Dexamethasone

Pronunciation: DEX-a-METH-a-sone
Class: Glucocorticoid, Corticosteroid

Trade Names

Baycadron
- Elixir, oral 0.5 mg per 5 mL

Dexamethasone
- Tablets 0.5 mg
- Tablets 0.75 mg
- Tablets 1 mg
- Tablets 1.5 mg
- Tablets 2 mg
- Tablets 4 mg
- Tablets 6 mg
- Solution, oral 0.5 mg per 5 mL

Dexamethasone Intensol
- Concentrate, oral 1 mg/mL

DexPak 6 Day Taper Pak
- Tablets (21 tablets) 1.5 mg

DexPak 10 Day Taper Pak
- Tablets (35 tablets) 1.5 mg

DexPak 13 Day Taper Pak
- Tablets (51 tablets) 1.5 mg

Maxidex
- Suspension, ophthalmic 0.1%

Zema-Pak 6 Day
- Tablets (21 tablets) 1.5 mg

Zema-Pak 10 Day
- Tablets (35 tablets) 1.5 mg

Zema-Pak 13 Day
- Tablets (51 tablets) 1.5 mg

Apo-Dexamethasone (Canada)
ratio-Dexamethasone (Canada)
Dexamethasone Sodium Phosphate

Dexamethasone Sodium Phosphate
- Injection 4 mg/mL
- Injection 10 mg/mL

Dexasol
- Solution, ophthalmic 0.1%

Ozurdex
- Implant, intravitreal 0.7 mg

PMS-Dexamethasone (Canada)

Pharmacology

Synthetic long-acting glucocorticoid that depresses formation, release, and activity of endogenous mediators of inflammation, including prostaglandins, kinins, histamine, liposomal enzymes, and complement expression. It also modifies the body's immune response.

Pharmacokinetics

Absorption

Following intravitreal implantation, plasma dexamethasone concentrations were below the lower limit of quantitation (50 pg/mL) in the majority of patients.

Metabolism

Metabolized in the liver by CYP3A4.

Elimination

The half—life is 1.8 to 3.5 h.

Onset

Rapid (injection).

Duration

Short (injection).

Special Populations

Elderly

Plasma concentrations following intravitreal implant did not appear to be related to age.

Gender

Plasma concentrations following intravitreal implant did not appear to be related to gender.

Body weight

Plasma concentrations following intravitreal implant did not appear to be related to body weight.

Indications and Usage

Testing of adrenal cortical hyperfunction; management of allergic and inflammatory ophthalmic processes, allergic states, cerebral edema associated with primary or metastatic brain tumor, collagen diseases, craniotomy or head injury, dermatologic diseases, edematous states (caused by nephrotic syndrome), endocrine disorders, GI diseases, hematologic disorders, multiple sclerosis, neoplastic diseases, renal diseases, respiratory diseases, rheumatic disorders, trichinosis with neurologic or myocardial involvement, and tuberculous meningitis.

Intra-articular or soft-tissue administration

Short-term adjunctive treatment for conditions such as acute gouty arthritis, posttraumatic osteoarthritis, rheumatoid arthritis, and synovitis of osteoarthritis.

Intralesional administration

Treatment for conditions such as alopecia areata, discoid lupus erythematosus, keloids, and psoriatic plaques.

Intravitreal implant

Treatment of macular edema following branch retinal vein occlusion or central retinal vein occlusion; treatment of noninfectious uveitis affecting the posterior segment of the eye.

Ophthalmic

Treatment of steroid-responsive inflammatory conditions of palpebral and bulbar conjunctiva, lid, cornea, and anterior segment of globe; sympathetic ophthalmia; temporal arteritis; uveitis.

Otic (using ophthalmic solution)

Steroid-responsive inflammatory conditions of the external auditory meatus, such as allergic otitis externa.

Unlabeled Uses

Treatment of acute and chronic asthmatic bronchitis; acute calcium pyrophosphate deposition disease; adjunctive treatment for bacterial meningitis; adjunct treatment for brain neoplasm; adjunct treatment for fever caused by malignant neoplasm; airway-obstructing hemangioma in infants; cerebral ischemia; cerebri pseudomotor; connective tissue disease; croup; desquamative gingivitis; diagnosis of endogenous depression; hemolysis; localized cutaneous sarcoid; mixed breast and prostatic carcinoma; multiple myeloma; myasthenia gravis; nasal polyps; noncardiogenic pulmonary edema; nonrheumatic carditis; oral lesions associated with corticosteroid responsive disorder; organ transplant rejection; pemphigoid; pericarditis; polyarteritis nodosa; prevention of nausea and vomiting associated with chemotherapy, especially cisplatin-containing regimens; prophylaxis for acute mountain sickness; recurrent aphthous stomatitis; Reiter disease; relapsing polychondritis; respiratory distress syndrome; rheumatic fever; sarcoidosis; severe eczema; vasculitis.

