CENTER FOR DRUG EVALUATION AND
`RESEARCH
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`APPLICATION NUMBER:
`201655Orig1s000
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`PROPRIETARY NAME REVIEW(S)
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`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Surveillance and Epidemiology
`Office of Medication Error Prevention and Risk Management
`
`Proprietary Name Review
`
`Date:
`
`September 30, 2011
`
`Reviewer(s):
`
`Team Leader
`
`Deputy Director:
`
`Jibril Abdus-Samad, PharmD
`Division of Medication Error Prevention and Analysis
`Todd Bridges, RPh
`Division of Medication Error Prevention and Analysis
`Kellie Taylor, PharmD, MPH
`Division of Medication Error Prevention and Analysis
`Opana ER (Oxymorphone Hydrochloride) Extended-release Tablets
`Drug Name(s):
`5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, 30 mg, and 40 mg
`
`Application Type/Number: NDA 201655
`Applicant/sponsor:
`Endo Pharmaceuticals Inc.
`OSE RCM #:
`2011-2445
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`*** This document contains proprietary and confidential information that should not be released to
`the public.***
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`1
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`Reference ID: 3023353
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`CONTENTS
`
`1
`
`INTRODUCTION ........................................................................................................................... 3
`1.1
`Regulatory History.................................................................................................................. 3
`1.2
`Product Information ................................................................................................................ 3
`2 METHODS AND DISCUSSION.................................................................................................... 4
`2.1
`Proprietary Name Confusion .................................................................................................. 4
`2.2
`Formulation Differences ......................................................................................................... 4
`3 CONCLUSIONS ............................................................................................................................. 5
`4 REFERENCES ................................................................................................................................ 6
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`Reference ID: 3023353
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`2
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`1
`
`INTRODUCTION
`
`This review evaluates the proposed proprietary name, Opana ER, from a safety perspective.
`
`1.1
`
`REGULATORY HISTORY
`
`Opana ER (Oxymorphone Hydrochloride) extended-release tablets (NDA 021610) was approved on
`June 22, 2006. The Applicant submitted NDA 201655 on July 7, 2010 to propose an
`abuse-deterrent formulation of oxymorphone extended-release tablets.
`
`me
`However, the
`Applicant now intends to replace the currently marketed formulation approved under NDA 021610
`with the new formulation in NDA 201655 and therefore, proposes to continue using the
`Opana ER proprietary name per agreement with the Division of Analgesics, Anesthetics, and
`Addiction Products during an Endo/FDA teleconference held January 5, 2011. On January 7, 2011,
`NDA 201655 received a Complete Response due inability to establish bioequivalence of the proposed
`product to the reference product (NDA 021610). The Applicant proposes to establish bioequivalence
`in this submission.
`
`1.2
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`PRODUCT INFORMATION
`
`The Applicant designed the proposed product (NDA 201655) to be physically harder than the
`referenced formulation (NDA 021610) to serve as an abuse deterrent. Both products share the same
`product characteristics, with the exception that the proposed abuse deterrent formulation requires
`instructions to ensure complete swallowing. Once bioequivalence is established, there is no major
`safety issue with switching patients from the referenced formulation of Opana ER and the proposed
`abuse-deterrent formulation of Opana ER.
`
`Opana ER has a proposed indication for the relief of moderate to severe pain in patients requiring
`continuous, around-the-clock opioid treatment for an extended period of time. Opana ER tablets are to
`be swallowed whole and not to be broken, chewed, dissolved, or crushed. Opana ER tablets must be
`taken one tablet at a time, with enough water to ensure complete swallowing. Opana ER is to be
`administered every 12 hours with the following dose recommendations:
`
`0 Opioid naive patients - 5 mg every 12 hours
`
`0 Conversion from Opana to Opana ER — half the patient's total daily oral Opana dose as
`Opana ER, every 12 hours.
`
`0 Conversion from parenteral - administer 10 times the patient’s total daily parenteral
`oxymorphone dose as Opana ER in two equally divided doses [(intravenous dose x 10)
`divided by 2].
`
`0 Conversion from other oral opioids — follow Dose Conversion table in insert labeling.
`
`Opana ER is available as 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, 30 mg, and 40 mg tablets in bottles of
`100 tablets. Opana ER should be stored at 25°C (77°F); excursions permitted to 15°-30°C (59°—86°F)
`[See USP Controlled Room Temperature].
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`Reference ID: 3023353
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`3
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`2 METHODS AND DISCUSSION
`With the exception of the proposed abuse deterrent properties of the proposed product (201655), both
`the proposed product (NDA 201655), and the currently marketed product (NDA 021610) share the
`same product characteristics. Therefore, we reviewed previous OSE Reviews for Opana ER for
`medication errors involving proprietary name confusion. Additionally, we considered whether the
`new instructions to ensure complete swallowing could be safely managed under the same proprietary
`name Opana ER.
