ULTOMIRIS Concentrate for solution for infusion Ref.[50087] Active ingredients: Ravulizumab

Ravulizumab must be administered by a healthcare professional and under the supervision of a physician experienced in the management of patients with haematological, renal, neuromuscular, or neuroinflammatory disorders.

Posology

Adult patients with PNH, aHUS, gMG, or NMOSD

The recommended dosing regimen consists of a loading dose followed by maintenance dosing, administered by intravenous infusion. The doses to be administered are based on the patient’s body weight, as shown in Table 1. For adult patients (≥18 years of age), maintenance doses should be administered at a once every 8-week interval, starting 2 weeks after loading dose administration.

Dosing schedule is allowed to occasionally vary by ± 7 days of the scheduled infusion day (except for the first maintenance dose of ravulizumab), but the subsequent dose should be administered according to the original schedule.

Table 1. Ravulizumab weight-based dosing regimen for adult patients with body weight greater than or equal to 40 kg:

^* First maintenance dose is administered 2 weeks after loading dose.

Treatment initiation instructions in patients who are complement-inhibitor treatment-naïve or switching treatment from eculizumab are shown in Table 2.

Table 2. Ravulizumab treatment initiation instructions:

Paediatric patients with PNH or aHUS

Paediatric patients with body weight ≥40 kg

These patients should be treated in accordance with the adult dosing recommendations (See Table 1).

Paediatric patients with body weight ≥10 kg to <40 kg

The weight-based doses and dosing intervals for paediatric patients ≥10 kg to <40 kg are shown in Table 3.

For patients switching from eculizumab to ravulizumab, the loading dose of ravulizumab should be administered 2 weeks after the last eculizumab infusion, and then maintenance doses should be administered per weight-based dosing regimen shown in Table 3, starting 2 weeks after loading dose administration.

Table 3. Ravulizumab weight-based dosing regimen for paediatric patients with PNH or aHUS below 40 kg:

^* First maintenance dose is administered 2 weeks after loading dose

Ravulizumab has not been studied in paediatric patients with PNH who weigh less than 30 kg. The recommended posology for these patients is based on the posology used for paediatric patients with aHUS, on the basis of the pharmacokinetic/pharmacodynamic (PK/PD) data available in aHUS and PNH patients treated with ravulizumab.

PNH is a chronic disease and treatment with ravulizumab is recommended to continue for the patient’s lifetime, unless the discontinuation of ravulizumab is clinically indicated (see section 4.4).

In aHUS, ravulizumab treatment to resolve thrombotic microangiopathy (TMA) manifestations should be for a minimum duration of 6 months, beyond which length of treatment needs to be considered for each patient individually. Patients who are at higher risk for TMA recurrence, as determined by the treating healthcare provider (or clinically indicated), may require chronic therapy (see section 4.4).

In adult patients with gMG or NMOSD, treatment with ravulizumab has only been studied in the setting of chronic administration (see section 4.4).

Ravulizumab has not been studied in gMG patients with an MGFA Class V.

Supplemental dosing following treatment with plasma exchange (PE), plasmapheresis (PP), or intravenous immunoglobulin (IVIg)

Plasma exchange (PE), plasmapheresis (PP) and intravenous immunoglobulin (IVIg) have been shown to reduce ravulizumab serum levels. A supplemental dose of ravulizumab is required in the setting of PE, PP or IVIg (Table 4).

Table 4. Supplemental dose of ravulizumab after PP, PE, or IVIg:

Abbreviations: IVIg = intravenous immunoglobulin, kg = kilogram, PE = plasma exchange, PP = plasmapheresis

Special populations

Elderly

No dose adjustment is required for patients with PNH, aHUS, gMG, or NMOSD aged 65 years and over. There is no evidence indicating any special precautions are required for treating a geriatric population – although experience with ravulizumab in elderly patients with PNH, aHUS, or NMOSD in clinical studies is limited.

Renal impairment

No dose adjustment is required for patients with renal impairment (see section 5.2).

Hepatic impairment

The safety and efficacy of ravulizumab have not been studied in patients with hepatic impairment; however pharmacokinetic data suggest that no dose adjustment is required in patients with hepatic impairment.

