CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`208026Orig1s000
`
`PROPRIETARY NAME REVIEW(S)
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`PROPRIETARY NAME REVIEW
`Division of Medication Error Prevention and Analysis (DMEPA)
`Office of Medication Error Prevention and Risk Management (OMEPRM)
`Office of Surveillance and Epidemiology (OSE)
`Center for Drug Evaluation and Research (CDER)
`
`*** This document contains proprietary information that cannot be released to the
`public***
`
`Date of This Review:
`September 15, 2015
`Application Type and Number: NDA 208026
`Jentadueto XR (linagliptin and metformin HCl
`Product Name and Strength:
`extended-release) tablets, 5 mg/1000 mg and
`2.5 mg/1000 mg
`Multi-ingredient
`Rx
`Boehringer Ingelheim
`2015-1055053
`Sarah K. Vee, PharmD
`Yelena Maslov, PharmD
`
`Product Type:
`Rx or OTC:
`Applicant/Sponsor Name:
`Panorama #:
`DMEPA Primary Reviewer:
`DMEPA Team Leader:
`
`Reference ID: 3819956
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`(
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`1
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`2
`
`Contents
`INTRODUCTION........................................................................................................1
`1.1
`Regulatory History................................................................................................1
`1.2
`Product Information ..............................................................................................1
`RESULTS.....................................................................................................................2
`2.1 Misbranding Assessment ......................................................................................2
`2.2
`Safety Assessment.................................................................................................2
`CONCLUSIONS..........................................................................................................4
`3.1
`Comments to the Applicant...................................................................................4
`REFERENCES.............................................................................................................5
`4
`APPENDICES .....................................................................................................................5
`
`3
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`Reference ID: 3819956
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`

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`INTRODUCTION
`1
`This review evaluates the proposed proprietary name, Jentadueto XR, from a safety and
`misbranding perspective. The sources and methods used to evaluate the proposed name
`are outlined in the reference section and Appendix A respectively. The Applicant did not
`submit an external name study for this proposed proprietary name.
`
`REGULATORY HISTORY
`1.1
`The proposed root name, ‘Jentadueto’, for the approved immediate release product,
`linagliptin and metformin HCl, was previously assessed and found acceptable in OSE
`Proprietary Name Review #2011-31661, dated November 9, 2011, under NDA 201281,
`which was approved on January 30, 2012.
`
`PRODUCT INFORMATION
`1.2
`The following is a comparison of product characteristics for Jentadueto and Jentadueto
`XR. The product information for Jentadueto XR is provided in the July 27, 2015
`proprietary name submission.
`Table 1. Relevant Product Information for Jentadueto and Jentadueto XR
`Jentadueto (NDA 201281)
`Jentadueto XR (NDA 208026)
`January 30, 2012
`Pending
`JEN ta doo e’-toe
`JEN ta doo e’-toe XR
`
`Approval Date
`Intended
`Pronunciation
`Active
`Ingredient
`Indication of Use
`
`Route of
`Administration
`Dosage Form
`Strengths
`
`Dose &
`Frequency
`
`How Supplied
`
`Linagliptin and metformin HCl
`
`Linagliptin and metformin HCl
`extended-release
`combination product indicated as an adjunct to diet and exercise to improve
`glycemic control in adults with type 2 diabetes mellitus when treatment
`with both linagliptin and metformin is appropriate
`Oral
`
`Tablets
`2.5 mg/500 mg
`2.5 mg/850 mg
`2.5 mg/1000 mg
`1 tablet twice daily
`(max 2.5 mg linagliptin/1000 mg
`metformin twice daily)
`60 & 180 count bottles
`
`5 mg/1000 mg
`2.5 mg/1000 mg
`
`1 tablet once daily
`(max 5 mg linagliptin and 2000 mg
`metformin)
`5 mg/1000 mg
`30 & 90 count bottles
`
`2.5 mg/1000 mg
`
`1 Fava W. Proprietary Name Review for Jentadueto (NDA 201281). Silver Spring (MD): Food and Drug
`Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology,
`Division of Medication Error Prevention and Analysis (US); 2011 NOV 9. 29 p. OSE RCM No.: 2011-
`3166.
`
`Reference ID: 3819956
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`Storage
`
`60 & 180 count bottles
`
`Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see
`USP Controlled Room Temperature]. Protect from exposure to high
`humidity. Store in a safe place out of reach of children.
`
`2 RESULTS
`The following sections provide information obtained and considered in the overall
`evaluation of the proposed proprietary name.
`
`2.1 MISBRANDING ASSESSMENT
`The Office of Prescription Drug Promotion (OPDP) determined that the proposed name
`would not misbrand the proposed product. DMEPA and the Division of Metabolism and
`Endocrinology Products (DMEP) concurred with the findings of OPDP’s assessment of
`the proposed name.
`
`2.2 SAFETY ASSESSMENT
`The following aspects were considered in the safety evaluation of the name.
