Product Information for the User

Benlysta 200 mg Pre-filled Syringe

belimumab

This product 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 entire product information carefully before starting to use this product,because it contains important information for you.

• Keep this product information, as you may need to refer to it again.
• If you have any questions, consult your doctor.
• This product has been prescribed to you alone, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• Ifyouexperienceadverse effects,consult your doctor, even if they are not listed in this product information. See section 4.

Step-by-Step Instructions for the Pre-filled Syringe

Benlysta as a subcutaneous injection is a medication used for the treatment of lupus (systemic lupus erythematosus, SLE) in adults (18 years and older) whose disease remains very active despite standard treatment. Benlysta is also used in combination with other medications to treat adults 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 cell calledcells B.

Benlysta containsbelimumab(a monoclonal antibody). It reduces the number of cellsB in your blood by blocking the action of BLyS, a protein that helps prolong the survival of cellsB and is found at elevated levels in people with lupus.

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

No use Benlysta

• if you areallergicto belimumab or any of the other components of this medication (listed in section6).

• Inform your doctorif you think this may happen to you.

Warnings and precautions

Consult your doctor before starting to use Benlysta:

• if you have aninfectioncurrently or chronically or if you frequently contract infections. Your doctor will decide if you can be administered Benlysta
• if you are planning toget vaccinatedor have been vaccinatedin the last 30days. Some vaccines should not be administered just before or during treatment with Benlysta
• if lupus affects yournervous system
• if you haveHIVor low levels ofimmunoglobulins
• if you have, or have had,hepatitis BorC
• if you have undergone anorgan transplantor abone marrow transplantor astem cell transplant
• if you have suffered fromcancer
• if you have ever developed asevere skin rashorskin peelingand/orblisteringand/ormouth ulcersafter using Benlysta.

• Inform your doctorif you think you are affected by any of these circumstances.

Depression and suicide

There have been reports of depression, suicidal ideation, and suicide attempts, including suicides during treatment with Benlysta. Inform your doctor if you have a history of these conditions. If you experience new symptoms or worsening of the same in any moment:

• Contact your doctor or go to the hospital immediately.

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

Severe skin reactions

Cases of Stevens-Johnson syndrome and toxic epidermal necrolysis related to treatment with Benlysta have been reported.

• Stop using Benlysta and seek medical attention immediately if you observe any of the symptoms described in section4.

Be aware of important symptoms

People taking medications that affect their immune system may be more exposed to the development of infections, including a rare but serious condition called progressive multifocal leukoencephalopathy (PML).

• Read the information “Increased risk of cerebral infection” in section4 of this leaflet.

To improve the traceability of this medication, you and your pharmacist should register the batch number of Benlysta. It is recommended that you note this information in case it is required in the future.

Children and adolescents

Do not administer Benlysta as a subcutaneous injection to children or adolescents under 18years of age.

Other medications and Benlysta

Inform your doctorif you are taking other medications, if you have taken them recently or if you may need to take any other medication.

Particularly, inform your doctor if you are being treated with medications that affect your immune system, including any medication that affects yourB cells (to treat cancer or inflammatory diseases).

The use of these medications in combination with Benlysta may make your immune system less effective. This could increase the risk of suffering a serious infection.

Pregnancy and breastfeeding

Contraception in fertile women

• Fertile womenshould use a reliable contraceptive methodwhile being treated with Benlysta and for at least 4months after the last dose.

Pregnancy

Benlysta is generally not recommended during pregnancy.

• Inform your doctor if you are pregnant,think you may be pregnant or intend to become pregnant.Your doctor will decide if you can use Benlysta.
• If you become pregnantwhile being treated with Benlysta, inform your doctor.

Breastfeeding

Inform your doctor if you are breastfeeding.Benlysta is likely to pass into breast milk. Your doctor will advise you if you should interrupt treatment with Benlysta while breastfeeding or if you should interrupt breastfeeding.

Driving and operating machines

Benlysta may have side effects that may make you less capable of driving or operating machines.

Important information about some excipients of Benlysta

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

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Benlysta must be injected under the skin on the same day of each week.

How to use

Adults (18 years and older)

Systémic lupus erythematosus (SLE)

The recommended dose is200 mg (complete content of one pen) once a week.

Lupus nephritis

The recommended dose may vary. Your doctor will indicate the suitable dose for you, which may be:

• 200 mg (complete content of one pen) once a week

or

• 400 mg (complete content of two pens in one day) once a week for 4 weeks. Subsequently, the recommended dose is 200 mg (complete content of one pen) once a week.

