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.
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. 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]). 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. 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. 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. 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). 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.
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. 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. If used, dexamethasone should be initiated before or concurrently with the first dose of anti-infective.
Dosage and Administration
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.
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. Children may be given a dosage of 0.02-0.3 mg/kg daily or 0.6-9 mg/m 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.
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. 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. 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.
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/m IM or IV 1 or 2 times daily.
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.
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.
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.
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; in some cases, additional IV or oral doses were administered for 24-72 hours. 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.
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. Dexamethasone should be initiated 10-20 minutes before or concurrently with the first dose of anti-infective. 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.
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. It has been suggested that continuation of corticosteroid therapy for at least 4 weeks may be associated with better outcomes than shorter regimens.
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.