Xolair Linked to Risk for Delayed-Onset Anaphylaxis

February 22, 2007 — Omalizumab subcutaneous injection (Xolair, made by Genentech, Inc) may be linked to life-threatening anaphylaxis, according to a warning from the US Food and Drug Administration (FDA).

Although most cases (71%) have occurred within 2 hours of omalizumab injection, some (13%) delayed-onset cases have been reported after 2 to more than 24 hours, according to an alert sent yesterday from MedWatch, the FDA's safety information and adverse event reporting program. The FDA notes that anaphylaxis can occur after any dose of omalizumab (including the first dose), even if past doses were well tolerated.

The warning was based on a review of 48 case reports submitted to the agency from June 2003 to December 2005 from an estimated 39,500 omalizumab-exposed patients. The review showed that the incidence of drug-related anaphylaxis was at least 0.1%.

Anaphylaxis occurred after the first dose of omalizumab in 40% of cases and after repeat administration in 56% of cases. Some patients experienced anaphylaxis after 2 years of chronic treatment.

Symptoms included bronchospasm, hypotension, syncope, urticaria, angioedema of the throat/tongue, dyspnea, cough, chest tightness, cutaneous angioedema, and generalized pruritus. Some patients required oxygen and parenteral medications. Pulmonary involvement and hypertension/syncope were reported in 96% and 13% of cases, respectively; 15% of these patients required hospitalization.

Healthcare professionals are advised to provide direct medical supervision during omalizumab administration and to observe patients for at least 2 hours after each injection. Trained personnel should be able to recognize anaphylaxis and treat it appropriately with available medication and equipment.

The FDA advises discontinuation of omalizumab in patients who experience a severe hypersensitivity reaction; in the case reports, all 5 patients who were rechallenged with omalizumab after resolution of anaphylaxis experienced a recurrence of similar symptoms.

Patients receiving omalizumab therapy should be informed of the risk for anaphylaxis, the potential for delayed reactions, and advised to be on the lookout for symptoms such as wheezing, cough, chest tightness, or increased trouble with breathing; dizziness, fainting, rapid or weak heartbeat; swelling in the mouth and difficulty swallowing; flushing, itching, hives, or a sensation of warmth; and vomiting, diarrhea, or abdominal cramping.

In addition, patients should be advised to carry medical information and be fully prepared to begin treatment for anaphylaxis, including use of an epinephrine auto-injector and obtaining immediate medical attention for recognized symptoms.

Omalizumab is indicated for the treatment of moderate to severe persistent asthma in patients aged 12 years and older who have a positive skin test or in vitro reactivity to a perennial aeroallergen whose symptoms are inadequately controlled with inhaled corticosteroids.

Healthcare professionals are encouraged to report omalizumab-related adverse events to the FDA's MedWatch reporting program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.