AHFS Class:

• Adrenals 68:04

Generic Name(s):

• Dexamethasone

• Dexamethasone Sodium Phosphate

Dexamethasone is a synthetic glucocorticoid.

Dexamethasone is used principally as an anti-inflammatory or immunosuppressant agent. Because it has only minimal mineralocorticoid properties, the drug is inadequate alone for the management of adrenocortical insufficiency. If dexamethasone is used in the treatment of this condition, concomitant therapy with a mineralocorticoid is also required.

Diagnostic Uses

Dexamethasone inhibits pituitary corticotropin (ACTH) release and decreases output of endogenous corticosteroids when given in an amount which does not itself appreciably affect levels of urinary 17-hydroxycorticosteroids. This effect is used in the dexamethasone suppression test for the diagnosis of Cushing's syndrome and the differential diagnosis of adrenal hyperplasia and adrenal adenoma.

Cancer Chemotherapy-induced Nausea and Vomiting

Dexamethasone regimens are used extensively for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy†.100,101,102,103,104,129,130,131,140 To prevent chemotherapy-induced nausea and vomiting associated with chemotherapy regimens with a high emetic risk (i.e., incidence of emesis exceeds 90% if no antiemetics are administered), the American Society of Clinical Oncology (ASCO) currently recommends a 3-drug antiemetic regimen consisting of dexamethasone, aprepitant, and a type 3 serotonin (5-HT₃) receptor antagonist (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron [not commercially available in the US]).140 The antiemetic combination of dexamethasone, aprepitant, and a 5-HT₃ receptor antagonist also is preferred in patients receiving combination chemotherapy with an anthracycline and cyclophosphamide.140 For patients receiving other chemotherapy of moderate emetic risk (i.e., incidence of emesis without antiemetics exceeds 30% but does not exceed 90%), ASCO recommends a 2-drug antiemetic regimen consisting of dexamethasone and a 5-HT₃ receptor antagonist.140 For patients receiving chemotherapy regimens with a low emetic risk (i.e., incidence of emesis without antiemetics exceeds 10% but does not exceed 30%), ASCO recommends dexamethasone alone on the first day of chemotherapy.140 Antiemetics can be prescribed on an as needed basis in patients receiving chemotherapy with a minimal antiemetic risk (incidence of emesis is less than 10% without antiemetics).140 For the prevention of delayed emesis in patients receiving cisplatin or other chemotherapy associated with a high emetic risk, these authorities currently recommend a 2-drug combination of dexamethasone and aprepitant.140 (See Uses: Cancer Chemotherapy-induced Nausea and Vomiting, in the Corticosteroids General Statement 68:04.)

Bacterial Meningitis

There is some evidence that short-term adjunctive therapy with IV dexamethasone may decrease the incidence of audiologic and/or neurologic sequelae in infants and children with Haemophilus influenzae meningitis and possibly may provide some benefit in patients with Streptococcus pneumoniae meningitis.127,141,142 The American Academy of Pediatrics (AAP) and other clinicians suggest that use of adjunctive dexamethasone therapy may be considered during the initial 2-4 days of anti-infective therapy in infants and children 6-8 weeks of age or older with known or suspected bacterial meningitis, especially in those with suspected or proven H. influenzae infection.127,141 If used, dexamethasone should be initiated before or concurrently with the first dose of anti-infective.127,141

Coronavirus Disease 2019 (COVID-19)

Dexamethasone has been used as adjunctive therapy in the treatment of serious complications from coronavirus disease 2019 (COVID-19)†.1004,1005,1006,1007,1013 Patients with severe COVID-19 may develop a systemic inflammatory response that can result in lung injury and multisystem organ dysfunction.1005 The potent anti-inflammatory effects of corticosteroids (e.g., dexamethasone) may prevent or mitigate these deleterious effects.1005

