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Cortisone Acetate

Pronunciation

Class: Adrenals
ATC Class: H02AB10
VA Class: HS051
CAS Number: 50-04-4

Introduction

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

Uses for Cortisone Acetate

Treatment of a wide variety of diseases and conditions; principally used 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.b c e

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

Glucocorticoid therapy is not curative; rarely indicated as the primary method of treatment.c Supportive therapy used adjunctively with other indicated therapies.c

Adrenocortical Insufficiency

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

Cortisone or hydrocortisone (in conjunction with liberal salt intake) are the corticosteroids of choice for replacement therapy in patients with adrenocortical insufficiency because these drugs have both glucocorticoid and mineralocorticoid properties.b c e Concomitant administration of a more potent mineralocorticoid (fludrocortisone) may be required in some patients, especially infants.

Adrenogenital Syndrome

Lifelong glucocorticoid treatment of congenital adrenogenital syndrome.b c e

In salt-losing forms, cortisone or hydrocortisone is preferred in conjunction with liberal salt intake; an additional mineralocorticoid may be necessary through ≥5–7 years of age.c After early childhood, a glucocorticoid alone is used for long-term therapy throughout life.c

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.c

Hypercalcemia

Treatment of hypercalcemia associated with malignancy.b c e

Usually ameliorates hypercalcemia associated with bone involvement in multiple myeloma.c

Treatment of hypercalcemia associated with sarcoidosis.c

Treatment of hypercalcemia associated with vitamin D intoxication.c

Not effective for hypercalcemia caused by hyperparathyroidism.c

Thyroiditis

Treatment of granulomatous (subacute, nonsuppurative) thyroiditis.b c e

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

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

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

Rheumatic Disorders and Collagen Diseases

Short-term palliative treatment of acute episodes or exacerbations and systemic complications of rheumatic disorders (e.g., psoriatic arthritis, rheumatoid arthritis, juvenile arthritis, ankylosing spondylitis, posttraumatic osteoarthritis, acute and subacute bursitis, synovitis of osteoarthritis, acute nonspecific tenosynovitis, epicondylitis, acute gouty arthritis) and collagen diseases (e.g., systemic lupus erythematosus, acute rheumatic carditis, systemic dermatomyositis [polymyositis]) refractory to more conservative therapy. b c e

Relieves inflammation and suppresses symptoms, but does notaffect disease progression.c

Maintenance therapy (e.g., rheumatoid arthritis, acute gouty arthritis, or systemic lupus erythematosus) as part of a total treatment program in selected patients when more conservative therapies have proven ineffective; however, rarely indicated as maintenance therapy.c

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

Controls acute manifestations of rheumatic carditis more rapidly than salicylates and may be life-saving in certain conditions; however, cannot prevent valvular damage. No better than salicylates for long-term treatment.c

Used adjunctively for severe systemic complications of Wegener’s granulomatosis; however, cytotoxic therapy is the treatment of choice.c

Primary treatment to control symptoms and prevent severe, often life-threatening complications in patients with dermatomyositis and polymyositis, polyarteritis nodosa, relapsing polychondritis, polymyalgia rheumatica, and giant-cell (temporal) arteritis, or mixed connective tissue disease syndrome.c May require high dosage for acute situations; after obtaining a response, continue drug at a low dosage for long periods.c

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

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

Dermatologic Diseases

Treatment of acute exacerbations 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 that are unresponsive to conservative therapy.b c e

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

Chronic skin disorders are seldom an indication for systemic glucocorticoids.c

Used for severe psoriasis but rarely indicated systemically; if used, exacerbation may occur when the drug is withdrawn or dosage is decreased.c

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

Allergic Conditions

Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment; for control of acute manifestations, including angioedema, bronchial asthma, contact or atopic dermatitis, serum sickness, allergic symptoms of trichinosis, urticarial transfusion reactions, drug hypersensitivity reactions, and severe seasonal or perennial rhinitis.b c e

Reserve systemic therapy for acute conditions and severe exacerbations.c

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

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

Ocular Disorders

Used to suppress a variety of allergic and nonpyogenic ocular inflammations and to reduce scarring in ocular injuries.c

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

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

Less severe allergic and inflammatory allergic conditions of the eye are treated with topical (to the eye) corticosteroids; treat systemically in difficult cases of anterior segment eye disease and when deeper ocular structures are involved.c

