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.[54049] [54074] Systemic absorption of topical hydrocortisone is minimal in adults, but theoretically could cause systemic adverse reactions, especially if applied to a large surface area and/or if occlusive dressings are used. 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 suppression will require increased doses of corticosteroid therapy during periods of physiologic stress or infectious conditions, even after the drug has been discontinued. 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.[54049] [54138] A withdrawal syndrome unrelated to adrenocortical insufficiency can occur after sudden discontinuance of corticosteroid therapy. This syndrome includes symptoms such as loss of appetite, lethargy, stomach upset, pyrexia, muscle and joint pain, 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 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), acne vulgaris, hirsutism, menstrual irregularity, and a decrease in carbohydrate and glucose tolerance.[32057] [54049] In some patients, systemic absorption of rectal or topical corticosteroids can produce these effects, but these are uncommon when the duration of use is limited. 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.

Glucocorticoids, such as hydrocortisone, are responsible for protein metabolism, and prolonged therapy can result in various musculoskeletal manifestations, including: myopathy (myalgia, muscle wasting, muscle weakness, 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 humoral heads. These effects are more likely to occur in older or debilitated patients. 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 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.[24837] Postmenopausal women, in particular, should be monitored for signs of osteoporosis during corticosteroid therapy. 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.

Adverse GI effects associated with long-term oral corticosteroid administration, such as hydrocortisone, include nausea, vomiting, and anorexia with subsequent weight loss. Appetite stimulation with weight gain, diarrhea, constipation, abdominal pain and/or distention, hiccups, esophageal ulceration, gastritis, and pancreatitis have also been reported with systemic therapy. Peptic ulcers with possible subsequent GI bleeding and GI perforation have been reported. 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.[24362] While most of these studies did not utilize endoscopy, it is unlikely that corticosteroids contribute to the development of peptic ulcer disease. 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).[66033]

The following adverse reactions (listed in decreasing order of occurrence) are reported with topical corticosteroids such as hydrocortisone and may occur more often when used with an occlusive dressing: skin irritation (including burning), pruritus, xerosis (dry skin), folliculitis, hypertrichosis, acneiform rash/eruptions, skin hypopigmentation, perioral dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, and miliaria. Erythema, telangiectasia, purpura, and maculopapular rash may also occur. Although skin atrophy usually occurs after prolonged use of topical corticosteroids, this effect may occur even with short-term use on intertriginous or flexor areas, or on the face. If irritation develops, discontinue topical corticosteroids and institute appropriate therapy. The anti-inflammatory activity of topical corticosteroids may also mask manifestations of infection. In the presence of dermatological infections, institute the use of an appropriate antifungal or antibacterial agent. If a favorable response does not promptly occur, discontinue the corticosteroid until the infection has been adequately controlled. Various adverse dermatologic effects reported during systemic corticosteroid therapy include skin atrophy, diaphoresis or sweating, striae, acneiform rash, alopecia, xerosis, lupus-like symptoms, perineal pain and irritation, purpura, rash, telangiectasia, facial erythema, petechiae, ecchymosis, and easy bruising. Hypersensitivity reactions may manifest as allergic dermatitis, urticaria, anaphylactoid reactions, and/or angioedema. 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). 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. Hydrocortisone should not be applied directly on or near healing wounds. Skin ulcer may develop in patients with markedly impaired circulation who use topical corticosteroids.

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.[30943] [65096] [65097] 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.[54049] [54074] 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).[66033]

Corticosteroids are divided into 2 classes: mineralocorticoids and glucocorticoids. Mineralocorticoids alter electrolyte and fluid balance by facilitating sodium retention and hydrogen and potassium excretion at the level of the distal renal tubule, resulting in edema and hypertension. Mineralocorticoids can cause fluid retention; electrolyte disturbances (hypokalemia, hypokalemic metabolic alkalosis, hypernatremia, hypocalcemia); edema; and hypertension. Prolonged administration of glucocorticoids, such as hydrocortisone, also can result in edema and hypertension. 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.[24362] Congestive heart failure can occur in susceptible patients. In a study, an increased risk of heart failure was observed for medium-dose glucocorticoid use as compared with nonuse. At the beginning of the study, patients were at least 40 years of age and had not been hospitalized for cardiovascular disease. Medium exposure was defined as less than 7.5 mg daily of prednisolone or the equivalent given orally, rectally, or parenterally.[30697]

Adverse neurologic effects have been reported during prolonged corticosteroid therapy, such as hydrocortisone, including headache, insomnia, amnesia and memory impairment, increased motor activity, impaired cognition, neuritis, paresthesias, ischemic peripheral neuropathy, malaise, vertigo, restlessness, ischemic peripheral neuropathy, seizures, and EEG changes. Increased intracranial pressure with papilledema (pseudotumor cerebri) usually follows discontinuation of treatment. Mental status changes including depression, anxiety, euphoria, personality changes, emotional lability, delirium, dementia, hallucinations, irritability, mania, mood swings, schizophrenic reactions, withdrawn behavior, and psychosis also have been reported. Emotional lability and psychotic problems can be exacerbated by corticosteroid therapy.

