NUCORT

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

Route-Specific Administration

Oral Administration
-Administer with meals to minimize indigestion or GI irritation.
-If given once daily, administer in the morning to coincide with the body's normal cortisol secretion.
Oral Solid Formulations
Tablets
-May be crushed and mixed with a small amount of liquid just prior to administration for patients unable to swallow tablets.
-Crushed tablets are recommended over oral suspension in patients with congenital adrenal hyperplasia due to results of a study showing hydrocortisone cypionate suspension (Cortef suspension) was not bioequivalent to the tablets.

Sprinkle capsules
-Open before use. Do NOT swallow the capsules; small children may choke. Do NOT chew or crush the granules. Do NOT allow the granules to get wet; they may stick to the capsule.
-Do NOT use the sprinkle granules in nasogastric or gastric tubes; it may cause tube blockage.
-Do NOT add the granules to liquid; it may result in dose reductions and a bitter taste. Administer granules by directly pouring into the patient's mouth, pouring into a spoon and placing in the patient's mouth, or sprinkling onto a spoonful of cold or room temperature soft food (e.g., yogurt or fruit puree).
-Swallow the granules within 5 minutes of administration to avoid a bitter taste; the outer taste masking cover can dissolve.
-After administration, immediately follow with ingestion of fluids (e.g., water, milk, breast milk, or formula) to ensure all granules are swallowed.
-If the full dose is not administered (e.g., regurgitating, vomiting of granules), a repeat dose may be required to avoid adrenal insufficiency.
-Consider the potential for dosing inaccuracy when switching patients from another oral hydrocortisone formulation that has been manipulated (e.g., split or crushed tablets, compounded formulations) due to differences in hydrocortisone exposure. Closely monitor patients after switching to the sprinkle capsules to ensure the same degree of hydrocortisone exposure is provided. An increased dosage may be necessary if symptoms of adrenal insufficiency occur.

Oral Liquid Formulations
Oral Suspension
-Shake well before administering. Measure dosage with calibrated measuring device.

Extemporaneous Compounding-Oral
Hydrocortisone 2 mg/mL Oral Suspension
NOTE: ASHP recommends hydrocortisone 2 mg/mL as the compounded oral liquid standard concentration.
-Grind six 10 mg hydrocortisone tablets (60 mg total) into a fine powder in a mortar.
-Add 10 drops of suspending vehicle (Oral Mix, Medisca) to the powder and triturate to make a smooth paste.
-Continue to add 5 to 10 mL of the suspending vehicle to the powder paste, mixing well after each addition, up to a final volume of 30 mL.
-Storage: The resulting suspension is stable at 4 and 25 degrees C for at least 90 days in amber, plastic prescription bottles and oral syringes.

Hydrocortisone 2.5 mg/mL Oral Suspension
-Dissolve 0.02 g of methyl hydroxybenzoate, 0.08 g of propyl hydroxybenzoate, 0.6 g of citric acid monohydrate, and 10 mL of syrup BP in hot water to make the vehicle.
-Triturate the cooled vehicle with 1 g of sodium carboxymethylcellulose and allow the solution to stand overnight.
-Weigh out 250 mg of hydrocortisone powder or grind twelve and one-half (12.5) 20 mg hydrocortisone tablets into a fine powder in a glass mortar.
-Combine the ground tablets or the 250 mg of hydrocortisone powder with 0.5 mL of polysorbate 80 and triturate.
-Add the vehicle to the hydrocortisone powder mixture and transfer to amber plastic bottles.
-Add enough water to bring the total volume to 100 mL.
-Storage: The resulting suspension is chemically stable at 5 and 25 degrees C for 90 days; however, a 30-day expiration is suggested due to the lack of antimicrobial preservative.



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.
-Reconstitute hydrocortisone sodium phosphate or hydrocortisone sodium succinate with the diluent provided by the manufacturer (Act-O-Vial) or with 2 mL bacteriostatic water or saline for injection (100 mg plain vial).
-Storage: Store reconstituted solution at room temperature (68 to 77 degrees F [20 to 25 degrees C]). Discard unused solution after 3 days.
-Only hydrocortisone sodium phosphate or hydrocortisone sodium succinate may be administered intravenously. NEVER administer hydrocortisone acetate suspension intravenously.
Intravenous Administration
IV Push
-Use only hydrocortisone sodium phosphate or hydrocortisone sodium succinate.
-Inject each 100 mg of the reconstituted solution over at least 30 seconds. For doses of 500 mg or more, administer over at least 10 minutes.

Intermittent IV Infusion
-Add the desired dose of the reconstituted injection to 50 to 1,000 mL of 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or 5% Dextrose and 0.9% Sodium Chloride Injection.
-Diluted solutions are stable for at least 4 hours.

Intramuscular Administration
-Use only hydrocortisone, hydrocortisone sodium phosphate, or hydrocortisone sodium succinate.
-Inject deeply into a large muscle mass (e.g., anterolateral thigh). Rotate sites of injection.
-Do NOT administer hydrocortisone IM into the deltoid muscle as subcutaneous atrophy occurs with high frequency after such use.
-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.



Topical Administration
Cream/Ointment/Lotion Formulations
-Cream, lotion, or ointment: Apply sparingly as a thin film and rub gently into the cleansed affected area. Occlusive dressings may be necessary for severe conditions. However, occlusive dressings should be used very cautiously, if at all, in young pediatric patients due to increased systemic absorption.

Other Topical Formulations
-Solution or gel: Apply sparingly in a thin film and rub gently into the cleansed affected area. Occlusive dressings may be necessary for severe conditions. However, occlusive dressings should be used very cautiously, if at all, in young pediatric patients due to increased systemic absorption.
-Aerosol: Shake the container gently once or twice each time before using. Spray each 4 square inch area for about 1 to 2 seconds from a distance of about 15 cm.



Rectal Administration
-Suppository: Instruct patient or caregiver about the proper use of suppository. Unwrap the suppository prior to insertion. Moisten the suppository with water prior to insertion. If suppository is too soft because of storage in a warm place, chill in the refrigerator for 30 minutes or run cold water over it before removing the wrapper.

Prolonged systemic administration of physiologic replacement dosages of corticosteroid therapy usually does not cause adverse effects. The severity of the adverse effects associated with prolonged administration of pharmacological dosages of corticosteroids increases with duration and frequency of therapy. Short-term administration of large doses typically does not cause adverse effects, but long-term administration can lead to adrenocortical atrophy and generalized protein depletion.

Pharmacologic doses of systemic corticosteroids administered for prolonged periods can result in physiological dependence due to hypothalamic-pituitary-adrenal (HPA) suppression. Pediatric patients may absorb proportionally larger amounts of topical corticosteroids compared to adults due to a larger skin surface to body mass ratio and, therefore, may be at increased risk of systemic adverse reactions, especially if applied to a large surface area and/or if occlusive dressings are used. HPA axis suppression and increased intracranial pressure have been reported in pediatric patients receiving topical corticosteroids. Increased intracranial pressure with papilledema (i.e., pseudotumor cerebri) has also been reported with withdrawal of glucocorticoid therapy. 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 drug on alternate days may help to alleviate this adverse effect. Patients with HPA axis 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. Gradual discontinuation of prolonged oral corticosteroid therapy is recommended, since HPA suppression can last for up to 12 months after 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 after sudden discontinuance of corticosteroid therapy. This syndrome includes symptoms such as pyrexia, arthralgia, myalgia, and malaise. These effects are believed to be due to the sudden change in corticosteroid concentration rather than to low corticosteroid concentrations.

Prolonged systemic hydrocortisone therapy can adversely affect the endocrine system, resulting in hypercorticism (Cushing's syndrome including fat abnormalities such as buffalo hump and moon face), hirsutism, acne vulgaris, menstrual irregularity, or a decrease in carbohydrate and glucose tolerance. In some patients, systemic absorption of rectal or topical corticosteroids can produce these effects, but they are relatively uncommon with limited duration of use. Percutaneous absorption of hydrocortisone is dependent on many factors including the vehicle, the integrity of the epidermal barrier, duration of use, and use of an occlusive dressing. Children may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios.

Corticosteroids, such as hydrocortisone, are responsible for protein metabolism, and prolonged therapy can result in various musculoskeletal manifestations, including: myopathy (myalgia, muscle wasting, muscle weakness), bone matrix atrophy (osteopenia, osteoporosis), bone fractures such as vertebral compression fractures or fractures of long bones, and avascular necrosis of femoral or humoral heads. Because of retardation of bone growth, pediatric patients receiving prolonged corticosteroid therapy may have growth inhibition. In a population based study, the risk of 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 or greater of prednisone. Because bone development is critical in pediatric patients, monitoring is warranted in patients receiving high-doses or chronic corticosteroid treatment. Glucocorticoids interact with calcium metabolism at many sites, including decreasing the synthesis by osteoblasts of the principle 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 the most important. Glucocorticoids do not modify vitamin D metabolism. Intra-articular injections of corticosteroids can cause Charcot-like arthropathy and postinjection flare. Atrophy at the site of injection has been reported after administration of soluble glucocorticoids. Tendon rupture has also been reported.

