Deflazacort

Deflazacort is used to treat Duchenne muscular dystrophy (DMD).

Deflazacort is available under the following different brand names: Emflaza.

Dosage Forms and Strengths

Tablet

• 6 mg
• 18 mg
• 30 mg
• 36 mg

Oral Suspension

• 22.75 mg/mL

Dosage Considerations – Should be Given as Follows:

Duchenne Muscular Dystrophy

• Indicated for Duchenne muscular dystrophy (DMD)
• Adults and children 2 years and older: 0.9 mg/kg/day orally once daily
• Children under 2 years: Safety and efficacy not established
• If tablets are used, round up to the nearest possible dose; may use any combination of tablet strengths to achieve calculated dose
• If the oral suspension is used, round up to the nearest tenth of a milliliter (mL)
• When discontinuing treatment, gradually decrease the dose is administered for more than a few days
• If tablets are used, round up to the nearest possible dose; may use any combination of tablet strengths to achieve calculated dose
• If the oral suspension is used, round up to the nearest tenth of a milliliter (mL)
• When discontinuing treatment, gradually decrease the dose is administered for more than a few days

Dosage Modifications

Coadministration with CYP3A4 inhibitors

• Moderate or strong CYP3A4 inhibitors: Give one third the recommended deflazacort dose
• Example: Reduce a 36-mg/day dose to 12 mg/day when used with moderate or strong CYP3A4 inhibitors

Coadministration with CYP3A4 inducers

• Moderate or strong CYP3A4 inducers: Avoid use

Renal impairment

• Mild, moderate, or severe: No dose adjustment is required

Hepatic impairment

• Mild or moderate: No dose adjustment required
• Severe: Not studied

Dosing Considerations

Assessments before initiating treatment

• Administer all immunizations according to immunization guidelines
• Administer live-attenuated or live vaccines at least 4-6 weeks before starting treatment

Side effects of Deflazacort include:

• Cushingoid appearance
• Weight gain
• Increased appetite
• Upper respiratory tract infection
• Cough
• Urinary frequency

Less common side effects of deflazacort include:

• Runny or stuffy nose
• Excess unwanted hair growth
• Central obesity
• Redness
• Irritability
• Abdominal discomfort
• Eye disorders: increased earing
• Gastrointestinal disorders: indigestion/heartburn, nausea,
• General disorders and administration site conditions: Thirst
• Infections: stye, impetigo, influenza, outer ear infection, sore throat, tooth abscess, urinary tract infection (UTI), viral infection
• Injury, poisoning and procedural complications: Back injury, contusion, face injury, fibula fracture, greenstick fracture, heat exhaustion
• Investigations: Glucose urine present, heart rate irregular
• Musculoskeletal and connective tissue disorders: Back pain, muscle spasms, muscle pain, neck mass, neck pain, pain in extremities
• Nervous system disorders: Dizziness, psychomotor hyperactivity
• Psychiatric disorders: Affect lability, aggression, depression, emotional disorder, middle insomnia, mood altered, mood swings, sleep disorder
• Renal and urinary disorders: Abnormal coloration of urine, painful urination, hypertonic bladder
• Reproductive system and breast disorders: Testicular pain
• Respiratory, thoracic, and mediastinal disorders: Hypoventilation, runny nose
• Skin and subcutaneous tissue disorders: Acne, hair loss, dermatitis
• Vascular disorders: Hot flush

Postmarketing side effects of deflazacort reported include:

• Blood and lymphatic system disorders: Leukocytosis
• Cardiac disorder: Heart failure
• Eye disorders: Chorioretinopathy, corneal or scleral thinning
• Gastrointestinal disorders: Acute pancreatitis (especially in children), hemorrhage, peptic ulceration, perforation of peptic ulcer
• General disorders and administration site conditions: Fluid retention (edema), impaired healing
• Immune system disorders: Hypersensitivity including anaphylaxis
• Metabolism and nutrition disorders: Impaired carbohydrate tolerance with increased requirement for antidiabetic therapy, negative protein and calcium balance, potassium loss and hypokalemic alkalosis when co-administered with beta2-agonist and xanthines
• Musculoskeletal and connective tissue disorders: Avascular necrosis, muscle wasting, negative nitrogen balance, tendonitis and tendon rupture when co-administered with quinolones, vertebral and long bone fractures
• Nervous system disorders: Aggravation of epilepsy, increased intracranial pressure with papilledema in children (pseudotumor cerebri) usually after treatment withdrawal, spinning sensation (vertigo)
• Psychiatric disorders: Anxiety, cognitive dysfunction including confusion and amnesia, delusions, hallucinations, mania, suicidal thoughts
• Skin and subcutaneous tissue disorders: Toxic epidermal necrolysis
• Vascular disorders: Thromboembolism, in particular in patients with underlying conditions associated with increased thrombotic tendency, benign intracranial hypertension

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Severe interactions of deflazacort include:

• mifepristone

Deflazacort has serious interactions with at least 77 different drugs.

Deflazacort has moderate interactions with at least 222 different drugs.

Deflazacort has mild interactions with at least 68 different drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

This medication contains deflazacort. Do not take Emflaza if you are allergic to deflazacort or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Hypersensitivity to deflazacort or to any of the inactive ingredients

Effects of Drug Abuse

• No information available.

Short-Term Effects

• See "What Are Side Effects Associated with Using Deflazacort?"

