CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICA TION NUMBER:
`
`2 1-994
`
`‘
`
`PROPRIETARY NAME REVIEW; S t
`
`

`

`
`CONSULTATION RESPONSE
`DIVISION OF MEDICATION ERRORS AND TECHNICAL SUPPORT
`
`
`OFFICE OF DRUG SAFETY.
`
`(White Oak Mail Sto 4447)
`
`
`
`DOCUMENT DATES: October 14,
`2005; November 9, 2005; November
`22, 2005; November 18, 2005
`
`March 15, 2006
`
`
`
`DATE RECEIVED:
`DESIRED COMPLETION DATE: ODS CONSULT #: 05-0269 and
`
`05-0269—1, 05-0269—2
`December 15, 2005
`
`
`
`
`
`
`PDUFA DATE: September 21, 2006
`
`
`
`
`Janice Soreth, MD.
`
`
`Director, Division of Anti-Infective and Opthalmologic Products
`
` THROUGH: Linda Kim—Jung, Phann.D., Team Leader
`
`
`
`Denise Toyer, Pharm.D., Deputy Director
`- Carol Holquist, R.Ph., Director
`Division of Medication Errors and Technical Support
`
`
`
`
`FROM:
`
`
`
`
`
`Laura L. Pincock, Pharrn.D., Safety Evaluator
`Division of Medication Errors and Technical Support
`
`PRODUCT NAME:
`Travatan Z (primary)
`
`Travatan _(secondary)
`
`Travatan r-wt'tertiary)
`
`(Travopros't Ophthalmic Solution)
`
`0.004%
`
`
`NDA #:
`21—994
`1.
`
`‘3';
`
`NDA SPONSOR:
`A‘lcon Research, Limited
`RECOMMENDATIONS:
`
`2. DMETS recommends implementation of the label and labeling revisions outlined in section III of this
`review to minimize potential errors with the use of this product.
`
`
`1. DMETS does not recommend the use of the proprietary names “Travatan Z”,“Travatan W, or “Travatan
`
`
`
`
`
`
`
`'3. DDMAC finds the proprietary names “Travatan Z,” “Travatanm ’ and “Travatan W’ are acceptable
`from a promotional perspective.
`
`DMETS would appreciate feedback of the final outcome of this consult. We would be willing to meet
`with the Division for further discussion, if needed. If you have fiirther questions or need clarifications,
`| please contacthiane Smith, project manager, at 301—796-0538.
`
`
`
`

`

`Division of Medication Errors and Technical Support (DMETS)
`
`Office of Drug Safety
`HFD-420; White Oak Mail Stop 4447
`Center for Drug Evaluation and Research
`
`PROPRIETARY NAME REVIEW
`
`DATE OF REVIEW:
`
`January 13, 2006 ,
`
`NDA#
`
`21-994'
`
`NAME OF DRUG:
`
`Travatan Z (primary)
`Travatan / (secondary)
`.
`Travatan '4 (tertiary)
`(Travoprost Opthalmic Solution)
`0.004%
`
`NDA HOLDER:
`
`Alcon Research, Limited
`
`
`***NOTE: This review contains proprietary and confidential information that should not be
`released to the public.***
`
`INTRODUCTION:
`
`This consult was written in response to a request from the Division of Anti—Infective and Opthalmology
`Products for assessment of the proprietary names, “Travatan Z” (primary),“Travatan e—qsecondary),
`and “Travatan Mtertiary) regarding potential name confusion with other proprietary and/or
`established drug names.
`
`Er
`
`Travatan Opthalmic Solution was approved March 16, 2001. This application is a product line extension
`V of Travatan. In this application, Alcon is proposing a Benzalkonium Chloride—free (BAC-free)
`formulation of travoprost ophthalmic solution for which they propose the tradename “Travatan Z.” The
`indication and dosing regimen for the new formulation will be identical to the currently formulation.
`The Sponsor plans to continue marketing Travatan Opthalmic Solution in addition to the new BAC-free
`formulation.
`
`DMETS discussed the use of modifiers with the Review Division at a meeting on
`February 3, 2006. DMETS conveyed that we generally discourage the use of modifiers which may be
`meaningless to healthcare practitioners and patients as the modifier can be misinterpreted and lead to
`medication errors. At the time, DMETS was particularly concerned with the modifiers “Z” and “A
`“Z” is often misinterpreted as the number “2,” and “ ”‘13 already in'use with commonly known
`connotations (i.e., anti-fungal, antifibrillation, etc.), which differ from the intended meaning for the
`‘ Modifier for Travatan. The Review Division acknowledged’they understood DMETS’ concerns
`with the use of modifiers. However, the Review Division indicated that the new formulation was a
`different product, would not be considered interchangeable with the current formulation, and that the
`modifier was intended to accompany the Travatan name to differentiate the two products
`
`

