Summary of Product Characteristics: Information for the Patient

Briumvi 150 mg Concentrate for Solution for Infusion

ublituximab

This medicine is subject to additional monitoring, which will expedite the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this summary of product characteristics carefully before starting to take this medicine, as it contains important information for you.

• Keep this summary of product characteristics, as you may need to refer to it again.
• If you have any questions, consult your doctor.
• If you experience any adverse effects, consult your doctor or nurse, even if they are not listed in this summary of product characteristics. See section 4.

What is Briumvi

Briumvi contains the active ingredient ublituximab. It is a type of protein known as a monoclonal antibody. Antibodies act by binding to specific targets in the body.

What is Briumvi used for

Briumvi is used to treat adults with recurrent forms of multiple sclerosis (EMR), in which the patient has relapses (recurrences) followed by periods with milder or no symptoms.

What is multiple sclerosis

Multiple sclerosis (MS) affects the central nervous system, particularly the nerves of the brain and spinal cord. In MS, some white blood cells called B lymphocytes, which are part of the immune system (the body's defense system), act incorrectly and attack a protective layer (called the myelin sheath) that surrounds nerve cells, causing inflammation and damage. The degradation of the myelin sheath prevents nerves from functioning correctly and causes MS symptoms. MS symptoms depend on the part of the central nervous system affected and may include walking and balance problems, muscle weakness, numbness, double vision and blurred vision, coordination problems, and bladder problems.

In recurrent forms of MS, the patient has repeated episodes of symptoms (recurrences) that may appear suddenly over a few hours or gradually over several days. Symptoms disappear or improve between recurrences, but damage can accumulate and lead to permanent disability.

How does Briumvi work

Briumvi works by binding to a target called CD20 on the surface of B lymphocytes. B lymphocytes are a type of white blood cell that is part of the immune system. In multiple sclerosis, the immune system attacks the protective layer that surrounds nerve cells. In this process, B lymphocytes are involved. Briumvi acts on B lymphocytes and eliminates them, thereby reducing the likelihood of recurrence, alleviating symptoms, and slowing disease progression.

You should not receive Briumvi:

• if you areallergicto ublituximab or any of the other components of this medication (listed in section 6);
• if you have a severe infection;
• if you have been told that you have severe immune system problems; or
• if you have cancer.

If you are unsure, consult your doctor before starting Briumvi treatment.

Warnings and precautions

Inform your doctor before starting Briumvi treatmentif you meet any of the following criteria. Your doctor may decide to postpone your Briumvi treatment or that you cannot receive Briumvi if:

• you have aninfection. Your doctor will wait for the infection to resolve before administering Briumvi.
• you have ever hadhepatitis Bor are a carrier of the hepatitis B virus. This is because medications like Briumvi can reactivate the hepatitis B virus. Before starting Briumvi treatment, your doctor will check if you are at risk of hepatitis B infection. Patients who have had hepatitis B or are carriers of the hepatitis B virus will undergo blood tests and be under close medical supervision for signs of hepatitis B infection.
• you have recently received any vaccine or may receive a vaccine in the near future.
• you havecanceror have had cancer in the past. Your doctor may decide to postpone treatment.

Infusion-related reactions

• The most common adverse effect of Briumvi treatment is infusion-related reactions, a type of allergic reaction that occurs during or shortly after the administration of a medication. They can be severe.
• The symptoms of an infusion-related reaction may include, among others:

• itching on the skin
• hives
• redness of the face or skin
• throat irritation
• breathing difficulties
• swelling of the tongue or throat
• “wheezing” while breathing (sibilant sounds)
• chills
• fever
• headache
• dizziness
• sensation of fainting
• nausea
• abdominal pain (in the stomach)
• rapid heart rate

• Inform your doctor or nurse immediately if you have or think you may have an infusion-related reaction. Infusion-related reactions can occur during the infusion or up to 24 hours after it.
• To reduce the risk of infusion-related reactions, your doctor will administer other medications before each Briumvi infusion (see section 3) and you will be under close medical supervision during the infusion.
• If you experience an infusion reaction, your doctor may need to interrupt or slow down the infusion rate.

Infections

• Inform your doctor before receiving Briumvi if you have or think you may have an infection. Your doctor will wait for the infection to resolve before administering Briumvi.
• You may be more susceptible to infections with Briumvi. This is because the immune cells that Briumvi acts on also help fight infections.
• Inform your doctor or nurse immediately if you have an infection or any of the following signs of infection during or after Briumvi treatment:

• fever or chills
• persistent cough
• herpes (e.g., cold sores, shingles, or genital ulcers)

• Inform your doctor or nurse immediately if you think your MS is worsening or if you notice any new symptoms.This is because of a rare and potentially fatal brain infection called progressive multifocal leukoencephalopathy (PML), which can cause symptoms similar to MS. PML can occur in patients treated with medications like Briumvi and other MS treatments.
• Inform your partner or caregiverabout your Briumvi treatment. They may notice symptoms of PML that you do not notice, such as memory lapses, thinking problems, difficulty walking, vision loss, or changes in speech, which your doctor may need to investigate.

