What is dexamethasone?

Dexamethasone: A Potent Synthetic Glucocorticoid

Dexamethasone is a potent, long-acting synthetic glucocorticoid with significant anti-inflammatory, immunosuppressive, and anti-allergic properties that is approximately 25 times more potent than short-acting corticosteroids like hydrocortisone. 1

Pharmacological Properties

• Potency: 25 times more potent than hydrocortisone with a half-life of 36-72 hours 2
• Duration: Long-acting with a half-life of 36-72 hours 2
• Equivalent doses: 0.1 mg dexamethasone equals 10 mg hydrocortisone; 8 mg dexamethasone equals 200 mg hydrocortisone 2
• Formulations: Available as oral tablets, injectable solutions (IV/IM), and other preparations 3, 4
• Mineralocorticoid activity: Lacks significant mineralocorticoid activity, making it unsuitable as sole therapy for primary adrenal insufficiency 2

Clinical Applications

Oncology

• Chemotherapy-induced nausea/vomiting: Standard antiemetic prophylaxis in moderate to high emetic risk chemotherapy 5
  • High emetic risk: Dexamethasone 20 mg day 1, then 8 mg days 2-4
  • Moderate emetic risk: Dexamethasone 8 mg on day 1 (single dose)
  • Low emetic risk: Dexamethasone 8 mg (single dose) 5

Hematologic Malignancies

• Acute Lymphoblastic Leukemia (ALL): Core component of induction therapy alongside vincristine, anthracyclines, and asparaginase 5
  • Preferred over prednisone in many protocols due to better CNS penetration
  • Reduces risk of CNS relapse and improves event-free survival 5
  • Dosing typically 6 mg/m² daily for 28 days in pediatric protocols 5

Immunotherapy Complications

• Cytokine Release Syndrome (CRS):
  • Grade 2: Dexamethasone 10 mg IV every 12-24 hours 5
  • Grade 3-4: Dexamethasone 10 mg IV every 6 hours 5
• Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS):
  • Grade 2: Dexamethasone 10 mg IV, may repeat every 6-12 hours if no improvement
  • Grade 3: Dexamethasone 10 mg IV every 6 hours
  • Grade 4: High-dose methylprednisolone 1000 mg/day 5

Infectious Diseases

• Bacterial Meningitis: Adjunctive therapy to reduce neurological sequelae and hearing loss 5
  • Adults: 10 mg IV every 6 hours for 4 days
  • Children: 0.15 mg/kg IV every 6 hours for 4 days
  • Should be started before or with the first dose of antibiotics, but can be started up to 4 hours after antibiotics 5
  • Most beneficial for pneumococcal and H. influenzae meningitis 5

Perioperative Use

• PONV Prevention: Single dose of 4-5 mg has similar efficacy to 8-10 mg 5
  • The DREAMS trial confirmed that a single 8 mg dose reduced PONV for up to 72 hours 5

Side Effects and Risks

• Short-term use: Generally well-tolerated with minimal adverse effects 2

  • Hyperglycemia
  • Sleep disturbances
  • Epigastric burning sensation

• Long-term use: Significant adverse effects 6

  • Weight changes (typically weight loss in animal studies) 6
  • Metabolic disturbances (hyperglycemia, lipid abnormalities) 6
  • Bone metabolism abnormalities (reduced alkaline phosphatase) 6
  • Protein catabolism and muscle wasting 6
  • Immunosuppression

Special Considerations

• In ALL treatment, dexamethasone is associated with higher risk of osteonecrosis, infection, and induction mortality compared to prednisone, despite better CNS penetration 5
• For short-term use (<1 week), dexamethasone can be discontinued rapidly without tapering 2
• For longer use (>3 weeks), gradual tapering is recommended to prevent adrenal insufficiency 2
• When used for bacterial meningitis, dexamethasone should be discontinued if the causative organism is determined not to be H. influenzae or S. pneumoniae 5

Dosing Recommendations

• Single daily dosing is possible due to long half-life and excellent bioavailability 2
• Tapering schedule for prolonged use (from 16 mg): 12 mg/day for 2-3 days → 8 mg/day for 2-3 days → 4 mg/day for 2-3 days → 2 mg/day for 2-3 days before discontinuation 2
• Dose adjustments may be needed for patients taking CYP3A4 inducers or those who are obese 2

Dexamethasone's potency, long half-life, and minimal mineralocorticoid effects make it a valuable therapeutic option across multiple medical specialties, but its use must be balanced against potential adverse effects, particularly with prolonged administration.