SOLU-CORTEF Sterile Powder contains hydrocortisone sodium succinate as the active ingredient. Hydrocortisone sodium succinate is a white or nearly white, odorless, hygroscopic amorphous solid. It is very soluble in water and in alcohol, very slightly soluble in acetone and insoluble in chloroform. The chemical name is pregn-4-ene-3,20-dione,21-(3-carboxy-1-oxopropoxy)-11,17-dihydroxy-, monosodium salt, (11β)- and its molecular weight is 484.52.

The structural formula is represented below:

Hydrocortisone sodium succinate is an anti-inflammatory adrenocortical steroid. This highly water-soluble sodium succinate ester of hydrocortisone permits the immediate intravenous administration of high doses of hydrocortisone in a small volume of diluent and is particularly useful where high blood levels of hydrocortisone are required rapidly.

SOLU-CORTEF Sterile Powder is available in several packages for intravenous or intramuscular administration.

100 mg Plain—Vials containing hydrocortisone sodium succinate equivalent to 100 mg hydrocortisone, also 0.8 mg monobasic sodium phosphate anhydrous, 8.73 mg dibasic sodium phosphate dried. SOLU-CORTEF 100 mg plain does not contain diluent (see DOSAGE AND ADMINISTRATION, Preparation of Solutions).

ACT-O-VIAL® System (Single-Dose Vial) in four strengths

	100 mg	250 mg	500 mg	1000 mg
Hydrocortisone sodium succinate	ACT-O-VIAL Each 2 mL contains: (when mixed) equiv. to 100 mg Hydrocortisone	ACT-O-VIAL Each 2 mL contains: (when mixed) equiv. to 250 mg Hydrocortisone	ACT-O-VIAL Each 4 mL contains: (when mixed) equiv. to 500 mg Hydrocortisone	ACT-O-VIAL Each 8 mL contains: (when mixed) equiv. to1000 mg Hydrocortisone
Monobasic sodium phosphate anhydrous	0.8 mg	2 mg	4 mg	8 mg
Dibasic sodium phosphate dried	8.73 mg	21.8 mg	44 mg	87.32 mg
Benzyl alcohol added as preservative	18.1 mg	16.4 mg	33.4 mg	66.9 mg

When necessary, the pH of each formula was adjusted with sodium hydroxide so that the pH of the reconstituted solution is within the USP specified range of 7 to 8.

Last updated on RxList: 10/20/2009

When oral therapy is not feasible, and the strength, dosage form, and route of administration of the drug reasonably lend the preparation to the treatment of the condition, the intravenous or intramuscular use of SOLU-CORTEF Sterile Powder is indicated as follows:

Allergic states

Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in asthma, atopic dermatitis, contact dermatitis, drug hypersensitivity reactions, perennial or seasonal allergic rhinitis, serum sickness, transfusion reactions.

Dermatologic diseases

Bullous dermatitis herpetiformis, exfoliative erythroderma, mycosis fungoides, pemphigus, severe erythema multiforme (Stevens-Johnson syndrome).

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, hypercalcemia associated with cancer, nonsuppurative thyroiditis.

Gastrointestinal diseases

To tide the patient over a critical period of the disease in regional enteritis (systemic therapy) and ulcerative colitis.

Hematologic disorders

Acquired (autoimmune) hemolytic anemia, congenital (erythroid) hypoplastic anemia (Diamond-Blackfan anemia), idiopathic thrombocytopenic purpura in adults (intravenous administration only; intramuscular administration is contraindicated), pure red cell aplasia, selected cases of secondary thrombocytopenia.

Miscellaneous

Trichinosis with neurologic or myocardial involvement, tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy.

Neoplastic diseases

For the palliative management of leukemias and lymphomas.

Nervous System

Acute exacerbations of multiple sclerosis; cerebral edema associated with primary or metastatic brain tumor, or craniotomy.

Ophthalmic diseases

Sympathetic ophthalmia, uveitis and ocular inflammatory conditions unresponsive to topical corticosteroids.

