Ultomiris

Package leaflet: Information for the user

Ultomiris 300 mg/30 mL concentrate for solution for infusion

ravulizumab
Please read this leaflet carefully before you use this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What Ultomiris is and what it is used for

What Ultomiris is
Ultomiris is a medicine containing the active substance ravulizumab and belongs to a class of
medicines called monoclonal antibodies, which bind to a specific target in the body. Ravulizumab is
designed to bind to complement protein C5, which is part of the body's defense system known as the
“complement system”.

What Ultomiris is used for
Ultomiris is used to treat adult and pediatric patients weighing at least 10 kg with a disease called
paroxysmal nocturnal hemoglobinuria (PNH), including patients who have not been previously treated
with complement inhibitors and patients who have received eculizumab within the last 6 months. In
patients with PNH, the complement system is overactive and attacks their red blood cells, causing a
decrease in red blood cell count (anemia), fatigue, functional impairment, pain, abdominal pain, dark
urine, shortness of breath, difficulty swallowing, erectile dysfunction, and blood clots. By binding to
and blocking complement protein C5, this medicine can prevent complement proteins from attacking
red blood cells, thereby controlling the symptoms of the disease.

Ultomiris is also used to treat adult and pediatric patients weighing at least 10 kg with a disease
affecting the blood system and kidneys called atypical haemolytic uremic syndrome (aHUS), including
patients who have not been previously treated with complement inhibitors and patients who have
received eculizumab within the last 3 months. In patients with aHUS, the kidneys and blood vessels,
including platelets, can become inflamed, leading to a reduced 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 vulnerable blood
vessels, thereby controlling the symptoms of the disease, including kidney damage.

Ultomiris is also used to treat adult patients with a specific type of muscle disease called generalized
myasthenia gravis (gMG). In patients with gMG, muscles can be attacked and damaged by the immune
system, causing severe muscle weakness, impaired vision and mobility, shortness of breath, extreme
fatigue, risk of aspiration, and significantly impaired daily activities. Ultomiris can block the body's
inflammatory response and its ability to attack and destroy its own muscles, thereby improving muscle
contraction and reducing disease symptoms and their impact on daily 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 disorder that primarily affects
the optic nerves (of the eyes) 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 a malfunctioning
immune system, potentially leading to vision loss in one or both eyes, weakness or loss of movement in
the legs or arms, painful spasms, loss of sensation, bladder and bowel dysfunction, and significant
difficulties with daily activities. Ultomiris is able to block the body's abnormal immune response and
its ability to attack and destroy its own optic nerves and spinal cord, thereby reducing the risk of relapse
or NMOSD attacks.

2. What you need to know before using Ultomiris

Do not use Ultomiris

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

Warnings and precautions
Talk to your doctor before using Ultomiris.
Symptoms of meningococcal infection and other Neisseria infections
Because this medicine blocks the complement system, which is part of the body's defences against infections, using Ultomiris increases the risk of meningococcal infection caused by Neisseria meningitidis. These are serious infections affecting the membranes covering the brain, which can lead to inflammation of the brain (encephalitis) and spread into the bloodstream and throughout the body (sepsis).
Before starting treatment with Ultomiris, consult your doctor to ensure you receive vaccination against Neisseria meningitidis at least 2 weeks prior to starting therapy. If you cannot be vaccinated 2 weeks before treatment, your doctor will prescribe antibiotics to reduce the risk of infection for up to 2 weeks after vaccination. Make sure your meningococcal infection vaccination is not expired. 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 for you to take additional preventive measures.
Symptoms of meningococcal infection
Because it is important to detect and treat meningococcal infection quickly in patients receiving Ultomiris, you will be given a “Patient Alert Card” to carry with you at all times, listing the relevant signs and symptoms of meningococcal infection/sepsis/encephalitis.
If any of the following symptoms occur, 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 of the eyes to light

Treatment of meningococcal infection during travel
If you are planning to travel to a country where you may not be able to contact your doctor or temporarily unable to access medical care, your doctor may prescribe an antibiotic against Neisseria meningitidis for you to carry with you. If any of the symptoms listed above occur, you should take the prescribed course of antibiotics. Please note that you must consult a doctor as soon as possible, even if you feel better after taking the antibiotics.
Infections
Before starting treatment with Ultomiris, inform your doctor if you currently have any infections.
Infusion-related reactions
During administration of Ultomiris, infusion-related reactions (such as headache, lower back pain, and infusion-related pain) may occur. Some patients may experience allergic or hypersensitivity reactions (including anaphylaxis, a severe allergic reaction causing difficulty breathing or dizziness).
Children and adolescents
Patients under 18 years of age should be vaccinated against Haemophilus influenzae and pneumococcal infections.
Elderly
No special precautions are required for treatment of patients aged 65 years or older, although experience with Ultomiris in elderly patients with PNH, aHUS, or NMOSD in clinical trials 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 this medicine on the unborn child are unknown. Therefore, effective contraceptive methods must be used by women of childbearing age during treatment and for 8 months after treatment ends.
Pregnancy/breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before using this medicine.
Ultomiris is not recommended during pregnancy and in women of childbearing age who are not using contraceptive measures.
Driving and using machines
This medicine does not alter or alters negligibly the ability to drive vehicles or operate machinery.
Ultomiris contains sodium
After dilution with 9 mg/mL (0.9%) sodium chloride injection solution, this medicine contains 2.65 g of sodium (a main component of table salt) in 720 mL at the maximum dose. This corresponds to 133% of the maximum recommended daily dietary intake for an adult.
You should take this into account if you are on a low-sodium diet.
Ultomiris contains polysorbate
This medicine contains 6.0 mg of polysorbate 80 per vial, equivalent to 0.2 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use Ultomiris

At least 2 weeks before starting treatment with Ultomiris, your doctor will give you a
vaccine against meningococcal infections, if you have not previously received this vaccine or if your
vaccination has expired. 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 for up to
2 weeks after vaccination.
If your child is under 18 years of age, your doctor will administer a vaccine (unless vaccination has
already been performed) against Haemophilus influenzae and pneumococcal infections,
according to national vaccination recommendations for each age group.
Instructions for correct use
Your doctor will calculate the 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 once every
8 weeks for patients weighing more than 20 kg and every 4 weeks for patients weighing
less than 20 kg.
If you have previously received 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 according to body weight

