Benlysta

Belimumab has not been adequately studied in pregnant women. Belimumab can cross the placenta. A pregnancy registry has been established for monitoring the safety of belimumab in pregnant women. The number for the registry is 1-877-681-6296.

It is not known whether belimumab is excreted in human breast milk. Since antibodies are usually excreted in breast milk, mothers should consider not breastfeeding or discontinuing belimumab if they want to breastfeed.

BENLYSTA (belimumab) is indicated for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy.

Limitations Of Use

The efficacy of BENLYSTA has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. BENLYSTA has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of BENLYSTA is not recommended in these situations.

BENLYSTA
(ben-LIST-ah)
(belimumab) for injection, for intravenous use

BENLYSTA
(ben-LIST-ah)
(belimumab) injection, for subcutaneous use

What is the most important information I should know about BENLYSTA?

BENLYSTA can cause serious side effects. Some of these side effects may cause death. It is not known if BENLYSTA causes these serious side effects. Tell your healthcare provider right away if you have any of the symptoms listed below while receiving BENLYSTA

1. Infections. Symptoms of an infection can include:

• fever
• urinating often
• chills
• coughing up mucus
• pain or burning with urination
• warm, red, or painful skin or sores on your body

2. Heart Problems. Symptoms of heart problems can include:

• chest discomfort or pain
• nausea
• shortness of breath
• dizziness
• cold sweats
• discomfort in other areas of the upper body

3. Allergic (hypersensitivity) reactions. Serious allergic reactions can happen on the day of, or in the days after, receiving BENLYSTA and may cause death. Your healthcare provider will watch you closely while you are receiving BENLYSTA given intravenously (infusion) and after your infusion for signs of a reaction. Allergic reactions can sometimes be delayed. Tell your healthcare provider right away if you have any of the following symptoms of an allergic reaction following use of BENLYSTA:

• itching
• dizziness or fainting
• swelling of the face, lips, mouth, tongue, or throat
• headache
• trouble breathing
• nausea
• anxiousness
• skin rash
• low blood pressure

4. Mental health problems and suicide. Symptoms of mental health problems can include:

• thoughts of suicide or dying
• new or worse depression
• attempt to commit suicide
• acting on dangerous impulses
• trouble sleeping (insomnia)
• other unusual changes in your behavior or mood
• new or worse anxiety
• thoughts of hurting yourself or others

What is BENLYSTA?

BENLYSTA is a prescription medicine used to treat adults with active systemic lupus erythematosus (SLE or lupus) who are receiving other lupus medicines.

BENLYSTA contains belimumab which is in a group of medicines called monoclonal antibodies. Lupus is a disease of the immune system (the body system that fights infection). When given together with other medicines for lupus, BENLYSTA decreases lupus disease activity more than other lupus medicines alone.

• It is not known if BENLYSTA is safe and effective in people with severe active lupus nephritis or severe active central nervous system lupus.
• It is not known if BENLYSTA is safe and effective in children.

Do not use BENLYSTA if you:

• are allergic to belimumab or any of the ingredients in BENLYSTA. See the end of this Medication Guide for a complete list of ingredients in BENLYSTA.

Before you receive BENLYSTA, tell your healthcare provider about all of your medical conditions, including if you:

