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.

What is Haegarda?

Haegarda is a man-made form of a protein in blood that helps control swelling in the body. People with a condition called Hereditary Angioedema (HAE) do not have enough of this protein. Hereditary Angioedema can cause attacks of swelling and symptoms such as stomach problems or trouble breathing.

Haegarda is an injectable medicine used to prevent swelling and/or painful attacks in patients 6 years of age and older with Hereditary Angioedema.

Haegarda should not be used to treat an acute HAE attack. In case of an acute HAE attack, initiate individualized treatment as discussed with your health care professional.

Warnings

You should not use Haegarda if you have experienced life-threatening immediate hypersensitivity reactions (allergic reactions), including anaphylaxis, to the product.

Before taking this medicine

You should not use Haegarda if have ever had a life-threatening allergic reaction to c1 esterase inhibitor.

To make sure Haegarda is safe for you, tell your doctor if you have:

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

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

Haegarda 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 Haegarda?

Use Haegarda exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets.

Haegarda is injected under the skin. A healthcare provider will give your first dose and may teach you how to properly use the medication by yourself.

Read and carefully follow any Instructions for Use provided with your medicine. Prepare an injection only when you are ready to give it. Ask your doctor or pharmacist if you don’t understand all instructions.

Storing unopened vials: Store in a refrigerator or at cool room temperature and use until expiration date. Protect from light and do not freeze.

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

After mixing Haegarda, use the injection right away or store at room temperature and use within 8 hours.

Haegarda 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.

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.

Dosing information

Usual Adult Dose for Hereditary Angioedema:

Haegarda is intended for self-administration after reconstitution at a dose of 60 International Units (IU) per kg body weight by subcutaneous (S.C.) injection twice weekly (every 3 or 4 days). The patient or caregiver should be trained on how to administer the subcutaneous injection.

Use: routine prophylaxis to prevent Hereditary Angioedema (HAE) attacks 

Usual Pediatric Dose for Hereditary Angioedema:

Haegarda is intended for self-administration after reconstitution at a dose of 60 International Units (IU) per kg body weight by subcutaneous (S.C.) injection twice weekly (every 3 or 4 days). The patient or caregiver should be trained on how to administer the subcutaneous injection.

Use: routine prophylaxis to prevent Hereditary Angioedema (HAE) attacks in patients 6 years of age and older

What happens if I miss a dose?

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

Keep Haegarda 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 Haegarda?

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

Haegarda side effects

Get emergency medical help if you have signs of an allergic reaction to Haegarda: 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 Haegarda 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. You may report side effects to FDA .

What other drugs will affect Haegarda?

Tell your doctor about all your other medicines, especially:

• testosterone; or
• birth control pills.

What is Kalbitor?

Kalbitor is used to treat attacks of hereditary angioedema (an immune system disorder). This medicine is for use in adults and children at least 12 years old.

Kalbitor is not a cure for hereditary angioedema.

Kalbitor may also be used for other purposes not listed in this medication guide.

Warnings

You should not be treated with Kalbitor if you are allergic to ecallantide. Ecallantide can cause a serious allergic reaction within 1 hour after receiving an injection. Symptoms include wheezing, cough, trouble breathing or swallowing, itching, hives, dizziness, fainting, or swelling in your face or throat Tell your doctor if you have a history of any type of allergy.

In an emergency situation it may not be possible to tell your caregivers about your health conditions. Make sure any doctor caring for you afterward knows you have received this medicine.

Before receiving this medicine

You should not be treated with Kalbitor if you are allergic to ecallantide.

If possible before you receive Kalbitor, tell your doctor if you have a history of any type of allergy.

It is not known whether Kalbitor will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether ecallantide passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

In an emergency situation it may not be possible to tell your caregivers if you are pregnant or breast-feeding. Make sure any doctor caring for your pregnancy or your baby knows you have received this medicine.

How is Kalbitor given?

Kalbitor is injected under the skin. A healthcare provider will give you this injection.

You will be watched closely after receiving your injection, to make sure you do not have an allergic reaction to the medication.

Kalbitor is usually given in 3 separate injections. If you still have symptoms of the angioedema attack, more injections may be given within 24 hours.

Dosing information

Usual Adult Dose for Hereditary Angioedema:

30 mg subcutaneously in three 10 mg injections; may repeat an additional 30 mg within 24 hours if attack persists.

Usual Pediatric Dose for Hereditary Angioedema:

12 years and older: 30 mg subcutaneously in three 10 mg injections; may repeat an additional 30 mg within 24 hours if attack persists.

