ULTOMIRIS 300 mg/3 ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Ultomiris 300 mg/3 ml Concentrate for Solution for Infusion

ravulizumab

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Ultomiris and what is it used for
2. What you need to know before you use Ultomiris
3. How to use Ultomiris
4. Possible side effects
5. Storage of Ultomiris
6. Contents of the pack and other information

1. What is Ultomiris and what is it used for

What is Ultomiris

Ultomiris is a medicine that contains the active substance ravulizumab and belongs to a class of medicines called monoclonal antibodies, which bind to a specific target in the body. Ravulizumab has been designed to bind to the complement protein C5, which is part of the body's defense system called the "complement system".

What is Ultomiris used for

Ultomiris is used to treat adult and pediatric patients with a body weight of 10 kg or more with a disease called paroxysmal nocturnal hemoglobinuria (PNH), including patients who have not been treated with a complement inhibitor and patients who have received eculizumab for at least the last 6 months. In patients with PNH, the complement system is overactive and attacks red blood cells, leading to a reduction in the number of red blood cells (anemia), fatigue, functional impairment, pain, abdominal pain, dark-colored urine, shortness of breath, difficulty swallowing, erectile dysfunction, and blood clots. By binding to and blocking the complement protein C5, this medicine can prevent the complement proteins from attacking red blood cells and thus control the symptoms of the disease.

Ultomiris is also used to treat adult and pediatric patients with a body weight of 10 kg or more with a disease that affects the blood system and kidneys, called atypical hemolytic uremic syndrome (aHUS), including patients who have not been treated with a complement inhibitor and patients who have received eculizumab for at least 3 months. In patients with aHUS, the kidneys and blood vessels, including platelets, can become inflamed, leading to a reduction in the number of blood cells (thrombocytopenia and anemia), reduced or lost kidney function, blood clots, fatigue, and functional impairment. Ultomiris can block the body's inflammatory response and its ability to attack and destroy its own vulnerable blood vessels, thus controlling the symptoms of the disease, such as kidney damage.

Ultomiris is also used to treat adult patients with a type of disease that affects the muscles, called generalized myasthenia gravis (gMG). In patients with gMG, the immune system can attack and damage the muscles, leading to significant muscle weakness, vision and mobility disturbances, difficulty breathing, extreme fatigue, risk of aspiration, and marked deterioration in daily activities. Ultomiris can block the body's inflammatory response and its ability to attack and destroy its own muscles, thus improving muscle contraction and reducing the symptoms of the disease and its impact on daily activities. Ultomiris is specifically indicated for patients who continue to be symptomatic despite treatment with other therapies.

Ultomiris is also used to treat adult patients with a disease of the central nervous system that primarily affects the optic nerves (of the eye) and spinal cord, called neuromyelitis optica spectrum disorder (NMOSD). In patients with NMOSD, the optic nerves and spinal cord are attacked and damaged by the malfunctioning immune system, leading to vision loss in one or both eyes, weakness or loss of movement in the legs or arms, painful spasms, loss of sensation, problems with bladder and bowel function, and great difficulties with daily activities. Ultomiris can block the abnormal immune response and the body's ability to attack and destroy its own optic nerves and spinal cord, reducing the risk of NMOSD relapse or crisis.

2. What you need to know before you use Ultomiris

Do not use Ultomiris

• if you are allergic to ravulizumab or any of the other ingredients of this medicine (listed in section 6);
• if you have not been vaccinated against meningococcal infection;
• if you have a meningococcal infection.

Warnings and precautions

Consult your doctor before starting treatment with Ultomiris.

Symptoms of meningococcal and other Neisseria infections

Since the medicine blocks the complement system, which is part of the body's defenses against infections, the use of Ultomiris increases the risk of meningococcal infection caused by Neisseria meningitidis. These are serious infections that affect the lining of the brain, which can cause brain inflammation (encephalitis), and can spread to the blood and body (sepsis).

Consult your doctor before starting treatment with Ultomiris to ensure that you are vaccinated against Neisseria meningitidis at least 2 weeks before starting treatment. If you cannot be vaccinated at least 2 weeks before starting treatment with Ultomiris, your doctor will prescribe antibiotics to reduce the risk of infection until 2 weeks after vaccination. Make sure your meningococcal vaccination is up to date. You should also be aware that vaccination may not always prevent this type of infection. In accordance with national recommendations, your doctor may consider it necessary to take additional measures to prevent infection.