The National Institutes of Health (NIH) COVID-19 Treatment Guidelines Panel issued guidelines for the treatment of COVID-19, including recommendations for the use of corticosteroids in patients with COVID-19.1005 The NIH panel recommends against the use of dexamethasone in nonhospitalized adults and adults hospitalized with COVID-19 who do not require supplemental oxygen.1005 The NIH panel recommends the use of dexamethasone in hospitalized adults who require supplemental oxygen or are receiving mechanical ventilation or extracorporeal membrane oxygenation (ECMO).1005 The NIH panel states that it is not known at this time whether other corticosteroids will have a similar benefit as dexamethasone.1005 However, if dexamethasone is not available, the panel recommends using alternative corticosteroids (e.g., hydrocortisone, methylprednisolone, prednisone).1005 (See Uses: Coronavirus Disease 2019 [COVID-19] and Dosage: Coronavirus Disease 2019 [COVID-19] in the Corticosteroids General Statement 68:04.)

Data regarding potential adverse effects of dexamethasone in patients with COVID-19, efficacy in combination with other treatments (e.g., remdesivir, tocilizumab, baricitinib), and efficacy in other patient populations (e.g., pediatric patients, pregnant women) are insufficient to date.1005 Although concomitant use of dexamethasone and remdesivir has not been rigorously studied, the NIH panel states there is a theoretical rationale for using dexamethasone plus remdesivir in patients with rapidly progressing COVID-19 and clinically important drug interactions are not expected.1005 Specifically, the NIH guideline panel recommends concomitant use of dexamethasone and remdesivir in hospitalized patients requiring increasing amounts of supplemental oxygen or use of dexamethasone alone when combined therapy with remdesivir cannot be used or is unavailable in such patients.1005 Similarly, the NIH panel recommends the use of dexamethasone alone or in combination with remdesivir in hospitalized patients requiring high-flow oxygen or noninvasive ventilation.1005 For such patients who were recently hospitalized with rapidly increasing oxygen needs and systemic inflammation, the panel also recommends the addition of baricitinib or tocilizumab to either monotherapy with dexamethasone or combination therapy with dexamethasone and remdesivir.1005 For hospitalized COVID-19 patients requiring invasive mechanical ventilation or ECMO, the NIH panel recommends therapy with dexamethasone alone, although dexamethasone in combination with remdesivir may be considered in patients who were recently intubated.1005 For those receiving invasive mechanical ventilation or ECMO who are within 24 hours of ICU admission with rapid respiratory decompensation, the NIH panel recommends dexamethasone in combination with tocilizumab.1005 Clinicians should consult the most recent NIH COVID-19 treatment guidelines for additional information on use of corticosteroids in patients with COVID-19.1005

The World Health Organization (WHO) Guideline Development Group also issued guidelines for the use of systemic corticosteroids in patients with COVID-19.1006 For the treatment of patients with nonsevere COVID-19, the WHO Guideline Development Group suggests not using systemic corticosteroids, regardless of hospitalization status;1006 however, if the clinical condition of such patients worsens (e.g., increased respiratory rate, signs of respiratory distress, or hypoxemia), systemic corticosteroids are recommended for treatment.1006 The WHO Guideline Development Group strongly recommends the use of systemic corticosteroids over no systemic corticosteroid therapy for the treatment of patients with severe and/or critical COVID-19, regardless of hospitalization status.1006 This treatment recommendation includes critically ill patients with COVID-19 who could not be hospitalized or receive oxygen supplementation because of resource limitations.1006 The WHO Guideline Development Group also recommends the concomitant use of systemic corticosteroids with an interleukin (IL-6) inhibitor (e.g., sarilumab, tocilizumab) for patients with severe or critical COVID-19.1006 These experts recommend against discontinuing systemic corticosteroids in patients with nonsevere COVID-19 who are receiving systemic corticosteroids for chronic conditions (e.g., chronic obstructive pulmonary disease [COPD], autoimmune diseases).1006 Clinicians should consult the most recent WHO COVID-19 treatment guidelines for additional information.1006