What happens if I miss a dose?

Because you will receive Kalbitor in a medical setting, you are not likely to miss a dose.

What happens if I overdose?

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur and would be treated quickly.

What should I avoid after receiving Kalbitor?

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

Kalbitor side effects

Tell your caregivers right away if you have any of these signs of an allergic reaction to Kalbitor within 1 hour after receiving your injection:

• chest pain or tightness, fast or weak heartbeat;
• wheezing, cough, throat irritation, trouble breathing;
• hoarse voice, tight feeling in your throat, trouble swallowing;
• swelling of your lips, tongue, or throat;
• swelling or redness in your face;
• itching, rash, or hives;
• flushing (warmth, redness, or tingly feeling);
• sneezing, runny or stuffy nose; or
• dizziness, feeling like you might pass out.

An allergic reaction to ecallantide can cause symptoms that are similar to the signs of hereditary angioedema. Your caregivers will watch you closely and will quickly treat an allergic reaction to ecallantide.

Common Kalbitor side effects may include:

• headache;
• nausea, diarrhea;
• fever;
• stuffy nose, sore throat; or
• skin reactions where the medicine was injected (redness, rash, itching, bruising, swelling).

What is lanadelumab?

Lanadelumab (Takhzyro) is used to prevent hereditary angioedema (HAE), lanadelumab helps to reduce the number and severity of hereditary angioedema attacks. Lanadelumab works by lowering the activity of a protein called kallikrein which helps to prevent the swelling and related symptoms of HAE. Lanadelumab is usually given every two weeks as an injection under the skin using a ready-to-use, prefilled syringe. The dose depends on age and can change to every 4 weeks if symptoms have improved.

Hereditary angioedema is a rare condition that causes rapid attacks of swelling in areas under the skin around the face, arms, legs, and also the throat, which can be life-threatening if it blocks off the airways. People with hereditary angioedema have high levels of a protein called bradykinin, which makes fluid leak fluid into the surrounding tissue, causing swelling attacks. Lanadelumab-flyo works by blocking another protein in the blood called ‘kallikrein’, which in turn reduces the level of bradykinin, which helps to prevent the swelling and symptoms of angioedema.

Lanadelumab approval by the FDA was originally on February 3, 2023, and it is now approved to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 2 years and older. FDA approval was supported by data from HELP Study, the HELP OLE Study and the Phase 3 SPRING Study (NCT SHP643-301).

Lanadelumab is a plasma kallikrein inhibitor (monoclonal antibody).

Before taking this medicine

You should not use lanadelumab if you are allergic to it or any of the inactive ingredients. For a full list of ingredients in Takhzyro see the Ingredients section at the bottom of this page.

Lanadelumab is not approved for use by anyone younger than 2 years old.

This medicine can affect the results of certain medical tests. Tell any doctor who treats you that you are using lanadelumab.

Pregnancy

• If you are pregnant or planning to become pregnant. It is not known if lanadelumab can harm your unborn baby.
• Tell your doctor if you are pregnant or plan to become pregnant.

Breastfeeding

• If you are breastfeeding or plan to breastfeed. It is not known if lanadelumab passes into your breastmilk.
• Talk to your healthcare provider about the best way to feed your baby while using this medicine.

How should I use lanadelumab?

Use this medicine exactly as it was prescribed for you. Follow all directions on your prescription label and read all medication guides or instruction sheets.

Your healthcare provider should show you or your caregiver, how to prepare and inject your dose of lanadelumab before you inject yourself for the first time. Do not try to inject this medicine unless you have been trained by your healthcare provider.

• Take the medicine out of the refrigerator and let it reach room temperature for 15 minutes before injecting your dose.
• Do not shake.
• If using the Single-Dose Vial (bottle) prepare your injection only when you are ready to give it within the next 2 hours.
• Lanadelumab is given as an injection under your skin (subcutaneous) by healthcare provider, a caregiver or yourself.
• For detailed instructions with diagrams on how to use the prefilled syringe or single-dose glass vial
• Each Single-Dose Vial of this medicine is for one use only. Throw it 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.

Lanadelumab dosing information

Usual dose for adult and pediatric patients 12 years and older for hereditary angioedema:

• Initial dose: 300 mg subcutaneously once every 2 weeks.
• Maintenance dose: a 4-week dosing interval may be considered if the patient is well-controlled (e.g., attack free) for more than 6 months.

