1. Clinical Overview
Deflazacort is a synthetic, oxazoline derivative glucocorticoid with potent anti-inflammatory and immunosuppressive properties. It is a prodrug that is rapidly hydrolyzed to its active metabolite, 21-desacetyl deflazacort, which binds to the glucocorticoid receptor. It is considered to have a potentially more favorable side effect profile compared to other corticosteroids like prednisolone, particularly with respect to weight gain, glucose metabolism, and bone mineral density, though it is not devoid of typical steroid side effects. It is widely used in India for various inflammatory and autoimmune conditions.
| Onset | Duration | Bioavailability |
|---|---|---|
| Clinical effects are typically observed within 1-2 hours of oral administration. | Approximately 24-36 hours, allowing for once-daily dosing. | Approximately 70-80% of an oral dose is systemically available. |
2. Mechanism of Action
Deflazacort is a prodrug converted to its active metabolite, 21-desacetyl deflazacort. This metabolite binds to cytoplasmic glucocorticoid receptors, forming a complex that translocates to the nucleus. It modulates gene transcription by binding to glucocorticoid response elements (GREs), leading to increased synthesis of anti-inflammatory proteins (transactivation) and repression of genes encoding for pro-inflammatory cytokines like IL-1, IL-2, IL-6, TNF-α, and prostaglandins (transrepression).
3. Indications & Uses
- Rheumatoid Arthritis
- Systemic Lupus Erythematosus (SLE)
- Polymyositis and Dermatomyositis
- Severe Asthma
- Allergic Conditions (severe, refractory)
- Nephrotic Syndrome
- Duchenne Muscular Dystrophy (to slow disease progression)
4. Dosage & Administration
Adult Dosage: Initial dose varies widely by condition: Typically 0.25 to 1.5 mg/kg/day (approx 18mg to 108mg for 72kg adult). For anti-inflammatory/immunosuppressive therapy, starting dose is often 30-90 mg/day in single or divided doses, tapered to the lowest effective maintenance dose (e.g., 6-18 mg/day).
Administration: Administer orally, preferably in the morning with or immediately after food to reduce GI irritation. The tablet should be swallowed whole with a glass of water. Do not crush or chew. For once-daily dosing, take in the morning to mimic the body's natural cortisol rhythm and reduce insomnia.
5. Side Effects
Common side effects may include:
- Increased appetite
- Weight gain (less than prednisolone)
- Insomnia
- Mood changes (euphoria, irritability)
- Dyspepsia, heartburn
- Fluid retention, edema
- Cushingoid appearance (moon face, buffalo hump) with long-term use
- Skin thinning, easy bruising
- Hirsutism
- Menstrual irregularities
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Ketoconazole, Itraconazole | Inhibits CYP3A4, increasing deflazacort levels and toxicity | Major |
| Rifampicin, Phenytoin, Carbamazepine | Induces CYP3A4, decreasing deflazacort efficacy | Major |
| NSAIDs (e.g., Ibuprofen, Diclofenac) | Increased risk of gastrointestinal ulceration and bleeding | Major |
| Warfarin | Altered anticoagulant effect (may increase or decrease INR) | Moderate |
| Diuretics (e.g., Furosemide, Hydrochlorothiazide) | Enhanced potassium loss, leading to severe hypokalemia | Major |
| Antidiabetic drugs (Insulin, Metformin) | Corticosteroids antagonize hypoglycemic effect, requiring dose adjustment | Major |
| Live Vaccines (MMR, Varicella, OPV) | Risk of disseminated vaccine-induced infection | Contraindicated |
| Digoxin | Risk of digitalis toxicity due to hypokalemia | Moderate |
7. Patient Counselling
- DO take the medicine exactly as prescribed by your doctor. Do not stop suddenly.
- DO take it with food or milk to avoid stomach upset.
- DO inform all your doctors and dentists that you are taking this medicine.
- DO carry a steroid alert card.
- DONT take any live vaccines (like MMR, chickenpox) without consulting your doctor.
- DONT take over-the-counter NSAIDs (like ibuprofen) without asking your doctor.
- DONT change the dose or schedule on your own.
8. Toxicology & Storage
Overdose: Acute overdose is unlikely to cause acute life-threatening toxicity but would be expected to exaggerate its pharmacological effects: severe Cushingoid symptoms, hyperglycemia, hypertension, fluid and electrolyte disturbances (hypokalemia, metabolic alkalosis), psychosis, and profound immunosuppression.
Storage: Store below 30°C. Protect from light and moisture. Keep the container tightly closed. Keep out of reach of children. Do not use after the expiry date printed on the pack.