What are the contraindications to dexamethasone?

Contraindications to Dexamethasone

Dexamethasone has no absolute contraindications in life-threatening emergencies, but should be avoided or used with extreme caution in patients with active systemic fungal infections, uncontrolled bacterial infections without concurrent antimicrobial therapy, and live virus vaccinations.

Infectious Disease Contraindications

Fungal Infections

• Active systemic fungal infections represent a critical contraindication to dexamethasone therapy, as corticosteroids suppress Dectin-1 receptor activation on antigen-presenting cells, impairing the immune response to fungal pathogens 1
• Dexamethasone reduces production of IL-12, IL-23, and TNF-alpha while increasing IL-10 secretion, creating an immunosuppressive environment that facilitates fungal proliferation 1
• If dexamethasone is essential for other indications (e.g., cerebral edema), antifungal prophylaxis must be strongly considered 2, 3

Bacterial Infections Without Antimicrobial Coverage

• In patients with suspected bacterial meningitis, dexamethasone should only be administered when empirical broad-spectrum antibiotics are given concurrently 2
• The Society of Critical Care Medicine recommends avoiding high-dose corticosteroids (equivalent to hydrocortisone >300 mg/day or prednisolone >75 mg/day) in septic patients, as they significantly increase hospital-acquired infections without reducing mortality 4
• For community-acquired pneumonia, the American Thoracic Society strongly recommends against routine corticosteroid use due to increased secondary infection rates and hyperglycemia 5

Viral Infections

• Early in the COVID-19 pandemic, WHO and multiple international guidelines contraindicated corticosteroids for viral pneumonia outside of clinical trials 2
• Live virus vaccinations should be avoided during dexamethasone therapy due to risk of disseminated viral infection 6

Clinical Context-Specific Cautions

Pre-existing Gastrointestinal Disease

• High-dose dexamethasone (96 mg/day) carries significant gastrointestinal toxicity risk, with documented cases of fatal peptic ulcers, GI perforation, sigmoid perforation, and rectal bleeding 2
• Patients with peptic ulcer disease, diverticulitis, or inflammatory bowel disease require careful risk-benefit assessment 7

Cardiovascular Considerations

• Dexamethasone can cause hypertension, fluid retention, and electrolyte disturbances 7
• In patients receiving CAR T-cell therapy, cardiovascular complications including atrial fibrillation, ventricular tachycardia, cardiac arrest, and heart failure have been documented with concurrent dexamethasone use 2

Metabolic Disorders

• The American Diabetes Association notes that dexamethasone increases blood glucose by approximately 13 mg/dL in non-diabetic patients within 12 hours 4
• Hyperglycemia requiring therapy occurred in 76% of dexamethasone-treated ARDS patients versus 70% of controls 8
• Patients with uncontrolled diabetes require intensive glucose monitoring and insulin adjustment 4

Relative Contraindications Requiring Dose Modification

Pediatric Populations

• In children with immune thrombocytopenia (ITP), the American Society of Hematology recommends preferring prednisone (2-4 mg/kg/day for 5-7 days, max 120 mg) over dexamethasone 4
• Higher dexamethasone doses (10 mg/m²/day for 21 days) in pediatric ALL patients increase risk of osteonecrosis and infection compared to standard dosing (6 mg/m²/day) 3

Neurologic Conditions

• Pre-existing peripheral neuropathy represents a relative contraindication when dexamethasone is combined with bortezomib, requiring dose attenuation or alternative agents 2

Common Pitfalls to Avoid

• Never delay dexamethasone in suspected bacterial meningitis while awaiting diagnostic confirmation—administer steroids before or with the first antibiotic dose for maximum efficacy 2, 4
• Do not abruptly discontinue dexamethasone after prolonged use (>14 days)—taper over 4-6 weeks minimum to prevent adrenal insufficiency and inflammatory rebound 4, 3
• Avoid prophylactic dexamethasone before axicabtagene ciloleucel CAR T-cell therapy—this may increase risk of grade 4 and prolonged neurologic toxicities 2
• Do not use dexamethasone routinely in aspiration pneumonia or non-severe community-acquired pneumonia—reserve for refractory septic shock only 5

When Benefits Outweigh Contraindications

Despite relative contraindications, dexamethasone remains indicated in specific life-threatening scenarios:

• Bacterial meningitis with concurrent appropriate antibiotics 2, 4
• Established moderate-to-severe ARDS (reduces mortality by 15.3% and increases ventilator-free days by 4.8 days) 8
• Spinal cord compression (improves ambulation from 63% to 81% when ambulatory before treatment) 2
• Grade 3-4 immune effector cell-associated neurotoxicity syndrome 2, 3