Dexamethasone — Drug Monograph

Brand names: Decadron, Dexamethasone Intensol

Drug class: Corticosteroid

Mechanism of Action

Dexamethasone is a highly potent synthetic fluorinated glucocorticoid with approximately 25–30 times the anti-inflammatory potency of hydrocortisone and minimal mineralocorticoid activity. It binds to intracellular glucocorticoid receptors (GR-α), and the ligand-receptor complex translocates to the nucleus where it regulates gene transcription via glucocorticoid response elements (GREs). In hematologic malignancies, dexamethasone induces apoptosis in lymphoid and myeloma cells by activating intrinsic apoptotic pathways, inhibiting NF-κB signaling, downregulating anti-apoptotic proteins…

FDA Indications

• Multiple myeloma — component of VRd (bortezomib/lenalidomide/dexamethasone; SWOG S0777 trial, 2017), DRd (daratumumab/lenalidomide/dexamethasone; MAIA trial, 2019), and numerous other standard regimens
• Acute lymphoblastic leukemia — induction and consolidation regimens
• Hodgkin and non-Hodgkin lymphoma — component of DHAP, ICE salvage regimens and others
• Cerebral edema associated with primary or metastatic brain tumors and neurosurgical procedures
• Chemotherapy-induced nausea and vomiting (CINV) — antiemetic prophylaxis for moderately and highly emetogenic regimens
• Adrenal insufficiency and inflammatory/allergic conditions (broad FDA labeling)

Common Side Effects

• Hyperglycemia and worsening of diabetes mellitus
• Insomnia and mood disturbances (euphoria, irritability, anxiety)
• Increased appetite and weight gain
• Fluid retention and edema
• Hypertension
• Immunosuppression and increased infection susceptibility
• GI upset, dyspepsia, peptic ulceration
• Muscle weakness (proximal myopathy)
• Cushingoid features with prolonged use
• Hypokalemia

Clinical Pearl

In multiple myeloma, dose reduction of dexamethasone from 40 mg weekly to 20 mg weekly (low-dose dexamethasone, Ld) dramatically improves tolerability and OS compared to high-dose schedules without sacrificing efficacy, as demonstrated in the E4A03 trial — low-dose became the standard backbone. Patients on dexamethasone-containing myeloma regimens with IMiDs should receive VTE prophylaxis (aspirin, LMWH, or DOAC depending on risk score), as the combination carries a 10–25% VTE risk without…

Related Therapies & Mechanisms

• Methylprednisolone (Solu-Medrol) — Corticosteroid · Lymphoma
• Prednisone (Deltasone) — Corticosteroid · Lymphoma
• Cyclophosphamide (Cytoxan) — Lymphoma
• Doxorubicin (Adriamycin) — Lymphoma