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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 021995/S-033
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` NDA 022044/S-034
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` NDA 202270/S-009
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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 & Dohme Corp.
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` Attention: Lou Ann Eader, Ph.D.
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` Director, Worldwide Regulatory Affairs
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` 351 N. Sumneytown Pike
` P. O. Box 1000, UG2CD-48
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` North Wales, PA 19454-1099
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` Dear Dr. Eader:
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` Please refer to your Supplemental New Drug Applications (sNDAs) dated March 2, 2015,
` received on March 2, 2015, submitted under section 505(b) of the Federal Food, Drug, and
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` Cosmetic Act (FDCA) for the following:
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`Reference ID: 3740629
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`•
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`•
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`•
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` Januvia (sitagliptin) tablets;
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` Janumet (sitagliptin and metformin HCl) tablets;
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` Janumet XR (sitagliptin and metformin Extended Release) tablets.
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` These “Changes Being Effected” supplemental new drug applications propose the following
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` changes: pruritus has been added to the list of adverse reactions identified during post-marketing
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` use these products, expired Recent Major Changes have been deleted from the Highlights section
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` of the Prescribing Information, cross-references have been corrected under Warnings and
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` Precautions in the Highlights section, an editorial revision has been made in the cross-reference
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` to the Medication Guide in the Highlights section, and additional minor editorial revisions have
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` been made throughout the full prescribing information.
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` APPROVAL & LABELING
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`We have completed our review of these supplemental applications. They are approved, effective
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`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
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`201.57(d)(8) regarding the length of Highlights of prescribing information.
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` NDA 021995/S-033; NDA 022044/S-034; NDA 202270/S-009
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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 the content of
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`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
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`automated drug registration and listing system (eLIST), as described at
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`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
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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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` 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 that includes labeling changes
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`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
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`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
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`changes approved in this supplemental application, as well as annual reportable changes and
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`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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`should provide appropriate annotations, including supplement number(s) and annual report
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`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
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`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
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`administration are required to contain an assessment of the safety and effectiveness of the
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`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
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`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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`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
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`(3) the package insert(s) to:
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`Reference ID: 3740629
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` NDA 021995/S-033; NDA 022044/S-034; NDA 202270/S-009
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` Page 3
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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
` 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 314.81(b)(3)(i)]. Form
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`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
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
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`more information about submission of promotional materials to the Office of Prescription Drug
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`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
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`(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)
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`796-4945.
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`Sincerely,
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`{See appended electronic signature page}
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`
`Jean-Marc Guettier, M.D.
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`Director
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`Division of Metabolism and Endocrinology Products
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`Office of Drug Evaluation II
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`Center for Drug Evaluation and Research
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`ENCLOSURES:
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`NDA 021995 Content of Labeling
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`Package Insert
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`Medication Guide (last approved August 19, 2013)
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`NDA 022044 Content of Labeling
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`Package Insert
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`Medication Guide (last approved September 11, 2013)
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`NDA 202270 Content of Labeling
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`Package Insert
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`Medication Guide (last approved February 12, 2014)
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`Reference ID: 3740629
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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/
`----------------------------------------------------
`
`JEAN-MARC P GUETTIER
`04/27/2015
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`Reference ID: 3740629
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`