`

`PRODUCT INFORMATION
`
`“Travatan Z/Travatan Q/Travatah N is a Benzalkonium Chloride—free (BAC-free) formulation of
`Travoprost Ophthalmic Solution, which is currently marketed under the proprietary name Travatan
`Opthalmic Solution. Travatan Z/Travatan \. Travatan "' IS a modified formulation of Travatan and
`contains an alternate preservative. According to the sponsor, the suffix “Z” is intended-to denote “zero
`BAC,”'the suffix ‘ .1...’ is intended to denote “alternate preservative,” and the suffix ‘_.'_'
`is intended to
`
`denote
`" Travatan and Travatan Z/Travataw‘/ Travatan ”have the same
`indication, conCentration (0.004%), size (2.5 mL or 5 mL), and dosage regimen (one dropin the affected
`eye(s) once dailyin the evening).
`'
`
`Travoprost is a synthetic prostaglandin F20t analogue. Travoprost free acid is a selective prostanoid
`receptor agonist which is believed to reduce intraocular pressure by increasing trabecular meshwork and
`uveoscleral outflow. The exact mechanism of action is unknown at this time. Travatan Z/Travatan
`
`'5 fl‘ravatanv—‘is proposed to be indicated for the reduction of elevated intraocular pressure in patients
`with open-angle glaucoma or ocular hypertension Who are intolerant of other intraocular pressure
`lowering medications or insufficiently responsive (failed to achieve targeted intraocular pressure
`determined after multiple measurements over time) to another intraocular pressure lowering medication.
`The recommended dosage is onedrop in the affected eye(s) once daily in the evening. The dosage Of
`Travatan Z/Travatan -——.~'1‘ravatan "Should not exceed once daily since it has been shown that more
`frequent administratiOn of travoprost may decrease the intraocular pressure lowering effect. Travatan
`. Z/Travatan ~—-—5Fravatan‘.will be supplied in two sizes of Alcon’s oval DROP-TAINER® package
`system (2.5 mL fill in 4 mL bottle and 5 mL fill in-7.5 mL bottle).
`‘
`
`II.
`
`RISK ASSESSMENT:
`
`The medication error staff of DMETS conducted a search of severalstandard published drug product
`reference textsl’2 as well as several FDA databases3’4 for existing drug names which sound-alike or
`look-alike to. Travatan Z/Travatanwvflfravatan 7" 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 US. Patent and Trademark Office’s Text and Image Database was also conducteds.
`An expert panel discussion was conducted to review all findings from the searches.
`In addition,
`DMETS conducted three prescription analysis studies for each proposed name 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 errors in handwriting and verbal communication of the
`name.
`
`
`
`' MICROMEDEX Integrated Index, 2006, MICROMEDEX, Inc. 6200 South Syracuse Way, Suite 300, EnglewOod Colorado
`80111-4740 which includes all products/databases within ChemKnowledge, DrugKnowledge and RegsKnowledge Systems
`:Facts and Comparisons, online version,Facts and Comparisons, St Louis, MO.
`3AMF Decision Support system [DSS], the Division of Medication Errors and Technical Support [DMETS] database of
`Propnetary name consultation requests, New Drug Approvals 98-06, and the electronic online version of the FDA Orange
`Book
`'
`
`4Phonetic and Orthographic Computer Analysis (POCA)
`’ WWW location httpL'v.ww.usp_o.gmfrmdbiindex. html
`I
`
`. 3
`
`