Spontaneous intestinal perforation (GI perforation) has occurred in premature neonates receiving hydrocortisone for the prevention of chronic lung disease. Enrollment in 2 prospective, placebo-controlled trials (n = 51 to 360) was stopped early due to a significantly higher incidence of intestinal perforation in premature neonates receiving hydrocortisone (9% to 16%) compared to patients receiving placebo (0 to 2%); the majority of patients with intestinal perforation also received indomethacin or ibuprofen. Gastroenteritis (50%), vomiting (39%), and diarrhea (11%) were reported in pediatric patients receiving oral granules for up to 29 months during an open-label trial (n = 18). Dental caries (11%) and genitourinary operation (11%) were also reported. Other adverse gastrointestinal (GI) reactions associated with systemic corticosteroid administration include abdominal distension, hepatomegaly, appetite stimulation with weight gain, pancreatitis, esophageal ulceration, and nausea. Peptic ulcers with possible subsequent GI bleeding and GI perforation have been reported. Elevated hepatic enzymes, usually reversible upon discontinuation of therapy, have also occurred with systemic corticosteroids. Bladder and bowel dysfunction have been reported after intrathecal administration. Although it was once believed that corticosteroids contributed to the development of peptic ulcer disease, in a published 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.

Topical preparations of hydrocortisone may be associated with local adverse reactions and skin irritation including acneiform rash, allergic contact dermatitis, erythema, folliculitis, hypertrichosis, miliaria, perioral dermatitis, pruritus, skin atrophy, skin hypopigmentation, telangiectasia, and xerosis. Various adverse dermatologic reactions reported during systemic corticosteroid therapy include acne, alopecia, xerosis, erythema, skin hypopigmentation, skin hyperpigmentation, rash, skin atrophy, suppression of reactions to skin tests, diaphoresis, facial erythema, petechiae, ecchymosis, and easy bruising. Hypersensitivity reactions may manifest as allergic dermatitis, urticaria, angioedema, and/or anaphylactoid reactions. Parenteral corticosteroid therapy has also produced scarring and other types of injection site reaction (e.g., induration, delayed pain or soreness, subcutaneous and cutaneous atrophy, and sterile abscesses). Avoid injection of hydrocortisone into the deltoid muscle due to high incidence of subcutaneous atrophy. Paresthesias (burning or tingling) in the perineal area may occur after IV injection of corticosteroids.

In general, excessive use of systemic or topical corticosteroids can lead to impaired wound healing. Do not apply hydrocortisone directly on or near healing wounds. Use of topical corticosteroids in patients with markedly impaired circulation may lead to skin ulcer development.

Fever (56%), viral upper respiratory tract infection (44%), viral infection (33%), otitis media viral (17%), increased body temperature (11%), bronchitis (11%), pharyngitis (11%), respiratory tract infection (11%), and rhinitis (11%) were reported in pediatric patients receiving oral granules for up to 29 months during an open-label trial (n = 18). Corticosteroid therapy (systemic or topical) can mask the symptoms of infection and may result in secondary systemic or localized infections. Avoid systemic use of corticosteroids, such as hydrocortisone, in patients with an active infection unless adequately controlled by anti-infective agents. 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 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 also may 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 corticosteroids should be advised to avoid exposure to measles or varicella (chickenpox) and, if exposed to these diseases, to seek medical advice immediately. Additionally, health care providers should monitor steroid recipients for signs of an opportunistic fungal infection as cases of candidiasis have been reported with the use of corticosteroids. The development of Kaposi's sarcoma has been associated with prolonged administration of corticosteroids.

Systemic administration of corticosteroids, such as hydrocortisone, can result in edema, fluid retention, sodium retention, electrolyte disturbances (hypokalemia, hypokalemic metabolic alkalosis, hypernatremia, hypocalcemia), and hypertension. Congestive heart failure can occur in susceptible patients. In a review of 93 studies of corticosteroid use, hypertension was found to develop 4 times as often in steroid recipients compared to control groups. Other cardiovascular adverse reactions reported with systemic corticosteroids include bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, hypertrophic cardiomyopathy (premature neonates), myocardial rupture after recent myocardial infarction, pulmonary edema, syncope, sinus tachycardia, thromboembolism, phlebitis, and vasculitis.

Conjunctivitis was reported in 28% of pediatric patients receiving hydrocortisone oral granules for up to 29 months during an open-label trial (n = 18). Ocular effects, such as corneal perforation, exophthalmos, posterior subcapsular cataracts, retinopathy, central serous chorioretinopathy (CSCR), or ocular hypertension, can result from prolonged use of glucocorticoids and could result in glaucoma, or ocular nerve damage including optic neuritis, particularly with systemic use. Temporary or permanent visual impairment, including blurred vision and blindness, has been reported with corticosteroid administration by several routes of administration. If injectable systemic steroid therapy is continued for more than 6 weeks, monitor intraocular pressure. Also, evaluate any patient who develops changes in vision during corticosteroid therapy for ocular hypertension. Ocular hypertension and cataracts leading to visual impairment have also occurred after prolonged topical application of corticosteroids to the skin around the eye. Case reports describe visual impairment patients using topical corticosteroids for eczema of the face; although, use of hydrocortisone has been reported to be safer for short-term use around eye area. The visual impairment was secondary to the onset of ocular hypertension. Such adverse effects, if they occur, could lead to blindness. Cataracts have also been reported with topical corticosteroids, usually with large doses or therapy more than 6 months. The mechanism of corticosteroid-induced cataract formation is uncertain but may involve disruption of sodium-potassium pumps in the lens epithelium leading to accumulation of water in lens fibers and agglutination of lens proteins. Hydrocortisone can reduce host resistance to infection. Secondary fungal and viral infections of the eye (ocular infection) can be masked or exacerbated by corticosteroid therapy. Investigate the possibility of fungal infection if patients have persistent corneal ulceration.

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 diabetes mellitus may also occur. Rectal and topical corticosteroids have also been reported to cause hyperglycemia and glucosuria in some patients, but these are relatively uncommon when used for limited durations. Percutaneous absorption of hydrocortisone is dependent on many factors including the vehicle, duration of use, the integrity of the epidermal barrier, and use of an occlusive dressing. Children may be more susceptible to systemic absorption with topical use due to their larger skin surface to body mass ratios.

Adverse neurologic effects have been reported during prolonged corticosteroid therapy, such as hydrocortisone, including headache, insomnia, vertigo, restlessness, ischemic peripheral neuropathy, neuritis, seizures, and EEG changes. Arachnoiditis, meningitis, paresis, paraplegia, and sensory disturbances have been reported after intrathecal administration. Mental status changes including depression, anxiety, euphoria, personality changes, mood swings, and psychosis also have been reported. Emotional lability and psychotic problems can be exacerbated by corticosteroid therapy.

Tolerance (tachyphylaxis) may occur with the prolonged use of topical corticosteroids. Tolerance is usually described as a decreased acute vasoconstrictive response to the agent after a period of days to weeks. This may explain the dramatic responses noted initially by patients early in topical corticosteroid treatment and an apparent diminished response with time. Tolerance is reversible and may be attenuated by interrupted or cyclic schedules of application (e.g., hydrocortisone is given for 2 to 3 weeks, followed by a 1-week intermission). It is unclear if tolerance or tachyphylaxis actually occurs or is due to patient adherence to topical corticosteroid regimen.

Tumor lysis syndrome (TLS) has been reported during postmarketing surveillance of systemic corticosteroids alone or in combination with other chemotherapeutic agents in patients with malignancies, including hematological malignancies and solid tumors. Patients at high risk of TLS, such as patients with tumors that have a high proliferative rate, high tumor burden and high sensitivity to cytotoxic agents, should be monitored closely and appropriate precautions should be taken.

Systemic corticosteroid therapy, such as hydrocortisone, can mask the symptoms of infection. Although the FDA-approved product labeling states that systemic hydrocortisone is 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 use of systemic hydrocortisone 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. Avoid use of systemic corticosteroids in patients with cerebral malaria. 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. Further, chemoprophylaxis is advised if prolonged corticosteroid therapy is needed. Advise patients receiving immunosuppressive doses of systemic corticosteroids to avoid exposure to viral infections (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 chicken pox, prophylaxis with varicella zoster immune globulin may be indicated. Pediatric patients dependent on systemic corticosteroids should undergo anti-varicella-zoster virus antibody testing. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin may be indicated. Use corticosteroids with caution in patients with ocular herpes infection due to the risk of corneal perforation; avoid the use of corticosteroids in active ocular herpes infection. Initiate or continue therapy with topical corticosteroids to areas of infection, including tuberculosis of the skin, dermatologic fungal infection, and cutaneous or systemic viral infection (e.g., herpes infection, measles, varicella), only if the appropriate anti-infective treatment is instituted. If the infection does not respond to the antimicrobial therapy, discontinue the concurrent use of the topical corticosteroid until the infection is controlled.

