BRIUMVI 150 мг Концентрат для инфузионного раствора

Содержание инструкции

1. Briumvi 150 mg concentrate for solution for infusion
   1. What is Briumvi and what is it used for
   2. What you need to know before you are given Briumvi
   3. How Briumvi is administered
   4. Possible side effects
   5. How to store Briumvi
   6. Package Contents and Other Information

Briumvi 150 mg concentrate for solution for infusion

ublituximab
Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicine. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before you are given 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.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

• 1. What Briumvi is and what it is used for
• 2. What you need to know before you are given Briumvi
• 3. How Briumvi is given
• 4. Possible side effects
• 5. How to store Briumvi
• 6. Contents of the pack and other information

1. What is Briumvi and what is it used for

What is Briumvi
Briumvi contains the active ingredient ublituximab, a type of protein called a monoclonal antibody.
Antibodies work by binding to specific targets in the body.

What is Briumvi used for
Briumvi is used to treat adult patients with relapsing forms of multiple sclerosis (RMS), in whom the
patient experiences relapses (exacerbations) followed by periods with milder or absent symptoms.

What is multiple sclerosis
Multiple sclerosis (MS) affects the central nervous system, especially the nerves in the brain and the
spinal cord. In MS, some white blood cells called B cells, which are part of the
immune system (the body's defense system), do not function properly and attack the
protective layer (so-called myelin sheath) surrounding nerve cells, causing damage and
inflammation. Destruction of the myelin sheath prevents nerves from functioning properly and causes the symptoms of MS. The symptoms of MS depend on the part of the nervous
system affected and may include problems with balance and walking, muscle weakness, numbness, double vision, blurred vision, poor coordination, and bladder problems.
In relapsing forms of MS, the patient has repeated attacks of symptoms (relapses), which can
appear suddenly, within hours, or slowly, over several days. Between

relapses, symptoms disappear or improve, but damage can accumulate and lead to
permanent disability.

How does Briumvi work?
Briumvi works by binding to a target present on the surface of B cells, called CD20. B cells are a type of white blood cells that are part of the immune system. In multiple
sclerosis, the immune system attacks the protective layer surrounding nerve cells. B
cells are involved in this process. Briumvi targets and eliminates B cells and therefore reduces the
likelihood of having a relapse, relieves symptoms, and slows the progression of the disease.

2. What you need to know before you are given Briumvi

You must not be given Briumvi:

• if you are allergicto ublituximab or any of the other ingredients of this medicine (listed in section 6),
• if you have a serious infection,
• if you have been told you have serious problems with your immune system, or
• if you have cancer.

If you are not sure, ask your doctor before you are given Briumvi.

Warnings and precautions
Talk to your doctor before you are given Briumviif any of the following conditions apply to you. Your doctor may decide to postpone treatment with Briumvi, or decide that you cannot receive Briumvi if:

• you have an infection. Your doctor will wait for the infection to resolve before giving you Briumvi;
• you have had hepatitis B in the past or are a carrier of the hepatitis B virus. This is because medicines like Briumvi can cause the hepatitis B virus to become active again. Before treatment with Briumvi, your doctor will check that you are not at risk of developing a hepatitis B infection. Patients who have had hepatitis B or are carriers of the virus will undergo blood tests and will be monitored by the doctor to detect any signs of hepatitis B infection;
• you have recently received any vaccine or may receive a vaccine in the near future;
• you have a canceror have had cancer in the past. Your doctor may decide to postpone treatment.

Infusion-related reactions

• Infusion-related reactions are the most common side effect of treatment with Briumvi. These are allergic reactions that develop while the medicine is being given, or shortly after. These reactions can be serious.
• The symptoms of an infusion-related reaction can include:
• itching of the skin
• hives
• redness of the face or skin
• irritation of the throat
• difficulty breathing
• swelling of the tongue or throat
• wheezing
• chills
• fever
• headache
• dizziness
• feeling faint
• nausea
• abdominal pain (stomach ache)
• fast heartbeat.
• Tell your doctor or nurse immediately if you have or suspect you have an infusion-related reaction.Infusion-related reactions can occur during the infusion or up to 24 hours after the infusion.
• To reduce the risk of infusion-related reactions, your doctor will give you other medicines before each infusion of Briumvi (see section 3) and will closely monitor you during the infusion.
• If you have an infusion-related reaction, it may be necessary to stop the infusion or slow down the infusion rate.

