Cinryze is a man-made form of a protein that occurs naturally in the blood stream and helps control swelling in the body. People with a condition called hereditary angioedema do not have enough of this protein. Hereditary angioedema can cause attacks of swelling and symptoms such as stomach problems or trouble breathing.

Cinryze is used to prevent attacks of angioedema.

The Berinert brand of complement C1 esterase inhibitor is used to treat attacks of angioedema.

Warnings

You should not use Cinryze if have ever had a life-threatening allergic reaction to complement C1 esterase inhibitor.

Before you receive Cinryze, tell your doctor if you have a history of stroke or blood clot.

Do not give this medication to a child without medical advice.

You may be shown how to use Cinryze in an IV at home. Cinryze comes with patient instructions for safe and effective use. Follow all directions carefully. Ask your doctor or pharmacist if you have any questions.

Do not self-inject Cinryze if you do not fully understand how to give the injection and properly dispose of used needles, IV tubing, and other items used to inject the medicine. Be sure you understand how to properly mix and store the medication. Stop your IV infusion and get emergency medical help if you have any of these signs of an allergic reaction: hives; wheezing or difficult breathing; feeling like you might pass out; or swelling of your face, lips, tongue, or throat.

Cinryze is made from human plasma (part of the blood) which may contain viruses and other infectious agents. Donated plasma is tested and treated to reduce the risk of it containing infectious agents, but there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

Before taking this medicine

You should not use Cinryze if have ever had a life-threatening allergic reaction to complement C1 esterase inhibitor.

Tell your doctor if you have ever had:

• a stroke or blood clot;
• heart problems; or
• an “in-dwelling” catheter.

Tell your doctor if you are pregnant or breast-feeding.

Cinryze is made from donated human plasma and may contain viruses or other infectious agents. Donated plasma is tested and treated to reduce the risk of contamination, but there is still a small possibility it could transmit disease. Ask your doctor about any possible risk.

How should I use Cinryze?

Use Cinryze exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Cinryze is injected into a vein through an IV.

You may be shown how to use injections at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of needles, IV tubing, and other items used.

Cinryze is usually given every 3 or 4 days to prevent angioedema attacks.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Cinryze is a powder medicine that must be mixed with a liquid (diluent) before using it. If you are using this medicine at home, you will need to use two vials to make up a single dose. Follow all directions carefully. Be sure you understand how to properly mix and store the medicine.

Gently swirl but do not shake the mixed medicine or you may ruin it. Prepare your dose only when you are ready to give yourself an injection.

The powder and diluent mixture should be clear and colorless. Mixed Cinryze should be clear or slightly blue in color. Do not use the mixed medicine if it has changed colors or has particles in it. Call your pharmacist for new medicine.

Each single-use vial (bottle) of Cinryze is for one use only. Throw it away after one use, even if there is still medicine left inside.

Cinryze contains no preservative. Once you have pierced the rubber top of a vial with a needle, you must use that vial right away or throw it away.

Store the unmixed dry powder in a refrigerator or at cool room temperature. Protect from light and do not freeze. Throw away any unused vial after the expiration date on the label has passed.

After mixing Cinryze with the diluent, use the injection right away or store the mixture at room temperature and use it within 3 hours.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof “sharps” disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Dosing information

Usual Adult Dose for Hereditary Angioedema:

For routine prophylaxis against angioedema attacks in HAE patients.
1,000 Units by intravenous infusion at a rate of 1 mL per minute (1,000 units/ 10 mL) every 3 or 4 days.

What happens if I miss a dose?

Call your doctor for instructions if you miss a dose.

Keep this medicine on hand at all times to prevent angioedema, especially while traveling.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What should I avoid after using Cinryze?

Follow your doctor’s instructions about any restrictions on food, beverages, or activity.

Cinryze side effects

Get emergency medical help if you have signs of an allergic reaction to Cinryze: hives; chest tightness, fast heartbeats, feeling light-headed; wheezing or difficult breathing, blue lips or gums; or swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• sudden numbness or weakness on one side of the body;
• pain, swelling, warmth, or redness in an arm or leg;
• sudden severe headache, confusion, problems with vision, speech, or balance;
• chest pain while taking deep breaths; or
• fast heart rate.

Common Cinryze side effects may include:

• unusual or unpleasant taste in your mouth;
• headache, dizziness;
• nausea, vomiting;
• pain, bruising, itching, swelling, bleeding, warmth, or a hard lump where the medicine was injected;
• stuffy nose, sore throat;
• rash; or
• fever.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

What other drugs will affect Cinryze?