`

`EXPERT PANEL DISCUSSION {EPD}
`
`An Expert Panel discussion was held by DMETS to gather professional opinions on the
`safety of the proprietary names Travatan Z, Travatan Mand Travatan --.- Potential
`concerns regarding drug marketing and promotion related to the proposed names were also
`discussed. This group is 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.
`
`1. DDMAC has no objections to the tradenames “Travatan Z,” “Travatan -- ‘ and “Travatan
`1" from a promotional perspective.
`
`2. EPD panelists stated that the proposed modifier “Z” could be misinterpreted as the number
`‘4277‘
`
`3. EPD panelists stated that the proposed modifier‘ -"‘could be misinterpreted as a medical
`
`abbreviation for “mmW; ”W Another panelist
`stated that‘ -—— could be misinterpreted as the medical abbreviations “AD” (right ear) or
`“OD” (right eye).
`
`4. EPD panelists stated that the proposed modifier‘—- couldbe misinterpreted because the
`modifier ‘r"18 usedin currently marketed prescription and non—prescription drug products
`andis associated with different meanings than“ —~—~/ ‘.
`-=- also means. M
`
`5. The Expert Panel identified five proprietary names that were thought to have the potential for
`look-alike confusion with Travatan Z, Travatan fiand Travatan ”’7 These products are a}?
`listed in Table 1 (page 5), along with the dosage forms available and usual dosage.
`. f
`
`‘
`
`Appears This Way
`On Original
`
`

`

`Table 1: TRAVATAN fFRAVATAN AP/TRAVATAN AF: Potential Sound-Alike/Look—Alike Names Identified by
`DMETS Exert Panel
`
`3,,
`
`,.4,
`
`.
`
`..
`
`,
`
`au‘
`
`2:3;
`
`Travatan
`
`Travaprost
`Opthalmic Solution: 0.004%
`2.5 mL and 5 mL bottles
`
`Trexatyn*** Pralatrexate
`Injection: 20 mg/mL
`
`4
`
`'
`
`Truvada
`
`Teveten
`
`Emtricitabine/Tenofovir
`Tablets: 200 mg/3OO mg
`,
`
`Eprosartan
`Tablets: 400 mg, 600 mg
`.
`.
`
`'
`
`.
`
`,
`
`_
`
`p
`
`.
`
`‘
`
`
`
`' .
`
`I drop once daily in the evening instilled LA
`into affected eye(s)
`
`4 L
`
`A
`
`Dose of IBS mg/m2 to [70 mg/m2
`administered IV push over 3 minutes to
`5 minutes (with possible dose reduction
`to 67.5 mg/m2 per defined toxicity
`'
`i
`2 weeks
`1 tablet (emtricitabine 200 mg; tenofovir LA
`300 mg) orally once daily, with or
`without food.
`
`Initially, 600 mg orally once daily, when LA
`used as monotherapy in euvolemic
`patients. Adjust dosage based on clinical
`response. The usual dosage range is 400
`mg to 800 mg/day PO, given in l or 2
`divided doses. The maximum dosage is
`900 m /da .
`
`'
`
`Travasol
`
`'
`Amino Acids
`Solution: varying concentrations
`'
`‘
`'
`
`*Frequently used, not all-inclusive.
`**LA (look-alike), SA (sound-alike)
`***Name -,endin ao roval. Not FOI releasable.
`
`Administered for nutritional support as
`part of a parenteral nutrition order.
`Given intravenously and'ofde'red in
`milliliters er hour as secified.
`,
`
`LA
`
`.
`
`B.
`
`PRESCRIPTION ANALYSIS STUDIES
`
`'
`
`.25
`
`l .
`
`Methodology:
`
`.
`Nine separate studies (three for each name) were conducted within the Centers of the
`FDA for the proposed proprietary names to determine the degree of confusion ofTravatan
`Z, Travatang-g and Travatarm with marketed US. drug names (proprietary and
`established) due to similarity in visual appearance with handwritten prescriptions or
`
`verbal pronunciation of the drug name; The set of studies (i.e., inpatient, outpatient, and
`verbal study for each name) employed a total of 124 health care professionals
`(pharmacists, physicians, and nurses). This exercise was conducted in an attempt to
`simulate the prescription ordering process. An inpatient order and an outpatient
`prescription were written for each name, each consisting of a combination of marketed
`and unapproved drug products and a prescription for Travatan Z, Travatan "for
`Travatan/(see pages 6-7). 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.
`
`

