ULTOMIRIS 300 mg Concentrate For Infusion Solution

Зміст інструкції

1. Ultomiris 300 mg/30 mL concentrate for solution for infusion
   1. What is Ultomiris and what is it used for
   2. What you need to know before you use Ultomiris
   3. How to use Ultomiris
   4. Possible side effects
   5. How to store Ultomiris
   6. Contents of the pack and other information
2. Ultomiris 1100 mg/11 mL concentrate for solution for infusion
   1. What is Ultomiris and what is it used for
   2. What you need to know before you use Ultomiris
   3. How to use Ultomiris
   4. Possible side effects
   5. How to store Ultomiris
   6. Contents of the pack and other information
3. Ultomiris 300 mg/3 mL concentrate for solution for infusion
   1. What is Ultomiris and what is it 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

Ultomiris 300 mg/30 mL concentrate for solution for infusion

ravulizumab

Read this leaflet carefully before you start to 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even 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 you use 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 is Ultomiris and what is it used for

What is Ultomiris
Ultomiris is a medicine that contains the active substance ravulizumab and belongs to a class of
medicines called monoclonal antibodies, which bind to a specific target present
in the body. Ravulizumab is designed to bind to 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 weighing 10 kg or more who have a disease called
paroxysmal nocturnal hemoglobinuria (PNH), including patients
not treated with complement inhibitors and patients who have received eculizumab for at least the
last 6 months. In patients with PNH, the complement system is overactive and
attacks their red blood cells, leading to a decrease in the number of red blood cells (anemia),
fatigue, functional limitations, 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 10 kg or more who have a disease that affects the blood system and kidneys, called atypical hemolytic
uremic syndrome (aHUS), including patients not treated with complement inhibitors and patients who
have received eculizumab for at least the last 3 months. In patients with aHUS, the kidneys and blood vessels, including platelets, can become inflamed, which can lead to a decrease in the
number of blood cells (thrombocytopenia and anemia), a reduction or loss of kidney function, blood clots, fatigue, and functional limitations. Ultomiris can block the body's inflammatory response and its ability to attack and destroy its own 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 disease that
affects the muscles, called generalized myasthenia gravis (GMG). In patients with GMG, the
muscles can be attacked and damaged by the immune system, which can lead 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 the symptoms of the
disease and its 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 disease of the central nervous system
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 the
spinal cord are attacked and damaged by an improperly functioning immune system, which can lead 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 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 a
recurrence or attack of NMOSD.

2. What you need to know before you use Ultomiris

Do not use Ultomiris

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

Warnings and precautions
Talk to your doctor before using Ultomiris.

Symptoms of meningococcal infection and other infections caused byNeisseria
Since the medicine blocks the complement system, which is part of the body's defenses
against infections, the use of Ultomiris increases the risk of meningococcal infection caused by

Neisseria meningitidis. These are serious infections that affect the membranes surrounding the
brain and can cause inflammation of the brain (encephalitis) and spread to the blood and
throughout the body (sepsis).
Talk to your doctor before starting treatment with Ultomiris to make sure you receive the
vaccination against Neisseria meningitidisat least 2 weeks before starting therapy. If you
cannot be vaccinated 2 weeks before, your doctor will prescribe antibiotics to reduce the risk of
infection for up to 2 weeks after you have been vaccinated. Make sure your vaccination against
meningococcal infection is not expired. You should also know that vaccination may not always
prevent this type of infection. In accordance with national recommendations, your doctor may
consider it necessary for you to take additional measures to prevent infection.
Symptoms of meningococcal infection
Due to the importance of quickly identifying and treating meningococcal infection in patients
receiving Ultomiris, you will be given a “Patient Card” to carry with you at all times that
lists the relevant signs and symptoms of meningococcal infection/sepsis/encephalitis.
If you experience any of the following symptoms, you should immediately inform your doctor:

• headache with nausea or vomiting
• headache and fever
• headache with stiffness of the neck or back
• fever
• fever and rash
• confusion
• muscle aches 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 will not
be able to temporarily receive medical care, your doctor may prescribe an antibiotic against

Neisseria meningitidisto take with you. If you develop any of the symptoms described above, you should take
the course of antibiotics as prescribed. Keep in mind that you should still see a doctor
as soon as possible, even if you feel better after taking the antibiotics.

Infections
Before starting treatment with Ultomiris, tell your doctor if you have any ongoing infections.

Infusion-related reactions
Infusion reactions (reactions related to the intravenous infusion) such as headache, lower back pain and
infusion-related pain may occur during the administration of Ultomiris. Some patients may experience
allergic or hypersensitivity reactions (including anaphylaxis, a severe allergic reaction that causes
difficulty breathing or dizziness).

Children and adolescents
Patients under 18 years of age should be vaccinated against infections caused by

Haemophilus influenzaeand pneumococcus.

Elderly
No special precautions are necessary for the treatment of patients aged 65 years or older,
although experience with Ultomiris in elderly patients with EPN, SEUa or NMOSD in clinical
trials is limited.

