Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied AGAMREE oral suspension is an orange flavored homogeneous white to off-white suspension, containing 40 mg/mL of vamorolone. AGAMREE is supplied as 100 mL in 125 mL glass bottle packaged with one bottle adapter, two 5 mL oral syringes, and an Instructions for Use: NDC 69616-264-38. 16.2 Storage and Handling Store the bottle upright at room temperature between 20°C to 25°C (68°F to 77°F). Excursions permitted between 15°C to 30°C (59°F to 86°F) in the original carton. See USP controlled room temperature. After opening, store the bottle upright in a refrigerator 2°C to 8°C (36°F to 46°F). Do not freeze. Discard any unused AGAMREE oral suspension remaining after 3 months of first opening the bottle.; 16.1 How Supplied AGAMREE oral suspension is an orange flavored homogeneous white to off-white suspension, containing 40 mg/mL of vamorolone. AGAMREE is supplied as 100 mL in 125 mL glass bottle packaged with one bottle adapter, two 5 mL oral syringes, and an Instructions for Use: NDC 69616-264-38.; Principal Display Panel – 100 mL Carton Label NDC 69616-264-38 100 mL AGAMREE ® (vamorolone) Oral suspension Rx only 40 mg/mL For Oral Administration Only Catalyst Pharmaceuticals, Inc. label-01; Principal Display Panel – 100 mL Carton Label NDC 69616-265-38 100 mL AGAMREE ® (vamorolone) Oral suspension Rx only 40 mg/mL For Oral Administration Only Date of first Opening: _______ / ______ / _______ label-02
- 16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied AGAMREE oral suspension is an orange flavored homogeneous white to off-white suspension, containing 40 mg/mL of vamorolone. AGAMREE is supplied as 100 mL in 125 mL glass bottle packaged with one bottle adapter, two 5 mL oral syringes, and an Instructions for Use: NDC 69616-264-38. 16.2 Storage and Handling Store the bottle upright at room temperature between 20°C to 25°C (68°F to 77°F). Excursions permitted between 15°C to 30°C (59°F to 86°F) in the original carton. See USP controlled room temperature. After opening, store the bottle upright in a refrigerator 2°C to 8°C (36°F to 46°F). Do not freeze. Discard any unused AGAMREE oral suspension remaining after 3 months of first opening the bottle.
- 16.1 How Supplied AGAMREE oral suspension is an orange flavored homogeneous white to off-white suspension, containing 40 mg/mL of vamorolone. AGAMREE is supplied as 100 mL in 125 mL glass bottle packaged with one bottle adapter, two 5 mL oral syringes, and an Instructions for Use: NDC 69616-264-38.
- Principal Display Panel – 100 mL Carton Label NDC 69616-264-38 100 mL AGAMREE ® (vamorolone) Oral suspension Rx only 40 mg/mL For Oral Administration Only Catalyst Pharmaceuticals, Inc. label-01
- Principal Display Panel – 100 mL Carton Label NDC 69616-265-38 100 mL AGAMREE ® (vamorolone) Oral suspension Rx only 40 mg/mL For Oral Administration Only Date of first Opening: _______ / ______ / _______ label-02
Overview
AGAMREE (vamorolone) oral suspension contains vamorolone, a corticosteroid. Vamorolone [17α,21-dihydroxy-16α-methyl-pregna-1,4,9(11)-triene-3,20-dione] is a white to off-white powder with a molecular formula of C 22 H 28 O 4 and a molecular weight of 356.46 g/mol. Its structural formula is: Vamorolone is freely soluble in methanol and dioxane and sparingly soluble in ethanol and acetone. AGAMREE for oral administration is available as an oral suspension in a strength of 40 mg/mL. The oral suspension contains vamorolone and the following inactive ingredients: citric acid (monohydrate), disodium phosphate, glycerin, hydrochloric acid (for pH adjustment), orange flavor, sodium benzoate, sucralose, water, and xanthan gum. Structural Formula
Indications & Usage
AGAMREE is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 2 years of age and older. AGAMREE is a corticosteroid indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 2 years of age and older. ( 1 )
Dosage & Administration
The recommended dosage is 6 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 300 mg for patients weighing more than 50 kg. ( 2.2 ) In patients with mild to moderate hepatic impairment, the recommended dosage is 2 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 100 mg for patients weighing more than 50 kg. ( 2.3 ) Decrease dosage gradually when administered for more than one week. ( 2.7 ) 2.1 Assessments Prior to First Dose of AGAMREE Administer all immunizations according to immunization guidelines prior to starting AGAMREE. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting AGAMREE [see Warnings and Precautions ( 5.8 )]. 2.2 Dosing Information The recommended dosage of AGAMREE is 6 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 300 mg for patients weighing more than 50 kg. Some patients may respond to a dose of 2 mg/kg daily. Doses may be titrated down to 2 mg/kg/day as needed, based on individual tolerability. 2.3 Recommended Dosage for Hepatic Impairment The recommended dosage of AGAMREE in patients with mild (Child-Pugh A) to moderate (Child-Pugh B) hepatic impairment is 2 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 100 mg for patients weighing more than 50 kg [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )] . Doses may be titrated down based on individual tolerability. 