CENTER FOR DRUG EVALUATION AND
`
`RESEARCH
`
`APPLICA TION NUMBER:
`
`22-044
`
`PROPRIETARY NAME REVIEW! S)
`
`

`

`CONSULTATION RESPONSE
`
`}
`
`DIVISION OF MEDICATION ERRORS AND TECHNICAL SUPPORT
`OFFICE OF SURVEILLANCE AND EPIDEMIOLOGY
`
`(DMETS; HEB-420)
`
`DATE RECEIVED:
`
`October 11, 2006
`
`February 2, 2007
`
`
`
`
`DESIRED COMPLETION DATE: OSE CONSULT #: 2006-462
`
`
`
`
`
`PDUFA DATE:
`DATEOF DOCUMENT:
`
`
`March 31, 2007
`May 31, 2006 and July 24, 2006
`'
`Mary Parks, M.D., Director,
`
`Division of Metabolism and Endocrine Products, HFD—SlO
`
`THROUGH: Denise Toyer, PharmD, Deputy Director
`Carol Holquist, RPh, Director
`
`
`_ Division of Medication Err6rs and Technical Support
`
`
`Tselaine Jones Smith, PharmD, Safety Evaluator
`
`Division of Medication Errors and Technical Support
`
`PRODUCT NAME:
`NDA SPONSOR: Merck
`
`
`Janumet
`
`(Sitagliptin Phosphate and Metformin'
`
`Hydrochloride) Tablets
`
`. 50 mg/SOO mg and 50 mg/ 1000 mg
`
`
` I NDA #: 22—044
`
`
`RECOMMENDATIONS:
`.
`1. DMETS does not recommend the use of the proprietary name, Janumet.
`
`
`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.
`
`
`
`
`‘ .
`
`
`DDMAC finds the proprietary name, Janumet, acceptable from a promotional perspective.
`
`
`4. DMETS recommends that the Division contact Richard Lostritto, Chair of the CDER Labeling and
`Nomenclature COmmittee, for proper guidance on this salt nomenclature issue as outlined in Section II of this
`
`review.
`’
`i
`'
`'
`'
`‘
`
`
`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 further questions or need clarifications, please contact
`
`Sammie Beam, Project Manager, at 301-796-0080.
`
`

`

`Division of Medication Errors and Technical Support (DMETS)
`Office of Surveillance and Epidemiology
`HFD-420; W0 22; Mail Stop 4447
`Center for Drug Evaluation and Research
`
`PROPRIETARY NAME LABEL AND LABELING REVIEW
`
`DATE OF REVIEW:
`
`December 11, 2006
`
`NBA #:
`
`22—044
`
`‘
`
`NAME OF DRUG:
`
`Janumet
`
`(Sitagliptin Phosphate and Metfonnin Hydrochloride) Tablets
`50 mg/SOO mg and 50 mg/IOOO mg
`
`NDA HOLDER:
`
`Merck
`
`"
`
`I.
`
`INTRODUCTION:
`
`This consult was written in response to a request from, the Division of Metabolism and Endocrine
`Products (HFD-S 10), for assessment of the proprietary name, Janumet, regarding potential name
`confusion with other proprietary or established drug names. Container labels, carton and insert labeling
`were provided for review and comment.
`
`PRODUCT INFORMATION
`
`Janumet contains two oral antihyperglycemic drugs used in the management of type 2 diabetes:
`sitagliptin phosphate and metformin hydrochloride. Janumet is indicated as an adjunct to diet and
`exercise to improve glycemic control in patients with Type 2 Diabetes Mellitus who are not adequately ;
`controlled on metformin or sitagliptin alone or in patients already being treated with the combination of
`sitagliptin and metformin. The dosage of Janumet should be individualized on the basis of the patient’s
`current regimen, effectiveness, and tolerability while not exceeding the maximum recommended dose of
`100 mg sitagliptin and 2000 mg metformin. Janumet should be given twice daily with meals, with
`gradual dose escalation. The starting dose should be based on the patient’s current regimen. Janumet will
`be supplied as 50 mg/SOO mg and 50 mg/ 1000 mg tablets.
`
`II.
`
`RISK ASSESSMENT:
`
`The medication error staff of DMETS conducted a search of the intemet, several standard published
`drug product reference textsl’2 as well as several FDA databases3’4 for existing drug names which
`sound-alike or look-alike to Janumet 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
`
`
`
`l 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.
`2 Facts and Comparisons, online version, Facts and Comparisons, St. Louis, MO.
`3 AMF Decision Support System [DSS], the Division of Medication Errors and Technical Support [DMETS] database of
`Proprietary name consultation requests, New Drug Approvals 98-07, and the electronic online version of the FDA Orange
`Book.
`
`4 Phonetic and Orthographic Computer Analysis (POCA)
`
`