Other medicines and Ultomiris
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines.

Pregnancy, breastfeeding and fertility
Women of childbearing potential
The effects of the medicine on the unborn child are unknown. Therefore, effective contraceptive methods
should be used by women of childbearing potential during treatment and for up to 8 months after the end
of treatment.
Pregnancy/breastfeeding
If you are pregnant, suspect you are pregnant, are planning to become pregnant or are breastfeeding,
ask your doctor or pharmacist for advice before using this medicine.
Ultomiris is not recommended during pregnancy and in women of childbearing potential who are not using
contraceptive measures.

Driving and using machines
This medicine does not or negligibly alters the ability to drive and operate machines.

Ultomiriscontains sodium
After dilution with sodium chloride 9 mg/mL (0.9%) injectable solution, this medicine
contains 2.65 g of sodium (the main component of table salt) in 720 mL at the maximum dose.
This is equivalent to 133% of the maximum recommended daily intake with the diet of
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
can cause allergic reactions. Tell 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 received this vaccine previously 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 less than 18 years of age, the doctor will administer a vaccine (unless the
vaccination has already been performed) against infections caused by Haemophilus influenzaeand pneumococcus,
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 administered 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 EPN, SEUa, MGg or NMOSD called
eculizumab, the loading dose must be administered 2 weeks after the last infusion of
eculizumab.

Table 1: Ultomiris dosage regimen based on body weight
Ultomiris is administered by infusion (drip) into a vein. The infusion will take approximately
2 hours.

If you receive more Ultomiristhan you should
If you suspect you have accidentally received a dose of Ultomiris higher than prescribed,
ask your doctor for advice.

If you miss an appointment for Ultomiris administration
If you miss an appointment, consult your doctor immediately and refer to the following section
“If you stop treatment with Ultomiris”.

If you stop treatment with Ultomiris for EPN
Stopping or interrupting treatment with Ultomiris may cause the symptoms of EPN to return
with greater intensity. 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
can cause:

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

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

• A significant reduction in the number of platelets (thrombocytopenia),
• A significant increase in red blood cell destruction,
• An increase in lactate dehydrogenase (LDH) levels, a laboratory marker of red blood cell destruction,
• A reduction in urine production (kidney problems),
• An increase in creatinine levels in the serum (kidney problems),
• Confusion or changes in alertness levels,
• Vision changes,
• 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 stop treatment with Ultomiris for MGg
Stopping or interrupting treatment with Ultomiris may cause the symptoms of MGg to return
Contact 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 to recur
Contact 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 questions about using this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Before treatment, your doctor will discuss 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 should inform your doctor immediately.

Other side effects
If you have any doubts 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 tired (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, indigestion after meals (dyspepsia)
• Hives, skin rash, itchy skin (pruritus)
• Muscle pain (myalgia) and muscle spasms
• Flu-like illness, chills, weakness (asthenia)
• Infusion-related reaction
• Allergic reaction (hypersensitivity)

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

• Meningococcal infection
• Severe allergic reaction causing difficulty breathing or dizziness (anaphylactic reaction)
• Disseminated gonococcal infection

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly
through 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 which is stated on the pack after “Exp”. The expiry
date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 ° C).
Do not freeze.
Store in the original package to protect the medicine from light.
After dilution with sodium chloride 9 mg/mL (0.9%) injectable solution, the medicine must
be used immediately, within 24 hours if refrigerated or within 6 hours at room temperature.
Do not dispose of any medicine in wastewater. Ask your pharmacist how to dispose of medicines that
you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Ultomiris contains

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

This medicine 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 of 1).
Ultomiris is a solution from clear to translucent, with a slightly whitish 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 on this medicine, contact the local representative of the marketing
authorisation holder:

Lietuva
UAB AstraZeneca Lietuva
Tel: +370 5 2660550

België/Belgique/Belgien
Alexion Pharma Belgium
Tél/Tel: +32 0 800 200 31

България
AstraZeneca България ЕООД
Teл.: +359 24455000

Luxembourg/Luxemburg
Alexion Pharma Belgium
Tél/Tel: +32 0 800 200 31

Česká republika
AstraZeneca Czech Republic s.r.o.
Tel: +420 222 807 111

Magyarország
AstraZeneca Kft.
Tel.: +36 1 883 6500

Danmark
Alexion Pharma Nordics AB

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

Deutschland
Alexion Pharma Germany GmbH
Tel: +49 (0) 89 45 70 91 300

Nederland
Alexion Pharma Netherlands B.V.
Tel: +32 (0)2 548 36 67

Norge
Alexion Pharma Nordics AB
Tlf: +46 (0)8 557 727 50

Ελλάδα
AstraZeneca A.E.
Τηλ: +30 210 6871500

Eesti
AstraZeneca
Tel: +372 6549 600

Österreich
Alexion Pharma Austria GmbH
Tel: +41 44 457 40 00

España
Alexion Pharma Spain, S.L.
Tel: +34 93 272 30 05

Polska
AstraZeneca Pharma Poland Sp. z o.o.
Tel.: +48 22 245 73 00

France
Alexion Pharma France SAS
Tél: +33 1 47 32 36 21

Portugal
Alexion Pharma Spain, S.L. - Sucursal em
Portugal
Tel: +34 93 272 30 05

Hrvatska
AstraZeneca d.o.o.
Tel: +385 1 4628 000

România
AstraZeneca Pharma SRL
Tel: +40 21 317 60 41

Ireland
Alexion Europe SAS
Tel: +353 1 800 882 840

Slovenija
AstraZeneca UK Limited
Tel: +386 1 51 35 600

Ísland
Alexion Pharma Nordics AB
Sími: +46 0 8 557 727 50

Slovenská republika
AstraZeneca AB, o.z.
Tel: +421 2 5737 7777

Italia
Alexion Pharma Italy srl
Tel: +39 02 7767 9211

Suomi/Finland
Alexion Pharma Nordics AB
Puh/Tel: +46 0 8 557 727 50

Κύπρος
Alexion Europe SAS
Τηλ: +357 22490305

Sverige
Alexion Pharma Nordics AB
Tel: +46 0 8 557 727 50

Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

Other sources of information
More detailed information on this medicine 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/30 mL concentrate for solution for infusion

• 1- How Ultomiris is 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 medicine, the name and batch number of the
medicine administered must be clearly recorded.

• 2- Before administrationDilution must be carried out in accordance with good practice guidelines, in particular with respect 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 colour change.
• 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 to the infusion the appropriate amount of sodium chloride 9 mg/mL (0.9%) solution for injection, according to the instructions in the following table.

Table 1: Reference table for loading dose administration
Body weight at the time of treatment.
Ultomiris must be diluted using only sodium chloride 9 mg/mL (0.9%) solution for injection.
For EPN and SEUa indications only.

Table 2: 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%) solution for injection.
For EPN and SEUa indications only.

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

• Gently shake the infusion bag containing the diluted Ultomiris solution to allow complete mixing of the medicine and diluent. Ultomiris must not be shaken.
• Allow the diluted solution to warm to room temperature (18 °C - 25 °C) before administration by exposing it to ambient air for approximately 30 minutes.
• The diluted solution must not be heated in a microwave oven or by any heat source other than room temperature.
• Discard any unused portion remaining 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 medicine is not used immediately after dilution, the storage times 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 a syringe pump or an infusion pump. The diluted Ultomiris solution does not need to be protected from light during administration to the patient. The patient must be monitored for one hour after the infusion. If an adverse event occurs during the administration of Ultomiris, the infusion may be slowed or stopped at the physician’s discretion.
• 4- Special precautions for handling and storageStore in a refrigerator (2 °C – 8 °C). Do not freeze. Store in the original package to protect the medicine from light. Do not use this medicine after the expiry date which is stated on the pack after “Exp”. The expiry date refers to the last day of that month.

The unused medicine and waste materials derived from such medicine must be disposed of in accordance
with local regulations.

Ultomiris 1100 mg/11 mL concentrate for solution for infusion

ravulizumab

Read this leaflet carefully before you use this medicine as 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 pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even 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 you use 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 is Ultomiris and what is it used for

What is Ultomiris
Ultomiris is a medicine that contains the active substance ravulizumab and belongs to a class of
medicines called monoclonal antibodies, which bind to a specific target present
in the body. Ravulizumab has been designed to bind to 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 weighing 10 kg or more with a disease called
paroxysmal nocturnal hemoglobinuria (PNH), including patients
not treated with complement inhibitors and patients who have received eculizumab at least in the
last 6 months. In patients with PNH, the complement system is overactive and
attacks their red blood cells, causing a decrease in the number of red blood cells (anemia),
fatigue, functional limitations, 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, thus controlling the symptoms of the disease.
Ultomiris is also used to treat adult and pediatric patients weighing 10 kg or more with a disease that affects the blood system and kidneys, called atypical hemolytic
uremic syndrome (aHUS), including patients not treated with complement inhibitors and patients who
have received eculizumab at least in the last 3 months. In patients with aHUS, the kidneys and blood
vessels, including platelets, can become inflamed, which can lead to a decrease in the
number of blood cells (thrombocytopenia and anemia), a reduction or loss of kidney function, blood clots, fatigue, and functional limitations. 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, including kidney damage.
Ultomiris is also used to treat adult patients with a specific type of disease that
affects the muscles, called generalized myasthenia gravis (GMG). In patients with GMG, the
muscles can be attacked and damaged by the immune system, which can cause 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, thus improving muscle contraction and reducing the symptoms of the
disease and its 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 disease of the central nervous
system 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 the
spinal cord are attacked and damaged by an improperly functioning immune system, which can lead 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 is able to block the body's abnormal immune response and its ability to
attack and destroy its own optic nerves and spinal cord, thus reducing the risk of a
recurrence or attack of NMOSD.