Vaccines

• Inform 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 any vaccine before starting Briumvi treatment. You should receive a type of vaccine called live or attenuated vaccines at least 4 weeks before starting Briumvi treatment. During Briumvi treatment, you should not receive live or attenuated vaccines until your doctor tells you that your immune system is no longer weakened.
• Whenever possible, you should receive another type of vaccine called inactivated vaccines at least 2 weeks before starting Briumvi treatment. If you want to receive inactivated vaccines during Briumvi treatment, consult your doctor.

Children and adolescents

Briumvi is not indicated for children and adolescents under 18 years old. This is because it has not yet been studied in this age group.

Other medications and Briumvi

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. In particular, inform your doctor:

• if you are taking, have taken recently, or may need to take medications that affect the immune system, such as chemotherapy, immunosuppressants (except corticosteroids), or other medications used to treat MS. This is because they can have a cumulative effect on the immune system.
• if you plan to receive any vaccine (see “Warnings and precautions” above).

If you meet any of these criteria (or are unsure), consult your doctor before starting Briumvi treatment.

Pregnancy and breastfeeding

• Inform your doctor before starting Briumvi treatment if you are pregnant, think you may be pregnant, or plan to become pregnant. This is because Briumvi can cross the placenta and affect the fetus.
• Do not use Briumvi if you are pregnant unless you have discussed it with your doctor. Your doctor will weigh the benefits of taking Briumvi for you against the risk to the fetus.
• If you have a child and have received Briumvi during pregnancy, it is essential to inform your child's doctor that you have received Briumvi, so the doctor can recommend when your child should be vaccinated.
• The passage of Briumvi into breast milk is unknown. Consult your doctor about the best way to feed your child if you receive Briumvi.

Female contraception

If you can become pregnant (conceive), you should use contraceptive methods:

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

Driving and operating machinery

It is unlikely that Briumvi will affect your ability to drive or operate machinery.

Briumvi contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per dose; it is essentially “sodium-free”.

A healthcare professional with experience in administering this treatment will give you Briumvi. They will closely monitor you while you are receiving this medication. This is in case you experience any side effects. You will always receive Briumvi through an IV (intravenous infusion).

Medications you will receive before receiving Briumvi

Before receiving Briumvi, you will be given other medications to prevent or reduce possible side effects such as infusion-related reactions (see sections 2 and 4 for information on infusion-related reactions).

You will receive a corticosteroid and an antihistamine before each infusion, and you may also receive other medications to reduce fever.

How much Briumvi you will receive and how often you will receive it

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

How Briumvi is administered

• A healthcare professional will give you Briumvi. Briumvi must be diluted before administration. A healthcare professional will perform the dilution. It will be administered as an IV infusion into a vein.
• You will be closely monitored during the administration of Briumvi and for at least 1 hour after the administration of the first two infusions. This is in case you experience any side effects such as an infusion-related reaction. The infusion may be slowed, temporarily interrupted, or permanently stopped if you experience a severe infusion-related reaction (see sections 2 and 4 for information on infusion-related reactions).

If you miss a Briumvi infusion

• If you miss a Briumvi infusion, consult your doctor to reschedule it as soon as possible. Do not wait for the next scheduled infusion.
• It is essential to receive each infusion at the scheduled time to get the full benefit of Briumvi.

If you stop treatment with Briumvi

• It is essential to continue treatment until you and your doctor decide it is no longer beneficial for you.
• Some side effects may be related to low levels of B lymphocytes. After stopping treatment with Briumvi, you may experience these side effects until your B lymphocyte levels return to normal.
• Before starting any new medications, inform your doctor when you last received a Briumvi infusion.

If you have any other questions about using this medication, ask your doctor.

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

The following side effects have been reported with Briumvi:

Severe side effects

Perfusion-related reactions

• Perfusion-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, they are mild reactions, but some severe reactions may occur.
• Inform your doctor or nurse immediately if you experience signs or symptoms of a perfusion-related reaction during infusion or within 24 hours after infusion.The symptoms may include, among others:

• itching on the skin
• hives
• redness of the face or skin
• throat irritation
• breathing difficulties
• swelling of the tongue or throat
• “wheezing” when breathing (sibilant sounds)
• chills
• fever
• headache
• dizziness
• sensation of fainting
• nausea
• abdominal pain (in the stomach)
• rapid heart rate

• If you experience a perfusion-related reaction, you will be given medications to treat it, and it may be necessary to slow down or stop the infusion. When the reaction has subsided, the infusion may be resumed. If the perfusion-related reaction is potentially fatal, your doctor will permanently discontinue treatment with Briumvi.

Infections

• You may be more susceptible to infections with Briumvi. Some of them may be severe. The following infections have been observed in patients treated with Briumvi in the EM:

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

• upper respiratory tract infections (nose and throat infections)
• respiratory tract infections

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

• lower respiratory tract infections (pulmonary infections such as bronchitis or pneumonia)
• herpetic infections (fever blisters [herpes labialis] or shingles)

• Inform your doctor or nurse immediately if you notice any of the following signs of infection:

• fever or chills
• persistent cough
• herpes (e.g., fever blisters [herpes labialis], shingles, or genital ulcers)

Your doctor will wait for the infection to resolve before administering Briumvi.

