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 or renal disorders.

Posology

Adult patients with PNH and aHUS

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).

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 are administered once every 8 weeks, starting 2 weeks after loading dose administration, as shown in Table 1.

Table 1. Ravulizumab weight-based dosing regimen:

^* Maintenance dose is administered 2 weeks after loading dose.

There is no experience of concomitant PE/PI (plasmapheresis or plasma exchange, or fresh frozen plasma infusion) use with ravulizumab. Administration of PE/PI may reduce ravulizumab serum levels.

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).

Special populations

Elderly

No dose adjustment is required for patients with PNH and aHUS 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 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

Paediatric patients with PNH and aHUS with body weight ≥40 kg are treated in accordance with the adult dosing recommendations. The weight-based doses and dosing intervals for paediatric patients ≥10 kg to <40 kg are shown in Table 2.

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 2, starting 2 weeks after loading dose administration.

Table 2. Ravulizumab weight-based dosing regimen for paediatric patient with PNH and aHUS below 40 kg:

^* Maintenance dose is administered 2 weeks after loading dose.

Data to support safety and efficacy of ravulizumab for patients with body weight below 10 kg are limited. Currently available data are described in section 4.8 but no recommendation on a posology can be made for patients below 10 kg body weight.

Ravulizumab has not been studied in paediatric patients with PNH who weigh less than 30 kg. The posology of ravulizumab for paediatric patients less than 30 kg 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.

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.

In the absence of compatibility studies, 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 concentrated at 100 mg/mL (3 mL and 11 mL vials) must be diluted to a final concentration of 50 mg/mL.

Ultomiris concentrate for solution for infusion presented as 3 mL and 11 mL vials (100 mg/mL) must be diluted prior to administration by intravenous infusion using a syringe-type pump or an infusion pump over a minimal period of 0.4 to 1.3 hours (25 to 75 minutes) depending on body weight (see Table 3 below).

Table 3. 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.

Ultomiris 300 mg/30 mL concentrate for solution for infusion

Ultomiris concentrated at 10 mg/mL (30 ml vial) must be diluted to a final concentration of 5 mg/mL.

Ultomiris concentrate for solution for infusion presented as 30 mL vial (10 mg/mL) must be diluted prior to administration by intravenous infusion using a syringe-type pump or an infusion pump over a minimal period of 1.3 to 3.3 hours (77 to 194 minutes) depending on body weight (see Table 4 below).

Table 4. Dose administration rate for Ultomiris 300 mg/30 mL concentrate for solution for infusion:

^a Body weight at time of treatment.

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

No case of overdose has been reported to date.

Patients who experience overdose should have immediate interruption of their infusion and be closely monitored.

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 3 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 16. 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 17. 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.

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 4 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 18. 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 19. 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.

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