Hereditary angioedema (HAE) is a genetic disorder that causes episodes of severe swelling of the hands, feet, face, throat, and other areas of the body. Not every attack has a known trigger, but stress or injury might lead to episodes.
There are three types of HAE. People with type 1 HAE have low levels of a protein called C1 esterase inhibitor (C1-INH), while those with type 2 HAE have normal C1-INH levels but with a protein that doesn’t work correctly. Both types are caused by mutations in the gene that encodes C1-INH. A third, very rare type of HAE occurs in people with normal C1-INH levels and function; mutations in certain genes are thought to cause it. Treatment is similar for all types and includes the use of on-demand medications during an attack as well as short-term and long-term preventive medications.
Medications
There are two kinds of hereditary angioedema (HAE) treatments: preventive and on-demand.
Preventive or Prophylactic Therapies People with HAE take this type of medication regularly to help ward off an HAE attack. These medications can also reduce the frequency and severity of your symptoms. A doctor may recommend long-term prophylactic medications to reduce the overall burden of attacks, but might prescribe short-term preventive medicines ahead of a surgical or dental procedure that puts stress on the body.
On-Demand or Acute Treatments This type of therapy helps to stop an attack that’s already in progress. Everyone with HAE should have access to an on-demand therapy, as prophylactic medications may not be 100 percent effective.
Currently, the U.S. Food and Drug Administration (FDA) has approved nine medicines to prevent or treat HAE attacks. All except one have approval for people to self-administer the medications without the help of a medical professional. For support in accessing and paying for HAE medications, the U.S. Hereditary Angioedema Foundation offers tailored services and community support. You can get in touch with them here if you have or care for someone with HAE and need additional resources.
Preventive Medications
Drug Name
Details
Andembry (garadacimab-gxii)
A once-monthly injection for people 12 and over; can be self-injected
Cinryze (C1 esterase inhibitor [human])
For people 6 and older, it’s delivered intravenously and is approved for self-administration.
Dawnzera (donidalorsen)
Offers the longest time between doses, every four or eight weeks; can be self-administered via auto-injector
Delivered by injection, for people 6 and older; can be self-administered
Orladeyo (berotralstat)
An oral, once-daily plasma kallikrein inhibitor for patients 12 and older
Takhzyro (lanadelumab-flyo)
A plasma kallikrein inhibitor (monoclonal antibody) for patients 2 and older; it’s an injection approved for self-administration.
On-Demand Medications
Drug Name
Details
Berinert (C1 esterase inhibitor [human])
An IV infusion you can administer yourself; approved for adults and children
Ekterly (sebetralstat)
An oral treatment for people 12 and older
Firazyr (icatibant injection)
A bradykinin B2 receptor antagonist for people 18 and older; it’s an injection that can be self-administered.
Icatibant (generic)
An self-injectable bradykinin B2 receptor antagonist for people 18 and older
Kalbitor (ecallantide)
For patients 12 and older. Delivered by subcutaneous injection administered by a healthcare professional.
Ruconest (C1 esterase inhibitor [recombinant])
A plasma-free recombinant C1-inhibitor concentrate for adults and adolescents; it’s an intravenous infusion that can be self-administered.
C1 Esterase Inhibitors (C1-INH)
These work by replacing C1-INH in the blood. C1-INH is a protein that helps regulate swelling and inflammation. By returning levels of C1-INH to normal, these injected medications can either prevent attacks from happening or treat HAE episodes as they occur.
The FDA has approved several C1-INH treatments for HAE, and two types are currently available. Plasma-derived C1-INH comes directly from part of human blood, while technicians create recombinant C1-INH using genetic engineering in host cells.
Plasma-derived C1-INH inhibitors are suitable for adults and children and include the brands:
Cinryze (C1 esterase inhibitor [human])
Haegarda (C1 esterase inhibitor [human])
Berinert (C1 esterase inhibitor [human])
Only one recombinant C1-INH medication for HAE, Ruconest, is available for adults and adolescents with HAE though it is contraindicated in people allergic to rabbits. People take Cinryze or Haegarda to prevent HAE attacks and Berinert or Ruconest to treat active HAE episodes.
Haegarda comes as a powder meant to be mixed with liquid and injected under the skin (subcutaneous injection). You or a caregiver can administer the injection at home. People who’d prefer that a healthcare professional carry this out can also receive the injection in the clinic.
Berinert, Cyrinze, and Ruconest require injection into a vein (intravenous) rather than under the skin because rapid action is necessary during an episode. After receiving training from a healthcare provider, you can self-adminster these drugs.
