Emflaza

Name: Emflaza

How should this medicine be used?

Deflazacort comes as a tablet and a suspension (liquid) to take by mouth. It is usually taken once a day with or without food. Take deflazacort at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take deflazacort exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

If you cannot swallow the tablet whole, you may crush the tablet and mix with applesauce. The mixture should be taken immediately.

Shake the suspension well before each use to mix the medication evenly. Use the measuring device to measure the dose of deflazacort and slowly add the dose to 3 to 4 ounces (90 to 120 mL) of milk or fruit juice and take immediately. Do not mix deflazacort suspension with grapefruit juice.

Your doctor may need to change your dose of deflazacort if you experience unusual stress on your body such as surgery, illness, or infection. Tell your doctor if your symptoms improve or get worse or if you get sick or have any changes in your health during your treatment.

Do not stop taking deflazacort without talking to your doctor. Stopping the drug abruptly may cause symptoms such as loss of appetite, an upset stomach, vomiting, drowsiness, confusion, headache, fever, joint and muscle pain, peeling skin, and weight loss. Your doctor will probably decrease your dose gradually to allow your body to adjust before stopping the drug completely. Watch for these side effects if you are gradually decreasing your dose and after you stop taking the tablets or oral suspension. If these problems occur, call your doctor immediately.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

Other uses for this medicine

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Emflaza Overview

Emflaza is a brand name medication. For more information about Emflaza see its generic Deflazacort

What should I avoid while taking Emflaza (deflazacort)?

Grapefruit and grapefruit juice may interact with deflazacort and lead to unwanted side effects. Avoid the use of grapefruit products while taking deflazacort.

Avoid being near people who are sick or have infections. Call your doctor for preventive treatment if you are exposed to chicken pox or measles. These conditions can be serious or even fatal in people who are using steroid medicine.

Do not receive a "live" vaccine while using deflazacort, or you could develop a serious infection. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

What other drugs will affect Emflaza (deflazacort)?

Tell your doctor about all your current medicines and any you start or stop using, especially:

  • insulin or oral diabetes medicine;

  • thyroid medication;

  • St. John's wort;

  • an antibiotic, antifungal medicine;

  • an antidepressant;

  • antiviral medicine (such as medicine to treat hepatitis C or HIV/AIDS);

  • heart or blood pressure medicine;

  • seizure medication;

  • tuberculosis medication; or

  • NSAIDs (nonsteroidal anti-inflammatory drugs)--aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others.

This list is not complete. Other drugs may interact with deflazacort, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Cautions for Emflaza

Contraindications

Hypersensitivity to deflazacort or any of the inactive ingredients in deflazacort.1

Warnings/Precautions

Alterations in Endocrine Function

Corticosteroids, such as deflazacort, can cause serious and life-threatening alterations in endocrine function, especially with chronic use. Monitor patients receiving deflazacort for Cushing’s syndrome, hyperglycemia, and adrenal insufficiency after deflazacort withdrawal. In addition, patients with hypopituitarism, primary adrenal insufficiency or congenital adrenal hyperplasia, altered thyroid function, or pheochromocytoma may be at increased risk for adverse endocrine events.1

Risk of Adrenal Insufficiency Following Corticosteroid Withdrawal

Corticosteroids produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, with the potential for the development of secondary adrenal insufficiency after withdrawal of corticosteroid treatment. Acute adrenal insufficiency can occur if corticosteroids are withdrawn abruptly, and can be fatal. The degree and duration of adrenocortical insufficiency produced is variable among patients and depends on the dose, frequency, and duration of corticosteroid therapy. The risk is reduced by gradually tapering the corticosteroid dose when withdrawing treatment. This 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. For patients already taking corticosteroids during times of stress, the dosage may need to be increased.1

A steroid “withdrawal syndrome”, seemingly unrelated to adrenocortical insufficiency, may also occur following abrupt discontinuance of corticosteroids. This syndrome includes symptoms such as anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, desquamation, myalgia, and/or weight loss. These effects are thought to be due to the sudden change in corticosteroid concentration rather than to low corticosteroid levels.1

