Dexamethasone by Rising Pharmaceuticals, Inc. / Lyne Laboratories, Inc. DEXAMETHASONE elixir

Dexamethasone by

Drug Labeling and Warnings

Dexamethasone by is a Prescription medication manufactured, distributed, or labeled by Rising Pharmaceuticals, Inc., Lyne Laboratories, Inc.. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

DESCRIPTION

Each 5 mL (teaspoonful) contains:
Dexamethasone, USP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.5 mg

Also contains:
Benzoic Acid, USP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.1%
  (as preservative)
Alcohol (% v/v) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1%

Inactive Ingredients: artificial raspberry flavor; citric acid; FD&C red no. 40; sucrose; propylene glycol and purified water. It may also contain sodium citrate dihydrate.

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

Dexamethasone, a synthetic adrenocortical steroid, is a white to practically white, odorless, crystalline powder. It is stable in air. It is practically insoluble in water. The molecular weight is 392.47. It is designated chemically as 9-fluoro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione. The molecular formula is C22H29FO5 and the structural formula is:

CLINICAL PHARMACOLOGY

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

1. Endocrine Disorders: Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the first choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular importance).
   Congenital adrenal hyperplasia
   Nonsuppurative thyroiditis
   Hypercalcemia associated with cancer
2. Rheumatic Disorders: As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in:
   Psoriatic arthritis
   Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy)
   Ankylosing spondylitis
   Acute and subacute bursitis
   Acute nonspecific tenosynovitis
   Acute gouty arthritis
   Post-traumatic osteoarthritis
   Synovitis of osteoarthritis
   Epicondylitis
3. Collagen Diseases: During an exacerbation or as maintenance therapy in selected cases of:
   Systemic lupus erythematosus
   Acute rheumatic carditis
4. Dermatologic Diseases:
   Pemphigus
   Bullous dermatitis herpetiformis
   Severe erythema multiforme (Stevens-Johnson syndrome)
   Exfoliative dermatitis
   Mycosis fungoides
   Severe psoriasis
   Severe seborrheic dermatitis
5. Allergic States: Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment:
   Seasonal or perennial allergic rhinitis
   Bronchial asthma
   Contact dermatitis
   Atopic dermatitis
   Serum sickness
   Drug hypersensitivity reactions
6. Ophthalmic Diseases: Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa, such as:
   Allergic conjunctivitis
   Keratitis
   Allergic corneal marginal ulcers
   Herpes zoster ophthalmicus
   Iritis and iridocyclitis
   Chorioretinitis
   Anterior segment inflammation
   Diffuse posterior uveitis and choroiditis
   Optic neuritis
   Sympathetic ophthalmia
7. Respiratory Diseases:
   Symptomatic sarcoidosis
   Loeffler's syndrome not manageable by other means
   Berylliosis
   Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy
   Aspiration pneumonitis
8. Hematologic Disorders:
   Idiopathic thrombocytopenic purpura in adults
   Secondary thrombocytopenia in adults
   Acquired (autoimmune) hemolytic anemia
   Erythroblastopenia (RBC anemia)
   Congenital (erythroid) hypoplastic anemia
9. Neoplastic Diseases: For palliative management of:
   Leukemia and lymphomas in adults
   Acute leukemia of childhood
10. Edematous States: To induce a diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus
11. Gastrointestinal Diseases: To tide the patient over a critical period of the disease in:
    Ulcerative colitis
    Regional enteritis
12. Miscellaneous:
    Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy
    Trichinosis with neurologic or myocardial involvement
13. Diagnostic testing of adrenocortical hyperfunction.

CONTRAINDICATIONS

Systemic fungal infections
Hypersensitivity to this product

WARNINGS

In patients on corticosteroid therapy subjected to 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 maybe 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 opticnerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses.

Usage in Pregnancy: Since adequate human reproduction studies have not been done with corticosteroids, use of these drugs in pregnancy or in women of childbearing potential requires that the anticipated benefits be weighed against the possible hazards to the mother and embryo or fetus. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.

Corticosteroids appear in breast milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other unwanted effects. Mothers taking pharmacologic doses of corticosteroids should be advised not to nurse.

Average and large doses of hydrocortisone or cortisone 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 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 Elixir 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

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 because of possible 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 should be gradual.

Psychic derangements may appear when corticosteroids are used,ranging from euphoria, insomnia, mood swings, personality changes, andsevere 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, 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 corticosteroids be taken with meals and antacids taken between meals to help to prevent peptic ulcer.

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

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 ofpotentiation not substantiated by studies.

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

Information for Patients:

Persons who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay.