`
`2.2.1 United States Adopted Names (USAN) Search
`There is no USAN stem present in the proprietary name2.
`
`2.2.2 Components of the Proposed Proprietary Name
`The proposed proprietary name contains two components: 1) the proposed root name,
`Jentadueto, and 2) the modifier XR. The Applicant indicated in their submission that the
`proposed root name, Jentadueto, has no derivation and the modifier ‘XR’ is an
`abbreviation for “extended release”. An analysis of the proposed root name and
`appropriateness of the modifier is discussed in Sections 2.2.6 and 2.2.7 respectively.
`
`2.2.3 FDA Name Simulation Studies
`Sixty-nine practitioners participated in DMEPA’s prescription studies. The responses did
`not overlap with any currently marketed products nor did the responses sound or look
`similar to any currently marketed products or any products in the pipeline. The most
`common misinterpretation was ‘G’ for the ‘J’. Appendix B contains the results from the
`verbal and written prescription studies.
`
`2.2.4 Comments from Other Review Disciplines at Initial Review
`In response to the OSE, August 21, 2015 e-mail, DMEP did not forward any comments
`or concerns relating to the proposed proprietary name at the initial phase of the review.
`
`2USAN stem search conducted on September 2, 2015.
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`Reference ID: 3819956
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`2.2.5 Medication Error Data Selection of Cases
`We searched the FDA Adverse Event Reporting System (FAERS) database using the
`strategy listed in Table 2 (see Appendix A1 for a description of FAERS database) for
`name confusion errors involving Jentadueto that would be relevant for this review.
`
`Table 2. FAERS Search Strategy
`Search Date
`August 31, 2015
`Jentadueto [product name]
`Drug Name
`Event (MedDRA Terms) DMEPA Official Proprietary Name Review
`Search Terms Event List:
`Product name confusion (PT)
`Medication error (PT)
`Intercepted medication error (PT)
`Drug dispensing error (PT)
`Intercepted drug dispensing error (PT)
`Circumstance or information capable of
`leading to a medication error (PT)
`January 1, 2012 to August 31, 2015
`
`Date Limits
`No cases were identified.
`
`2.2.6 Analysis of Proposed Root Name
`
`The proposed root name, ‘Jentadueto’, for the approved immediate release product,
`linagliptin and metformin HCl, was previously assessed and found acceptable in OSE
`Proprietary Name Review #2011-3166, dated November 9, 2011, under NDA 201281
`and has been on the market since early 2012.
`
`2.2.7 Analysis of Modifier XR
`in
`An
`immediate-release
`linagliptin and metformin HCl product, available
`2.5 mg/500 mg, 2.5 mg/850 mg, 2.5 mg/1000 mg strengths and administered twice a day,
`is currently approved. We have not identified any cases of name confusion related to the
`root name, Jentadueto. According to the Applicant, Jentadueto XR is an extended-release
`formulation taken once daily. The modifier ‘XR’ is used to differentiate the linagliptin
`and metformin HCl extended-release formulation from the linagliptin and metformin HCl
`immediate-release formulation. This modifier is commonly used for product line
`extensions to distinguish an extended-release formulation taken once daily from the
`immediate-release formulation (e.g., Janumet XR, Actoplus Met XR, or Glucophage
`XR). The difference in frequency of administration indicates a need to differentiate this
`product from the immediate-release linagliptin and metformin HCl formulation in terms
`of nomenclature.
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`Reference ID: 3819956
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`Furthermore, post-marketing medication errors have identified cases of chewing,
`splitting, and crushing of extended-release products. In some cases, the reporters indicate
`they were unaware the product was an extended-release formulation. Therefore, the
`addition of the modifier may minimize some of these errors.
`
`We note that omission and oversight of a modifier is cited in literature as a common
`cause of medication error3. Postmarketing experience shows that the introduction of
`product line extensions result in medication errors if the modifier is omitted and the
`product characteristics are similar or overlap. However, the alternative to using a
`modifier to distinguish this product from the currently marketed products is to use a
`totally different root name. However, introducing a new proprietary name for this product
`also carries a risk of medication errors, specifically, therapeutic duplication and
`overdoses. These errors may have greater associated safety risks then the omission or
`oversight of the modifier. Therefore, for the aforementioned reasons listed, we find that
`the proprietary name ‘Jentadueto XR,’ although not free from the risk of error, offers a
`safe approach to naming this product.
`Furthermore, we recommend that the Applicant uses container labels and carton labeling
`as a means to differentiate the products to help minimize selection errors.
`
`2.2.8 Communication of DMEPA’s Analysis at Midpoint of Review
`DMEPA communicated our findings to DMEP via e-mail on September 4, 2015. At that
`time we also requested additional information or concerns that could inform our review.
`Per e-mail correspondence from DMEP on September 8, 2015, they stated no additional
`concerns with the proposed proprietary name, Jentadueto XR.
`
`3 CONCLUSIONS
`The proposed proprietary name is acceptable.
