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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 021995/S-017
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`SUPPLEMENT APPROVAL
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` RELEASE REMS REQUIREMENT
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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 Application (sNDA) dated and received March 19,
`2010, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
`JANUVIA (sitagliptin) Tablets, 25 mg, 50 mg, and 100 mg.
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`We also acknowledge receipt of your amendments dated November 12 and December 13, 2010,
`and January 26, February 4, and March 25, 2011. We also acknowledge receipt of your risk
`evaluation and mitigation strategy (REMS) assessment dated March 25, 2011.
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`This supplemental new drug application provides for the addition of information regarding
`postmarketing reports of worsening renal function, including acute renal failure (sometimes
`requiring dialysis) to the package insert and corresponding text in the Medication Guide.
`This supplemental NDA also provides for a proposed REMS modification requesting the
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`elimination of the approved REMS.
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`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
`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, using the FDA
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`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 Medication Guide) and include
`the labeling changes proposed in any pending “Changes Being Effected” (CBE) supplements
`and any annual reportable changes not included in the enclosed labeling.
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`Reference ID: 2933439
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`

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`NDA 021995/S-017
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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
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` 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 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.
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`We request that the labeling approved today be available on your website within 10 days of
`receipt of this letter.
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`The REMS for JANUVIA (sitagliptin) Tablets was originally approved on February 26, 2010.
`The REMS consists of a Medication Guide and a timetable for submission of assessments of the
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`REMS.
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`In our letter dated December 28, 2010, we notified you that a REMS modification was required
`for JANUVIA (sitagliptin) Tablets to ensure that the benefits of the drug outweigh the risks of
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`worsening renal function, including acute renal failure (sometimes requiring dialysis). We
`indicated that your proposed REMS must include a modification to the Medication Guide to
`include information about the risk of renal failure.
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`We acknowledge receipt of your proposed modified REMS in your January 26, 2011
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`submission. We also acknowledge receipt of your submission dated March 25, 2011, which
`included a REMS assessment, a report on the status of your postapproval study required under
`section 505(o) to investigate a safety issue, and a proposed REMS modification requesting the
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`elimination of the approved REMS.
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`We have determined that it is no longer necessary to include the Medication Guide as an element
`of the approved REMS, and that a REMS is no longer necessary to ensure that the benefits of
`JANUVIA (sitagliptin) Tablets outweigh its risks. Therefore, we agree with your proposal and a
`REMS for JANUVIA (sitagliptin) Tablets is no longer required.
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`We remind you that the Medication Guide will continue to be part of the approved labeling in
`accordance with 21 CFR 208.
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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
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`Reference ID: 2933439
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`

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`NDA 021995/S-017
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`Page 3
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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
`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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`All promotional materials that include representations about your drug product must be promptly
`revised to be consistent with the labeling changes approved in this supplement, including any
`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
`should include prominent disclosure of the important new safety information that appears in the
`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
`to comply with 21 CFR 314.70(a)(4) to the address above or by fax to 301-847-8444.
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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, please contact 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 Parks, M.D.
`Director
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`Division of Metabolism & Endocrinology Products
`Center for Drug Evaluation and Research
`Food and Drug Administration
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`Enclosures:
` Package Insert (submitted Februrary 4, 2011)
` Medication Guide (submitted January 26, 2011)
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`Reference ID: 2933439
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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
`04/14/2011
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`Reference ID: 2933439
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