2.4 Important Preparation and Administration Instructions Shake AGAMREE oral suspension well for about 30 seconds before administration. Use only the oral syringe provided with the product. After withdrawing the appropriate dose into the oral syringe, dispense directly into the mouth. Discard any unused AGAMREE oral suspension remaining after 3 months of first opening the bottle. 2.5 Switching from Corticosteroid Treatment to AGAMREE Patients can be switched from oral corticosteroid treatment (such as prednisone or deflazacort) to AGAMREE without treatment interruption or period of prior corticosteroid dosage reduction to minimize the risk for adrenal insufficiency. Patients switching after long-term treatment with oral corticosteroids should start AGAMREE at a dosage of 6 mg/kg/day. 2.6 Dosage Modification for Use with Strong CYP3A4 Inhibitors The recommended dosage of AGAMREE when administered with strong CYP3A4 inhibitors is 4 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 200 mg for patients weighing more than 50 kg [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )]. Doses may be titrated down based on individual tolerability. 2.7 Discontinuation Dosage of AGAMREE must be decreased gradually if the drug has been administered for more than one week [see Warnings and Precautions ( 5.1 )].
Warnings & Precautions
Alterations in Endocrine Function: Hypothalamic-pituitary-adrenal axis suppression, cushingoid features, and hyperglycemia can occur. Monitor patients for these conditions with chronic use of AGAMREE. ( 2.7 , 5.1 ) Immunosuppression and Increased Risk of Infection: Increased risk of new infections, exacerbation, dissemination, or reactivation of latent infections, which can be severe and at times fatal; signs and symptoms of infections may be masked. ( 5.2 ) Alterations in Cardiovascular/Renal Function: Monitor for elevated blood pressure and monitor sodium and potassium levels in patients chronically treated with AGAMREE. ( 5.3 ) Gastrointestinal Perforation: Increased risk in patients with certain GI disorders; signs and symptoms may be masked. ( 5.4 ) Behavioral and Mood Disturbances: May include euphoria, insomnia, mood swings, personality changes, severe depression, and psychosis. ( 5.5 ) Effects on Bones: Monitor for decreases in bone mineral density with chronic use of AGAMREE. ( 5.6 ) Ophthalmic Effects: May include cataracts, infections, and glaucoma; monitor intraocular pressure in patients chronically treated with AGAMREE. ( 5.7 ) Vaccination: Do not administer live or live attenuated vaccines to patients receiving immunosuppressive doses of corticosteroids. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting AGAMREE. ( 5.8 ) 5.1 Alterations in Endocrine Function Corticosteroids, such as AGAMREE, can cause serious and life-threatening alterations in endocrine function, especially with chronic use. Monitor patients receiving AGAMREE for Cushing's syndrome, hyperglycemia, and adrenal insufficiency after AGAMREE 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. Risk of Adrenal Insufficiency Following Withdrawal AGAMREE produces reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, with the potential for the development of secondary adrenal insufficiency after withdrawal. Acute adrenal insufficiency can occur if AGAMREE is withdrawn abruptly, and could be fatal. The degree and duration of adrenocortical insufficiency produced is variable among patients and depends on the dose and duration of therapy. The risk of adrenal insufficiency is reduced by gradually tapering the dose when withdrawing treatment. The insufficiency may persist, however, for months after discontinuation of prolonged therapy; therefore, in any situation of stress occurring during that period of discontinuation, supplementation with a systemic corticosteroid is recommended. For patients already taking corticosteroids during times of stress, the dosage may need to be increased. 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 too low corticosteroid levels. Cushing's Syndrome Cushing's syndrome (hypercortisolism) occurs with prolonged exposure to exogenous corticosteroids, including AGAMREE, and 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. 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 in patients treated with AGAMREE. For patients with hyperglycemia, anti-diabetic treatment should be initiated or adjusted accordingly. 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 AGAMREE and levothyroxine is required, administration of AGAMREE should precede the initiation of levothyroxine therapy to reduce the risk of adrenal crisis. 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. 5.2 Immunosuppression and Increased Risk of Infection Corticosteroids, including AGAMREE, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. Corticosteroids can: reduce resistance to new infections exacerbate existing infections increase the risk of disseminated infections increase the risk of reactivation or exacerbation of latent infections mask some signs of infection Corticosteroid-associated infections can be mild but can be severe, and at times fatal. The rate of infectious complications increases with increasing corticosteroid dosages. Monitor for the development of infection and consider AGAMREE withdrawal or dosage reduction as needed. Tuberculosis If AGAMREE is used to treat a condition in patients with latent tuberculosis or tuberculin reactivity, reactivation of tuberculosis may occur. Closely monitor such patients for reactivation. During prolonged AGAMREE therapy, patients with latent tuberculosis or tuberculin reactivity should receive