Ultomiris is administered by infusion (drip) into a vein. The infusion will take approximately 2 hours.
If you receive more Ultomiris than you should
If you suspect that you have accidentally received a higher dose of Ultomiris than prescribed, consult your doctor.
If you miss an appointment for Ultomiris administration
If you miss an appointment, contact your doctor immediately and refer to the following section “If you stop treatment with Ultomiris”.
If you stop treatment with Ultomiris for PNH
Stopping or interrupting treatment with Ultomiris may cause PNH symptoms to return more severely. Your doctor will discuss the possible side effects with you and explain the risks. Your doctor will monitor you closely for at least 16 weeks.
The risks of stopping Ultomiris include increased destruction of red blood cells, which may cause:

• Increased levels of lactate dehydrogenase (LDH), a laboratory marker of red blood cell destruction,
• A significant reduction in the number of red blood cells (anaemia),
• Dark urine,
• Fatigue,
• Abdominal pain,
• Shortness of breath,
• Difficulty swallowing,
• Erectile dysfunction (impotence),
• Confusion or changes in alertness,
• Chest pain or angina,
• Increased serum creatinine levels (kidney problems), or
• Thrombosis (blood clot formation). If you experience any of these symptoms, contact your doctor.

If you stop treatment with Ultomiris for aHUS
Stopping or interrupting treatment with Ultomiris may cause aHUS symptoms to return. Your doctor will discuss the possible side effects with you and explain the risks. Your doctor will monitor you closely.
The risks of stopping Ultomiris include increased damage to small blood vessels, which may cause:

• A significant reduction in platelet count (thrombocytopenia),
• A significant increase in red blood cell destruction,
• Increased levels of lactate dehydrogenase (LDH), a laboratory marker of red blood cell destruction,
• A significant reduction in urine production (kidney problems),
• Increased serum creatinine levels (kidney problems),
• Confusion or changes in alertness,
• Vision disturbances,
• Chest pain or angina,
• Shortness of breath,
• Abdominal pain, diarrhoea, or
• Thrombosis (blood clot formation).

If you experience any of these symptoms, contact your doctor.
If you stop treatment with Ultomiris for gMG
Stopping or interrupting treatment with Ultomiris may cause gMG symptoms to return. Speak to your doctor before stopping treatment with Ultomiris. Your doctor will discuss the possible side effects with you and explain the risks. Your doctor will also monitor you closely.
If you stop treatment with Ultomiris for NMOSD
Stopping or interrupting treatment with Ultomiris may cause NMOSD symptoms to return. Speak to your doctor before stopping treatment with Ultomiris. Your doctor will discuss the possible side effects with you and explain the risks. Your doctor will also monitor you closely.
If you have any doubts about how to use this medicine, speak to your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Before starting treatment, your doctor will discuss the possible side effects with you and explain the risks and benefits of Ultomiris.

Serious side effects
The most serious side effect is meningococcal infection, including meningococcal sepsis and meningococcal encephalitis.
If you experience any of the symptoms of meningococcal infection (see section 2, Symptoms of meningococcal infection), you must inform your doctor immediately.

Other side effects
If you have any questions about the meaning of the side effects listed below, ask your doctor for clarification.

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

• Headache
• Dizziness
• Diarrhoea, nausea, abdominal pain
• Fever, feeling of fatigue (tiredness)
• Infection of the upper respiratory tract
• 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)
• Hives, rash, itchy skin (pruritus)
• Muscle pain (myalgia) and muscle spasms
• Influenza-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 causing breathing difficulties or dizziness (anaphylactic reaction)
• Disseminated gonococcal infection

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ultomiris

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "Exp". The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C).
Do not freeze.
Keep in the original packaging to protect from light.
After dilution with 9 mg/mL (0.9%) sodium chloride solution for injection, the medicine should be used immediately, within 24 hours if refrigerated or within 6 hours at room temperature.
Do not dispose of medicines via wastewater. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Ultomiris contains

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

This medicinal product contains sodium (see section 2 “Ultomiris contains sodium”).
Description of the appearance of Ultomiris and contents of the pack
Ultomiris is supplied as a concentrate for solution for infusion (30 mL in a vial –
pack size: 1).
Ultomiris is a solution ranging from clear to slightly opalescent, slightly whitish in colour, practically free from 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
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Lietuva
België/Belgique/Belgien UAB AstraZeneca Lietuva
Alexion Pharma Belgium Tel: +370 5 2660550
Tél/Tel: +32 0 800 200 31
България Luxembourg/Luxemburg
АстраЗенека България ЕООД Alexion Pharma Belgium
Teл.: +359 24455000 Tél/Tel: +32 0 800 200 31
Česká republika Magyarország
AstraZeneca Czech Republic s.r.o. AstraZeneca Kft.
Tel: +420 222 807 111 Tel.: +36 1 883 6500
Danmark Malta
Alexion Pharma Nordics AB Alexion Europe SAS
Tlf.: +46 0 8 557 727 50 Tel: +353 1 800 882 840
Deutschland Nederland
Alexion Pharma Germany GmbH Alexion Pharma Netherlands B.V.
Tel: +49 (0) 89 45 70 91 300 Tel: +32 (0)2 548 36 67
Eesti Norge
AstraZeneca Alexion Pharma Nordics AB
Tel: +372 6549 600 Tlf: +46 (0)8 557 727 50
Ελλάδα Österreich
AstraZeneca A.E. Alexion Pharma Austria GmbH
Τηλ: +30 210 6871500 Tel: +41 44 457 40 00
España Polska
Alexion Pharma Spain, S.L. AstraZeneca Pharma Poland Sp. z o.o.
Tel: +34 93 272 30 05 Tel.: +48 22 245 73 00
France Portugal
Alexion Pharma France SAS Alexion Pharma Spain, S.L. - Sucursal em
Tél: +33 1 47 32 36 21 Portugal
Tel: +34 93 272 30 05
Hrvatska România
AstraZeneca d.o.o. AstraZeneca Pharma SRL
Tel: +385 1 4628 000 Tel: +40 21 317 60 41
Ireland Slovenija
Alexion Europe SAS AstraZeneca UK Limited
Tel: +353 1 800 882 840 Tel: +386 1 51 35 600
Ísland Slovenská republika
Alexion Pharma Nordics AB AstraZeneca AB, o.z.
Sími: +46 0 8 557 727 50 Tel: +421 2 5737 7777
Italia Suomi/Finland
Alexion Pharma Italy srl Alexion Pharma Nordics AB
Tel: +39 02 7767 9211 Puh/Tel: +46 0 8 557 727 50
Κύπρος Sverige
Alexion Europe SAS Alexion Pharma Nordics AB
Τηλ: +357 22490305 Tel: +46 0 8 557 727 50
Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency, http://www.ema.europa.eu/ .
<------------------------------------------------------------------------------------------------------------------------>
The following information is intended exclusively for healthcare professionals:

