Usual Adult Dose for Paroxysmal Nocturnal Hemoglobinuria

Weight-based dosing regimen:
40 KG TO LESS THAN 60 KG:

• Loading dose: 2400 mg IV
• Maintenance dose: 3000 mg IV every 8 weeks starting 2 weeks after the loading dose

60 KG TO LESS THAN 100 KG:

• Loading dose: 2700 mg IV
• Maintenance dose: 3300 mg IV every 8 weeks starting 2 weeks after the loading dose

100 KG OR GREATER:

• Loading dose: 3000 mg IV
• Maintenance dose: 3600 mg IV every 8 weeks starting 2 weeks after the loading dose

Comments:

• Dilution of this drug should be to a final concentration of 50 mg/mL for the 3 mL and 11 ML vials or 5 mg/mL for the 30 mL vials.
• The number of drug vials to be diluted is determined by the patient's weight and the prescribed dose. Review the manufacturer's instructions for preparation and administration details.

Use: For the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH)

Usual Adult Dose for Hemolytic Uremic Syndrome

Weight-based dosage regimen:
40 KG TO LESS THAN 60 KG:

• Loading dose: 2400 mg IV
• Maintenance dose: 3000 mg IV every 8 weeks starting 2 weeks after the loading dose

60 KG TO LESS THAN 100 KG:

• Loading dose: 2700 mg IV
• Maintenance dose: 3300 mg IV every 8 weeks starting 2 weeks after the loading dose

100 KG OR GREATER:

• Loading dose: 3000 mg IV
• Maintenance dose: 3600 mg IV every 8 weeks starting 2 weeks after the loading dose

Treatment duration: Minimum of 6 months, then each patient should be considered individually evaluating risks and benefits of chronic treatment.

Comments:

• Dilution of this drug should be to a final concentration of 50 mg/mL for the 3 mL and 11 ML vials or 5 mg/mL for the 30 mL vials.
• The number of drug vials to be diluted is determined by the patient's weight and the prescribed dose. Review the manufacturer's instructions for preparation and administration details.
• This drug is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

Use: For the treatment of atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA)

Usual Adult Dose for Myasthenia Gravis

Weight-based dosing regimen:
40 KG TO LESS THAN 60 KG:

• Loading dose: 2400 mg IV
• Maintenance dose: 3000 mg IV every 8 weeks starting 2 weeks after the loading dose

60 KG TO LESS THAN 100 KG:

• Loading dose: 2700 mg IV
• Maintenance dose: 3300 mg IV every 8 weeks starting 2 weeks after the loading dose

100 KG OR GREATER:

• Loading dose: 3000 mg IV
• Maintenance dose: 3600 mg IV every 8 weeks starting 2 weeks after the loading dose

Comments:

• Dilution of this drug should be to a final concentration of 50 mg/mL for the 3 mL and 11 ML vials or 5 mg/mL for the 30 mL vials.
• The number of drug vials to be diluted is determined by the patient's weight and the prescribed dose. Review the manufacturer's instructions for preparation and administration details

Use: Treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive.

Usual Pediatric Dose for Hemolytic Uremic Syndrome

Weight-based dosing regimen:
PATIENTS ONE MONTH AND OLDER WEIGHING 5 KG OR GREATER:
5 KG TO LESS THAN 10 KG:

• Loading dose: 600 mg IV
• Maintenance dose: 300 mg IV every 4 weeks starting 2 weeks after the loading dose

10 KG TO LESS THAN 20 KG:

• Loading dose: 600 mg IV
• Maintenance dose: 600 mg IV every 4 weeks starting 2 weeks after the loading dose

20 KG TO LESS THAN 30 KG:

• Loading dose: 900 mg IV
• Maintenance dose: 2100 mg IV every 8 weeks starting 2 weeks after the loading dose

30 KG TO LESS THAN 40 KG:

• Loading dose: 1200 mg IV
• Maintenance dose: 2700 mg IV every 8 weeks starting 2 weeks after the loading dose