Conjunctivitis was reported in 28% of pediatric patients receiving hydrocortisone oral granules for up to 29 months during an open-label trial (n = 18).[66033] 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.[32057] [60551]Temporary or permanent visual impairment, including blurred vision and blindness, has been reported with corticosteroid administration by several routes of administration. If systemic steroid therapy is continued for more than 6 weeks, monitor intraocular pressure; evaluate any patient who develops changes in vision for ocular hypertension. Ocular hypertension and cataracts leading to visual impairment have also been reported after prolonged 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, but usually with large doses or longer durations of 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.[24813] 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.[68700] 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.

Hypercholesterolemia, atherosclerosis, fat embolism, sinus tachycardia, palpitations, bradycardia, syncope, vasculitis, necrotizing angiitis, thrombosis, thromboembolism, and phlebitis have been associated with systemic corticosteroid therapy, such as hydrocortisone. Glucocorticoid use appears to increase the risk of cardiovascular events such as myocardial infarction, left ventricular rupture (in persons who recently experienced a myocardial infarction), angina, angioplasty, coronary revascularization, stroke, transient ischemic attack, cardiomegaly, arrhythmia exacerbation and ECG changes, hypertrophic cardiomyopathy (in premature infants), congestive heart failure and pulmonary edema, cardiac arrest or cardiovascular death. As determined from observational data, the rate of cardiovascular events was 17 per 1,000 person-years among 82,202 non-users of glucocorticoids. In contrast, the rate was 23.9 per 1,000 person-years among 68,781 glucocorticoid users. Furthermore, the rate of cardiovascular events was 76.5 per 1,000 person-years for high exposure patients. After adjustment for known covariates by multivariate analysis, high-dose glucocorticoid use was associated with a 2.56-fold increased risk of cardiovascular events as compared with nonuse. At the beginning of the study, patients were at least 40 years of age and had not been hospitalized for cardiovascular disease. High glucocorticoid exposure was defined as at least 7.5 mg daily of prednisolone or the equivalent given orally, rectally, or parenterally whereas medium exposure was defined as less than the above dosage by any of the 3 routes. Low-dose exposure was defined as inhaled, topical, or nasal usage only.[30697]

Tolerance 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).

Because of retardation of bone growth, children receiving prolonged systemic corticosteroid therapy (e.g., hydrocortisone) may have growth inhibition. Growth inhibition has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients. Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects, especially if used in excessive dosage, over large body surface areas, or with occlusive dressings.

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

Allergic contact dermatitis with topical corticosteroids such as hydrocortisone is usually diagnosed by observing a failure to heal. Appropriate diagnostic patch testing may help with the diagnosis.

Dizziness and anemia have been reported with corticosteroid use such as hydrocortisone. Corticosteroids may decrease serum concentrations of vitamin C (ascorbic acid) and vitamin A, which may rarely produce symptoms of vitamin A deficiency or vitamin C deficiency. Some loss of folic acid may also be caused by corticosteroid use; glossitis may be noted. Dental caries (11%) and genitourinary operation (11%) were reported in pediatric patients receiving oral granules for up to 29 months during an open-label trial (n = 18).[66033]

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.[32057] [54049]

Hydrocortisone is contraindicated in people with known hypersensitivity to hydrocortisone or the constituents within the specific product chosen. Rare instances of anaphylactoid reactions have occurred during corticosteroid therapy.[32057] [54049] [62343] True corticosteroid hypersensitivity reactions are rare. While a hypersensitivity reaction could be to a specific salt of the corticosteroid (i.e., hydrocortisone sodium succinate), patients who have demonstrated a prior hypersensitivity reaction to hydrocortisone should receive any form of hydrocortisone with extreme caution. 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. Such patients should be carefully monitored during and following the administration of any corticosteroid.[27616] [27642]

