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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 21-372/S-008/S-010
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`Helsinn Healthcare SA
`US Representative: August Consulting
`Attention: Craig Lehmann, Pharm.D.
` Authorized Representative
`515 Capital of Texas Hwy, Suite #150
`Austin, TX 78746
`
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`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/1.5 mL intravenous injection for:
`• S-008: the prevention of postoperative nausea and vomiting for up to 24 hours following
`surgery
`• 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.
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`
`
`Package Insert Label
`• Delete the underlined numbering for 6.1, 6.2, 14.1, and 14.2 in the “FULL PRESCRIBING
`INFORMATION.”
`In the “HIGHLIGHTS OF PRESCRIBING INFORMATION” section “INDICATIONS
`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 hours following surgery.” Delete the word
` in the second sentence.
`In the “FULL PRESCRIBING 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
` in the second sentence.
`
`•
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`•
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`

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`NDA 21-372/S-008/S-010
`Page 2
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`•
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`•
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`•
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`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
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`compared to placebo.”
`In the “FULL PRESCRIBING INFORMATION” 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
`• 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.
`• Revise the color scheme for the proprietary name so that the entire name is presented in one
`color font.
`• 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.
`
`•
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`Carton Labeling
`• Revise the color scheme of the proprietary name so that the entire name is presented in one
`color font.
`• 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.
`• Eliminate the use of trailing zeroes.
`
`
`We also acknowledge your submission dated February 29, 2008 in which you agreed to the following:
`• 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.
`
`•
`
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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). These revisions are terms of the approval of these 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.”
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`

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`NDA 21-372/S-008/S-010
`Page 3
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`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 study required 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.
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`
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` Final Report Submission: December 13, 2008
`
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`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
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`

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`NDA 21-372/S-008/S-010
`Page 4
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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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`If you have any questions, call Jagjit Grewal, Regulatory Project Manager, at (301) 796-0846.
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`MEDWATCH
`Food and Drug Administration
`5515 Security Lane
`HFD-001, Suite 5100
`Rockville, MD 20852
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`Sincerely,
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`{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
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`Enclosure: Package Insert Label
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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/
`---------------------
`Joyce Korvick
`2/29/2008 07:34:28 PM
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