Asthma

Adjunct for moderate to severe exacerbations of asthma and for maintenance in persistent asthma.c

Systemic (oral or IV) glucocorticoids are used for treatment of moderate to severe acute exacerbations of asthma (oral prednisone usually preferred); speeds resolution of airflow obstruction and reduces rate of relapse.c f g k

Because onset of effects is delayed, do not use alone for emergency treatment.c

Early systemic glucocorticoid therapy is particularly important for asthma exacerbations in infants and children.c f g

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.c f g

For severe persistent asthma once initial control is achieved, high dosages of inhaled corticosteroids are preferable to oral glucocorticoids for maintenance because inhaled corticosteroids have fewer systemic effects.f g

Maintenance therapy with low doses of an orally inhaled corticosteroid is preferred treatment for adults and children with mild persistent asthma (i.e., patients with daytime symptoms of asthma > twice weekly but <once daily, and nocturnal symptoms of asthma >twice per month).c f g

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.c f g

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

COPD

For severe exacerbations of COPD, a short (e.g., 10–14 days) course of oral glucocorticoids can be added to existing therapy.h

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.c h

Not for long-term treatment of COPD.c

Sarcoidosis

Management of symptomatic sarcoidosis.b c e

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

Advanced Pulmonary and Extrapulmonary Tuberculosis

Adjunctive systemic 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.b e

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).

Systemic adjunctive glucocorticoids may reduce sequelae (e.g., intellectual impairment) and/or improve survival in moderate to severe tuberculous meningitis.

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.

Systemic adjunctive glucocorticoids hasten the resolution of pain, dyspnea, and fever associated with tuberculous pleurisy.

Lipid Pneumonitis

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

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).

Prevents early deterioration in oxygenation associated with antipneumocystis therapy; initiate adjunctive glucocorticoid therapy as early as possible in moderate to severe pneumocystis pneumonia.

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.

Löffler’s Syndrome

Symptomatic relief of acute manifestations of symptomatic Löffler’s syndrome not manageable by other means.b c e

Berylliosis

Symptomatic relief of acute manifestations of berylliosis.b c e

Aspiration Pneumonitis

Symptomatic relief of acute manifestations of aspiration pneumonitis.b c e

Hematologic Disorders

Management of acquired (autoimmune) hemolytic anemia, idiopathic thrombocytopenic purpura (ITP), secondary thrombocytopenia, erythroblastopenia (RBC anemia), congenital (erythroid) hypoplastic anemia (Diamond-Blackfan syndrome), and pure red cell aplasia.b c e

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

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

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

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

Pericarditis

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

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

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

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

Glucocorticoids may cause thinning of developing scar and myocardial rupture.

Management of tuberculous pericarditis. (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.b c e

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

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

Low dosages of glucocorticoids, in conjunction with other supportive therapy, may occasionally be useful for patients unresponsive to usual therapy for chronic conditions.c

Crohn’s Disease

Management of mild to moderately active and moderate to severely active Crohn’s disease.

Many experts state that glucocorticoids should not be used for the management of mild to moderately active disease because of the high incidence of adverse effects and their use should be reserved for patients with moderate 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 switched to an equivalent regimen of an oral glucocorticoid.

Do not use glucocorticoids for maintenance therapy; usually do not prevent relapses and may produce severe adverse effects with long-term administration.

Glucocorticoids have been used in the management of moderate 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, acute leukemias in children).b c e

Treatment of breast cancer. Glucocorticoids alone not as effective as other agents (e.g., cytotoxic agents, hormones, antiestrogens); reserve for unresponsive disease.c

Glucocorticoids alone or as a component of various combination chemotherapeutic regimens for palliative treatment of advanced, symptomatic (i.e., painful) hormone-refractory prostate cancer.

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.c

Myasthenia Gravis

Management of myasthenia gravis, usually when there is an inadequate response to anticholinesterase therapy.

