For Intravenous or Intramuscular Administration DESCRIPTION

1 1 solu - cortef hydrocortisone sodium succinate for injection, USP For Intravenous or Intramuscular Administration DESCRIPTION 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-o xopropoxy)-11,17-dihydroxy-, monosodium salt, (11 )- and its molecular weight is 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.

2 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 mg monobasic sodium phosphate anhydrous, mg dibasic sodium phosphate dried. solu - cortef 100 mg plain does not contain diluent (see DOSAGE and Administration , Preparation of Solutions). 2 ACT-O-VIAL System (Single-Dose Vial) in four strengths: 100 mg ACT-O-VIAL250 mg ACT-O-VIAL500 mg ACT-O-VIAL 1000 mg ACT-O-VIAL Each 2 mL contains: (when mixed) Each 2 mL contains: (when mixed) Each 4 mL contains: (when mixed) Each 8 mL contains: (when mixed) Hydrocortisone sodium succinate equiv. to 100 mg Hydrocor-tisone equiv. to 250 mg Hydrocor-tisone equiv. to 500 mg Hydrocor-tisone equiv.

3 To 1000 mg Hydrocor- tisone Monobasic sodium phosphate anhydrous mg 2 mg 4 mg 8 mg Dibasic sodium phosphate dried mg mg 44 mg mg Benzyl alcohol added as preservative mg mg mg 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. ACTIONS Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have saltretaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs are primarily 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 response to diverse stimuli.

4 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. 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. INDICATIONS 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 3condition, solu - cortef Sterile Powder is indicated for Intravenous or Intramuscular use in the following conditions: 1.

5 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) Acute adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; mineralocorticoid supplementation may be necessary, particularly when synthetic analogs are used) Preoperatively and in the event of serious trauma or illness, in patients with known adrenal insufficiency or when adrenocortical reserve is doubtful Shock unresponsive to conventional therapy if adrenocortical insufficiency exists or is suspected Congenital adrenal hyperplasia Nonsuppurative thyroiditis Hypercalcemia associated with cancer 2.

6 Rheumatic Disorders As adjunctive therapy for short-term Administration (to tide the patient over an acute episode or exacerbation) in: Post-traumatic osteoarthritis Acute and subacute bursitis Synovitis of osteoarthritis Epicondylitis Rheumatoid arthritis, including juvenile Acute nonspecific tenosynovitis rheumatoid arthritis (selected cases Acute gouty arthritis may require low-dose maintenance Psoriatic arthritis therapy) Ankylosing spondylitis 3. Collagen Diseases During an exacerbation or as maintenance therapy in selected cases of: Systemic lupus erythematosus Acute rheumatic carditis Systemic dermatomyositis (polymyositis) 4.

7 Dermatologic Diseases Pemphigus Bullous dermatitis herpetiformis Severe erythema multiforme (Stevens- Severe seborrheic dermatitis Johnson syndrome) Severe psoriasis Exfoliative dermatitis Mycosis fungoides 5. Allergic States Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in: Bronchial asthma Drug hypersensitivity reactions Contact dermatitis Urticarial transfusion reactions Atopic dermatitis Acute noninfectious laryngeal edema Serum sickness (epinephrine is the drug Seasonal or perennial allergic rhinitis of first choice) 6.

8 Ophthalmic Diseases Severe acute and chronic allergic and inflammatory processes involving the eye, such as: 4 Herpes zoster ophthalmicus Sympathetic ophthalmia Iritis, iridocyclitis Anterior segment inflammation Chorioretinitis Allergic conjunctivitis Diffuse posterior uveitis and choroiditis Allergic corneal marginal ulcers Optic neuritis Keratitis 7. Gastrointestinal Diseases To tide the patient over a critical period of the disease in: Ulcerative colitis (systemic therapy) Regional enteritis (systemic therapy) 8. Respiratory Diseases Symptomatic sarcoidosis Loeffler s syndrome not manageable Berylliosis by other means Fulminating or disseminated pulmonary Aspiration pneumonitis tuberculosis when used concurrently with appropriate antituberculous chemotherapy 9.

9 Hematologic Disorders Acquired (autoimmune) hemolytic anemia Erythroblastopenia (RBC anemia) Idiopathic thrombocytopenic purpura Congenital (erythroid) hypoplastic in adults (IV only; IM Administration anemia is contraindicated) Secondary thrombocytopenia in adults 10. Neoplastic Diseases For palliative management of: Leukemias and lymphomas in adults Acute leukemia of childhood 11. 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 12. Nervous System Acute exacerbations of multiple sclerosis 13. Miscellaneous Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy Trichinosis with neurologic or myocardial involvement CONTRAINDICATIONS The use of solu - cortef Sterile Powder is contraindicated in premature infants because the 100 mg, 250 mg, 500 mg and 1000 mg ACT-O-VIAL System contain benzyl alcohol.

10 Benzyl alcohol has been reported to be associated with a fatal "Gasping Syndrome" in premature infants. solu - cortef Sterile Powder is also contraindicated in systemic fungal infections and patients with known hypersensitivity to the product and its constituents. WARNINGS Exposure to excessive amounts of benzyl alcohol has been associated with increased toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare 5reports of deaths, primarily in pre-term 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.