This document discusses deflazacort, a dissociated glucocorticoid that is similar in efficacy to conventional glucocorticoids like prednisone but with reduced side effects. It summarizes several studies comparing deflazacort to prednisone/prednisolone and methylprednisolone in treating conditions like asthma, rheumatoid arthritis, and nephrotic syndrome. The studies found that deflazacort was as effective as the other steroids in improving symptoms but had fewer adverse effects on bone density, blood glucose control, growth, and body composition. Deflazacort has a similar safety profile to prednisolone but may be better tolerated for long-term use

1. “DEFLAZACORT”
Search Of A Safe & Effective
Dissociated Glucocorticoid
Prof.(Dr.) Annasaheb. J. Dhumale.
HeadofDepartmentofMedicine,
ChiefMedicalOncologist&Haematologist,
ShriShankaracharyaInstituteofMedicalSciences(SSIMS)
Bhilai(C.G).INDIA.PIN-490020
drajdhumale@gmail.com

2. CORTICOSTEROID
• Glucocorticoids are the most important and
frequently used class of anti-inflammatory &
immunosuppressive drugs.
• It is used to treat a number of conditions like:
Asthma, Rheumatoid arthritis, Severe allergies…
• It was first used in clinical practice in 1949 for
the treatment of Rheumatoid arthritis.

3. CORTICOSTEROID
• The currently available ones impair many healthy
anabolic processes warranting caution during both
short-term and long-term use.
• Research has been focused on elaboration of
selectively acting novel oral steroid that possess the
same efficacy in conditions for which they are used
today but with reduction in one or more of the dose-
limiting side effects.

4. A DISSOCIATED GLUCOCORTICOID
Dissociated Therapeutic Effects from Side Effects
Drugs that preferentially induce
“Transrepression” &
not “Transactivation”
should be as effective as standard
GCs with fewer side effects
“DEFLAZACORT”
Such A Dissociated Glucocorticoid

5. Deflazacort -Side Effect Profile
Deflazacort shares all side-effect profiles of prednisolone such as:
• candidiasis,
• cataract,
• dyspepsia, peptic ulcer,
• drug psychosis,
• growth retardation,
• hirsutism,
• impaired glucose
tolerance,
• hypertension,
• hypokalaemia,
• muscle weakness,
• osteoporosis,
• pathological fracture,
• steroid facies, and
• delayed wound healing.

6. DEFLAZACORT
A Dissociated Glucocorticoid
Similar in efficacy as conventional GCs
• Anti-inflammatory
• Immunosuppressive
With less metabolic side effects
• Osteoporosis
• Diabetes/ Impaired GTT
• Cushing’s Syndrome
• Growth Retardation
• Skin atrophy
• Hypertension

7. DEFLAZACORT
Clinical Pharmacology
• Deflazacort is a prodrug, which is converted rapidly to
the active metabolite.
• Deflazacort is a synthetic derivative of prednisolone
• Cmax (of 21-desacetyldeflazacort) = 116 ng/ml
• Tmax = 1.3 h : AUC = 280 ng/ml.h
• Terminal half-life = 1.3 h
• Elimination : 70% renal + 30% hepatic

8. DEFLAZACORT
Deflazacort 6 mg is equivalent to:
Prednisolone………………..5 mg
Methylprednisolone………...4 mg
Betamethasone……………..750 mcg
Dexamethasone………….....750 mcg
Hydrocortisone………………20 mg
Cortisone acetate……………25 mg
Triamcinolone………………..4 mg

9. • Prednisolone : deflazacort is 1:1.2
• Methylprednisone : deflazacort is 1:1.5
DEFLAZACORT
Equipotency of dose

10. DEFLAZACORT
A Faster Corticosteroid
Onset time and onset of action are dependent upon tmax.
Pharm Res. 1995 Jul;12(7):1096-100.