PATIENTS OVER 40 KG HAVE THE SAME DOSING AS ADULT PATIENTS:
40 KG TO LESS THAN 60 KG:

• Loading dose: 2400 mg IV
• Maintenance dose: 3000 mg IV every 8 weeks starting 2 weeks after the loading dose

60 KG TO LESS THAN 100 KG:

• Loading dose: 2700 mg IV
• Maintenance dose: 3300 mg IV every 8 weeks starting 2 weeks after the loading dose

100 KG OR GREATER:

• Loading dose: 3000 mg IV
• Maintenance dose: 3600 mg IV every 8 weeks starting 2 weeks after the loading dose

Comments:

• Dilution of this drug should be to a final concentration of 50 mg/mL for the 3 mL and 11 ML vials or 5 mg/mL for the 30 mL vials.
• The number of drug vials to be diluted is determined by the patient's weight and the prescribed dose. Review the manufacturer's instructions for preparation and administration details

Uses:

• For the treatment of pediatric patients one month and older with paroxysmal nocturnal hemoglobinuria (PNH).
• For the treatment of pediatric patients one month and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA)

Usual Pediatric Dose for Paroxysmal Nocturnal Hemoglobinuria

Weight-based dosing regimen:
PATIENTS ONE MONTH AND OLDER WEIGHING 5 KG OR GREATER:
5 KG TO LESS THAN 10 KG:

• Loading dose: 600 mg IV
• Maintenance dose: 300 mg IV every 4 weeks starting 2 weeks after the loading dose

10 KG TO LESS THAN 20 KG:

• Loading dose: 600 mg IV
• Maintenance dose: 600 mg IV every 4 weeks starting 2 weeks after the loading dose

20 KG TO LESS THAN 30 KG:

• Loading dose: 900 mg IV
• Maintenance dose: 2100 mg IV every 8 weeks starting 2 weeks after the loading dose

30 KG TO LESS THAN 40 KG:

• Loading dose: 1200 mg IV
• Maintenance dose: 2700 mg IV every 8 weeks starting 2 weeks after the loading dose

PATIENTS OVER 40 KG HAVE THE SAME DOSING AS ADULT PATIENTS:
40 KG TO LESS THAN 60 KG:

• Loading dose: 2400 mg IV
• Maintenance dose: 3000 mg IV every 8 weeks starting 2 weeks after the loading dose

60 KG TO LESS THAN 100 KG:

• Loading dose: 2700 mg IV
• Maintenance dose: 3300 mg IV every 8 weeks starting 2 weeks after the loading dose

100 KG OR GREATER:

• Loading dose: 3000 mg IV
• Maintenance dose: 3600 mg IV every 8 weeks starting 2 weeks after the loading dose

Comments:

• Dilution of this drug should be to a final concentration of 50 mg/mL for the 3 mL and 11 ML vials or 5 mg/mL for the 30 mL vials.
• The number of drug vials to be diluted is determined by the patient's weight and the prescribed dose. Review the manufacturer's instructions for preparation and administration details

Uses:

• For the treatment of pediatric patients one month and older with paroxysmal nocturnal hemoglobinuria (PNH).
• For the treatment of pediatric patients one month and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA)

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

No adjustment recommended.

Precautions

US FDA requires a medication guide to assure safe use. For additional information: www.fda.gov/drugs/drug-safety-and-availability/medication-guides

US BOXED WARNINGS:
SERIOUS MENINGOCOCCAL INFECTIONS:

• Life-threatening meningococcal infections/sepsis have occurred in patients treated with this drug and may become rapidly life-threatening or fatal if not recognized.
• Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
• Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose unless the risks of delaying therapy outweigh the risks of developing a meningococcal infection.
• Vaccination reduces, but does not eliminate, the risk of meningococcal infection.
• Monitor for meningococcal infections and evaluate immediately if infection is suspected.
• This drug is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the ULTOMIRIS REMS, prescribers must enroll in the program. For additional information: http://www.accessdata.fda.gov/scripts/cder/rems/index.cfm