`

`Travatan Z
`
`a the affected eye every evening”
`
`“Travatan Z, dispense 1, instill 1 drop into
`
`Results for Travatan Z:
`
`Ten respondents in the inpatient written study interpreted Travatan Z as the
`currently marketed product Travatan. One respondent in the inpatient handwritten
`study interpreted the letter Z as the number 8. The majority of misinterpretations
`were misspelled/phonetic variations of the proposed name, Travatan Z. See
`Appendix A for the complete listing of interpretations from the verbal and written
`studies.
`
`Travatan - >
`
`A.
`
`-,
`
`eye every evening ”
`
`“Travatan #99“: instill one drop into each
`
`Results for Travatan M
`
`Two respondents in the outpatient written study interpreted Travatan was the
`currently marketed product Travatan. The majority of misinterpretations were
`misspelled/phonetic variations of the proposed name, Travatan M See
`Appendix B for the complete listing of interpretations from the verbal and written V
`studies.
`
`

`

`e.
`
`Travatan /'
`
`Outpatient RX.
`
`“Travatan “‘7 number 1, instill 1 drop into
`both eyes QHS”
`
`-“N... . _
`
`_.IL___,In@22st
`l
`
`f.
`
`Results for Travatan
`
`\o—J
`
`None of the interpretations of the proposed name overlap, sounds similar, or looks
`similar to any currently marketed U.S. product. One respondent'stated that the
`modifier 1/ implies antifungal. If the drug is not (saw. '1, the dis
`misleading.” Another respondent stated that “The meaning of the suffix letters
`21$ quite unclear and could cause errors.” The majority of misinterpretations
`were misspelled/phonetic variations of the proposed name, Travatan \rSee
`Appendix C for the complete listing of interpretations from the verbal and written
`studies.
`
`ADVERSE EVENT REPORTING SYSTEM (AERS)
`
`DMETS conducted a search of the Adverse Event Reporting System (AERS) for medication
`errors aSsociated with Travatan. The preferred terms “Pharmaceutical Product Complaint,”
`‘4:
`‘
`“Treatment Noncompliance,” “Medication Error,” Accidental Exposure,” “Underdose,”
`“Intercepted Medication Error,” “Circumstance or Information Capable of Leading to Medication
`Error,” “Drug Prescribing Error,” and “Drug Dispensing Error” were used. AERS searches were
`run forTravatan and also between Travatan and the currently marketed-products Teveten,
`Travasol, and Truvada. No cases of medication errors associated with Travatan were identified.
`
`7,
`
`SAFETY EVALUATOR RISK ASSESSMENT
`
`'1.
`
`Travatan Z Name Review
`
`'In reviewing the proprietary name Travatan Z, the primary concerns identified from the
`Expert Panel related to look-alike and sound-alike confusion with Travatan, Teveten,
`TTavaso‘l, Truvada, and Trexatyn. Upon further review of the names gathered from EPD,
`independent analysis, and POCA, the name Truvada was not reviewed further due to a
`lack of convincing look-alike/sound-alike similarities with Travatan Z, in addition to
`numerous differentiating product characteristics such as the product strength, indicatiOn
`for use, and dosage formulation.
`In the AERS search, DMETS found no existing
`confusion between Travatan and Teveten or Travasol. Therefore, Teveten and TraVasol
`will not be discussed further.
`
`

