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Hydrocortisone (Systemic)

Brand names: A-hydroCort, Cortef, Solu-CORTEF
Drug class: Adrenals
ATC class: H02AB09
VA class: HS051
CAS number: 50-23-7

Medically reviewed by on Feb 28, 2023. Written by ASHP.


Glucocorticoid secreted by the adrenal cortex; also exhibits mineralocorticoid activity.

Uses for Hydrocortisone (Systemic)

Treatment of a wide variety of diseases and conditions principally for glucocorticoid effects as an anti-inflammatory and immunosuppressant agent and for its effects on blood and lymphatic systems in the palliative treatment of various diseases.

When used for anti-inflammatory and immunosuppressant properties, synthetic glucocorticoids that have minimal mineralocorticoid activity are preferred.

Adrenocortical Insufficiency

Corticosteroids are administered in physiologic dosages to replace deficient endogenous hormones in patients with adrenocortical insufficiency.

Hydrocortisone or cortisone (in conjunction with liberal salt intake) is usually the corticosteroid of choice for replacement therapy in patients with adrenocortical insufficiency, because these drugs have both glucocorticoid and mineralocorticoid properties. Concomitant administration of a more potent mineralocorticoid (fludrocortisone) may be required in some patients.

In suspected or known adrenal insufficiency, parenteral therapy may be used preoperatively or during serious trauma, illness, or shock unresponsive to conventional therapy.

Adrenogenital Syndrome

Lifelong glucocorticoid treatment of congenital adrenogenital syndrome.

In salt-losing forms, cortisone or hydrocortisone is preferred in conjunction with liberal salt intake; an additional mineralocorticoid may be necessary in conjunction through at least 5–7 years of age.

A glucocorticoid, usually alone, for long-term therapy after early childhood.

In hypertensive forms, a “short-acting” glucocorticoid with minimal mineralocorticoid activity (e.g., prednisone) is preferred; avoid long-acting glucocorticoids (e.g., dexamethasone) because of tendency toward overdosage and growth retardation.


Treatment of hypercalcemia associated with malignancy.

Usually ameliorates hypercalcemia associated with bone involvement in multiple myeloma.

Treatment of hypercalcemia associated with sarcoidosis [off-label].

Treatment of hypercalcemia associated with vitamin D intoxication [off-label].

Not effective for hypercalcemia caused by hyperparathyroidism [off-label].


Treatment of granulomatous (subacute, nonsuppurative) thyroiditis.

Anti-inflammatory action relieves fever, acute thyroid pain, and swelling.

May reduce orbital edema in endocrine exophthalmos (thyroid ophthalmopathy).

Usually reserved for palliative therapy in severely ill patients unresponsive to salicylates and thyroid hormones.

Rheumatic Disorders and Collagen Diseases

Short-term adjunctive treatment of acute episodes or exacerbations and systemic complications of rheumatic disorders (e.g., rheumatoid arthritis, juvenile arthritis, psoriatic arthritis, acute gouty arthritis, posttraumatic osteoarthritis, synovitis of osteoarthritis, epicondylitis, acute nonspecific tenosynovitis, ankylosing spondylitis, Reiter syndrome [off-label], rheumatic fever [off-label] [especially with carditis]) and collagen diseases (e.g., acute rheumatic carditis, systemic lupus erythematosus, dermatomyositis [polymyositis], polyarteritis nodosa, vasculitis) refractory to more conservative measures.

Relieves inflammation and suppresses symptoms but not disease progression.

Rarely indicated as maintenance therapy.

May be used as maintenance therapy (e.g., in rheumatoid arthritis, acute gouty arthritis, systemic lupus erythematosus, acute rheumatic carditis) as part of a total treatment program in selected patients when more conservative therapies have proven ineffective.

Glucocorticoid withdrawal is extremely difficult if used for maintenance; relapse and recurrence usually occur with drug discontinuance.

Local injection can provide dramatic relief initially for articular manifestations of rheumatic disorders (e.g., rheumatoid arthritis) that involve only a few persistently inflamed joints or for inflammation of tendons or bursae; inflammation tends to recur and sometimes is more intense after drug cessation.

Local injection can prevent invalidism by facilitating movement of joints that might otherwise become immobile.

Controls acute manifestations of rheumatic carditis more rapidly than salicylates and may be life-saving; cannot prevent valvular damage and no better than salicylates for long-term treatment.

Adjunctively for severe systemic complications of Wegener’s granulomatosis, but cytotoxic therapy is the treatment of choice.

Primary treatment to control symptoms and prevent severe, often life-threatening complications of dermatomyositis and polymyositis, polyarteritis nodosa, relapsing polychondritis, polymyalgia rheumatica and giant-cell (temporal) arteritis, or mixed connective tissue disease syndrome. High dosage may be required for acute situations; after a response has been obtained, drug must often be continued for long periods at low dosage.

Polymyositis associated with malignancy and childhood dermatomyositis may not respond well.

Rarely indicated in psoriatic arthritis, diffuse scleroderma (progressive systemic sclerosis), acute and subacute bursitis, or osteoarthritis; risks outweigh benefits.

