Ultomiris 1100 mg/11 ml concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Ultomiris 1100 mg/11 ml concentrate for solution for infusion

ravulizumab

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

• Keep this leaflet, as 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the 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 has been 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 with a body weight of at least 10 kg who have a disease called paroxysmal nocturnal hemoglobinuria (PNH), including patients who have not previously been treated with a complement inhibitor and patients who have received eculizumab for at least the past 6 months. In patients with PNH, the complement system is overactive and attacks red blood cells, leading to a reduction in red blood cell count (anemia), fatigue, functional impairment, pain, abdominal pain, dark-colored urine, shortness of breath, difficulty swallowing, erectile dysfunction, and blood clots. By binding to and blocking complement protein C5, this medicine can prevent complement proteins from attacking red blood cells and thereby control the symptoms of the disease.

Ultomiris is also used to treat adult and pediatric patients with a body weight of at least 10 kg who have a disease affecting the blood system and kidneys called atypical hemolytic uremic syndrome (aHUS), including patients who have not been treated with a complement inhibitor and patients who have received eculizumab for at least 3 months. In patients with aHUS, the kidneys and blood vessels, including platelets, may become inflamed, which can lead 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 its own vulnerable blood vessels, thereby controlling disease symptoms such as kidney injury.

Ultomiris is also used to treat adult patients with a type of muscle disease called generalized myasthenia gravis (gMG). In patients with gMG, the immune system may attack and damage the body's own muscles, leading to significant muscle weakness, visual and mobility disturbances, difficulty breathing, extreme fatigue, risk of aspiration, and marked impairment in daily activities. Ultomiris can block the body's inflammatory response and its ability to attack and destroy its own muscles, thereby improving muscle contraction, reducing disease symptoms, and lessening the disease's 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 disease that primarily affects the optic nerves (of the eye) and spinal cord, called neuromyelitis optica spectrum disorder (NMOSD). In patients with NMOSD, the optic nerves and spinal cord are attacked and damaged by an abnormal immune response, which may lead 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 major 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 NMOSD relapse or attacks.

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 currently have a meningococcal infection.

Warnings and precautions

Talk to your doctor before starting to use Ultomiris.

Symptoms of meningococcal infections and other Neisseria infections

Because 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 lining of the brain, which can lead to brain inflammation (encephalitis), and may spread to the blood and throughout the body (sepsis).

Talk to your doctor before starting Ultomiris to ensure you are vaccinated against Neisseria meningitidis at least 2 weeks before starting treatment. If you cannot be vaccinated 2 weeks in advance, your doctor will prescribe antibiotics to reduce the risk of infection for up to two weeks after vaccination. Make sure your meningococcal vaccination is up to date. You should also be aware that vaccination may not always prevent this type of infection. According to national recommendations, your doctor may consider additional preventive measures necessary.

Symptoms of meningococcal infection

Because it is important to identify and treat meningococcal infection quickly in patients receiving Ultomiris, you will be given a “patient card,” which you must carry with you at all times. It contains a list of relevant signs and symptoms of meningococcal infection/sepsis/encephalitis.

If you experience any of the following symptoms, contact 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 plan to travel to an area where you cannot contact your doctor or where you may not have access to medical treatment for some time, your doctor may prescribe an antibiotic against Neisseria meningitidis for you to carry with you. If you experience any of the symptoms described above, you must take the prescribed course of antibiotics. Remember that you still need to see a doctor as soon as possible, even if you feel better after taking the antibiotic.

Infections

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

Infusion-related reactions

When Ultomiris is administered, you may experience infusion-related reactions such as headache, lower back pain, and pain associated with the infusion. 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 patients

No special precautions are required for treating patients aged 65 years or older, although clinical trial experience with Ultomiris in elderly patients with PNH, aHUS, or NMOSD is limited.

Other medicines and Ultomiris

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy, breastfeeding, and fertility

Women of childbearing age

The effects of this medicine on the fetus are unknown. Therefore, effective contraceptive methods should be used during treatment and for 8 months after treatment ends in women of childbearing age.

