Solu-Cortef

Solu-Cortef is part of the drug classes:

• Corticosteroids acting locally

• Corticosteroids for local oral treatment

• Antiinflammatory Corticosteroids

• Corticosteroids, weak group I

• Corticosteroids, weak, other combinations

• Corticosteroids/antiinfectives/mydriatics in combination

• Glucocorticoids

• If you need to store Solu-Cortef at home, talk with your doctor, nurse, or pharmacist about how to store it.

Solu-Cortef Sterile Powder is an anti-inflammatory glucocorticoid that contains hydrocortisone sodium succinate as the active ingredient. Solu-Cortef Sterile Powder is available in several packages for intravenous or intramuscular administration.

100 mg PlainVials containing hydrocortisone sodium succinate equivalent to 100 mg hydrocortisone, 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).

The diluent, as part of the packaging presentation for the ACT-O-VIAL® system, is comprised of Water for Injection only, and does not contain any preservative.

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.

The chemical name for hydrocortisone sodium succinate 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 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.

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 intramusculat 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, select 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.

Solu-Cortef Sterile Powder is contraindicated in systemic fungal infections and 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 intrathecal administration. Reports of severe medical events have been associated with this route of administration.

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's 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. 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 non-specific 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 decreased metabolism of corticosteroids in patients with cirrhosis.

Musculoskeletal

Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (e.g., 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 corticosteroids 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 creatine 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.

Other

Pheochromocytoma crisis, which can be fatal, has been reported after administration of systemic corticosteroids. In patients with suspected pheochromocytoma, consider the risk of pheochromocytoma crisis prior to administering corticosteroids.

Information for Patients

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.

Drug Interactions

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

When corticosteroids are administered concomitantly with potassium-depleting agents (e.g., 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.

Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance (see PRECAUTIONS: Drug Interactions, Hepatic Enzyme Inhibitors).

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.

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.

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

Serum concentrations of isoniazid may be decreased.

Cholestyramine may increase the clearance of corticosteroids.

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

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

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

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

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

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.

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.

Corticosteroids may suppress reactions to skin tests.

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).

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.

Corticosteroids have been shown to impair fertility in male rats.

Pregnancy

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

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.

Because of possible physical incompatilitbilites, 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 that 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, Neurologic-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:

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 Solu-Cortef 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-O-VIAL, 0.36 osmolar; 250 mg ACT-O-VIAL, 500 mg ACT-O-VIAL, and 1000 mg ACT-O-VIAL, 0.57 osmolar. (Isotonic saline=0.28 osmolar.)

NDC 0009-0825-01

Solu-Cortef®

(hydrocortisone
sodium succinate
for injection, USP)

100 mg*

For IM or IV use
Preservative-Free

Rx only

Single-Dose Vial
2 mL Act-O-Vial®
NDC 0009-0013-05

Solu-Cortef®

(hydrocortisone sodium
succinate for injection, USP)

250 mg*

For IM or IV use
Preservative-Free
Rx only

NDC 0009-0005-01

Single-Dose Vial
8 mL Act-O-Vial®

Solu-Cortef®

(hydrocortisone
sodium succinate
for injection, USP)

1000 mg*

For intramuscular or
intravenous use

Preservative-Free

Rx only

Pfizer Injectables