In one randomized, controlled, open-label study (NCT04381936; RECOVERY), the effect of potential treatments (including low-dose dexamethasone) on all-cause mortality in hospitalized patients with COVID-19 was evaluated.1004 In the treatment arm evaluating dexamethasone, 2104 patients were randomized to receive dexamethasone (6 mg once daily orally or IV for up to 10 days) plus standard care and 4321 patients were randomized to receive standard care alone.1004 Preliminary data analysis indicated that overall 28-day mortality was reduced in patients receiving dexamethasone compared with those receiving standard care alone, with the greatest benefit observed in patients requiring mechanical ventilation at enrollment.1004 Overall, 22.9% of patients receiving dexamethasone and 25.7% of those receiving standard care died within 28 days of study enrollment.1004 In patients receiving dexamethasone, the incidence of death was lower than that in the standard care group among those receiving invasive mechanical ventilation (29.3 versus 41.4%) and among those receiving supplemental oxygen without invasive mechanical ventilation (23.3 versus 26.2%).1004 However, no survival benefit was observed with dexamethasone and there was a possibility of harm in patients who did not require respiratory support at enrollment.1004 Dexamethasone also was associated with a reduction in 28-day mortality among patients with symptoms for more than 7 days compared with those having more recent symptom onset.1004 In addition, dexamethasone treatment was associated with a shorter duration of hospitalization and a greater probability of discharge within 28 days with the greatest effect observed among patients receiving invasive mechanical ventilation at baseline.1004

In another randomized, controlled, open-label, multicenter study (NCT04327401; CoDEX), the effect of dexamethasone on the number of ventilator-free days was evaluated in patients with COVID-19-associated moderate or severe acute respiratory distress syndrome (ARDS) who were receiving mechanical ventilation.1007 In the dexamethasone treatment group, 151 patients were randomized to receive dexamethasone (20 mg IV once daily for 5 days followed by 10 mg IV once daily for another 5 days or until ICU discharge) plus standard care and 148 patients were randomized to receive standard care alone.1007 The primary study end point was ventilator-free days (defined as number of days alive and free from mechanical ventilation) during the first 28 days.1007 Preliminary data analysis indicated that use of IV dexamethasone plus standard care was associated with a higher mean number of ventilator-free days (6.6 days) compared with those receiving standard care alone (4 days).1007 Although there was no clinically important difference in all-cause mortality at 28 days between the treatment groups, the trial was terminated early after results of the RECOVERY trial became available and, therefore, was likely underpowered to determine secondary outcomes such as mortality.1007 Dexamethasone was not associated with an increased risk of adverse effects in this study population of critically ill COVID-19 patients.1007

In a prospective meta-analysis of studies using systemic corticosteroids (i.e., dexamethasone, hydrocortisone, or methylprednisolone) from the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, data were pooled from 7 randomized clinical trials in 12 countries that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19.1013 The primary outcome was all-cause mortality up to 30 days after randomization to treatment.1013 Administration of systemic corticosteroids was associated with lower all-cause mortality at 28 days compared with usual care or placebo (222 deaths among 678 patients who received corticosteroids and 425 deaths among 1025 patients who received usual care or placebo).1013 The effect of corticosteroids on reduced mortality was observed in critically ill patients who were and were not receiving mechanical ventilation at randomization and also in patients from the RECOVERY trial who required supplemental oxygen with or without noninvasive ventilation, but who were not receiving invasive mechanical ventilation at the time of randomization.1013 The odds ratios for the association between corticosteroids and mortality were similar for dexamethasone and hydrocortisone.1013 The optimal dosage and duration of corticosteroid treatment could not be determined from this analysis; however, there was no evidence suggesting that a higher dosage of corticosteroids was associated with greater benefit than a lower dosage.1013 The authors also concluded that there was no suggestion of an increased risk of serious adverse effects associated with corticosteroid use.1013

For additional information on use of corticosteroids for the treatment of COVID-19, see Uses: Coronavirus Disease 2019 (COVID-19) in the Corticosteroids General Statement 68:04.

