Ultomiris

ULTOMIRIS is a complement inhibitor indicated for:

• the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH). (
  1.1 Paroxysmal Nocturnal Hemoglobinuria

  ULTOMIRIS is indicated for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH).
  )
• the treatment of adult and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA). (
  1.2 Atypical Hemolytic Uremic Syndrome

  ULTOMIRIS is indicated for the treatment of adult and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA).

  Limitations of Use:

  ULTOMIRIS is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).
  )
  
  
  Limitations of Use:
  
  
  ULTOMIRIS is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).
• the treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive. (
  1.3 Generalized Myasthenia Gravis

  ULTOMIRIS is indicated for the treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive.
  )
• the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody-positive. (
  1.4 Neuromyelitis Optica Spectrum Disorder

  ULTOMIRIS is indicated for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody-positive.
  )

• See Full Prescribing Information for instructions on dosage, preparation, and administration. (
  2.1 Important Dosage Information

  ULTOMIRIS is intended to be administered only as an intravenous infusion in adult or pediatric patients one month of age and older.
  ,
  2.2 Recommended Vaccination and Prophylaxis for Meningococcal Infection

  Vaccinate patients against meningococcal infection (serogroups A, C, W, Y and B) according to current ACIP recommendations at least 2 weeks prior to initiation of ULTOMIRIS

  [see Warnings and Precautions (5.1)]

  .

  If urgent ULTOMIRIS therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible.

  Healthcare providers who prescribe ULTOMIRIS must enroll in the ULTOMIRIS and SOLIRIS REMS

  [see Warnings and Precautions (5.2)]

  .
  ,
  2.3 Recommended Dosage for Intravenous Administration in Adult and Pediatric Patients with PNH or aHUS, and in Adult Patients with gMG or NMOSD

  The recommended intravenous (IV) ULTOMIRIS loading and maintenance dosing in adult and pediatric patients, one month of age or older weighing 5 kg or greater, with PNH or aHUS, or in adult patients with gMG or NMOSD weighing 40 kg or greater, is based on the patient's body weight, as shown in Table 1, with maintenance doses administered every 4 or 8 weeks, starting 2 weeks after loading dose.

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

  Following a missed IV ULTOMIRIS dose, the patient should contact their health care provider immediately.

  Table 1: IV Administration of ULTOMIRIS Weight-Based Dosing Regimen – PNH, aHUS, gMG, or NMOSDSee Table 4and Table 5for selection of the proper total volume and maximum infusion rate

  [see Dosage and Administration (2.5)]

  Indications	Body Weight Range (kg)	Loading Dose (mg)See Table 2for ULTOMIRIS treatment initiation instruction and timing of loading dose and maintenance dose	Maintenance Dose (mg) and Dosing Interval
  PNH or aHUS	5 to less than 10	600	300	Every 4 weeks
  	10 to less than 20	600	600
  	20 to less than 30	900	2,100	Every 8 weeks
  	30 to less than 40	1,200	2,700
  PNH, aHUS, gMG, or NMOSD	40 to less than 60	2,400	3,000	Every 8 weeks
  	60 to less than 100	2,700	3,300
  	100 or greater	3,000	3,600

  Refer to Table 2 for treatment initiation instructions in patients who are complement inhibitor treatment-naïve or switching treatment from eculizumab.

  Table 2: IV Administration of ULTOMIRIS Treatment Initiation Instructions – PNH, aHUS, gMG, or NMOSD

  Population	Weight-based ULTOMIRIS Loading Dose	Time of First ULTOMIRIS Weight-based Maintenance Dose
  Not currently on ULTOMIRIS or eculizumab treatment	At treatment start	2 weeks after ULTOMIRIS loading dose
  Currently treated with eculizumab	At time of next scheduled eculizumab dose	2 weeks after ULTOMIRIS loading dose
  ,
  2.4 Dosing Considerations

  Supplemental Dose of ULTOMIRIS

  Plasma exchange (PE), plasmapheresis (PP), and intravenous immunoglobulin (IVIg) have been shown to reduce ULTOMIRIS serum levels. A supplemental dose of ULTOMIRIS is required in the setting of PE, PP, or IVIg (Table 3).

