Table 2 Suggested follow-up of patients treated with plasma- derived C1 inhibitor (C1-INH) Baseline assessment Test Frequency prior to starting C1-INH LFTs HIV serology HepB-surface ag HCV-Ab Give hepatitis B vaccine LFTs Baseline Baseline Baseline Baseline Baseline (series of 3 injections) Every 12 months Twelve-month intervals Note: Presently no guidelines exist for serial assessment of patients on C1-INH in the US and the table includes information that is expected to be included in future guidelines. Abbreviation: LFTs, liver function tests. from 5 to 40 mg/m2 intravenously, and 29 of 40 (72.5%) patients reported signiﬁcant improvement within 4 hours, which was statistically signiﬁcant compared with 2 of 8 (25%) in placebo. This is a promising study which demonstrates that Ecallantide® may be another potent therapy for acute HAE attacks in the near future (Schneider et al 2007). Icatibant (Jerini, Berlin, Germany) is yet another product being studied for the treatment of acute HAE attacks. Icatibant is a synthetic agent that can be administered intravenously or subcutaneously. It is similar in structure to bradykinin and acts as a selective bradykinin-2 receptor antagonist. One uncontrolled study examined Icatibant at 3 different intravenous doses and 2 different subcutaneous doses (Bork et al 2007). The median time to onset of symptom relief was reduced from the historical data of 42 hours without treat- ment to 1.16 hours with Icatibant. While this study was not a controlled trial, it demonstrated good evidence of potential beneﬁts of this therapy. Where C1-INH concentrate is unavailable, fresh frozen plasma (FFP) has also been used with success to treat acute attacks of angioedema (Pickering et al 1969). However, because FFP also contains other substrates, including kininogens, there is a potential to worsen some acute attacks of HAE (Rosen and Austen 1969). Despite this potential risk, several groups still treat acute attacks of HAE with FFP when C1-INH concentrate is unavailable (Prematta et al 2007) with the knowledge that the beneﬁt and adverse effect proﬁle of C1-INH is superior to that of FFP. As mentioned above, C1-INH concentrate has been available for greater than 20 years in parts of Europe for the treatment of acute HAE attacks, and it is currently considered the standard of care in many countries (Gompels et al 2005). However, C1-INH concentrate is unavailable in Therapeutics and Clinical Risk Management 2008:4(5) Plasma-derived C1 inhibitor for hereditary angioedema many countries including the US. Currently, two different companies are involved in clinical trials to introduce C1-INH to the US. CSL Behring (Marburg, Germany) is investigating Berinert P®, while Lev Pharmaceuticals (New York, NY, USA) is investigating Cinryze® for approval in the US. The purpose of this paper is to review the current literature on C1-INH concentrate and evaluate its safety and efﬁcacy in the treatment of HAE. Methods The literature was searched to review the data demonstrating the efﬁcacy and safety of C1-INH for the treatment of acute HAE attacks. The following search terms were used in PubMed and OVID: C1 esterase inhibitor, C1-inhibitor, C1 inhibitor, and hereditary angioedema treatment. English- language articles were searched from 1966 to the present to look for studies demonstrating the efﬁcacy and the safety of C1-INH concentrate. Results In 1980, Gadek et al (1980) published a manuscript on the treatment of HAE with C1-INH protein that was removed from pooled plasma via chromatography. They referred to 1 unit (U) of C1-INH as being the amount of C1-INH found in 1 mL of plasma, which is still the terminology used. The group demonstrated the effect of puriﬁed C1-INH in vivo in patients with HAE when given between 410 and 1000 U of C1 inhibitor to 8 patients with HAE. 3 patients were given the product during asymptomatic periods and 5 patients were given the inhibitor during acute HAE attacks. All of the symptomatic patients experienced improvement of symptoms with C1-INH infusion. Their symptoms began to improve within 30 minutes and were completely resolved within 5–7 hours. C1-INH and C4 levels were measured after plasma infusion. Gadek et al demonstrated that C1-INH lev- els peaked rapidly and dropped quickly; however, C4 levels peaked approximately 6 hours after the C1-INH levels, and the C4 levels remained elevated for a much longer period of time. None of the patients demonstrated any adverse reactions related to C1-INH concentrate treatment. Waytes et al (1996) published the first randomized, double-blind, placebo-controlled trial on C1-INH concentrate. This product was puriﬁed from plasma and vapor-heated to inactivate viruses. The group tested C1-INH concentrate used as both a prophylactic agent and as an agent to treat acute attacks of HAE. The infusion dose of C1-INH was 25 U/kg body weight in both groups. The prophylactic group was investigated as a cross-over study in which 6 patients were 977