Kathleen Louden

November 07, 2014

CHICAGO — Subcutaneous icatibant (Firazyr, Shire) in the emergency department can eliminate the need for invasive airway management in patients with life-threatening angioedema due to cardiac medications, according to a new study.

In all seven patients who received the drug, angioedema visibly decreased within an hour of administration, reported lead investigator Mark DeBard, MD, from the Ohio State University Wexler Medical Center in Columbus.

"All of these patients were about to have an invasive airway maneuver, and nobody needed one after icatibant treatment," Dr DeBard told Medscape Medical News here at the American College of Emergency Physicians 2014 Scientific Assembly.

Icatibant, a bradykinin B₂ receptor antagonist, was approved by the US Food and Drug Administration in 2011 for treatment of hereditary angioedema in adults. It has been used off-label to prevent tracheotomy in patients with acute angioedema stemming from the use of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin receptor blockers.

About 0.1% to 1.0% of patients taking ACE inhibitors or angiotensin receptor blockers experience angioedema, according to Dr DeBard, and some progress to life-threatening oral edema.

However, the average $9600 wholesale cost of icatibant limits its use to patients experiencing airway compromise. "It's an incredibly expensive drug, but for the few patients with the most severe drug-induced angioedema, its use seems justified," he said.

In their study, Dr DeBard and colleagues retrospectively reviewed patients in the emergency department with drug-induced angioedema in need of imminent invasive airway management, such as endotracheal intubation, cricothyrotomy, and tracheotomy.

The team assessed outcomes at Wexler Medical Center and another university-affiliated hospital for a 10-month period before the protocol of administering subcutaneous icatibant 30 mg for life-threatening drug-induced angioedema was implemented (January to October 2011), and for a 10-month period after it was implemented (May 2013 to February 2014)

In the two study periods, there were 110 cases with a diagnostic code for angioedema; 105 were associated with ACE inhibitors and 5 were associated with angiotensin receptor blockers.

Hospital stays were shorter and costs were much lower for the seven icatibant-treated patients than for the other patients. And none of the icatibant-treated patients experienced adverse effects, including hypertension, Dr DeBard reported.

Table. Outcomes for Angioedema Patients

Parameter Before Icatibant After Icatibant
Total cases of angioedema, n 93 143
Patients admitted, n 18 32
Invasive airway intervention, n 6 1
Drug-induced angioedema 44 66
   ACE inhibitor, n 42 63
   Angiotensin receptor blocker, n 2 3
Mean hospital stay, days    
   No icatibant 7.7 6.0
   Icatibant 0.5
Mean hospital costs, $    
   No icatibant 17,878 15,137
   Icatibant 5951


A multicenter clinical trial (NCT01919801) investigating icatibant for patients with ACE inhibitor-induced angioedema is expected to be completed next year, according to the drug manufacturer.

One of the investigators from that trial, Phillip Levy, MD, from Wayne State University in Detroit, said the early results look promising.

The reduction in angioedema after icatibant treatment is dramatic, Dr Levy reported during a research highlights session. "It's like deflating a balloon," he said.

"The cost of the drug may influence treatment decisions," he said, "but for now, we don't have any viable treatment that works as well."

A conference delegate wondered whether fresh frozen plasma would work in patients with drug-induced angioedema.

"Fresh frozen plasma has not been proven to work well in these patients, to my knowledge, and has not been shown to avoid invasive airway maneuvers," Dr DeBard told Medscape Medical News.

It is too early to recommend icatibant for this off-label use, said Angela Mills, MD, from the University of Pennsylvania Perelman School of Medicine in Philadelphia. "I want to see results from a multicenter trial and cost analyses."

Dr DeBard has disclosed no relevant financial relationships. Dr Levy is an investigator for clinical trials of icatibant. Dr Mills has received consulting fees from Insys Therapeutics and Novartis.

American College of Emergency Physicians (ACEP) 2014 Scientific Assembly: Poster abstract 36. Presented October 27, 2014.


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