Nephrotic Syndrome and Lupus Nephritis

Treatment of idiopathic nephrotic syndrome without uremia.b c e

Induce diuresis and remission of proteinuria in nephrotic syndromeb c e (e.g., idiopathic type) secondary to primary renal disease, especially when there is minimal renal histologic change.c

Treatment of lupus nephritis.b c e

Trichinosis

Treatment of trichinosis with neurologic or myocardial involvement.b c e

Cortisone Acetate Dosage and Administration

General

Alternate-day Therapy

  • If used for prolonged therapy, consider an alternate-day dosage regimen.a c

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

  • If alternate-day therapy is preferred, only use a “short-acting” glucocorticoid that suppresses the HPA axis <1.5 days after a single oral dose (e.g., cortisone, hydrocortisone, prednisone, methylprednisolone).c

  • 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.c

Discontinuance of Therapy

  • Following long-term therapy with pharmacologic dosages, very gradually withdraw systemic glucocorticoids until recovery of HPA-axis function occurs.a c e (See Adrenocortical Insufficiency under Cautions.)

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

  • In one suggested regimen, decrease by 12.5–25 mg every 3–7 days until the physiologic dose (25 mg) is reached.c

  • Other recommendations state that decrements usually should not exceed 12.5 mg every 1–2 weeks; in alternate-day therapy, decrements should not exceed 25 mg every 1–2 weeks.c

  • When physiologic dosage (25 mg) is reached, substitute single 20-mg oral morning doses of hydrocortisone.c 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.c

  • If disease flares during withdrawal, increase dosage and withdraw more gradually.c

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

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

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

Administration

Oral Administration

Administer orally as tablets.a b e

To decrease gastric irritation, take immediately before, during, or after meals, or with food or milk.c e Some experts recommend antacids between meals to help prevent peptic ulcer formation.e

Dosage

Available as cortisone acetate; dosage expressed in terms of the salt.a

Individualize dosage carefully according to the diagnosis, severity, prognosis, probable duration of the disease, and patient response and tolerance.c e

After a satisfactory response is obtained, decrease dosage in small decrements to the lowest level that maintains an adequate clinical response, and discontinue the drug as soon as possible.a b c e

Long-term therapy should not be initiated without due consideration of its risks.c If necessary, administer in the smallest dosage possible.c Continual monitoring is recommended for signs that indicate dosage adjustment is necessary (e.g., remission or exacerbations of the disease, stress [surgery, infection, trauma]).a b c e

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

Pediatric Patients

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

Usual Dosage
Oral

0.7–10 mg/kg daily or 20–300 mg/m2 daily in 4 divided doses.a

Adults

Usual Dosage
Oral

Initially, 25–300 mg daily.a b e

Special Populations

Hepatic Impairment

Cirrhosis: Lower dosage may be required; select dosage with caution.e (See Hepatic Impairment under Cautions.)

Renal Impairment

No specific dosage recommendations at this time.b e

Geriatric Patients

No specific dosage recommendations at this time.b e

Thyroid Conditions

Changes in thyroid status may necessitate adjustment of glucocorticoid dosage.c (See Special Populations under Pharmacokinetics.)

Cautions for Cortisone Acetate

Contraindications

  • Known hypersensitivity to cortisone or any ingredient in the formulation.b c e

  • Systemic fungal infections.b e

  • Concurrent administration of live virus or live, attenuated vaccines in patients receiving immunosuppressive doses of corticosteroids.b c e (See Immunosuppression under Cautions and also Specific Drugs and Laboratory Tests under Interactions.)

Warnings/Precautions

Warnings

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).c

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

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 c e

Withdraw cortisone very gradually following long-term therapy with pharmacologic dosages.b c e (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.c

Until recovery occurs, signs and symptoms of adrenal insufficiency may develop if subjected to stress (e.g., surgery, trauma, infection), and replacement therapy may be required. c

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

Immunosuppression

Increased susceptibility to infections secondary to glucocorticoid-induced immunosuppression.b e (See Increased Susceptibility to Infection under Cautions.)

Administration of live virus vaccines, including smallpox, is contraindicated in patients receiving immunosuppressive dosages of glucocorticoids.b c e If inactivated viral or bacterial vaccines are administered to such patients, may not obtain the expected serum antibody response.b c e The USPHS Advisory Committee on Immunization Practices (ACIP) and American Academy of Family Physicians (AAFP) state that administration of live virus vaccines usually is not contraindicated in patients receiving corticosteroid therapy under the following circumstances:

  • short-term (<2 weeks) therapy

  • low to moderate dosage

  • long-term alternate-day treatment with short-acting preparations

  • maintenance physiologic dosages (replacement therapy)

  • topical, ophthalmic, intra-articular, bursal, or intratendon administration.c

Increased Susceptibility to Infection

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

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.b

Infections may be mild, but they can be severe or fatal, and localized infections may disseminate.b The rate of occurrence of infectious complications increases with increasing corticosteroid doses.b

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

Some infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome, particularly in children.b Children and adults who are not likely to have been exposed to varicella or measles should avoid exposure to these infections while receiving glucocorticoids.b

If exposure to varicella or measles occurs in susceptible patients, treat appropriately (e.g., VZIG, IG, acyclovir).b e Fatal outcome (e.g., in those developing hemorrhagic varicella) may not always be avoided even if appropriate therapy is initiated aggressively.

