Action And Clinical Pharmacology: Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic, which are readily absorbed from the gastrointestinal tract.
Cortisone is a natural product of the adrenal cortex. Cortisone acetate is a synthetic steroid with the basic actions and effects of other glucocorticoids.
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.
Indications And Clinical Uses: Endocrine Disorders: Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of 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.
Rheumatic Disorders: As adjunctive therapy for short-term administration during an acute episode or exacerbation of: 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.
Collagen Diseases: During an exacerbation or as maintenance therapy in selected cases of: systemic lupus erythematosus, acute rheumatic carditis, systemic dermatomyositis (polymyositis).
Dermatologic Diseases: pemphigus, bullous dermatitis herpetiformis, severe erythema multiforme (Stevens-Johnson syndrome), exfoliative dermatitis, mycosis fungoides, severe psoriasis, severe seborrheic dermatitis.
Allergic States: Control of severe or incapacitating allergic conditions not responsive to adequate trials of conventional treatment in: seasonal or perennial allergic rhinitis, bronchial asthma, contact dermatitis, atopic dermatitis, serum sickness, drug hypersensitivity reactions.
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.
Respiratory Diseases: symptomatic sarcoidosis, Leffler’s syndrome not manageable by other means, berylliosis, fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy, aspiration pneumonitis.
Hematologic Disorders: idiopathic thrombocytopenic purpura in adults, secondary thrombocytopenia in adults, acquired (autoimmune) hemolytic anemia, erythroblastopenia (RBC anemia), congenital (erythroid) hypoplastic anemia.
Neoplastic Diseases: For palliative management of: leukemias and lymphomas in adults, acute leukemia of childhood.
Edematous States: To induce diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type, or that due to lupus erythematosus.
Gastrointestinal Diseases: During a critical period of the disease in: ulcerative colitis, regional enteritis.
Miscellaneous: Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy; trichinosis with neurologic or myocardial involvement.
Contra-Indications: Systemic fungal infections.
Hypersensitivity to any component of this product.
Tuberculosis whether active or healed, ocular herpes simplex and acute psychoses are usually absolute contraindications to systemic steroid therapy.
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 patient 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.
Manufacturers’ Warnings In Clinical States: In patients on corticosteroid therapy subjected to any 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, corticosteroid 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.
Corticosteroids may exacerbate systemic fungal infections and therefore should not be used in the presence of such infections unless they are needed to control drug reactions due to amphotericin B. Moreover, there have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive failure.
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.
In cerebral malaria, the use of corticosteroids is associated with prolongation of coma and 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 spent time in the tropics or any patient with unexplained diarrhea.
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.
Corticosteroids should be used cautiously in patients with ocular herpes simplex for fear of corneal perforation.
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.
Pregnancy: Pregnancy is a relative contraindication to corticosteroid therapy, particularly during the first trimester, because fetal abnormalities have been observed in experimental animals. 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 possible hazards to 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.
Lactation: Corticosteroids appear in breast milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other unwanted effects in the breast-feeding infant. Mothers taking pharmacologic doses of corticosteroids should be advised not to nurse.
Precautions: The preparation should be used only with full cognizance of the characteristic activity of systemic corticosteroid preparations and the varied responses to therapy. Prolonged corticosteroid therapy usually causes a reduction in the activity and size of the adrenal cortex.
The lowest effective dose of corticosteroid should be used to control the condition under treatment, and when reduction in dosage is possible, the reduction must be gradual.
Patients should be advised to inform subsequent physicians of the prior use of corticosteroids.
Cortisone causes gluconeogenesis; therefore, hyperglycemia and glycosuria may occur, glucose tolerance may be altered, and diabetes mellitus may be aggravated. Close observation of diabetic patients is recommended.
Following prolonged therapy, withdrawal of corticosteroids may result in symptoms of the corticosteroid withdrawal syndrome including fever, myalgia, arthralgia, and malaise. This may occur in patients even without evidence of adrenal insufficiency.
There is an enhanced effect of corticosteroids in patients with hypothyroidism and in those with cirrhosis.
Psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.
Steroids should be used with caution in nonspecific ulcerative colitis, if there is a probability of impending perforation, abscess, or other pyogenic infection, diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, renal insufficiency, hypertension, osteoporosis, and myasthenia gravis. Signs of peritoneal irritation following gastrointestinal perforation in patients receiving large doses of corticosteroids may be minimal or absent. Fat embolism has been reported as a possible complication of hypercortisonism.
When large doses are given, some authorities advise that corticosteroids be taken with meals and antacids be taken between meals to help to prevent peptic ulcer.
Growth and development of infants and children on prolonged corticosteroid therapy should be carefully followed.
Steroids may increase or decrease motility and number of spermatozoa in some patients.
Drug Interactions: ASA should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia.
Phenytoin, phenobarbital, ephedrine, and rifampin may enhance the metabolic clearance of corticosteroids resulting in decreased blood levels and lessened physiologic activity, thus requiring adjustment in corticosteroid dosage.
The prothrombin time should be checked frequently in patients who are receiving corticosteroids and coumarin anticoagulants at the same time because of reports that corticosteroids have altered the response to these anticoagulants. Studies have shown that the usual effect produced by adding corticosteroids is inhibition of response to coumarins, although there have been some conflicting reports of potentiation not substantiated by studies.