11. DEFLAZACORT
A Potent Corticosteroid

12. DEFLAZACORT
A Safer Corticosteroid
Drugs. 1995 Aug;50(2):317-33

13. DEFLAZACORT
Safety

14. DEFLAZACORT
Bone Sparing Action
• Compared with prednisone or betamethasone,
Deflazacort causes-
– a smaller decrease in intestinal calcium absorption
– less renal calcium excretion
• Studies on bone mineral density also support the
benefit of Deflazacort compared with prednisone

15. DEFLAZACORT vs PREDNISONE
On BMD
0.8
0.84
0.82
0.75
0.5
0.55
0.6
0.65
0.7
0.75
0.8
0.85
Deflazacort Prednisolone
BMD(g/cm2) Base line
12 months
Outcome
At 1 year, patients taking Deflazacort showed increase in BMD while
those taking prednisolone showed marked drop in BMD
Messina OD et al. J Rheumatol 1992; 19: 1520-6

16. DEFLAZACORT vs PREDNISONE
Blood Glucose Control
Parameters at 4 week Deflazacort Prednisone
Plasma Glucose (mg%) 139 169
Insulin Requirement (U/d) 29 47
Patients 10 insulin treated diabetics requiring steroid
treatment
Treatment Deflazacort : 30 mg/day
Prednisone : 25 mg/day
Duration 4 weeks
Bruno A et al. Arch Intern Med. 1987 Apr;147(4):679-80.

17. DEFLAZACORT vs PREDNISONE
Blood Glucose Control
8.5
8.81
10.71
7
7.5
8
8.5
9
9.5
10
10.5
11
Average Pretreatment
for DFZ & PDN
Deflazacort Prednisone
HbA1C(%oftoalHb)
Bruno A et al. Arch Intern Med. 1987 Apr;147(4):679-80
Conclusion : Deflazacort, should prove advantageous in insulin-
treated diabetics who require steroid treatment

18. DEFLAZACORT vs METHYLPREDNISONE
Effect on Growth
Conclusion: Deflazacort therapy might improve linear growth and lean body mass
and prevent excessive bone loss and fat accumulation. It also leads to an improvement
in lipoprotein profile without reduction in insulin sensitivity
Design Prospective, open, randomized, parallel group
study on 31 prepubertal renal transplant patients
Treatment Deflazacort : 0.30 mg/kg/day, 15 patients
methylprednisone : 0.20 mg/day, 16 patients
Duration 36 months
Ferraris et al. pediatr nephrol (2007) 22: 734-741

19. DEFLAZACORT vs METHYLPREDNISONE
Effect on Growth
Ferraris et al. pediatr nephrol (2007) 22: 734-741

20. DEFLAZACORT
Sparing Effect on Growth & Skeletal Maturation
In spite of large intra-individual and inter-individual
variability, Deflazacort has a lower negative impact on
indicators of growth* than prednisolone
* e.g., height, statural age, skeletal age and body weight velocities
(i.e. the increase/year)
Aicardi G et al. Br J Rheumatol. 1993 May;32 Suppl 2:39-43

21. DEFLAZACORT
Dosage
• Doses of Deflazacort usually lie in the range
0.25-1.5 mg/kg once daily or in divided doses
– Juvenile chronic arthritis: The usual maintenance
dose is between 0.25-1.0 mg/kg/day
– Nephrotic syndrome: Initial dose of usually 1.5
mg/kg/day followed by down titration according to
clinical need
– Bronchial asthma: The initial dose should be
between 0.25 - 1.0 mg/kg Deflazacort on alternate
days.

22. DEFLAZACORT
Withdrawal
• In patients who have reached approximately 9 mg per
day dose of deflazacort for greater than 3 weeks,
withdrawal should not be abrupt
• Withdrawal should be slow in patients receiving doses
greater than 48 mg daily of deflazacort

23. DEFLAZACORT
Safety
• Well tolerated in long term studies up to 4-5 years

24. DEFLAZACORT
Usage (Indications)
• Asthma/ COPD
• Sarcoidosis/ ILD
• Nephrotic syndrome
• Renal transplantation
• RA & Juvenile Chronic Arthritis
• Allergies
• SLE
• Pemphigus, Lichen Planus

25. DEFLAZACORT
Clinical Trials
Chest Medicine & Allergy

26. DEFLAZACORT
Acute Exacerbation of Chronic Asthma
Patients 29, with >=40% reduction in FEV1
Steroid
Treatment
Deflazacort : 1.5 mg/kg/d
Prednisone : 1 mg/kg/d
Duration 12 weeks
Markham A et al.Drugs 50(2); 1995: 317-33

27. DEFLAZACORT
Acute Exacerbation of Chronic Asthma
Forced Vital Capacity
71.5
76.1
8181.4
66
68
70
72
74
76
78
80
82
84
Deflazacort Prednisone
(%)
Base End Point
The forced vital capacity increased significantly from 76.1 to 81.4%
Markham A et al.Drugs 50(2); 1995: 317-33