Paediatric population

The safety and efficacy of ravulizumab in children with a body weight below 10 kg with PNH or aHUS have not been established. Currently available data are described in section 4.8 but no recommendation on a posology can be made.

The safety and efficacy of ravulizumab in children with gMG or NMOSD have not been established. No data are available.

Method of administration

For intravenous infusion only.

This medicinal product must be administered through a 0.2 μm filter and should not be administered as an intravenous push or bolus injection.

Ultomiris 300 mg/30 mL concentrate for solution for infusion must not be mixed with Ultomiris

300 mg/3 mL or 1 100 mg/11 mL concentrates for solution for infusion.

Ultomiris 300 mg/3 mL and 1 100 mg/11 mL concentrates for solution for infusion

Ultomiris concentrate for solution for infusion is presented as 3 mL and 11 mL vials (100 mg/mL) and must be diluted to a final concentration of 50 mg/mL. Following dilution, Ultomiris is to be administered by intravenous infusion using a syringe-type pump or an infusion pump over a minimal period of 0.17 to 1.3 hours (10 to 75 minutes) depending on body weight (see Table 5 and Table 6 below).

Table 5. Dose administration rate for Ultomiris 300 mg/3 mL and 1 100 mg/11 mL concentrates for solution for infusion:

^a Body weight at time of treatment.
^b For PNH and aHUS indications only.

Table 6. Dose administration rate for supplemental doses of Ultomiris 300 mg/3 mL and 1 100 mg/11 mL concentrates for solution for infusion:

^a Body weight at time of treatment.
^b Refer to Table 4 for selection of ravulizumab supplemental dose.

Ultomiris 300 mg/30 mL concentrate for solution for infusion

Ultomiris concentrate for solution for infusion is presented as 30 mL vial (10 mg/mL) and must be diluted to a final concentration of 5 mg/mL. Following dilution, Ultomiris is to be administered by intravenous infusion using a syringe-type pump or an infusion pump over a minimal period of 0.4 to 3.3 hours (22 to 194 minutes) depending on body weight (see Table 7 and Table 8 below).

Table 7. Dose administration rate for Ultomiris 300 mg/30 mL concentrate for solution for infusion:

^a Body weight at time of treatment.
^b For PNH and aHUS indications only.

Table 8. Dose administration rate for supplemental doses of Ultomiris 300 mg/30 mL concentrate for solution for infusion:

^a Body weight at time of treatment.
^b Refer to Table 4 for selection of ravulizumab supplemental dose

For instructions on dilution of the medicinal product before administration, see section 6.6.

Patients who experience overdose should have immediate interruption of their infusion and be closely monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted.

Ultomiris 300 mg/3 mL and 1 100 mg/11 mL concentrates for solution for infusion:

18 months.

After dilution, the medicinal product should be used immediately. However, chemical and physical stability of the diluted product have been demonstrated for up to 24 hours at 2°C-8°C and up to 4 hours at room temperature.

Ultomiris 300 mg/30 mL concentrate for solution for infusion:

30 months.

After dilution, the medicinal product should be used immediately. However, chemical and physical stability of the diluted product have been demonstrated for up to 24 hours at 2°C-8°C and up to 6 hours at room temperature.

Store in a refrigerator (2°C–8°C).

Do not freeze.

Keep the vial in the outer carton in order to protect from light.

For storage conditions after dilution of the medicinal product, see section 6.3.

Pack size of one vial.

Ultomiris 300 mg/3 mL concentrate for solution for infusion: 3 mL of sterile concentrate in a vial (Type I glass) with a stopper and a seal.

Ultomiris 1 100 mg/11 mL concentrate for solution for infusion: 11 mL of sterile concentrate in a vial (Type I glass) with a stopper and a seal.

Ultomiris 300 mg/30 mL concentrate for solution for infusion: 30 mL of sterile concentrate in a vial (Type I glass) with a stopper and a seal.

Each vial is intended for single use only.

Ultomiris 300 mg/3 mL and 1 100 mg/11 mL concentrates for solution for infusion

This medicinal product requires dilution to a final concentration of 50 mg/mL.

Aseptic technique must be used.