`

`US. Patent and Trademark Office’s Text and Image Database was also conducteds, The Saegis6
`- Pharma-In-Use database was searched for drug names with potential for confusion 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 errors in handwriting and verbal communication of the name.
`Following completion of these initial components, an overall risk assessment is conducted that does
`not evaluate the name alone. The assessment considers the findings from above and more
`importantly integrates post-marketing experience in assessing the risk-of name confusion, product
`label/labeling, and product packaging. Because it is the product that is inserted into the complex and
`unpredictable U.S. healthcare environment, all product characteristics must be considered in the
`overall safety evaluator risk assessment.
`
`A.
`
`EXPERT PANEL DISCUSSION tEPD)
`
`An Expert Panel discussion was held by DMETS to gather professional. opinions on the
`safety of the proprietary name Janumet. Potential concerns regarding drug marketing and _
`promotion related to the proposed name(s) 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 anumber of standard references when making a
`decision on the acceptability of a proprietary name.
`
`1.
`
`2.
`
`DDMAC finds the proprietary name, Janumet, acceptable from a promotional
`perspective.
`
`The Expert Panel identified the following twenty proprietary names that were thought to ;
`have the potential for confusion with Janumet: Sinemet, Januvia, Avandamet, Jantoven,
`Anzemet, Janupap, Genapap, Temovate, Tenuate, Janumine, Janimine, Tagamet,
`Junovan, Tirosint, Sinumist SR, Benemid, PanMist, Prinivil, Penovel and Genhemat.
`
`B.
`
`. PRESCRIPTION ANALYSIS STUDIES
`
`1 .
`
`Methodology:
`
`Three separate studies were conducted within the Centers of the FDA for the proposed
`proprietary name to determine the degree of confusion of Janumet with marketed US.
`drug names (proprietary and established) due to Similarity in visual appearance with
`handwritten prescriptions or verbal pronunciation of the drug name. These studies
`employed a total of 122 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 of a
`combination of marketed and unapproved drug products and a prescription for Janumet
`(see page 4). These prescriptions were optically scanned and one prescription was
`
`SWWW locationhh2g3;//wwwuspto.gov/tmdb/index.html.
`6Data provided by Thomson & Thomson’s SAEGIS TM Online Service, available at www.thomson-thomsoncom
`3
`
`

`

`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.
`
`HANDWRITTEN PRESCRIPTION
`Outpatient RX:
`
`VERBAL PRESCRIPTION
`
`
`
`Janumet 50 mg/SOO mg
`#15
`
`Take 1 tablet by mouth twice a
`day with meals.
`
`2.
`
`Results:
`
`'\uar“.
`
`Seventeen (n= 17) respondents provided interpretations close in spelling to Sinemet. For
`example, written inpatient, outpatient and voice mail orders were interpreted as Samumet
`or Samimet, which look and sound similar to Sinemet. Sinemet is a currently marketed
`U.S. product that is indicated for the treatment of Parkinson’s disease. See appendix A for
`the complete listing of interpretations from the verbal and written studies.
`
`L:
`
`SAFETY EVALUATOR RISK ASSESSMENT
`
`In reviewing the proprietary name, Janumet, twenty names were identified as having the potential
`to look and sound similar to Janumetz. Sinumist SR, Jantoven, Anzemet, Janupap, Genapap,
`Temovate, Tenuate, Janumine, Janimine, Tagamet, Junovan, Tirosint, Benemid, PanMist,
`Prinivil, Penovel, Genhemat, Sinemet, Januvia and Avandamet.
`
`DMETS conducted prescription studies to simulate the prescription ordering process. Although
`there was no positive finding Where an exact interpretation of Sinemet, seventeen respondents
`from the Janumet study misinterpreted the name as Samumet or Samimet, which look and sound
`similar to Sinemet, an already existing U.S. marketed drug product.
`
`Upon initial review of the aforementioned names, it was determined that sixteen names lacked
`convincing look-alike and sound—alike similarities with Janumet. In addition to there not being
`additional information on the drug name or the drug being taken off the market, the products also
`had numerous differentiating product characteristics such as product strength, indication for use,
`frequency of administration, prescription status, patient population and/or dosage formulation.
`The seventeenth name, Sinumist SR, has some visual similarity to Janumet. However, the
`differences in product characteristics such as indication, strength, dose, and patient population
`minimize the risk of confusion.
`
`