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

Use with great care in patients with known or suspected Strongyloides (threadworm) infection.b Immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.b

Do not use in the management of cerebral malaria; drug is not effective and can have detrimental effects (prolongation of coma, higher incidence of pneumonia, and GI bleeding).c e

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

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

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

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).

Possible tendon rupture, particularly of the Achilles tendon.e

Osteoporosis and related fractures are one of the most serious adverse effects of long-term glucocorticoid therapy.e To minimize the risk of glucocorticoid-induced bone loss, use the smallest possible effective dosage and duration. Use topical and inhaled preparations whenever possible. Withdraw glucocorticoids if osteoporosis develops, unless use is life-saving.c

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

Glucocorticoid-induced bone loss can be both prevented and treated. Obtain baseline measurement of bone mineral density (BMD) at the lumbar spine and/or hip when initiating long-term (e.g., >6 months) glucocorticoid therapy and initiate appropriate preventive therapy. Repeat longitudinal measurements as often as every 6 months to detect possible bone loss. Annual follow-up probably is sufficient in patients who are receiving therapy to prevent bone loss.

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.

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. 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.

Fluid and Electrolyte Disturbances

Sodium retention with resultant edema, potassium loss, and hypertension may occur with average or large doses of cortisone.b c e Edema, hypokalemic alkalosis, and CHF (in susceptible patients) may occur.c e

Dietary salt restriction is advisable, and potassium supplementation may be necessary.b c e

Causes increased calcium excretion and possible hypocalcemia.b c e

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 c e

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

Use with caution in ocular herpes simplex; risk of corneal perforation.b e

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 c e

May increase or decrease motility and number of sperm in some men.c e

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

Hypothyroidism may produce an exaggerated response to glucocorticoids.b c e

Cardiovascular Effects

Use with extreme caution in recent MI; suggested association between use of glucocorticoids and left ventricular free-wall rupture.c e

May increase blood coagulability and precipitate intravascular thrombosis, thromboembolism, and thrombophlebitis.c Use with caution in patients with thromboembolic disorders.c

General Precautions

Monitoring

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

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

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

Nervous System Effects

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

Use with caution in patients with myasthenia gravis,b particularly if receiving anticholinesterase therapy. (See Specific Drugs and Laboratory Tests under Interactions.)

May cause increased intracranial pressure with papilledema (pseudotumor cerebri), usually after treatment.e

GI Effects

Use 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.b e

Use with caution in active or latent peptic ulcer.b c e Manifestations of peritoneal irritation following GI perforation may be minimal or absent in patients receiving corticosteroids.c Consider antiulcer therapy in patients at increased risk of peptic ulcer formation.c

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 c e

Kaposi’s sarcoma reported in patients receiving glucocorticoid therapy; remission may occur if glucocorticoid is discontinued.b

May suppress skin test reactions.b e (See Specific Drugs and Laboratory Tests under Interactions.)

Specific Populations

Pregnancy

Category C. (First trimester: Category D).d

Observe infants carefully for signs of hypoadrenalism if substantial doses received during pregnancy.b e

Lactation

Distributed into milk.c e Discontinue nursing if taking pharmacologic doses.e

May suppress growth, interfere with endogenous glucocorticoid production, or cause other adverse effects in nursing infants.c

Pediatric Use

Perform periodic evaluations of height, weight, ocular pressure, and BP in pediatric patients receiving glucocorticoid therapy.c Evaluate for the presence of infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis.c

Long-term use may delay growth and maturation in infants and children; monitor carefully.b c Titrate dosage to the lowest effective level.c Alternate-day therapy with glucocorticoids that cause shorter HPA-axis suppression than does dexamethasone (e.g., prednisone, cortisone, methylprednisolone) may minimize growth suppression; institute if growth suppression occurs.c

Glucocorticoid-induced osteoporosis and associated fractures are common in children and adolescents receiving long-term systemic therapy; 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.

