Berinert

Generic name: complement C1 esterase inhibitor
Drug class: Hereditary angioedema agents

Medically reviewed by  A Ras MD.

What is Berinert?

Berinert is a prescription medicine that is used to treat swelling attacks in people with hereditary angioedema (HAE).

Description

BERINERT is a human plasma-derived, purified, pasteurized, lyophilized concentrate of C1 esterase inhibitor to be reconstituted for intravenous administration. BERINERT is prepared from large pools of human plasma from US donors. The potency of C1 esterase inhibitor is expressed in International Units (IU), which is related to the current WHO Standard for C1 esterase inhibitor products.

C1 esterase inhibitor is a soluble, single-chain glycoprotein containing 478 amino acid residues organized into three beta-sheets and eight or nine alpha-helices.4 The heavily glycosylated molecule has an apparent molecular weight of 105 kD, of which the carbohydrate chains comprise 26% to 35%.5

Each 500 IU vial of reconstituted BERINERT contains 400-625 IU C1 esterase inhibitor, 50 to 80 mg total protein, 85 to 115 mg glycine, 70 to 100 mg sodium chloride, and 25 to 35 mg sodium citrate.

All plasma used in the manufacture of BERINERT is obtained from US donors and is tested using serological assays for hepatitis B surface antigen and antibodies to HIV-1/2 and HCV. Additionally, the plasma is tested with Nucleic Acid Testing (NAT) for HBV, HCV, HIV-1 and HAV and found to be non-reactive (negative). In addition, the plasma is also tested by NAT for Human Parvovirus B19. Only plasma that has passed virus screening is used for production, and the limit for Parvovirus B19 in the fractionation pool is set not to exceed 104 IU of Parvovirus B19 DNA per mL.

The manufacturing process for BERINERT includes multiple steps that reduce the risk of virus transmission. The virus inactivation/reduction capacity consists of three steps:

• Pasteurization in aqueous solution at 60°C for 10 hours
• Hydrophobic interaction chromatography
• Virus filtration (also called nanofiltration) by two filters, 20 nm and 15 nm, in series

Mechanism of Action

C1 esterase inhibitor is a normal constituent of human plasma and belongs to the group of serine protease inhibitors (serpins) that includes antithrombin III, alpha1-protease inhibitor, alpha2-antiplasmin, and heparin cofactor II. As with the other inhibitors in this group, C1 esterase inhibitor has an important inhibiting potential on several of the major cascade systems of the human body, including the complement system, the intrinsic coagulation (contact) system, the fibrinolytic system, and the coagulation cascade. Regulation of these systems is performed through the formation of complexes between the proteinase and the inhibitor, resulting in inactivation of both and consumption of the C1 esterase inhibitor.

C1 esterase inhibitor, which is usually activated during the inflammatory process, inactivates its substrate by covalently binding to the reactive site. C1 esterase inhibitor is the only known inhibitor for the subcomponent of the complement component 1 (C1r), C1s, coagulation factor XIIa, and kallikrein. Additionally, C1 esterase inhibitor is the main inhibitor for coagulation factor XIa of the intrinsic coagulation cascade.

HAE patients have low levels of endogenous or functional C1 esterase inhibitor. Although the events that induce HAE 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.6

Administration of BERINERT to patients with C1 esterase inhibitor deficiency replaces the missing or malfunctioning protein in patients. The plasma concentration of C1 esterase inhibitor in healthy volunteers is approximately 270 mg/L.7

Before taking Berinert, tell your doctor:

• If you are allergic to Berinert; any part of this medicine; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Berinert with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take Berinert?

• Tell all of your health care providers that you take Berinert. This includes your doctors, nurses, pharmacists, and dentists.
• Unsafe allergic effects may rarely happen.
• Keep epinephrine with you at all times.
• Blood clots have happened with Berinert. The chance may be raised if you have a certain type of catheter or device in a vein or if you take certain drugs like estrogens or androgens. The chance may be raised if you have ever had heart or blood vessel disease, stroke, thick blood, or a blood clot. The chance may also be raised if you have not been able to move around for some time. Talk with your doctor.
• This medicine is made from human plasma (part of the blood) and may have viruses that may cause disease. This medicine is screened, tested, and treated to lower the chance that it carries an infection. Talk with the doctor.
• If using Berinert to treat swelling of the face, lips, tongue, or throat, get medical help right away after using it.
• Talk with the doctor before you travel. You will need to bring enough of Berinert for use during travel.
• If your weight changes, talk with your doctor. The dose of Berinert may need to be changed.
• Tell your doctor if you are pregnant, plan on getting pregnant, or are breast-feeding. You will need to talk about the benefits and risks to you and the baby.

How is Berinert best taken?

Use Berinert as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a vein.
• If you will be giving yourself the shot, your doctor or nurse will teach you how to give the shot.
• This medicine needs to be mixed before use. Follow how to mix as you were told by the doctor.
• If stored in a refrigerator, let Berinert come to room temperature before mixing. Do not heat Berinert.
• Do not use if it has been frozen.
• Do not use if the solution is cloudy, leaking, or has particles.
• Do not give if the solution is not clear and colorless.
• Use the dose within 8 hours after mixing.
• Throw away any part left over after the dose is given.
• Throw away needles in a needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow all local rules for getting rid of it. Talk with a doctor or pharmacist if you have any questions.

What do I do if I miss a dose?

• This medicine is used on an as needed basis. Do not use more often than told by the doctor.

What are the side effects of Berinert that I need to call my doctor about immediately?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Very bad dizziness or passing out.
• Change in color of mouth to blue.
• A fast heartbeat.
• Very bad headache.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Call your doctor right away if you have signs of a blood clot like chest pain or pressure; coughing up blood; shortness of breath; swelling, warmth, numbness, change of color, or pain in a leg or arm; or trouble speaking or swallowing.

What are some other side effects of Berinert?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach or throwing up.
• Headache.
• Bad taste in your mouth.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

If overdose is suspected:

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out Berinert?

• Store at room temperature or in a refrigerator. Do not freeze.
• Store in the original container to protect from light.
• After mixing, do not refrigerate or freeze.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.

Label

PRINCIPAL DISPLAY PANEL – 500 IU VIAL LABEL

PRINCIPAL DISPLAY PANEL – KIT CARTON

• NDC 63833-825-02
  One single-dose Vial and Sterile Water for Injection, USP
  500 IU
• C1 Esterase Inhibitor
  (Human)
• BERINERT®
• For Intravenous Use Only.
• Manufactured by:
  CSL Behring GmbH
  35041 Marburg, Germany
  US License No. 1765
  Distributed by:
  CSL Behring LLC
  Kankakee, IL 60901 USA
• CSL Behring

SRC: NLM .