Systemic corticosteroids, such as hydrocortisone, can aggravate Cushing's syndrome; avoid use in patients with Cushing's syndrome. Prolonged administration of pharmacological doses of systemic corticosteroids or topical preparations (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 systemic and topical corticosteroids in pediatric patients. Adrenocortical insufficiency, adrenal crisis, and death may occur after abrupt discontinuation of prolonged systemic therapy. Adrenal crisis may also be induced by stressful events such as infections or surgery; patients may require higher doses of corticosteroids. Symptoms of adrenocortical insufficiency include poor feeding, fatigue, low muscle tone, joint pain, nausea, vomiting, hypoglycemia, low blood pressure, and electrolyte disturbances. Switch patients unable to take oral medications (i.e., severely ill or vomiting) to parenteral corticosteroid formulations until recovered. Once oral medications are tolerated, gradually reduce the steroid dosage during the acute event. A withdrawal syndrome unrelated to adrenocortical insufficiency may occur after 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 (more than 2 weeks) gradually. HPA axis suppression can last for up to 12 months after cessation of systemic therapy. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the topical corticosteroid. HPA axis-suppressed patients may need supplemental corticosteroid treatment during periods of physiologic stress, such as surgery, acute blood loss, or infection, 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 hydrocortisone in situations of increased stress. Conditions that increase systemic absorption of topical corticosteroids include use over large surface areas, prolonged use, use in areas where the epidermal barrier is disrupted (i.e., skin abrasion), and the use of an occlusive dressing. Pediatric patients may absorb proportionally larger amounts of topical corticosteroids compared to adults due to a larger skin surface to body mass ratio and, therefore, may be at increased risk of systemic adverse reactions. Evaluate patients receiving large doses of hydrocortisone applied to a large surface area periodically for evidence of HPA axis suppression and/or manifestations of Cushing's syndrome. If these effects are noted, attempt withdrawal of the drug, a reduction in the frequency of application, or substitution of a less potent corticosteroid.

Patients receiving high-dose systemic corticosteroid therapy, such as hydrocortisone, for any period of time are at risk to develop immunosuppression; patients receiving moderate doses of systemic corticosteroids for short periods or low doses for prolonged periods may also be at risk. When given in combination with other immunosuppressive agents, there is a risk of over-immunosuppression.

Do not use topical corticosteroids to treat acne vulgaris, acne rosacea, or perioral dermatitis as they may exacerbate these conditions. Topical corticosteroids may delay the healing of non-infected wounds, such as venous stasis ulcers. Use topical hydrocortisone preparations with caution in patients with markedly impaired circulation or peripheral vascular disease; skin ulceration has been reported in these patients following topical corticosteroid use.

Corticosteroid therapy, such as hydrocortisone, has been associated with left ventricular free-wall rupture in patients with recent myocardial infarction; use cautiously in these patients.

Systemic corticosteroids, such as hydrocortisone, can cause edema and weight gain. Use with caution in patients with congestive heart failure, hypertension, or renal disease as this can cause an exacerbation of their condition.

Chronic corticosteroid therapy, such as hydrocortisone, in pediatric patients may cause growth inhibition due to hypothalamic-pituitary-adrenal axis suppression and inhibition of bone growth. Because bone development is critical in pediatric patients, monitoring is warranted in patients receiving high-dose or chronic corticosteroid treatment. Prolonged systemic corticosteroid therapy can lead to osteoporosis, vertebral compression fractures, aseptic necrosis of femoral and humoral heads, and pathologic fractures of long bones secondary to decreased bone formation, increased bone resorption, and protein catabolism. A high-protein diet may alleviate or prevent the adverse effects associated with protein catabolism.

Systemic corticosteroids, such as hydrocortisone, 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 in patients with diabetes mellitus, changes in insulin, oral antidiabetic agent dosage, and/or diet may be required. Use topical corticosteroids with caution in patients with diabetes mellitus. Exacerbation of diabetes may occur with systemic absorption of the topical corticosteroid. Use of topical corticosteroids may further delay healing of skin ulcers in diabetic patients.

Oral corticosteroids, such as hydrocortisone, can cause gastrointestinal (GI) irritation. Use systemic corticosteroids with caution in patients with active or latent peptic ulcer disease, GI disease, diverticulitis, nonspecific ulcerative colitis, or intestinal anastomosis (because of the possibility of perforation). While used for the short-term treatment of acute exacerbations of chronic inflammatory bowel disease such as ulcerative colitis and Crohn's disease, avoid use of corticosteroids in patients where there is a possibility of impending GI perforation, abscess, or pyogenic infection. Some patients may require long-term corticosteroid therapy to suppress disease activity, but generally this practice is not recommended.

Use systemic corticosteroids, such as hydrocortisone, with extreme caution in patients with psychosis, emotional instability, and seizure disorder because the drugs can exacerbate these conditions. Do not use high doses of systemic corticosteroids 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.

Use systemic corticosteroids, such as hydrocortisone, with caution in patients with myasthenia gravis who are being treated with anticholinesterase agents. A generalized acute myopathy has been reported with the use of high-dose corticosteroids in patients with disorders of neuromuscular transmission, such as myasthenia gravis. Ocular and respiratory muscles may be involved and may result in quadriparesis; elevations in creatine kinase may also occur. Recovery from the myopathy after discontinuation of corticosteroids may take weeks to years.

Systemic corticosteroids rarely may increase blood coagulability, causing intravascular thrombosis, thrombophlebitis, and thromboembolism. Therefore, use systemic corticosteroids, such as hydrocortisone, with caution in patients with preexisting coagulopathy (e.g., hemophilia) or thromboembolic disease. Hydrocortisone use via IM administration for immune thrombocytopenia/idiopathic thrombocytopenic purpura (ITP) is contraindicated.

Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of systemic corticosteroids, such as hydrocortisone. Killed or inactivated vaccines may be administered to patients receiving immunosuppressive doses of corticosteroids; however, the response to vaccination may be diminished. 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 concern about the safety of immunization with live-virus vaccines. Corticosteroid therapy usually does not contraindicate vaccination with live-virus vaccines when such therapy is of short-term (< 2 weeks); low to moderate dose; long-term alternate day treatment with short-acting preparations; maintenance physiologic doses (replacement therapy); or administration topically (skin or eye), by aerosol, or by intra-articular, bursal or tendon injection. 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 weeks. Consider patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy unimmunized and revaccinate at least 3 months after discontinuation of therapy. In patients who have received high-dose, systemic corticosteroids for >= 2 weeks, it is recommended to wait at least 3 months after discontinuation of therapy before administering a live-virus vaccine.

Some commercially available formulations of hydrocortisone injection may contain sulfites. Sulfites may cause allergic reactions in some people. Use these formulations with caution in patients with known sulfite hypersensitivity. Patients with asthma are more likely to experience this sensitivity reaction than non-asthmatic patients.

Hypertrophic cardiomyopathy may develop after parenteral administration of hydrocortisone to premature neonates, therefore appropriate diagnostic evaluation and monitoring of cardiac function and structure should be performed. Several commercial formulations of hydrocortisone injection are contraindicated in premature neonates because these products contain benzyl alcohol. Use these formulations of hydrocortisone with caution in 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 dosages 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.

Hydrocortisone is contraindicated in patients with hypersensitivity to the drug or any of its components. True corticosteroid hypersensitivity reactions are rare. While a hypersensitivity reaction could be to a specific salt of the corticosteroid (i.e., hydrocortisone sodium succinate), administer any form of hydrocortisone with extreme caution in patients who have demonstrated a prior hypersensitivity reaction to hydrocortisone. It is possible, though also rare, that such patients will display cross-hypersensitivity to other corticosteroids; there have been reports that a cross-sensitivity between hydrocortisone and methylprednisolone may exist. 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. Carefully monitor such patients during and after the administration of any corticosteroid.

Use corticosteroids with caution in patients with glaucoma or any other visual disturbance. Corticosteroids are well known to cause cataracts and can exacerbate glaucoma during long-term administration. Assess patients receiving chronic corticosteroid therapy periodically for cataract formation. There is also an increase in the propensity for secondary fungal, viral, or bacterial ocular infection. Avoid ophthalmic administration of topical hydrocortisone preparations. Visual impairment, ocular hypertension, and worsened cataracts have been reported with ocular exposure to other high potency topical corticosteroids. Preexisting glaucoma may be aggravated if hydrocortisone is applied in the periorbital area. Consider an ophthalmologist referral for patients who present with symptoms of blurred vision or other visual disturbances.