`

`The remaining three (n=3) names, Sinemet, Januvia and Avandamet, are described in Table l
`which includes their available dosage forms and their usual doses. Upon flirther analysis
`Avandamet was considered to have minimal risk of confusion. The reason this name was
`
`discarded and considered acceptable is described in Table l. The remaining names of concern are
`Sinemet and Januvia which are discussed in detail below.
`
`Tablerl: PotentialSoundAlike/LookAllke Names Identified b DMETS Exert Panel
`
`Sinemet
`
`A.
`I Carb1dopa/Levoddpa Tablets
`10 mg/ 100 mg, 25 mg/ 100 mg and
`25 mg/250 mg
`
`Initial: Carbidopa 50 mg/levodopa l 00 mg three
`times a day
`
`
`
`Sitagliptin Phosphate
`Tablets: 25 mg, 50 mg, and 100 mg
`
`Avandamet
`
`'
`
`Rosiglitazone and Metfonnin HCl
`Tablets
`‘
`l mg/SOO mg, 2 mg/SOO mg and 4
`mg/SOO mg
`2 mg/ 1000 mg and 4 mg/ 1000 mg
`
`Dosage adj ustment: alternate tablet strengths
`may be substituted according to individual
`carbido o a/levodo . a re a uirements
`
`200 mg once daily (monotherapy)
`100 mg once daily (combination therapy with
`metforrnin HCl)
`Januvia is given without regard to food
`
`Initial dose should be based on current dose of
`rosiglitazone and/or metformin; daily dose
`should be divided and given with meals
`
`'
`
`o Strengths of
`rrosiglitazone
`(Avandamet) and
`sitagliptin
`(Janumet)
`0 Sound of first
`
`two syllables
`(Avanda- vs.
`Janu)
`
`1.
`
`Sinemet look-alike similarities to Janumet
`
`DMETS believes Sinemet is problematic because it poses strong orthographic
`characteristics to Janumet making it difficult to differentiate the two names when
`scripted. This similarity increases the likelihood for confusion between the two drugs
`which can lead to medication errors. Moreover, postmarketing experience has shown that
`when names are very similar, product differences may not necessarily prevent medication
`errors from ocCuning between the products
`
`Sinemet and Janumet can look-alike when scripted because of the similarity of the
`beginning letters (‘8’ vs. ‘J’) and the middle letters (—‘ine-’ vs. ‘—anu—’). In addition, both
`names have the same ending letters (‘-met’), thereby making the two names difficult to
`differentiate in writing.
`
`JM 5:“ “31 MW?
`
`Sinemet and Janumet differ in frequency of administration (three times a day vs. twice a
`day) and indication (Parkinson’s disease vs. Type 2 diabetes). However, Sinemet and
`
`5
`
`

