C1-Esterase Inhibitor (Recombinant) (Monograph)

Brand name: Ruconest
Drug class: Complement Inhibitors

Medically reviewed by Drugs.com on May 10, 2024. Written by ASHP.

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Introduction

Biosynthetic (recombinant DNA-origin) preparation of complement 1 (C1)-esterase inhibitor.

C1-esterase inhibitor is a naturally occurring inhibitor of certain serine proteases (e.g., C1 complement, kallikrein, coagulation factor XIIa, plasmin) involved in the complement, coagulation (contact), and fibrinolytic systems.

Uses for C1-Esterase Inhibitor (Recombinant)

Hereditary Angioedema

Treatment and prevention^{† [off-label]} of acute angioedema attacks in adults and adolescents with hereditary angioedema (HAE).

Clinical studies were conducted principally in patients with abdominal, facial, or peripheral angioedema; efficacy in patients with laryngeal HAE attacks not established.

Guidelines generally support consideration of C1-esterase inhibitor (recombinant) among other options for treatment of HAE attacks, and for prevention^{† [off-label]} of HAE attacks when first-line options are not available.

C1-Esterase Inhibitor (Recombinant) Dosage and Administration

General

Patient Monitoring

• Monitor for severe hypersensitivity reactions (e.g., urticaria, chest tightness, wheezing, hypotension, anaphylaxis) during and after administration of C1-esterase inhibitor (recombinant).

• Monitor patients with known risk factors for thromboembolism closely during and after administration of C1-esterase inhibitor (recombinant).

Other General Considerations

• Initial training on the administration of C1-esterase inhibitor (recombinant) therapy should only occur under the supervision of a qualified healthcare professional experienced in the treatment of HAE; subsequent self-administration by the patient or caregiver is permitted after appropriate training is provided.

Administration

IV Administration

Do not mix or administer with any other drug or solution.

Vials are for single use only; discard any unused portions.

Reconstitution

Allow vials of drug and diluent (sterile water for injection) to reach room temperature prior to reconstitution.

Reconstitute vial containing 2100 units of C1-esterase inhibitor (recombinant) with 14 mL of sterile water for injection. Add diluent slowly to avoid forceful impact on the powder. Gently swirl vial to ensure complete dissolution. Resultant solution contains 150 units/mL. If more than 1 vial is required to obtain a dose, may pool reconstituted contents of multiple vials into a single administration device (i.e., syringe).

Administer reconstituted solutions immediately or within 8 hours if stored at 2–8°C.

Rate of Administration

Administer by IV injection over approximately 5 minutes.

Dosage

Dosage of C1-esterase inhibitor (recombinant) is expressed in international units (IU, units). One unit of C1-esterase inhibitor (recombinant) is equivalent to the C1-esterase-inhibiting activity present in 1 mL of pooled normal plasma.

Pediatric Patients

Hereditary Angioedema

Treatment of Hereditary Angioedema Attacks

IV

Adolescents 13–17 years of age: 50 units/kg (up to 4200 units) for patients weighing <84 kg; 4200 units in patients weighing ≥84 kg.

May administer a second dose if attack symptoms persist.

Routine Prophylaxis† [off-label] of Hereditary Angioedema Attacks

IV

Adolescents 13–17 years of age: 50 units/kg (up to 4200 units) in patients weighing <84 kg or 4200 units in patients weighing ≥84 kg, administered once or twice weekly, has been used.

Adults

Hereditary Angioedema

Treatment of Hereditary Angioedema Attacks

IV

50 units/kg (up to 4200 units) for patients weighing <84 kg; 4200 units in patients weighing ≥84 kg.

May administer a second dose if attack symptoms persist.

Routine Prophylaxis † [off-label]of Hereditary Angioedema Attacks

IV

50 units/kg (up to 4200 units) in patients weighing <84 kg or 4200 units in patients weighing ≥84 kg, administered once or twice weekly, has been used.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Use

No specific dosage recommendations at this time.

Cautions for C1-Esterase Inhibitor (Recombinant)

Contraindications

• Known hypersensitivity to rabbits or rabbit-derived products.

• Known life-threatening immediate hypersensitivity, including anaphylaxis, to C1-esterase inhibitor preparations.

Warnings/Precautions

Hypersensitivity

Risk of severe hypersensitivity reactions (e.g., urticaria, chest tightness, wheezing, hypotension, anaphylaxis). If a hypersensitivity reaction occurs, discontinue C1-esterase inhibitor (recombinant) and initiate appropriate treatment.