Systemic corticosteroids, including hydrocortisone, may cause immunosuppression and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. Corticosteroids can: 1) Reduce resistance to new infections, 2) Exacerbate existing infections, 3) Increase the risk of disseminated infections, 4) Increase the risk of reactivation or exacerbation of latent infections 5) Mask some signs of infection. Corticosteroid-associated infections can be mild but can be severe and at times fatal. The rate of infectious complications increases with increasing corticosteroid dosages. Monitor for the development of infection and consider corticosteroid withdrawal or dosage reduction as needed. Do not administer hydrocortisone injection by an intraarticular, intrabursal, or intratendinous route in the presence of acute local infection. If hydrocortisone is used to treat a condition in patients with latent tuberculosis (TB) or tuberculin reactivity, reactivation of TB may occur. Closely monitor such patients for TB reactivation. During prolonged hydrocortisone therapy, patients with latent TB or tuberculin reactivity should receive chemoprophylaxis. Viral infection, such as varicella zoster (chickenpox or shingles) and measles can have a serious or even fatal course in non-immune patients taking corticosteroids; other herpes infection (herpes simplex) may also disseminate in immunosuppressed individuals. Corticosteroids should be used with caution, if at all, in patients with ocular herpes simplex. In corticosteroid-treated patients who have not had these diseases or are nonimmune, avoid exposure of these people to these viral infections. If a corticosteroid-treated patient is exposed to varicella, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If varicella develops, consider treatment with antiviral. If a corticosteroid-treated patient is exposed to measles, prophylaxis with immunoglobulin (IG) may be indicated. Hepatitis B exacerbation/reactivation can occur in patients who are hepatitis B virus carriers treated with immunosuppressive dosages of corticosteroids, including hydrocortisone. Reactivation can also occur infrequently in corticosteroid-treated people who appear to have resolved hepatitis B infection. Screen patients for hepatitis B infection before initiating immunosuppressive (e.g., prolonged) treatment with systemic corticosteroids. For individuals who show evidence of hepatitis B infection, consult providers with expertise in managing hepatitis B regarding monitoring and consideration for hepatitis B antiviral therapy. Systemic hydrocortisone and rectal enema use is contraindicated in the presence of a systemic fungal infection. Corticosteroids, including hydrocortisone, may exacerbate systemic fungal infections; therefore, avoid corticosteroid use in the presence of a fungal infection unless a corticosteroid is needed to control drug reactions. If a fungal infection develops during chronic corticosteroid therapy, corticosteroid withdrawal or dosage reduction is recommended. Corticosteroids, including hydrocortisone, may activate latent amebiasis. Latent or active amebiasis should be ruled out before initiating hydrocortisone in people who have spent time in the tropics or have unexplained diarrhea. Corticosteroids, including hydrocortisone, should be used with great care in the presence of known or suspected Strongyloides (threadworm) helminth infection. Corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia. In selected patients from strongyloidiasis endemic areas who need systemic corticosteroids, consider administering prophylactic treatment. Also avoid corticosteroids, including hydrocortisone, in people with cerebral malaria.[32057] [54049] [66033] [62343] In the presence of infection during topical, rectal topical, or rectal suppository hydrocortisone therapy, the use of an appropriate antifungal, antiviral, or antibacterial agent should be instituted. If a favorable response does not occur promptly, the topical or rectal corticosteroid should be discontinued until the infection has been adequately controlled.[54060] [54365] [54372] [62344]

Systemic effects of corticosteroids, including prolonged topical use, may result in hypothalamic-pituitary-adrenal (HPA) suppression and/or manifestations of Cushing's syndrome in some patients. Adrenocortical insufficiency, adrenal crisis, and death may occur after abrupt discontinuation of prolonged systemic therapy. Adrenal suppression and increased intracranial pressure have been reported with the use and/or withdrawal of systemic and topical corticosteroids in pediatric patients. Adrenal crisis may also be induced by stressful events such as infections or surgery; patients may require higher doses of corticosteroids during times of stress. 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. Withdrawal from prolonged systemic corticosteroid therapy should be gradual. 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 surgical procedures, 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. Patients receiving large doses of hydrocortisone applied to a large surface area should be evaluated periodically for evidence of HPA axis suppression and/or manifestations of Cushing's syndrome. If these effects are noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent corticosteroid.[32057] [54049] [62343] [43359] [54074] [54137] [54138] [66033]

Topical corticosteroids should not be used 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.[51799] [54074] [54365] [54372] [62344]

High doses of systemic corticosteroids, including hydrocortisone, should not be used for the treatment of traumatic brain injury. Results from a multicenter, randomized, placebo-controlled study with methylprednisolone hemisuccinate, an IV corticosteroid, showed an increase in early (at 2 weeks) and late (at 6 months) mortality in patients with head trauma who did not have other clear indications for corticosteroid treatment.[54049]

