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For intramuscular injection only
NOT FOR INTRAVENOUS USE
Cortisone acetate, a synthetic adrenocortical steroid, 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 empirical formula is C 23 H 30 O 6 and the structural formula is:
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CORTONE* Acetate (Cortisone Acetate) Injectable Suspension is a sterile suspension containing 50 mg per milliliter of cortisone acetate in an aqueous medium (pH 5.0 to 7.0). Inactive ingredients per mL: sodium chloride, 9 mg; polysorbate 80, 4 mg; sodium carboxymethylcellulose, 5 mg; Water for Injection q.s. 1 mL. Benzyl alcohol, 9 mg, added as preservative.
No attempt should be made to alter CORTONE Acetate Injectable Suspension. Diluting it or mixing it with other substances may affect the state of suspension or change the rate of absorption and reduce its effectiveness.
*Registered trademark of MERCK & CO., INC.
CORTONE Acetate Injectable Suspension has a slow onset but long duration of action when compared with more soluble preparations. When daily corticosteroid therapy is required and oral therapy is not feasible, the required daily dosage may be given in a single intramuscular injection of this preparation.
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' immune responses to diverse stimuli.
When oral therapy is not feasible:
Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy
Trichinosis with neurologic or myocardial involvement.
Hypersensitivity to any component of this product
Because rare instances of anaphylactoid reactions have occurred in patients receiving parenteral corticosteroid therapy, appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of allergy to any drug. Anaphylactoid and hypersensitivity reactions have been reported for CORTONE Acetate Injectable Suspension (see ADVERSE REACTIONS ).
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, 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 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.
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.
Average and large doses of cortisone or hydrocortisone 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.
Patients who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in non-immune patients on corticosteroids. In such patients who have not had these diseases, particular care should be taken to avoid exposure. The risk of developing a disseminated infection varies among individuals and can be related to the dose, route and duration of corticosteroid administration as well as to the underlying disease. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If chickenpox develops, treatment with antiviral agents may be considered. If exposed to measles, prophylaxis with immune globulin (IG) may be indicated. (See the respective package inserts for VZIG and IG for complete prescribing information.)
Similarly, corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.
The use of CORTONE Acetate Injectable Suspension 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.
CORTONE Acetate Injectable Suspension, like many other steroid formulations, is sensitive to heat. Therefore, it should not be autoclaved when it is desirable to sterilize the exterior of the vial.
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.
Corticosteroids should be used cautiously in patients with ocular herpes simplex for fear of corneal perforation.
The lowest possible dose of corticosteroid should be used to control the condition under treatment, and when reduction in dosage is possible, the reduction must be gradual.
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.
Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia.
Steroids should be used with caution in nonspecific ulcerative colitis, if there is a probability of impending perforation, abscess, or other pyogenic infection, also in 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 antacids be administered between meals to help to prevent peptic ulcer.
Steroids may increase or decrease motility and number of spermatozoa in some patients.
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.
Injection of a steroid into an infected site is to be avoided.
Information for Patients
Susceptible patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay.
Pediatric Use
Growth and development of pediatric patients on prolonged corticosteroid therapy should be carefully followed.
Fluid and electrolyte disturbances
Sodium retention
Fluid retention
Congestive heart failure in susceptible patients
Potassium loss
Hypokalemic alkalosis
Hypertension
Muscle weakness
Steroid myopathy
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
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
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
Posterior subcapsular cataracts
Increased intraocular pressure
Glaucoma
Exophthalmos
Metabolic
Negative nitrogen balance due to protein catabolism
Cardiovascular
Myocardial rupture following recent myocardial infarction (see )
Other
Anaphylactoid or hypersensitivity reactions
Thromboembolism
Weight gain
Increased appetite
Nausea
Malaise
The following additional adverse reactions are related to parenteral corticosteroid therapy:
Rare instances of blindness associated with intralesional therapy around the face and head
Hyperpigmentation or hypopigmentation
Subcutaneous and cutaneous atrophy
Sterile abscess
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 LD 50 of cortisone acetate in female mice was 1405 mg/kg.
For intramuscular injection only
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 20 to 300 mg a day depending on the disease being treated. In less severe diseases doses lower than 20 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' response is satisfactory. If a satisfactory clinical response does not occur after a reasonable period of time, discontinue CORTONE Acetate Injectable Suspension 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.
No. 7069--CORTONE Acetate Injectable Suspension is a white, mobile suspension, each mL containing 50 mg cortisone acetate, and is supplied as follows:
NDC 0006-7069-10 in 10 mL vials.
Sensitive to heat. Do not autoclave.
Protect from freezing.
7411918 Issued February 1997