DESCRIPTION:

Dexamethasone sodium phosphate is a water-soluble inorganic ester of dexamethasone.  It occurs as a white or slightly yellow crystalline powder, is odorless or has a slight odor of alcohol, is exceedingly hygroscopic and is freely soluble in water. 

Dexamethasone sodium phosphate is an adrenocortical steroid anti-inflammatory drug. 

Chemically, dexamethasone sodium phosphate is 9-Fluoro-11ß,17,21-trihydroxy-16α-methylpregna-1, 4-diene-3,20-dione 21-(dihydrogen phosphate) disodium salt and has the following structural formula:

 

Dexamethasone Sodium Phosphate Injection, USP is a sterile solution of dexamethasone sodium phosphate in water for injection for intravenous (IV), intramuscular (IM), intra-articular, soft-tissue or intralesional use. 

Each mL contains dexamethasone sodium phosphate equivalent to dexamethasone phosphate 4 mg or dexamethasone 3.33 mg; benzyl alcohol 10 mg added as preservative; sodium citrate dihydrate 11 mg; sodium sulfite 1 mg as an antioxidant; Water for Injection q.s.  Citric acid and/or sodium hydroxide may have been added for pH adjustment (7.0 to 8.5).  Air in the container is displaced by nitrogen.

CLINICAL PHARMACOLOGY:

Dexamethasone sodium phosphate has a rapid onset but short duration of action when compared with less soluble preparations.  Because of this, it is suitable for the treatment of acute disorders responsive to adrenocortical steroid therapy. 

Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states.  Their synthetic analogs, including dexamethasone, 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 responses to diverse stimuli. 

At equipotent anti-inflammatory doses, dexamethasone almost completely lacks the sodium-retaining property of hydrocortisone and closely related derivatives of hydrocortisone.

INDICATIONS AND USAGE:

Intravenous or Intramuscular Injection 
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, those products labeled for intravenous or intramuscular use are indicated as follows:
•  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 syntheticanalogs 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
•  Rheumatic Disorders
           As adjunctive therapy for short-term administration(to tide the patient over an acute episode or exacerbation)in:
           Post-traumatic osteoarthritis
           Synovitis of osteoarthritis
           Rheumatoid arthritis, including juvenile rheumatoid arthritis(selected cases may require low-dose maintenance therapy)
           Acute and subacute bursitis
           Epicondylitis
           Acute nonspecific tenosynovitis
           Acute gouty arthritis
           Psoriatic arthritis
           Ankylosing spondylitis
• Collagen Diseases
           During an exacerbation or as maintenance therapy in selected cases of:
           Systemic lupus erythematosus
           Acute rheumatic carditis
           Dermatologic Diseases
           Pemphigus
           Severe erythema multiforme (Stevens-Johnson syndrome)
           Exfoliative dermatitis
           Bullous dermatitis herpetiformis
           Severe seborrheic dermatitis
           Severe psoriasis
           Mycosis fungoides
•  Allergic States
           Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in:
           Bronchial asthma
           Contact dermatitis
           Atopic dermatitis
           Serum sickness
           Seasonal or perennial allergic rhinitis
           Drug hypersensitivity reactions
           Urticarial transfusion reactions
           Acute noninfectious laryngeal edema (epinephrine is the drug of first choice)
•  Ophthalmic Diseases
           Severe acute and chronic allergic and inflammatory processes involving the eye, such as:
           Herpes zoster ophthalmicus
           Iritis, iridocyclitis
           Chorioretinitis
           Diffuse posterior uveitis and choroiditis
           Optic neuritis
           Sympathetic ophthalmia
           Anterior segment inflammation
           Allergic conjunctivitis
           Keratitis
           Allergic corneal marginal ulcers
•  Gastrointestinal Diseases
          To tide the patient over a critical period of the disease in:
           Ulcerative colitis(Systemic therapy)
           Regional enteritis(Systemic therapy)
•  Respiratory Diseases
          Symptomatic sarcoidosis
           Berylliosis
           Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy Loeffler’s syndrome not manageable by other means
           Aspiration pneumonitis
•  Hematologic Disorders
          Acquired(autoimmune hemolytic anemia Idiopathic thrombocytopenic purpura in adults(IV only; IM administration is contraindicated)
           Secondary thrombocytopenia in adults
           Erythroblastopenia(RBC anemia)
           Congenital(erythroid hypoplastic anemia
•  Neoplastic Diseases
           For palliative management of:
           Leukemias and lymphomas in adults
           Acute leukemia of childhood
•  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
•  Miscellaneous
            Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy richinosis with neurologic or myocardial involvement
•  Diagnostic testing of adrenocortical hyperfunction
•  Cerebral Edema associated with primary or metastatic brain tumor, craniotomy, or head injury.
           Use in cerebral edema is not a substitute for careful neurosurgical evaluation and definitive management such as neurosurgery or other specific therapy.

