Get continuous protection that lasts up to 8 weeks between infusions with ULTOMIRIS1,a
Getting your patients with atypical‑HUS started on their ULTOMIRIS treatment journey begins with understanding the ULTOMIRIS weight-based dosing regimen. Become familiar with the dosing details to help your patients navigate their path to treatment.
For treatment of atypical-HUS in adult and pediatric patients 1 month of age and older. Not indicated in STEC‑HUS.1
aStarting 2 weeks after the loading dose, maintenance doses are administered once every 4 or 8 weeks (depending on body weight).1
An overview: ULTOMIRIS 100 mg/mL dosing
The recommended dosing regimen in adult and pediatric patients 1 month of age or older with atypical‑HUS weighing ≥5 kg consists of a loading dose followed by maintenance doses, administered by intravenous infusion.1
Initiating ULTOMIRIS with no prior treatment
Loading dose of ULTOMIRIS should be administered as outlined below.
Maintenance doses are administered once every 4 or 8 weeks (depending on body weight), starting 2 weeks after the loading dose.
Switching to ULTOMIRIS from eculizumab therapy
Loading dose of ULTOMIRIS should be administered as outlined below, 2 weeks after the last eculizumab infusion.
Maintenance doses are administered once every 4 or 8 weeks (depending on body weight), starting 2 weeks after the loading dose.
Calculate: Atypical‑HUS weight-based dosing for the 100 mg/mL formulation1
Enter a patient’s body weight at the time of treatment to determine the appropriate loading and maintenance doses as well as the frequency of the maintenance dose.
This calculator tool is for reference only. See the full dosing chart below and the recommended weight-based dosing regimen for atypical-HUS in section 2.3 of the ULTOMIRIS Prescribing Information.
300 mg/3mL vials
bStarting 2 weeks after the loading dose, maintenance doses are administered once every 4 or 8 weeks (depending on body weight).1
cThe 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.1
dAdministration 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.1
Preparing and administering the ULTOMIRIS infusion
Steps to prepare ULTOMIRIS1 (part 1)
- Step 1 Weigh patient
Determine how many ULTOMIRIS vials are needed based on patient weight and prescribed dose (see reference tables below)
- Vials should be stored at refrigeration temperatures (2°C–8°C, 36°F–46°F), protected from light
- Each vial of ULTOMIRIS is intended for single dose only
- Step 3Allow ULTOMIRIS vials to come to room temperature (18°C–25°C, 64°F–77°F) naturally without using any heat source
- Step 4Visually inspect each ULTOMIRIS vial to be sure there is no particulate or precipitate (if either, do not use)
Using aseptic technique, withdraw the volume of ULTOMIRIS (corresponding to the prescribed dose) from the appropriate number of vials and add to an equal volume (1:1) of 0.9% Sodium Chloride Injection, USP, in an infusion bag (see reference tables below)
- ULTOMIRIS is supplied in 2 single-dose vials (1100 mg/11 mL and 300 mg/3 mL) to enable an optimal vial mix for each weight cohort, ensuring there is no product wastage
- ULTOMIRIS 100 mg/mL (3 mL and 11 mL) vials should not be mixed together
- ULTOMIRIS requires dilution to a final concentration of 50 mg/mL for the 3 mL and 11 mL vials
- Step 6Gently mix the solution by swirling (do not shake or introduce air bubbles)
Steps to administer ULTOMIRIS1 (part 2)
Administer the solution immediately to the patient through a 0.2- or 0.22-micron filter
- If the solution is not administered immediately, the solution can be stored at refrigeration (2°C–8°C, 36°F–46°F) for ≤24 hours, taking into account the expected infusion time. Do not freeze the solution
- When administering stored (refrigerated) solution, be sure to bring to room temperature naturally before administering, and be sure to administer within 4 hours if prepared with ULTOMIRIS 3 mL or 11 mL vials
- Step 8 The length of infusion time will vary based on the dose as determined by the patient’s weight, but the rate of infusion should not exceed the maximum for each dose (see reference tables below)
Monitor patient for 1 hour following infusion to ensure no signs or symptoms of an infusion-related reaction occur
- If an adverse reaction occurs during the administration of ULTOMIRIS, the infusion may be slowed or stopped at the discretion of the physician. Interrupt ULTOMIRIS infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur
- Some signs of infusion-related reaction include lower back pain, drop in blood pressure, infusion-related pain, elevation in blood pressure, and limb discomfort
eBody weight at time of treatment.1
fDilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.1
How to: Infuse ULTOMIRIS 100 mg/mL
Learn the step-by-step instructions for how to properly prepare and administer the ULTOMIRIS 100 mg/mL infusion.
Important vaccination information1
Enroll in ULTOMIRIS REMS
Due to the risk of meningococcal infections, ULTOMIRIS 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.
Prescribers must counsel patients about the risk of meningococcal infection/sepsis, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccines.
Vaccinate to reduce infection risk
Vaccinate patients for meningococcal disease according to current ACIP guidelines to reduce the risk of serious infection.
