Hydrocortisone (Systemic)

AHFS Class: Adrenals (68:04)

ATC Class: H02AB09
VA Class: HS051

Compound F

Cortisol

View the associated AHFS monograph.

Brands: A-hydroCort^® , Cortef^® , Hydrocortone^® , Solu-Cortef^®; also available generically.

Introduction

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

Uses

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.^{a b}

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

Adrenocortical Insufficiency

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

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.^{a b} Concomitant administration of a more potent mineralocorticoid (fludrocortisone) may be required in some patients.^b

In suspected or known adrenal insufficiency, parenteral therapy may be used preoperatively or during serious trauma, illness, or shock unresponsive to conventional therapy.^{c d e}

In shock, IV therapy in conjunction with other therapy for shock is essential; hydrocortisone is preferred.^b

Adrenogenital Syndrome

Lifelong glucocorticoid treatment of congenital adrenogenital syndrome.^{a c d f}

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.^b

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

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.^b

Hypercalcemia

Treatment of hypercalcemia associated with malignancy.^{a b c d e f}

Usually ameliorates hypercalcemia associated with bone involvement in multiple myeloma.^b

Treatment of hypercalcemia associated with sarcoidosis†.^b

Treatment of hypercalcemia associated with vitamin D intoxication†.^b

Not effective for hypercalcemia caused by hyperparathyroidism†.^b

Thyroiditis

Treatment of granulomatous (subacute, nonsuppurative) thyroiditis.^{a c d e f}

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

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

Usually reserved for palliative therapy in severly ill patients unresponsive to salicylates and thyroid homones.^b

Rheumatic Disorders and Collagen Diseases

Short-term palliative 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†, rheumatic fever† [especially with carditis]) and collagen diseases (e.g., acute rheumatic carditis, systemic lupus erythematosus, dematomyositis† [polymyositis], polyareteristis nodosa†, vasculitis†) refractory to more conservative measures.^{a c d f}

Relieves inflammation and suppresses symptoms but not disease progression.^b

Rarely indicated as maintenance therapy.^b

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.^{a b c d f}

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

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;^b inflammation tends to recur and sometimes is more intense after drug cessation.^b

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

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.^b

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

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†.^b 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.^b

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

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

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

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.^{a c d f}

Usually reserved for acute exacerbations unresponsive to conservative therapy.^b

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

For control of severe or incapacitating allergic conditions (e.g., contact dermatitis, atopic dermatitis) intractable to adequate trials of conventional treatment.^{a c d e f}

Chronic skin disorders seldom an indication for systemic glucocorticoids.^b

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.^b

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

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

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.^{a b c d f}

Systemic therapy usually reserved for acute conditions and severe exacerbations.^b

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

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.^b

Ocular Disorders

To suppress a variety of allergic and nonpyogenic ocular inflammations.^b

To reduce scarring in ocular injuries†.^b

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).^{a c d}

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

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

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

Asthma

Adjunctively for moderate to severe exacerbations of asthma and for maintenance in persistent asthma.^{b j 554 556}

Systemically (oral or IV) for treatment of moderate to severe acute exacerbations of asthma (oral prednisone usually preferred); speeds resolution of airflow obstruction and reduces rate of relapse.^{j 554 556}

Because onset of effects is delayed, do not use alone for emergency treatment.^{b 556 637}

Early systemic glucocorticoid therapy particularly important for asthma exacerbations in infants and children.^{j 554 556}

In hospital management of an acute asthma exacerbation, may give systemic adjunctive glucocorticoids if response to oral inhalation therapy is not immediate, if oral corticosteroids were used as self-medication prior to hospitalization, or if the episode is severe.^{b 556}

For severe persistent asthma once intial control is achieved, high dosages of inhaled corticosteroids are preferable to oral glucocorticoids for maintenance because inhaled corticosteroids have fewer systemic effects.^{554 556}

