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Data Sheet

SOLU CORTEF

Sterile hydrocortisone sodium succinate for injection, USP

Two compartment vial of 100 mg

Presentation

SOLU CORTEF is a white or nearly white odourless, hygroscopic amorphous solid, available in act-o-vials containing 100mg, hydrocortisone sodium succinate and bacteriostatic water.

Uses

Actions

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.

Hydrocortisone sodium succinate has the same metabolic and anti-inflammatory action 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

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

Hypercalcaemia associated with cancer

Nonsuppurative thyroiditis

Rheumatic Disorders:

As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in:

Collagen Diseases:

During an exacerbation or as maintenance therapy in selected cases of:

Dermatologic Diseases:

Allergic States:

Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in:

Ophthalmic Diseases:

Severe acute and chronic allergic and inflammatory processes involving the eye, such as:

Gastrointestinal Diseases:

To tide the patient over a critical period of the disease in -

Respiratory Diseases:

Haematologic Disorders:

Neoplastic Diseases:

For palliative management of:

Oedematous States:

To induce diuresis or remission of proteinuria in the nephrotic syndrome, without uraemia, or the idiopathic type or that due to lupus erythematosus.

Nervous System:

Acute exacerbations of multiple sclerosis.

Medical Emergencies:

SOLU-CORTEF is indicated in the treatment of:

  1. Shock secondary to adrenocortical insufficiency or shock unresponsive to conventional therapy when adrenal cortical insufficiency may be present; and
  2. Acute allergic disorders (status asthmaticus, anaphylactic reactions, insect stings, etc.) following epinephrine.

Although there are no well controlled (double-blind, placebo) clinical trials, data from experimental animal models indicate that corticosteroids may be useful in haemorrhagic, traumatic and surgical shock in which standard therapy (e.g. fluid replacement etc) has not been effective.

Miscellaneous:

Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy.

Trichinosis with neurologic or myocardial involvement.

Dosage and Administration

The 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. hydrocortisone sodium succinate equivalent to 100 mg of hydrocortisone) 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 stabilised - usually not beyond 48 to 72 hours. Although adverse effects associated with high dose, short-term corticoid therapy are uncommon, peptic ulceration may occur. Prophylactic antacid therapy may be indicated.

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 product such as one containing methylprednisolone sodium succinate which causes little or no sodium retention.

The initial dose of SOLU-CORTEF is 100 mg to 500 mg or more (hydrocortisone equivalent of hydrocortisone sodium succinate) depending on the severity of the condition.

This dose may be repeated at intervals of 2, 4, or 6 hours as indicated by the patient's responses and clinical condition. While the dose may be reduced for infants and children, it is governed more by the severity of the condition and response of the patient than by age or body weight but should not be less than 25 mg daily.

Patients subjected to severe stress following corticosteroid therapy should be observed closely for signs and symptoms of adrenocortical insufficiency.

Corticosteroid therapy is an adjunct to, and not a replacement for, conventional therapy.

Contraindications

Systemic fungal infections.

Known hypersensitivity to components.

Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.

Warnings and Precautions

Warnings

In patients on corticosteroid therapy subjected to unusual stress, increased dosage or rapidly acting corticosteroids before, during and after the stressful situation is indicated.

Corticosteroids may mask some signs of infection, and new infections may appear during their use. There may be decreased resistance and inability to localise infection when corticosteroids are used. Infections with any pathogen including viral, bacterial, fungal, protozoan or helminthic infections, in any location in the body, may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents that affect cellular immunity, humoral immunity, or neutrophil function. 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.

The use of hydrocortisone sodium succinate 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 appropriate antituberculosis 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.

Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered to patients receiving immunosuppressive doses of corticosteroids; however, the response to such vaccines may be diminished. Indicated immunisation procedures may be undertaken in patients receiving non-immunosuppressive doses of corticosteroids.

Hydrocortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion.

Because rare instances of anaphylactoid reactions (e.g., bronchospasm) 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.

This product contains benzyl alcohol. Benzyl alcohol has been reported to be associated with a fatal "Gasping Syndrome" in premature infants.

Although recent studies have not been conducted with hydrocortisone or other corticosteroids, studies of methylprednisolone sodium succinate in septic shock suggest that increased mortality may occur in some subgroups of patients at higher risk (i.e., elevated creatinine greater than 2.0 mg% or with secondary infections).

General Precautions

Growth may be suppressed in children receiving long-term, daily-divided dose glucocorticoid therapy. The use of such a regimen should be restricted to the most serious indications.