In osteoarthritis, intra-articular injections may be beneficial but should be limited in number as joint damage may occur.

Dermatologic Diseases

Treatment of pemphigus and pemphigoid, bullous dermatitis herpetiformis, severe erythema multiforme (Stevens-Johnson syndrome), exfoliative dermatitis, uncontrollable eczema, cutaneous sarcoidosis, mycosis fungoides, lichen planus, severe psoriasis, and severe seborrheic dermatitis.

Usually reserved for acute exacerbations unresponsive to conservative therapy.

Early initiation of systemic glucocorticoid therapy may be life-saving in pemphigus vulgaris and pemphigoid, and high or massive doses may be required.

For control of severe or incapacitating allergic conditions (e.g., contact dermatitis, atopic dermatitis) intractable to adequate trials of conventional treatment.

Chronic skin disorders seldom an indication for systemic glucocorticoids.

Intralesional or sublesional injections occasionally indicated for localized chronic skin disorders (e.g., keloids, psoriatic plaques, alopecia areata, discoid lupus erythematosus, granuloma annulare) unresponsive to topical therapy.

Rarely indicated for psoriasis; if used, exacerbation may occur when the drug is withdrawn or dosage is decreased.

Rarely indicated for alopecia (areata, totalis, or universalis); may stimulate hair growth, but hair loss returns when the drug is discontinued.

Allergic Conditions

For control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment and control of acute manifestations, including anaphylactic and anaphylactoid reactions, angioedema, acute noninfectious laryngeal edema, serum sickness, allergic symptoms of trichinosis, urticarial transfusion reactions, drug hypersensitivity reactions, and severe seasonal or perennial rhinitis.

Systemic therapy usually reserved for acute conditions and severe exacerbations.

For acute conditions, usually used in high dosage and with other therapies (e.g., antihistamines, sympathomimetics).

Reserve prolonged treatment of chronic allergic conditions for patients with disabling conditions unresponsive to more conservative therapy and when risks of long-term glucocorticoid therapy are justified.

Ocular Disorders

To suppress a variety of allergic and nonpyogenic ocular inflammations.

To reduce scarring in ocular injuries.

For the treatment of severe acute and chronic allergic and inflammatory processes involving the eye and adnexa (e.g., allergic conjunctivitis, keratitis, allergic corneal marginal ulcers, herpes zoster ophthalmicus, iritis and iridocyclitis, chorioretinitis, diffuse posterior uveitis and choroiditis, anterior segment inflammation, optic neuritis, sympathetic ophthalmia).

Acute optic neuritis optimally treated with initial high-dose IV therapy followed by chronic oral therapy. Can slow progression to clinically definite multiple sclerosis.

Less severe allergic and inflammatory allergic conditions of the eye are treated with topical (to the eye) corticosteroids.

Systemically in stubborn cases of anterior segment eye disease and when deeper ocular structures are involved.


Corticosteroids are used as adjunctive treatment of acute asthma exacerbations and for maintenance treatment of persistent asthma.

Systemic glucocorticoids (usually prednisone, prednisolone, and dexamethasone) are used for treatment of moderate to severe acute exacerbations of asthma; speeds resolution of airflow obstruction and reduces rate of relapse.


The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline states that oral glucocorticoids play a role in the acute management of COPD exacerbations, but have no role in the chronic daily treatment of COPD because of the lack of benefit and high rate of systemic complications.


Management of symptomatic sarcoidosis.

Systemic glucocorticoids are indicated for hypercalcemia; ocular, CNS, glandular, myocardial, or severe pulmonary involvement; or severe skin lesions unresponsive to intralesional injections of glucocorticoids.


Treatment of fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous therapy.

Lipid Pneumonitis

Promotes the breakdown or dissolution of pulmonary lesions and eliminates sputum lipids in lipid pneumonitis.

Coronavirus Disease 2019 (COVID-19)

Adjunctive therapy in the treatment of serious complications from COVID-19.

Loeffler’s Syndrome

Symptomatic relief of acute manifestations of symptomatic Loeffler’s syndrome not manageable by other means.


Symptomatic relief of acute manifestations of berylliosis.

Aspiration Pneumonitis

Symptomatic relief of acute manifestations of aspiration pneumonitis.

Postnatal Use for Bronchopulmonary Dysplasia

Has been used for prevention or treatment of bronchopulmonary dysplasia in very low-birth-weight infants (i.e., <1.5 kg) who require mechanical ventilation. However, the AAP states that routine use of systemic glucocorticoids in such patients is not recommended.

May provide short-term pulmonary benefits but does not reduce mortality and is associated with an increased risk of serious adverse effects (e.g., hyperglycemia, hypertension, GI bleeding or intestinal perforation, hypertrophic obstructive cardiomyopathy, poor weight gain, poor growth of head circumference) and long-term sequelae (e.g., neurodevelopmental delay, cerebral palsy, impaired cognitive function, and stunted growth at or before school age).

Hematologic Disorders

Management of acquired (autoimmune) hemolytic anemia, idiopathic thrombocytopenic purpura (ITP), secondary thrombocytopenia, erythroblastopenia, or congenital (erythroid) hypoplastic anemia.

