Flogging a dead pony: FDA Update on Black Box Warning

[Guest guest]

Nan here....the FDA site is a pain to navigate, so I cut and paste.

http://www.fda.gov/cder/drug/InfoSheets/HCP/omalizumabHCP.htm

Boy, is the FDA hyping up " the shot should only be giving in medical settings " .

I wonder how many doctors this is going to scare.

Nan-->who, I guess, should be grateful that I can get the injection at

the doctor's office, instead of the infusion center.

---------FROM FDA WEB

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FDA ALERT [2/2007, updated 7/2007]: This Alert highlights important

revisions to the full prescribing information for Xolair. The updated

full prescribing information for Xolair (July 2007) includes a new

Boxed WARNING, updated WARNINGS, PRECAUTIONS, and ADVERSE

REACTIONS--Postmarketing Spontaneous Reports. A New Medication Guide

[PDF] about the risk of anaphylaxis following administration of Xolair

is to be distributed with each dose of Xolair.. These revisions

address the risk of anaphylaxis following treatment with Xolair. The

implications of this new labeling for healthcare professionals who

administer Xolair are summarized below. Xolair is approved to treat

adults and adolescents (12 years of age and above) with moderate to

severe persistent asthma who have a positive skin test or in vitro

reactivity to a perennial aeroallergen and whose symptoms are

inadequately controlled with inhaled corticosteroids.

Recommendations and considerations for healthcare professionals:

Anaphylaxis, presenting as bronchospasm, hypotension, syncope,

urticaria, and/or angioedema of the throat or tongue has been reported

to occur after administration of Xolair.

* Anaphylaxis has occurred as early as after the first dose of

Xolair, but also has occurred beyond one year after beginning regular

treatment with Xolair.

* Due to the risk of anaphylaxis, Xolair should only be

administered to patients in a healthcare setting under direct medical

supervision by providers who:

o Are prepared to identify and treat anaphylaxis after

Xolair treatment

o Know anaphylaxis can occur after any dose of Xolair, even

if past doses were well tolerate

o Know the onset of anaphylaxis can be delayed after administratiom

o Observe patients for an appropriate period of time

following each Xolair injection

o Have trained personnel, medications, and equipment for the

treatment of life-threatening anaphylaxis available when administering

Xolair. Medical personnel administering Xolair should be prepared to

recognize and treat anaphylaxis

* Inform patients receiving Xolair treatment of their chance of

developing anaphylaxis (including anaphylaxis delayed for 24 hours or

more following Xolair treatment) and how to treat it if it occurs.

The " Information for the patient " section below provides more detail.

o Give patients the Medication Guide [PDF] for Xolair and

instruct them to read it before starting treatment with Xolair and

before each subsequent dose

o Inform patients of the signs and symptoms of anaphylaxis

o Instruct patients to seek immediate care should such symptoms occur

* Discontinue Xolair in patients who experience a severe

hypersensitivity reaction

* Report patients who have adverse events including anaphylaxis or

hypersensitivity to the FDA's MedWatch program (see reporting

information at the bottom of this page)

* Periodically reassess the need for continued Xolair therapy

based upon the patient's disease severity and level of asthma control

Information for the patient: Physicians who are prescribing Xolair

should discuss with their patients:

* Because of the chance of anaphylaxis with Xolair, patients

should receive Xolair treatment in a doctor's office and be observed

for an appropriate period of time after each treatment

* Anaphylaxis can be serious and life-threatening. Signs and

symptoms of anaphylaxis include:

o Wheezing, shortness of breath, cough, chest tightness, or

trouble breathing

o Low blood pressure, dizziness, fainting, rapid or weak

heartbeat, anxiety, or feeling of " impending doom "

o Swelling of the throat or tongue, throat tightness, hoarse

voice, or trouble swallowing

o Flushing, itching, hives, or feeling warm

* Anaphylaxis can occur with the first dose or after any dose of Xolair

* Anaphylaxis can begin 24 hours or more after Xolair treatment

* To tell your healthcare provider right away if you have symptoms

of anaphylaxis after receiving Xolair, and

* To get emergency medical attention immediately if any symptoms

of anaphylaxis appear after leaving the doctor's office

* Carry medical contact information and be fully prepared to begin

treatment for anaphylaxis

* You should not receive Xolair if you have ever had an allergic

reaction to a Xolair injection

* Do not change or stop taking any of your other asthma

medications unless otherwise instructed to do so by a healthcare

provider

* Patients may not see immediate improvement in their asthma after

beginning Xolair therapy

Background Information and Data

Clinical trial experience

Three cases of anaphylaxis were identified among the 3,507 subjects

exposed to Xolair in premarketing clinical trials. Reports of

anaphylaxis were based on investigator judgment in relationship to the

study drug. The time to onset of anaphylaxis after administration of

Xolair in these three patients was:

* 90 minutes in two patients

* 2 hours in one patient.

In addition to these three cases, there were two cases of dyspnea

and/or wheezing with urticaria that were not reported as anaphylaxis,

but met the diagnostic criteria for anaphylaxis that were used to

define the postmarketing cases (see below). One of these patients

developed localized urticaria, dyspnea, coughing, and wheezing after

receiving the first dose of Xolair. The second patient experienced

urticaria, dyspnea, and hot flushes the day after receiving the third

dose of Xolair.

Postmarketing Cases

Based on a review of 124 spontaneous case reports and an estimated

exposure of about 57,300 patients from June 2003 to December 2006, the

frequency of anaphylaxis attributed to Xolair use was estimated to be

at least 0.2% of treated patients. Because adverse reactions are

reported voluntarily, the actual frequency of anaphylaxis and percent

of patients with onset during specific time periods after

administration of Xolair may differ from these estimates and this case

series. The case definition of anaphylaxis used for this review

included either skin or mucosal tissue involvement, and, either airway

compromise, and/or reduced blood pressure with or without associated

symptoms; and a temporal relationship with Xolair administration with

no other identifiable cause.

Symptoms and signs of anaphylaxis in these reported cases included

bronchospasm, hypotension, syncope, urticaria, angioedema of the

throat or tongue, dyspnea, cough, chest tightness, cutaneous

angioedema, and generalized pruritus. Some patients required oxygen

and parenteral medications. Pulmonary involvement, including

bronchospasm, dyspnea, cough, or chest tightness, was reported in 89%

of the cases. Hypotension or syncope was reported in 14% of cases.

Fifteen percent of patients required hospitalization. A previous

history of anaphylaxis unrelated to Xolair was reported in 24% of the

cases. The list below provides information about the time to onset of

anaphylaxis following Xolair administration for these patients.

• 30 minutes or less 35%

• Greater than 30 to 60 minutes 16%

• Greater than 60 to 90 minutes 2%

• Greater than 90 to 120 minutes 6%

• Greater than 2 hours to 6 hours 5%

• Greater than 6 to 12 hours 14%

• Greater than 12 to 24 hours 8%

• Greater than 24 hours (up to 4 days) 5%

• Unknown 9%

Of the reported cases of anaphylaxis, 39% occurred after the first

dose of Xolair, 19% occurred with the second dose, 10% occurred with

the third dose, and the rest after subsequent doses. One case

occurred after 39 doses (after 19 months of continuous therapy,

anaphylaxis occurred when treatment was restarted following a 3 month

gap). Twenty-three patients who experienced anaphylaxis were

re-challenged with Xolair; among them, 18 had a recurrence of similar

symptoms of anaphylaxis. Four patients who experienced urticaria and

not anaphylaxis were re-challenged with Xolair and developed

anaphylaxis upon re-challenge.

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