Decadron - Drug Monograph

Introduction

Decadron (dexamethasone) is a potent, long-acting synthetic glucocorticoid with significant anti-inflammatory and immunosuppressive properties. As a corticosteroid, it is approximately 25 times more potent than hydrocortisone and 6-7 times more potent than prednisone. First approved by the FDA in 1958, Decadron remains a cornerstone therapy across multiple medical specialties including endocrinology, oncology, rheumatology, and neurology due to its diverse physiological effects.

Mechanism of Action

Decadron exerts its effects through genomic and non-genomic pathways. Its primary mechanism involves diffusion across cell membranes and binding to cytoplasmic glucocorticoid receptors. The drug-receptor complex translocates to the nucleus where it binds to glucocorticoid response elements (GREs) on DNA, modulating gene transcription. This results in:

• Inhibition of pro-inflammatory cytokine production (IL-1, IL-2, IL-6, TNF-α)
• Decreased synthesis of inflammatory mediators (prostaglandins, leukotrienes)
• Reduced migration of inflammatory cells to sites of inflammation
• Stabilization of lysosomal membranes
• Inhibition of fibroblast proliferation

Decadron also induces lipocortin synthesis, which inhibits phospholipase A2, thereby preventing the release of arachidonic acid from membrane phospholipids.

Indications

• Endocrine disorders: Primary and secondary adrenocortical insufficiency, congenital adrenal hyperplasia, hypercalcemia of malignancy
• Rheumatic disorders: Rheumatoid arthritis, acute gouty arthritis
• Collagen diseases: Systemic lupus erythematosus, acute rheumatic carditis
• Dermatologic diseases: Pemphigus, severe erythema multiforme, exfoliative dermatitis
• Allergic states: Bronchial asthma, contact dermatitis, serum sickness
• Ophthalmic diseases: Allergic conjunctivitis, keratitis, optic neuritis
• Respiratory diseases: Symptomatic sarcoidosis, berylliosis, aspiration pneumonitis
• Hematologic disorders: Idiopathic thrombocytopenic purpura, acquired hemolytic anemia
• Neoplastic diseases: Palliative management of leukemias and lymphomas
• Edematous states: To induce diuresis in nephrotic syndrome
• Gastrointestinal diseases: Ulcerative colitis, regional enteritis
• Neurologic conditions: Cerebral edema associated with primary or metastatic brain tumors

• Prevention of chemotherapy-induced nausea and vomiting
• Spinal cord compression from metastatic cancer
• COVID-19-related cytokine storm (during pandemic emergency use)
• Croup in pediatric patients
• Autoimmune hepatitis flare management

Dosage and Administration

Dosage must be individualized based on disease severity and patient response. Use the lowest effective dose for the shortest possible duration.

• Anti-inflammatory/immunosuppressive: 0.75-9 mg daily in divided doses
• Cerebral edema: Initial 10 mg IV followed by 4 mg IM every 6 hours
• Chemotherapy-induced nausea: 8-20 mg IV 30 minutes before chemotherapy
• Dexamethasone suppression test: 1 mg orally at 11 PM

• Anti-inflammatory/immunosuppressive: 0.08-0.3 mg/kg/day in divided doses
• Croup: 0.6 mg/kg IM (single dose, maximum 16 mg)
• Bacterial meningitis: 0.15 mg/kg/dose QID for 4 days

No dosage adjustment typically required, but monitor for fluid retention and hypertension

Use with caution; impaired metabolism may lead to increased systemic exposure

• Oral: With food to minimize GI upset
• Intravenous: Administer undiluted over 1-4 minutes or as infusion
• Intramuscular: Administer deep IM into large muscle mass
• Intra-articular: For local effect in joint spaces
• Topical: For dermatological conditions

Pharmacokinetics

• Oral: Rapid and nearly complete (80-90% bioavailability)
• IM: Rapid absorption with peak concentrations in 1 hour

• Volume of distribution: 0.8-1.5 L/kg
• Protein binding: 77% (primarily to albumin)
• Crosses placenta and blood-brain barrier

• Hepatic metabolism via CYP3A4 to inactive metabolites
• Minimal first-pass metabolism

• Half-life: 36-54 hours (plasma), 36-72 hours (biological)
• Excretion: Primarily renal (unchanged drug <10%)
• Clearance: 0.111-0.173 L/h/kg

