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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`NDA 022249/S-005
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`Cephalon Inc.
`Attention: Carol S. Marchione
`Senior Director and Group Leader
`41 Moores Road
`Frazer, PA 19355
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`Dear Ms. Marchione:
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`Please refer to your supplemental new drug application dated January 15, 2010, and received
`January 15, 2010, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
`(FDCA) for Treanda® (bendamustine hydrochloride).
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`We acknowledge receipt of your submission dated February 5, 2010.
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` SAFETY LABELING CHANGES
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`Reference is also made to our letter dated December 15, 2009, notifying you, under Section
`505(o)(4) of the FDCA, of new safety information that we believe should be included in the
`labeling for Treanda® (bendamustine hydrochloride). This information pertains to the risk of
`adverse reactions including extravasation or infiltration events, some requiring hospitalization.
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`This supplemental new drug application provides for revisions to the labeling for Treanda®
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` (bendamustine hydrochloride). The agreed upon changes to the language included in our
`December 15, 2009, letter are as follows (additions are noted by underline and deletion are noted
`by strikethrough).
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`1. In the section Highlights of Prescribing Information, sub-section Recent Major Changes, the
`following was added:
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`Warnings and Precautions, Extravasation (5.7)
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`01/2010
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`2. In the section Highlights of Prescribing Information, sub-section Warnings and Precautions,
`the following was added:
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`Extravasation: Take precautions to avoid extravasation, including monitoring intravenous
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`infusion site during and after administration. (5.7)
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`Use in Pregnancy: Fetal harm can occur when administered to a pregnant woman. Women
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`should be advised to avoid becoming pregnant when receiving TREANDA. (5.75.8, 8.1)
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`NDA 022249/S-005
`Page 2
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`3. In the section Highlights of Prescribing Information the following was added:
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`Revised 02/201010/2009
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`4. In the section Full Prescribing Information: Contents, the following was added:
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`5.7 Extravasation
`5.75.8 Use in Pregnancy
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`5. In the section Full Prescribing Information, sub-section 5 Warnings and Precautions, the
`following was added:
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`5.7 Extravasation
`There are postmarketing reports of bendamustine extravasations resulting in hospitalizations
`from erythema, marked swelling, and pain. Precautions should be taken to avoid
`extravasation, including monitoring of the intravenous infusion site for redness, swelling,
`pain, infection, and necrosis during and after administration of TREANDA (bendamustine
`hydrochloride). There are postmarketing reports of bendamustine extravasations resulting in
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` hospitalizations from tissue necrosis, erythema, marked swelling, pain, fever, and infection.
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`5.75.8 Use in Pregnancy
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`6. In the section Full Prescribing Information, sub-section Use in Specific Populations, the
`following was added:
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`8.1 Pregnancy
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`Pregnancy Category D [See Warnings and Precautions (5.75.8)]
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`7. At the end of the label, the following was added:
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`©2008-20092010 Cephalon, Inc., or its affiliates. Label Code:
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`00016287.03XXXXXXXX.XX
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`We have completed our review of this supplemental 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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`NDA 022249/S-005
`Page 3
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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, please submit the content
`of labeling [21 CFR 314.50(l)(1)(i)] 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). For administrative purposes, please designate this submission, “SPL for
`approved NDA 022249/S-005”.
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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
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`promotional materials, and the package insert(s), at the time of initial dissemination or publication,
`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
`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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`NDA 022249/S-005
`Page 4
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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 Alberta Davis-Warren, Regulatory Project Manager, at
`(301) 796-3908.
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`Sincerely,
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` {See appended electronic signature page}
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`Robert L. Justice, M.D., M.S.
`Director
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`Division of Drug Oncology Products
`Office of Oncology Drug Products
`Center for Drug Evaluation and Research
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`
`Enclosure
`Content of Labeling
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`Application
`Type/Number
`--------------------
`NDA-22249
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`Submission
`Type/Number
`--------------------
`SUPPL-5
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`Submitter Name
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`Product Name
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`--------------------
`CEPHALON INC
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`------------------------------------------
`TREANDA
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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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`ROBERT L JUSTICE
`02/26/2010
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