`

`Janumet share overlapping dosage forms (tablets) Additionally, both products are
`combination products where the strengths are expressed for both active ingredients and
`their denominators are numerically similar (10 mg/100 mg, 25 mg/100 mg vs.
`50 mg/1000 mg). Post marketing experience has shown that products that share these
`characteristics are more likely to be confused with each other in the marketplace thereby
`contributing to medication errors For example, in the Institute of Safe Medication
`Practices (ISMPT) Med-ER.R.S. August 2004 survey “Prescribing Combination
`Products”, practitioners indicated that both strengths for combination products are not
`always written regardless of whether both ingredients vary (24%) or if one ingredient has
`a fixed dosage strength and the other ingredient has a variable dosage strength (49%).
`Thus, if patients inadvertently receive Sinemet instead of Janumet, they can experience
`palpitations, arrhythmias, spasms and hypotension or hypertension. Conversely, if
`patients inadvertently receive Janumet instead of Sinemet, they can experience
`hypoglycemia. Furthermore, Janumet contains metformin which can increase the patients
`risk for lactic acidosis. Metformin has the following black box warning: “Lactic acidosis
`is a rare, but serious, metabolic complication that can occur from the metformin
`accumulation during treatment with Janumet when it occurs, it is fatal1n approximately
`50% of cases.’
`
`_ v...
`
`Thus, because of their visual similarity, similarity in dosage form and both products being
`combination products with similar numerical strengths, DMETS does not believe these
`products should be 00--marketed.
`
`2.
`
`Januvia look-alike similarities to Janumet
`
`DMETS believes Januvia is too similar on appearance to Janumet. This similarity stems
`from the shared prefix ‘Janu’ and similarities in the ending letters‘—Vi-’ in Januvia and
`‘-me—’ in Janumet when scripted. Although the upstroke of the letter ‘t’ at the end of
`Janumet may help to differentiate the two names, postmarketing experience has shown
`that names. with differences in their endings (‘-ia’ vs. ‘-et’) are overlooked, trail off or
`unrecognizable and may not necessarily prevent medication errors from occurring
`between the products. Avandia vs. Avandamet are illustrations of such errors.
`
`W :11 “gr/ma
`Januvia and Janumet share the same active ingredient (sitagliptin phosphate), indication
`(type 2 diabetes), auxiliary instructions (take with food), dosage form and similar
`strengths of sitagliptin phosphate (50 mg). Januvia is a single ingredient (sitagliptin)
`product expressed as 50 mg and dosed once daily whereas Janumet is a combination
`active ingredient (sitagliptin and metformin) expressed as 50 mg/SOO mg and
`50 mg/ 1000 mg and is dosed twice daily.
`
`Although there is a difference in the expression of strength and dose between the two
`products, postmarketing experience has shown errors with products that have similar
`product characteristics as those mentioned above. For example, there has been confusion
`between Avandia and Avandamet (OSE Review #05-0050) due to identical indication of
`use, similar name prefixes, shared active ingredient and strength (rosiglitazone: 1 mg,
`
`
`1‘ISMP August 2004 Question-ERR® survey on Prescribing Combination Products: http://wwwmed-errs.com/Question/Resulterr0408.asp
`6
`
`

`

`2 mg, and 4 mg), dosage form and proximity on pharmacy shelves. Similarly, DMETS
`anticipates errors between Janumet and Januvia because they overlap in strength (50 mg),
`auxiliary dosing instructions (take with food), shared active ingredient (sitagliptin),
`similar proprietary name prefixes (‘Janu-’) and route of administration. In addition, both
`Januvia and Janumet are manufactured by Merck.
`
`Furthermore, Janumet will be placed in close proximity to Januvia on pharmacy shelves,
`thereby increasing the risk of errors. Thus, if patients inadvertently receive Janumet
`instead of Januvia, they will be subject to the inappropriate treatment for diabetes.
`Moreover, if patients are already on metformin, they may be at increased risk for lactic
`acidosis due to the additional metformin contained in Janumet. Metformin haS'the
`following black box warning: “Lactic acidosis is a rare, but serious, metabolic
`complication that can occur from the metformin accumulation during treatment with
`Janumet; when it occurs, it is fatal in approximately 50% of cases.” On the other hand, if
`patients receive Januvia instead of Janumet, they are subject to the inappropriate
`treatment for type 2 diabetes due to the lack of metformin treatment in Januvia.
`
`Based on the similar names and product characteristics between Januvia and Janumet,
`along with post-marketing experience with similar diabetes products, DMETS does not
`recommend the use of the name Janumet.
`
`II.
`
`COMMENTS TO THE SPONSOR
`
`DMETS does not recommend the useof the proprietary name Janumet because of its visual similarity to
`Sinemet and Januvia. Additionally, the labels and labeling were reviewed from a medication error
`perspective and recommendations are provided below.
`
`A.
`
`Sinemet look-alike similarities to Janumet
`
`DMETS believes Sinemet is problematic because it poses strong orthographic characteristics to
`Janumet making it difficult to differentiate the two names when scripted. This similarity
`increases the likelihood for confusion between the two drugs which can lead to medication
`errors. Moreover, postmarketing experience has shown that when names are very similar, product
`differences may not necessarily prevent medication errors from occurring between'the products.
`
`Sinemet and Janumet can look-alike when scripted because of the similarity of the beginning
`letters (‘8’ vs. ‘J’) and the middle letters (—‘ine-’ vs. ‘-anu-’). In addition, both names have the ‘
`same ending letters (‘-met’), thereby making the two names difficult to differentiate in writing.
`
`‘9;wa 597/09
`
`Sinemet and Janumet differ in frequency of administration (three times a day vs. twice a day) and
`indication (Parkinson’s disease vs. Type 2 diabetes). However, Sinemet and Janumet share
`Overlapping dosage forms (tablets). Additionally, both products are combination products where
`the strengths are expressed for both active ingredients and their denominators are numerically
`similar (10 mg/100 mg, 25 mg/100 mg vs. 50 mg/1000 mg). Post marketing experience has
`shown that products that share these characteristics are more likely to be confused with each
`other in the marketplace thereby contributing to medication errors. For example, in the Institute
`
`7
`
`

