Deflazacort

Usage

Deflazacort is a glucocorticoid, a class of corticosteroids, primarily prescribed for the treatment of Duchenne muscular dystrophy (DMD) in patients aged 5 years and older. It is also used for various inflammatory and autoimmune conditions, including rheumatoid arthritis, juvenile chronic arthritis, nephrotic syndrome, asthma, and allergic disorders. Its pharmacological classification is corticosteroid, specifically a glucocorticoid. Deflazacort works by binding to glucocorticoid receptors in the cytoplasm, which then translocate to the nucleus and modulate gene expression. This results in decreased inflammation by suppressing the immune system and reducing the production of inflammatory mediators.

Alternate Names

While “Deflazacort” is the generic name, brand names include Emflaza, Calcort, and DynaCort.

How It Works

Pharmacodynamics: Deflazacort exerts its effects by binding to intracellular glucocorticoid receptors. This complex then translocates to the nucleus, where it modulates the transcription of various genes involved in inflammatory and immune responses. The ultimate result is suppression of inflammation and immune function.

Pharmacokinetics: Deflazacort is administered orally and is well-absorbed from the gastrointestinal tract. It is metabolized in the liver to an active metabolite, 21-desacetyl deflazacort. It is primarily excreted via the kidneys.

Mode of Action: The drug acts by binding to glucocorticoid receptors, which leads to the regulation of gene expression. This modulation affects various inflammatory and immune processes, such as leukocyte migration, cytokine production, and antibody synthesis.

Receptor binding, enzyme inhibition, or neurotransmitter modulation: Deflazacort primarily binds to glucocorticoid receptors. While it does not directly inhibit enzymes or modulate neurotransmitters, its downstream effects can indirectly influence these processes.

Elimination pathways: Deflazacort, after metabolism in the liver, is mainly eliminated through renal excretion.

Dosage

Standard Dosage

Adults:

For inflammatory and autoimmune conditions other than DMD, the initial dose can range from 6 mg to 120 mg daily, adjusted based on disease severity and patient response. Maintenance doses typically range from 3 mg to 18 mg daily. For DMD, the dose is 0.9 mg/kg/day.

Children:

For DMD (age 5 and above): 0.9 mg/kg/day. For other conditions, 0.25-1.5 mg/kg/day, often administered on alternate days. Dosage is adjusted based on age, weight, and specific condition. Pediatric DMD patients younger than 5 have not had established dosage.

Special Cases:

• Elderly Patients: Monitor closely and start with the lowest effective dose due to increased risk of adverse effects.
• Patients with Renal Impairment: No specific dose adjustment is typically needed.
• Patients with Hepatic Dysfunction: Monitor closely, especially in severe impairment, and consider dose reduction.
• Patients with Comorbid Conditions: Careful monitoring and dose adjustment may be needed for patients with diabetes, cardiovascular disease, hypertension, and other conditions.

Clinical Use Cases

Deflazacort’s use in specific clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations usually aligns with the treatment of underlying conditions and not for these procedures themselves. Dosage depends on the specific condition being treated and overall patient context.

Dosage Adjustments

Adjustments are necessary based on individual patient response, disease activity, and the presence of renal or hepatic impairment. Concomitant use of CYP3A4 inhibitors necessitates a dose reduction to one-third of the recommended dose. Avoid concomitant use with CYP3A4 inducers.

Side Effects

Common Side Effects

Weight gain, increased appetite, fluid retention, insomnia, mood changes, increased risk of infections.

Rare but Serious Side Effects

Osteoporosis, avascular necrosis, cataracts, glaucoma, immunosuppression, hyperglycemia, hypertension, Cushing’s syndrome.

Long-Term Effects

Growth retardation in children, adrenal suppression, osteoporosis, increased risk of infections.

Adverse Drug Reactions (ADR)

Severe allergic reactions, adrenal crisis, severe infections.

