Frequently Asked Questions Questions about Berinert? See what other healthcare professionals have asked and how their questions have been answered.

Hereditary Angioedema FAQ

What is hereditary angioedema (HAE)?

HAE is a rare, inherited disease that results in a quantitative and/or qualitative deficiency in C1 esterase inhibitor (C1-INH), the primary regulator of inflammation and vascular permeability. The disease affects only about 1:10,000 to 1:50,000 individuals.2, 3 As a result of the deficiency, people living with HAE develop acute, recurrent episodes of localized edema, which may occur in the extremities, abdomen, face, and throat.4

What are the typical signs and symptoms observed in patients with HAE?

HAE can produce episodes of nonpitting, nonerythematous swelling in the abdomen, face, and throat. The number of episodes an individual may experience is unpredictable. Some people experience weekly attacks, while others may go years without an attack.7 Laryngeal edema poses the greatest risk for patients with HAE, due to the chance of asphyxiation.7

The swelling associated with an attack often gets worse over a period of 12 hours to 24 hours, and typically resolves within 72 hours. However, symptoms can last up to five days.4, 7 Unlike allergic reactions, there is no itching or redness with HAE.2, 4 In addition, patients with abdominal swelling often experience severe abdominal pain and nausea, which can be accompanied by vomiting and diarrhea.7, 9

HAE episodes are usually asymmetrical and localized to a single area of the body, but simultaneous or closely spaced attacks can also occur.4, 5 Attacks may be migratory, starting in one location and then spreading to another before resolving. Migratory attacks may spread from site to site over the course of a few days.2, 5

How can I differentiate between HAE and conditions that present with similar symptoms?

HAE is often misdiagnosed because its symptoms mimic those of more common conditions that result in angioedema. Misdiagnosis is more likely if no family history is available. However, HAE can be confirmed with proper blood tests to evaluate C4 serum concentration and C1-INH function. 5

HAE patients are often subjected to nonessential medical procedures, such as laparoscopy; ineffective treatments, such as administration of antihistamines; and/or unnecessary psychiatric referrals (due to unexplained or recurrent abdominal pain. 5

HAE is rare, but can be fatal if not properly diagnosed.

Ask your patients the 8 questions below. Three or more positive answers may suggest a diagnosis of HAE, and testing is recommended.

Remember these 8 to differentiate:

YES NO
1. Unexplained edema?15
2. Asymmetric swelling attacks to the extremities?7
3. Unexplained abdominal pain?9,a
4. Recurrent attacks?15
5. Family history of similar episodes?8,b
6. Symptoms (eg, fatigue, tingling, or nausea) signaling the onset of an attack?16
7. Antihistamines, epinephrine, or corticosteroids provide little relief?7
8. Angioedema without urticaria?1

a The majority of patients with HAE will have abdominal attacks that cause pain, nausea, vomiting, and/or diarrhea.9
b Up to 75% of patients will have a positive family history for HAE; the remaining 25% of patients may develop de novo mutations.8

Berinert FAQ

Which types of HAE does Berinert treat?

Berinert treats the two most common types of HAE (Type I and Type II). In Type I HAE, the body does not produce enough C1-1NH. Approximately 85% of people living with the disease have Type I.2 In Type II HAE, the body produces C1- INH that does not function correctly.2 Type III is a very rare form of HAE.

How does Berinert treat HAE?

Administration of Berinert to patients with C1 esterase inhibitor deficiency replaces the missing or malfunctioning protein in patients.

Berinert is the only C1 esterase inhibitor (C1-INH) approved for on-demand treatment of acute abdominal, facial, or laryngeal attacks of hereditary angioedema (HAE) in adults and pediatrics. The safety and efficacy of Berinert for prophylactic therapy have not been established.

Berinert is approved for patient self-administration after proper training by a healthcare professional.

How fast does Berinert provide relief?

Berinert delivers fast relief:

Berinert Median Time to Onset of Symptoms Relief Chart

In clinical trial, median time to onset of relief of abdominal or facial attack is 48 minutes; median time to complete relief is 4.9 hours.*

In clinical trial, median time to onset of relief of laryngeal attack is 15 minutes; median time to complete relief is 8.4 hours.

*In clinical trial, onset of relief was experienced within 4 hours by 69.8% of treatment group and 42.9% of placebo group. For subjects who did not respond within that time frame, study design allowed for use of rescue medication as follows: placebo for 20 IU/kg body weight Berinert treatment group and 20 IU/kg body weight Berinert for placebo group.