High or even massive dosages decrease bleeding tendencies and normalize blood counts; does not affect the course or duration of hematologic disorders.

Glucocorticoids, immune globulin IV (IGIV), or splenectomy are first-line therapies for moderate to severe ITP, depending on the extent of bleeding involved.

May not affect or prevent renal complications in Henoch-Schoenlein purpura.

Insufficient evidence of effectiveness in aplastic anemia in children, but widely used.


Corticosteroids have been used in the treatment of shock. The Surviving Sepsis Campaign guidelines suggest the use of IV corticosteroids for adults with septic shock and an ongoing requirement for vasopressor therapy; however, the optimal dose, timing of initiation, and duration remain uncertain.

The typical corticosteroid used in adults with septic shock is IV hydrocortisone (200 mg daily given as 50 mg IV every 6 hours or as a continuous infusion).

GI Diseases

Short-term palliative therapy for acute exacerbations and systemic complications of ulcerative colitis, regional enteritis, and celiac disease.

Do not use if a probability of impending perforation, abscess, or other pyogenic infection.

Rarely indicated for maintenance therapy in chronic GI diseases (e.g., ulcerative colitis, celiac disease) since does not prevent relapses and may produce severe adverse reactions with long-term administration.

Occasionally, low dosages, in conjunction with other supportive therapy, may be useful for disease unresponsive to the usual therapy indicated for chronic conditions.

Crohn’s Disease

Oral corticosteroids may be used for short-term treatment of moderate to severely active Crohn's disease.

Neoplastic Diseases

Alone or as a component of various chemotherapeutic regimens in the palliative treatment of neoplastic diseases of the lymphatic system (e.g., leukemias and lymphomas in adults and acute leukemias in children).

Treatment of breast cancer; glucocorticoids alone not as effective as other agents (e.g., cytotoxic agents, hormones, antiestrogens) and should be reserved for unresponsive disease.

Organ Transplants

In massive dosage, used concomitantly with other immunosuppressive drugs to prevent rejection of transplanted organs.

Incidence of secondary infections is high with immunosuppressive drugs; limit to clinicians experienced in their use.


Treatment of trichinosis with neurologic or myocardial involvement.

Nephrotic Syndrome and Lupus Nephritis

Treatment of idiopathic nephrotic syndrome without uremia.

Can induce diuresis and remission of proteinuria in nephrotic syndrome secondary to primary renal disease, especially when there is minimal renal histologic change.

Treatment of lupus nephritis.

Bacterial Meningitis

Has been used in the treatment of bacterial meningitis.

In a Cochrane review, corticosteroids were found to reduce hearing loss and neurological sequelae, but did not improve overall mortality. The benefits were limited to high-income countries; there was no beneficial effect of corticosteroid therapy in low-income countries.

Hydrocortisone (Systemic) Dosage and Administration


  • Route of administration and dosage depend on the condition being treated and the patient response.

Alternate-day Therapy

  • Alternate-day therapy in which a single dose is administered every other morning is the dosage regimen of choice for long-term oral glucocorticoid treatment of most conditions. This regimen provides relief of symptoms while minimizing adrenal suppression, protein catabolism, and other adverse effects.

  • Some conditions (e.g., rheumatoid arthritis, ulcerative colitis) require daily glucocorticoid therapy because symptoms of the underlying disease cannot be controlled by alternate-day therapy.

Discontinuance of Therapy

  • A steroid withdrawal syndrome consisting of lethargy, fever, and myalgia can develop following abrupt discontinuance. Symptoms often occur without evidence of adrenal insufficiency (while plasma glucocorticoid concentrations were still high but were falling rapidly).

  • If used for only brief periods (a few days) in emergency situations, may reduce and discontinue dosage quite rapidly.

  • Very gradually withdraw systemic glucocorticoids until recovery of HPA-axis function occurs following long-term therapy with pharmacologic dosages. (See Adrenocortical Insufficiency under Warnings.)

  • Exercise caution when transferring from systemic glucocorticoid to oral or nasal inhalation corticosteroid therapy.

  • Many methods of slow withdrawal or “tapering” have been described.

  • In one suggested regimen, decrease by 10–20 mg every 3–7 days until the physiologic dose (20 mg) is reached.

  • Other recommendations state that decrements usually should not exceed 10 mg every 1–2 weeks. After 2–4 weeks, may decrease hydrocortisone dosage by 2.5 mg every week until a single morning dosage of 10 mg daily is reached.

  • For certain acute allergic conditions (e.g., contact dermatitis such as poison ivy) or acute exacerbations of chronic allergic conditions, glucocorticoids may be administered short term (e.g., for 6 days). Administer an initially high dose on the first day of therapy, and then withdraw therapy by tapering the dose over several days.


Administer orally, by IV injection or infusion, or by IM injection.

May be administered by sub-Q injection (as hydrocortisone sodium phosphate; no longer commercially available in US) or administered for local effect by intra-articular, intralesional, or soft-tissue injection (as hydrocortisone acetate; no longer commercially available in US).