Meningococcal infection symptoms

Given the importance of identifying and treating meningococcal infection quickly in patients receiving Ultomiris, you will be given a "patient card" that you should always carry with you, which contains a list of relevant signs and symptoms of meningococcal infection/sepsis/encephalitis.

If you experience any of the following symptoms, you should inform your doctor immediately:

• headache with nausea or vomiting;
• headache and fever;
• headache with neck or back stiffness;
• fever;
• fever and rash;
• confusion;
• muscle pain with flu-like symptoms;
• eye sensitivity to light.

Treatment of meningococcal infection during travel

If you plan to travel to a region where you may not be able to contact your doctor or receive medical treatment for some time, your doctor may prescribe an antibiotic against Neisseria meningitidis for you to take with you. If you experience any of the symptoms described above, you should take the antibiotic cycle as prescribed. Remember that you still need to see a doctor as soon as possible, even if you feel better after taking the antibiotic.

Infections

Before using Ultomiris, inform your doctor if you have any infection.

Infusion-related reactions

When Ultomiris is administered, you may experience infusion-related reactions (drip) such as headache, lower back pain, and infusion-associated pain. Some patients may experience allergic reactions or hypersensitivity reactions (including anaphylaxis, a severe allergic reaction that causes difficulty breathing or dizziness).

Children and adolescents

Patients under 18 years of age should be vaccinated against Haemophilus influenzae and pneumococcal infections.

Elderly patients

No special precautions are required for the treatment of patients 65 years of age or older, although experience with Ultomiris in elderly patients with PNH, aHUS, or NMOSD in clinical studies is limited.

Other medicines and Ultomiris

Inform your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Pregnancy, breastfeeding, and fertility

Women of childbearing age

The effects of the medicine on the fetus are not known. Therefore, effective contraceptive methods should be used during treatment and for up to 8 months after the end of treatment in women of childbearing age.

Pregnancy/Breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Ultomiris is not recommended during pregnancy or in women of childbearing age who do not use contraceptives.

Driving and using machines

The influence of this medicine on the ability to drive and use machines is negligible or non-existent.

Ultomiris contains sodium

Once diluted with sodium chloride 9 mg/ml (0.9%) solution for injection, this medicine contains 0.18 g of sodium (main component of cooking/table salt) in 72 ml at the maximum dose. This is equivalent to 9.1% of the maximum recommended daily intake of sodium for an adult. You should be aware of this if you are on a low-sodium diet.

Ultomiris contains polysorbate

This medicine contains 1.5 mg of polysorbate 80 per vial, equivalent to 0.5 mg/ml. Polysorbates can cause allergic reactions. Inform your doctor if you have any known allergy.

3. How to use Ultomiris

At least 2 weeks before starting treatment with Ultomiris, your doctor will administer a vaccine against meningococcal infections if you have not been vaccinated before or if your vaccination is not up to date. If you cannot be vaccinated at least 2 weeks before starting treatment with Ultomiris, your doctor will prescribe antibiotics to reduce the risk of infection until 2 weeks after vaccination.

If your child is under 18 years of age, your doctor will administer a vaccine (if not already done) against Haemophilus influenzae and pneumococcal infections according to local vaccination recommendations for each age group.

Instructions for proper use

Your doctor will calculate your dose of Ultomiris based on your body weight, as shown in Table 1. The first dose is called the loading dose. Two weeks after receiving the loading dose, you will be given a maintenance dose of Ultomiris, which will be repeated every 8 weeks for patients who weigh more than 20 kg and every 4 weeks for patients who weigh less than 20 kg.

If you were previously receiving another medicine for PNH, aHUS, gMG, or NMOSD called eculizumab, the loading dose should be administered 2 weeks after the last infusion of eculizumab.

Table 1. Ultomiris dosing regimen based on weight

For patients with PNH and aHUS only.

Ultomiris is administered by infusion (drip) into a vein. The infusion will last approximately 45 minutes.

If you receive more Ultomiris than you should

If you suspect that you have been accidentally given a higher dose of Ultomiris than prescribed, contact your doctor for advice.

If you miss an appointment to receive Ultomiris

If you miss an appointment, contact your doctor immediately for advice and refer to the section "If you stop treatment with Ultomiris" below.

