Deflazacort

Approved Indications:

• Duchenne Muscular Dystrophy (DMD):
• For long-term maintenance treatment in boys aged ≥5 years to slow disease progression and preserve muscle strength.
• Inflammatory and Autoimmune Conditions:
• Short‑term relief of symptoms of various conditions (e.g., rheumatoid arthritis, polymyalgia rheumatica, systemic lupus erythematosus, asthma exacerbations) when oral glucocorticoid therapy is appropriate.
• Used where corticosteroid-sparing effect is desired due to lower metabolic adverse effect profile.

Clinically Accepted Off‑label Uses:

• Corticosteroid-responsive conditions such as certain dermatologic, rheumatologic, neurologic, and ophthalmologic disorders.
• Addison’s disease maintenance (rare).
• Nephrotic syndrome (frequently used in pediatric protocols).

Adults:

• Anti-inflammatory/Immunosuppressive Use:
• Typical starting dose: 6–18 mg once daily (equivalent to 5–15 mg prednisone). Daily dose adjusted based on disease severity and tapering schedule.
• Severe Inflammation or Autoimmune Flare:
• Initial doses up to 30 mg/day may be used, then tapered to lowest effective maintenance dose.

Children:

• Duchenne Muscular Dystrophy (DMD):
• 0.9 mg/kg/day orally once daily (maximum ~36 mg/day). Alternate-day dosing may be used to reduce side effects.
• Duration: typically ≥24 months, with reassessment and adjustment according to clinical response.
• Other pediatric indications:
• Weight-based equivalent to prednisone/prednisolone (standard glucocorticoid regimens).

Special Populations:

• Renal/Hepatic Impairment:
• No standard adjustment; use caution in severe impairment.
• Elderly:
• Use lowest effective dose; monitor closely for metabolic and bone effects.

Administration Route:

• Oral tablets; take in the morning with food to reduce gastric irritation and mimic circadian cortisol rhythm.

Deflazacort is a synthetic glucocorticoid prodrug that is rapidly converted by plasma esterases into its active metabolite, 21‑desacetyl deflazacort. It binds to the glucocorticoid receptor, which translocates to the nucleus and modulates gene expression—upregulating anti-inflammatory proteins and downregulating pro-inflammatory cytokines. Compared to prednisone, deflazacort has a favorable therapeutic index with reduced effects on glucose and lipid metabolism and less impact on bone mineral density and growth in children.

Absorption:

• Rapid and complete absorption after oral administration; peak active metabolite levels reached within 1–2 hours.

Distribution:

• Volume of distribution ~0.5 L/kg.
• Plasma protein binding ~40–60%.

Metabolism:

• Deflazacort is a prodrug hydrolyzed by esterases to active metabolite 21-desacetyl deflazacort; further metabolized via hepatic CYP3A4 to inactive metabolites.

Elimination:

• Half‑life of active metabolite ~1.5 to 3 hours.
• Excreted primarily via urine (approximately 60%) and feces.

• Pregnancy:
• FDA Category C. Animal studies show fetal effects at high doses; human data limited. Use only if maternal benefit outweighs potential risks. Monitor fetal growth and amniotic fluid.
• Lactation:
• Active metabolite is excreted in breast milk; caution advised. Breastfeeding may continue if low dose and infant monitored for adrenal suppression or growth impact.

• Primary Class: Glucocorticoid
• Subclass: Synthetic corticosteroid prodrug with anti‑inflammatory and immunosuppressive properties

• Known hypersensitivity to deflazacort or any excipients.
• Systemic fungal infections unless concurrently treated.
• Live or attenuated vaccines during high-dose therapy.
• Uncontrolled infections (relative contraindication).

• Adrenal Suppression: Gradually taper dose; abrupt cessation may precipitate adrenal crisis.
• Growth Suppression in Children: Monitor growth periodically; dose sparing strategies advised.
• Osteoporosis and Bone Health: Long-term use decreases bone density; monitor bone markers and supplement calcium/vitamin D; consider bisphosphonates in high-risk patients.
• Hyperglycemia and Diabetes: Monitor blood glucose; use caution in diabetics.
• Hypertension and Fluid Retention: Monitor blood pressure and electrolytes.
• Risk of Infection: Immunosuppression increases susceptibility; avoid live vaccines; monitor for opportunistic infections.
• Psychiatric Effects: Monitor for mood changes, euphoria, insomnia, or depression.
• GI Effects: Risk of peptic ulcer disease; consider gastroprotective agents in high-risk individuals.

Common:

• Weight gain (due to appetite increase and fluid retention)
• Gastrointestinal upset (dyspepsia)
• Insomnia or mood changes
• Hypertension
• Increased blood glucose
• Acne and facial rounding (“moon face”)

Less Common:

• Growth retardation in children
• Osteopenia/osteoporosis
• Gastric ulceration or GI bleeding
• Muscle weakness (myopathy)

Rare/Serious:

• Adrenal insufficiency if stopped abruptly
• Severe infections (e.g., tuberculosis, fungal sepsis)
• Psychiatric disturbances (e.g., psychotic reaction)
• Pancreatitis
• Cataracts or ocular hypertension with prolonged use

Timing and Dose‑Dependence:

• Metabolic and GI effects often manifest with moderate to high doses and over weeks to months.
• Some effects (e.g., mood, insomnia) may appear early.
• Growth and bone effects accumulate with chronic use.

• CYP3A4 Inhibitors (e.g., ketoconazole, ritonavir): May increase deflazacort levels; monitor for corticosteroid excess; consider dose reduction.
• CYP3A4 Inducers (e.g., rifampin, carbamazepine): May decrease deflazacort efficacy; may require dose increase.
• NSAIDs or Anticoagulants: Additive GI bleeding risk; monitor closely.
• Live Vaccines: Contraindicated in immunosuppressed; risk of disseminated infection.
• Diabetic Medications: May require adjustment due to hyperglycemic effects.

• DMD Clinical Guidelines (2019–2024): Deflazacort endorsed as first‑line steroid in DMD due to better growth and metabolic profile compared to prednisone/prednisolone.
• Endocrine Society: Updated recommendations emphasize bone-protective strategies and growth monitoring with pediatric steroid use.
• EMA & FDA advisories: Highlight risk of adrenal suppression and recommend standardized tapering protocols.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light; keep in original container.
• Do not freeze.
• Handling Precautions: No special handling needed; wash hands after handling tablets if dose splitting.
• Use: Tablets should be swallowed whole; do not crush or chew.