• think you have an infection or have infections that keep coming back. You should not receive BENLYSTA if you have an infection unless your healthcare provider tells you to. See “What is the most important information I should know about BENLYSTA?”
• have or have had mental health problems such as depression or thoughts of suicide.
• have recently received a vaccination or if you think you may need a vaccination. If you are receiving BENLYSTA, you should not receive live vaccines.
• are allergic to other medicines.
• are receiving other biologic medicines, monoclonal antibodies or IV infusions of cyclophosphamide (CYTOXAN).
• have or have had any type of cancer.
• are pregnant or plan to become pregnant. It is not known if BENLYSTA will harm your unborn baby. Females who are able to become pregnant should talk to their healthcare provider about whether or not they will use birth control (contraception) and receive BENLYSTA. If BENLYSTA is recommended, you should use an effective method of birth control while receiving BENLYSTA and for at least 4 months after the final dose of BENLYSTA. Tell your healthcare provider right away if you become pregnant during your treatment with BENLYSTA or if you think you may be pregnant.
  • If you become pregnant while receiving BENLYSTA, talk to your healthcare provider about enrolling in the BENLYSTA Pregnancy Registry. You can enroll in this registry by calling 1- 877-681-6296. The purpose of this registry is to monitor the health of you and your baby.
• are breastfeeding or plan to breastfeed. It is not known if BENLYSTA passes into your breast milk. You and your healthcare provider should talk about whether or not you should receive BENLYSTA and breastfeed.

Tell your healthcare provider about all the medicines you take, including prescription and over-thecounter medicines, vitamins, and herbal supplements.

Know the medicines you take. Keep a list of your medicines with you to show to your healthcare provider and pharmacist when you get a new medicine.

How will I receive BENLYSTA?

When administered intravenously (by vein)

• You will be given BENLYSTA by a healthcare provider through a needle placed in a vein (IV infusion). It takes about 1 hour to give you the full dose of BENLYSTA.
• Your healthcare provider will tell you how often you should receive BENLYSTA.
• Your healthcare provider may give you medicines before you receive BENLYSTA to help reduce your chance of having a reaction. A healthcare provider will watch you closely while you are receiving BENLYSTA and after your infusion for signs of a reaction. A healthcare provider will review the signs and symptoms of possible allergic reactions that could happen after your infusion.

When administered subcutaneously (under your skin)

• Use BENLYSTA exactly as your healthcare provider tells you to.
• Read the Instructions for Use that comes with BENLYSTA for instructions about the right way to give your injections at home.
• BENLYSTA may be prescribed as a single-dose autoinjector or as a single-dose prefilled syringe.
• Before you use BENLYSTA, your healthcare provider will show you or your caregiver how to give the injections and review the signs and symptoms of possible allergic reactions.
• BENLYSTA is injected under your skin (subcutaneously) of your stomach (abdomen) or thigh.
• Use BENLYSTA 1 time a week on the same day each week.
• If you miss your dose of BENLYSTA on your planned day, inject a dose as soon as you remember. Then, inject your next dose at your regularly scheduled time or continue weekly dosing based on the new day injected. In case you are not sure when to inject BENLYSTA, call your healthcare provider. Do not use 2 doses on the same day to make up for a missed dose.

What are the possible side effects of BENLYSTA?

BENLYSTA can cause serious side effects, including:

See “What is the most important information I should know about BENLYSTA?”

• Progressive multifocal leukoencephalopathy (PML). PML is a serious and life-threatening brain infection. Your chance of getting PML may be higher if you are treated with medicines that weaken your immune system, including BENLYSTA. PML can result in death or severe disability. If you notice any new or worsening medical problems such as those below, tell your healthcare provider right away:
  • memory loss
  • trouble thinking
  • dizziness or loss of balance
  • difficulty talking or walking
  • loss of vision
• Cancer. BENLYSTA may reduce the activity of your immune system. Medicines that affect the immune system may increase your risk of certain cancers.

The most common side effects of BENLYSTA include:

• nausea
• leg or arm pain
• diarrhea
• fever
• stuffy or runny nose and sore throat (nasopharyngitis)
• persistent cough (bronchitis)
• trouble sleeping (insomnia)
• depression
• headache (migraine)
• pain, redness, itching, or swelling at the site of injection (when given subcutaneously)

These are not all the possible side effects of BENLYSTA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store BENLYSTA?

• Store autoinjectors and prefilled syringes in the refrigerator at 36°F to 46°F (2°C to 8°C). Do not freeze.
• Keep BENLYSTA autoinjectors and prefilled syringes in the original package until time of use to protect from light.
• Do not shake. Keep away from heat.
• Do not use and do not place back in the refrigerator if left out at room temperature for more than 12 hours.
• Safely throw away medicine that is out of date or no longer needed.

