Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - ultomiris

Document Subject

Generated Narrative: MedicinalProductDefinition mp1d2f698bc3b19bc75adea93b8b5c0811

identifier: http://ema.europa.eu/identifier/EU/1/19/1371/001

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: Ultomiris 300 mg/3 mL concentrate for solution for infusion

type: Full name

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part: nan

type: Invented name part

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part: nan

type: Scientific name part

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Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-1d2f698bc3b19bc75adea93b8b5c0811

identifier: http://ema.europa.eu/identifier/EU/1/19/1371/001

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - ultomiris

Attesters

What is in 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

What is Ultomiris Ultomiris is a medicine that contains the active substance ravulizumab and it belongs to a class of medicines called monoclonal antibodies, that attach to a specific target in the body. Ravulizumab has been designed to attach to the C5 complement protein, which is a part of the body s defence system called the complement system .

What is Ultomiris used for Ultomiris is used to treat adult and children patients 10 kg and over with a disease called paroxysmal nocturnal haemoglobinuria (PNH), including patients untreated with 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 their red blood cells, which can lead to low blood counts (anaemia), tiredness, difficulty in functioning, pain, abdominal pain, dark urine, shortness of breath, difficulty swallowing, erectile dysfunction and blood clots. By attaching to and blocking the C5 complement protein, this medicine can stop complement proteins from attacking red blood cells and so control symptoms of the disease.

Ultomiris is also used to treat adult and children patients 10 kg and over with a disease affecting the blood system and kidney called atypical haemolytic uremic syndrome (aHUS), including patients untreated with complement inhibitor and patients who have received eculizumab for at least 3 months. In patients with aHUS, their kidneys and blood vessels, including platelets, can be inflamed which can lead to low blood counts (thrombocytopenia and anaemia), reduced or lost kidney function, blood clots, tiredness and difficulty in functioning. Ultomiris can block the body s inflammatory response, and its ability to attack and destroy its own vulnerable blood vessels and so control symptoms of the disease including injury to the kidneys.

Ultomiris is also used to treat adult patients with a certain type of disease affecting the muscles called generalised Myasthenia Gravis (gMG). In patients with gMG, their muscles can be attacked and damaged by the immune system which can lead to profound muscle weakness, impaired vision and mobility, shortness of breath, extreme fatigue, risk for aspiration, and markedly impaired activities of daily living. Ultomiris can block the body s inflammatory response, and its ability to attack and destroy its own muscles to improve muscle contraction, thereby reducing symptoms of the disease and impact of the disease on the activities of daily living. 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 mainly affects the optic (eye) nerves and the spinal cord called Neuromyelitis Optica Spectrum Disorder (NMOSD). In patients with NMOSD, the optic nerves and spinal cord are attacked and damaged by the immune system working incorrectly, which can lead to loss of sight in one or both eyes, weakness or loss of movement in the legs or arms, painful spasms, loss of feeling, problems with bladder and bowel function and marked difficulties with activities of daily living. Ultomiris can block the body s abnormal immune response, and its ability to attack and destroy its own optic nerves and spinal cord, which reduces the risk of a relapse or attack of NMOSD.

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 meningococcal infection.

Warnings and precautions
Talk to your doctor before using Ultomiris.

Meningococcal and other Neisseria infections symptoms Because the medicine blocks the complement system, which is part of the body s defences against infection, the use of Ultomiris increases your risk of meningococcal infection caused by Neisseria meningitidis. These are severe infections affecting the linings of the brain which can cause inflammation of the brain (encephalitis) and can spread throughout the blood and body (sepsis).

Consult your doctor before you start Ultomiris to be sure that you receive vaccination against Neisseria meningitidis at least 2 weeks before beginning therapy. If you cannot be vaccinated 2 weeks beforehand, your doctor will prescribe antibiotics to reduce the risk of infection until 2 weeks after you have been vaccinated. Ensure that your current meningococcal vaccination is up to date. You should also be aware that vaccination may not always prevent this type of infection. In accordance with national recommendations, your doctor might consider that you need supplementary measures to prevent infection.

Meningococcal infection symptoms

Because of the importance of rapidly identifying and treating meningococcal infection in patients who receive Ultomiris, you will be provided a Patient card to carry with you at all times, listing 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 a stiff neck or stiff back
• fever
• fever and rash
• confusion
• muscle aches with flu-like symptoms
• eyes sensitive to light

Treatment for meningococcal infection while travelling

If you are travelling in a region where you are unable to contact your doctor or will be temporarily unable to receive medical treatment, your doctor may prescribe an antibiotic against Neisseria meningitidis to bring with you. If you experience any of the symptoms described above, you should take the course of antibiotics as prescribed. You should bear in mind that you should still see a doctor as soon as possible, even if you feel better after having taken the antibiotics.