How does on-demand treatment benefit my patients?

On-demand treatment helps patients take control of their HAE by treating at the first sign of an HAE attack, which can occur suddenly, frequently, and without warning.

If patients have no other option besides receiving treatment in a hospital, there could be delays in treatment, or inappropriate or insufficient treatment of an HAE attack. This contributes to the morbidity and social and economic disadvantage associated with HAE. All patients should, therefore, be considered for training in self-administration of on-demand medications.11

Patients might notice certain symptoms that signal the onset of an attack. These warning signs can prompt early treatment—and early treatment can help reduce the time to relief. After proper training from a healthcare professional or specialty pharmacy infusion nurse, patients are better prepared to recognize early symptoms and self-administer Berinert at the first sign of an HAE attack. Having a fast and reliable on-demand treatment plan can help put them in control of their HAE and increase their independence.1

All patients should have an on-demand treatment plan, even if they are on prophylactic therapy. Current prophylactic therapies are not 100% effective and breakthrough attacks may occur. Even in cases where patients experience 2 to 4 attacks per month, patients may be able to better manage their HAE by treating each attack at the first sign with Berinert.11

What is the mechanism of action for Berinert?

C1-INH regulates and prevents the generation of bradykinin through multiple pathways. Although the events that induce attacks of angioedema in HAE patients are not well defined, it has been postulated that increased vascular permeability and the clinical manifestation of HAE attacks may be primarily mediated through contact system activation. Suppression of contact system activation by C1 esterase inhibitor through the inactivation of plasma kallikrein and factor XIIa is thought to modulate this vascular permeability by preventing the generation of bradykinin.

Administration of Berinert to patients with C1 esterase inhibitor deficiency replaces the missing or malfunctioning protein in patients.

Berinert replaces the missing C1-INH protein in multiple pathways. C1-INH exerts its effect by acting as a brake on target proteases in multiple systems, including the complement system, kallikrein-kinin system (KKS), fibrinolytic system, and coagulation cascade. By preventing the initial fall of various “dominoes” early in these cascades, C1-INH inhibits the production of bradykinin, a potent mediator of vascular permeability that occurs downstream in the KKS. Without this regulation, individuals with hereditary angioedema develop spontaneous episodes of localized cutaneous or mucous membrane edema.5, 6, 12

Taking a closer look, C1-INH has a reactive loop, which attracts and traps the target protease. Once the protease is trapped, the chain is cleaved and the C1-INH molecule springs closed like a mousetrap, forming a covalent bond with the enzyme.5

What is the demonstrated efficacy of Berinert in clinical trials?

In the I.M.P.A.C.T. 1 study, a randomized, double-blind, placebo-controlled study, Berinert was shown to be safe and effective for the treatment of acute abdominal or facial attacks of hereditary angioedema (HAE) in adults and adolescents. The safety and efficacy of Berinert for prophylactic therapy have not been established.12

In the study, the median time to onset of symptom relief was significantly shorter with Berinert than with placebo.12 In addition, the proportion of patients with worsened intensity of clinical HAE abdominal and facial symptoms between 2 hours and 4 hours after the start of treatment was significantly lower with Berinert than with placebo.12

In the I.M.P.A.C.T. 2 study, a non-placebo extension study, median time to onset of relief in patients being treated for laryngeal HAE attacks was 15 minutes.

Has the safety of Berinert been evaluated in pediatric patients?

Yes. A US-European Registry Study (N=18, age range 5–11 years) demonstrated safety similar to that observed in adults.

Safety and efficacy were also evaluated in placebo-controlled and open-label extension studies (N=12, age range 10–16 years).

What is the half-life of Berinert?

The half-life of Berinert is 16.7 hours in pediatrics and 18.4 hours in adults.

What were the adverse reactions to Berinert in clinical trials?

No serious adverse events or adverse events leading to discontinuation of treatment occurred within 4 hours after study treatment.12

Adverse reactions occurring up to 4 hours after initial infusion in more than 4% of subjects, irrespective of causality, included: nausea, dysgeusia, abdominal pain.

† The study protocol specified that adverse events that began within 72 hours of blinded study medication administration, irrespective of the investigator's assessment of causality, were to be classified as at least possibly related to study medication (ie, adverse reactions).

‡ The following abdominal symptoms were identified in the protocol as associated with HAE abdominal attacks: abdominal pain, bloating, cramps, nausea, vomiting, and diarrhea.

What is the manufacturing process for Berinert?