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; Osteoporosis; Aseptic necrosis of femoral and humeral heads	Vertebral compression fractures; Loss of muscle mass; Pathologic fracture of long bones; Tendon rupture
Gastrointestinal:
	Pancreatitis; Abdominal distention; Peptic ulcer with possible perforation and hemorrhage	Ulcerative esophagitis; Perforation of the small and large bowel, particularly in patients with inflammatory bowel disease
Dermatologic:
	Impaired wound healing; Thin fragile skin; Erythema; May suppress reactions to skin tests	Petechiae and ecchymoses; Increased sweating; Other cutaneous reactions, such as allergic dermatitis, urticaria, angioneurotic edema
Neurologic:
	Convulsions; Vertigo; Headache; Psychic Disturbances	Increased intracranial pressure with papilledema (pseudotumor cerebri) usually after treatment
Endocrine:
	Menstrual irregularities; Development of cushingoid state; Manifestations of latent diabetes mellitus; Secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery, or illness	Decreased carbohydrate tolerance; Suppression of growth in children; Increased requirements for insulin or oral hypoglycemic agents in diabetes; 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:
	Hypersensitivity; Thromboembolism; Weight gain; Increased appetite	Nausea; Malaise; Hiccups

SPL UNCLASSIFIED SECTION

To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharmaceuticals, Inc. at 1-866-562-4597 or FDA at 1-800-FDA-1088 or www.FDA.gov/medwatch

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 LD50 of dexamethasone in female mice was 6.5 g/kg.

DOSAGE & ADMINISTRATION

For oral administration: DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE AND THE RESPONSE OF THE PATIENT.
The initial dosage varies from 0.75 to 9 mg a day depending on the disease being treated. In less severe diseases doses lower than 0.75 mg may suffice, while in severe diseases doses higher than 9 mg may be required. The initial dosage should be maintained or adjusted until the patient’s response is satisfactory. If satisfactory clinical response does not occur after a reasonable
period of time, discontinue Dexamethasone Elixir and transfer the patient to other therapy.
After a favorable initial response, the proper maintenance dosage should be determined by decreasing the initial dosage in small amounts to the lowest dosage that maintains an adequate clinical
response.
Patients should be observed closely for signs that might require dosage adjustment, including changes in clinical status resulting from remissions or exacerbations of the disease, individual drug responsiveness, and the effect of stress (e.g., surgery, infection, trauma). During stress it may be necessary to increase dosage temporarily.
If the drug is to be stopped after more than a few days of treatment, it usually should be withdrawn gradually.
The following milligram equivalents facilitate changing to Dexamethasone Elixir from other glucocorticoids:

Dexamethasone; Elixir	Methylprednisolone; and; Triamcinolone	Prednisolone; and; Prednisone	Hydrocortisone	Cortisone
0.75 mg =	4 mg =	5 mg =	20 mg =	25 mg

Dexamethasone suppression tests
1. Tests for Cushing’s syndrome.
Give 1 mg of Dexamethasone orally at 11:00 p.m. Blood is drawn for plasma cortisol determination at 8:00 a.m. the following morning.
For greater accuracy, give 0.5 mg of Dexamethasone orally every 6 hours for 48 hours. Twenty-four hour urine collections are made for determination of 17-hydroxycorticosteroid excretion.
2. Test to distinguish Cushing’s syndrome due to pituitary ACTH excess from Cushing’s syndrome due to other causes.
Give 2 mg of Dexamethasone orally every 6 hours for 48 hours. Twenty-four hour urine collections are made for determination of 17-hydroxycorticosteroid excretion.

HOW SUPPLIED

Dexamethasone Elixir, USP 0.5 mg/5 mL is supplied as a clear, red, raspberry-flavored liquid in the following size:
   8 fl oz (237 mL) bottle (NDC: 64980-509-24)

RECOMMENDED STORAGE

Store at 20˚-25˚C (68˚-77˚F) [See USP Controlled Room Temperature].

KEEP TIGHTLY CLOSED

AVOID FREEZING

Dispense in a tight container as defined in the USP.

Rx Only

Manufactured for:

Rising Pharmaceuticals, Inc.
Saddle Brook, NJ 07663

Manufactured by:

Lyne Laboratories, Inc.
Brockton, MA 02301

R7-12/17

PRINCIPAL DISPLAY PANEL

Rising®       NDC: 64980-509-24

Dexamethasone
Elixir, USP

0.5 mg/5 mL

Contains 5.1% Alcohol (% v/v)

NET: 8 fl oz (237 mL)       Rx only

INGREDIENTS AND APPEARANCE

DEXAMETHASONE 
dexamethasone elixir

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 64980-509
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
Dexamethasone (UNII: 7S5I7G3JQL) (Dexamethasone - UNII:7S5I7G3JQL)	Dexamethasone	0.5 mg  in 5 mL

Inactive Ingredients
Ingredient Name	Strength
BENZOIC ACID (UNII: 8SKN0B0MIM)
ALCOHOL (UNII: 3K9958V90M)
ANHYDROUS CITRIC ACID (UNII: XF417D3PSL)
FD&C RED NO. 40 (UNII: WZB9127XOA)
SUCROSE (UNII: C151H8M554)
PROPYLENE GLYCOL (UNII: 6DC9Q167V3)
WATER (UNII: 059QF0KO0R)
TRISODIUM CITRATE DIHYDRATE (UNII: B22547B95K)

Product Characteristics
Color	RED (clear)	Score
Shape		Size
Flavor	RASPBERRY (artificial raspberry flavor)	Imprint Code
Contains

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 64980-509-24	237 mL in 1 BOTTLE, PLASTIC; Type 0: Not a Combination Product	08/01/2011

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA090891	08/01/2011

Labeler - Rising Pharmaceuticals, Inc. (041241766)

Registrant - Lyne Laboratories, Inc. (053510459)

Establishment
Name	Address	ID/FEI	Business Operations
Lyne Laboratories, Inc.		053510459	MANUFACTURE(64980-509)