Thrombotic Events

Risk of thromboembolic events. Reported with plasma-derived C1-esterase inhibitor at recommended doses in patients with underlying risk factors (e.g., presence of indwelling venous catheter/access device, history of thrombosis, underlying atherosclerosis, use of oral contraceptives or certain androgens, morbid obesity, immobility).

Closely monitor patients with known risk factors for thromboembolism.

Immunogenicity

Potential for immunogenicity with use of all therapeutic proteins, including C1-esterase inhibitor (recombinant). Development of non-neutralizing antibodies to C1-esterase inhibitor (recombinant) reported in clinical trials; however, clinically important effects not observed.

Specific Populations

Pregnancy

No adequate and well-controlled studies in pregnant women. Limited postmarketing data in pregnant women; risk with use cannot be definitively ruled out.

Lactation

Not known whether C1-esterase inhibitor (recombinant) is distributed into human milk. Consider benefits of breastfeeding along with the potential for adverse effects to the breast-fed infant and the mother's clinical need for the drug.

Pediatric Use

Safety and efficacy not established in pediatric patients <13 years of age; use of the drug in adolescents 13–17 years of age is supported by data from approval studies.

Geriatric Use

Insufficient experience in patients >65 years of age to determine whether geriatric patients respond differently than younger patients.

Hepatic Impairment

Pharmacokinetics not evaluated in patients with hepatic impairment.

Renal Impairment

Pharmacokinetics not evaluated in patients with renal impairment.

Common Adverse Effects

Adverse effects (≥2%): headache, nausea, diarrhea.

Drug Interactions

No formal drug interaction studies to date.

C1-Esterase Inhibitor (Recombinant) Pharmacokinetics

Absorption

Plasma Concentrations

Peak plasma concentrations attained in approximately 0.3 hours following a single 50-unit/kg dose in asymptomatic patients.

Distribution

Extent

Not known whether distributed into human milk.

Elimination

Half-life

Approximately 2.5 hours following a 50-unit/kg dose in asymptomatic patients.

Exhibits nonlinear clearance.

Elimination half-life has been reported to be shorter than that of plasma-derived C1-esterase inhibitor due to differences in glycosylation.

Stability

Storage

Parenteral

Powder for Injection

2–25°C; do not freeze. Store in original container and protect from light.

May store reconstituted solutions at 2–8°C for up to 8 hours; do not freeze.

Actions

• Serine protease inhibitor that principally regulates the activation of the complement and intrinsic coagulation (e.g., contact system) pathways. Also plays a role in the fibrinolytic system.

• Regulates contact system activation by inhibiting plasma kallikrein and coagulation factor XIIa; such actions prevent formation of bradykinin, the presumed mediator of increased vascular permeability in HAE.

• Blocks both the spontaneous activation of C1 complement and formation of activated C1 complement, suppressing the classical complement pathway.

• Also exhibits inhibitory effects on plasmin.

• Binds to and forms irreversible complexes with target protease, which are then inactivated and removed from circulation.

• Biosynthetic (recombinant DNA origin) preparation of human C1-esterase inhibitor produced from the milk of transgenic (genetically modified) rabbits. Undergoes a series of viral reduction steps (e.g., pasteurization, precipitation, nanofiltration, chromatography) to reduce risk of viral transmission.

• Structurally and functionally similar to plasma-derived C1-esterase inhibitor.

Advice to Patients

• Importance of discussing potential risks and benefits of therapy with the patient prior to prescribing or administering the drug.

• Importance of instructing patients to read the manufacturer's product information and instructions for use.

• Importance of clinicians providing clear instructions and training on proper IV administration technique to patients self-administering C1-esterase inhibitor (recombinant). Advise patients to record the lot number of the C1-esterase inhibitor (recombinant) vial used each time the drug is administered.

• Risk of thrombotic events; advise patients to immediately report any signs and symptoms of thrombosis (e.g., new-onset swelling and pain or discoloration in the limbs with warmth in the affected area; worsening chest pain or discomfort with deep breathing; shortness of breath; unexplainable rapid pulse; loss of sensation or motor ability; weakness on one side of the body). Advise patients with risk factors that they are at an increased risk for thrombosis.

• Importance of patients immediately informing a clinician if any signs or symptoms of hypersensitivity (e.g., urticaria, chest tightness, wheezing, hypotension, anaphylaxis) occur during or after administration of C1-esterase inhibitor (recombinant).

• Importance of females informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of informing patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

C1-esterase inhibitor (recombinant) is distributed via specialty pharmacies. For more information, visit Ruconest Solutions at: [Web]

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