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.
Per ULTOMIRIS Prescribing Information:
ULTOMIRIS treatment of atypical-HUS should be a minimum duration of 6 months, after which treatment duration should be individualized.
Minimum duration 6 months
6-month minimum treatment duration with ULTOMIRIS
Due to the heterogeneous nature of atypical-HUS events and patient-specific risk factors, treatment duration beyond the initial 6 months should be individualized1
Considerations for treating beyond 6 months
Some of these factors to consider include:
Failure to achieve complete TMA response after a minimum 6-month treatment with complement inhibitor1,3
High-risk factors for TMA relapse (eg, age, genetic predisposition, personal/family history, end-stage renal disease, renal transplant, extrarenal symptoms, ongoing complement-amplifying conditions, biopsy, and underlying pathophysiology/
Patients exhibiting clinical/individual needs for maintaining therapy/disease management1,3,4
A longer treatment duration may be considered for your patients
Discontinuation assessment should be based on clinical judgment, including minimal TMA relapse risk and complete TMA response1,3
Risks associated with treatment discontinuation
13.5xfold higher rate of TMA was observed in patients who discontinued complement inhibitor therapy vs patients who stayed on therapy2,a
Patients at the highest risk for TMA post-discontinuation included those with pediatric disease onset, genetic or autoimmune complement abnormalities, and a history of multiple TMAs.
The study showed a trend toward reduced renal function compared to patients who continued treatment.
There are no specific data on ULTOMIRIS discontinuation.1
aIn a long-term, prospective, observational study of eculizumab.2
Assessing patients post-discontinuation
Ongoing monitoring for TMA should be performed in your patients for at least 12 months1
Laboratory and clinical signs of TMA should be closely monitored
There are no specific data on ULTOMIRIS discontinuation
Tips for identifying TMA post-discontinuation
• Signs of clinical symptoms of TMA,1 and • ≥25% change in at least 2 of the following1,b • Decreased platelet countc • Increased serum creatinined • Increased serum LDHd
If TMA complications occur after ULTOMIRIS discontinuation, reinitiation of ULTOMIRIS treatment or appropriate organ-specific supportive measures may be considered.1
bObserved concurrently and confirmed by a second measurement 28 days apart with no interruption.
cChange from baseline or peak value during ULTOMIRIS treatment.
dChange from baseline or nadir level during ULTOMIRIS treatment.
How to order ULTOMIRIS
Find out how to get access to all of the tools necessary to get your patients started on ULTOMIRIS, including how to place an order.ORDER ULTOMIRIS
- ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
- Menne J, et al. BMC Nephrol. 2019;20(1):125.
- Laurence J. Clin Adv Hematol Oncol. 2020;18(4):221-230.
- Fakhouri F, et al. Clin J Am Soc Nephrol. 2017;12(1):50-59.
- Asif A, et al. Nephrol. 2017;30(3):347-362.
IMPORTANT SAFETY INFORMATION INCLUDING BOXED WARNING
WARNING: SERIOUS MENINGOCOCCAL INFECTIONS
Life-threatening meningococcal infections/sepsis have occurred in patients treated with ULTOMIRIS. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early.
- 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 of ULTOMIRIS, unless the risks of delaying ULTOMIRIS therapy outweigh the risk of developing a meningococcal infection. See Warnings and Precautions for additional guidance on the management of the risk of meningococcal infection.
- Vaccination reduces, but does not eliminate, the risk of meningococcal infections. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected.
Because of the risk of serious meningococcal infections, ULTOMIRIS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ULTOMIRIS REMS.
- Patients with unresolved Neisseria meningitidis infection.
- Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying ULTOMIRIS treatment outweigh the risks of developing a meningococcal infection.
WARNINGS AND PRECAUTIONS
Serious Meningococcal Infections
Life-threatening meningococcal infections have occurred in patients treated with ULTOMIRIS. The use of ULTOMIRIS increases a patient’s susceptibility to serious meningococcal infections (septicemia and/or meningitis). Meningococcal disease due to any serogroup may occur.
Vaccinate or revaccinate for meningococcal disease according to the most current ACIP recommendations for patients with complement deficiencies. Immunize patients without history of meningococcal vaccination at least 2 weeks prior to the first dose of ULTOMIRIS. Patients who initiate ULTOMIRIS treatment less than 2 weeks after receiving meningococcal vaccine(s) must receive appropriate prophylactic antibiotics until 2 weeks after vaccination.
The benefits and risks of antibiotic prophylaxis for prevention of meningococcal infections in patients receiving ULTOMIRIS have not been established. Consider discontinuation of ULTOMIRIS in patients who are undergoing treatment for serious meningococcal infection.
Due to the risk of meningococcal infections, ULTOMIRIS is available only through a restricted program under a REMS called ULTOMIRIS REMS.
Under the ULTOMIRIS REMS, prescribers must enroll in the program. Prescribers must counsel patients about the risk of meningococcal infection/sepsis, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccines.