  Table 3: Supplemental Dose of ULTOMIRIS after PE, PP, or IVIgSee Table 6for selection of the proper total volume and maximum infusion rate

  [see Dosage and Administration (2.5)]

  Body Weight Range (kg)	Most Recent ULTOMIRIS Dose (mg)	Supplemental Dose (mg) following each PE or PP Intervention	Supplemental Dose (mg) following Completion of an IVIg Cycle
  Abbreviations: IVIg = intravenous immunoglobulin; PE = plasma exchange; PP = plasmapheresis
  40 to less than 60	2,400	1,200	600
  	3,000	1,500
  60 to less than 100	2,700	1,500	600
  	3,300	1,800
  100 or greater	3,000	1,500	600
  	3,600	1,800
  Timing of ULTOMIRIS Supplemental Dose		Within 4 hours following each PE or PP intervention	Within 4 hours following completion of an IVIg cycle
  ,
  2.5 Preparation and Administration

  Preparation of ULTOMIRIS Vials for Intravenous Administration

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

  ULTOMIRIS vials are for intravenous administration by a healthcare provider and are intended for intravenous administration only.

  Dilute before use.

  Use aseptic technique to prepare ULTOMIRIS as follows:

  • 1.000000000000000e+00
    The number of vials to be diluted is determined based on the individual patient's weight and the prescribed dose

    [see Dosage and Administration (2.3)]

    .
  • 2.000000000000000e+00
    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.
  • 3.000000000000000e+00
    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.

  The product should be mixed gently. Do not shake.

  Protect from light.

  Do not freeze.

  Refer to Table 4 (loading doses), Table 5 (maintenance doses), and Table 6 (supplemental doses)for IV preparation and minimum infusion duration.

  • 4.000000000000000e+00
    Administer the prepared solution immediately following preparation.
  • 5.000000000000000e+00
    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 4 hours.

  Intravenous Administration of ULTOMIRIS (Healthcare Providers)

  Only administer as an intravenous infusion through a 0.2 or 0.22 micron filter.

  Dilute ULTOMIRIS to a final concentration of 50 mg/mL.

  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.

  After administration of ULTOMIRIS, flush the entire line with 0.9% Sodium Chloride Injection, USP.

  Table 4: Loading Dose Reference Table for ULTOMIRIS

  Body Weight Range (kg) Body weight at time of treatment.	Loading Dose (mg)	ULTOMIRIS Volume (mL)	Volume of NaCl DiluentDilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.(mL)	Total Volume (mL)	Minimum Infusion Time (hr)	Maximum Infusion Rate (mL/hr)
  5 to less than 10For PNH and aHUS indications only.	600	6	6	12	1.4	9
  10 to less than 20	600	6	6	12	0.8	15
  20 to less than 30	900	9	9	18	0.6	30
  30 to less than 40	1,200	12	12	24	0.5	48
  40 to less than 60	2,400	24	24	48	0.8	60
  60 to less than 100	2,700	27	27	54	0.6	90
  100 or greater	3,000	30	30	60	0.4	150

  Table 5: Maintenance Dose Reference Table for ULTOMIRIS

  Body Weight Range (kg)Body weight at time of treatment.	Maintenance Dose (mg)	ULTOMIRIS Volume (mL)	Volume of NaCl DiluentDilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.(mL)	Total Volume (mL)	Minimum Infusion Time (hr)	Maximum Infusion Rate (mL/hr)
  5 to less than 10For PNH and aHUS indications only.	300	3	3	6	0.8	8
  10 to less than 20	600	6	6	12	0.8	15
  20 to less than 30	2,100	21	21	42	1.3	33
  30 to less than 40	2,700	27	27	54	1.1	50
  40 to less than 60	3,000	30	30	60	0.9	67
  60 to less than 100	3,300	33	33	66	0.7	95
  100 or greater	3,600	36	36	72	0.5	144

  Table 6: Supplemental Dose Reference Table for ULTOMIRIS

  Body Weight Range (kg)Body weight at time of treatment.	Supplemental Dose (mg)	ULTOMIRIS Volume (mL)	Volume of NaCl DiluentDilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.(mL)	Total Volume (mL)	Minimum Infusion Time (hr)	Maximum Infusion Rate (mL/hr)
  Note: Refer to Table 3 for selection of ravulizumab supplemental dose
  40 to less than 60	600	6	6	12	0.25	48
  	1,200	12	12	24	0.42	57
  	1,500	15	15	30	0.5	60
  60 to less than 100	600	6	6	12	0.20	60
  	1,500	15	15	30	0.36	83
  	1,800	18	18	36	0.42	86
  100 or greater	600	6	6	12	0.17	71
  	1,500	15	15	30	0.25	120
  	1,800	18	18	36	0.28	129

  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 1 hour following completion of the infusion for signs or symptoms of an infusion-related reaction.
  )
• Dilute ULTOMIRIS before use. (
  2.5 Preparation and Administration

  Preparation of ULTOMIRIS Vials for Intravenous Administration

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

  ULTOMIRIS vials are for intravenous administration by a healthcare provider and are intended for intravenous administration only.