When corticosteroids are administered concomitantly with potassium-depleting diuretics, patients should be observed closely for development of hypokalemia.
Adverse Reactions: 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 subsequent 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 cerebri) 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 diabetes; hirsutism.
Ophthalmic: posterior subcapsular cataracts, increased intraocular pressure, glaucoma, exophthalmos.
Metabolic: negative nitrogen balance due to protein catabolism.
Cardiovascular: myocardial rupture following recent myocardial infarction (see Warnings).
Others: hypersensitivity, thromboembolism, weight gain, increased appetite, nausea, malaise.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: 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 in female mice was 1 405 mg/kg.
Dosage And Administration: Therapy is governed by the following general principles: 1. Dosage must be individualized according to the severity of the disease and the response of the patient. The severity, prognosis, and expected duration of the disease and the reaction of the patient to medication are primary factors in determining dosage. (For infants and children, the recommended doses usually will have to be reduced, but dosage should be dictated by the severity of the condition rather than by age or body weight.)
2. Corticosteroid therapy is an adjunct to, not a replacement of conventional therapy, which should be instituted as indicated.
3. Dosage must be decreased or therapy discontinued gradually when administration has been continued for more than a few days.
4. Continued supervision of the patient after cessation of corticosteroids is essential, since there may be a sudden reappearance of severe manifestations of the disease for which the patient was treated.
In acute conditions where prompt relief is urgent, large doses are permissible and may be mandatory for a short period.
In chronic conditions requiring long-term therapy, the lowest dosage that provides adequate, but not necessarily complete, relief should be used. If a high dosage for prolonged periods is considered essential, patients must be observed closely for signs that might necessitate a reduction in dosage or discontinuance of the corticosteroid.
Chronic conditions are subject to periods of spontaneous remission. When such periods occur, corticosteroids should be discontinued gradually.
Routine laboratory studies such as urinalysis, 2-hour postprandial blood sugar, determinations of blood pressure and body weight, and a chest x-ray should be carried out at regular intervals during prolonged therapy. Periodic determinations of serum potassium are advisable if large doses are being used. Upper gastrointestinal x-rays should be taken when treatment is prolonged, in patients with history of ulcer or when there is gastric distress.
The daily requirement should be divided into 4 doses.
Specific Dosage Recommendations: In chronic, usually nonfatal diseases, including endocrine and chronic rheumatic disorders, edematous states, respiratory and gastrointestinal diseases, some dermatologic diseases and hematologic disorders, start with a low dose (25 to 50 mg a day) and gradually increase dosage to the smallest amount that gives the desired degree of symptomatic relief.
When symptoms have been suppressed adequately, dosage should be maintained at the minimum amount capable of providing sufficient relief without excessive hormonal effects.
In chronic adrenocortical insufficiency, 10 to 25 mg a day, or occasionally more, with 4 to 6 g of sodium chloride or 1 to 3 mg of desoxycorticosterone acetate. When immediate support is mandatory, one of the soluble corticosteroid preparations (i.e., dexamethasone sodium phosphate injection) which may be effective within minutes after parenteral administration, can be lifesaving.
In congenital adrenal hyperplasia, the usual daily dose is 15 to 50 mg.
In acute, nonfatal diseases, including allergic states, ophthalmic diseases, acute and subacute rheumatic disorders, dosage ranges between 75 and 150 mg a day; however, higher doses are necessary in some patients. Since the course of these conditions is self-limited, prolonged maintenance therapy is not usually necessary.
In chronic, potentially fatal diseases such as systemic lupus erythematosus, pemphigus, symptomatic sarcoidosis, the recommended initial dosage is 75 to 150 mg a day; higher doses are necessary in some patients.
As soon as adequate relief is obtained, the dosage should be reduced gradually to the minimum amount that will produce the desired therapeutic effect.
When the disease is acute and life-threatening (e.g., acute rheumatic carditis, crisis of systemic lupus erythematosus, severe allergic reactions, pemphigus, neoplastic diseases), the initial dosage is between 125 and 300 mg a day, administered in at least 4 divided doses; this dosage may have to be increased in some patients to establish control. As soon as control is attained, the dosage should be reduced gradually to the minimum amount that will maintain relief.
When an extremely rapid onset of action is desired, one of the soluble corticosteroid preparations (dexamethasone sodium phosphate injection) may be administered i.v. for the first 2 or 3 doses.
Epinephrine is the drug of immediate choice in severe allergic reactions. Cortisone tablets are useful either concurrently or as supplementary therapy.
Availability And Storage: 5 mg: Each white, discoid shaped, flat, compressed tablet, with a beveled edge, unscored with MSD 126 on one side, contains: cortisone acetate 5 mg. Also contains lactose. Gluten- and tartrazine-free. Bottles of 50.
25 mg: Each white, discoid shaped, flat, compressed tablet, with a beveled edge, scored on one side with MSD 219 on the other side, contains: cortisone acetate 25 mg. Also contains lactose. Gluten- and tartrazine-free. Bottles of 100. (Shown in Product Recognition Section)
CORTONE® Tablets MSD Cortisone Acetate Corticosteroid