DEXAMETHASONE

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
-Administer with food to minimize GI upset.
-If given once daily, give in the morning to coincide with the body's normal cortisol secretion.
-IV formulation has been given orally for the treatment of croup.
Oral Liquid Formulations
Intensol (Dexamethasone Oral Concentrate)
-1 mg/mL concentrated solution; contains 30% alcohol.
-Draw up appropriate dose, using only the calibrated dropper provided with product.
-Mix dose with liquid or semi-solid food such as water, juice, soda, applesauce, or pudding and stir the preparation for a few seconds.
-Consume the entire mixture immediately; do not store for future use.



Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Some injectable formulations contain benzyl alcohol ; avoid the use of these formulations in premature neonates, and use with caution in neonates.
Intravenous Administration
Dexamethasone Sodium Phosphate solution for injection
IV Push
-Doses of less than 10 mg can be administered, undiluted, by direct slow IV push over 3 to 5 minutes.

Intermittent IV Infusion
-Dilute high-dose therapy (i.e., greater than 10 mg) with an appropriate volume of Dextrose 5% Injection or ).9% Sodium Chloride for Injection and infuse over a minimum of 10 minutes.
-Storage: Use diluted solutions within 24 hours.

Intramuscular Administration
Dexamethasone Sodium Phosphate solution for injection
-Inject deeply into a large muscle mass (e.g., anterolateral thigh or deltoid [children and adolescents only]). Aspirate prior to injection to avoid injection into a blood vessel.
-Rotate sites of injection.
-In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.



Ophthalmic Administration
Dexamethasone ophthalmic solution or suspension
-Apply topically to the eye.
-For ophthalmic suspensions: Shake well prior to each administration.
-Instruct patient on appropriate instillation technique.
-Do not touch the tip of the dropper or tube to the eye, fingertips, or other surface.
-To prevent contamination, each dropper is for 1 individual, do not share among patients.

Pharmacologic doses of systemic corticosteroids (e.g. dexamethasone) administered for prolonged periods can result in physiological dependence due to hypothalamic-pituitary-adrenal (HPA) suppression. Exogenously administered corticosteroids exert a negative feedback effect on the pituitary, inhibiting the secretion of adrenocorticotropin (ACTH). This results in a decrease in ACTH-mediated synthesis of endogenous corticosteroids and androgens by the adrenal cortex. The severity of secondary adrenocortical insufficiency varies among individuals and is dependent on the dose, frequency, time of administration, and duration of therapy. Systemic administration of the drug on alternate days may help to alleviate this adverse effect. Patients with HPA suppression will require increased doses of corticosteroid therapy during periods of physiologic stress. Acute adrenal insufficiency and even death can occur with abrupt discontinuation of therapy. Discontinuation of prolonged oral corticosteroid therapy should be gradual since HPA suppression can last for up to 12 months following cessation of therapy. Patients may continue to need supplemental corticosteroid treatment during periods of physiologic stress or infectious conditions, even after the drug has been discontinued. A withdrawal syndrome unrelated to adrenocortical insufficiency can occur following sudden discontinuance of corticosteroid therapy. This syndrome includes symptoms such as appetite loss, malaise, lethargy, nauseousness, head pain/ache, joint pain, muscle pain, fever, exfoliative dermatitis, loss of weight, and hypotension. These effects are believed to be due to the sudden change in corticosteroid concentration rather than to low corticosteroid levels. Increased intracranial pressure with papilledema (i.e., pseudotumor cerebri) has also been reported with the withdrawal of glucocorticoid therapy.

Prolonged dexamethasone therapy can adversely affect the endocrine system, resulting in hypercorticism (Cushing's syndrome including fat abnormalities such as buffalo hump and moon face), hypertrichosis or hirsutism, menstrual irregularity, or reduced carbohydrate and glucose metabolism. Systemic corticosteroids are a common cause of drug-induced hyperglycemia. In the hospital setting, there is evidence that more than 50% of the patients receiving high-dose systemic steroids develop hyperglycemia, with many more having at least 1 episode of hyperglycemia or a mean blood glucose of 140 mg/dL or greater. Long-term use produces metabolic and endocrine effects that include insulin resistance that may lead to new diagnoses of diabetes mellitus (DM) in patients without a history of hyperglycemia or DM prior to corticosteroid use. Glucosuria (glycosuria) and aggravation of existing DM may also occur.

Endogenous glucocorticoids are responsible for protein metabolism; prolonged therapy with pharmaceutical glucocorticoids like dexamethasone can result in various musculoskeletal and joint manifestations. In a population-based study, the risk of bone fractures was increased in children and adolescents (age 4 to 17 years) receiving more than 4 courses of oral corticosteroids or doses 30 mg/day and higher of prednisone. Because of the retardation of bone growth, pediatric patients receiving prolonged corticosteroid therapy may have growth inhibition. Bone development is critical in pediatric patients, and monitoring of growth and for adverse bone and joint effects is warranted in patients receiving high-doses or chronic corticosteroid treatment. A variety of musculoskeletal and joint-related side effects, including myopathy (myalgia, muscle wasting, muscle weakness or myasthenia, and quadriplegia), arthralgia, tendon rupture, bone matrix atrophy (osteoporosis and osteopenia), bone fractures such as vertebral compression fractures or fractures of long bones, and avascular necrosis of femoral or humeral heads, have been reported with prolonged corticosteroid use. Of note, abrupt cessation of corticosteroids can cause arthralgia and myalgia. Glucocorticoids interact with calcium metabolism at many sites, including decreasing the synthesis by osteoblasts of the principal proteins of bone matrix, malabsorption of calcium in both the nephron and the gut, and reduction of sex hormone concentrations. Although all of these actions probably contribute to glucocorticoid-induced osteoporosis, the actions on osteoblasts are most important. Glucocorticoids do not modify vitamin D metabolism. Intra-articular injections of corticosteroids can cause Charcot-like arthropathy and post-injection flare. Atrophy at the site of injection has been reported following administration of soluble glucocorticoids.

Adverse gastrointestinal (GI) effects associated with systemic corticosteroid (e.g., dexamethasone) administration include nausea and vomiting. Abdominal distention, appetite stimulation, weight gain, pancreatitis, gastritis, hiccups, peptic ulcer with possible GI perforation and GI bleeding, perforation of the small and large bowel (particularly in patients with inflammatory bowel disease), and esophageal ulceration (ulcerative esophagitis) have also been reported. Although it was once believed that corticosteroids contributed to the development of peptic ulcer disease, in a review of 93 studies of corticosteroid use, the incidence of peptic ulcer disease was not found to be higher in steroid recipients compared to control groups. While most of these studies did not utilize endoscopy, it is unlikely that corticosteroids contribute to the development of peptic ulcer disease.

Corticosteroid therapy including dexamethasone can mask the symptoms of infection and should generally be avoided during an acute viral, fungal, or bacterial infection. Leukocytosis is a common physiologic effect of systemic corticosteroid therapy and may need to be differentiated from the leukocytosis that occurs with inflammatory or infectious processes. Immunosuppression from corticosteroids is most likely to occur in patients receiving high-dose (e.g., equivalent to 1 mg/kg or more of prednisone daily), systemic corticosteroid therapy for any period of time, particularly in conjunction with corticosteroid-sparing drugs (e.g., troleandomycin) and/or concomitant immunosuppressant agents; however, patients receiving moderate dosages of systemic corticosteroids for short periods or low dosages for prolonged periods may also be at risk. Corticosteroid-induced immunosuppression may result in the activation of latent viral (e.g., herpes) or bacterial (e.g., tuberculosis) infections and should not be used in patients with an active infection except when appropriate anti-infective therapy is instituted concomitantly. Patients receiving immunosuppressive doses of corticosteroids should be advised to avoid exposure to measles or varicella (chickenpox) and, if exposed to these diseases, to seek medical advice immediately. Monitoring systemic corticosteroid recipients for signs of opportunistic fungal infection is recommended, as cases of oropharyngeal candidiasis have been reported. Development of Kaposi's sarcoma has also been associated with prolonged administration of corticosteroids; discontinuation of the corticosteroid may result in clinical improvement. Bronchitis was noted in 5% of dexamethasone ophthalmic implant recipients during clinical trials in adults and at an incidence higher than with placebo; secondary ophthalmic infection or exacerbation of infection has also been reported with other ophthalmic and intraocular dosage forms.


