`
`DRUG
`
`PRODUCTS
`
`WITH
`
`THERAPEUTIC
`
`EQUIVALENCE
`EVALUATIONS
`
`34”‘ EDITION
`
`THE PRODUCTS IN THIS LIST HAVE BEEN APPROVED UNDER
`
`SECTION 505 OF THE FEDERAL FOOD, DRUG, AND COSMETIC ACT.
`
`U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
`FOOD AND DRUG ADMINISTRATION
`CENTER FOR DRUG EVALUATION AND RESEARCH
`OFFICE OF MEDICAL PRODUCTS AND TOBACCO
`OFFICE OF GENERIC DRUGS
`
`2014
`
`
`
`APPROVED DRUG PRODUCTS
`
`with
`
`THERAPEUTIC EQUIVALENCE EVALUATIONS
`
`The products in this list have been approved under section 505 of the
`Federal Food, Drug, and Cosmetic Act. This volume is current through
`December 31, 2013.
`
`34"‘ EDITION
`
`U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
`FOOD AND DRUG ADMINISTRATION
`CENTER FOR DRUG EVALUATION AND RESEARCH
`OFFICE OF MEDICAL PRODUCTS AND TOBACCO
`OFFICE OF GENERIC DRUGS
`
`2014
`
`0002
`
`
`
`FOOD AND DRUG ADMINISTRATION
`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`APPROVED DRUG PRODUCTS
`
`wflh
`
`Therapeutic Equivalence Evaluations
`
`CONTENTS
`
`PAGE
`
`PREFACE TO THIRTY FOURTH
`
`1
`1.1
`
`INTRODUCTION ................................................................................................................. ..vi
`Content and Exclusion .................................................................................................... ..vi
`
`Therapeutic Equivalence-Related Terms ....................................................................... ..vi
`1.2
`Statistical Criteria for Bioequivalence ........................................................................... .. viii
`1.3
`Reference Listed Drug ..................................................................................................... ..x
`1.4
`General Policies and Legal Status ................................................................................. ..xi
`1.5
`Practitioner/User Responsibilities ................................................................................... ..xi
`1.6
`Therapeutic Equivalence Evaluations Codes ............................................................... .. xiii
`1.7
`Description of Special Situations ................................................................................... ..xx
`1.8
`Therapeutic Equivalence Code Change for a Drug Entity ........................................... .. xxii
`1.9
`1.10 Change of the Therapeutic Equivalence Evaluation for a Single Product .................. .. xxiii
`1.11
`Discontinued Section .................................................................................................. .. xxiii
`
`1.12 Changes to the Orange Book ..................................................................................... .. xxiii
`1.13 Availability of the Edition ............................................................................................. .. xxiv
`
`2
`
`HOW TO USE THE DRUG PRODUCTS LISTS ............................................................ ..2-1
`
`2.1
`2.2
`2.3
`
`Key Sections for Using the Drug Product Lists ................................................... ..2-1
`Drug Product Illustration ............................................................................... ..2-3
`Therapeutic Equivalence Evaluations Illustration ............................................... ..2-4
`
`DRUG PRODUCT LISTS
`
`Prescription Drug Product List ................................................................................. ..3-1
`OTC Drug Product List .......................................................................................... ..4-1
`Drug Products with Approval under Section 505 of the Act Administered
`by the Center for Biologics Evaluation and Research List ....................................... ..5-1
`Discontinued Drug Product List ................................................................................ ..6-1
`Orphan Products Designations and Approvals List
`...................................................... ..7-1
`Drug Products Which Must Demonstrate in vivo Bioavailability
`Only if Product Fails to Achieve Adequate Dissolution .................................................. ..8-1
`
`APPENDICES
`A. Product Name Index ................................................................................ ..A-1
`
`B. Product Name Index Listed by Applicant ...................................................... ..B-1
`C. Uniform Terms ........................................................................................ ..C-1
`
`PATENT AND EXCLUSIVITY INFORMATION ADDENDUM ............................................ ..AD1
`
`A. Patent and Exclusivity Lists .................................................................... ..ADA1
`B. Patent and Exclusivity Terms .................................................................. ..ADB1
`
`0003
`
`
`
`FOOD AND DRUG ADMINISTRATION
`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`APPROVED DRUG PRODUCTS
`
`with
`
`Therapeutic Equivalence Evaluations
`
`PREFACE TO THIRTY FOURTH EDITION
`
`The publication, Approved Drug Products with Therapeutic Equivalence
`Evaluations (the List, commonly known as the Orange Book),
`identifies drug
`products approved on the basis of safety and effectiveness by the Food and
`Drug Administration (FDA) under the Federal Food, Drug, and Cosmetic Act
`(the
`Act). Drugs on the market approved only on the basis of safety (covered by
`the ongoing Drug Efficacy Study Implementation [DESI]
`review [e.g., Donnatal®
`Tablets and Librax® Capsules] or pre—1938 drugs [e.g., Phenobarbital
`Tablets]) are not included in this publication.
