Coronavirus disease (COVID-19): Dexamethasone

16 October 2021 | Q&A

Last updated 16 October 2020

Corticosteroids are lifesaving medicines recommend for patients with severe or critical COVID-19*. They should be given along with current standard of care for COVID-19 which includes oxygen and other medications .  

They should not be given to patients with non-severe* COVID-19, and when given in such cases it could be harmful to patients’ health.

*A patient has severe COVID-19 when they have signs of pneumonia, severe respiratory distress, and their blood oxygen level is low. A patient has critical COVID-19 when they need life sustaining treatment, have acute respiratory distress syndrome, or have septic shock (evidence of injury to other organs). More.

Dexamethasone is a corticosteroid used in a wide range of conditions for its anti-inflammatory and immunosuppressant effects.

It was tested in hospitalized patients with COVID-19 in the United Kingdom’s national clinical trial RECOVERY and was found to have benefits for critically ill patients.

According to preliminary findings shared with WHO (and now available as a preprint), for patients on ventilators, the treatment was shown to reduce mortality by about one third, and for patients requiring only oxygen, mortality was cut by about one fifth.

 

Corticosteroids are given as a pill or via injection, depending on formulation

Patients with severe or critical COVID-19 should be given low dose corticosteroids for 7-10 days. The daily dose depends on the corticosteroid being used.

 

Eligible patients were randomly allocated between several treatment arms. Dexamethasone was administered as an oral (liquid or tablets) or intravenous preparation, at a dose of 6 mg once daily for ten days, in one of the arms.

In pregnancy or breastfeeding women, patients were randomized to prednisolone (a milder corticosteroid) 40 mg administered by mouth.

WHO recommends that patients who have severe or critical COVID-19 receive corticosteroids. 

 

Patients with severe or critical COVID-19 develop an overstimulation of the immune system, which can be very harmful to their health. Corticosteroids act to suppress this overstimulation.

 

When taken for a short period of time, corticosteroids are generally safe and not associated with serious side effects. Corticosteroids can increase blood glucose levels in patients and it is recommended that all individuals have their blood sugar monitored.

Possible complications from corticosteroids include poor wound healing, immunosuppression (which can increase risk for other infections), and elevated blood sugar, which if not monitored can lead to diabetic ketoacidosis or uncontrolled diabetes. When used for a period longer than two weeks, corticosteroids may be associated with adverse events such as the development of glaucoma, cataracts, fluid retention, high blood pressure, weight gain, osteoporosis (weak bones), and mood swings, confusion, or irritation. 

 

Yes, dexamethasone solution for injection 4mg/ml in 1ml ampoules, manufactured by Kern Pharma SL, Spain, has been prequalified for its use in the management of diseases associated with HIV/AIDS, but not for COVID-19.

Another dexamethasone injection product is currently under assessment.

Manufacturers interested in prequalifying their product can contact the Prequalification Team at [email protected]  for further information.

WHO recommends that all patients, even those without diabetes, should have their blood sugar monitored since corticosteroids can increase blood glucose levels.

Certain patients should be monitored closely when receiving corticosteroids since they are at increased risk of developing complications. These include people with diabetes, cancer, open wounds following traumatic injuries, severe burns, or malnourishment. Patients taking immunosuppressants/immunomodulators, with severe immunodeficiencies should also be monitored along with intravenous drug users. 

Dexamethasone was used in the Recovery Trial in oral (liquid or tablets) or intravenous preparation 6 mg once daily for ten days.

In pregnancy or breastfeeding women, prednisolone 40 mg administered by mouth (or intravenous hydrocortisone 80 mg twice daily) should be used instead of dexamethasone.

  • Note: It is permitted to switch between the two routes of administration according to clinical circumstances.

Source: Page 9 of 35 RECOVERY [V6.0 2020-05-14] ISRCTN50189673 EudraCT 2020-001113-21

Corticosteroids are readily available at a low cost globally. WHO has acquired a small stock of corticosteroids for distribution to resource limited settings that may have reduced supply or pipeline. 

Corticosteroids are listed in the WHO model list of essential medicines.

 

Dexamethasone is generally safe. It presents a favourable benefit-risk profile, particularly in patients with severe forms of pneumonia, while the benefit is less prominent in patients with non-severe pneumonia. As the treatment is short, even at high doses, corticosteroids are not associated with serious side effects. Potentially higher blood glucose levels (hyperglycaemia) are temporary.

Prolonged use (I.e., used for more than two weeks) may be associated with adverse events such as glaucoma, cataract, fluid retention, hypertension, psychological effects (e.g., mood swings, memory issues, confusion or irritation), weight gain, or increased risk of infections and osteoporosis.

To reiterate: All these adverse events are not associated with short term use (with the exception of hyperglycaemia that can worsen diabetes).

 

They can be used in children and the elderly. In pregnancy, the Recovery trial used prednisolone orally or hydrocortisone by intravenous infusion instead of dexamethasone. Steroids are ubiquitous in terms of geographic use.

Yes. Dexamethasone is off-patent and has been marketed in different formulations (e.g., tablets, liquid, solution for injection) for many years. It is generally available in most countries. There are several manufacturers of the product. One manufacturer has already been prequalified by WHO (Kern Pharma in Spain) while another is under assessment.

The most common formulations are:

  • Tablets: 0.5mg, 0.75mg, 1mg, 1.5mg, 2mg, 4mg and 6mg
  • Oral Solution: 0.5mg/5ml, 20mg/5ml and 1mg/ml (concentrate)
  •  Injectable suspension: 4mg/ml, 20mg/5ml

In recent years there have been occasional reports of shortages of this product. It is important to quickly understand the projected volumes for COVID-19 utilization and manufacturing capacity to help assess the impact for existing indications and the potential need for substitute therapies, to ensure all patients retain access to a safe, effective, quality, affordable product to meet their therapeutic needs.

Dexamethasone is an off-patent, common supportive treatment option and is generally affordable. WHO 2016 and 2019 surveys of different health facilities in low- and middle-income countries indicate that dexamethasone was available to patients at a median price of $0.33 per 4mg/ml injection ampoules (range: US$0.13-$3.5). Major UN procurers may be able to supply dexamethasone for a median price of $0.092 per 4mg/ml injection ampoule.

There are likely no restrictions, as dexamethasone is authorized worldwide.

There are 21 records of falsified dexamethasone in the WHO Global Surveillance and Monitoring System database with the most recent one received from the Eastern Mediterranean in February 2020.

It is expected that, following the high level of publicity given to the medicines, incidents of substandard and/or falsified dexamethasone products will occur. This is based on experience with reports of falsified chloroquine products when hydroxychloroquine was thought to be a potential treatment for COVID19

Increased vigilance throughout all supply chains and due diligence in any procurement activities are essential. Member States and regulatory authorities are encouraged to promptly report any incidents of substandard or falsified dexamethasone to the WHO global surveillance and monitoring system.