The route of administration and dosage of dexamethasone and its derivatives depend on the condition being treated and the response of the patient. IM or IV therapy is generally reserved for patients who are not able to take the drugs orally or for use in an emergency situation. Dosage for infants and children should be based on the severity of the disease and the response of the patient rather than on strict adherence to dosage indicated by age, body weight, or body surface area. After a satisfactory response is obtained, dosage should be decreased in small decrements to the lowest level that maintains an adequate clinical response, and the drug should be discontinued as soon as possible. Patients should be continually monitored for signs that indicate dosage adjustment is necessary, such as remissions or exacerbations of the disease and stress (surgery, infection, trauma). Following long-term therapy, dexamethasone should be withdrawn gradually. (See the Corticosteroids General Statement 68:04.)

Dexamethasone

Dexamethasone is administered orally as tablets, elixir, solution, or concentrate solution. The oral concentrate may be diluted in juice or other flavored liquid diluent or in semisolid food (e.g., applesauce) prior to administration.

The usual initial adult dosage of dexamethasone may range from 0.75-9 mg daily, depending on the disease being treated, and the drug usually is administered in 2-4 divided doses. In less severe diseases, dosages lower than 0.75 mg daily may be sufficient while severe diseases may require dosages higher than 9 mg daily.144 Children may be given a dosage of 0.02-0.3 mg/kg daily or 0.6-9 mg/m² daily, administered in 3 or 4 divided doses.

When dexamethasone is given for the prevention of chemotherapy-induced nausea and vomiting†, single doses or once-daily doses of the drug usually are given.140

Diagnostic Uses

When dexamethasone suppression is used as a screening test for Cushing's syndrome, 0.5 mg of dexamethasone is administered orally every 6 hours for 48 hours after baseline 24-hour urinary 17-hydroxycorticosteroid (17-OHCS) concentrations are determined. During the second 24 hours of dexamethasone administration, urine is collected and analyzed for 17-OHCS. Alternatively, after a baseline plasma cortisol determination, a 1-mg oral dose of dexamethasone may be administered at 11 p.m. and plasma cortisol determined at 8 a.m. the following morning. Plasma cortisol and urinary output of 17-OHCS are depressed following dexamethasone administration in normal individuals but remain at basal levels in patients with Cushing's syndrome. To distinguish adrenal tumor from adrenal hyperplasia, 2 mg of dexamethasone is administered orally every 6 hours for 48 hours. During the second 24 hours of dexamethasone administration, urine is collected and analyzed for 17-OHCS. Urinary 17-OHCS levels are decreased in patients with adrenal hyperplasia and remain at basal levels in patients with adrenocortical tumors.

Cancer Chemotherapy-induced Nausea and Vomiting

When oral dexamethasone is used to prevent chemotherapy-induced nausea and vomiting† associated with cancer chemotherapy regimens with a high emetic risk in adults, the American Society of Clinical Oncology (ASCO) currently recommends that 12 mg of dexamethasone be administered with or without aprepitant prior to chemotherapy on the first day followed by 8 mg administered once daily on days 2-4.140 When oral dexamethasone is given in combination with aprepitant in patients receiving chemotherapy regimens of moderate emetic risk, ASCO currently recommends that a single 12-mg dose of the drug be given prior to chemotherapy on the first day.140,143 In patients receiving chemotherapy of low emetic risk, ASCO recommends dexamethasone be given alone as a single 8-mg dose prior to chemotherapy on the first day.140

Coronavirus Disease 2019 (COVID-19)

When oral dexamethasone is used for adjunctive therapy in adults with coronavirus disease 2019 (COVID-19)†, the National Institutes of Health (NIH) COVID-19 Treatment Guidelines Panel recommends a dosage of 6 mg once daily for up to 10 days or until hospital discharge, whichever comes first.1005 The World Health Organization (WHO) Guideline Development Group recommends dexamethasone 6 mg once daily for 7-10 days.1006