`

`Additionally, DMETS conducted prescription studies to simulate the prescription ordering
`process. Ten respondents in the inpatient handwritten study interpreted Travatan Z as the
`currently marketed product Travatan. One respondent in the inpatient handwritten study
`interpreted the letter Z as the number 8. Although there are limitations to the predictive
`value of these studies, primarily due to small sample size, we have acquired safety
`concerns due to the positive interpretation with this drug product. A positive finding with
`a small sample size may indicate a high risk and potential for medication errors when
`extrapolated to the general US. population.
`
`a.
`
`i
`
`Travatan Z looks similar to Travatan. According to the sponsor, the modifier ‘Z’
`is intended to denote “zero BAC”.
`In general, DMETS discourages the use of
`modifiers which may be meaningless to healthcare practitioners and patients as
`the modifier can be misinterpreted and lead to medication errors.
`In this instance,
`it is not likely that the modifier ‘Z’ will be interpreted as “zero BAC.” Rather, it
`is likely that the ‘2’ would be misinterpreted as “zero preservative”, which is not
`an accurate representation for the new formulation.
`
`a)
`
`Travatan and Travatan Z look similar because they share the same root name,
`Travatan. DMETS is concerned, because with the exception of the modifier “Z
`prescriptions for Travatan and Travatan Z will be written for the same indication,
`concentration (0.004%) , package size (2.5 mLor 5 mL), and dosage regimen
`(one dropin the affected eye(s) once daily in the evening). Thus, if the “Z”
`modifier is overlooked or misinterpreted, a medication error could occur and the
`patient would receive the Travatan product instead, This is potentially
`troublesome if the patient is allergic or sensitive to Benzalkonium Chloride, and
`the doctor intended the patient to receive the BAC—free formulation.
`Additionally, DMETS notes that the suffix letter “Z” is often confused with the
`number “2” and can result in a medication error.
`
`3
`
`W2 A}
`
`Additionally, one respondent in the DMETS’ inpatient handwritten study
`misinterpreted the letter Z as the number “8”. If the “Z” in Travatan Z is
`misinterpreted as the number “2” or the number “8”, the patient could receive
`two or eight bottles of the Travatan product Which contains BAC, also
`problematic if the patient is allergic or sensitive to BAC. At our meeting with the
`Review Division on February 3, 2006, the Division stated that this error is
`unlikely to be clinically significant. However, if the Z is misinterpreted as the
`number “2” or number “8”, the pharmacist or patient could also interpret the
`numeral as the number of eye drops to be administered, leading the patient to
`instill double or eight-times the usual dose of the wrong Travatan product. This
`is potentially troublesome. Therefore, DMETS does not recommend use of the
`modifier “Z” in the proprietary name Travatan Z because the modifier is
`meaningless and may be misleading which may lead to medication errors.
`
`‘
`
`

`

`Travatan Z may look similar to Trexatyn***. Trexatyn*** is an injectable
`
`cytotoxic agent related to methotrexate and other related dihydrofolate reductase
`inhibitors. This product in under review at FDA under the proprietary names
`Neofol (primary)*** and Trexatyn (secondary)*** (IND 52, 604). DMETS did
`not recommend the use of the name Neofol*** but had no objections to
`
`Trexatyn*** in ODS Consults # 05-0072 and # 05-0072-1. Trexatyn*** is
`administered via intravenous push over three to five minutes at doses of 135— 170
`mg/m2 per defined toxicity criteria, given once every two weeks. The
`orthographic similarity stems from the fact that both names begin with the letters
`_“Tr—” and end with the letter ‘n’. Additionally, the letter ‘x’ in Trexatyn*** may
`resemble the letter ‘v’ in Travatan depending on how it is scripted which also
`contributes to the look—alike similarities of the names. Furthermore, each name
`
`has an upstoke from the letter ‘t’ located in a similar position within the name.
`However, the name Trexatyn*** contains a downstroke from the letter ‘y’ which
`may help to differentiate the names when scripted. Furthermore, the letter ‘Z’
`modifier in the name Travatan Z may helpto differentiate between the two names.
`
`TREXATYN
`TRAVATAN z
`
`fat—ma»{were
`. T*‘flizvtvém1W—
`
`3’
`
`Additionally, there are different product characteristics that may help to
`distinguish the two products such as: dosage form (injectable vs. ophthalmic
`solution), dose (1 drop vs. 135- 170 mg/m2 or the milligram dose based on the
`patient’ 3 body surface area), and marketed strength (20 mg/mL vs. 0.004%).
`Because Trexatyn*** is an injectable product requiring refrigeration and Travatan
`Z is an ophthalmic product stored at room‘ temperature, it is not likely that these '1,
`two products will be stored together in close proximity, and thus, there is low
`potential for product selection error. Furthermore, thedifferent dosing frequency
`(once daily vs once every two weeks) will help to further differentiate between
`the two names. Moreover, since Travatan Zis an ophthalmic product, the affected
`eye(s) (OD, 0U, OS, etc ) are likely to be indicated on a prescription which will
`further aidin differentiating this name pair. Since both products are available
`with only one strength, the product strength may be omitted on a preseliption for
`either product. However, a prescription for Trexatyn*** will contain the
`prescribed dose (135-170 mg/m2 or the milligram dose based on the patient’s
`body surface area) which will differentiate between the two names. Furthermore,
`since Trexatyn*** is a chemotherapeutic agent, it will be ordered on
`chemotherapeutic order forms and administered in a clinical setting where dosage
`preparation and administration is performed by healthcare professionals who are
`familiar with its use. Thus, the orthographic differences along with the different
`product characteristics, especially route of administration, dose, and dosing
`frequency will help minimize the potential for confusion between these two drug ’
`products.
`
`

