Deflazacort - Drug Monograph

Introduction

Deflazacort is a synthetic corticosteroid with anti-inflammatory and immunosuppressive properties. It is a prodrug that is rapidly converted to its active metabolite, 21-desdeflazacort, following oral administration. Deflazacort was initially developed in the 1960s and received FDA approval in 2017 for the treatment of Duchenne muscular dystrophy (DMD). It offers a distinct side effect profile compared to other corticosteroids, with potentially less weight gain but increased risk of certain other adverse effects.

Mechanism of Action

Deflazacort exerts its effects through binding to intracellular glucocorticoid receptors. The drug-receptor complex translocates to the nucleus where it modulates gene transcription. This results in:

• Inhibition of inflammatory cytokine production
• Decreased migration of inflammatory cells
• Stabilization of lysosomal membranes
• Suppression of lymphocyte proliferation
• Reduction of capillary permeability

In DMD, deflazacort helps preserve muscle strength and function by reducing inflammation and potentially modulating dystrophin-deficient muscle pathology.

Indications

• Treatment of Duchenne muscular dystrophy (DMD) in patients 2 years of age and older

• Inflammatory and autoimmune disorders (similar to other corticosteroids)
• Nephrotic syndrome
• Rheumatoid arthritis
• Asthma exacerbations
• Allergic conditions

Dosage and Administration

• Recommended dosage: 0.9 mg/kg orally once daily
• Alternative dosage: 1.2 mg/kg orally once daily for patients who cannot swallow tablets (using oral suspension)
• Tablets should be taken with food to improve absorption

• Hepatic impairment: Use with caution; consider dose reduction
• Renal impairment: No specific dosage adjustment recommended
• Geriatric patients: Use lowest effective dose
• Pediatric patients: Safety established down to age 2 years

• Approximately 6 mg deflazacort = 5 mg prednisone
• Taper gradually when switching from other corticosteroids

Pharmacokinetics

• Rapidly absorbed following oral administration
• Time to peak concentration: 1.5-2 hours
• Food increases bioavailability by approximately 30%

• Active metabolite (21-desdeflazacort) is approximately 40% protein-bound
• Widely distributed throughout body tissues

• Rapidly hydrolyzed by esterases to active metabolite 21-desdeflazacort
• Hepatic metabolism via CYP3A4

• Elimination half-life: 1.1-1.9 hours (deflazacort); 6-8 hours (active metabolite)
• Primarily excreted in urine (70%) with minor fecal elimination

Contraindications

• Hypersensitivity to deflazacort or any component of the formulation
• Systemic fungal infections
• Concomitant administration of live or live-attenuated vaccines during immunosuppressive therapy

Warnings and Precautions

• Increased susceptibility to infections, including opportunistic infections
• May mask signs and symptoms of infection

• Hyperglycemia, glucose intolerance, and diabetes mellitus
• Adrenal suppression with prolonged therapy
• Cushingoid appearance
• Growth suppression in children

• Hypertension
• Sodium and water retention
• Hypokalemia

• Increased risk of gastrointestinal perforation
• Pancreatitis
• Peptic ulcer disease

• Osteoporosis and vertebral compression fractures
• Aseptic necrosis of femoral and humeral heads
• Myopathy

• Cataracts
• Glaucoma

• Euphoria, insomnia, mood swings, personality changes
• Depression to severe psychiatric symptoms

• Impaired wound healing
• Kaposi's sarcoma

Drug Interactions

• May increase deflazacort exposure
• Consider dose reduction

• May decrease deflazacort exposure
• Consider dose adjustment

• Reduced immune response to vaccines
• Avoid live vaccines during treatment

• May alter response to anticoagulants

• May require adjustment of antidiabetic medications

• Increased risk of GI ulceration

• Enhanced potassium-wasting effects

Adverse Effects

• Cushingoid appearance
• Weight gain
• Increased appetite
• Hirsutism
• Nasopharyngitis

• Hypertension
• Glycosuria
• Psychomotor hyperactivity
• Rash
• Pollakiuria

• Adrenal insufficiency
• Severe infections
• Gastrointestinal perforation
• Ocular effects (cataracts, glaucoma)
• Cardiovascular events
• Osteoporosis and fractures

Monitoring Parameters

• Complete medical history and physical examination
• Height and weight (especially in children)
• Blood pressure
• Ophthalmologic examination
• Bone mineral density assessment (if long-term therapy anticipated)
• Laboratory tests: CBC, electrolytes, glucose, lipid profile

• Blood pressure at each visit
• Height and weight in children (every 3-6 months)
• Blood glucose regularly
• Electrolytes periodically
• Ophthalmologic exams annually
• Bone density monitoring (every 1-2 years for long-term therapy)
• Signs and symptoms of infection
• Assessment for adrenal insufficiency during stress or tapering

Patient Education

• Take with food to improve absorption and reduce GI upset
• Do not stop medication abruptly; follow prescribed tapering schedule
• Report any signs of infection (fever, sore throat) immediately
• Monitor for hyperglycemia symptoms (increased thirst, urination)
• Report vision changes or eye pain
• Inform all healthcare providers of deflazacort use
• Carry medical identification indicating corticosteroid use
• Avoid close contact with people who have contagious illnesses
• Follow recommended vaccination schedules (avoid live vaccines)
• Maintain adequate calcium and vitamin D intake
• Report any mood changes or psychiatric symptoms
• Notify provider if undergoing surgery or dental procedures

References

1. FDA Prescribing Information: Emflaza (deflazacort) tablets and oral suspension. 2017. 2. Griggs RC, et al. Efficacy and safety of deflazacort vs prednisone for Duchenne muscular dystrophy: A systematic review and meta-analysis. Neurology. 2018;90(1):e40-e48. 3. McDonald CM, et al. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: A prospective cohort study. Lancet. 2018;391(10119):451-461. 4. Schijman AG, et al. Comparative efficacy and safety of deflazacort versus prednisone in inflammatory and autoimmune disorders: A systematic review. Eur J Clin Pharmacol. 2020;76(9):1209-1221. 5. Birnkrant DJ, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: Respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. 2018;17(4):347-361. 6. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Deflazacort. Updated 2023. 7. Lexicomp Online [Internet]. Hudson (OH): Wolters Kluwer. Deflazacort. Updated 2023.