`

`of Safe Medication Practices (ISMPT) Med-E.R.RS. August 2004 survey “Prescribing
`Combination Products”, practitioners indicated that both strengths for combination products are
`not always written regardless of whether both ingredients vary (24%) or if one ingredient has a
`fixed dosage strength and the other ingredient has a variable dosage strength (49%). Thus, if
`patients inadvertently receive Sinemet instead of Janumet, they can experience palpitations,
`arrhythmias, spasms and hypotension or hypertension. Conversely, if patients inadvertently
`receive Janumet instead of Sinemet, they can experience hypoglycemia. Furthermore, Janumet
`contains metformin which can increase the patients risk for lactic acidosis. Metforrnin has the
`following black box warning: “Lactic acidosis is a rare, but serious, metabolic complication that
`can occur from the metformin accumulation during treatment with .l‘anumet; when it occurs, it is
`fatal in approximately 50% of cases.”
`
`Thus, because of their visual similarity, similarity in dosage form and both products being
`combination products with similar numerical strengths, DMETS does not believe these products
`should be co—marketed.
`.,
`
`B.
`
`Januvia look-alike similarities to Janumet
`
`DMETS believes Januvia is too similar on appearance to Janumet. This similarity stems from the
`shared prefix ‘Janu’ and similarities in the ending letters‘-vi—’ in Januvia and ‘—me-’ in Janumet
`when scripted. Although the upstroke of the letter ‘t’ at the end of Janumet may help to
`differentiate the two names, postmarketing experience has shown that names with differences in
`their endings (‘-ia’ vs. ‘-et’) are overlooked, trail off or unrecognizable and may not necessarily
`prevent medication errors from occurring between the products. Avandia vs. Avandamet are
`illustrations of such errors.
`
`a'-~...../'
`
`Januvia and Janumet share the same active ingredient (sitagliptin phosphate), indication (type 2
`diabetes), auxiliary instructions (take with food), dosage form and similar strengths of sitagliptin
`phosphate (50 mg). Januvia is a single ingredient (sitagliptin) product expressed as 50 mg and
`dosed once daily whereas Janumet is a combination active ingredient (sitagliptin and metformin)
`expressed as 50 mg/500 mg and 50 mg/1000 mg and is dosed twice daily.
`I
`
`Although there is a difference in the expression of strength and dose between the two products,
`postmarketing experience has 'shown errors with products that have similar product
`characteristics as those mentioned above. For example, there has been confusion between
`Avandia and Avandamet (OSE Review #05-0050) due to identical indication of use, similar
`name prefixes, shared active ingredient and strength (rosiglitazone: 1 mg, 2 mg, and 4 mg),
`dosage form and proximity on pharmacy shelves. Similarly, DMETS anticipates errors between
`Janumet and Januvia because they overlap in strength (50 mg), auxiliary dosing instructions (take
`with food), shared active ingredient (sitagliptin), similar proprietary name prefixes (‘Janu-’) and
`route of administration. In addition, both Januvia and Janumet are manufactured by Merck.
`
`Furthermore, Janumet will be placed in close proximity to Januvia on pharmacy shelves, thereby
`increasing the risk of errors. Thus, if patients inadvertently receive Janumet instead of Januvia,
`
`
`l ISMP August 2004 Question-ERR® survey on Prescribing Combination Products: http://www.med—errs.com/Question/Resulterr0408.asp
`8
`
`

