CORTISONE ACETATE TABLETS, USP

Rev. 07/16

Rx Only

Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic, which are readily absorbed from the gastrointestinal tract.

Cortisone acetate is a white or practically white, odorless, crystalline powder. It is stable in air. It is insoluble in water. The molecular weight is 402.49. It is designated chemically as 21-(acetyloxy)-17-hydroxypregn-4-ene-3,11,20-trione. The molecular formula is C23H30O6 and the structural formula is:

Cortisone Acetate Tablets, USP contain 25 mg of cortisone acetate in each tablet.

Inactive ingredients are Anhydrous Lactose, Colloidal Silicon Dioxide, Magnesium Stearate, Microcrystalline Cellulose, Sodium Lauryl Sulfate, and Sodium Starch Glycolate.

Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. They are also 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.

1. Endocrine Disorders

Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the first choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular importance).

Congenital adrenal hyperplasia Nonsuppurative thyroiditis Hypercalcemia associated with cancer

2. Rheumatic Disorders

As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in:

Psoriatic arthritis

Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy) Ankylosing spondylitis

Acute and subacute bursitis Acute nonspecific tenosynovitis Acute gouty arthritis

Post-traumatic osteoarthritis Synovitis of osteoarthritis Epicondylitis

3. Collagen Diseases

During an exacerbation or as maintenance therapy in selected cases of:

Systemic lupus erythematosus

Acute rheumatic carditis

Systemic dermatomyositis (polymyositis)

4. Dermatologic Diseases

Pemphigus

Bullous dermatitis herpetiformis

Severe erythema multiforme (Stevens-Johnson syndrome) Exfoliative dermatitis

Mycosis fungoides

Severe psoriasis

Severe seborrheic dermatitis

5. Allergic States

Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment:

Seasonal or perennial allergic rhinitis

Bronchial asthma Contact dermatitis Atopic dermatitis Serum sickness

Drug hypersensitivity reactions

6. Ophthalmic Diseases

Severe acute and chronic allergic and inflammatory processes

involving the eye and its adnexa, such as: Allergic conjunctivitis

Keratitis

Allergic corneal marginal ulcers Herpes zoster ophthalmicus Iritis and iridocyclitis Chorioretinitis

Anterior segment inflammation

Diffuse posterior uveitis and choroiditis

Optic neuritis

Sympathetic ophthalmia

7. Respiratory Diseases

Symptomatic sarcoidosis

Loeffler’s syndrome not manageable by other means

Berylliosis

Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculosis chemotherapy Aspiration

pneumonitis

8. Hematologic Disorders

Idiopathic thrombocytopenic purpura in adults Secondary thrombocytopenia in adults Acquired (autoimmune) hemolytic anemia

Erythroblastopenia (RBC anemia)

Congenital (erythroid) hypoplastic anemia

9. Neoplastic Diseases

For palliative management of: Leukemias and lymphomas in adults Acute leukemia of childhood

10. Edematous States

To induce a diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus

erythematosus

11. Gastrointestinal Diseases

To tide the patient over a critical period of the disease in: Ulcerative colitis

Regional enteritis

12. Miscellaneous

Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy

Trichinosis with neurologic or myocardial involvement

• Systemic fungal infections
• Hypersensitivity to this product

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

Drug-induced secondary adrenocortical insufficiency may result from too rapid withdrawal of corticosteroids and may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. If the patient is receiving steroids already, dosage may have to be increased. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently.

Corticosteroids may mask some signs of infection, and new infections may appear during their use. There may be decreased resistance and inability to localize infection when corticosteroids are used. Moreover, corticosteroids may affect the nitroblue-tetrazolium test for bacterial infection and produce false negative results.

In cerebral malaria, a double-blind trial has shown that the use of corticosteroids is associated with prolongation of coma and a higher incidence of pneumonia and gastrointestinal bleeding.

Corticosteroids may activate latent amebiasis. Therefore, it is recommended that latent or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has time in the tropics or any patient with unexplained diarrhea.

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

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 virus vaccines, including smallpox, is contraindicated in individuals receiving immunosuppressive doses of corticosteroids. If inactivated viral or bacterial vaccines are administered to individuals receiving immunosuppressive doses of corticosteroids, the expected serum antibody response may not be obtained. However, immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy, e.g., for Addison’s disease.

Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have 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 chickenpox, 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 chickenpox develops, treatment with antiviral agents may be considered.

The use of cortisone acetate tablets 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.

Literature reports suggest an apparent association between use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with corticosteroids should be used with great caution in these patients.

Usage in pregnancy: Since adequate human reproduction studies have not been done with corticosteroids, use of these drugs in pregnancy or in women of childbearing potential requires that the anticipated benefits be weighed against the possible 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.

Corticosteroids appear in breast milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other unwanted effects. Mothers taking pharmacologic doses of corticosteroids should be advised not to nurse.

Fluid and Electrolyte Disturbances

        Sodium retention

        Fluid retention

        Congestive heart failure in susceptible patients

        Potassium loss Hypokalemic alkalosis Hypertension

Musculoskeletal Muscle weakness Steroid myopathy Loss of muscle mass Osteoporosis

        Vertebral compression fractures

        Aseptic necrosis of femoral and humeral heads

        Pathologic fracture of long bones

        Tendon rupture

Gastrointestinal

        Peptic ulcer with possible perforation and hemorrhage Perforation of the small and large bowel, particularly in patients with inflammatory bowel disease

        Pancreatitis Abdominal distention Ulcerative esophagitis

Dermatologic

        Impaired wound healing

        Thin fragile skin

        Petechiae and ecchymoses

        Erythema

        Increased sweating

        May suppress reactions to skin tests

          Other cutaneous reactions, such as allergic dermatitis, urticaria, angioneurotic edema

Neurologic

        Convulsions

        Increased intracranial pressure with papilledema (pseudotumor cerbri) usually after treatment

        Vertigo

        Headache

        Psychic disturbances

Endocrine

        Menstrual irregularities Development of cushingoid state Suppression of growth in children

        Secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery, or illness 

        Decreased carbohydrate tolerance

        Manifestations of latent diabetes mellitus

        Increased requirements for insulin or oral hypoglycemic agents in diabetics

        Hirsutism

Ophthalmic

        Posterior subcapsular cataracts Increased intraocular pressure Glaucoma

        Exophthalmos

Metabolic

        Negative nitrogen balance due to protein catabolism

Cardiovascular

        Myocardial rupture following recent myocardial infarctions (see WARNINGS).

Other Hypersensitivity Thromboembolism Weight gain Increased appetite Nausea

        Malaise

To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-877-233-2001, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Reports of acute toxicity and/or death following overdosage of glucocorticoids are rare. In the event of overdosage, no specific antidote is available; treatment is supportive and symptomatic.

The intraperitoneal LD50 of cortisone acetate in female mice was 1405 mg/kg.

For Oral Administration

DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE AND THE RESPONSE OF THE PATIENT.

The initial dosage varies from 25 to 300 mg a day depending on the disease being treated. In less severe diseases doses lower than 25 mg may suffice, while in severe diseases doses higher than 300 mg may be required. The initial dosage should be maintained or adjusted until the patient’s response is satisfactory. If satisfactory clinical response does not occur after a reasonable period of time, discontinue cortisone acetate tablets and transfer the patient to other therapy.

After a favorable initial response, the proper maintenance dosage should be determined by decreasing the initial dosage in small amounts to the lowest dosage that maintains an adequate clinical response.

Patients should be observed closely for signs that might require dosage adjustment, including changes in clinical status resulting from remissions or exacerbations of the disease, individual drug responsiveness, and the effect of stress (e.g., surgery, infection, trauma). During stress it may be necessary to increase dosage temporarily.

If the drug is to be stopped after more than a few days of treatment, it usually should be withdrawn gradually.

Cortisone Acetate Tablets, USP 25 mg: White, Round, Scored Tablet; Imprinted “West-ward 202.”

Bottles of 100 tablets.                                                    NDC 0143-9700-01

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Manufactured by: HIKMA Pharmaceuticals P.O. Box 182400

Amman 11118 – Jordan

Distributed by:

West-Ward Pharmaceuticals Corp.

Eatontown, NJ 07724 USA

Revised July 2016

NDC 0143-9700-01

Cortisone Acetate

Tablets, USP

25 mg

Rx Only

100 Tablets