NBA 21-372
`
`Page 8
`
`Attachment One
`
`PALO—99-03
`
`Clinical & Statistical Study Report: Volume 1.117, page 1
`
`Synopsis: Volume 1.117, page 4
`
`Protocol: Volume 1.118, page 5
`
`List of Investigators: Volume 1.119, page 1
`
`Related Publications: Volume 1.120, page 138
`
`Palo-99-04
`
`Clinical & Statistical Study Report: Volume 1.135. page 1
`
`Synopsis: Volume 1.135, page 4
`
`Protocol: Volume 1.136, page 4
`
`List ofInvestigators: Volume 1.136, page 257
`
`Related Publications: Volume 1.137, page 404
`
`Palo-99-05
`
`Clinical & Statistical Study Report: Volume 1.156, page 1
`
`Synopsis:_ Volume 1.156, page 4
`
`Protocol: Volume 1.157, page 5
`
`List of Investigators: Volume 1.158, page 1
`
`Related Publications: Volume 1.160, page 146
`
`

`

`NDA 21-372
`
`Page 9
`
`cc:
`
`.
`
`.
`
`Draft: BKS/November l, 2002
`Final: BKS/November ], 2002
`Filename: reviews/Palonosetron Admin Review.doc
`
`ADMINISTRATIVE REVIEW
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Brian Strongin
`11/1/02 03:52:38 PM
`CSO
`
`

`

`Reda'cted .
`
`l'7‘
`
`pages of trade
`
`Secrét and/or
`
`'confidential
`
`

`

`07/25/2003 09:00 FAX
`
` :zsztzzasstsszsztzats
`
`88:
`TX REPORT
`:3:
`
`3888888883$8288888333
`
`TRANSMISSION OK
`
`
`
`07/25 08:58
`ST. TIME
`
`
`02'20
`USAGE T
`
`16
`PCS . SENT
`
`RESULT
`OK
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`
`
`TX/RX NO
`
`CONNECTION TEL
`CONNECTION ID
`
`2509
`
`915123479375
`
`Oflice of Drug Evaluation 11]
`
`Food and Drug Administration
`Center for Drug Evaluafiou and Research
`
`FACSIMILE TRANSMITTAL SHEET
`
`
`
`Fax number: (512) 347-9375
`
`DATE: July 25, 2003
`To: Craig Lehmann (Us Agent)
`Rom: Brian Su-ongin
`
`Divin'cm of Gasmintesn'nnl E: Coagulation
`Company: 14ch Healthcm SA
`Drug Producu
`
`Fax number: (301) 443-9285
`
` Phone number: (301) 827-7473 Phone number: (512)347-1755
`
`
`Subject: Approval Lem for NBA 21-372. EIjoy!
`
`
`
`Total no. of pages including cover:
`
`)6 |
`
`Comments:
`
`
`
`IIPJC)
`ETYES
`])ouunenth3bexnafled:
`
`
`THIS DOCUMENT IS INTENDED ONLY FOR THE USE OF THE PARTY TO WHOM IT IS ADDRESSED
`AND MAY CONTAIN INFORMATION THAT IS PRMLEGED. CONFIDENTIAL, AND PROTECTED
`FROM DISCLOSURE UNDER APPLICABLE LAW.
`
`Formamu: Len: 1',Top: 2'.
`
`Section mm Continuum. Head: dist-arr: from edge: 0.31'
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`-__________,__.._a_-___
`
`Julie Beitz'
`7/25/03 08:45:03 AM
`
`

`

`Office of Drug Evaluation III
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`
`
`
`
`FACSIMILE TRANSMITTAL SHEET
`
`DATE: July 11, 2003
`
`
`To: Craig Lehmann (US Agent)
`
`
`Company: Helsinn Healthcare SA
`
`
`Fax number: (512) 347-9375
`
`
`Phone number: (512)347-1755
`
`
`From: Brian Strongin
`
`
`
`Division ofGastrointestinal & Coagulation
`Drug Products
`Fax number: (301)443-9285
`
`
`
`
`
`Phone number: (301) 827-7473
`
`FDA Mark-Up of Your Proposed Package Insert Submitted September, 2002 for NDA 21-372;
`Subject
`Palonosetron
`
`
`
`Total no. of pages including cover: 3
`
`Cements:
`
`A clean copy of our mark-up of your proposed package insert submitted September 25. 2002 is
`attached. I have also e-mailed this labeling. When you send your response, please mark-up the
`clean copy so that your changes are clearly indicated. Please note that we are talking with the
`Office of Medical Policy about including the comparator names because of the potential for
`comparative claims and may have additional changes. Please refer to section llI.A.4 in the draft
`Guidance for industry on the Clinical Studies Section of Labeling for Prescription Drugs and
`Biologics — Content and Format. Thanks.
`
`
`
`M NO
`CI YES
`Document to be mailed:
`
`
`THIS DOCUMENT IS INTENDED ONLY FOR THE USE OF THE PARTY TO WHOM IT IS ADDRESSED
`AND MAY CONTAIN INFORMATION THAT IS PRIVILEGEDI CONFIDENTIAL, AND PROTECTED
`FROM DISCLOSURE UNDER APPLICABLE LAW.
`
`h\
`
`