These preventive medications need to be administered every three to four days.
Depending on the medication, side effects might include headache, nausea, vomiting, a bad taste in the mouth, fever or chills, injection site redness or pain, runny nose, sneezing, watery eyes, a sore throat, or dizziness. See a doctor about symptoms suggesting an allergic reaction, such as hives, rash, itching, breathing or swallowing difficulties, blue-tinted lips and skin, swelling of your face, tongue, or throat, sweating, hoarseness, lightheadedness, or fainting.
“Plasma-derived C1-esterase inhibitor is approved for long-term prophylaxis (Cinryze) and treatment of acute attacks (Cinryze and Berinert),” confirms Meng Chen, MD, a clinical assistant professor in pulmonary, allergy, and critical care medicine at Stanford Medicine in California. “Recombinant C1-esterase inhibitor has approval for the treatment of acute attacks (Ruconest).”
Dr. Chen states that both types of C1-esterase inhibitors are considered effective, and testing has not occurred to check whether one type carries more risks than the other. “Both are generally well tolerated with rare adverse events. However, people who are allergic to rabbits should not receive Ruconest, given that rabbits play a role in its production,” Chen says.
Kallikrein Inhibitors
This class of medications comprises monoclonal antibodies, which target and block the activity of a specific enzyme. Kallikrein inhibitors disrupt the enzyme kallikrein, which interacts with C1-INH, to prevent swelling.
Kallikrein inhibitors include:
lanadelumab (Takhzyro)
berotralstat (Ordaleyo)
sebetralstat (Ekterly)
Lanadelumab is a subcutaneous injection; berotralstat or sebetralstat can be taken as a daily pill. Lanadelumab and berotralstat are preventive medications, while sebetralstat is the first oral pill that’s available to treat acute attacks.
Common side effects differ between kallikrein inhibitors but may include abdominal pain, vomiting, diarrhea, back pain, gastroesophageal reflux disease (GERD), injection site reactions, upper respiratory infections, headache, rash, and dizziness.
Bradykinin B2 Receptor Antagonists
These medications target bradykinin, a molecule involved in causing HAE episodes. This enzyme affects the widening of blood vessels, and excess kallikrein during HAE can break down too many other blood components into bradykinin. This increases blood vessel dilation in the airways and gut, contributing to HAE swelling.
Bradykinin B2 receptor antagonists can treat symptoms during an HAE attack. They include:
icatibant (Firazyr)
ecallantide (Kalbitor)
Icatibant is only suitable for adults, while adolescents and adults can use ecallantide. Side effects can involve burning, numbness, swelling, pain, a feeling of pressure, and warmth. Headaches, nausea, fever, rash, and dizziness are also common side effects. As both medications are subcutaneous injections, itching, redness, pain, irritation, hives, and bruising might also occur.
Activated Factor XIIa (FXIIa) Inhibitors
The most recently approved HAE medication is garadacimab (Andembry), a preventive monoclonal antibody that targets the protein factor XIIa (FXIIa) in the blood.
This protein in plasma kicks off a chain reaction known as the kallikrein-kinin cascade, which triggers HAE attacks. By targeting factor 12a, garadacimab blocks the cascade at the top, unlike other HAE therapies that target kallikrein or bradykinin, which occur further down the chain. “The advantage of activated factor IIa inhibitors blocking the HAE response close to the top of the kallikrein-kinin cascade is in blocking the downstream inflammatory cascade that leads to swelling during HAE attacks,” Chen says.
People with HAE take garadacimab as a monthly subcutaneous injection. It comes as a prefilled pen for self-injection, known as an auto-injector, which delivers the medication in 15 or fewer seconds.
Lifestyle Changes
There may be certain modifications you can make to reduce your chances of an HAE attack, though lifestyle changes aren’t a substitute for medical treatment.
Recognize Triggers
While there aren’t universal triggers, some people notice that certain activities or events tend to precede an HAE attack. Recognizing which of these triggers can be avoided or mitigated can help you make lifestyle changes and choices that may reduce your chances of an HAE attack. Known triggers include:
Physical stress, such as impact or pressure on the body during long hikes or strength workouts
Certain medications, including angiotensin-converting enzyme (ACE) inhibitors or contraceptives containing estrogen
Surgical procedures (such as dental surgery)
Infections
Psychological stress, possibly
Hormonal changes during menstruation, pregnancy, or menopause
Insect bites
While certain factors — like hormonal fluctuations — are beyond your control, you can manage others. For instance, you can take a short-term preventive medication before dental surgery to reduce your risk of an HAE attack.
