DEXAMED

• Therapeutic Category
  • Hormones
  • Adrenal hormones and synthetic substitutes
• Pharmaceutical Form : Syrup
• Composition : Each 5 ml contains: Dexamethasone 0.5 mg
• Active Substance : Dexamethasone

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

Indications:

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

1. 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

1. Collagen Diseases: During an exacerbation or as maintenance therapy in selected cases of:

• Systemic lupus erythematosus
• Acute rheumatic carditis

1. Dermatologic Diseases:

• Pemphigus
• Bullous dermatitis herpetiformis
• Severe erythema multiforme (Stevens-Johnson syndrome)
• Exfoliative dermatitis
• Mycosis fungoides
• Severe psoriasis
• Severe seborrheic dermatitis

1. 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

1. 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

1. 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

1. Hematologic Disorders:

• Idiopathic thrombocytopenic purpura in adults
• Secondary thrombocytopenia in adults
• Acquired (autoimmune) hemolytic anemia
• Erythroblastopenia (RBC anemia)
• Congenital (erythroid) hypoplastic anemia

1. Neoplastic Diseases: For palliative management of:

• Leukemia and lymphomas in adults
• Acute leukemia of childhood

1. Edematous States: To induce a diuresis or remission of proteinuria in the nephrotic syndrome of the idiopathic type without uremia or that due to lupus erythematosus
2. Gastrointestinal Diseases: To tide the patient over a critical period of the disease in:

• Ulcerative colitis
• Regional enteritis

1. Miscellaneous:

• Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy
• Trichinosis with neurologic or myocardial involvement

1. 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 may be impaired, salt and/or a mineralocorticoid should be administered concurrently.
• Corticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppression.
• 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.
• In cerebral malaria, a 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.
• 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.
• 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.

• 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; these agents should be used with caution in patients with congestive heart failure, hypertension, or renal insufficiency. When corticosteroids are administered concomitantly with potassium-depleting diuretics, patients should be observed closely for development of hypokalemia. 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.

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

• 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 anti-tuberculous regimen.
• Administration of live or 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. Routine administration of vaccines or toxoids should be deferred until corticosteroid therapy is discontinued if possible.

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.
• 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. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.
• 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. Fat embolism has been reported as a possible complication of hypercortisonism.
• When large doses are given, it is advised 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.
• 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.
• 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.
• 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. Special consideration should be given to patients at increased risk of osteoporosis (e.g., postmenopausal women) before initiating corticosteroid therapy.

Drug Interactions:

• Aminoglutethimide may diminish adrenal suppression by corticosteroids.
• 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.
• Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance
• 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.
• Co-administration of corticosteroids and warfarin usually results in inhibition of response to warfarin; therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect.
• Corticosteroids may increase blood glucose concentrations; therefore dosage adjustments of antidiabetic agents may be required.
• Serum concentrations of isoniazid may be decreased.
• Cholestyramine may increase the clearance of corticosteroids.
• Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently, Convulsions have been reported with this concurrent use.
• 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.
• Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia.
• 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 may decrease the hepatic metabolism of certain corticosteroids, thereby increasing their effect.
• 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 increase 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 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.
• Concomitant use of aspirin (or other nonsteroidal anti-inflammatory 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.
• 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.
• Corticosteroids may suppress reactions to skin tests.
• Co-administration with thalidomide should be employed cautiously, as toxic epidermal necrolysis has been reported with concomitant use.
• The prothrombin time should be checked frequently in patients who are receiving corticosteroids and coumarin anticoagulants at the same time because corticosteroids have altered the response to these anticoagulants

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. 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 dos.

Geriatric use:

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.

Pregnancy and lactation:

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.

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, Vertebral compression fractures, Aseptic necrosis of femoral and humeral heads, Pathologic fracture of long bones, Tendon rupture

Gastrointestinal: Peptic ulcer with possible 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

Other cutaneous reactions: 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 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

Other: Hypersensitivity, Thromboembolism, Weight gain, increased appetite, Nausea, Malaise, Hiccups.

Dosage and Administration:

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, Dexamethasone should be discontinued and the patient should be transferred 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, if the drug is to be stopped after more than a few days of treatment, it usually should be withdrawn gradually.

The following schedule explains milligram equivalent and facilitates changing to Dexamethasone from other glucocorticoids:

 

Dexamethasone	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.

Overdosage:

In the event of overdosage, no specific antidote is available; treatment is supportive and symptomatic.

Storage conditions: Store at room temperature (20 – 25) °C. Away from light and moisture

Do not freeze

Discard opened bottle after 90 days

How supplied: 100 ml