BENLYSTA 120 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Benlysta 120mg powder for concentrate for solution for infusion

Benlysta 400mg powder for concentrate for solution for infusion

belimumab

This medicine is subject to additional monitoring, which will help to quickly identify new safety information. You can contribute by reporting any side effects you may have. The last section of this leaflet includes information on how to report side effects.

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Benlysta and what is it used for

Benlysta as an infusion is a medicine used to treat lupus (systemic lupus erythematosus, SLE) in adults and children (from 5 years of age) whose disease remains very active despite standard treatment. Benlysta is also used in combination with other medicines to treat adults (from 18 years of age) with active lupus nephritis (kidney inflammation associated with lupus).

Lupus is a disease in which the immune system (the system that fights infections) attacks its own cells and tissues, causing inflammation and organ damage. It can affect any organ in the body and is thought to involve a type of white blood cells called B cells.

Benlysta contains belimumab(a monoclonal antibody). It reduces the number of B cells in your blood by blocking the action of BLyS, a protein that helps to prolong the survival of B cells and is found at high levels in people with lupus.

You will be given Benlysta along with your usual treatment for lupus.

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

Do not give Benlysta

• if you are allergicto belimumab or any of the other ingredients of this medicine (listed in section 6).

• Tell your doctorif you think this may apply to you

Warnings and precautions

Talk to your doctor before you are given Benlysta:

• if you have a current or chronic infectionor if you get infections often (see section 4). Your doctor will decide if you can be given Benlysta
• if you are planning to be vaccinatedor have been vaccinated in the last 30 days. Some vaccines should not be given just before or during treatment with Benlysta
• if lupus affects your nervous system
• if you have HIVor low levels of immunoglobulins
• if you have or have had hepatitis Bor C
• if you have had an organ transplantor a bone marrow transplantor stem cell transplant
• if you have had cancer
• if you have ever developed a severe skin rashor skin peeling, blisteringand/or mouth ulcersafter using Benlysta.

• Tell your doctorif you think any of these circumstances apply to you.

Depression and suicide

There have been reports of depression, suicidal thoughts and attempts, including suicide during treatment with Benlysta. Tell your doctor if you have a history of these conditions. If you experience new symptoms or worsening of them at any time:

• Contact your doctor or go immediately to the hospital.

If you feel depressed or have thoughts of self-harm or suicide, it may be helpful to tell a close family member or friend and ask them to read this leaflet. You might ask them to tell you if they notice any changes in your mood or behavior.

Severe skin reactions

There have been reports of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with Benlysta treatment.

• Stop using Benlysta and seek medical attention immediatelyif you notice any of the symptoms described in section 4.

Be aware of important symptoms

People taking medicines that affect their immune system may be more prone to developing infections, including a rare but serious brain infection called progressive multifocal leukoencephalopathy(PML).

• Read the information “Increased risk of brain infection” in section 4 of this leaflet.

• To improve the traceability of this medicine, you and your healthcare professional should record the batch number of Benlysta. It is recommended that you note this information in case it is needed in the future.

Children and adolescents

This medicine is not indicated for use in:

• children under 5 years (with SLE)
• children and adolescents (under 18 years) with active lupus nephritis

Other medicines and Benlysta

Tell your doctorif you are taking other medicines, if you have recently taken or might take any other medicine.

In particular, tell your doctor if you are being treated with medicines that affect your immune system, including any medicine that affects your B cells(to treat cancer or inflammatory diseases).

Using these medicines in combination with Benlysta may make your immune system less effective. This could increase the risk of you getting a serious infection.

Pregnancy and breastfeeding

Contraception for women who may become pregnant

• Use a reliable method of contraceptionwhile you are being treated with Benlysta and for at least 4 months after the last dose.

Pregnancy

Benlysta is not normally recommended during pregnancy.

• Tell your doctorif you are pregnant, think you may be pregnant or plan to become pregnant. Your doctor will decide if you can be given Benlysta.
• If you become pregnantwhile being treated with Benlysta, tell your doctor.

Breastfeeding

Tell your doctorif you are breastfeeding. Benlysta may pass into breast milk. Your doctor will advise whether you should stop treatment with Benlysta while you are breastfeeding or stop breastfeeding.

Driving and using machines

Benlysta may have effects that can make you less able to drive or use machines.

Benlysta contains polysorbate80

Benlysta 120mg powder for concentrate for solution for infusion:This medicine contains 0.6 mg of polysorbate 80 in each vial.

Benlysta 400mg powder for concentrate for solution for infusion:This medicine contains 2.0 mg of polysorbate 80 in each vial.