Instructions for Use for Healthcare Professionals

Handling of Ultomiris 300 mg/30 mL concentrate for solution for infusion
1- How is Ultomiris supplied?
Each vial of Ultomiris contains 300 mg of active substance in 30 mL of solution.
In order to improve the traceability of the biological medicinal product, the name and batch number of the administered medicinal product must be clearly recorded.
2- Prior to administration
Dilution must be performed in accordance with good practice standards, particularly with regard to aseptic technique.
In the absence of compatibility studies, Ultomiris 300 mg/30 mL concentrate for solution for infusion must not be mixed with Ultomiris 300 mg/3 mL or 1100 mg/11 mL concentrates for solution for infusion.
Ultomiris must be prepared for administration by a qualified healthcare professional using aseptic technique.

• Visually inspect the Ultomiris solution for the presence of particles and discoloration.
• Withdraw the required amount of Ultomiris from the vial(s) using a sterile syringe.
• Transfer the recommended dose into an infusion bag.
• Dilute Ultomiris to a final concentration of 5 mg/mL (initial concentration divided by 2) by adding the appropriate amount of 9 mg/mL (0.9%) sodium chloride injection solution, according to the instructions in the table below.

Table 1: Dosing reference table for loading dose administration

Body weight at the time of treatment.
Ultomiris must be diluted using only a 9 mg/mL (0.9%) sodium chloride injectable solution.
Only for the PNH and aHUS indications.
Table 2: Reference table for maintenance dose administration

Body weight at the time of treatment.
Ultomiris must be diluted using only an injectable solution of sodium chloride 9 mg/mL (0.9%).
Only for the indications PNH and aHUS.
Table 3: Reference table for administration of the supplementary dose

Body weight at the time of treatment.
Ultomiris must be diluted using only an injectable solution of sodium chloride 9 mg/mL (0.9%).

• Gently swirl the infusion bag containing the diluted Ultomiris solution to ensure complete mixing of the medicinal product and diluent. Do not shake Ultomiris.
• Allow the diluted solution to warm to room temperature (18 °C – 25 °C) before administration by leaving it exposed to ambient air for approximately 30 minutes.
• The diluted solution must not be heated in a microwave or by any other heat source apart from room temperature.
• Discard any unused portion remaining in the vial.
• The prepared solution should 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 duration must not exceed 24 hours at 2 °C – 8 °C, or 6 hours at room temperature, taking into account the expected infusion time.

3 - Administration

• Do not administer Ultomiris as a rapid intravenous injection or bolus.
• Ultomiris must be administered only by intravenous infusion.
• The diluted Ultomiris solution must be administered by intravenous infusion over approximately 2 hours, using an infusion pump or syringe pump. It is not necessary to protect the diluted Ultomiris solution from light during administration to the patient. The patient must be monitored for one hour after the infusion. If an adverse event occurs during administration of Ultomiris, the infusion may be slowed or stopped at the physician's discretion.

4 - Special precautions for handling and storage
Store in a refrigerator (2 °C – 8 °C). Do not freeze. Keep in the original packaging to protect the medicinal product from light.
Do not use this medicinal product after the expiry date stated on the carton after “Exp”. The expiry date refers to the last day of that month.
Any unused medicinal product and waste materials derived from such medicinal product should be disposed of in accordance with local regulations.

Package leaflet: Information for the user

Ultomiris 1100 mg/11 mL concentrate for solution for infusion

ravulizumab
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What Ultomiris is and what it is used for

What Ultomiris is
Ultomiris is a medicine containing the active substance ravulizumab and belongs to a class of
medicines called monoclonal antibodies, which bind to a specific target in the body.
Ravulizumab is designed to bind to complement protein C5, which is part of the body's defense system known as the “complement system”.

What Ultomiris is used for
Ultomiris is used to treat adult and pediatric patients weighing at least 10 kg with a disease called paroxysmal nocturnal hemoglobinuria (PNH), including patients who have not been previously treated with complement inhibitors and those who have received eculizumab within the last 6 months. In patients with PNH, the complement system is overactive and attacks their red blood cells, causing a reduction in red blood cell count (anemia), fatigue, functional impairment, pain, abdominal pain, dark urine, shortness of breath, difficulty swallowing, erectile dysfunction, and blood clots. By binding to and blocking complement protein C5, this medicine can prevent complement proteins from attacking red blood cells, thereby controlling the symptoms of the disease.

Ultomiris is also used to treat adult and pediatric patients weighing at least 10 kg with a disease affecting the blood system and kidneys called atypical hemolytic uremic syndrome (aHUS), including patients who have not been previously treated with complement inhibitors and those who have received eculizumab within the last 3 months. In patients with aHUS, the kidneys and blood vessels, including platelets, may become inflamed, leading to a reduction in blood cell counts (thrombocytopenia and anemia), reduced or lost kidney function, blood clots, fatigue, and functional impairment. Ultomiris can block the body's inflammatory response and its tendency to attack and destroy its own vulnerable blood vessels, thereby controlling disease symptoms, including kidney damage.