chemoprophylaxis. Varicella Zoster and Measles Viral Infections Varicella and measles can have a serious or even fatal course in non-immune patients taking corticosteroids, including AGAMREE. In corticosteroid-treated patients who have not had these diseases or are non-immune, particular care should be taken to avoid exposure to varicella and measles. If an AGAMREE-treated patient is exposed to varicella, prophylaxis with varicella zoster immunoglobulin may be indicated. If varicella develops, treatment with antiviral agents may be considered. If an AGAMREE-treated patient is exposed to measles, prophylaxis with immunoglobulin may be indicated. Hepatitis B Virus Reactivation Hepatitis B virus reactivation can occur in patients who are hepatitis B carriers treated with immunosuppressive dosages of corticosteroids, including AGAMREE. Reactivation can also occur infrequently in corticosteroid-treated patients who appear to have resolved hepatitis B infection. Screen patients for hepatitis B infection before initiating immunosuppressive (e.g., prolonged) treatment with AGAMREE. For patients who show evidence of hepatitis B infection, recommend consultation with physicians with expertise in managing hepatitis B regarding monitoring and consideration for hepatitis B antiviral therapy. Fungal Infections Corticosteroids, including AGAMREE, may exacerbate systemic fungal infections; therefore, avoid AGAMREE use in the presence of such infections unless AGAMREE is needed to control drug reactions. For patients on chronic AGAMREE therapy who develop systemic fungal infections, AGAMREE withdrawal or dosage reduction is recommended. Amebiasis Corticosteroids, including AGAMREE, may activate latent amebiasis. Therefore, it is recommended that latent amebiasis or active amebiasis be ruled out before initiating AGAMREE in any patients who have spent time in the tropics or patients with unexplained diarrhea. Strongyloides Infestation Corticosteroids, including AGAMREE, should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, 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. Cerebral Malaria Avoid corticosteroids, including AGAMREE, in patients with cerebral malaria. 5.3 Alterations in Cardiovascular/Renal Function Corticosteroids, including AGAMREE, 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. AGAMREE should be used with caution in patients with congestive heart failure, hypertension, or renal insufficiency. Literature reports suggest an association between use of corticosteroids and left free wall rupture after a recent myocardial infarction; therefore, therapy with AGAMREE should be used with great caution in these patients. 5.4 Gastrointestinal Perforation There is an increased risk of gastrointestinal perforation with use of corticosteroids 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. Avoid AGAMREE if there is a probability of impending perforation, abscess, or other pyogenic infections; diverticulitis; fresh intestinal anastomoses; or active or latent peptic ulcer. 5.5 Behavioral and Mood Disturbances Potentially severe psychiatric adverse reactions may occur with systemic corticosteroids, including AGAMREE. 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. In Study 1, psychiatric adverse reactions were reported in 21% of patients on AGAMREE 6 mg/kg, 10% of patients on AGAMREE 2 mg/kg, and 14% of patients on placebo. Psychiatric adverse reactions reported on AGAMREE resolved without requiring treatment or drug discontinuation. In adults, psychiatric adverse reactions with corticosteroids usually involve hypomanic or manic symptoms (e.g., euphoria, insomnia, mood swings) during treatment and depressive episodes after discontinuation of treatment. In children receiving corticosteroids, psychiatric adverse reactions usually involve hyperactivity symptoms (e.g., irritability, aggressive behavior, increased frequency of tantrums, and mood swings) and sleep disorder during 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. 5.6 Effects on Bones Decreased Bone Mineral Density Corticosteroids, such as AGAMREE, 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 AGAMREE. Avascular Necrosis Corticosteroids may cause avascular necrosis. 5.7 Ophthalmic Effects The use of corticosteroids, such as AGAMREE, 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. Intraocular pressure may become elevated in some patients taking corticosteroids. If treatment with AGAMREE is continued for more than 6 weeks, monitor intraocular pressure. 5.8 Immunizations Administer all immunizations according to immunization guidelines prior to starting AGAMREE. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting AGAMREE. Patients on AGAMREE may receive concurrent vaccinations, except for live-attenuated or live vaccines. 5.9 Effects on Growth and Development Long-term use of corticosteroids, including AGAMREE, can have negative effects on growth and development in children. 5.10 Myopathy Patients receiving corticosteroids 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. Clinical improvement or recovery after stopping corticosteroids may require weeks to years. 5.11 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 of Kaposi's sarcoma. 5.12 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 AGAMREE with caution in patients who have or may be predisposed to thromboembolic disorders. 5.13 Anaphylaxis Rare instances of anaphylaxis have occurred in patients receiving corticosteroid therapy.