Geriatric Use

With prolonged therapy, muscle wasting, muscle pain or weakness, delayed wound healing, 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; especially serious in geriatric or debilitated patients.c

Postmenopausal women are especially prone to osteoporosis; use with caution.c (See Musculoskeletal Effects under Warnings.)

Hepatic Impairment

Use with caution in cirrhosis; exaggerated glucocorticoid response.b c e

Renal Impairment

Use with caution in patients with renal insufficiency.b c

Common Adverse Effects

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

Interactions for Cortisone Acetate

Metabolized by CYP3A4.c

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (decreased cortisone clearance).c

Inducers of CYP3A4: Potential pharmacokinetic interaction (increased cortisone clearance).c

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Amphotericin B

May enhance the potassium-wasting effect of glucocorticoidsc

Monitor for development of hypokalemiac

Anticoagulants, oral

Conflicting reports of diminished as well as enhanced response to anticoagulantsb c e

Monitor coagulation indices frequentlyb c e

Anticholinesterase agents

Severe weakness with concomitant use of anticholinesterase agents and corticosteroids in patients with myasthenia gravisc

If possible, withdraw anticholinesterase therapy ≥24 hours before initiating corticosteroid therapyc

Antidiabetic therapy

Glucocorticoids may increase blood glucose concentrations

May require dosage adjustment of concurrent insulin and/or oral hypoglycemics

Barbiturates

Possible increased metabolism of cortisonec

May require increases in the dosage of cortisonec

Cyclosporine

Possible increased activity of cyclosporine and corticosteroidsc

Seizures reported with concomitant usec

Consider possibility of exacerbated toxicity (seizures), as well as need for dosage adjustment with concomitant usec

Diuretics, potassium-depleting (e.g., thiazides, furosemide, ethacrynic acid)

May enhance the potassium-wasting effects of glucocorticoidsc e

Monitor for development of hypokalemiac e

Ephedrine

Possible increased metabolism of cortisonec e

May require increases in the dosage of cortisonec e

Estrogens

May potentiate effects of glucocorticoidsc

May be necessary to decrease corticosteroid dosage when estrogen is initiated or increase corticosteroid dosage when estrogen is discontinuedc

Ketoconazole

Possible decreased metabolism of corticosteroidsb c

May require decreases in the dosage of cortisonec

NSAIAs

Increases the risk of GI ulcerationc

Decreased serum salicylate concentrations;c when corticosteroids are discontinued, serum salicylate concentration may increase possibly resulting in salicylate intoxicationc

Use concurrently with cautionb c

Observe closely for adverse effects of either drugc

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

Phenytoin

Possible increased metabolism of cortisoneb c e

May require increases in the dosage of cortisonec e

Rifampin

Possible increased metabolism of cortisoneb c e

May require increases in the dosage of cortisoneb c e

Tests for nitroblue tetrazolium

May produce false-negative results in the nitroblue tetrazolium test for systemic bacterial infectionc e

Tests for thyroid function

May decrease iodine 131 uptake and protein-bound iodine concentrations, making it difficult to monitor the therapeutic response of patients receiving the drugs for thyroiditisc

Tests involving skin antigens

Depresses skin reactivity to antigen-antibody interactionsb c

Troleandomycin

Possible decreased metabolism of cortisonec

May require decreases in the dosage of cortisonec

Vaccines and toxoids

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

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

Can aggravate neurologic reactions to some vaccines (supraphysiologic dosages) c

Live virus vaccines contraindicated in individuals receiving immunosuppressive cortisone dosesb

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

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

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

Cortisone Acetate Pharmacokinetics

Absorption

Bioavailability

Readily absorbed after oral administration.c

Duration

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

Distribution

Extent

Most corticosteroids are rapidly removed from blood and distributed to muscles, liver, skin, intestines, and kidneys in animals.c

Cortisone crosses the placenta and is distributed into milk.c

Elimination

Metabolism

Principally in liver to hydrocortisone, the active metabolite.c Further metabolized in most tissues (principally in the liver) to inactive compounds.c

Elimination Route

Excreted principally by the kidneys, mainly as metabolites.c

Special Populations

Metabolic clearance may be decreased in patients with hypothyroidism and increased in those with hyperthyroidism.c (See Dosage under Dosage and Administration.)