Cushing’s Syndrome

Cushing’s syndrome (hypercortisolism) occurs with prolonged exposure to exogenous corticosteroids, including deflazacort. 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.1

Hyperglycemia

Corticosteroids can increase blood glucose, worsen pre-existing diabetes, predispose those on long-term therapy to diabetes mellitus, and may reduce the effect of anti-diabetic drugs. Monitor blood glucose at regular intervals. For patients with hyperglycemia, anti-diabetic treatment should be initiated or adjusted accordingly.1

Considerations for Use in Patients with Altered Thyroid Function

Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate a dose adjustment of the corticosteroid. When concomitant administration of corticosteroids and levothyroxine is required, administration of the corticosteroid should precede the initiation of levothyroxine therapy to reduce the risk of adrenal crisis.1

Pheochromocytoma Crisis

There have been reports of pheochromocytoma crisis, which can be fatal, after administration of systemic corticosteroids. In patients with suspected or identified pheochromocytoma, consider the risk of pheochromocytoma crisis prior to administering corticosteroids.1

Immunosuppression and Increased Risk of Infection

Corticosteroids, including deflazacort, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic. Corticosteroids reduce resistance to new infections, exacerbate existing infections, increase the risk of disseminated infections, increase the risk of reactivation or exacerbation of latent infections, and mask some signs of infection. These infections can be severe, and at times fatal. The degree to which the dose, route, and duration of corticosteroid administration correlates with the specific risks of infection is not well characterized; however, the rate of occurrence of infectious complications increases with increasing doses of corticosteroids.1

Monitor for the development of infection and consider withdrawal of corticosteroids or reduction of the dose of corticosteroids as needed. 1

Varicella Zoster and Measles Viral Infections

Chickenpox caused by varicella zoster virus and measles can have a serious or even fatal course in non-immune children or adults on corticosteroids, including deflazacort. In children or adults who have not had these diseases, particular care should be taken to avoid exposure. If a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If a patient is exposed to measles, prophylaxis with immune globulin (IG) may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.1

Hepatitis B Virus Reactivation

Hepatitis B virus reactivation can occur in patients who are hepatitis B carriers undergoing treatment with immunosuppressive drugs including corticosteroids. Reactivation can also occur in patients who appear to have resolved hepatitis B infection.1

Fungal Infections

Corticosteroids may exacerbate systemic fungal infections and therefore should not be used in the presence of such infections. For patients on corticosteroids who develop systemic fungal infections, withdrawal of corticosteroids or reduction of the dose of corticosteroids is recommended.1

Amebiasis

Corticosteroids may activate latent amebiasis. Therefore, it is recommended that latent amebiasis or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has spent time in the tropics, or any patient with unexplained diarrhea.1

Strongyloides Infestation

In patients with known or suspected Strongyloides (threadworm) infestation, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia. For patients on corticosteroids who develop known or suspected Strongyloides (threadworm) infestation, withdrawal of corticosteroids or reduction of the dose of corticosteroids is recommended.1

Alterations in Cardiovascular/Renal Function

Corticosteroids, including deflazacort, can cause elevation of blood pressure, salt, and water retention, and increased excretion of potassium and calcium. Monitor blood pressure and assess for signs and symptoms of volume overload. Monitor serum potassium levels. Dietary salt restriction and potassium supplementation may be necessary. Deflazacort should be used with caution in patients with congestive heart failure, hypertension, or renal insufficiency.1

Literature reports suggest an association between use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with deflazacort should be used with great caution in these patients.1

Gastrointestinal Perforation

There is an increased risk of gastrointestinal perforation during corticosteroid use in patients with certain gastrointestinal disorders such as active or latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, and non-specific ulcerative colitis. Signs of gastrointestinal perforation, such as peritoneal irritation, may be masked in patients receiving corticosteroids.1

Avoid corticosteroids if there is a probability of impending perforation, abscess, or other pyogenic infections; diverticulitis; fresh intestinal anastomoses; or active or latent peptic ulcer.1