  Dilute before use.

  Use aseptic technique to prepare ULTOMIRIS as follows:

  • 1.000000000000000e+00
    The number of vials to be diluted is determined based on the individual patient's weight and the prescribed dose

    [see Dosage and Administration (2.3)]

    .
  • 2.000000000000000e+00
    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.
  • 3.000000000000000e+00
    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.

  The product should be mixed gently. Do not shake.

  Protect from light.

  Do not freeze.

  Refer to Table 4 (loading doses), Table 5 (maintenance doses), and Table 6 (supplemental doses)for IV preparation and minimum infusion duration.

  • 4.000000000000000e+00
    Administer the prepared solution immediately following preparation.
  • 5.000000000000000e+00
    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 4 hours.

  Intravenous Administration of ULTOMIRIS (Healthcare Providers)

  Only administer as an intravenous infusion through a 0.2 or 0.22 micron filter.

  Dilute ULTOMIRIS to a final concentration of 50 mg/mL.

  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.

  After administration of ULTOMIRIS, flush the entire line with 0.9% Sodium Chloride Injection, USP.

  Table 4: Loading Dose Reference Table for ULTOMIRIS

  Body Weight Range (kg) Body weight at time of treatment.	Loading Dose (mg)	ULTOMIRIS Volume (mL)	Volume of NaCl DiluentDilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.(mL)	Total Volume (mL)	Minimum Infusion Time (hr)	Maximum Infusion Rate (mL/hr)
  5 to less than 10For PNH and aHUS indications only.	600	6	6	12	1.4	9
  10 to less than 20	600	6	6	12	0.8	15
  20 to less than 30	900	9	9	18	0.6	30
  30 to less than 40	1,200	12	12	24	0.5	48
  40 to less than 60	2,400	24	24	48	0.8	60
  60 to less than 100	2,700	27	27	54	0.6	90
  100 or greater	3,000	30	30	60	0.4	150

  Table 5: Maintenance Dose Reference Table for ULTOMIRIS

  Body Weight Range (kg)Body weight at time of treatment.	Maintenance Dose (mg)	ULTOMIRIS Volume (mL)	Volume of NaCl DiluentDilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.(mL)	Total Volume (mL)	Minimum Infusion Time (hr)	Maximum Infusion Rate (mL/hr)
  5 to less than 10For PNH and aHUS indications only.	300	3	3	6	0.8	8
  10 to less than 20	600	6	6	12	0.8	15
  20 to less than 30	2,100	21	21	42	1.3	33
  30 to less than 40	2,700	27	27	54	1.1	50
  40 to less than 60	3,000	30	30	60	0.9	67
  60 to less than 100	3,300	33	33	66	0.7	95
  100 or greater	3,600	36	36	72	0.5	144

  Table 6: Supplemental Dose Reference Table for ULTOMIRIS

  Body Weight Range (kg)Body weight at time of treatment.	Supplemental Dose (mg)	ULTOMIRIS Volume (mL)	Volume of NaCl DiluentDilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.(mL)	Total Volume (mL)	Minimum Infusion Time (hr)	Maximum Infusion Rate (mL/hr)
  Note: Refer to Table 3 for selection of ravulizumab supplemental dose
  40 to less than 60	600	6	6	12	0.25	48
  	1,200	12	12	24	0.42	57
  	1,500	15	15	30	0.5	60
  60 to less than 100	600	6	6	12	0.20	60
  	1,500	15	15	30	0.36	83
  	1,800	18	18	36	0.42	86
  100 or greater	600	6	6	12	0.17	71
  	1,500	15	15	30	0.25	120
  	1,800	18	18	36	0.28	129

  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 1 hour following completion of the infusion for signs or symptoms of an infusion-related reaction.
  )
• Only administer as an intravenous infusion through a 0.2 or 0.22 micron filter. (
  2.5 Preparation and Administration

  Preparation of ULTOMIRIS Vials for Intravenous Administration

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

  ULTOMIRIS vials are for intravenous administration by a healthcare provider and are intended for intravenous administration only.

  Dilute before use.

  Use aseptic technique to prepare ULTOMIRIS as follows:

  • 1.000000000000000e+00
    The number of vials to be diluted is determined based on the individual patient's weight and the prescribed dose

    [see Dosage and Administration (2.3)]

    .
  • 2.000000000000000e+00
    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.
  • 3.000000000000000e+00
    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.

