Deflazacort

Deflazacort may be found in some form under the following brand names:

• Emflaza

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.

Usual Adult Dose for Muscular Dystrophy:

0.9 mg/kg orally once a day

Comments:
-If tablets are used, round up to the nearest possible dose
-If oral suspension is used, round up to the nearest tenth of a milliliter (mL).
-If this drug is administered for more than a few days, do not abruptly discontinue.
-Dose modifications are recommended for use with CYP450 3A4 inhibitors and inducers (see dose adjustments).

Use: Treatment of Duchenne muscular dystrophy.

Usual Pediatric Dose for Muscular Dystrophy:

5 years or older: 0.9 mg/kg orally once a day

Comments:
-If tablets are used, round up to the nearest possible dose
-If oral suspension is used, round up to the nearest tenth of a milliliter (mL).
-If this drug is administered for more than a few days, do not abruptly discontinue.
-Dose modifications are recommended for use with CYP450 3A4 inhibitors and inducers (see dose adjustments).

Use: Treatment of Duchenne muscular dystrophy.

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

Administration

• Warn patients and/or caregivers to not stop taking deflazacort abruptly or without first checking with their healthcare providers as there may be a need for gradual dose reduction to decrease the risk of adrenal insufficiency.1

• Deflazacort may be taken with or without food.1

• Deflazacort tablets may be taken whole or crushed and taken immediately after mixing with applesauce. 1

• Deflazacort oral suspension must be shaken well prior to measuring out each dose with the enclosed oral dispenser.1

• The deflazacort oral suspension dose may be placed in 3–4 ounces of juice or milk, mixed thoroughly, and immediately administered. Do not take with grapefruit juice.1

• Discard any unused deflazacort oral suspension remaining after 1 month of first opening the bottle.1

Increased Risk of Infection

• Tell patients and/or caregivers to inform their healthcare provider if the patient has had recent or ongoing infections or if they have recently received a vaccine. Medical advice should be sought immediately if the patient develops fever or other signs of infection. Patients and/or caregivers should be made aware that some infections can potentially be severe and fatal.1

• Warn patients who are on corticosteroids to avoid exposure to chickenpox or measles and to alert their healthcare provider immediately if they are exposed.1

Alterations in Cardiovascular/Renal Function

• Inform patients and/or caregivers that deflazacort can cause an increase in blood pressure and water retention. If this occurs, dietary salt restriction and potassium supplementation may be needed.1

Behavioral and Mood Disturbances

• Advise patients and/or caregivers about the potential for severe behavioral and mood changes with deflazacort and encourage them to seek medical attention if psychiatric symptoms develop.1

Decreases in Bone Mineral Density

• Advise patients and/or caregivers about the risk of osteoporosis with prolonged use of deflazacort, which can predispose the patient to vertebral and long bone fractures.1

Ophthalmic Effects

• Inform patients and/or caregivers that deflazacort may cause cataracts or glaucoma and advise monitoring if corticosteroid therapy is continued for more than 6 weeks.1

Vaccination

• Advise patients and/or caregivers that the administration of live or live attenuated vaccines are not recommended. Inform them that killed or inactivated vaccines may be administered, but the responses cannot be predicted.1

Serious Skin Rashes

• Instruct patients and/or caregivers to seek medical attention at the first sign of a rash.1

Drug Interactions

• Certain medications can cause an interaction with deflazacort. Advise patients and/or caregivers to inform their healthcare provider of all the medicines the patient is taking, including over-the-counter medicines (such as insulin, aspirin or other NSAIDS), dietary supplements, and herbal products. Inform patients and/or caregivers that alternate therapy, dosage adjustment, and/or special test(s) may be needed during the treatment.1

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For deflazacort, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to deflazacort or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of deflazacort in children 5 years of age and older. However, safety and efficacy have not been established in children younger than 5 years of age. Because of deflazacort oral suspension containing benzyl alcohol, use in children younger than 5 years of age is not recommended.

