Refla24 mg

FDA-Approved Indication: Duchenne Muscular Dystrophy

Refla is FDA-approved (established indication) for the treatment of Duchenne muscular dystrophy (DMD) in patients 2 years of age and older. Refla is used to help slow the decline in muscle strength associated with this genetic muscle-wasting disease.

Broader Anti-Inflammatory and Immunosuppressive Uses (Guideline-Supported/Off-Label Outside the US)

Outside the United States - including in Bangladesh, where Refla is widely prescribed - Refla is also used as a general corticosteroid for a broad range of inflammatory, allergic, and autoimmune conditions. These uses are guideline-supported or established in regional clinical practice but are not part of the US FDA-approved label for Refla:

• Allergic/hypersensitivity conditions: anaphylaxis (adjunct), severe hypersensitivity reactions, acute and chronic bronchial asthma exacerbations
• Rheumatologic/connective tissue disorders: rheumatoid arthritis, juvenile chronic (idiopathic) arthritis, polymyalgia rheumatica, systemic lupus erythematosus, dermatomyositis, mixed connective tissue disease, polyarteritis nodosa, sarcoidosis
• Dermatologic conditions: pemphigus, bullous pemphigoid, pyoderma gangrenosum
• Renal disorders: minimal change nephrotic syndrome, acute interstitial nephritis
• Cardiac: rheumatic carditis
• Gastrointestinal: ulcerative colitis, Crohn's disease (adjunct)
• Ophthalmic: uveitis, optic neuritis
• Hematologic: autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura
• Oncologic (adjunct): acute lymphoblastic leukemia, malignant lymphoma, multiple myeloma, as part of combination chemotherapy regimens
• Transplantation: immunosuppression to prevent/treat organ transplant rejection

Dosing and duration for each condition should be individualized by a qualified physician.

Each Deflazacort tablet contains Deflazacort INN as the active ingredient, available in strengths of 6 mg, 18 mg, 24 mg, 30 mg, and 36 mg. Deflazacort is also available as an oral suspension (22.75 mg/mL) and, in some markets, an oral syrup (6 mg/5 mL).

Refla is a corticosteroid (glucocorticoid) medicine used to reduce inflammation and calm an overactive immune system. In the United States, Refla is FDA-approved specifically for Duchenne muscular dystrophy in children aged 2 years and older, where Refla helps preserve muscle strength. In many other countries, including Bangladesh, Refla is also used more broadly for allergic, autoimmune, and inflammatory conditions such as asthma, arthritis, and certain kidney and blood disorders. Refla works by binding to glucocorticoid receptors and suppressing inflammatory pathways throughout the body. Because Refla affects multiple body systems, Refla should only be used under close medical supervision, with the dose tailored to each patient's condition.

Corticosteroid (Glucocorticoid)

Deflazacort is a prodrug that is rapidly converted by esterases in the body to Deflazacort's pharmacologically active metabolite, 21-desDFZ. This active metabolite binds to the glucocorticoid receptor, producing anti-inflammatory and immunosuppressive effects, including inhibition of phospholipase A2 (which reduces the production of inflammatory mediators) and suppression of the release of pro-inflammatory cytokines and other immune mediators. Through these actions, Deflazacort reduces inflammation, edema, and immune-mediated tissue damage across multiple organ systems.

• Take Refla by mouth, generally once daily, at approximately the same time each day.
• Refla tablets and oral suspension may be taken with or without food; taking Refla with food or a light meal may help reduce stomach upset.
• Do not take Refla with grapefruit or grapefruit juice, as grapefruit can increase Refla levels in the body.
• Shake the Refla oral suspension well before measuring each dose, and use an accurate oral dosing syringe or cup, not a household spoon.
• Swallow Refla tablets whole, or as directed by your doctor or pharmacist.
• Do not stop taking Refla suddenly, especially after using Refla for more than a few days - the dose of Refla must be tapered down gradually under medical supervision.
• If a dose of Refla is missed, take the missed dose as soon as remembered unless it is almost time for the next dose of Refla; do not double the dose.
• Keep all follow-up appointments so your doctor can monitor your response to Refla and adjust the dose of Refla as needed.

• CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, fluconazole, diltiazem, verapamil, grapefruit juice): These drugs can significantly increase blood levels of the active metabolite of Refla by inhibiting the breakdown of Refla; the dose of Refla may need to be reduced to about one-third of the usual dose.
• CYP3A4 inducers (e.g., rifampicin, rifabutin, carbamazepine, phenytoin, phenobarbitone, efavirenz): These drugs speed up the breakdown of Refla's active metabolite, reducing the effectiveness of Refla; concurrent use with strong inducers should generally be avoided.
• NSAIDs (e.g., ibuprofen, diclofenac, aspirin): Combining NSAIDs with Refla increases the risk of gastrointestinal irritation, ulceration, and bleeding.
• Potassium-depleting diuretics and other drugs affecting potassium (e.g., furosemide, thiazide diuretics, amphotericin B): Refla increases potassium excretion, so combined use with these drugs raises the risk of hypokalemia; potassium levels should be monitored.
• Antidiabetic medications (insulin, oral hypoglycemic agents): Refla can raise blood glucose levels and reduce the effectiveness of antidiabetic medications, so doses of diabetes medications may need to be adjusted.
• Live or live-attenuated vaccines: Refla suppresses the immune response, so live vaccines should not be given during Refla therapy at immunosuppressive doses; vaccination should be completed before starting Refla where possible.
• Other immunosuppressants (e.g., other corticosteroids, methotrexate, cyclosporine): Combined use of these drugs with Refla increases the overall risk of infection due to additive immune suppression.
• Neuromuscular blocking agents (e.g., pancuronium): Concurrent use of neuromuscular blocking agents with Refla has been associated with an increased risk of acute myopathy, particularly affecting respiratory muscles.

Common Side Effects

• Cushingoid appearance (rounded face, fat redistribution)
• Weight gain and increased appetite
• Hirsutism (excess hair growth)
• Upper respiratory tract infection, nasopharyngitis, cough
• Irritability and behavioral changes
• Abdominal discomfort, nausea, constipation
• Frequent urination (pollakiuria)
• Skin changes: acne, erythema, striae, skin thinning
• Headache, back pain

Serious Side Effects - Seek Medical Attention

• Signs of adrenal insufficiency (severe fatigue, weakness, dizziness, low blood pressure, vomiting) - especially if Refla is stopped abruptly
• Signs of infection (fever, sore throat, unusual fatigue) that may be masked by Refla
• Severe stomach pain, black or bloody stools, vomiting blood (possible GI ulcer/perforation)
• Vision changes, eye pain (possible cataracts, glaucoma, or increased intraocular pressure)
• Severe mood changes, depression, confusion, or psychosis
• Signs of blood clots (leg swelling/pain, chest pain, shortness of breath)
• Bone pain or fractures (possible osteoporosis or avascular necrosis)
• Severe skin reaction (blistering, peeling skin, rash with fever) - possible toxic epidermal necrolysis
• Muscle weakness, especially affecting breathing muscles
• Signs of heart failure (swelling, shortness of breath, rapid weight gain)
• Symptoms of high blood sugar (increased thirst, frequent urination, confusion)

Pregnancy

Refla readily crosses the placenta. As with other corticosteroids, use of Refla during pregnancy has been associated with a small increase in the risk of orofacial clefts when Refla is used in the first trimester, and with intrauterine growth restriction and lower birth weight when Refla is used later in pregnancy. Refla should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus, and only under close medical supervision. Infants born to mothers who received substantial doses of Refla during pregnancy should be monitored for signs of adrenal insufficiency.

Breastfeeding

Corticosteroids, including Refla, pass into breast milk. Low to moderate doses of Refla are generally considered unlikely to cause adverse effects in a breastfed infant, but higher or prolonged doses of Refla could theoretically affect infant growth or adrenal function. A doctor should weigh the mother's need for Refla against the possible effects on the breastfed infant, and the infant should be monitored if the mother is taking Refla.