Infections

• Talk to your doctor before you are given Briumvi if you have or suspect you have an infection. Your doctor will wait for the infection to resolve before giving you Briumvi.
• If you are given Briumvi, you may be more likely to develop infections, because the immune cells targeted by Briumvi also help to fight infections.
• Tell your doctor or nurse immediately if you develop an infection or notice any of these signs of infection, during or after treatment with Briumvi:
• fever or chills
• cough that does not go away
• herpes (e.g. cold sores, shingles or genital herpes)
• Tell your doctor or nurse immediately if you think your MS is getting worse or if you notice the appearance of new symptoms,as there is a very rare and potentially life-threatening brain infection called “progressive multifocal leukoencephalopathy” (PML) that can cause symptoms similar to those of MS. PML can occur in patients taking medicines like Briumvi and other medicines used to treat MS.
• Tell your partner or caregiverabout your treatment with Briumvi, as they may notice symptoms of PML that you are not aware of, such as memory loss, difficulty thinking, difficulty walking, loss of vision or changes in speech, which your doctor may want to investigate.

Vaccinations

• Tell your doctor if you have recently received any vaccine or may receive a vaccine in the near future.
• Your doctor will check if you need vaccinations before starting treatment with Briumvi. Any vaccinations with a live or live-attenuated vaccine must be given at least 4 weeks before starting treatment with Briumvi. During treatment with Briumvi, you should not be given live or live-attenuated vaccines until your doctor tells you that your immune system is no longer weakened.
• Any vaccinations with inactivated vaccines should be given at least 2 weeks before starting treatment with Briumvi, when possible. If you want to be vaccinated with inactivated vaccines during treatment with Briumvi, ask your doctor.

Children and adolescents
Briumvi is not intended for use in children and adolescents under 18 years of age, as it has not yet been studied in this age group.

Other medicines and Briumvi
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. In particular, tell your doctor:

• if you are taking, have recently taken or might take medicines that affect the immune system, such as chemotherapy, immunosuppressants (except corticosteroids) or other medicines used to treat MS, as they may have an additive effect on the immune system;
• if you are planning to be vaccinated (see above “Warnings and precautions”).

If any of these conditions apply to you (or if you are not sure), ask your doctor before you are given Briumvi.

Pregnancy and breastfeeding

• If you are pregnant, suspect you are pregnant or are planning to become pregnant, tell your doctor before you are given Briumvi. This is because Briumvi can cross the placenta and have effects on the baby.
• If you are pregnant, do not use Briumvi unless you have discussed it with your doctor. The doctor will assess the benefit of treatment with Briumvi for you against the risk to the baby.
• If you have had a baby after receiving Briumvi during pregnancy, it is important to tell your pediatrician, so that they can advise you when your baby can be vaccinated.
• It is not known whether Briumvi passes into breast milk. Ask your doctor how best to feed your baby if you are using Briumvi.

Contraception in women
If you are able to become pregnant (conceive), you will need to use contraceptive measures:

• during treatment with Briumvi and
• for at least 4 months after the last infusion of Briumvi.

Driving and using machines
It is unlikely that Briumvi will affect your ability to drive and use machines.

Briumvi contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, that is to say it is essentially ‘sodium-free’.

3. How Briumvi is administered

Briumvi will be administered to you by a doctor or a nurse experienced in the use of this treatment,
who will closely monitor you during the administration of the medicine in case you
experience any undesirable effects. Briumvi will always be administered via intravenous
infusion (intravenous infusion).

Medicines administered before treatment with Briumvi
Before receiving Briumvi, you will be administered other medicines to prevent or reduce possible
undesirable effects, such as infusion-related reactions (for information on infusion-related
reactions, see paragraphs 2 and 4).
Before each infusion you will receive a corticosteroid and an antihistamine, and you may also receive
medicines to reduce fever.

At what doses and with what frequency will Briumvi be administered to you

• The first dose of Briumvi will be 150 mg. This infusion will last 4 hours.
• The second dose of Briumvi will be 450 mg and will be administered 2 weeks after the first dose. This infusion will last 1 hour.
• Subsequent doses of Briumvi will be 450 mg and will be administered 24 weeks after the first dose and, subsequently, every 24 weeks. These infusions will last 1 hour.

How Briumvi is administered

• Briumvi will be administered to you by a doctor or a nurse. Before administration, Briumvi must be diluted. The dilution will be carried out by a healthcare professional. The medicine will be administered to you via infusion into a vein (intravenous infusion).
• You will be closely monitored during the infusion of Briumvi and for at least 1 hour after the administration of the first two infusions, in case you experience any undesirable effects, such as infusion-related reactions. In case of an infusion-related reaction, the infusion may be slowed down, temporarily suspended or permanently discontinued depending on its severity (for information on infusion-related reactions, see paragraphs 2 and 4).