Tell your doctor about all your other medicines, especially:

• testosterone; or
• birth control pills.

This list is not complete. Other drugs may interact with complement C1 esterase inhibitor, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Cinryze Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for Cinryze.Cinryze (C1 Esterase Inhibitor (Human)) – Takeda Pharmaceuticals U.S.A., Inc.

Cimzia injection is used to treat Crohn’s disease, rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, polyarticular juvenile idiopathic arthritis, and non-radiographic axial spondyloarthritis in certain patients. Cimzia works to reduce inflammation and improve symptoms by blocking a protein called TNFα (tumor necrosis factor alpha).  Cimzia (certolizumab  pegol) belongs to the drug class TNF alfa inhibitors.

In autoimmune conditions, like Crohn’s disease, rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, and non-radiographic axial spondyloarthritis inflammation can be caused or worsened when TNF is released in the body. By Cimzia blocking TNFα there is less inflammation so symptoms of the condition improve.

Cimzia first received FDA approval on April 22, 2008, for moderate to severe active Crohn’s disease in adults who have an inadequate response to conventional therapy to reduce signs and symptoms of the disease and to maintain clinical response. Since then, it has also been approved for specific adult patients with rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, and non-radiographic axial spondyloarthritis.

Cimzia Indications

Cimzia FDA-approved indications for adults are 

• Crohn’s disease for reducing signs and symptoms and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.
• active rheumatoid arthritis  that is moderate to severe
• active psoriatic arthritis
• active ankylosing spondylitis 
• active non-radiographic axial spondyloarthritis with objective signs of inflammation
• plaque psoriasis that is moderate to severe in patients who are candidates for systemic therapy or phototherapy.

Cimzia FDA-approved indication for patients 2 years of age and older is 

• active polyarticular juvenile idiopathic arthritis (pJIA)

Cimzia side effects

Common Cimzia side effects may include rash, pain or burning when you urinate, and cold symptoms such as stuffy nose, sneezing, and a sore throat.

Serious Cimzia side effects

Get emergency medical help if you have signs of an allergic reaction to Cimzia: hives, difficulty breathing, swelling of your face, lips, tongue, or throat.

Serious and sometimes fatal infections may occur during treatment with Cimzia. Tell your doctor if you have signs of infection, such as fever, chills, cough, sweating, muscle pain, open sores or skin wounds, unusual tiredness, feeling short of breath, painful urination, diarrhea, or weight loss.

Call your doctor right away if you have any of these symptoms of lymphoma:

• chest pain, cough, feeling short of breath;
• swelling in your neck, underarm, or groin (this swelling may come and go);
• fever, night sweats, itching, weight loss, feeling tired;
• feeling full after eating only a small amount; or
• pain in your upper stomach that may spread to your back or shoulder.

Stop using Cimzia and call your doctor at once if you have Cimzia side effect symptoms of:

• shortness of breath (even with mild exertion), swelling, rapid weight gain;
• pale skin, easy bruising or bleeding;
• a new growth on your skin (may be red or purple), or any change in the size or color of a mole, freckle, or bump on your skin;
• nerve problems – vision problems, dizziness, numbness or tingly feeling, muscle weakness in your arms or legs;
• liver problems – loss of appetite, right-sided stomach pain, tiredness, jaundice (yellowing of the skin or eyes); or
• new or worsening symptoms of lupus – joint pain, and a skin rash on your cheeks or arms that worsens in sunlight.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

Warnings

Cimzia affects your immune system. Serious and sometimes fatal infections may occur.

Your risk of infection may be higher if you have diabetes, HIV, a weak immune system, hepatitis B, chronic infections, if you use certain medications, or if you live in or travel to certain areas.

Call your doctor at once if you have symptoms such as fever, chills, cough, diarrhea, night sweats, flu symptoms, or skin sores.

Using Cimzia may also increase your risk of developing certain types of cancer, including a rare fast-growing type of lymphoma that can be fatal.

Do not receive a “live” vaccine while you are being treated with Cimzia.

Do NOT use this medicine if you have had a serious hypersensitivity reaction to certolizumab pegol or to any of the inactive ingredients. 

Before taking this medicine

You should not use Cimzia if you are allergic to certolizumab. You may not be able to use Cimzia if you have symptoms of an infection such as fever, chills, cough, skin sores, shortness of breath, weight loss, diarrhea, or painful urination.