Corticosteroid therapy including dexamethasone can mask the symptoms of infection and should be avoided during an acute viral, fungal, or bacterial infection. Leukocytosis is a common physiologic effect of systemic corticosteroid therapy and may need to be differentiated from the leukocytosis that occurs with inflammatory or infectious processes. Immunosuppression is most likely to occur in patients receiving high-dose (e.g., equivalent to 1 mg/kg or more of prednisone daily), systemic corticosteroid therapy for any period of time, particularly in conjunction with corticosteroid-sparing drugs (e.g., troleandomycin) and/or concomitant immunosuppressant agents; however, patients receiving moderate dosages of systemic corticosteroids for short periods or low dosages for prolonged periods may also be at risk. Corticosteroids can reactivate tuberculosis and should not be used in patients with a history of active tuberculosis except when chemoprophylaxis is instituted concomitantly. Patients receiving immunosuppressive doses of dexamethasone should be advised to avoid exposure to measles or varicella (chickenpox) and, if exposed to these diseases, to seek medical advice immediately. Monitoring systemic corticosteroid recipients for signs of opportunistic fungal infection is recommended, as cases of oropharyngeal candidiasis have been reported. The development of Kaposi's sarcoma has also been associated with prolonged administration of corticosteroids; discontinuation of the corticosteroid may result in clinical improvement.

Various adverse dermatologic effects reported during systemic corticosteroid therapy include skin atrophy (thin fragile skin), increased sweating (hyperhidrosis), acne vulgaris, striae, acneiform rash, alopecia, xerosis, perineal pain and irritation, purpura, rash (unspecified), telangiectasia, facial erythema, petechiae, ecchymosis or easy bruising, and suppression of reactions to skin tests. An increased susceptibility to skin ulcer may occur in patients with impaired circulation. Hypersensitivity reactions may manifest as allergic dermatitis, urticaria, anaphylactoid reactions, and/or angioedema. Burning or tingling in the perineal area may occur following IV injection of corticosteroids. Parenteral corticosteroid therapy has also produced skin hypopigmentation, skin hyperpigmentation, scarring, and other types of injection site reaction (e.g., induration, delayed pain or soreness, subcutaneous and cutaneous atrophy, and sterile abscesses).

In general, excessive use of systemic corticosteroids can lead to impaired wound healing.

Use of systemic dexamethasone can result in edema and fluid retention due to sodium retention, electrolyte disturbances (hypokalemia, hypokalemic metabolic alkalosis, hypernatremia, hypocalcemia), and hypertension. Other cardiovascular adverse reactions reported with systemic corticosteroids include bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, hypertrophic cardiomyopathy (premature neonates), myocardial rupture after recent myocardial infarction, pulmonary edema, syncope, sinus tachycardia, thromboembolism, phlebitis, and vasculitis. Increased blood pressure was noted in 13% of dexamethasone ophthalmic insert recipients for one of the intraocular products during clinical trials in adults.

Adverse neurologic effects have been reported during prolonged systemic dexamethasone administration and include insomnia, vertigo or dizziness, restlessness, amnesia and memory impairment, increased motor activity, impaired cognition, paresthesias, ischemic peripheral neuropathy, seizures, neuritis, and EEG changes. Mental disturbances, including depression, anxiety, euphoria, personality changes, emotional lability, delirium, dementia, hallucinations, irritability, mania, mood swings, schizophrenic reactions, withdrawn behavior, and psychosis have also been reported; emotional lability and psychotic problems can be exacerbated by corticosteroid therapy. Headache may be a sign of elevated intracranial pressure. Arachnoiditis, meningitis, paresis, paraplegia, and sensory disturbances have occurred after intrathecal administration. Serious neurologic events, some resulting in death, have been reported with epidural injection of corticosteroids. Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke. Headache was noted in 1% to 4% of dexamethasone ophthalmic insert/implant recipients during clinical trials in adults, at incidences higher than with placebo.

Ocular effects, such as exophthalmos, posterior subcapsular cataracts, retinopathy, or ocular hypertension, can result from prolonged use of corticosteroids and could result in glaucoma or ocular nerve damage including optic neuritis. Secondary bacterial, fungal, and viral ocular infections can be exacerbated by corticosteroid therapy. Postmarketing use of systemic dexamethasone has also been associated with cases of blurred vision. Consider referring patients who develop ocular symptoms or use systemic corticosteroid-containing products for more than 6 weeks to an ophthalmologist for evaluation. The most frequent adverse reactions to ophthalmic dexamethasone are visual impairment (i.e., visual acuity and field defects), secondary ocular infection (including viral and fungal infections) exacerbation, and perforation of the globe. Filtering blebs have rarely been reported when topical steroids have been used after cataract surgery. Temporary or permanent visual impairment has been reported with corticosteroid use by several routes of administration including intranasal and ophthalmic. Ophthalmic preparations of dexamethasone can cause increased intraocular pressure, the magnitude of which depends on the frequency and duration of dosing. If ophthalmic dexamethasone preparations are used for 10 days or longer, measure intraocular pressure routinely. Ocular irritation including transient stinging, burning or tearing and keratoconjunctivitis may occur during the use of ophthalmic dexamethasone. Allergic reactions have also been reported; ocular pruritus can occur. Ocular discomfort (10%) and eye irritation (1%) were the most frequently reported adverse reactions in clinical studies with dexamethasone ophthalmic suspension. All other adverse reactions from these studies occurred with a frequency of less than 1% including keratitis, conjunctivitis, dry eye (xerophthalmia), photophobia, blurred vision, ocular pruritus, foreign body sensation, increased lacrimation, abnormal ocular sensation, eyelid margin crusting, and ocular hyperemia. Postmarketing adverse reactions with dexamethasone ophthalmic suspension use include corneal erosion, dizziness, ocular pain, eyelid ptosis, headache, hypersensitivity reactions, and mydriasis. Intravitreal injections have been associated with endophthalmitis, ocular inflammation, and retinal detachment. Prolonged use of ophthalmic dexamethasone therapy can result in ocular hypertension, optic nerve damage, and visual defects. The incidence of cataracts in adults with initial use of the intravitreal implant is 5% within the first 6 months; however, the overall incidence after a second intravitreal implant injection is higher after 1 year. Ocular hypertension and cataracts have also occurred after prolonged application of corticosteroids to the skin around the eye. In clinical trials, the use of the intravitreal implant has resulted in ocular hemorrhage (conjunctival hemorrhage) in 22% of adult patients, ocular pain in 8% of patients, conjunctival hyperemia in 7% of patients, and vitreous detachment in 2% of patients. Increased ocular pressure (IOP) occurred in 25% of patients receiving the intravitreal implant and peaked at 60 days, returning to baseline by day 180. During the initial treatment period with the intravitreal implant, 1% of patients required laser or surgical procedures to manage elevated IOP. Secondary ocular infection may also occur with the use of the intravitreal implant.

Cases of elevated hepatic enzymes (usually reversible upon discontinuation) and hepatomegaly have been associated with systemic corticosteroid receipt such as dexamethasone.

Epidural administration of corticosteroids should be used with great caution. Rare, but serious adverse events, including cortical blindness, stroke, spinal cord infarction, paralysis, seizures, nerve injury, brain edema, and death have been reported after epidural administration of corticosteroid injections. These events have been reported with and without the use of fluoroscopy. Many cases were temporally associated with the corticosteroid injections; adverse reactions occurred within minutes to 48 hours after the corticosteroid injections. Some cases of neurologic events were confirmed through magnetic resonance imaging (MRI) or computed tomography (CT) scan. Many patients did not recover from the reported adverse effects. Discuss the benefits and risks of epidural corticosteroid injections with patients. If the decision is made to proceed with epidural administration, counsel patients to seek medical attention immediately if they experience symptoms such as vision changes, tingling in arms or legs, any symptoms of stroke, or seizures.