Prepare Ultomiris concentrate for solution for infusion as follows:

1. The number of vials to be diluted is determined based on the individual patient’s weight and the prescribed dose, see section 4.2.

2. Prior to dilution, the solution in the vials should be visually inspected; the solution should be free of any particulate matter or precipitation. Do not use if there is evidence of particulate matter or precipitation.

3. The calculated volume of medicinal product is withdrawn from the appropriate number of vials and diluted in an infusion bag using sodium chloride 9 mg/mL (0.9%) solution for injection as diluent. Refer to the administration reference tables below. The product should be mixed gently. It should not be shaken.

4. After dilution, the final concentration of the solution to be infused is 50 mg/mL.

5. The prepared solution should be administered immediately following preparation unless it is stored at 2°C-8°C. If stored at 2°C-8°C, allow the diluted solution to warm to room temperature prior to administration. Do not administer as an intravenous push or bolus injection. Refer to the Table 5 and Table 6 for minimum infusion duration. Infusion must be administered through a 0.2 μm filter.

6. If the medicinal product is not used immediately after dilution, storage times must not exceed 24 hours at 2 °C – 8 °C or 4 hours at room temperature taking into account the expected infusion time.

Table 25. Loading dose administration reference table for Ultomiris 300 mg/3 mL and 1 100 mg/11 mL concentrates for solution for infusion:

^a Body weight at time of treatment.
^b Ultomiris should only be diluted using sodium chloride 9 mg/mL (0.9%) solution for injection.

Table 26. Maintenance dose administration reference table for Ultomiris 300 mg/3 mL and 1 100 mg/11 mL concentrates for solution for infusion:

^a Body weight at time of treatment.
^b Ultomiris should only be diluted using sodium chloride 9 mg/mL (0.9%) solution for injection.

Table 27. Supplemental dose administration reference table for Ultomiris 300 mg/3 mL and 1 100 mg/11 mL concentrates for solution for infusion:

^a Body weight at time of treatment
^b Ultomiris should be only diluted using sodium chloride 9 mg/mL (0.9 %) solution for injection

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Ultomiris 300 mg/30 mL concentrate for solution for infusion

This medicinal product requires dilution to a final concentration of 5 mg/mL. Aseptic technique must be used. Prepare Ultomiris concentrate for solution for infusion as follows:

1. The number of vials to be diluted is determined based on the individual patient’s weight and the prescribed dose, see section 4.2.

2. Prior to dilution, the solution in the vials should be visually inspected; the solution should be free of any particulate matter or precipitation. Do not use if there is evidence of particulate matter or precipitation.

3. The calculated volume of medicinal product is withdrawn from the appropriate number of vials and diluted in an infusion bag using sodium chloride 9 mg/mL (0.9%) solution for injection as diluent. Refer to the administration reference tables below. The product should be mixed gently. It should not be shaken.

4. After dilution, the final concentration of the solution to be infused is 5 mg/mL.

5. The prepared solution should be administered immediately following preparation unless it is stored at 2°C-8°C. If stored at 2°C-8°C, allow the diluted solution to warm to room temperature prior to administration. Do not administer as an intravenous push or bolus injection. Refer to the Table 7 and Table 8 for minimum infusion duration. Infusion must be administered through a 0.2 μm filter.

6. If the medicinal product is not used immediately after dilution, storage times must not exceed 24 hours at 2°C-8°C or 6 hours at room temperature taking into account the expected infusion time.

Table 28. Loading dose administration reference table for Ultomiris 300 mg/30 mL concentrate for solution for infusion:

^a Body weight at time of treatment.
^b Ultomiris should only be diluted using sodium chloride 9 mg/mL (0.9%) solution for injection.

Table 29. Maintenance dose administration reference table for Ultomiris 300 mg/30 mL concentrate for solution for infusion:

^a Body weight at time of treatment.
^b Ultomiris should only be diluted using sodium chloride 9 mg/mL (0.9%) solution for injection.

Table 30. Supplemental dose administration reference table for Ultomiris 300 mg/30 mL concentrate for solution for infusion:

^a Body weight at time of treatment.
^b Ultomiris should only be diluted using sodium chloride 9 mg/mL (0.9%) solution for injection.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.