`

`Travatan / ’Name Review
`
`In reviewing the proprietary name Travatan "‘j the primary concerns identified from the
`Expert Panel related to look-alike confusion with Travatan and use of the modifier TS.
`
`Additionally, DMETS conducted prescription studies to simulate the prescription ordering
`process. Two respondents in the outpatient handwritten study misinterpreted Travatan \
`as the currently marketed product Travatan. The majority of misinterpretations were
`misspelled/phonetic variations of the proposed name, Travatan -—-
`'
`
`According to the sponsor, the suffix “~—” is intended to denote “alternate preservative”.
`As we stated previously in the discussion for Travatan Z (see page 8), DMETS is
`concerned with the use of modifiers that may be meaningless to healthcare practitioners
`and patients. Additionally, there are safety concerns with the modifier “3.,
`EPD
`panelists stated that ‘—-- could be misinterpreted because it is a commonly used medical
`abbreviation for “WNW us list of
`abbreviations is not all inclusive). Another panelist stated that “/—- could be
`misinterpreted as “AD” (right ear) or “OD” (right eye) if not scripted clearly. The
`Institute for Same Medication Practices (ISMP) maintains a “List of Error-Prone
`Abbreviations, Symbols, and Dose Designations” and the abbreviations “AD” and “OD”
`are on the list as often misinterpreted.
`If the modifier ‘--" is interpreted as “OD”,
`misinterpretation may result with both the pharmacist and patient as to whether Travatan
`e‘should be administered into only the right eye rather than both eyes or just the left
`'eye. It is- potentially troublesome if the modifier ",_.. is misinterpreted as “AD”, as the
`patient could be directed to instill the ophthalmic solution into their right ear. A
`pharmacist may be able to intercept the misinterpretation, knowing that Travatan is an
`ophthalmic product used to decrease intraocular pressure and should not be administered
`into the ear; however, nurses and patients may not be able to identify an error.
`i,
`Additionally, DMETS notes that there are several ophthalmic products that may be
`ordered with an “off-label” indication with directions to instill drops into the ear. This is
`a well recognized off—label use for some ophthalmic products and thus, it is not unlikely
`that healthcare practitioners (e.g., pharmacists, nurses) may not question the order.
`' DMETS is unable to ascertain the clinical significance of a patient instilling Travatan into
`their ear. DMETS does not recommend use of the modifier “ win the proprietary name
`Travatan AP.
`I
`I
`I
`
`,
`
`Travatan “"~ Name Review
`
`In reviewing the proprietary name Travatan ‘7 the primary concerns identified from the
`Expert Panel related to look—alike confusion confusion with Travatan and use of the
`modifier ’—~
`'
`
`Additionally, DMETS conducted prescription studies to simulate the prescription ordering
`process. None of the interpretations of the proposed name, Travatan v, overlap, sound
`
`10
`
`