`

`Lpages redacted from thissection of
`
`the approval package consisted of draft labeling
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Brian Strongin '
`7/11/03 10:28:30 AM
`CSO
`
`

`

`Lehmann, Craig
`
`From:
`\t:
`
`subject:
`
`Lehmann, Craig
`Tuesday, July 22, 2003 8:40 AM
`Brian Strongin (E-mail)
`NDA 21-372, Sponsor-proposed revised labeling dated July 22, 2003. in follow-up to FDA
`teleconterence held July 21, 2003
`
`Dear Mr. Strongin:
`
`In follow-up to the FDA labeling teleconference held yesterday, please find attached the subject Sponsor-proposed revised
`labeling as we discussed. Proposed revisions are highlighted in yellow.
`
`Please let me know it you wish further information.
`
`I will call you shortly.
`
`Best Regards,
`Craig
`
` ID}. 21-372 Spanso.’
`
`Proposed La . ..
`
`1
`
`0003
`
`

`

`pages redacted from this section of
`the approval package consisted of draft labeling
`
`

`

` Reda'cted 5 _
`
`pages of trade
`
`

`

`
`
`CONSULTATION RESPONSE
`
`
`
`DIVISION OF MEDICATION ERRORS AND TECHNICAL SUPPORT
`OFFICE OF DRUG SAFETY
`
`(DMETS; HEB—420)
`
` DATE RECEIVED: January 9, 2003
`DUE DATE: February 18, 2003
`
`
`
`ODS CONSULT #2 02-0068-2 -
`
`
`
`
`
`
`Director, Division of Gastrointestinal and Coagulation Drug Products
`HFD-l 80
`
`
`
`THROUGH: Brian Strongin
`
`'
`Project Manager, Division of Gastrointestinal and Coagulation Drug Products
`HFD-l 80
` .
`IND SPONSOR: Helsinn Healthcare SA
`
` Palonosetron Hydrochloride Injection)
`
`0.25 mg (0.05 mg/mL)
`
`
`
`
`
`TO:
`
`
`
`Robert Justice, M.D.
`
`
`
`IND #:
`
`l
`
`SAFETY EVALUATOR: Charlie Hoppes, R.Ph., MPH.
`
`
`
`In response to a consult from the Division of Gastrointestinal and Coagulation Drug Products
`SUMMARY:
`{FD-180), the Division of Medication Errors and Technical Support (DMETS) conducted a review of the
`iditional information submitted by the sponsor re arding the proposed proprietary namekj DMETS
`reviousl ' did not recommend the use of the name
`See ODS Consult # 02-0068) W
`. The
`RECOMMENDATIONS: DMETS does not recommend the use of the proprietary namek
`studies, in addition to the information on additional discriminating features and context of use submitted by
`the sponsor have not
`rovided a persuasive argument to diminish our concerns with potential confusion
`betweerClandi
`iHowever, after review of additional information submitted by the
`sponsor and the fact that the firm will not market this product with the 0.75 mg strength, DMETS
`has no objections to use of the proprietary name, Aloxi. In addition, DMETS recommends
`implementation ofthe labeling revision outlined in section IV ofthis review to minimize potential errors
`with the use of this roduct.
`
`
`
`
`
`
`
`
`
`
`
`
`i
`
`'
`
`. F3!
`
`'
`
`[SI
`
`' Division ofMedication Errors and Technical Support
`
`Carol Holquist, R.Ph.
`Deputy Director
`
`Office of Drug Safety
`Phone: (301) 827—3242
`
`Fax: (301) 443-9664
`
`Jerry Phillips, R.Ph.
`Associate Director
`
`
`Office ofDrug Safety
`
`
`Center for Drug Evaluation and Research
`Food and Dru- Administration
`
`

