Safe Off-Label Use of Icatibant as Treatment for Acute Hereditary Angioedema Attacks in a Pediatric Patient

Introduction Hereditary angioedema (HAE) is a rare, potentially life-threatening disease characterized by recurrent attacks of subcutaneous and submucosal swelling. Currently, only intravenous (IV) therapies are approved in the USA for treatment of HAE attacks in children younger than 12. IV therapy is difficult for caregivers to administer to young children, and these patients often require care in the emergency department (ED) for administration, delaying resolution. Subcutaneous injection allows earlier therapy, decreasing risk of more serious complications of acute attacks and reducing need for ED-level care. Icatibant is a selective antagonist of the bradykinin B2 receptor and administered subcutaneously. In the European Union (EU) and Canada, it is approved down to the age of 2. Here, we describe a single case of a 6-year-old female with HAE type 1 for whom icatibant was safely used off-label for an acute attack with resolution of her symptoms. Case Description Despite previous success with Berinert for abortion of peripheral attacks, this patient’s family was frustrated with long wait times and care in the ED. Given a sibling’s success with icatibant, review of preexisting literature, and the Canadian package insert, we opted to prescribe this off-label as a rescue using shared-decision making. She was initially given icatibant 0.4 mg/kg for abortive treatment in the ED. Eventually, the patient was approved through her insurance to use icatibant 15 mg SQ for attacks, and lanadelumab was also initiated for maintenance therapy given increasing attack frequency through manufacturer assistance and eventual insurance approval through assistance of a multidisciplinary team. The only adverse event was injection site pain, and her attack frequency decreased. Discussion This case illustrates the potential for safe off-label use of icatibant down to 2 years of age for acute attacks of HAE. Penn State Health has been prescribing and administering icatibant down to 2 years of age despite being off-label, and we hope this work encourages FDA approval and other institutions to make icatibant available as a weight-adjusted dose as an option for abortive treatment until oral rescue medications are available to reduce drug burden in pediatrics.