Contraindications

Systemic infections (unless treated with specific anti-infective therapy), hypersensitivity to deflazacort, concomitant administration of live vaccines.

Drug Interactions

CYP3A4 inhibitors increase deflazacort levels, requiring dose reduction. CYP3A4 inducers decrease deflazacort levels. Interactions can occur with medications such as antibiotics, anticoagulants, and antihypertensives. Alcohol, grapefruit juice, and smoking can also influence drug metabolism.

Pregnancy and Breastfeeding

Deflazacort should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is unknown whether deflazacort is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Drug Profile Summary

• Mechanism of Action: Binds to glucocorticoid receptors, modulating gene expression and suppressing inflammation.
• Side Effects: Weight gain, increased appetite, fluid retention, mood changes, increased risk of infection, osteoporosis, hyperglycemia, hypertension.
• Contraindications: Systemic infections, hypersensitivity, live vaccines.
• Drug Interactions: CYP3A4 inhibitors and inducers, various medications.
• Pregnancy & Breastfeeding: Use with caution; potential fetal risks exist.
• Dosage: DMD: 0.9 mg/kg/day; other conditions: variable, adjusted according to the disease and patient response.
• Monitoring Parameters: Blood pressure, blood glucose, bone density, growth in children, signs of infection.

Popular Combinations

Deflazacort may be combined with other immunosuppressants for certain conditions, though specific combinations are highly condition-dependent and should be considered on a case-by-case basis.

Precautions

• General Precautions: Pre-existing infections, diabetes, hypertension, osteoporosis, hepatic/renal impairment.
• Specific Populations: Close monitoring in children, elderly, and pregnant/breastfeeding women.
• Lifestyle Considerations: Dietary adjustments may be needed due to potential weight gain and metabolic effects. Driving or operating machinery may be affected due to potential side effects like mood changes and insomnia.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Deflazacort?

A: For DMD in patients 5 years and older, it is 0.9 mg/kg/day. For other conditions, dosage varies depending on the specific disease, severity, and patient response. It can range from 6 mg to 120 mg daily initially, with maintenance doses typically from 3 mg to 18 mg daily. Pediatric dosing for other conditions (excluding DMD) is usually 0.25-1.5 mg/kg/day.

Q2: What are the most common side effects?

A: Common side effects include weight gain, increased appetite, fluid retention, insomnia, mood swings, and increased susceptibility to infections.

Q3: How does Deflazacort differ from other corticosteroids?

A: It is considered to have a better safety profile regarding growth retardation in children and bone mineral density compared to some other corticosteroids, but this is not a guarantee for any individual patient.

Q4: What are the serious side effects to be aware of?

A: Serious side effects can include osteoporosis, avascular necrosis, cataracts, glaucoma, immunosuppression, hyperglycemia, hypertension, and Cushing’s syndrome.

Q5: What are the contraindications for Deflazacort use?

A: Contraindications include systemic infections (unless under concurrent anti-infective therapy), hypersensitivity to deflazacort, and live vaccinations.

Q6: How should Deflazacort be administered?

A: It is administered orally, once daily, and can be taken with or without food. Tablets can be swallowed whole or crushed and mixed with applesauce. The oral suspension should be mixed with juice or milk before administration.

Q7: Are there any specific drug interactions to consider?

A: Yes, significant interactions can occur with CYP3A4 inhibitors (requiring dose reduction) and inducers. Consult drug interaction resources before co-prescribing.

Q8: What precautions should be taken in patients with renal or hepatic impairment?

A: While no specific dose adjustments are usually necessary for renal impairment, patients with hepatic dysfunction, especially severe impairment, should be closely monitored, and a dose reduction may be considered.

Q9: Can Deflazacort be used in pregnant or breastfeeding women?

A: Deflazacort should be used during pregnancy only if the potential benefit outweighs the risk to the fetus. Exercise caution when administering to breastfeeding mothers, as its excretion in human milk isn’t fully understood.