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`Food and Drug Administration
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`Silver Spring MD 20993
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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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` NDA 21-976/S-017
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`Reference ID: 2876620
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` SUPPLEMENT APPROVAL
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`Tibotec, Inc.
`Attention: Charles Zezza Ph.D., MBA
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` Director
`J&J Pharmaceutical Research and Development (J&J PRD)
`On behalf of Tibotec, Inc.
`920 Route 202
`Raritan, NJ 08869
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`Dear Dr. Zezza:
`
`Please refer to your Supplemental New Drug Application (sNDA) dated February 19, 2010,
`received March 3, 2010, submitted under section 505(b) of the Federal Food, Drug, and
`Cosmetic Act (FDCA) for PREZISTA® (darunavir) 75 mg, 150 mg, 400 mg and 600 mg
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`Tablets.
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`We acknowledge receipt of your amendments dated March 23, 2010, May 4, 2010, May 5, 2010,
`May 21, 2010, June 1, 2010, June 16, 2010, July 6, 2010, July 23, 2010, August 13, 2010,
`September 16, 2010, September 24, 2010, October 8, 2010, October 26, 2010, November 19,
`2010, December 3, 2010 and December 7, 2010.
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`This Prior Approval supplemental new drug application provides for a new dosing regimen,
`800/100 mg darunavir/ritonavir, once daily, in treatment-experienced HIV-1 infected patients
`with no darunavir resistance associated substitutions based on the results of Study TMC114­
`C229. The Patient Package Insert was revised to include the new dosing regimen and to provide
`a more user friendly label to prevent and/or reduce medication errors. In addition, all references
`to the 300 mg tablets were deleted and Hepatotoxicity and Severe Skin Reactions sections were
`added to Patient Counseling-Instructions for Use of the Package Insert.
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`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
`text.
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`We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of
`prescribing information. This waiver applies to all future supplements containing revised
`labeling unless we notify you otherwise.
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`

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` NDA 21-976/S-017
`Page 2
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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, using the FDA
`automated drug registration and listing system (eLIST), the content of labeling
`[21 CFR 314.50(l)] in structured product labeling (SPL) format, as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm, that is
`identical to the enclosed labeling (text for the package insert, text for the patient package insert)
`and include the labeling changes proposed in any pending “Changes Being Effected” (CBE)
`supplements and any annual reportable changes not included in the enclosed labeling.
`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.
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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
`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
`administration are required to contain an assessment of the safety and effectiveness of the
`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
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`We are waiving the pediatric study requirement for ages 0 to < 3 years because there is evidence
`strongly suggesting that the drug product would be unsafe in this pediatric group.
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`We are deferring submission of your pediatric study of once a day dosing in treatment-
`experienced patients between ages 3 and < 18 years for this application because this product is
`ready for approval for use in adults and the pediatric study has not been completed.
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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:
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`Reference ID: 2876620
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`

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`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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` NDA 21-976/S-017
`Page 3
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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 Division of Drug Marketing, Advertising, and Communications
`(DDMAC), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`LETTERS TO HEALTH CARE PROFESSIONALS
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`If you decide to issue a letter communicating important safety-related information about this
`drug product (i.e., a “Dear Health Care Professional” letter), we request that you submit, at least
`24 hours prior to issuing the letter, an electronic copy of the letter to this NDA to the following
`address:
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`MedWatch Program
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`Office of Special Health Issues
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`Food and Drug Administration
`10903 New Hampshire Ave
`Building 32, Mail Stop 5353
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`Silver Spring, MD 20993
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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).
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`If you have any questions, call Stacey Min, Pharm.D., Regulatory Project Manager, at (301) 796­
`4253.
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`Sincerely,
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`
`{See appended electronic signature page}
`
`Debra Birnkrant, M.D.
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`Director
`Division of Antiviral Products
`Office of Antimicrobial Products
`Center for Drug Evaluation and Research
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`Reference ID: 2876620
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` NDA 21-976/S-017
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`Page 4
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`ENCLOSURE: Content of Labeling
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`Reference ID: 2876620
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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/
`----------------------------------------------------
`
`JEFFREY S MURRAY
`12/13/2010
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`Reference ID: 2876620
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`