Renal diseases

To induce diuresis or remission of proteinuria in idiopathic nephrotic syndrome or that due to lupus erythematosus.

Respiratory diseases

Berylliosis, fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy, idiopathic eosinophilic pneumonias, symptomatic sarcoidosis.

Rheumatic disorders

As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in acute gouty arthritis; acute rheumatic carditis; ankylosing spondylitis; psoriatic arthritis; rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy). For the treatment of dermatomyositis, temporal arteritis, polymyositis, and systemic lupus erythematosus.

NOTE: CONTAINS BENZYL ALCOHOL (see WARNINGS and PRECAUTIONS: Pediatric Use)

Because of possible physical incompatibilities, Solu-Cortef should not be diluted or mixed with other solutions.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

This preparation may be administered by intravenous injection, by intravenous infusion, or by intramuscular injection, the preferred method for initial emergency use being intravenous injection. Following the initial emergency period, consideration should be given to employing a longer acting injectable preparation or an oral preparation.

Therapy is initiated by administering SOLU-CORTEF Sterile Powder intravenously over a period of 30 seconds (e.g., 100 mg) to 10 minutes (e.g., 500 mg or more). In general, high dose corticosteroid therapy should be continued only until the patient's condition has stabilized-usually not beyond 48 to 72 hours. When high dose hydrocortisone therapy must be continued beyond 48-72 hours, hypernatremia may occur. Under such circumstances it may be desirable to replace SOLU-CORTEF with a corticoid such as methylprednisolone sodium succinate which causes little or no sodium retention.

The initial dose of SOLU-CORTEF Sterile Powder is 100 mg to 500 mg, depending on the specific disease entity being treated. However, in certain overwhelming, acute, life-threatening situations, administration in dosages exceeding the usual dosages may be justified and may be in multiples of the oral dosages.

This dose may be repeated at intervals of 2, 4 or 6 hours as indicated by the patient's response and clinical condition.

It Should Be Emphasized that Dosage Requirements are Variable and Must Be Individualized on the Basis of the Disease Under Treatment and the Response of the Patient. After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage that maintains an adequate clinical response is reached. Situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment. In this latter situation it may be necessary to increase the dosage of the corticosteroid for a period of time consistent with the patient's condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.

In the treatment of acute exacerbations of multiple sclerosis, daily doses of 800 mg of hydrocortisone for a week followed by 320 mg every other day for one month are recommended (see PRECAUTIONS, Neuro-psychiatric).

In pediatric patients, the initial dose of hydrocortisone may vary depending on the specific disease entity being treated. The range of initial doses is 0.56 to 8 mg/kg/day in three or four divided doses (20 to 240 mg/m²bsa/day).

For the purpose of comparison, the following is the equivalent milligram dosage of the various glucocorticoids:

Cortisone, 25	Triamcinolone, 4
Hydrocortisone, 20	Paramethasone, 2
Prednisolone, 5	Betamethasone, 0.75
Prednisone, 5	Dexamethasone, 0.75
Methylprednisolone, 4

These dose relationships apply only to oral or intravenous administration of these compounds. When these substances or their derivatives are injected intramuscularly or into joint spaces, their relative properties may be greatly altered.

Preparation of Solutions 100 mg Plain-For intravenous or intramuscular injection, prepare solution by aseptically adding not more than 2 mL of Bacteriostatic Water for Injection or Bacteriostatic Sodium Chloride Injection to the contents of one vial. For intravenous infusion, first prepare solution by adding not more than 2 mL of Bacteriostatic Water for Injection to the vial; this solution may then be added to 100 to 1000 mL of the following: 5% dextrose in water (or isotonic saline solution or 5% dextrose in isotonic saline solution if patient is not on sodium restriction).

DIRECTIONS FOR USING THE ACT-O-VIAL SYSTEM

1. Press down on plastic activator to force diluent into the lower compartment.
2. Gently agitate to effect solution.
3. Remove plastic tab covering center of stopper.
4. Sterilize top of stopper with a suitable germicide.
5. Insert needle squarely through center of stopper until tip is just visible. Invert vial and withdraw dose.