Generally reserve IM or IV therapy for patients who are not able to take the drug orally or for use in an emergency situation. After the initial emergency period, consider a longer-acting injectable corticosteroid preparation or oral administration of a corticosteroid.

Oral Administration

Administer hydrocortisone orally as tablets.

IV Administration

Administer hydrocortisone sodium succinate by IV injection or infusion.


Reconstitute for IV injection with bacteriostatic water for injection or bacteriostatic 0.9% sodium chloride injection according to the manufacturer’s instructions.


For IV infusion, further dilute the reconstituted hydrocortisone sodium succinate solutions with 5% dextrose, 0.9% sodium chloride, or 5% dextrose in 0.9% sodium chloride injection to a concentration of 0.1–1 mg/mL.

Rate of Administration

When the drug is administered by direct IV injection, administer over a period of at least 30 seconds.

IM Injection

Administer hydrocortisone sodium succinate by IM injection.


Reconstitute for IM injection with bacteriostatic water for injection or bacteriostatic 0.9% sodium chloride injection according to the manufacturer’s instructions.


Available as hydrocortisone and hydrocortisone sodium succinate; dosage expressed in terms of hydrocortisone.

After a satisfactory response is obtained, dosage should be decreased in small decrements to the lowest level that maintains an adequate clinical response, and discontinue the drug as soon as possible.

Monitor patients continually for signs that indicate dosage adjustment is necessary, such as remissions or exacerbations of the disease and stress (surgery, infection, trauma).

High dosages may be required for acute situations of certain rheumatic disorders and collagen diseases; after a response has been obtained, drug often must be continued for long periods at low dosage.

High or massive dosages may be required in the treatment of pemphigus, exfoliative dermatitis, bullous dermatitis herpetiformis, severe erythema multiforme, or mycosis fungoides. Early initiation of systemic glucocorticoid therapy may be life-saving in pemphigus vulgaris. Reduce dosage gradually to the lowest effective level, but discontinuance may not be possible.

Massive dosages may be required for the treatment of shock.

If used orally for prolonged anti-inflammatory therapy, consider an alternate-day dosage regimen. Following long-term therapy, withdraw gradually.

Pediatric Patients

Base pediatric dosage on severity of the disease and the response of the patient rather than on strict adherence to dosage indicated by age, body weight, or body surface area.

Usual Dosage

Hydrocortisone: 0.56–8 mg/kg daily or 16–240 mg/m2 daily, administered in 3 or 4 divided doses.


Hydrocortisone sodium succinate: 0.16–1 mg/kg or 6–30 mg/m2 IV 1 or 2 times daily.


Hydrocortisone sodium succinate: 0.16–1 mg/kg or 6–30 mg/m2 IM 1 or 2 times daily.

Coronavirus Disease 2019 (COVID-19)†

When a corticosteroid is used, NIH COVID-19 Treatment Guidelines Panel recommends dexamethasone (0.15 mg/kg [maximum 6 mg] given IV or orally once daily for up to 10 days). If dexamethasone not available, may consider equivalent dosages of an alternative corticosteroid (e.g., hydrocortisone). Consult most recent NIH COVID-19 treatment guidelines for additional information on use of corticosteroids in pediatric patients with COVID-19.


Usual Dosage

Hydrocortisone: Initially, 10–320 mg daily (usually administered in 3 or 4 divided doses), depending on the disease being treated.


Hydrocortisone sodium succinate: 100 mg to 8 g daily. 100–500 mg IV initially, and every 2–10 hours as needed.


Hydrocortisone sodium succinate: 100 mg to 8 g daily. 100–500 mg IM initially and every 2–10 hours as needed.


Life-threatening shock: Massive doses of hydrocortisone sodium succinate such as 50 mg/kg by direct IV injection (over a period of one to several minutes) initially and repeated in 4 hours and/or every 24 hours if needed.

Alternatively, 0.5–2 g by direct IV injection (over a period of one to several minutes) initially and repeated at 2- to 6-hour intervals as required.

In such cases, administer by direct IV injection over a period of one to several minutes.

Continue high-dose therapy only until the patient’s condition has stabilized and usually not beyond 48–72 hours.

If massive corticosteroid therapy is needed beyond 72 hours, use a corticosteroid which causes less sodium retention (e.g., methylprednisolone sodium succinate or dexamethasone sodium phosphate) to minimize the risk of hypernatremia.

Coronavirus Disease 2019 (COVID-19)†

NIH COVID-19 Treatment Guidelines Panel recommends hydrocortisone 160 mg daily given in 2–4 divided doses. WHO Guidelines Development Group recommends hydrocortisone 50 mg every 8 hours for 7–10 days. Consult most recent NIH and WHO COVID-19 treatment guidelines for additional information on use of corticosteroids in patients with COVID-19.

Cautions for Hydrocortisone (Systemic)


  • Known hypersensitivity to hydrocortisone, any ingredient in the respective formulation, or any other corticosteroid.

  • Systemic fungal infections unless needed to control drug reactions due to amphotericin B.

  • Concurrent administration of live virus vaccines in patients receiving immunosuppressive doses of corticosteroids.