Tell your doctor if you have ever had tuberculosis, or anyone in your household has tuberculosis. Also tell your doctor if you have recently traveled. Tuberculosis and some fungal infections are more common in certain parts of the world, and you may have been exposed during travel.

Cimzia may cause a rare type of lymphoma (cancer) of the liver, spleen, and bone marrow that can be fatal. This has occurred mainly in teenagers and young men with Crohn’s disease or ulcerative colitis. However, anyone with an inflammatory autoimmune disorder may have a higher risk of lymphoma. Talk with your doctor about your own risk.

Tell your doctor if you have ever had:

• a chronic infection;
• hepatitis B (or if you are a carrier of the virus);
• lymphoma or other types of cancer;
• a blood cell disorder;
• congestive heart failure;
• a seizure;
• an allergy to latex;
• numbness or tingling, or a nervous system disorder such as multiple sclerosis; or
• if you are scheduled to receive any vaccines, or have recently been vaccinated with BCG (Bacille Calmette-Guerin).

It is not known whether Cimzia will harm an unborn baby. Tell your doctor if you are pregnant. Your name may be listed on a pregnancy registry to track the effects of Cimzia on the baby.

It may not be safe to breast-feed a baby while you are using this medicine. Ask your doctor about any risks.

Cimzia is not approved for use by anyone younger than 18 years old.

How is Cimzia given?

Cimzia is injected under the skin. A healthcare provider may teach you how to use the medication by yourself properly.

Cimzia is usually given every 2 to 4 weeks. You may need to use more than 1 injection to get a full dose. Follow your doctor’s dosing instructions very carefully.

Read and carefully follow any Instructions for Use provided with your medicine. Do not use Cimzia if you don’t understand all instructions for proper use. Ask your doctor or pharmacist if you have questions.

Prepare your injection only when you are ready to give it. Do not use if the medicine looks cloudy, has changed colors, or has particles in it. Call your pharmacist for new medicine.

Cimzia can increase your risk of bleeding or infection by changing the way your immune system works. You will need frequent medical tests.

Store Cimzia in its original carton in the refrigerator. Protect from light and do not freeze.

Take the syringe out of the refrigerator and let it reach room temperature before injecting your dose.

Unopened prefilled syringes may also be stored at room temperature for up to 7 days, away from heat and light. Throw away any prefilled syringe not used within 7 days. Do not put it back in the refrigerator.

Each prefilled syringe is for one use only. Throw away after one use, even if there is still medicine left inside.

Use a needle and syringe only once and then place them in a puncture-proof “sharps” container. Follow state or local laws about how to dispose of this container. Keep it out of the reach of children and pets.

If you’ve ever had hepatitis B, using Cimzia can cause this virus to become active or get worse. You may need frequent liver function tests while using this medicine and for several months after you stop.

Before you start treatment with Cimzia, your doctor may perform tests to make sure you do not have tuberculosis or other infections.

Dosing information

Usual Adult Cimzia Dose for Rheumatoid Arthritis

Initial Cimzia dose: 400 mg subcutaneously (given as two subcutaneous injections of 200 mg) at weeks 0, 2, and 4, followed by 200 mg subcutaneously every other week
Maintenance Cimzia dose: 400 mg subcutaneously every 4 weeks can be considered
Use: For the treatment of adults with moderately to severely active rheumatoid arthritis (RA)

Usual Adult Cimzia Dose for Psoriatic Arthritis

Initial dose: 400 mg subcutaneously (given as two subcutaneous injections of 200 mg) at weeks 0, 2, and 4, followed by 200 mg subcutaneously every other week
Use: For the treatment of adult patients with active psoriatic arthritis (PsA)

Usual Adult Dose for Ankylosing Spondylitis

Initial dose: 400 mg subcutaneously (given as two subcutaneous injections of 200 mg) at weeks 0, 2, and 4, followed by 200 mg subcutaneously every 2 weeks or 400 mg subcutaneously every 4 weeks
Use: For the treatment of adults with active ankylosing spondylitis

Usual Adult Cimzia Dose for Crohn’s Disease

Initial dose: 400 mg subcutaneously (given as two subcutaneous injections of 200 mg) at weeks 0, 2, and 4
Maintenance dose: 400 mg subcutaneously every 4 weeks
Use: For reducing signs and symptoms of Crohn’s disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy

Usual Adult Dose for Plaque Psoriasis

Initial dose: 400 mg subcutaneously (given as 2 subcutaneous injections or 200 mg) every other week
For certain patients with body weight <=90 kg: 400 mg (given as 2 subcutaneous injections or 200 mg) at weeks 0, 2, and 4 followed by 200 mg every other week can be considered
Use: For the treatment of adults with moderate-to-severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy

Usual Adult Dose for Non-Radiographic Axial Spondyloarthritis

Initial dose: 400 mg subcutaneously (given as two subcutaneous injections of 200 mg) at weeks 0, 2, and 4, followed by 200 mg subcutaneously every 2 weeks or 400 mg subcutaneously every 4 weeks
Use: For the treatment of adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation.