Further dilution is not necessary for intravenous or intramuscular injection. For intravenous infusion, first prepare solution as just described. The 100 mg solution may then be added to 100 to 1000 mL of 5% dextrose in water (or isotonic saline solution or 5% dextrose in isotonic saline solution if patient is not on sodium restriction). The 250 mg solution may be added to 250 to 1000 mL, the 500 mg solution may be added to 500 to 1000 mL and the 1000 mg solution to 1000 mL of the same diluents. In cases where administration of a small volume of fluid is desirable, 100 mg to 3000 mg of SOLUCORTEF may be added to 50 mL of the above diluents. The resulting solutions are stable for at least 4 hours and may be administered either directly or by IV piggyback.

When reconstituted as directed, pH's of the solutions range from 7 to 8 and the tonicities are: 100 mg ACT-0-VIAL, .36 osmolar; 250 mg ACT-O-VIAL, 500 mg ACT-O-VIAL, and the 1000 mg ACT-0VIAL, .57 osmolar. (Isotonic saline-.28 osmolar.)

SOLU-CORTEF Sterile Powder is available in the following packages:

100 mg Plain-NDC 0009-0825-01

100 mg ACT-0-VIAL (Single-Dose Vial) 2 mL-NDC 0009-0900-13

25 x 2 mL-NDC 0009-0900-20

250 mg ACT-O-VIAL (Single-Dose Vial) 2 mL-NDC 0009-0909-08

25 x 2 mL-NDC 0009-0909-16

500 mg ACT-O-VIAL (Single-Dose Vial)-NDC 0009-0912-05

1000 mg ACT-O-VIAL (Single-Dose Vial)-NDC 0009-0920-03

Storage Conditions

Store unreconstituted product at controlled room temperature 20° to 25( C (68° to 77( F).

Store solution at controlled room temperature 20° to 25( C (68° to 77( F) and protect from light.

Use solution only if it is clear. Unused solution should be discarded after 3 days.

Pharmacia & Upjohn, Kalamazoo, Michigan 49001, USA.

Last updated on RxList: 10/20/2009

The following adverse reactions have been reported with Solu-Cortef or other corticosteroids:

Allergic reactions: allergic or hypersensitivity reactions, anaphylactoid reaction, anaphylaxis, angioedema.

Cardiovascular: Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction (see WARNINGS), pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis.

Dermatologic: Acne, allergic dermatitis, burning or tingling (especially in the perineal area, after intravenous injection), cutaneous and subcutaneous atrophy, dry scaly skin, ecchymoses and petechiae, edema, erythema, hyperpigmentation, hypopigmentation, impaired wound healing, increased sweating, rash, sterile abscess, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria.

Endocrine: Decreased carbohydrate and glucose tolerance, development of cushingoid state, glycosuria, hirsutism, hypertrichosis, increased requirements for insulin or oral hypoglycemic agents in diabetes, manifestations of latent diabetes mellitus, menstrual irregularities, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), suppression of growth in pediatric patients.

Fluid and electrolyte disturbances: Congestive heart failure in susceptible patients, fluid retention, hypokalemic alkalosis, potassium loss, sodium retention.

Gastrointestinal: Abdominal distention, bowel/bladder dysfunction (after intrathecal administration), elevation in serum liver enzyme levels (usually reversible upon discontinuation), hepatomegaly, increased appetite, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease), ulcerative esophagitis.

Metabolic: Negative nitrogen balance due to protein catabolism.

Musculoskeletal: Aseptic necrosis of femoral and humeral heads, Charcot-like arthropathy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, postinjection flare (following intra-articular use), steroid myopathy, tendon rupture, vertebral compression fractures.

Neurologic/Psychiatric: Convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, insomnia, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychic disorders, vertigo. Arachnoiditis, meningitis, paraparesis/paraplegia, and sensory disturbances have occurred after intrathecal administration (see WARNINGS, Neurologic).