Ultomiris is also used to treat adult patients with a specific type of muscle disease called generalized myasthenia gravis (gMG). In patients with gMG, muscles may be attacked and damaged by the immune system, leading to severe muscle weakness, impaired vision and mobility, shortness of breath, extreme fatigue, risk of aspiration, and significantly impaired daily activities. Ultomiris can block the body's inflammatory response and its ability to attack and destroy its own muscles, thereby improving muscle contraction and reducing disease symptoms and their impact on daily 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 disorder that primarily affects the optic nerves (of the eyes) 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 a malfunctioning immune system, potentially leading to loss of vision in one or both eyes, weakness or loss of movement in the legs or arms, painful spasms, loss of sensation, bladder and bowel dysfunction, and significant difficulties in daily activities. Ultomiris is able to block the body's abnormal immune response and its ability to attack and destroy its own optic nerves and spinal cord, thereby reducing the risk of relapse or NMOSD attacks.

2. What you need to know before using Ultomiris

Do not use Ultomiris

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

Warnings and precautions
Talk to your doctor before using Ultomiris.
Symptoms of meningococcal infection and other Neisseria infections
Since this medicine blocks the complement system, which is part of the body's defenses against infections, using Ultomiris increases the risk of meningococcal infection caused by Neisseria meningitidis. These are serious infections affecting the membranes covering the brain, which can lead to brain inflammation (encephalitis) and spread into the bloodstream and throughout the body (sepsis).
Consult your doctor before starting treatment with Ultomiris to ensure you receive vaccination against Neisseria meningitidis at least 2 weeks before starting therapy. If you cannot be vaccinated 2 weeks beforehand, your doctor will prescribe antibiotics to reduce the risk of infection for up to 2 weeks after vaccination. Make sure your meningococcal infection vaccination is not expired. 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 for you to take additional measures to prevent infection.
Symptoms of meningococcal infection
Because it is important to detect and treat meningococcal infection quickly in patients receiving Ultomiris, you will be given a “Patient Alert Card” to carry with you at all times, listing the relevant signs and symptoms of meningococcal infection/sepsis/encephalitis.
If any of the following symptoms occur, 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 of the eyes to light

Treatment of meningococcal infection while traveling
If you are planning to travel to a country where you will not be able to contact your doctor or temporarily lack access to medical care, your doctor may prescribe an antibiotic against Neisseria meningitidis for you to carry with you. If any of the symptoms described above occur, you should take the prescribed course of antibiotics. Keep in mind that you must still consult a doctor as soon as possible, even if you feel better after taking the antibiotics.
Infections
Before starting treatment with Ultomiris, inform your doctor if you currently have any infections.
Infusion-related reactions
During administration of Ultomiris, infusion-related reactions (such as headache, lower back pain, and infusion-related pain) may occur. Some patients may experience allergic or hypersensitivity reactions (including anaphylaxis, a severe allergic reaction causing difficulty breathing or dizziness).
Children and adolescents
Patients under 18 years of age should be vaccinated against Haemophilus influenzae and pneumococcal infections.
Elderly
No special precautions are required for treating patients aged 65 years or older, although experience with Ultomiris in elderly patients with PNH, aHUS, or NMOSD in clinical trials 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 potential
The effects of this medicine on the unborn child are unknown. Therefore, effective contraceptive methods must be used in women of childbearing potential during treatment and for up to 8 months after treatment ends.
Pregnancy/breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
Ultomiris is not recommended during pregnancy or in women of childbearing potential who are not using contraceptive measures.
Driving and using machines
This medicine does not affect or has a negligible effect on the ability to drive and use machines.
Ultomiris contains sodium
After dilution with 9 mg/mL (0.9%) sodium chloride solution for injection, this medicine contains 0.18 g of sodium (the main component of table salt) in 72 mL at the maximum dose. This corresponds to 9.1% of the maximum daily recommended dietary intake for an adult.
You should take this into account if you are on a low-sodium diet.
Ultomiris contains polysorbate
This medicine contains 5.5 mg of polysorbate 80 per vial, equivalent to 0.5 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

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 previously received this vaccine or if your
vaccination has expired. 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 for up to
2 weeks after vaccination.
If your child is under 18 years of age, your doctor will administer a vaccine (unless vaccination
has already been performed) against Haemophilus influenzae and pneumococcal infections,
according to national vaccination recommendations for each age group.
Instructions for correct use
The dose of Ultomiris will be calculated by your doctor based on your body weight, as indicated 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 once every
8 weeks for patients weighing more than 20 kg and every 4 weeks for patients weighing
less than 20 kg.
If you have previously received another medicine for aHUS, PNH, gMG or NMOSD called
eculizumab, the loading dose should be administered 2 weeks after the last infusion of
eculizumab.
Table 1: Ultomiris dosing regimen according to body weight

For patients with aHUS and PNH only.
Ultomiris is administered by intravenous infusion (drip) into a vein. The infusion will take approximately
45 minutes.
If you receive more Ultomiris than prescribed
If you suspect that you have accidentally received a dose of Ultomiris higher than prescribed,
consult your doctor.
If you miss an appointment for Ultomiris administration
If you miss an appointment, contact your doctor immediately and refer to the following
section “If you discontinue treatment with Ultomiris”.
If you discontinue treatment with Ultomiris for PNH
Stopping or interrupting treatment with Ultomiris may cause the symptoms of PNH to return with increased severity. Your doctor will discuss with you the possible adverse effects and explain the risks. Your doctor will monitor you closely for at least 16 weeks.
The risks of discontinuing Ultomiris include increased destruction of red blood cells, which
may cause:

• Increased levels of lactate dehydrogenase (LDH), a laboratory marker of red blood cell destruction,
• A significant reduction in red blood cell count (anemia),
• Dark urine,
• Fatigue,
• Abdominal pain,
• Shortness of breath,
• Difficulty swallowing,
• Erectile dysfunction (impotence),
• Confusion or changes in alertness,
• Chest pain or angina,
• Increased serum creatinine levels (kidney problems), or
• Thrombosis (blood clot formation).

