300 mg/3 ml concentrate for infusion solution
BBN
What Ultomiris is and what it is used for
What Ultomiris is
Ultomiris is a drug that contains the active substance ravulizumab and belongs to a drug class called monoclonal antibodies that bind to a specific target in the body. Ravulizumab has been designed to bind to the C5 complement protein, which is part of the body’s defense system known as the ‘complement system’.
What Ultomiris is used for
Ultomiris is used to treat adults and children weighing 10 kg or more with a condition called paroxysmal nocturnal hemoglobinuria (PNH), including patients who have not been treated with complement inhibitors and patients who have received eculizumab in the past 6 months. In patients with PNH, the complement system is overactive and attacks the red blood cells, which can lead to low blood cell counts ( anemia ), fatigue, difficulty 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 drug can prevent the complement proteins from attacking the red blood cells in the organs and can thus control the symptoms of the disease.
Ultomiris is also used to treat patients who weigh 10 kg or more with a disease affecting the blood and kidneys called atypical hemolytic uraemic syndrome (aHUS), including patients who have not been treated with complement inhibitors and patients who have received eculizumab for at least 3 months. In patients with aHUS, the kidneys and blood vessels, and even the platelets, can become inflamed. It can lead to low blood counts (too low numbers of platelets [lack of platelets ] and red blood cells[anemia]), impaired or lost kidney function, blood clots, fatigue, and general low functioning. Ultomiris can block the body’s inflammatory reaction and its ability to attack and destroy its sensitive blood vessels, and can thus control the symptoms of the disease, e.g. kidney damage.
Ultomiris is also used to treat adult patients with a certain 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 pronounced muscle weakness, impaired vision and mobility, shortness of breath, extreme fatigue, risk of aspiration (risk of food and drink ending up in the windpipe instead of the esophagus) and marked impairment of daily activities. Ultomiris can block the body’s inflammatory response and its ability to attack and destroy muscles to improve muscle contraction, thereby reducing the symptoms of the disease and the impact of the disease on activities of daily living. Ultomiris is especially intended for patients who still have symptoms, despite treatment with other medicines.
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 a meningococcal infection.
Warnings and precautions
Talk to your doctor before using Ultomiris.
Symptoms of infection with meningococcus and other types of Neisseria
Because the medicine blocks the complement system, which is part of the body’s defense against infection, using Ultomiris increases the risk that you will get a meningococcal infection caused by Neisseria meningitides. These are severe infections that affect the meninges and can spread in the blood and body ( sepsis [blood poisoning]).
Talk to your doctor before starting Ultomiris to make sure you are vaccinated against Neisseria meningitides 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 until 2 weeks after the vaccination. Make sure your current meningococcal vaccination is up to date. You should also know that vaccination does not always prevent this type of infection. By national recommendations, your doctor may consider that you need additional measures to prevent infection.
Symptoms of meningococcal infection
As it is important to quickly identify and treat meningococcal infection in patients receiving Ultomiris, you will be given a ‘patient card’ to carry with you at all times. The card states the relevant signs and symptoms of meningococcal infection/blood poisoning.
If you experience any of the following symptoms, you must inform your doctor immediately:
- 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
- light-sensitive eyes.
Treatment for meningococcal infection during travel
If you are traveling in a region where you cannot contact your doctor or are temporarily unable to receive medical treatment, your doctor may prescribe antibiotics against Neisseria meningitides that you can take with you. If you get any of the symptoms described above, you must take the antibiotic course as prescribed. You need to remember to still see a doctor as soon as possible, even if you feel better after taking the antibiotics.
Infection you
Before receiving Ultomiris, inform your doctor if you have any infections.
Infusion reactions
When Ultomiris is given, you may have infusion reactions (reactions to the drip) such as headache, low back pain, and infusion-related pain. Some patients may experience an allergic or hypersensitivity reaction (including anaphylaxis, a severe allergic reaction that causes difficulty breathing or dizziness).
Older
No special precautions are required when treating patients 65 years of age and older, although experience with Ultomiris in elderly patients with PNH and aHUS in clinical trials is limited.
Children and young people
Patients under 18 years of age must be vaccinated against Haemophilus influenza and pneumococcal infections.
Other medicines and Ultomiris
Tell your doctor or pharmacist if you are using, have recently used, or might be using other medicines.
Pregnancy, breastfeeding, and fertility
Fertile women
The drug’s effects on an unborn child are not known. Fertile women must therefore use an effective contraceptive method during treatment and for up to 8 months after the end of treatment.
Pregnancy/breastfeeding
If you are pregnant or breastfeeding, 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 or for women of childbearing potential who are not using contraception.
Driving ability and use of machinery
This medicine has no or negligible effect on the ability to drive and use machines.
Ultomiris contains sodium
After dilution with sodium chloride 9 mg/ml (0.9%) solution for injection, this medicinal product contains 0.18 g of sodium (the main component of common/table salt) in 72 ml at the maximum dose. This corresponds to 9.1% of the maximum recommended daily intake of sodium for adults.
This should be taken into account if you have been prescribed a low-salt diet.
How to use Ultomiris
At least 2 weeks before you start treatment with Ultomiris, your doctor will give you a vaccine against meningococcal infections, if you have not already received this or if the vaccination is no longer protective. 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 under 18 years of age, the doctor will vaccinate the child (if not already done) against Haemophilus influenza and pneumococcal infections according to national vaccination recommendations for each age group.
