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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 22406/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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` Janssen Pharmaceuticals, Inc.
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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 November 26, 2013,
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`received November 26, 2013, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for XARELTO® (rivaroxaban) Tablets, 10 mg.
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`We acknowledge receipt of your amendments dated January 22 and February 25, 2014.
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`This supplemental new drug application provides for revisions to the labeling for XARELTO®
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`(rivaroxaban) Tablets, 10 mg, pertaining to the risk of neuraxial hematoma.
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`APPROVAL & LABELING
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` We have completed our review of this supplemental application, as amended. It is approved,
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` effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
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` text.
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` We note that your February 25, 2014, submission includes final printed labeling (FPL) for your
` package insert and Medication Guide. We have not reviewed this FPL. You are responsible for
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` assuring that the wording in this printed labeling is identical to that of the approved content of
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` labeling in the structured product labeling (SPL) format.
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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: 3466293
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` NDA22406/S009
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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,
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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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`All promotional materials that include representations about your drug product must be promptly
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`revised to be consistent with the labeling changes approved in this supplement, including any
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`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
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`should include prominent disclosure of the important new safety information that appears in the
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`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
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`to comply with 21 CFR 314.70(a)(4) to the address above or by fax to 301-847-8444.
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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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`Reference ID: 3466293
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` NDA22406/S009
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` Page 3
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` If you have any questions, contact Janet G. Higgins, Regulatory Project Manager, at
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` (240) 402-0330.
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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 Division 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(S):
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`Content of Labeling
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`Reference ID: 3466293
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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
`03/06/2014
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`Reference ID: 3466293
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