Behavioral and Mood Disturbances

Potentially severe psychiatric adverse reactions may occur with systemic corticosteroids, including deflazacort. Symptoms typically emerge within a few days or weeks of starting treatment and may be dose-related. These reactions may improve after either dose reduction or withdrawal, although pharmacologic treatment may be necessary. Psychiatric adverse reactions usually involve hypomanic or manic symptoms (e.g., euphoria, insomnia, mood swings) during treatment and depressive episodes after discontinuation of treatment. Inform patients or caregivers of the potential for behavioral and mood changes and encourage them to seek medical attention if psychiatric symptoms develop, especially if depressed mood or suicidal ideation is suspected.1

Effects on Bones

Decreased Bone Mineral Density

Corticosteroids, including deflazacort, decrease bone formation and increase bone resorption both through their effect on calcium regulation (i.e., decreasing absorption and increasing excretion) and inhibition of osteoblast function. This, together with a decrease in the protein matrix of the bone secondary to an increase in protein catabolism and reduced sex hormone production, may lead to inhibition of bone growth in pediatric patients and the development of bone loss at any age. Bone loss can predispose patients to vertebral and long bone fractures. Consider a patient’s risk of osteoporosis before initiating corticosteroid therapy. Monitor bone mineral density in patients on long-term treatment with deflazacort.1

Avascular Necrosis

Corticosteroids, including deflazacort, may cause avascular necrosis.1

Ophthalmic Effects

Use of corticosteroids, including deflazacort, may produce posterior subcapsular cataracts. Corticosteroids may also cause glaucoma with possible damage to the optic nerves, and may increase the risk of secondary ocular infections caused by bacteria, fungi, or viruses. Corticosteroids are not recommended for patients with active ocular herpes simplex. 1

Intraocular pressure may become elevated in some patients taking corticosteroids. If treatment with deflazacort is continued for more than 6 weeks, monitor intraocular pressure.1

Vaccination

Administration of live or live attenuated vaccines is not recommended in patients receiving immunosuppressive doses of corticosteroids, including deflazacort. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines.1

Killed or inactivated vaccines may be administered during corticosteroid therapy; however, the response to such vaccines cannot be predicted.1

Patients on corticosteroid therapy, including deflazacort, may exhibit a diminished response to toxoids and live or inactivated vaccines because of inhibition of antibody response.1

Serious Skin Rashes

Toxic epidermal necrolysis has been reported with the use of deflazacort with symptoms beginning within 8 weeks of starting treatment. Discontinue at the first sign of rash, unless the rash is clearly not drug related.1

Effects on Growth and Development

Long-term use of corticosteroids, including deflazacort, can have negative effects on growth and development in children.1

Myopathy

Patients receiving corticosteroids, including deflazacort, and concomitant therapy with neuromuscular blocking agents (e.g., pancuronium) or patients with disorders of neuromuscular transmission (e.g., myasthenia gravis) may be at increased risk of developing acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.1

Kaposi’s Sarcoma

Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement.1

Risk of Serious Adverse Reactions in Infants Because of Benzyl Alcohol Preservative

Deflazacort oral suspension contains benzyl alcohol and is not approved for use in pediatric patients less than 5 years of age. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low birth weight infants treated with benzyl alcohol-preserved drugs. The “gasping syndrome” is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known (deflazacort oral suspension contains 10.45 mg of benzyl alcohol per mL; deflazacort tablets do not contain benzyl alcohol).1

Thromboembolic Events

Observational studies have shown an increased risk of thromboembolism (including venous thromboembolism), particularly with higher cumulative doses of corticosteroids. It is unclear if risk differs by daily dose or duration of use. Use deflazacort with caution in patients who have or may be predisposed to thromboembolic disorders.1

Anaphylaxis

Rare instances of anaphylaxis have occurred in patients receiving corticosteroid therapy, including deflazacort.1

Specific Populations

Pregnancy

Corticosteroids 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. There are no adequate and well-controlled studies with deflazacort in pregnant women to inform drug-associated risks.1

