Xie ZL, Liu MJ, et al. 2024. Associations of chronotype with anxiety, depression and insomnia among general adult population: A cross-sectional study in Hubei, China. Journal of Affective Disorders 351: 250–8. URL: doi.org/10.1016/j.jad.2024.01.188 (accessed 29 April 2024).
  7. Hertenstein E, Feige B, Gmeiner T, et al. 2019. Insomnia as a predictor of mental disorders: A systematic review and meta-analysis. Sleep Medicine Reviews 43: 96–105. URL: doi.org/10.1016/j.smrv.2018.10.006 (accessed 29 April 2024).
  8. Reeve S, Nickless A, Sheaves B, et al. 2018. Insomnia, negative affect, and psychotic experiences: Modelling pathways over time in a clinical observational study. Psychiatry Research 269: 673–80. URL: doi.org/10.1016/j.psychres.2018.08.090 (accessed 29 April 2024).
  9. Kobza AO, Herman D, Papaioannou A, et al. 2021. Understanding and managing corticosteroid-induced osteoporosis. Open Access Rheumatology: Research and Reviews 13: 177–90. URL: www.tandfonline.com/doi/full/10.2147/OARRR.S282606 (accessed 4 April 2024).
  10. Weinstein RS. Glucocorticoid-induced osteonecrosis. 2012. Endocrine 41(2): 183-90. URL: link.springer.com/article/10.1007/s12020-011-9580-0 (accessed 4 April 2024).
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