CONTRAINDICATIONS:

• In patients with unresolved Neisseria meningitidis infection
• Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying treatment outweigh the risks of developing a meningococcal infection

Safety and efficacy have not been established in pediatric patients younger than one month with PNH or aHUS.
Safety and efficacy have not been established in patients younger than 18 years with Myasthenia Gravis who are AChR antibody positive.
This drug is not indicated for the treatment of Shiga toxin E. Coli related hemolytic uremic syndrome (STEC-HUS).

Consult WARNINGS section for additional precautions.

Dialysis

No adjustment recommended.

Other Comments

Administration advice:

• Healthcare professionals who prescribe this drug must enroll in the ULTOMIRIS REMS.
• Vaccinate patients for meningococcal disease according to current guidelines to reduce the risk of serious infection.
• Provide 2 weeks of antibacterial drug prophylaxis to patients if this drug must be initiated immediately and vaccines are administered less than 2 weeks before.
• The dosing schedule can vary within 7 days of the scheduled infusion day (except for the first maintenance dose) but the subsequent dose should be administered according to the original schedule.
• When converting from eculizumab to this drug, administer the loading dose of this drug 2 weeks after the last eculizumab dose and then administer maintenance doses once every 8 weeks or every 4 weeks (depending on body weight) starting 2 weeks after loading dose administration.
• Administer only as an IV infusion.
• If an adverse reaction occurs during administration, the infusion may be slowed or stopped at the discretion of the physician.
• Patients should be monitored at least for one hour following the completion of the infusion.
• Administration of PE/PI (plasmapheresis or plasma exchange) and IV immunoglobulin reduce the serum levels of this drug, and a supplemental dose will be required.
• This drug is not indicated for the treatment of Shiga toxin E. coli related hemolytic uremic syndrome (STEC_HUS).

Storage requirements:

• Store unused vials in the refrigerator at 2C to 8C (36F to 46F) in the original carton to protect from light. Do not freeze. Do not shake.

Reconstitution/preparation techniques:

• Each vial is intended for single-dose only.
• Use aseptic technique to prepare this drug as follows:
• The number of vials to be used is based on patient weight and the desired dose (see manufacturer's prescribing information).
• Do not use if there is particulate matter or precipitation in the original vial.
• Withdraw the calculated volume from the appropriate number of vials and dilute in an infusion bag using 0.9% sodium chloride injection to a final concentration of 50 mg/mL for the 3 mL and 11 mL vials, or 5 mg/mL for the 30 mL vial size.
• The product should be mixed gently, without shaking.
• Administer the prepared solution immediately following preparation through a 0.2 or 0.22-micron filter.
• If the diluted solution is not used immediately, store in refrigerator at 2C to 8C (36F to 46F) not exceeding 24 hours. When removed from refrigeration, administer the infusion solution within 4 to 6 hours (see manufacturer's prescribing information).

IV compatibility:

• This drug should only be mixed with 0.9% sodium chloride injection.

Patient advice:

• Read the Patient Information and Instructions for Use.
• This drug can increase the risk of meningococcal infection/sepsis and you will be required to receive meningococcal vaccination at least 2 weeks prior to starting treatment.
• Vaccination may not prevent meningococcal infection. Symptoms may include headache with nausea or vomiting, headache and a fever, headache with a stiff neck or stiff back, fever, fever and a rash, confusion, muscle aches with flu-like symptoms; eyes sensitive to light. Report symptoms immediately to your healthcare provider.
• This drug increases risk of other infections. Report any symptoms of infection.
• Carry your Patient Safety Card with you at all times. This card describes symptoms which, if experienced, should be promptly reported.
• You will be monitored by your health care provider from 16 weeks to 12 months after discontinuation.