If you experience any of these symptoms, contact your doctor.
If you discontinue treatment with Ultomiris for aHUS
Stopping or interrupting treatment with Ultomiris may cause the symptoms of aHUS to return. Your doctor will discuss with you the possible adverse effects and explain the risks. Your doctor will monitor you closely.
The risks of discontinuing Ultomiris include increased damage to small blood vessels, which
may cause:

• A significant reduction in platelet count (thrombocytopenia),
• A significant increase in red blood cell destruction,
• Increased levels of lactate dehydrogenase (LDH), a laboratory marker of red blood cell destruction,
• Reduced urine output (kidney problems),
• Increased serum creatinine levels (kidney problems),
• Confusion or changes in alertness,
• Vision disturbances,
• Chest pain or angina,
• Shortness of breath,
• Abdominal pain, diarrhea, or
• Thrombosis (blood clot formation).

If you experience any of these symptoms, contact your doctor.
If you discontinue treatment with Ultomiris for gMG
Stopping or interrupting treatment with Ultomiris may cause the symptoms of gMG to return. Consult your doctor before discontinuing treatment with Ultomiris. Your doctor will discuss with you the possible adverse effects and explain the risks. Your doctor will also monitor you closely.
If you discontinue treatment with Ultomiris for NMOSD
Stopping or interrupting treatment with Ultomiris may cause the symptoms of NMOSD to return. Consult your doctor before discontinuing treatment with Ultomiris. Your doctor will discuss with you the possible adverse effects and explain the risks. Your doctor will also monitor you closely.
If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Before treatment, your doctor will discuss the possible side effects with you and explain the risks and
benefits of Ultomiris.
Serious side effects
The most serious side effect is meningococcal infection, including meningococcal sepsis and
meningococcal encephalitis.
If you experience any of the symptoms of meningococcal infection (see section 2 Symptoms of
meningococcal infection), you must inform your doctor immediately.
Other side effects
If you have any questions about the meaning of the side effects listed below, please ask your doctor.
Very common (may affect more than 1 in 10 people):

• Headache
• Dizziness
• Diarrhoea, nausea, abdominal pain
• Fever, feeling of fatigue (tiredness)
• 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, upset stomach after meals (dyspepsia)
• Hives, skin rash, itchy skin (pruritus)
• Muscle pain (myalgia) and muscle spasms
• Influenza-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 causing breathing difficulties or dizziness (anaphylactic reaction)
• Disseminated gonococcal infection

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist,
or nurse. You can also report side effects directly via the national reporting system referred to in
Annex V. By reporting side effects, you can help provide more information on the safety of this
medicine.

5. How to store Ultomiris

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after “Exp”. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C).
Do not freeze.
Keep in the original packaging to protect the medicine from light.
After dilution with 9 mg/mL (0.9%) sodium chloride injectable solution, the medicine should be used immediately, within 24 hours if refrigerated or within 4 hours at room temperature.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Ultomiris contains

• The active substance is ravulizumab. Each vial of solution contains 1100 mg of ravulizumab.
• The other components are: disodium phosphate heptahydrate, monosodium phosphate monohydrate, polysorbate 80, arginine, sucrose, water for injections.

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

Description of the appearance of Ultomiris and contents of the pack
Ultomiris is supplied as a concentrate for solution for infusion (11 mL in a vial – pack size: 1).
Ultomiris is a translucent, clear to slightly yellow solution, practically free from 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

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Alexion Pharma Belgium UAB AstraZeneca Lietuva
Tél/Tel: +32 0 800 200 31 Tel: +370 5 2660550

България Luxembourg/Luxemburg
АстраЗенека България ЕООД Alexion Pharma Belgium
Teл.: +359 24455000 Tél/Tel: +32 0 800 200 31

Česká republika Magyarország
AstraZeneca Czech Republic s.r.o. AstraZeneca Kft.
Tel: +420 222 807 111 Tel.: +36 1 883 6500

Danmark Malta
Alexion Pharma Nordics AB Alexion Europe SAS
Tlf.: +46 0 8 557 727 50 Tel: +353 1 800 882 840

Deutschland Nederland
Alexion Pharma Germany GmbH Alexion Pharma Netherlands B.V.
Tel: +49 (0) 89 45 70 91 300 Tel: +32 (0)2 548 36 67

Eesti Norge
AstraZeneca Alexion Pharma Nordics AB
Tel: +372 6549 600 Tlf: +46 (0)8 557 727 50

Ελλάδα Österreich
AstraZeneca A.E. Alexion Pharma Austria GmbH
Τηλ: +30 210 6871500 Tel: +41 44 457 40 00

España Polska
Alexion Pharma Spain, S.L. AstraZeneca Pharma Poland Sp. z o.o.
Tel: +34 93 272 30 05 Tel.: +48 22 245 73 00

France Portugal
Alexion Pharma France SAS Alexion Pharma Spain, S.L. - Sucursal em Portugal
Tél: +33 1 47 32 36 21 Tel: +34 93 272 30 05

Hrvatska România
AstraZeneca d.o.o. AstraZeneca Pharma SRL
Tel: +385 1 4628 000 Tel: +40 21 317 60 41

Ireland Slovenija
Alexion Europe SAS AstraZeneca UK Limited
Tel: +353 1 800 882 840 Tel: +386 1 51 35 600

Ísland Slovenská republika
Alexion Pharma Nordics AB AstraZeneca AB, o.z.
Sími: +46 0 8 557 727 50 Tel: +421 2 5737 7777

Italia Suomi/Finland
Alexion Pharma Italy srl Alexion Pharma Nordics AB
Tel: +39 02 7767 9211 Puh/Tel: +46 0 8 557 727 50

Κύπρος Sverige
Alexion Europe SAS Alexion Pharma Nordics AB
Τηλ: +357 22490305 Tel: +46 0 8 557 727 50

Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/ .