Usual dose for Polyarticular Juvenile Idiopathic Arthritis  patients 2 years of age and older)

Dose is weight dependant, every other week:

10 kg (22 lbs) to less than 20 kg (44 lbs): dose 100 mg initially and at week 2 and 4, followed by maintenance dose of 50 mg every other week
20 kg (44 lbs) to less than 40 kg (88 lbs): dose 200 mg initially and at week 2 and 4, followed by a maintenance dose of 100 mg every other week
Greater than or equal to 40 kg (88 lbs): dose 400 mg initially and at week 2 and 4, followed by  a maintenance dose of 200 mg every other week 

General Cimzia Dosing Information

• Rotate injection sites.
• Do not inject into skin that is tender, bruised, red, or hard.
• When a 400 mg dose is needed (given as 2 subcutaneous injections of 200 mg), injections should occur at separate sites in the thigh or abdomen.
• This drug can be given as monotherapy or concomitantly with non-biological disease modifying anti-rheumatic drugs (DMARDs).
• The use of this drug in combination with biological DMARDs or another tumor necrosis factor (TNF) blocker therapy is not recommended.

Cimzia is available as 200 mg lyophilized powder in a single-dose vial and 200 mg/mL solution in a single-dose prefilled syringe

Withdrawal from Cimzia

Your healthcare profession will guide you on how long you will use Cimzia.
Withdrawal from Cimzia may be required if you have severe allergic reactions.  Clinical trials have also studied reducing the dose of Cimza and stopping Cimza after sustained low disease activity in treating rheumatoid arthritis. However, the NCT01521923 clinical study failed to meet its primary endpoint.

What happens if I miss a dose?

Call your doctor for instructions if you miss a dose of Cimzia.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What should I avoid while receiving Cimzia?

Avoid injecting Cimzia into scars or stretch marks, or into skin that is red, bruised, swollen, hard, or tender.

Ask your doctor before receiving any vaccine while you are being treated with Cimzia.

Avoid being near people who are sick or have infections. Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

Berotralstat (Orladeyo) is a prescription medication used to reduce the frequency of hereditary angioedema (HAE) attacks in patients 12 years and older. It works by inhibiting plasma kallikrein, an enzyme that contributes to excessive bradykinin production, which leads to swelling and inflammation in HAE. It is not used for the treatment of acute HAE attacks.

Berotralstat capsule is taken once daily with food 

Berotralstat brand name is Orladeyo, by BioCryst Pharmaceuticals, Inc.

Berotralstat FDA approval was granted for the prevention of recurrent HAE attacks in patients 12 years and older on December 3, 2020, after positive results from Clinical Trial 1 (NCT3485911). The results from 24-week Trial 1 demonstrated that Berotralstat patients had:

• 30% reduction in HAE attack rate 110mg daily
• 44.2% reduction in HAE attack rate 150mg daily

How does berotralstat work?

In hereditary angioedema, excessive kallikrein activity results in high levels of bradykinin, causing blood vessel leakage and swelling. 

Berotralstat mechanism of action is a plasma kallikrein inhibitor that binds to plasma kallikrein, reducing its activity and helping to prevent angioedema attacks.

Berotralstat side effects

Common berotralstat side effects

Common side effects of berotralstat include:

• Abdominal pain (16%)
• Vomiting (12%)
• Diarrhea (12%)
• Heartburn (7%)
• Back pain (6%)

These common side effects occurred in patients taking berotralstat 110mg or 50 mg once daily in 24-week (Part 1) data from a 3-part, double-blind parallel-group, placebo-controlled clinical trial Trial 1 (NCT3485911).  

Serious Side Effects

QT prolongation (irregular heart rhythm) – may occur if more than one capsule is taken per day. Do not take more than one capsule a day.

Severe allergic reactions – seek emergency help if you experience:

• Hives
• Swelling of face, lips, or throat
• Difficulty breathing

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

Warnings & Precautions

• QT Prolongation Risk: Do not exceed 150 mg per day.

