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`DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
`Food and Drug Administration
`Rockville, MD 20857
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`NDA 21-976/S-003
`NDA 21-976/S-004
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`Tibotec, Inc.
`Attention: Jenny Z. Lin, Pharm.D.
`Sr. Manager, Global Regulatory Affairs
`1020 Stony Hill Road, Suite 300
`Yardley, PA 19067
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`Dear Dr. Lin:
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`Please refer to your supplemental new drug applications dated March 28, 2007 and August 6,
`2007 received March 28, 2007 and August 6, 2007, respectively, submitted under section 505(b)
`of the Federal Food, Drug, and Cosmetic Act for Prezista™ (darunavir) tablets.
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`We acknowledge receipt of your submissions dated September 27, 2007, October 29, 2007,
`February 4, 2008, and March 3, 2008.
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`The supplement dated March 28, 2007 provides for updates to the CLINICAL
`PHARMACOLOGY section of the package insert to include data from 6 pharmacokinetic, drug
`interaction Phase 1 trials.
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`The “Changes Being Effected” supplemental new drug application dated August 6, 2007
`provides for updates to the WARNINGS, PRECAUTIONS AND ADVERSE EVENTS section
`of the package insert to include hepatotoxicity information and updates to PRECAUTIONS’,
`Table 11 to include information regarding a potential drug-drug interaction with rosuvastatin.
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`We completed our review of these applications, as amended. These applications are approved,
`effective on the date of this letter, for use as recommended in the agreed-upon labeling text
`enclosed below.
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`As soon as possible, but no later than 14 days from the date of this letter, please submit the
`content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format as described
`at http://www.fda.gov/oc/datacouncil/spl.html that is identical to the enclosed labeling (text for
`the package insert, text for the patient package insert). Upon receipt, we will transmit that
`version to the National Library of Medicine for public dissemination. For administrative
`purposes, please designate this submission, “SPL for approved NDA 21-976/S003 and S004.”
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`In addition, within 21 days of the date of this letter, amend any pending applications for this
`NDA with content of labeling in structured product labeling (SPL) format to include the changes
`approved in these applications.
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`- 2 –
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`NDA 21-976/S003
`NDA 21-976/S004
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`Marketing the product with FPL that is not identical to the approved labeling text and in the
`required format may render the product misbranded and an unapproved new drug.
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`The Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed the
`revised product labeling and has determined that it contains significant new risk information
`relating to your drug product. We are hereby requesting that all promotional materials for your
`drug product that include representations about your drug product be revised to include the new
`risk information immediately. These revisions should include prominent disclosure of the
`important new information described in the WARNINGS and PRECAUTIONS sections that
`appear in the revised package labeling. Please submit a written response to this request on or
`before March 14, 2008, stating whether you intend to comply with this request, to the Food and
`Drug Administration, Center for Drug Evaluation and Research, Division of Drug Marketing,
`Advertising, and Communications by facsimile at (301)796-9878 or at 5901-B Ammendale
`Road, Beltsville, MD 20705.
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`In addition, submit three copies of the introductory promotional materials that you propose to use
`for this product. Submit all proposed materials in draft or mock-up form, not final print. Send
`one copy to the Division of Antiviral Products and two copies of both the promotional materials
`and the package insert directly to:
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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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`If you issue a letter communicating important information about this drug product (i.e., a “Dear
`Health Care Professional” letter), we request that you submit a copy of the letter to this NDA and
`a copy to the following address:
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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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`MEDWATCH
`Food and Drug Administration
`5515 Security Lane
`HFD-001, Suite 5100
`Rockville, MD 20852
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`- 3 –
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`NDA 21-976/S003
`NDA 21-976/S004
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`If you have any questions, please call Tanima Sinha, M.S., Regulatory Project Manager, at (301)
`796-0812.
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`Sincerely,
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`{See appended electronic signature page}
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`Debra Birnkrant, MD
`Director
`Division of Antiviral Products
`Office of Antimicrobial Products
`Center for Drug Evaluation and Research
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`Enclosure: final agreed upon labeling
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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 Murray
`3/7/2008 01:20:27 PM
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