Pregnancy/Breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Ultomiris is not recommended during pregnancy or in women of childbearing age who are not using contraception.

Driving and using machines

The effect of this medicine on the ability to drive and use machines is negligible or none.

Ultomiris contains sodium

When diluted with sodium chloride 9 mg/ml (0.9%) solution for injection, this medicine contains 0.18 g of sodium (the main component of table/cooking salt) in 72 ml at the maximum dose. This corresponds to 9.1% of the maximum recommended daily sodium 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 0.53 mg/kg. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How to use Ultomiris

At least 2 weeks before starting treatment with Ultomiris, your doctor will administer a meningococcal infection vaccine if you have not been previously vaccinated or if your vaccination is not up to date. If you cannot be vaccinated at least 2 weeks before starting Ultomiris treatment, your doctor will prescribe antibiotics to reduce the risk of infection until 2 weeks after you have been vaccinated.

If your child is under 18 years of age, your doctor will administer a vaccine (if not already given) against Haemophilus influenzae and pneumococcal infections according to current local vaccination recommendations for each age group.

Instructions for proper use

Your doctor will calculate your dose of Ultomiris based on your body weight, as shown in Table 1. The first dose is called the loading dose. Two weeks after receiving the loading dose, you will be given a maintenance dose of Ultomiris, which will then be repeated every 8 weeks for patients weighing more than 20 kg and every 4 weeks for patients weighing less than 20 kg.

If you were previously receiving another medicine for PNH, aHUS, gMG, or NMOSD called eculizumab, the loading dose should be administered 2 weeks after the last eculizumab infusion.

Table 1. Ultomiris dosing regimen based on weight

Body weight range (kg)	Loading dose (mg)	Maintenance dose (mg)
10 to less than 20a	600	600
20 to less than 30a	900	2100
30 to less than 40a	1200	2700
40 to less than 60	2400	3000
60 to less than 100	2700	3300
more than 100	3000	3600

a For patients with PNH and aHUS only.

Ultomiris is administered by intravenous infusion (drip). The infusion will last approximately 45 minutes.

If you receive more Ultomiris than you should

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

If you miss an appointment to receive Ultomiris

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

If you interrupt treatment with Ultomiris for PNH

If you interrupt or stop treatment with Ultomiris, symptoms of PNH may reappear with greater severity. Your doctor will discuss the possible adverse effects and explain the risks to you. In addition, you will be closely monitored for at least 16 weeks.

Risks of interrupting treatment with Ultomiris include an increased destruction of red blood cells, which may cause the following:

• An increase in your lactate dehydrogenase (LDH) levels, a laboratory marker of red blood cell destruction,
• A significant decrease in red blood cell count (anemia),
• Dark-colored urine,
• Fatigue,
• Abdominal pain,
• Shortness of breath,
• Difficulty swallowing,
• Erectile dysfunction (impotence),
• Confusion or change in alertness level,
• Chest pain or angina,
• Increased serum creatinine levels (kidney problems), or
• Thrombosis (blood clots).

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

If you interrupt treatment with Ultomiris for aHUS

If you interrupt or stop treatment with Ultomiris, symptoms of aHUS may reappear. Your doctor will discuss the possible adverse effects and explain the risks to you. In addition, you will be closely monitored.

Risks of interrupting treatment with Ultomiris include increased damage to small blood vessels, which may cause the following:

• A significant decrease in platelet count (thrombocytopenia),
• A marked increase in red blood cell destruction,
• An increase in your lactate dehydrogenase (LDH) levels, a laboratory marker of red blood cell destruction,
• Reduced urination (kidney problems),
• Increased serum creatinine levels (kidney problems),
• Confusion or change in alertness level,
• Changes in vision,
• Chest pain or angina,
• Shortness of breath,
• Abdominal pain, diarrhea, or
• Thrombosis (blood clots).

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

If you interrupt treatment with Ultomiris for gMG

If you interrupt or stop treatment with Ultomiris, symptoms of gMG may reappear. Consult your doctor before interrupting treatment with Ultomiris. Your doctor will discuss the possible adverse effects and risks with you. In addition, you will be closely monitored.