`2.1 PROPRIETARY NAME CONFUSION
`OSE Review 2010-2081 documented 5 reports of wrong drug errors involving proprietary name
`confusion with Opana 10 mg and Opana ER 10 mg. Confusion between immediate- and extended-
`release formulations of the same product is likely to occur when there are overlapping strengths and
`the products share the same root name (Opana). To minimize this issue, DMEPA recommends
`Applicants develop extended-release products that do not have overlapping strengths with the
`immediate-release formulation. However, because the Applicant developed Opana ER with an
`overlapping strength (Opana 10 mg and Opana ER 10 mg), we recommended labeling differentiation
`to minimize wrong drug errors during the pre-marketing review of NDA 021610 and in review of a
`prior approval supplement in OSE Reviews 03-0105-3 and 2008-43, respectively. In this submission
`NDA 201655, the Applicant has further enhanced the differentiation of the container labels of
`Opana ER compared to Opana and this should help to further reduce confusion.
`In addition, labeling review for this application, OSE Review 2011-2466 dated September 2, 2011,
`there were no AERS reports involving proprietary name confusion with Opana ER and other drugs
`products.
`Furthermore, the Agency has previously approved the nomenclature approach using the proprietary
`name of the referenced formulation for the proposed abuse deterrent formulation, in which both
`products were bioequivalent and shared the same product characteristics.
`2.2 FORMULATION DIFFERENCES
`The proposed formulation differs from the referenced formulation in that the proposed formulation is
`designed to make the tablet harder to resist crushing or breaking. There are approved products that
`are designed similarly to resist crushing or breaking, such as the reformulated OxyContin***
`(Oxycodone Hydrochloride) Extended-release Tablets and the recently approved Oxecta***
`(Oxycodone Hydrochloride, USP) Tablets. There have been reports of difficulty swallowing the
`reformulated OxyContin*** primarily in patients with underlying gastrointestinal disorders.
`Subsequently, the labeling of OxyContin*** and Oxecta*** provides instructions in the insert labeling
`and Medication Guide to prevent swallowing difficulty. Thus, we find it acceptable to communicate
`the new instructions to ensure complete swallowing of the proposed abuse deterrent formulation of
`Opana ER through labeling, similar to the currently marketed products, OxyContin*** and Oxecta***.
`
`
`*** This document contains proprietary and confidential information that should not be released to the
`public.***
`
`Reference ID: 3023353
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`4
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`3 CONCLUSIONS
`Our evaluation of Opana ER did not identify any safety concerns with the proposed name that are not
`addressed through labeling. The revised container labels for Opana ER provide improved
`differentiation from Opana. There were no AERS reports of proprietary name confusion with
`Opana ER and other drug products. The new instructions for the proposed formulation to ensure
`complete swallowing can be communicated through labeling, as is the case for approved products that
`utilize a similar design as an abuse deterrent. Additionally, the Agency has previously approved the
`nomenclature approach of using the proprietary name of the referenced formulation for the proposed
`abuse deterrent formulation, in which both products were bioequivalent and shared the same product
`characteristics. Thus, DMEPA has no objection to the proprietary name, Opana ER, for this product
`at this time. However, if any of the proposed product characteristics as stated in this review are
`altered, DMEPA rescinds this finding and the name must be resubmitted for review. The conclusions
`upon re-review are subject to change.
`Additionally, the proposed proprietary name must be re-reviewed 90 days prior to approval of the
`NDA.
`If you have further questions or need clarifications, please contact Danyal Chaudhry, OSE project
`manager, at 301-796-3813.
`
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`Reference ID: 3023353
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`4 REFERENCES
`1. OSE Reviews
`1. Abdus-Samad, J. OSE Review 2011-2446: DMEPA Label and Labeling Review for
`Opana ER, September 2, 2011
`2. Abdus-Samad, J. OSE Review 2010-2081: DMEPA Medication Review for Opana ER,
`October 28, 2010
`3. Arnwine, Kristina C. OSE Review 2008-43: DMEPA Label and Labeling Review for
`Opana ER, February 27, 2008
`4. Duffy, Felicia. OSE Review 03-0105-3: DMEPA Label and Labeling Review for
`Opana ER, June 12, 2006
`2. Drugs@FDA (http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm)
`Drugs@FDA contains most of the drug products approved since 1939. The majority of
`labels, approval letters, reviews, and other information are available for drug products
`approved from 1998 to the present. Drugs@FDA contains official information about FDA
`approved brand name, generic drugs, therapeutic biological products, prescription and over-
`the-counter human drugs and discontinued drugs and “Chemical Type 6” approvals.
`3. USAN Stems (http://www.ama-assn.org/ama/pub/category/4782.html)
`USAN Stems List contains all the recognized USAN stems.
`4. Division of Medication Error Prevention and Analysis Proprietary Name Consultation
`Request
`Compiled list of proposed proprietary names submitted to the Division of Medication Error
`Prevention and Analysis for review. The list is generated on a weekly basis from the Access
`database/tracking system.
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`Reference ID: 3023353
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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/
`----------------------------------------------------
`
`JIBRIL ABDUS-SAMAD
`10/03/2011
`
`KELLIE A TAYLOR
`10/03/2011
`
`Reference ID: 3023353
`
`