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.

Steroids should be used with caution in non-specific ulcerative colitis, if there is a probability of impending perforation, abscess or other pyogenic infections, also in diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, renal insufficiency, hypertension, osteoporosis, and myasthenia gravis.

An acute myopathy has been described 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 generalised, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevations of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.

Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy. Discontinuation of corticosteroids may result in clinical remission.

Pregnancy & Lactation

Some animal studies have shown that corticosteroids, when administered to the mother at high doses, may cause foetal malformations. Adequate human reproductive studies have not been done with corticosteroids. Therefore the use of this drug in pregnancy, nursing mothers, or women of childbearing potential requires that the benefits of the drug be carefully weighed against the potential risk to the mother and embryo or foetus. Since there is inadequate evidence of safety in human pregnancy, this drug should be used in pregnancy only if clearly needed.

Corticosteroids readily cross the placenta. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy must be carefully observed and evaluated for signs of adrenal insufficiency. There are no known effects of corticosteroids on labour and delivery.

Corticosteroids are excreted in breast milk.

There is no evidence that corticosteroids are carcinogenic, mutagenic or impair fertility.

Adverse Effects

The following are typical for all systemic corticosteroids. Their inclusion in this list does not necessarily indicate that the specific event has been observed with this particular formulation.

Fluid and Electrolyte Disturbances:

Musculoskeletal:

Gastrointestinal:

Increase in alanine transaminase (ALT, SGPT), aspartate transaminase (AST, SGOT) and alkaline phosphatase have been observed following corticosteroid treatment. These changes are usually small, not associated with any clinical syndrome, and are reversible upon discontinuation.

Dermatologic:

Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy.

Neurological:

Endocrine:

Ophthalmic:

Metabolic:

Immune System:

Miscellaneous:

The product contains benzyl alcohol which has been associated with a fatal "Gasping Syndrome" in premature infants.

Interactions

The pharmacokinetic interactions listed below are potentially clinically important. Drugs that induce hepatic enzymes such as phenobarbital, phenytoin and rifampin may increase the clearance of corticosteroids and may require increases in corticosteroid dose to achieve the desired response.

Drugs such as troleandomycin and ketoconazole may inhibit the metabolism of corticosteroids and thus decrease their clearance. Therefore the dose of corticosteroid should be titrated to avoid steroid toxicity.

Corticosteroids may increase the clearance of chronic high dose aspirin. This could lead to decreased salicylate serum levels or increase the risk of salicylate toxicity when corticosteroid is withdrawn. Aspirin should be used cautiously in conjunction with corticosteroids in patients suffering from hypoprothrombinaemia.

The effect of corticosteroids on oral anticoagulants is variable. There are reports of enhanced as well as diminished effects of anticoagulant when given concurrently with corticosteroids. Therefore coagulation indices should be monitored to maintain the desired anticoagulant effect.

Overdosage

Reports of acute toxicity and metabolic disturbances with glucocorticoids are rare but do occur. There is no clinical syndrome of acute overdosage with SOLU CORTEF (hydrocortisone sodium succinate). Hydrocortisone is dialysable. Acute overdose may possibly aggravate pre-existing disease states such as ulceration of the gastrointestinal tract, electrolyte disturbances, infections, diabetes and oedema.

Repeated frequent doses (daily or several times per week) over a protracted period may result in a Cushingoid state. The possibility of adrenal suppression should be guarded against by gradual diminution of dose levels over a period of time.

In the event of acute overdose, treatment is symptomatic and supportive, including respiratory and cardiovascular function. In chronic toxicity, fluids and electrolytes should be monitored closely. Serum levels are not clinically useful.

Pharmaceutical Precautions

Store below 25° C. Use reconstituted solution within 72 hours after mixing.

Medicine Classification

Prescription medicine.

Package Quantities

SOLU CORTEF is available in the following pack sizes:

100 mg act-o-vial

Further Information

Preparation of Solutions

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

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 centre of stopper.
  4. Sterilize top of stopper with a suitable germicide.
  5. Insert needle squarely through centre 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). In cases where administration of a small volume of fluid is desirable, 100 mg to 3000 mg (hydrocortisone equivalent of hydrocortisone sodium succinate) 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 "piggy-back."

SOLU CORTEF is a registered trademark.

Name and Address

Pfizer New Zealand Ltd
PO Box 3998
Auckland
New Zealand

Toll Free Number: 0800 736 363

Date of Preparation

21 April 2008

(Ref: CDS 09/02/99)