Before taking this medicine

Before taking Orladeyo for HAE make sure this medicine is safe for you, tell your doctor if you have ever had:

• Liver or Kidney Disease: Inform your doctor before taking Orladeyo.
• Not Approved for Children Under 12.

Pregnancy

Tell your healthcare professional if you are pregnant or planning to become pregnant as it is not known if Orladeyo can harm your unborn baby. 

Breastfeeding 

Tell your healthcare professional if you are breastfeeding or planning to breastfeed as it is not known if Orladeyo passes into breast milk. Talk to your healthcare professional about the best way to feed your baby.

Berotralstat dosage & administration

• Recommended Dosage: One 150 mg capsule taken once daily with food.
• Dose adjustments may be necessary for patients with moderate or severe liver impairment or with persistent gastrointestinal GI reactions
• Do not take more than one capsule per day, as it may lead to serious heart rhythm issues (QT prolongation).

What happens if I miss a dose?

• Take as soon as you remember.
• Skip the missed dose if it is almost time for your next dose.
• Do not double up on doses.

What happens if I overdose?

• Call the Poison Help Line or seek emergency medical attention immediately.

What other drugs will affect this medicine?

Berotralstat may interact with other medications, including:

• P-gp inducers – avoid use with Orladeyo.
• CYP2D6, CYP3A4, or P-gp substrates – monitor closely or dose titrate narrow therapeutic index medications that are predominantly metabolized by CYP2D6, CYP3A4 or are P-gp substrates when co-administered with Orladeyo.

Berinert is used to treat acute abdominal, facial, or laryngeal hereditary angioedema (HAE) attacks in adults and children. It is given by intravenous injection by a healthcare provider although appropriately trained patients may self-administer it.

Berinert is a man-made form of a protein that occurs naturally in the bloodstream and helps control swelling in the body. People with HAE do not have enough of this protein. 

Berinert gained FDA approval on October 12, 2009. There is no generic or biosimilar available.

• Berinert is used to treat attacks of angioedema. The Cinryze and Haegarda brands are used to prevent attacks of angioedema. 

Berinert Side Effects

Most Common Side Effects

• An increase in pain severity associated with HAE
• An unusual or unpleasant taste in your mouth.

Serious Side Effects and Warnings

Hypersensitivity Reactions

Do not use Berinert, C1 Esterase Inhibitor (Human), if you have experienced life-threatening allergic reactions or severe hypersensitivity to the product. Inform your healthcare provider of all medications you are taking and of any medical conditions, especially any history of blood-clotting problems. Get emergency medical help if you have signs of an allergic reaction to Berinert, such as:

• hives
• chest tightness
• fast heartbeats
• feeling light-headed
• wheezing or difficulty breathing
• blue lips or gums
• swelling of your face, lips, tongue, or throat.

Blood clots

Blood clots (thromboembolic events) have occurred in patients receiving Berinert. Tell your healthcare provider if you have a history of heart or blood vessel disease, stroke, or blood clots, or if you have thick blood, an indwelling catheter/access device in a vein, or have been immobile for some time. Certain medications, such as birth control pills, may also increase your risk of clotting problems. Report to your physician or an emergency room any signs and symptoms of a blood clot, such as:

• pain and/or swelling or discoloration of an arm or leg
• warmth over the affected area
• unexplained shortness of breath
• chest pain or discomfort that worsens on deep breathing
• rapid pulse
• numbness or weakness on one side of the body.

Infection Risk

Because Berinert is made from human plasma, there is still a very small risk that it may transmit infectious agents, including viruses and, theoretically, the agents of Creutzfeldt-Jakob Disease (CJD) and its variant form (vCJD), even though it has been screened.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects.

Before taking this medicine

Absolute Contraindications

You should not use Berinert if you have ever had a life-threatening allergic reaction to a complement C1 esterase inhibitor.

Caution Needed

Before receiving Berinert, tell your healthcare provider if you have ever had:

• A stroke or blood clot;
• Heart problems
• An “in-dwelling” catheter.

Tell your doctor if you are pregnant or breastfeeding.

Berinert is made from donated human plasma and may contain viruses or other infectious agents. Donated plasma is tested and treated to reduce the risk of contamination, but there is still a small possibility it could transmit disease. Ask your doctor about any possible risks.

HAE Attacks: What to Do

If you have been trained to self-administer Berinert, immediately prepare the prescribed dose at the first symptoms of an attack. Seek immediate medical attention and do not begin to self-administer if an HAE attack has progressed to a point where you will be unable to prepare or administer a dose of Berinert.