Manage Stress and Tend to Your Mental Health
Psychological stress is commonly reported to be a trigger for HAE attacks. Plus, HAE has shown a range of psychological effects in narrative studies, including depression, anxiety, isolation, and feeling paranoid about the risk of attacks. This can lead to a cycle in which depression, anxiety, and post-traumatic stress disorders (PTSD) develop because of the attacks but also trigger further attacks.
“Mental health support is important for protecting mental health with HAE,” confirms Chen. “Addressing the psychological impact of HAE is important for the treatment plan. This can help improve the overall quality of life for the patient and mitigate stress, which may trigger HAE attacks.”
The following strategies can help you manage stress:
Get regular physical activity.
Practice relaxation techniques, like mindfulness meditation, yoga, or breathwork.
Get enough sleep.
Eat a healthy, balanced diet.
Don’t smoke and limit your alcohol consumption.
Spend time with family and friends, and also make time for yourself and your interests.
The Takeaway
Treatment for hereditary angioedema (HAE) involves both preventive and on-demand medications. Formulations include oral pills, injections, and IV infusions, most of which can be self-administered.
Lifestyle modifications, such as recognizing and avoiding personal triggers like stress or physical exertion, can complement medical treatment and potentially reduce the frequency of HAE episodes.
Managing stress and maintaining mental health are key components in addressing HAE, as psychological stress can both result from and contribute to the incidence of attacks.
Always discuss any new symptoms or severe attacks with your doctor.
EDITORIAL SOURCES
Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy. We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.
Zuraw BL et al. Hereditary Angioedema With Normal C1 Inhibitor: An Updated International Consensus Paper on Diagnosis, Pathophysiology, and Treatment. Clinical Reviews in Allergy and Immunology. March 7, 2025.
Pawaskar D et al. Pharmacokinetic/pharmacodynamic modeling for dose selection for the first‐in‐human trial of the activated Factor XII inhibitor garadacimab (CSL312). Clinical and Translational Science. December 8, 2021.
Zarnowski J et al. Dietary and physical trigger factors in hereditary angioedema: Self-conducted investigation and literature overview. Allergologie Select. November 14, 2024.
Savarese L et al. Psychology and Hereditary Angioedema: A Systematic Review. Allergy and Asthma Proceedings. January 2021.
Savarese L et al. Psychological Processes in the Experience of Hereditary Angioedema in Adult Patients: An Observational Study. Orphanet Journal of Rare Diseases. January 9, 2021.
Jon E. Stahlman, MD, has been a practicing allergist for more than 25 years. He is currently the section chief of allergy and immunology at Children’s Healthcare of Atlanta's Scottish Rite campus and the senior physician at The Allergy & Asthma Center in Atlanta. He served as the president of the Georgia Allergy Society, has been named a Castle Connolly Top Doctor, and was listed as a Top Doctor by Atlanta magazine. His research interests include new therapies for asthma and allergic rhinitis as well as the use of computerized monitoring of lung function.
He received his bachelor's and medical degrees from Emory University. He completed his pediatric residency at Boston Children’s Hospital and his fellowship in allergy and clinical immunology at Harvard University’s Boston Children’s Hospital and Brigham and Women’s Hospital. After his training, Dr. Stahlman conducted two years of clinical research at Boston Children’s Hospital and was part of the faculty at Harvard Medical School, where he taught medical students and allergy and immunology fellows.
Stahlman is board-certified and recertified in allergy and clinical immunology. He served as a principal investigator on phase 2 through 4 studies that are responsible for most of the U.S. Food and Drug Administration–approved therapies for allergies and asthma available today.
Outside of the office, he centers his interests around his wife and three daughters, coaching soccer for many years, and his hobbies include cycling and triathlons.
Adam is a freelance writer and editor based in Sussex, England. He loves creating content that helps people and animals feel better. His credits include Medical News Today, Greatist, ZOE, MyLifeforce, and Rover, and he also spent a stint as senior updates editor for Screen Rant.
As a hearing aid user and hearing loss advocate, Adam greatly values content that illuminates invisible disabilities. (He's also a music producer and loves the opportunity to explore the junction at which hearing loss and music collide head-on.)
In his spare time, Adam enjoys running along Worthing seafront, hanging out with his rescue dog, Maggie, and performing loop artistry for disgruntled-looking rooms of 10 people or less.