Changing your dosing day

Administer a dose on the new day (even if less than a week has passed since your last dose). Continue with the new weekly schedule from that day.

Benlysta injection

Your doctor or nurse will show you or your caregiver how to inject Benlysta. The first injection with the pre-filled pen of Benlysta will be supervised by your doctor or nurse at the medical center. After being trained on how to use the pen, your doctor or nurse will indicate when you or your caregiver can start administering the medication without supervision. Your doctor or nurse will also indicate to which signs and symptoms you should be attentive when using Benlysta, as severe allergic reactions may occur (see"Allergic reactions"in section 4).

Benlysta is injected under the skin in the abdominal area or the upper thigh area.

The subcutaneous injection of Benlysta should not be injected into a vein (byintravenous route).

Instructions for the use of the pre-filled pen are given at the end of this leaflet.

Using more Benlysta than you should

If this happens, contact your doctor or nurse immediately, who will monitor you for any signs or symptoms of adverse effects and treat these symptoms if necessary. If possible, show them the packaging or this leaflet.

Missing a dose of Benlysta

Inject the missed dose as soon as you remember and then continue with your regular weekly schedule as usual or start a new weekly schedule from the day you injected the missed dose.

If you do not realize you have missed a dose until the time of the next dose, simply inject your next dose as planned.

Stopping treatment with Benlysta

Your doctor will decide if you need to stop using Benlysta.

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

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

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

Allergic reactions - seek medical attention immediately

Benlysta may cause an injection-related reaction or an allergic reaction (hypersensitivity). These are common side effects (may affect up to 1 in 10people). They may be occasionally severe (rare, affecting up to 1 in 100people) and put the patient's life at risk. It is more likely that these severe adverse reactions 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 injection-related reaction, consult your doctor or nurse immediatelyorvisit the emergency department of your nearest hospital:

• swelling of the face, lips, mouth, or tongue
• asthma, difficulty breathing, or difficult breathing
• skin rash
• pruritic papules or hives.

In rare cases, Benlysta may also cause late-onset, less severe reactions, usually 5 to 10days after injection. These include symptoms such as skin rash, feeling unwell, fatigue, muscle pain, headache, or facial swelling.

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

• Inform your doctor or nurse.

Infections

Benlysta may increase your risk of contracting infections, including urinary tract and respiratory tract infections. These infections are very common and may affect more than 1 in 10people. Some infections may be severe and, in rare cases, may cause death.

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

• fever and/or chills
• cough, respiratory problems
• diarrhea, vomiting
• urinary frequency or burning sensation while urinating
• hot, red, or painful skin or skin lesions on your body.

• Inform your doctor or nurse immediately.

Depression and suicide

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

• Contact your doctor or go to the hospital immediately.

Increased risk of cerebral infection

Medicines that weaken your immune system, such as Benlysta, may increase the risk of contracting a rare but severe and potentially fatal brain infection calledprogressive multifocal leukoencephalopathy(PML).

The symptomsof PML include:

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

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

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

• Inform your doctor immediatelyif you experience any change in these symptoms.

Other possible side effects:

Very common side effects

May affect more than 1 in 10people:

• urinary tract infections (see “infections” section above).

Common side effects

May affect up to 1 in 10people:

• high temperature or fever
• reactions at the injection site, for example: skin rash, redness, itching, or swelling of the skin where Benlysta has been injected
• pruritic papules, hives, or skin rash
• low white blood cell count (may be seen in blood tests)
• nasal, throat, or stomach infection
• hand or foot pain
• migraine
• feeling unwell, diarrhea.

Reporting side effects

If you experience any type of side effect, consult your doctor or nurse, evenif it is apossibleside effect that does not appear in this leaflet. You can also report them directly through thenational reporting system included in theAppendixV. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging and on the label after CAD. The expiration date is the last day of the month indicated.

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

Do not freeze.

Store in the original packaging to protect it from light.

A single preloaded pen can be stored at room temperature (up to 25ºC) for a maximum period of 12 hours, as long as it is protected from light. Once removed from the refrigerator, the penmust be used within the following 12 hours or discarded.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and the medication that you no longer need.This will help protect the environment.

Composition of Benlysta

The active ingredient is belimumab.

Each ml of the pre-filled pen contains 200 mg of belimumab.

The other components are arginine hydrochloride, histidine, histidine hydrochloride monohydrate, polisorbate 80, sodium chloride, and water for injection. See “Important information about some excipients of Benlysta” in section 2 for more information.