Maintenance therapy with low doses of an orally inhaled corticosteroid is preferred treatment for adults and children with mild persistent asthma^{b 554 556} (i.e., patients with daytime symptoms of asthma more than twice weekly but less than once daily, and nocturnal symptoms of asthma more than twice per month).^{b 554}

Orally as an adjunct to other therapy to speed resolution of all but the mildest exacerbations of asthma when response to a short-acting inhaled β₂-agonist is not prompt or sustained after 1 hour or in those who have a history of severe exacerbations.^{b 554 556}

Oral glucocortocoids with minimal mineralocorticoid activity and relatively short half-life (e.g., prednisone, prednisolone, methylprednisolone) are preferred.⁵⁵⁶

COPD

For severe exacerbations of COPD, a short (e.g., 1–2 weeks) course of oral glucocorticoids can be added to existing therapy.^{564 565 624}

Effects in stable COPD are much less dramatic than in asthma, and role of glucocorticoids in the management of stable COPD is limited to very specific indications.⁶²⁴

Sarcoidosis

Management of symptomatic sarcoidosis.^{a b c d f}

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

Advanced Pulmonary and Extrapulmonary Tuberculosis

Systemically as adjunctive therapy with effective antimycobacterial agents (e.g., streptomycin, isoniazid) to suppress manifestations related to the host’s inflammatory response to the bacillus (Mycobacterium tuberculosis) and ameliorate complications in severe pulmonary or extrapulmonary tuberculosis.^a

Adjunctive glucocorticoid therapy may enhance short-term resolution of disease manifestations (e.g., clinical and radiographic abnormalities) in advanced pulmonary tuberculosis and also may reduce mortality associated with certain forms of extrapulmonary disease (e.g., meningitis, pericarditis).^{585 586 587 591 592 595 596 597}

Systemic adjunctive glucocorticoids may reduce sequelae (e.g., intellectual impairment) and/or improve survival in moderate to severe tuberculous meningitis.^{585 586 587 591 592 597}

Systemic adjunctive glucocorticoid therapy rapidly reduces the size of pericardial effusions and the need for drainage procedures and decreases mortality (probably through control of hemodynamically threatening effusion) in acute tuberculous pericarditis.^{585 586 595 596}

Hastens the resolution of pain, dyspnea, and fever associated with tuberculous pleurisy.^{b 585 586 591 595 596}

Lipid Pneumonitis

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

Pneumocystis jiroveci Pneumonia

Systemic adjunctive glucocorticoids decrease the likelihood of deterioration of oxygenation, respiratory failure, and/or death in moderate to severe Pneumocystis jiroveci (Pneumocystis carinii) pneumonia in acquired immunodeficiency syndrome† (AIDS).^{430 431 432 433 434 435}

Prevents early deterioration in oxygenation associated with antipneumocystis therapy; initiate adjunctive glucocorticoid therapy as early as possible in moderate to severe pneumocystis pneumonia.^{430 431 432 433 434 435 456}

Not known whether patients with mild pneumocystis pneumonia (arterial oxygen pressure >70 mm Hg or arterial-alveolar gradient <35 mm Hg on room air) will have clinically important benefit with adjunctive glucocorticoid therapy.

Other glucocorticoids (e.g., oral prednisone, parenteral methylprednisolone) generally are preferred.^{430 433 435}

Loeffler’s Syndrome

Symptomatic relief of acute manifestations of symptomatic Loeffler’s syndrome not manageable by other means.^{a b c d e f}

Berylliosis

Symptomatic relief of acute manifestations of berylliosis.^{a b c d e f}

Aspiration Pneumonitis

Symptomatic relief of acute manifestations of aspiration pneumonitis.^{a b c d e f}

Anthrax

Adjunct to anti-infective therapy in the treatment of anthrax† in an attempt to ameliorate toxin-mediated effects associated with Bacillus anthracis infections.^{612 613}

For cutaneous anthrax† if there are signs of systemic involvement or extensive edema involving the neck and thoracic region, ⁶¹² anthrax meningitis†,⁶¹² and inhalational anthrax† that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism if extensive edema, respiratory compromise, or meningitis is present.⁶¹¹