`

`Din‘sion of Medication Errors and Technical Support (DMETS)
`Office of Drug Safety
`HFD—420; Rm. Parklawn Room 6—34
`
`Center for Drug Evaluation and Research
`
`PROPRIETARY NAME REVIEW
`
`DATE OF REVIEW:
`
`February 25, 2003
`
`1ND#
`
`\- Z:
`
`)
`
`NAME OF DRUG: LJ
`(Palonosetron Hydrochloride Injection)
`0.25 mg (0.05 mg/mL)
`
`IND HOLDER:
`
`Helsinn Healthcare SA
`
`I.
`
`INTRODUCTION:
`
`This consult is in response to a December 26, 2002, submission from August Consulting, an
`
`Authorized Representative for the IND, requesting reconsideration ofthe proprietary name,
`Reference is made to ODS Consult # 02—0068, dated May 7, 2002, in which the
`Division of Medication Errors and Technical Support tDMETS) found the nameVJj
`
`
`objectionable due to the sound-alike potential with't _,
`.
`il'he sponsor has currently submitted
`additional information, including an independentanalysis conducted by thei
`_-
`to support approval of the proprietary name,l
`1
`j Container labels and canon labeling were
`reviewed for possible interventions in minimizing medication errors.
`
`j
`
`)Aloxi and?“
`The s onsor initially proposed two proprietary names in addition tf
`_
`nd Aloxi were reviewed on May 7, 2002 (ODS Consult #02-0068) and found
`unacceptable from a safety perspective as wast‘M/hich was reviewed on August 22, 2002
`(ODS Consult #02-0068-1).
`
`A?
`
`In a correspondence dated April 5, 2002, the sponsor explained that one product strength, either
`0.25 mg or 0.75 mg will be selected for the NDA and marketing based on phase 3 efficacy data.
`The project manager was contacted on March 12, 2003, and informed DMETS that the firm will
`market the 0.25mg strength.
`
`PRODUCT INFORMATION
`
`t
`
`Sis the proposed proprietary name for Palonosetron Hydrochloride Injection.
`Palonosetron’s proposed indication is for the prevention of acute and delayed nausea and
`vomiting associated with initial and repeated courses of emetogenic cancer chemotherpy,
`including highly emetogenic chemotherapy. The recommended dosage is 0.25 mg once daily in a
`single intravenous dose. This product is intended to be administered once per c motherapy
`cycle, approximately every 2-5 weeks depending on the chemotherapy regimenfflvill be
`
`supplied as 0.05 ngmL in a 5 mL vial.
`
`

`

`/
`u. RISK ASSESSMENT :1
`
`
`A.
`
`i
`
`- conducted two studies to evaluate the potential for error between
`The ”"
`kind currently marketed brand/generic drug products. The
`concentrated evaluation methods in four areas. In Section A, lOOphysicians evaluated
`(flor sound-alike/look-alike similarity, medical term Similarity, and hyperbole issues.
`ection B involved 100 participating pharmacists in interpretation studies of verbal and
`handwritten prescriptions for potential name confusion.
`In S ction C, a computerized
`analysis ofphonologic and orthographic similarities betweenbnd existing drug names
`
`,was conducted.
`
`In Section D, a Nomenclature Advisory Board reviewed the safety data for
`
`1. Section A
`
`)and identify any
`-i
`"‘ asked 100 participating physicians to view the test name,‘
`existing brand or generic names that they considered similar to the test name based on
`sound and/or appearance. They also determined ifthere were any medical terms that
`could be Similar to the test name. The participants evaluated the proposed name for any
`relationship to “hyperbole or false claims.” Verbal and handwritten prescriptions of the
`proposed proprietary name were collected from 100 participating physicians to be used in
`Section B of the study. The physicians provided oral and handwritten interpretations of
`the following
`Brescription.
`
`
`Li»
`I Vpush — over 30 seconds, 30 minutes prior to chemotherapy
`
`
`fas having sound—alike
`-— identified the names Celebrex, Centrax, Sinemer, and
`similarity and Avonex, Celebrex, Centrax, andivl as having look/alike similarity.
`The medical term Cervix was thought to have similarities withC: Also, 1% of
`physicians responding thought that the nameL—lwas suggestive of an antibiotic.
`
`DMETS Re_sn_onse:
`
`Although ‘ Jidicates that 270 physicians were asked to participate in this phase of the
`study, the response rate was only 37% (100 physicians). «motes that this is a “typical”
`response rate for a survey of this type. However, there are limitations in the predictive
`value of these studies, primarily due to the sample size.
`It is not indicative as to what will
`occur once the drug is widely prescribed. Additionally, DMETS notes that this study
`asked physicians, instead of pharmacists, to identify anyi’yjksound—alike or look-alike
`products. Physicians do not usually interpret prescriptions and thus the section would
`have been more effective if pharmacists had been included. This issue is also dependent
`upon the specialty of the physician. However, —- did not provide any medical specialty
`information on the respondents.
`
`)nd Sinemet in the
`DMETS considered the potential for name confusion betweeri
`review dated May 7, 2002, and decided that the risk of dispensing the wrong medication
`should be low based on lack of convincing sound—alike Similarities and differences
`3
`
`

`

`
`between the medications. DMETS continues to have concerns with the sound-alike
`
`
`physicians in the
`Of other names identif1
`\and_
`properties betweeri
`METS believes the
`study as having sound-alike or look-alike similarity withL
`risk of confusion)5 minimal given the differences between the drug characteristics and
`lack of convincing look-alike and sound-alike potential. The term “cervix” should not
`present confusion for the name(
`lsince the context for use would lessenlthe
`potential for errors.
`
`Section B — Handwritten 'and Verbal Analysis: Pharmacists
`
`~— provided one hundred pharmacists g50 retail and 50 hospital) with a verbal and written
`
`prescription (see above sample) for\
`1The objective ofthis phase15 to determine if
`any of the sample(!
`hirescriptions would be interpreted as a currently marketed
`brand or established name product. All of the respondents correctly identified the name
`rq‘Wfrom verbal and handwritten prescriptions.
`
`
`DMETS Response:
`
`As noted with the physician response rate, '" indicates that the response rate in this
`portion ofthe study was 39% (100 pharmacists). Again, there are limitations in the
`predictive value ofthese studies, primarily due to the sample size. Written and verbal
`prescriptions were collected from the physicians. Therefore, each of the one hundred
`pharmacists would have received a verbal and handwritten prescription to review. This
`methodology introduces bias because the participating pharmacists would have exposure
`to the drug name before evaluation ofthe second sample.
`
`The inclusion of “chemo” in the signatura (leush over 30 sec, 30 min. prior (0 chemo.)
`for these prescriptions presented contains a link to the indication of use for the proposed
`product and provides a clue to the reader that this product may have something to do with
`chemotherapy. Additionally, it is h:ghly unlikely that pharmacists would misinterpret a
`prescription as “when the sample contained the detailed directionsin the
`aforementioned signatura A more challenging test of confusion would have been a
`
`prescription that orderedk_
`\‘as directed”, without reference to indication or route of
`administration.
`
`1n the verbal prescription conducted by DMETS; «l—fiq‘lwas ordered as follows:
`
`CA0” mg
`One
`Use as directed
`
`(
`
`in the
`One study participant misunderstood the verbal order fork?) to be;
`above examge provided by DMETS, a pharmacist who inadvertently misinterpreted
`tits“xwould most likely question the order since i
`not associated
`with a “mmg’dosing amount. However, postmarketing experience has also shown errors
`occurring with products having look-alike and/or sound—alike names regardless of other
`
`differentiating factors. Therefore, DMETS has concerns with the sound-alike potential
`betweem . anQ
`
`
`
`

