What are the side effects of dexamethasone (corticosteroid)?

Dexamethasone Side Effects

Dexamethasone has a favorable side effect profile when used as a single dose or short course (≤2 weeks), but prolonged use or high doses are associated with serious adverse events including gastrointestinal perforation, hyperglycemia, psychiatric disturbances, and in neonates, neurodevelopmental impairment.

Dose and Duration-Dependent Toxicity

The severity and frequency of side effects correlate directly with both dose and duration of therapy:

High-Dose Regimens (≥96 mg/day or ≥0.5 mg/kg/day)

• Serious gastrointestinal complications occur in 14% of patients, including fatal ulcer hemorrhage, rectal bleeding, gastrointestinal perforation of undetermined origin, and sigmoid colon perforation 1
• High-dose dexamethasone (96 mg IV daily) for spinal cord compression resulted in significantly more serious adverse events compared to standard dosing (16 mg daily), leading to abandonment of the high-dose regimen 1
• In neonates, high-dose dexamethasone (0.5 mg/kg/day) causes neurodevelopmental impairment and hippocampal neuronal degeneration, effects not seen with hydrocortisone 2

Moderate-Dose Extended Therapy

• Patients receiving dexamethasone 8 mg BID for 1 week, then 4 mg BID for 1 week, followed by open-label continuation (mean total exposure 243 mg over 27 days) experienced Grade 3+ adverse events in 65% versus 15% in unexposed patients (OR 15.1,95% CI 1.4-160.8) 3
• Hospitalization occurred in 23% of patients receiving moderate-dose extended therapy 3

Low-Dose Short-Course Therapy

• Single doses of 4-10 mg have rare adverse effects, with the most common being elevated serum glucose, epigastric burning, and sleep disturbances 2
• A single 8 mg dose for postoperative nausea/vomiting showed no increase in adverse events compared to placebo 2
• Low-dose dexamethasone (≤0.2 mg/kg/day) in neonates may decrease adverse effects seen with higher doses 2

Common Side Effects by System

Metabolic and Endocrine

• Hyperglycemia is the most frequent adverse effect, occurring in 76% of ICU patients receiving dexamethasone versus 70% of controls 4
• Elevated serum glucose levels occur commonly even with short courses 2, 5
• Cushingoid features develop with prolonged use (average 23 weeks in primary brain tumor patients) 5
• Suppression of the hypothalamic-pituitary-adrenal axis, particularly problematic during stress, trauma, or surgery 6
• Manifestations of latent diabetes mellitus and increased insulin requirements in diabetics 6

Gastrointestinal

• Peptic ulceration may occur even with high-dose short-term therapy (48-72 hours) 6
• Epigastric burning is common with single doses 2
• Serious complications (perforation, hemorrhage) occur primarily with high-dose regimens 1

Neuropsychiatric

• Psychiatric disorders including insomnia (31%), neuropsychiatric symptoms (18%), and sleep disturbances are frequent 2, 3, 5
• Increased alertness and restlessness during nighttime 2
• In neonates, dexamethasone specifically alters hippocampal synaptic plasticity, associative memory formation, and decreases hippocampal volume—effects not seen with hydrocortisone 2
• Psychic disturbances and pseudotumor cerebri (increased intracranial pressure with papilledema) after treatment 6

Infectious Complications

• New infections (pneumonia, sepsis) occurred in 24% of dexamethasone-treated ICU patients versus 25% of controls 4
• Dyspepsia occurred in 21% and infections in 17% of cancer patients receiving dexamethasone 3
• Despite theoretical immunosuppression concerns, single-dose dexamethasone does not increase postoperative wound infections or anastomotic leakage 2

Cardiovascular

• Peripheral edema is a frequent complication with prolonged use 5
• Myocardial rupture following recent myocardial infarction 6
• Thromboembolism 6

Ophthalmic

• Posterior subcapsular cataracts with prolonged use 6
• Increased intraocular pressure and glaucoma 6

Other Notable Effects

• Weight gain and increased appetite 6
• Menstrual irregularities 6
• Growth suppression in children 6
• Anaphylactoid or hypersensitivity reactions (rare) 6

Critical Clinical Considerations

Neonatal Population

Dexamethasone binds only to glucocorticoid receptors, causing hippocampal neuronal degeneration and necrosis in animal models, whereas hydrocortisone binds both mineralocorticoid and glucocorticoid receptors without these effects 2. This mechanistic difference explains the neurodevelopmental impairment seen specifically with neonatal dexamethasone exposure.

Duration-Dependent Risk

Symptom relief from dexamethasone is greatest initially with few side effects, but toxicity increases substantially over time while symptom relief diminishes 5. In brain tumor patients, the average duration of dexamethasone intake was 23 weeks for primary tumors and 7 weeks for metastases, with side effects accumulating throughout 5.

Dose Optimization

• For antiemetic prophylaxis, 4-5 mg doses have clinical effects similar to 8-10 mg doses with presumably fewer side effects 2
• When combined with other antiemetics (5-HT3 antagonists, aprepitant), dexamethasone doses should be reduced (e.g., 12 mg on day of chemotherapy, 8 mg daily on days 2-4) 2
• For postoperative analgesia in tonsillectomy, doses of at least 0.15 mg/kg in children or 8 mg total in adults are needed for analgesic effect 2

Immunosuppressive Concerns

The long-term oncological survival effects of dexamethasone's immunosuppressive properties remain unknown in surgical cancer patients 2. However, short-term use does not increase infection rates in most surgical contexts 2.