Injection of hydrocortisone may result in dermal and/or subdermal changes forming depressions in the skin at the injection site. In order to minimize the incidence of subdermal and dermal atrophy, care must be exercised not to exceed recommended doses in injections. Injection into the deltoid muscle should be avoided because of a high incidence of subcutaneous atrophy. Use topical corticosteroids, such as hydrocortisone, for brief periods, or under close medical supervision in patients with evidence of pre-existing skin atrophy. Prolonged use of a topical corticosteroid, and the application of the steroid to thin areas of skin appear to increase the risk for atrophy. Use of lower potency topical corticosteroids may be necessary in some patients.

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

Epidural administration of corticosteroids such as hydrocortisone 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 epidural corticosteroid administration, with events occurring within minutes to 48 hours after administration. Some cases of neurologic events were confirmed using 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. In addition, intrathecal administration of hydrocortisone sodium succinate injection is contraindicated. Severe medical events, including arachnoiditis, meningitis, paraparesis, paraplegia, and sensory disturbances, have been reported after intrathecal administration.

Use hydrocortisone with caution in patients with hypothyroidism or hyperthyroidism. The metabolic clearance of corticosteroids is decreased in patients with hypothyroidism and increased in patients with hyperthyroidism. Doses of hydrocortisone may need to be adjusted in patients with changes in thyroid status.

The metabolic clearance of corticosteroids, such as hydrocortisone, is decreased in patients with hepatic disease, such as cirrhosis. Use with caution in patients with hepatic disease.

Use hydrocortisone with caution in patients with diagnosed or suspected pheochromocytoma. Pheochromocytoma crisis, which can be fatal, has been reported after administration of systemic corticosteroids. Consider the risk of pheochromocytoma crisis prior to administering corticosteroids in any patients with suspected pheochromocytoma.

Tumor lysis syndrome (TLS) has been reported in patients with neoplastic disease, including hematological malignancies and solid tumors, following the use of systemic corticosteroids alone or in combination with other chemotherapeutic agents. Patients at high risk of TLS, such as patients with tumors that have a high proliferative rate, high tumor burden and high sensitivity to cytotoxic agents, should be monitored closely and appropriate precautions should be taken.

Description: Hydrocortisone is a steroid hormone secreted by the adrenal cortex. Commercially, it is available as the unchanged hormone and as various salts. Hydrocortisone is the preferred glucocorticoid for replacement therapy in pediatric patients with acute and chronic adrenal insufficiency due to its mineralocorticoid activity. In pediatric patients with chronic adrenal insufficiency, hydrocortisone is preferred over more potent corticosteroids, such as dexamethasone, due to a lower risk of adverse reactions, especially growth suppression. Some patients with adrenal insufficiency may require concomitant administration of a more potent mineralocorticoid, such as fludrocortisone. Systemic hydrocortisone is also used off-label in pediatric patients for refractory hypotension due to shock, prevention of chronic lung disease (neonates), and refractory hypoglycemia (neonates). Pediatric guidelines state hydrocortisone may or may not be used for fluid- and vasopressor-refractory septic shock. Low potency topical corticosteroids, such as hydrocortisone base and acetate formulations, are the safest for chronic use and may be used on the face or intertriginous areas, with occlusion, and in infants and young children. Systemic corticosteroids may be added to other long-term maintenance medications in the management of uncontrolled severe persistent asthma and short courses may be used in the management of asthma exacerbation; however, systemic hydrocortisone is rarely used for asthma and prednisone, prednisolone or methylprednisolone are mostly used instead. Systemic formulations of hydrocortisone are FDA-approved in pediatric patients (age not specified); other formulations are approved for use in patients of varying ages depending on the specific product.

General dosing information for systemic therapy:
-Dosage requirements are variable. Individualize dosage based on the condition being treated and the response of the patient.
-Closer monitoring may be required in pediatric patients receiving hydrocortisone suspension. Crushed tablets are recommended over oral suspension in pediatric patients with CAH due to results of a study showing hydrocortisone cypionate suspension (Cortef) was not bioequivalent to the tablets.
-Gradual withdrawal of hydrocortisone 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 10 mg/m2/day of hydrocortisone) and discontinue after assessment of adrenal function has demonstrated recovery.