`

`Section C — Computer-Assisted Analysis
`
`:7 tonducted a “comprehensive search ofmedical references” to identify brand and
`established names that may sound-alike or look—alike to the proposed namei:
`Fourteen names were identified. x analyzed the names using their "
`”—3—“
`
`_
`.
`_
`' database and using a “Phonological and Orthographical Similarity
`Analysis.” I The “Phonological and Orthographical Similarity Analysis” identifies a
`threshold of similarity between (fl and the fourteen products identified during the
`search of the medical references. The objective of this analysis is to identify the
`‘similarity between the proposed proprietary name and any sound-alike or look-alike
`
`product.’
`identified 14 proprietary names as having look-alike and/or
`sound-alike potential with the proposed namel
`) . ~ :oncludes that the results
`
`7
`
`“...show infreguent overlap in product profiles among purportedly similar drug names.
`
`and that, “ .
`world practice.”
`
`ill be distinguished from other products, including
`
`-, in real-
`
`DMETS Response:
`
`‘DMETS does not have concerns with the proprietary
`With the exception oil, __
`_/"‘
`Analysis, due to lack of convincing
`names identified by — i the
`look-alikeflsound-alike similarities and the presence of differentiating features.
`AlthouglL
`filandl'
`lhave some distinguishing features, both are injectable drug
`products intended for single dose for a specified period of time. DMETS has the
`following comments concerning the methodology employed by ‘ ) determine
`phonologic and orthographic similarity between name pairs:
`-
`The phonologic and orthographic devices yield results which in some cases have
`no resemblance to the study name. Exam les from this study are “Vanocin” and
`“Vexol”, which bear little resemblance toi-
`\
`The order of syllables must not play a factor in the phonolo ic similarity rating or
`the bigram measure. For example, although “vex” inf
`homes as the second
`syllable, it is the first syllable in Vexol. Vexollgiclth‘e highest rating in the bigram
`measure even though it sounds little likei
`V ‘l
`
`-
`
`
`
`Section D - Pharmacists’ Anal sis — N
`
`Ten actively practicing retail and hos ital, harrnacists provided an independent analysis
`of the proposed proprietary nameS
`by considering its potential for error and
`potential for patient harm in the event of an error. The pharmacists were provided with
`the product concept and profile information fox
`'as well as research data from all
`sections of the study, and were asked to evaluate this information. The pharmacists
`evaluated all of the data obtained during this stud and determined that based on their
`experience the risk ofname confiJsion betweenfindl .
`is minimal. The
`review board’s analysis was favorable forCYKey differentiating features between
`andKAwere summarized in an Executive Summary.
`
`DMETS Response:
`
`
`
`M ._
`The
`
`l
`
`has submitted information to support the proposed pro rieta
`inalso specifically details the safety profile between the names}
`5
`
`name,
`nd
`
`

`

`i
`
`S DM®chowledges comments regarding differences in the distribution of
`“ andi-
`S / states that __
`is most frequently purchased
`by the Orthopedist from the wholesaler and administered by intra—articular injection in the
`office. DMETS agrees that under these conditions, it would be unlikely for an error
`
`involving confusion between — and\
`0 occur. However, it is possible that
`an orthopedic outpatient clinic located in a hospital could order : from the hospital
`pharmacy. _Such a-verbal order might easily be misunderstood as('\j Although
`DMETS’ primary concern is confusion of
`an
`in the hospital setting, it is
`important to note that
`_—~
`is available through intemet sources such as Destination
`Rx and Drugstorecom and may be ordered through retail pharmacies as well. DMETS
`
`agrees with the l
`that one possible distribution route is that the patient
`purchases _—‘ 1nd brings it to the physician for intra-articular injection. This __
`scenario presents one additional opportunity for coyfusion between f” and—xii
`
`If a prescription for _“ is inadvertently misinterpreted asT/fflghe pharmacist
`
`may not question the strength since f— is available without a strength andL)
`will be available in only one strength (0.25 mg/5 mL). Conversely, a prescription for
`ay be ordered without a strength since only one strength ofi;’:will be
`available in the marketplace.
`
`DMETS also acknowledges differences in physician prescribing population, practice
`setting, and patient populations for these two products. However, postmarketing
`experience has also shown errors occurring with products having look-alike and/or sound-
`alike names regardless of other differentiating factors.
`
`is mainly distributed directly to physicians, there is some
`In summary, although _‘
`potential that — ' will be kept on hospital pharmacy shelves. Confusion for this name
`pair may occur during initial marketing when product reco
`ition is low. DMETS has
`concerns regarding the safety of concurrent marketing 01‘.
`hind N because of
`the positive response in the DM TS rescription study, the strong sound-alike properties
`ofthese products, and that both
`nd 7“ are injectable drug products intended
`for single dose administration for a specified period of time.
`
`'
`
`Ill.
`
`RISK ASSESSMENT - ALOX]:
`
`In a review dated May 7, 2002 (ODS Consult #02-0068), DMETS found the name Aloxi
`unacceptable. In part, that decision was made because of the shared numerals in the
`strengths of those products, Aloxi 0.75 mg, and Alora 0.075 mg.
`It has come to the
`attention of'DMETS that Aloxi will not be marketed with the 0.75 mg strength. Because
`of other differences between the products including route of administration and dosage
`form (ltransdermal patch vs. parenteral product for intravenous use), and the differences in
`physician prescribing population, practice setting, and patient populations for these two
`products, DMETS has reconsidered the safety profile of Aloxi and does not object to the
`use of the proprietary name in the marketplace.
`
`