When oral dexamethasone is used for adjunctive therapy in pediatric patients with COVID-19†, the NIH panel recommends 0.15 mg/kg (maximum dosage 6 mg) once daily for up to 10 days.1005

If dexamethasone is not available, equivalent dosages of alternative corticosteroids may be considered.1005 For additional information, see Dosage: Coronavirus Disease 2019 (COVID-19), in the Corticosteroids General Statement 68:04. Clinicians also should consult the most recent NIH and WHO COVID-19 treatment guidelines for additional information on use of corticosteroids in patients with COVID-19.1005,1006

Dexamethasone Sodium Phosphate

Dexamethasone sodium phosphate may be administered by intra-articular, intrasynovial, intralesional, soft-tissue, IM, or IV injection, or by IV infusion. IM or IV administration of dexamethasone sodium phosphate is indicated in emergency situations or when oral therapy is not feasible. Although dexamethasone sodium phosphate is rapidly absorbed from IM injection sites, the slower rate of absorption compared to IV administration should be kept in mind. When dexamethasone sodium phosphate is administered by IV infusion, the drug can be added to dextrose or sodium chloride injections.

Dosage of dexamethasone sodium phosphate is expressed in terms of dexamethasone phosphate. IM or IV dosage depends on the condition being treated and the patient's response, but usually ranges from 0.5-24 mg daily. Some clinicians state that children may be given 6-40 mcg/kg or 0.235-1.25 mg/m² IM or IV 1 or 2 times daily.

Shock

In life-threatening shock, massive doses of dexamethasone phosphate (such as 1-6 mg/kg as a single IV injection or a 40-mg IV injection repeated every 2-6 hours if needed) have been recommended by some clinicians. Alternatively, 20 mg may be administered IV initially followed by continuous IV infusion of 3 mg/kg per 24 hours. High-Dose therapy should be continued only until the patient's condition has stabilized and usually should not be continued beyond 48-72 hours.

Cerebral Edema

In the management of cerebral edema, 10 mg of dexamethasone phosphate is usually given IV followed by 4 mg IM every 6 hours until the symptoms of cerebral edema subside. Response usually is evident within 12-24 hours, and dosage may be reduced after 2-4 days and gradually discontinued over a period of 5-7 days. When possible, oral dexamethasone (1-3 mg 3 times daily) should replace IM administration of the drug. In patients with recurrent or inoperable brain tumors, dexamethasone phosphate in a maintenance dosage of 2 mg IM or IV 2 or 3 times daily may be effective in relieving symptoms of increased intracranial pressure.

Allergic Conditions

In the management of acute self-limited allergic conditions or acute exacerbations of chronic allergic disorders, one manufacturer recommends administration of 4-8 mg of dexamethasone phosphate IM on the first day; 3 mg of dexamethasone orally in 2 divided doses on the second and third days; 1.5 mg orally in 2 divided doses on the fourth day; and a single oral daily dose of 0.75 mg on the fifth and sixth days; then the drug is discontinued.

Inflammatory Diseases

For intra-articular, intrasynovial, intralesional, or soft-tissue injection, the dosage of dexamethasone phosphate varies with the degree of inflammation and the size and location of the affected area. For large joints such as the knee, 2-4 mg may be used. For smaller joints, 0.8-1 mg may be adequate. The dose for bursae is 2-3 mg and for ganglia, 1-2 mg. For soft-tissue injection, dosage varies from 0.4-1 mg in tendon sheath inflammation to as much as 2-6 mg for soft tissue infiltration. Injections may be repeated from once every 3-5 days (for bursae) to once every 2-3 weeks (for joints).

