Prescribing Information: Information for the User

Ultomiris 1100 mg/11 ml Concentrate for Solution for Infusion

ravulizumab

Read this entire prescribing information carefully before you start using this medicine, because it contains important information for you.

• Keep this prescribing information, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prescribing information. See section 4.

What is Ultomiris

Ultomiris is a medication that contains the active ingredient ravulizumab and belongs to a class of medications 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 difficulty, pain, abdominal pain, dark urine, shortness of breath, difficulty swallowing, erectile dysfunction, and blood clots. By binding to and blocking the complement protein C5, this medication can prevent 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 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, may 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 difficulty. 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 (MGg). In patients with MGg, the immune system can attack and damage their own muscles, leading to significant muscle weakness, vision and mobility changes, difficulty breathing, extreme fatigue, risk of aspiration, and a significant decline 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, reducing disease symptoms, and the impact of the disease 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 the spinal cord, called neuromyelitis optica spectrum disorder (NMOSD). In patients with NMOSD, the optic nerves and spinal cord are attacked and damaged by the incorrect functioning of the 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 significant difficulties with daily activities. Ultomiris can block the abnormal immune response of the body and its ability to attack and destroy its own optic nerves and spinal cord, thus reducing the risk of relapse or NMOSD crisis.

No use Ultomiris

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

Advertencias y precauciones

Consult your doctor before starting to use Ultomiris.

Síntomas de infecciones meningocócicas y otras infecciones porNeisseria

Since the medication 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 byNeisseria meningitidis. This is a serious infection that affects the lining of the brain,which can cause inflammation of the brain (encephalitis),and can spread to the blood and body (sepsis).

Consult your doctor before starting to use Ultomiris to ensure that you are vaccinated againstNeisseria meningitidisat least 2 weeks before starting treatment. If you cannot be vaccinated 2 weeks before, your doctor will prescribe antibiotics to reduce the risk of infection until 2 weeks after being vaccinated. Make sure your meningococcal vaccination is up to date. Also, be aware that it is possible that the 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.

Síntomas de la infección meningocócica

Given the importance of identifying and quickly treating meningococcal infection 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 must 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;
• Sensitivity to light.

Tratamiento de la infección meningocócica durante los viajes

If you plan to travel to a region where you cannot contact your doctor or where you cannot receive medical treatment for some time, your doctor may prescribe an antibiotic againstNeisseria meningitidisfor you to carry with you. If you experience any of the symptoms described above, you must take the prescribed antibiotic cycle. Remember that even if you feel better after taking the antibiotic, you must see a doctor as soon as possible.

Infecciones

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

Reacciones asociadas a la perfusión

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

Niños y adolescentes

Patients under 18 years old must be vaccinated againstHaemophilusinfluenzaeand pneumococcal infections.

Pacientes de edad avanzada

No special precautions are required for the treatment of patients 65 years or older, although experience with Ultomiris in elderly patients with HPN, SHUa or TENMO in clinical studies is limited.

Otros medicamentos y Ultomiris

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Embarazo, lactancia y fertilidad

Mujeres en edad fértil

The effects of the medication on the fetus are unknown. Therefore, effective contraceptive methods should be used during treatment and for8monthsafter completing treatment in fertile women.

Embarazo/Lactancia

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

Ultomiris is not recommended during pregnancy or in fertile women who do not use contraceptives.

Conducción y uso de máquinas

The influence of this medication on the ability to drive and use machines is negligible or insignificant.

Ultomiris contains sodium

Once diluted with 9 mg/ml (0.9%) sodium chloride injection solution, this medication contains0.18g of sodium (main component of table salt/for cooking) in 72 ml at the maximum dose. This is equivalent to 9.1% of the recommended maximum daily sodium intake for an adult. You should be aware of this if you are following a low-sodium diet.

Ultomiris contains polysorbate

This medication contains5.5mg of polysorbate80 in each vial, equivalent to0.5mg/ml. Polysorbates can cause allergic reactions. Inform your doctor if you have any known allergies.

At least 2 weeks before starting treatment with Ultomiris, your doctor will

administer a vaccine against meningococcal infections if you have not been vaccinated previously 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 you have been vaccinated.

If your child is under 18 years old, your doctor will administer a vaccine (if not already done) againstHaemophilus influenzaeand pneumococcal infections in accordance with 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 administered a maintenance dose of Ultomiris, which will be repeated subsequently every 8 weeks for patients weighing more than 20 kg and every 4 weeks for patients weighing less than 20 kg.

If you previously received another medication for PNH, aSHU, MGg, or TENMO calledeculizumab, the loading dose must be administered 2weeks after the last infusion ofeculizumab.

Table 1. Dosing regimen of Ultomiris based on body weight

aFor patients with PNH and aSHU only.

Ultomiris is administered through infusion (drip) into a vein. The infusion will last approximately45minutes.

If you receive more Ultomiris than prescribed

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

If you missed a scheduled appointment for Ultomiris

If you missed a scheduled appointment, contact your doctor immediately for advice and refer to the section “If you interrupt treatment with Ultomiris” below.

If you interrupt treatment with Ultomiris for PNH

If you interrupt or discontinue treatment with Ultomiris, it is possible that PNH symptoms will recur with greater severity. Your doctor will discuss possible side effects and explain the risks. Additionally, they will closely monitor you for at least 16 weeks.