`

`IV.
`
`LABELING, PACKAGING, AND SAFETY RELATED ISSUES:
`
`In review ofthe container labels and carton labeling ofCDDMETS has focused on
`safety issues relating to possible medication errors and has identified one area ofpossible
`improvement, which might minimize potential user error.
`
`GENERAL COMMENT
`
`Revise the strength on container labels and carton labeling as follows:
`
`025 mg/5 mL
`(0.05 mg/mL)
`
`V. RECOMMENDATIONS:
`
`A. DMETS does not recommend the use of the proprietary name: The studies, in
`addition to the information on additional discriminating features and context of use
`submitted by the sponsor, have not provide a ersuasive argument to diminish our
`concerns with potential confusion between
`ndl
`1
`
`After review of additional information submitted by the sponsor and the fact that the firm
`will not market this product with the 0.75 mg strength, DMETS has no objections to use
`of the proprietary name, Aloxi.
`
`DMETS recommends implementation ofthe labeling revision outlined in section IV of
`this review to minimize potential errors with the use of this product.
`
`
`
`<63/
`
`Charlie l-Ioppes, R.Ph., M.P.H.
`Safety Evaluator
`Division of Medication Errors and Technical Support
`Office of Drug Safety
`
`Concur:
`
`/‘3
`Alina Mahmud, R.Ph.:§/
`Team Leader
`
`'
`
`Division of Medication Errors and Technical Support
`Office ofDrug Safety
`
`

`

`.--------------------------—---.--n.-------------»------.-—------..------..---------—--------9---—----------n-.-
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Charles Hoppés
`3/18/03 01:38:55 PM
`PHARMACIST
`
`Alina Mahmud
`3/18/03 01:50:39 PM
`PHARMACIST
`
`Jerry Phillips
`3/18/03 02:00:08 PM
`DIRECTOR
`
`

`

`
`CONSULTATION RESPONSE
`
`i
`
`DIVISION OF MEDICATION ERRORS AND TECHNICAL SUPPORT
`OFFICE OF DlRUG SAFETY
`
`ODS CONSULT #: 02-0068-1
`
`(DMETS; HFD—420)
`
`DUE DATE: Sept. 17,2002
`
`
`
`Robert Justice, MD.
`Director, Division of Gastrointestinal and Coagulation Drug Products
`
`HFD-l 80
`
`
`
`
`
`
`
`THROUGH: Brian SUongin
`Project Manager
`HFD- l 80
`
`
`IND SPONSOR: Helsinn Healthcare SA
`
`(Palonosctron Hydrochloride Injection)
`0.25 mg (0.05 mg/mL) and
`
`
`
`
`_
`IND #:
`
`SAFETY EVALUATOR: Tia M. Harper-Velazquez, PharmD.
`
`In response to a consult from the Division of Gastrointestinal and Coagulation Drug Products,
`,UMMARY:
`HFD-l 80, the Division of Medication Errors and Technical Support (DMETS) conducted a review ofthe proposed
`proprietary nameDo detemiine the potential for confusion with approved proprietary and established
`names as well as ending names.
`__
`DMETS RECOMMENDATION: DMETS does not recommend the use oi‘thc proprietary name,
`
`
`
`
`
`The firm should be notified that this name with its associated labels and labeling must be re-evaluated upon
`submission ofthe NDA and approximately 90 days prior to the expected approval ofthe NDA. A re—review of the
`name prior to NBA approval will rule out any objections based upon approvals of other proprietary names or
`established names from the signature date of this document forward.
`
`
`
`/S/
`
`45’
`
`Jerry Phillips, R.Ph.
`
`
`Carol Holquist, R.Ph.
`Deputy Director
`
`Division of Medication Errors and Technical Support
`Office of Drug Safety
`Phone: (30]) 827-3242
`
`
`
`
`
`
`
`Fax: (301)443-5161
`
`
`
`Associate Director
`Office of Drug Safety
`Center for Drug Evaluation and Research
`Food and Drug Administration
`
`
`
`
`