2. What you need to know before you use Ultomiris

Do not use Ultomiris

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

Warnings and precautions
Talk to your doctor before using Ultomiris.

Symptoms of meningococcal infection and other infections caused byNeisseria
Since the medicine blocks the complement system, which is part of the body's defenses
against infections, the use of Ultomiris increases the risk of meningococcal infection caused by

Neisseria meningitidis. These are serious infections that affect the membranes surrounding the
brain and can cause inflammation of the brain (encephalitis) and spread to the blood and
body (sepsis).
Talk to your doctor before starting treatment with Ultomiris to make sure you receive the
vaccination against Neisseria meningitidis, at least 2 weeks before starting therapy. If you cannot
be vaccinated 2 weeks before, your doctor will prescribe antibiotics to reduce the risk of
infection for up to 2 weeks after being vaccinated. Make sure your vaccination against
meningococcal infection is not expired. You should also know that vaccination may not always
prevent this type of infection. In accordance with national recommendations, your doctor may
consider it necessary for you to take additional measures to prevent infection.
Symptoms of meningococcal infection
Due to the importance of quickly identifying and treating meningococcal infection in patients
receiving Ultomiris, you will be given a “Patient Card” to carry with you at all times that
lists the relevant signs and symptoms of meningococcal infection/sepsis/encephalitis.
If you experience any of the following symptoms, you should immediately inform your doctor:

• headache with nausea or vomiting
• headache and fever
• headache with stiffness of the neck or back
• fever
• fever and rash
• confusion
• muscle aches with flu-like symptoms
• sensitivity of the eyes to light

Treatment of meningococcal infection while traveling
If you are planning a trip to a country where you will not be able to contact your doctor or will not
be able to temporarily receive medical care, your doctor may prescribe an antibiotic against

Neisseria meningitidisto carry with you. If you develop any of the symptoms described above, you should take
the course of antibiotics as prescribed. Keep in mind that you should still see a doctor
as soon as possible, even if you feel better after taking the antibiotics.

Infections
Before starting treatment with Ultomiris, tell your doctor if you have any ongoing infections.

Infusion-related reactions
During the administration of Ultomiris, infusion reactions (reactions related to the IV) 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 that causes difficulty breathing or dizziness).

Children and adolescents
Patients under 18 years of age should be vaccinated against infections caused by

Haemophilus influenzaeand pneumococcus.

Elderly
No special precautions are necessary for the treatment of patients aged 65 years or older, although
experience with Ultomiris in elderly patients with EPN, SEUa or NMOSD in clinical trials is limited.

Other medicines and Ultomiris
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines.

Pregnancy, breastfeeding and fertility
Women of childbearing potential
The effects of the medicine on the unborn child are unknown. Therefore, effective contraceptive methods should be
used by women of childbearing potential during treatment and up to 8 months after the end of
treatment.
Pregnancy/breastfeeding
If you are pregnant, suspect you are pregnant, are planning to become pregnant or are breastfeeding, ask your doctor or
pharmacist for advice before using this medicine.
Ultomiris is not recommended during pregnancy and in women of childbearing potential who are not using
contraceptive measures.

Driving and using machines
This medicine does not alter or negligibly alters the ability to drive and operate
machinery.

Ultomiriscontains sodium
After dilution with sodium chloride 9 mg/mL (0.9%) injectable solution, this medicine
contains 0.18 g of sodium (the main component of table salt) in 72 mL at the
maximum dose. This is equivalent to 9.1% of the maximum recommended daily intake with the diet
of 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
can cause allergic reactions. Tell 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 received this vaccine before 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 less than 18 years of age, the doctor will administer a vaccine (unless the
vaccination has already been performed) against infections caused by Haemophilus influenzaeand pneumococcus,
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 EPN, SEUa, MGg or NMOSD called
eculizumab, the loading dose must be administered 2 weeks after the last infusion of
eculizumab.

Table 1: Ultomiris dosage regimen based on body weight

Only for patients with EPN and SEUa.
Ultomiris is administered by infusion (drip) into a vein. The infusion will take approximately
45 minutes.

If you receive more Ultomiristhan you should
If you suspect that you have accidentally received a dose of Ultomiris higher than prescribed,
ask your doctor for advice.

If you miss an appointment for Ultomiris administration
If you miss an appointment, consult your doctor immediately and refer to the following section
“If you stop treatment with Ultomiris”.

If you stop treatment with Ultomiris for EPN
Stopping or interrupting treatment with Ultomiris may cause the symptoms of EPN to reappear
with greater intensity. 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 can cause:

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

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

If you stop treatment with Ultomiris for SEUa
Stopping or interrupting treatment with Ultomiris may cause the symptoms of SEUa to reappear.
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 can cause:

• A significant reduction in the number of platelets (thrombocytopenia),
• A significant increase in the destruction of red blood cells,
• An increase in lactate dehydrogenase (LDH) levels, a laboratory marker of red blood cell destruction,
• A reduction in urine production (kidney problems),
• An increase in creatinine levels in the serum (kidney problems),
• Confusion or changes in alertness,
• Visual impairment,
• Chest pain or angina,
• Shortness of breath,
• Abdominal pain, diarrhea or
• Thrombosis (formation of blood clots).

