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U.S. Department of Health and Human Services

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Shire Pharmaceuticals Warning Letter 2011

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 

Silver Spring, MD 20993 


TRANSMITTED BY FACSIMILE


Angus Russell
Chief Executive Officer
Shire Pharmaceuticals, Inc.
725 Chesterbrook Blvd.
Wayne, PA 19087-5637


RE: NDA 021977
Vyvanse® (lisdexamfetamine dimesylate) Capsules, CII
MACMIS #19828


WARNING LETTER


Dear Mr. Russell:


The Division of Drug Marketing, Advertising, and Communications (DDMAC) of the U.S. Food and Drug Administration (FDA) has reviewed a magnet (LDX1617) for Vyvanse (lisdexamfetamine dimesylate) Capsules, CII (Vyvanse) of Shire Pharmaceuticals, Inc. (Shire). Photographs of this piece were taken at a pediatric medical office in 2011 and submitted as part of a complaint to the DDMAC Bad Ad Program. The magnet is violative because it makes representations regarding the use of Vyvanse, but omits the full indication and risks associated with the use of the drug. Thus, the magnet misbrands the drug in violation of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 352(a) and 321(n). Cf. 21 CFR 202.1(e)(3)(i), (ii); (e)(5) & (e)(6)(i). These violations are concerning from a public health perspective because they suggest that Vyvanse is safer and more effective than has been demonstrated.


Background


According to its FDA-approved product labeling (PI),1 Vyvanse is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children. The efficacy of Vyvanse in the treatment of ADHD was established in children aged 6-12 years. The INDICATIONS AND USAGE section of the PI also includes information regarding special diagnostic considerations, the need for comprehensive treatment, and long-term use.


Vyvanse is associated with a number of serious risks, some of which are fatal, including a Boxed Warning concerning the potential for abuse. Vyvanse has numerous Contraindications, including use in patients with advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncratic reaction to sympathomimetic amines, glaucoma, agitated states, history of drug abuse; and use during or within 14 days following the administration of monoamine oxidase inhibitors. The PI includes Warnings related to serious cardiovascular events, psychiatric adverse events, long-term suppression of growth, seizures, and visual disturbances. The PI also contains a general Precaution regarding overdosage and use in patients who use other sympathomimetic drugs, as well as Precautions for patients with tics and Tourette’s syndrome. The most common adverse reactions associated with the use of Vyvanse include upper abdominal pain, decreased appetite, dizziness, dry mouth, irritability, insomnia, nausea, vomiting, and decreased weight.


Omission of Indication and Risk Information


Promotional materials are misleading if they fail to reveal facts that are material in light of the representations made by the materials or with respect to the consequences that may result from the use of the drug as recommended or suggested by the materials.


Photographs, submitted as part of this Bad Ad complaint, show a promotional magnet for Vyvanse. Scanning from top to bottom, the magnet includes the product trade and established names, certain claims described below, images of six different dosage strengths of Vyvanse capsules, and the statement, “Your Vyvanse sales representative is.” Immediately below this statement there is a clear plastic sleeve, which, at the time the photographs were taken, included a Shire sales representative’s business card. Behind the clear plastic sleeve, the magnet contains printed risk information. As explained further below, the design of this magnet resulted in the inserted business card covering the majority of risk information.


The presentation includes the following claims (emphasis in original):


• “Vyvanse™ CII . . .
The First Prodrug Stimulant” (magnet)


• “Vyvanse – Titrate to achieve maximum efficacy and tolerability” (magnet)


• “Shire US Inc.
your ADHD Support Company™” (magnet)


• “[Sales representative name] . . .
ADHD sales” (business card)


The totality of this presentation makes representations about the use of Vyvanse in the treatment of ADHD. However, this promotional piece fails to adequately communicate the full indication for Vyvanse including important information regarding special diagnostic considerations, the need for comprehensive treatment, and long-term use.
 

The magnet also fails to adequately disclose risk information associated with the use of Vyvanse. As mentioned above, DDMAC notes that risk information is printed on the lower-half of the magnet below the statement, “Your Vyvanse sales representative is.” However, as a practical matter, this information is not communicated to the viewer. The magnet is designed for a Shire ADHD sales representative to place his or her business card in the sleeve, thus covering the majority of the important risk information. For example, a photograph that was submitted as part of this Bad Ad complaint shows a business card positioned in the sleeve of the magnet such that only the most common adverse reactions are visible. Presenting the risk information in this manner is not sufficient to ensure that the claims on the magnet are truthful and non-misleading. This omission of risk information is particularly concerning given that the PI for Vyvanse discusses numerous risks, including a Boxed Warning regarding the potential for abuse.


As a result, the totality of this presentation misleadingly suggests that Vyvanse is safer and more effective than has been demonstrated by substantial evidence or substantial clinical experience. We note that the statement, “Please see accompanying Full Prescribing Information, including Boxed Warning,” is included on the bottom of the magnet; however, this statement does not mitigate the omission of indication and risk information.


Conclusion and Requested Action


For the reasons discussed above, the magnet misbrands Vyvanse in violation of the Act, 21 U.S.C. 352(a) and 321(n). Cf. 21 CFR 202.1(e)(3)(i), (ii); (e)(5) & (e)(6)(i).


DDMAC requests that Shire immediately cease the dissemination of violative promotional materials for Vyvanse such as those described above. Please submit a written response to this letter on or before May 20, 2011, stating whether you intend to comply with this request, listing all promotional materials (with the 2253 submission date) for Vyvanse that contain violations such as those described above, and explaining your plan for discontinuing use of such violative materials. Because the violations described above are serious, we request, further, that your submission include a comprehensive plan of action to disseminate truthful, non-misleading, and complete corrective messages about the issues discussed in this letter to the audience(s) that received the violative promotional 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, or facsimile at 301-847-8444. In all future correspondence regarding this matter, please refer to MACMIS# 19828 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 Vyvanse comply with each applicable requirement of the Act and FDA implementing regulations.


Failure to correct the violation discussed above may result in FDA regulatory action, including seizure or injunction, without further notice.


Sincerely,
{See appended electronic signature page}
Thomas W. Abrams, RPh, MBA
Director
Division of Drug Marketing,
Advertising, and Communications
Reference ID: 2943099
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This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature.
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/s/
----------------------------------------------------
THOMAS W ABRAMS
05/06/2011
Reference ID: 2943099

 

The magnet that is the subject of this letter is dated March 2008. Therefore, the PI referred to in this letter is the one approved in December 2007; however, the most recent version of the approved PI was approved in March 2011.

 

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