`

`RM”.)
`
`they will be subject to the inappropriate treatment for diabetes. Moreover, if patients are already
`on metformin, they may be at increased risk for lactic acidosis due to the additional metformin
`contained in Janumet. Metformin has the following black box warning: “Lactic acidosis is a rare,
`but serious, metabolic complication that can occur from the metformin accumulation during
`treatment with Janumet; when it occurs, it is fatal in approximately 50% of cases.” On the other
`hand, if patients receive Januvia instead. of Janumet, they are subject to the inappropriate
`treatment for type 2 diabetes due to the lack of metformin treatment in Januvia.
`
`Based on the similar names and product characteristics between Januvia and Janumet, along with
`post-marketing experience with similar diabetes products, DMETS does not recommend the use
`of the name Janumet.
`
`DMETS reviewed the labels and labeling from a safety perspective and have identified the following
`areas of possible improvement, which might minimize potential user error.
`
`1.
`
`GENERAL COMMENTS“
`
`a.
`
`b.
`
`0.
`
`d.
`
`Because of the experiences we have learned from post-marketing errors with drug
`products having similar propriety prefixes and identical established names, it will be
`imperative to educate healthcare providers and patients about the differences between
`Januvia and Janumet. Selection errors may also occur because these products will be
`stored in close proximity on pharmacy shelves and the product poses similar labels
`because they are from the same manufacturer. .When placing this product into a busy
`clinic, pharmacy, or inpatient unit the wrong product will likely be dispensed especially if
`healthcare providers are unaware of the introduction of this new product. Thus, it is
`'
`important to distinguish the Januvia labels and labeling from Janumet in addition to
`educating health care providers and patients about its existence and product differences.
`Distinct labeling and education prior to launch, during launch and during postmarketing
`are'critical in order to minimize confusion between Januvia and Janumet. The labeling,
`packaging, and product appearance can aid in the prevention of medication errors with
`Januvia and Janumet.
`
`We note the availability of a 60 count Sample. Samples are generally made available in
`smaller quantities. This amount is equivalent to a one month supply of medication
`making it more like a unit of use bottle for commercial sale rather than a sample.
`Therefore, we recommend that the quantity of the sample be reduced to a one week
`supply or less._
`
`The principal display panel contains a graphic with numbers inside a circle. DMETS
`acknowledges that the sponsor is trying to provide healthcare practitioners with
`identifying characteristics of the tablet; however without identification as to what this
`graphic indicates, it may be confusing because of its area of placement and its
`.
`prominence on the label. Postmarketing errors have shown these numbers to be
`misinterpreted to indicate the strength or net quantity. We recommend decreasing the size
`of the graphic and relocating it to the side panel in order to decrease confusion with the
`strength,
`'
`
`The colors representing the product strength are being used interchangeably on the
`sample labels and stock labels (see below). Revise in order to ensure that there is
`consistency with the font colors of the different strengths.
`9
`
`

`

`
` Revise so that the font
`colors are the same
`
`
`
`Figure 1C. Janumet 50 mg/SOO mg
`
`
`Revise so that the font
`
`colors are the same
`
`
`
`\fimmfivqmmhmnm
`
`91034:: an M1 mm mm:
`
`.113";ch scum now.
`9:;arm»: gem-F,
`midi".51mm n 15-))‘2
`(Kb-8’?) rmumemu:
`
`hr: mmFt: on,
`Ian: rx Quantum
`mag—SD-nmmuu
`
`e,- ma wmuma Gavan
`
`Gama m m «a:
`
`I0]ND.I,A9
`’717202
`‘
`
`,Qiflfitfllflm,
`
`
`50.31000
`
`‘ *
`
`(Jmumet’
`SWImHmm
`5071000”
`
`
`
`can mm
`
`Figure 11); Janumet 50 mg/ 1000 mg
`
`10
`
`