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

If you stop treatment with Ultomiris for MGg
Stopping or interrupting treatment with Ultomiris may cause the symptoms of MGg to reappear.
Contact your doctor before stopping treatment with Ultomiris. Your doctor will discuss with you the
possible side effects 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 the NMOSD to reappear.
Contact your doctor before stopping treatment with Ultomiris. Your doctor will discuss with you the
possible side effects and explain the risks. Your doctor will also monitor you closely.
If you have any questions about using this medicine, talk to your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Before treatment, your doctor will discuss 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 symptoms of meningococcal infection (see section 2 Symptoms of meningococcal
infection), you should inform your doctor immediately.

Other side effects
If you have any doubts 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 tired (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, discomfort in the stomach after meals (dyspepsia)
• Hives, skin rash, itchy skin (pruritus)
• Muscle pain (myalgia) and muscle spasms
• Flu-like illness, chills, weakness (asthenia)
• Infusion-related reaction
• Allergic reaction (hypersensitivity)

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

• Meningococcal infection
• Severe allergic reaction causing difficulty breathing or dizziness (anaphylactic reaction)
• Disseminated gonococcal infection

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly
through 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 which is stated on the pack after “Exp”. The expiry
date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 ° C).
Do not freeze.
Store in the original package to protect the medicine from light.
After dilution with sodium chloride 9 mg/mL (0.9%) injectable solution, the medicine must
be used immediately, within 24 hours if refrigerated or within 4 hours at room temperature.
Do not dispose of any medicine in wastewater. Ask your pharmacist how to dispose of medicines that
you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Ultomiris contains

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

This medicine 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 of 1).
Ultomiris is a translucent solution, from clear to pale yellow 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
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 on this medicine, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Alexion Pharma Belgium
Tél/Tel: +32 0 800 200 31

Lietuva
UAB AstraZeneca Lietuva
Tel: +370 5 2660550

България
AstraZeneca България ЕООД
Teл.: +359 24455000

Luxembourg/Luxemburg
Alexion Pharma Belgium
Tél/Tel: +32 0 800 200 31

Česká republika
AstraZeneca Czech Republic s.r.o.
Tel: +420 222 807 111

Magyarország
AstraZeneca Kft.
Tel.: +36 1 883 6500

Danmark
Alexion Pharma Nordics AB
Tlf.: +46 0 8 557 727 50

Malta
Alexion Europe SAS
Tel: +353 1 800 882 840

Deutschland
Alexion Pharma Germany GmbH
Tel: +49 (0) 89 45 70 91 300

Nederland
Alexion Pharma Netherlands B.V.
Tel: +32 (0)2 548 36 67

Norge
Alexion Pharma Nordics AB
Tlf: +46 (0)8 557 727 50

Ελλάδα
AstraZeneca A.E.
Τηλ: +30 210 6871500

Eesti
AstraZeneca
Tel: +372 6549 600

Österreich
Alexion Pharma Austria GmbH
Tel: +41 44 457 40 00

España
Alexion Pharma Spain, S.L.
Tel: +34 93 272 30 05

Polska
AstraZeneca Pharma Poland Sp. z o.o.
Tel.: +48 22 245 73 00

France
Alexion Pharma France SAS
Tél: +33 1 47 32 36 21

Portugal
Alexion Pharma Spain, S.L. - Sucursal em
Portugal
Tel: +34 93 272 30 05

Hrvatska
AstraZeneca d.o.o.
Tel: +385 1 4628 000

România
AstraZeneca Pharma SRL
Tel: +40 21 317 60 41

Ireland
Alexion Europe SAS
Tel: +353 1 800 882 840

Slovenija
AstraZeneca UK Limited
Tel: +386 1 51 35 600

Ísland
Alexion Pharma Nordics AB
Sími: +46 0 8 557 727 50

Slovenská republika
AstraZeneca AB, o.z.
Tel: +421 2 5737 7777

Italia
Alexion Pharma Italy srl
Tel: +39 02 7767 9211

Suomi/Finland
Alexion Pharma Nordics AB
Puh/Tel: +46 0 8 557 727 50

Κύπρος
Alexion Europe SAS
Τηλ: +357 22490305

Sverige
Alexion Pharma Nordics AB
Tel: +46 0 8 557 727 50

Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

Other sources of information
More detailed information on this medicine 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 Ultomiris is supplied?Each vial of Ultomiris contains 1,100 mg of active substance in 11 mL of solution.

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

• 2- Before administrationDilution must be carried out in accordance with good practice guidelines, in particular with respect to aseptic procedures.

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 colour change.
• 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 to the infusion the appropriate amount of sodium chloride 9 mg/mL (0.9%) injection solution, according to the instructions in the following table.

