`NDA 202895/S-27
`
`
`
`SUPPLEMENT APPROVAL
`
`
`Janssen Products, LP
`Attention: Karen Gerry, BSc.
`Associate Director, Global Regulatory Affairs
`1125 Trenton-Harbourton Road
`Titusville, NJ 08560
`
`
`
`Dear Ms. Gerry:
`
`Please refer to your supplemental new drug applications (sNDAs) dated and received November
`30, 2018, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for PREZISTA® (darunavir) 75 mg, 150 mg, 600 mg and 800 mg tablets
`(NDA 021976) and PREZISTA® (darunavir) 100 mg/mL, oral solution (NDA 202895).
`
`These Prior Approval supplemental new drug applications provide for revisions to the following
`sections of the Prescribing Information:
`
`
`
` CONTRAINDICATIONS:
`o Ranolazine and dronedarone were removed from their respective drug categories
`
`(“Antianginal” and “Antiarrhythmic”) and placed with the addition of ivabradine
`under the new category of “Cardiac Disorders”
`o Naloxegol was added under the new category of “Opioid Antagonist”
`
`
`
`
` WARNINGS AND PRECAUTIONS:
`o Update to Section 5.8 “Immune Reconstitution Syndrome”, with the addition of
`
`
`autoimmune hepatitis
`
`
`
` DRUG INTERACTIONS, Table 10, was updated:
`o Antifungals: information on use of isavuconazole
`
`o Antimycobacterials: removal of cobicistat
`
`o Cardiac Disorders: new category added with drugs previously listed under “Other
`
`Agents, Antiarrhythmics and Antianginal” moved to this category. Added
`information on use of ivabradine
`o Systemic/Inhaled/ Nasal/Ophthalmic Corticosteroids: addition of prednisone as a
`
`corticosteroid less affected by strong CYP3A inhibitor relative to other
`corticosteroids
`o Herbal product: removal of cobicistat
`
`o Hormonal Contraceptives: recategorization of heading, previously read “Oral
`
`contraceptives/estrogen”
`o Immunosuppressant/neoplastic: information on use of irinotecan
`
`
`Reference ID: 4439882
`
`
`
`NDA 021976/S-56
`NDA 202895/S-27
`Page 2
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`
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`
`
`
`o Opioid Antagonist: information on use of naloxegol
`
`o Urinary Antispasmodics: information on use of fesoterodine and solifenacin
`
`
`Ivabradine and naloxegol were added to the Patient Package Insert under the heading
`“Who should not take PREZISTA?, Do not take PREZISTA with any medicine that
`contains:”.
`
`
`APPROVAL & LABELING
`
`We have completed our review of these applications, as amended. They are 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
`
`Please note that we have previously granted a waiver of the requirements of 21 CFR
`201.57(d)(8) regarding the length of Highlights of Prescribing Information.
`
`CONTENT OF LABELING
`
`
`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 FDA.gov.1 Content of
`labeling must be identical to the enclosed labeling (text for the Prescribing Information and
`Patient Package Insert), 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.
`
`Information on submitting SPL files using eList may be found in the guidance for industry SPL
`
` Standard for Content of Labeling Technical Qs and As.2
`
`The SPL will be accessible from publicly available labeling repositories.
`
`
`Also within 14 days, amend all pending supplemental applications that include labeling changes
`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 Microsoft Word format, that includes the
`changes approved in this supplemental application, as well as annual reportable changes. To
`facilitate review of your submission(s), 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).
`
`
`
`
`
` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`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: 4439882
`
`
`
`
`
`NDA 021976/S-56
`NDA 202895/S-27
`Page 3
`
`
`
` PROMOTIONAL MATERIALS
`
`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 Prescribing Information to:
`
`
`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
`For more information about submitting promotional materials in eCTD format, see the draft
`guidance for industry Providing Regulatory Submissions in Electronic and Non-Electronic
`Format-Promotional Labeling and Advertising Materials for Human Prescription Drugs.3
`
`You must submit final promotional materials and Prescribing Information, accompanied by a
`Form FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)].
`Form FDA 2253 is available at FDA.gov.4 Information and Instructions for completing the form
`
`can be found at FDA.gov.5 For more information about submission of promotional materials to
`the Office of Prescription Drug Promotion (OPDP), see FDA.gov.6
`
`
`
`REPORTING REQUIREMENTS
`
`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, contact Philip Villasurda, Regulatory Project Manager, at
`Philip.Villasurda@fda.hhs.gov or call at (301) 796-2586 or (301) 796-1500.
`
`
`
`
`
`
`
`3 When final, this guidance will represent the FDA’s current thinking on this topic. For the most recent
`version of a guidance, check the FDA guidance web page at
`https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`
`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`
`
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`
`
`6 http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm
`
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`
`Reference ID: 4439882
`
`
`
`NDA 021976/S-56
`NDA 202895/S-27
`Page 4
`
`
`
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`ENCLOSURE(S):
`
` Content of Labeling
`o Prescribing Information
`
`o Patient Package Insert
`
`
`
`
`
`
`
`
`
`Sincerely,
`
` {See appended electronic signature page}
`
`
`Debra Birnkrant, M.D.
`
`Director
`Division of Antiviral Products
`Office of Antimicrobial Products
`Center for Drug Evaluation and Research
`
`U.S. Food and Drug Administration
`
`
`Silver Spring, MD 20993
`www.fda.gov
`
`
`Reference ID: 4439882
`
`
`
`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/
`------------------------------------------------------------
`
`POONAM MISHRA
`05/28/2019 04:09:54 PM
`on behalf of Debra Birnkrant
`
`Reference ID: 4439882
`
`