Usual dose for pediatric patients 6 years to less than 12 years old for hereditary angioedema:

• Initial dose: 150 mg subcutaneously once every 2 weeks.
• Maintenance dose: a 4-week dosing interval may be considered if the patient is well-controlled (e.g., attack free) for more than 6 months.

Usual dose for pediatric patients 2 years to less than 6 years old dose for hereditary angioedema:

• Dose: 150 mg administered subcutaneously every 4 weeks.
• Self-injection is not recommended in children 2 years to less than 12 years.

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 .

Lanadelumab side effects

The most common lanadelumab side effects are:

• injection site reactions (pain, redness, and bruising)
• upper respiratory infections
• headache
• rash
• dizziness
• diarrhea
• muscle aches.

Lanadelumab may cause serious side effects, including allergic reactions. Allergic reactions may happen with lanadelumab. Call your healthcare provider or get emergency help right away if you have any of the following symptoms of allergic reactions:

• wheezing
• difficulty breathing
• chest tightness
• fast heartbeat
• faintness
• rash
• hives

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

What other drugs will affect lanadelumab?

Other drugs may affect lanadelumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Lanadelumab Package Insert

Review the Takhzyro Package Insert for more detailed information about lanadelumab. Discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

Ingredients

Active Ingredient: lanadelumab-flyo

Inactive Ingredients: citric acid monohydrate, histidine, sodium chloride, polysorbate 80 and sodium phosphate, dibasic, dihytrate.

Storage

• Store the prefilled syringes and vials refrigerated at 36°F to 46°F (2°C to 8°C).
• Do not freeze.
• Do not shake.
• Keep the prefilled syringe and vial in the original carton to protect from light.’

Manufacturer

• Takeda Pharmaceuticals U.S.A., Inc.
• Lexington, MA 02421.

Lanadelumab 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 lanadelumab.Takhzyro (lanadelumab-flyo) – Takeda Pharmaceuticals U.S.A., Inc.

What is Orladeyo?

Orladeyo capsules are used to prevent attacks of hereditary angioedema (HAE), in adults and children aged 12 years and older. Orladeyo works by blocking plasma kallikrein, an enzyme that leads to the production of bradykinin, a substance that causes swelling and pain in hereditary angioedema.

Orladeyo is a once-daily capsule used as a preventative treatment for hereditary angioedema.

Hereditary angioedema is a rare and potentially life-threatening genetic disorder that causes an attack of rapid swelling in the face, throat, arms, legs, or around the abdomen. 

Orladeyo FDA approval was granted to BioCryst Pharmaceuticals, Inc., on December 3, 2020. Orladeyo FDA approval is for the prevention of hereditary angioedema (HAE) attacks in adults and pediatric patients 12 years and older. 

Orladeyo is not used for treating a hereditary angioedema attack that has already begun.

How does Orladeyo work?

In hereditary angioedema, a C1 esterase deficiency leads to the overactivation of plasma kallikrein, which causes high levels of bradykinin, a protein that causes blood vessels to widen and leak, and results in swelling and pain of angioedema attacks.

Orladeyo mechanism of action is by binding to plasma kallikrein which controls excess bradykinin generation, reducing the risk of angioedema attacks

Orladeyo (berotralstat) is from a class of medicines called kallikrein inhibitors.

How well does Orladeyo work?

Orladeyo was shown to be effective in treating hereditary angioedema, with positive results from a 48-week Clinical trial APeX-2 (NCT03485911), which demonstrated that Orladeyo patients had a:

• 67% reduction in hereditary angioedema attack rate using 150mg daily
• 52% reduction in hereditary angioedema attack rate using 110mg daily

Orladeyo side effects

Common Orladeyo side effects 

Common Orladeyo side effects may include: 

• Stomach pain (10%)
• Indigestion (10%)
• Vomiting (10%)
• Diarrhea (10%)
• Back pain (2%) 

These common side effects occurred in 10% or more of Orladeyo patients taking 110mg in the  24-week (Part 1) clinical trial called Trial 1.  Gastrointestinal side effects including abdominal pain, vomiting, and diarrhea occurred more frequently in patients receiving Orladeyo 150 mg. These side effects usually occurred when first starting treatment and became less frequent over time.

Serious side effects

Allergic reaction. Get emergency medical help if you have signs of an allergic reaction to this medicine with symptoms of hives; difficulty breathing; and swelling of your face, lips, tongue, or throat.

