In September 2016, the FDA issued additional warnings and precautions for Berinert related to:
Hypersensitivity reactions may occur. Epinephrine should be immediately available to treat any acute severe hypersensitivity reactions following discontinuation of administration.
Berinert is made from human plasma and may contain infectious agents, (e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease [CJD] agent) that can cause disease.
Laryngeal HAE attacks: Following self-administration of Berinert for laryngeal HAE attacks, advise patients to immediately seek medical attention.
On June 22, 2017 the FDA issued approval, under the Orphan Drug Designation, for Haegarda, a plasma-derived concentrate of C1 esterase inhibitor (Human), for subcutaneous use twice weekly. The approved indications are, "For routine prophylaxis to prevent HAE attacks in adolescents and adult patients" (FDA, 2017). Haegarda carries the same warnings and precautions as Berinert related to severe hypersensitivity, TE events and potential transmission of infectious agents. Haegarda is contraindicated in individuals who have experienced life-threatening hypersensitivity reactions, including anaphylaxis to C1-INH preparations or its excipients. The safety and efficacy of Haegarda was demonstrated in a prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, cross-over phase III trial. The COMPACT trial (Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy) included 90 subjects with type I or II HAE who had had four or more attacks in a consecutive 2-month period within the 3 months before screening. Eligible subjects were 12 years of age or older and had a clinical and central laboratory diagnosis of type I or II HAE (that is, a functional C1 inhibitor activity of < 50% and C4 antigen level below the normal level). Trial participants were randomly assigned to one of four treatment sequences in a crossover design, each involving two 16-week treatment periods. Trial subjects self-administered Haegarda subcutaneously twice weekly with either 40 IU or 60 IU per kilogram of body weight. The treatment phase was followed by a 16-week period when placebo was given or vice versa for those who had received placebo in the first phase who were then given Haegarda for the second 16-week period. The primary efficacy endpoint was the number of attacks of HAE, and secondary efficacy endpoints were the proportion of subjects who responded to Haegarda, which was defined as a = 50% reduction in the number of attacks, as compared with placebo, and the number of times that rescue medication was used.
The study results showed that both doses of Haegarda reduced the rate of HAE attacks (mean difference with 40 IU, -2.42 attacks per month; 95% confidence interval [CI], -3.38 to -1.46; and mean difference with 60 IU, -3.51 attacks per month; 95% CI, -4.21 to -2.81; p<0.001 for both comparisons).
en dit doet Berinert en Haegarda ook geen goed in verglijking mt Ruco, bij de ene kans op gekke koeieziekte en de andere 2x/week en dan mr 50% vermindering op aanvallen..