Systemic corticosteroid therapy, such as hydrocortisone, has been associated with left ventricular free-wall rupture in patients with recent myocardial infarction, and should therefore be used cautiously in these patients.[32057] [54049]

Systemic corticosteroids, such as systemic hydrocortisone, can cause edema and weight gain. Use with caution in patients with congestive heart failure, hypertension, or renal disease/insufficiency due to the potential for corticosteroid treatment to exacerbate these conditions.[32057] [54049]

Chronic corticosteroid therapy, such as hydrocortisone, may cause growth inhibition in pediatric patients; linear growth retardation and delayed weight gain have been reported with both systemic and topical corticosteroid therapy in pediatric patients. Because bone development is critical in pediatric patients, monitor patients receiving high-dose or chronic corticosteroid treatment. Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (e.g., decreasing absorption and increasing excretion) and inhibition of osteoblast function. This, together with a decrease in the protein matrix of the bone secondary to an increase in protein catabolism, and reduced sex hormone production, may lead the development of osteopenia and osteoporosis at any age. Special consideration should be given to people at increased risk of osteoporosis (e.g., postmenopausal females) before initiating corticosteroid therapy.[32057] [54049] [54074]

Systemic corticosteroids, such as hydrocortisone, may decrease glucose tolerance, produce hyperglycemia, and aggravate or precipitate diabetes mellitus. This may especially occur in those predisposed to diabetes mellitus. When corticosteroid therapy is necessary in people with diabetes mellitus, changes in insulin, oral antidiabetic agent dosage, and/or diet may be required.[32057] [54049] [62343] Topical corticosteroids should also be used with caution in people with diabetes mellitus as exacerbation of diabetes may occur or use may delay healing of skin ulcers.[43359] [54074] [54077] Metabolic clearance of systemic corticosteroids is decreased in hypothyroidism and increased in hyperthyroidism. There is an enhanced effect of corticosteroids in people with hypothyroidism. Changes in thyroid disease status may necessitate adjustment in systemic hydrocortisone dosage.[32057] [54049] [62343]

Prolonged use of systemic corticosteroids may produce posterior subcapsular cataracts, increased intraocular pressure or glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infection due to bacteria, fungi or viruses. The use of systemic corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes.[32057] [54049] [62343] Care should be taken to avoid ocular exposure during the application of topical corticosteroid products as eye irritation may occur.[54074] [54365] [54372] [60551] The propensity of topical corticosteroids to produce ocular effects is uncertain, even when applied to the face. Prolonged periorbital application of high potency topical corticosteroids may result in visual effects including increased intraocular pressure, glaucoma or cataracts, but such events have only been published as limited case reports. However, there is no evidence to date that less potent topical corticosteroid application to the face results in ocular complications.[67068]

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. Epidural lipomatosis has been reported with hydrocortisone sodium succinate injection.[54049] Epidural administration of corticosteroids should be used with great caution. Rare, but serious adverse reactions, including cortical blindness, stroke, spinal cord infarction, paralysis, seizures, nerve injury, brain edema, and death have been associated with epidural administration of injectable corticosteroids. These events have been reported with and without the use of fluoroscopy. Many cases were temporally associated with the corticosteroid injection; reactions occurred within minutes to 48 hours after injection. 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 the patient before treatment. If a decision is made to proceed with corticosteroid epidural administration, counsel patients to seek emergency medical attention if they experience symptoms after injection such as vision changes, tingling in the arms or legs, dizziness, severe headache, seizures, or sudden weakness or numbness of face, arm, or leg.[57053]

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.[54278] Although skin atrophy may be caused by any topical steroid, the risk of this effect increases with long-term use, use of high potency formulas, high occlusion vehicles, amount of medication applied, application to steroid-sensitive areas or thin skin (e.g., face, groin, rectal area, or axilla), and use in older adults. Many of the adverse cutaneous effects are reversible upon therapy discontinuation with the exception of atrophic striae.[54074] [65541] [65543]

Systemic corticosteroid use may be associated with neuro-psychiatric effects ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychosis. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids. Inform patients or caregivers of the potential for mood and behavioral changes with systemic hydrocortisone treatment and encourage them to seek medical attention if psychiatric symptoms develop, especially if depressed mood (depression) or suicidal ideation is suspected.[32057] [54049] [62343]

An acute myopathy has been observed with the use of high doses of systemic corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.[32057] [54049]