The risks of interrupting treatment with Ultomiris include an increase in red blood cell destruction, which may produce the following:

• an increase in your lactate dehydrogenase (LDH) levels, a laboratory marker of red blood cell destruction;
• a notable 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 level;
• chest pain or angina;
• an increase in serum creatinine levels (kidney problems); or
• thrombosis (blood clots).

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

If you interrupt treatment with Ultomiris for aSHU

If you interrupt or discontinue treatment with Ultomiris, it is possible that aSHU symptoms will recur. Your doctor will discuss possible side effects and explain the risks. Additionally, they will closely monitor you.

The risks of interrupting treatment with Ultomiris include an increase in damage to small blood vessels, which may produce the following:

• a notable decrease in the number of platelets (thrombocytopenia);
• an increase in red blood cell destruction;
• an increase in your 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 level;
• vision changes;
• chest pain or angina;
• shortness of breath;
• abdominal pain, diarrhea; or
• thrombosis (blood clots).

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

If you interrupt treatment with Ultomiris for MGg

If you interrupt or discontinue treatment with Ultomiris, it is possible that MGg symptoms will recur. Consult your doctor before interrupting treatment with Ultomiris. Your doctor will discuss possible side effects and explain the risks. Additionally, they will closely monitor you.

If you interrupt treatment with Ultomiris for TENMO

If you interrupt or discontinue treatment with Ultomiris, it is possible that TENMO symptoms will recur. Consult your doctor before interrupting treatment with Ultomiris. Your doctor will discuss possible side effects and explain the risks. Additionally, they will closely monitor you.

If you have any other questions about the use of this medication, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Your doctor will inform you about possible side effects and explain the risks and benefits of Ultomiris before starting treatment.

Severe side effects

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

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

Other side effects

If you are unsure about the side effects listed below, 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 (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 discomfort after meals (dyspepsia)
• Urticaria, rash, itching on the skin (pruritus)
• Muscle pain (myalgia) and muscle spasms
• Influenza-like illness, chills, weakness (asthenia)
• Reaction associated with infusion
• Allergic reaction (hypersensitivity)

Rare(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 side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directlythrough theSpanish System for Pharmacovigilance of Medicines for Human Use: www.notificaRAM.es.

By reporting side effects, you can contribute to providing more information about the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box after CAD. The expiration date is the last day of the month indicated.

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

Do not freeze.

Store in the original packaging to protect it from light.

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

Medicines should not be thrown away through drains. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Ultomiris

• The active ingredient is ravulizumab. Each vial of solution contains 1100 mg of ravulizumab.
• The other components are: dibasic sodium phosphate heptahydrate, monobasic sodium phosphate monohydrate, polisorbate 80, arginine, sucrose, and water for injection preparations.

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

Appearance of the product and contents of the pack

Ultomiris is presented as a concentrate for solution for infusion (11 ml in a vial; pack size of 1).

Ultomiris is a transparent to translucent, yellowish solution and is practically free of particles.

Marketing Authorization Holder

Alexion Europe SAS

103-105, rue Anatole France

92300 Levallois-Perret

France

Responsible Person

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

UK

Further information about this medicine can be obtained by contacting the local representative of the marketing authorization holder:

Last update of this leaflet:September 2024.

Other sources of information

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

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This information is intended solely for healthcare professionals:

Instructions for use for healthcare professionals

Handling of Ultomiris1100mg/11ml concentrate for solution for infusion

1-How is Ultomiris administered?

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

To improve the traceability of the biological medicine, the name and batch number of the administered medicine must be clearly recorded.

2-Before administering the medicine

The dilution must be carried out in accordance with good practices, especially in terms of asepsis.

In the absence of compatibility studies, Ultomiris 1100 mg/11 ml concentrate for solution for infusion should 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 that it does not contain particles or color changes.
• Withdraw the required amount of Ultomiris from the vial or vials using a sterile syringe.
• Transfer the recommended dose to a perfusion 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%) injection solution to the perfusion as per the instructions in the following table.

Table 1. Reference table for administration of loading dose

aBody weight at the time of treatment.

bUltomiris must be diluted only with sodium chloride 9 mg/ml (0.9%) injection solution.

cOnly for HPN and SHUa indications.

Table 2. Reference table for administration of maintenance dose

aBody weight at the time of treatment.

bUltomiris must be diluted only with sodium chloride 9 mg/ml (0.9%) injection solution.

cOnly for HPN and SHUa indications.

Table 3. Reference table for administration of supplementary dose

aBody weight at the time of treatment.

bUltomiris must be diluted only with sodium chloride 9 mg/ml (0.9%) injection solution.

• Gently agitate the perfusion bag with the diluted Ultomiris solution to ensure that the medicine and diluent are well mixed. Ultomiris should not be agitated.
• The diluted solution should be allowed to reach room temperature (18°C–25°C) before administration, being exposed to ambient air for approximately 30 minutes.
• The diluted solution should not be heated in a microwave oven or any other heat source other than room temperature.
• Dispose of any remaining medicine 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 medicine is not used immediately after dilution, the 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.

3- Administration

• Do not administer Ultomiris by direct intravenous injection or in a bolus injection.
• Ultomiris should only be administered by intravenous infusion.
• The diluted Ultomiris solution should be administered by intravenous infusion over approximately 45 minutes using a syringe pump or infusion pump. There is no need to protect the diluted Ultomiris solution from light during administration to the patient.

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

4- Special conditions for storage and handling

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

Do not use this medicine after the expiry date that appears on the box after CAD. The expiry date is the last day of the month indicated.

The disposal of unused medicine and all materials that have come into contact with it should be carried out in accordance with local regulations.