Other side effects

Common(may affect up to 1 in 10 people)

• neutropenia (low neutrophil count, a type of white blood cell)
• pain in an extremity (arms or legs)

Reporting side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect not listed in this prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

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

Healthcare professionals will store Briumvi in the hospital or clinic under the following conditions:

• This medication should not be used after the expiration date appearing on the box and on the vial label after “CAD”. The expiration date is the last day of the month indicated.
• This medication should be stored in refrigerator (between 2 °C and 8 °C). Do not freeze. The vial should be stored in the outer packaging to protect it from light.

It is recommended to use the product immediately after dilution. If not used immediately, the storage times during use and the conditions before use are the responsibility of the healthcare professional and normally should not exceed 24 hours between 2 °C and 8 °C and subsequently 8 hours at room temperature.

Medicines should not be disposed of through drains. This will help protect the environment.

Composition of Briumvi

• The active ingredient is ublituximab. Each vial contains 150 mg of ublituximab in 6 ml at a concentration of 25 mg/ml.
• The other components are sodium chloride, trisodium citrate dihydrate, polisorbate 80, hydrochloric acid, and water for injection.

Appearance of the product and contents of the pack

• Briumvi is a transparent to opalescent and colorless to yellowish solution.
• It is presented as a concentrate for solution for infusion.
• This medicinal product is available in packs containing 1 vial (glass vial with 6 ml of concentrate).

Marketing authorization holder

Neuraxpharm Pharmaceuticals, S.L.

Avda. Barcelona 69

08970 Sant Joan Despí - Barcelona

Spain

Responsible person

Millmount Healthcare

Block 7, City North Business Campus

Stamullen

Co. Meath

Ireland

K32 YD60

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

Other sources of information

Further information about this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

This information is intended for healthcare professionals only:

Read the summary of product characteristics or the package leaflet for more information.

Dosage

• First and second doses

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 should be maintained between each dose of Briumvi.

Figure 1: Dosage and calendar of Briumvi

Treatment of RRPs before infusion

• Treatment should be initiated and supervised by a healthcare professional with experience who has access to adequate medical support for treating severe reactions such as infusion-related reactions (RRPs).

• Premedication for RRPs

Two medications should be administered as premedication before each infusion of Briumvi to reduce the frequency and severity of RRPs:

• 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.

Additionally, premedication with an antipyretic (e.g., paracetamol) may also be considered.

Instructions for dilution

• Briumvi should be prepared by a healthcare professional using aseptic technique. Do not agitate the vial.
• The product is intended for single use.
• Do not use the solution if it has changed color or contains any solid particles.
• The medicinal product Briumvi should be diluted before administration. Briumvi solutions for intravenous administration are prepared by diluting the product in an infusion bag containing sodium chloride 0.9 % solution. For the first infusion, dilute one vial of the product in the infusion bag (150 mg/250 ml) to a final concentration of approximately 0.6 mg/ml. For subsequent infusions, dilute three vials of the product in the infusion bag (450 mg/250 ml) to a final concentration of approximately 1.8 mg/ml.
• Before starting the intravenous infusion, the contents of the infusion bag should be at room temperature.

Administration form

• After dilution, Briumvi is administered as an intravenous infusion through a dedicated line.
• Briumvi infusions should not be administered as a slow intravenous infusion or as a bolus.

Table 1: Dosage and calendar of Briumvi

1The duration of the infusion may be longer if the infusion is interrupted or slowed.

2The first subsequent dose should be administered 24 weeks after the first infusion.

Treatment of RRPs during and after infusion

Patients should be monitored during the infusion and for at least 1 hour after the completion of the first two infusions.

During infusion

• Adjustments to the infusion in case of RRP

In case of RRP during an infusion, the following adjustments should be taken into account.

Life-threatening RRP

If there are signs of a potentially life-threatening or incapacitating RRP during an infusion, the infusion should be stopped immediately and the patient should be given appropriate treatment. In these patients, treatment with Briumvi should be discontinued permanently (see section 4.3).

Severe RRP

If a patient experiences a severe RRP, the infusion should be stopped immediately and the patient should be given symptomatic treatment. The infusion should only be restarted once all symptoms have resolved. When restarting the infusion, start at half the infusion rate applied at the time of the RRP. If the infusion rate is tolerated, increase the infusion rate as described in Table 1.

Mild to moderate RRP

If a patient experiences a mild to moderate RRP, the infusion rate should be reduced to half the infusion rate applied at the time of the event. This reduced infusion rate should be maintained for at least 30 minutes. If the reduced infusion rate is tolerated, the infusion rate may be increased as described in Table 1.

After infusion

• Patients treated with Briumvi should be observed for at least 1 hour after the completion of the first two infusions for signs of RRP.
• Healthcare professionals should inform patients that RRP may occur within 24 hours after infusion.

Shelf life

Unopened vial

3 years

Diluted solution for intravenous infusion

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