CONTRAINDICATIONS:

Systemic fungal infections (see WARNINGS regarding amphotericin B).  Hypersensitivity to any component of this product, including sulfites (see WARNINGS).

WARNINGS:

Because rare instances of anaphylactoid reactions have occurred in patients receiving parenteral corticosteroid therapy, appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of allergy to any drug.  Anaphylactoid and hypersensitivity reactions have been reported for dexamethasone sodium phosphate (see ADVERSE REACTIONS).

Dexamethasone sodium phosphate injection contains sodium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.  The overall prevalence of sulfite sensitivity in the general population is unknown and probably low.  Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

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 due to amphotericin B.   Moreover, there have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive failure.

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

Drug-induced secondary adrenocortical insufficiency may result from too rapid withdrawal of corticosteroids and may be minimized by gradual reduction of dosage.  This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted.  If the patient is receiving steroids already, dosage may have to be increased.  Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently.

Corticosteroids may mask some signs of infection, and new infections may appear during their use.  There may be decreased resistance and inability to localize infection when corticosteroids are used.  Moreover, corticosteroids may affect the nitroblue-tetrazolium test for bacterial infection and produce false negative results.

In cerebral malaria, a double-blind trial has shown that the use of corticosteroids is associated with prolongation of coma and a higher incidence of pneumonia and gastrointestinal bleeding.

Corticosteroids may activate latent amebiasis.  Therefore, it is recommended that latent or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has spent time in the tropics or any patient with unexplained diarrhea.

Prolonged use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses.

Average and large doses of cortisone or hydrocortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium.  These effects are less likely to occur with the synthetic derivatives except when used in large doses.  Dietary salt restriction and potassium supplementation may be necessary.  All corticosteroids increase calcium excretion.

Administration of live virus vaccines, including smallpox, is contraindicated in individuals receiving immunosuppressive doses of corticosteroids.  If inactivated viral or bacterial vaccines are administered to individuals receiving immunosuppressive doses of corticosteroids, the expected serum antibody response may not be obtained.  However, immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy, e.g., for Addison’s disease.

Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals.  Chickenpox and measles, for example, can have a more serious or even fatal course in non-immune children or adults on corticosteroids.  In such children or adults who have not had these diseases, particular care should be taken to avoid exposure.  How the dose, route and duration of corticosteroid administration affects the risk of developing a disseminated infection is not known.  The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known.  If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated.  If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated.  (See the respective package inserts for complete VZIG and IG prescribing information).  If chickenpox develops, treatment with antiviral agents may be considered.

The use of dexamethasone sodium phosphate 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.

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.

PRECAUTIONS:

This product, like many other steroid formulations, is sensitive to heat.  Therefore, it should not be autoclaved when it is desirable to sterilize the exterior of the vial.

Following prolonged therapy, withdrawal of corticosteroids may result in symptoms of the corticosteroid withdrawal syndrome including fever, myalgia, arthralgia, and malaise.  This may occur in patients even without evidence of adrenal insufficiency.

There is an enhanced effect of corticosteroids in patients with hypothyroidism and in those with cirrhosis.

Corticosteroids should be used cautiously in patients with ocular herpes simplex for fear of corneal perforation.

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

Psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression to frank psychotic manifestations.  Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.

Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia.