Long-Term Effects

• Ophthalmic effects: May include cataracts, infections, and glaucoma; monitor intraocular pressure if used for more than 6 weeks
• Effects on bones: Monitor for decreases in bone mineral density with long-term use
• Cushing syndrome (hypercortisolism) occurs with prolonged exogenous corticosteroid exposure; symptoms include hypertension, truncal obesity and thinning of the limbs, purple striae, facial rounding, facial plethora, muscle weakness, easy and frequent bruising with thin fragile skin, posterior neck fat deposition, osteopenia, acne, amenorrhea, hirsutism and psychiatric abnormalities
• See "What Are Side Effects Associated with Using Deflazacort?"

Cautions

• Known hypersensitivity; instances of hypersensitivity, including anaphylaxis, have occurred with corticosteroid therapy
• Alterations in cardiovascular/renal function: Monitor for elevated blood pressure and sodium levels, and for decreased potassium levels
• Gastrointestinal perforation: Increased risk with certain gastrointestinal disorders (e.g., active/latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, ulcerative colitis); signs and symptoms may be masked
• Behavioral and mood disturbances: May include euphoria, insomnia, mood swings, personality changes, severe depression, and psychosis
• Effects on bones: Monitor for decreases in bone mineral density with long-term use
• Ophthalmic effects: May include cataracts, infections, and glaucoma; monitor intraocular pressure if used for more than 6 weeks
• Myopathy may occur with concomitant neuromuscular blocking agents or disorders of neuromuscular transmission (e.g., myasthenia gravis)
• Kaposi sarcoma reported in patients receiving corticosteroid therapy, most often for chronic conditions; discontinuation of corticosteroids may result in clinical improvement
• Oral suspension contains benzyl alcohol and is not approved for use in children aged under 5 years; serious and fatal adverse reactions including (gasping syndrome) can occur in neonates and low-birth-weight infants treated with benzyl alcohol-preserved drugs
• Observational studies have shown an increased risk of thromboembolism (including VTE), particularly with higher cumulative doses of corticosteroids

Alterations in endocrine function

• Corticosteroids can cause serious and life-threatening alterations in endocrine function, especially with long-term use
• Corticosteroids produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression and potentially develop secondary adrenal insufficiency after withdrawal of corticosteroid treatment
• Acute adrenal insufficiency can occur if corticosteroids are withdrawn abruptly, and can be fatal; the risk is reduced by gradually tapering the dose
• Adrenal insufficiency may persist, however, for months after discontinuation of prolonged therapy; therefore, in any situation of stress occurring during that period of discontinuation, corticosteroid therapy should be reinstituted
• Cushing syndrome (hypercortisolism) occurs with prolonged exogenous corticosteroid exposure; symptoms include hypertension, truncal obesity and thinning of the limbs, purple striae, facial rounding, facial plethora, muscle weakness, easy and frequent bruising with thin fragile skin, posterior neck fat deposition, osteopenia, acne, amenorrhea, hirsutism and psychiatric abnormalities
• Corticosteroid may increase blood glucose, worsen pre-existing diabetes, predispose those on long-term therapy to diabetes mellitus, and may reduce the effect of antidiabetic drugs; monitor blood glucose at regular intervals and if needed, antidiabetic treatment should be initiated
• Corticosteroid metabolic clearance is decreased in patients with hypothyroidism and increased in patients with hyperthyroidism
• Pheochromocytoma crisis, which can be fatal, has been reported after administration of systemic corticosteroids

Immunosuppression and increased risk of infection

• Increased risk of new, exacerbation, dissemination, or reactivation of latent infections, which can be severe and at times fatal; signs and symptoms of infection may be masked
• Monitor for development of infection and consider withdrawal of corticosteroids or reduction of the dose of corticosteroids as needed
• Varicella zoster virus exposure: Prophylaxis with varicella zoster immune globulin (VZIG) may be indicated; if chickenpox/varicella zoster develops, treatment with antiviral agents may be considered
• Measles exposure: Prophylaxis with immunoglobulin (IG) may be indicated
• Hepatitis B virus reactivation can occur in patients who are hepatitis B carriers undergoing treatment with immunosuppressive drugs including corticosteroids; reactivation can also occur with resolved hepatitis B infection
• Fungal infections
  • If a systemic fungal infection develops, withdrawal of corticosteroids or dose reduction is recommended
  • Amebiasis: Corticosteroids may activate latent amebiasis; rule out latent or active amebiasis before initiating corticosteroids in any patient who has spent time in the tropics or other patients with unexplained diarrhea
  • Strongyloides (threadworm) infestation: Corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination of widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia; withdrawal of corticosteroids or dose reduction is recommended

Drug interaction overview

• Active metabolite of deflazacort, 21-desDFZ, is a substrate of CYP3A4
• Coadministration of deflazacort with moderate or strong CYP3A4 inducers significantly decreases exposure of the active metabolite; avoid coadministration
• Coadministration with neuromuscular blocking drugs (e.g., pancuronium) may increase risk of acute myopathy
• Caution if co-administered with other drugs that decrease serum potassium; monitor serum potassium or use an alternant drug
• Vaccines
  • Immunosuppressive doses of corticosteroids may interfere with efficacy of live or live-attenuated vaccines
  • Patients on deflazacort may receive concurrent vaccinations, except for live-attenuated or live vaccines

Pregnancy and Lactation

Corticosteroids such as deflazacort should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism. Consult your doctor.

Systemically administered corticosteroids such as deflazacort appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for deflazacort, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.