`

`similar, or looks similar to any currently marketed U.S. product. However, one
`respondent stated that the modifier “—2 implies antifungal. If the drug is not antifungal,
`the f is misleading.” Another respondent stated that “The meaning of the suffix letters
`/ T/rs quite unclear and could cause errors.” The majority of misinterpretations were
`misspelled/phonetic variations of the proposed name, Travatan ‘
`
`is
`Travatan looks similar to Travatan ”—‘According to the sponsor, the suffix "———-
`intended to denote‘‘altemate formulation’. There are safety concerns with the modifier
`“ ___ The EPD panelists stated that " \could be misinterpreted because the modifier
`’ve'” is used in currently marketed prescription drug products including. Diprolene ——-’
`
`7
`_
`), Betapace ‘ N M , and SSD 7:“ “WWW”,
`The modifier ‘ \is also commonly used in no-nprescription products such as Lotrimin
`
`~<--
`wmw-~W"M ".) Thus, the modifieriv-a has many connotations
`in the marketplace and may resultin confusion with healthcare professionals. DMETS
`does riot recommend use of the modifier‘ 7‘ in the proprietary name Travatan ‘- _
`
`I
`
`III.
`
`COMMENTS TO THE SPONSOR:
`
`DMETS does not recommend the use of the proprietary name “Travatan Z”,“Travatan .——-—-,~ or “Travatan
`
`In reviewing the proprietary names, the primary concerns related to use of the modifiers and the
`potential for look-alike confusion with the currently marketed Travatan Opthalmic Solution.
`
`A.
`
`Travatan Z looks similar to Travatan. According to the sponsor, the modifier ‘Z’ is intended to
`denote “zero BAC”.
`In general, DMETS discourages the use of modifiers which may be
`meaningless to healthcare practitioners and patients. It1s not likely that the modifier ‘Z’ will be
`interpreted as‘‘zero BAC.” Rather, it is likely that the ‘Z’ would be misinterpreted as “zero
`preservative”, which is not an accurate representation for thenew formulation.
`
`Travatan and Travatan Z look similar because they share the same root name, Travatan. DMETS
`is concerned, because with the exception of the modifier “Z”, prescriptions for Travatan and
`a,
`Travatan Z will be written for the same indication, concentration (0.004%) , package size (2.5
`f
`mL or 5 mL), and, dosage regimen (one drop in the affected eye(s) once daily in the evening).
`Thus, if the Z modifier is overlooked or misinterpreted, a medication error could occur and the
`patient would receive the Travatan product instead. This is potentially troublesome if the patient
`is allergic or sensitive to Benzalkonium Chloride, and the doctor intended the patient to receive
`the BAC-free formulation. Additionally, DMETS notes that the suffix letter “Z” is often
`confused with the number “2” and can result in a medication error.
`
`Additionally, one respondent in the DMETS’ inpatient handwritten study interpreted the letter Z
`as the number “8”. If the “Z” in Travatan Z is interpreted as the number “2” or the number “8”,
`the patient could receive two or eight bottles of the Travatan product which contains BAC, also
`problematic if the patient is allergic or sensitive to BAC. DMETS is unable to ascertain the
`clinical significance of the patient receiving the wrong formulation. At our meeting with the
`
`11
`
`

