Released by FDA:  12/9/04.  Posted by FDA:  12/23/04

Ketan Patel
Associate Manager, Marketed Products Support
Global Regulatory Affairs
Schering Corporation
2000 Galloping Hill Road
Kenilworth, NJ 07033

Re:   NDA #: 20-831
         Foradil Aerolizer® (formoterol fumarate inhalation powder) 12mcg
         MACMIS #: 12472

Dear Mr. Patel:

The Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed a professional detail aid (FST1797) for Foradil@ Aerolizer® (formoterol fumarate inhalation powder) 12 mcg (Foradil) submitted by Schering Corporation (Schering) under cover of Form FDA 2253.  DDMAC has concluded that the detail aid is false or misleading in violation of Sections 502(a) and 201 (n) of the Federal Food, Drug, and Cosmetics Act (Act) (21 USC 352(a) and 321(n)) because it broadens the indication for Foradil and fails to reveal important risk information, thereby encouraging the potentially unsafe use of Foradil.

Background

Foradil is a long-acting selective beta₂-adrenergic receptor agonist, that, when inhaled, acts locally in the lung as a bronchodilator.  According to the Indications and Usage section of the approved product labeling (PI):

FORADIL AEROLIZER is indicated for long-term, twice-daily (morning and evening) administration in the maintenance treatment of asthma and in the prevention of bronchospasm in adults and children 5 years of age and older with reversible obstructive airways disease, including patients with symptoms of nocturnal asthma, who require regular treatment with inhaled, short-acting, beta₂agonists.  It is not indicated for patients whose asthma can be managed by occasional use of inhaled, short-acting, beta₂-agonnsts.

FORADIL AEROLIZER is also indicated for the acute prevention of exerciseinduced bronchospasm (EIB) in adults and children 5 years of age and older, when administered on an occasional, as-needed basis.

FORADIL AEROLIZER can be used to treat asthma concomitantly with shortacting beta₂-agonists, inhaled or systemic corticosteroids, and theophylline therapy (see PRECAUTIONS, Drug Interactions).  A satisfactory clinical response to FORADIL AEROLIZER does not eliminate the need for continued treatment with an anti-inflammatory agent.

FORADIL AEROLIZER is indicated for the long-term, twice daily (morning and evening) administration in the maintenance treatment of bronchoconstriction in patients with Chronic Obstructive Pulmonary Disease including chronic bronchitis and emphysema.

Use of Foradil is inappropriate in certain settings and is associated with numerous risks as stated in the Contraindications, Warnings, Precautions, and Adverse Reactions sections of the PI.  For example, the PI includes the following bolded warnings:

IMPORTANT INFORMATION: FORADIL AEROLIZER SHOULD NOT BE INITIATED IN PATIENTS WITH SIGNFICANTLY WORSENING OR ACUTELY DETERIORATING ASTHMA, WHICH MAY BE A LIFE-THREATENING CONDITION.  The use of FORADIL AEROLIZER in this setting is inappropriate.

FORADIL AEROLIZER IS NOT A SUBSTITUTE FOR INHALED OR ORAL CORTICOSTEROIDS.  Corticosteroids should not be stopped or reduced at the time FORADIL AEROLIZER is initiated. (See PRECAUTIONS, Information for Patients and the accompanying Patient Instructions For Use.)

When beginning treatment with FORADIL AEROLIZER, patients who have been taking inhaled, short-acting beta₂-agonists on a regular basis (e.g., four times a day) should be instructed to discontinue the regular use of these drugs and use them only for symptomatic relief of acute asthma symptoms (see PRECAUTIONS, Information for Patients).

Broadening of Indication

The first page of the detail aid presents the name of the product, "Foradil@ Aerolizer® (formoterol fumarate inhalation powder) 12 mcg," and the claim "FOR YOUR PATIENTS WITH COPD, ASTHMA, OR EXERCISE-INDUCED BRONCHOSPASM (EIB)...."  The Indications section of the PI specifically states that Foradil "is not indicated for patients whose asthma can be managed by occasional use of inhaled, short-acting, beta₂-agoinsts."  The presentation improperly suggests that Foradil can be used for any type or severity of asthma.  In addition, the Warnings section of the PI states, "FORADIL AEROLIZER should not be initiated in patients with significantly worsening or acutely deteriorating asthma, which may be a life-threatening condition" and "The use of FORADIL AEROLIZER in this setting is inappropriate."  Therefore, your presentation raises significant public health and safety concerns because you are promoting the use of Foradil in an inappropriate situation.

Failure to Reveal Important Risk Information

The detail aid presents the indication for Foradil but fails to reveal any risk information that is critical to its appropriate use.  We note that the detail aid states, "Please see full prescribing information."  However, this reference to the full prescribing information does not mitigate the complete omission of risk information in the detail aid.  By failing to reveal any of the important risk information, Schering misleadingly suggests that Foradil is safer than has been demonstrated by substantial evidence or substantial clinical experience.

Conclusion and Requested Action

The detail aid broadens the indication for Foradil and fails to reveal risk information associated with the use of Foradil.  Accordingly, the detail aid violates sections 502(a) and 201 (n) of the Act, 21 USC 352(a) and 321(n), and misbrands Foradil.

DDMAC requests that Schering immediately cease the dissemination of promotional materials for Foradil that contain claims that are the same as or similar to those described above. Please submit a written response to this letter on or before December 23, 2004 describing your intent to comply with this request, listing all promotional materials for Foradil that contain claims that are the same as or similar to those described above, and explaining your plan for discontinuing use of these materials. Please direct your response to me at the Food and Drug Administration, Division of Drug Marketing, Advertising, and Communications, HFD-42, Rm. 813-45, 5600 Fishers Lane, Rockville, Maryland 20857, facsimile at 301-5946771.  In all future correspondence regarding this matter, please refer to MACMIS ID # 12472 in addition to the NDA number.  We remind you that only written communications are considered official.

The violations discussed in this letter do not necessarily constitute an exhaustive list.  It is your responsibility to ensure that your promotional materials for Foradil comply with each applicable requirement of the Act and FDA implementing regulations.

Sincerely,

Jialynn Wang, Pharm.D.
LT, USPHS
Regulatory Review Officer
Division of Drug Marketing,
  Advertising, and Communications