If you miss an infusion of Briumvi

• If you miss an infusion of Briumvi, agree with your doctor to receive it as soon as possible. Do not wait until the next scheduled infusion.
• To fully benefit from Briumvi, it is important that you receive each infusion at the time it is scheduled.

If you stop treatment with Briumvi

• It is important that you continue treatment until you and your doctor believe that it is benefiting you.
• Some undesirable effects may be related to low levels of B cells. These undesirable effects may continue to occur even after stopping treatment with Briumvi, until B cell levels return to normal.
• Before starting to take any other medicine, inform your doctor of the date of your last Briumvi infusion.

If you have any questions 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.
The following side effects have been reported for Briumvi:

Serious side effects
Infusion-related reactions

• Infusion-related reactions are the most common side effect of treatment with Briumvi (very common: may affect more than 1 in 10 people). In most cases, these are mild reactions, but some serious reactions can also occur.
• Tell your doctor or nurse immediately if you experience any of the signs orsymptoms of an infusion-related reaction, during the infusion or up to 24 hours afterthe infusion.Symptoms may include, but are not limited to:
• skin itching
• hives
• redness of the face or skin
• throat irritation
• difficulty breathing
• swelling of the tongue or throat
• wheezing
• chills
• fever
• headache
• dizziness
• feeling faint
• nausea
• abdominal pain (stomach ache)
• fast heartbeat.
• If you experience an infusion-related reaction, you will be given medicines to treat it and it may be necessary to slow down or stop the infusion. Once the reaction has stopped, the infusion may continue. If the infusion-related reaction is life-threatening, your doctor will permanently stop treatment with Briumvi.

Infections

• If you are given Briumvi, you may be more likely to develop infections, some of which can be serious. The following infections have been observed in patients treated with Briumvi for MS:
• Very common(may affect more than 1 in 10 people)
• upper respiratory tract infections (infections of the nose and throat)
• respiratory tract infections
• Common(may affect up to 1 in 10 people)
• lower respiratory tract infections (lung infection such as bronchitis or pneumonia)
• herpes infections (cold sores or shingles)
• Uncommon(may affect up to 1 in 100 people)
• infection of the membranes surrounding the brain and spinal cord (meningitis), infection of the brain (encephalitis) or both (meningoencephalitis)
• Tell your doctor or nurse immediately if you notice any of these signs of infection:
• fever or chills
• cough that does not go away
• herpes (e.g. cold sores, shingles or genital herpes)
• headache with fever, stiff neck, sensitivity to light, nausea, confusion, seizures, change in personality, incoordination (ataxia), altered consciousness and/or coma. These may be symptoms of an infection of the membranes surrounding the brain and spinal cord (meningitis), an infection of the brain (encephalitis) or both (meningoencephalitis), which can be fatal.

The doctor will wait for the infection to resolve before giving you Briumvi.

Other side effects
Common(may affect up to 1 in 10 people)

• neutropenia (low levels of neutrophils, a type of white blood cells)
• pain in the limbs (arms or legs)

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. 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 Briumvi

Store in a refrigerator (2 °C – 8 °C).
Briumvi will be stored by healthcare professionals at the hospital or clinic under the following
conditions:

• This medicine must not be used after the expiry date which is stated on the outer packaging and on the vial label after ‘Exp’. The expiry date refers to the last day of that month.
• This medicine must be stored in a refrigerator (2 °C - 8 °C). It must not be frozen. The vial must be kept in the outer packaging to protect the medicine from light.

It is recommended to use the medicine immediately after dilution. If not used
immediately, the storage times and conditions before use are the responsibility
of the healthcare professional and generally should not exceed 24 hours at a temperature between 2 °C
and 8 °C and, subsequently, 8 hours at room temperature.
Do not dispose of any medicine in wastewater. This will help protect the environment.

6. Package Contents and Other Information

What Briumvi contains

• The active ingredient is ublituximab. Each vial contains 150 mg of ublituximab in 6 mL at a concentration of 25 mg/mL.
• The other ingredients are sodium chloride, sodium citrate, polysorbate 80, hydrochloric acid and water for injections.

Description of the appearance of Briumvi and package contents

• Briumvi is a solution from clear to opalescent, from colorless to slightly yellow.
• It is supplied as a concentrate for infusion solution.
• This medicine is available in packs of 1 or 3 vials (glass vials containing 6 mL of concentrate). Not all pack sizes may be marketed.