Ophthalmic: Exophthalmoses, glaucoma, increased intraocular pressure, posterior subcapsular cataracts, rare instances of blindness associated with periocular injections.

Other: Abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, injection site infections following non-sterile administration (see WARNINGS), malaise, moon face, weight gain.

Aminoglutethimide

Aminoglutethimide may lead to a loss of corticosteroid-induced adrenal suppression.

Amphotericin B injection and potassium-depleting agents

When corticosteroids are administered concomitantly with potassium-depleting agents (i.e., amphotericin-B, diuretics), patients should be observed closely for development of hypokalemia. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure.

Antibiotics

Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance. (see DRUG INTERACTIONS, Hepatic Enzyme Inhibitors)

Anticholinesterases

Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy.

Anticoagulants, oral

Coadministration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect.

Antidiabetics

Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required.

Antitubercular drugs

Serum concentrations of isoniazid may be decreased.

Cholestyramine

Cholestyramine may increase the clearance of corticosteroids.

Cyclosporine

Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with this concurrent use.

Digitalis glycosides

Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia.

Estrogens, including oral contraceptives

Estrogens may decrease the hepatic metabolism of certain corticosteroids, thereby increasing their effect.

Hepatic Enzyme Inducers (e.g., barbiturates, phenytoin, carbamazepine, rifampin)

Drugs which induce cytochrome P450 3A4 enzyme activity may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased.

Hepatic Enzyme Inhibitors (e.g., ketoconazole, macrolide antibiotics such as erythromycin and troleandomycin)

Drugs which inhibit cytochrome P450 3A4 have the potential to result in increased plasma concentrations of corticosteroids.

Ketoconazole

Ketoconazole has been reported to significantly decrease the metabolism of certain corticosteroids by up to 60%, leading to an increased risk of corticosteroid side effects.

Nonsteroidal anti-inflammatory agents (NSAIDS)

Concomitant use of aspirin (or other nonsteroidal anti-inflammatory agents) and corticosteroids increases the risk of gastrointestinal side effects. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids.

Skin tests

Corticosteroids may suppress reactions to skin tests.

Vaccines

Patients on prolonged corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. Routine administration of vaccines or toxoids should be deferred until corticosteroid therapy is discontinued if possible (see WARNINGS, Infections, Vaccination).

Last updated on RxList: 10/20/2009

General

This product contains benzyl alcohol which is potentially toxic when administered locally to neural tissue. Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol. The amount of benzyl alcohol from medications is usually considered negligible compared to that received in flush solutions containing benzyl alcohol. Administration of high dosages of medications containing this preservative must take into account the total amount of benzyl alcohol administered. The amount of benzyl alcohol at which toxicity may occur is not known. If the patient requires more than the recommended dosages or other medications containing this preservative, the practitioner must consider the daily metabolic load of benzyl alcohol from these combined sources (see WARNINGS and PRECAUTIONS: Pediatric Use)

Injection of Solu-Cortef may result in dermal and/or subdermal changes forming depressions in the skin at the injection site. In order to minimize the incidence of dermal and subdermal atrophy, care must be exercised not to exceed recommended doses in injections. Injection into the deltoid muscle should be avoided because of a high incidence of subcutaneous atrophy.

Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroid therapy (see ADVERSE REACTIONS).

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

Results from one multicenter, randomized, placebo-controlled study with methylprednisolone hemisuccinate, an IV corticosteroid, showed an increase in early (at 2 weeks) and late (at 6 months) mortality in patients with cranial trauma who were determined not to have other clear indications for corticosteroid treatment. High doses of systemic corticosteroids, including Solu-Cortef, should not be used for the treatment of traumatic brain injury.

Cardio-renal

Average and large doses of corticosteroids 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.

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.

Endocrine

Hypothalamic-pituitary adrenal (HPA) axis suppression. Cushing's syndrome, and hyperglycemia. Monitor patients for these conditions with chronic use. Corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Drug induced secondary adrenocortical insufficiency 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.

