CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICA TION NUMBER:
`21-372/8008/8010
`
`APPROVAL LETTER
`
`

`

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`=2" ‘{ DEPARTMENTOFHEALTH&HUMANSERVICES
`
`’I‘ann MH—Food and Drug Administration
`Rockviile, MD 20857
`
`PublicHealthService
`
`NDA 21-372/S-008/S-010
`
`Helsinn Healthcare SA
`
`_ US Representative: August Consulting
`Attention: Craig Lehmann, PharmD.
`Authorized Representative
`515 Capital of Texas Hwy, Suite #150
`Austin, TX 78746
`
`Dear Dr. Lehmann (US Agent):
`
`Please refer to your supplemental new drug applications dated April 27, 2007, received May 4, 2007,
`submitted under section 505 (b) of the Federal Food, Drug, and Cosmetic Act for Aloxi (palonosetron
`hydrochloride), 0.075 mg/1.5 mL Intravenous Injection.
`
`We acknowledge receipt of your submissions dated April 27, 2007; June 21, 2007; June 27, 2008; June
`28, 2007; July 11, 2007; July 18, 2007; July 27,2007; September 6, 2007; October 9, 2007; October
`31, 2007; November 2, 2007; November 5, 2007; December 6, 2007; January 14, 2008; February 7,
`2008; February 8, 2008; February 19, 2008; February 20, 2007; February 21, 2008; February 22, 2008;
`and February 29, 2008.
`‘
`
`These supplemental new drug applications provide for the use of Aloxi (palonosetron hydrochloride)
`0.075 mg/l .5 mL intravenous injection for:
`0
`S-008: the prevention of postoperative nausea and vomiting for up to 24 hours following
`surgery
`
`0
`
`S-010:
`
`the removal of QT safety information currently found in the label
`
`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 and with
`the editorial revisions listed below.
`
`_
`'
`Package Insert Label
`0 Delete the underlined numbering for 6.1, 6.2, 14.1, and 14.2 in the “FULL PRESCRIBING
`INFORMATIO .”
`
`o
`
`In the “HIGHLIGHTS OF PRESCRIBING INFORMATION” section “INDICATIONS
`
`0
`
`AND USAGE,” add the words “(PONV) for up to 24 hours following surgery” after the
`first sentence to read “Prevention of postoperat
`ausea and vomiting (PONV) for up to
`24 heurs following surgery.” Delete the word l:lin the second sentence.
`In the “FULL PRESCRIBTNG INFORMATION” section 1.2 “Postoperative Nausea and
`Vomiting,” add the words “(PONV) for up to 24 hours following surgery” at the end of the
`first sentence to read “Prevention of postoperative nausea and vomiting (PONV) for up to
`24 hours following surgery.” Delete the word l::]in the second sentence.
`
`

`

`NDA 21-372/8—008/8-010 ‘
`Page 2
`
`0
`
`0
`
`0
`
`In the “FULL PRESCRIBING INFORMATION” section 14.2 “Postoperative Nausea and
`Vomiting,” delete the words[:::] and add “compared to” in the first
`paragraph following Table 6
`ron 0.075 mg reduced the severity of nausea
`compared to placebo.”
`In the “FULL PRESCRIBING INFORMATIO ” section 14.2 “Postoperative Nausea and
`Vomiting,” delete the word [:and add “formally” in first paragraph following
`Table 6 to read “Analyses o
`ary endpoints indicate that palonosetron 0.075 mg
`was numerically better than placebo, however, statistical significance was not formally
`demonstrated.”
`In the section “Patient Information,” delete the last bullet under “What is ALOXI used
`for?”
`
`Container Label
`0 Revise the color scheme for the 0.075 mg/1.5 mL strength to ensure it is adequately
`differentiated from the 0.25 mg/5 mL strength.
`0 Revise the color scheme for the proprietary name so that the entire name is presented in one
`color font.
`_
`0 Revise the color of the font utilized for the established name and product strength so that it
`provides adequate contrast against the grey backround.
`Increase the prominence of the established name and product strength.
`
`0
`
`4
`Carton Labeling
`o Revise the color scheme of the proprietary name so that the entire name is presented in one
`color font.
`_
`0 Revise the color of the font utilized or the established name and product strength so that it
`provides adequate contrast against the grey backround.
`Increase the prominence of the established name and product strength.
`0
`0 Eliminate the use of trailing zeroes.
`
`We also acknowledge your submission dated February 29, 2008 in which you agreed to the following:
`0 Resolve the expression of palonosetron nomenclature and dosage strength on the carton
`label, container label, and in the package insert to present the milligram strength consistent
`with the established name, similar to other FDA-approved product labels.
`Include a “New Strength” banner on the principal display panel of the carton for period of
`up to approximately six months provided the you can exhaust product inventory which
`includes this banner which may take longer than 6 months.
`
`0
`
`As soon as possible, but no later than 14 days from the date ofthis 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). These revisions are terms of the approval ofthese applications. 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 supplement NDA 21-372/S-008/S-
`010.”
`
`

