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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
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`NDA 021995/S-042
`NDA 022044/S-043
`NDA 202270/S-018
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`Merck Sharp & Dohme Corp.
`Attention: Lou Ann Eader, PhD
`Director, Worldwide Regulatory Affairs
`351 N. Sumneytown Pike
`P.O. Box 1000, UG2C-50
`North Wales, PA 19454-1099
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`Dear Dr. Eader:
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`Please refer to your Supplemental New Drug Applications (sNDA) dated and received
`August 9, 2017, and your amendments, submitted under section 505(b) of the Federal Food,
`Drug, and Cosmetic Act (FDCA) for Januvia (sitagliptin) tablets and Janumet XR (sitagliptin and
`metformin HCl extended-release) tablets.
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`We also refer to your sNDAs dated and received August 9, 2017, submitted pursuant to section
`505(b)(2) of the FDCA for Janumet (sitagliptin and metformin HCl) tablets.
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`These supplemental new drug applications propose the following changes:
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`For Januvia, this supplement proposes to harmonize the dosing recommendations for patients
`with renal impairment in the previously approved label for Janumet and Janumet XR dated
`January 18, 2017.
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`For Januvia, Janumet, and Janumet XR, these supplements propose changes to the clinical
`pharmacology and drug interaction information in the label in accord with the February 2013
`Guidance for Implementing the PLR Content and Format.
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`For Januvia, Janumet, and Janumet XR, these supplements propose revisions to the prescribing
`information in accord with the Pregnancy and Lactation Labeling Rule (PLLR) as described in
`the December 2014 Draft Guidance for Industry.
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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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`Reference ID: 4219849
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`

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`NDA 021995/S-042
`NDA 022044/S-043
`NDA 202270/S-018
`Page 2
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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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`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 prescribing information 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, 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(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
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`Reference ID: 4219849
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`

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`NDA 021995/S-042
`NDA 022044/S-043
`NDA 202270/S-018
`Page 3
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`Because none of these criteria apply to your supplemental applications, you are exempt from this
`requirement.
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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 Richard Whitehead, M.S., Regulatory Project Manager, at
`(301) 796-4945.
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`Sincerely,
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`{See appended electronic signature page}
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`Mary T. Thanh Hai, M.D.
`Deputy Director
`Office of Drug Evaluation II
`Office of New Drugs
`Center for Drug Evaluation and Research
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`ENCLOSURES:
`Content of Labeling
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`Prescribing Information
` Medication Guides (approved 08/10/2017)
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`Reference ID: 4219849
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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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`MARY T THANH HAI
`02/09/2018
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`Reference ID: 4219849
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