Dexamethasone is contraindicated in patients with a hypersensitivity to the drug or any of its components. Although true corticosteroid hypersensitivity is rare, it is possible, though also rare, that such patients will display cross-hypersensitivity to other corticosteroids. It is advisable that patients who have a hypersensitivity reaction to any corticosteroid undergo skin testing, which, although not a conclusive predictor, may help to determine if hypersensitivity to another corticosteroid exists. Such patients should be carefully monitored during and following the administration of any corticosteroid.

Prolonged administration of pharmacological doses of systemic, nasal, inhaled or topical corticosteroids (resulting in systemic absorption) may result in hypothalamic-pituitary-adrenal (HPA) suppression and/or manifestations of Cushing's syndrome in some patients. Adrenal suppression and increased intracranial pressure have been reported with the use and/or withdrawal of various corticosteroid formulations in pediatric patients. Acute adrenal insufficiency and even death may occur following abrupt discontinuation of systemic therapy. In addition, a withdrawal syndrome unrelated to adrenocortical insufficiency may occur following sudden discontinuation of corticosteroid therapy. These effects are thought to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid concentrations. Withdraw prolonged systemic corticosteroid therapy (duration of treatment of more than 2 weeks) gradually. HPA suppression can last for up to 12 months following cessation of systemic therapy. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the topical corticosteroid. HPA-suppressed patients may need supplemental corticosteroid treatment during periods of physiologic stress, such as post-surgical stress, acute blood loss, or infectious conditions, even after the corticosteroid has been discontinued. Encourage patients currently receiving chronic corticosteroid therapy or who have had corticosteroids discontinued within the last 12 months to carry identification advising the need for administration of corticosteroids in situations of increased stress.

Pediatric-specific issues should be considered prior to treatment initiation with systemic corticosteroids, such as dexamethasone. The potential for growth inhibition should be monitored during prolonged therapy in pediatric patients, and the potential for growth effects should be weighed against the clinical benefit obtained and the availability of other treatment alternatives. Prolonged systemic corticosteroid therapy can lead to osteopenia, osteoporosis, vertebral compression fractures, aseptic necrosis of femoral and humeral heads, and pathologic fractures of long bones secondary to decreased bone formation, increased bone resorption, and protein catabolism in any patient. A high-protein diet may alleviate or prevent the adverse effects associated with protein catabolism. Pediatric patients are more susceptible to the effects on bone. Chronic systemic dexamethasone therapy may cause growth inhibition in pediatric patients due to hypothalamic-pituitary-adrenal axis suppression and inhibition of bone growth. Corticosteroids should be titrated to the lowest effective dose. Because bone development is critical in pediatric patients, the use of the lowest effective dose is recommended to minimize the occurrence of systemic adverse effects. Monitor growth routinely.

Patients receiving high-dose (e.g., equivalent to 1 mg/kg or more of prednisone daily) or systemic corticosteroid therapy, such as dexamethasone, for any period of time, particularly in conjunction with corticosteroid-sparing drugs (e.g., troleandomycin) are at risk to develop immunosuppression; however, patients receiving moderate dosages of systemic corticosteroids for short periods or low dosages for prolonged periods also may be at risk. Treatment with topical or inhaled corticosteroids lessens the risk of immunosuppression; although localized effects may be seen in some patients. When given in combination with other immunosuppressive agents, there is a risk of over-immunosuppression. Intra-articularly injected corticosteroids are systemically absorbed and may cause immunosuppression. Advise patients to contact their health care provider if they develop fever or other signs or symptoms of an infectious process. Local injection of a corticosteroid into a previously infected joint is not usually recommended. Examine any joint fluid to exclude a septic process. Injection into unstable joints is generally not recommended.

If surgery is required, patients should advise their physician that they received prolonged systemic corticosteroid therapy, such as dexamethasone, within the last 12 months and state the disease for which they were being treated. For systemic therapy, identification cards that include disease state, type and dose of corticosteroid, and physician should always be carried with the patient. Long-acting dexamethasone injection preparations, which are no longer marketed in the U.S., are not suitable for use in acute stress situations. To avoid drug-induced adrenal insufficiency, a supportive corticosteroid dosage may be required in times of stress (such as trauma, surgery, or severe illness) both during treatment with these injections and for a year afterward.

Corticosteroids may increase the risks related to infections with any pathogen, including viral, bacterial, fungal, protozoan, or helminth infection. The degree to which the dose, route, and duration of corticosteroid administration correlate with the specific risks of infection is not well characterized, however, with increasing doses of corticosteroids, the rate of occurrence of infectious complications increases. Corticosteroids may also mask some signs of current infection. Although the FDA-approved product labeling states that corticosteroids are contraindicated in patients with systemic fungal infections, most clinicians believe that systemic corticosteroids can be administered to these patients as long as appropriate therapy is administered simultaneously. Avoid the use of dexamethasone in patients with a fungal infection or bacterial infection that is not adequately controlled with anti-infective agents. Activation of latent disease or exacerbation of intercurrent infection due to pathogens such as Amoeba, Candida, Cryptococcus, Mycobacterium, Nocardia, Pneumocystis, or Toxoplasma can occur in patients receiving systemic corticosteroids. Rule out infection with latent or active amebiasis before initiating corticosteroid therapy in patients who have spent time in the tropics or who have unexplained diarrhea. Use corticosteroids with caution in patients with known or suspected Strongyloides (threadworm) infestation as the immunosuppressive effects may lead to disseminated infection, severe enterocolitis, and sepsis. Reserve systemic corticosteroid therapy in active tuberculosis for patients with fulminating or disseminated disease and only in conjunction with appropriate antituberculosis therapy. Reactivation of tuberculosis may occur in patients with latent tuberculosis or tuberculin reactivity; close observation for disease reactivation is needed if corticosteroids are indicated in such patients. Furthermore, chemoprophylaxis is advised if prolonged corticosteroid therapy is needed. Advise patients receiving immunosuppressive doses of systemic corticosteroids to avoid exposure to persons with a viral infection (i.e., measles or varicella) because these diseases may be more serious or even fatal in immunosuppressed patients. Instruct patients to get immediate medical advice if exposure occurs. If exposed to chickenpox, prophylaxis with varicella-zoster immune globulin may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin may be indicated. Avoid the use of corticosteroids in active ocular herpes infection due to the risk of corneal perforation. Corticosteroids should not be used in cerebral malaria. The use of ophthalmic dexamethasone formulations is contraindicated in most forms of cornea and conjunctiva viral ocular infection including herpes simplex virus epithelial keratitis, ocular vaccinia, and ocular varicella, and also in mycobacterial infection of the eye and fungal diseases of the eye.

Do not use high doses of systemic corticosteroids such as dexamethasone for the treatment of traumatic brain injury. An increase in early mortality (at 2 weeks) and late mortality (at 6 months) was noted in patients with head trauma who were determined not to have other clear indications for corticosteroid treatment; in the trial, patients received methylprednisolone hemisuccinate.

Corticosteroid therapy, including systemic dexamethasone therapy, has been associated with left ventricular free-wall rupture in patients with recent myocardial infarction, and should therefore be used cautiously in these patients. As sodium retention with resultant edema and potassium loss may occur in patients receiving systemic corticosteroids, these agents should be used with caution in patients with congestive heart failure, hypertension, or renal disease or insufficiency.

Systemic corticosteroids, such as dexamethasone, may decrease glucose tolerance, produce hyperglycemia, and aggravate or precipitate diabetes mellitus. This may especially occur in patients predisposed to diabetes mellitus. When corticosteroid therapy is necessary for patients with diabetes mellitus, changes in insulin, oral antidiabetic agent dosage, and/or diet may be required.