Contraindications
AGAMREE is contraindicated in patients with known hypersensitivity to vamorolone or to any of the inactive ingredients of AGAMREE. Instances of hypersensitivity, including anaphylaxis, have occurred in patients receiving corticosteroid therapy [see Warnings and Precautions ( 5.13 )]. Hypersensitivity to vamorolone or any of the inactive ingredients in AGAMREE ( 4 )
Adverse Reactions
The following serious adverse reactions are discussed in more detail in other sections: Alterations in Endocrine Function [see Warnings and Precautions ( 5.1 )] Immunosuppression and Increased Risk of Infection [see Warnings and Precautions ( 5.2 )] Alterations in Cardiovascular/Renal Function [see Warnings and Precautions ( 5.3 )] Gastrointestinal Perforation [see Warnings and Precautions ( 5.4 )] Behavioral and Mood Disturbances [see Warnings and Precautions ( 5.5 )] Effects on Bones [see Warnings and Precautions ( 5.6 )] Ophthalmic Effects [see Warnings and Precautions ( 5.7 )] Immunizations [see Warnings and Precautions ( 5.8 )] Effects on Growth and Development [see Warnings and Precautions ( 5.9 )] Myopathy [see Warnings and Precautions ( 5.10 )] Kaposi's Sarcoma [see Warnings and Precautions ( 5.11 )] Thromboembolic Events [see Warnings and Precautions ( 5.12 )] Anaphylaxis [see Warnings and Precautions ( 5.13 )] The most common adverse reactions (>10% for AGAMREE and greater than placebo) are cushingoid features, psychiatric disorders, vomiting, weight increased, and vitamin D deficiency. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Catalyst Pharmaceuticals, Inc. at 1-844-347-3277 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. Common Adverse Reactions in Clinical Studies Table 1 lists the adverse reactions that occurred in ≥ 5% of the patients treated with AGAMREE 6 mg/kg/day (N=28) or AGAMREE 2 mg/kg/day (N=30) and that occurred more frequently than in the patients who received placebo (N=29) in Study 1 [see Clinical Studies ( 14 )] , which was 24 weeks and included patients with DMD between the ages of 4 and 7 years. Table 1: Adverse Reactions in Patients with DMD that Occurred in ≥ 5% of Patients Treated with AGAMREE and More Frequently than in Patients Who Received Placebo During 24 Weeks (Study 1) 1 Includes the following adverse reactions that occurred more frequently in the AGAMREE group than in placebo: abnormal behavior, aggression, agitation, anxiety, irritability, mood altered, sleep disorder, and stereotypy. Adverse Reaction AGAMREE 2 mg/kg/d (N=30) % AGAMREE 6 mg/kg/d (N=28) % Placebo (N=29) % Cushingoid Features 7 29 0 Psychiatric disorders 1 7 21 14 Vomiting 17 14 7 Weight increased 0 11 3 Vitamin D deficiency 7 11 0 Cough 10 7 3 Headache 7 7 3 Diarrhea 3 7 3 Increased appetite 3 7 3 Rhinitis 3 7 3 In a separate open-label safety study of pediatric patients aged 2 to less than 4 years (n=16) and pediatric patients aged 7 to less than 18 years (n=16) with DMD, adverse reactions were similar to those seen in the Study 1 pediatric patients.
Drug Interactions
Strong CYP3A4 inhibitors: The maximum recommended daily dose is 4 mg/kg up to a maximum daily dosage of 200 mg for patients weighing more than 50 kg. ( 2.6 , 7.1 ) 7.1 Effect of Other Drugs on Vamorolone Co-administration of AGAMREE with itraconazole, a strong CYP3A4 inhibitor, increases vamorolone exposure [see Clinical Pharmacology ( 12.3 )] . Reduce the dosage of AGAMREE in patients when strong CYP3A4 inhibitors are used concomitantly [see Dosage and Administration ( 2.6 )] . No dosage adjustments are required when AGAMREE is concomitantly administered with moderate or weak CYP3A4 inhibitors.
Storage & Handling
16.2 Storage and Handling Store the bottle upright at room temperature between 20°C to 25°C (68°F to 77°F). Excursions permitted between 15°C to 30°C (59°F to 86°F) in the original carton. See USP controlled room temperature. After opening, store the bottle upright in a refrigerator 2°C to 8°C (36°F to 46°F). Do not freeze. Discard any unused AGAMREE oral suspension remaining after 3 months of first opening the bottle.
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