CINRYZE

CINRYZE contains the active ingredient C1 esterase inhibitor, human. It is a C1 inhibitor prepared from human plasma. CINRYZE is available in a single concentration of 500 units of powder and solvent for the preparation of a solution for injection.

Mechanism of action C1 inhibitor belongs to the protein superfamily of serine protease inhibitors or serpins. The main function of serpins is to regulate the activity of serine proteases. The C1 inhibitor is a plasma-derived single-chain glycoprotein that consists of 478 amino acids when mature and has an apparent molecular weight of 105 kD. the C1 inhibitor inhibits the complement system by attaching to C1r and C1s, two of the active enzyme subunits of the first component of the complement system (C1) of the classical pathway of complement activation, and by attaching to mannose-binding, lectin-associated serine proteases of the lectin pathway.

Primary substrate of activated C1 enzyme is C4; uninhibited C1 leads to decreased C4 levels. C1 is the major inhibitor of contact activation and regulates the contact system and intrinsic coagulation pathway by binding to and thereby inactivating kallikrein and factor XIIa. Because these pathways are part of enzyme amplification cascades, their activation spontaneously or induced by a trigger can lead to unrestrained activation and swelling in the absence of C1 inhibitor. Pharmacodynamic Effects In clinical studies, intravenous administration of Cinryze resulted in a significant increase in systemic levels of C1 inhibitor antigen and functional C1 inhibitor within 1 hour of administration. Administration of C1 inhibitor causes an increase in serum levels of C1 inhibitor activity and temporarily restores the natural regulation of the contact, complement, and fibrinolysis systems, thereby controlling swelling or susceptibility to swelling. Low serum C4 levels often correlate with HAE attacks. Treatment with Cinryze caused an increase in C4 levels after 12 hours. After 12 hours, there was a statistically significant (p = 0.0017) difference in mean changes from baseline between treatment groups; demonstrating the association between treatment with Cinryze and an increase in C4 activity (Cinryze + 2.9 mg/dl versus placebo + 0.1 mg/dl).

Use in adults, adolescents and children (2 years and older) with hereditary angioedema (HAE). Use for acute treatment or prophylactic administration prior to medically indicated surgery in patients with angioedema attacks. Routine prophylaxis against angioedema attacks in adults, adolescents, and children (6 years and older) with severe and recurrent attacks of hereditary angioedema (HAE) in whom oral prophylactic treatments are not tolerated or do not provide adequate protection, or in patients who cannot be adequately treated with repeated acute treatments.

After reconstitution, one vial contains 500 I.U. of C1 inhibitor (human) per 5 ml corresponding to a concentration of 100 I.U./ml. One I.U. corresponds to the amount of C1 inhibitor present in 1 ml of normal human plasma