Cancer Chemotherapy-induced Nausea and Vomiting

The optimum dosage of dexamethasone phosphate for the prevention of cancer chemotherapy-induced nausea and vomiting† has not been established, but the usual dose has been 8-20 mg IV before administration of the chemotherapy;100,101,102,103,104,140 in some cases, additional IV or oral doses were administered for 24-72 hours.101,102,103,104,140 ASCO currently recommends that dexamethasone phosphate be given in single 8-mg doses when used IV in patients receiving moderately emetogenic chemotherapy; this initial IV dose may be followed by single oral 8-mg doses on days 2 and 3.140

Bacterial Meningitis

When dexamethasone is used for adjunctive therapy in selected patients with bacterial meningitis†, a dosage of 0.15 mg/kg of dexamethasone phosphate given IV 4 times daily for the first 2-4 days of anti-infective therapy has been recommended for infants, children, and adults.110,112,113,114,115,116,119,127,128,136,141 Dexamethasone should be initiated 10-20 minutes before or concurrently with the first dose of anti-infective.141 Dexamethasone should not be given to patients who have already received anti-infective therapy; administration of dexamethasone in this circumstance is unlikely to improve patient outcome.141

Tuberculous Meningitis

For reducing the risk of sequelae and improving survival in patients with tuberculous meningitis, an IM dexamethasone phosphate dosage of 8-12 mg daily tapered over 6-8 weeks has been effective; higher dosages appear to provide no additional benefit and may be associated with more frequent adverse effects.137,139 It has been suggested that continuation of corticosteroid therapy for at least 4 weeks may be associated with better outcomes than shorter regimens.137,138 (See Respiratory Diseases: Advanced Pulmonary and Extrapulmonary Tuberculosis, in Uses in the Corticosteroids General Statement 68:04.)

Coronavirus Disease 2019 (COVID-19)

When IV dexamethasone is used for adjunctive therapy in adults with coronavirus disease 2019 (COVID-19)†, the NIH COVID-19 Treatment Guidelines Panel recommends a dosage of 6 mg once daily for up to 10 days or until hospital discharge, whichever comes first.1004,1005 The WHO Guidelines Development Group recommends dexamethasone 6 mg once daily for 7-10 days.1006

When IV dexamethasone is used for adjunctive therapy in pediatric patients with COVID-19†, the NIH panel recommends 0.15 mg/kg (maximum dosage 6 mg) once daily for up to 10 days.1005

If dexamethasone is not available, equivalent dosages of alternative corticosteroids may be considered.1005 For additional information, see Dosage: Coronavirus Disease 2019 (COVID-19), in the Corticosteroids General Statement 68:04. Clinicians also should consult the most recent NIH and WHO COVID-19 treatment guidelines for additional information on use of corticosteroids in patients with COVID-19.1005,1006

Other Uses

To prevent hyaline membrane disease (respiratory distress syndrome [RDS]) in premature infants†, 4 mg of dexamethasone phosphate has been given IM to the mother 3 times daily for 2 days before delivery.

Chemistry and Stability

Chemistry

Dexamethasone is a synthetic glucocorticoid. Dexamethasone occurs as a white to practically white, odorless, crystalline powder and is practically insoluble in water and sparingly soluble in alcohol. Dexamethasone sodium phosphate occurs as a white or slightly yellow, crystalline powder that is odorless or has a slight odor of alcohol. Dexamethasone sodium phosphate is very hygroscopic and is freely soluble in water and slightly soluble in alcohol.

Commercially available dexamethasone sodium phosphate injection has a pH of 7.5-10.5. Dexamethasone oral solution is alcohol-free and the elixir and oral concentrate contain 3.8-5.7% and about 30% alcohol, respectively.

Stability

Dexamethasone sodium phosphate injection is heat labile and must not be autoclaved. Dexamethasone preparations should generally be stored at a temperature less than 40°C, preferably between 15-30°C, unless otherwise specified by the manufacturer.

Dexamethasone sodium phosphate injection has been reported to be incompatible with various drugs, but the compatibility depends on several factors (e.g., concentrations of the drugs, resulting pH, temperatures). Specialized references should be consulted for more specific compatibility information.

Additional Information

For further information on chemistry, pharmacology, pharmacokinetics, uses, cautions, drug interactions, laboratory test interferences, and dosage and administration of dexamethasone, see the Corticosteroids General Statement 68:04. For EENT uses, see 52:08.08.

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