Contraindications

Coadministration with live virus vaccines; hypersensitivity to any component of the products; IM use in idiopathic thrombocytopenic purpura; intranasal use in untreated localized infections involving nasal mucosa; ophthalmic use in acute superficial herpes simplex keratitis, fungal diseases of ocular structures, vaccinia, varicella, and ocular tuberculosis; systemic fungal infections; topical monotherapy in primary bacterial infections.

Intravitreal implant

Active or suspected ocular or periocular infections, including most viral diseases of the cornea and conjunctiva including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases; advanced glaucoma; known hypersensitivity to any components of the product.

Dosage and Administration

Acute Allergic Disorders
Adults First day

IM Dexamethasone sodium phosphate 4 or 8 mg.

Second and third days

PO 1.5 mg twice daily.

Fourth day

PO 0.75 mg twice daily.

Fifth and sixth days

PO 0.75 mg daily.

Seventh day

No treatment.

Eighth day

Follow-up visit.

Macular edema
Adults

Intravitreal 1 implant (0.7 mg) inserted into each affected eye.

Posterior segment uveitis
Adults

Intravitreal 1 implant (0.7 mg) inserted into each affected eye.

Steroid responsive inflammatory ophthalmic conditions
Ophthalmic suspension Adults

Ophthalmic Instill 1 or 2 drops in conjunctival sac. In mild disease, drops may be used up to 4 to 6 times daily. In severe disease, drops may be used hourly and tapered to discontinuation as inflammation subsides.

Ophthalmic solution Adults

Ophthalmic Instill 1 or 2 drops into conjunctival sac every hour during the day and every 2 h during the night. When a favorable response is observed, reduce dose to 1 drop every 4 h. Then, 1 drop 3 to 4 times daily may be sufficient.

Steroid-responsive inflammatory otic conditions
Adults

Otic Instill ophthalmic solution 3 or 4 drops directly into the aural canal 2 or 3 times daily. When favorable response is obtained, gradually reduce dose and eventually discontinue.

Dexamethasone
Initial dose Adults

PO 0.75 to 9 mg/day.

Children

PO 0.02 to 0.3 mg/kg/day in 3 or 4 divided doses.

Acute exacerbations of multiple sclerosis Adults

PO 30 mg daily for 7 days, followed by 4 to 12 mg every other day for 30 days.

Brain tumors Adults

PO 2 mg 2 to 3 times daily.

Suppression tests Cushing syndrome Adults

PO 1 mg at 11 PM or 0.5 mg every 6 h for 48 h.

To distinguish pituitary adrenocorticotropic hormone excess caused by Cushing syndrome from other causes Adults

PO 2 mg every 6 h for 48 h.

Dexamethasone Sodium Phosphate
Acute Allergic Disorders Adults First day

IM 4 or 8 mg.

Second and third days

PO 1.5 mg twice daily.

Fourth day

PO 0.75 mg twice daily.

Fifth and sixth days

PO 0.75 mg daily.

Seventh day

No treatment.

Eighth day

Follow-up visit.

Brain tumors Adults

IV / IM 2 mg 2 to 3 times daily.

Cerebral edema Adults

IV 10 mg, then 4 mg IM every 6 h until max response.

Intra-articular, intralesional, or soft-tissue Adults

Large joints, 2 to 4 mg; small joints, 0.8 to 1 mg; bursae, 2 to 3 mg; tendon sheaths, 0.4 to 1 mg; soft-tissue infiltration, 2 to 6 mg; ganglia, 1 to 2 mg.

Ophthalmic solution Adults

Instill 1 to 2 drops into conjunctival sac every 1 h during the day and every 2 h during the night.

Systemic Adults

IV / IM 0.5 to 9 mg/day.

Unresponsive shock Adults

IV 1 to 6 mg/kg as a single injection or 40 mg followed by repeated IV injections every 2 to 6 h.

General Advice

  • Withdraw treatment gradually after long-term therapy.
  • Ophthalmic suspension: Shake well before using.
  • Intravitreal implant: Refer to manufacturer's full package insert for administration technique.

Storage/Stability

Refer to the package inserts for directions on how to store each particular form of dexamethasone.

Elixir

Store at 59° to 86°F. Avoid freezing.

Injection

Store at 68° to 77°F. Protect from light and freezing.

Ophthalmic suspension

Store upright at 46° to 80°F.

Oral solution

Store at 68° to 77°F. Do not freeze. Protect from light.