For the treatment of primary adrenocortical insufficiency (e.g., Addison's Disease, congenital adrenal hyperplasia, adrenogenital syndrome) or secondary adrenocortical insufficiency:
Oral dosage (tablet):
Neonates: 8 to 20 mg/m2/day PO given in 3 divided doses initially; individualize dosage to minimize symptoms of adrenal insufficiency while avoiding growth retardation and Cushingoid symptoms that occur with overdosage. A usual dose of 2.5 to 5 mg/day PO 3 times daily has been recommended by the American Academy of Pediatrics (AAP). Doses more than 20 mg/m2/day PO have been associated with loss of height and shorter adult height. Patients with primary adrenal insufficiency may require higher initial doses than those with secondary adrenal insufficiency. Hydrocortisone cypionate suspension (Cortef) and hydrocortisone tablets are not bioequivalent; therefore, the suspension is not recommended for the treatment of patients with congenital adrenal hyperplasia (CAH). Neonates and infants with classic CAH also require treatment with fludrocortisone (0.05 to 0.3 mg/day PO given in 1 to 2 divided doses) and sodium chloride supplementation (1 to 2 g/day or 17 to 34 mEq/day PO divided and given with several feedings).
Infants: 8 to 20 mg/m2/day PO given in 3 divided doses initially; individualize dosage to minimize symptoms of adrenal insufficiency while avoiding growth retardation and Cushingoid symptoms that occur with overdosage. A usual dose of 2.5 to 5 mg/day PO 3 times daily has been recommended by the American Academy of Pediatrics (AAP). Doses more than 20 mg/m2/day PO have been associated with loss of height and shorter adult height. Patients with primary adrenal insufficiency may require higher initial doses than those with secondary adrenal insufficiency. Hydrocortisone cypionate suspension (Cortef) and hydrocortisone tablets are not bioequivalent; therefore, the suspension is not recommended for the treatment of patients with congenital adrenal hyperplasia (CAH). Neonates and infants with classic CAH also require treatment with fludrocortisone (0.05 to 0.3 mg/day PO given in 1 to 2 divided doses) and sodium chloride supplementation (1 to 2 g/day or 17 to 34 mEq/day PO divided and given with several feedings).
Children and Adolescents: 8 to 20 mg/m2/day PO given in 3 divided doses initially; individualize dosage to minimize symptoms of adrenal insufficiency while avoiding growth retardation and Cushingoid symptoms that occur with overdosage. A usual dose of 5 to 10 mg/day PO 3 times daily has been recommended by the American Academy of Pediatrics. Doses more than 17 mg/m2/day in adolescents have been associated with loss of height and shorter adult height. Patients with primary adrenal insufficiency may require higher initial doses than those with secondary adrenal insufficiency. Hydrocortisone cypionate suspension (Cortef) and hydrocortisone tablets are not bioequivalent; therefore, the suspension is not recommended for the treatment of patients with congenital adrenal hyperplasia (CAH). Patients with classic CAH also require treatment with fludrocortisone (0.05 to 0.3 mg/day PO given in 1 to 2 divided doses).
Oral dosage (granules):
Neonates: 8 to 10 mg/m2/day PO given in 3 divided doses initially. Higher doses may be needed based on patient's age and symptoms of the disease. Lower starting doses may be sufficient in patients with residual but decreased endogenous cortisol production. Round the dose to the nearest 0.5 or 1 mg. Individualize doses to minimize symptoms of adrenal insufficiency while avoiding growth retardation and Cushingoid symptoms that occur with overdosage. Patients may need higher doses during acute febrile illness, gastroenteritis, surgery, or major trauma. Use the same total daily dose when switching patients from oral hydrocortisone therapy to the oral granules. If symptoms of adrenal insufficiency occur after switching, increase the total daily dosage of the oral granules.
Infants: 8 to 10 mg/m2/day PO given in 3 divided doses initially. Higher doses may be needed based on patient's age and symptoms of the disease. Lower starting doses may be sufficient in patients with residual but decreased endogenous cortisol production. Round the dose to the nearest 0.5 or 1 mg. Individualize doses to minimize symptoms of adrenal insufficiency while avoiding growth retardation and Cushingoid symptoms that occur with overdosage. Patients may need higher doses during acute febrile illness, gastroenteritis, surgery, or major trauma. Use the same total daily dose when switching patients from oral hydrocortisone therapy to the oral granules. If symptoms of adrenal insufficiency occur after switching, increase the total daily dosage of the oral granules.
Children and Adolescents: 8 to 10 mg/m2/day PO given in 3 divided doses initially; older pediatric patients may have their daily dose divided by 2 and administered twice daily. Higher doses may be needed based on patient's age and symptoms of the disease. Lower starting doses may be sufficient in patients with residual but decreased endogenous cortisol production. Round the dose to the nearest 0.5 or 1 mg. Individualize doses to minimize symptoms of adrenal insufficiency while avoiding growth retardation and Cushingoid symptoms that occur with overdosage. Patients may need higher doses during acute febrile illness, gastroenteritis, surgery, or major trauma. Use the same total daily dose when switching patients from oral hydrocortisone therapy to the oral granules. If symptoms of adrenal insufficiency occur after switching, increase the total daily dosage of the oral granules.
-for normal physiologic replacement:
Oral dosage:
Infants and Children: 8 to 10 mg/m2/day PO in 3 divided doses; initial doses up to 12 mg/m2/day have also been recommended. Administer the highest doses in the morning and at lunchtime with a lower dose in the evening to replicate normal physiological cortisol secretion.
-for adrenal crisis prophylaxis in patients with known or suspected adrenal insufficiency with other acute stressors (e.g., febrile illness more than 38.5 degrees Celsius, gastroenteritis with dehydration, major trauma):
Intramuscular or Intravenous Dosage:
Neonates: 50 mg/m2 IM will provide 6 to 8 hours of coverage. If the patient's condition does not improve or worsens during this time, initiate IV stress dosing (3 to 4 times the daily maintenance dose divided every 6 hours). Alternatively, an initial dose of 25 mg IM has been recommended for patients with congenital adrenal hyperplasia.
Infants: 50 mg/m2 IM will provide 6 to 8 hours of coverage. If the patient's condition does not improve or worsens during this time, initiate IV stress dosing (3 to 4 times the daily maintenance dose divided every 6 hours). Alternatively, an initial dose of 25 mg IM has been recommended for patients with congenital adrenal hyperplasia.
Children 1 to 5 years: 50 mg/m2 IM will provide 6 to 8 hours of coverage. If the patient's condition does not improve or worsens during this time, initiate IV stress dosing (3 to 4 times the daily maintenance dose divided every 6 hours). Alternatively, an initial dose of 50 mg IM has been recommended for patients with congenital adrenal hyperplasia.
Children and Adolescents 6 to 17 years: 50 mg/m2 IM will provide 6 to 8 hours of coverage. If the patient's condition does not improve or worsens during this time, initiate IV stress dosing (3 to 4 times the daily maintenance dose divided every 6 hours). Alternatively, an initial dose of 100 mg IM has been recommended for patients with congenital adrenal hyperplasia.
Oral dosage:
Neonates: 30 to 50 mg/m2/day PO given in 3 to 4 divided doses (approximately triple the daily maintenance dose) is commonly recommended. Varying recommendations of increases in the daily maintenance dose anywhere from 2 to 10 times have been made depending on the level of stress and the patient's individual needs. Hydrocortisone cypionate suspension (Cortef) and hydrocortisone tablets are not bioequivalent; therefore, the suspension is not recommended for the treatment of patients with congenital adrenal hyperplasia (CAH).
Infants, Children, and Adolescents: 30 to 50 mg/m2/day PO given in 3 to 4 divided doses (approximately triple the daily maintenance dose) is commonly recommended. Varying recommendations of increases in the daily maintenance dose anywhere from 2 to 10 times have been made depending on the level of stress and the patient's individual needs. Hydrocortisone cypionate suspension (Cortef) and hydrocortisone tablets are not bioequivalent; therefore, the suspension is not recommended for the treatment of patients with congenital adrenal hyperplasia (CAH).
Rectal dosage*:
Infants, Children, and Adolescents: 100 mg/m2/dose PR every 8 hours has been recommended as an alternative to parenteral administration in patients who cannot tolerate oral administration due to illness. Due to large interindividual differences in bioavailability, higher doses (150 to 200 mg/m2/dose PR) may be required in patients who do not show an adequate response (serum cortisol concentration more than 1,000 nmol/L 3 hours after administration). It is recommended that the patient's response to rectal hydrocortisone be tested prior to use during illness. In a study of patients with adrenal insufficiency (n = 57, age 1 month to 17 years), 43 patients responded adequately to a dose of 100 mg/m2 rectally. Risk factors for failed response included younger age and obesity. Suppositories used in this study were compounded in a Witepsol W45 base.
-for adrenal crisis prophylaxis in patients with known or suspected adrenal insufficiency undergoing surgery accompanied by general anesthesia:
Intravenous or Intramuscular dosage:
Neonates: 50 mg/m2 IV 30 to 60 minutes prior to induction of anesthesia with repeat doses of 50 mg/m2/dose IV every 6 hours or as a continuous infusion until the patient has recovered. For patients with congenital adrenal hyperplasia (CAH), 2 mg/kg/dose IV at induction of anesthesia with repeat doses every 4 hours or as a continuous IV infusion for prolonged procedures or recovery times has also been recommended. Alternatively, an initial stress dose of 25 mg IM followed by IV doses equivalent to 3 to 4 times the daily maintenance dose divided every 6 hours has been recommended.
Infants: 50 mg/m2 IV 30 to 60 minutes prior to induction of anesthesia with repeat doses of 50 mg/m2/dose IV every 6 hours or as a continuous infusion until the patient has recovered. For patients with congenital adrenal hyperplasia (CAH), 2 mg/kg/dose IV at induction of anesthesia with repeat doses every 4 hours or as a continuous IV infusion for prolonged procedures or recovery times has also been recommended. Alternatively, an initial stress dose of 25 mg IM followed by IV doses equivalent to 3 to 4 times the daily maintenance dose divided every 6 hours has been recommended.
Children 1 to 5 years: 50 mg/m2 IV 30 to 60 minutes prior to induction of anesthesia with repeat doses of 50 mg/m2/dose IV every 6 hours or as a continuous infusion until the patient has recovered. For patients with congenital adrenal hyperplasia (CAH), 2 mg/kg/dose IV at induction of anesthesia with repeat doses every 4 hours or as a continuous IV infusion for prolonged procedures or recovery times has also been recommended. Alternatively, an initial stress dose of 50 mg IM followed by IV doses equivalent to 3 to 4 times the daily maintenance dose divided every 6 hours has been recommended.
Children and Adolescents 6 to 17 years: 50 mg/m2 IV 30 to 60 minutes prior to induction of anesthesia with repeat doses of 50 mg/m2/dose IV every 6 hours or as a continuous infusion until the patient has recovered. For patients with congenital adrenal hyperplasia (CAH), 2 mg/kg/dose IV at induction of anesthesia with repeat doses every 4 hours or as a continuous IV infusion for prolonged procedures or recovery times has also been recommended. Alternatively, an initial stress dose of 100 mg IM followed by IV doses equivalent to 3 to 4 times the daily maintenance dose divided every 6 hours has been recommended.
-for the treatment of acute adrenocortical insufficiency:
Intravenous or Intramuscular dosage:
Neonates: 2 mg/kg/dose [weight-based], 10 to 25 mg/dose [flat dose], or 50 to 100 mg/m2/dose [BSA-based] IV or IM load, followed by 10 to 25 mg/day [flat dose] or 50 to 100 mg/m2/day [BSA-based] IV or IM in divided doses at 6-hour intervals for 24 hours.
Infants: 2 mg/kg/dose [weight-based], 10 to 25 mg/dose [flat dose], or 50 to 100 mg/m2/dose [BSA-based] IV or IM load, followed by 10 to 25 mg/day [flat dose] or 50 to 100 mg/m2/day [BSA-based] IV or IM in divided doses at 6-hour intervals for 24 hours.
Children 1 to 5 years: 2 mg/kg/dose (Max: 100 mg) [weight-based], 25 to 50 mg/dose [flat dose], or 50 to 100 mg/m2/dose [BSA-based] IV or IM load, followed by 25 to 50 mg/day [flat dose] or 50 to 100 mg/m2/day [BSA-based] IV or IM in divided doses at 6-hour intervals for 24 hours.
Children and Adolescents 6 to 17 years: 2 mg/kg/dose (Max: 100 mg) [weight-based], 50 to 100 mg/dose [flat dose], or 50 to 100 mg/m2/dose [BSA-based] IV or IM load, followed by 50 to 100 mg/day [flat dose] or 50 to 100 mg/m2/day [BSA-based] IV or IM in divided doses at 6-hour intervals for 24 hours.