An acute myopathy has been observed with the use of high doses of systemic corticosteroids, most often occurring in patients with neuromuscular disease disorders (e.g., myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatinine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.

Existing emotional instability or psychosis may be aggravated by corticosteroids. Psychiatric derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychosis. Use dexamethasone with caution in patients with a seizure disorder; systemic steroids can lower the seizure threshold.

Metabolic clearance of corticosteroids is decreased in hypothyroidism and increased in hyperthyroidism. Changes in thyroid disease status of a patient may necessitate an adjustment in systemic dexamethasone dosage.


Systemic corticosteroids should be used with caution in patients with active or latent peptic ulcer disease, diverticulitis, fresh intestinal anastomoses, and nonspecific ulcerative colitis, since steroids may increase the risk of a gastrointestinal (GI) perforation. Signs of peritoneal irritation following GI perforation in patients receiving corticosteroids may be minimal or absent. Corticosteroids should not be used in patients where there is a possibility of impending GI perforation, abscess, or pyogenic infection. There is an enhanced effect due to decreased metabolism of systemic corticosteroids in patients with severe hepatic disease with cirrhosis.[

Systemic corticosteroids, like dexamethasone, may cause impaired wound healing. Ophthalmic and ocular dosage forms may cause impairment of wound healing within or near the site of application.

Prolonged use of corticosteroids including dexamethasone may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. Corticosteroids can cause cataracts and exacerbate pre-existing glaucoma. Periodically assess patients receiving corticosteroids chronically for cataract formation, visual disturbance, or increased intraocular pressure. Consider referring patients who develop ocular symptoms or use systemic corticosteroid-containing products for more than 6 weeks to an ophthalmologist for evaluation. Ophthalmic dexamethasone is more likely than other ophthalmic agents to increase intraocular pressure, so intraocular pressure should be measured every 2 to 4 weeks for the first 2 months of therapy, and every 1 to 2 months thereafter. Ophthalmic dexamethasone therapy should be undertaken with caution in patients with a history of open-angle glaucoma, myopia, Krukenberg's spindle, or diabetes because these patients have an increased risk of developing ocular hypertension during therapy. The dexamethasone intravitreal implant is contraindicated in patients with glaucoma who have cup to disc ratio more than 0.8. Ophthalmic dexamethasone should be used with caution in patients with corneal abrasion. Dexamethasone intravitreal implant is contraindicated in patients who have a tear or a rupture of posterior ocular lens capsule; these patients with an absent or torn posterior capsule of the lens are at increased risk of migration of the intravitreal implant into the anterior chamber. Laser posterior capsulotomy in pseudophakic patients is not a contraindication for the dexamethasone intravitreal implant. The safety and efficacy of dexamethasone intravitreal implant, ophthalmic injection suspension, and ophthalmic insert have not been established in pediatric patients.

Corticosteroid therapy usually does not contraindicate vaccination with live-virus vaccines when such therapy is of short-term (less than 2 weeks); low to moderate dose; long-term alternate-day treatment with short-acting preparations; maintenance physiologic doses (replacement therapy); ophthalmic administration, or by intra-articular, bursal or tendon injection. The immunosuppressive effects of steroid treatment differ, but many clinicians consider a dose equivalent to either 2 mg/kg/day or 20 mg/day of prednisone as sufficiently immunosuppressive to raise a concern about the safety of immunization with live-virus vaccines. In general, patients with severe immunosuppression due to large doses of corticosteroids should not receive vaccination with live-virus vaccines. When cancer chemotherapy or immunosuppressive therapy is being considered (e.g., for patients with Hodgkin's disease or organ transplantation), vaccination should precede the initiation of chemotherapy or immunotherapy by 2 or more weeks. Patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated at least 3 months after discontinuation of therapy. In patients who have received high-dose, systemic corticosteroids for 2 or more weeks, it is recommended to wait at least 3 months after discontinuation of therapy before administering a live-virus vaccine.

The routine use of high-dose (more than 0.5 mg/kg/day) dexamethasone for either the prevention or treatment of chronic lung disease in premature neonates is not recommended by the American Academy of Pediatrics (AAP) due to a lack of survival benefit and concern about long-term adverse outcomes, particularly increased rates of cerebral palsy. Studies utilizing lower doses of dexamethasone (less than 0.2 mg/kg/day) have not reported increased rates of adverse neurodevelopmental effects; however, due to the small number of patients included in these studies, the AAP states that there is insufficient evidence to recommend the use of low-dose dexamethasone and further study is warranted. In a geographical cohort study of 148 extremely premature adolescents (born younger than 28 weeks gestation), 55 (37%) received postnatal dexamethasone (mean cumulative dose 7.7 mg/kg) during the neonatal period. Patients receiving dexamethasone had smaller total brain tissue volume (mean difference -3.6%, p = 0.04) and smaller white matter, thalami, and basal ganglia volumes (p less than 0.05 for all) when compared with participants who did not receive postnatal dexamethasone. There was also a trend of smaller total brain and white matter volumes with increased dose of postnatal dexamethasone. Avoid use of dexamethasone injectable formulations containing benzyl alcohol in premature neonates and neonates. Administration of benzyl alcohol to neonates can result in 'gasping syndrome,' which is a potentially fatal condition characterized by metabolic acidosis and CNS, respiratory, circulatory, and renal dysfunction; it is also characterized by high concentrations of benzyl alcohol and its metabolites in the blood and urine. While the minimum amount of benzyl alcohol at which toxicity may occur is not known, 'gasping syndrome' has been associated with benzyl alcohol dosage more than 99 mg/kg/day in neonates and low-birth-weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic failure, renal failure, hypotension, bradycardia, and cardiovascular collapse. Rare cases of death, primarily in premature neonates, have been reported. Further, an increased incidence of kernicterus, especially in small, premature neonates has been reported. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources. Premature neonates, neonates with a low birth weight, and patients who receive a high dose may be more likely to develop toxicity.

In utero exposure to dexamethasone can lead to hypoadrenalism in neonates. Monitor neonates born to mothers who have taken substantial doses of corticosteroids during pregnancy for signs of hypoadrenalism.

Dexamethasone ophthalmic solutions are sometimes used off-label in the ear for otic conditions. Otic dexamethasone use is contraindicated for use in patients with tympanic membrane perforation.

Some commercially available formulations of dexamethasone injection or ophthalmic solution may contain sulfites; some parenteral products also contain benzyl alcohol. Sulfites and benzyl alcohol may cause allergic reactions in some people. They should be used with caution in patients with known sulfite hypersensitivity or benzyl alcohol hypersensitivity. Patients who have asthma are more likely to experience a sulfite sensitivity reaction than non-asthmatic patients.

Description: Dexamethasone is a potent synthetic glucocorticoid with little to no mineralocorticoid activity used for physiologic replacement in patients with adrenal insufficiency and at pharmacologic doses as an anti-inflammatory or immunosuppressive agent. Although hydrocortisone is the preferred glucocorticoid for replacement therapy in pediatric patients with adrenal insufficiency whose linear growth is incomplete, dexamethasone has also been used safely with close monitoring. Due to the lack of mineralocorticoid activity, dexamethasone alone may not be adequate replacement in patients with certain types of adrenal insufficiencies, such as classic congenital adrenal hyperplasia. Dexamethasone is used in pediatric patients for the management of various respiratory disorders, including acute treatment of croup and asthma. Systemic corticosteroids may be added to other long-term maintenance medications in the management of uncontrolled severe persistent asthma. Once stabilization of asthma is achieved, regular attempts should be made to reduce or eliminate the use of systemic corticosteroids due to the side effects associated with chronic administration. Short courses of treatment may be used in the management of asthma exacerbations. Although it has also been used for the management of other respiratory diseases including prophylaxis of laryngeal edema after extubation, bronchiolitis in infants, and prevention of chronic lung disease in premature neonates, most experts recommend reserving use in these disorders to high-risk patients due to lack of efficacy data and risk of serious adverse effects. The American Academy of Pediatrics does not recommend the use of systemic corticosteroids for bronchiolitis in any setting. Other off-label uses in pediatric patients include the prevention of chemotherapy-induced nausea and vomiting and the adjunctive treatment of bacterial meningitis. Anti-inflammatory activity of dexamethasone is approximately 25 to 30 times more potent than hydrocortisone, 6 to 7 times more potent than prednisone and 5 to 6 times more potent than methylprednisolone. Systemic and ophthalmic formulations of dexamethasone are FDA-approved in pediatric patients; otic formulations are not FDA-approved for use in pediatric patients.