• If you self-administer to treat a laryngeal attack, immediately seek medical attention afterward.
• If you self-administer for an abdominal attack, inform your physician so that other possible causes can be ruled out.
• Call your doctor right away if swelling is not controlled after using Berinert.

Dosage and Administration

Standard Dose of Berinert for Acute HAE Attacks

• All ages: 20 units per kilogram of body weight
• Administration route: Intravenous (IV) injection
• Infusion rate: Approximately 4 mL per minute.

How to Administer Berinert at Home

Before You Begin

Berinert can be self-administered at home after proper training from your healthcare provider. Never attempt administration without receiving complete instructions from your doctor or nurse on:

• Proper injection technique
• Safe handling and disposal of medical supplies
• Recognition of adverse reactions

Always read the complete package insert and patient information guide before use.

Step-by-Step Preparation

Mixing Instructions

Berinert comes as a lyophilized powder (freeze-dried) that requires reconstitution before use:

1. Gather supplies: powder vial, diluent (sterile water), transfer needle, and IV supplies
2. Mix carefully: Add diluent to powder vial using proper sterile technique
3. Swirl gently: Rotate the vial slowly to dissolve. Do not shake (shaking can damage the protein)
4. Inspect solution: Final mixture should be clear and colorless
   • Do not use if cloudy, discolored, or contains particles
   • Contact your pharmacy for a replacement.

Single-Use Vial Policy

• Each vial is for one-time use only
• Discard any remaining medication after administration
• No preservatives: Once punctured, use immediately or discard.

Safety and Disposal Guidelines

Sharps and Medical Waste Disposal

• Use each needle and syringe only once
• Place all sharps in an FDA-approved, puncture-resistant container
• Follow local and state regulations for medical waste disposal
• Keep disposal containers away from children and pets
• Ask your pharmacist for sharps container recommendations.

When to Contact Your Healthcare Provider

• Difficulty with the administration technique
• Questions about preparation or storage
• Cloudy or discolored medication
• Any concerns about side effects.

What happens if I miss a dose?

Call your doctor for instructions if you miss a dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What should I avoid after using Berinert?

Follow your doctor’s instructions about any restrictions on food, beverages, or activity.

What other drugs will affect Berinert?

Tell your doctor about all your other medicines, especially:

• testosterone; or
• birth control pills.

This list is not complete. Other drugs may interact with complement C1 esterase inhibitors, including prescription and over-the-counter medicines, vitamins, and herbal products.

Storage

Unmixed Powder Storage

• Refrigerate (preferred) or store at controlled room temperature
• Protect from light
• Do not freeze
• Check expiration date before each use

Mixed Solution Storage

• Best practice: Use immediately after reconstitution
• Alternative: Room temperature storage up to 8 hours maximum

Berinert ingredients

Each Berinert vial contains 500 IU of C1 esterase inhibitor as a lyophilized concentrate for reconstitution with 10 mL of Sterile Water for Injection, USP provided.

Who makes Berinert?

Berinert is manufactured by CSL Behring, a global biopharmaceutical company specializing in plasma-derived and recombinant therapeutic products.

CSL Behring is headquartered in King of Prussia, Pennsylvania, USA. CSL Behring is a subsidiary of CSL Limited, which has global headquarters in Melbourne, Australia.

Berinert Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Benlysta is used to treat active systemic lupus erythematosus (SLE) or lupus nephritis (LN) in people 5 years and older, who weigh at least 15 kg (33 lb), and are receiving standard therapy. Benlysta is a monoclonal antibody given by injection every 2 to 4 weeks. Clinical trials show that when Benlysta is combined with other lupus medicines, it reduces disease activity more effectively than other medicines alone.

• Benlysta is not recommended for severe active central nervous system lupus because it has not been studied in this population.

Benlysta (belimumab) first gained FDA approval on March 9, 2011, and was the first lupus treatment specifically designed to target the underlying autoimmune process that causes lupus. 

How Does Benlysta Work? Mechanism of Action

Benlysta is a BLyS-specific inhibitor that works by blocking the BLyS protein that keeps harmful B-cells alive and active. This reduces B-cell survival and decreases autoantibody production, reducing the overactive immune response behind lupus flares and symptoms such as fatigue and joint pain.

Unlike broad immunosuppressants that affect your entire immune system, Benlysta specifically targets the cells and proteins involved in lupus.

Benlysta (belimumab) belongs to the drug class called B-lymphocyte stimulator (BLyS)-specific inhibitors.

What is the cost of Benlysta?