Additional information on the REMS requirements is available at www.ultomirisrems.com or 1-888-765-4747.
Patients may have increased susceptibility to infections, especially with encapsulated bacteria, such as infections caused by Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Children treated with ULTOMIRIS may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP guidelines. If ULTOMIRIS is administered to patients with active systemic infections, monitor closely for worsening infection.
Monitoring Disease Manifestations after ULTOMIRIS Discontinuation
ULTOMIRIS treatment of aHUS should be a minimum duration of 6 months. Due to heterogeneous nature of aHUS events and patient-specific risk factors, treatment duration beyond the initial 6 months should be individualized. There are no specific data on ULTOMIRIS discontinuation. After discontinuing treatment with ULTOMIRIS, patients should be monitored for clinical symptoms and laboratory signs of TMA complications for at least 12 months.
TMA complications post-discontinuation can be identified if any of the following is observed: Clinical symptoms of TMA include changes in mental status, seizures, angina, dyspnea, thrombosis or increasing blood pressure. In addition, at least two of the following laboratory signs observed concurrently and results should be confirmed by a second measurement 28 days apart with no interruption: a decrease in platelet count of 25% or more as compared to either baseline or to peak platelet count during ULTOMIRIS treatment; an increase in serum creatinine of 25% or more as compared to baseline or to nadir during ULTOMIRIS treatment; or, an increase in serum LDH of 25% or more as compared to baseline or to nadir during ULTOMIRIS treatment. If TMA complications occur after discontinuation, consider reinitiation of ULTOMIRIS treatment or appropriate organ-specific supportive measures.
Thromboembolic Event Management
The effect of withdrawal of anticoagulant therapy during treatment with ULTOMIRIS has not been established. Treatment should not alter anticoagulant management.
Intravenous or subcutaneous administration of ULTOMIRIS may result in systemic infusion-related reactions, including anaphylaxis and hypersensitivity reactions. In clinical trials, infusion-related reactions occurred in approximately 1% of patients treated with ULTOMIRIS. These events included lower back pain, drop in blood pressure, elevation in blood pressure, limb discomfort, drug hypersensitivity (allergic reaction), dysgeusia (bad taste), and drowsiness. These reactions did not require discontinuation of ULTOMIRIS. If signs of cardiovascular instability or respiratory compromise occur, interrupt ULTOMIRIS infusion and institute appropriate supportive measures.
Injection Site Reactions-Subcutaneous administration
27% (23/84) of patients treated with subcutaneous administration of ULTOMIRIS experienced injection site reactions which included application site rash, device allergy, infusion site pain, infusion site reaction, injection site bruising, injection site erythema, injection site hematoma, injection site induration, injection site inflammation, injection site pain, injection site pruritus, injection site rash, injection site reaction, injection site swelling, injection site urticaria, medical device site bruise, medical device site erythema, medical device site hematoma, medical device site induration, medical device site pruritus, medical device site rash, and medical device site reaction.
Allergies to Acrylic Adhesives
The on-body injector of ULTOMIRIS uses acrylic adhesive. For patients with a known allergy to acrylic adhesive, use of this product may result in an allergic reaction. Premedication can be considered, and supportive measures should be instituted if signs of allergy appear.
Most common adverse reactions in patients with aHUS (incidence ≥20%) were upper respiratory tract infection, diarrhea, nausea, vomiting, headache, hypertension and pyrexia. Serious adverse reactions were reported in 42 (57%) patients with aHUS receiving ULTOMIRIS. The most frequent serious adverse reactions reported in more than 2 patients (2.7%) treated with ULTOMIRIS were hypertension, pneumonia and abdominal pain. In clinical studies, clinically relevant adverse reactions in <10% of patients include viral tonsillitis in adults and viral infection in pediatric patients and in 3% of adult patients include infusion-related reactions.
Adverse Reactions for Subcutaneous Administration of ULTOMIRIS
Most common adverse reactions (≥10%) with ULTOMIRIS subcutaneous administration via On Body Injector in adult patients with PNH were local injection site reactions, diarrhea, and headache.
Plasma Exchange, Plasmapheresis, and Intravenous Immunoglobulins
Concomitant use of ULTOMIRIS with plasma exchange (PE), plasmapheresis (PP), or intravenous immunoglobulin (IVIg) treatment can reduce serum ravulizumab concentrations and requires a supplemental dose of ULTOMIRIS.
Neonatal Fc Receptor Blockers
Concomitant use of ULTOMIRIS with neonatal Fc receptor (FcRn) blockers (e.g., efgartigimod) may lower systemic exposures and reduce effectiveness of ULTOMIRIS. Closely monitor for reduced effectiveness of ULTOMIRIS.
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).
Limitation of Use:
ULTOMIRIS is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC‑HUS).
Subcutaneous Use in Adult Patients with aHUS
Subcutaneous administration of ULTOMIRIS is not approved for use in pediatric patients.
Please see accompanying full Prescribing Information for ULTOMIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections/sepsis.