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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 022304/S-007, S-008, S-009, S-011, S-012
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`Food and Drug Administration
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`Silver Spring, MD 20993
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`SUPPLEMENTS APPROVAL
`RELEASE REMS REQUIREMENT
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`
`Janssen Research & Development, L.L.C.
` on behalf of Janssen Pharmaceuticals, Inc.
`920 Route 202 South
`P.O. Box 300
`Raritan, NJ 08869
`
`Attention: Tania Hillmer, MS, RAC
`Associate Director, Regulatory Affairs
`
`
`Dear Ms. Hillmer:
`
`Please refer to your following Supplemental New Drug Applications (sNDAs) submitted under
`section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Nucynta (tapentadol)
`immediate-release (IR) oral tablets, 50 mg, 75 mg, and 100 mg.
`
`
`Supplement Number Submission Date
`S-007
`December 16, 2010
`S-008
`December 21, 2010
`S-009
`March 16, 2011
`S-011
`August 25, 2011
`S-012
`November 29, 2011
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`Receipt Date
`December 16, 2010
`December 21, 2010
`March 16, 2011
`August 26, 2011
`November 29, 2011
`
`
`We acknowledge receipt of your amendments to Supplement-8 dated July 12, 2012, and May 10,
`2013, and your risk evaluation and mitigation strategy (REMS) assessment dated November 29,
`2011.
`
`
`S-007, submitted as a “Changes Being Effected” supplemental new drug application, provides
`for the addition of “Angioedema” to section 6 ADVERSE REACTIONS, subsection 6.3 Post-
`marketing Experience of the Package Insert.
`
`
`S-008, submitted as a “Prior Approval” supplemental new drug application, proposes revisions to
`the Package Insert and Medication Guide with the addition of “hypersensitivity” as a
`contraindication, proposes additional revisions to the Medication Guide to describe
`“angioedema” as a possible side effect, and, as amended on July 12, 2012, following discussions
`with FDA, proposes withdrawal of the Medication Guide as part of the Nucynta IR tablet
`labeling.
`
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`
`
`Reference ID: 3339910
`
`

`

`NDA 022304/ S-007, S-008,
` S-009, S-011, and S-012
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`Page 2
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`S-009, submitted as a “Changes Being Effected” supplemental new drug application, provides
`for the addition of “Diarrhea” to section 6 ADVERSE REACTIONS, subsection 6.3 Post-
`marketing Experience of the Package Insert.
`
`
`S-011, submitted as a “Changes Being Effected” supplemental new drug application, provides
`for the addition of “Palpitations” to section 6 ADVERSE REACTIONS, subsection 6.3 Post-
`marketing Experience of the Package Insert.
`
`
`S-012, submitted as a “Prior Approval” supplemental new drug application, proposes to
`eliminate the requirement for the approved REMS for Nucynta IR tablets.
`
`We have completed our review of these supplemental applications, as amended. They are
`approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-
`upon labeling text.
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`CONTENT OF LABELING
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`
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`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
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling text for the physicians, 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.
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`Information on submitting SPL files using eLIST may be found in the guidance for industry
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`titled “SPL Standard for Content of Labeling Technical Qs and As” at
`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 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 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-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).
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`We request that the labeling approved today be available on your website within 10 days of
`receipt of this letter.
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`
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`
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`Reference ID: 3339910
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`

`

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`NDA 022304/ S-007, S-008,
` S-009, S-011, and S-012
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`Page 3
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` RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`The REMS for Nucynta IR tablets was originally approved on November 20, 2008. The REMS
`consists of a Medication Guide and a timetable for submission of assessments of the REMS.
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`You propose that FDA no longer require a REMS for Nucynta IR tablets.
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`The requirement of a REMS for Nucynta IR tablets was, at the time of its approval, consistent
`with the Agency’s policies concerning drug products with Medication Guides to address serious
`and significant public health concerns under the standard in 21 CFR 208.1. However, during the
`four years of marketing history of Nucynta IR tablets, the concerns about this product having
`distinctive properties indicating a high potential for abuse did not manifest as serious adverse
`events of abuse/misuse any different or worse than other immediate-release oral opioids which
`do not have Medication Guides. We agree with your proposal that the Medication Guide be
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`eliminated as part of the approved labeling for Nucynta IR tablets. We agree also that the REMS
`for Nucynta IR tablets can now be eliminated.
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`Therefore, a REMS for Nucynta IR tablets is no longer required.
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`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/opacom/morechoices/fdaforms/cder.html;
`instructions are provided on page 2 of the form. For more information about submission of
`promotional materials to the Office of Prescription Drug Promotion (OPDP), see
`http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`All promotional materials that include representations about your drug product must be promptly
`revised to be consistent with the labeling changes approved in this supplement, including any
`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
`should include prominent disclosure of the important new safety information that appears in the
`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
`to comply with 21 CFR 314.70(a)(4) to the address above or by fax to 301-847-8444.
`
`
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`Reference ID: 3339910
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`

`

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`NDA 022304/ S-007, S-008,
` S-009, S-011, and S-012
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`Page 4
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` REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`If you have any questions, call Dominic Chiapperino, Ph.D., Senior Regulatory Health Project
`Manager, at (301) 796-1183.
`
`
`Sincerely,
`
` {See appended electronic signature page}
`
` Bob A. Rappaport, M.D.
`
` Director
`Division of Anesthesia, Analgesia, and Addiction
`Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`
`Content of Labeling
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`
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`Reference ID: 3339910
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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/
`----------------------------------------------------
`
`BOB A RAPPAPORT
`07/11/2013
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`Reference ID: 3339910
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`