  The product should be mixed gently. Do not shake.

  Protect from light.

  Do not freeze.

  Refer to Table 4 (loading doses), Table 5 (maintenance doses), and Table 6 (supplemental doses)for IV preparation and minimum infusion duration.

  • 4.000000000000000e+00
    Administer the prepared solution immediately following preparation.
  • 5.000000000000000e+00
    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 4 hours.

  Intravenous Administration of ULTOMIRIS (Healthcare Providers)

  Only administer as an intravenous infusion through a 0.2 or 0.22 micron filter.

  Dilute ULTOMIRIS to a final concentration of 50 mg/mL.

  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.

  After administration of ULTOMIRIS, flush the entire line with 0.9% Sodium Chloride Injection, USP.

  Table 4: Loading Dose Reference Table for ULTOMIRIS

  Body Weight Range (kg) Body weight at time of treatment.	Loading Dose (mg)	ULTOMIRIS Volume (mL)	Volume of NaCl DiluentDilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.(mL)	Total Volume (mL)	Minimum Infusion Time (hr)	Maximum Infusion Rate (mL/hr)
  5 to less than 10For PNH and aHUS indications only.	600	6	6	12	1.4	9
  10 to less than 20	600	6	6	12	0.8	15
  20 to less than 30	900	9	9	18	0.6	30
  30 to less than 40	1,200	12	12	24	0.5	48
  40 to less than 60	2,400	24	24	48	0.8	60
  60 to less than 100	2,700	27	27	54	0.6	90
  100 or greater	3,000	30	30	60	0.4	150

  Table 5: Maintenance Dose Reference Table for ULTOMIRIS

  Body Weight Range (kg)Body weight at time of treatment.	Maintenance Dose (mg)	ULTOMIRIS Volume (mL)	Volume of NaCl DiluentDilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.(mL)	Total Volume (mL)	Minimum Infusion Time (hr)	Maximum Infusion Rate (mL/hr)
  5 to less than 10For PNH and aHUS indications only.	300	3	3	6	0.8	8
  10 to less than 20	600	6	6	12	0.8	15
  20 to less than 30	2,100	21	21	42	1.3	33
  30 to less than 40	2,700	27	27	54	1.1	50
  40 to less than 60	3,000	30	30	60	0.9	67
  60 to less than 100	3,300	33	33	66	0.7	95
  100 or greater	3,600	36	36	72	0.5	144

  Table 6: Supplemental Dose Reference Table for ULTOMIRIS

  Body Weight Range (kg)Body weight at time of treatment.	Supplemental Dose (mg)	ULTOMIRIS Volume (mL)	Volume of NaCl DiluentDilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.(mL)	Total Volume (mL)	Minimum Infusion Time (hr)	Maximum Infusion Rate (mL/hr)
  Note: Refer to Table 3 for selection of ravulizumab supplemental dose
  40 to less than 60	600	6	6	12	0.25	48
  	1,200	12	12	24	0.42	57
  	1,500	15	15	30	0.5	60
  60 to less than 100	600	6	6	12	0.20	60
  	1,500	15	15	30	0.36	83
  	1,800	18	18	36	0.42	86
  100 or greater	600	6	6	12	0.17	71
  	1,500	15	15	30	0.25	120
  	1,800	18	18	36	0.28	129

  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 1 hour following completion of the infusion for signs or symptoms of an infusion-related reaction.
  )

Injection:

• 300 mg/3 mL (100 mg/mL) solution in a single-dose vial. (
  3 DOSAGE FORMS AND STRENGTHS

  Injection:

  • 300 mg/3 mL (100 mg/mL) solution in a single-dose vial.
  • 1,100 mg/11 mL (100 mg/mL) solution in a single-dose vial.

  Injection: 300 mg/3 mL or 1,100 mg/11 mL (100 mg/mL) as a translucent, clear to yellowish color solution in a single-dose vial.
  )
• 1,100 mg/11 mL (100 mg/mL) solution in a single-dose vial. (
  3 DOSAGE FORMS AND STRENGTHS

  Injection:

  • 300 mg/3 mL (100 mg/mL) solution in a single-dose vial.
  • 1,100 mg/11 mL (100 mg/mL) solution in a single-dose vial.

  Injection: 300 mg/3 mL or 1,100 mg/11 mL (100 mg/mL) as a translucent, clear to yellowish color solution in a single-dose vial.
  )

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ULTOMIRIS during pregnancy. Healthcare providers and patients may call 1-833-793-0563 or go to www.UltomirisPregnancyStudy.com to enroll in or to obtain information about the registry.