cortisone acetate
Cortone

Available forms
Available by prescription only
Injection: 50 mg/ml suspension
Tablets: 5 mg, 10 mg, 25 mg

Indications and dosages
 Adrenal insufficiency, allergy, inflammation. Adults: 25 to 300 mg P.O. or 20 to 300 mg I.M. daily or on alternate days. Dosage is highly individualized, depending on severity of disease.
Children: 0.7 to 10 mg/kg/day or 20 to 300 mg/m² P.O. daily in four divided doses; or 0.2 to 1.25 mg/ kg/day or 7 to 37.5 mg/m² I.M. once or twice daily. Dosage must be highly individualized.

Pharmacodynamics
Adrenocorticoid replacement: Cortisone acetate is an adrenocorticoid with both glucocorticoid and mineralocorticoid properties. A weak anti-inflammatory agent, drug has only about 80% of the anti-inflammatory activity of an equal weight of hydrocortisone. It’s a potent mineralocorticoid, however, having twice the potency of prednisone. Cortisone (or hydrocortisone) is usually the drug of choice for replacement therapy in patients with adrenal insufficiency. It’s usually not used for inflammatory or immunosuppressant activity because of the extremely large doses that must be used and because of the unwanted mineralocorticoid effects. Injectable form has a slow onset but a long duration of action. It’s usually used only when the oral dosage form can’t be used.

Pharmacokinetics
Absorption: Absorbed readily after oral administration.
Distribution: Distributed rapidly to muscle, liver, skin, intestines, and kidneys. Cortisone is extensively bound to plasma proteins (transcortin and albumin). Only the unbound portion is active. Cortisone is distributed into breast milk and through the placenta.
Metabolism: Metabolized in the liver to the active metabolite hydrocortisone, which in turn is metabolized to inactive glucuronide and sulfate metabolites. Duration of hypothalamic-pituitary-adrenal (HPA) axis suppression is 1 to 1 1/2 days.
Excretion: Inactive metabolites and small amounts of unmetabolized drug are excreted by the kidneys. Insignificant quantities of the drug are also excreted in feces. Biological half-life of cortisone is 8 to 12 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or its components and in those with systemic fungal infections. Use cautiously in patients with renal disease, recent MI, GI ulcer, hypertension, osteoporosis, diabetes mellitus, hypothyroidism, cirrhosis, diverticulitis, ulcerative colitis, recent intestinal anastomosis, thromboembolic disorders, seizures, myasthenia gravis, heart failure, tuberculosis, ocular herpes, emotional instability, or psychotic tendencies.

Interactions
Drug-drug. Amphotericin B, diuretics: Enhances hypokalemia. Monitor serum blood levels closely, especially potassium.
Antacids, cholestyramine, colestipol: Decreases cortisone’s effect by adsorbing corticosteroid, decreasing amount absorbed. Monitor patient carefully.
Barbiturates, phenytoin, rifampin: Decreases corticosteroid effects. Monitor patient closely.
Cardiac glycosides: Hypokalemia may increase risk of toxicity in patients concurrently receiving cardiac glycosides. Avoid use together.
Estrogens: May reduce cortisone metabolism and prolong cortisone half-life. Avoid use together.
Inactivated vaccines, toxoids: Cortisone may have diminished response to toxoids or inactivated vaccines. Avoid use together.
Insulin, oral antidiabetics: Causes increased risk of hyperglycemia. Adjust antidiabetic dosage as needed.
Isoniazid, salicylates: Increases metabolism of isoniazid and salicylates. Use together cautiously.
NSAIDs: May increase risk of GI ulceration. Avoid use together.
Oral anticoagulants: Cortisone may inhibit response to anticoagulants. Monitor PT and INR.
Drug-lifestyle. Alcohol use: Increases risk of gastric irritation and GI ulceration. Advise patient to avoid alcohol.

Adverse reactions
CNS: euphoria, insomnia, psychotic behavior, pseudotumor cerebri, vertigo, headache, paresthesia, seizures.
CV: heart failure, hypertension, edema, arrhythmias, thrombophlebitis, thromboembolism.
EENT: cataracts, glaucoma.
GI: peptic ulcer, GI irritation, increased appetite, pancreatitis, nausea, vomiting.
GU: increased urine glucose and calcium levels, menstrual irregularities.
Metabolic: cushingoid symptoms (moonface, buffalo hump, central obesity), hypokalemia, hyperglycemia, carbohydrate intolerance, hypercholesterolemia, hypocalcemia, acute adrenal insufficiency may follow increased stress (infection, surgery, trauma) or abrupt withdrawal after long-term therapy.
Musculoskeletal: muscle weakness, osteoporosis, growth suppression in children.
Skin: delayed wound healing, acne, various skin eruptions, atrophy at I.M. injection sites, hirsutism.
Other: susceptibility to infections.

Effects on lab test results
• May increase blood glucose and cholesterol levels. May decrease potassium, calcium, T₃, and T₄ levels.

Overdose and treatment
Acute ingestion, even in massive doses, is rarely a problem. Toxic signs and symptoms rarely occur if the drug is used for less than 3 weeks, even in large dosages. However, long-term use causes adverse physiologic effects.

Special considerations
• Most adverse reactions to corticosteroids are dose- or duration-dependent.
 ALERT Don’t withdraw drug abruptly because abrupt withdrawal may cause rebound inflammation, fatigue, weakness, arthralgia, fever, dizziness, lethargy, depression, fainting, orthostatic hypotension, dyspnea, anorexia, hypoglycemia. After prolonged use, sudden withdrawal may be fatal.
 ALERT Check for sensitivity to any other corticosteroid. Drug isn’t for I.V. use. For better results and less toxicity, give a once-daily dose in the morning. • Drug therapy suppresses reactions to skin tests; causes false-negative results in the nitroblue tetrazolium test for systemic bacterial infections; and decreases ¹³¹I uptake and protein-bound iodine levels in thyroid function tests.
Pediatric patients
• Long-term use of cortisone in children and adolescents may delay growth and maturation.
Geriatric patients
• Use with caution in elderly patients in whom osteoporosis is more likely to develop.

Patient education
• Inform patient of potential adverse reactions.
• Tell patient not to discontinue drug abruptly or without medical consent.
• Advise patient to avoid exposure to viral infections (such as measles and chicken pox) and to call if such exposure occurs.
• Instruct patient to carry a card indicating his need for supplemental glucocorticoids during stress. This card should contain prescriber’s name, medication, and dose taken.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use