Hydrocortisone should be used with caution in active or latent peptic ulcer disease, diverticulitis, fresh intestinal anastomoses, and non-specific ulcerative colitis, since these conditions may increase the risk of a GI perforation. Signs of peritoneal irritation following gastrointestinal perforation in patients receiving corticosteroids may be minimal or absent.[32057] [54049] Local contraindications to the use of intrarectal steroids (e.g., suppositories, foams, enemas) include GI obstruction, abscess, GI perforation, peritonitis, fresh intestinal anastomoses, extensive fistulas and sinus tracts.[60551] [62343] [67787]

Patients with severe hepatic disease, such as cirrhosis, can have an exaggerated response to systemic corticosteroids, such as hydrocortisone.[32057] [54049] [62343]

Intramuscular (IM) administration of hydrocortisone injections is contraindicated in patients with idiopathic or immune thrombocytopenic purpura (ITP).[54049] [54246]

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.[32057] [54049]

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.[32057] [54049]

Kaposi's sarcoma has been reported to occur in individuals during systemic corticosteroid therapy, such as systemic hydrocortisone, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement of Kaposi's sarcoma.[32057] [54049]

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.[32057] [54049] 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 (less than 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 or more. 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 or more, it is recommended to wait at least 3 months after discontinuation of therapy before administering a live-virus vaccine.[43236]

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 a '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. Hypertrophic cardiomyopathy may develop after administration of hydrocortisone to premature neonates, therefore appropriate diagnostic evaluation and monitoring of cardiac function and structure should be performed.[54049]

Systemic and rectal preparations of hydrocortisone must be used with caution during human pregnancy. Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Complications, including cleft palate, stillbirth, and premature abortion, have been reported during animal studies. If hydrocortisone must be used during pregnancy, the potential risks should be discussed with the patient. However, insufficient treatment of an underlying condition (e.g., Addison's disease) during pregnancy is also associated with fetal and maternal risks and the mother may require additional monitoring to ensure adequate replacement during pregnancy and in the postpartum period as requirements return to pre-pregnancy levels. Infants born to mothers who have taken substantial doses of corticosteroids during pregnancy should be monitored for signs of hypoadrenalism.[32057] [54049] [54060] [62343] Topical application of hydrocortisone warrants caution during pregnancy as there are no adequate and well-controlled studies. Topical corticosteroids should not be used in large amounts, on large areas, or for prolonged periods of time in pregnant women. Guidelines recommend mild to moderate potency agents, such as topical hydrocortisone, over potent topical corticosteroids, which should be used in short durations. Fetal growth restriction and a significantly increased risk of low birthweight has been reported with use of potent or very potent topical corticosteroids during the third trimester, particularly when using more than 300 grams. Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals.[42474] [62348] [62792] Systemic corticosteroids have been shown to impair fertility in male rats.[32057] [54049]

Use systemic hydrocortisone with caution in breast-feeding patients. Its use has not been well studied during breast-feeding; however, cortisol is a normal component of breast milk.[32057] [54049] [54060] [62343] Other corticosteroids (prednisone and prednisolone) are usually considered compatible with breast-feeding.[70364] [70365] Topical hydrocortisone is compatible with breast-feeding. It is not known whether topical hydrocortisone could result in sufficient systemic absorption to produce detectable quantities in breast milk.[42474] [62348] However, most dermatologists stress that topical corticosteroids can be safely used during lactation and breast-feeding.[62791] If applied topically, care should be used to ensure the infant will not come into direct contact with the area of application, such as the breast.[70364] [70365]

According to the Beers Criteria, systemic corticosteroids are considered potentially inappropriate medications (PIMs) for use in geriatric patients with delirium or at high risk for delirium; avoid when possible in these patient populations due to the possibility of new-onset delirium or exacerbation of the current condition. Oral and parenteral corticosteroids may be required for conditions such as exacerbation of chronic obstructive pulmonary disease (COPD) but should be prescribed in the lowest effective dose and for the shortest possible duration.[63923]

Some commercially available formulations of hydrocortisone acetate cream, ointment, and hydrocortisone shampoo may contain sulfites like sodium metabisulfite. Sodium metabisulfite may cause sulfite hypersensitivity and allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.[54365] While hydrocortisone sodium phosphate injection also contained sodium metabisulfite in the formulation, this product is no longer marketed in the U.S.[54246] Some injectable formulations of hydrocortisone contained benzyl alcohol and were to be used with caution in those patients with benzyl alcohol hypersensitivity; however, these injections are no longer marketed in the U.S.[54246]