Intravitreal implant, ophthalmic solution

Store at 59° to 86°F.

Tablets

Store at 68° to 77°F. Protect from moisture and light.

Drug Interactions

Aminoglutethimide

May decrease dexamethasone-induced adrenal suppression.

Amphotericin B

Cardiac enlargement and CHF have been reported.

Anticholinesterases

May antagonize anticholinesterase effects in myasthenia gravis.

Anticoagulants, oral

May alter anticoagulant dose requirements.

Antidiabetic agents

Dexamethasone may increase blood glucose levels, necessitating antidiabetic agent dosage adjustments.

Aprepitant

Dexamethasone plasma levels may be elevated and the half-life prolonged, increasing the pharmacologic effects and adverse reactions.

Cholestyramine, epinephrine

Dexamethasone plasma levels may be reduced, decreasing the efficacy.

Cyclosporine

Activity of cyclosporine and dexamethasone may be increased. In addition, convulsions have been reported.

CYP3A4 substrates (eg, erythromycin, indinavir)

Plasma levels may be reduced by dexamethasone, decreasing efficacy.

Digoxin

Because of possible dexamethasone-induced hypokalemia, the risk of arrhythmias may be increased.

Hepatic enzyme inducers (eg, barbiturates, carbamazepine, phenytoin, rifampin)

Dexamethasone plasma levels may be reduced, decreasing the efficacy. In addition, seizure control with phenytoin may be altered.

Hepatic enzyme inhibitors (eg, azole antifungal agents [eg, ketoconazole], estrogens including oral contraceptives, macrolide antibiotics [eg, erythromycin])

Dexamethasone plasma levels may be elevated, increasing the pharmacologic effects and adverse reactions. In addition, ketoconazole can inhibit adrenal corticosteroid synthesis, causing adrenal insufficiency during dexamethasone withdrawal.

NSAIDs, salicylates

Risk of GI adverse reactions may be increased. In addition, salicylate levels and efficacy may be reduced.

Potassium-depleting agents (eg, amphotericin B, loop and thiazide diuretics)

Risk of hypokalemia may be increased.

Thalidomide

Use with caution; TEN has been reported with concurrent use of dexamethasone.

Laboratory Test Interactions

May cause increased levels of urine glucose and serum cholesterol; decreased serum levels of potassium, T 3 and T 4 ; decreased uptake of thyroid 131-iodine; false-negative nitroblue-tetrazolium test; altered brain scan results; suppression of skin test reactions. False-negative results for the dexamethasone suppression test may occur in patients receiving indomethacin.

Adverse Reactions

Cardiovascular

Arrhythmias, bradycardia, cardiac arrest, cardiac enlargement, CHF, circulatory collapse, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent MI, pulmonary edema, syncope, tachycardia, thromboembolism, vasculitis.

CNS

Convulsions, emotional instability, euphoria, headache, increased appetite, increased intracranial pressure with papilledema (pseudotumor cerebri, usually following discontinuation of treatment), insomnia, malaise, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychic disorders, vertigo.

Dermatologic

Acne; allergic dermatitis; dry, scaly skin; ecchymosis and petechiae; erythema; impaired wound healing; increased sweating; rash; striae; suppression of skin test reactions; thin, fragile skin; thinning scalp hair; urticaria.

EENT

Exophthalmos, glaucoma, increased IOP, posterior subcapsular cataracts.

Electrolytes

Fluid retention, hypokalemic alkalosis, potassium loss, sodium retention.

Endocrine

Decreased carbohydrate and glucose tolerance, development of cushingoid state, glycosuria, hirsutism, hyperglycemia, hypertrichosis, increased requirements for insulin or oral hypoglycemic agents in diabetes, manifestation of latent diabetes mellitus, menstrual irregularities, secondary adrenocortical and pituitary unresponsiveness, suppression of growth in children.

GI

Abdominal distention, hiccups, nausea, pancreatitis, peptic ulcer and possible perforation and hemorrhage, perforation of the small and large intestine, ulcerative esophagitis.

Genitourinary

Decreased or increased motility and number of spermatozoa.

Hepatic

Elevation in serum liver enzyme levels, hepatomegaly.

Hypersensitivity

Anaphylactoid reactions, anaphylaxis, angioedema.

Metabolic-Nutritional

Abnormal fat deposits, moon face, negative nitrogen balance caused by protein catabolism, weight gain.

Musculoskeletal

Aseptic necrosis of femoral and humeral heads, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, steroid myopathy, tendon rapture, vertebral compression fractures.

Ophthalmic

Intravitreal implant

IOP increased (25%); conjunctival hemorrhage (22%); eye pain (8%); conjunctival hyperemia (7%); cataract, ocular hypertension (5%); vitreous detachment (2%).