  • IM administration for conditions prone to bleeding (e.g., idiopathic thrombocytopenic purpura [ITP]).

  • Hydrocortisone sodium succinate injection preparations containing benzyl alcohol in premature infants. (See Pediatric Use under Cautions.)



Nervous System Effects

May precipitate mental disturbances ranging from euphoria, insomnia, mood swings, depression and anxiety, and personality changes to frank psychoses. Use may aggravate emotional instability or psychotic tendencies.

Use with caution in patients with myasthenia gravis receiving anticholinesterase therapy.

Serious, potentially permanent, and sometimes fatal adverse neurologic events (e.g., spinal cord infarction, paraplegia, quadriplegia, cortical blindness, stroke, seizures, nerve injury, brain edema) reported rarely, often within minutes to 48 hours following epidural glucocorticoid injection given either with or without fluoroscopic guidance.

FDA states efficacy and safety of epidural glucocorticoid administration not established; not FDA-labeled for this use. (See Advice to Patients.)

Adrenocortical Insufficiency

When given in supraphysiologic doses for prolonged periods, glucocorticoids may cause decreased secretion of endogenous corticosteroids by suppressing pituitary release of corticotropin (secondary adrenocortical insufficiency).

The degree and duration of adrenocortical insufficiency is highly variable among patients and depends on the dose, frequency and time of administration, and duration of glucocorticoid therapy.

Acute adrenal insufficiency (even death) may occur if the drugs are withdrawn abruptly or if patients are transferred from systemic glucocorticoid therapy to local (e.g., inhalation) therapy.

Withdraw hydrocortisone very gradually following long-term therapy with pharmacologic dosages. (See Discontinuance of Therapy under Dosage and Administration.)

Adrenal suppression may persist up to 12 months in patients who receive large dosages for prolonged periods.

Until recovery occurs, signs and symptoms of adrenal insufficiency may develop if subjected to stress (e.g., infection, surgery, trauma) and replacement therapy may be required. Since mineralocorticoid secretion may be impaired, sodium chloride and/or a mineralocorticoid should also be administered.

If the disease flares up during withdrawal, dosage may need to be increased and followed by a more gradual withdrawal.


Increased susceptibility to infections secondary to glucocorticoid-induced immunosuppression. Certain infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome in such patients. (See Increased Susceptibility to Infection under Warnings.)

Administration of live virus vaccines, including smallpox, is contraindicated in patients receiving immunosuppressive dosages of glucocorticoids. If inactivated viral or bacterial vaccines are administered to such patients, the expected serum antibody response may not be obtained. May undertake immunization procedures in patients receiving glucocorticoids as replacement therapy (e.g., Addison’s disease).

Increased Susceptibility to Infection

Glucocorticoids, especially in large doses, increase susceptibility to and mask symptoms of infection.

Infections with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic infections in any organ system, may be associated with glucocorticoids alone or in combination with other immunosuppressive agents; reactivation of latent infections may occur.

Infections may be mild, but they can be severe or fatal, and localized infections may disseminate.

Do not use, except in life-threatening situations, in patients with viral infections or bacterial infections not controlled by anti-infectives.

Some infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome, particularly in children.

Children and any adult who are not likely to have been exposed to varicella or measles should avoid exposure to these infections while receiving glucocorticoids.

If exposure to varicella or measles occurs in susceptible patients, treat appropriately (e.g., VZIG, IG).

Prolonged use of systemic corticosteroids in patients with COVID-19 may increase risk of reactivation of latent infections (e.g., HBV, herpesvirus, strongyloidiasis, tuberculosis). Risk of reactivation of latent infections following a 10-day course of dexamethasone (6 mg once daily) or equivalent corticosteroid therapy (e.g., hydrocortisone) not well established. When initiating hydrocortisone in patients with COVID-19, consider appropriate screening and treatment to reduce the risk of Strongyloides hyperinfection in those at high risk (e.g., patients from tropical, subtropical, or warm, temperate regions or those engaged in agricultural activities) and reduce the risk of fulminant reactivation of HBV.

May exacerbate fungal infections and should not be used in the presence of such infection unless needed to control drug reactions to amphotericin B; however, cases of cardiac enlargement and CHF have been reported with concomitant use of hydrocortisone and amphotericin B.

Not effective and can have detrimental effects (prolongation of coma, higher incidence of pneumonia and GI bleeding) in the management of cerebral malaria.

Can reactivate tuberculosis. Include chemoprophylaxis in patients with a history of active tuberculosis undergoing prolonged glucocorticoid therapy. Observe closely for evidence of reactivation. Restrict use in active tuberculosis to those with fulminating or disseminated tuberculosis in which glucocorticoids are used in conjunction with appropriate chemoprophylaxis.

Can reactivate latent amebiasis. Exclude possible amebiasis in any patient who has been in the tropics or who has unexplained diarrhea prior to initiating therapy.