Keep BENLYSTA and all medicines out of the reach of children.

General information about the safe and effective use of BENLYSTA.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use BENLYSTA for a condition for which it was not prescribed. Do not give BENLYSTA to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about BENLYSTA. You can ask your healthcare provider or pharmacist for information about BENLYSTA that is written for healthcare professionals.

What are the ingredients in BENLYSTA?

Active ingredient: belimumab.

Inactive ingredients (intravenous): citric acid, polysorbate 80, sodium citrate, sucrose.

Inactive Ingredients (subcutaneous): L-arginine hydrochloride, L-histidine, L-histidine monohydrochloride, polysorbate 80, sodium chloride.

Instructions for Use

BENLYSTA
(ben-LIST-ah)
(belimumab) injection, for subcutaneous use

Prefilled Syringe

Read this Instructions for Use before you start to use BENLYSTA and each time you refill your prescription. There may be new information. You should also receive training from your healthcare provider on how to use the prefilled syringe the right way. If you do not follow these instructions the prefilled syringe may not work properly. BENLYSTA is for use under the skin only (subcutaneous).

Important Storage Information

• Keep refrigerated until 30 minutes before use.
• Keep in the original package until time of use to protect from light.
• Do not freeze BENLYSTA.
• Keep away from heat.
• Do not use and do not place back in the refrigerator if BENLYSTA is left out for more than 12 hours.
• Keep out of the reach of children.

Important Warnings

• The prefilled syringe should be used only 1 time and then thrown away. See below, “Dispose of used prefilled syringe and inspect.”
  • Do not share your BENLYSTA prefilled syringe with other people. You may give other people a serious infection, or get a serious infection from them.
  • Do not shake the prefilled syringe.
  • Do not use if dropped onto a hard surface.
  • Do not remove the Needle Cap until right before the injection.

BENLYSTA Prefilled Syringe Parts Before use

After Use – Needle is covered by Needle Guard

Supplies needed for the injection

BENLYSTA Prefilled Syringe

Alcohol Swab (not included)

Gauze Pad or Cotton Ball (not included)

Sharps Container (not included)

1. Gather and check supplies

Gather supplies

• Remove 1 sealed tray containing a prefilled syringe from the refrigerator.
• Find a comfortable, well-lit, and clean surface and place the following supplies within reach:
  • BENLYSTA Prefilled Syringe
  • Alcohol Swab (not included)
  • Gauze Pad or Cotton Ball (not included)
  • Sharps Container (not included)
• Do not perform the injection if you do not have all the supplies listed.

Check expiration date

• Peel back the film of the tray and remove the prefilled syringe by holding the middle of the syringe body.
• Check the expiration date on the prefilled syringe. See Figure A.

Figure A

• Do not use if the expiration date has passed.

2 Prepare and inspect the BENLYSTA Prefilled Syringe

Allow to come to room temperature

• Allow the prefilled syringe to sit at room temperature for 30 minutes. See Figure B.

Figure B

• Do not warm the prefilled syringe in any other way. For example, do not warm in a microwave oven, hot water, or in direct sunlight.
• Do not remove the Needle Cap during this step.

Inspect BENLYSTA solution

• Look in the Inspection Window to check that the BENLYSTA solution is colorless to slightly yellow in color. See Figure C.

Figure C

• It is normal to see 1 or more air bubbles in the solution.
  • Do not use if the solution looks cloudy, discolored, or has particles.

3. Choose and clean the injection site

Choose the injection site

• Choose where to inject (abdomen or thigh). See Figure D.
• Avoid injecting into the same site each time or in areas where the skin is tender, bruised, red, or hard.

Figure D

• Do not inject within 2 inches of the belly button.

Clean the injection site

• Wash your hands.
• Clean the injection site by wiping it with an Alcohol Swab. Allow the skin to air dry. See Figure E.

