HAE Treatments

  Three products now FDA-approved!
- Cinryze, approved to prevent HAE attacks.
- Berinert, approved for treating acute facial and abdominal HAE attacks
- Kalbitor, approved for treating acute attacks in patients 16 yrs and older

Please contact the HAEA's Patient Services group for more information:
Donna Davis donna-davis@haea.org, (808) 216-1029 or
Michelle Williamson michellewilliamson@haea.org, (972) 814-5205

Treatment of acute attacks

Two products have recently been approved by the FDA to treat acute HAE attacks:

• Berinert^® brand of C1-inhibitor has been FDA-approved for treating acute facial and abdominal HAE attacks. The product is delivered intravenously. Contact your HAEA regional Patient Services Representative (see list below) for more information.
• Kalbitor^®, from Dyax Corp., was approved in December 2009 to treat acute HAE attacks in patients 16 years of age and older. The product is delivered through subcutaneous injections and is estimated to be available in the US in early 2010.

Maintaining airway patency is the primary concern for patients with laryngeal edema. If the airway is threatened, the patient should be intubated by an experienced physician.¹ In addition, the capability for emergency tracheostomy should be readily available.¹ Because gastrointestinal edema usually involves excruciating pain, frequent vomiting, and the potential for hypotension, therapy should include aggressive fluid replacement and pain management. Clinicians report that Zofran, Compazine, and Phenergan are effective in reducing nausea and vomiting, while morphine or other narcotics are routinely used to relieve attack related abdominal pain. Some physicians use fresh frozen plasma in the acute attack setting, but this therapy is considered controversial because in addition to C1 inhibitor, fresh frozen plasma contains substrates of the complement and kinin systems that could produce a vasoactive peptide and cause an attack exacerbation.³

Short term preventive treatment

Short-term therapy is necessary for patients who do not require ongoing preventive treatment, but are facing dental procedures or elective surgery. Current practice calls for daily high dose androgen therapy (600-800mgs of danazol) for at least four days prior to surgery and four days afterward⁴. Fresh frozen plasma can be used to prevent attacks when a patient is facing an emergency procedure. This is because administering fresh frozen plasma prophylactically to an asymptomatic patient does not pose the risk of exacerbation that is seen when given during an acute attack.

Long term preventive treatment

Some patients experience only infrequent and mild attacks and therefore require no long-term therapy. Clinicians generally recommend long term therapy for patients who experience more than one attack per month, or who believe that the disease significantly interferes with their life style.

In Oct 2008, ViroPharma received FDA approval for Cinryze, the company's C1 inhibitor concentrate product, as an attack prevention therapy. The European brand of this product has an impressive safety record spanning three decades. Cinryze, the version that is now available in the US offers enhanced assurance by adding double nano filtration.

ViroPharma has put together an infrastructure, Cinryze Solutions, to make Cinryze available to every HAE patient that could benefit from the medicine. Please contact the HAEA's Patient Services group for more information:

Donna Davis donna-davis@haea.org, (808) 216-1029 or
Michelle Williamson michellewilliamson@haea.org, (972) 814-5205.

Drugs currently available for long-term therapy are the 17 alpha alkylated androgens danazol and oxandrolone. 17 alpha alkylated androgens produce an increase in C1-inhibitor levels, but the exact mechanism of how they do so has not been precisely defined.

The dose of anabolic androgens used to treat HAE should be titrated down to find the lowest dose that prevents attacks. A reasonable starting dose for danazol is 200 mg/day and 5 mg/day for oxandrolone. If good control is obtained, it is reasonable to try and reduce the dosages by 50 mg/week and 2.5 mg/week respectively after 4 weeks. Clinicians report that many patients are well controlled on 200 mg/day danazol or 2.5 mg/day oxandrolone, but it is not unusual to see patients that require higher or lower doses. There is subset of patients for whom androgens are not effective at any dose.

Professor Zuraw notes that it is important to base androgen dosages on the clinical effect and not laboratory values.² In addition, the side effects of anabolic androgens are dose related, with the most important side effects being hepatotoxicity and virilization.² Professor Zuraw advises that patients taking anabolic androgens should have their liver enzymes checked every six months.² Since hepatic adenomas have been reported as a consequence of anabolic androgens, Professor Zuraw recommends ultrasound examination of the liver in the presence of consistently elevated liver enzymes.² A class of drugs called antifibrinolytics have been shown to prevent attacks in some patients, but their use has largely been abandoned in the US because androgens have proven to be much more effective than antifibrinolytics

Treating children with HAE

Fortunately, most prepubescent children with HAE do not suffer from frequent attacks and infrequent flares affecting the abdomen can be managed by using pain relievers and anti nausea agents. The small number of severely affected children who experience frequent and severe attacks must be managed on a case by case basis. Two studies done in the US indicate that oxandrolone may be the androgen of choice for children with HAE so severe that treatment is warranted.^{5, 6} Professor Zuraw noted good results using 2.5 mg once or twice a week in treating severely affected children.²