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Dexamethasone
is a synthetic adrenocortical steroid used for its potent anti-inflammatory and
immunosuppressive effects in disorders of many organ systems including cancers.
Dexamethasone is a synthetic adrenocortical steroid used for
its potent anti-inflammatory and immunosuppressive effects in disorders of many
organ systems including cancers.1
The initial findings from a recent clinical trial (RECOVERY)
found dexamethasone to be a lifesaver for critically ill COVID-19 patients. It
has shown to reduce mortality by about 1/3rd and 1/5th in
patients with COVID-19 requiring ventilator and oxygen support, respectively.2
Pharmacological Class:
Glucocorticosteroid
COVID-19: WHO supports the preliminary results from
the recovery trial suggesting dexamethasone to be a promising lifesaving drug
in patients with severe respiratory complications of COVID-19.2
Other Indications: Dexamethasone
is used to treat many disease conditions like primary or secondary
adrenocortical insufficiency, rheumatic disorders, exacerbation or as
maintenance therapy in patients with collagen diseases, allergic states,
dermatologic diseases, ophthalmic diseases, gastrointestinal diseases,
respiratory diseases, neoplastic diseases and hematologic disorders, edematous
states, meningitis and Cerebral Edema
associated with primary or metastatic brain tumor, craniotomy, or head injury.3
Almost 5% of all COVID-19 patients develop acute respiratory
distress syndrome (ARDS). It is assumed that inflammation and cytokine storm is
involved in the pathophysiological pathway to ARDS in COVID-19 patients. Dexamethasone
readily diffuses through the host cell membranes and binds to the
glucocorticoid receptor in the cell cytoplasm, which triggers a cascade of reactions
suppressing pro-inflammatory cytokines (IL-1, IL-2, IL-6, IL-8, TNF, and
IFN-gamma). Dexamethasone also inhibits the over activation of macrophages
which is responsible for cytokine storm. Thus dexamethasone exerts both, immuosuppressive
as well as anti-inflammatory effects, thereby providing relief to the COVID-19
patients with severe complications like ARDS. 4, 5, 6
Dosage as per clinical study on COVID-19 patients1
Recommended dosage for other indications3
Absorption via the intramuscular route is slower than via
the intravenous route. The oral bioavailability of oral dexamethasone ranges
between 70%-80%. It is approximately 77%
protein bound in plasma. Dexamethasone is 6-hydroxylated by CYP3A4 to 6α- and
6β-hydroxydexamethasone. It is <10% eliminated in urine. Other
pharmacokinetic parameters are mentioned below in the table:
|
Parameters |
6 mg oral
dexamethasone |
4 mg intravenous
dexamethasone |
|
AUC(0.∞) (μg l−1 h) |
774 |
626 |
|
t1/2 (h) |
6.9 |
9.0 |
|
Volume of distribution (l kg−1) |
1.09 |
0.94 |
|
Mean residence time (h) |
12.4 |
10.3 |
|
Clearance (l h−1) |
7.7 |
6.4 |
AUC(0,∞), area under the concentration–time curve to
infinity; t1/2, terminal half-life.
Contraindicated in3
Common
Uncommon
Very rare
Dexamethasone reduces mortality rate by up to 1/3rd in COVID-19 hospitalized patients with severe respiratory complications: A recent randomized clinical trial tested a range of potential treatments for COVID-19, including low-dose dexamethasone. In this study, 2104 patients were randomized to receive dexamethasone 6 mg once a day (orally or IV) for 10 days. These patients were compared with 4321 patients who were randomized to usual care alone. Among the patients who received usual care alone, 28-day mortality was found to be highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%). Dexamethasone was found to reduce deaths by one-third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75]; p=0.14).8
Early dexamethasone use may reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe acute respiratory distress syndrome (ARDS): A multicentre, randomized controlled trial in a network of 17 ICUs in teaching hospitals across Spain was performed to evaluate the effects of dexamethasone in ARDS. A total of 277 patients with established ARDS were included in the study and were randomized to 139 patients in the dexamethasone group and 138 in the control group. The primary outcome of the study was the number of ventilator-free days at 28 days while the secondary outcome was all-cause mortality 60 days post-randomization. The mean number of ventilator-free days was higher in the dexamethasone group than in the control group (between-group difference 4·8 days [95% CI 2·57 to 7·03]; p<0·0001). At 60 days, 29 (21%) patients in the dexamethasone group and 50 (36%) patients in the control group had died (between-group difference -15·3% [-25·9 to -4·9]; p=0·0047). There was no significant difference in the proportion of adverse events between the dexamethasone group and control group.10
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