Figure E

• Do not touch this area again before giving the injection.

4. Prepare for the injection

Remove the Needle Cap

• Do not remove the Needle Cap until right before you give the injection.
• Hold the prefilled syringe by the body and with the Needle facing away from you. Remove the Needle Cap by pulling it straight off. See Figure F.

Figure F

• You may see a drop of liquid at the end of the Needle. This is normal.
• Do not let the Needle touch any surface.
• Do not push any air bubbles out of the prefilled syringe.
• Do not put the Needle Cap back onto the prefilled syringe.
• Keep your hands away from the Plunger to avoid pushing it before injecting.

5. Inject BENLYSTA

Insert the Needle

• Hold the prefilled syringe in one hand and use your free hand to gently pinch the skin around the injection site. See Figure G.
• Insert the entire Needle into the pinched area of the skin at a slight 45-degree angle using a dartlike motion.

Figure G

• After the Needle is completely inserted, release the pinched skin.

Complete the injection

• Push the Plunger all the way down until all of the solution is injected. See Figure H.

Figure H

• While keeping your hold on the syringe, slowly move your thumb back, allowing the Plunger to rise up. The Needle will automatically rise up into the Needle Guard. See Figure I.

Figure I

6. Dispose of used prefilled syringe and inspect

Dispose of the used prefilled syringe

Throw away (dispose of) the used syringe and Needle Cap in a Sharps Container. See Figure J.

• Put your used syringe and sharps in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and syringes in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that:
  • is made of a heavy-duty plastic,
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • is upright and stable during use,
  • is leak-resistant, and
  • properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to: http://www.fda.gov/safesharpsdisposal.
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Figure J

Inspect the injection site

• There may be a small amount of blood at the injection site. If needed, press a Cotton Ball or Gauze Pad on the injection site.
• Do not rub the injection site.

Additional information

For more information about BENLYSTA, go to www.BENLYSTA.com or call 1-877-423-6597.

Instructions for Use

BENLYSTA
(ben-LIST-ah)
(belimumab) injection, for subcutaneous use

Prefilled Autoinjector

Read this Instructions for Use before you start to use BENLYSTA and each time you refill your prescription. There may be new information. You should also receive training from your healthcare provider on how to use the autoinjector the right way. If you do not follow these instructions the autoinjector may not work properly. BENLYSTA is for use under the skin only (subcutaneous).

Important Storage Information

• Keep refrigerated until 30 minutes before use.
• Keep in the original package until time of use to protect from light.
• Do not freeze BENLYSTA. Keep away from heat.
• Do not use and do not place back in the refrigerator if BENLYSTA is left out for more than 12 hours.
• Keep out of the reach of children.

Important Warnings

• The autoinjector should be used only 1 time and then thrown away. See below, “Dispose of used autoinjector and inspect.”
  • Do not share your BENLYSTA Autoinjector with other people. You may give other people a serious infection, or get a serious infection from them.
  • Do not shake the autoinjector.
  • Do not use if dropped onto a hard surface.
  • Do not remove the Ring Cap until right before the injection.

BENLYSTA Autoinjector Parts

Supplies needed for the injection

BENLYSTA Autoinjector

Alcohol Swab (not included)

Gauze Pad or Cotton Ball (not included)

Sharps Container (not included)

1. Gather and check supplies

Gather supplies

• Remove 1 sealed tray containing an autoinjector from the refrigerator.
• Find a comfortable, well-lit, and clean surface and place the following supplies within reach:
  • BENLYSTA Autoinjector
  • Alcohol Swab (not included)
  • Gauze Pad or Cotton Ball (not included)
  • Sharps Container (not included)
• Do not perform the injection if you do not have all the supplies listed.

Check expiration date

• Peel back the film of the tray and remove the autoinjector.
• Check the expiration date on the autoinjector. See Figure A.

Figure A

• Do not use if the expiration date has passed.

2. Prepare and inspect the BENLYSTA Autoinjector

Allow to come to room temperature

• Allow the autoinjector to sit at room temperature for 30 minutes. See Figure B.

Figure B

• Do not warm the autoinjector in any other way. For example, do not warm in a microwave oven, hot water, or in direct sunlight.
• Do not remove the Ring Cap during this step.

Inspect BENLYSTA solution

• Look in the Inspection Window to check that the BENLYSTA solution is colorless to slightly yellow in color. See Figure C.

Figure C

• It is normal to see 1 or more air bubbles in the solution.
• Do not use if the solution looks cloudy, discolored, or has particles.

3. Choose and clean the injection site

Choose the injection site

• Choose where to inject (abdomen or thigh). See Figure D.
• Avoid injecting into the same site each time or in areas where the skin is tender, bruised, red, or hard.

Figure D

• Do not inject within 2 inches of the belly button.

Clean the injection site

• Wash your hands.
• Clean the injection site by wiping it with an Alcohol Swab. Allow the skin to air dry. See Figure E.

Figure E

• Do not touch this area again before giving the injection.

4. Prepare for the injection

Remove the Ring Cap

• Do not remove the Ring Cap until right before you give the injection.
• Remove the Ring Cap by pulling or twisting it off. The Ring Cap may be twisted off in either a clockwise or counter-clockwise direction. See Figure F.

Figure F

• Do not put the Ring Cap back onto the autoinjector.

Position the autoinjector

• Hold the autoinjector comfortably so that you can see the Inspection Window. It is important that you can look at the Inspection Window while giving the injection. You will look at the Inspection Window to:
  • see that the purple indicator is moving while you are injecting.
  • see that the purple indicator has stopped to make sure that the dose is complete. See Figure G.

Figure G

• Position the autoinjector straight over the injection site at a 90-degree angle. Make sure the Gold Needle Guard is flat on the skin.

5. Inject BENLYSTA

Start the injection

• Firmly press the autoinjector all the way down onto the injection site and hold in place. See Figure H.
• This will insert the needle and start the injection.

Figure H

• You may hear a “first click” at the start of the injection and see the Purple Indicator start to move through the Inspection Window. See Figure I.

Figure I

Complete the injection

• Continue to hold the autoinjector down until you see that the Purple Indicator has stopped moving.

You may hear a “second click” a few seconds before the Purple Indicator stops moving. See Figure J.

Figure J

• The injection may take up to 15 seconds to complete.
• When the injection is complete, lift the autoinjector from the injection site.

6. Dispose of used autoinjector and inspect

Dispose of the used autoinjector

Throw away (dispose of) the used autoinjector and Ring Cap in a Sharps Container. See Figure K.

• Put your used autoinjector in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that:
  • is made of a heavy-duty plastic,
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • is upright and stable during use,
  • is leak-resistant, and
  • properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information
• about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to: http://www.fda.gov/safesharpsdisposal.

Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Figure K

Inspect the injection site

• There may be a small amount of blood at the injection site. If needed, press a Cotton Ball or Gauze Pad on the injection site.
• Do not rub the injection site.

Additional information

For more information about BENLYSTA, go to www.BENLYSTA.com or call 1-877-423-6597.

Do not receive Benlysta if you are allergic to Benlysta or any of the ingredients in Benlysta.

Benlysta can cause serious side effects. Some of these side effects may cause death. It is not known if Benlysta causes these serious side effects. Tell your healthcare provider right away if you have any of the symptoms listed below while receiving Benlysta.    1.  Infections. Symptoms of an infection can include: 

• fever  
• chills 
• pain or burning with urination 
• urinating often  
• bloody diarrhea 
• coughing up mucus 

  2.  Heart Problems. Symptoms of heart problems can include: 

• chest discomfort or pain 
• shortness of breath 
• cold sweats 
• nausea 
• dizziness 
• discomfort in other areas of the upper body 

  3.  Mental health problems and suicide. Symptoms of mental health problems can include: 

• thoughts of suicide or dying 
• attempt to commit suicide 
• trouble sleeping (insomnia) 
• new or worse anxiety  
• new or worse depression 
• acting on dangerous impulses 
• other unusual changes in your behavior or mood 
• thoughts of hurting yourself or others

4.  Cancer. Benlysta may reduce the activity of your immune system. Medicines that affect the immune system may increase your risk of certain cancers.  

5.  Allergic (hypersensitivity) and infusion reactions. Serious allergic or infusion reactions can happen on the day of or the day after receiving Benlysta and may cause death. Tell your healthcare provider right away if you have any of the following symptoms of an allergic or infusion reaction:

• itching
• swelling of the face, lips, mouth, tongue, or throat
• trouble breathing
• anxiousness 
• low blood pressure 
• dizziness or fainting 
• headache 
• nausea 
• skin rash, redness, or swelling 

Your healthcare provider will watch you closely while you are receiving Benlysta and after your infusion for signs of a reaction.    6. Progressive multifocal leukoencephalopathy (PML). PML is a serious and life-threatening brain infection. Your chance of getting PML may be higher if you take medications that weaken your immune system, including Benlysta. PML can result in death or severe disability. If you notice any new or worsening medical problems such as those below, tell your healthcare provider right away:

• memory loss
• trouble thinking
• dizziness or loss of balance
• difficulty talking or walking
• loss of vision

If you are currently being treated with Benlysta, it is recommended you do not receive live vaccines. 

Do not receive or use this medication if you are allergic to Benlysta or to any of its ingredients. 

• Store autoinjectors and prefilled syringes in the refrigerator at 36°F to 46°F (2°C to 8°C). Do not freeze.
• Keep Benlysta and all other medications out of the reach of children. 
• Keep Benlysta autoinjectors and prefilled syringes in the original package until time of use to protect from light.
• Do not shake. Keep away from heat.
• Do not use and do not place back in the refrigerator if left out at room temperature for more than 12 hours.
• Safely throw away medicine that is out of date or no longer needed.

Immunosuppressive agent; recombinant fully human IgG1 lambda monoclonal antibody that inhibits soluble B-lymphocyte stimulator (BLyS).1 3 4 5

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Belimumab

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IV infusion	120 mg	Benlysta	Human Genome Services, (also promoted by GlaxoSmithKline)
		400 mg	Benlysta	Human Genome Services, (also promoted by GlaxoSmithKline)

A nurse or other trained health professional will give you this medicine. It is given through a needle placed into one of your veins or as a shot under your skin, usually in the stomach or thighs. You or your caregiver may be trained to prepare and inject this medicine at home. Be sure that you understand how to use the medicine.

If this medicine is given through a vein in your arm, it must be injected by your doctor slowly and your IV tube will need to stay in place for 1 hour.

If you use this medicine at home, you will be shown the body areas where this shot can be given. Use a different body area each time you give yourself a shot. Keep track of where you give each shot to make sure you rotate body areas. This will help prevent skin problems from the injections. Do not inject into skin areas that are tender, red, bruised, or hard.

This medicine comes with a Medication Guide and patient instructions. Read and follow these instructions carefully. Ask your doctor or pharmacist if you have any questions.

This medicine is available in three forms: a vial (glass container), a prefilled syringe, or an autoinjector. The prefilled syringe and autoinjector are the dosage forms you can use at home.

Check the liquid in the prefilled syringe or autoinjector. It should be colorless or slightly yellow. Do not use the medicine if the liquid is cloudy, discolored, or has particles in it. Do not shake.

Allow the medicine to warm to room temperature for 30 minutes before you use it. Do not warm it in any other way.

Do not remove the needle cap from the prefilled syringe or the ring cap from the autoinjector until you are ready to use it.

You might not use all of the medicine in each prefilled syringe or autoinjector. Use each prefilled syringe and autoinjector only one time. Do not save an open syringe or autoinjector.

You may also receive medicines to help prevent allergic reactions to the injection.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form:
  • For lupus:
    • Adults—200 milligrams (mg) injected under your skin once a week.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store in the refrigerator. Do not freeze.

Store this medicine in its original container until you are ready to use it. Keep it refrigerated until 30 minutes before use. Do not use and do not place this medicine back in the refrigerator if it has been left out for more than 12 hours.

Throw away used needles in a hard, closed container that the needles cannot poke through. Keep this container away from children and pets.

Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Benlysta during pregnancy. Healthcare professionals are encouraged to register patients by calling 1-877-681-6296.

Risk Summary

Limited data on use of Benlysta in pregnant women, from observational studies, published case reports, and postmarketing surveillance, are insufficient to determine whether there is a drug-associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with SLE [see Clinical Considerations]. Monoclonal antibodies, such as belimumab, are actively transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero-exposed infant [see Clinical Considerations]. In an animal combined embryo-fetal and pre- and post-natal development study with monkeys that received belimumab by intravenous administration, there was no evidence of embryotoxicity or fetal malformations with exposures approximately 9 times (based on intravenous administration) and 20 times (based on subcutaneous administration) the exposure at the maximum recommended human dose (MRHD). Belimumab-related findings in monkey fetuses and/or infants included reductions of B-cell counts, reductions in the density of lymphoid tissue B-lymphocytes in the spleen and lymph nodes, and altered IgG and IgM titers. The no-adverse-effect-level (NOAEL) was not identified for these findings; however, they were reversible within 3 to 12 months after the drug was discontinued [see Data]. Based on animal data and the mechanism of action of belimumab, the immune system in infants of treated mothers may be adversely affected. It is unknown, based on available data, whether immune effects, if identified, are reversible [see Clinical Pharmacology (12.1)].

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk: Pregnant women with SLE are at increased risk of adverse pregnancy outcomes, including worsening of the underlying disease, premature birth, spontaneous abortion, and intrauterine growth restriction. Maternal lupus nephritis increases the risk of hypertension and preeclampsia/eclampsia. Passage of maternal anti-phospholipid antibodies across the placenta may result in adverse neonatal outcomes, including neonatal lupus and congenital heart block.

Fetal/Neonatal Adverse Reactions: Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to Benlysta in utero. Monitor an infant of a treated mother for B-cell reduction and other immune dysfunction [see Warnings and Precautions (5.7)].

Data

Animal Data: In a combined embryo-fetal and pre- and post-natal development study, pregnant cynomolgus monkeys received belimumab at intravenous doses of 0, 5, or 150 mg/kg every 2 weeks from confirmation of pregnancy at Gestation Days (GD) 20 to 22, throughout the period of organogenesis (up to approximately GD 50), and continuing to either the day of scheduled cesarean section (GD 150 [late third trimester]) or the day of parturition. There was no evidence of maternal toxicity, embryotoxicity, or teratogenicity at exposure approximately 9 times the MRHD of 10 mg/kg intravenously or 20 times the MRHD of 200 mg subcutaneously (on an AUC basis with maternal animal intravenous doses up to 150 mg/kg). Belimumab-related findings in mothers included reductions of immature and mature B-cell counts and in fetuses and/or infants included reductions of immature and mature B-cell counts, reductions in the density of lymphoid tissue B-lymphocytes in the spleen and lymph nodes, reduced spleen weights, increased IgG titers, and reduced IgM titers. B-cell counts in infant monkeys exposed to belimumab in utero recovered by 3 months of age and in mothers after 1 year. IgG and IgM levels in infant monkeys recovered by 6 months of age and the reductions in B-lymphocytes in the lymph nodes and spleen were reversed by 1 year of age. Belimumab crossed the placenta, as it was detected in fetal cord blood and amniotic fluid on GD 150.

Lactation

Risk Summary

No information is available on the presence of belimumab in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Belimumab was detected in the milk of cynomolgus monkeys; however, due to species-specific differences in lactation physiology, animal data may not predict drug levels in human milk. Maternal IgG is known to be present in human milk. If belimumab is transferred into human milk, the effects of local exposure in the gastrointestinal tract and potential limited systemic exposure in the infant to belimumab are unknown. The lack of clinical data during lactation precludes clear determination of the risk of Benlysta to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Benlysta, and any potential adverse effects on the breastfed child from Benlysta or from the underlying maternal condition.

Females and Males of Reproductive Potential

Contraception

Following an assessment of benefit versus risk, if prevention of pregnancy is warranted, females of reproductive potential should use effective contraception during treatment and for at least 4 months after the final treatment.

Pediatric Use

Safety and effectiveness of Benlysta have not been established in children.

Geriatric Use

Clinical studies of Benlysta did not include sufficient numbers of subjects aged 65 or older to determine whether they respond differently from younger subjects. Use with caution in elderly patients.

Renal Impairment

The safety and efficacy of Benlysta were evaluated in studies that included patients with SLE who had mild (creatinine clearance [CrCl] ≥60 and <90 mL/min), moderate (CrCl ≥30 and <60 mL/min), or severe (CrCl ≥15 and <30 mL/min) renal impairment. No dosage adjustment is recommended in patients with renal impairment.

Hepatic Impairment

No formal trials were conducted to examine the effects of hepatic impairment on the pharmacokinetics of belimumab. No dosage adjustment is recommended in patients with hepatic impairment.

Racial Groups

In Trial 2 and Trial 3 (intravenous dosing), SLE Responder Index-4 (SRI-4) response rates were lower for black patients receiving Benlysta plus standard therapy relative to black patients receiving placebo plus standard therapy [see Clinical Studies (14.1)]. In Trial 4 (subcutaneous dosing), SRI-4 response was slightly higher for black patients receiving Benlysta plus standard therapy relative to black patients receiving placebo plus standard therapy, but the treatment difference was not as large as that observed in the overall population and no definitive conclusion can be drawn from this subgroup analysis [see Clinical Studies (14.2)]. Caution should be used when considering treatment with Benlysta in black/African-American patients.

Belimumab is a human IgG1λ monoclonal antibody specific for soluble human B lymphocyte stimulator protein (BLyS, also referred to as BAFF and TNFSF13B). Belimumab has a molecular weight of approximately 147 kDa. Belimumab is produced by recombinant DNA technology in a murine cell (NS0) expression system.

Intravenous Infusion

Benlysta (belimumab) for injection is a sterile, white to off-white, preservative‑free, lyophilized powder in a single-dose vial for reconstitution and dilution prior to intravenous infusion. Benlysta for injection is supplied as 120 mg per vial and 400 mg per vial and requires reconstitution with Sterile Water for Injection, USP (1.5 mL and 4.8 mL, respectively) to obtain a concentration of 80 mg/mL [see Dosage and Administration (2.1)]. After reconstitution, each vial allows for withdrawal of 1.5 mL (120 mg) or 5 mL (400 mg). Each mL delivers 80 mg belimumab, citric acid (0.16 mg), polysorbate 80 (0.4 mg), sodium citrate (2.7 mg), and sucrose (80 mg), with a pH of 6.5.

The vial stoppers are not made with natural rubber latex.

Subcutaneous Injection

Benlysta (belimumab) injection is a sterile, preservative-free, clear to opalescent, and colorless to pale yellow solution for subcutaneous use. It is supplied in a 1-mL single-dose prefilled autoinjector with a fixed 27-gauge, half-inch needle or in a 1-mL single-dose prefilled syringe with a fixed 27-gauge, half-inch needle with a needle guard. Each 1 mL delivers 200 mg belimumab, L-arginine hydrochloride (5.3 mg), L-histidine (0.65 mg), L-histidine monohydrochloride (1.2 mg), polysorbate 80 (0.1 mg), and sodium chloride (6.7 mg), with a pH of 6.0.

The autoinjectors and prefilled syringes are not made with natural rubber latex.