Infections

General

Patients who are on corticosteroids are more susceptible to infections than are healthy individuals. There may be decreased resistance and inability to localize infection when corticosteroids are used. Infection with any pathogen (viral, bacterial, fungal, protozoan or helminthic) in any location of the body may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents.

These infections may be mild, but can be severe and at times fatal. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases. Corticosteriods may also mask some signs of current infection. Do not use intra-articularly, intrabursally or for intratendinous administration for local effect in the presence of acute local infection.

Fungal infections

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. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure (see CONTRAINDICATIONS and PRECAUTIONS: DRUG INTERACTIONS, Amphotericin B injection and potassium-depleting agents).

Special pathogens

Latent disease may be activated or there may be an exacerbation of intercurrent infections due to pathogens, including those caused by Amoeba, Candida, Cryptococus, Mycobacterium, Nocardia, Pneumocystis, Toxoplasma.

It is recommended that latent amebiasis or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has spent time in the tropics or in any patient with unexplained diarrhea.

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.

Corticosteroids should not be used in cerebral malaria. There is currently no evidence of benefit from steroids in this condition.

Tuberculosis

The use of corticosteroids 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.

Vaccination

Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered. However, the response to such vaccines can not be predicted. Immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy, e.g., for Addison's disease.

Viral infections

Chicken pox and measles can have a more serious or even fatal course in pediatric and adult patients on corticosteroids. In pediatric and adult patients who have not had these diseases, particular care should be taken to avoid exposure. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chicken pox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chicken pox develops, treatment with antiviral agents should be considered.

Neurologic

Reports of severe medical events have been associated with the intrathecal route of administration (see ADVERSE REACTIONS, Neurologic/Psychiatric).

Ophthalmic

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 bacteria, fungi, or viruses. The use of oral corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes. Corticosteroids should be used cautiously in patients with ocular herpes simplex because of corneal perforation. Corticosteroids should not be used in active ocular herpes simplex.

General

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. The lowest possible dose of corticosteroid should be used to control the condition under treatment. When reduction in dosage is possible, the reduction should be gradual.

Since complications of treatment with glucocorticoids are dependent on the size of the dose and the duration of treatment, a risk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent therapy should be used.

Kaposi sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement.

Cardio-renal

As sodium retention with resultant edema and potassium loss may occur in patients receiving corticosteroids, these agents should be used with caution in patients with congestive heart failure, hypertension, or renal insufficiency.

Endocrine

Drug-induced secondary adrenocortical insufficiency 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. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently. Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in dosage.

Gastrointestinal

Steroids should be used with caution in active or latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, and nonspecific ulcerative colitis, since they may increase the risk of a perforation. Signs of peritoneal irritation following gastrointestinal perforation in patients receiving corticosteroids may be minimal or absent.

There is an enhanced effect due to increased metabolism of corticosteroids in patients with cirrhosis.

Musculoskeletal

Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (i.e., decreasing absorption and increasing excretion) and inhibition of osteoblast function. This, together with a decrease in the protein matrix of the bone secondary to an increase in protein catabolism, and reduced sex hormone production, may lead to inhibition of bone growth in pediatric patients and the development of osteoporosis at any age. Special consideration should be given to patients at increased risk of osteoporosis (i.e., postmenopausal women) before initiating corticosteroid therapy.

Local injection of a steroid into a previously infected site is not usually recommended.

Neurologic-psychiatric

Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not show that they affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect. (See DOSAGE AND ADMINISTRATION.)

An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatinine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.

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.

Ophthalmic

Intraocular pressure may become elevated in some individuals. If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No adequate studies have been conducted in animals to determine whether corticosteroids have a potential for carcinogenesis or mutagenesis.

Steroids may increase or decrease motility and number of spermatozoa in some patients.

Pregnancy

Teratogenic effects

Pregnancy Category C.

Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose. Animal studies in which corticosteroids have been given to pregnant mice, rats, and rabbits have yielded an increased incidence of cleft palate in the offspring. There are no adequate and well-controlled studies in pregnant women. Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Infants born to mothers who have received corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.

