NDA 021995/S-050
`NDA 022044/S-052
`NDA 202270/S-026
`
`
`
`
`SUPPLEMENT APPROVAL
`
`
`
`Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc.
`Attention: Holly Davidson
`Associate Principal Scientist, Regulatory Liaison
`351 N. Sumneytown Pike
`P. O. Box 1000, UG-2C-50
`North Wales, PA 19454-1099
`
`Dear Ms. Davidson:
`
`Please refer to your supplemental new drug applications (sNDAs) and your
`amendments, submitted under section 505(b) and pursuant to section 505(b)(2) of the
`Federal Food, Drug, and Cosmetic Act (FDCA) for the following:
`
`
`NDA Number Supplement
`Number
`S-050
`
`NDA 021995
`
`NDA 022044
`
`S-052
`
`NDA 202270
`
`S-026
`
`Product Name
`
`Januvia (sitagliptin)
`tablets
`Janumet (sitagliptin and
`metformin hydrochloride)
`tablets
`Janumet XR (sitagliptin
`and metformin
`hydrochloride extended-
`release) tablets
`
`Date of Submission and
`Receipt
`April 13, 2022
`
`April 13, 2022
`
`April 13, 2022
`
`
`These Prior Approval sNDAs provide for the addition of ‘tubulointerstitial nephritis’ to
`section 6.2 Postmarketing Experience of the Prescribing Information (PI), as requested
`in our December 20, 2021, Supplement Request letter, as well as the removal of the
`sitagliptin pregnancy registry information from section 8.1 Pregnancy of the PI and
`Medication Guide for Januvia, Janumet, and Janumet XR.
`
`APPROVAL & LABELING
`
`We have completed our review of these applications, as amended. They are approved,
`effective on the date of this letter, for use as recommended in the enclosed agreed-
`upon labeling.
`
`
`
`Reference ID: 5001938
`
`

`

`NDA 021995/S-050
`NDA 022044/S-052
`NDA 202270/S-026
`Page 2
`
`
`WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
`
`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.
`
`CONTENT OF LABELING
`
`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
`FDA.gov.1 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.
`
`Information on submitting SPL files using eList may be found in the guidance for
`industry SPL Standard for Content of Labeling Technical Qs and As.2
`
`The SPL will be accessible from publicly available labeling repositories.
`
`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 Microsoft Word
`format, that includes the changes approved in this supplemental application, as well as
`annual reportable changes. To facilitate review of your submission(s), 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).
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`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.
`
`
`
`1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
`Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 5001938
`
`

`

`NDA 021995/S-050
`NDA 022044/S-052
`NDA 202270/S-026
`Page 3
`
`
`Because none of these criteria apply to your application, you are exempt from this
`requirement.
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and
`promotional labeling. For information about submitting promotional materials, see the
`final guidance for industry Providing Regulatory Submissions in Electronic and Non-
`Electronic Format-Promotional Labeling and Advertising Materials for Human
`Prescription Drugs.3
`
`You must submit final promotional materials and Prescribing Information, 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 FDA.gov.4 Information and
`Instructions for completing the form can be found at FDA.gov.5
`
`PATENT LISTING REQUIREMENTS
`
`
`Pursuant to 21 CFR 314.53(d)(2) and 314.70(f), certain changes to an approved NDA
`submitted in a supplement require you to submit patent information for listing in the
`Orange Book upon approval of the supplement. You must submit the patent information
`required by 21 CFR 314.53(d)(2)(i)(A) through (C) and 314.53(d)(2)(ii)(A) and (C), as
`applicable, to FDA on Form FDA 3542 within 30 days after the date of approval of the
`supplement for the patent information to be timely filed (see 21 CFR
`314.53(c)(2)(ii)). You also must ensure that any changes to your approved NDA that
`require the submission of a request to remove patent information from the Orange Book
`are submitted to FDA at the time of approval of the supplement pursuant to 21 CFR
`314.53(d)(2)(ii)(B) and 314.53(f)(2)(iv).
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`
`
`
`
`
`3 For the most recent version of a guidance, check the FDA guidance web page at
`https://www.fda.gov/media/128163/download.
`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 5001938
`
`

`

`NDA 021995/S-050
`NDA 022044/S-052
`NDA 202270/S-026
`Page 4
`
`
`If you have any questions, call Michael Oyewole, Regulatory Project Manager, at
`(301) 796-3897.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Monika Houstoun, Pharm.D., M.P.H.
`Deputy Director for Safety
`Division of Diabetes, Lipid Disorders, and Obesity
`Office of Cardiology, Hematology,
`Endocrinology, and Nephrology
`Office of New Drugs
`Center for Drug Evaluation and Research
`
`
`ENCLOSURES:
`• Content of Labeling (Prescribing Information and Medication Guide) for Januvia,
`Janumet, and Janumet XR.
`
`
`
`
`
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 5001938
`
`

`

`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`MONIKA A HOUSTOUN
`06/21/2022 04:00:27 PM
`
`Reference ID: 5001938
`
`(
`
`
`
`