Agamree

Treatment with AGAMREE should only be initiated by specialist physicians with experience in the management of Duchenne muscular dystrophy. Posology The recommended dose of vamorolone is 6 mg/kg once daily in patients weighing less than 40 kg.

In patients weighing 40 kg and above, the recommended dose of vamorolone is 240 mg (equivalent to 6 ml) once daily. Daily dose may be down-titrated to 4 mg/kg/day or 2 mg/kg/day based on individual tolerability. Patients should be maintained at the highest tolerated dose within the dose range.

4). Dose tapering should be done progressively over weeks, by steps of approximately 20% decrease from the previous dose level. The duration of each tapering step should be adjusted depending on individual tolerability. Special populations Hepatic impairment No dose adjustment is required for patients with mild hepatic impairment (Child-Pugh class A).

2). Patients with severe hepatic impairment (Child-Pugh class C) should not be treated with vamorolone. 3 and

7%). These reactions are dose-dependent, usually reported in the first months of treatment and tend to decline or stabilise over time with continuous treatment. Vamorolone leads to the suppression of the hypothalamic-pituitary-adrenal axis, which correlates with dose and the duration of treatment.

4). Tabulated list of adverse reactions The adverse reactions are listed below according to MedDRA system organ class and frequency. The table contains adverse reactions in patients treated in the placebo-controlled study for patients treated with vamorolone 6 mg/kg/day (Pool 1).

The frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to 8 < 1/1 000), very rare (< 1/10 000) (including isolated cases), not known (cannot be estimated from the available data).

6%). 7%). In the clinical study, cushingoid features were reported as mild to moderate “weight gain in the face”, or “rounded face”. 6% in Month 6 to 12 in vamorolone 6 mg/kg/day) and did not result in discontinuation of treatment. 7% in 6 mg/kg/day, no patient in 2 mg/kg/day or placebo).

The majority of behaviour problems occurred in the first 3 months of treatment and resolved without treatment discontinuation. 1% for vamorolone 2 mg/kg/day). Weight gain Vamorolone is associated with increase in appetite and weight.

9% in month 0 to 6 vs 0% in months 6 to 12). 9%). 4). 4). Paediatric population The adverse events in paediatric patients with DMD treated with vamorolone were similar in frequency and type in patients 4 years of age and older. The type and frequency of adverse events in patients older than 7 years were consistent with those seen in 4 to 7-year old patients.

There is no available information on the effects of vamorolone on pubertal development. 9 A higher frequency of behaviour problems was observed in patients <5 years compared to patients ≥5 years when treated with vamorolone 2-6 mg/kg/day.

4. Paediatric population The safety and efficacy of AGAMREE in children below 4 years of age has not been established. Method of administration AGAMREE is for oral use. 2). The oral suspension requires redispersing by shaking the bottle prior to dosing.

Only the oral syringe provided with the medicinal product should be used to measure the dose of AGAMREE in ml. After the appropriate dose is withdrawn into the oral syringe, it should be dispensed directly into the mouth. The oral syringe should be disassembled after use, rinsed under running cold tap water and air dried.

It should be stored in the box until next use. An oral syringe may be used for up to 45 days, then it should be discarded and the second oral syringe provided in the pack should be used. 6). 1. Severe liver impairment (Child-Pugh class C).

4). 4 Special warnings and precautions for use Alterations in endocrine function Vamorolone causes alterations in endocrine function, especially with chronic use. In addition, patients with altered thyroid function, or pheochromocytoma may be at increased risk for endocrine effects.

Risk of adrenal insufficiency Vamorolone produces dose-dependent and reversible suppression of the hypothalamic-pituitary- adrenal axis (HPA-axis), potentially resulting in secondary adrenal insufficiency, which may persist for months after discontinuation of prolonged therapy.

The degree of chronic adrenal insufficiency produced is variable among patients and depends on the dose, and duration of therapy. Acute adrenal insufficiency (also known as adrenal crisis) can occur during a period of increased stress or if vamorolone dose is reduced or withdrawn abruptly.

This condition can be fatal. Symptoms of adrenal crisis may include excess fatigue, unexpected weakness, vomiting, dizziness or confusion. 2). During periods of increased stress, such as acute infection, traumatic injuries or surgical procedure, patients should be monitored for signs of acute adrenal insufficiency and the regular treatment with AGAMREE should be temporarily supplemented with systemic hydrocortisone to prevent the risk of adrenal crisis.

1. Severe liver impairment (Child-Pugh class C). 4).