Stability

Storage

Oral

Tablets

20–25°C;b e protect from light and moisture.e

Actions

  • Principally an anti-inflammatory or immunosuppressant agent; exhibits potent anti-inflammatory activity and some mineralocorticoid properties.b c e

  • In physiologic doses, replaces deficient endogenous hormones.b c e

  • In pharmacologic doses, decreases inflammation and suppresses the immune response.c

  • Stabilizes leukocyte lysosomal membranes, preventing release of destructive acid hydrolases from leukocytes; reduces leukocyte adhesion to capillary endothelium; inhibits macrophage accumulation in inflamed areas, and reduces capillary wall permeability and edema formation.c

  • Antagonizes histamine activity and release of kinin from substrates; reduces fibroblast proliferation, collagen deposition, and subsequent scar tissue formation.c

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

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

  • Reduces intestinal absorption and increases renal excretion of calcium.c

  • Suppresses release of corticotropin (adrenocorticotropic hormone, ACTH) from the pituitary; resulting in cessation of endogenous corticosteroid secretion (secondary adrenocortical insufficiency).c

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

  • Promotes sodium reabsorption, and potassium and hydrogen excretion, along with subsequent water retention through a mineralocorticoid action on the part of the renal distal tubule that facilitates sodium transport.b

Advice to Patients

  • In patients receiving long-term therapy, importance of reducing dose gradually and not discontinuing the drug abruptly.b c

  • Importance of informing patients that corticosteroids may decrease bone mineral density.b c

  • Importance of patients on long-term glucocorticoid therapy taking adequate calcium and vitamin D, either through diet or supplementation.c

  • 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.c

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

  • Importance of carrying identification cards listing the diseases being treated, the glucocorticoid regimen, and the name and telephone number of the clinician.c

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

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.a c

  • Importance of regular follow-up visits and of promptly notifying clinician of dizziness, severe or continuing headaches, swelling of feet or lower legs, or unusual weight gain.c

  • Importance of taking only as prescribed; do not increase dosage or duration of therapy unless otherwise instructed by a clinician.a b

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

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

Preparations

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

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

Cortisone Acetate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder

Oral

Tablets

25 mg*

Cortisone Acetate (scored)

Qualitest, West-ward

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

a. AHFS drug information 2007. McEvoy GK, ed. Cortisone acetate. Bethesda, MD: American Society of Health-System Pharmacists; 2007:3045-3046.

b. Pharmacia and Upjohn Company. Cortisone acetate tablets prescribing information. New York, NY; 2002 Feb.

c. AHFS drug information 2007. McEvoy GK, ed. Corticosteroids general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 3024-3037.

d. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 7th ed. Baltimore, MD: Williams & Wilkins; 2005:385.

e. West-ward Pharmaceutical Corp. Cortisone acetate tablets, USP prescribing information. Eatontown, NJ; 2003 Dec.

f. National Asthma Education and Prevention Program. Expert panel report II: guidelines for the diagnosis and management of asthma. Update on selected topics 2002. J Allergy Clin Immunol. 2002; 110(Suppl 5):S141-219.

g. National Institutes of Health, National Heart, Lung, and Blood Institute. Global Initiative for asthma: global strategy for asthma management and prevention NHLBI/WHO Workshop Report. Bethesda, MD: National Institutes of Health. 2002 Feb. NIH/NHLBI Publication No. 02-3659. Available at: . Accessed 2002 Sep 26.

h. National Heart, Lung, and Blood Institute/World Health Organization. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Bethesda, MD: National Heart, Lung, and Blood Institute, Global Initiative for Chronic Obstructive Lung Disease, World Health Organization; 2001. Available at: http://www.goldcopd.com/workshop/index.html. Accessed 2002 Sep 26.

i. Walsh LJ, Wong CA, Oborne J et al. Adverse effects of oral corticosteroids in relation to dose in patients with lung disease. Thorax. 2001; 56:279-84. [PubMed 11254818]

j. Bello CE, Garrett SD. Therapeutic issues in oral glucocorticoid use. Lippincotts Prim Care Pract. 1999; 3:333-41. [PubMed 10711134]

k. Behrman RE, Kliegman RM, Jenson HB, eds. Acute inflammatory airway obstruction. In: Nelson textbook of pediatrics. 17th ed. Philadelphia: Saunders; 2004:1407-8.

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