Table 1: Reference table for loading dose administration
Body weight at the time of treatment.
Ultomiris must be diluted using only sodium chloride 9 mg/mL (0.9%) injection solution.
For EPN and SEUa indications only.

Table 2: 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%) injection solution.
For EPN and SEUa indications only.

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

• Gently shake the infusion bag containing the diluted Ultomiris solution to allow complete mixing of the medicine and diluent. Ultomiris must not be shaken.
• Allow the diluted solution to warm to room temperature (18°C - 25°C) before administration by exposing it to ambient air for approximately 30 minutes.
• The diluted solution must not be heated in a microwave oven or by any heat source other than room temperature.
• Discard any unused portion remaining 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 medicine is not used immediately after dilution, the storage time 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 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. The diluted Ultomiris solution does not need to be protected from light during administration to the patient. The patient must be monitored for one hour after the infusion. If an adverse event occurs during the administration of Ultomiris, the infusion may be slowed or stopped at the physician’s discretion.
• 4- Special precautions for handling and storageStore in a refrigerator (2 °C – 8 °C). Do not freeze. Store in the original packaging to protect the medicine from light. Do not use this medicine after the expiry date which is stated on the pack after “Exp”. The expiry date refers to the last day of that month.

The unused medicine and waste materials derived from such medicine must be disposed of in
accordance with local regulations.

Ultomiris 300 mg/3 mL concentrate for solution for infusion

ravulizumab

Read this leaflet carefully before you use this medicine as 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even 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 you use 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 is Ultomiris and what is it used for

What is Ultomiris
Ultomiris is a medicine that contains the active substance ravulizumab and belongs to a class of
medicines called monoclonal antibodies, which bind to a specific target present
in the body. Ravulizumab is designed to bind to the C5 protein of the complement, 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 weighing 10 kg or more with a disease called
paroxysmal nocturnal hemoglobinuria (PNH), including patients
not treated with complement inhibitors and patients who have received eculizumab for at least
the last 6 months. In patients with PNH, the complement system is overactive and
attacks their red blood cells, causing a decrease in the number of red blood cells (anemia),
fatigue, functional limitations, pain, abdominal pain, dark urine, shortness of breath, difficulty
swallowing, erectile dysfunction, and blood clots. By binding to and blocking the C5 protein of the complement
system, this medicine can prevent complement proteins from attacking red blood cells, thus controlling the symptoms of the disease.
Ultomiris is also used to treat adult and pediatric patients weighing 10 kg or more with a disease that affects the blood system and kidneys, called atypical hemolytic
uremic syndrome (aHUS), including patients not treated with complement inhibitors and patients who
have received eculizumab for at least the last 3 months. In patients with aHUS, the kidneys and blood vessels, including platelets, can become inflamed, which can cause a decrease in the
number of blood cells (thrombocytopenia and anemia), a reduction or loss of kidney function, blood clots, fatigue, and functional limitations. 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, including kidney damage.
Ultomiris is also used to treat adult patients with a specific type of disease that
affects the muscles, called generalized myasthenia gravis (GMG). In patients with GMG, the
muscles can be attacked and damaged by the immune system, which can cause 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, thus improving muscle contraction and reducing the symptoms of the
disease and its 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 disease of the central nervous system
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 the
spinal cord are attacked and damaged by an improperly functioning immune system, which can lead 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 is able to block the body's abnormal immune response and its ability to
attack and destroy its own optic nerves and spinal cord, thus reducing the risk of a
recurrence or attack of NMOSD.

2. What you need to know before using Ultomiris

Do not use Ultomiris

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

Warnings and precautions
Talk to your doctor before using Ultomiris.

Symptoms of meningococcal infection and other infections caused byNeisseria
Since the medicine blocks the complement system, which is part of the body's defenses
against infections, the use of Ultomiris increases the risk of meningococcal infection caused by

Neisseria meningitidis. These are serious infections that affect the membranes surrounding the
brain and can cause inflammation of the brain (encephalitis) and spread to the blood and
throughout the body (sepsis).
Talk to your doctor before starting treatment with Ultomiris to make sure you receive the
vaccination against Neisseria meningitidis, at least 2 weeks before starting therapy. If you cannot
be vaccinated 2 weeks before, your doctor will prescribe antibiotics to reduce the risk of
infection for up to 2 weeks after being vaccinated. Make sure your vaccination against
meningococcal infection is not expired. You should also know that vaccination may not always
prevent this type of infection. In accordance with national recommendations, your doctor may
consider it necessary for you to take additional measures to prevent infection.
Symptoms of meningococcal infection
Due to the importance of quickly identifying and treating meningococcal infection in patients
receiving Ultomiris, you will be given a “Patient Card” to carry with you at all times that
lists the relevant signs and symptoms of meningococcal infection/sepsis/encephalitis.
If you experience any of the following symptoms, you should immediately inform your doctor:

• headache with nausea or vomiting
• headache and fever
• headache with stiffness of the neck or back
• fever
• fever and rash
• confusion
• muscle aches 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 will not
be able to temporarily receive medical care, your doctor may prescribe you an antibiotic against

Neisseria meningitidisto take with you. If you develop any of the symptoms described above, you should take
the course of antibiotics as prescribed. Keep in mind that you should still see a doctor
as soon as possible, even if you feel better after taking the antibiotics.

