Label: 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 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 label carefully before starting to use this medicine,because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• Ifyouexperienceadverse effects,consult your doctor, even if they are not listed in this label. See section 4.

Benlysta as an infusion is a medication used for the treatment of lupus (systemic lupus erythematosus, SLE) in adults and children (5 years and older) whose disease remains very active despite standard treatment. Benlysta is also used in combination with other medications to treat adults (18 years of age and older) 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 calledB cells.

Benlysta containsbelimumab(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 elevated levels in people with lupus.

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

Do not administer 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 Benlysta is administered to you:

• if you have aninfectioncurrently or chronically, or if you frequently contract infections (see section4). Your doctor will decide if Benlysta can be administered to you.
• if you are planning toget vaccinatedor have been vaccinated in the last 30days. Some vaccines should not be administered 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 transplantorstem cell transplant
• if you have hadcancer
• if you have ever developed asevere skin rashorskin peeling,blistering, and/ormouth ulcersafter using Benlysta.

• Inform your doctorif you think you may be 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 existing ones at any time:

• 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 if your mood or behavior changes.

Severe skin reactions

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

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

Be aware of important symptoms

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

• Read the information “Increased risk of brain infection” in section4 of this leaflet.
• For improved tracking of this medication, you and your pharmacist should record the batch number of Benlysta. It is recommended that you note this information in case it is required in the future.
• Children and adolescents

This medication is not indicated for use in:

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

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 your B 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 developing a serious infection.

Pregnancy and breastfeeding

Contraception in potentially 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 plan to become pregnant.Your doctor will decide if Benlysta can be administered to you.
• If you become pregnantwhile being treated with Benlysta, inform your doctor.

Breastfeeding

Inform your doctor if you are breastfeeding.It is likely that Benlysta may pass into breast milk. Your doctor will advise you whether to stop treatment with Benlysta while breastfeeding or to stop breastfeeding.

Driving and operating machinery

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

Important information about some excipients of Benlysta

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

A nurse or doctor will administer Benlysta through an intravenous infusion in your vein for one hour.

Adults and children (5 years and older)

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

Medications administered before an infusion

Before Benlysta administration, your doctor may administer other medications to help reduce any reactions related to the infusion. These may include a type of medication called antihistamines and other medications to prevent your temperature from increasing. You will be closely monitored, and if you experience any reaction, it will be treated.

Discontinuation of Benlysta treatment

Your doctor will decide if it is necessary to discontinue Benlysta administration.

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 a reaction related toinfusionor 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 reactionswill occurduring the first or second day of treatment with Benlysta, but may be delayed and occur several days later.

If you experience any of the following symptoms of an allergic reaction or infusion-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
• hives with itching or swelling (urticaria).

In rare cases, Benlysta may also cause late-onset, less severe reactions, usually 5 to 10days afterinfusion.

This includes 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, with younger children at a higher risk. 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, painful urination
• 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 yourimmune 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 affectmore than 1 in 10people:

• bacterial infections (see “infections” section above).

Common side effects

May affectup to 1 in 10people:

• fever or high temperature
• hives with itching, swelling (urticaria), 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.

The disposal of unused medication and all materials that have been in contact with it, will be carried out in accordance with local regulations.

Composition of Benlysta

• The active ingredient is belimumab.

Each vial of 5 ml contains 120 mg of belimumab.

Each vial of 20 ml contains 400 mg of belimumab.

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

• The other components are citric acid monohydrate (E330), sodium citrate (E331), sucrose, and polisorbate 80.See “Important information about some excipients of Benlysta” in section 2 for more information.

Appearance of Benlysta and contents of the pack

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 closure foil.

It contains 1 vial in each pack.

Marketing Authorization Holder

GlaxoSmithKline (Ireland) Limited

12 Riverwalk

Citywest Business Campus

Dublin 24

Ireland

Responsible for manufacturing

GlaxoSmithKline Manufacturing S.P.A.

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

Parma

Italy

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Last update of this leaflet:

The detailed information on this medicine 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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This information is intended solely for healthcare professionals:

Instructions for use and handling – reconstitution, dilution, and administration

To improve the traceability of biological medicines, it should be clearly recorded the commercial name and batch number of the medicine administered.

1)How to reconstitute Benlysta

The reconstitution and dilution should be performed under aseptic conditions.

Leave the vial between 10 and 15 minutes until it reaches room temperature (between 15?C and 25?C).

To reconstitute and dilute, it is recommended to use a 21-25 gauge needle to pierce the stopper of the vial.

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

Vial of 120mg

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

Vial of 400mg

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

The water for injection should be directed towards the wall of the vial to minimize foam formation. Gently remove the vial for 60seconds. Allow the vial to reach room temperature (between 15?C and 25?C) during reconstitution, gently remove the vial for 60seconds every 5minutes until the powder is dissolved.Do not shake.Normally, the reconstitution is completed 10-15 minutes after adding the water, but it may take up to30minutes. Protect the reconstituted solution from sunlight.

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

2)Before diluting Benlysta

Once the reconstitution is complete, the solution should be opalescent and colorless to pale yellow, and without particles. However, small air bubbles are acceptable and expected to appear.

Vial of 120 mg

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

Vial of 400mg

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

3)How to dilute the infusion solution

The reconstituted medicine is diluted to 250ml with sodium chloride9mg/ml (0.9%), sodium chloride 4.5mg/ml (0.45%), or Ringer lactateinjection solution. For patients with a body weight of 40 kg or less, 100 ml bags of these diluents may be used, provided that the resulting concentration of belimumab in the infusion bag does not exceed 4 mg/ml.

The intravenous solutions of 5% glucose are incompatible with Benlysta and should not be used.

From a 250ml bag or infusion bottle of sodium chloride9mg/ml (0.9%), sodium chloride 4.5mg/ml (0.45%), or Ringer lactateinjection solution, withdraw and discard a volume equivalent to the volume of the reconstituted Benlysta solution needed for the patient's dose.Then, add the necessary volume of the reconstituted Benlysta solution to the bag or infusion bottle. Gently invert the bag or bottle to mix the solution. Any unused solution in the vials should be discarded.

Visually check the Benlysta solution before administration to detect any foreign particles or discoloration. Discard the solution if any foreign particles or discoloration are observed.

The reconstituted solution, if not used immediately, should be protected from direct sunlight and should be stored in the refrigerator between 2?C and 8?C. The diluted solutions in sodium chloride9mg/ml (0.9%), sodium chloride 4.5mg/ml (0.45%), or Ringer lactateinjection solutionshould be stored between2?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.

4)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 polyvinyl chloride or polyolefin bags.