For the treatment of septic shock* and/or hypotension* in patients whose blood pressure is poorly responsive to adequate fluid resuscitation and vasopressor therapy:
Intravenous dosage (hydrocortisone sodium succinate):
Neonates: 1 mg/kg/dose IV every 8 to 12 hours for 1 to 5 days has been studied (combined n from 3 studies = 89, gestational age 23 to 40 weeks). An initial loading dose of 2 mg/kg IV was used in 1 retrospective study and another prospective, observational study used a higher maintenance dose of 3 to 6 mg/kg/day IV divided 2 to 4 times daily in a small number of patients (n = 5) with severe capillary leak syndrome and/or previous steroid treatment. Guidelines state hydrocortisone may or may not be used for fluid- and vasopressor-refractory septic shock.
Infants and Children 1 month to 2 years: 2 mg/kg [weight-based], 25 mg [flat-dose], or 100 mg/m2 [BSA-based] IV bolus, followed by 1 to 2 mg/kg/day [weight-based] or 50 to 100 mg/m2/day [BSA-based] IV in divided doses at 6-hour intervals or as a continuous IV infusion. Infusions up to 50 mg/kg/day may be required to reverse shock short-term; however, this recommendation is based on very limited data that did not demonstrate improvement in mortality. Guidelines state hydrocortisone may or may not be used for fluid- and vasopressor-refractory septic shock.
Children 3 to 12 years: 2 mg/kg (Max: 100 mg) [weight-based], 50 mg [flat-dose], or 100 mg/m2 [BSA-based] IV bolus, followed by 1 to 2 mg/kg/day [weight-based] or 50 to 100 mg/m2/day [BSA-based] IV in divided doses at 6-hour intervals or as a continuous IV infusion. Infusions up to 50 mg/kg/day may be required to reverse shock short-term; however, this recommendation is based on very limited data that did not demonstrate improvement in mortality. Guidelines state hydrocortisone may or may not be used for fluid- and vasopressor-refractory septic shock.
Adolescents: 2 mg/kg (Max: 100 mg) [weight-based], 100 mg [flat-dose], or 100 mg/m2 [BSA-based] IV bolus, followed by 1 to 2 mg/kg/day [weight-based] or 50 to 100 mg/m2/day [BSA-based] IV in divided doses at 6-hour intervals or as a continuous IV infusion. Infusions up to 50 mg/kg/day may be required to reverse shock short-term; however, this recommendation is based on very limited data that did not demonstrate improvement in mortality. Guidelines state hydrocortisone may or may not be used for fluid- and vasopressor-refractory septic shock.

For the treatment of acute episodes or exacerbation of inflammatory bowel disease (Crohn's disease or ulcerative colitis):
Intramuscular or Intravenous dosage:
Children and Adolescents: 0.56 to 8 mg/kg/day or 20 to 240 mg/m2/day IM or IV given in 3 to 4 divided dose 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.
Oral dosage:
Children and Adolescents: A general dose range of 0.56 to 8 mg/kg/day or 16 to 240 mg/m2/day PO given in 3 to 4 divided doses has been recommended. 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 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 acute gouty arthritis, ankylosing spondylitis, rheumatoid arthritis, juvenile rheumatoid arthritis (JRA)/juvenile idiopathic arthritis (JIA), post-traumatic osteoarthritis, or psoriatic arthritis:
Oral dosage:
Infants, Children, and Adolescents: A general dose range of 0.56 to 8 mg/kg/day or 16 to 240 mg/m2/day PO given in 3 to 4 divided doses has been recommended. Adjust according to patient response.
Intramuscular or Intravenous dosage:
Infants, Children, and Adolescents: 0.56 to 8 mg/kg/day or 20 to 240 mg/m2/day IM or IV 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 non-rheumatic inflammation including acute and subacute bursitis, epicondylitis, and acute non-specific tenosynovitis:
Oral dosage:
Infants, Children, and Adolescents: A general dose range of 0.56-8 mg/kg/day or 16-240 mg/m2/day PO given in 3-4 divided doses has been recommended. Adjust according to patient response.

For the management of nephrotic syndrome to induce diuresis or decrease proteinuria:
Oral dosage:
Infants, Children, and Adolescents: A general dose range of 0.56-8 mg/kg/day or 16-240 mg/m2/day PO given in 3-4 divided doses has been recommended. Adjust according to patient response.
Intramuscular or Intravenous dosage:
Infants, Children, and Adolescents: 0.56-8 mg/kg/day or 20-240 mg/m2/day IM or IV given in 3-4 divided dose is the FDA-approved general dosage range. Adjust according to patient response.

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:
-for the urgent treatment of severe conditions such as anaphylaxis, angioedema, acute noninfectious laryngeal edema, or transfusion-related reactions:
Intravenous dosage (hydrocortisone sodium succinate injection):
Infants, Children, and Adolescents: The FDA-approved general dosage range is 0.56 to 8 mg/kg/day or 20 to 240 mg/m2/day IV given in 3 to 4 divided doses. Adjust according to patient response. In certain acute, life-threatening situations, higher doses may be justified. Corticosteroids are not indicated as initial treatment for anaphylaxis, but can be given as adjunctive therapy after the administration of epinephrine.
-for the non-emergent treatment of hypersensitivity or allergic conditions:
Oral dosage:
Infants, Children, and Adolescents: The initial dosage may vary from 20 to 240 mg/day PO, given in 2 to 4 divided doses, depending on the specific condition being treated. Adjust to patient response. General pediatric weight-based dose range: 0.56 to 8 mg/kg/day or 16 to 240 mg/m2/day PO, given in 3 to 4 divided doses.

For the treatment of corticosteroid-responsive dermatoses (e.g., alopecia areata, atopic dermatitis, bullous dermatitis herpetiformis, contact dermatitis including Rhus dermatitis due to poison ivy, poison oak, poison sumac, diaper dermatitis, discoid lupus erythematosus, eczema, exfoliative dermatitis, graft-versus-host disease (GVHD), insect bites or stings, granuloma annulare, keloids, lichen striatus, lichen planus, lichen simplex, necrobiosis lipoidica diabeticorum, pemphigus, phimosis, pityriasis rosea, polymorphous light eruption, pompholyx (dyshidrosis), pruritus, psoriasis, sarcoidosis, seborrheic dermatitis, or xerosis):
-for mild-to-moderate corticosteroid-responsive dermatoses:
Topical dosage (hydrocortisone or hydrocortisone acetate cream, foam, gel, lotion, ointment, or solution):
Infants, Children, and Adolescents: Apply a thin layer topically to the affected skin area(s) 2 to 4 times daily.
Topical dosage (hydrocortisone butyrate cream, ointment, or solution):
Infants, Children, and Adolescents: Apply a thin layer topically to the affected skin area(s) 2 to 3 times daily.
-for mild to moderate atopic dermatitis:
Topical dosage (hydrocortisone or hydrocortisone acetate cream, foam, gel, lotion, ointment, or solution):
Infants, Children, and Adolescents: Apply a thin layer topically to the affected skin area(s) 2 times daily until symptoms resolve. If no improvement within 2 weeks, reassess diagnosis. Proactive, intermittent application of topical corticosteroids 1 to 2 times weekly to areas that commonly flare is recommended to help prevent relapses.
Topical dosage (hydrocortisone butyrate cream, ointment, or solution):
Infants, Children, and Adolescents: Apply a thin layer topically to the affected skin area(s) 2 times daily until symptoms resolve. Proactive, intermittent application of topical corticosteroids 1 to 2 times weekly to areas that commonly flare is recommended to help prevent relapses.
Topical dosage (hydrocortisone butyrate lipocream and lotion):
Infants, Children, and Adolescents 3 months to 17 years: Apply a thin layer topically to the affected skin area(s) 2 times daily until symptoms resolve. If no improvement within 2 weeks, reassess diagnosis. Safety and efficacy have not been established beyond 4 weeks of therapy. Proactive, intermittent application of topical corticosteroids 1 to 2 times weekly to areas that commonly flare is recommended to help prevent relapses.
-for the treatment of diaper dermatitis:
Topical dosage (hydrocortisone or hydrocortisone acetate 0.5% to 2.5% cream or ointment):
Infants, Children, and Adolescents: Apply a thin layer topically to the affected area(s) 2 to 4 times daily for up to 2 weeks. Avoid the use of tight-fitting diapers or plastic pants on persons being treated in the diaper area as these may act as an occlusive dressing.
-for the treatment of GVHD:
Topical dosage (hydrocortisone or hydrocortisone acetate 1% cream, gel, lotion, ointment, or solution):
Infants, Children, and Adolescents: Apply a thin layer topically to the affected skin area(s) 2 times daily. The FDA-approved dosage is a thin layer topically to the affected skin area(s) 2 to 4 times daily.
-for the treatment of phimosis:
Topical dosage (hydrocortisone or hydrocortisone acetate 1% cream, lotion, ointment, or solution):
Infants, Children, and Adolescents: Apply a thin layer topically to the affected skin area(s) 2 times daily for 4 to 8 weeks. The FDA-approved dosage is a thin layer topically to the affected skin area(s) 2 to 4 times daily.
Topical dosage (hydrocortisone butyrate cream, ointment, or solution):
Infants, Children, and Adolescents: Apply a thin layer topically to the affected skin area(s) 2 times daily for 4 to 8 weeks. The FDA-approved dosage is a thin layer topically to the affected skin area(s) 2 to 3 times daily.
-for the treatment of psoriasis:
Topical dosage (hydrocortisone or hydrocortisone acetate cream, foam, gel, lotion, ointment, or solution):
Infants, Children, and Adolescents: Apply a thin layer topically to the affected skin area(s) 2 to 4 times daily. Guidelines recommend topical corticosteroids as monotherapy for short-term treatment of localized psoriasis.
Topical dosage (hydrocortisone butyrate cream, ointment, or solution):
Infants, Children, and Adolescents: Apply a thin layer topically to the affected skin area(s) 2 to 3 times daily. Guidelines recommend topical corticosteroids as monotherapy for short-term treatment of localized psoriasis.

