Deflazacort is a synthetic glucocorticoid developed to have similar anti-inflammatory effects as prednisone but with fewer side effects. It is well absorbed orally and converted to its active metabolite. While it shares many side effects with prednisone like osteoporosis and growth retardation, studies have shown Deflazacort may cause less bone loss, weight gain, Cushingoid features, and growth suppression in children. It is typically administered at higher doses than prednisone due to lower potency. Dosage should be individualized and gradually reduced when stopping treatment.

1. Deflazacort
Introduction
Glucocorticoids are the most important and frequently
used class of anti-inflammatory drugs, but 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. Deflazacort(DFZ) , an oxazoline
derivative of prednisolone is a step in this direction.

2. Pharmacological Properties
Fig 1. Chemical structure of Deflazacort

3. DFZ, a D-ring substituted synthetic steroid ,was
introduced in 1969 . Its anti-inflammatory and
immunosuppressive effects have been used in
treating various diseases and are comparable to
other steroids. Clinical studies have indicated that
the average potency ratio of deflazacort to
prednisolone is 0.69-0.89 and 6 mg of deflazacort is
equivalent to 5 mg of prednisolone. However, the
therapeutic dosage ratio has been reported to
range from 1:1.2 to 1:1.5 across individual disease
conditions.

4. Pharmacokinetics
Orally administered deflazacort is well absorbed and is
immediately converted by plasma esterases to the
pharmacologically active metabolite deflazacort-21-hydroxide (D
21-OH), which achieves peak plasma concentrations in 1.5 to 2
h. It is 40% protein bound and has no affinity for corticosteroid
binding globulin (transcortin) and binds to plasma protein and
blood cells instead, crossing the blood-brain barrier in very low
concentrations. These pharmacokinetic and biochemical
properties of deflazacort may prevent it from reaching the
hypothalamic or pituitary circulation during the first years;
however, after a long-term treatment, deflazacort levels could
increase in the central nervous system and finally produce
effects similar to other glucocorticoids. Its plasma elimination
half-life is 1.1 to 1.9 h. Elimination takes place primarily through
the kidneys; 70% of the administered dose is excreted in the
urine, and the remaining 30% is eliminated through the feces.

5. Preclinical safety data
Safety studies have been carried out in the rat, dog,
mouse and monkey. Teratogenic effects
demonstrated in rodents and rabbits are
typical of those caused by other glucocorticoids.
Deflazacort was not found to be carcinogenic in the
mouse, but studies in the rat produced
carcinogenic findings consistent with the findings
obtained using other glucocorticoids.

6. Therapeutic Use
• Duchenne dystrophy
• Nephrotic syndrome
• Juvenile idiopathic arthritis
• Asthma
• Renal transplant
• Idiopathic thrombocytopenic purpura
• Drug-resistant epilepsy of childhood
• Other disorders :
Published data in children, evaluating deflazacort in other common
disorders such as systemic lupus erythematosus (SLE), dermatomyositis,
rheumatic carditis, various dermatological conditions, acute lymphoblastic
leukaemia, and lymphoma continues to be sparse. Deflazacort was
generally as effective as the comparative drug, and more effective than
placebo, in controlled trials.

7. Side Effect Profile
Deflazacort shares all side-effect profiles of
prednisolone such as candidiasis, cataract,
dyspepsia, peptic ulcer, drug psychosis, impaired
glucose tolerance, growth retardation, hirsutism,
hypertension, hypokalaemia, muscle weakness,
osteoporosis, pathological fracture, steroid facies,
and delayed wound healing. Of the limited
studies in children, adverse effects commonly
reported include cushingoid features,
osteoporosis, weight gain, glucose intolerance
and growth retardation. Children are more
vulnerable to their side-effects, particularly to
effects on growth and adrenal suppression

8. Osteoporosis:
Deflazacort proved to be less harmful to the cancellous bone
than
prednisolone in the only prospective, comparative, long-term
histomorphometric study available to date. Research reveals
that OPG
(Osteoprotegerin) and RANKL (receptor activator of NF-KB
ligand) are
osteoblast-derived proteins, responsible for inhibition and
stimulation of
bone resorption respectively. Studies in adults have
demonstrated a
favorable ratio of serum RANKL: OPG, implying a potentially
lesser
bone loss with deflazacort.