Geriatric

No information is available on the relationship of age to the effects of deflazacort in geriatric patients.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking deflazacort, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using deflazacort with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Adenovirus Vaccine Type 4, Live
• Adenovirus Vaccine Type 7, Live
• Bacillus of Calmette and Guerin Vaccine, Live
• Desmopressin
• Influenza Virus Vaccine, Live
• Measles Virus Vaccine, Live
• Mumps Virus Vaccine, Live
• Poliovirus Vaccine, Live
• Rotavirus Vaccine, Live
• Rubella Virus Vaccine, Live
• Smallpox Vaccine
• Typhoid Vaccine
• Varicella Virus Vaccine
• Yellow Fever Vaccine

Using deflazacort with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac
• Acemetacin
• Aldesleukin
• Amtolmetin Guacil
• Aprepitant
• Atazanavir
• Bemiparin
• Boceprevir
• Bosentan
• Bromfenac
• Bufexamac
• Bupropion
• Carbamazepine
• Celecoxib
• Choline Salicylate
• Ciprofloxacin
• Clarithromycin
• Clonixin
• Cobicistat
• Conivaptan
• Crizotinib
• Cyclosporine
• Dexibuprofen
• Dexketoprofen
• Diclofenac
• Diflunisal
• Diltiazem
• Dipyrone
• Dronedarone
• Droxicam
• Efavirenz
• Enzalutamide
• Erythromycin
• Etodolac
• Etofenamate
• Etoricoxib
• Etravirine
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Floctafenine
• Fluconazole
• Flufenamic Acid
• Flurbiprofen
• Fluvoxamine
• Fosphenytoin
• Ibuprofen
• Idelalisib
• Imatinib
• Indinavir
• Indomethacin
• Itraconazole
• Ketoconazole
• Ketoprofen
• Ketorolac
• Lopinavir
• Lornoxicam
• Loxoprofen
• Lumacaftor
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Mitotane
• Modafinil
• Morniflumate
• Nabumetone
• Nadroparin
• Nafcillin
• Naproxen
• Nefazodone
• Nelfinavir
• Nepafenac
• Niflumic Acid
• Nilotinib
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Phenobarbital
• Phenylbutazone
• Phenytoin
• Piketoprofen
• Piroxicam
• Posaconazole
• Pranoprofen
• Primidone
• Proglumetacin
• Propyphenazone
• Proquazone
• Rifampin
• Ritonavir
• Rofecoxib
• Salicylic Acid
• Salsalate
• Saquinavir
• Sodium Salicylate
• St John's Wort
• Sulindac
• Telaprevir
• Telithromycin
• Tenoxicam
• Tiaprofenic Acid
• Tolfenamic Acid
• Tolmetin
• Valdecoxib
• Verapamil
• Voriconazole

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using deflazacort with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use deflazacort, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other Medical Problems

The presence of other medical problems may affect the use of deflazacort. Make sure you tell your doctor if you have any other medical problems, especially:

• Adrenal problems or
• Amebiasis, inactive or
• Blood clotting problems or
• Cataracts or
• Congestive heart failure or
• Cushing's syndrome (adrenal gland problem) or
• Diabetes or
• Eye infection (eg, herpes infection of the eyes) or
• Glaucoma or
• Heart attack, recent or
• Hepatitis B infection or
• Hyperglycemia (high blood sugar) or
• Hypertension (high blood pressure) or
• Infection (eg, bacterial, virus, or fungal) or
• Kidney disease, severe or
• Mood changes, including depression or
• Myasthenia gravis (severe muscle weakness) or
• Osteoporosis (weak bones) or
• Peptic ulcer, active or history of or
• Personality changes or
• Pheochromocytoma (adrenal tumor) or
• Stomach or intestinal problems (eg, diverticulitis, ulcerative colitis) or
• Thyroid problems or
• Tuberculosis, inactive or
• Weak immune system (eg, Kaposi sarcoma)—Use with caution. May make these conditions worse.

• Fungal infections—Should not be used in patients with these conditions.

Deflazacort is a corticosteroid prodrug; its active metabolite, 21-desDFZ, acts on the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects. The precise mechanism by which deflazacort exerts its therapeutic effects in patients with Duchenne muscular dystrophy is unknown.

Metabolism

Rapidly converted by esterases to 21-desDFZ (active metabolite); 21-desDFZ metabolized by CYP3A4 to several metabolites (inactive)

Excretion

Urine (~68%; 18% as 21-desDFZ)

Time to Peak

1 hour (range: 0.25 to 2 hours); delayed by 1 hour with a high-fat meal

Protein Binding

~40%

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Oral: Administer with or without food.