`The main criterion for the
`inclusion of any product is that the product is the subject of an application
`with an effective approval that has not been withdrawn for safety or efficacy
`reasons.
`Inclusion of products on the List is independent of any current
`regulatory action through administrative or judicial means against a drug
`product.
`In addition,
`the List contains therapeutic equivalence evaluations
`for approved multisource prescription drug products.
`These evaluations have
`been prepared to serve as public information and advice to state health
`agencies, prescribers, and pharmacists to promote public education in the area
`of drug product selection and to foster containment of health care costs.
`Therapeutic equivalence evaluations in this publication are not official FDA
`actions affecting the legal status of products under the Act.
`
`To contain drug costs, virtually every
`Background of the Publication.
`state has adopted laws and/or regulations that encourage the substitution of
`drug products.
`These state laws generally require either that substitution be
`limited to drugs on a specific list (the positive formulary approach) or that
`it be permitted for all drugs except those prohibited by a particular list
`(the negative formulary approach). Because of the number of requests in the
`late 1970s for FDA assistance in preparing both positive and negative
`formularies, it became apparent that FDA could not serve the needs of each
`state on an individual basis.
`The Agency also recognized that providing a
`single list based on common criteria would be preferable to evaluating drug
`products on the basis of differing definitions and criteria in various state
`laws. As a result, on May 31, 1978,
`the Commissioner of the Food and Drug
`Administration sent a letter to officials of each state stating FDA‘s intent
`to provide a list of all prescription drug products that are approved by FDA
`for safety and effectiveness, along with therapeutic equivalence
`determinations for multisource prescription products.
`
`It included only
`in January l979.
`The List was distributed as a proposal
`currently marketed prescription drug products approved by FDA through new drug
`applications (NDAs) and abbreviated new drug applications (ANDAs) under the
`provisions of Section 505 of the Act.
`
`The therapeutic equivalence evaluations in the List reflect FDA‘s
`application of specific criteria to the multisource prescription drug products
`on the List approved under Section 505 of the Act.
`These evaluations are
`presented in the form of code letters that indicate the basis for the
`evaluation made.
`An explanation of the code appears in the Introduction.
`
`A complete discussion of the background and basis of FDA‘s therapeutic
`equivalence evaluation policy was published in the Federal Register on
`January 12, 1979 (44 FR 2932).
`The final rule, which includes FDA‘s responses
`to the public comments on the proposal, was published in the Federal Register
`iv
`
`0004
`
`
`
`The first publication, October 1980, of
`on October 31, 1980 (45 FR 72582).
`the final version of the List incorporated appropriate corrections and
`additions.
`Each subsequent edition has included the new approvals and made
`appropriate changes in data.
`
`the President signed into law the Drug Price
`l984,
`On September 24,
`Competition and Patent Term Restoration Act
`(l984 Amendments).
`The 1984
`Amendments require that FDA, among other things, make publicly available a
`list of approved drug products with monthly supplements.
`The Approved Drug
`Products with Therapeutic Equivalence Evaluations publication and its monthly
`Cumulative Supplements satisfy this requirement.
`The Addendum to this
`publication identifies drugs that qualify under the l984 Amendments for
`periods of exclusivity (during which ANDAs or applications described in
`Section 505(b)(2) of the Act for those drugs may not be submitted for a
`specified period of time and, if allowed to be submitted, would be tentatively
`approved) and provides patent information concerning the listed drugs which
`also may delay the approval of ANDAs or Section 505(b)(2) applications.
`The
`Addendum also provides additional information that may be helpful to those
`submitting a new drug application to the Agency.