Berinert is made from human blood plasma. Berinert and the human plasma from which it's made have been processed and screened to remove or inactivate known viruses. The screening steps include:

  • Pasteurization (heat treatment for 10 hours) in aqueous solution
  • Hydrophobic interaction chromatography
  • Virus nanofiltration
    • Because Berinert is made from human plasma, the risk that it may transmit infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated.

Berinert Infusion FAQ

How is Berinert administered?

Berinert is a lyophilized concentrate (500 IU) that requires reconstitution with 10 mL of sterile water (included). No refrigeration is required. Treatment is given as an intravenous infusion, via self-administration or by a healthcare professional.

Each Berinert kit consists of 1 carton containing 1 single-use vial of Berinert that must be used within 8 hours of reconstitution, any extra must be discarded, one 10-mL vial of diluent (sterile water), 1 Mix2Vial® transfer set, and 1 alcohol swab.

The Mix2Vial® transfer set automatically transfers the right amount of diluent into the Berinert vial. For step-by-step instructions on how to prepare Berinert for administration, please see the self-administration step-by-step guide, video, or full prescribing information for Berinert.

What is the recommended Berinert dosage?

The recommended Berinert dosage is 20 units (IU) per kilogram body weight, with a recommended infusion rate of 4 mL/minute. For example, a 70-kg patient would require 1400 IU, infused over 7 minutes.

This individualized weight-based dosing enables you to optimize the correct infusion amount for each patient. No dose adjustments are required for pediatric patients. Dosing is based on weight for all patients on Berinert.

How does room-temperature storage for Berinert benefit my patients?

Room-temperature storage for Berinert means that convenient relief is ready anytime, anywhere. Berinert is ready to use, easy to transport, and can be kept at home or any place where the temperature is between 36°F and 77°F.

Berinert has a 30-month shelf life, which will help minimize your patients' concerns about maintaining an emergency supply. Specialty and hospital pharmacists can rest assured that the product will not lose potency or require replacement during storage.

Where can I get information on training my patients to self-administer Berinert?

Before your patients self-administer Berinert, it is important that they undergo training from a healthcare professional. It is also vital for patients to recognize symptoms of their HAE attacks, learn how to monitor their symptoms, and treat their attacks. BEN can help arrange training for your patients through qualified specialty pharmacy providers and can provide training materials as well.

If a patient self-administers to treat a laryngeal attack, he or she should immediately seek medical attention afterward.

Berinert Billing and Resources FAQ

What is the Berinert Expert Network (B.E.N.®)?

Berinert Expert Network (B.E.N.) is a comprehensive support network for healthcare professionals and patients who depend on Berinert. B.E.N. provides access to all of the individualized support programs, enabling healthcare professionals to receive support from a single phone call:

  • Starting a patient on Berinert
  • Insurance coverage, verification, and appeals
  • Access to Berinert patient financial assistance programs
  • Coding and billing assistance
  • Authorized distributor information
  • Information about HAE
  • Connection to the U.S. Hereditary Angioedema Association (HAEA)

Is there financial assistance to help my patients afford Berinert?

Living with HAE can be a heavy burden to bear, but it shouldn't also be a financial burden. Help your patients take control of their HAE attacks and the cost of treatment. The Berinert Co-Pay BENefit* is a financial assistance program designed to cover their eligible out-of-pocket co-pay expenses—up to $12,000 per year.

*The Berinert Co-Pay BENefit is available for new or existing Berinert patients. Patients MUST be 12 years of age or older, a U.S. resident, and insured in the U.S. Patients covered by state- or federally funded programs, such as Medicare, Medicaid, and Veterans Health Insurance, are NOT eligible.

B.E.N. provides value-added support for patients to assist them in starting their Berinert and affording their therapy.

  • CSL Behring Assurance℠ insurance gap protection program
  • Patient Assistance program for customers who may not be able to afford their medication
  • Berinert Co-Pay BENefit covers up to $12,000 in out-of-pocket treatment expenses

Is there a support network for my HAE patients starting Berinert?

Our B.E.N. P.A.L.S.® (Peer Advocates for Learning and Support) are HAE patients who offer guidance and support to your HAE patient new to Berinert. Your patient receives a helping hand from experienced HAE patients who can help answer nonmedical questions related to their Berinert therapy.

What is the process for starting a new patient on Berinert?

Starting a new patient on Berinert is an easy process, and our B.E.N. Care Coordinators can guide you and your staff the entire way.

The first step is to download the Berinert referral form. Fill it out and fax the form to B.E.N. at 866-415-2162. If you have any questions while completing the Berinert referral form, please contact your local CSL Behring representative, or call B.E.N. at 877-236-4423.

This form begins the process to get Berinert into the hands of the patient and enrolls the patient into the B.E.N. program. A B.E.N. Care Coordinator will be in touch with your office if any additional information is required or any clarification from the patient is necessary.

The B.E.N. Care Coordinators will work quickly to secure insurance approval for the patient and to partner with a specialty pharmacy to provide product and support.

How do I order Berinert?

CSL Behring is dedicated to making Berinert available to patients and healthcare professionals when and where it is needed. Berinert is available via a range of national and regional specialty pharmacies and distributors.

If you need contact information for these organizations, please call B.E.N. toll-free 24/7 at 1-877-BEN-4HAE (1-877-236-4423).

Ready to order Berinert? Download the Berinert Coding Guide. Print a copy of this coding guide and keep it handy when diagnosing and ordering Berinert or when filing insurance claims on behalf of your patients. All codes listed in this guide are for informational purposes and this is not an exhaustive list. Always verify current coding requirements directly with the payer being billed, as government and third-party billing codes may change over time.

What is the CSL Behring commitment to people affected by HAE?

We are a proud supporter of the US Hereditary Angioedema Association (HAEA), a nonprofit patient advocacy organization dedicated to expediting US approval of safer and more effective HAE therapies. The organization provides a wide range of services that include clinical trial placement, physician referrals, education, and individualized patient case management.

CSL Behring is a world leader in specialty biopharmaceuticals and is committed to people around the world with rare and serious conditions, such as hereditary angioedema (HAE). We are dedicated to making a difference in the HAE community through education, services, and other resources for patients and families affected by the condition.

CSL Behring has established the Berinert Expert Network (B.E.N.®), a resource designed to help you and your staff.

We sponsor AllAboutHAE.com, an online resource for the community of HAE patients, families, and healthcare professionals seeking more information about HAE symptoms and living with HAE.

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Important Safety Information

BERINERT®, C1 Esterase Inhibitor (Human), is a plasma-derived concentrate of C1 Esterase Inhibitor (Human), indicated for the treatment of acute abdominal, facial or laryngeal attacks of hereditary angioedema (HAE) in adult and pediatric patients. The safety and efficacy of BERINERT for prophylactic therapy have not been established.

BERINERT is contraindicated in individuals with a history of life-threatening systemic reactions to C1 esterase inhibitor preparations (including anaphylaxis).

Monitor patients for early signs of allergic or hypersensitivity reactions (including hives, generalized urticaria, chest tightness, wheezing, hypotension, and anaphylaxis). If hypersensitivity is suspected, immediately discontinue administration of BERINERT and initiate appropriate treatment. Epinephrine should be immediately available for treatment of acute severe hypersensitivity reactions.

Serious arterial and venous thromboembolic (TE) events have been reported following administration of recommended doses of C1 Esterase Inhibitor (Human) products to patients with HAE. Risk factors may include presence of an indwelling venous catheter/access device; prior history of thrombosis; underlying atherosclerosis; use of oral contraceptives or certain androgens; morbid obesity; and immobility. Weigh benefits/risks before administering to patients with known risk factors for TE events and closely monitor such patients during and after BERINERT administration. TE events also have been reported with C1 Esterase Inhibitor (Human) products when used for unapproved indications at higher than recommended doses.

Appropriately trained patients may self-administer BERINERT upon recognition of an HAE attack. Advise patients to seek medical attention immediately following selfadministration for laryngeal attacks, and to seek medical attention if progress of any attack makes them unable to properly prepare or administer dose of BERINERT.

BERINERT is derived from human plasma. The risk of transmission of infectious agents, including viruses and theoretically, the agents of Creutzfeldt-Jakob Disease (CJD) and its variant form (vCJD), cannot be completely eliminated.

The most serious adverse reaction reported in subjects who received BERINERT in clinical studies was an increase in severity of pain associated with HAE. Dysgeusia was the most common adverse reaction reported in over 4% of subjects and more frequently than in the placebo group.

BERINERT has not been evaluated in pregnant women or nursing mothers, and should be used only if clearly needed. In clinical trials, the half-life of BERINERT was shorter and clearance was faster in children than in adults; the clinical implication of this difference is not known.

Please see full prescribing information for BERINERT, including the patient product information.

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