Marketing Authorisation Holder
Neuraxpharm Pharmaceuticals, S.L.
Avda. Barcelona 69
08970 Sant Joan Despí - Barcelona
Spain

Manufacturer
Neuraxpharm Pharmaceuticals, S.L.
Avda. Barcelona 69
08970 Sant Joan Despí
Barcelona - Spain
For further information on this medicine, contact the local representative of the marketing authorisation holder:

België/Belgique/Belgien
Neuraxpharm Belgium
Tél/Tel: +32 (0)2 732 56 95

Lietuva
Neuraxpharm Pharmaceuticals, S.L.
Tel:+34 93 475 96 00

България
Neuraxpharm Pharmaceuticals, S.L.
Teл.: +34 93 475 96 00

Luxembourg/Luxemburg
Neuraxpharm France
Tél/Tel: +32 474 62 24 24

Česká republika
Neuraxpharm Bohemia s.r.o.
Tel: +420 739 232 258

Magyarország
Neuraxpharm Hungary Kft.
Tel.: +3630 464 6834

Danmark
Neuraxpharm Sweden AB
Tlf.: +46 (0)8 30 91 41
(Sverige)

Malta
Neuraxpharm Pharmaceuticals, S.L.
Tel.:+34 93 475 96 00

Deutschland
neuraxpharm Arzneimittel GmbH
Tel: +49 2173 1060 0

Nederland
Neuraxpharm Netherlands B.V.
Tel.: +31 70 208 5211

Eesti
Neuraxpharm Pharmaceuticals, S.L.
Tel: +34 93 475 96 00

Norge
Neuraxpharm Sweden AB
Tlf:+46 (0)8 30 91 41
(Sverige)

Österreich
Neuraxpharm Austria GmbH
Tel.:+ 43 (0) 1 208 07 40

España
Neuraxpharm Spain, S.L.U.
Tel: +34 93 475 96 00

Ελλάδα
Brain Therapeutics IKE
Τηλ: +302109931458

Polska
Neuraxpharm Polska Sp. z.o.o.
Tel.: +48 783 423 453

FrancePortugal
Neuraxpharm Portugal, Unipessoal Lda
Tel: +351 910 259 536

Hrvatska
Neuraxpharm Pharmaceuticals, S.L.
Tel: +34 93 475 96 00

Ireland
Neuraxpharm Ireland Ltd
Tel: +353 (0)1 428 7777
Neuraxpharm France
Tél: +33 1.53.62.42.90

România
Neuraxpharm Pharmaceuticals, S.L.
Tel: +34 93 475 96 00

Slovenija
Neuraxpharm Pharmaceuticals, S.L.
Tel: +34 93 475 96 00

Ísland
Neuraxpharm Sweden AB
Sími: +46 (0)8 30 91 41
(Svíþjóð)

Slovenská republika
Neuraxpharm Slovakia a.s.
Tel: +421 255 425 562

Italia
Neuraxpharm Italy S.p.A.
Tel: +39 0736 980619

Suomi/Finland
Neuraxpharm Sweden AB
Puh/Tel: +46 (0)8 30 91 41
(Ruotsi/Sverige)

Κύπρος
Brain Therapeutics IKE
Τηλ: +302109931458

Sverige
Neuraxpharm Sweden AB
Tel: +46 (0)8 30 91 41

Latvija
Neuraxpharm Pharmaceuticals, S.L.
Tel: +34 93 475 96 00

Other sources of information
More detailed information on this medicine is available on the website of the European Medicines Agency, https://www.ema.europa.eu .

The following information is intended exclusively for healthcare professionals:
Read the SmPC for further information.

Dosage

• First and second dose

The first dose is administered as an intravenous infusion of 150 mg (first infusion), followed by an intravenous infusion of 450 mg 2 weeks later (second infusion).

• Subsequent doses

Subsequent doses of Briumvi are administered as a single intravenous infusion of 450 mg every 24 weeks (Table 1). The first subsequent dose of 450 mg should be administered 24 weeks after the first infusion. A minimum interval of 5 months must be maintained between one dose of Briumvi and the next.