General dosing information for systemic therapy:
-Dosage requirements are variable. Individualize doses based on the condition being treated and the response of the patient.
-Gradual withdrawal of dexamethasone after high-dose or prolonged therapy is recommended due to the possibility of hypothalamic-pituitary-adrenal (HPA) axis suppression. The following recommendations for withdrawal of corticosteroids based on the duration of therapy have been made: less than 2 weeks-may abruptly discontinue; 2 to 4 weeks-taper dose over 1 to 2 weeks; more than 4 weeks-taper slowly over 1 to 2 months to physiologic dose (approximately equivalent to 10 mg/m2/day of hydrocortisone) and discontinue after assessment of adrenal function has demonstrated recovery.
-In general, when oral therapy is not an option, the same dose can be given IV.
-In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

For the treatment of primary adrenocortical insufficiency (e.g., Addison's Disease, congenital adrenal hyperplasia) or secondary adrenocortical insufficiency:
Oral dosage:
Infants, Children, and Adolescents: 0.15 to 0.375 mg/m2/day PO once daily has been recommended for patients with congenital adrenal hyperplasia. Although most experts recommend hydrocortisone as first-line treatment of adrenal insufficiency in pediatric patients whose linear growth is incomplete due to a lower incidence of growth suppression, other authors have stated that dexamethasone may be used safely with close monitoring and individualization of dose based on growth, bone age, and hormone levels. Liquid formulations of dexamethasone are recommended for more precise titration of doses. 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day PO given in 3 to 4 divided doses is the FDA-approved general dosage range. Parenteral therapy may be needed in acute insufficiency.
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day IV or IM given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response.

For hypothalamic-pituitary-adrenal (HPA) suppression diagnosis (e.g., dexamethasone suppression tests):
-for use as a test for Cushing's syndrome:
Oral dosage:
Children and Adolescents: 25 to 30 mcg/kg/dose PO (Max: 2 mg/dose PO) given at 11:00 p.m. with a plasma cortisol concentration measured at 8:00 a.m. the following morning. A plasma cortisol concentration of less than 5 mcg/dL occurs in normal individuals but not those with Cushing's syndrome. Measure a dexamethasone concentration concurrently with the cortisol concentration to ensure adequacy of the dexamethasone dose.
-for use as a test to distinguish Cushing's syndrome secondary to pituitary ACTH excess from Cushing's syndrome secondary to other causes:
Oral dosage:
Children and Adolescents: 120 mcg/kg/dose PO (Max: 8 mg/dose PO) given at 11:00 p.m. with a plasma cortisol concentration measured at 8:00 a.m. the following morning. A decrease in the morning cortisol of 20% or more from baseline had a 97.5% sensitivity and 100% specificity in distinguishing patients with Cushing disease from those with primary adrenal disorders in a retrospective study (n = 125, age 3 to 18 years). Measure a dexamethasone concentration concurrently with the cortisol concentration to ensure adequacy of the dexamethasone dose. Alternatively, a 2 day test consisting of 30 mcg/kg/day PO on day 1 and 120 mcg/kg/day PO on day 2, each given in 4 divided doses, has been recommended. Cortisol concentrations are suppressed in patients with pituitary cushing syndrome after the larger dose but not the smaller dose; cortisol concentrations are not suppressed after dexamethasone in patients with adrenocorticotropic hormone-independent Cushing syndrome.

For the treatment of allergic disorders including anaphylaxis, anaphylactic shock, or anaphylactoid reactions, angioedema, acute noninfectious laryngeal edema, hypersensitivity reactions (drug or food allergy), transfusion-related reactions, urticaria, serum sickness, and severe perennial allergies or seasonal allergies, including allergic rhinitis:
Oral dosage (dexamethasone):
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day PO given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response. Corticosteroids are not indicated as initial treatment for anaphylaxis, but can be given as adjunctive therapy after the administration of epinephrine.
Intravenous or Intramuscular dosage (dexamethasone sodium phosphate injection):
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day IV or IM given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response. Corticosteroids are not indicated as initial treatment for anaphylaxis, but can be given as adjunctive therapy after the administration of epinephrine.

For asthma exacerbation:
Oral dosage:
Infants, Children, and Adolescents: 0.6 mg/kg/dose PO as a single dose or once daily for 2 days. Max: 16 mg/dose. Administer dexamethasone IV or IM initially for the treatment of severe respiratory conditions or those compromising the airway. Single or 2-day regimens of dexamethasone have shown similar efficacy, less vomiting, and improved compliance when compared to a 5-day course of oral prednisone or prednisolone. Use of dexamethasone for longer than 2 days may increase the potential for metabolic side effects. Although prednisone, prednisolone, or methylprednisolone are the systemic corticosteroids of choice for the management of moderate to severe asthma exacerbations, other corticosteroids such as dexamethasone, given in equipotent daily doses are likely to be as effective. Of note, 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day PO given in 3 to 4 divided doses is the FDA-approved initial dosage range for dexamethasone; however, this is significantly lower than the range used in clinical practice.
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 0.6 mg/kg/dose IV or IM as a single dose or once daily for 2 days. Max: 16 mg/dose. Single-dose regimens ranging from 0.3 to 1.7 mg/kg/dose have been reported. Max: 36 mg/dose. In a study of young children with moderate exacerbations, a single day regimen of parenteral dexamethasone resulted in similar efficacy as a 5-day course of oral prednisolone. Use of dexamethasone for longer than 2 days may increase the potential for metabolic side effects. Although prednisone, prednisolone, or methylprednisolone are the systemic corticosteroids of choice for the management of moderate to severe asthma exacerbations, other corticosteroids such as dexamethasone, given in equipotent daily doses are likely to be as effective. Of note, 0.5 to 9 mg per day IV or IM is the FDA-approved initial dosage range depending on the condition being treated; however, higher doses are sometimes used in clinical practice.

For the treatment of laryngotracheobronchitis (croup)*:
Oral dosage:
Infants, Children, and Adolescents: 0.15 to 0.6 mg/kg/dose (Usual Max: 16 mg/dose) PO as a single dose.
Intravenous and Intramuscular dosage:
Infants, Children, and Adolescents: 0.15 to 0.6 mg/kg/dose (Usual Max: 16 mg/dose) IV or IM as a single dose.

For the prevention of extubation failure in patients at increased risk for laryngeal edema (i.e., laryngeal edema prophylaxis*):
Intravenous dosage:
Neonates: Various regimens have been used. 0.25 mg/kg/dose IV every 8 hours for 3 doses with the first dose given approximately 4 hours prior to scheduled extubation was studied in a prospective, randomized trial in 50 premature neonates (mean gestational age, 27.7 to 28.7 weeks) who were at high risk for airway edema. The rate of postextubation stridor and reintubation was significantly lower in the dexamethasone group compared to the placebo group. A systematic review of clinical trials of dexamethasone for the prevention of extubation failure recommends therapy be reserved for use in high risk neonates, such as those with repeated or prolonged intubations, due to a lack of benefit in low risk neonates and the risk of adverse effects. Use preservative-free products for administration to neonates when possible.
Infants, Children, and Adolescents: 0.5 mg/kg/dose (Max: 10 mg/dose) IV every 6 hours for 6 doses with the first dose given 6 to 12 hours prior to extubation. One prospective, randomized study (n = 153) found no significant difference in the risk of postextubation stridor, the average number of racemic epinephrine treatments, or the number of patients requiring reintubation in patients receiving dexamethasone compared to those receiving placebo. Another prospective, randomized study (n = 66) found that dexamethasone-treated patients had a significantly lower rate of postextubation stridor at 10 minutes, 6 hours, and 12 hours but not 24 hours and fewer patients requiring epinephrine or reintubation compared to placebo-treated patients. A systematic review of clinical trials of dexamethasone for the prevention of postextubation stridor concluded that therapy may be beneficial in high-risk patients, such as those with underlying airway anomalies or multiple airway manipulations.

For the treatment of respiratory conditions including aspiration pneumonitis, idiopathic eosinophilic pneumonitis, berylliosis, or Loeffler's syndrome:
Oral dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day PO given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response. Administer dexamethasone IV or IM initially for the treatment of severe respiratory conditions or those compromising the airway.
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day IV or IM given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response.

For the treatment of bronchiolitis*:
Oral dosage:
Infants: Due to the lack of consistent efficacy data and the high risk of adverse effects, the American Academy of Pediatrics does not recommend systemic corticosteroids for the management of bronchiolitis in any setting. However, other authors state corticosteroids may be beneficial in severely ill or mechanically ventilated patients. One randomized trial of 800 infants seen in the emergency department used 1 mg/kg PO once (Max: 10 mg/dose) followed by 0.6 mg/kg/dose PO once daily (Max: 10 mg/dose) for 5 days. Dexamethasone in combination with nebulized epinephrine was effective in reducing hospital admissions by day 7 of illness compared to treatment with dexamethasone alone, epinephrine alone, or placebo. In a study of 200 infants (median age 3.5 months) with an asthma risk, as determined by eczema or a family history of asthma in a first-degree relative, dexamethasone 1 mg/kg (single dose) PO then 0.6 mg/kg/dose PO once daily for 4 more days was administered with salbutamol. In infants receiving dexamethasone with salbutamol, the time to readiness for discharge was 18.6 hours vs. 27.1 hours in patients not receiving dexamethasone (p = 0.015). In contrast, 1 mg/kg/dose PO (Max: 12 mg/dose) given as a single dose did not reduce hospitalization rates, Respiratory Assessment Change Scores (RACS), length of hospitalization for those patients who required admission, or subsequent hospitalizations within 7 days compared to placebo in another large, randomized trial (n = 600).
Intravenous dosage:
Infants: Due to the lack of consistent efficacy data and the high risk of adverse effects, the American Academy of Pediatrics does not recommend systemic corticosteroids for the management of bronchiolitis in any setting. However, other authors state corticosteroids may be beneficial in severely ill or mechanically ventilated patients. 0.15 mg/kg/dose IV every 6 hours for 48 hours with the first dose administered within 24 hours of mechanical ventilation was used in patients with respiratory syncytial virus. In a post hoc analysis of patients with bronchiolitis (n = 39), the mean duration of mechanical ventilation and of supplemental oxygen were significantly shorter in patients receiving dexamethasone compared to those receiving placebo (4.9 and 7.7 days vs. 9.2 and 11.3 days, respectively); no differences were seen in the length of intensive care unit or hospital stay.

For the prevention of chronic lung disease (CLD)* in mechanically ventilated neonates:
Intravenous dosage:
Premature neonates: Numerous dosing schedules have been studied. The Dexamethasone: A Randomized Trial (DART) study (n = 70, median gestational age 25 weeks) used the following tapering dose schedule over 10 days: 0.075 mg/kg/dose IV twice daily for 3 days, followed by 0.05 mg/kg/dose IV twice daily for 3 days, followed by 0.025 mg/kg/dose IV twice daily for 2 days, followed by 0.01 mg/kg/dose IV twice daily for 2 days. This dosing regimen facilitated extubation by day 10 but did not significantly improve mortality or oxygen dependence at 36 weeks; follow-up at 2 years of age did not indicate any significant adverse neurodevelopmental outcomes in neonates treated with dexamethasone. Use is somewhat controversial, and most experts suggest using low doses and careful patient selection. The American Academy of Pediatrics (AAP) recommends against the use of high-dose dexamethasone (more than 0.5 mg/kg/day) due to the risk of short- and long-term adverse effects, including neurodevelopmental effects. Late corticosteroid therapy (initiated after 7 days of age) may be preferred over early therapy (initiated at less than 7 days of age). Late therapy may reduce neonatal mortality without significantly increasing potential adverse long-term neurodevelopmental outcomes.

INVESTIGATIONAL USE: For adjunctive use in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection*, the virus that causes coronavirus disease 2019 (COVID-19)*:
-for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection*, the virus that causes coronavirus disease 2019 (COVID-19)* in hospitalized patients:
Oral dosage:
Children and Adolescents: 0.15 mg/kg/dose (Max: 6 mg/dose) PO once daily for up to 10 days, although data are limited. The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend dexamethasone (with or without remdesivir) for hospitalized pediatric patients who require high-flow oxygen or noninvasive ventilation. Dexamethasone (without remdesivir) is also recommended for pediatric patients requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO). The addition of baricitinib or tocilizumab may be considered for patients who do not have rapid (e.g., within 24 hours) improvement in oxygenation after initiation of dexamethasone. Corticosteroids are not routinely recommended for pediatric patients who require only conventional oxygen, but corticosteroids can be considered in combination with remdesivir for patients with increasing oxygen needs, particularly adolescents. The use of dexamethasone for treatment of severe COVID-19 in pediatric patients who are profoundly immunocompromised has not been evaluated and may be harmful; in such cases, treatment should be considered on a case-by-case basis.
Intravenous dosage:
Children and Adolescents: 0.15 mg/kg/dose (Max: 6 mg/dose) IV once daily for up to 10 days, although data are limited. The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend dexamethasone (with or without remdesivir) for hospitalized pediatric patients who require high-flow oxygen or noninvasive ventilation. Dexamethasone (without remdesivir) is also recommended for pediatric patients requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO). The addition of baricitinib or tocilizumab may be considered for patients who do not have rapid (e.g., within 24 hours) improvement in oxygenation after initiation of dexamethasone. Corticosteroids are not routinely recommended for pediatric patients who require only conventional oxygen, but corticosteroids can be considered in combination with remdesivir for patients with increasing oxygen needs, particularly adolescents. The use of dexamethasone for treatment of severe COVID-19 in pediatric patients who are profoundly immunocompromised has not been evaluated and may be harmful; in such cases, treatment should be considered on a case-by-case basis.
-for the treatment of hyperinflammation in pediatric coronavirus disease 2019 (COVID-19)*:
Oral dosage:
Children and Adolescents: 0.15 to 0.3 mg/kg/dose (Max: 6 mg/dose) PO once daily for up to 10 days is recommended as first-line immunomodulatory treatment in patients with persistent oxygen requirements due to COVID-19.
Intravenous dosage:
Children and Adolescents: 0.15 to 0.3 mg/kg/dose (Max: 6 mg/dose) IV once daily for up to 10 days is recommended as first-line immunomodulatory treatment in patients with persistent oxygen requirements due to COVID-19.

For the treatment of cerebral edema associated with primary or metastatic brain tumor, craniotomy, or head injury:
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: Initially, 1 to 1.5 mg/kg/dose IV, then 1 to 1.5 mg/kg/day IV in divided doses every 3 to 4 hours was used in conjunction with hyperventilation, control of body temperature, barbiturates, and continuous intracranial and arterial pressure monitoring in pediatric patients with severe head injury (n = 24, age 3 months to 14 years). 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day IV or IM given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response. Use is not a substitute for neurosurgical evaluation and definitive management such as neurosurgery, etc.
Oral dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day PO given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response. Use is not a substitute for neurosurgical evaluation and definitive management such as neurosurgery, etc.