Antenatal Use in Preterm Labor

Short-course IM betamethasone or dexamethasone are preferred in selected women with preterm labor to hasten fetal maturation† (e.g., lungs, cerebral blood vessels), including women with preterm premature rupture of membranes, preeclampsia, or third-trimester hemorrhage.^{529 530 532 539 541} Insufficient experience to evaluate efficacy of hydrocortisone.⁶²¹

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.^{a b c d f}

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

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.^b

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

Shock

Although IV glucocorticoids may be life-saving in shock secondary to adrenocortical insufficiency (see Adrenocortical Insufficiency under Uses), the value of the drugs in the treatment of shock resulting from other causes† is controversial.^b

Management of shock should be based on specific treatment of the primary cause and secondary abnormalities, and glucocorticoids, if used, should be regarded only as adjunctive supportive treatment.

Value in adjunctive treatment of septic shock† is particularly controversial.^{399 400 401 409 410 411 412 413 414 415 416 418} Conflicting evidence regarding effects of high-dose regimens on morbidity and mortality in septic shock.^{402 401 409 410 416 417 418 426}

Pericarditis

To reduce the pain, fever, and inflammation of pericarditis†, including that associated with MI.^b

Glucocorticoids can provide effective symptomatic relief, but aspirin considered the treatment of choice for postmyocardial infarction pericarditis because of greater evidence establishing benefit.⁵⁸²

Important to distinguish between pain caused by pericarditis and that caused by ischemia since management will differ.⁵⁸²

Consider possibility that cardiac rupture may account for recurrent pain since use of glucocorticoids may be a risk factor in its development.⁵⁸²

Glucocorticoids may cause thinning of developing scar and myocardial rupture.^{582 583 584}

Management of tuberculous pericarditis.^{585 586 595 596} (See Advanced Pulmonary and Extrapulmonary Tuberculosis under Uses.)

GI Diseases

Short-term palliative therapy for acute exacerbations and systemic complications of ulcerative colitis, regional enteritis, and celiac disease†.^{a b c d f}

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

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.^b

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

Crohn’s Disease

Management of mildly to moderately active and moderately to severely active Crohn’s disease.^f

Some experts state that conventional glucocorticoids should not be used for the management of mildly to moderately active disease, because of the high incidence of adverse effects and their use should be reserved for patients with moderately to severely active disease.

Parenteral glucocorticoids recommended for patients with severe fulminant Crohn’s disease†. Once patients respond to parenteral therapy, they should gradually be swiched to an equivalent regimen of an oral glucocorticoid.

Glucocorticoids should not be used for maintenance therapy of Crohn’s disease, because they usually do not prevent relapses and the drugs may produce severe adverse reactions with long-term administration.

Glucocorticoids have been used in the management of moderately to severely active Crohn’s disease and in mild esophageal or gastroduodenal Crohn’s disease† in pediatric patients.

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).^{a b c d e f}

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.^b

Glucocorticoids alone or as a component of various combination chemotherapeutic regimens for palliative treatment of advanced, symptomatic (i.e., painful) hormone-refractory prostate cancer.^{544 545 546 547 549 550}

Head Injury

Efficacy of glucocorticoid therapy is not established in patients with head injury; such therapy can be detrimental and is associated with a substantial increase in risk of death. Use to improve outcome or reduce intracranial pressure not recommended in patients with head injury.