`

`CONTAINER LABEL (Professional Sample
`
`t)
`
`
`
`a.
`
`b.
`
`c.
`
`(1.
`
`See COMMENTS la, lc, 1d and 2a.
`
`Delete the graphic encircling the proprietary name, Janumet, as it distorts the appearance
`of the proprietary name.
`
`The principal display panel includes “No. 674X’. However,this information is not
`identified as to what it represents. Delete this information as it may be misinterpreted as
`the strength or the net quantity or clearly identify what each of these number represents.
`
`DMETS cannot discern from the presentation whether the ~_—— container is a bottle,
`blister, or pouch. Ifthis is a pouch, ensure that the proprietary name, established name,
`strength, and expiration date remain intact after the pouch is open. Additionally, if this is
`a blister configuration, please ensure that this information is intact even after each and
`every tablet has been removed from the packaging configuration.
`
`"
`
`e.
`
`Revise the statement ‘Sample-Not For Sale’ to read ‘Professional Sample — Not for sale’
`and increase the prominence of the statement.
`
`Increase the font size to
`the same size as the
`strength
`
`
`
`
`
` hum" x L var-mum mu - 3,
`mummm. ‘ 3n“
`
`mujxwummumm
`.mxmasx‘.‘ ~ rrr,
`-
`mam:
`
`may,
`Hanan emncotn:
`Museum-mum
`non mm an
`5"
`... mm~m‘im"
`
`
`
`
`
`
`Remove as it
`is duplicative.
`
`mammals.
`
`f.
`
`g.
`
`Increase the font size of the unit designation to the same size as that of the strength.
`
`DMETS notes that the strength is presented twice on the principal display panel. Delete
`the presentation of this information (in the white box) as it is duplicative.
`
`wwm..-
`
`
`
`See Comments 5b, 5d and5 f.
`
`7.
`
`CARTON LABELING,(Professional Sample-4 Patient Packs)
`
`a.
`
`b.
`
`See COMMENTS la, lc, 1d, 2a, 5b, Sc, Se and 5f.
`
`DMETS notes that the strength is presented twice on both the principal display panel and
`on the side panels. Additionally, expression of strength is presented without a unit
`designation (i.e., mg). Delete the expression of strength without the unit designation as it
`is duplicative and incomplete.
`
`12
`
`

`

`W/MMannem-Lts
`5071000”
`
`with the strength, move to
`
`Delete graphic as it
`side panel
`distorts the appearance
`‘
`
`
`of the proprietary name
`(sitadrpiin/metfixmin Haliabieis
`
`
`
`
`
`In order to avoid confusion
`
`mW
`
`INSERT LABELING
`
`See COMMENT 2a.
`
`PATIENT INFORMATION SHEET
`
`See COMMENT 2a.
`
`Appears This Way
`On Original
`
`13
`
`

`

`Appendix A ‘
`
`
`Ingatient
`Out n atiellt
`Samimet
`Samimet
`
`
`Sanumet
`
`Sanumet
`~ Samimet
`
`Janunet
`
`la'numet
`Janmmet
`Lamimet
`
`Samimet
`
`Lamunet
`
`Sanumet
`
`Lanumet
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Jamumet
`
`Lamimet
`
`14
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Tselaine Jones—Smith
`3/14/2007 03:39:01 PM
`DRUG SAFETY OFFICE REVIEWER
`
`‘
`
`Denise Toyer
`3/15/2007 02:02;01 PM
`DRUG SAFETY OFFICE REVIEWER
`’r
`
`Carol Holquist
`3/15/2007 02:26:14 PM
`DRUG SAFETY OFFICE REVIEWER
`
`\.
`
`"KM"
`
`Appears This Way
`» On Original
`
`