The list price for Benlysta injection is just over $1,200 per single dose (sold in a 4-pack for just over $4,800), while Benlysta infusion pricing varies based on patient weight.

Most insurance plans cover Benlysta, with over 95% of lupus patients nationwide having coverage.

Eligible commercially insured patients may qualify for the Benlysta Copay program, which can reduce out-of-pocket costs to as little as $0, with up to $9,450 in annual assistance. 

Benlysta Side Effects

Common Side Effects

The most common side effects of Benlysta are:

• Nausea
• Diarrhea
• Fever
• Stuffy or runny nose and sore throat (nasopharyngitis)
• Persistent cough (bronchitis)
• Trouble sleeping (insomnia)
• Leg or arm pain
• Depression
• Headache (migraine)
• Pain, redness, itching, or swelling at the site of the injection (when given subcutaneously).

Serious Side Effects

Benlysta can cause serious side effects, including:

• Progressive multifocal leukoencephalopathy (PML). This 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.

See also Warnings below.

These are not all the possible side effects of Benlysta. Call your doctor for medical advice about side effects.

Warnings

Immunosuppressive agents, including Benlysta, can cause serious side effects. Some of these side effects may cause death. 

Benlysta may increase the risk of infection, some of which may be serious, leading to hospitalization or death. Benlysta should be used with caution in patients with severe or chronic infections. Your healthcare provider may withhold your treatment with Benlysta if you develop a new infection during treatment. Tell your healthcare provider right away if you have any of the following symptoms of an infection:

• Fever
• Urinating often
• Chills
• Coughing up mucus
• Pain or burning with urination
• Warm, red, or painful skin or sores on your body.

Should not be given to people with a history of serious hypersensitivity reactions to Benlysta, belimumab, or any of the ingredients in the formulation. Serious hypersensitivity reactions, including anaphylaxis and infusion-related 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 intravenously 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 a benlysta infusion:

• Itching
• Low blood pressure
• Swelling of the face, lips, mouth, tongue, or throat
• Dizziness or fainting
• Headache
• Trouble breathing
• Nausea
• Anxiousness
• Skin rash.

Symptoms of mental health problems, including suicidal thoughts and actions, can occur with Benlysta. Tell your healthcare provider right away if you have any of the following symptoms:

• 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.

Before Receiving Benlysta

Absolute Contraindications

Do not receive Benlysta if you have previously had an anaphylactic reaction to Benlysta.

Caution Needed

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.
• 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 or monoclonal antibodies
• Have or have had any type of cancer
• Are pregnant or plan to become pregnant
• Are breastfeeding or plan to breastfeed.

Pregnancy

It is not known if Benlysta will harm an unborn baby. You should talk to your healthcare provider about whether to prevent pregnancy while on Benlysta.

If you choose to prevent pregnancy, 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.
• The purpose of this registry is to collect information about the health of you and your baby.

Breastfeeding

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.

How will I receive Benlysta?

Benlysta is available as IV infusions at a healthcare facility every 2-4 weeks, or subcutaneous injections for home use weekly or fortnightly.

• Both are equally effective; your doctor will recommend the best option.

How is a Benlysta infusion given?

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.

How is a Benlysta injection given?

Your healthcare provider will tell you how often and how much of Benlysta you should use. Use Benlysta exactly as your healthcare provider tells you to.

• Read the Instructions for Use that comes with your medicine for instructions about the right way to give Benlysta injections at home.
• Benlysta may be prescribed as a single-dose autoinjector or as a single-dose prefilled syringe.
  • The single-dose autoinjector is for use in adults and children 5 years of age and older.
  • The single-dose prefilled syringe is for use in adults 18 years of age and older.
  • For children under 10 years of age, Benlysta must be given by a healthcare provider or a trained caregiver.
• Remove from the refrigerator and allow it to reach room temperature for 30 minutes.
• Benlysta is injected under the skin (subcutaneously) of your stomach (abdomen) or thigh.
• Rotate injection sites
• Avoid skin that is bruised, tender, red, or hard.
• Use Benlysta on the same day each week or the same day every 2 weeks, as your healthcare provider tells you.

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.

What Happens if I Miss a Dose?

If you miss your subcutaneous 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 dosing based on the new day injected. In case you are not sure when to inject Benlysta, call your healthcare provider.

Call your doctor for instructions if you miss an appointment for your IV Benlysta infusion.