If you stop treatment with Ultomiris for PNH

If you stop or discontinue treatment with Ultomiris, it is possible that the symptoms of PNH may return with greater severity. Your doctor will discuss the possible side effects and risks with you. Additionally, your doctor will closely monitor you for at least 16 weeks.

The risks of stopping treatment with Ultomiris include an increased destruction of red blood cells, which can lead to:

• an increase in lactate dehydrogenase (LDH) levels, a laboratory marker of red blood cell destruction;
• a significant decrease in the number of red blood cells (anemia);
• dark-colored urine;
• fatigue;
• abdominal pain;
• shortness of breath;
• difficulty swallowing;
• erectile dysfunction (impotence);
• confusion or change in level of alertness;
• chest pain or angina;
• an increase in serum creatinine levels (kidney problems); or
• blood clots (thrombosis).

If you experience any of these symptoms, contact your doctor.

If you stop treatment with Ultomiris for aHUS

If you stop or discontinue treatment with Ultomiris, it is possible that the symptoms of aHUS may return. Your doctor will discuss the possible side effects and risks with you. Additionally, your doctor will closely monitor you.

The risks of stopping treatment with Ultomiris include an increased damage to small blood vessels, which can lead to:

• a significant decrease in the number of platelets (thrombocytopenia);
• a significant increase in the destruction of red blood cells;
• an increase in lactate dehydrogenase (LDH) levels, a laboratory marker of red blood cell destruction;
• reduced urination (kidney problems);
• an increase in serum creatinine levels (kidney problems);
• confusion or change in level of alertness;
• changes in vision;
• chest pain or angina;
• shortness of breath;
• abdominal pain, diarrhea; or
• blood clots (thrombosis).

If you experience any of these symptoms, contact your doctor.

If you stop treatment with Ultomiris for gMG

If you stop or discontinue treatment with Ultomiris, it is possible that the symptoms of gMG may return. Consult your doctor before stopping treatment with Ultomiris. Your doctor will discuss the possible side effects and risks with you. Additionally, your doctor will closely monitor you.

If you stop treatment with Ultomiris for NMOSD

If you stop or discontinue treatment with Ultomiris, it is possible that the symptoms of NMOSD may return. Consult your doctor before stopping treatment with Ultomiris. Your doctor will discuss the possible side effects and risks with you. Additionally, your doctor will closely monitor you.

If you have any further questions on the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Your doctor will discuss the possible side effects and risks with you before you start treatment with Ultomiris.

Serious side effects

The most serious side effect is meningococcal infection, which includes meningococcal sepsis and meningococcal encephalitis.

If you experience any symptoms of meningococcal infection (see section 2 Symptoms of meningococcal infection), inform your doctor immediately.

Other side effects

If you are not sure what the following side effects are, ask your doctor to explain them to you.

Very common(may affect more than 1 in 10 people):

• headache
• dizziness
• diarrhea, nausea, abdominal pain
• fever, fatigue
• upper respiratory tract infection
• common cold (nasopharyngitis)
• back pain, joint pain (arthralgia)
• urinary tract infection

Common(may affect up to 1 in 10 people):

• vomiting, stomach upset after eating (dyspepsia)
• hives, rash, itching (pruritus)
• muscle pain (myalgia) and muscle spasms
• flu-like illness, chills, weakness (asthenia)
• infusion-related reaction
• allergic reaction (hypersensitivity)

Uncommon(may affect up to 1 in 100 people):

• meningococcal infection
• severe allergic reaction that causes difficulty breathing or dizziness (anaphylactic reaction)
• disseminated gonococcal infection

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Ultomiris

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after CAD. The expiry date is the last day of the month shown.

Store in a refrigerator (between 2 °C and 8 °C).

Do not freeze.

Store in the original packaging to protect from light.

After dilution with sodium chloride 9 mg/ml (0.9%) solution for injection, the medicinal product should be used immediately, or within 24 hours if stored in a refrigerator or within 4 hours if stored at room temperature.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Ultomiris

• The active substance is ravulizumab. Each vial of solution contains 300 mg of ravulizumab.
• The other ingredients are: disodium phosphate heptahydrate, sodium phosphate monohydrate, polysorbate 80, arginine, sucrose, and water for injections.

This medicine contains sodium (see section 2 “Ultomiris contains sodium”).

Appearance and Package Contents of the Product

Ultomiris is presented as a concentrate for solution for infusion (3 ml in a vial; pack size of 1).

