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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 021995/S-015 and S-018
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`Food and Drug Administration
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`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Merck Sharp and Dohme Corp.
`Attention: Richard J. Swanson, Ph.D.
`Director, Regulatory Affairs
`P.O. Box 1000, UG2C-50
`North Wales, PA 19454-1099
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`Dear Dr. Swanson:
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`Please refer to your supplemental new drug applications (sNDAs) dated and received
`December 23, 2009 (S-015) and May 28, 2010 (S-018), submitted under section 505(b) of the
`Federal Food, Drug, and Cosmetic Act (FDCA) for Januvia (sitagliptin) tablets.
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`We acknowledge receipt of your amendment to both applications dated September 3, 2010.
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`These “Prior Approval” supplemental new drug applications propose to include information
` regarding the incidence of pancreatitis associated with the use of sitagliptin in controlled clinical
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`trials in the Clinical Trials Experience section of the package insert for Januvia (S-015), and the
`addition of "constipation, headache, vomiting" in the Postmarketing Experience section of the
`package insert, and corresponding patient-friendly text in the Medication Guide for Januvia
`(S-018).
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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. However, please note the following with regards to supplement S-018:
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`1. Your proposal to include “constipation; vomiting; headache” in Section 6.2 (Postmarketing
`Experience) of the package insert for Januvia is acceptable.
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`(b) (4)
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` NDA 21995/S-015 and S-018
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`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, using the FDA
`automated drug registration and listing system (eLIST), the content of labeling
`[21 CFR 314.50(l)] in structured product labeling (SPL) format, as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm, that is
`identical to the enclosed labeling (text for the package insert) and include the labeling changes
`proposed in any pending “Changes Being Effected” (CBE) supplements. Information on
`submitting SPL files using eLIST may be found in the guidance for industry titled “SPL
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`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 for this NDA, including
`pending “Changes Being Effected” (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.
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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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`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
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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.(b)(3)(i)]. Form FDA
`2253 is available at http://www.fda.gov/opacom/morechoices/fdaforms/cder.html; instructions
`are provided on page 2 of the form. For more information about submission of promotional
`materials to the Division of Drug Marketing, Advertising, and Communications (DDMAC), see
`http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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` NDA 21995/S-015 and S-018
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`Page 3
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` LETTERS TO HEALTH CARE PROFESSIONALS
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`If you decide to issue a letter communicating important safety-related information about this
`drug product (i.e., a “Dear Health Care Professional” letter), we request that you submit, at least
`24 hours prior to issuing the letter, an electronic copy of the letter to this NDA, to
`CDERMedWatchSafetyAlerts@fda.hhs.gov, and to the following address:
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`MedWatch Program
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`Office of Special Health Issues
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`Food and Drug Administration
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`10903 New Hampshire Ave
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`Building 32, Mail Stop 5353
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`Silver Spring, MD 20993
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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 Mehreen Hai, Ph.D., Regulatory Project Manager, at
`(301) 796-5073.
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`Sincerely,
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` {See appended electronic signature page}
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`Mary H. Parks, M.D.
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` Director
`Division of Metabolism and Endocrinology Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`Enclosures:
`Package Insert
`Medication Guide (as previously approved on February 26, 2010)
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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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`MARY H PARKS
`09/24/2010
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`Reference ID: 2840390
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