ULTOMIRIS 1100 mg/11 ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Ultomiris 1100 mg/11 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 Package Leaflet

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 Ultomiris is 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 clot formation, 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 muscle disease 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 changes, difficulty breathing, extreme fatigue, risk of aspiration, and marked deterioration in daily life activities. Ultomiris can block the body's inflammatory response and its ability to attack and destroy its own muscles, thus improving muscle contraction, reducing the symptoms of the disease, and its impact on daily life activities. Ultomiris is specifically indicated for patients who remain symptomatic despite treatment with other therapies.

Ultomiris is also used to treat adult patients with a central nervous system disease 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 immune system's malfunction, 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 significant difficulties with daily life 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 brain lining, which can cause brain inflammation (encephalitis), and can spread to the blood and the 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. According to 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, 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 (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 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 table/cooking 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 5.5 mg of polysorbate 80 in each 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 weighing more than 20 kg and every 4 weeks for patients weighing 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 eculizumab infusion.

Table 1. Ultomiris dosing regimen based on weight

a For patients with PNH and aHUS only.

Ultomiris is administered by infusion (drip) into a vein. The infusion will take 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, you will be closely monitored 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 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, you will be closely monitored.

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 red blood cell destruction;
• 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 alertness;
• vision changes;
• 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, you will be closely monitored.

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, you will be closely monitored.

If you have any other questions about 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 Meningococcal infection symptoms), 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, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Agency's online platform: 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 1100 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 (11 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:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: https://www.ema.europa.eu/, and on the Spanish Agency for Medicines and Health Products (AEMPS) web site (http://www.aemps.gob.es/). There are also links to other web sites on rare diseases and orphan medicines.

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This information is intended only for healthcare professionals:

Instructions for use for healthcare professionals

Handling of Ultomiris1100mg/11ml concentrate for solution for infusion

1- How is Ultomiris supplied?

Each vial of Ultomiris contains 1100 mg of active substance in 11 ml of product solution.

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

2- Before administering the medicinal product

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

In the absence of compatibility studies, Ultomiris 1100 mg/11 ml concentrate for solution for infusion must not be mixed with Ultomiris 300 mg/30 ml concentrate for solution for infusion.

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

• Visually inspect the Ultomiris solution to check for 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 must 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 must 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 complementary dose

a Body weight at the time of treatment.

b Ultomiris must 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 that the medicinal product and diluent are well mixed. Ultomiris must not be shaken.
• Allow the diluted solution to reach room temperature (18 °C–25 °C) before administration, leaving it exposed to ambient air for approximately 30 minutes.
• The diluted solution must 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 must be administered immediately after preparation. The infusion must be administered through a 0.2 µm filter.
• If the medicinal product is not used immediately after dilution, the storage times must 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.

3- Administration

• Do not administer Ultomiris by direct intravenous injection or by bolus injection.
• Ultomiris must 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 an infusion pump. It is not necessary to protect the diluted Ultomiris solution from light during administration to the patient.

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

4- Special storage and handling conditions

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 will be carried out in accordance with local regulations.