AGAMREE Dosage & Rx Info | Uses, Side Effects

Agamree Generic Name & Formulations

Legal Class

General Description

Vamorolone 40mg/mL; oral susp; orange-flavor.

Pharmacological Class

Corticosteroid.

How Supplied

Susp (100mL)—1 (w. oral syringes)

Storage

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.

Manufacturer

Catalyst Pharmaceuticals

Generic Availability

Mechanism of Action

Vamorolone is a corticosteroid that acts through the glucocorticoid receptor to exert antiinflammatory and immunosuppressive effects. The precise mechanism by which vamorolone exerts its effect in patients with DMD is unknown.

Agamree Indications

Indications

Duchenne muscular dystrophy (DMD).

Agamree Dosage and Administration

Adults and Children

<2yrs: not established. Shake well before administration. Use only the oral syringe provided. Take with a meal. ≥2yrs: 6mg/kg orally once daily (for >50kg: up to max 300mg/day). Doses may be titrated down to 2mg/kg/day, as needed based on tolerability. Mild to moderate hepatic impairment: 2mg/kg/day (for >50kg: up to max 100mg/day); may titrate down based on tolerability. Concomitant strong CYP3A4 inhibitors: 4mg/kg/day (for >50kg: up to max 200mg/day); may titrate down based on tolerability. Switching from oral corticosteroid treatment (eg, prednisone or deflazacort): can switch without treatment interruption or dose reduction. If switching after long-term oral corticosteroid therapy: initiate at 6mg/kg/day.

Agamree Contraindications

Not Applicable

Agamree Boxed Warnings

Not Applicable

Agamree Warnings/Precautions

Warnings/Precautions

Increased risk of infection (eg, viral, bacterial, fungal, protozoan, helminthic); may mask signs/symptoms. If exposed to chickenpox or measles, consider prophylactic passive immune therapy; if varicella develops, consider treatment with antivirals. Hepatitis B virus reactivation: screen for hepatitis B infection prior to initiation. Systemic fungal infections, active ocular herpes simplex: not recommended. Latent or acute amebiasis. Strongyloides infestation. Cushing’s syndrome. Hyperglycemia. Hypopituitarism. Adrenal insufficiency. Congenital adrenal hyperplasia. Thyroid disorders. Pheochromocytoma. Supplement with additional steroids during period of stress. CHF. Hypertension. Renal insufficiency. Recent MI. Risk for GI perforation. Peptic ulcer. Diverticulitis. Intestinal anastomoses. Ulcerative colitis. Psychotic tendencies. Risk for osteoporosis; monitor bone mineral density (esp. on long-term therapy). Complete all immunizations according to guidelines prior to initiation. Myasthenia gravis. Thromboembolic disorders. Monitor weight, growth, BP, fluid, electrolyte balance, blood glucose, and IOP (if therapy >6weeks). Avoid abrupt cessation. Severe hepatic impairment. Pregnancy. Nursing mothers.

Agamree Pharmacokinetics

Absorption

Median T_max: ~2 hours (range, 0.5–5 hours).

Distribution

Apparent volume of distribution: 162 L. Plasma protein bound: 88.1% (in vitro).

Metabolism

Metabolized via multiple phase 1 and 2 metabolic pathways (eg, glucuronidation, hydroxylation, reduction). Metabolism is mediated via CYP3A4/5, CYP2C8, UGT1A3, UGT2B7, and UGT2B17.

Elimination

Renal (~48%), fecal (~30%). Half-life: ~2 hours.

Agamree Interactions

Interactions

Potentiated by strong CYP3A4 inhibitors (eg, itraconazole); reduce dose. Concomitant levothyroxine: give corticosteroid first. May need to adjust dose of antidiabetic agents. Increased risk of acute myopathy with concomitant neuromuscular blockers (eg, pancuronium).

Agamree Adverse Reactions

Adverse Reactions

Cushingoid features, psychiatric disorders, vomiting, weight increase, vitamin D deficiency, cough, headache; HPA axis suppression, adrenocortical insufficiency, avascular necrosis, posterior subcapsular cataracts, glaucoma, Kaposi's sarcoma; rare: anaphylaxis.

Agamree Clinical Trials

Clinical Trials

The approval was based on data from the randomized, double-blind, placebo- and active-controlled phase 2b VISION-DMD study (ClinicalTrials.gov Identifier: NCT03439670), which evaluated the efficacy and safety of vamorolone in ambulant boys 4 to less than 7 years of age with DMD. Patients (N=121) were randomly assigned to receive vamorolone orally at daily doses of 2mg/kg or 6mg/kg, prednisone 0.75mg/kg/day, or placebo.

Treatment with vamorolone 6mg/kg/day met the primary endpoint demonstrating superiority in change from baseline in time to stand test (TTSTAND) velocity at 24 weeks vs placebo (treatment difference, 0.06 [95% CI, 0.023-0.098] rises/second from baseline [P =.002]). This corresponded to a clinically relevant improvement in TTSTAND in the vamorolone 6mg/kg/day arm (from 6.0 to 4.6 seconds) and deterioration in the placebo arm (from 5.4 to 5.5 seconds).

Vamorolone was also found to be superior to placebo across multiple secondary endpoints, including TTSTAND velocity for 2mg/kg/day (P =.02), 6-minute walk test (6MWT) for 6mg/kg/day (P =.002) and 2mg/kg/day (P =.004), and time to run/walk 10 meters (TTRW) for 6mg/kg/day (P =.002).

No statistically significant differences were observed between vamorolone 6mg/kg/day and prednisone across all endpoints. The analysis showed that height percentile declined in patients treated with prednisone but not among those who received vamorolone (P =.02).

The use of vamorolone in patients 2 years to less than 4 years of age and 7 to less than 18 years of age is supported by findings of efficacy and safety in patients 4 to less than 7 years of age with DMD and by pharmacokinetic and safety data.

Agamree

PAGE CONTENTS