Cerebral Malaria

Glucocorticoids are not effective and can have detrimental effects in the management of cerebral malaria caused by Plasmodium falciparum; no longer recommended for this condition.^b

Multiple Sclerosis

Glucocorticoids are drugs of choice for the management of acute relapses of multiple sclerosis†.⁵⁷⁴

Anti-inflammatory and immunomodulating effects accelerate neurologic recovery by restoring the blood-brain barrier, reducing edema, and possibly improving axonal conduction.⁵⁷⁴

Shortens the duration of relapse and accelerates recovery; remains to be established whether the overall degree of recovery improves or the long-term course is altered.^{419 420 421 422 423 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 574}

Myasthenia Gravis

Management of myasthenia gravis†, usually when there is an inadequate response to anticholinesterase therapy.^{627 628}

Parenterally for the treatment of myasthenic crisis.⁶²⁹

Organ Transplants

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

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

Trichinosis

Treatment of trichinosis with neurologic or myocardial involvement.^{a c d f}

Nephrotic Syndrome and Lupus Nephritis

Treatment of idiopathic nephrotic syndrome without uremia.^{a c d f f}

Can induce diuresis and remission of proteinuria in nephrotic syndrome^{a b c d f} secondary to primary renal disease, especially when there is minimal renal histologic change.^b

Treatment of lupus nephritis.^{a b c d}

Dosage and Administration

General

• Route of administration and dosage depend on the condition being treated and the patient response.^{a b}

• 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.^b This regimen provides relief of symptoms while minimizing adrenal suppression, protein catabolism, and other adverse effects.^b

• 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.^b

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

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

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

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

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

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

• Other recommendations state that decrements usually should not exceed 10 mg every 1–2 weeks.^b 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.^b

• 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).^{a b} Administer an initially high dose on the first day of therapy, and then withdraw therapy by tapering the dose over several days.^{a b}

Administration

Administer orally, by IV injection or infusion, or IM or sub-Q injection.^a

Administer for local effect by intra-articular, intralesional, or soft-tissue injection.^g

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

Hydrocortisone. Administer orally as tablets.^a

Hydrocortisone Sodium Phosphate. Administer by IV injection or by IV infusion.^a Usually given parenterally at 12-hour intervals.

Dilution of Hydrocortisone Sodium Phosphate. When administered by IV infusion, the drug can be added to dextrose or sodium chloride injections.^a

Hydrocortisone Sodium Succinate. Administer by IV injection or by IV infusion.^a

Reconstitution of Hydrocortisone Sodium Succinate. Reconstitute for IV injection with bacteriostatic water for injection or bacteriostatic 0.9% sodium chloride injection according to the manufacturer’s instructions.^a

Dilution of Hydrocortisone Sodium Succinate. 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.^a

Rate of Administration of Hydrocortisone Sodium Succinate. When the drug is administered by direct IV injection, administer over a period of at least 30 seconds.^a

Hydrocortisone Sodium Phosphate. Administer by IM injection.^a Usually the drug is given parenterally at 12-hour intervals.^a

Hydrocortisone Sodium Succinate. Administer by IM injection.^a

Reconstitution of Hydrocortisone Sodium Succinate. Reconstitute for IM injection with bacteriostatic water for injection or bacteriostatic 0.9% sodium chloride injection according to the manufacturer’s instructions.^a

Hydrocortisone Sodium Phosphate. Administer by sub-Q injection.^a Usually the drug is given parenterally at 12-hour intervals.^a

Hydrocortisone Acetate. Administer by intra-articular, intrasynovial, intrabursal, intralesional, or soft-tissue injection.^a

Systemic absorption of hydrocortisone acetate from intra-articular injection sites is usually complete within 24–48 hours.^a

A local anesthetic, such as procaine hydrochloride, may be infiltrated into the soft tissue surrounding the joint and/or injected into the joint before the administration of hydrocortisone acetate.^a Alternatively, the local anesthetic may be mixed in the syringe with hydrocortisone acetate suspension immediately prior to administration.^a

Dosage

Available as hydrocortisone, hydrocortisone acetate, hydrocortisone sodium phosphate, and hydrocortisone sodium succinate; dosage of hydrocortisone sodium phosphate and sodium succinate is expressed in terms of hydrocortisone and dosage of hydrocortisone acetate is expressed in terms of hydrocortisone acetate.^{c d e f g m}

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.^{a b}

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.^b

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

Massive dosages may be required for the treatment of shock.^b

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

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.^a

Usual Dosage.