Figure 1: Dose and dosage schedule of Briumvi

First infusion	Second infusion	Subsequent infusions
Day 1	and d Day 15 a n	Every 6 months

Management of IRRs before infusion

• Treatment with Briumvi must be initiated and supervised by a healthcare professional experienced in managing severe reactions, such as severe infusion-related reactions (IRRs).
• Premedication for IRRs

Before each infusion of Briumvi, the following two premedications must be administered to reduce the frequency and severity of IRRs:

• 100 mg of methylprednisolone or 10-20 mg of dexamethasone (or equivalent) approximately 30-60 minutes before each infusion of Briumvi;
• diphenhydramine approximately 30-60 minutes before each infusion of Briumvi. An antipyretic (e.g. paracetamol) may also be considered for premedication.

Instructions for dilution

• Briumvi must be prepared by a healthcare professional using aseptic technique. Do not shake the vial.
• The product is for single use only.
• Do not use the solution if the colour appears altered or if there are foreign particles present.
• The Briumvi medicinal product must be diluted before administration. Solutions of Briumvi for intravenous administration are prepared by diluting the medicinal product in an infusion bag containing an isotonic solution of 0.9% sodium chloride. For the first

infusion, dilute one vial of medicinal product in the infusion bag (150 mg/250 mL) to achieve a final concentration of approximately 0.6 mg/mL. For subsequent infusions, dilute three vials of medicinal product in the infusion bag (450 mg/250 mL) to achieve a final concentration of approximately 1.8 mg/mL.

• Before starting the intravenous infusion, the contents of the infusion bag must be at room temperature.

Route of administration

• After dilution, Briumvi is administered by intravenous infusion through a dedicated line.
• Briumvi infusions must not be administered by rapid intravenous infusion or bolus.

Table 1: Dose and dosage schedule of Briumvi

The duration of the infusion may be longer if the infusion is interrupted or slowed down.
The first subsequent infusion must be administered 24 weeks after the first infusion.

Management of IRRs during and after infusion
Patients must be monitored during the infusion and for at least one hour after completion of the first two infusions.

During the infusion

• Modifications of the infusion in case of IRRs

If an IRR occurs during the infusion, take the following steps.

Potentially life-threatening IRRs
If signs of a potentially life-threatening or disabling IRR occur during an infusion, the infusion must be stopped immediately and the patient must receive appropriate treatment. In these patients, Briumvi must be discontinued permanently (see section 4.3).

Severe IRRs
If the patient experiences a severe IRR, the infusion must be stopped immediately and the patient must receive symptomatic treatment. The infusion should only be resumed after resolution of all symptoms. When resuming the infusion, start at an infusion rate equal to half of that used when the IRR occurred. If tolerated, the infusion rate may be increased as indicated in Table 1.

Mild to moderate IRRs
If the patient experiences a mild to moderate IRR, the infusion rate must be reduced by half compared to that used when the event occurred. This reduced rate must be maintained for at least 30 minutes. If tolerated, the infusion rate may then be increased as indicated in Table 1.

After the infusion

• Patients treated with Briumvi must be monitored for at least one hour after completion of the first two infusions to identify any symptoms of IRRs.
• Physicians must warn patients that an IRR may occur within 24 hours after the infusion.

Shelf life
Unopened vial
3 years
Diluted solution for intravenous infusion

• Chemical and physical stability in use has been demonstrated for 24 hours at a temperature between 2 and 8 °C, and subsequently for 8 hours at room temperature.
• From a microbiological point of view, the prepared infusion must be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should not normally exceed 24 hours at a temperature between 2 and 8 °C, and subsequently 8 hours at room temperature, unless the dilution was carried out in controlled and validated aseptic conditions.
• If the intravenous infusion cannot be completed during the same day, the remaining solution must be discarded.

Annex IV
Scientific conclusions and justification for the variation of the terms of the marketing authorisation(s)
Scientific conclusions
Taking into account the assessment of the Pharmacovigilance and Risk Assessment Committee (PRAC) of the Periodic Safety Update Report(s) (PSUR) for ublituximab, the scientific conclusions of the PRAC are as follows:
Based on available data on encephalitis/meningitis/meningoencephalitis from clinical trials and spontaneous reports, including, in seven cases, a close temporal relationship, and based on a plausible mechanism of action, the PRAC considers that a causal relationship between ublituximab and encephalitis/meningitis/meningoencephalitis is at least a reasonable possibility and therefore concludes that the product information for medicines containing ublituximab should be updated accordingly.
Having examined the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the related overall conclusions and with the justification of the recommendation.

Justification for the variation of the terms of the marketing authorisation
Based on the scientific conclusions on ublituximab, the CHMP considers that the benefit-risk ratio of the medicinal product(s) containing ublituximab is unchanged, subject to the proposed changes to the product information.
The CHMP recommends the variation of the terms of the marketing authorisation(s).