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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 22406/S-015
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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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` Janssen Research & Development, LLC
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` Attention: Huy Q. Truong
` Associate Director, Global Regulatory Affairs
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` 920 Highway 202, South
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` P.O. Box 300
` Raritan, NJ 08869
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`Dear Mr. Truong:
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`Please refer to your Supplemental New Drug Application (sNDA) dated December 10, 2014,
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`received December 10, 2014, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for Xarelto® (rivaroxaban) Tablets.
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`This “Changes Being Effected” supplemental new drug application provides for the addition of
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`“thrombocytopenia” as an adverse reaction and replaces the adverse reaction term “cytolytic
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`hepatitis” with “hepatitis (including hepatocellular injury)” in section 6.2 Postmarketing
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`Experience, of the United States Package Insert.
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application. It is approved, effective on the
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`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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`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
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`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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`Reference ID: 3676584
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` NDA 22406/S-015
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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 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,
` 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
`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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`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 Toni Cox, Regulatory Project Manager, at (301) 240-402-4775.
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`Sincerely,
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`{See appended electronic signature page}
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`Robert C. Kane, MD
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`Deputy Director for Safety
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`Division of Hematology Products
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`Office of Hematology Oncology Products
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`Center for Drug Evaluation and Research
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`ENCLOSURE:
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`Content of Labeling
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`Reference ID: 3676584
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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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`ROBERT C KANE
`12/19/2014
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`Reference ID: 3676584
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