Contraindications

• Systemic fungal infections (unless treating adrenal insufficiency)
• Known hypersensitivity to dexamethasone or components
• Live virus vaccinations during immunosuppressive therapy
• Intrathecal administration (risk of severe adverse effects)
• Active or latent tuberculosis (unless concurrent anti-tuberculosis therapy)
• Active peptic ulcer disease
• Uncontrolled hypertension or congestive heart failure

Warnings and Precautions

• Corticosteroids can cause serious and fatal infections due to immunosuppression
• Avoid administration in patients with known or suspected strongyloides infection (risk of hyperinfection)

• Adrenal suppression may occur with prolonged therapy; taper gradually
• Increased mortality in community-acquired pneumonia when used empirically
• Psychiatric reactions including euphoria, insomnia, mood swings, depression
• Ocular effects: Cataracts, glaucoma, corneal perforation
• Musculoskeletal: Osteoporosis, vertebral compression fractures, avascular necrosis
• Cardiovascular: Hypertension, sodium and water retention, hypokalemia
• Gastrointestinal: Peptic ulceration, pancreatitis, perforation
• Dermatological: Impaired wound healing, skin atrophy, purpura
• Metabolic: Hyperglycemia, glucose intolerance, lipid abnormalities

Drug Interactions

• Enzyme inducers (phenytoin, rifampin, carbamazepine): Increased dexamethasone clearance → reduced efficacy
• Enzyme inhibitors (ketoconazole, itraconazole): Decreased dexamethasone clearance → increased toxicity
• Anticoagulants: Altered response to anticoagulants; monitor INR closely
• Diuretics: Enhanced potassium wasting; increased risk of hypokalemia
• NSAIDs: Increased risk of GI ulceration and bleeding
• Live vaccines: Reduced immune response; avoid administration
• Antidiabetic agents: Reduced hypoglycemic effect; may require dosage adjustment
• CYP3A4 substrates: Potential for altered metabolism of co-administered drugs

Adverse Effects

• Insomnia
• Increased appetite
• Weight gain
• Fluid retention
• Mood changes
• Hyperglycemia
• Hypertension

• Anaphylaxis
• Severe infections
• Avascular necrosis
• Osteoporosis with fractures
• Adrenal insufficiency
• Cushing's syndrome
• Posterior subcapsular cataracts
• Pancreatitis
• Psychosis
• Thromboembolic events

Monitoring Parameters

• Complete blood count with differential
• Comprehensive metabolic panel (electrolytes, glucose, liver function)
• Blood pressure and weight
• Bone density scan if long-term therapy anticipated
• Tuberculosis screening
• Ophthalmologic examination

• Blood glucose (fasting and postprandial)
• Electrolytes (especially potassium)
• Blood pressure at each visit
• Weight regularly
• Signs of infection
• Mood and psychological status
• Growth velocity in children
• Bone density annually if long-term therapy

Not routinely performed; clinical response guides therapy

Patient Education

• Take exactly as prescribed; do not stop abruptly
• Take oral doses with food to minimize stomach upset
• Report any signs of infection (fever, sore throat)
• Monitor blood sugar if diabetic; medication may increase levels
• Weigh yourself regularly and report sudden weight gain
• Report mood changes, sleep disturbances, or vision changes
• Inform all healthcare providers about Decadron use
• Carry medical identification indicating steroid use
• Avoid exposure to illnesses; practice good hygiene
• Do not receive live vaccines while taking this medication
• Maintain adequate calcium and vitamin D intake
• Regular exercise helps maintain bone strength
• Rise slowly from sitting/lying position to prevent dizziness

• Pregnancy: Category C; use only if potential benefit justifies risk
• Breastfeeding: Excreted in milk; use cautiously
• Pediatrics: Monitor growth velocity
• Elderly: Increased risk of hypertension, osteoporosis, and glucose intolerance

References

1. Dexamethasone. In: Lexicomp Online [database]. Hudson, OH: Wolters Kluwer Clinical Drug Information, Inc.; 2023. 2. Dexamethasone. In: Drug Facts and Comparisons. St. Louis, MO: Wolters Kluwer Health, Inc.; 2023. 3. Liu D, Ahmet A, Ward L, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9(1):30. 4. Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol. 2011;335(1):2-13. 5. Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci (Lond). 1998;94(6):557-572. 6. American Society of Health-System Pharmacists. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2023. 7. National Institutes of Health. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases; 2012. 8. Fardet L, Petersen I, Nazareth I. Prevalence of long-term oral glucocorticoid prescriptions in the UK over the past 20 years. Rheumatology (Oxford). 2011;50(11):1982-1990.