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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
`Silver Spring, MD 20993
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`SUPPLEMENT APPROVAL
`FULFILLMENT OF POSTMARKETING REQUIREMENTS
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`NDA 021928/S-045, S-046
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`Pfizer, Inc.
`235 E. 42nd Street
`New York, NY 10017
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`Attention:
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`Lilya I. Donohew, PhD
`Senior Director, Worldwide Regulatory Affairs
`
`
`Dear Dr. Donohew:
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`Please refer to your Supplemental New Drug Applications (sNDAs) dated and received August
`2, 2018, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for CHANTIX (varenicline) Tablet.
`
`These Prior Approval supplemental new drug applications propose:
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`S-045: labeling revisions based on the results of the “required postmarketing study
`commitment” Pregnancy Cohort study A3051078, regarding the safety of varenicline use
`during pregnancy.
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`S-046: labeling revisions based on the results of the postmarketing requirement study
`A3051148, regarding the cardiovascular safety of varenicline.
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`APPROVAL & LABELING
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`We have completed our review of these supplemental applications, as amended. They are
`approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-
`upon labeling text.
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`WAIVER OF HIGHLIGHTS SECTION
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`Please note that we have previously granted a waiver of the requirements of 21 CFR
`201.57(d)(8) regarding the length of Highlights of prescribing information.
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`Reference ID: 4272050
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`

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`NDA 021928/S-045
`NDA 021928/S-046
`Page 2
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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
`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
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm.
`Content of labeling must be identical to the enclosed labeling text for the package insert and
`Medication Guide, with the addition of any labeling changes in pending “Changes Being
`Effected” (CBE) supplements, as well as annual reportable changes not included in the enclosed
`labeling.
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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
`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 that include labeling changes
`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
`changes approved in this supplemental application, as well as annual reportable changes and
`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
`should provide appropriate annotations, including supplement number(s) and annual report
`date(s).
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`REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`active ingredients (which includes new salts and new fixed combinations), new indications, new
`dosage forms, new dosing regimens, or new routes of administration are required to contain an
`assessment of the safety and effectiveness of the product for the claimed indication in pediatric
`patients unless this requirement is waived, deferred, or inapplicable.
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`Because none of these criteria apply to your application, you are exempt from this requirement.
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`FULFILLMENT OF REQUIRED POSTMARKETING STUDY COMMITMENT
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`We have received your submission dated August 2, 2017, containing the final report for the
`following “required postmarketing study commitment” listed in our May 10, 2006, NDA
`Approval Letter;
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`1544-3
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`To conduct a prospective epidemiologic cohort study in pregnant women who are
`smokers and who are exposed to varenicline at the time of conception or any time
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`Reference ID: 4272050
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`

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`NDA 021928/S-045
`NDA 021928/S-046
`Page 3
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`during pregnancy. This information will be used to assess the potential risk to the
`fetus and/or live born infant.
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`We have reviewed your submission and conclude that the above required postmarketing study
`commitment has been fulfilled.
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`FULFILLMENT OF POSTMARKETING REQUIREMENT
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`We have received your submission dated August 2, 2017, containing the final report for the
`following postmarketing requirement listed in our September 22, 2011, New Postmarketing
`Requirement letter.
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`1544-5
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`Conduct an extension of the randomized, double-blind, active- and placebo
`controlled trial to compare the risk of clinically significant neuropsychiatric
`events in individuals using Chantix (varenicline), bupropion, nicotine replacement
`therapy, or placebo, as aids to smoking cessation. The non-treatment, 28-week
`extension trial will be aimed at collecting and comparing data on cardiovascular
`safety for all participants, allowing for a total of 52 weeks of cardiovascular safety
`data collection.
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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 is a required postmarketing study commitment listed in the May 10,
`2006, letter, that is still open.
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
`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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`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
`For more information about submitting promotional materials in eCTD format, see the draft
`Guidance for Industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
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`Reference ID: 4272050
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`

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`NDA 021928/S-045
`NDA 021928/S-046
`Page 4
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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
`FDA 2253 is available at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
`more information about submission of promotional materials to the Office of Prescription Drug
`Promotion (OPDP), see 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
`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Priyanka Kumar, Regulatory Project Manager, at (240) 402-3722.
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`Sincerely,
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`{See appended electronic signature page}
`
`Judith A. Racoosin, MD, MPH
`Deputy Director for Safety
`Division of Anesthesia, Analgesia,
` and Addiction Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`Content of Labeling
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`
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`Reference ID: 4272050
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`

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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
`06/01/2018
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`Reference ID: 4272050
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