<------------------------------------------------------------------------------------------------------------------------>
The following information is intended for healthcare professionals only:

Instructions for use for healthcare professionals

Handling of Ultomiris 1100 mg/11 mL concentrate for solution for infusion
1- How is Ultomiris supplied?
Each Ultomiris vial contains 1,100 mg of active substance in 11 mL of solution.
To improve traceability of the biological medicinal product, the name and batch number of the administered medicine must be clearly recorded.
2- Prior to administration
Dilution must be performed in accordance with good practice standards, particularly maintaining aseptic conditions.
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 for administration by a qualified healthcare professional using aseptic technique.

• Visually inspect the Ultomiris solution for the presence of particles and discoloration.
• Withdraw the required amount of Ultomiris from the vial(s) using a sterile syringe.
• Transfer the recommended dose into an infusion bag.
• Dilute Ultomiris to a final concentration of 50 mg/mL (initial concentration divided by 2) by adding the appropriate volume of 9 mg/mL (0.9%) sodium chloride injectable solution to the infusion, according to the instructions in the table below.

Table 1: Dosing reference table for loading dose administration

Body weight at the time of treatment.
Ultomiris must be diluted using only a 9 mg/mL (0.9%) sodium chloride injectable solution.
For EPN and aHUS indications only.
Table 2: Dosing schedule reference table for maintenance dose administration

Body weight at the time of treatment.
Ultomiris must be diluted using only sodium chloride 9 mg/mL (0.9%) injectable solution.
For EPN and aHUS indications only.
Table 3: Reference table for administration of the supplemental dose

Body weight at the time of treatment.
Ultomiris must be diluted using only a 9 mg/mL (0.9%) sodium chloride injectable solution.

• Gently mix the infusion bag containing the diluted Ultomiris solution to ensure complete mixing of the medicinal product and diluent. Do not shake Ultomiris.
• Allow the diluted solution to warm to room temperature (18°C - 25°C) before administration by leaving it exposed to room air for approximately 30 minutes.
• The diluted solution must not be heated in a microwave oven or by using any heat source other than room temperature.
• Discard any unused portion remaining in the vial.
• The prepared solution should 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 2°C - 8°C, or 4 hours at room temperature, taking into account the expected infusion time.

3 - Administration

• Do not administer Ultomiris as a rapid intravenous injection or bolus.
• Ultomiris must be administered only 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. It is not necessary to protect the diluted Ultomiris solution from light during administration to the patient. The patient must be monitored for one hour after the infusion. If an adverse event occurs during administration of Ultomiris, the infusion may be slowed or stopped at the physician's discretion.

4 - Special precautions for handling and storage
Store in a refrigerator (2°C – 8°C). Do not freeze. Store in the original packaging to protect the medicinal product from light.
Do not use this medicinal product after the expiry date stated on the carton after “Exp”. The expiry date refers to the last day of that month.
Any unused medicinal product and waste material derived from such medicinal product must be disposed of in accordance with local regulations.

Patient Information Leaflet: Information for the User

Ultomiris 300 mg/3 mL concentrate for solution for infusion

ravulizumab
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What Ultomiris is and what it is used for

What Ultomiris is
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 is designed to bind to complement protein C5, which is part of the body's defense system known as the “complement system”.

What Ultomiris is used for
Ultomiris is used to treat adult and pediatric patients weighing at least 10 kg with a disease called paroxysmal nocturnal hemoglobinuria (PNH), including patients who have not been treated with complement inhibitors and those who have received eculizumab within the last 6 months. In patients with PNH, the complement system is overactive and attacks their own red blood cells, causing a decrease in red blood cell count (anemia), fatigue, functional impairment, pain, abdominal pain, dark urine, shortness of breath, difficulty swallowing, erectile dysfunction, and blood clots. By binding to and blocking complement protein C5, this medicine can prevent complement proteins from attacking red blood cells, thereby controlling the symptoms of the disease.

Ultomiris is also used to treat adult and pediatric patients weighing at least 10 kg with a disease affecting the blood system and kidneys called atypical haemolytic uremic syndrome (aHUS), including patients who have not been treated with complement inhibitors and those who have received eculizumab within the last 3 months. In patients with aHUS, the kidneys and blood vessels, including platelets, may become inflamed, leading to a reduced 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 vulnerable blood vessels, thereby controlling the symptoms of the disease, including kidney damage.

Ultomiris is also used to treat adult patients with a specific type of muscle disease called generalized myasthenia gravis (gMG). In patients with gMG, muscles may be attacked and damaged by the immune system, leading to severe muscle weakness, impaired vision and mobility, shortness of breath, extreme fatigue, risk of aspiration, and significantly impaired daily activities. Ultomiris can block the body's inflammatory response and its ability to attack and destroy its own muscles, thereby improving muscle contraction and reducing disease symptoms and their impact on daily 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 disorder primarily affecting the optic nerves (of the eyes) and spinal cord, called neuromyelitis optica spectrum disorder (NMOSD). In patients with NMOSD, the optic nerves and spinal cord are attacked and damaged by a malfunctioning immune system, potentially leading to vision loss in one or both eyes, weakness or loss of movement in the arms or legs, painful spasms, loss of sensation, bladder and bowel dysfunction, and significant difficulties with daily activities. Ultomiris can block the body's abnormal immune response and its ability to attack and destroy its own optic nerves and spinal cord, thereby reducing the risk of relapse or NMOSD attacks.

2. What you should know before using Ultomiris

Do not use Ultomiris

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

Warnings and precautions
Talk to your doctor before using Ultomiris.
Symptoms of meningococcal infection and other Neisseria infections
Since this medicine blocks the complement system, which is part of the body's defences against infections, using Ultomiris increases the risk of meningococcal infection caused by Neisseria meningitidis. These are serious infections affecting the membranes covering the brain, which can lead to brain inflammation (encephalitis) and may spread into the bloodstream and throughout the body (sepsis).
Consult your doctor before starting treatment with Ultomiris to ensure you receive vaccination against Neisseria meningitidis at least 2 weeks before starting therapy. If you cannot be vaccinated 2 weeks prior, your doctor will prescribe antibiotics to reduce the risk of infection until 2 weeks after vaccination. Check that your meningococcal infection vaccination has not expired. 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 for you to take additional preventive measures.
Symptoms of meningococcal infection
Because it is important to detect and treat meningococcal infection quickly in patients receiving Ultomiris, you will be given a “Patient card” to carry with you at all times, listing the relevant signs and symptoms of meningococcal infection/sepsis/encephalitis.
If any of the following symptoms occur, 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 of the eyes to light

Treatment of meningococcal infection during travel
If you are planning to travel to a country where you may not be able to contact your doctor or temporarily access medical care, your doctor may prescribe an antibiotic against Neisseria meningitidis for you to carry with you. If any of the symptoms described above occur, you should take the prescribed course of antibiotics. Please note that you must consult a doctor as soon as possible, even if you feel better after taking the antibiotics.
Infections
Before starting treatment with Ultomiris, inform your doctor if you currently have any infections.
Infusion-related reactions
During administration of Ultomiris, infusion-related reactions (infusion reactions) may occur, such as headache, lower back pain, and infusion-related pain. Some patients may experience allergic or hypersensitivity reactions (including anaphylaxis, a severe allergic reaction causing difficulty breathing or dizziness).
Children and adolescents
Patients under 18 years of age should be vaccinated against Haemophilus influenzae and pneumococcal infections.
Elderly
No special precautions are required for treatment of patients aged 65 years 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 taking, have recently taken, or might take any other medicines.
Pregnancy, breast-feeding and fertility
Women of childbearing potential
The effects of this medicine on the unborn child are unknown. Therefore, effective contraceptive methods must be used in women of childbearing potential during treatment and for up to 8 months after treatment ends.
Pregnancy/breast-feeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breast-feeding, consult your doctor or pharmacist before using this medicine.
Ultomiris is not recommended during pregnancy or in women of childbearing potential who are not using contraceptive measures.
Driving and using machines
This medicine does not affect or has negligible effect on the ability to drive and use machines.
Ultomiris contains sodium
After dilution with 9 mg/mL (0.9%) sodium chloride injection solution, this medicine contains 0.18 g of sodium (the main component of table salt) in 72 mL at the maximum dose. This corresponds to 9.1% of the maximum recommended daily dietary intake for an adult.
You should take this into account 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 may cause allergic reactions. Inform your doctor if you have known allergies.

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 previously received this vaccine or if your vaccination has expired. 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 for up to 2 weeks after vaccination.
If your child is under 18 years of age, your doctor will administer a vaccine (unless vaccination has already been performed) against Haemophilus influenzae and pneumococcal infections, according to national vaccination recommendations for each age group.
Instructions for proper use
Your doctor will calculate the dose of Ultomiris based on your body weight, as indicated in Table 1. The first dose is called the "loading dose." Two weeks after receiving the loading dose, you will receive 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 have previously received another medicine for aHUS, PNH, gMG or NMOSD called eculizumab, the loading dose should be administered 2 weeks after the last infusion of eculizumab.
Table 1: Ultomiris dosing regimen according to body weight

For patients with aHUS and PNH only.
Ultomiris is administered by intravenous 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 accidentally received a higher dose of Ultomiris than prescribed, consult your doctor.
If you miss an appointment for Ultomiris administration
If you miss an appointment, contact your doctor immediately and refer to the following section “If you interrupt treatment with Ultomiris”.
If you interrupt treatment with Ultomiris for aHUS
Stopping or interrupting treatment with Ultomiris may cause a return of aHUS symptoms with increased severity. Your doctor will discuss the possible side effects with you and explain the risks. Your doctor will closely monitor you for at least 16 weeks.
The risks of stopping Ultomiris include increased destruction of red blood cells, which may cause:

• Increased levels of lactate dehydrogenase (LDH), a laboratory marker of red blood cell destruction,
• A significant reduction in the number of red blood cells (anaemia),
• Dark urine,
• Fatigue,
• Abdominal pain,
• Shortness of breath,
• Difficulty swallowing,
• Erectile dysfunction (impotence),
• Confusion or changes in alertness,
• Chest pain or angina,
• Increased serum creatinine levels (kidney problems), or
• Thrombosis (blood clot formation).

If you experience any of these symptoms, contact your doctor.
If you interrupt treatment with Ultomiris for PNH
Stopping or interrupting treatment with Ultomiris may cause a return of PNH symptoms. Your doctor will discuss the possible side effects with you and explain the risks. Your doctor will closely monitor you.
The risks of stopping Ultomiris include increased damage to small blood vessels, which may cause:

• A significant reduction in platelet count (thrombocytopenia),
• A significant increase in red blood cell destruction,
• Increased levels of lactate dehydrogenase (LDH), a laboratory marker of red blood cell destruction,
• Reduced urine output (kidney problems),
• Increased serum creatinine levels (kidney problems),
• Confusion or changes in alertness,
• Vision disturbances,
• Chest pain or angina,
• Shortness of breath,
• Abdominal pain, diarrhoea, or
• Thrombosis (blood clot formation).

If you experience any of these symptoms, contact your doctor.
If you interrupt treatment with Ultomiris for gMG
Stopping or interrupting treatment with Ultomiris may cause a return of gMG symptoms. Please consult your doctor before stopping treatment with Ultomiris. Your doctor will discuss the possible side effects with you and explain the risks. Your doctor will also closely monitor you.
If you interrupt treatment with Ultomiris for NMOSD
Stopping or interrupting treatment with Ultomiris may cause a return of NMOSD symptoms. Please consult your doctor before stopping treatment with Ultomiris. Your doctor will discuss the possible side effects with you and explain the risks. Your doctor will also closely monitor you.
If you have any questions about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Before treatment, your doctor will discuss the possible side effects with you and explain the risks and benefits of Ultomiris.

Serious side effects
The most serious side effect is meningococcal infection, including meningococcal sepsis and meningococcal encephalitis.
If you experience any of the symptoms of meningococcal infection (see section 2, Symptoms of meningococcal infection), you must inform your doctor immediately.

Other side effects
If you have any doubts about the meaning of the side effects listed below, please ask your doctor for clarification.

