WARNINGS
General Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroid therapy (see ADVERSE REACTIONS ).
Increased dosage of rapidly acting corticosteroids is indicated in patients on corticosteroid therapy subjected to any unusual stress before, during, and after the stressful situation.
Cardio-Renal Average and large doses of corticosteroids can cause elevation of blood pressure, sodium 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.
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.
Endocrine Corticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppression with the potential for corticosteroid insufficiency after withdrawal of treatment.
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.
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.
Infections General Patients who are on corticosteroids are more susceptible to infections than are healthy individuals.
There may be decreased resistance and inability to localize infection when corticosteroids are used.
Infection with any pathogen (viral, bacterial, fungal, protozoan or helminthic) in any location of the body may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents.
These infections may be mild to severe.
With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases.
Corticosteroids may also mask some signs of current infection.
Fungal Infections Corticosteroids may exacerbate systemic fungal infections and therefore should not be used in the presence of such infections unless they are needed to control life-threatening drug reactions.
There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure (see PRECAUTIONS : Drug Interactions : Amphotericin B injection and potassium-depleting agents ).
Special Pathogens Latent disease may be activated or there may be an exacerbation of intercurrent infections due to pathogens, including those caused by Amoeba , Candida , Cryptococcus , Mycobacterium , Nocardia , Pneumocystis , Toxoplasma .
It is recommended that latent amebiasis 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.
Similarly, corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation.
In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.
Corticosteroids should not be used in cerebral malaria.
Tuberculosis The use of corticosteroids 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.
Vaccination Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.
Killed or inactivated vaccines may be administered.
However, the response to such vaccines cannot be predicted.
Immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy, e.g., for Addison’s disease.
Viral infections Chickenpox and measles can have a more serious or even fatal course in pediatric and adult patients on corticosteroids.
In pediatric and adult patients who have not had these diseases, particular care should be taken to avoid exposure.
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 immune globulin (IG) may be indicated.
(See the respective package inserts for VZIG and IG for complete prescribing information.) If chickenpox develops, treatment with antiviral agents should be considered.
Ophthalmic 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 bacteria, fungi, or viruses.
The use of oral corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes.
Corticosteroids should not be used in active ocular herpes simplex.
DRUG INTERACTIONS
Drug Interactions Aminoglutethimide Aminoglutethimide may diminish adrenal suppression by corticosteroids.
Amphotericin B injection and potassium-depleting agents When corticosteroids are administered concomitantly with potassium-depleting agents (e.g., amphotericin B, diuretics), patients should be observed closely for development of hypokalemia.
In addition, there have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure.
Antibiotics Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance (see Drug Interactions: Hepatic Enzyme Inducers, Inhibitors and Substrates).
Anticholinesterases 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.
Anticoagulants, Oral Co-administration 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.
Antidiabetics Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required.
Antitubercular Drugs Serum concentrations of isoniazid may be decreased.
Cholestyramine Cholestyramine may increase the clearance of corticosteroids.
Cyclosporine Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently.
Convulsions have been reported with this concurrent use.
Dexamethasone Suppression Test (DST) 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.
Digitalis Glycosides Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia.
Ephedrine Ephedrine may enhance the metabolic clearance of corticosteroids, resulting in decreased blood levels and lessened physiologic activity, thus requiring an increase in corticosteroid dosage.
Estrogens, including Oral Contraceptives Estrogens may decrease the hepatic metabolism of certain corticosteroids, thereby increasing their effect.
Hepatic Enzyme Inducers, Inhibitors and Substrates Drugs which induce cytochrome P450 3A4 (CYP 3A4) enzyme activity ( e.g., barbiturates, phenytoin, carbamazepine, rifampin ) may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased.
Drugs which inhibit CYP 3A4 ( e.g., ketoconazole, macrolide antibiotics such as erythromycin ) have the potential to result in increased plasma concentrations of corticosteroids.
Dexamethasone is a moderate inducer of CYP 3A4.
Co-adminstration with other drugs that are metabolized by CYP 3A4 ( e.g., indinavir, erythromycin ) may increase their clearance, resulting in decreased plasma concentration.
Ketoconazole Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects.
In addition, ketoconazole alone can inhibit adrenal corticosteroid synthesis and may cause adrenal insufficiency during corticosteroid withdrawal.
Nonsteroidal Anti-Inflammatory Agents (NSAIDS) Concomitant use of aspirin (or other nonsteroidal antiinflammatory 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.
Phenytoin In post-marketing experience, there have been reports of both increases and decreases in phenytoin levels with dexamethasone co-administration, leading to alterations in seizure control.
Skin Tests Corticosteroids may suppress reactions to skin tests.
Thalidomide Co-administration with thalidomide should be employed cautiously, as toxic epidermal necrolysis has been reported with concomitant use.
Vaccines Patients on 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 ).
OVERDOSAGE
Treatment of overdosage is by supportive and symptomatic therapy.
In the case of acute overdosage, according to the patient’s condition, supportive therapy may include gastric lavage or emesis.
DESCRIPTION
Dexamethasone Tablets 0.5, 0.75, 1, 1.5, 2, 4 and 6 mg USP, Dexamethasone Oral Solution, 0.5 mg per 5 mL and Dexamethasone Intensol ™ Oral Solution (Concentrate), 1 mg per mL are for oral administration.
Each tablet contains: Dexamethasone 0.5, 0.75, 1, 1.5, 2, 4, or 6 mg Each 5 mL of Oral Solution contains: Dexamethasone……………………………………………….
0.5 mg Each mL of Intensol ™ Oral Solution (Concentrate) contains: Dexamethasone……………………………………………….
1 mg Alcohol 30% Inactive Ingredients The tablets contain lactose monohydrate, magnesium stearate, starch, sucrose, cosmetic ochre (1 mg), D&C Yellow No.
10 (0.5, 4 mg), FD&C Blue No.
1 (0.75, 1.5 mg), FD&C Green No.
3 (4, 6 mg), FD&C Red No.
3 (1.5 mg), FD&C Red No.
40 (1.5 mg), and FD&C Yellow No.
6 (0.5, 4 mg).
The oral solution contains citric acid, disodium edetate, flavoring, glycerin, methylparaben, propylene glycol, propylparaben, sorbitol and water.
The Intensol ™ oral solution contains alcohol, benzoic acid, citric acid, disodium edetate, propylene glycol, and water.
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 formula is C 22 H 29 FO 5 .
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 and the structural formula is: Structural formula
HOW SUPPLIED
Dexamethasone Tablets USP: 0.75 mg pale blue, scored tablet (Identified 54 960).
NDC 21695-290-30: Bottles of 30 tablets.
Store and Dispense: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Dispense in a tight, light-resistant container as defined in the USP/NF.
GERIATRIC USE
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.
In particular, the increased risk of diabetes mellitus, fluid retention and hypertension in elderly patients treated with corticosteroids should be considered.
INDICATIONS AND USAGE
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, and serum sickness.
Dermatologic Diseases Bullous dermatitis herpetiformis, exfoliative erythroderma, mycosis fungoides, pemphigus, and severe erythema multiforme (Stevens-Johnson syndrome).
Endocrine Disorders Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; may be used in conjunction with synthetic mineralocorticoid analogs where applicable; in infancy mineralocorticoid supplementation is of particular importance), congenital adrenal hyperplasia, hypercalcemia associated with cancer, and nonsuppurative thyroiditis.
Gastrointestinal Diseases To tide the patient over a critical period of the disease in regional enteritis and ulcerative colitis.
Hematologic Disorders Acquired (autoimmune) hemolytic anemia, congenital (erythroid) hypoplastic anemia (Diamond-Blackfan anemia), idiopathic thrombocytopenic purpura in adults, pure red cell aplasia, and selected cases of secondary thrombocytopenia.
Miscellaneous Diagnostic testing of adrenocortical hyperfunction, trichinosis with neurologic or myocardial involvement, tuberculous meningitis with subarachnoid block or impending block when used 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, craniotomy, or head injury.
Ophthalmic Diseases Sympathetic ophthalmia, temporal arteritis, uveitis, and ocular inflammatory conditions unresponsive to topical corticosteroids.
Renal Diseases To induce a 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, polymyositis, and systemic lupus erythematosus.
PEDIATRIC USE
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 (patients >2 years of age), and aggressive lymphomas and leukemias (patients >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 hypothalamic-pituitary-adrenal (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.
PREGNANCY
Pregnancy Teratogenic Effects: Pregnancy Category C 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 substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.
NUSRING MOTHERS
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 discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
INFORMATION FOR PATIENTS
Information for Patients Patients should be warned not to discontinue the use of corticosteroids abruptly or without medical supervision.
As prolonged use may cause adrenal insufficiency and make patients dependent on corticosteroids, they should advise any medical attendants that they are taking corticosteroids and they should seek medical advice at once should they develop an acute illness including fever or other signs of infection.
Following prolonged therapy, withdrawal of corticosteroids may result in symptoms of the corticosteroid withdrawal syndrome including, myalgia, arthralgia, and malaise.
Persons who are on 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.