Hereditary angioedema (HAE) is treated with a combination of on-demand medications to stop active swelling episodes and preventive therapies to reduce how often attacks occur. Treatment has transformed over the past decade, with multiple targeted drugs now available that address the root cause of swelling rather than just managing symptoms. Most people with HAE can achieve significant attack reduction, and some newer therapies come as pills or self-administered injections rather than IV infusions.
Why HAE Swelling Happens
HAE results from mutations in a gene called SERPING1, which leads to a shortage of functional C1 inhibitor, a protein that normally keeps certain immune pathways in check. Without enough of it, your body overproduces a molecule called bradykinin. Bradykinin forces the walls of small blood vessels to become more permeable, allowing fluid to leak into surrounding tissue. That fluid buildup is what causes the deep, painful swelling in the skin, gut, and sometimes the airway.
This is fundamentally different from allergic swelling. Antihistamines, epinephrine, and corticosteroids don’t work for HAE because histamine isn’t driving the process. Every approved HAE treatment works by either replacing the missing C1 inhibitor protein, blocking the enzyme that produces bradykinin, or blocking bradykinin itself from activating its receptor on blood vessel walls.
Treating an Active Attack
The 2025 World Allergy Organization guidelines recommend treating attacks as early as possible, ideally at the first sign of swelling. First-line options for stopping an active episode include intravenous C1 inhibitor replacement, icatibant (a bradykinin receptor blocker given as a subcutaneous injection), or sebetralstat (an oral kallikrein inhibitor). Ecallantide, another kallikrein inhibitor given by subcutaneous injection, is considered second-line, reserved for situations where first-line options aren’t available.
For most people, the practical difference between these comes down to how they’re administered. Icatibant is a single subcutaneous injection you can give yourself at home, which means you can treat an attack the moment symptoms start rather than waiting to reach a clinic. IV C1 inhibitor replacement requires either a healthcare setting or training in self-administered IV infusion. Sebetralstat, as an oral option, offers the simplest route for on-demand use. As a last resort, fresh frozen plasma can be used if none of the targeted therapies are accessible, though it carries a higher risk of side effects.
Long-Term Prevention
If you’re experiencing frequent or severe attacks, preventive therapy can dramatically reduce how often they happen. The current first-line options for long-term prophylaxis include subcutaneous C1 inhibitor concentrate, lanadelumab, berotralstat, garadacimab, and donidalorsen. Each works through a slightly different mechanism, but all target the bradykinin pathway.
Lanadelumab is a subcutaneous injection given every two to four weeks. In clinical trials, it reduced attack frequency by 73% to 87% compared to placebo, bringing the average from roughly two attacks per month down to as few as one every four months. Subcutaneous C1 inhibitor concentrate, injected twice weekly, achieved an 84% reduction in attacks in trials, dropping the rate from about four attacks per month to 0.5.
Berotralstat stands out as the only oral pill among the first-line preventive options, taken once daily. Its most common side effects are gastrointestinal: nausea, diarrhea, stomach pain, and heartburn. People with a history of heart rhythm problems or liver or kidney disease should discuss these with their doctor before starting it, as it can affect heart rhythm in rare cases.
Second-line preventive options include IV C1 inhibitor, attenuated androgens (older steroid-like drugs kept at the lowest effective dose), and antifibrinolytics. These are generally reserved for people who can’t access, tolerate, or afford first-line therapies.
Short-Term Prevention Before Procedures
Dental work, surgery, and other procedures that involve physical trauma to the head, neck, or airway can trigger HAE attacks. For these situations, short-term prophylaxis with IV C1 inhibitor concentrate is the first-line approach, typically given shortly before the procedure. If IV C1 inhibitor isn’t available, attenuated androgens or fresh frozen plasma can be used as alternatives. Even with short-term prophylaxis, keeping an on-demand treatment available during and after the procedure is standard practice.
Self-Administration at Home
Because HAE attacks are unpredictable, the ability to treat yourself at home is one of the most important practical aspects of managing the condition. Both subcutaneous and intravenous self-administration are possible with proper training, though subcutaneous injections are simpler to learn.
For subcutaneous injections, the basic process involves cleaning the injection site with an alcohol pad, pinching the skin, inserting the needle at a 45 to 90 degree angle, and slowly pushing the medication in. You rotate injection sites each time to avoid skin damage. The supplies are straightforward: a syringe, appropriate needles, alcohol pads, gauze, and a sharps container for disposal. Most HAE specialty centers or home infusion companies provide hands-on training until you’re comfortable doing it independently.
IV self-infusion requires more training, including learning to access a vein and manage the infusion set, but many people with HAE master it. The payoff is significant: being able to treat an attack within minutes at home rather than spending hours in an emergency room where staff may not be familiar with HAE.
Treatment for Children
HAE can cause attacks in childhood, and treatment options vary by age. For children under 12, the FDA-approved options are more limited. Plasma-derived C1 inhibitor replacement therapies are approved for treating acute attacks and for preventive use in this age group. Danazol, an attenuated androgen, is also approved for prophylaxis in children, though androgens carry concerns about growth and development that make them less desirable for long-term use in young patients. Many of the newer targeted therapies were initially studied and approved in adolescents and adults aged 12 and older, with pediatric studies ongoing to expand access to younger children.
One-Time Treatments on the Horizon
The most significant shift in HAE treatment may come from therapies designed to be given once rather than repeatedly. A CRISPR-based gene editing therapy called NTLA-2002, developed by Intellia Therapeutics, is in clinical development. It uses a single IV infusion to permanently edit the gene responsible for producing kallikrein (the enzyme that generates bradykinin) in liver cells. If successful, this could eliminate or drastically reduce attacks without ongoing medication. Donidalorsen, an antisense therapy that degrades the genetic instructions for kallikrein production in the liver, has already been included in the 2025 WAO guidelines as a first-line preventive option, though it requires periodic dosing rather than a one-time treatment.