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 1 month of age and older with a disease called Paroxysmal Nocturnal Haemoglobinuria (PNH). 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 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 both adult and children 1 month of age and older with a disease affecting the blood system and kidney called atypical Haemolytic Uremic Syndrome (aHUS). 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 generalized 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.

Do not use Ultomiris:

-              If you are allergic to ravulizumab, proteins derived from mouse products, other monoclonal antibodies, 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 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 safety card’ to carry with you at all times, listing relevant signs and symptoms of meningococcal infection/sepsis.

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 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 and aHUS 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

Ultomiris is not recommended during pregnancy and in women of childbearing potential not using contraception. 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.

Driving and using machines

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

Ultomiris contains sodium

This medicine when diluted with sodium chloride 9 mg/mL (0.9%) solution for injection for IV administration 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

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

Your dose will be worked out 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 another medicine for PNH and aHUS called Soliris, the loading dose should be given 2 weeks after the last Soliris infusion.

Table 1: Ultomiris weight-based dosing regimen

^a For patients with PNH and aHUS only.

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 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 was meningococcal infection/sepsis. 

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 

-              Feeling tired (fatigue)

-              Upper respiratory tract infection

-              Common cold (nasopharyngitis)

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

-              Dizziness 

-              Abdominal pain, vomiting, stomach discomfort after meals (dyspepsia) 

-              Rash, itchy skin (pruritus), hives  

-              Joint pain (arthralgia), back pain, muscle pain (myalgia) and muscle spasms

-              Fever (pyrexia), influenza like illness, feeling tired (asthenia) 

-              Infusion related reaction

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

-              Meningococcal infection

-              Chills

-              Hypersensitivity, serious allergic reaction which causes difficulty in breathing or dizziness

(anaphylactic reaction) 

-              Gonococcal infection

Keep this medicine out of the reach and sight 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.

Do not shake.

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.