Steroids should be used with caution in nonspecific ulcerative colitis, if there is a probability of impending perforation, abscess, or other pyogenic infection, also in diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, renal insufficiency, hypertension, osteoporosis, and myasthenia gravis.  Signs of peritoneal irritation following gastrointestinal perforation in patients receiving large doses of corticosteroids may be minimal or absent.  Fat embolism has been reported as a possible complication of hypercortisonism.

When large doses are given, some authorities advise that antacids be administered between meals to help to prevent peptic ulcer.

Growth and development of infants and children on prolonged corticosteroid therapy should be carefully followed.

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

Phenytoin, phenobarbital, ephedrine, and rifampin may enhance the metabolic clearance of corticosteroids resulting in decreased blood levels and lessened physiologic activity, thus requiring adjustment in corticosteroid dosage.  These interactions may interfere with dexamethasone suppression tests which should be interpreted with caution during administration of these drugs.

False negative results in the dexamethasone suppression test (DST) in patients being treated with indomethacin have been reported.  Thus, results of the DST should be interpreted with caution in these patients.

The prothrombin time should be checked frequently in patients who are receiving corticosteroids and coumarin anticoagulants at the same time because of reports that corticosteroids have altered the response to these anticoagulants.  Studies have shown that the usual effect produced by adding corticosteroids is inhibition of response to coumarins, although there have been some conflicting reports of potentiation not substantiated by studies.

When corticosteroids are administered concomitantly with potassium-depleting diuretics, patients should be observed closely for development of hypokalemia.

Intra-articular injection of a corticosteroid may produce systemic as well as local effects.

Appropriate examination of any joint fluid present is necessary to exclude a septic process.

A marked increase in pain accompanied by local swelling, further restriction of joint motion, fever, and malaise is suggestive of septic arthritis.  If this complication occurs and the diagnosis of sepsis is confirmed, appropriate antimicrobial therapy should be instituted.

Injection of a steroid into an infected site is to be avoided.

Corticosteroids should not be injected into unstable joints.

Patients should be impressed strongly with the importance of not overusing joints in which symptomatic benefit has been obtained as long as the inflammatory process remains active.

Frequent intra-articular injection may result in damage to joint tissues. 

The slower rate of absorption by intramuscular administration should be recognized.

ADVERSE REACTIONS:

Fluid and electrolyte disturbances:

        Sodium retention

        Fluid retention

        Congestive heart failure in susceptible patients

        Potassium loss

        Hypokalemic alkalosis

        Hypertension

Musculoskeletal:

        Muscle weakness

        Steroid myopathy

        Loss of muscle mass

        Osteoporosis

        Pathologic fracture of long bones

        Vertebral compression fractures

        Aseptic necrosis of femoral and humeral heads

        Tendon rupture

Gastrointestinal:

        Peptic ulcer with possible subsequent perforation and hemorrhage

        Perforation of the small and large bowel, particularly in patients with inflammatory bowel disease

        Pancreatitis

        Abdominal distention

        Ulcerative esophagitis

Dermatologic:

        Impaired wound healing

        Thin fragile skin

        Petechiae and ecchymoses

        Erythema

        Increased sweating

        May suppress reactions to skin tests

        Burning or tingling, especially in the perineal area (after IV injection)

        Other cutaneous reactions, such as allergic dermatitis, urticaria, angioneurotic edema

Neurologic:

        Convulsions

        Increased intracranial pressure with papilledema (pseudotumor cerebri) usually after treatment

        Vertigo

        Headache

        Psychic disturbances

Endocrine:

        Menstrual irregularities

        Development of cushingoid state

        Suppression of growth in children

        Secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery, or illness

        Decreased carbohydrate tolerance

        Manifestations of latent diabetes mellitus

        Increased requirements for insulin or oral hypoglycemic agents in diabetics

        Hirsutism

Ophthalmic:

        Posterior subcapsular cataracts

        Increased intraocular pressure

        Glaucoma

        Exophthalmos

Metabolic:

        Negative nitrogen balance due to protein catabolism

Cardiovascular:

        Myocardial rupture following recent myocardial infarction (see WARNINGS)

Other:

        Anaphylactoid or hypersensitivity reactions

        Thromboembolism

        Weight gain

        Increased appetite

        Nausea

        Malaise

        Hiccups

        The following additional adverse reactions are related to parenteral corticosteroid therapy:

        Rare instances of blindness associated with intralesional therapy around the face and head

        Hyperpigmentation or hypopigmentation

        Subcutaneous and cutaneous atrophy

        Sterile abscess

        Post-injection flare (following intra-articular use)

        Charcot-like arthropathy

OVERDOSAGE:

Reports of acute toxicity and/or death following overdosage of glucocorticoids are rare.  In the event of overdosage, no specific antidote is available; treatment is supportive and symptomatic.