For the treatment of pruritus and inflammatory effects of corticosteroid-responsive dermatoses and dermatologic disorders, including atopic dermatitis, bullous dermatitis herpetiformis, contact dermatitis, cutaneous T-cell lymphoma (CTCL) or mycosis fungoides, exfoliative dermatitis, pemphigus, severe seborrheic dermatitis, severe erythema multiforme, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis* (TEN):
-for the treatment of atopic dermatitis, bullous dermatitis herpetiformis, contact dermatitis, cutaneous T-cell lymphoma (CTCL) or mycosis fungoides, exfoliative dermatitis, pemphigus, severe seborrheic dermatitis, and severe erythema multiforme:
Oral dosage (dexamethasone):
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day PO in 3 to 4 divided doses, initially. Adjust dose according to response.
Intravenous or Intramuscular dosage (dexamethasone sodium phosphate):
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day IV or IM in 3 to 4 divided doses. Adjust dose according to response.
-for the treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis* (TEN):
Intravenous or Intramuscular dosage (dexamethasone sodium phosphate, standard dose):
Infants, Children, and Adolescents: 0.1 to 0.3 mg/kg/dose IV or IM once daily, then taper dose over 7 to 10 days.
Intravenous or Intramuscular dosage (dexamethasone sodium phosphate, pulse dose):
Infants, Children, and Adolescents: 1 to 1.5 mg/kg/dose IV or IM once daily for 3 days.

For the treatment of rheumatic and related disorders such as acute rheumatic carditis, systemic dermatomyositis (polymyositis), systemic lupus erythematosus (SLE), temporal arteritis, and symptomatic sarcoidosis or for adjunctive therapy in the treatment of rheumatic and nonrheumatic inflammatory disorders such as acute gouty arthritis, ankylosing spondylitis, rheumatoid arthritis, juvenile rheumatoid arthritis (JRA)/juvenile idiopathic arthritis (JIA), post-traumatic osteoarthritis, acute and subacute bursitis, epicondylitis, acute nonspecific tenosynovitis, or psoriatic arthritis:
Oral dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day PO given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response.
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day IV or IM given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response.

For the treatment of acute episodes or exacerbation of inflammatory bowel disease (Crohn's disease or ulcerative colitis):
Oral dosage:
Children and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day PO given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response. Because of the potential complications of steroid use, steroids should be used selectively and in the lowest dose possible for the shortest duration as possible.
Intravenous or Intramuscular dosage:
Children and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day IV or IM given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response. Because of the potential complications of steroid use, steroids should be used selectively and in the lowest dose possible for the shortest duration as possible.

For the treatment of corticosteroid-responsive hematologic disorders such as autoimmune hemolytic anemia, erythroblastopenia, and congenital hypoplastic anemia:
Oral dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day PO given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response.
Intravenous and Intramuscular dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day IV or IM given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response.

For the management of nephrotic syndrome to induce diuresis or decrease proteinuria:
Oral dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day PO given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response.
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day IV or IM given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response.

For chemotherapy-induced nausea/vomiting* and chemotherapy-induced nausea/vomiting prophylaxis*:
Intravenous or Oral dosage:
Children and Adolescents: 10 to 14 mg/m2/dose IV is usually used prior to chemotherapy. A 5-HT3 antagonist is usually given along with dexamethasone for highly-emetogenic chemotherapy. An example regimen: dexamethasone 10 mg/m2/dose IV once daily, along with ondansetron. Some patients receive repeat dosing every 12 hours, either IV or PO, but optimal regimens for repeat dosing are not established. For chemotherapy that is less emetogenic, doses as low as 6 mg/m2/dose PO have been given. The optimal dose of steroids for chemotherapy-induced nausea/vomiting (CINV) in children is not determined, and there are safety considerations.

For post-operative nausea/vomiting (PONV) prophylaxis*:
Intravenous dosage:
Children and Adolescents: Dexamethasone 0.015 mg/kg/dose IV (Max: 5 mg/dose IV) in combination with ondansetron 0.1 mg/kg/dose (Max: 4 mg) is recommended first-line for postoperative vomiting prophylaxis in children by the Society for Ambulatory Anesthesiology. 0.15 to 1 mg/kg/dose IV (Max: 8 to 25 mg/dose IV) given as a single intraoperative dose reduces the incidence of postoperative nausea/vomiting in the first 24 hours, improves postoperative pain control, and decreases the time to resumption of soft/solid diet without adverse effects and is recommended in patients undergoing tonsillectomy.

For the adjunctive treatment of bacterial meningitis*:
NOTE: For CNS infections related to tuberculosis, see tuberculosis.
Intravenous dosage:
Infants, Children, and Adolescents: 0.15 mg/kg/dose IV every 6 hours for 2 to 4 days for H. influenzae type b; administer the first dose 10 to 20 minutes before or concomitantly with the first dose of antimicrobial agent. Do not administer to patients who have already received antimicrobial therapy as this is unlikely to improve patient outcome. Use in pneumococcal meningitis is controversial and may be considered in those older than 6 weeks of age after weighing the possible benefits and risks.
Oral dosage:
Infants, Children, and Adolescents: 0.15 mg/kg/dose PO every 6 hours for 2 to 4 days for H. influenzae type b; administer the first dose 10 to 20 minutes before or concomitantly with the first dose of antimicrobial agent. Do not administer to patients who have already received antimicrobial therapy as this is unlikely to improve patient outcome. Use in pneumococcal meningitis is controversial and may be considered in those older than 6 weeks of age after weighing the possible benefits and risks.

For the treatment of drug-susceptible tuberculosis infection or drug-resistant tuberculosis infection as adjunctive therapy in combination with antituberculous therapy:
-for the treatment of tuberculosis infection as adjunctive therapy in combination with antituberculous therapy in persons without HIV:
Oral dosage:
Infants, Children, and Adolescents: 0.3 to 0.6 mg/kg/dose PO once daily for 4 to 6 weeks, then taper dose over 2 to 4 weeks. Guidelines recommend as adjunct therapy for meningitis. Routine use outside of CNS involvement is not recommended; however, select patients may benefit.
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 0.3 to 0.6 mg/kg/dose IV or IM once daily for 4 to 6 weeks, then taper dose over 2 to 4 weeks. Guidelines recommend as adjunct therapy for meningitis. Routine use outside of CNS involvement is not recommended; however, select patients may benefit.
-for the treatment of tuberculosis infection as adjunctive therapy in combination with antituberculous therapy in persons with HIV:
Oral dosage:
Infants and Children: 0.3 to 0.6 mg/kg/dose PO once daily for 4 to 6 weeks, then taper dose over 2 to 4 weeks. Guidelines recommend as adjunct therapy for meningitis. Routine use outside of CNS involvement is not recommended; however, select patients may benefit.
Adolescents: 0.3 to 0.4 mg/kg/dose PO once daily for 2 to 4 weeks, then taper by 0.1 mg/kg/dose weekly until 0.1 mg/kg/dose, and then 4 mg PO once daily and taper by 1 mg/dose weekly for a total duration of 12 weeks. Guidelines recommend as adjunct therapy for meningitis. Routine use outside of CNS involvement is not recommended; however, select patients may benefit.
Intravenous or Intramuscular dosage:
Infants and Children: 0.3 to 0.6 mg/kg/dose IV or IM once daily for 4 to 6 weeks, then taper dose over 2 to 4 weeks. Guidelines recommend as adjunct therapy for meningitis. Routine use outside of CNS involvement is not recommended; however, select patients may benefit.
Adolescents: 0.3 to 0.4 mg/kg/dose IV or IM once daily for 2 to 4 weeks, then taper by 0.1 mg/kg/dose weekly until 0.1 mg/kg/dose, and then 4 mg IV or IM once daily and taper by 1 mg/dose weekly for a total duration of 12 weeks. Guidelines recommend as adjunct therapy for meningitis. Routine use outside of CNS involvement is not recommended; however, select patients may benefit.

For the treatment of hypercalcemia related to cancer or for the treatment of nonsuppurative thyroiditis:
Oral dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day PO given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response.
Intravenous and Intramuscular dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day IV or IM given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response.

