EMFLAZA SIDE EFFECTS

SIDE EFFECTS

The following serious adverse reactions are discussed in more detail in other sections:

• Alterations in Endocrine Function.
• Immunosuppression and Increased Risk of Infection.
• Alterations in Cardiovascular/Renal Function.
• Gastrointestinal Perforation.
• Behavioral and Mood Disturbances.
• Effects on Bones.
• Ophthalmic Effects.
• Immunizations.
• Serious Skin Rashes.
• Effects on Growth and Development.
• Myopathy.
• Kaposi’s Sarcoma.
• Risk of Serious Adverse Reactions in Infants because of Benzyl Alcohol Preservative.
• Thromboembolic Events.
• Anaphylaxis.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In Study 1 [see Clinical Studies], the adverse reactions that were associated with deflazacort treatment discontinuation, in decreasing order of frequency, were weight increased, obesity, cataract, and sleep disorder.

Most Common Adverse Reactions In Clinical Studies

Table 1 lists the adverse reactions that occurred in ≥ 5% of patients in the 0.9 mg/kg/day deflazacort-treated group and that occurred more frequently than in placebo patients in Study 1, which included patients with DMD between the ages of 5 and 15 years.

Table 1: Adverse Reactions that Occurred in ≥ 5% of Deflazacort-Treated Patients and Occurred More Frequently than in Placebo Patients with DMD (Study 1)

Common adverse reactions (≥ 5% of deflazacort-treated patients) that occurred over 52 weeks of exposure to deflazacort 0.9 mg/kg/day in Study 1 and at a higher rate than deflazacort 0.9 mg/kg/day in the 12-week placebo-controlled phase of the trial include Cushingoid appearance (60%), hirsutism (35%), weight increased (28%), erythema (28%), central obesity (25%), abdominal pain/abdominal pain upper (18% combined), pollakiuria (15%), constipation (10%), irritability (10%), abnormal behavior (9%), pyrexia (9%), back pain (7%), rash (7%), contusion (6%), nausea (6%), psychomotor hyperactivity (6%), epistaxis (6%), and skin striae (6%).

Study 1 also evaluated a higher dosage of deflazacort (1.2 mg/kg/day). Compared with the 0.9 mg/kg/day dosage, deflazacort 1.2 mg/kg/day over 52 weeks was associated with a higher incidence of certain adverse reactions, including Cushingoid appearance (69%), erythema (49%), hirsutism (37%), headache (34%), weight increased (32%), constipation (15%), abdominal pain upper (14%), skin striae (11%), acne (11%), and abdominal discomfort (8%). As there was no additional benefit with the 1.2 mg/kg/day dose of deflazacort, use of EMFLAZA 1.2 mg/kg/day is not recommended for the treatment of DMD.

In an additional clinical study of two years duration with extended follow-up (Study 2), many of the same adverse reactions were observed. In addition, musculoskeletal events associated with long-term steroid use were also observed, including muscle weakness, tendon disorder, and osteopenia.

Less Common Adverse Reactions Observed In Clinical Studies

Other adverse reactions (≥ 1% frequency in any deflazacort treatment group and greater than placebo) that were observed during the 12-week placebo-controlled phase of Study 1 are shown below.

Eye Disorders: Lacrimation increased

Gastrointestinal Disorders: Dyspepsia, nausea, gastrointestinal disorder

General Disorders and Administration Site Conditions: Thirst

Infections: Hordeolum, impetigo, influenza, otitis externa, pharyngitis, tooth abscess, urinary tract infection, 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, myalgia, neck mass, neck pain, pain in extremity

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: Chromaturia, dysuria, hypertonic bladder

Reproductive System and Breast Disorders: Testicular pain

Respiratory, Thoracic, and Mediastinal Disorders: Hypoventilation, rhinorrhea

Skin and Subcutaneous Tissue Disorders: Acne, alopecia, dermatitis acneiform

Vascular Disorders: Hot flush

Postmarketing Experience

The following adverse reactions have been reported during post-approval use of deflazacort worldwide or during post-approval use of other corticosteroids. These reactions are reported voluntarily from a population of uncertain size; therefore, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure.

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: Edema, impaired healing

Immune System Disorders: Hypersensitivity including anaphylaxis

Metabolism and Nutrition Disorders: Impaired carbohydrate tolerance with increased requirement for anti-diabetic therapy, negative protein and calcium balance, potassium loss and hypokalemic alkalosis when co-administered with beta 2-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 intra-cranial pressure with papilledema in children (pseudotumor cerebri) usually after treatment withdrawal, 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.

SRC: NLM .