`
`The Agency intends to use this publication to further its objective of
`obtaining input and comment on the publication itself and related Agency
`procedures. Therefore, if you have comments on how the publication can be
`improved, please send them to the Director, Division of Labeling and Program
`Support, HFD—6lO, Office of Generic Drugs, Center for Drug and Evaluation and
`Research, 7620 Standish Place, Rockville, MD 20855.
`Comments received are
`publicly available to the extent allowable under the Freedom of Information
`regulations.
`
`0005
`
`
`
`LINTRODUCHON
`
`1.1 content and Exclusion
`
`(1) approved prescription drug
`The List is composed of four parts:
`products with therapeutic equivalence evaluations;
`(2) approved
`over—the—counter
`(OTC) drug products for those drugs that may not be marketed
`without NDAs or ANDAs because they are not covered under existing OTC
`monographs;
`(3) drug products with approval under Section 505 of the Act
`a
`administered by the Center for Biologics Evaluation and Research; and (4)
`cumulative list of approved products that have never been marketed, are for
`exportation, are for military use, have been discontinued from marketing, or
`have had their approvals withdrawn for other than safety or efficacy reasons
`subsequent to being discontinued from marketing.l This publication also
`includes indices of prescription and OTC drug products by trade or established
`name (if no trade name exists) and by applicant name (holder of the approved
`application). All established names for active ingredients generally conform
`to official compendial names or United States Adopted Names
`(USAN) as
`prescribed in (21 CFR 299.4(e)).
`The latter list includes applicants’ names
`as abbreviated in this publication;
`in addition, a list of uniform terms is
`provided.
`
`An Addendum contains drug patent and exclusivity information for the
`Prescription, OTC, Discontinued Drug Product Lists, and for the Drug Products
`with Approval under Section 505 of the Act Administered by the Center for
`Biologics Evaluation and Research.
`The publication may include additional
`information that the Agency deems appropriate to disseminate.
`
`the publication had excluded OTC drug products
`Prior to the 6th Edition,
`and drug products with approval under Section 505 of the Act administered by
`the Center for Biologics Evaluation and Research because the main purpose of
`the publication was to provide information to states regarding FDA's
`recommendation as to which generic prescription drug products were acceptable
`candidates for drug product selection.
`The 1984 Amendments required the
`Agency to begin publishing an up—to—date list of all marketed drug products,
`OTC as well as prescription,
`that have been approved for safety and efficacy
`and for which new drug applications are required.
`
`some drug products are given tentative
`Under the l984 Amendments,
`approvals.
`The Agency will not include drug products with tentative approval
`in the List. Tentative approval lists are available at ANDA (Generic) Drug
`Approvals. When the tentative approval becomes a full approval
`through a
`subsequent action letter to the application holder,
`the Agency will list the
`drug product and the final approval date in the appropriate approved drug
`product list.
`
`Distributors or repackagers of products on the List are not identified.
`Because distributors or repackagers are not required to notify FDA when they
`shift their sources of supply from one approved manufacturer to another, it is
`not possible to maintain complete information linking product approval with
`the distributor or repackager handling the products.
`
`1.2 Therapeutic Equivalence-Related Terms
`
`Pharmaceutical Equivalents. Drug products are considered pharmaceutical
`equivalents if they contain the same active ingredient(s), are of the same
`
`1 Newly approved products are added to parts 1, 2, or 3, of the List, depending on the dispensing
`requirements (prescription or OTC) or approval authority, unless the Orange Book staff is
`otherwise notified before publication.
