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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 203496/S-006
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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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`United Therapeutics Corp.
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`Attention: Nicole Wilkerson
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`Regulatory Affairs Manager
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`55 TW Alexander Drive
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`PO Box 14186
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`Research Triangle Park, NC 27709
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`Dear Ms. Wilkerson:
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`Please refer to your Supplemental New Drug Application (sNDA) dated and received August 1, 2016,
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`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Orenitram
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`(treprostinil) 0.125 mg, 0.25 mg, 1 mg, 2.5 mg and 5 mg Extended Release Tablets.
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`We acknowledge receipt of your amendments dated October 21 and December 7, 2016.
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`This supplemental new drug application provides for the following revisions to the approved labeling for
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`Orentram (additions are shown as underlined text and deletions are shown as strikethrough text):
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`1. Under ADVERSE REACTIONS, the following section was added:
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`6.2 Post-Marketing Experience
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`The following adverse reactions have been identified during postapproval use of
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`Orenitram: dizziness, dyspepsia, vomiting, myalgia, and arthralgia. Because these
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`reactions are reported voluntarily from a population of uncertain size, it is not always
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`exposure.
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`2. The revision date was updated.
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`There are no other changes from the last approved package insert and patient package insert.
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended, and it is approved, effective
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`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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`As soon as possible, but no later than 14 days from the date of this letter, submit the content of labeling
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`[21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA automated drug
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`registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content of
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`Reference ID: 4045427
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` NDA 203496/S-006
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` Page 2
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` labeling must be identical to the enclosed labeling (text for the package insert), with the addition of any
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` labeling changes in pending “Changes Being Effected” (CBE) supplements, as well as annual reportable
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`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 titled “SPL
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` Standard for Content of Labeling Technical Qs and As at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/UCM0723
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` 92.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 for this
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` NDA, including CBE supplements for which FDA has not yet issued an action letter, with the content of
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` labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the changes approved in this
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` supplemental application, as well as annual reportable changes and annotate each change. To facilitate
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` review of your submission, provide a highlighted or marked-up copy that shows all changes, as well as a
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` clean Microsoft Word version. The marked-up copy should provide appropriate annotations, including
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` supplement number(s) and annual report date(s).
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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
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`and 314.81).
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`If you have any questions, please call:
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`Lori Anne Wachter, RN, BSN, RAC
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`Regulatory Project Manager for Safety
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`(301) 796-3975
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`Sincerely,
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`{See appended electronic signature page}
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`Mary Ross Southworth, PharmD.
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`Deputy Director for Safety
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`Office of Drug Evaluation I
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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: 4045427
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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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`MARY R SOUTHWORTH
`01/24/2017
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`Reference ID: 4045427
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`(
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