Dexamethasone Elixir: Package Insert / Prescribing Info

Dexamethasone Elixir 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:

Dexamethasone Elixir - 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 for Dexamethasone Elixir

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.

Immunosuppression and Increased Risk of Infection

Corticosteroids, including Dexamethasone Elixir, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens.
Corticosteriods can:

• Reduce resistance to new infections
• Exacerbate existing infections
• Increase the risk of disseminated infections
• Incease the risk of reactivation or exacerbation of latent infections
• Mask some signs of infection

Corticosteriod-associated infections can be mild but can be severe and at times fatal. The rate of infectious complications increases with increasing corticosteriod dosages.

Monitor for the development of infection and consider Dexamethasone Elixir withdrawal or dosage reduction as needed.

Tuberculosis

If Dexamethasone Elixir is used to treat a condition in patients with latent tuberculosis or tuberculin reactivity, reactivation of tuberculosis may occur. Closely monitor such patients for reactivation. During prolonged Dexamethasone Elixir therapy, patients with latent tuberculosis or tuberculin reactivity should receive chemoprophylaxis.

Varicella Zoster and Measles Viral Infections

Varicella and measles can have a serious or even fatal course in non-immune patients taking corticosteriods, including Dexamethasone Elixir. In corticosteriod-treated patients who have not had these diseases or are non-immune, particular care should be taken to avoid exposure to varicella and measles:

• If a Dexamethasone Elixir-treated patient is exposed to varicella, prophylaxis with varicella zoster immune globulin may be indicated. If varicella develops, treatment with antiviral agents may be considered.
• If a Dexamethasone Elixir-treated patient is exposed to measles, prophylaxis with immunoglobulin may be indicated.

Hepatitis B Virus Reactivation

Hepatitis B Virus reactivation can occur in patients who are hepatitis B carriers treated with immunosuppressive dosages of corticosteriods, including Dexamethasone Elixir. Reactivation can also occur infrequently in corticosteriod-treated patients who appear to have resolved hepatitis B infection.

Screen patients for hepatitis B infection before intiating immunosuppressive (e.g., prolonged) treatment with Dexamethasone Elixir. For patients who show evidence of hepatitis B infection, recommend consultation with physcians with expertise in managing hepatitis B regarding monitoring and consideration for hepatitis B antiviral therapy.

Fungal Infections

Corticosteriods, including Dexamethasone Elixir, may exacerbate systemic fungal infections; therefore, avoid Dexamethasone Elixir use in the presence of such infections unless Dexamethasone Elixir is needed to control drug reactions. For patients on chronic Dexamethasone Elixir therapy who develop systemic fungal infections, Dexamethasone Elixir withdrawal or dosage reduction is recommended.

Amebiasis

Corticosteriods, including Dexamethasone Elixir, may activate latent amebiasis. Therefore, it is recommended that latent amebiasis or active amebiasis be ruled out before intiating Dexamethasone Elixir in patients who have spent time in the tropics or patients with unexplained diarrhea.

Strongyloides Infestation

Corticosteriods, including Dexamethasone Elixir, should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, cortcosteriod-induced immunosupression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.

Cerebral Malaria

Avoid corticosteriods, including Dexamethasone Elixir, in patients with cerebral malaria.

Kaposi's Sarcoma

Kaposi's Sarcoma has been reported to occur in patients receiving corticosteriod therapy, most often for chronic conditions.

Discontinuation of corticosteriods may result in clinical improvement of Kaposi's Sarcoma.

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.

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.

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.

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.

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, 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, 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 of potentiation not substantiated by studies.

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

Adverse Reactions/Side Effects

To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc. at 1-844-874-7464 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.

Dexamethasone Elixir Dosage and 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 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 is Dexamethasone Elixir 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

Distributed by:

Rising Pharma Holdings, Inc.

East Brunswick, NJ 08816

Manufactured by:

Lyne Laboratories, Inc.
Brockton, MA 02301

R10-03/24

Each 5 mL (teaspoonful) contains:

Dexamethaosne, USP.....0.5 mg

Also contains:

Benzoic Acid, USP (as preservative).....0.1%

Alcohol (%v/v).....5.1%

USUAL ADULT DOSAGE: See accompanying package insert.

WARNINGS: KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN.

In case of accidental overdose, seek professional assistance or contact a Poison Control Center immediately.

Store at 20º – 25ºC (68º – 77ºF)
[see USP Controlled Room Temperature].
KEEP TIGHTLY CLOSED
AVOID FREEZING

Dispense in a tight container as defined in the USP.

Distributed by:

Rising Pharma Holdings, Inc.

East Brunswick, NJ 08816

Manufactured by:

Lyne Laboratories, Inc.

Brockton, MA 02301

R10-03/24

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