For the use of a Registered Medical Practitioner, Hospital or Laboratory only.
1. Description
Defstead is Deflazacort, a glucocorticoid and an oxazoline derivative of prednisolone with anti-inflammatory and immunosuppressive activity.
2. Composition
Each Tablet of Defstead-6 contains Deflazacort 6 mg and each tablet of Defstead-30 contains Deflazacort 30 mg.
3. Dosage Form
Tablet
4. Pharmacology
Pharmacodynamics
Deflazacort is a synthetic glucocorticoid that is rapidly converted to its active metabolite, 21-desacetyldeflazacort, after oral administration.
The active metabolite binds to intracellular glucocorticoid receptors (GRs) in target cells. The drug–receptor complex translocates to the nucleus where it regulates the transcription of glucocorticoid-responsive genes, resulting in anti-inflammatory and immunosuppressive effects.
Pharmacokinetics
Absorption
Deflazacort is well absorbed after oral administration.
It is rapidly deacetylated in plasma to the active metabolite 21-desacetyldeflazacort.
Time to peak plasma concentration (Tmax): Approximately 1.5–2 hours for the active metabolite.
Food may delay the rate of absorption but does not significantly affect the extent of absorption.
Distribution
The active metabolite is approximately 40% protein bound, primarily to plasma proteins other than corticosteroid-binding globulin.
It is widely distributed throughout body tissues and crosses the placenta.
Small amounts are excreted into breast milk.
Metabolism
Deflazacort is a prodrug that undergoes rapid hydrolysis to 21-desacetyldeflazacort, the pharmacologically active metabolite.
The active metabolite is further metabolised in the liver to inactive metabolites.
Elimination
Elimination half-life (active metabolite): Approximately 1.1–1.9 hours.
Pharmacodynamic effects persist longer than the plasma half-life because of glucocorticoid receptor-mediated gene regulation.
Metabolites are eliminated primarily in the urine, with a smaller proportion excreted in the faeces.
5. Indications
This medication is a glucocorticoid, prescribed for anti-inflammatory conditions and used as an immunosuppressant. It is a prodrug. Deflazacort is indicated in a wide variety of conditions viz. Nephrotic Syndrome, Transplantation, Systemic Lupus Erythematosus, Uveitis, Duchenne Muscular Dystrophy.
6. Contraindications
The medicine is contraindicated in patients who are receiving immunosuppressive vaccines, who have infections and hypersensitivity.
7. Precautions
Caution should be exercised in patients with history of adrenal suppression, infections (ex-chickenpox, shingles, measles) children, elderly, tuberculosis, muscle pain, recent heart attack, high blood pressure, heart failure, liver failure, kidney impairment, sugar, increased eye pressure, osteoporosis, corneal damage, epilepsy, peptic ulcer, under active thyroid, during pregnancy and breastfeeding.
8. Drug Interactions
- Deflazacort’s active metabolite is metabolised by CYP3A4. Moderate or strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin, phenobarbital) reduce exposure and should be avoided; strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) increase exposure — consider dose reduction.
- NSAIDs: increased risk of gastrointestinal ulceration and bleeding.
- Diuretics, amphotericin B and β2-agonists: increased risk of hypokalaemia.
- Antidiabetic agents: corticosteroids raise blood glucose; dose adjustment may be needed.
- Oral anticoagulants: response may be altered; monitor INR.
- Live vaccines should be avoided during immunosuppressive therapy.
9. Adverse Effects
Long-term use of high doses of Deflazacort may cause ‘Cushing’s syndrome’. These side-effects usually return to normal once the treatment has been stopped.
10. Dosage & Administration
Defstead tablets should be taken with food.
- Adult: Initially, up to 120 mg daily
- Maintenance: 3-18 mg/day
- Child: 0.25-1.5 mg/kg/day on alternate days
In cases of hepatic impairment, dose reductions may be needed.
Conversion of dose from Prednisolone to Deflazacort: 6 mg of Deflazacort has approximately the same anti-inflammatory potency as 5 mg Prednisolone.
11. Overdosage
No data available.
12. Storage
Store in a dry place at a temperature not exceeding 30°C. Protect from light. Keep the medicine out of reach of children.
Additional Information
Additional pharmacology information
Deflazacort is an inactive prodrug, which is converted rapidly to the active metabolite 21-desacetyldeflazacort. Maximum concentrations of 21-desacetyldeflazacort averaged 116 ng/mL and were observed after 1.3 hours. The terminal half-life was 1.3 hours. 21-Desacetyldeflazacort was cleared significantly faster than both Methylprednisolone and Prednisolone.
Pharmacokinetics of deflazacort in renal transplanted and haemodialysed children: Deflazacort (DFZ) pharmacokinetics was evaluated in fifteen paediatric patients on chronic haemodialysis or after renal transplantation and in three normal children. After overnight fasting, oral DFZ 0.26+/-0.01 mg/kg (mean +/- SEM) was given. Serial blood samples were collected for 360 min and analyzed by HPLC for 21-hydroxy-DFZ (21-HO-DFZ). Serum concentration profiles and pharmacokinetic parameters were similar in patients on haemodialysis, renal transplant recipients and normal children. Elimination of half-life was longer in the 9 ciclosporin-treated subjects (108.0+/-13.6 min) than in the other nine (71.2+/-8.3 min; p <0.02). The finding suggests that from a pharmacokinetic point of view, DFZ dose adjustment for renal function is not necessary in children with chronic renal failure or after renal transplantation.
13. Presentation
10 tablets in a strip, 10 strips in a Box.