Vamorolone
FDA Drug Information • Also known as: Agamree
- Brand Names
- Agamree
- Dosage Form
- SUSPENSION
- Product Type
- DRUG FOR FURTHER PROCESSING
Description
11 DESCRIPTION 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
What Is Vamorolone Used For?
1 INDICATIONS AND 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 and Administration
2 DOSAGE AND 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 )].
Side Effects (Adverse Reactions)
6 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
7 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.
Contraindications
4 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 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary AGAMREE is indicated for use for the treatment of DMD, which is a disease of young male patients. However, corticosteroids in general 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 data on the use of AGAMREE during pregnancy. 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 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 clinical studies. Intrauterine growth restriction and decreased birth weight appear to be dose-related; however, the underlying maternal condition may also contribute to these risks (see Clinical Considerations and Data ) . Animal reproduction studies have not been conducted with AGAMREE. Animal reproduction studies conducted with 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. 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. Clinical Considerations Fetal/Neonatal Adverse Reactions Hypoadrenalism may occur in infants born to mothers receiving corticosteroids during pregnancy. Infants should be carefully observed for signs of hypoadrenalism, such as poor feeding, irritability, weakness, and vomiting, and...
Overdosage
10 OVERDOSAGE Treatment of acute overdosage of vamorolone is by immediate supportive and symptomatic therapy. Gastric lavage or emesis can be considered.
How Supplied
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.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.