28. DEFLAZACORT
Clinical Trials
ENT

29. DEFLAZACORT
Allergic Rhinitis
ARIA pocket guidelines
Steroid Type of steroid Action Side effects Comments

30. DEFLAZACORT
Allergy
• Deflazacort & its active metabolite 21-desacetyl-
deflazacort have stronger anti-allergic effects
than prednisolone as evidenced by inhibition of
– passive cutaneous anaphylaxis
– arthus reaction
– delayed type of hypersensitivity
Omote M et al. Arzneim-Forsch/Drug Res 1994; 44(1): 149-153

31. DEFLAZACORT
Allergic & Non-allergic Chronic Rhinosinusitis
Background : Predominant Th2 pattern (characterized by
antibody production) reported in allergic and nonallergic
chronic rhinosinusitis in asthmatic children
Patients 30 (16 allergic/14 non-allergic) asthmatic children (9 yrs)
Steroid
Treatment
Deflazacort 1 mg/kg x 2D; 0.5 mg/kg x 4D; 0.25 mg/kg x 4D
Duration 10 days
Tosca MA et al. Pediatr Allergy Immunol. 2003 Jun;14(3):238-41.

32. DEFLAZACORT
Nasal Polyps
Cassano P et al Acta Otorhinolaryngol Ital. 1996 Aug; 16(4): 334-8
Patients 30
Steroid
Treatment
Deflazacort + Fluticasone propionate topical
Duration 24 months
Conclusion: High tolerability in all patients and to the high
percentage of good and very good short and medium term results were
obtained

33. DEFLAZACORT
Clinical Trials
Rheumatology & Orthopedics

34. DEFLAZACORT vs METHYL PREDNISOLONE
Rheumatoid Arthritis
Patients 20 of RA (10 in each group)
Treatment Deflazacort : 30 mg/day
Methylprednisolone : 16 mg/day
Paracetamol as needed (No DMARDs/ NSAIDs)
Duration 6 months
Outcome :
Deflazacort & Methylprednisolone significantly reduced simple
joint count, pain & morning stiffness while improved grip strength
Auteri A et al. Int J Immunother 1994; X(2): 67-75

35. DEFLAZACORT vs METHYL PREDNISOLONE
Rheumatoid Arthritis
17.2 17.6
7.9
9.4
0
5
10
15
20
Deflazacort Methyl Prednisolone
Richieindex
Baseline
Endpoint
Reduction in Simple Joint Count
2.3 2.25
1.1 1.1
0
0.5
1
1.5
2
2.5
Deflazacort Methylprednisolonehours
Baseline
Endpoint
Reduction in Pain
Auteri A et al. Int J Immunother 1994; X(2): 67-75

36. DEFLAZACORT vs METHYL PREDNISOLONE
Rheumatoid Arthritis
Reduction in Morning Stiffness Improvement in Grip Strength
65
73.5
29.5
38
0
10
20
30
40
50
60
70
80
Deflazacort Methylprednisolone
hours
Baseline
Endpoint
64.5
70.5
105.5
99
0
20
40
60
80
100
120
Deflazacort Methylprednisolone
mmHg
Baseline
Endpoint
Auteri A et al. Int J Immunother 1994; X(2): 67-75

37. DEFLAZACORT vs PREDNISOLONE
In Patients With Chronic Inflammatory Disorders
Patients 26 (17 RA + 4 Polymyalgia Rheumatica + 2 Eczema +
3 Mixed connective tissue disease)
Treatment Deflazacort : 24 mg/day
Prednisone : 20 mg/day
Duration 15 days & then titrated till 90 days
Gray RES et al. Arthritis & Rheumatism 1991; 34(3): 287-295

38. DEFLAZACORT vs PREDNISOLONE
In Patients With Chronic Inflammatory Disorders
Conclusion :
• Deflazacort is an effective anti-inflammatory corticosteroid
with lesser side effects than prednisone in stimulating daily
calcium loss & in inhibiting endogenous cortisol secretion
• Thus Deflazacort may be better tolerated for longer
periods of time in patients with chronic inflammatory
conditions requiring glucocorticoid treatment
Gray RES et al. Arthritis & Rheumatism 1991; 34(3): 287-295