`

`Division of Medication Errors and Technical Support (DMETS)
`Office of Drug Safety
`HFD—420; Rm. 6-34
`Center for Drug Evaluation and Research
`
`PROPRIETARY NAME REVIEW
`
`DATE OF REVIEW:
`
`August 22, 2002
`
`IND#
`
`G
`
`NAME OF DRUG: ‘3
`(Palonosetron Hydrochloride Injection)
`
`0.25 mg (0.05 mg/mL)
`#
`
`IND HOLDER:
`
`Helsinn Healthcare SA
`
`1.
`
`INTRODUCTION:
`
`This consult is written in response to a request from the Division ofDivision of Gastrointestinal and
`Coagulation Drug Products for an assessment of the proposed proprietary name,
`Draft container
`labels and carton labeling were not submitted with this consult since this application is in the IND phase.
`
`PRODUCT INFORMATION
`
`(
`
`is the proposed proprietary name for Palonosetron Hydrochloride Injection. Palonosetron
`hydrochloride is indicated for the prevention of acute and delayed nausea and vomiting associated with
`initial and repeated courses ofemetogenic cancer chemothera y, including highly emetogenic
`chemotherapy. The recommended dose is 0.25 mgi
`ias a sin le intravenous dose administered
`as a 30 second bolus 30 minutes prior to emetogenic chemotherapyflbil] be administered once
`per chemotherapy cycle, approximately every 2 to 5 weeks, depending on the chemotherapy regimen.
`
`II. RISK ASSESSMENT:
`
`The medication error staff of DMETS conducted a search of several standard published drug product
`reference texts” as well as several FDA databases3 for existing drug names which sound alike or
`look alike to a degree where potential confusion between drug names could occur under the usual
`
`’MICROMEDEX Healthcare Intranet Series, 2000, MICROMIEDEX, Inc., 6200 south Syracuse Way, Suite 300, Englewood,
`Colorado 80] l l-4740, which includes the following published texts: DrugDex, Poisindex, Martindale (Parfrtt K (Ed),
`Martindale: The Complete Drug Reference. London: Pharmaceutical Press. Electronic version), Index Nominum, and
`PDR/Physician‘s Desk Reference (Medical Economics Company Inc, 2000).
`2 Facts and Comparisons, online version, Facts and Comparisons, St. Louis, MO.
`3 The Established Evaluation System [EES], the Division of Medication Errors and Technical Suppon [DMETS] database of
`. Proprietary name consultation requests, New Drug Approvals 98-00, and the electronic online version of the FDA Orange
`Book.
`
`WVWW location http://“vmuuspto.gov/tmdb/indexhtml.
`5 Data provided by Thomson 8; Thomson’s SAEGIS T” Online Service, available at www.thomson-thomson.com
`
`4.
`
`

`

`clinical practice settings. A search of the electronic online version ofthe US. Patent and Trademark
`Office’s Text and Image Database‘1 and the Saegis5 Pharma-In-U'se database were also conducted. An
`expert panel discussion was conducted to review all findings from the searches.
`In addition,
`DMETS conducted three prescription analysis studies consisting of two written prescription studies
`(inpatient and outpatient) and one verbal prescription study, involving health care practitioners
`within FDA. This exercise was conducted to simulate the prescription ordering process in order to
`evaluate potential'errorsjn handwriting and verbal communication of the name.
`
`A. EXPERT PANEL DISCUSSION
`
`An Expert Panel discussion was held by DMETS to gather professional opinions on the safety of
`the proprietary namel‘
`Potential concerns regarding drug marketing and promotion related
`to the proposed name were also discussed. This grousz composed of DMETS Medication
`Errors Prevention Staff and representation from the Division of Drug Marketing, Advertising,
`and Communications (DDMAC). The group relies on their clinical and other professional
`experiences and a number of standard references when making a decision on the acceptability of
`a proprietary name.
`
`I. The Expert Panel identified four proprietary names that were thought to have the potential for
`confusion witli
`[I hese products are listed in table 1 (see below), along with the usual
`dosage and available dosage forms.
`
`2. DDMAC did not have concerns about the name lflvith regard to promotional claims.
`
`Table 1: Potential Sound-Alike/Luok-Alike Names Identified by DMETS Expert Panel
`
`k
`
`Oracit
`
`
`
`Dosa_e form(s ,‘Established name
`Palonosetron HCL Injection
`0.25 mg (0.05 mg/mL) or
`____
`
`Oral Citrate Solution
`
`Usual adult dose‘
`0.25 mg 5—— in a single dose,
`intravenously each chemotherapy
`c Th, 2 -
`- roximatel everv 2- 5 weeks.
`
`”LA/SA
`
`490 mg sodium citrate and 640 mg citric meals and before bedtime.
`acid er 5 mL.
`
`Omnicef
`
`Cefdinir Capsules 300 mg
`Oral Suspension 125 mg/5 ml.
`
`600 mg per day for 10 days, either as
`once-daily or twice—daily dosing.
`
`“SA
`
`Ansaid
`
`Flurbiprofen Tablets
`
`200 to 300 mg per day in 2-4 divided
`
`"SA
`
`Emcyt
`
`'
`
`Estramustine Phosphate Sodium
`
`14 mg/kg/day in 3 or 4 divided doses
`
`“SA
`
`unhoshate (12.5 m_ sodium/catsule
`‘Frequently used, not all-inclusive.
`”L/A (look—alike), S/A (sound-alike)
`
`B. PRESCRIPTION ANALYSIS STUDIES
`
`1. Methodology:
`
`Three separate studies were conducted within FDA for the proposed proprietary name to
`determine the degree ofconfusion 01C__\with other US. drug names due to similarity in
`visual appearance with handwritten prescriptions or verbal pronunciation of the drug name.
`3
`
`