Instructions for correct use
Your doctor will calculate your dose of Ultomiris based on your body weight, as shown in Table 1. Your first dose is called a loading dose. Two weeks after receiving your loading dose, you will receive a maintenance dose of Ultomiris which is then repeated once every eight weeks for patients weighing more than 20 kg and every four weeks for patients weighing less than 20 kg.
If you have previously received another medicine for PNH or aHUS called eculizumab, the loading dose should be given 2 weeks after the last eculizumab infusion.
Table 1: Weight-based dosing regimen for Ultomiris
| Body weight range (kg) | Loading dose (mg) | Maintenance dose (mg) |
| 10 to less than 20 a | 600 | 600 |
| 20 to less than 30 a | 900 | 2,100 |
| 30 to less than 40 a | 1,200 | 2,700 |
| 40 to less than 60 | 2,400 | 3,000 |
| 60 to less than 100 | 2,700 | 3,300 |
| 100 or more | 3,000 | 3,600 |
an Only for patients with PNH and aHUS.
Ultomiris is given by infusion (drip) into a vein. Infusion one takes about 45 minutes.
If you have been given too much Ultomiris
If you suspect that you have received a higher dose of Ultomiris than prescribed, contact your doctor for advice.
If you forget a visit where you were supposed to get Ultomiris
If you miss an appointment, contact your doctor immediately for advice and see the section below “If you stop using Ultomiris”.
If you stop using Ultomiris
If you stop using Ultomiris for PNH
If you stop or stop treatment with Ultomiris, your PNH symptoms may come back and be more severe. 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 increased breakdown of your red blood cells, which can cause:
- increase in levels of lactate dehydrogenase (LDH), a laboratory marker of red blood cell breakdown
- 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 altered attention
- chest pain or angina
- increase in serum creatinine level (problems with the kidneys)
- thrombosis (blood clot).
Contact your doctor if you experience any of these symptoms.
If you stop using Ultomiris for aHUS
If you stop or stop treatment with Ultomiris, your aHUS symptoms may 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 increased damage to the small blood vessels, which can cause:
- significant reduction in the number of blood platelets ( thrombocytopenia )
- significantly increased breakdown of red blood cells
- increase in levels of lactate dehydrogenase (LDH), a laboratory marker of red blood cell breakdown
- decreased urine output (problems with the kidneys)
- increase in serum creatinine level (problems with the kidneys)
- confusion or altered attention
- vision changes
- chest pain or angina
- shortness of breath
- abdominal pain, diarrhea
- thrombosis (blood clot).
Contact your doctor if you experience any of these symptoms.
If you stop using Ultomiris for gMG
If you interrupt or stop treatment with Ultomiris, your gMG symptoms may return. Talk to your doctor before stopping Ultomiris. The doctor will discuss possible side effects and risks with you. The doctor will also want to monitor you closely.
If you have any further questions about this medicine, ask your doctor.
Possible side effects
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 before starting your treatment.
The most serious side effect is meningococcal infection/sepsis.
If you get any of the symptoms of meningococcal infection (see section 2 “Symptoms of meningococcal infection”), you must inform your doctor immediately.
If you are unsure of what is meant by the side effects below, ask the doctor to explain them to you.
Very common (may affect more than 1 in 10 people):
- headache
- diarrhea, nausea
- fatigue (exhaustion)
- upper respiratory tract infection
- common cold ( nasopharyngitis )
Common (may affect up to 1 in 10 people):
- dizziness
- abdominal pain, vomiting, indigestion ( dyspepsia )
- skin rash, itching of the skin (pruritus), hives
- joint pain ( arthralgia ), back pain, muscle pain ( myalgia ), and muscle cramps
- fever ( pyrexia ), flu-like illness, feeling tired ( asthenia )
- infusion-related reaction.
Uncommon (may affect up to 1 in 100 people):
- meningococcal infection
- overindulge
- severe allergic reaction causing difficulty breathing or dizziness ( anaphylactic reaction ), hypersensitivity
- gonococcal infection
How to store Ultomiris
Keep this medicine out of the sight and reach of children.
Use before the expiry date stated on the carton after “EXP”. The expiration date is the last day of the specified month.
Store in a refrigerator (2 °C–8 °C).
Do not freeze.
Store in the original packaging. Light sensitive.
After dilution with sodium chloride 9 mg/ml (0.9%) solution for injection, the drug should be used immediately, or within 24 hours if stored in a refrigerator or within 4 hours at room temperature.
Medicines should not be thrown down the drain. Ask the pharmacist how to dispose of medications that are no longer used. These measures will help to protect the environment.
Contents of the packaging and other information
Contents declaration
- The active substance is eculizumab. One vial contains 300 mg of eculizumab.
- Other ingredients are disodium phosphate heptahydrate, sodium dihydrogen phosphate monohydrate, polysorbate 80, arginine, sucrose, and water for injections.
This medicine contains sodium (see section 2 “Ultomiris contains sodium”).
Appearance and package sizes of the medicine
Ultomiris is available as a concentrate for infusion, solution (3 ml in a vial – 1 in each package).
Ultomiris is a transparent, clear to the yellowish solution, which is practically free of particles.
Marketing Authorisation Holder
Alexion Europe SAS
103-105, rue Anatole France
92300 Levallois-Perret
France
Manufacturer
Alexion Pharma International Operations Unlimited Company
Alexion Dublin Manufacturing Facility
College Business and Technology Park
Blanchardstown Rd North
Dublin 15 R925
Ireland
Almac Pharma Services (Ireland) Limited
Finnabair Industrial Estate
Dundalk
Co. Louth A91 P9KD
Ireland
Almac Pharma Services Limited
22 Seagoe Industrial Estate
Craigavon, Armagh BT63 5QD
UK