COMPOSITIONS AND EXCIPIENTS
Each Tablet of Dexacort contains:
- Active substance: 0.5 mg , 0.75 mg , 1.5 mg , 4 mg , 6 mg of Dexamethasone.
- Excipients: Anhydrous lactose, Croscarmellose sodium, Magnesium stearate, Cellulose microcrystalline, Stearic acid, Yellow colorant E110 (For 0.5 mg),Blue colorant (For 0.75 mg), Red colorant E127 (For 4 mg), Green colorant (For 6 mg).
CLINICAL PHARMACOLOGY
Glucocorticoids, naturally occurring and synthetic, are adrenocortical steroids that are readily absorbed from the gastrointestinal tract. Glucocorticoids cause varied metabolic effects. In addition, they modify the body’s immune responses to diverse stimuli. Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have sodium-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs including dexamethasone are primarily used for their anti-inflammatory effects in disorders of many organ systems.
At equipotent anti-inflammatory doses, dexamethasone almost completely lacks the sodium-retaining property of hydrocortisone and closely related derivatives of hydrocortisone.
INDICATIONS
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, seasonal or perennial allergic rhinitis and serum sickness.
Dermatologic Diseases: Bullous dermatitis herpetiformis, exfoliative erythroderma, mycisis fungoides, pemphigus, and severe erythema multiforme (Stevens-Johnson syndrome).
Endocrine Disorders: Primary or secondary adrenocortical insufficiency, 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 (Diamon-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 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 in acute gouty arthritis, acute rheumatic carditis, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, including juvenile rheumatoid arthritis. For the treatment of dermatomyositis, polymyositis, and systemic lupus erythematosus.
CONTRAINDICATIONS
Systemic fungal infections. Dexamethasone tablets are contraindicated in patients who are hypersensitive to any components of this product.
WARNINGS
General: Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroid therapy.
Cardio-Renal: Average and large doses of corticosteroids can cause elevation of blood pressure, sodium and water retention, and increased excretion of potassium. All corticosteroids increase calcium excretion.
Endocrine: Corticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppression with the potential for corticosteroid insufficiency after withdrawal of treatment. 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 healthy individuals. 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.
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.
Corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation.
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.
Viral infections: Chickenpox and measles can have a more serious or even fatal course in pediatric and adults patients on corticosteroids.
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.
If chickenpox develops, treatment with antiviral agents may 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.
PRECAUTIONS
General: The lowest possible dose of corticosteroids should be used to control the condition under treatment. When reduction in dosage is possible, the reduction should be gradual.
Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement.
Cardio-Renal: As sodium retention with resultant edema and potassium loss may occur in patients receiving corticosteroids, these agents should be used with caution in patients with congestive heart failure, hypertension, or renal insufficiency.
Endocrine: Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently.
Gastrointestinal: Steroids should be used with caution in active or latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, and nonspecific ulcerative colitis, since they may increase the risk of a perforation.
There is an enhanced effect due to decreased metabolism of corticosteroids in patients with cirrhosis.
Musculoskeletal: Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (i.e., decreasing absorption and increasing excretion) and inhibition of osteoblast function. This, together with a decrease in the protein matrix of the bone secondary to an increase in protein catabolism, and reduced sex hormone production, may lead to inhibition of bone growth in pediatric patients and the development of osteoporosis at any age. Special consideration should be given to patients at increased risk of osteoporosis (e.g., postmenopausal women) before initiating corticosteroid therapy.
Neuro-Psychiatric: Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not show that they affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect.
An acute myopathy has been observed 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 generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatinine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
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.
Ophthalmic: lntraocular pressure may become elevated in some individuals. If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored.
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.
DRUG INTERACTIONS
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.
Antibiotics: Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance.
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: may increase the clearance of corticosteroids.
Cyclosporine: Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently.
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: decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects.
Nonsteroidal Anti-Inflammatory Agents (NSAIDS): Concomitant use of aspirin (or other nonsteroidal anti-inflammatory agents) and corticosteroids increases the risk of gastrointestinal side effects.
Phenytoin: 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.
Pregnancy:
Teratogenic Effects: Pregnancy Category C
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.
Nursing Mothers:
Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects.
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.
Pediatric Use:
The efficacy and safety, the adverse effects of corticosteroids in the pediatric population are similar to those in adult’s 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.
Pediatric patients who are treated with corticosteroids by any route, including systemically administered corticosteroids, may experience a decrease in their growth velocity. pediatric patients should be titrated to the lowest effective dose.
Geriatric Use
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.
ADVERSE REACTIONS
The following adverse reactions have been reported with dexamethasone or other corticosteroids and they are listed alphabetically, under each subsection:
Allergic Reactions: Anaphylactoid reaction, anaphylaxis, angioedema.
Cardiovascular: Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial
rupture following recent myocardial infarction, edema, pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis.
Dermatologic: Acne, allergic dermatitis, dry scaly skin, ecchymoses and petechiae, erythema, impaired wound healing, increased sweating, rash, striae, suppression of reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria.
Endocrine: Decreased carbohydrate and glucose tolerance, development of cushingoid state, hyperglycemia, glycosuria, hirsutism, hypertrichosis, increased requirements for insulin or oral hypoglycemic agents in diabetes, manifestations of latent diabetes mellitus, menstrual irregularities, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), suppression of growth in pediatric patients.
Fluid and Electrolyte Disturbances: Congestive heart failure in susceptible patients, fluid retention, hypokalemic alkalosis, potassium loss, sodium retention.
Gastrointestinal: Abdominal distention, elevation in serum liver enzyme levels, hepatomegaly, increased appetite, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, perforation of the small and large bowel, ulcerative esophagitis.
Metabolic: Negative nitrogen balance due to protein catabolism.
Musculoskeletal: Aseptic necrosis of femoral and humeral heads, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, steroid myopathy, tendon rupture, vertebral compression fractures.
Neurological/Psychiatric: Convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually after treatment, insomnia, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychic disorders, vertigo.
Ophthalmic: Exophthalmos, glaucoma, increased intraocular pressure, posterior subcapsular cataracts.
Other: Abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, malaise, moon face, weight gain.
DOSAGE AND ADMINISTRATION
The initial dose varies from 0.75 to 9 mg a day depending on the disease being treated.
It should be emphasized that dosage requirements are variable and must be individualized on the basis of the disease under treatment and the response of the patient.
After a favorable initial response is noted, the proper maintenance dosage should be determined by decreasing the initial dosage in small decrements at appropriate time intervals until the lowest dosage that maintains an adequate clinical response is reached.
Situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient’s individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment .In this latter situation it may be necessary to increase the dosage of the corticosteroid for a period of time consistent with the patient’s condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.
In the treatment of acute exacerbations of multiple sclerosis, daily doses of 30 mg of dexamethasone for a week followed by 4 to 12 mg every other day for one month have been shown to be effective.
In paediatric patients, the initial dose of dexamethasone may vary depending on the specific disease entity being treated. The range of initial doses is 0.02 to 0.3 mg/kg/day in three or four divided doses (0.6 to 9 mg/m2bsa/day).
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.
STORAGE CONDITIONS
Store at temperature between 20° – 25°C, in the original packaging.
PACKAGING
Dexacort is supplied as blister stripes (Aluminum-white P.V.D.C), each strip contains 10 tablets and each pack contains 2 strips. (20 Tablets per pack)