Corticosteroids, including deflazacort, readily cross the placenta. Adverse developmental outcomes, including orofacial clefts (cleft lip, with or without cleft palate) and intrauterine growth restriction, and decreased birth weight, have been reported with maternal use of corticosteroids, including deflazacort, during pregnancy. Some epidemiologic studies report an increased risk of orofacial clefts from about 1 per 1000 infants to 3 to 5 per 1000 infants; however, a risk for orofacial clefts has not been observed in all studies. Intrauterine growth restriction and decreased birth weight appear to be dose-related; however, the underlying maternal condition may also contribute to these risks. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. 1

Animal reproduction studies have not been conducted with deflazacort. Animal reproduction studies conducted with other corticosteroids in pregnant mice, rats, hamsters, and rabbits using clinically relevant doses have shown an increased incidence of cleft palate. An increase in embryofetal death, intrauterine growth retardation, and constriction of the ductus arteriosus were observed in some animal species. 1

Multiple cohort and case-controlled studies in humans suggest that maternal corticosteroid use during the first trimester increases the rate of cleft lip, with or without cleft palate, from about 1/1000 infants to 3–5/1000 infants. Two prospective case-controlled studies showed decreased birth weight in infants exposed to maternal corticosteroids in utero.1

Lactation

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for deflazacort and any potential adverse effects on the breastfed infant from deflazacort. There are no data on the effects on milk production.1

Pediatric Use

The safety and effectiveness of deflazacort for the treatment of DMD have been established in patients 5 years of age and older. Use of deflazacort in pediatric patients is supported by a multicenter, randomized, double-blind, placebo- and active-controlled study in 196 males.1

Safety and effectiveness of deflazacort have not been established in pediatric patients less than 5 years of age.1

Deflazacort oral suspension contains benzyl alcohol and is not approved for use in pediatric patients less than 5 years of age. Serious adverse reactions including fatal reactions and “gasping syndrome” occurred in premature neonates and low birth weight infants in the neonatal intensive care unit who received drugs containing benzyl alcohol as a preservative. In these cases, benzyl alcohol dosages of 99 to 234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine (blood levels of benzyl alcohol were 0.61 to 1.378 mmol/L). Additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Preterm, low-birth weight infants may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known (deflazacort oral suspension contains 10.45 mg of benzyl alcohol per mL; deflazacort tablets do not contain benzyl alcohol).1

Oral administration of deflazacort (0, 0.1, 0.3, and 1.0 mg/kg/day) to juvenile rats from postnatal day 21 to 80 resulted in decreased body weight gain and adverse effects on skeletal development (including decreased cellularity of growth plate and altered bone distribution) and on lymphoid tissue (decreased cellularity). A no-effect dose was not identified. In addition, neurological and neurobehavioral abnormalities were observed at the mid and/or high dose. Plasma 21-desDFZ exposure (AUC) at the lowest dose tested (0.1 mg/kg/day) was lower than that in humans at the recommended human dose of deflazacort (0.9 mg/kg/day).1

Geriatric Use

DMD is largely a disease of children and young adults; therefore, there is no geriatric experience with deflazacort.1

Renal Impairment

No dose adjustment is required in patients with mild, moderate, or severe renal impairment.1

Hepatic Impairment

No dose adjustment is required in patients with mild or moderate hepatic impairment. There is no clinical experience in patients with severe hepatic impairment, and a dosing recommendation cannot be provided for patients with severe hepatic impairment. 1

Common Adverse Effects

The most common adverse reactions (≥10% for deflazacort and greater than placebo) are cushingoid appearance, increased weight, increased appetite, upper respiratory tract infection, cough, pollakiuria, hirsutism, central obesity, and nasopharyngitis.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

  • Moderate or strong CYP3A4 inhibitors: Give one-third of the recommended dosage of deflazacort.1

  • Avoid use of moderate or strong CYP3A4 inducers with deflazacort, as they may reduce efficacy.1

Dosage and administration

2.1       Dosing Information

The recommended oral dosage of Emflaza is approximately 0.9 mg/kg/day once daily.  If tablets are used, round up to the nearest possible dose. Any combination of the four Emflaza tablet strengths can be used to achieve this dose. If the oral suspension is used, round up to the nearest tenth of a milliliter (mL).