For the treatment of acute leukemias including acute lymphocytic leukemia (ALL):
Oral dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day PO given in 3 to 4 divided doses is the FDA-approved general dosage range ; however, doses may vary according to the specific protocol used.
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day IV or IM given in 3 to 4 divided doses is the FDA-approved general dosage range ; however, doses may vary according to the specific protocol used.

To mitigate the effects of acute spinal cord compression* or large mediastinal masses* that are causing respiratory failure in patients with cancer:
Intravenous dosage:
Infants, Children, and Adolescents: 1 to 2 mg/kg IV load followed by 0.25 to 0.5 mg/kg/dose IV every 6 hours. Max: 16 mg/dose.

For the treatment of acute exacerbations of multiple sclerosis:
Oral dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day PO given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response.
Intravenous* or Intramuscular dosage*:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day IV or IM given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response.

For the treatment of corticosteroid-responsive ocular inflammation of the palpebral and bulbar conjunctiva, cornea, and anterior segment inflammation of the globe, such as allergic conjunctivitis, eyelid acne rosacea, superficial punctate keratitis, herpes zoster ocular infection associated keratitis, iritis, cyclitis, uveitis, and selected infective bacterial conjunctivitis and viral conjunctivitis, when the inherent hazard of steroid use is accepted to obtain an advisable diminution in edema and inflammation and for corneal abrasion, corneal ulcer, or corneal injury from chemical or thermal ocular burns or penetration of foreign bodies:
Ophthalmic dosage (0.1% ophthalmic suspension):
Children and Adolescents: 1 to 2 drops in the affected eye(s) every hour for severe disease and every 4 to 6 hours for mild disease. Taper dose to discontinuation as inflammation subsides.
Oral dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day PO in 3 to 4 divided doses, initially. Adjust according to patient response.
Intravenous or Intramuscular dosage (dexamethasone sodium phosphate):
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day IV or IM in 3 to 4 divided doses. Adjust according to patient response.

For the treatment of neurologic or myocardial involvement associated with trichinosis:
Oral dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day PO given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response.
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day IV or IM given in 3 to 4 divided doses is the FDA-approved general dosage range. Adjust according to patient response.

For the treatment of acute altitude sickness*, including the treatment of high altitude cerebral edema*:
Oral dosage:
Infants, Children, and Adolescents: 0.15 mg/kg/dose (Max: 4 mg/dose) PO every 6 hours until symptoms resolve. May add acetazolamide for high altitude cerebral edema.
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 0.15 mg/kg/dose (Max: 4 mg/dose) IV or IM every 6 hours until symptoms resolve. May add acetazolamide for high altitude cerebral edema.

For the treatment of pharyngitis*:
Oral dosage:
Children and Adolescents 5 to 17 years: 0.6 mg/kg/dose (Max: 10 mg/dose) PO once daily for 1 to 2 days.
Intramuscular dosage:
Children and Adolescents 5 to 17 years: 0.6 mg/kg/dose (Max: 10 mg/dose) IM once daily for 1 to 2 days.

For the treatment of neurocysticercosis* as adjunctive therapy in combination with antiparasitics:
Oral dosage:
Children and Adolescents: 0.1 to 0.2 mg/kg/day PO starting 3 days before antiparasitics and continuing for the duration of therapy. Titrate based on clinical response. Taper over 6 to 8 weeks after antiparasitic therapy is complete to avoid rebound symptoms.

Maximum Dosage Limits:
Corticosteroid dosage must be individualized and is highly variable depending on the nature and severity of the disease, and on patient response.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Glucocorticoids are naturally occurring hormones that prevent or suppress inflammation and immune responses when administered at pharmacological doses. At the molecular level, unbound glucocorticoids readily cross cell membranes and bind with high affinity to specific cytoplasmic receptors. This binding induces a response by modifying transcription and, ultimately, protein synthesis to achieve the steroid's intended action. Such actions can include: inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of the inflammatory response, and suppression of humoral immune responses. Some of the net effects include reduction in edema or scar tissue and a general suppression in an immune response. The degree of clinical effect is normally related to the dose administered. The anti-inflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, collectively called lipocortins. Lipocortins, in turn, control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of the precursor molecule arachidonic acid. Likewise, the numerous adverse effects related to corticosteroid use usually depend on the dose administered and the duration of therapy.

Pharmacokinetics: Dexamethasone is administered via oral, intravenous, intramuscular, intraarticular, intravitreal, ophthalmic and otic routes. Circulating drug binds weakly to plasma proteins (primarily albumin), with only the unbound portion of a dose being active. Systemic dexamethasone is quickly distributed into the kidneys, intestines, skin, liver, and muscle. Systemic dexamethasone is metabolized by the liver to inactive metabolites. These inactive metabolites, as well as a small portion of unchanged drug, are excreted in the urine. The plasma elimination half-life of dexamethasone in adults is approximately 2.4 to 3.4 hours, whereas the biological half-life is 36 to 72 hours.

Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4 and P-glycoprotein (P-gp)
Dexamethasone is a substrate for CYP3A4 and P-gp. Dexamethasone is an inducer of CYP3A4.


-Route-Specific Pharmacokinetics
Oral Route
Dexamethasone is rapidly and well absorbed after oral administration. In adults, bioavailability has been reported to be in the range of approximately 60% to 100%, with no significant differences between the elixir and tablet formulations. Peak concentrations occur 1 to 2 hours after oral administration. However, 1 study of 13 patients (aged 14 to 28 years) with congenital adrenal hyperplasia reported a mean time to peak concentrations for oral dexamethasone of 45 minutes (range 30 to 120 minutes).

Intravenous Route
Peak concentrations were reached approximately 60 minutes after single-dose administration of IV dexamethasone in neonates.


-Special Populations
Pediatrics
Neonates
Clearance of dexamethasone in neonates is a function of gestational age with premature neonates having a slower clearance. In a pharmacokinetic study in 9 neonates (mean gestational age (GA) 27.3 weeks [range 25 to 30 weeks]; mean postnatal age 21.8 days), mean clearance was 1.69 mL/kg/minute in neonates with a GA younger than 27 weeks compared with 7.57 mL/kg/minute in neonates with a GA older than 27 weeks. Corresponding elimination half-life values were 10.2 and 4.9 hours, respectively. The mean volume of distribution (Vd) was 1.78 L/kg, which was also correlated with GA (1.26 vs. 2.19 L/kg for neonates with GA younger than 27 weeks and older than 27 weeks, respectively). The mean volume of distribution was higher than what has been reported in adults (0.77 L/kg). Another study in 7 extremely low birth weight neonates (mean GA 25.6 weeks; mean birth weight 735 g) found similar results after the administration of single-dose IV dexamethasone. In this study, mean values for clearance, Vd, and elimination half-life were 2.4 mL/kg/minute, 1.9 L/kg, and 9.26 hours, respectively.

Infants, Children, and Adolescents
Pharmacokinetics of dexamethasone in children are similar to adults. In a pharmacokinetic study in 12 children (4 months to 16 years) who received IV dexamethasone (0.1 to 0.3 mg/kg/dose), the mean elimination half-life of dexamethasone was 4.34 hours (range 2.33 to 9.54 hours), which is similar to that reported in adults. The mean volume of distribution was 2.07 L/kg (range 0.48 to 8.99 L/kg). Another study that included adolescents and adults (14 to 28 years) reported a mean elimination half-life of 3.53 hours (range 2.18 to 4.5 hours) after dexamethasone administration.

Hepatic Impairment
Pharmacokinetic data are unavailable in pediatric patients with hepatic impairment. However, in adult patients with chronic liver disease, dexamethasone clearance is reduced and the elimination half-life is prolonged.

Renal Impairment
Pharmacokinetic data are unavailable in pediatric patients with renal impairment. However, in adult patients with renal impairment, dexamethasone clearance is increased and the elimination half-life is shorter. This is due to decreased protein binding of dexamethasone to albumin in uremic patients.