Nursing Mothers

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Because of the potential for serious adverse reactions in nursing infants from corticosteroids, a decision should be made whether to continue nursing, or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

This product contains benzyl alcohol as a preservative. Benzyl alcohol, a component of this product, has been associated with serious adverse events and death, particularly in pediatric patients. The “gasping syndrome”, (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages > 99 mg/kg/day in neonates and low-birth-weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birthweight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.

The efficacy and safety of corticosteroids in the pediatric population are based on the well-established course of effect of corticosteroids which is similar in pediatric and adult populations. Published studies provide evidence of efficacy and safety in pediatric patients for the treatment of nephrotic syndrome ( > 2 years of age), and aggressive lymphomas and leukemias ( > 1 month of age). Other indications for pediatric use of corticosteroids, e.g., severe asthma and wheezing, are based on adequate and well-controlled trials conducted in adults, on the premises that the course of the diseases and their pathophysiology are considered to be substantially similar in both populations.

The adverse effects of corticosteroids in pediatric patients are similar to those in adults (see ADVERSE REACTIONS). Like adults, pediatric patients should be carefully observed with frequent measurements of blood pressure, weight, height, intraocular pressure, and clinical evaluation for the presence of infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis. Pediatric patients who are treated with corticosteroids by any route, including systemically administered corticosteroids, may experience a decrease in their growth velocity. This negative impact of corticosteroids on growth has been observed at low systemic doses and in the absence of laboratory evidence of HPA axis suppression (i.e., cosyntropin stimulation and basal cortisol plasma levels). Growth velocity may therefore be a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The linear growth of pediatric patients treated with corticosteroids should be monitored, and the potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of treatment alternatives. In order to minimize the potential growth effects of corticosteroids, pediatric patients should be titrated to the lowest effective dose.

Geriatric Use

Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Last updated on RxList: 10/20/2009

Treatment of acute overdosage is by supportive and symptomatic therapy. For chronic overdosage in the face of severe disease requiring continuous steroid therapy, the dosage of the corticosteroid may be reduced only temporarily, or alternate day treatment may be introduced.

SOLU-CORTEF Sterile Powder is contraindicated in patients with known hypersensitivity to the product and its constituents.

Intramuscular corticosteroid preparations are contraindicated for idiopathic thrombocytopenic purpura.

SOLU-CORTEF Sterile Powder is contraindicated for use in premature infants because the formulation contains benzyl alcohol. (See WARNINGS and PRECAUTIONS: Pediatric Use)

SOLU-CORTEF Sterile Powder is contraindicated for intrathecal administration. Reports of severe medical events have been associated with this route of administration.

Last updated on RxList: 10/20/2009

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

Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs are primarily used for their anti-inflammatory effects in disorders of many organ systems.

Hydrocortisone sodium succinate has the same metabolic and anti-inflammatory actions as hydrocortisone. When given parenterally and in equimolar quantities, the two compounds are equivalent in biologic activity. The highly water-soluble sodium succinate ester of hydrocortisone permits the immediate intravenous administration of high doses of hydrocortisone in a small volume of diluent and is particularly useful where high blood levels of hydrocortisone are required rapidly. Following the intravenous injection of hydrocortisone sodium succinate, demonstrable effects are evident within one hour and persist for a variable period. Excretion of the administered dose is nearly complete within 12 hours. Thus, if constantly high blood levels are required, injections should be made every 4 to 6 hours. This preparation is also rapidly absorbed when administered intramuscularly and is excreted in a pattern similar to that observed after intravenous injection.

Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune response to diverse stimuli.

Last updated on RxList: 10/20/2009

Patients should be warned not to discontinue the use of corticosteroids abruptly or without medical supervision, to advise any medical attendants that they are taking corticosteroids and to seek medical advice at once should they develop fever or other signs of infection. Persons who are on corticosteroids should be warned to avoid exposure to chicken pox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay.

