Ruconest

Generic name: c1 esterase inhibitor recombinant injection
Drug class: Hereditary angioedema agents

Medically reviewed by  A Ras MD.

What is Ruconest?

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

Description

RUCONEST is a recombinant analogue of human complement component 1 esterase inhibitor for intravenous injection. RUCONEST is purified from the milk of transgenic rabbits, and supplied as a sterile, preservative-free, white/off-white lyophilized powder for reconstitution for injection. One U of rhC1INH activity is defined as the equivalent of C1 esterase inhibiting activity present in 1 mL of pooled normal plasma.

 

RUCONEST is a soluble, single-chain glycoprotein containing 478 amino acids, with a molecular mass of 68 kDa, of which approximately 22% comprises oligosaccharide structures. The primary and secondary structures of the molecule and target protease selectivity are consistent with those of plasma-derived C1 esterase inhibitor.

 

Each vial of RUCONEST contains 2100 U of rhC1INH, 937 mg of sucrose, 83.3 mg of sodium citrate dihydrate and 1.0 mg of citric acid monohydrate. After reconstitution with 14 mL of sterile Water for Injection, each vial of RUCONEST contains 150 U of rhC1INH per 1 mL in a 20 mM sodium citrate buffer with a pH of 6.8. RUCONEST does not contain preservatives and each vial is for single use only.

 

RUCONEST is purified from the milk of transgenic rabbits. The rabbits are maintained in a closed colony that is controlled and routinely monitored for specific pathogens. The skimmed milk is screened for adventitious contaminants prior to further manufacture. The manufacturing process has been validated to demonstrate adequate capacity for removal and/or inactivation of viruses. RUCONEST contains less than 0.002% of host-related impurities.

 

Table 4. Viral reduction capacity of the rhC1INH manufacturing process
a MLV: Murine leukemia virus; REO-3: Reovirus type 3; ORF: Scab-mouth ORF virus; FCV: Feline calicivirus; PPV: Porcine parvovirus;

SP BB: SP Sepharose BB; SD: Solvent/detergent; Q HP: Q Sepharose HP; Zn FF: Zinc Chelating Sepharose FF;

Not added to the total reduction factor since independence of clearance mechanism has not been experimentally verified;

d Not applicable since indicated model virus is not enveloped;

e Not tested because SD chemicals are present in the starting material.

Virus Reduction Factor (Log 10)

Step

MLV a

REO 3

ORF

FCV

PPV

SP BB chromatography b

1.8

2.2 c

1.5 c

2.3

1.5 b

SD incubation b

≥ 5.8

NA d

3.7

NA

NA

Q HP chromatography b

NT e

4.8

NT

0.8 c

2.2

Zn FF chromatography b

1.1 c

3.2 c

3.3

1.9 c

0.4 c

Nanofiltration

≥ 5.5

≥ 6.5

≥ 5.8

≥ 6.9

5.8

Total reduction factor

≥ 13.1

≥ 11.3

≥ 12.8

≥ 9.2

8.0

 

Mechanism of Action

C1 esterase inhibitor (C1INH) is a normal constituent of human blood and is one of the serine protease inhibitors (serpins). The primary function of C1INH is to regulate the activation of the complement and contact system pathways. Regulation of these systems is performed through the formation of complexes between the protease and the inhibitor, resulting in inactivation of both and consumption of the C1INH.

 

C1INH exerts its inhibitory effect by irreversibly binding several proteases (target proteases) of the contact and complement systems. The effect of RUCONEST on the following target proteases was assessed in vitro: activated C1s, kallikrein, factor XIIa and factor XIa. Inhibition kinetics were found to be comparable with those observed for plasma-derived human C1INH.

 

HAE patients have low levels of endogenous or functional C1INH. Although the events that induce attacks of angioedema in HAE patients are not well defined, it is thought that contact system activation, and resulting increased vascular permeability lead to the clinical manifestation of HAE attacks. Suppression of contact system activation by C1INH through the inactivation of plasma kallikrein and factor XIIa is thought to modulate vascular permeability by preventing the generation of bradykinin. 5

 

Administration of RUCONEST increases plasma levels of functional C1INH activity.

Before taking Ruconest, tell your doctor:

  • If you are allergic to rabbits.
  • If you are allergic to Ruconest; 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 Ruconest 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 Ruconest?

  • Tell all of your health care providers that you take Ruconest. This includes your doctors, nurses, pharmacists, and dentists.
  • Allergic side effects may rarely happen.
  • Blood clots have happened with Ruconest. 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.
  • Talk with the doctor before you travel. You will need to bring enough of Ruconest for use during travel.
  • If your weight changes, talk with your doctor. The dose of Ruconest may need to be changed.
  • Most of the time, 1 dose is enough to treat an attack. Sometimes, a second dose may be needed. Talk with the doctor to find out what to do after using a dose of Ruconest.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Ruconest while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

How is Ruconest best taken?

Use Ruconest 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 Ruconest come to room temperature before mixing. Do not heat Ruconest.
  • Do not use if the solution is cloudy, leaking, or has particles.
  • Do not use if solution changes color.
  • Throw away any part left over after the dose is given.
  • Store in a refrigerator if not using right away.
  • Use the dose within 8 hours after mixing.
  • 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 taken on an as needed basis. Do not take more often than told by the doctor.
  • Do not give more than 2 doses a day.

What are the side effects of Ruconest 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.
  • Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
  • Very bad dizziness or passing out.
  • Change in color of mouth to blue.
  • A fast heartbeat.
  • Very bad headache.
  • 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 Ruconest?

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:

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 Ruconest?

  • Store at room temperature or in a refrigerator. Do not freeze.
  • Store in the original container to protect from light.
  • 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

PACKAGE LABEL/PRINCIPAL DISPLAY PANEL – 2100 U VIAL LABEL

  • RUCONEST®
  • C1 esterase inhibitor (recombinant)
  • 2100 U
  • NDC 71274-350-01
  • For intravenous use only.
  • For single patient use.
  • See prescribing information for directions for use.
  • Rx only

 

label

PACKAGE LABEL/PRINCIPAL DISPLAY PANEL – 2100 U CARTON

  • RUCONEST®
  • C1 esterase inhibitor (recombinant)
  • 2100 U
  • NDC 71274-350-02
  • For intravenous use only.
  • For single patient use.
  • See prescribing information for directions for use.
  • Rx only

 

 

carton

 

SRC: NLM .

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