`

`These studies employed a total of 16 health care professionals (pharmacists, physicians, and
`nurses). This exercise was conducted in an attempt to simulate the prescription ordering process.
`An inpatient order and outpatient prescriptions were written, each consisting ofa combination of
`marketed and unapproved drug products and a prescription fort
`\(see below). These
`prescriptions were optically scanned and one prescription was delivered to a random sample of
`the participating health professionals via e-mail.
`In addition, the outpatient orders were recorded
`on voice mail. The voice mail messages were then sent to a random sample of the participating
`health professionals for their interpretations and review. After receiving either the written or
`verbal prescription orders, the participants sent their interpretations of the orders via e-mail to the
`medication error staff.
`
`Ougpati ent RX :
`
`
`
`\
`
`VERBAI. PRESCRIPTION
`
`
`
` HANDWRITTEN PRESCRIPTION
`
`
`
`
`
`
`
`[25 mg, take 1
`
`before clinic.
`
`time today at 1pm
`
`@159} K‘-
`
`Inpatient RX:
`
`Results:
`
`The results are summarized in Table 2.
`
`Table 2
`
`
`
`
`
`
`
`
`
`
`
`
` # of
`Correctly
`# of Participants.
`Incorrectly
`Responses
`Interpreted
`Interpreted
`
`
`%
`%
`%
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`

`

`I Incorrect Name Written (Outpatient)
`
`D Correct Name
`
`lZZ of 22 (100%) of the participants
`Among the verbal prescription study participants {orig
`interpreted the name incorrect] . The majority ofthe incorrect name interpretations were
`phonetic variations of
`The incorrect responses were Onacet (8), Anacet (3), Alacet (2),
`Alasert (1), Amacet (J), Anafetle (I), Anasept (1), Onoce! (1), Oniset (1), Onofect (1),
`Onosene (1), and Ulcer (1).
`
`Among the written prescription study participants {060 of4l(73%) participants
`interpreted the name incorrectly. The majority of the responses were misspelled variations of
`
`j. The incorrect responses were Onieit (10), Oracit (I), Orzici‘tQJN Omicit (I , Onieeffl),
`
`51),
`
`3),
`
`\
`
`Orieit (I), Oureit (I), Ovicil (2), Ancer (1), Omcit (I), Omovit (I)
`Oniut (I), Onuit (2), and Onvit (I).
`
`SAFETY EVALUATOR RISK ASSESSMENT:
`
`‘3’, the primary concerns raised were related to four
`In reviewing the proprietary name i
`look-alike and/or sound-alike names: Oracit, Omnicef, Ansaid, and Emcyt.
`
`In this case,
`We conducted prescription studies to simulate the prescription ordering process.
`there was confirmation thatl Would be confused with'Oracit, a product that is currently
`marketed in the United States. One respondent from the written outpatient study interpreted the
`name to be Oracit. Additionally, two patients from the written outpatient study interpreted the
`name asQ
`)a phonetic variation of the name Oracit.
`
`Oracit is an oral citrate solution that contains the active ingredients sodium citrate and Citric acid.
`Oracit is used as a systemic and urinary alkalinizer, and is indicated for the treatment of
`metabolic acidosis, particularly when caused by renal tubular acidosis.
`It is also used in
`situations where long-tenn maintenance of alkaline urine is desirable. For example, in the
`treatment ofpatients with uric acid and cystine calculi ofthe urinary tract, and in conjunction
`with un'cosurics in gout therapy, to prevent uric acid nephropathy. The recommended dose of
`Oracit is 15 to 30 mL diluted with water, taken after meals, and before bedtime. Oracit and
`)can sound similar when pronounced, and look similar when s