Last updated on RxList: 10/20/2009

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

HYDROCORTISONE SODIUM SUCCINATE - INJECTION

(HYE-droe-KOR-ti-sone SOE-dee-um SUX-i-nate)

COMMON BRAND NAME(S): A-Hydrocort, Solu-Cortef

USES: This medication is used to treat various conditions such as severe allergic reactions, arthritis, blood diseases, breathing problems, certain cancers, eye diseases, intestinal disorders, and skin diseases. It decreases your body's natural defensive response and reduces symptoms such as swelling and allergic-type reactions. Hydrocortisone is a corticosteroid hormone (glucocorticoid). This injectable form of hydrocortisone is used when a similar drug cannot be taken by mouth or when a very fast treatment is needed, especially in patients with severe medical conditions.

This drug may also be used with other medications as a replacement for certain hormones.

HOW TO USE: This medication is given by slow injection into a vein or directly into a muscle by a health care professional as directed by your doctor. Follow your doctor's directions carefully. Dosage is based on your medical condition and response to treatment. Do not increase your dose or use this drug more often than prescribed without consulting your doctor. Before using this product, check it visually for particles or discoloration. If either is present, do not use the liquid.

If you have been using this medication for a long time, do not suddenly stop using it without your doctor's approval. Your dose may need to be gradually decreased to reduce symptoms such as weakness, weight loss, nausea, or extreme tiredness.

If you are giving yourself injections at home, learn how to prepare and inject this medication properly. Ask your doctor, pharmacist, or nurse any questions you may have about how to give yourself hydrocortisone. Learn how to store and discard needles, medical supplies, and any unused medication safely. Consult your pharmacist. Never reuse needles or syringes.

Tell your doctor if your condition persists or worsens.

SIDE EFFECTS: Stomach upset, headache, dizziness, menstrual period changes, trouble sleeping, increased appetite, weight gain, or pain/redness/swelling at the injection site may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: bone/joint pain, easy bruising/bleeding, black stools, vomit that looks like coffee grounds, severe stomach/abdominal pain, increased thirst/urination, fast/slow/pounding/irregular heartbeat, shortness of breath, swelling of the ankles/feet, tendon pain, persistent weight gain, puffy face, unusual hair growth, thinning skin, slow wound healing, signs of infection (e.g., persistent fever/cough/sore throat, painful urination, eye pain/discharge), muscle weakness/pain, mental/mood changes (e.g., mood swings, depression, agitation), vision changes, seizures, unusual skin growths.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using hydrocortisone, tell your doctor or pharmacist if you are allergic to it; or to other corticosteroids (e.g., prednisone); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: current fungal infections.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: other infections (e.g., tuberculosis, threadworm), bleeding problems, blood clots, brittle bones (osteoporosis), high blood pressure, certain heart problems (e.g., congestive heart failure, recent heart attack), diabetes, certain eye diseases (e.g., cataracts, herpes infection, glaucoma), kidney disease, severe liver disease (cirrhosis), mental/mood conditions (e.g., psychosis, anxiety, depression), seizures, stomach/intestinal problems (e.g., diverticulitis, ulcer, ulcerative colitis), underactive thyroid gland (hypothyroidism), untreated mineral problems (e.g., low potassium or calcium).

This drug may make you dizzy. Use caution while driving, using machinery, or doing any activity that requires alertness.

This medication may mask signs of infection or put you at greater risk of developing very serious infections. Report to your doctor any injuries or signs of infection (e.g., persistent sore throat/cough/fever, pain during urination, muscle aches) that occur while using this medication or within 12 months after stopping it.

If you have been using this medication for a long time, your body may not be able to make enough natural steroids while you are under stress due to infection, surgery, or injury. Your dose may need to be adjusted. If you have stopped using this drug within the past 12 months, you may need to start using it again if your body is under severe stress. Consult your doctor for more details. Tell your doctor immediately if any of these side effects occur: unusual weakness, sudden weight loss, dizziness.

Do not have immunizations, vaccinations, or skin tests unless specifically directed by your doctor. Live vaccines may cause serious problems (e.g., infection) if given while you are using this medication. Avoid contact with people who have recently received oral polio vaccine or flu vaccine inhaled through the nose.