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

• Headache
• Dizziness
• Diarrhoea, nausea, abdominal pain
• Fever, feeling of fatigue (tiredness)
• 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)
• Hives, rash, itchy skin (pruritus)
• Muscle pain (myalgia) and muscle spasms
• Influenza-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 causing breathing difficulties or dizziness (anaphylactic reaction)
• Disseminated gonococcal infection

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ultomiris

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "Exp". The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C).
Do not freeze.
Keep in the original packaging to protect the medicine from light.
After dilution with 9 mg/mL (0.9%) sodium chloride solution for injection, the medicine must be used immediately, within 24 hours if refrigerated or within 4 hours at room temperature.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Ultomiris contains

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

This medicinal product contains sodium (see section 2 “Ultomiris contains sodium”).
Description of the appearance of Ultomiris and contents of the pack
Ultomiris is supplied as a concentrate for solution for infusion (3 mL in a vial – pack of 1).
Ultomiris is a translucent, clear to slightly yellowish solution, practically free from 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

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Alexion Pharma Belgium UAB AstraZeneca Lietuva
Tél/Tel: +32 0 800 200 31 Tel: +370 5 2660550
България Luxembourg/Luxemburg
АстраЗенека България ЕООД Alexion Pharma Belgium
Teл.: +359 24455000 Tél/Tel: +32 0 800 200 31
Česká republika Magyarország
AstraZeneca Czech Republic s.r.o. AstraZeneca Kft.
Tel: +420 222 807 111 Tel.: +36 1 883 6500
Danmark Malta
Alexion Pharma Nordics AB Alexion Europe SAS
Tlf.: +46 0 8 557 727 50 Tel: +353 1 800 882 840
Deutschland Nederland
Alexion Pharma Germany GmbH Alexion Pharma Netherlands B.V.
Tel: +49 (0) 89 45 70 91 300 Tel: +32 (0)2 548 36 67
Eesti Norge
AstraZeneca Alexion Pharma Nordics AB
Tel: +372 6549 600 Tlf: +46 (0)8 557 727 50
Ελλάδα Österreich
AstraZeneca A.E. Alexion Pharma Austria GmbH
Τηλ: +30 210 6871500 Tel: +41 44 457 40 00
España Polska
Alexion Pharma Spain, S.L. AstraZeneca Pharma Poland Sp. z o.o.
Tel: +34 93 272 30 05 Tel.: +48 22 245 73 00
France Portugal
Alexion Pharma France SAS Alexion Pharma Spain, S.L. - Sucursal em
Tél: +33 1 47 32 36 21 Portugal
Tel: +34 93 272 30 05
Hrvatska România
AstraZeneca d.o.o. AstraZeneca Pharma SRL
Tel: +385 1 4628 000 Tel: +40 21 317 60 41
Ireland Slovenija
Alexion Europe SAS AstraZeneca UK Limited
Tel: +353 1 800 882 840 Tel: +386 1 51 35 600
Ísland Slovenská republika
Alexion Pharma Nordics AB AstraZeneca AB, o.z.
Sími: +46 0 8 557 727 50 Tel: +421 2 5737 7777
Italia Suomi/Finland
Alexion Pharma Italy srl Alexion Pharma Nordics AB
Tel: +39 02 7767 9211 Puh/Tel: +46 0 8 557 727 50
Κύπρος Sverige
Alexion Europe SAS Alexion Pharma Nordics AB
Τηλ: +357 22490305 Tel: +46 0 8 557 727 50
Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency, http://www.ema.europa.eu/.
<------------------------------------------------------------------------------------------------------------------------>
The following information is intended for healthcare professionals only:

Instructions for use for healthcare professionals

Handling of Ultomiris 300 mg/3 mL 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.
To enhance traceability of the biological medicinal product, the name and batch number of the administered medicine must be clearly recorded.
2- Prior to administration
Dilution must be performed in accordance with good practice standards, particularly with regard to aseptic technique.
In the absence of compatibility studies, 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 for administration by a qualified healthcare professional using aseptic technique.

• Visually inspect the Ultomiris solution for the presence of particles and discoloration.
• Withdraw the required amount of Ultomiris from the vial(s) using a sterile syringe.
• Transfer the recommended dose into an infusion bag.
• Dilute Ultomiris to a final concentration of 50 mg/mL (initial concentration divided by 2) by adding the appropriate volume of 9 mg/mL (0.9%) sodium chloride injection solution, according to the instructions in the table below.

Table 1: Dosing reference table for loading dose administration

Body weight at the time of treatment.
Ultomiris must be diluted using only a 9 mg/mL (0.9%) sodium chloride injectable solution.
For EPN and aHUS indications only.
Table 2: Maintenance dose administration reference table

Body weight at the time of treatment.
Ultomiris must be diluted using only an injectable solution of sodium chloride 9 mg/mL (0.9%).
For EPN and aHUS indications only.
Table 3: Reference table for administration of the supplementary dose

Body weight at the time of treatment.
Ultomiris must be diluted using only a 9 mg/mL (0.9%) sodium chloride injectable solution.

• Gently mix the infusion bag containing the diluted Ultomiris solution to ensure complete mixing of the medicinal product and diluent. Do not shake Ultomiris.
• Allow the diluted solution to warm to room temperature (18°C - 25°C) before administration by leaving it exposed to ambient air for approximately 30 minutes.
• The diluted solution must not be heated in a microwave oven or by any other heat source apart from ambient temperature.
• Discard any unused portion remaining in the vial.
• The prepared solution should 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 duration must not exceed 24 hours at 2°C - 8°C, or 4 hours at room temperature, taking into account the expected infusion time.

3 - Administration

• Do not administer Ultomiris as a rapid intravenous injection or bolus.
• Ultomiris must be administered only by intravenous infusion.
• The diluted Ultomiris solution should 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 must be monitored for one hour after the infusion. If an adverse event occurs during administration of Ultomiris, the infusion may be slowed or stopped at the physician's discretion.

4 - Special precautions for handling and storage
Store in a refrigerator (2°C – 8°C). Do not freeze. Keep the medicine in its original packaging to protect it from light.
Do not use this medicinal product after the expiry date stated on the carton after “Expiry”. The expiry date refers to the last day of that month.
Any unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with local regulations.