• Adrenal suppression and tapering (do not stop abruptly): Long-term use of Refla suppresses the body's natural cortisol production (HPA axis suppression). Stopping Refla suddenly after prolonged use can cause acute adrenal insufficiency, which can be life-threatening; the dose of Refla must always be reduced gradually under medical supervision.
• Increased risk of infection: Refla suppresses the immune system, increasing susceptibility to viral, bacterial, fungal, and parasitic infections, and can mask the usual signs of infection (such as fever), delaying diagnosis and treatment.
• Osteoporosis and growth suppression: Long-term Refla use decreases bone mineral density, increasing the risk of fractures in adults, and can suppress linear growth in children; bone health and growth in children should be monitored during prolonged Refla therapy.
• Cushingoid effects: Prolonged use of Refla commonly causes a Cushingoid appearance (facial rounding, central weight gain, purple striae) and, in severe cases, Cushing's syndrome with associated metabolic and psychiatric effects.
• Hyperglycemia: Refla can raise blood glucose levels and unmask or worsen diabetes mellitus; blood glucose should be monitored, particularly in patients with existing diabetes or risk factors for diabetes.
• Ophthalmic effects: Prolonged Refla use (more than 6 weeks) can cause posterior subcapsular cataracts, glaucoma, and increased intraocular pressure; regular eye examinations are recommended during long-term Refla therapy.
• Cardiovascular and fluid effects: Refla can cause fluid and salt retention, elevated blood pressure, and potassium loss; Refla should be used with caution in patients with hypertension, heart failure, or renal impairment.
• Gastrointestinal risk: Refla should be used with caution in patients with active or prior peptic ulcer disease, diverticulitis, or ulcerative colitis, due to an increased risk of GI perforation or bleeding with Refla.
• Psychiatric effects: Refla may cause mood swings, insomnia, anxiety, depression, or, rarely, psychosis, particularly at higher doses of Refla.
• Serious skin reactions: Rare but serious skin reactions, including toxic epidermal necrolysis, have been reported with Refla; discontinue Refla and seek medical attention if a severe skin reaction occurs.
• Live vaccines: Live or live-attenuated vaccines should not be given to patients receiving immunosuppressive doses of Refla.
• Use with caution in specific conditions: Refla should be used cautiously in patients with myasthenia gravis, epilepsy, hypothyroidism, ocular herpes simplex, or a history of psychiatric illness.

There is no specific antidote for Refla overdose. In cases of acute overdose of Refla, treatment with gastric lavage or induced emesis may be considered, but only if directed by a healthcare professional or poison control - do not induce vomiting on your own unless instructed to do so. Management is otherwise supportive and symptomatic. Chronic overexposure to Refla (excessive dosing over time) may require temporary dose reduction or a switch to alternate-day dosing under medical guidance. If Refla overdose is suspected, contact emergency medical services or a poison control center immediately.

Store Refla according to the product label. In general, keep Refla in a cool, dry place below 25°C, protected from light and moisture, and out of the reach of children. Do not use Refla after the expiry date printed on the pack.

Children

Refla is FDA-approved for Duchenne muscular dystrophy in children 2 years of age and older, and is also used more broadly for pediatric inflammatory and autoimmune conditions. Long-term corticosteroid use, including use of Refla, can suppress growth in children; height and growth should be monitored regularly during prolonged Refla therapy, and growth typically resumes after Refla is discontinued in most cases. The oral suspension formulation of Refla (which may contain benzyl alcohol) should not be used in infants under 2 years of age.

Elderly

No specific dose adjustment of Refla is required based on age alone in elderly patients, but elderly patients receiving Refla should be monitored closely, as age-related conditions such as osteoporosis, diabetes, and hypertension can make the adverse effects of Refla more serious.

Renal Impairment

No specific dose adjustment of Refla is generally required in renal impairment; standard precautions for corticosteroid use apply.

Hepatic Impairment

In patients with significant hepatic impairment, blood levels of Refla's active metabolite may increase; Refla should be used with caution and the dose of Refla monitored carefully in these patients.

Diabetic Patients

Refla can raise blood glucose levels; patients with diabetes may need closer glucose monitoring and adjustment of their antidiabetic medications while taking Refla.

For acute conditions (such as a severe allergic reaction or an asthma exacerbation), Refla is typically used as a short course at a higher dose, then tapered and stopped once the condition resolves. For chronic conditions, including Duchenne muscular dystrophy and long-term autoimmune or inflammatory diseases, Refla is often continued for months to years at the lowest effective dose. Whenever Refla has been used for more than a few days, Refla must be tapered off gradually under medical supervision rather than stopped suddenly, to allow the body's own cortisol production to recover and to avoid adrenal insufficiency.

Corticosteroid; Glucocorticoid; Anti-inflammatory and immunosuppressive agent

Deflazacort is a prodrug converted to Deflazacort's active metabolite, 21-desDFZ, which binds to the glucocorticoid receptor. This receptor binding modulates gene transcription, reducing the production of inflammatory mediators (including inhibition of phospholipase A2) and suppressing the migration and activity of immune cells, resulting in anti-inflammatory and immunosuppressive effects.

Refla is FDA-approved for the treatment of Duchenne muscular dystrophy in children 2 years of age and older, based on clinical trial data in boys aged 5 to 15 years, with safety and efficacy in younger children (2 to 5 years) extrapolated from this data. Refla is also used more broadly in pediatric patients outside the US for conditions such as juvenile chronic (idiopathic) arthritis, nephrotic syndrome, and acute severe asthma, generally at doses of 0.25-1.5 mg/kg/day depending on the condition. Because long-term use of Refla and other corticosteroids can suppress linear growth in children, height, weight, and growth velocity should be monitored regularly throughout Refla treatment, and a pediatric specialist should be involved in long-term management.