Dosing Information

Intravenous Dosing of Benlysta for Active SLE or Lupus Nephritis

• 10 mg/kg at 2-week intervals for the first 3 doses and at 4-week intervals thereafter.
• Administer over 1 hour.
• Consider prophylactic premedications for infusion reactions and hypersensitivity reactions.

Subcutaneous Dosing of Benlysta for Active SLE or Lupus Nephritis

Active SLE:

• Adults: 200 mg once weekly
• Pediatric patients (≥40 kg): 200 mg once weekly
• Pediatric patients (15 kg to <40 kg): 200 mg every 2 weeks.

Active Lupus Nephritis:

• Adults: 400 mg once weekly for 4 doses, then 200 mg once weekly
• Pediatric patients (≥40 kg): 400 mg once weekly for 4 doses, then 200 mg once weekly
• Pediatric patients (15 kg to <40 kg): 200 mg once weekly for 4 doses, then 200 mg every 2 weeks.

Note: The 400 mg dose requires two 200 mg injections. Prefilled syringes have not been studied in children under 18 years.

How Long Until Benlysta Works?

Most patients improve within 2-6 months, though responses vary:

• Some notice reduced fatigue and joint pain as early as 8 weeks
• Most begin seeing improvements in lupus symptoms within 2-6 months
• Full benefits may take up to 12 months to develop

Continue treatment as prescribed, even without immediate results, because Benlysta works gradually to suppress your overactive immune response.

What to Avoid While Taking Benlysta

Live Vaccines

Do not receive live vaccines while taking Benlysta, as they may not work properly and could cause infection. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, chickenpox, shingles, and the nasal flu vaccine. Inactivated vaccines like the flu injection are generally safe and recommended. Always discuss vaccination plans with your healthcare provider.

Sick Contacts

Avoid close contact with people who are sick or have infections, as Benlysta may weaken your immune system.

Drug Interactions

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take:

• Other biologics, such as rituximab. Research does not support using Benlysta with other biologics due to increased risk of serious infections and reactions.

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.

Benlysta J Code

Benlysta J code is J0490 (Injection, belimumab, 10 mg).

Storage Instructions

Store autoinjectors and prefilled syringes at 36°F to 46°F (2°C to 8°C) until use and keep in their original carton to protect from light until use.

• Do not freeze
• Do not shake
• Avoid exposure to heat

Do not use Benlysta if it has been left out of the refrigerator for more than 12 hours.

Benlysta Ingredients

Active ingredient: belimumab

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

Inactive ingredients (SC): L-arginine hydrochloride, L-histidine, L-histidine monohydrochloride, polysorbate 80, sodium chloride

Available as:

• Intravenous (IV): Single-dose vial: 120 mg or 400 mg lyophilized powder for reconstitution
• Subcutaneous (SC): Prefilled syringe: 200 mg/mL (adults 18+) and autoinjector: 200 mg/mL (ages 5+)

Manufacturer

Benlysta is made by GlaxoSmithKline LLC, Philadelphia, PA 19104.

Frequently Asked Questions

Is Benlysta a chemotherapy drug?

No. Benlysta is a targeted biologic therapy that specifically blocks the BLyS protein involved in lupus. Unlike chemotherapy drugs that kill rapidly dividing cells throughout the body, Benlysta selectively reduces overactive B-cells without the widespread cellular damage associated with chemotherapy.

Can I travel while taking Benlysta?

Yes, you can travel while receiving Benlysta, but you will need to plan ahead. 

• Subcutaneous Benlysta injections:
  • Bring enough medication plus extra for delays
  • Pack in carry-on luggage with a cooling pack (not frozen)
  • Bring a prescription and a doctor’s letter
  • Research medication import requirements for international destinations.
• Intravenous Benlysta Infusions:
  • Coordinate with a healthcare provider to find infusion centers at your destination
  • Consider adjusting the dosing schedule around travel dates.

Will Benlysta cure my lupus?

No, Benlysta will not cure Lupus. However, Benlysta can significantly help manage lupus by reducing disease activity, decreasing frequency and severity of flares, improving symptoms like fatigue and joint pain, potentially slowing organ damage, and improving quality of life.

Can I drink alcohol while taking Benlysta?

There are no specific restrictions on alcohol with Benlysta. However, other lupus medications (like methotrexate or NSAIDs) that you may be taking may interact with alcohol. Alcohol can also worsen lupus symptoms such as fatigue and depression and impair immune function, increasing infection risk.

Talk to your healthcare provider about drinking alcohol with Benlysta. 

Benlysta Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for Benlysta.Benlysta (belimumab) – GlaxoSmithKline LLC