`

`Review Division on February 2, 2006, the Division was stated that this error is unlikely to be
`clinically significant. Regardless, DMETS does not recommend use of the modifier “Z” in the
`proprietary name Travatan Z because the modifier is meaningless and may contribute to
`medication errors.
`
`In reviewing the proprietary name Travatan ~, the primary concerns identified from the Expert
`
`Panel related to look-alike confusion with Travatan and use of the modifier ‘
`
`Additionally, DMETS conducted prescription studies to simulate the prescription ordering
`process. Two respondents in the outpatient handwritten study interpreted Travatan --’ as the
`currently marketed product Travatan. The majority of misinterpretations were
`misspelled/phonetic variations of the proposed name, Travatan W
`
`According to the Sponsor, the suffix 9"” is intended to denote “alternate preservative”. As we
`stated previously in the discussion for Travatan Z (see section A), DMETS is concerned with the
`use of modifiers that may be meaningless to healthcare practitioners and patients. Additionally,
`there are safety concerns with the modifier“~— EPD panelists stated that '\ could be
`
`misinterpreted because it is a commonly used medical abbreviation for ”a...
`
`1, mm
`and' ~» “...— (this list of abbreviationsis not all inclusive). Another
`panelist stated that‘«a.»'could be misinterpreted as “AD” (right ear) or “OD” (right eye) if not
`scripted clearly. The Institute for Same Medication Practices (ISMP) maintains a “List of Error-
`Prone Abbreviations, Symbols, and Dose Designations” and the abbreviations “AD” and “OD”
`are on the list as often misinterpreted.
`If the modifier ‘--—-‘is interpreted as “OD”,
`
`. misinterpretation may result with both the pharmacist and patientasto .whether Travatar
`should be administered into only the right eye, rather than both eyes or only the left eye. It is
`potentially troublesome if the modifier ‘ ‘f“'is misinterpreted as “AD”, as the patient could be
`directed to instill the ophthalmic solution into their right ear. A pharmacist may be able to
`intercept the misinterpretation, knowing that Travatan is an ophthalmic product used to decrease
`intraocular pressure and should not be administered into the ear; however, nurses and patients
`may not be able to identify an error. DMETS notes that there are several ophthalmic products
`that may be ordered with an “off—label” indiCation with directions to instill drops into the ear.
`Many nurses are aware of this and may not be as likely to question an order for Travatan
`ophthalmic solution to be administered in the ear. DMETS is unable to ascertain the clinical
`significance of a patient instilling Travatan into their ear. DMETS does not recommend use of
`the modifier ‘V"“"" in the proprietary name Travatan "
`
`3%
`
`r~<~
`
`13’l
`
`“D
`
`In reviewing the proprietary name Travatan ’(«the primary concerns identified from the Expert
`Panel related to look—alike confusion with Travatan and use of the modifier “*"°"
`
`Additionally, DMETS conducted prescription studies to simulate the prescription ordering
`process None of the interpretations of the prOposed name, Travatan —*overlap, sound similar,
`or looks similar to any currently marketed U. S. product However, one respondent stated that the
`modifier‘”"Tfirplies
`If the drugIS no
`.1e ”is miSleading.” Another
`respondent stated that “The meaning of the suffix letters _....,t is quite unclear and could cause
`
`12
`
`

`

`errors.” The majoritv of misinterpretations were misspelled/phonetic variations of the proposed
`name, Travatan
`‘_
`
`Travatan looks similar to Travatan 3““According to the sponsor, the suffix ’-»-~ ' is intended to
`denote “alternate formulation”. There are safety concerns with the modifier“ M“- The EPD
`
`panelists stated that“ ’ ’ could be misinterpreted because the modifier “ r“ is used in currently
`
`marketed prescription drug products including, Diprolene ”T (“
`1”), Betapace
`
`“TIT W”
`?”), and SSD “T“Anti—fungal?”). The modifier"“"’ is also commonly
`usedin non—prescription 1)roducts such as Lotrimin" (‘ Mmm-—-——-—-—-~—-—-__
`1.
`Thus, the modifier “ / has many connotations in the marketplace and may result111 confusion
`with healthcare professionals. DMETS does not recommend use of the modifierW in the
`proprietary name Travatan /'
`
`In review of the container labels, carton and insert labeling of Travatan Z/Travatan W+Travatan
`
`/'DMETS has attempted to focus on safety issues relating to possible medication errors.
`DMETS has identified several areas of possible improvement, which might minimize potential
`error.
`
`1.
`
`GENERAL COMMENTS
`
`a.
`
`b.
`
`DMETS notes that the draft container labels and carton labeling were submitted in
`black and white text, without the use of colors, graphics, fonts or other methods of
`formatting. Thus, it is not possible to fully assess if there'are any safety concerns
`due tothe labels and labeling because the information provided did not reflect the
`label and labeling presentation that will actually be used in the marketplace.
`Please forward copies of the revised labels and labeling, in color and reflective of
`the presentation that will actually be used in the marketplace, when they are
`available.
`
`DMETS recommends that the Travatan