39. DEFLAZACORT
Clinical Trials
Nephrology

40. DEFLAZACORT vs PREDNISOLONE
In Patients With Nephrotic Syndrome
Patients 40 children (20 in each group) of steroid dependent
idiopathic nephrotic syndrome
Steroid Treatment Deflazacort / Prednisone dosage as calculated by
equipotency ratio = 0.8
Duration 1 year
Follow-up 5.5 yrs
Broyer M et al. Pediatric Nephrol 1997; 11: 418-422

41. DEFLAZACORT vs PREDNISOLONE
In Patients With Nephrotic Syndrome
Broyer M et al. Pediatric Nephrol 1997; 11: 418-422
Outcomes:
Prednisolone Deflazacort
Increase In body wt 3.9 kg 1.7kg
Cushing’symptoms More Less
Conclusion : Deflazacort was more effective than prednisolone in
limiting relapses & with less side effects

42. DEFLAZACORT vs PREDNISOLONE
In Patients With Nephrotic Syndrome
Patients 29 with proteinuria > 3 g/24 hrs
Steroid
Treatment
Prednisone 80 mg/day & then tapered
Deflazacort 96 mg/day & then tapered
Duration 1 year
Olgaard K et al. Calcif Tissue Int 1992; 50: 490-497

43. DEFLAZACORT vs PREDNISOLONE
In Patients With Nephrotic Syndrome
Olgaard K et al. Calcif Tissue Int 1992; 50: 490-497
9.9
8
1.1 1.4
0
2
4
6
8
10
12
Deflazacort Prednisone
Grams
Baseline
Endpoint
Urinary Protein
5.3
2
0
1
2
3
4
5
6
Prednisone Deflazacort
%
Prednisone
Deflazacort
Bone Loss Per Year

44. Cochrane Review
DEFLAZACORT vs PREDNISOLONE
In Patients With Nephrotic Syndrome
Patients Pediatric Patients from 19 trials
Steroid
Treatment
Prednisone (1 mg/kg/d)
Deflazacort (1.2 mg/kg/d)
Duration 1-2 years
Outcomes:
• Deflazacort was significantly more effective in maintaining
remission than prednisone in children who frequently relapsed
• There was no increase in adverse events
Hodson M et al. The Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD001533

45. DEFLAZACORT
Clinical Trials
Urology

46. DEFLAZACORT + TAMSULOSIN
For Ureteric Stone Expulsion After ESWL
Patients 98 (lower ureteric stones of > 5mm)
Treatment 4 groups
1= Control; 2= DFZ; 3 = TAM; 4 = DFZ + TAM
Deflazacort : 6 mg/day
Tamsulosin : 0.4 mg/day
Duration 5-7 days
Conclusion : When ESWL is associated with adjuvant therapy acting upon
the intramural ureteral tract, expulsion time is significantly shortened,
especially with Deflazacort + tamsulosin
Alfa-1 adrenergic receptors blockade by tamsulosin causes smooth muscle cell
relaxation of ureter & Deflazacort reduces edema

47. DEFLAZACORT
Clinical Trials
Pediatrics

48. DEFLAZACORT
Moderate Acute Asthma in Children
Gartner S et al. An Pediatr (Barc) 2004; 61(3): 207-12
Conclusion :
Deflazacort & Prednisolone show similar efficacy in improving pulmonary
function & in producing clinical improvement

49. DEFLAZACORT vs PREDNISOLONE
In Patients With Nephrotic Syndrome
Olgaard K et al. Calcif Tissue Int 1992; 50: 490-497
9.9
8
1.1 1.4
0
2
4
6
8
10
12
Deflazacort Prednisone
Grams
Baseline
Endpoint
Urinary Protein
5.3
2
0
1
2
3
4
5
6
Prednisone Deflazacort
%
Prednisone
Deflazacort
Bone Loss Per Year

50. DEFLAZACORT
Clinical Trials
Renal Transplant

51. DEFLAZACORT vs METHYLPREDNISONE
Renal Transplant
Design Prospective, open, randomized, parallel group
study on 31 prepubertal renal transplant patients
Treatment Deflazacort : 0.30 mg/kg/day, 15 patients
methylprednisone : 0.20 mg/day, 16 patients
Duration 36 months
Ferraris et al. pediatr nephrol (2007) 22: 734-741
Conclusion: Deflazacort therapy might improve linear growth and lean body mass
and prevent excessive bone loss and fat accumulation. It also leads to an improvement
in lipoprotein profile without reduction in insulin sensitivity