Musculoskeletal Effects

Muscle wasting, muscle pain or weakness, delayed wound healing, and atrophy of the protein matrix of the bone resulting in osteoporosis, vertebral compression fractures, aseptic necrosis of femoral or humeral heads, or pathologic fractures of long bones are manifestations of protein catabolism that may occur during prolonged therapy with glucocorticoids. These adverse effects may be especially serious in geriatric or debilitated patients. A high-protein diet may help to prevent adverse effects associated with protein catabolism.

An acute, generalized myopathy can occur with the use of high doses of glucocorticoids, particularly in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis) or in patients receiving concomitant therapy with neuromuscular blocking agents (e.g., pancuronium).

Osteoporosis and related fractures are one of the most serious adverse effects of long-term glucocorticoid therapy. The American College of Rheumatology (ACR) has published guidelines on prevention and treatment of glucocorticoid-induced osteoporosis. Recommendations are made according to a patient's risk of fracture.

Fluid and Electrolyte Disturbances

Sodium retention with resultant edema, potassium loss, and elevation of blood pressure may occur with average or large doses of hydrocortisone. Edema and CHF (in susceptible patients) may occur.

Dietary salt restriction is advisable and potassium supplementation may be necessary.

Increased calcium excretion and possible hypocalcemia.

Ocular Effects

Prolonged use may result in posterior subcapsular and nuclear cataracts (particularly in children), exophthalmos, and/or increased IOP which may result in glaucoma or may occasionally damage the optic nerve.

May enhance the establishment of secondary fungal and viral infections of the eye.

Cortical blindness has occurred following epidural glucocorticoid injection.

Do not use in patients with active ocular herpes simplex infections for fear of corneal perforation.

Endocrine and Metabolic Effects

Administration over a prolonged period may produce various endocrine disorders including hypercorticism (cushingoid state) and amenorrhea or other menstrual difficulties. Corticosteroids have also been reported to increase or decrease motility and number of sperm in some men.

May decrease glucose tolerance, produce hyperglycemia, and aggravate or precipitate diabetes mellitus, especially in patients predisposed to diabetes mellitus. If glucocorticoid therapy is required in patients with diabetes mellitus, changes in insulin or oral antidiabetic agent dosage or diet may be necessary.

Exaggerated response to the glucocorticoids in hypothyroidism.

Cardiovascular Effects

Use with extreme caution in recent MI since an association between use of glucocorticoids and left ventricular free-wall rupture has been suggested.

Sensitivity Reactions

Anaphylactic and hypersensitivity reactions.

Tartrazine Sensitivity

Certain tablet formulations contain the dye tartrazine (FD&C yellow No. 5), which may cause allergic reactions including bronchial asthma in susceptible individuals. Although the incidence of tartrazine sensitivity is low, it frequently occurs in patients who are sensitive to aspirin.

Sulfite Sensitivity

Some commercially available formulations contain sulfites that may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals. Overall prevalence of sulfite sensitivity in the general population is unknown but probably low; appears to occur more frequently in asthmatic than in nonasthmatic individuals.

General Precautions


Prior to initiation of long-term glucocorticoid therapy, perform baseline ECGs, blood pressures, chest and spinal radiographs, glucose tolerance tests, and evaluations of HPA-axis function in all patients.

Perform upper GI radiographs in patients predisposed to GI disorders, including those with known or suspected peptic ulcer disease.

During long-term therapy, perform periodic height, weight, chest and spinal radiographs, hematopoietic, electrolyte, glucose tolerance, and ocular and blood pressure evaluations.

GU Effects

Increased or decreased motility and number of sperm in some men.

GI Effects

Corticosteroids should be used with caution in patients with diverticulitis, nonspecific ulcerative colitis (if there is a probability of impending perforation, abscess, or other pyogenic infection), or those with recent intestinal anastomoses.

Use with caution in patients with active or latent peptic ulcer. Manifestations of peritoneal irritation following GI perforation may be minimal or absent in patients receiving corticosteroids. Suggest concurrent administration of antacids between meals to prevent peptic ulcer formation in patients receiving high dosages of corticosteroids.

Dermatologic Effects

Various dermatologic effects (i.e., impaired wound healing, skin atrophy and thinning, acne, increased sweating, hirsutism, facial erythema, striae, petechiae, ecchymoses, easy bruising) are associated with systemic glucocorticoids.

Kaposi’s sarcoma reported in patients receiving glucocorticoids; discontinuance may result in clinical remission.

Specific Populations


Category C.


Glucocorticoids are distributed into milk and could suppress growth, interfere with endogenous glucocorticoid production, or cause other adverse effects in nursing infants. Discontinue nursing (in mothers taking pharmacologic doses) because of potential risk to nursing infants.

Pediatric Use

The effects of glucocorticoids on the pathophysiology and course of diseases considered to be similar in adults and children. Evidence of safety and efficacy of corticosteroids in pediatric patients is based on treatment of nephrotic syndrome (in patients >2 years of age) and aggressive leukemias and lymphomas (in patients >1 month of age). Evidence of safety and efficacy in other pediatric indications (e.g., severe asthma and wheezing) is based on controlled trials in adults.

Adverse effects in pediatric patients are similar to those in adults. As in adults, perform periodic evaluations of height, weight, IOP, and BP. Children, like adults, also should undergo clinical evaluation for the presence of infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis.