If you interrupt treatment with Ultomiris for NMOSD

If you interrupt or stop treatment with Ultomiris, symptoms of NMOSD may reappear. Consult your doctor before interrupting treatment with Ultomiris. Your doctor will discuss the possible adverse effects and risks with you. In addition, you will be closely monitored.

If you have any further questions about the use of this medicine, ask your doctor.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone will experience them.

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

Serious adverse effects

The most serious adverse 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), inform your doctor immediately.

Other adverse effects

If you are unsure about the meaning of the adverse effects listed below, please ask your doctor to explain them.

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

• Headache
• Dizziness
• Diarrhea, nausea, abdominal pain
• Fever, tiredness (fatigue)
• Upper respiratory tract infection
• Common cold (nasopharyngitis)
• Back pain, joint pain (arthralgia)
• Urinary tract infection

Common (may affect up to 1 in 10 people):

• Vomiting, stomach discomfort after meals (dyspepsia)
• Hives, rash, itching of the 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 difficulty breathing or dizziness (anaphylactic reaction)
• Disseminated gonococcal infection

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V.

By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Ultomiris

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

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of the month indicated.

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

Do not freeze.

Keep in the original packaging to protect from light.

After dilution with sodium chloride 9 mg/ml (0.9 %) solution for injection, the medicine should be used immediately, or within 24 hours if stored refrigerated, or within 4 hours if stored at room temperature.

Medicines should not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the container and additional information

Composition of Ultomiris

• The active substance is ravulizumab. Each vial of solution contains 1100 mg of ravulizumab.
• The other components are: disodium phosphate heptahydrate (E 339), monosodium phosphate monohydrate (E 339), polysorbate 80 (E 433), arginine, sucrose, and water for injections.

This medicinal product contains sodium and polysorbate 80 (see section 2 “Ultomiris contains sodium” and “Ultomiris contains polysorbate”).

Appearance of the product and contents of the container

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

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

Marketing Authorization 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 Authorization Holder:

Belgium/Belgium/Belgium Alexion Pharma Belgium Tel/Tel: +32 0 800 200 31	Lithuania UAB AstraZeneca Lietuva Tel: +370 5 2660550
	Luxembourg/Luxembourg Alexion Pharma Belgium Tel/Tel: +32 0 800 200 31
Czech Republic AstraZeneca Czech Republic s.r.o. Tel: +420 222 807 111	Hungary AstraZeneca Kft. Tel.: +36 1 883 6500
Denmark Alexion Pharma Nordics AB Tlf.: +46 (0) 8 557 727 50	Malta Alexion Europe SAS Tel: +353 1 800 882 840
Germany Alexion Pharma Germany GmbH Tel: +49 (0) 89 45 70 91 300	Netherlands Alexion Pharma Netherlands B.V. Tel: +32 (0) 2 548 36 67
Estonia AstraZeneca Tel: +372 6549 600	Norway Alexion Pharma Nordics AB Tlf: +46 (0) 8 557 727 50
Greece AstraZeneca A.E. Tel: +30 210 6871500	Austria Alexion Pharma Austria GmbH Tel: +41 44 457 40 00
Spain Alexion Pharma Spain, S.L.U. Tel: +34 93 272 30 05	Poland 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
Croatia AstraZeneca d.o.o. Tel: +385 1 4628 000	Romania AstraZeneca Pharma SRL Tel: +40 21 317 60 41
Ireland Alexion Europe SAS Tel: 1 800 882 840	Slovenia AstraZeneca UK Limited Tel: +386 1 51 35 600
Iceland Alexion Pharma Nordics AB Sími: +46 (0) 8 557 727 50	Slovakia AstraZeneca AB, o.z. Tel: +421 2 5737 7777
Italy Alexion Pharma Italy srl Tel: +39 02 7767 9211	Finland/Suomi Alexion Pharma Nordics AB Puh/Tel: +46 (0) 8 557 727 50
Cyprus Alexion Europe SAS Tel: +357 22490305	Sweden Alexion Pharma Nordics AB Tel: +46 (0) 8 557 727 50
Latvia SIA AstraZeneca Latvija Tel: +371 67377100

Date of the last review of this leaflet: 0

Other sources of information

Detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu, and on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/). Links to other websites on rare diseases and orphan medicinal products are also available.