`

`NDA 21-372/S—008/S—010
`
`Page 3
`
`Submit final printed carton and container labels that are identical to the submitted carton and
`immediate container labels dated October 9, 2007, except for including the revisions listed and the
`agreed upon revisions in your submission dated February 29, 2008, as soon as they are available, but
`no more than 30 days after they are printed. Please submit these labels electronically according to the
`guidance for industry titled Providing Regulatory Submissions in Electronic Format — Human
`Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications
`(October 2005). Alternatively, you may submit 12 paper copies, with 6 of the copies individually
`mounted on heavy-weight paper or similar material. For administrative purposes, designate this
`submission “Final Printed Carton and Container Labels for approved NDA 21—372/S-008/S-010.”
`Approval of this submission by FDA is not required before the labeling is used.
`
`Marketing the product with FPL that is not identical to the approved labeling text may render the
`product misbranded and an unapproved new drug.
`'
`
`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 in pediatric patients unless this requirement is waived, deferred,
`or inapplicable. We are waiving the pediatric study requirement for ages 0 to 1 month of age because
`necessary studies are impossible or highly impractical because there are too few children in this age
`group to study. We are deferring submission of your pediatric study for ages 1 month to 16 years for
`this application because the drug is ready for approval for use in adults and the pediatric studies have
`not been completed.
`
`Your deferred pediatric studyrequired by section 505B(a) of the Food, Drug, and Cosmetic Act are
`required postmarketing study commitments. The status of this postmarketing study must be reported
`annually according to 21 CFR 314.81 and section 505B(a)(3)(B) of the Food, Drug, and Cosmetic Act.
`This commitment is listed below.
`
`1. Deferred pediatric study under PREA to evaluate (1) the safety and tolerability of two doses of
`I.V. palonosetron for the prevention of postoperative nausea and vomiting, and (2) the efficacy of
`these two I.V. palonosetron doses to prevent postoperative nausea and vomiting.
`
`Final Report Submission: December 13, 2008
`
`Submit final study reports to this NDA. For administrative purposes, all submissions related to
`this/these pediatric postmarketing study commitment(s) must be clearly designated “Required
`Pediatric Study Commitments”.
`
`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 Gastroenterology Products and two copies of both the promotional materials and the
`package inserts directly to:
`
`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
`
`

`

`NDA 21-372/S-008/S-010
`
`Page 4
`
`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:
`
`MEDWATCH
`
`Food and Drug Administration
`5515 Security Lane
`HFD—001, Suite 5100
`Rockville, MD 20852
`
`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, call Jagjit Grewal, Regulatory Project Manager, at (301) 796-0846.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Joyce Korvick, M.D., MPH
`Deputy Division Director
`Division of Gastroenterology Products
`Office of Drug Evaluation III
`Center for Drug Evaluation and Research
`
`Enclosure: Package Insert Label
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Joyce Korvick
`2/29/2008 07:34:28 PM
`
`