Infections Before starting Ultomiris, inform your doctor if you have any infections.

Infusion-related reactions When Ultomiris is given, you may experience reactions to the infusion (drip) (infusion reaction) such as headache, lower back pain, and infusion-related pain. Some patients may experience allergic or hypersensitivity reactions (including anaphylaxis, a serious allergic reaction which causes difficulty breathing or dizziness).

Children and adolescents Patients less than 18 years of age must be vaccinated against Haemophilus influenzae and pneumococcal infections.

Elderly There are no special precautions needed for the treatment of patients aged from 65 years and over, although experience with Ultomiris in elderly patients with PNH, aHUS, or NMOSD in clinical studies is limited.

Other medicines and Ultomiris
Tell your doctor or pharmacist if you are using or have recently used or might use any other medicines.

Pregnancy, breast-feeding, and fertility

Women of childbearing potential

The effects of the medicine on an unborn child are not known. Therefore, effective contraception during treatment and up to 8 months after treatment should be used in women who are able to get pregnant.

Pregnancy/ Breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine. Ultomiris is not recommended during pregnancy and in women of childbearing potential not using contraception.

Driving and using machines This medicine has no or negligible influence on the ability to drive and use machines.

Ultomiris contains sodium Once diluted with sodium chloride 9 mg/mL (0.9%) solution for injection, this medicine contains 2.65 g sodium (main component of cooking/table salt) in 720 mL at the maximal dose. This is equivalent to 133 % of the recommended maximum daily dietary intake of sodium for an adult. You should take this into consideration if you are on a controlled sodium diet.

At least 2 weeks before you start treatment with Ultomiris, your doctor will give you a vaccine against meningococcal infections if you have not previously had one or if your vaccination is outdated. If you cannot be vaccinated at least 2 weeks before you start treatment with Ultomiris, your doctor will prescribe antibiotics to reduce the risk of infection until 2 weeks after you have been vaccinated. If your child is less than 18 years, your doctor will administer a vaccine (if not yet done) against Haemophilus influenzae and pneumococcal infections according to the national vaccination recommendations for each age group.

Instructions for proper use Your dose of Ultomiris will be calculated by your doctor, based on your body weight, as shown in Table 1. Your first dose is called the loading dose. Two weeks after receiving your loading dose, you will be given a maintenance dose of Ultomiris, and this will then be repeated once every 8 weeks for patient above 20 kg and every 4 weeks for patient less than 20 kg.

If you were previously receiving Ultomiris subcutaneously (given under the skin through an on-body injector), no loading dose is required. Ultomiris intravenous maintenance dose should be given 1 week after the last dose of Ultomiris subcutaneous formulation.

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

Table 1: Ultomiris weight-based dosing regimen Body weight range (kg) Loading dose (mg) Maintenance dose (mg) 10 to less than 20a 20 to less than 30a 2,30 to less than 40a 1,2,40 to less than 2,3,60 to less than 2,3,above 3,3,a For patients with PNH and aHUS only.

Ultomiris is given by infusion (drip) into a vein. The infusion will take approximately 2 hours.

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

If you forget an appointment to receive Ultomiris
If you forget an appointment, please contact your doctor immediately for advice and see section below If you stop using Ultomiris .

If you stop using Ultomiris for PNH Interrupting or ending treatment with Ultomiris may cause your PNH symptoms to return with greater severity. Your doctor will discuss the possible side effects with you and explain the risks. Your doctor will want to monitor you closely for at least 16 weeks.

The risks of stopping Ultomiris include an increase in the destruction of your red blood cells, which may cause:

• An increase in your lactate dehydrogenase (LDH) levels, a laboratory marker of destruction of red blood cells,
• A significant fall in your red blood cell counts (anaemia),
• Dark urine,
• Fatigue,
• Abdominal pain,
• Shortness of breath,
• Difficulty swallowing,
• Erectile dysfunction (impotence),
• Confusion or change in how alert you are,
• Chest pain, or angina,
• An increase in your serum creatinine level (problems with your kidneys), or
• Thrombosis (blood clotting).
  If you have any of these symptoms, contact your doctor.

If you stop using Ultomiris for aHUS
Interrupting or ending treatment with Ultomiris may cause your aHUS symptoms to come back. Your doctor will discuss the possible side effects with you and explain the risks. Your doctor will want to monitor you closely.

