C1-Esterase Inhibitor (Recombinant)

1-10%

Headache (9%)

Nausea (2%)

Diarrhea (2%)

Postmarketing Reports

Abdominal pain

Rash

Biosynthetic (recombinant DNA-origin) preparation of complement 1 (C1)-esterase inhibitor.1 9 15 31

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.1 2 6 7 10 12 19 23

Contraindications

• Known hypersensitivity to rabbits or rabbit-derived products.1 16

• Known life-threatening immediate hypersensitivity, including anaphylaxis, to C1-esterase inhibitor preparations.1

Warnings/Precautions

Thrombotic Events

Risk of thromboembolic events.1 28 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).1 28

Clinical studies to date have not suggested an increased thrombotic risk with C1-esterase inhibitor (recombinant).15 22 32 37

Closely monitor patients with known risk factors for thromboembolism.1

Immunogenicity

Potential for immunogenicity with use of all therapeutic proteins, including C1-esterase inhibitor (recombinant).1 Development of non-neutralizing antibodies to C1-esterase inhibitor (recombinant) reported in clinical trials; however, clinically important effects not observed.1 37

Sensitivity Reactions

Risk of severe hypersensitivity reactions (e.g., urticaria, chest tightness, wheezing, hypotension, anaphylaxis).1 (See Contraindications under Cautions.) Anaphylaxis was reported in an individual with preexisting allergy to rabbit protein.1 37

If hypersensitivity occurs, discontinue drug immediately and initiate appropriate treatment.1 Because symptoms of hypersensitivity can resemble acute attacks of HAE, carefully consider treatment method.1

Specific Populations

Category B.1

No adequate and well-controlled studies in pregnant women.1 30 Animal studies suggest a possibility of adverse embryofetal effects.1

Not known whether C1-esterase inhibitor (recombinant) is distributed into human milk.1 Use with caution.1

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.1 25

Insufficient experience in patients >65 years of age to determine whether geriatric patients respond differently than younger patients.1

Pharmacokinetics not evaluated in patients with hepatic impairment.1

Pharmacokinetics not evaluated in patients with renal impairment.1

Common Adverse Effects

Headache,17 18 20 21 32 nausea,21 32 diarrhea.18 21 32

No formal drug interaction studies to date.1 9