Tablets: Administer whole or may crush and mix with applesauce (administer applesauce mixture immediately).

Suspension: Shake well; measure prescribed dose with provided dispenser, mix thoroughly with 3 to 4 ounces of juice or milk and administer immediately. Do not mix or administer with grapefruit juice.

Concerns related to adverse effects:

• Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully.

• Anaphylaxis: Rare cases of anaphylaxis have occurred in patients receiving corticosteroids.

• Immunosuppression: Prolonged use of corticosteroids may increase the incidence of secondary infection, cause activation of latent infections, mask acute infection (including fungal infections), prolong or exacerbate existing infections, or limit response to killed or inactivated vaccines. Exposure to chickenpox or measles should be avoided. Close observation is required in patients with latent tuberculosis and/or TB reactivity; restrict use in active TB (only in conjunction with antituberculosis treatment). Avoid use in patients with active ocular herpes simplex. Hepatitis B reactivation can occur in patients who are hepatitis B carriers. Amebiasis should be ruled out in any patient with recent travel to tropic climates or unexplained diarrhea prior to initiation of corticosteroids. Use with extreme caution in patients with Strongyloides infections; hyperinfection, dissemination and fatalities have occurred.

• Kaposi sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi sarcoma (case reports); if noted, discontinuation of therapy should be considered (Goedert 2002).

• Myopathy: Acute myopathy has been reported with high dose corticosteroids, usually in patients with neuromuscular transmission disorders; may involve ocular and/or respiratory muscles; monitor creatinine kinase; recovery may be delayed.

• Ocular effects: Prolonged use may cause posterior subcapsular cataracts, glaucoma (with possible nerve damage), and increased intraocular pressure. Consider routine eye exams in chronic users.

• Psychiatric disturbances: Corticosteroid use may cause psychiatric disturbances, including depression, euphoria, insomnia, mood swings, and personality changes. Preexisting psychiatric conditions may be exacerbated by corticosteroid use.

• Skin reactions: Toxic epidermal necrolysis has been reported within 8 weeks of starting treatment; discontinue at first sign of rash, unless rash is clearly not drug-related.

• Thromboembolic events: Higher cumulative doses of corticosteroids have been associated with an increased risk of thromboembolism. Use caution in patients with a history of or at increased risk for thromboembolic disorders.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with heart failure and/or hypertension; use has been associated with fluid retention, electrolyte disturbances, and hypertension. Use with caution following acute MI; corticosteroids have been associated with myocardial rupture.

• Diabetes: Use with caution in patients with diabetes mellitus; may alter glucose production/regulation leading to hyperglycemia.

• Gastrointestinal disease: Use with caution in patients with GI diseases (diverticulitis, fresh intestinal anastomoses, ulcerative colitis, active or latent peptic ulcer, abscess or other pyogenic infections) due to perforation risk. Avoid use if there is a probability of impending perforation, abscess, or other pyogenic infection.

• Hepatic impairment: Use with caution in patients with severe hepatic impairment.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis; exacerbation of symptoms has occurred especially during initial treatment with corticosteroids.

• Osteoporosis: Use with caution in patients with or who are at risk for osteoporosis; high doses and/or long-term use of corticosteroids have been associated with increased bone loss, osteoporotic fractures, and avascular necrosis.

• Pheochromocytoma: Use with caution in patients with pheochromocytoma; cases of pheochromocytoma crisis, which can be fatal, have been reported with corticosteroids.

• Renal impairment: Use with caution in renal impairment; fluid retention may occur.

• Seizure disorders: Use with caution in patients with a history of seizure disorder.

• Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid ones.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric: May affect growth velocity; growth should be routinely monitored in pediatric patients.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP 1997; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Other warnings/precautions:

• Discontinuation of therapy: Withdraw therapy with gradual tapering of dose.

• Stress: Patients may require higher doses when subject to stress (ie, trauma, surgery, severe infection).

5 years or older: 0.9 mg/kg orally once a day

Comments:
-If tablets are used, round up to the nearest possible dose
-If oral suspension is used, round up to the nearest tenth of a milliliter (mL).
-If this drug is administered for more than a few days, do not abruptly discontinue.
-Dose modifications are recommended for use with CYP450 3A4 inhibitors and inducers (see dose adjustments).

Use: Treatment of Duchenne muscular dystrophy.

No adjustment recommended

Data not available