Polysorbates can cause allergic reactions. Tell your doctor if you or your child have any known allergies

Benlysta contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; this is, essentially “sodium-free”. However, before Benlysta is given to you or your child, it is mixed with a solution that contains sodium. Talk to your doctor if you or your child are on a low-salt diet.

3. How Benlysta is given

A nurse or doctor will give you Benlysta through a drip in your vein (intravenous infusion) over one hour.

Adults and children (from 5 years of age)

Your doctor will decide the correct dose based on your body weight. The recommended dose is 10 mg per kilogram (kg) of body weight.

Benlysta is given on the first day of treatment and again on days 14 and 28. After this, Benlysta is given once every 4 weeks.

Medicines given before an infusion

Before Benlysta is given, your doctor may give you other medicines that help to reduce any reaction related to the infusion. These may include a type of medicine called antihistamines and other medicines to prevent you from getting a high temperature. You will be closely monitored and if you have any reaction, it will be treated.

Stopping treatment with Benlysta

Your doctor will decide if it is necessary to stop Benlysta treatment.

4. Possible side effects

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

Stop using Benlysta and seek medical attention immediatelyif you notice any of the following symptoms of a severe skin reaction:

• red patches on the trunk, often with blisters in the centre, skin peeling, mouth ulcers, genital and eye ulcers. These severe skin reactions can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome and toxic epidermal necrolysis). These side effects have been reported with an unknown frequency (cannot be estimated from the available data).

Allergic reactions - get medical help immediately

Benlysta may cause an infusion-related reaction or an allergic reaction (hypersensitivity). These are common side effects (may affect up to 1 in 10 people). They can be occasionally serious (uncommon, affecting up to 1 in 100 people), and life-threatening. It is more likely that these serious side effects will occur during the first or second day of treatment with Benlysta, but they may be delayed and occur several days later.

If you experience any of the following symptoms of an allergic reaction or infusion-related reaction contact your doctor or nurse immediatelyor go to the Accident and Emergency department of your nearest hospital:

• swelling of the face, lips, mouth or tongue
• wheezing, difficulty breathing or breathlessness
• skin rash
• itchy rash or hives.

In rare cases, less severe late reactions to Benlysta can also occur, usually 5 to 10 days after the infusion.

These include symptoms such as skin rash, feeling unwell, tiredness, muscle pain, headache or swelling of the face.

If you experience these symptoms,especially if you notice two or more at the same time:

• Tell your doctor or nurse.

Infections

Benlysta may make you more likely to get infections, including urinary tract and respiratory infections, younger children may be at higher risk. These infections are very common and may affect more than 1 in 10 people. Some infections can be serious and, in rare cases, can be life-threatening.

If you have any of the following symptoms of an infection:

• Fever and/or chills
• Cough, breathing problems
• Diarrhoea, vomiting
• Pain when urinating, frequent urination
• Hot, red or painful skin or skin lesions on your body.

• Tell your doctor or nurse immediately.

Depression and suicide

There have been reports of depression, suicidal thoughts and attempts during treatment with Benlysta. Depression may affect up to 1 in 10 people, suicidal thoughts or attempts may affect up to 1 in 100 people. If you feel depressed, have thoughts of self-harm or other concerning thoughts or are depressed and notice that you are getting worse or developing new symptoms:

• Contact your doctor or go immediately to the hospital.

Increased risk of brain infection

Medicines that weaken your immune system, such as Benlysta, may increase the risk of getting a rare but serious and potentially life-threatening brain infection called progressive multifocal leukoencephalopathy(PML).

Symptomsof PML include:

• memory loss
• problems thinking
• difficulty speaking or walking
• loss of vision.

• Tell your doctor immediatelyif you have any of these symptoms or similar problems that have lasted for several days.

If you already had these symptoms before starting treatment with Benlysta:

• Tell your doctor immediatelyif you notice any change in these symptoms.

Other possible side effects:

Very common side effects

May affect more than 1 in 10people:

• bacterial infections (see “Infections” above).

Common side effects

May affect up to 1 in 10people:

• high temperature or fever
• itchy rash, hives, skin rash
• low levels of white blood cells (can be seen in blood tests)
• infection of the nose, throat or stomach
• pain in hands or feet
• migraine
• feeling unwell, diarrhoea.

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are 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.

5. Storage of Benlysta

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 and on the label after EXP. The expiry date refers to the last day of the month shown.

Store in a refrigerator (2 ?C to 8 ?C).

Do not freeze.

Store in the original package to protect from light.

Disposal of unused medicine and all materials that have come into contact with it should be done in accordance with local regulations.

6. Container Contents and Additional Information

Composition of Benlysta

• The active substance is belimumab.

Each 5 ml vial contains 120 mg of belimumab.

Each 20 ml vial contains 400 mg of belimumab.