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

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

2-Before administering the medicine

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

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

• Visually inspect the Ultomiris solution to ensure it does not contain particles or show any discoloration.
• Withdraw the required amount of Ultomiris from the vial(s) using a sterile syringe.
• Transfer the recommended dose to an infusion bag.
• Dilute Ultomiris to achieve a final concentration of 50 mg/ml (initial concentration divided by 2) by adding the appropriate amount of sodium chloride 9 mg/ml (0.9%) injectable solution to the infusion according to the instructions in the following table.

Table 1. Dosing reference table for administration of the loading dose

Body weight range (kg)a	Loading dose (mg)	Volume of Ultomiris (ml)	Volume of diluent NaClb (ml)	Total volume (ml)	Minimum infusion duration Minutes (hours)
≥10 to <20c	600	6	6	12	45 (0.8)
≥20 to <30c	900	9	9	18	35 (0.6)
≥30 to <40c	1200	12	12	24	31 (0.5)
≥40 to <60	2400	24	24	48	45 (0.8)
≥60 to <100	2700	27	27	54	35 (0.6)
≥100	3000	30	30	60	25 (0.4)

a Body weight at the time of treatment.

b Ultomiris must be diluted only with sodium chloride 9 mg/mL (0.9%) injection solution.

c For aHUS and PNH indications only.

Table 2. Maintenance dose administration reference table

Body weight range (kg)a	Maintenance dose (mg)	Volume of Ultomiris (ml)	Volume of NaCl diluent (ml)b	Total volume (ml)	Minimum infusion duration Minutes (hours)
≥10 to <20c	600	6	6	12	45 (0.8)
≥20 to <30c	2100	21	21	42	75 (1.3)
≥30 to <40c	2700	27	27	54	65 (1.1)
≥40 to <60	3000	30	30	60	55 (0.9)
≥60 to <100	3300	33	33	66	40 (0.7)
≥100	3600	36	36	72	30 (0.5)

a Body weight at the time of treatment.

b Ultomiris must be diluted only with sodium chloride 9 mg/mL (0.9%) injection solution.

c For aHUS and PNH indications only.

Table 3. Complementary dose administration reference table

Body weight range (kg)a	Supplemental dose (mg)	Volume of Ultomiris (ml)	Volume of diluent NaClb (ml)	Total volume (ml)	Minimum infusion duration Minutes (hours)
≥40 to <60	600	6	6	12	15 (0.25)
1200	12	12	24	25 (0.42)
1500	15	15	30	30 (0.5)
≥60 to <100	600	6	6	12	12 (0.20)
1500	15	15	30	22 (0.36)
1800	18	18	36	25 (0.42)
≥100	600	6	6	12	10 (0.17)
1500	15	15	30	15 (0.25)
1800	18	18	36	17 (0.28)

a Body weight at the time of treatment.

b Ultomiris must be diluted only with sodium chloride 9 mg/mL (0.9%) injectable solution.

• Gently agitate the infusion bag containing the diluted Ultomiris solution to ensure the medication and diluent are well mixed. Do not shake Ultomiris.
• Allow the diluted solution to reach 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 or any other heat source except room temperature.
• Discard any unused portion of the medication remaining in the vial.
• The prepared solution should be administered immediately after preparation. The infusion must be administered through a 0.2 µm filter. After administration of Ultomiris, flush the entire line with 0.9% sodium chloride injection, USP.
• If the medication is not used immediately after dilution, storage times must not exceed 24 hours at a temperature between 2 °C and 8 °C or 4 hours at room temperature, taking into account the planned infusion time.

3- Administration

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

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

4- Special storage and handling conditions

Store in a refrigerator (between 2 °C and 8 °C). Do not freeze. Keep in the original packaging to protect 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 the month indicated.

Disposal of unused medication and all materials that have come into contact with it must be carried out in accordance with local regulations.