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

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

> IM— Hydrocortisone sodium phosphate: 0.16–1 mg/kg or 6–30 mg/m² IM 1 or 2 times daily.^a Hydrocortisone sodium succinate: 0.16–1 mg/kg or 6–30 mg/m² IM 1 or 2 times daily.^a

Usual Dosage.

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

> IV— Hydrocortisone sodium phosphate: Initially, 15–240 mg IV daily depending on the disease being treated.^a In life-threatening situations, extremely high parenteral dosage may be justified and may be a multiple of the usual oral dosage.^a Hydrocortisone sodium succinate: 100 mg to 8 g daily.^a 100–500 mg IV initially, and every 2–10 hours as needed.^a

> IM— Hydrocortisone sodium phosphate: 15–240 mg IM daily, depending on the disease being treated.^a In life-threatening situations, extremely high parenteral dosage may be justified and may be a multiple of the usual oral dosage.^a Hydrocortisone sodium succinate: 100 mg to 8 g daily.^a 100–500 mg IM initially and every 2–10 hours as needed.^a

> Sub-Q— Hydrocortisone sodium phosphate: 15–240 mg daily depending on the disease being treated.^a In life-threatening situations, extremely high parenteral dosage may be justified and may be a multiple of the usual oral dosage.^a

> Intra-articular, Intrasynovial, Intrabursal, or Intralesional Injection, or Soft-tissue Injection— Varies depending on location, size, and degree of inflammation.^a Large joints (e.g., knee): 25–50 mg of hydrocortisone acetate; may repeat once every 1–4 weeks.^a Smaller joints: 10–25 mg of hydrocortisone acetate; may repeat once every 1–4 weeks.^a Bursae: 25–50 mg of hydrocortisone acetate; may repeat once every 3–5 days.^a Ganglia: 10–25 mg;^a repeat as needed.Soft-tissues: 5–12.5 mg for tendon sheath inflammation and 25–75 mg for soft tissue infiltration;^a repeat as needed.

Shock†.

> IV— 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.^a 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.^a In such cases, administer by direct IV injection over a period of one to several minutes.^a Continue high-dose therapy only until the patient’s condition has stabilized and usually not beyond 48–72 hours.^a 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.^a

Cautions

Contraindications

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

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

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

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

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

Warnings/Precautions

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).^b

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.^b

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.^{b d}

Withdraw hydrocortisone very gradually following long-term therapy with pharmacologic dosages.^{b c} (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.^{b c}

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.^b Since mineralocorticoid secretion may be impaired, sodium chloride and/or a mineralocorticoid should also be administered.^{b c}

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

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

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

Increased Susceptibility to Infection. Glucocorticoids, especially in large doses, increase susceptibility to and mask symptoms of infection.^{f c f}

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.^{417 477 485 486 599 603 c f}

Infections may be mild, but they can be severe or fatal, and localized infections may disseminate.^{417 477 485 486 599 603 c f}

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

Some infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome, particularly in children.^{486 487 488 489 490 491 492 493 494 603 614 615 c f}

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.^{486 487 488 489 603 c f}

If exposure to varicella or measles occurs in susceptible patients, treat appropriately (e.g., VZIG, IG, acyclovir).^{486 487 488 489 603 c f}

Fatal outcome (e.g., in those developing hemorrhagic varicella) may not always be avoided even if appropriate therapy is initiated aggressively.^{489 493}

Immunosuppression may result in activation of latent infection or exacerbation of intercurrent infections (e.g., those caused by Candida, Mycobacterium, Toxoplasma, Strongyloides, Pneumocystis, Cryptococcus, Nocardia, Ameba).⁵⁹⁹

Use with great care in patients with known or suspected Strongyloides (threadworm) infection.^{417 477 485 486 599} Immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.^{417 485 486 599 603}

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.^d

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

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

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

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.^b These adverse effects may be especially serious in geriatric or debilitated patients.^b A high-protein diet may help to prevent adverse effects associated with protein catabolism.^b

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).^{417 599 c}

Tendon rupture, particularly of the Achilles tendon.^{477 485 486 599 603 c}

Osteoporosis and related fractures are one of the most serious adverse effects of long-term glucocorticoid therapy.^{572 622}

To minimize the risk of glucocorticoid-induced bone loss, the smallest possible effective dosage and duration should be used.⁵⁷² Topical and inhaled preparations should be used whenever possible.⁵⁷²

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

Withdraw glucocorticoids if osteoporosis develops, unless their use is life-saving.