With long-term use, may delay growth and maturation in children and adolescents. Monitor carefully the growth and development of pediatric patients receiving prolonged corticosteroid therapy. Titrate dosage to the lowest effective level. Alternate-day therapy may minimize growth suppression and should be instituted if growth suppression occurs.

Some commercially available injections contain benzyl alcohol as a preservative. Administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates (when large amounts administered [100–400 mg/kg daily]), although causal relationship not established.

Some manufacturers state that benzyl alcohol-containing injectable preparations are contraindicated in premature infants and use should be avoided whenever possible; AAP states that presence of small amounts in a commercially available injection should not proscribe its use when the medication is indicated in neonates and comparable benzyl alcohol-free preparations are not available.

Safety and efficacy of dexamethasone and other corticosteroids (e.g., hydrocortisone) for COVID-19 treatment not fully evaluated in pediatric patients. Use caution when extrapolating recommendations for adults with COVID-19 to pediatric patients <18 years of age. The NIH COVID-19 Treatment Guidelines Panel recommends use of dexamethasone (see Pediatric Patients under Dosage, in Dosage and Administration) for hospitalized pediatric patients with COVID-19 who are receiving high-flow oxygen, noninvasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO); dexamethasone not routinely recommended for pediatric patients who require only low levels of oxygen support (i.e., nasal cannula only). If dexamethasone not available, the NIH panel states that alternative corticosteroids (e.g., hydrocortisone) at equivalent dosages may be considered. Use of corticosteroids for treatment of severe COVID-19 in pediatric patients who are profoundly immunocompromised not evaluated to date and may be harmful; therefore, the NIH panel states consider such use only on a case-by-case basis. IV corticosteroids have been used as first-line therapy in pediatric patients with multisystem inflammatory syndrome in children (MIS-C); however, the NIH panel recommends consultation with a multidisciplinary team when considering and managing immunomodulating therapy for children with this condition. Optimal choice and combination of immunomodulating therapies for children with MIS-C not definitely established. Consult the most recent NIH COVID-19 treatment guidelines for additional information on use of corticosteroids in pediatric patients with COVID-19.

Geriatric Use

With prolonged therapy, muscle wasting, muscle pain or weakness, delayed wound healing, and atrophy of the protein matrix of the bone resulting in osteoporosis, vertebral compression fractures, aseptic necrosis of femoral or humeral heads, or pathologic fractures of long bones may occur. May be especially serious in geriatric or debilitated patients.

Before initiating glucocorticoid therapy in postmenopausal women, consider that such women are especially prone to osteoporosis.

Use with caution in patients with osteoporosis.

Hepatic Impairment

Patients with cirrhosis show an exaggerated response to glucocorticoids.

Renal Impairment

Use with caution.

Common Adverse Effects

Associated with long-term therapy: bone loss, cataracts, indigestion, muscle weakness, back pain, bruising, oral candidiasis. (See Warnings/Precautions under Cautions.)

Interactions for Hydrocortisone (Systemic)

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: potential pharmacokinetic interaction (decreased hydrocortisone clearance).

Inducers of CYP3A4: potential pharmacokinetic interaction (increased hydrocortisone clearance).

Specific Drugs




Amphotericin B

Cases of cardiac enlargement and CHF reported with use of hydrocortisone to control adverse reactions to amphotericin B

Anticoagulants, oral

Conflicting reports of alterations in the anticoagulant response

Monitor prothrombin time frequently


Possible increase in metabolic clearance of hydrocortisone

Increased hydrocortisone dosage may be necessary

Diuretics, potassium-depleting

Enhance the potassium-wasting effects of glucocorticoids

Monitor for development of hypokalemia


Possible increase in metabolic clearance of hydrocortisone

Increased hydrocortisone dosage may be necessary


Estrogens may potentiate effects of hydrocortisone

Dosage adjustment of hydrocortisone may be required if estrogens are added to or withdrawn from a stable dosage regimen


Possible decrease in metabolic clearance of hydrocortisone

Inhibits adrenal corticosteroid synthesis, causing adrenal insufficiency during corticosteroid withdrawal

May need a reduction in dosage of hydrocortisone to avoid potential adverse effects

Macrolide antibiotics

Possible decrease in metabolic clearance of hydrocortisone

May need a reduction in dosage of hydrocortisone to avoid potential adverse effects


Increases the risk of GI ulceration

Decreased serum salicylate concentrations. When corticosteroids are discontinued, serum salicylate concentration may increase possibly resulting in salicylate intoxication

Use concurrently with caution

Observe patients receiving both drugs closely for adverse effects of either drug

May be necessary to increase salicylate dosage when corticosteroids are administered concurrently or decrease salicylate dosage when corticosteroids are discontinued

Use aspirin and corticosteroids with caution in hypoprothrombinemia


Possible increase in metabolic clearance of hydrocortisone

Increased dosage of hydrocortisone may be necessary


Possible increase in metabolic clearance of hydrocortisone

Increased dosage of hydrocortisone may be necessary

Vaccines and toxoids

May cause a diminished response to toxoids and live or inactivated vaccines

May potentiate replication of some organisms contained in live, attenuated vaccines

