Cinryze

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

Medically reviewed by  A Ras MD.

What is Cinryze?

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

Description

CINRYZE (C1 esterase inhibitor [human]) (Freeze-Dried Powder for Reconstitution) is a sterile, stable, lyophilized preparation of C1 esterase inhibitor derived from human plasma. CINRYZE is manufactured from human plasma purified by a combination of filtration and chromatographic procedures. CINRYZE potency is expressed by its C1 esterase inhibitor activity measured with a validated chromogenic assay. 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. One International Unit (IU) corresponds to the amount of C1 esterase inhibitor present in 1 mL of normal plasma.

The specific activity of CINRYZE is 4.0 to 9.0 U/mg protein. The purity is ≥ 90% human C1 esterase inhibitor. Following reconstitution with 5 mL of Sterile Water for Injection, USP, each vial contains approximately 500 IU of functionally active C1 esterase inhibitor, pH 6.6 to 7.4, and an osmolality between 200 to 400 mosmol/kg.

CINRYZE, when reconstituted with 5 mL of Sterile Water for Injection, USP contains the following excipients: 4.1 mg/mL sodium chloride, 21 mg/mL sucrose, 2.6 mg/mL trisodium citrate, 2.0 mg/mL L-Valine, 1.2 mg/mL L-Alanine, and 4.5 mg/mL L-Threonine.

The following manufacturing steps are designed to reduce the risk of viral transmission:

  • Screening donors at U.S. licensed blood collection centers to rule out infection with Human Immunodeficiency Virus (HIV-1/HIV-2), Hepatitis B Virus, or Hepatitis C Virus.
  • Testing plasma pools by in-process NAT for parvovirus B19 via minipool testing and the limit of B19 in the manufacturing pool is set not to exceed 104 IU of B19 DNA per mL.
  • Use of two independent viral reduction steps in the manufacture of CINRYZE: pasteurization (heat treatment at 60°C for 10 hours in solution with stabilizers) and nano filtration through two sequential 15 nm filters.

These viral reduction steps, along with a step in the manufacturing process, PEG precipitation, have been validated in a series of in vitro experiments for their capacity to inactivate/remove a wide range of viruses of diverse physicochemical characteristics including: Human Immunodeficiency Virus (HIV), Hepatitis A Virus (HAV), and the following model viruses: Bovine Viral Diarrhea Virus (BVDV) as a model virus for HCV, Canine Parvovirus (CPV) as a model virus for Parvovirus B19, Pseudorabies Virus (PRV) as a model virus for large enveloped DNA viruses (e.g. herpes virus). Total mean log10 reductions are shown in Table 4.

Table 4 Log10 Virus Reduction Factor for Selected Viruses.
Process Step Enveloped Viruses – HIV Enveloped Viruses – BVDV Enveloped Viruses – PRV Non-enveloped Viruses – HAV Non-enveloped Viruses – CPV
PEG precipitation 5.1 ± 0.2 4.5 ± 0.3 6.0 ± 0.3 2.8 ± 0.2 4.2 ± 0.2
Pasteurization > 6.1 ± 0.2 > 6.7 ± 0.3 > 6.7 ± 0.2 2.8 ± 0.3 0.1 ± 0.3
Nano filtration > 5.6 ± 0.2 > 5.5 ± 0.2 > 6.4 ± 0.3 > 4.9 ± 0.2 > 4.5 ± 0.3
Total reduction > 16.8 > 16.7 > 19.1 > 10.5 > 8.7

 Mechanism of Action

C1 inhibitor is a normal constituent of human blood and is one of the serine proteinase inhibitors (serpins). The primary function of C1 inhibitor is to regulate the activation of the complement and intrinsic coagulation (contact system) pathway. C1 inhibitor also regulates the fibrinolytic system. Regulation of these systems is performed through the formation of complexes between the proteinases and the inhibitor, resulting in inactivation of both and consumption of the C1 inhibitor.

HAE patients have low levels of endogenous or functional C1 inhibitor. Although the events that induce attacks of angioedema in HAE patients are not well defined, it is thought by some that increased vascular permeability and the clinical manifestation of HAE attacks are primarily mediated through contact system activation. Suppression of contact system activation by C1 inhibitor through the inactivation of plasma kallikrein and factor XIIa is thought to modulate this vascular permeability by preventing the generation of bradykinin2. Administration of CINRYZE increases plasma levels of C1 inhibitor activity.

Before taking Cinryze, tell your doctor:

  • If you are allergic to Cinryze; 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 Cinryze 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 Cinryze?

  • Tell all of your health care providers that you take Cinryze. 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 Cinryze. 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.
  • This medicine will not treat HAE attacks. This medicine is only used to prevent these health problems. Talk with the doctor to if you have questions about how to treat HAE attacks.
  • Talk with the doctor before you travel. You will need to bring enough of Cinryze for use during travel.
  • If your weight changes, talk with your doctor. The dose of Cinryze 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 Cinryze best taken?

Use Cinryze 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 Cinryze come to room temperature before mixing. Do not heat Cinryze.
  • Do not use if it has been frozen.
  • Do not use if the solution is cloudy, leaking, or has particles.
  • This medicine is colorless to slightly blue after mixing. Do not use if the solution changes color.
  • Use within 3 hours of making.
  • 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?

  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

What are the side effects of Cinryze 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 Cinryze?

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 Cinryze?

  • 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 CARTON

  • NDC 42227-081-05
  • C1 esterase inhibitor
    (human)
  • CINRYZE®
  • 500 IU
  • FOR INTRAVENOUS INJECTION
  • Contains 1 single-dose vial.
  • Rx only
  • Derived from human plasma.
    Plasma derived products may
    carry a risk of transmitting
    infectious agents. Refer to the
    package insert for all Warnings
    and Precautions.
PRINCIPAL DISPLAY PANEL - 500 IU Vial Carton

SRC: NLM .