`
`vi
`
`0006
`
`
`
`PRESCRIPTION AND OTC DRUG PRODUCT PATENT AND EXCLUSIVITY LIST
`
`34TH EDITION - 2014 - APPROVED DRUG PRODUCT LIST
`
`ADA 39 Of 215
`
`See report footnote for information regarding report content
`
`APPL/PROD
`NO
`
`PATENT NO
`
`CYANOCOBALAMIN — NASCOBAL
`
`PATENT
`EXPIRATION
`DATE
`
`001
`
`N 021642
`
`, 2024
`Jun 1
`7229636
`Mar 12, 2024
`7404489
`Jun 0', 2024
`7879349
`Y L BENZAPRINE HYDR
`HL RIDE — AMRIX
`
`001
`
`N 021777
`
`Feb 26, 2025
`7387793
`Nov 1!, 2023
`7544372
`Nov 1!, 2023
`7790199
`Nov 1!, 2023
`7820203
`Nov 11, 2023
`7829121
`CYCLOBENZAPRINE HYDROCHLORIDE — AMRIX
`
`002
`
`N 021777
`
`7387793
`7544372
`7790199
`7820203
`7829121
`QYQLQSPQRINE — NEQRAL
`N 050715
`001
`5985321
`QYQLQSPQRINE — NEQRAL
`N 050715
`002
`5985321
`QYQLQSPQRINE — NEQRAL
`N 050715
`003
`5985321
`QYQLQSPQRINE — NEQRAL
`N 050716
`001
`5985321
`QYQLQSPQRINE — RE§TA§I§
`N 050790
`001
`5474979
`8629111
`QXSIEAMINE_BIIARIBAIE_:_BBQQXfiBl
`N 203389
`001
`8026284
`8129433
`CYSTEAMINE BITARTRATE — PROCYSBI
`
`Feb 26, 2025
`Nov 1!, 2023
`Nov 1!, 2023
`Nov 1!, 2023
`Nov 11, 2023
`
`Sep 26, 2014
`
`Sep 26, 2014
`
`Sep 26, 2014
`
`Sep 26, 2014
`
`May 17, 2014
`Aug 27, 2024
`
`Sep 22, 2027
`Jan 26, 2027
`
`N 203389
`
`002
`
`Y TEAMZNE HYDR
`
`N 200710
`
`001
`
`8026284
`8129433
`HL RIDE —
`
`Sep 22, 2027
`Jan 26, 2027
`Y TARAN
`
`QYTARABINE — DEPQQYT
`Mar 03, 2015
`N 021011
`001
`5723147
`DABIQATRAN ETEXILATE MESYLATE — PRADAXA
`N 0225‘2
`001
`6087380
`Feb 18, 2018
`7866474
`Aug 31, 2027
`7932273
`Sep 07, 2025
`DABIGATRAN ETEXILATE MESYLATE — PRADAXA
`
`PATENT
`coDEs
`
`)3 U—817
`DP
`)3 U—1152
`
`33
`
`33
`33
`
`33
`
`33
`33
`
`)3
`
`)3
`
`)3
`
`)3
`
`33
`)3
`
`)3
`
`33
`
`U—979
`
`U—1088
`
`U—979
`
`U—1088
`
`U—1399
`
`U—1399
`
`)3 U—806
`
`35 )3 U—1089
`DP
`3S )3
`
`002
`
`N 0225 2
`
`6087380
`7866474
`7932273
`DABRAFENIB MESYLATE — TAFINLAR
`N 202806
`001
`7994185
`8415345
`DABBAEENlB_MESILAIE_:_IAElNLAB
`N 202806
`002
`7994185
`8415345
`DALFAMPRIDINE — AMPYRA
`
`Feb 18, 2018
`Aug 31, 2027
`Sep 07, 2025
`
`3S )3 U—1089
`33
`35 )3
`
`Jan 20, 2030
`Jan 20, 2030
`
`)3 U—1406
`DS
`DS 33 U—1406
`
`Jan 20, 2030
`Jan 20, 2030
`
`3S )3 U—1406
`DS
`)3 U—1406
`
`N 022250
`
`001
`
`5540938
`8007826
`8354437
`8440703
`
`Jul 30, 2018
`May 26, 2027
`Dec 22, 2026
`Apr 08, 2025
`
`U—1030
`U—1030
`U—1030
`U—1030
`
`PATENT
`DELIST
`REQUESTED
`
`EXCLUSIVITY
`coDE(s)
`
`EXCLUSIVITY
`EXPIRATION
`DATE
`
`NDF
`
`NDF
`
`NP
`ODE
`
`Apr 30, 2016
`
`Apr 30, 2016
`
`Oct 02, 2015
`Oct 02, 2019
`
`NCE
`
`Oct 19, 2015
`
`NCE
`
`Oct 19, 2015
`
`NCE
`ODE
`
`NCE
`ODE
`
`NCE
`ODE
`
`May 29, 2018
`May 29, 2020
`
`May 29, 2018
`May 29, 2020
`
`Jan 22, 2015
`Jan 22, 2017
`
`0007