DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
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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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`NDA 021976/S-016
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`Tibotec, Incorporated
`Attention: Susan Fiordeliso
`Sr. Manager, Global Regulatory Affairs
`1125 Trenton-Harbourton Rd.
`Titusville, NJ 08540
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`Dear Ms. Fiordeliso:
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`Please refer to your supplemental new drug application dated and received February 12, 2010,
`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
`PREZISTA® (darunavir) Tablet.
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`We also acknowledge receipt of your submissions dated March 12, 2010 and March 24, 2010.
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`Reference is also made to our letter dated January 13, 2010, notifying you, under Section 505(o)(4)
`of the FDCA, of new safety information that we believe should be included in the labeling for
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`PREZISTA (darunavir) Tablet. This information pertains to the risk of drug-drug interactions with
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`the use of protease inhibitors, including PREZISTA (darunavir).
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`This supplemental application provides for revisions to the labeling regarding coadministration
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`of certain drugs with PREZISTA (darunavir) Tablet.
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`The following changes are consistent with our January 13, 2010 Safety Labeling Change
`Notification letter: section 4 (CONTRAINDICATIONS) and section 7 (DRUG INTERACTIONS)
`of the labeling have been updated with the following information:
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` The addition of sildenafil as a contraindicated medication when prescribed for the
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`treatment of pulmonary arterial hypertension.
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`• The addition of the recommendation that salmeterol should not be coadministered.
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`• The addition of new dosing recommendations for bosentan and tadalafil when prescribed
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`for the treatment of pulmonary arterial hypertension.
`• The addition of new dosing recommendations for colchicine when prescribed for the
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`treatment of familial Mediterranean fever or gout.
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`Agreed-upon changes are as follow:
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`• The addition of new dosing recommendations for colchicine when prescribed for the
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`prophylaxis of gout.
`• The addition of the recommendation that colchicine should not be coadministered with
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`PREZISTA (darunavir) in patients with hepatic or renal impairment.
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` NDA 021976/S-016
`page 2
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`We have completed our review of this application, as amended. This application is approved,
`effective on the date of this letter, for use as recommended in the 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, 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 and include the labeling changes proposed in any pending
`“Changes Being Effected” (CBE) supplements. Information on submitting SPL files using eLIST
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`may be found in the guidance for industry titled “SPL Standard for Content of Labeling Technical
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`Qs and As” at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/UC
`M072392.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 pending
`“Changes Being Effected” (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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`We request that the revised labeling approved today be available on your website within 10 days of
`receipt of this letter.
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`PROMOTIONAL MATERIALS
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`All promotional materials for your drug product that include representations about your drug
`product must be promptly revised to make it consistent with the labeling changes approved in this
`supplement, including any new safety information [21 CFR 314.70(a)(4)]. The revisions to 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 following address or by facsimile at
`301-847-8444:
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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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`In addition, as required under 21 CFR 314.81(b)(3)(i), you must submit your updated final
`promotional materials, and the package insert(s), at the time of initial dissemination or publication,
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`accompanied by a Form FDA-2253, directly to the above address. For instruction on completing
`the Form FDA 2253, see page 2 of the Form. For more information about submission of
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` NDA 021976/S-016
`page 3
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`promotional materials to the Division of Drug Marketing, Advertising, and Communications
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`(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 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 an electronic copy of the
`letter to both this NDA and to the following address:
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`MedWatch
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`Food and Drug Administration
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`5600 Fishers Lane, Room 12B05
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`Rockville, MD 20857
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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, please contact Amalia Himaya, Regulatory Project Manager, at
`(301) 796-3391 or the Division’s main number at (301) 796-1500.
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`Sincerely,
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` {See appended electronic signature page}
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`Debra Birnkrant, M.D.
`Director
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`Division of Antiviral Products
`Office of Antimicrobial Products
`Center for Drug Evaluation and Research
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`Enclosure
`Content of Labeling
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`Application
`Type/Number
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`NDA-21976
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`Submission
`Type/Number
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`SUPPL-16
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`Submitter Name
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`Product Name
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`--------------------
`CENTOCOR
`ORTHO BIOTECH
`INC
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`------------------------------------------
`PREZISTA
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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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`KENDALL A MARCUS
`04/26/2010
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