What are the uses and dosages of Deflazacort (corticosteroid)?

Deflazacort Uses and Dosages

Primary Indication: Duchenne Muscular Dystrophy (DMD)

Deflazacort is FDA-approved for treating Duchenne muscular dystrophy in patients 5 years and older at a dose of 0.9 mg/kg/day, and represents the only corticosteroid specifically approved for this indication. 1

When to Initiate Treatment

• Start deflazacort when boys with DMD reach a plateau or declining phase of disease, typically around 4-6 years of age when motor function begins to stabilize before decline 2
• Consider deflazacort as first-line over prednisone in patients with pre-existing weight concerns or behavioral issues, as it has a more favorable side effect profile in these domains 2
• The goal is preservation of ambulation and minimization of later respiratory, cardiac, and orthopedic complications 3

Standard Dosing Protocol

• The recommended dose is 0.9 mg/kg/day administered orally once daily 1
• Round up to the nearest possible tablet dose when using tablets (available as 6 mg, 18 mg, 30 mg, and 36 mg) 1
• Can be taken with or without food, but avoid grapefruit juice 1
• Tablets can be administered whole or crushed and mixed with applesauce 1

Evidence for Lower Dosing

A 2022 non-inferiority trial found that 0.45 mg/kg/day did not meet criteria for non-inferiority compared to 0.9 mg/kg/day in the overall population, with a mean difference of 24.8 meters in 6-minute walk distance favoring the higher dose 4. However, in younger boys (≤7 years) with better baseline function (6MWD >350m), the lower dose approached non-inferiority 4. Despite this, the FDA-approved dose of 0.9 mg/kg/day should be used as standard therapy 1.

Expected Benefits in DMD

• Slows decline in muscle strength and function 3, 5
• Prolongs ambulation by approximately 2 years 3, 5
• Reduces risk of scoliosis and need for spinal surgery 3
• Stabilizes pulmonary function 3
• May slow decline in cardiac function 3
• Benefits persist even after loss of ambulation, particularly for respiratory and orthopedic outcomes 3

Secondary Indications

Allergic Bronchopulmonary Aspergillosis/Mycosis (ABPA/ABPM)

• Dose: 0.75 mg/kg/day for 4 weeks 2
• Then decrease by half every 4 weeks for 2 months 2
• Followed by tapering by 6 mg every 2 weeks until discontinuation 2

Autoimmune Hepatitis

• Deflazacort serves as an alternative glucocorticoid in patients intolerant to standard prednisone therapy, with fewer reported steroid-related side effects 2

Nephrotic Syndrome (Pediatric)

• Alternative to prednisolone in pediatric patients with first episode of nephrotic syndrome 2
• Historical data from 1995 showed efficacy comparable to prednisone 6

Inflammatory Bowel Disease

• May be associated with lower risk of osteoporosis compared to other systemic steroids 2

Drug Interactions Requiring Dose Adjustment

CYP3A4 Inhibitors (Moderate or Strong)

• Reduce deflazacort dose to one-third of the recommended dose when co-administered with moderate or strong CYP3A4 inhibitors 1
• Example: 36 mg/day reduced to 12 mg/day 1

CYP3A4 Inducers (Moderate or Strong)

• Avoid concurrent use as they may reduce deflazacort efficacy 1

Discontinuation Protocol

Deflazacort must be tapered gradually when administered for more than a few days to prevent acute adrenal insufficiency, which can be fatal 1. The degree of HPA axis suppression is variable and depends on dose, frequency, and duration of therapy 1.

Mandatory Monitoring Requirements

Before Starting Treatment

• Complete all immunizations according to guidelines, particularly varicella 2, 1
• Administer live-attenuated or live vaccines at least 4-6 weeks prior to starting deflazacort 2, 1
• Provide families with a steroid card listing emergency-care considerations 3

During Treatment

• Annual ophthalmological examination to monitor for cataracts, which may develop more frequently than with prednisone 2
• Annual DEXA scans and vitamin D level monitoring despite potentially lower osteoporosis risk 2
• Height monitoring at least every 6 months in pediatric patients 2
• Monitor for Cushing's syndrome, hyperglycemia, and signs of adrenal insufficiency 1
• Monitor blood pressure, sodium levels, and potassium levels 1

Critical Safety Warnings

Contraindications

• Known hypersensitivity to deflazacort or any inactive ingredients (anaphylaxis has occurred) 1

Major Adverse Effects (≥10% incidence)

• Cushingoid appearance 1
• Weight gain and increased appetite 1
• Upper respiratory tract infections 1
• Hirsutism and central obesity 1
• Pollakiuria (frequent urination) 1

Serious Risks

• Immunosuppression with increased risk of severe or fatal infections (signs may be masked) 1
• Gastrointestinal perforation risk in patients with certain GI disorders (symptoms may be masked) 1
• Behavioral and mood disturbances including severe depression and psychosis 1
• Decreased bone mineral density with chronic use 1
• Serious skin rashes (discontinue at first sign unless clearly not drug-related) 1

Comparative Considerations

While prednisone at 0.75 mg/kg/day remains an effective alternative 3, 5, deflazacort offers a slightly different chronic risk profile with potentially less impact on weight gain in some patients 3. However, practice patterns vary widely internationally, with 29 different corticosteroid regimens documented across DMD treatment centers 7, reflecting ongoing uncertainty about optimal risk-benefit profiles despite clear evidence that corticosteroid therapy is essential for DMD management 3, 5.