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For intra-articular, intralesional, and soft tissue injection only.
Hydrocortisone acetate, a synthetic adrenocortical steroid, is a white to practically white, odorless, crystalline powder. It is insoluble in water and slightly soluble in alcohol and chloroform. The molecular weight is 404.50. It is designated chemically as 21-(acetyloxy)-11(beta),17-dihydroxypregn-4-ene-3,20-dione. The empirical formula is C 23 H 32 O 6 and the structural formula is:
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HYDROCORTONE* Acetate (Hydrocortisone Acetate) Injectable Suspension is a sterile suspension containing 50 mg per milliliter of hydrocortisone acetate in a suitable aqueous medium (pH -5.0 to 7.0). Inactive ingredients per mL: sodium chloride, 9 mg; polysorbate 80, 4 mg; sodium carboxymethylcellulose, 5 mg; and Water for Injection, q.s., 1 mL. Benzyl alcohol, 9 mg, added as preservative.
* Registered trademark of MERCK & CO., INC.
HYDROCORTONE Acetate Injectable Suspension has a slow onset but long duration of action when compared with more soluble preparations. Because of its insolubility, it is suitable for intra-articular, intralesional, and soft tissue injection where its anti-inflammatory effects are confined mainly to the area in which it has been injected, although it is capable of producing systemic hormonal effects.
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 effect in disorders of many organ systems.
Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body' immune responses to diverse stimuli.
Localized hypertrophic, infiltrated, inflammatory lesions of: lichen planus, psoriatic plaques, granuloma annulare, and lichen simplex chronicus (neurodermatitis)
Discoid lupus erythematosus
Necrobiosis lipoidica diabeticorum
Alopecia areata
May also be useful in cystic tumors of an aponeurosis or tendon (ganglia).
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.
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.
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.
This product, 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.
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.
Intra-articular injection of a corticosteroid may produce systemic as well as local effects.
Appropriate examination of any joint fluid present is necessary to exclude a septic process.
A marked increase in pain accompanied by local swelling, further restriction of joint motion, fever, and malaise is suggestive of septic arthritis. If this complication occurs and the diagnosis of sepsis is confirmed, appropriate antimicrobial therapy should be instituted.
Injection of a steroid into an infected site is to be avoided.
Corticosteroids should not be injected into unstable joints.
Patients should be impressed strongly with the importance of not overusing joints in which symptomatic benefit has been obtained as long as the inflammatory process remains active.
Frequent intra-articular injection may result in damage to joint tissues.
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 injection of corticosteroids:
Rare instances of blindness associated with intralesional therapy around the face and head
Hyperpigmentation or hypopigmentation
Subcutaneous and cutaneous atrophy
Sterile abscess
Postinjection flare (following intra-articular use)
Charcot-like arthropathy.
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.
NOT FOR INTRAVENOUS USE
For intra-articular, intralesional, and soft tissue injection only
DOSAGE AND FREQUENCY OF INJECTION ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE AND THE RESPONSE OF THE PATIENT.
The initial dose varies from 5 to 75 mg depending on the disease being treated and the size of the area to be injected. Frequency of injection depends on symptomatic response, and usually is once every two or three weeks. Severe conditions may require injection once a week. Frequent intra-articular injection may result in damage to joint tissues. If satisfactory clinical response does not occur after a reasonable period of time, discontinue HYDROCORTONE Acetate Injectable Suspension and transfer the patient to other therapy.
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, and individual drug responsiveness.
Some of the usual single doses are:
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For rapid onset of action, a soluble adrenocortical hormone preparation, such as DECADRON* Phosphate (Dexamethasone Sodium Phosphate) injection or HYDELTRASOL* (Prednisolone Sodium Phosphate) injection, may be given with HYDROCORTONE Acetate Injectable Suspension.
If desired, a local anesthetic may be used, and may be injected before HYDROCORTONE Acetate Injectable Suspension or mixed in a syringe with HYDROCORTONE Acetate Injectable Suspension and given simultaneously.
If used prior to intra-articular injection of the steroid, inject most of the anesthetic into the soft tissues of the surrounding area and instill a small amount into the joint.
If given together, mixing should be done in the injection syringe by drawing the steroid in first , then the anesthetic. In this way, the anesthetic will not be introduced inadvertently into the vial of steroid. The mixture must be used immediately and any unused portion discarded.
* Registered trademark of MERCK & CO., INC.
No. 7519--HYDROCORTONE Acetate Injectable Suspension is a white, mobile suspension, containing 50 mg hydrocortisone acetate in each mL, and is supplied as follows:
NDC 0006-7519-03 in 5 mL vials.
Sensitive to heat. Do not autoclave.
Protect from freezing.
7348729 Issued February 1997