9. The available but limited clinical trials in children
suggest that deflazacort has some bone-sparing
action as compared to prednisolone (when
measured in terms of a lesser decline in the whole
body mineral density). In general deflazacort
appears to have less effect than prednisone on
urinary calcium excretion, serum osteocalcin levels
and serum parathyroid hormone levels, parameters
implicated in the pathogenesis of corticosteroid-
induced osteoporosis. In 3 studies conducted to
evaluate its effects on bone mass/density
deflazacort therapy was associated with a smaller
loss of bone mass/density than prednisone.

10. Weight gain/obesity
Trials comparing deflazacort and prednisolone
have suggested a lesser increase in weight not
only in patients of Duchenne's muscular dystrophy
but also in those with nephrotic syndrome and
Juvenile Rheumatoid Arthritis and also in patients
of the post-renal transplant state.
Growth retardation: Deflazacort therapy has been
associated with a lesser decline in the growth
velocity and an stature improved after one to two
years.

11. Cushingoid symptoms
Broyer et al. and Ferraris et al., have
documented that the Cushingoid features
were less with deflazacort as compared to
prednisolone.

12. Glucose intolerance
Even presence of the pursuing trials, the metabolic effects of
deflazacort as compared to prednisolone in children are
scanty, it appears to favour deflazacort by reporting favorable
Insulin:Glucose ratio. Deflazacort 36mg administered 12 and 2
hours before oral glucose tolerance testing in volunteers with
familial history of non insulin-dependent diabetes mellitus
had less impact on glucose metabolism than prednisone
30mg.
Adrenal suppression: Wajchenberg et al suggested that
deflazacort‘s action in suppressing cortisol was confined to
the pituitary only while prednisolone was active on
both, pituitary and adrenals. Published clinical trials in
children comparing effect on the two glands are still awaited.

13. Pregnancy and Lactation
The ability of corticosteroids to cross the placenta varies with
individual drugs; however, deflazacort does cross the
placenta. As with all drugs, corticosteroids should only be
prescribed when the benefits to the mother and child
outweigh the risks. When corticosteroids are essential,
however, patients with normal pregnancies may be treated as
if they were in the non gravid state. No data are available for
deflazacort as regards excretion in breast milk. Doses of up to
50 mg daily of deflazacort are unlikely to cause systemic
effects in the infant. Infants of mothers taking higher doses
of this drug may have adrenal suppression, but the benefits
of breastfeeding are likely to outweigh any theoretical risk.

14. Dosage and Administration
Deflazacort is less potent than prednisone and is usually
administered in proportionally higher dosages on the basis
of body weight. In general, studies designed to determine
the dosage equivalence of deflazacort and prednisone
found deflazacort to be 25% less potent than prednisone,
a dosage ratio of 1:1.3.Six mg of deflazacort has
approximately the same anti-inflammatory potency as 5
mg prednisolone or prednisone.
Dosage should be individually titrated according to diagnosis,
severity of disease and patient response and tolerance.
The lowest dose that will produce an acceptable response
should be used .In more serious and life-threatening
conditions, high doses of deflazacort may be needed.

15. When deflazacort is used for long term in
relatively benign chronic diseases, the
maintenance dose should be kept as low as
possible. Dosage may be needed to increase
during periods of stress or during
exacerbation of illness. In patients with
hepatic impairment; blood levels of
deflazacort may be increased. In renal
impairment, no special precautions are
necessary other than those usually adopted
in patients receiving glucocorticoid therapy.

16. Deflazacort withdrawal
In patients who received higher physiological doses of
systemic corticosteroids (approximately 9 mg per day or
equivalent) for more than 3 weeks, withdrawal should not
be abrupt.
Dose reduction should be carried out largely based on
possibility of relapse of the disease due to reduction of
dose of corticosteroids. Clinical assessment of disease
process might be needed during withdrawal. If the disease
is unlikely to relapse on withdrawal of systemic
corticosteroids, but there is uncertainty regarding HPA
suppression, the dose of systemic corticosteroids can be
reduced rapidly to physiological doses. Once a daily dose
equivalent to 9 mg deflazacort is reached, dose reduction
should be slower to allow the HPA-axis to recover.

17. Over dosage :
Treatment is needed in cases of acute over
dosage is unlikely. The LD50 for the oral dose
is greater than 4000 mg/kg in laboratory
animals.