After reconstitution, the solution contains 80 mg of belimumab per ml.

• The other ingredients are citric acid monohydrate (E 330), sodium citrate (E 331), sucrose, and polysorbate 80 (E 433). See section 2 for more information on polysorbate 80 and sodium content.

Appearance of Benlysta and Container Contents

Benlysta is presented as a white to off-white powder for solution for infusion, in a glass vial sealed with a silicone rubber stopper and an aluminum seal.

It contains 1 vial in each carton.

Marketing Authorization Holder

GlaxoSmithKline (Ireland) Limited

12 Riverwalk

Citywest Business Campus

Dublin 24

Ireland

Manufacturer

GlaxoSmithKline Manufacturing S.P.A.

Strada Provinciale Asolana No. 90I-43056 San Polo di Torrile

Parma

Italy

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

Date of Last Revision of this Leaflet:

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu/ and on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

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This information is intended only for healthcare professionals:

Instructions for Use and Handling – Reconstitution, Dilution, and Administration

In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded.

1. How to Reconstitute Benlysta

Reconstitution and dilution should be performed under aseptic conditions.

Allow the vial to stand between 10 and 15 minutes until it reaches room temperature (between 15°C and 25°C).

For reconstitution and dilution, it is recommended to use a 21-25 gauge needle when piercing the vial stopper.

CAUTION: The 5 ml and 20 ml vials are reconstituted with different volumes of solvent, see below:

120 mg Vial

The 120 mg Benlysta single-dose vial is reconstituted with 1.5 ml of water for injection to obtain a final concentration of 80 mg/ml of belimumab.

400 mg Vial

The 400 mg Benlysta single-dose vial is reconstituted with 4.8 ml of water for injection to obtain a final concentration of 80 mg/ml of belimumab.

The flow of water for injection should be directed towards the vial wall to minimize foam formation. Gently swirl the vial for 60 seconds. Allow the vial to reach room temperature (between 15°C and 25°C) during reconstitution, gently swirl the vial for 60 seconds every 5 minutes until the powder is dissolved. Do not shake. Normally, reconstitution is complete within 10-15 minutes after adding water, but it may take up to 30 minutes. Protect the reconstituted solution from direct sunlight.

If a mechanical reconstitution device is used for Benlysta, the speed should not exceed 500 rpm and the vial should not be swirled for more than 30 minutes.

1. Before Diluting Benlysta

Once reconstitution is complete, the solution should be opalescent and colorless to pale yellow, and free of particles. However, small air bubbles are acceptable and expected.

120 mg Vial

After reconstitution, a volume of 1.5 ml (corresponding to 120 mg of belimumab) can be withdrawn from each 5 ml vial.

400 mg Vial

After reconstitution, a volume of 5 ml (corresponding to 400 mg of belimumab) can be withdrawn from each 20 ml vial.

1. How to Dilute the Solution for Infusion

The reconstituted medicinal product is diluted to 250 ml with sodium chloride 9 mg/ml (0.9%), sodium chloride 4.5 mg/ml (0.45%), or Ringer lactate solution for infusion. For patients whose body weight is less than or equal to 40 kg, 100 ml infusion bags of these diluents can be used, provided that the resulting concentration of belimumab in the infusion bag does not exceed 4 mg/ml.

Solutions for infusion of glucose 5% are incompatible with Benlysta and should not be used.

From a 250 ml (or 100 ml) infusion bag or bottle of sodium chloride 9 mg/ml (0.9%), sodium chloride 4.5 mg/ml (0.45%), or Ringer lactate solution for infusion, withdraw and discard a volume equivalent to the volume of the reconstituted Benlysta solution required for the patient's dose. Then, add the required volume of the reconstituted Benlysta solution to the infusion bag or bottle. Gently invert the bag or bottle to mix the solution. Any unused solution in the vials should be discarded.

Visually inspect the Benlysta solution before administration for any particulate matter or discoloration. Discard the solution if any particulate matter or discoloration is observed.

The reconstituted solution, if not used immediately, should be protected from direct sunlight and stored in a refrigerator between 2°C and 8°C. The diluted solutions in sodium chloride 9 mg/ml (0.9%), sodium chloride 4.5 mg/ml (0.45%), or Ringer lactate solution for infusion should be stored between 2°C and 8°C or at room temperature (between 15°C and 25°C).

The total time from reconstitution of Benlysta to completion of infusion should not exceed 8 hours.

1. How to Administer the Diluted Solution

Benlysta is administered by infusion over a period of 1 hour.

Benlysta should not be administered by infusion simultaneously in the same intravenous line with other agents.

No incompatibilities have been observed between Benlysta and polyvinylchloride or polyolefin infusion bags.

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