For the treatment of corticosteroid-responsive hematologic disorders, like acquired (autoimmune) hemolytic anemia, erythroblastopenia, and congenital hypoplastic anemia; OR for the palliative treatment of acute leukemias of childhood including acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), Hodgkin's disease, non-Hodgkin's lymphoma (NHL), or cutaneous T-cell lymphoma (CTCL) (aka mycosis fungoides):
Oral dosage:
Infants, Children, and Adolescents: A general dose range of 0.56-8 mg/kg/day or 16-240 mg/m2/day PO given in 3-4 divided doses has been recommended. Adjust according to patient response.
Intramuscular or Intravenous dosage:
Infants, Children, and Adolescents: 0.56-8 mg/kg/day or 20-240 mg/m2/day IM or IV given in 3-4 divided dose is the FDA-approved general dosage range. Adjust according to patient response.

For the treatment of respiratory inflammatory conditions including aspiration pneumonitis, berylliosis, or Loeffler's syndrome:
Oral dosage:
Infants, Children, and Adolescents: A general dose range of 0.56 to 8 mg/kg/day or 16 to 240 mg/m2/day PO given in 3 to 4 divided doses has been recommended. Administer hydrocortisone IV or IM initially for the treatment of severe respiratory conditions or those compromising the airway.
Intramuscular or Intravenous dosage (hydrocortisone sodium succinate injection):
Infants, Children, and Adolescents: 0.56 to 8 mg/kg/day or 20 to 240 mg/m2/day IM or IV given in 3 to 4 divided dose is the FDA-approved general dosage range. Adjust according to patient response.

For the prevention of chronic lung disease (CLD)*, specifically bronchopulmonary dysplasia (BPD)*:
Intravenous dosage:
Premature neonates: 1 mg/kg/day IV divided every 12 hours for 7 to 12 days then 0.5 mg/kg/day IV divided every 12 to 24 hours for 3 days, starting within the first 24 to 48 hours of life for premature neonates at high risk for BPD. Early systemic corticosteroids increase the rate of survival without BPD without adverse effects on neurodevelopment. However, an increased risk for late-onset sepsis may be associated with treatment. Do not administer with indomethacin prophylaxis due to increased potential for gastrointestinal perforation.

For the treatment of corticosteroid-responsive ophthalmic disorders, including allergic conjunctivitis (not controlled topically), allergic marginal corneal ulcer, anterior segment inflammation, chorioretinitis, herpes zoster ocular infection (herpes zoster ophthalmicus), iritis, keratitis, optic neuritis, diffuse posterior uveitis and choroiditis, or sympathetic ophthalmia:
Oral dosage:
Infants, Children, and Adolescents: A general dose range of 0.56-8 mg/kg/day or 16-240 mg/m2/day PO given in 3-4 divided doses has been recommended. Adjust according to patient response.
Intramuscular or Intravenous dosage:
Infants, Children, and Adolescents: 0.56-8 mg/kg/day or 20-240 mg/m2/day IM or IV given in 3-4 divided dose is the FDA-approved general dosage range. Adjust according to patient response.

For the treatment of hypercalcemia associated with cancer:
Intramuscular or Intravenous dosage (hydrocortisone sodium succinate injection):
Infants, Children, and Adolescents: 0.56 to 8 mg/kg/day or 20 to 240 mg/m2/day IM or IV given in 3 to 4 divided dose is the FDA-approved general dosage range. Adjust according to patient response.

For the treatment of refractory neonatal hypoglycemia*:
Intravenous or Oral dosage:
Neonates: 5 mg/kg/day IV or PO given in 2 divided doses has been recommended in patients not responding to glucose infusions of 12 to 15 mg/kg/minute.

For the treatment of drug-susceptible tuberculosis infection or drug-resistant tuberculosis infection as adjunctive therapy in combination with antituberculous therapy:
Oral dosage (tablets):
Infants, Children, and Adolescents: 8 to 16 mg/kg/day PO for 4 to 6 weeks, then taper 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.
Intramuscular or Intravenous dosage (hydrocortisone sodium succinate):
Infants, Children, and Adolescents: 8 to 16 mg/kg/day IV or IM for 4 to 6 weeks, then taper 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 neurologic or myocardial involvement associated with trichinosis:
Oral dosage:
Infants, Children, and Adolescents: A general dose range of 0.56-8 mg/kg/day or 16-240 mg/m2/day PO given in 3-4 divided doses has been recommended. Adjust according to patient response.
Intramuscular or Intravenous dosage:
Infants, Children, and Adolescents: 0.56-8 mg/kg/day or 20-240 mg/m2/day IM or IV given in 3-4 divided dose is the FDA-approved general dosage range. Adjust according to patient response.

For the treatment of nonsuppurative thyroiditis:
Oral dosage:
Infants, Children, and Adolescents: A general dose range of 0.56 to 8 mg/kg/day or 16 to 240 mg/m2/day PO given in 3 to 4 divided doses has been recommended. Adjust according to patient response.
Intramuscular or Intravenous dosage (hydrocortisone sodium succinate injection):
Infants, Children, and Adolescents: 0.56 to 8 mg/kg/day or 20 to 240 mg/m2/day IM or IV given in 3 to 4 divided dose is the FDA-approved general dosage range. Adjust according to patient response.

For the systemic treatment of severe inflammatory dermatoses, like severe exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, or psoriasis unresponsive to topical treatment:
Intramuscular or Intravenous dosage (hydrocortisone sodium succinate):
Infants, Children, and Adolescents: 0.56 to 8 mg/kg/day or 20 to 240 mg/m2/day IM or IV given in 3 to 4 divided dose is the FDA-approved general dosage range. Adjust according to patient response.
Oral dosage:
Infants, Children, and Adolescents: A general dose range of 0.56 to 8 mg/kg/day or 16 to 240 mg/m2/day PO given in 3 to 4 divided doses has been recommended. Adjust according to patient response.

For asthma exacerbation:
Oral dosage:
Children 6 to 11 years: Usual dose is 1 to 2 mg/kg/day PO (Max: 40 mg/day), given in divided doses. A 3 to 5-day course is usually sufficient for most pediatric patients. Titrate to patient response up to 8 mg/kg/day, given in divided doses. Oral corticosteroids (CS) are just as effective as IV for exacerbations. Although prednisone, prednisolone, or methylprednisolone are typically the systemic corticosteroids of choice, other CS such as hydrocortisone, given in equipotent daily doses are likely to be as effective. IV or IM CS may be used for the treatment of severe respiratory conditions or those compromising the airway.
Children and Adolescents 12 years and older: Usual pediatric dose is 1 to 2 mg/kg/day PO (Adult Usual: 200 mg/day), given in divided doses. A 3 to 5-day course is usually sufficient. FDA-approved Dose Range: 20 to 240 mg/day PO, given in 2 to 4 divided doses. Titrate to patient response. Oral corticosteroids (CS) are just as effective as IV for exacerbations. Although prednisone, prednisolone, or methylprednisolone are typically the systemic corticosteroids of choice, other CS such as hydrocortisone, given in equipotent daily doses are likely to be as effective. IV or IM CS may be used for the treatment of severe respiratory conditions or those compromising the airway.
Intravenous or Intramuscular dosage (hydrocortisone sodium succinate injection):
Infants and Children: 0.56 to 8 mg/kg/day or 20 to 240 mg/m2/day IM or IV given in 3 to 4 divided dose is the FDA-approved general dosage range. Adjust according to patient response. A 3 to 5-day course of corticosteroids is usually sufficient for most pediatric patients. An initial dose of 6 mg/kg IV followed by 8 to 10 mg/kg/day IV given in 4 divided doses for 1 to 2 days was used in 2 studies (age 2 months to 11 years) of pediatric patients with acute asthma.
Adolescents: 0.56 to 8 mg/kg/day or 20 to 240 mg/m2/day IM or IV given in 3 to 4 divided dose is the FDA-approved general dosage range. Adjust according to patient response. A 3 to 5-day course of corticosteroids is usually sufficient for most pediatric patients.