Appearance of the product and contents of the pack

Benlysta is supplied as a colourless to slightly yellow solution in a single-use pre-filled pen of 1 ml.

Available in packs of 1 or 4 pre-filled pens per pack and multi-packs that include 12 pre-filled pens (3 packs of 4 pre-filled pens).

Only some pack sizes may be marketed.

Marketing authorisation holder

GlaxoSmithKline (Ireland) Limited

12 Riverwalk

Citywest Business Campus

Dublin 24

Ireland

Manufacturer

GlaxoSmithKline Manufacturing S.P.A

Strada Provinciale Asolana, 90

43056 San Polo di Torrile

Parma

Italy

You can obtain more information about this medicinal product by contacting the local representative of the marketing authorisation holder:

Last update of the summary of product characteristics:

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu/, and on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

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Step-by-step instructions for use of the pre-filled pen

Weekly

Follow these instructions on how to use the pre-filled pen correctly. Not following these instructions may affect the proper functioning of the pre-filled pen. You should also receive training on how to use the pre-filled pen.

Benlysta isonlyfor administeringunder the skin(subcutaneously).

To improve the traceability of this medicinal product, you and your pharmacist should record the batch number of Benlysta. It is recommended that you note this information in case you need it in the future.

Storage

• Keep refrigerated until 30 minutes before use.

• Store in the original packaging to protect it from light.

• Keep out of the sight and reach of children.

• Do notfreeze.

• Do notuse if it has been left at room temperature for more than 12 hours.

Precautions

• The pre-filled pen should be used only once and then discarded.

• Do notshare your Benlysta pre-filled pen with another person.

• Do notshake.

• Do notuse if it has fallen onto a hard surface.

• Do notremove the cap from the pen until just before injection.

Parts of the Benlysta pre-filled pen

Materials needed for injection

1.Assemble and inspect the pre-filled pen

Allow it to reach room temperature

• Sit the pre-filled pen in the refrigerator for 30 minutes (Figure 1).

• Do notheat the pre-filled pen in any way, for example, in a microwave, hot water, or direct sunlight.

• Do notremove the cap from the pen during this step.

Inspect the Benlysta solution

• Magnify the inspection window to check that the Benlysta solution is colourless to slightly yellow (Figure 2).

It is normal to see one or more air bubbles in the solution.

• Do notuse the pre-filled pen if the solution appears cloudy, discoloured, or has particles.

2.Choose and clean the injection site

Choose the injection site

• Choose a site for the injection (abdomen or thigh) as shown inFigure 3.

• If you need 2 injections to complete your dose, leave at least 5 cm (2 inches) between each injection if you use the same site.
• Do notinject always in the same site. This is to avoid the skin becoming hardened.
• Do notinject in areas where the skin is sensitive, bruised, red, or hard.
• Do notinject within 5 cm of the navel.

Clean the injection site

• Wash your hands.

• Cleanthe site where the injection is going to be given with an alcohol wipe (Figure 4). Allow the skin to dry.

• Do nottouch this area again before administering the injection.

3.Prepare for injection

Remove the cap

• Do notremove the cap until immediately before the injection.

• Remove the cap by pulling it or turning it. The cap can be turned clockwise or anti-clockwise (Figure 5).

• Do notput the cap back on the pen.

Place the pen

• Hold the pen comfortably so that you can see the inspection window. This is important so that you can confirm that a full dose has been administered (Figure 6).

• If necessary, smooth the injection site by pulling or stretching the skin.
• Place the pen directly onto the injection site (at a 90° angle). Make sure the yellow safety guard is stuck to the skin.

4.Inject Benlysta

Start the injection

• Press the pen firmly downwards onto the injection site and keep it pressed (Figure 7).

This will insert the needle and start the injection.

You mayhear a first “click” at the start of the injection. You will see the purple indicator start to move across the inspection window (Figure 8).

Complete the injection

Continue holding the pen downwards until the purple indicator has stopped moving. You may hear a second “click” a few seconds before the purple indicator stops moving (Figure 9).

The injection may take up to 15 seconds to complete.

• When the injection is complete, lift the pen off the injection site.

5.Dispose of and inspect

Dispose of the used pen

• Do notput the cap back on the pen.

• Dispose of the used pen and cap in a puncture-proof container.

• Ask your doctor or pharmacist for information on how to dispose of a used pen or a container of used pens properly.

• Do notrecycle or throw the pen or container of used pens in household waste.

Inspect the injection site

You may see a small amount of blood at the injection site.

• Press gently with a cotton ball or gauze on the injection site.
• Do notrub the injection site.