Miscellaneous

Decreased resistance to infection, edema.

Precautions

Monitor

Intravitreal implant

Following the intravitreal injection, monitor patients for elevation in IOP and endophthalmitis. Monitoring may consist of a check for perfusion of the optic nerve head immediately after injection, tonometry within 30 min following the injection, and biomicroscopy between 2 and 7 days.


Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

May be more susceptible to adverse reactions from topical use than adults. Observe growth and development of infants and children on prolonged therapy.

Intravitreal implant, ophthalmic solution and suspension

Safety and efficacy not established in children.

Elderly

May require lower doses. Use with caution, usually starting at the low end of the dose range because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Intravitreal implant, ophthalmic suspension

No differences in safety and efficacy have been observed between elderly and younger patients.

Renal Function

Use cautiously; monitor renal function.

Sulfite Sensitivity

Some products may contain sodium bisulfite, which may cause allergic-type reactions in some patients.

Adrenal suppression

Prolonged therapy may lead to hypothalamic-pituitary-adrenal suppression.

Fluid and electrolyte balance

Can cause elevated BP, salt and water retention, and increased potassium and calcium excretion. Dietary salt restriction and potassium supplementation may be needed.

GI

Because of increased risk of perforation, use with caution in patients with diverticulitis, fresh intestinal anastomosis, latent peptic ulcers, or nonspecific ulcerative colitis.

Hepatitis

May be harmful in chronic active hepatitis positive for hepatitis B surface antigen.

Infections

May mask signs of infection. May decrease host-defense mechanisms to prevent dissemination of infection. May enhance establishment of secondary ocular infections.

Intravitreal injection

Associated with endophthalmitis, eye inflammation, increased IOP, and retinal detachments. Monitor patients following the injection.

Musculoskeletal

Bone formation may be decreased and bone resorption may be increased.

Neuropsychiatric

Psychic or psychotic manifestations may occur, including euphoria, insomnia, personality changes, and severe depression; in addition, emotional instability or psychotic tendencies may be exacerbated.

Ocular effects

May produce subcapsular cataracts, increased ocular pressure, and glaucoma.

Ocular herpes simplex

Use systemically with caution in patients with ocular herpes simplex because of possible corneal perforation; use intravitreal implant with caution in patients with a history of ocular herpes simplex and avoid use in patients with active infection.

Ophthalmic use

Prolonged use may result in glaucoma or other complications.

Stress

Increased dosage of rapidly acting corticosteroid may be needed before, during, and after stressful situations.

Withdrawal

Abrupt discontinuation may result in adrenal insufficiency. Discontinue gradually.

Overdosage

Symptoms

Acne, anorexia, arthralgia, central obesity, diabetes, dizziness, dyspnea, ecchymoses, electrolyte and fluid imbalance (chronic cushingoid changes), fainting, fever, hirsutism, hyperlipidemia, hypertension, hypoglycemia (acute overdose), infection, malaise, moon face, myalgia, myopathy, nausea, orthostatic hypotension, osteoporosis, peptic ulcer, sexual dysfunction, skin desquamation, striae.

Patient Information

  • Caution patient that stopping drug abruptly is dangerous and may cause adrenal insufficiency.
  • Explain that medication must be tapered to discontinue.
  • Instruct patient to avoid exposure to chickenpox or measles and to immediately notify health care provider if exposure occurs.
  • Teach patient or caregiver procedures for correctly administering specific form of drug (eg, ophthalmic).
  • Caution patient against receiving immunizations while drug is being taken.
  • Advise patient on long-term therapy to carry medication identification (eg, card, bracelet). In case of emergency, this information is important for treatment.
  • Instruct patient to avoid people with infections, particularly respiratory.
  • Teach patient to take oral forms with meals or snacks if GI irritation occurs.
  • Review guidelines for missed doses of particular product with patient.
  • Teach patient on long-term therapy how to keep a weight record.
  • Instruct patient to inform all of their health care providers that they are taking a steroid.
  • Review signs of infection and remind patient that fever, swelling, and redness may be masked in infection.
  • Review possible adverse reactions of dexamethasone with patient and instruct patient to report these to health care provider.
  • Inform patients that they may experience temporary blurring of their vision following intravitreal injection. Advise patients not to drive or operate machinery until this symptom has resolved.
  • Advise patients of the potential risks in the days following intravitreal injection of dexamethasone, including development of endophthalmitis or elevated IOP.
  • Advise patients to seek immediate care from an ophthalmologist if the eye becomes red, sensitive to light, painful, or develops a change in vision following injection of intravitreal implant.

Copyright © 2009 Wolters Kluwer Health.

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