ULTOMIRIS Solution for injection Ref.[10182] Active ingredients: Ravulizumab

2.1 Recommended Vaccination and Prophylaxis

Vaccinate patients for meningococcal disease according to current ACIP guidelines to reduce the risk of serious infection [see Warnings and Precautions (5.1, 5.2)].

Provide 2 weeks of antibacterial drug prophylaxis to patients if ULTOMIRIS must be initiated immediately and vaccines are administered less than 2 weeks before starting ULTOMIRIS therapy.

Healthcare professionals who prescribe ULTOMIRIS must enroll in the ULTOMIRIS REMS [see Warnings and Precautions (5.1)].

2.2 Recommended Weight-Based Dosage Regimen - PNH

The recommended dosing regimen in adult patients with PNH weighing 40 kg or greater, consists of a loading dose followed by maintenance dosing, administered by intravenous infusion. Administer the doses based on the patient's body weight, as shown in Table 1. Starting 2 weeks after the loading dose administration, begin maintenance doses at a once every 8-week interval.

The dosing schedule is allowed to occasionally vary within 7 days of the scheduled infusion day (except for the first maintenance dose of ULTOMIRIS); but the subsequent doses should be administered according to the original schedule.

Table 1. ULTOMIRIS Weight-Based Dosing Regimen - PNH:

2.3 Recommended Weight-Based Dosage Regimen - aHUS

The recommended dosing regimen in adult and pediatric patients one month of age and older with aHUS weighing 5 kg or greater, consists of a loading dose followed by maintenance dosing, administered by intravenous infusion. Administer the doses based on the patient's body weight, as shown in Table 2. Starting 2 weeks after the loading dose administration, begin maintenance doses once every 8 weeks or every 4 weeks (depending on body weight).

The dosing schedule is allowed to occasionally vary within 7 days of the scheduled infusion day (except for the first maintenance dose of ULTOMIRIS); but the subsequent doses should be administered according to the original schedule.

Table 2. ULTOMIRIS Weight-Based Dosing Regimen - aHUS:

2.4 Dosing Considerations

For patients switching from eculizumab to ULTOMIRIS, administer the loading dose of ULTOMIRIS 2 weeks after the last eculizumab infusion, and then administer maintenance doses once every 8 weeks or every 4 weeks (depending on body weight), starting 2 weeks after loading dose administration.

Administration of PE/PI (plasmapheresis or plasma exchange, or fresh frozen plasma infusion) may reduce ULTOMIRIS serum levels. There is no experience with administration of supplemental doses of ULTOMIRIS.

2.5 Preparation and Administration

Preparation of ULTOMIRIS

Each vial of ULTOMIRIS is intended for single-dose only.

ULTOMIRIS 100 mg/mL (3 mL and 11 mL vials) and 10 mg/mL (3o mL vials) should not be mixed together.

Use aseptic technique to prepare ULTOMIRIS as follows:

• The number of vials to be diluted is determined based on the individual patient's weight and the prescribed dose [see Dosage and Administration (2.2, 2.3)].
• Prior to dilution, visually inspect the solution in the vials; the solution should be free of any particulate matter or precipitation. Do not use if there is evidence of particulate matter or precipitation.
• Withdraw the calculated volume of ULTOMIRIS from the appropriate number of vials and dilute in an infusion bag using 0.9% Sodium Chloride Injection, USP to a final concentration of:
  • 50 mg/mL for the 3 mL and 11 mL vial sizes or
  • 5 mg/mL for the 30 mL vial size.The product should be mixed gently. Do not shake. Protect from light. Do not freeze.Refer to the following reference tables: Table 3 (loading doses) and Table 4 (maintenance doses) for ULTOMIRIS 100 mg/mL (3 mL and 11 mL vials) and Table 5 (loading doses) and Table 6 (maintenance doses) for ULTOMIRIS 10 mg/mL (30 mL vial).
• Administer the prepared solution immediately following preparation. Refer to Table 3 (loading doses) and Table 4 (Maintenance doses( for ULTOMIRIS 100 mg/mL (3 mL and 11mL vials) and Table 5 (loading doses) and Table 6 (maintenance doses) for ULTOMIRIS 10 mg/mL (30 mL vial) for minimum infusion duration. Infusion must be administered through a 0.2 or 0.22 micron filter.
• If the diluted ULTOMIRIS infusion solution is not used immediately, storage under refrigeration at 2°C-8°C (36°F-46°F) must not exceed 24 hours taking into account the expected infusion time. Once removed from refrigeration, administer the diluted ULTOMIRIS infusion solution within 6 hours if prepared with ULTOMIRIS 30 mL vials or within 4 hours if prepared with ULTOMIRIS 3 mL or 11 mL vials.

Administration of ULTOMIRIS

Only administer as an intravenous infusion.

Dilute ULTOMIRIS to a final concentration of:

• 50 mg/mL for the 3 mL and 11 mL vial sizes or
• 5 mg/mL for the 30 mL vial size.

Administer ULTOMIRIS only through a 0.2 or 0.22 micron filter.

Table 3. Loading Dose Reference Table for ULTOMIRIS 100 mg/mL (3 mL and 11 mL vials):

* Body weight at time of treatment
^† Dilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.

Table 4. Maintenance Dose Reference Table for ULTOMIRIS 100 mg/mL (3 mL and 11 mL vials):

* Body weight at time of treatment
^† Dilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.

Table 5. Loading Dose Reference Table for ULTOMIRIS 10 mg/mL (30 mL vial):

* Body weight at time of treatment.
^† Dilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.

Table 6. Maintenance Dose Reference Table for ULTOMIRIS 10 mg/mL (30 mL vial):

* Body weight at time of treatment.
^† Dilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.

Prior to administration, allow the admixture to adjust to room temperature (18°C-25°C, 64°F-77°F). Do not heat the admixture in a microwave or with any heat source other than ambient air temperature.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

If an adverse reaction occurs during the administration of ULTOMIRIS, the infusion may be slowed or stopped at the discretion of the physician. Monitor the patient for at least one hour following completion of the infusion for signs or symptoms of an infusion-related reaction.

Store ULTOMIRIS vials refrigerated at 2°C-8°C (36°F-46°F) in the original carton to protect from light. Do not freeze. Do not shake.

Refer to Dosage and Administration (2) for information on the stability and storage of diluted solutions of ULTOMIRIS.