C1 Esterase Inhibitor, Human

Pronunciation: ES-ter-ase in-HIB-a-tor
Class: Protein C1 inhibitor

Trade Names

Berinert
- Injection, lyophilized powder for solution 500 units

Cinryze
- Injection, lyophilized powder for solution 500 units

Pharmacology

Regulates the activation of the complement and intrinsic coagulation (contact system) pathway and also regulates the fibrinolytic system and the coagulation cascade.

Slideshow: Grapefruit and Medicines: A Possible Deadly Mix?

Pharmacokinetics

Absorption

C _max is 0.68 units/mL and T _max is 3.9 h as a single dose ( Cinryze ).

Distribution

V _ss is 11.1 to 56.1 mL/kg ( Berinert ).

Elimination

Half-life is 56 h (single-dose Cinryze ); 7.4 to 24.4 h ( Berinert ).

Special Populations

Pharmacokinetic studies have not been conducted in patients with renal impairment.

Pharmacokinetic studies have not been conducted in patients with hepatic impairment.

Pharmacokinetic studies have not been conducted in elderly patients.

Compared with adults, the half-life was shorter and clearance was faster ( Berinert ).

Pharmacokinetic studies have not been conducted based on gender.

Pharmacokinetic studies have not been conducted based on race.

Indications and Usage

Treatment of acute abdominal, facial, or laryngeal attacks of hereditary angioedema in adult and adolescent patients.

Routine prophylaxis against angioedema attacks in adolescent and adult patients with hereditary angioedema.

Contraindications

Life-threatening hypersensitivity reactions, including anaphylaxis, to these products.

Dosage and Administration

IV 20 units/kg.

IV 1,000 units every 3 or 4 d.

General Advice

• Consult manufacturer's prescribing information for preparation and administration guidelines.
• Administer Cinryze at a rate of 1 mL/min over 10 min.
• Administer Berinert by slow IV injection at a rate of 4 mL/min.
• Do not mix with other materials or medicinal products.

Storage/Stability

Store at 36° to 77°F. Do not freeze. Store vial in original carton to protect from light. Use reconstituted solution promptly or within 8 h if stored up to 77°F. Do not refrigerate or freeze the reconstituted solution. Dispose of all unused solution.

Store at 36° to 77°F. Do not freeze or use if frozen. Store vial in original carton to protect from light. Use reconstituted solution within 3 h of reconstitution. Dispose of all unused solution.

Drug Interactions

None well documented.

Adverse Reactions

Cardiovascular

Thromboembolic events including basilar artery thrombosis, deep venous thrombosis, multiple pulmonary microemboli, stroke, thrombosis, and transient ischemic attack (postmarketing).

CNS

Headache (19%); dizziness (2%).

Dermatologic

Rash (21%); pruritus (8%); erythema, erythema infectiosum (2%).

GI

Nausea (18%); vomiting (10%); abdominal pain or discomfort (7%); dysgeusia (5%); dry mouth (3%).

Local

Catheter-site pain (3%); infusion-related reaction (2%); infusion-site reactions (eg, erythema, hematoma, inflammation, rash), pain on injection, redness at injection site (postmarketing).

Musculoskeletal

Muscle spasms (2%).

Respiratory

Nasopharyngitis (7%); upper respiratory tract infection (2%).

Miscellaneous

Influenza-like illness (6%); pyrexia (5%); vulvovaginal mycotic infection (4%); hereditary angioedema, pain (2%); chills, fever, hypersensitivity/anaphylactic reactions, shock (postmarketing).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 13 y ( Berinert ); safety and efficacy not established in neonates, infants, or children ( Cinryze ).

Hypersensitivity

Severe hypersensitivity reactions may occur.

Human plasma

Because C1 inhibitor is prepared from human blood, there is a risk of transmitting infectious agents (eg, viruses), including Creutzfeldt-Jakob disease.

Thrombotic events

Have been reported when used at recommended and higher than recommended doses, as well as when used off-label.

Overdosage

Symptoms

Thrombosis.

Patient Information

• Instruct patients to immediately report the following to their health care provider: signs and symptoms of allergic hypersensitivity reactions, such as anaphylaxis, hives, hypotension, tightness of the chest, urticaria, and wheezing, or signs and symptoms of thrombosis, such as altered consciousness or speech, loss of sensation or motor power, new onset of swelling and pain in the limbs or abdomen, new-onset chest pain, or shortness of breath.
• Advise female patients to notify their health care provider if they become pregnant or intend to become pregnant during C1 inhibitor therapy.
• Advise patients to notify their health care provider if they are breast-feeding or plan to breast-feed.
• Advise patients to bring an adequate supply of medication when traveling.
• Inform patients that C1 inhibitor is made from human blood and may carry a risk of transmitting infectious agents (eg, viruses) and, theoretically, Creutzfeldt-Jakob disease.
• Advise patients to bring C1 inhibitor with them when they visit their health care provider and/or facility for an acute hereditary angioedema attack.

Copyright © 2009 Wolters Kluwer Health.