`

`"yoivision/omce):
`Tail: OSE, DSRCS, Attention: Nancy Clark
`
` DEPARTMENT OF HEALTH AND HUMAN SERVICES
` REQUEST FOR CONSULTATION
`PUBLIC HEALTH SERVICE
`FOOD AND DRUG ADMINISTRATION
`
`
`FROM:
`
`
`Lina AlJuburi, Regulatory Project Manager, DMEP
`
`
`
`W0 Bldg #22, Room 3103
`
`
`Ph#: 301—796-1168
`
`
`DATE
`
`TYPE OF DOCUMENT
`DATE OF DOCUMENT
`
`
`
`February 27, 2007
`
`
`
`
`NDA Labeling: PPI
`February 5, 2007
`NAME OF DRUG
`CLASSIFICATION OF DRUG
`PRIORITY CONSIDERATION
`DESIRED COMPLETION DATE
`
`
`
`
`
`Janumet (sitagliptin phosphate
`S
`antidiabetic
`
`
`
`March 20, 2007
`and metfonnin FDC) Tablet
`
`
`NAME OF FIRM: Merck & Co., Inc.
`
`
`
`REASON FOR REQUEST
`I. GENERAL
`
`
`
` El NEW PROTOCOL CI PRE—NDA MEETING El RESPONSE TO DEFICIENCY LETTER
`
`
`CI PROGRESS REPORT
`El END OF PHASE II MEETING
`I] FINAL PRINTED LABELING
`
`
`
`CI NEWCORRESPONDENCE
`CI RESUBMISSION
`CI LABELING REVISION
`‘CI DRUG ADVERTISING
`CI SAFETY/EFFICACY
`CI ORIGINAL NEW CORRESPONDENCE
`
`
`CI ADVERSE REACTION REPORT
`El PAPER NDA
`CI FORMULATIVE REVIEW
`
`
`
`El MANUFACTURING CHANGE/ADDITION
`El CONTROL SUPPLEMENT
`X OTHER (SPECIFYBELOIM: New PPI
`‘4'"
`E] MEETING PLANNED BY
`
`
`
`II. BIOMETRICS
`
`‘
`
`. STATISTICAL EVALUATION BRANCH
`.- Cl TYPE A OR B NDA REVIEW
`END OF PHASE II MEETING
`CONTROLLED STUDIES
`,5] PROTOCOL REVIEW
`I:I OTHER SPECIFY BELO
`
`3
`
`-
`
`
`
`CI DISSOLUTION
`CI BIOAVAILABILTY STUDIES
`' EI PHASE IV STUDIES
`
`STATISTICAL APPLICATION BRANCH
`
`III CHEMISTRY REVIEW
`
`
`B PHARMACOLOGY
`
`
`
`
`
`
`E] BIOPHARMACEUTICS
`U OTHER (SPECIFY BELOW):
`
`III. BIOPHARMACEUTICS
`
`El DEFICIENCY LETTER RESPONSE
`CI PROTOCOL~BIOPHARMACEUTICS
`CI IN-VIVO WAIVER REQUEST
`
`Iv. DRUG EXPERIENCE
`
`.
`
`.
`
`.
`
`.
`
`- El PHASE IV SURVEILLANCE/EPIDEMIOLOGY PROTOCOL
`Y El DRUG USE e.g. POPULATION EXPOSURE, ASSOCIATED DIAGNOSES
`4 El CASE REPORTS OF SPECIFIC REACTIONS (List below)
`CI COMPARATIVE RISK ASSESSMENT ON GENERIC DRUG GROUP
`
`El REVIEW OF MARKETING EXPERIENCE, DRUG USE AND SAFETY
`El SUMMARY OF ADVERSE EXPERIENCE
`[I POISON RISK ANALYSIS
`
`.
`
`,
`
`.
`
`.
`
`V. SCIENTIFIC INVESTIGATIONS
`
`Janumet (sitagliptin phosphate and metformin FDC) Tablet is for the treatment of type 2 diabetes.
`Please review the patient product information (PPI) for this NDA (document attached to this consult request form.)
`The NDA was submitted electronically as an eCTD submission and can be found in the edr.
`User fee goal date: Saturday, March 31, 2007
`Feel free to contact me with any questions. Many thanks, Lina
`
`COMMENTSISPECIAL INSTRUCTIONS:
`
`
`
`
`
`
`
`
`SIGNATURE OF REQUESTER
`
`~"SNATURE OF RECEIVER
`
`I
`
`I
`
`;
`
`-'
`
`;
`;
`I
`
`I
`
`I
`
`53
`i
`
`
`
`
`
`. .
`
`
`METHOD OF DELIVERY (Check one)
`_‘
`CI MAIL
`
`El HAND
`
`I
`
`SIGNATURE OF DELIVERER
`
`

`

`__4_'_ Page(s) Withheld '
`
`1__ § 552(b)(4) Trade Secret /‘Confider1tia1
`
`X—
`
`§ I552(b)(4) Draft Labeling '
`
`'
`
`I § 552(b)(5) Deliberative Process
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`/S/
`
`Lina Aljuburi
`2/27/2007 02:43:41 PM
`
`’2,,'I
`
`
`
`IR""1&wa
`
`Appears This Way
`On Original
`
`

`

`CONSULTATION RESPONSE
`
`‘;
`
`'
`
`DIVISION OF MEDICATION ERRORS AND TECHNICAL SUPPORT
`OFFICE OF SURVIELLANCE AND EPIDEMIOLOGY
`(DMETS; HEB-420)
`'
`
`DATE RECEIVED:
`
`DESIRED COMPLETION DATE OSE CONSULT #: 2007-666
`
`
`
`
`March 22, 2007
`March 27,2007
`
`
`PD