Infections
Before starting treatment with Ultomiris, tell your doctor if you have any ongoing infections.

Infusion-related reactions
Infusion reactions (reactions related to the intravenous infusion) such as headache, lower back pain, and infusion-related pain may occur during the administration of Ultomiris. Some patients may experience allergic or hypersensitivity reactions (including
anaphylaxis, a severe allergic reaction that causes difficulty breathing or dizziness).

Children and adolescents
Patients under 18 years of age must be vaccinated against infections caused by

Haemophilus influenzaeand pneumococcus.

Elderly
No special precautions are necessary for the treatment of patients aged 65 years or older,
although experience with Ultomiris in elderly patients with EPN, SEUa or NMOSD in clinical
trials is limited.

Other medicines and Ultomiris
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines.

Pregnancy, breastfeeding and fertility
Women of childbearing potential
The effects of the medicine on the unborn child are unknown. Therefore, effective contraceptive methods should be
used by women of childbearing potential during treatment and for up to 8 months after the end of
treatment.
Pregnancy/breastfeeding
If you are pregnant, suspect you are pregnant, are planning to become pregnant or are breastfeeding,
ask your doctor or pharmacist for advice before using this medicine.
Ultomiris is not recommended during pregnancy and in women of childbearing potential who are not using
contraceptive measures.

Driving and using machines
This medicine does not or negligibly alters the ability to drive and operate
machinery.

Ultomiriscontains sodium
After dilution with sodium chloride 9 mg/mL (0.9%) injectable 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 recommended maximum daily intake with the diet
of 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
can cause allergic reactions. Tell 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 received this vaccine before 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 less than 18 years of age, the doctor will administer a vaccine (unless the
vaccination has already been performed) against infections caused by Haemophilus influenzaeand pneumococcus,
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 EPN, SEUa, MGg or NMOSD called
eculizumab, the loading dose must be administered 2 weeks after the last infusion of
eculizumab.

Table 1: Ultomiris dosage regimen based on body weight

Only for patients with EPN and SEUa.
Ultomiris is administered by infusion (drip) into a vein. The infusion will take about
45 minutes.

If you receive more Ultomiristhan you should
If you suspect you have accidentally received a dose of Ultomiris higher than prescribed,
ask your doctor for advice.

If you forget an appointment for Ultomiris administration
If you forget an appointment, consult your doctor immediately and refer to the next section
“If you stop treatment with Ultomiris”.

If you stop treatment with Ultomiris for EPN
Stopping or interrupting treatment with Ultomiris may cause the symptoms of
EPN to reappear with greater intensity. Your doctor will discuss with you the possible side effects 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
can cause:

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

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

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

• A significant reduction in the number of platelets (thrombocytopenia),
• A significant increase in the destruction of red blood cells,
• An increase in lactate dehydrogenase (LDH) levels, a laboratory marker of red blood cell destruction,
• A reduction in urine production (kidney problems),
• An increase in creatinine levels in the serum (kidney problems),
• Confusion or changes in alertness,
• Visual impairment,
• Chest pain or angina,
• Shortness of breath,
• Abdominal pain, diarrhea or
• Thrombosis (blood clot formation).

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

If you stop treatment with Ultomiris for MGg
Stopping or interrupting treatment with Ultomiris may cause the symptoms of
MGg to reappear. Contact your doctor before stopping treatment with Ultomiris. Your doctor
will discuss with you the possible side effects 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 the NMOSD to reappear.
Contact your doctor before stopping treatment with Ultomiris. Your doctor
will discuss with you the possible side effects and explain the risks. Your doctor will also monitor you
closely.
If you have any doubts about the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Before treatment, your doctor will discuss 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 symptoms of meningococcal infection (see section 2 Symptoms of meningococcal
infection), you should inform your doctor immediately.

Other side effects
If you have any doubts 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 tired (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, discomfort in the stomach after meals (dyspepsia)
• Hives, skin rash, itchy skin (pruritus)
• Muscle pain (myalgia) and muscle spasms
• Flu-like illness, chills, weakness (asthenia)
• Infusion-related reaction
• Allergic reaction (hypersensitivity)

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

• Meningococcal infection
• Severe allergic reaction causing difficulty breathing or dizziness (anaphylactic reaction)
• Disseminated gonococcal infection

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly
through the national reporting system listed in Appendix V. By reporting side effects you can help to
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 which is stated on the pack after “Exp”. The expiry
date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 ° C).
Do not freeze.
Store in the original package to protect the medicine from light.
After dilution with sodium chloride 9 mg/mL (0.9%) injectable solution, the medicine must
be used immediately, within 24 hours if refrigerated or within 4 hours at room temperature.
Do not dispose of any medicine in wastewater. Ask your pharmacist how to dispose of medicines that
you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Ultomiris contains