2.2       Discontinuation

Dosage of Emflaza must be decreased gradually if the drug has been administered for more than a few days [see Warnings and Precautions (5.1)].

2.3       Important Preparation and Administration Instructions

Emflaza Tablets and Oral Suspension can be taken with or without food.

Emflaza Tablets
Emflaza Tablets can be administered whole or crushed and taken immediately after mixing with applesauce.

Emflaza Oral Suspension
Shake Emflaza Oral Suspension well before administration.

Use only the oral dispenser provided with the product.  After withdrawing the appropriate dose into the oral dispenser, slowly add the Emflaza Oral Suspension into 3 to 4 ounces of juice or milk and mix well.  The dose should then be administered immediately.  Do not administer Emflaza with grapefruit juice [see Drug Interactions (7.1)]. 

Discard any unused Emflaza Oral Suspension remaining after 1 month of first opening the bottle.

2.4       Dosage Modification for Use with CYP3A4 Inhibitors and Inducers

CYP3A4 Inhibitors
Give one third of the recommended dosage when Emflaza is administered with moderate or strong CYP3A4 inhibitors. For example, a 36 mg per day dose would be reduced to a 12 mg per day dose when used with moderate or strong CYP3A4 inhibitors [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

CYP3A4 Inducers
Avoid use with moderate or strong CYP3A4 inducers with Emflaza [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

How supplied/storage and handling

16.1       How Supplied

Emflaza Tablets

  • 6 mg are white, round with “6” debossed on one side. They are supplied as follows:
    NDC 42998-501-01       Bottle of 100 tablets
  • 18 mg are white, round with “18” debossed on one side. They are supplied as follows:
    NDC 42998-502-03       Bottle of 30 tablets
  • 30 mg are white, oval with “30” debossed on one side. They are supplied as follows:
    NDC 42998-503-03       Bottle of 30 tablets
  • 36 mg are white, oval with “36” debossed on one side. They are supplied as follows:
    NDC 42998-504-03       Bottle of 30 tablets

Emflaza Oral Suspension

  • 22.75 mg/mL is a whitish colored suspension. Supplied as 13 mL in a 20 mL bottle packaged with two 1 mL oral dispensers.

      NDC 42998-505-21

16.2       Storage and Handling

Store at 20°C to 25°C (68°F to 77°F). Excursion permitted between 15°C to 30°C (59°F to 86°F). See USP controlled room temperature.

Discard any unused Emflaza Oral Suspension remaining after 1 month of first opening the bottle.

Emflaza Side Effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Serious and sometimes fatal infections may occur during treatment with deflazacort. Stop using this medicine and call your doctor right away if you have signs of infection such as:

  • sudden weakness or ill feeling, fever, chills, sore throat;
  • sores or white patches in your mouth or throat;
  • skin sores, warmth or redness under the skin;
  • stomach cramps, vomiting, diarrhea, bloody or tarry stools, rectal irritation;
  • pain or burning when you urinate;
  • night sweats; or
  • rapid weight loss.

Call your doctor at once if you have:

  • blurred vision, tunnel vision, eye pain, or seeing halos around lights;
  • unusual changes in mood or behavior, severe depression, trouble sleeping;
  • shortness of breath (even with mild exertion), swelling in your hands or feet;
  • the first sign of any skin rash, no matter how mild;
  • possible signs of long-term steroid use--weight gain (especially in your face or your upper back and torso); unusual bruising, slow wound healing, thinning skin, acne, increased body hair; weight changes; changes in menstrual periods; feeling tired, anxious, or irritable; or
  • signs of low adrenal gland hormones--worsening tiredness or muscle weakness, feeling light-headed, nausea, vomiting, loss of appetite, diarrhea, and weight loss.

Common side effects may include:

  • cold symptoms such as stuffy nose, sneezing, sore throat, cough;
  • increased growth of body hair;
  • increased appetite, weight gain; or
  • changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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