The oral LD 50 of dexamethasone in female mice was 6.5 g/kg.  The intravenous LD 50 of dexamethasone sodium phosphate in female mice was 794 mg/kg.

DOSAGE AND ADMINISTRATION:

Dexamethasone sodium phosphate injection, 4 mg/mL– For intravenous, intramuscular, intra-articular, intralesional, and soft tissue injection.

Dexamethasone sodium phosphate injection can be given directly from the vial, or it can be added to Sodium Chloride Injection or Dextrose Injection and administered by intravenous drip.

Solutions used for intravenous administration or further dilution of this product should be preservative free when used in the neonate, especially the premature infant.

When it is mixed with an infusion solution, sterile precautions should be observed.  Since infusion solutions generally do not contain preservatives, mixtures should be used within 24 hours.

DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE AND THE RESPONSE OF THE PATIENT.

HOW SUPPLIED:

Product No.	NDC No.
PRX16501	63323-165-16	Dexamethasone Sodium Phosphate Injection, USP (equivalent to 4 mg per mL dexamethasone phosphate) 1 mL fill, in a 2 mL flip-top vial, packaged in 25.
PRX16505	63323-165-26	Dexamethasone Sodium Phosphate Injection, USP (equivalent to 20 mg per 5 mL [4 mg per mL] dexamethasone phosphate) 5 mL fill, in a 5 mL flip-top vial, packaged in 25.

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].  Protect from freezing.  Sensitive to heat.  Do not autoclave.
 
Protect from light. Store container in carton until contents have been used.
 
Do not use if precipitate is present.

REFERENCES:

1. Cavanagh, D.; Singh, K.B.: Endotoxin shock in pregnancy and abortion, in: “Corticosteroids in the Treatment of Shock”, Schumer, W.; Nyhus, L.M., Editors, Urbana, University of Illinois Press, 1970, pp. 86-96.
2. Dietzman, R.H.; Ersek, R.A.; Bloch, J.M.; Lillehei, R.C.: High-output, low-resistance gram-negative septic shock in man, Angiology 20: 691-700, Dec. 1969.
3. Frank, E.: Clinical observations in shock and management (In: Shields, T.F., ed.: Symposium on current concepts and management of shock), J. Maine Med. Ass. 59: 195-200, Oct. 1968.
4. Oaks, W. W.; Cohen, H.E.: Endotoxin shock in the geriatric patient, Geriat. 22: 120-130, Mar. 1967.
5. Schumer, W.; Nyhus, L.M.: Corticosteroid effect on biochemical parameters of human oligemic shock, Arch. Surg. 100: 405-408, Apr. 1970.

PremierProRx ® is a registered trademark of Premier, Inc., used under license.

Manufactured by:
Fresenius Kabi 
Lake Zurich, IL 60047

451449

www.fresenius-kabi.us

Issued: August 2015

DRUG: Dexamethasone Sodium Phosphate

GENERIC: DEXAMETHASONE SODIUM PHOSPHATE

DOSAGE: INJECTION, SOLUTION

ADMINSTRATION: INTRAMUSCULAR

NDC: 70518-0872-0

PACKAGING: 1 mL in 1 VIAL

ACTIVE INGREDIENT(S):

• DEXAMETHASONE SODIUM PHOSPHATE 4mg in 1mL

INACTIVE INGREDIENT(S):

• BENZYL ALCOHOL
• SODIUM HYDROXIDE
• CITRIC ACID MONOHYDRATE
• SODIUM CITRATE
• SODIUM SULFITE