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` NDA 021995/S-046
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` NDA 022044/S-047
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` NDA 202270/S-020
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`
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`SUPPLEMENT APPROVAL
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`
`
`
` Merck Sharp & Dohme Corp.,
`
`
`
` Attention: Lou Ann Eader, Ph.D.
` Director, Global Regulatory Affairs
`
` 351 N. Sumneytown Pike, P. O. Box 1000
`
`
` UG-2D-44
` North Wales, PA 19454-1099
`
`
`
`
` Dear Dr. Eader:
`
` Please refer to your supplemental new drug applications (sNDAs) dated and received
`
`
`
`
`
`
` June 18, 2019, submitted under section 505(b) and pursuant to section 505(b)(2) of the
` Federal Food, Drug, and Cosmetic Act (FDCA) for Januvia (sitagliptin) tablets, Janumet
`
`
`
`
` (sitagliptin and metformin HCl) tablets, and Janumet XR (sitagliptin and metformin HCl
` extended-release) tablets.
`
`
`
`
`
` We also refer to our letter dated May 3, 2019, notifying you, under Section 505(o)(4) of
`
` the FDCA, of new safety information that we believe should be included in the labeling
`
`
` for dipeptidyl peptidase-4 (DPP-4) inhibitors, including Januvia, Janumet, and Janumet
`
`
`
`
` XR. This information pertains to the risk of rhabdomyolysis.
`
`
`
` This supplemental new drug applications provide for revisions to the labeling for
`
`
`
`
`
`
` Januvia, Janumet, and Janumet XR, consistent with our May 3, 2019 letter.
`
` APPROVAL & LABELING
`
`We have completed our review of this application. It is approved, effective on the date of
`
`this letter, for use as recommended in the enclosed agreed-upon labeling.
`
`
`
`
`WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
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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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`Reference ID: 4456147
`
`

`

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` NDA 021995/S-046
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` NDA 022044/S-047
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` NDA 202270/S-020
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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
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`
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`content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using
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`
`
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`
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`the FDA automated drug registration and listing system (eLIST), as described at
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`FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
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`Prescribing Information and Medication Guide), with the addition of any labeling
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`changes in pending “Changes Being Effected” (CBE) supplements, as well as annual
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`reportable changes not included in the enclosed labeling.
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`
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`Information on submitting SPL files using eList may be found in the guidance for
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`industry SPL Standard for Content of Labeling Technical Qs and As.2
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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
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`changes for this NDA, including CBE supplements for which FDA has not yet issued an
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`
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`action letter, with the content of labeling [21 CFR 314.50(l)(1)(i)] in Microsoft Word
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`
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`format, that includes the changes approved in this supplemental application, as well as
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`annual reportable changes. To facilitate review of your submission(s), provide a
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`highlighted or marked-up copy that shows all changes, as well as a clean Microsoft
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`Word version. The marked-up copy should provide appropriate annotations, including
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`
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`supplement number(s) and annual report date(s).
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`REQUIRED PEDIATRIC ASSESSMENTS
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`
`
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
`
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`new active ingredients (which includes new salts and new fixed combinations), new
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`indications, new dosage forms, new dosing regimens, or new routes of administration
`
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`are required to contain an assessment of the safety and effectiveness of the product for
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`the claimed indication in pediatric patients unless this requirement is waived, deferred,
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`or inapplicable.
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`
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`Because none of these criteria apply to your application, you are exempt from this
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`requirement.
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
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` 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: 4456147
`
`

`

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` NDA 021995/S-046
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` NDA 022044/S-047
`
` NDA 202270/S-020
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` Page 3
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`
` REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
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`
`
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`(21 CFR 314.80 and 314.81).
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`
`
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` If you have any questions, call Richard Whitehead, M.S., Regulatory Project Manager,
` at (301) 796-4945.
`
`
`
`
`Sincerely,
`
`
`
`{See appended electronic signature page}
`
`
`William Chong, M.D.
`
`Deputy Director (Acting)
`
`
`Division of Metabolism and Endocrinology Products
`
`Office of Drug Evaluation II
`
`
`Center for Drug Evaluation and Research
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`
`
`ENCLOSURES:
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`
`
`
`• Content of Labeling for Januvia, Janumet, and Janumet XR
`o Prescribing Information
`
`
`o Medication Guides (approved February 8, 2018)
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`
`
`
`
`
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`Reference ID: 4456147
`
`

`

`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/
`------------------------------------------------------------
`
`WILLIAM H CHONG
`07/01/2019 07:52:27 AM
`
`Reference ID: 4456147
`
`(
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`