Can aggravate neurologic reactions to some vaccines (supraphysiologic dosages)

Live virus vaccines contraindicated in individuals receiving immunosuppressive hydrocortisone doses

Defer routine administration of vaccines or toxoids until corticosteroid therapy is discontinued

May need serologic testing to ensure adequate antibody response for immunization; additional doses of the vaccine or toxoid may be necessary

May undertake immunization procedures in patients receiving nonimmunosuppressive doses of glucocorticoids or in patients receiving glucocorticoids as replacement therapy (e.g., Addison’s disease)

Hydrocortisone (Systemic) Pharmacokinetics



Readily absorbed after oral administration. Following IM administration, absorption of the water-soluble sodium succinate salt is rapid.


The duration of anti-inflammatory activity of hydrocortisone approximately equals the duration of HPA-axis suppression, about 1.25–1.5 days for a single 250-mg oral dose.



Most glucocorticoids are removed rapidly from the blood and distributed to muscle, liver, skin, intestines, and kidneys. Glucocorticoids appear in breast milk and cross the placenta.

Plasma Protein Binding

Extensively bound to corticosteroid-binding globulin (transcortin) and albumin.

Special Populations

Patients with low serum albumin concentrations may be more susceptible to effects of glucocorticoids than those with normal serum albumin concentrations.



Metabolized in most tissues, but primarily in the liver, to inactive compounds.

Elimination Route

Inactive metabolites are excreted by the kidneys, primarily as glucuronides and sulfates, but also as unconjugated products. Small amounts of unmetabolized drugs are also excreted in urine.


Following oral or IV administration of hydrocortisone, 1.5–3.5 hours.

Special Populations

Metabolic clearance may be decreased in patients with hypothyroidism and increased in those with hyperthyroidism.





Well-closed containers at 20–25°C.


Powder for Injection

Hydrocortisone sodium succinate: Store unreconstituted at 20–25°C.

Store reconstituted solution at 20–25°C; protect from light. Discard unused solutions after 3 days.


  • Principally an anti-inflammatory or immunosuppressant agent.

  • Exhibits potent anti-inflammatory activity and some mineralocorticoid properties.

  • Decreases inflammation by stabilizing leukocyte lysosomal membranes, preventing release of destructive acid hydrolases from leukocytes; or reducing leukocyte adhesion to capillary endothelium.

  • Inhibits macrophage accumulation in inflamed areas.

  • Reduces capillary wall permeability and edema formation.

  • Antagonizes histamine activity and release of kinin from substrates.

  • Reduces fibroblast proliferation, collagen deposition, and subsequent scar tissue formation.

  • Stimulates erythroid cells of bone marrow, prolongs survival time of erythrocytes and platelets, and produces neutrophilia and eosinopenia.

  • Promotes gluconeogenesis, redistribution of fat from peripheral to central areas of the body, and protein catabolism, which results in negative nitrogen balance.

  • Reduces intestinal absorption and increases renal excretion of calcium.

  • Suppresses the immune response by reducing activity and volume of the lymphatic system, producing lymphocytopenia.

  • Decreases immunoglobulin and complement concentrations and passage of immune complexes through basement membranes.

  • Depresses reactivity of tissue to antigen-antibody interactions.

  • In pharmacologic doses, suppresses release of corticotropin (ACTH) from the pituitary, thus, the adrenal cortex ceases secretion of endogenous corticosteroids (secondary adrenocortical insufficiency); degree and duration of HPA axis suppression depends on dose, frequency, and time of administration, and duration of therapy.

Advice to Patients

  • In patients receiving long-term therapy, importance of not discontinuing the drug abruptly.

  • Importance of notifying a clinician of any infections, signs of infections (e.g., fever, sore throat, pain during urination, muscle aches), or injuries that develop during therapy or within 12 months after therapy is discontinued.

  • When surgery is required, importance of informing the attending physician, dentist, or anesthesiologist of recent (within 12 months) glucocorticoid therapy.

  • Advise patients receiving orally inhaled glucocorticoid therapy who are currently being withdrawn or who have been withdrawn from systemic therapy to immediately resume full therapeutic dosages of systemic glucocorticoids and to contact their clinician for further instructions during stressful periods (e.g., severe infection, severe asthmatic attack).

  • In immunosuppressed patients, importance of avoiding exposure to certain infections (e.g., chickenpox, measles) and of obtaining medical advice if such exposure occurs.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name



Dosage Forms


Brand Names






5 mg*

Cortef (scored)


Hydrocortisone Tablets

10 mg*

Cortef (scored)


Hydrocortisone Tablets

20 mg*

Cortef (scored)


Hydrocortisone Tablets

Hydrocortisone Sodium Succinate


Dosage Forms


Brand Names



For injection

100 mg (of hydrocortisone)





250 mg (of hydrocortisone)



500 mg (of hydrocortisone)



1 g (of hydrocortisone)



AHFS DI Essentials™. © Copyright 2023, Selected Revisions February 28, 2023. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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