Cortisone Acetate - Pharmacia and Upjohn Company

Cortisone acetate is a glucocorticoid. Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic, which are readily absorbed from the gastrointestinal tract. Cortisone acetate is a white to practically white, odorless, crystalline powder. It is insoluble in water; freely soluble in chloroform; soluble in dioxane; sparingly soluble in acetone; slightly soluble in alcohol.

The chemical name for cortisone acetate is pregn-4-ene-3,11,20-trione, 21-(acetyloxy)-17-hydroxy and the molecular weight is 402.49. The structural formula is represented below:

Cortisone Acetate Tablets are available in 2 strengths: 5 mg or 10 mg. Inactive ingredients: calcium stearate, corn starch, lactose, mineral oil, sorbic acid, sucrose.

Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs are primarily used for their potent anti-inflammatory effects in disorders of many organ systems.

Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli.

Systemic fungal infections and known hypersensitivity to components.

In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated.

Corticosteroids may mask some signs of infection, and new infections may appear during their use. Infections with any pathogen including viral, bacterial, fungal, protozoan or helminthic infections, in any location of the body, may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents that affect cellular immunity, humoral immunity, or neutrophil function.¹

These infections may be mild, but can be severe and at times fatal. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases.² There may be decreased resistance and inability to localize infection when corticosteroids are used.

Prolonged use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses.

Usage in pregnancy: Since adequate human reproduction studies have not been done with corticosteroids, the use of these drugs in pregnancy, nursing mothers or women of childbearing potential requires that the possible benefits of the drug be weighed against the potential hazards to the mother and embryo or fetus. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy, should be carefully observed for signs of hypoadrenalism.

Average and large doses of hydrocortisone or cortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion.

Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered to patients receiving immunosuppressive doses of corticosteroids; however, the response to such vaccines may be diminished. Indicated immunization procedures may be undertaken in patients receiving nonimmunosuppressive doses of corticosteroids.

The use of cortisone acetate in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate antituberculous regimen.

If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis.

Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in non-immune children or adults on corticosteroids. In such children or adults who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route and duration of corticosteroid administration affects the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chicken pox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chicken pox develops, treatment with antiviral agents may be considered. Similarly, corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroidinduced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.

Fluid and electrolyte disturbances

• Sodium retention
• Potassium loss
• Fluid retention
• Hypokalemic alkalosis
• Congestive heart failure in susceptible patients
• Hypertension

Musculoskeletal

• Muscle weakness
• Vertebral compression fractures
• Steroid myopathy
• Aseptic necrosis of femoral and humeral heads
• Loss of muscle mass
• Osteoporosis
• Tendon rupture, particularly of the Achilles tendon
• Pathologic fracture of long bones

Gastrointestinal

• Peptic ulcer with possible perforation and hemorrhage
• Abdominal distention
• Ulcerative esophagitis
• Pancreatitis
• Increases in alanine transaminase (ALT, SGPT), aspartate transaminase (AST, SGOT) and alkaline phosphatase have been observed following corticosteroid treatment. These changes are usually small, not associated with any clinical syndrome and are reversible upon discontinuation.

Dermatologic

• Impaired wound healing
• Facial erythema
• Thin fragile skin
• Increased sweating
• Petechiae and ecchymoses
• May suppress reactions to skin tests

Neurological

• Increased intracranial pressure with papilledema (pseudotumor cerebri) usually after treatment
• Convulsions
• Vertigo
• Headache

Endocrine

• Menstrual irregularities
• Suppression of growth in children
• Development of Cushingoid state
• Decreased carbohydrate tolerance
• Secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery or illness
• Manifestations of latent diabetes mellitus
• Increased requirements for insulin or oral hypoglycemic agents in diabetics

Ophthalmic

• Posterior subcapsular cataracts
• Glaucoma
• Increased intraocular pressure
• Exophthalmos

Metabolic

• Negative nitrogen balance due to protein catabolism

The initial dosage of cortisone acetate may vary from 25 to 300 mg per day depending on the specific disease entity being treated. In situations of less severity, lower doses will generally suffice; while in selected patients higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period of time there is a lack of satisfactory clinical response, cortisone acetate should be discontinued and the patient transferred to other appropriate therapy. IT SHOULD BE EMPHASIZED THAT DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE UNDER TREATMENT AND THE RESPONSE OF THE PATIENT. After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment; in this latter situation it may be necessary to increase the dosage of cortisone acetate for a period of time consistent with the patient's condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.

Cortisone Acetate Tablets, USP are available in the following strengths and package sizes:

5 mg

(white, round, scored, imprinted UPJOHN 15)

        Bottles of 50                NDC 0009-0015-01

10 mg

(white, round, scored, imprinted UPJOHN 23)

        Bottles of 100              NDC 0009-0023-01

Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP].

¹ Fekety R. Infections associated with corticosteroids and immunosuppressive therapy. In: Gorbach SL, Bartlett JG, Blacklow NR, eds.Infectious Diseases. Philadelphia: WBSaunders Company 1992:1050–1.

² Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticoids.Rev Infect Dis 1989:11(6):954–63.

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810 931 813

692851

Revised February 2002