For the treatment of severe perennial allergies or seasonal allergies, including allergic rhinitis, that are intractable to adequate trials of conventional treatment:
Oral dosage:
Infants, Children, and Adolescents: The initial dosage may vary from 20 to 240 mg/day PO, given in 2 to 4 divided doses, depending on the specific condition being treated. Adjust to patient response. General pediatric weight-based dose range: 0.56 to 8 mg/kg/day or 16 to 240 mg/m2/day PO, given in 3 to 4 divided doses.

For the treatment of thyrotoxicosis*, including thyroid storm*:
Intravenous dosage:
Infants and Children 1 to 2 years: 2 mg/kg [weight-based] or 25 mg [flat-dose] IV bolus then 6.25 mg IV every 6 hours for 24 hours. Alternatively, 100 to 150 mg/m2/day IV in divided doses every 8 hours.
Children 3 to 12 years: 2 mg/kg (Max: 100 mg) [weight-based] or 50 mg [flat-dose] IV bolus then 12.5 mg IV every 6 hours for 24 hours. Alternatively, 100 to 150 mg/m2/day (Max: 100 mg/dose) IV in divided doses every 8 hours.
Adolescents: 2 mg/kg (Max: 100 mg) [weight-based] or 100 mg [flat-dose] IV bolus then 25 mg IV every 6 hours for 24 hours. Alternatively, 100 to 150 mg/m2/day (Max: 100 mg/dose) IV in divided doses every 8 hours.

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

Patients with Hepatic Impairment Dosing
Hydrocortisone is a synthetic preparation of the steroid hormone cortisol and does not undergo bioconversion in the liver to active form; it appears no systemic dosage adjustments are necessary in patients with hepatic disease. There is an enhanced effect due to decreased metabolism of corticosteroids in patients with cirrhosis.

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: Endogenous corticosteroids are secreted by the adrenal cortex, and their effects are believed to be due to enzyme modification rather than to a direct hormone-induced action. Corticosteroids are loosely classified into two categories, mineralocorticoids and glucocorticoids, depending on their primary pharmacological activity. Mineralocorticoids alter electrolyte and fluid balance by facilitating sodium resorption and hydrogen and potassium excretion at the level of the distal renal tubule, resulting in edema and hypertension. Glucocorticoids exert some mineralocorticoid effects but are also involved in a number of other metabolic pathways including regulation of protein, carbohydrate, lipid, and nucleic acid metabolism; maintenance of cardiac and vascular response to vasoconstrictors; regulation of extracellular water and promotion of free water excretion; suppression of the inflammatory response; lowering of capillary permeability; and modulation of central nervous system processing and behavior. Hydrocortisone possesses both mineralocorticoid actions and glucocorticoid actions.

Glucocorticoids 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 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 immune response. 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. The degree of clinical effect and the numerous adverse effects related to corticosteroid use usually depend on the dose administered and the duration of therapy.

Early anti-inflammatory effects of topical corticosteroids include the inhibition of macrophage and leukocyte movement and activity in the inflamed area by reversing vascular dilation and permeability. Later inflammatory processes such as capillary production, collagen deposition, and keloid (scar) formation also are inhibited by corticosteroids. Clinically, these actions correspond to decreased edema, erythema, pruritus, plaque formation and scaling of the affected skin.

In the treatment of asthma, corticosteroids block the late phase allergic response to allergens. Mediators involved in the pathogenesis of asthma include histamine, leukotrienes (slow releasing substance of anaphylaxis, SRS-A), eosinophil chemotactic factor of anaphylaxis (ECF-A), neutrophil chemotactic factor (NCF), cytokines, hydroxyeicosatetraenoic acids, prostaglandin-generating factor of anaphylaxis (PGF-A), prostaglandins, major basic protein, bradykinin, adenosine, peroxides, and superoxide anions. Different cell types are responsible for release of these mediators including airway epithelium, eosinophils, basophils, lung parenchyma, lymphocytes, macrophages, mast cells, neutrophils, and platelets. Corticosteroids inhibit the release of these mediators as well as inhibit IgE synthesis, attenuate mucous secretion and eicosanoid generation, up-regulate beta-receptors, promote vasoconstriction, and suppress inflammatory cell influx and inflammatory processes. Clinical effects in asthma include a reduction in bronchial hyperresponsiveness to allergens, a decreased number of asthma exacerbations, and an improvement in FEV1, peak-flow rate, and respiratory symptoms. Since corticosteroid effects take several hours to days to become clinically noticeable, they are ineffective for primary treatment of severe acute bronchospastic attacks or for status asthmaticus.

Pharmacokinetics: Hydrocortisone is administered via oral, parenteral, topical, and rectal routes. Circulating drug binds extensively to plasma proteins (92% to 93%), and only the unbound portion of a dose is active. Systemic hydrocortisone is quickly distributed into the kidneys, intestines, skin, liver, and muscle. Systemic hydrocortisone 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 biological half-life of hydrocortisone is 8 to 12 hours.

Affected cytochrome P450 isoenzymes: none


-Route-Specific Pharmacokinetics
Oral Route
Hydrocortisone is rapidly absorbed after an oral dose with an absolute bioavailability of 96% in adult subjects. Peak effects occur within 1 to 2 hours.

Intravenous Route
Peak effects of hydrocortisone after IV administration occur within 1 hour. Excretion of the dose is nearly complete within 12 hours.

Intramuscular Route
After intramuscular administration of hydrocortisone, the onset and duration of action depend on the type of injection and the extent of the local blood supply.

Topical Route
Systemic absorption after topical application of hydrocortisone is dependant on the vehicle, the state of the skin at the application site, the use of occlusive dressings, and the age of the patient. Absorption is increased in areas that have skin damage, inflammation, or where the stratum corneum is thin such as the eyelids, genitalia, and face. Factors that can increase systemic absorption of topical hydrocortisone include occlusive dressings, large surface area, frequent application, longer duration of treatment, increased humidity or temperature, and younger age. In a study of pediatric patients (n = 38, age 1 month to 14.4 years) with mild, moderate, or severe atopic or seborrheic dermatitis percutaneous absorption of hydrocortisone cream, assessed by the maximum post-application serum cortisol, was significantly higher in patients younger than 18 months of age and in patients with severe disease.

Other Route(s)
Rectal Route
When a suppository containing hydrocortisone acetate is administered rectally, about 26% of a dose is absorbed in normal subjects; absorption may vary across abraded or inflamed surfaces. Hydrocortisone rectal suspension is partially absorbed after rectal administration. In patients with ulcerative colitis, up to 50% of hydrocortisone was absorbed when administered as the rectal suspension.

Intra-articular Route
The onset and duration of action depend on type of hydrocortisone injection and the extent of the local blood supply.


-Special Populations
Pediatrics
Neonates
The half-life of hydrocortisone is prolonged in premature (8 to 12 hours) and term (4 hours) neonates compared to adults (1.7 to 2.1 hours).

Children and Adolescents
During an open-label trial of pediatric patients (n = 24) with adrenocortical insufficiency, hydrocortisone oral granules (1 to 4 mg based on body surface area) increased median cortisol concentrations from baseline to 19.4 mcg/dL (range 12.5 to 52.4 mcg/dL) at Cmax (60 minutes post-dose). Cortisol clearance was significantly increased in pubertal patients (n = 20, age 10.6 to 16.8 years) compared to prepubertal (n = 14, age 6.1 to 11 years) and postpubertal patients (n = 6, age 17.2 to 20.3 years) with congenital adrenal hyperplasia. Volume of distribution was higher in pubertal patients compared to prepubertal and postpubertal patients; however, only the difference between pubertal and prepubertal patients reached statistical significance. The mean clearance and volume distribution of free cortisol after a single dose of hydrocortisone 15 mg/m2 IV were 4,787.7 mL/minute and 540.7 L, respectively, in the pubertal group. Mean clearance in the prepubertal and postpubertal groups was 2,477.4 mL/minute and 3,001.8 mL/minute, respectively; mean volume of distribution in these 2 groups was 237 L and 276.6 L, respectively. There were no significant differences in half-life between the 3 groups (mean half-life 67.2 minutes, 77.1 minutes, and 62.5 minutes in the prepubertal, pubertal, and postpubertal groups, respectively).

Hepatic Impairment
Hydrocortisone is a synthetic preparation of the steroid hormone cortisol and does not undergo bioconversion in the liver to active form. There is an enhanced effect due to decreased metabolism of corticosteroids in patients with cirrhosis.