52. Ferraris et al. pediatr nephrol (2007) 22: 734-741
DEFLAZACORT vs METHYLPREDNISONE
Renal Transplant

53. DEFLAZACORT
Clinical Trials
Dermatology

54. DEFLAZACORT
In Pemphigus Vulgaris
• Deflazacort + azathioprine reported to be a preferred
therapy for pemphigus vulgaris
• Esophageal involvement in 67.8% pts. which normalized
with deflazacort therapy
Galloro G et al. Digest Liver Dis 2005; 37(3): 195-199
Mignogna MD et al. J Oral Pathol Med. 2000 Apr;29(4):145-52.

55. DEFLAZACORT
Clinical Trials
Neurology

56. Outcome
• Improvement observed in <5 months
• Complete cure (full recovery of facial motor function) in 95.6%
Conclusion : This study supports early steroid treatment in Bell’s
Palsy
One yearDuration
Inj. Prednisolone 60 mg IM followed by equipotent
dose deflazacort (72 mg) which was tapered off
Treatment
47 with Idiopathic Facial (Bell’s) PalsyPatients
Hurtado Garcia JF et al. Acta Otorrinolaringol Esp. 1997 Apr;48(3):177-81
DEFLAZACORT
Bell’s palsy

57. DEFLAZACORT
In DMD-An Update
• Deflazacort attenuates loss of dystrophic myofiber integrity
by up-regulating the activity of the calcineurin phosphatase
in calcineurin/NF-AT pathway & has prophylactic effect
• Deflazacort treatment can attenuate DMD progression,
extend ambulation, and maintain muscle strength
• Patients who had been receiving deflazacort for > 3 years
were more likely to have preserved cardiac function
St-Pierre SJ et al FASEB J. 2004 Dec;18(15):1937-9

58. DEFLAZACORT
In DMD-An 8 years follow up
Patients 79 patients of DMD
Treatment Deflazacort : 0.9 mg/kg at beginning, mean dose:
0.69 ± 0.2 mg/kg, 37 patients
Untreated group: 42 patients
Duration 8 years
Conclusion : The overall Impact on quality of life appears positive
Sylvie Houde et al, Pediatric Neurology 2008, 38, 200-204

59. DEFLAZACORT
In DMD

60. DEFLAZACORT
In Drug Resistant Epilepsy
Design Open, non blinded, randomized study on 35 children with
drug resistant epilepsy
Treatment Deflazacort : 0.75 mg/kg, 19 patients
Hydrocortisone: 10 mg/kg for 1 month, 5 mg/kg for 1 month,
2.5 mg/kg for 1 month, 1 mg/kg for 1 month, 1 mg/kg
alternate days for 1 month, 16 patients
Duration 12 months

61. DEFLAZACORT
In Drug Resistant Epilepsy

62. SUMMARY

63. DEFLAZACORT
Summary
• The options today to reduce side effects with GCs now
includes Deflazacort
• Deflazacort, a “dissociated” glucocorticoid, has desired
anti-inflammatory & immunomodulatory actions but with
negligible metabolic side effects on
– Bone - Glucose
– Fat - Suppression of HPA
– Mineralocorticoid activity - Affect on skeletal growth

64. DEFLAZACORT vs COVENTIONAL GCs
Clinical Benefits of The Second Generation GCs
• Equal efficacy with less side effects
• Bone sparing effect/ less osteoporosis
• Safe in children (does not affect growth velocity)
• Non-diabetogenic, so safe in diabetics
• Less cushingoid features, better compliance
• Patients may cope better to anesthetic/ surgical stress
(less HPA axis suppression)
• Safety in cardiovascular pts. (less sodium & water
retention)

65. DEFLAZACORT
At the end
• Deflazacort has definite advantage in diabetics,
osteoporosis patients and in children ( nephrotics) likely
to require its long term use.
• Treatment with deflazacort may cause less serious
metabolic sequalae than treatment with prednisolone,
• Deflazacort should be generally reserved for the treatment
of patients predisposed to, or who develop intolerable
metabolic disease effects while on steroids.

66. DEFLAZACORT
To Conclude
Hence,Deflazacort, a second generation
glucocorticoid, may
represent an important step towards
“Search for a Effective & Safe
Glucocorticoid”

67. Thank You