D rash, lightheadedness, and fever.43 In an open-label study, the adverse
D rash, lightheadedness, and fever.43 In an open-label study, the adverse events most frequently related to nanofiltered C1-esterase X-396 chemical information inhibitor were headache (5.5 ), nausea (4.1 ), rash (2.7 ), erythema (2.1 ), and diarrhea (2.1 ). The risk of experiencing a hypersensitivity reaction to the nanofiltered C1-esterase inhibitor is low.95 An increased risk for thrombotic events was seen in preclinical animal studies and in neonates undergoing cardiovascular surgery from off-label use of extremely PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26266977 high doses of C1-esterase inhibitor therapy.96,97 Studies conducted in humans show that a dose of up to 100 U/kg does not lead to thrombotic events.98,99 Nevertheless, thrombotic events have been reported with C1-esterase inhibitors; patients who are at risk for thrombosis should be monitored while on C1-esterase inhibitor therapy. It is noteworthy to mention that discontinuation resulting from an adverse event associated with nanofiltered human C1-esterase inhibitor is rare; in a recently completed open-label study, no patient discontinued study therapy because of an adverse event.95 Commercially available C1-esterase inhibitor products are derived from human blood and theoretically carry the risk of viral transmission (eg, parvovirus B19, hepatitis B, hepatitis C, and human immunodeficiency virus). Initial development of human plasma-derived C1-esterase inhibitor was complicated by the need for purification steps to reduce the transmission of viral diseases. Viral inactivation and removal steps in the production of C1-esterase inhibitor were introduced in the mid-1980s.85 The approval of Berinert-P (CSL Behring GmbH, Marburg, Germany; C1-esterase inhibitor, human) in Europe in PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/29072704 1985 brought to market a formulation that used numerous steps to reduce viral transmission, including careful donor screening and viral contaminant eliminationand inactivation through adsorption, precipitation, and pasteurization steps.92,100 More recently, manufacturing of another C1-esterase inhibitor formulation has incorporated a nanofiltration step through 2 serial 15-nm filters to reduce transmission of enveloped and nonenveloped viruses and possibly prions.43,101 It is important to note that, as a result of these purification measures, no cases of virus transmission have been attributed to the purified preparations of C1esterase inhibitor currently available.42,46,87,95,100,CLINICAL EXPERIENCE DISCUSSIONThe manifestations and severity of HAE are highly variable and unpredictable, which necessitates individualized therapeutic approaches. Worldwide, a variety of treatment options are used to manage the disease. On-demand therapy for attacks with C1-esterase inhibitor is sometimes used as a patient’s sole method of treatment or it may be used to treat breakthrough attacks in patients who are taking long-term prophylaxis.103 Home therapy refers to treatment given by the patient (self-administration) or a trained caregiver outside of a healthcare facility. On-demand home therapy with C1esterase inhibitor has proven successful in selected patients and offers patients the possibility of earlier treatment and better symptom control103?06; however, this use is not currently approved in the United States. For prophylaxis, oral attenuated androgens or IV C1-esterase inhibitor are at the forefront. Home therapy is only approved with the nanofiltered C1-esterase inhibitor that is approved for routine prophylaxis against angioedema attacks in adolescents and adults in the United St.