Avoid contact with people who have chickenpox or measles unless you have previously had these diseases (e.g., in childhood). If you are exposed to one of these infections and you have not previously had it, seek immediate medical attention.

If you have a history of ulcers, or if you take large doses of aspirin or other arthritis medication, limit alcoholic beverages while using this medication to decrease the risk of stomach/intestinal bleeding. Consult your doctor or pharmacist for more details.

Before having surgery, tell your doctor or dentist that you are using this medication or have used it within the last 12 months.

If you have diabetes, this drug may increase your blood sugar levels. Check your blood glucose levels regularly as directed by your doctor. Tell your doctor immediately if you have symptoms such as increased thirst and urination. Your anti-diabetic medication or diet may need to be adjusted.

Caution is advised when using this drug in the elderly because they may be more sensitive to its side effects, especially osteoporosis. Talk with your doctor about ways to prevent bone loss.

Caution is advised when using this drug for a long time in children. This medication may temporarily slow down a child's rate of growth, but it will probably not affect final adult height. Monitor your child's height periodically.

A preservative (benzyl alcohol) that may be found in this product or in the liquid used to mix this product can infrequently cause serious (sometimes fatal) problems if given in large amounts (more than 100 milligrams per kilogram daily) to an infant during the first months of life. The risk is also greater with low-birth-weight infants. Symptoms include sudden gasping, low blood pressure, or a very slow heartbeat. If you notice any of these symptoms in your newborn, report them to the doctor immediately. If possible, a preservative-free product should be used when treating newborns.

This medication should be used only when clearly needed during pregnancy. There have been rare reports of harm to an unborn baby when corticosteroids are used during pregnancy. Discuss the risks and benefits with your doctor. Infants born to mothers who have been using this medication for an extended time may have low levels of corticosteroid hormone. Tell your doctor immediately if you notice symptoms such as persistent nausea/vomiting, severe diarrhea, or weakness in your newborn.

This medication passes into breast milk. Although there have been no reports of harm to nursing infants, consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: aldesleukin, large doses of aspirin and aspirin-like drugs (salicylates such as salsalate), birth control pills/patch/ring, "blood thinners" (e.g., warfarin), bupropion, drugs for diabetes, drugs that cause potassium loss (e.g., amphotericin B, diuretics such as hydrochlorothiazide, furosemide), estrogens, mifepristone, natalizumab, nonsteroidal anti-inflammatory drugs (NSAIDs such as indomethacin, ibuprofen), quinolone antibiotics (e.g., levofloxacin), drugs affecting liver enzymes that remove hydrocortisone from your body (e.g., aprepitant, azole antifungals such as ketoconazole, macrolide antibiotics such as erythromycin, rifamycins such as rifampin, certain anti-seizure medications such as phenytoin and phenobarbital), herbal products (e.g., licorice).

Check all prescription and nonprescription medicine labels carefully since many medications contain pain relievers/fever reducers (NSAIDs such as aspirin, ibuprofen, or naproxen) that may increase the risk of stomach bleeding from this drug. Low-dose aspirin should be continued if prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually at dosages of 81-325 milligrams per day). Consult your doctor or pharmacist for more details.

This medication may interfere with certain laboratory tests (including skin tests), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., blood counts, blood glucose/mineral levels, blood pressure, bone density tests, height/weight measurements, eye examinations, X-rays) should be performed periodically to monitor your progress or check for side effects during long-term treatment. Consult your doctor for more details.

Lifestyle changes that help reduce the risk of bone loss (osteoporosis) during long-term treatment include doing weight-bearing exercise, getting adequate calcium and vitamin D, stopping smoking, and limiting alcohol. Talk with your doctor about lifestyle changes that might benefit you.

If you use this medication for prolonged periods, you should wear or carry identification stating that you are using it.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

After mixing and dilution in correct IV fluids, the drug may be kept at room temperature for up to 72 hours if protected from light Consult your pharmacist for details. Discard any unused liquid.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised September 2008 Copyright(c) 2008 First DataBank, Inc.