`If you have any questions or need clarifications, please contact Terrolyn Thomas, OSE
`project manager, at 240-402-3981.
`
`COMMENTS TO THE APPLICANT
`3.1
`If any of the proposed product characteristics as stated in your July 27, 2015 submission
`are altered prior to approval of the marketing application, the name must be resubmitted
`for review.
`
`3 Lesar TS. Prescribing Errors Involving Medication Dosage Forms. J Gen Intern Med. 2002; 17(8): 579-
`587.
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`Reference ID: 3819956
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`4
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`REFERENCES
`
`1. USAN Stems (http://www.ama-assn.org/ama/pub/physician-resources/medical-
`science/united-states-adopted-names-council/naming-guidelines/approved-stems.page)
`USAN Stems List contains all the recognized USAN stems.
`
`APPENDICES
`Appendix A
`FDA’s Proprietary Name Risk Assessment evaluates proposed proprietary names for
`misbranding and safety concerns.
`1. Misbranding Assessment: For prescription drug products, OPDP assesses the
`name for misbranding concerns. . For over-the-counter (OTC) drug products, the
`misbranding assessment of the proposed name is conducted by DNDP. OPDP or
`DNDP evaluates proposed proprietary names to determine if the name is false or
`misleading, such as by making misrepresentations with respect to safety or
`efficacy. For example, a fanciful proprietary name may misbrand a product by
`suggesting that it has some unique effectiveness or composition when it does not
`(21 CFR 201.10(c)(3)). OPDP or DNDP provides their opinion to DMEPA for
`consideration in the overall acceptability of the proposed proprietary name.
`2. Safety Assessment: The safety assessment is conducted by DMEPA, and
`includes the following:
`a. Preliminary Assessment: We consider inclusion of USAN stems or other
`characteristics that when incorporated into a proprietary name may cause or
`contribute to medication errors (i.e., dosing interval, dosage form/route of
`administration, medical or product name abbreviations, names that include or
`suggest the composition of the drug product, etc.) See prescreening checklist
`below in Table 2*. DMEPA defines a medication error as any preventable event
`that may cause or lead to inappropriate medication use or patient harm while the
`medication is in the control of the health care professional, patient, or consumer. 4
`
`4 National Coordinating Council for Medication Error Reporting and Prevention.
`http://www nccmerp.org/aboutMedErrors.html. Last accessed 10/11/2007.
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`Appendix A1: Description of FAERS
`The FDA Adverse Event Reporting System (FAERS) is a database that contains
`information on adverse event and medication error reports submitted to FDA. The
`database is designed to support the FDA's postmarket safety surveillance program for
`drug and therapeutic biologic products. The informatic structure of the FAERS database
`adheres to the international safety reporting guidance issued by the International
`Conference on Harmonisation. FDA’s Office of Surveillance and Epidemiology codes
`adverse events and medication errors to terms in the Medical Dictionary for Regulatory
`Activities (MedDRA) terminology. Product names are coded using the FAERS Product
`Dictionary. More information about FAERS can be found at:
`http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/Adv
`erseDrugEffects/default.htm.
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`Appendix B: Prescription Simulation Samples and Results
`Figure 1. Jentadueto XR Study (Conducted on 8/7/2015)
`
`Handwritten Requisition Medication Order
`Medication Order:
`
`Verbal Prescription
`Jentadueto XR 2.5 mg/1000 mg
`1 tab by mouth daily
`
`Outpatient Prescription:
`
`FDA Prescription Simulation Responses (Aggregate 1 Rx Studies Report)
`Study Name: Jentadueto XR
`244 People Received Study
`69 People Responded
`Total
`INTERPRETATION
`CHENTADUATO XR
`CHENTEDUETO XR
`CHENTODUETTO XR
`GENINUENTO XR
`GENTA DUETTO XR
`GENTADUENTO XR
`GENTADUETA XR
`GENTADUETO XR
`GENTADUETTO XR
`GENTADUOTO XR
`JENTADEUTO ER
`JENTADUENTO XR
`JENTADUETO SR
`JENTADUETO XR
`JENTADVETO XR
`JENTDUETO
`JENUADUETO XR
`
`20
`26
`OUTPATIENT VOICE
`0
`1
`0
`1
`0
`1
`0
`1
`0
`1
`0
`3
`0
`1
`18
`4
`0
`1
`0
`1
`1
`0
`0
`2
`1
`0
`6
`3
`0
`0
`0
`0
`0
`0
`
`23
`INPATIENT TOTAL
`0
`1
`0
`1
`0
`1
`0
`1
`0
`1
`0
`3
`0
`1
`2
`24
`0
`1
`0
`1
`0
`1
`0
`2
`0
`1
`18
`27
`1
`1
`1
`1
`1
`1
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`Reference ID: 3819956
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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`SARAH K VEE
`09/15/2015
`
`YELENA L MASLOV
`09/15/2015
`
`Reference ID: 3819956
`
`