Ultomiris is a clear to translucent solution, yellowish in color, and practically free of particles.

Marketing Authorisation Holder

Alexion Europe SAS

103-105, rue Anatole France

92300 Levallois-Perret

France

Manufacturer

Alexion Pharma International Operations Limited

Alexion Dublin Manufacturing Facility

College Business and Technology Park

Blanchardstown Road North

Dublin 15, D15 R925

Ireland

Almac Pharma Services (Ireland) Limited

Finnabair Industrial Estate

Dundalk

Co. Louth A91 P9KD

Ireland

Almac Pharma Services Limited

22 Seagoe Industrial Estate

Craigavon, Armagh BT63 5QD

United Kingdom

You can request more information about this medicine by contacting the local representative of the marketing authorisation holder:

Date of Last Revision of this Leaflet:September 2024.

Other Sources of Information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.

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This information is intended only for healthcare professionals:

Instructions for Use for Healthcare Professionals

Handling of Ultomiris300mg/3ml Concentrate for Solution for Infusion

1. How is Ultomiris Supplied?

Each vial of Ultomiris contains 300 mg of active substance in 3 ml of solution.

In order to improve the traceability of the biological medicinal product, the name and batch number of the administered product should be clearly recorded.

1. Before Administering the Medicinal Product

Dilution should be performed in accordance with good practice guidelines, particularly with regard to asepsis.

In the absence of compatibility studies, Ultomiris 300 mg/3 ml concentrate for solution for infusion should not be mixed with Ultomiris 300 mg/30 ml concentrate for solution for infusion.

Ultomiris should be prepared by a qualified healthcare professional using an aseptic technique.

• Visually inspect the Ultomiris solution to ensure it is free of particles or color changes.
• Withdraw the required amount of Ultomiris from the vial or vials using a sterile syringe.
• Transfer the recommended dose to an infusion bag.
• Dilute Ultomiris to a final concentration of 50 mg/ml (initial concentration divided by 2) by adding the appropriate amount of sodium chloride 9 mg/ml (0.9%) solution for injection to the infusion, according to the instructions in the following table.

Table 1. Reference Table for Administration of the Loading Dose

a Body weight at the time of treatment.

b Ultomiris should be diluted only with sodium chloride 9 mg/ml (0.9%) solution for injection.

c For HPN and SHUa indications only.

Table 2. Reference Table for Administration of the Maintenance Dose

a Body weight at the time of treatment.

b Ultomiris should be diluted only with sodium chloride 9 mg/ml (0.9%) solution for injection.

c For HPN and SHUa indications only.

Table 3. Reference Table for Administration of the Supplemental Dose

a Body weight at the time of treatment.

b Ultomiris should be diluted only with sodium chloride 9 mg/ml (0.9%) solution for injection.

• Gently shake the infusion bag with the diluted Ultomiris solution to ensure the medicinal product and diluent are well mixed. Ultomiris should not be shaken.
• Allow the diluted solution to reach room temperature (18 °C – 25 °C) before administration, by leaving it exposed to ambient air for approximately 30 minutes.
• The diluted solution should not be heated in a microwave or other heat source, other than room temperature.
• Discard any remaining medicinal product in the vial.
• The prepared solution should be administered immediately after preparation. The infusion should be administered through a 0.2 µm filter.
• If the medicinal product is not used immediately after dilution, storage times should not exceed 24 hours at a temperature between 2 °C and 8 °C or 4 hours at room temperature, taking into account the planned infusion time.

1. Administration

• Do not administer Ultomiris by direct intravenous injection or bolus injection.
• Ultomiris should only be administered by intravenous infusion.
• The diluted Ultomiris solution will be administered by intravenous infusion over approximately 45 minutes using a syringe pump or infusion pump. It is not necessary to protect the diluted Ultomiris solution from light during administration to the patient.

The patient should be monitored for one hour after the infusion. If an adverse reaction occurs during the administration of Ultomiris, the infusion may be interrupted or the rate of infusion reduced, at the discretion of the physician.

1. Special Conditions for Storage and Handling

Store in a refrigerator (between 2 °C and 8 °C). Do not freeze. Store in the original packaging to protect from light.

Do not use this medicine after the expiry date which is stated on the carton after CAD. The expiry date is the last day of the month shown.

Disposal of unused medicinal product and all materials that have come into contact with it should be done in accordance with local regulations.