Ultomiris 300 mg/3 ml concentrado para solucion para perfusion

Prescribing Information: Information for the User

Ultomiris 300 mg/3 ml Concentrate for Solution for Infusion

ravulizumab

Read this entire prescribing information carefully before starting to use this medicine, as 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 other people 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".

For what Ultomiris is used

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 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 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, reducing symptoms of the disease, 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.

Do not 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.

Warnings and precautions

Consult your doctor before starting to use Ultomiris.

Symptoms of meningococcal infections and other infections byNeisseria

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. You should also be aware that it is possible that the vaccination will not always prevent this type of infection. According to national recommendations, your doctor may consider it necessary to take additional measures to prevent infection.

Symptoms of meningococcal infection

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;
• light sensitivity.

Treatment of meningococcal infection during travel

If you plan to travel to an area 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.

Infections

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

Reactions associated with infusion

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 reactions or hypersensitivity (including anaphylaxis, a severe allergic reaction that causes difficulty breathing or dizziness).

Children and adolescents

Patients under 18 years old must be vaccinated againstHaemophilus influenzaeand pneumococcal infections.

Older patients

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

Other medications and Ultomiris

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

Pregnancy, breastfeeding, and fertility

Women of childbearing age

No effects of the medication on the fetus are known. Therefore, effective contraceptive methods should be used during treatment and for8monthsafter completing treatment in women of childbearing age.

Pregnancy/Breastfeeding

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 women of childbearing age who do not use contraceptives.

Driving and operating machinery

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

Ultomiris contains sodium

Once diluted with 9 mg/ml (0.9%) sodium chloride injection solution, this medication contains 0.18 g 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 contains 1.5 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 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 being 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 Ultomiris dose 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 forHPN, the SHUa, the MGg, or the TENMOcalled eculizumab, the loading dose should be administered 2 weeks after the last eculizumab infusion.

Table 1. Ultomiris dosing schedule based on body weight

aFor patients with HPN and SHUa only.

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

If you receive more Ultomiris than you should

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 HPN

If you interrupt or discontinue treatment with Ultomiris, it is possible that the symptoms of HPN will reappear with greater severity. Your doctor will discuss the possible adverse 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 the destruction of red blood cells, which may produce the following:

• An increase in your 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;
• Dyspnea;
• Dysphagia;
• 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 SHUa

If you interrupt or discontinue treatment with Ultomiris, it is possible that the symptoms of SHUa will reappear. Your doctor will discuss the possible adverse 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 significant decrease in the number of platelets (thrombocytopenia);
• A notable increase in red blood cell destruction;
• An increase in your lactate dehydrogenase (LDH) levels, a laboratory marker of red blood cell destruction;
• Reduced urine output (kidney problems);
• An increase in serum creatinine levels (kidney problems);
• Confusion or change in alertness level;
• Changes in vision;
• Chest pain or angina;
• Dyspnea;
• 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 the symptoms of MGg will reappear. Consult your doctor before interrupting treatment with Ultomiris. Your doctor will discuss the possible adverse 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 the symptoms of TENMO will reappear. Consult your doctor before interrupting treatment with Ultomiris. Your doctor will discuss the possible adverse 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 adverse effects, although not everyone will experience them.

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

Severe Adverse Effects

The most severe adverse 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 Adverse Effects

If you are unsure about the adverse 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
• 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 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 Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Use: www.notificaRAM.es.

By reporting adverse 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 disposed of 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 300 mg of ravulizumab.
• The other components are: sodium phosphate dibasic heptahydrate, sodium phosphate monobasic monohydrate, polisorbate 80, arginine, sucrose, and water for injection.

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 (3 ml in a vial; pack size of 1).

Ultomiris is a transparent to slightly opalescent, yellowish solution and is practically free from 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 on this medicinal product 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 on this medicinal product 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 Ultomiris300mg/3ml concentrate for solution for infusion

1. How is Ultomiris administered?

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

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

1. Before administering the medicinal product

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

Unless compatibility studies have been carried out, Ultomiris 300 mg/3 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 that it does not contain particles or changes in color.
• 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%) injection solution to the infusion according to the instructions in the following table.

Table 1. Reference table for administration of the 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 the 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 the 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 infusion bag with the diluted Ultomiris solution to ensure that the medicinal product and the diluent are well mixed. Ultomiris must not be agitated.
• The diluted solution must be allowed to reach room temperature (18 °C–25 °C) before administration, leaving it exposed to the ambient air for approximately 30 minutes.
• The diluted solution must not be heated in a microwave oven or any other heat source other than room temperature.
• Dispose of 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.

1. Administration

• Do not administer Ultomiris by direct intravenous injection or in a bolus injection.
• Ultomiris must only be administered by intravenous infusion.
• The diluted Ultomiris solution must be administered by intravenous infusion over approximately 45 minutes using a syringe pump or an infusion pump. No protection of the diluted Ultomiris solution from light is required during administration to the patient.

The patient must be observed for at least one hour after the 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.

1. Special conditions for storage and handling

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

Do not use this medicinal product 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 medicinal product and all materials that have come into contact with it must be carried out in accordance with local regulations.