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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
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` Silver Spring MD 20993
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` NDA 021928/S-031
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` SUPPLEMENT APPROVAL
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` FULFILLMENT OF POSTMARKETING REQUIREMENT
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`Pfizer, Inc.
`235 E. 42nd Street
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`New York, NY 10017
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`Attention: Lilya I. Donohew, PhD
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`Senior Director, Worldwide Regulatory Affairs
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`Dear Dr. Donohew:
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`Please refer to your Supplemental New Drug Application (sNDA) dated May 21, 2012, received
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`May 21, 2012, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
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`(FDCA) for Chantix (varenicline) Tablets; 0.5 mg and 1 mg.
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`Reference is also made to your submissions dated February 10, and March 30, 2012, reporting on
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`the postmarketing requirement to conduct a meta-analysis evaluating the incidence of
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`cardiovascular adverse events in Chantix-treated patients compared to control patients in Pfizer
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`sponsored randomized clinical trials.
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`We acknowledge receipt of your amendments dated May 30, and October 15, 2012.
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`This Prior Approval supplement provides for revisions to the HIGHLIGHTS, WARNINGS
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` AND PRECAUTIONS /Cardiovascular Events, and PATIENT COUNSELING, sections of the
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` Package Insert, and Medication Guide, to include results from the cardiovascular meta-analysis of
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` varenicline clinical trials.
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` We have completed our review of this supplemental application, as amended. It is approved,
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` effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
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` text.
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` CONTENT OF LABELING
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` As soon as possible, but no later than 14 days from the date of this letter, submit the content of
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` labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
` automated drug registration and listing system (eLIST), as described at
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` http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
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`of labeling must be identical to the enclosed labeling text for the package insert and Medication
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`Guide, with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
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`supplements, as well as annual reportable changes not included in the enclosed labeling.
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`Reference ID: 3228878
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` NDA 021928/S-031
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` Page 2
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` Information on submitting SPL files using eLIST may be found in the guidance for industry
` titled “SPL Standard for Content of Labeling Technical Qs and As” at
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`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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`The SPL will be accessible from publicly available labeling repositories.
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` Also within 14 days, amend all pending supplemental applications for this NDA, including CBE
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` supplements for which FDA has not yet issued an action letter, with the content of labeling
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` [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the changes approved in this
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` supplemental application, as well as annual reportable changes and annotate each change. To
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` facilitate review of your submission, provide a highlighted or marked-up copy that shows all
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` changes, as well as a clean Microsoft Word version. The marked-up copy should provide
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` appropriate annotations, including supplement number(s) and annual report date(s).
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`FULFILLMENT OF POSTMARKETING REQUIREMENT
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`We have received your submissions dated February 10, and March 30, 2012, reporting on and
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`containing the final report for the following postmarketing requirement:
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`1804-1
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`Conduct a meta-analysis evaluating the incidence of cardiovascular adverse
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`events in Chantix-treated patients compared to control patients in Pfizer
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`sponsored randomized clinical trials. The study must include an analysis of all
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`serious adverse events with adjudication and an analysis of all adverse events
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`without adjudication.
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`We have reviewed your submission and conclude that the above requirement has been fulfilled.
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`We remind you that there are postmarketing requirements listed in the May 10, 2006, approval
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`letter and the March 12, and September 22, 2011, postapproval postmarketing requirement letters
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`that are still open.
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
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`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
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`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
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`Food and Drug Administration
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`Center for Drug Evaluation and Research
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`Office of Prescription Drug Promotion (OPDP)
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`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`Reference ID: 3228878
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` NDA 021928/S-031
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` Page 3
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` You must submit final promotional materials and package insert(s), accompanied by a Form
` FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
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` FDA 2253 is available at http://www.fda.gov/opacom/morechoices/fdaforms/cder.html;
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`instructions are provided on page 2 of the form. For more information about submission of
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`promotional materials to the Office of Prescription Drug Promotion (OPDP), see
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`http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
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`(21 CFR 314.80 and 314.81).
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` If you have any questions, call Ayanna Augustus, PhD, Regulatory Health Project Manager, at
` (301) 796-3980.
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` Sincerely,
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` {See appended electronic signature page}
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` Judith A. Racoosin, MD, MPH
` Deputy Director for Safety
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` Division of Anesthesia, Analgesia,
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` and Addiction Products
` Office of Drug Evaluation II
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`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
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`Content of Labeling
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`Reference ID: 3228878
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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.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
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`JUDITH A RACOOSIN
`12/11/2012
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`Reference ID: 3228878
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