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.

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.