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

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

Description of the appearance of Ultomirisand 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 solution, from clear to pale yellow 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
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 on this medicine, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Alexion Pharma Belgium
Tél/Tel: +32 0 800 200 31

Lietuva
UAB AstraZeneca Lietuva
Tel: +370 5 2660550

България
AstraZeneca България ЕООД
Teл.: +359 24455000

Luxembourg/Luxemburg
Alexion Pharma Belgium
Tél/Tel: +32 0 800 200 31

Česká republika
AstraZeneca Czech Republic s.r.o.
Tel: +420 222 807 111

Magyarország
AstraZeneca Kft.
Tel.: +36 1 883 6500

Danmark
Alexion Pharma Nordics AB
Tlf.: +46 0 8 557 727 50

Malta
Alexion Europe SAS
Tel: +353 1 800 882 840

Deutschland
Alexion Pharma Germany GmbH
Tel: +49 (0) 89 45 70 91 300

Nederland
Alexion Pharma Netherlands B.V.
Tel: +32 (0)2 548 36 67

Norge
Alexion Pharma Nordics AB
Tlf: +46 (0)8 557 727 50

Ελλάδα
AstraZeneca A.E.
Τηλ: +30 210 6871500

Eesti
AstraZeneca
Tel: +372 6549 600

Österreich
Alexion Pharma Austria GmbH
Tel: +41 44 457 40 00

España
Alexion Pharma Spain, S.L.
Tel: +34 93 272 30 05

Polska
AstraZeneca Pharma Poland Sp. z o.o.
Tel.: +48 22 245 73 00

France
Alexion Pharma France SAS
Tél: +33 1 47 32 36 21

Portugal
Alexion Pharma Spain, S.L. - Sucursal em
Portugal
Tel: +34 93 272 30 05

Hrvatska
AstraZeneca d.o.o.
Tel: +385 1 4628 000

România
AstraZeneca Pharma SRL
Tel: +40 21 317 60 41

Ireland
Alexion Europe SAS
Tel: +353 1 800 882 840

Slovenija
AstraZeneca UK Limited
Tel: +386 1 51 35 600

Ísland
Alexion Pharma Nordics AB
Sími: +46 0 8 557 727 50

Slovenská republika
AstraZeneca AB, o.z.
Tel: +421 2 5737 7777

Italia
Alexion Pharma Italy srl
Tel: +39 02 7767 9211

Suomi/Finland
Alexion Pharma Nordics AB
Puh/Tel: +46 0 8 557 727 50

Κύπρος
Alexion Europe SAS
Τηλ: +357 22490305

Sverige
Alexion Pharma Nordics AB
Tel: +46 0 8 557 727 50

Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

Other sources of information
More detailed information on this medicine is available on the website of the European Medicines
Agency, http://www.ema.europa.eu/ .
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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 Ultomiris is supplied?Each vial of Ultomiris contains 300 mg of active substance in 3 mL of solution.

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

• 2- Before administrationDilution must be carried out in accordance with good practice guidelines, in particular with respect to asepsis.

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 colour change.
• 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 to the infusion the appropriate amount of sodium chloride 9 mg/mL (0.9%) injection solution, according to the instructions in the following table.

Table 1: Reference table for loading dose administration
Body weight at the time of treatment.
Ultomiris must be diluted using only a sodium chloride 9 mg/mL (0.9%) injection solution.
For EPN and SEUa indications only.

Table 2: Reference table for maintenance dose administration

Body weight at the time of treatment.
Ultomiris must be diluted using only a sodium chloride 9 mg/mL (0.9%) injection solution.
For EPN and SEUa indications only.

Table 3: Reference table for supplementary dose administration
Body weight at the time of treatment.
Ultomiris must be diluted using only a sodium chloride 9 mg/mL (0.9%) injection solution.

• Gently swirl the infusion bag containing the diluted Ultomiris solution to allow complete mixing of the medicine and diluent. Ultomiris should not be shaken.
• Allow the diluted solution to warm to room temperature (18°C - 25°C) before administration by exposing it to ambient air for approximately 30 minutes.
• The diluted solution must not be heated in a microwave oven or by any heat source other than room temperature.
• Discard any unused portion remaining 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 medicine is not used immediately after dilution, storage times should not exceed 24 hours at 2 °C - 8 °C, or 4 hours at room temperature, taking into account the intended 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. The diluted Ultomiris solution does not need to be protected from light during administration to the patient. The patient should be monitored for one hour after the infusion. If an adverse event occurs during the administration of Ultomiris, the infusion may be slowed or stopped at the physician’s discretion.
• 4- Special precautions for handling and storageStore in a refrigerator (2 °C – 8 °C). Do not freeze. Store in the original package to protect the medicine from light. Do not use this medicine after the expiry date which is stated on the pack after “Exp”. The expiry date refers to the last day of that month.

Unused medicine or waste material from this medicine must be disposed of in accordance with
local regulations.