Glucocorticoid-induced bone loss can be both prevented and treated.^{572 622} Baseline measurement of bone mass density (BMD) at the lumbar spine and/or hip should be obtained when initiating long-term (e.g., exceeding 6 months) glucocorticoid therapy and appropriate preventive therapy should be initiated.⁶²² Longitudinal measurements may be repeated as often as every 6 months to detect possible bone loss.⁶²² Less frequent (e.g., annually) follow-up probably is sufficient in patients who are receiving therapy to prevent bone loss.⁶²²

Skeletal wasting is most rapid during the initial 6 months of therapy, and trabecular bone is affected to a greater degree than is cortical bone.⁵⁷²

Calcium and vitamin D supplementation, bisphosphonate (e.g., alendronate, risedronate), and a weight-bearing exercise program that maintains muscle mass are suitable first-line therapies aimed at reducing the risk of adverse bone effects.^{572 606 622}

Calcitonin may be considered as second-line therapy for patients who refuse or do not tolerate bisphosphonate therapy or in whom the drugs are contraindicated.⁶²²

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.^{b c} Edema and CHF (in susceptible patients) may occur.^{b c}

Dietary salt restriction is advisable and potassium supplementation may be necessary.^{b c}

Increased calcium excretion and posible hypocalcemia.^{b c}

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.^{b 553}

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

Do not use in patients with active ocular herpes simplex infections for fear of corneal perforation.^{b c}

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

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

Exaggerated response to the glucocorticoids in hypothyroidism.^{b c}

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.^b

Anaphylactic and hypersensitivity reactions.^{b d}

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.^b 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.^b

Monitoring. 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.^b

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

During long-term therapy, perform periodic height, weight, chest and spinal radiographs, hematopoietic, electrolyte, glucose tolerance, and ocular and blood pressure evaluations.^{551 599 605}

GU Effects. Increased or decreased motility and number of sperm in some men.^{b c}

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

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

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.^c

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.^b

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.^b

Kaposi’s sarcoma reported in patients receiving glucocorticoids; discontinuance may result in clinical remission.^{c d}

Pregnancy.

Category C.^d

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

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

Glucocorticoid-induced osteoporosis and associated fractures are common in children and adolescents receiving long-term systemic therapy. In addition, may prevent achievement of peak bone mass during adolescence by inhibiting bone formation. Methods for monitoring bone mineralization (e.g., dual-energy x-ray absorptiometry [DXA]) in children and adolescents are similar to those in adults.

Ensure children and adolescents consistently ingest adequate calcium and vitamin D either through diet or supplementation.

Some commercially available injections contain benzyl alcohol as a preservative.^b 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.^b

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.^b

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.^b May be especially serious in geriatric or debilitated patients.^b

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

Use with caution in patients with osteoporosis.^d

Hepatic Impairment. Patients with cirrhosis show an exaggerated response to glucocorticoids.^{b c}

Renal Impairment. Use with caution.^c

Common Adverse Effects

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

Interactions

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: potential pharmacokinetic interaction (decreased hydrocortisone clearance).^{c e}

Inducers of CYP3A4: potential pharmacokinetic interaction (increased hydrocortisone clearance).^{a c}

Specific Drugs

Pharmacokinetics

Absorption

Readily absorbed after oral administration.^b Following IM administration, absorption of the water-soluble sodium phosphate and sodium succinate salts is rapid; the rate of absorption of the lipid-soluble acetate is much slower.^b

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.^b

Distribution

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

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

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