QT prolongation. Taking more than one capsule a day may cause serious side effects of heart rhythm problems. QT prolongation is a heart rhythm problem that can happen in people who take more than one capsule a day. This condition can cause an abnormal heartbeat. Do not take more than one capsule a day.

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

Warnings

QT Prolongation Risk: An increase in QT prolongation can occur at dosages higher than the recommended 150 mg once daily dosage. 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 disease
• Kidney Disease (or if you are on dialysis)
• Heart rhythm problems.

Orladeyo is not approved for use by anyone younger than 12 years old.

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.

Orladeyo Dosing Information

Recommended Orladeyo dosage: One capsule (150 mg) taken orally once daily with food.

Dose adjustment for ongoing GI reactions: Gastrointestinal side effects can occur in some patients. If these side effects persist a reduce dose of 110mg once daily with food may be considered.

Dose adjustment for hepatic impairment:

• No adjustment is required for mild hepatic impairment (Child-Pugh Class A)
• For Patients with moderate or severe hepatic impairment (Child-Pugh B or C)  the recommended dose is one 110 mg capsule taken orally once daily with food

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 other drugs will affect this medicine?

Orladeyo 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.

What is Ruconest?

Ruconest is a manmade form of the c1 esterase inhibitor protein that occurs naturally in the bloodstream 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.

Ruconest is an injectable medicine used to treat acute angioedema attacks in in adult and adolescent patients with Hereditary Angioedema.

Ruconest is for use in adults and children who are at least 13 years old.

Warnings

You should not use Ruconest if you are allergic to rabbits or rabbit products (meat, fur, pelt).

You should not use Ruconest if you have experienced life-threatening immediate hypersensitivity reactions, including anaphylaxis, to this medicine or to any other C1 esterase inhibitor product.

Before taking this medicine

You should not use Ruconest if you are allergic to c1 esterase inhibitor, or:

• if you are allergic to rabbits or rabbit products (meat, fur, pelt); or
• if you have ever had a life-threatening allergic reaction to Ruconest or to another C1 esterase inhibitor (such as Berinert or Cinryze).

To make sure Ruconest is safe for you, tell your doctor if you have:

• coronary artery disease (hardened arteries); or
• a history of stroke or blood clot.

This medicine is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether c1 esterase inhibitor passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Ruconest is not approved for use by anyone younger than 13 years old.

How is Ruconest given?

Use Ruconest 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.

Ruconest is injected into a vein through an IV. You may be shown how to use an IV at home. Do not self-inject this medicine if you do not understand how to give the injection and properly dispose of used needles, IV tubing, and other items used to inject the medicine.

Ruconest is a powder medicine that must be mixed with a liquid (diluent) before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medicine. Ask your pharmacist what type of diluent can safely be mixed with this medicine powder.

Wash your hands before mixing the medicine or preparing your injection.

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

After mixing Ruconest, store in the refrigerator and use within 8 hours. Do not freeze.

Mixed medicine should be used right away if you keep it at room temperature.

c1 esterase inhibitor doses are based on weight. You may need to use two vials of Ruconest powder to make up a single dose. Carefully follow all mixing instructions provided with your medicine.

Each single-use vial (bottle) of this medicine is for one use only. Throw away after one use, even if there is still some medicine left in it after injecting your dose.

This medicine must be injected slowly, and the IV infusion should take about 5 minutes to complete.

A single dose of Ruconest is usually enough to treat an angioedema attack. You may need to use a second dose if your symptoms do not get better after just one dose.

Store the unmixed dry powder in a refrigerator or in a dark cool place. Keep the medicine protected from light and do not allow it to freeze. Throw away any unused vial after the expiration date on the label has passed.

What happens if I miss a dose?

Since Ruconest is used when needed, it does not have a daily dosing schedule. Call your doctor promptly if your symptoms do not improve after using this medicine.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

What should I avoid after using Ruconest?

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

Ruconest side effects

Get emergency medical help if you have signs of an allergic reaction to Ruconest: rash or hives; chest tightness, wheezing, difficult breathing; blue-colored lips or gums; fast heartbeats; feeling like you might pass out; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• sudden numbness or weakness (especially on one side of the body);
• sudden severe headache, slurred speech, problems with vision or balance; or
• pain, swelling, warmth, or redness in one or both legs.

Common Ruconest side effects may include:

• headache;
• diarrhea; or
• nausea.

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 Ruconest?

Other drugs may interact with c1 esterase inhibitor, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Ruconest 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 Ruconest.Ruconest (C1 Esterase Inhibitor (Recombinant)) – Pharming Americas BV