Richard Fosko, RPh, MPH, Director
Regulatory Affairs
Meda Pharmaceuticals, Inc. 
265 Davidson Avenue, Suite 300
Somerset, NJ 08873-4120

RE:  NDA #20-114
       ASTELIN^®(azelastine hydrochloride) Nasal Spray
       MACMIS #18201

Dear Mr. Fosko:

As part of its routine monitoring and surveillance program, the Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed a waiting room sign (sign), entitled “Astelin ‘House Cleaning’ Waiting Room Sign” (ID AST8079), for ASTELIN^® (azelastine hydrochloride) Nasal Spray (Astelin) submitted by Meda Pharmaceuticals Inc.  (Meda) under cover of Form FDA 2253 (2253).  The sign is misleading because it omits and minimizes important risk information associated with the use of Astelin, broadens the indication, and overstates the efficacy of the drug.  Thus, the sign misbrands Astelin in violation of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 352(a) & 321(n).  Cf. 21 CFR 202.1(e)(5), (6)(i) & (7)(viii). 

Background

According to its FDA-approved product labeling (PI):

Astelin^® Nasal Spray is indicated for the treatment of the symptoms of seasonal allergic rhinitis such as rhinorrhea, sneezing, and nasal pruritus in adults and children 5 years and older, and for the treatment of the symptoms of vasomotor rhinitis, such as rhinorrhea, nasal congestion and postnasal drip in adults and children 12 years and older. 

The Astelin PI includes a precaution regarding activities requiring mental alertness, which states:

In clinical trials, the occurrence of somnolence has been reported in some patients taking Astelin^® Nasal Spray; due caution should therefore be exercised when driving a car or operating potentially dangerous machinery while using Astelin^® Nasal Spray.  Concurrent use of Astelin^® Nasal Spray with alcohol or other CNS depressants should be avoided because additional reductions in alertness and additional impairment of CNS performance may occur. 

The most commonly reported adverse events associated with the use of Astelin include bitter taste, headache, somnolence, nasal burning, dysesthesia, and rhinitis.  Additionally, the adverse events that occurred more frequently than placebo in patients 5 to 12 years of age that were not represented in the adult population include rhinitis/cold symptoms, cough, conjunctivitis, and asthma. 

Omission and Minimization of Risk Information

Promotional materials are misleading if they fail to reveal facts that are material in light of representations made by the materials or with respect to consequences that may result from the use of the drug as recommended or suggested by the materials, and if they fail to present information about risks associated with a drug with a prominence and readability reasonably comparable with the presentation of information relating to the effectiveness of the drug.  Specifically, the sign includes the claims, “Allergic to house cleaning?” and “It’s a sign.  Time to toss the tissues with ASTELIN^®” in large, colorful font, along with a large visual of a box of tissues being tossed into a waste basket.  In contrast, the only risk information contained on the sign (a disclosure of common adverse events) is presented at the bottom of the sign after the indication for the drug in extremely small font size and in a single-spaced format that makes this information very difficult to read.  Furthermore, in contrast to the consumer-friendly claims on the sign, some of the risk information that is disclosed (i.e., “somnolence” and “rhinitis”) is presented in medical terminology that is not likely to be understood by consumers. 

This presentation also fails to disclose material risks associated with Astelin.  For example, it omits important material facts from the precautions section of the PI related to the risk of somnolence.  Additionally, the sign indicates the product is approved for patients 5 years of age and older, but fails to include the most common adverse events that occurred more frequently in patients 5 to 12 years of age that were not represented in the adult population (i.e., rhinitis/cold symptoms, cough, conjunctivitis, and asthma). 

We note the sign includes the bolded statement, “Please see accompanying full Prescribing Information” in small type.  However this does not mitigate the overall effect of this presentation, which undermines the communication of important risk information, thereby minimizing the risks associated with Astelin and suggesting that Astelin is safer than has been demonstrated. 

Broadening of Indication

The sign is misleading because it implies that Astelin is useful in a broader range of conditions or patients than has been demonstrated by substantial evidence or substantial clinical experience.  Specifically, it prominently presents the headline, “Allergic to house cleaning?” and suggests Astelin will treat such allergies.  House cleaning is typically associated with exposure to perennial allergens such as dust mites, molds, and pet dander.  Astelin is not approved to treat perennial allergens associated with perennial allergic rhinitis.  As noted in the background section, Astelin is indicated for the treatment of the symptoms of seasonal allergic rhinitis in adults and children 5 years and older and for the treatment of the symptoms of vasomotor rhinitis in adults and children 12 years and older.  While household cleaning products can trigger vasomotor rhinitis symptoms, the overall message of the sign is that Astelin can treat any allergen associated with house cleaning, such as the perennial allergens listed above, when this is not the case. 

Overstatement of Efficacy

Promotional materials are misleading if they suggest that a drug product is more effective than has been demonstrated by substantial evidence or substantial clinical experience.  Specifically, the sign presents the claim, “Time to toss the tissues with Astelin^®” along with a visual of a box of tissues being tossed into a waste basket.  This presentation misleadingly implies that treatment with Astelin will result in complete resolution of symptoms.  However, according to the PI, treatment with Astelin demonstrated improvement, not complete resolution, in symptom scores.  For example, the change from baseline in the Major Symptom Complex (MSC) scores for Astelin versus placebo in the three seasonal allergic rhinitis trials supporting two sprays per nostril twice daily were -3.05 vs.-1.07, -4.10 vs.-2.07, and -3.31 vs.-1.96.  The change from baseline in the Total Nasal Symptom Score (TNSS) for Astelin versus placebo in the two seasonal allergic rhinitis trials supporting one spray per nostril twice daily were -2.69 vs.  -1.31 and -3.68 vs.  -2.50.  We are not aware of substantial evidence or substantial clinical experience to support the implication that Astelin will result in complete resolution of symptoms. 

Conclusion and Requested Action

The sign is misleading because it omits and minimizes important risk information associated with the use of Astelin, broadens the indication, and overstates the efficacy of the drug.  For the reasons discussed above, the sign misbrands Astelin in violation of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 352(a) & 321(n). Cf. 21 CFR 202.1(e)(5), (6)(i) & (7)(viii). 

DDMAC requests that Meda immediately cease the dissemination of violative promotional materials for Astelin such as those described above.  Please submit a written response to this letter on or before February 9, 2009, stating whether you intend to comply with this request, listing all promotional materials (with the 2253 submission date) in use for Astelin that contain violations such as those described above, and explaining your plan for discontinuing use of such violative materials. 

Please direct your response to me at the Food and Drug Administration, Center for Drug Evaluation and Research, Division of Drug Marketing, Advertising, and Communications, 5901-B Ammendale Road, Beltsville, MD 20705-1266, facsimile at 301-847-8444.  In all future correspondence regarding this matter, please refer to MACMIS #18201 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 Astelin comply with each applicable requirement of the Act and FDA implementing regulations. 

Sincerely,

Robyn Tyler, Pharm.D., J.D. 
Regulatory Review Officer
Division of Drug Marketing,
Advertising, and Communications