The risks of stopping Ultomiris include an increase in small blood vessel damage, which may cause:

• A significant fall in your platelets (thrombocytopenia),
• A significant rise in destruction of your red blood cells,
• An increase in your lactate dehydrogenase (LDH) levels, a laboratory marker of destruction of red blood cells,
• Decreased urination (problems with your kidneys),
• An increase in your serum creatinine level (problems with your kidneys),
• Confusion or change in how alert you are,
• Change in your vision
• Chest pain, or angina,
• Shortness of breath,
• Abdominal pain, diarrhoea, or
• Thrombosis (blood clotting).

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

If you stop using Ultomiris for gMG Interrupting or stopping treatment with Ultomiris may cause your gMG symptoms to occur. Please speak to your doctor before stopping Ultomiris. Your doctor will discuss the possible side effects and risks with you. Your doctor will also want to monitor you closely.

If you stop using Ultomiris for NMOSD Interrupting or stopping treatment with Ultomiris may cause NMOSD relapse to occur. Please speak to your doctor before stopping Ultomiris. Your doctor will discuss the possible side effects and risks with you. Your doctor will also want to monitor you closely.

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

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Your doctor will discuss the possible side effects with you and explain the risks and benefits of Ultomiris with you prior to treatment.

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

If you are not sure what the side effects below are, ask your doctor to explain them to you.

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

• Headache
• Diarrhoea, nausea, abdominal pain
• Fever (pyrexia), feeling tired (fatigue)
• Upper respiratory tract infection
• Common cold (nasopharyngitis)
• Back pain, joint pain (arthralgia)

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

• Dizziness
• Vomiting, stomach discomfort after meals (dyspepsia)
• Hives, rash, itchy skin (pruritus)
• Muscle pain (myalgia) and muscle spasms
• Influenza like illness, chills, weakness (asthenia)
• Infusion-related reaction
• Allergic reaction (hypersensitivity)
• Urinary tract infection

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

• Meningococcal infection
• Serious allergic reaction which causes difficulty in breathing or dizziness (anaphylactic reaction)
• Gonococcal infection

Reporting of side effects If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

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 that month. Store in a refrigerator (2 C 8 C). Do not freeze.

Store in the original package in order 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 refrigerated or within 6 hours at room temperature.

Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Ultomiris contains

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

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

What Ultomiris looks like and contents of the pack Ultomiris is presented as a concentrate for solution for infusion (30 mL in a vial pack size of 1).
Ultomiris is a clear to translucent, slight whitish colour, practically free from particles solution.

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 RIreland

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgi /Belgique/Belgien Alexion Pharma Belgium T l/Tel: +32 0 800 200 Lietuva UAB AstraZeneca Lietuva Tel: +370 5 2660

Te .: +359 24455Luxembourg/Luxemburg Alexion Pharma Belgium T l/Tel: +32 0 800 200 esk republika AstraZeneca Czech Republic s.r.o. Tel: +420 222 807 Magyarorsz g AstraZeneca Kft. Tel.: +36 1 883 6Danmark Alexion Pharma Nordics AB Tlf: +46 0 8 557 727 Malta Alexion Europe SAS Tel: +353 1 800 882 Deutschland Alexion Pharma Germany GmbH Tel: +49 (0) 89 45 70 91 Nederland Alexion Pharma Netherlands B.V. Tel: +32 (0)2 548 36 Eesti AstraZeneca Tel: +372 6549 Norge Alexion Pharma Nordics AB Tlf: +46 (0)8 557 727
AstraZeneca A.E. : +30 210 6871 sterreich Alexion Pharma Austria GmbH Tel: +41 44 457 40 Espa a Alexion Pharma Spain, S.L. Tel: +34 93 272 30 Polska AstraZeneca Pharma Poland Sp. z o.o. Tel.: +48 22 245 73 France Alexion Pharma France SAS T l: +33 1 47 32 36 Portugal Alexion Pharma Spain, S.L. - Sucursal em Portugal
Tel: +34 93 272 30 Hrvatska AstraZeneca d.o.o. Tel: +385 1 4628 Rom nia AstraZeneca Pharma SRL Tel: +40 21 317 60 Ireland Alexion Europe SAS Tel: +353 1 800 882 Slovenija AstraZeneca UK Limited Tel: +386 1 51 35 sland Alexion Pharma Nordics AB S mi: +46 0 8 557 727 Slovensk republika AstraZeneca AB, o.z. Tel: +421 2 5737 7Italia Alexion Pharma Italy srl Tel: +39 02 7767 9Suomi/Finland Alexion Pharma Nordics AB Puh/Tel: +46 0 8 557 727
Alexion Europe SAS : +357 22490Sverige Alexion Pharma Nordics AB Tel: +46 0 8 557 727 Latvija SIA AstraZeneca Latvija Tel: +371 67377United Kingdom (Northern Ireland) Alexion Europe SAS Tel: +44 (0) 800 028 4This leaflet was last revised in

Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: