`

`>n'#21-038
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`un-UU mAME: Precedex (dexmedetomidine ncl injection)
`MC;
`[121/ 3 X1
`
`APPLICANT: ABBOTT LABORATORIES
`
`r”
`-\
`
`CHEMICAL & THERAPEUTIC CLASSAS
`
`
`
`Review C cles
`
`Review Cyclefl
`Submission Date:
`Receipt Date:
`Goal Date:
`Action:
`
`Review Cycle: 4
`Submission Date:
`Receipt Date:
`Goal Date:
`Action:
`
`
`Review Cycle: 1
`Submission Date:12-18-98
`3 Receipt Date1l2-18-98
`Goal Datezlz-l8-99
`ActionzAP
`
`Review Cycle: 3
`. Submission Date:
`Receipt Date:
`Goal Date:
`Action:
`
`-—
`
`
`
`WW
`
`PROJECT MANAGER/ CSO :Susmita Samanta
`Phone # & Office Room #:301-827-7410, 98-45
`
`‘
`
`MEDICALzPatricia Hartwell, M.D.. M.D.A. _
`
`CHEMISTRYzMichael Theodorakis, Ph.D.
`
`'
`
`‘
`
`PHARM/TOX:Harry Geyer, PILD.
`
`
`
`
` BlOPHARMACEUTICS:Suresh Doddapaneni, m.
`
`
`
`
`
`
`
`BIOMETRICS: Z.Jonathan Ma, Ph.D.
`
`ABUSE LIABILITY: BeLinda A. Hayes, Ph.D.
`
`M lCROBIOLOGIST: Patricia Hughes, PILD.
`
`Volume 1 of 4
`
`Administrative volume #(s): 1
`Clinical volume #(s): 2
`CMC volume #(s): 3
`
`Pharmacology/Toxicology volume #(s): 4
`
`
`
`

`

`ODE H ACTION PACKAGE TABLE or Commrs
`
`Application #21-038
`
`Drug Name: Precedex (dexmedetomidine Hydrochloride injection), 2 mL ampule/Z mL vial, 100
`mcg/mL
`Applicant-:Abbott Laboratories
`‘CSO/PM: Susmita Samanta
`
`ChemfI'her. Type: 1 S
`HFD] 70
`
`'
`.
`Phone: 301-827-7410
`
`Original Application Dates: December 18, 1998 Original Reeeipt Date: December 18, 1998
`
`
`7 CURRENT USER FEE GOAL DATE: December 18, l999DateTableofContentsCompleted:9/ 13/99
`..,
`n
`X (completed),
`'N/Atnoxappncable).
`or Comment
`
`'
`
`Adminmmmmmmgn
`
`ec "
`
`z
`
`Tab A-l
`
`Action Letter(s)
`
`
`Current ActionzAP
`
`Tab A- l 0
`
`Minutes ofMeetings:
`
`a. End-of-Phase II meeting......................................
`
`b. Pre-NDA meeting(s) ...........................
`
`........................
`
`c. Filing meeting .......................................................................
`
`d. Other meetings ......................................................................
`
`Tab A-l 1
`
`Advisory Committee Meeting:
`
`a. Questions Considered by the committee .......................................
`b. List 'of Attendees ....................................................................
`
`c. 24 Hour alert memorandum
`
`V Tab A-12
`
`Project Management Administrative Information (optional).........................
`
`
`
`
`
`
`
`~
`
`iTab A-2
`
`Tab A-3
`
`.
`__
`Tab‘Ai-4
`Tab A-S
`
`Tab A-6
`Tab A-7
`Tab A-8
`
`Tab A-9
`
`__
`Phase 4 Commitments:
`a. Copy of applicants communication committing to Phase 4 ................ ~.
`
`b. Agency Correspondence requesting Phase 4 Commitments ................
`
`FDA revised Labels & Labeling and Reviews:
`(Separate each version/cycle with a colored sheet)
`
`a. Package Insert .......................................................................
`
`b. Immediate Container and Carton Labels ...‘. ...................................
`Original Proposed Labeling ...............................................................
`Foreign Labeling:
`
`a. Foreign Marketing History........................................................
`
`b. Foreign Labeling and Review(s) .............1...................................
`
`2
`
`Labeling and Nomenclature Committee’s Tradename Review .....................
`Summary Memoranda (e.g., Division Director, Group Leader, Office) .........
`Copy of Patent Statement ..................................................................
`
`Exclusivity Checklist (and any requests for. exclusivity) .............................
`
`Debarrnent Statements ......................................................................
`
`Correspondences, Faxes, & Telecons ...................................................
`
`......................................
`
`

`

`
`
`ODE II ACTION PACKAGE TABLE or CONTENTS (continued)
`
`Application #21-038 Drug Name: Dexmedetomidine HCL
`
`X (completed).
`W W N/A (not applicable).
`_
`or Comment
`
`Tab B-l
`
`Clinical Reviews and Memoranda .......................................................
`
`Tab B-2
`Tab 13-3
`
`Tab B-4
`Tab .1815
`Tab B-6
`
`Tab Be7
`:Tab B-8
`
`Tab 8-9
`
`Safety Update Reviews
`Pediatric Page
`
`.........................
`.....................
`
`Summary of Safety (from the summary volume of the application) .................... _.
`
`Statistical (Clinical) Review and Memoranda ..........................................
`M Biopharmaceutics Review and Memoranda ............................................
`Abuse Liability Review ..............................'f.....................................
`
`DSI Audits ....................................................................-~..............
`Summar:y of Efficacy (from the summary volume of the application) ..................
`
`l!
`
`Section C:
`
`.
`
`'
`
`I
`
`.
`
`g .
`
`'
`
`.fl
`
`! A:
`
`X (completed),
`N/A (not applicable),
`
`Tabi'CT-l
`
`CMC Reviews and Memoranda
`
`.............................
`
`Tab C-Z
`
`DMF Reviews ..............................................................................
`
`Tab C-3
`
`EA Reviews/FONSI .......................................................................
`
`Tab C-4
`Tab 05
`
`Micro Review (validation of sterilization) ........a:...................................
`Statistical Review of drug stability ......................................................
`
`._
`
`Tab C-6
`
`Inspection of facilities => Decision:
`
`.
`
`Date:
`
`Tab C-7
`
`Methods Validation Information ........................................................
`
`
`
`X
`
`
`
`X (completed),
`SSLYLQILDL WWW N/A (not applicable),
`'-
`or Comment
`'
`
`Tab D-l
`
`Phannacology/Toxicology Reviews and Memoranda ...............................
`
`Tab D-Z
`
`Carcinogenicity Review (statistical)
`
`......................................
`
`‘ '
`
`Tab D-3
`
`CAC/Executive Committee Report .....................................................
`
`
`ADDITIONAL NOTES:
`
`
`
`

`

`:EABBBTT
`
`Hospital Products Division
`Abbot! Laboratories
`0-389, Bldg. mo
`200 Abbott Park Rm
`Abbott Park. lninois 600M157
`
`-
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`December 1 6. 1999
`CENTER FOR DRUG EvALUATIoN AND RESEARCH '-
`ANESTHETIC, CRITICAL CARE & ADDICTION DRUG PRODUCTS. HFD #170
`Attn: :DoCUMENT CCNTRDL RDCM 998-23
`5600— Fishers Lane
`-
`i
`' RoCkville. Maryland 20857-1706.
`
`ATl'ENTlON: Cynthia McCormick. M.D.
`Director
`
`Via Fax 301-480-8682:-
`(Paper Copy Via Mail):
`I
`
`4 _
`
`Re:
`
`NDA 21-038 Dexmedetomidine Hydrochloride Injection
`
`Abbott Laboratories amends the above-referenced new drug application for the subject drug
`product. The FDA and Abbott Laboratories had a teleconference on December 16. 1999 in
`whlch we discussed the proposed Phase 4 commitments for this drug. We attach the Phase 4
`commitments in Exhibit l. The Agency taxed these revised Phase 4 commitments toiAbbott
`Laboratories on December 16. 1999. Abbott Laboratories agrees to the proposed six points in
`the commitment.
`
`Please telephone me at your earliest convenience if l can provide any additional information.
`
`‘
`
`Sincerely,
`
`ABBOTT LABORATORIES
`
`Thomas F. Willer, Ph.D.
`Associate Director, Regulatory Affairs
`Hotpitai Products Division
`Phone:
`(647) 937-6845
`Fax:
`(847) 938-7867
`Internet: WILLEl'Fthdabbottcom
`
`TFW:tw
`
`- "
`
`g:12-991.tfw/57
`Attachment
`
`WZ‘d
`
`Lesa-assure) sewage 933 seen mace ee.‘ 91 33:1
`
`—————————_
`
`

`

`w
`
`I.;._
`
`-,
`
`PHASE 4 COMMITMENTS
`
`FOR
`
`NDA 21-038 DEXMEDETOMIDINE HYDROCHLORIDE INJECTION
`
`NOTE
`
`THIS DOCUMENT WAS FAXED TO ABBOTT LABORATORIES ON
`DECEMBER 15, 1999.
`.
`
`WE HAVEZMADE NO CHANGES TO THE DOCUMENT.
`
`
`
`V’E'd
`
`ABBA-BEHIJB) 316:1.” 538 688C! M5258 66: SI 330
`
`
`
`

`

`“,5...o-4
`
`‘a.4
`
`Phase 4 Commitment: for Deamedetomidine
`
`1.
`
`A two week shady in dogs. followed by atwo week recovery phase, should evaluate
`general mrdcology and efieets onthe I-IPA’asda. As the protocol has been prepared
`forthisstudyandreceivedagcncy approval,and aswcassuntethatthe actual study
`hasbecn initiated. werequestthatyou'r finalstudy rcporthc suhmittedtotheAganey -'
`within six months approval.
`‘3, .
`
`'
`
`A two week study in dogs should evaluate-dung: in drug metabolism renewing two-
`weelas of drug infusion. As the protocol has been prepared for this study and received
`.agcney'approval, andaswe assume thatthe 'actual studyhas been inin'atcd, we
`.requestthatyourfinal smdy rcporthc submitted-to the Agency within six months
`from approval
`'
`
`.
`
`-
`
`A study evaluating the efi’eets ofthe three major human metabolites which are absent
`in the rat and the dog should be conducted in a htnnan-relevatrt animal species or,
`alternatively, by.djrect adminimtion ofthese metabolites in an appropriate animal
`species. We request that you start this study within six months from approval; and
`that you submit your final report within one year from approval. ~
`
`Genotntcicity evaluations, including an in:Vitro human lymphocyte chromosomal
`aberration assay using the human liver S-Q~fiaetion as the metabolic activation system
`and a study to assess the effect oftemperature on the in vivo micronucleus assay in
`‘-mi'ee, should be conducted We requeSt that you startthcse snidies within six months ‘
`from approval and that you submit your final reports within one year from approval.
`:
`
`A long-term infusion study in patients should evaluate the pharmacokinetics, safety
`and extended efi'een'veneas of dexmedetornidine in the ICU setting. We request that
`you start this study within one year from approval and that you submit the final study
`report within two years and six months fipm approval.
`-'
`
`A second long-term, continuous infllsionshady should be performed in renal failure '
`patients. This study should include an adequate number ofpatients with mild.
`.
`‘
`h,'
`.
`moderate; and severe renal fiailurc, to fullytl _ sess that pan‘ertt population. Metabolite ‘
`levels should be quantified to assess theiiahmmulation with long-term use of
`'
`dexmedetomidinc in renal failure patientslzm’e request that you start this study within
`six months fiom approval and that you submit the final study report within three years
`from approval.
`'-
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`
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`Precedex"
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`a 2 ml. SingIc-uou
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`--
`Precedex’"
`DEXMEDETOMIDINE HCI INJECTION
`Eauivalent to
`
`—D
`
`exmedetomidine BASE
`F0: IV use. MUST BE DILUTED
`inn ll. :omm mo M9 at "manuals-M but no 9 M a! mum
`chum n I'll! «a mum. ”a mm a autumn-fin Ill charm
`no Mama at :nmw mount. an .I 05 :n n 01w cum. in mm
`Sun at cumulus 'wn "manna 15' n: r: M' In l‘fi
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`1530771180” YER/[S Mann Cit/UGO. It must. USA
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`
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`
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`Precedex"
`DEXMEDETOMIDINE HCL INJECTION
`For IV use
`MUST BE DILUTED
`mama; u mace a nu ua
`No.804-I2/99
`
`Equivalent to
`
`NDC onn 1538-01
`
`Bow
`Dexmedetomidine BASE
`
`“I“WWO
`
`VSI'I"I"WI-3
`
`mu 0| .5!
`3,: :1 .il mmnum mom puma II nuns
`
`1mm us Jam mun n a E. n no
`'Iummm Iva-mu: no Iumm ou sunnuo:
`au- uu-unmuua :- normal w; ununlu-
`.9; mm ul ”new: nun-go: go 6w 5 out me
`owwmpmuo u: hm ml Ina-we: w «an;
`
`

`

`
`
`Office of Postmarketin‘g Dr‘tig Risk AsSessment (OPDRA)
`
`HFD-400; Parklatvh Building Room 15B-03
`
`FDA Center for Drug Evaluation and Research
`
`EPROPRIETARY NAME hfivmw
`
`DATE oEl'itEViizwz
`
`H December 10, 1999
`
`NDA NUMBER:
`NAME OF DRUG:_-_.-
`NDA HOLDER:
`
`'
`
`‘
`21-038
`’Precedex'r”, “dexmedetomidine HCl injection)
`Abbott Laboratories, Hospital Products Division,
`I
`D-389, Building AP30, 200 Abbott Park Road,
`Abbott Park, Illinois 60064-6157
`
`1.
`
`INTRODUCTION
`
`This consult \\as written in response to a request from the Division of Anesthetic, Critical Care,
`and Addiction Drug Products (HFD- 170) for reassessment of the tradename (PrecedexTM) and an
`alternate ”W 1) proposed by the sponsor.
`
`W- :re initially submitted to thefiLabeling and Nomenclature Committee
`(LNC ) and were found to be unacceptable..Ihe sponsor contacted the Institute for Safe Medical
`Practices (ISMP), who provided an analysis of the name PrecedexTM using the ERRSTM method, in
`addition to other analyses. Although their analysis yielded an overall ERR—S'score for Precedex of 3.5
`(moderate trademark vulnerability), the ISMP disagreed with the LNC and did not believe that
`PrecedexTM posed any safety issues as raised by FDA,
`
`PrecedexTM (dexmedetomidineHCl injection).isan alphaz-adrenoreceptor antagonist that has been
`evaluated for use as a sedative with analgesic properties for use in an intensive care setting. The
`apparent patient population for which this product is intended for use is peri- or post-operative
`patients requiring intubation and assisted ventilation. The product is supplied'as a 2mL vial or
`ampouie of a 100mcg/mI.._ (base) solution, to be diluted for infusion prior to use. The usual adult
`dosage is initiated with a lmcg/kg loading dose given over 10 minutes, followed by a maintenance
`infusion of 0.2 to O7mcg/kg/hr, titrated to the desired effect. Effects of the drug havenot been studied
`be} end 24 hours
`
`
`
`

`

`Ii.
`
`SAFETY AND RISK ASSESSMENT
`
`A. Product name search, product availability and dosing comparison, and focus group
`
`The medication error staff of OPDRA conducted a search of several standard published drug
`product reference texts'""' as well as several FDA databasesiv for existing drug names which
`
`sound alike or look alike to PrecedexTM
`“ to a degree where potential confusion
`between drug names could occur under the usual clinical practice settings. A search of the
`electronic online version of the U.S. Patent and Trademark Office’5 Text and Image Database was -.
`also conducted. Some consideration and review were also given to soundalike and look-alike
`names prexiously noted by LNC and lSMP. An internal focus group discussion was conducted to
`revieu all findings from the searches.
`
`A number of product names were identifiedin the OPDRA focus group, by LNC, and b\ ISMP
`that were thought to have potential for confusion. These productsare listedin Table 1 (see
`Attachment 1) along with the dosage forms available, usual FDA-ap-‘proved dosage and other
`pertinent informauon Most of these product names were considered less likely sources of
`confusion, given that dexmedetomidine will be used1n intubated patients who cannot. take oral
`products and the majority of these are oral products. Usual dosing is also quite dissimilar.
`
`Howe1er. two products were identified bv OPDRA as having considerable potential for confusion.
`
`one with each proposed name
`(PrecedexTM)
`‘
`M) All three
`products are dosed based on body weight, must be prepared as infusions, and have a similar time
`for infusion of the initial dose (all less than one hour). The potential for serious adverse outcomes
`with inadvertent use (or non-use) of any of these products is also high.
`
`Handwritten and verbal analysis of proposed names
`
`
`
`
`A study was conducted within FDA employing health care professionals to evaluate potential
`
`errors in handwritten and verbal communications of the names Precedex an;
`‘This
`exercise was conducted in an attempt to simulate usualclinical practice settings. One of the
`following prescriptions was communicated per each FDA reviewer. Each reviewer was then
`requested to provide an interpretation of this prescription via email.
`
`
`HANDWR T1'EN PRESCRIPTIONS
`VERBAL PRESCRIPTlONS
`
`
`Precedex lV 70mcg in SOmL (total) 0.9 NaCl over
`Precedex 70mcg in normal saline given
`
`
`IO minutes folio“ed by l 4.mcg/hr for 24 hours
`lV over 10 minutes followed by 1.4mcg
`
`
`
`.
`u.
`-
`v
`4.
`.
`\
`I
`
`( n=2 l)
`per hour for 24 hours. (n=24)
`.1.
`an. .._:.._-_.-I.-l::...-- n- l\l
`
`‘W
`pc1 11uu1 1u1 an uuun \11' -4,
`
`
`' MICROMEDEX Healthcare lntranet Series. l999, MlCROMEDEX, Inc., 6200 South Syracuse Way, Suite 300.
`Englewood. Colorado 801 l 1-4740. which includes the following published texts: DrugDex, Poisindex, Manindale
`(Parfm K (Ed) Manindale: The Complete Drug Reference London: Pharmaceutical Press. Electronic version.)
`Emergindex Reprodisk Index Nominum and FDR/Physicians Desk Reference (Medical Economics Company Inc
`I“999).
`"American Drug Index. 42"" Edition. l999, Facts and Comparisons, St. Louis. MO.
`Facts and Comparisons. Updated October I999 Facts and Comparisons. St. Louis MO
`‘Drug Product Reference File [DPR] th’e Established Evaluation System [EES] the AMP Decision Support System
`[DSS]. the Labeling and Nomenclature Committee [LNC] database of Proprietary name consultation requests and the
`electronic online version ofthe FDA Orange Book.
`‘, WWW location http:l/www.ispto.gov/tmdb/index.hnnl.
`
`

`

`1,,
`
`Results of this exercise are providedin Tables 2,3, 4, and 5. A low response rate to this
`survey occurred, presumably due to the short time for review (<1 week), which makes
`interpretation of these data difficult. The majority of respondents provided misspelled
`variations of the drug names but these responses generally were phonetic variations of the
`
`name. Although
`as most consistently spelled correctly from verbal prescriptions,
`one respondent to the verbal surveys independently noted the potential for confusion with
`
`ZenapaxTM, given the similarityin name and dosing regimen to
`
`111.
`
`DRUG NOMENCLATURE issues
`
`A. The established drug name chosen by the manufacturer for this product, “dexmedetomidine
`l-iCl‘ for infusion” is apharmaceutical dosage form that15 not officially recognized by the
`united States Pharmacopeia1n their official compendia. Including the phrase “for
`infusion” in the established drug name is also a safety concern in that the user mav assume
`that the undiluted product15 ready for infusion, the reverse of the likelyintent ofthe
`manufacturer.
`
`We suggest that the established name be revised. based upon the USP/NFx-i. to
`“dexmedetomidine injection”. with appropriate labeling specifying that the product must
`be diluted.
`
`B. The current USP/NF standards also apply when specifying strength of the product for a
`drug that15 an l-lCl salt but dosinglS specifiedin terms of base equixalents We
`recommend the following revised statement:
`
`“Each 1 mL of Precedex. -——~—‘ '5 dexmedetomidine hydrochloride eguivalgt to
`100 mcg of dexmedetomidine and 9 m2 of sod1um chlonde in water.”
`
`IV.
`
`LABELING, PACKAGING AND SAFETY_RELATED ISSUES
`
`In reviewing the draft product package insert, container‘labels, and carton labeling for M .
`the pre\iously proposed trade name of this product, OPDRA has attempted to focus on safe“
`issues relating to potential medication errors. Many of theitems discussedm this consult involve
`issues normalh reviewed by the chemist and medical officer.
`
`We rex1e\\ed the draft product labeling f “—— and identified several labeling. packaging,
`and safet\ concerns.
`
`A. CARTON and CONTAINER LABELING (2 mL vials. 2 m1. ampoules)
`
`1. We suggest that “M
`
`be replaced with“nm
`We are recommending that the TOTAL drug content of the ampoule or vial be specified on
`the label instead of the mcg per mL content. Numerous medication error reports have been
`received where the entire contents of a parenteral drug product container have been
`administered, instead of the prescribed quantity of drug and its associated volume.
`
`
`
`‘1 USP 24/NF l9: U.S.-Phanna?opeia and National Formulary, I999, The United States Phannacopeial Convention,
`lnc.. Rockville. MD, p.21l2, “Injections".
`
`

`

`
`
`2. We recommend that “ For I.V. infiision only after dilution” be replaced with “MUST BE
`DILUTED”.
`
`3. Revise the content statement to “Each mL contains dexmedetomidine hydrochloride,
`equivalent to 100 mcg of dexmedetomidine and 9 mg of sodium chloride in water for
`injection.”
`
`'-
`
`4. We recommend that the‘ statement “Licensed from Orion CBrporation, Espoo, Finland” be
`deleted. CFR 201.1 sets forth various recommendations on the expression of relationship
`between a distributor, manufacturer, and/or labeler. The regulations do not allow others
`(e.gf,‘licensors) to be included. This information appears in the draft package insert. on the
`carton labeling, it provides unnecessary distraction in reading carton labels.
`
`5. “Preservative-free” and the statement “This solution is preservative-free and contains. no
`additives or chemical stabilizers” is not necessary, as the content is apparent from listed
`ingredients.
`" "
`2
`
`B. PACKAGE INSERT
`
`1. Delete all terminal zeros as they appear in the draft package insert under “Clinical
`Pharmacology. Clinical Trials, ICU Sedation” and especially under DOSAGE AND
`ADMINISTRATION when specifying the dose of dexmedetomidine. Specifically, “1.0
`meg/kg" should appear as “l meg/kg" in the package insert. Including terminal zeros
`increases the likelihood of 10-fold dosing errors occurring under usual clinical practice
`settings.
`
`l l
`
`l l
`
`l
`
`IJ
`
`L1)
`
`4. See also comments under CARTON and CONTAINER LABELING.
`
`APPEARS nus WAY
`on ORIGINAL
`
`
`
`

`

`
`
`V.
`
`RECOMMENDATIONS
`
`A. From a safety perspective, we do not recommend use of the proprietary names PrecedexTM or
`m product. _
`
`B. OPDRA recommends the above labeling and packaging revisions to encourage the safest possible
`use of this product. We are willing to revisit these issuesg'thhe Division receives another draft of
`the labeling from the manufacturer.
`'
`
`C. OPDRA recommends that the Labeling and Nomenclature Committee be advised of our
`comments concerning the established name of the product.
`
`'
`
`OPDRA would appreciate feedback-on the final outcome of this consult (e.g., copy of revised
`labels/labeling). We are willing to meet with the Division for further discussion as well. If-you have any
`questions concerning this review, please contact Carol Parner, R.Ph. at 301-827-3245.
`
`.‘arol Pamer, R.Ph.
`
`Safety Evaluator
`Qffice of Postmarketing Drug Risk Assessment (OPDRA)
`
`-
`
`Concur:
`
`.leri')~ Phillips. R.Ph.
`Associate Director for Medication Error Prevention
`
`Office of Postmarketing Drug Risk Assessment (OPDRA)
`
`cc:
`
`NDA 21-038
`
`_. w
`
`HFD-l70; Division Files/Laura Govemale, Project Manager
`HEB-170: Cynthia McCormick, Division Director
`HFD-400: Janos Bacsanyi. Safety Evaluator. DDREII, OPDRA
`HF0-400; Carol Parner, Safety. Evaluator, OPDRA
`HFD-JOO; Jerry Phillips, Associate Director, OPDRA
`HFDAOO; Peter Honig, Deputy Director, OPDRA
`HFD-OOZ; Murray Luinpkin, Acting Director, OPDRA
`
`
`
`

`

`4 A
`
`TTACHMENT 1
`. - ets
`TABLE 1: Product availability and dosing of potential sound-alike, look-alike -
`amducmm Dosage rams) —_er
`.‘recedex
`lOOrncg/mL (base) clear, colorless Loading. 1 meg/kg over lOminutes.
`
`1—CUuse for sedation of
`
`solution. 2mL vials or arnpoules. Maintenance: 0.2 to O.7mcg/kg/hr for 24hrs.
`Dilute to total volume SOrnL NS.
`
`intubated patients.
`
`Feridex l V.
`
`Decadron
`
`005ml/kg or 0. 56mg Fe/kg dilutedtn l00mL Contrast agent prior to
`ll .2mg Fe/mL. 5mL single dose
`DSW and infused over 30 minutes with filter. MRI. Look-alike (LIA)
`vial of black to reddish-brown
`—
`potential per OPDRA
`liquid. Contains dexntan.
`Shock: 1 to 6mg/kg lV_, infused or single dose, L/A per ISMP.
`4mg/mL, 24mg/mL. Clear,
`colorless sol'n in lleSmL‘vials as well as various other doses.
`
`
`
`
`. (4mg/mL); SmL vial
`" (4&24mg/mL)
`‘ Oral 50mgtablets.
`
`'
`
`‘-
`
`50mgoncedaily ,-_
`
`Oral capsules 400mg or
`suspension 90mg/5mL,
`180mg/5mL ceftibutin.
`
`Adults: 400mg per day for 10 days. Children:
`9 mg/kg per day for ID days. .-
`
`
`
`om 25mg.somg.ioomg tablets.
`om 15mg. so mg capsules.
`
`Casodex
`
`,
`
`Cedax
`
`Persdex
`
`Pecose
`.Prevacid
`Prnosec
`
`Sound-alike(S/A)per
`lSMP.
`
`S/A per lS-MP.
`
`W per ism.
`
`.
`
`~
`
`_
`
`'Procardia
`
`|Oral 10mg. 20mg capsules.
`
`l0 to 30mg up to 4 times a day
`
`|L/A per ISMP.
`
`Zantac
`
`' Parenteral: 25mg/mL sol‘n IMJV;
`premix 50mg/50mL
`
`I
`
`LIA, §/A per OPDRA.
`
`
`
`
`
`LIA, S/A per OPDRA.
`50mg IV or IM every 6 to 8 hours. Oral:
`
`150mg once or twice daily or 300mg daily
`
`0131:150,300mg caps, tabs; Syrup
`
`
`g lSmg/‘mL.
`
`
`{Zenapax
`lmg/kg diluted in SOmL‘NS, given over
`25mg‘5mL single dose vials
`
`
`
`lSminutes. Total of 5 doses at 14 day
`
`intervals.
`.
`
`i
`.
`
`
`0.25 to 0.5mg three times daily, up to 4mg
`total daily dose
`
`‘Frequently used, not all-inclusive. _
`
`lOral tablets 0.25, 0.5. l, 2mg
`
`L/A, S/A per OPDRA.
`
`
`
`
`
`

`

`
`
`-
`
`Table 2: Verbal Prescription: ,-~
`
`Table 3: Verbal Prescriptions (Preeedex)
`
`tamer
`'
`
`
`
`mm“ ll —
`m II —_
`
`
`
`—
`
`R‘A’
`Respondents Interpretations
`
`Preside);
`
`Presadex Precides I Presedex Presodex
`Respondents Interpretations
`
`,
`
`Table 4: Written Prescriptions \
`
`Table 5: Written Prescriptions (Precedex)
`
`Number of
`responses
`
`Number of
`responses
`
`'
`I
`
`
`
`
`....._...
`
`_
`_.
`Respondents Interpretations
`
`-_
`
`Preoedex
`
`Precidix
`Precedix
`Respondents interpretations
`
`Precedm
`
`

`

`Ea ABBOTT
`
`Hospital Products Division =
`Abbott Laboratories
`0-389. Bldg. APBO
`200 Abbott Park Road
`Abbott Park, llflnols 60064-6157
`
`'“
`
`November 17, 1999
`
`.—
`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`ANESTHETIC. CRITICAL CARE & ADDICTION DRUG PRODUCTS, HFD #170
`Attnzz DOCUMENT CONTROL ROOM #98—23
`' 5600 Fishers Lane
`
`Rockville, Maryland 20857-1706
`
`ATTENTION: Cynthia McCormick, M.D.
`'
`Director
`.
`
`Via Fax 301-443-7068
`(Paper Sent Via Mail)
`
`Re:
`
`NBA 21-038 Dexmedetomidine Hydrochloride Injection
`
`Abbott Laboratories hereby amends the above-referenced new drug application to submit two
`proposed brand names for this drug product. The Agency sent us a letter dated October 28.
`1999 concerning its review of our proposed brand name, PRECEDEX. This brand name is not
`acceptable. The Agency made the following comment:
`
`COMMENT:
`
`"We have reviewed your proposed proprietary names PRIMEDEX and
`PRECEDEX and have concluded that these names are unacceptable. The
`name PRECEDEX could present Iook-alike/sound-alike confusion with
`drug
`products
`"PERIDEX",
`"PREVACID",
`"PERCOCET",
`and
`"PERCODAN"..
`_
`
`-
`
`RESPONSE:
`
`Please provide alternatives (we suggest three) to your proposal for the
`proprietary name, and/or the rationale for retaining the proprietary name
`PRECEDEX.“ .
`
`In response to the Agency's consideration and non-acceptance of the proposed
`brand name PRECEDEX. Abbott Laboratories contacted the Institute for Safe
`Medical Practices (ISMP). We requested that ISMP evaluate PRECEDEX'in
`light of the Agency’s observations and concerns for look-alike / scund alike
`drug names. Dr. Michael Cohen, President. issued a report on the lnstitute‘s
`findings.
`For the ..convenience of
`the Agency, here is a summary using
`extracts/quotes from the ISMP report. Based on the 'ISMP detailed evaluation
`using a computer model, we believe that
`the proposed brand name of
`PRECEDEX does not pose safety issues raised by the Agency.
`
`5983”"
`Error Recognition and Revision Strategies
`Trademark Evaluation
`
`“" '
`
`The trademark vulnerability evaluation was performed using the ERRSW Model, which is a
`modification of Failure Mode and Effects Analysis (FMEA). FMEA, a technique also used by
`other industries such as the automobile and aerospace industries. can uncover design flaws or
`other product defects in such‘a way as to limit the consequences of human error.
`
`
`
`

`

`Cynthia McCormick, MD.
`Page Two
`November 17, 1 999
`
`Ei'-'lFiSm Model for Evaluating Trademark Vulnerability
`
`Practitioners who are likely to use the product in their practice setting performed a-saiety
`assessment for each trademark candidate. After the' proposed trademarks were scripted,
`respondents reviewed the handwnhen trademarks and pronounced each name according to
`pronunciation guidelines. While considering the environment and conditions under which the
`product willbe used, respondents identified potential problems arising from look-alike. sound-
`alikerand other types of nomenclature problems. Respondents also rated the overall suitability
`' of each trademark proposed for the new product.
`
`lnternet e-mail and FAX was used to" assemble data for analysis.
`A combination of
`Respondents included a total of 25 health care practitioners from the United States. In addition
`to being reviewed by health care practitioners, each proposed trademark was evaluated by the
`lSMP health professional staff under the Supervision of Michael Fl. Cohen,. MS, FASHP.
`president. Careful considerationwas given to how and where the drug will be used as well as
`the patient population that will be using the product. Also, factors related to drug procurement,
`storage. dispensing. handling and administration were considered.
`
`Additionally, each trademark candidate was reviewed from the perspective of FDA Labeling and
`Nomenclature Committee and USAN criteria.
`‘
`~
`
`The ERRSTM model also incorporates a highly sensitive automated computer screening method
`to make predictions about look-alike and sound-alike medication errors This method, which
`was developed by Dr. Bmce Lambert of the University of lllinois School of Pharmacy, relies on
`computerized measures of word to word similarity using the USP-Di and USAN dictionary
`databases for comparison.
`lSMP staff examined allznames with an edit distance to the
`proposed trademark of 3 or less, or trigram similarity of 0.3 or greater. Only those names
`deemed significant by lSMP staff are included in the analysis.
`For practical purposes,
`trademarks have been excludedrif used for OTC items or multi-source products unless the ‘mark
`was used for the originators product. Automated computer screening is used only to
`supplement practitioner review. As such, the process helps to assure that important name
`similarities are not overlooked during practitioner review.
`
`Scoring methods
`
`Overall trademark ratings were determined using a five point scale with 1 poorest and 6 best.
`Trademarks with a “high vulnerability” rating (1-2) are those with significant risk of patient harm
`it confused with similar dmg names or medical terminology. lSMP recommends that proposed
`trademarks with “high vulnerability"
`ratings not be considered for a medical product.
`Trademarks with a "low vulnerability" rating (4-5) are those with a lower risk of patient harm it
`confused with similar drug names or medical terminology. From a safety perspective,
`lSMP
`recommends that the trademark selected for the medical product be chosen from thcise
`proposed names with a “low vulnerability" rating. Trademarks rated as “moderate vulnerability“
`(2.5-3.5) may also be considered for use with medical products. However, their use should be
`carefully examined in light of the information revealed in the report that follows.
`
`Note: No trademark i1 completely free of possibleconfusion with another trademark in the
`complex health are system. ..The EFlRS‘m Model offers insights into possible problems that can
`help to identify trademarksthat could be error prone, but It cannot guarantee that trademarks
`' are error proof as long as humans are part of the process.
`’
`
`
`
`
`.v ‘A‘.
`pp
`.iph.~;-,
`
`
`

`

`Q/nthia McCormick. MD.
`Page Three
`November 17, 1999
`
`» Results
`
`PRECEDEX Overall score = 3.5 (moderate vulnerability) ._-.;
`
`
`
`a'
`look-alike confusion with DECADRON (dexamethasone; antiemet
`There'is slight
`;
`antiintlammatory agent) which is available as an injection, is closed on a mg/kg basis (so
`similar-to PRECEDEX's meg/kg dosing) and can be used in an intensive care setti g l e
`-al e
`PRECEDEX.
`Several other products were reported to have some potentialfor Io
`D
`' confusion. PERCOCET (oxycodone/acetaminophen combination; analgesic) and PER
`(oxycodone/aspinn combination; analgesic) might look similar to PRECEDEX when hand ritt
`However. they are both combination products, which are taken orally, and have a
`dosing schedulej The different environments in which these products are used redu
`chance of confusion. Some similarity also exists with PRECOSE (acarbose; antidiabetic ge
`PRILOSEC (omeprazole; used to treat various GI conditions) and PROCARDIA (nli
`'
`used to treat hypertension and angina). These agents are also oral products, and with
`dosing schedules and dosage strengths, the risk of mix-up with PRECEDEX is lessened.
`
`
`
`
`
`
`
`
`d o
`Sound-alike confusion exists with PERIDEX (chlorhexidine; used as a skin disinfectant
`treat gingivitis).
`It is available in liquid form, used as a “swish and spit" agent or as a opi
`,
`agent.
`lts clinical indications and method of ordering are very different from PRECED .
`little chance of confusion. CEDAX (ceftibuten; antibiotic) can sound somewhat simila wh n
`spoken. HOWever, 'it
`is available only in oral form, either as a capsule or powder
`suspension. and it is administered at a set dose and dosing interval
`(not dosed on a
`mg/kg basis). CASODEX (bicalutamide; antiandrogen used to treat prostate cancer)
`potential for sound-alike confusion) but it is a _5C_)__r_ng__ oral tablet. used in a different
`setting.
`_.
`:
`:
`
`_
`.
`._
`.
`CONCLUSION BY lSMP
`Based on the above information, this trademark can be cons