`
`NDA 021977 S-048
`NDA 208510 S-005
`NDA 021303 S-036
`NDA 022063 S-003
`
`
`SUPPLEMENT APPROVAL
`
`
`Takeda Pharmaceuticals U.S.A., Inc.
`Attention: Lynne Miller
`Senior Director, Global Regulatory Affairs Marketed Products
`95 Hayden Avenue
`Lexington, MA 02421
`
`Dear Ms. Miller:
`
`Please refer to your supplemental new drug applications (sNDA) dated and received
`January 13, 2022, and your amendments, submitted under section 505(b) of the
`Federal Food, Drug, and Cosmetic Act (FDCA) for Vyvanse (lisdexamfetamine
`dimesylate) capsules (NDA 021977), Vyvanse (lisdexamfetamine dimesylate) chewable
`tablets (NDA 208510), Adderall XR (mixed salts of a single-entity amphetamine product)
`extended release capsules (NDA 021303) and Mydayis (mixed salts of a single-entity
`amphetamine product) extended-release capsules (NDA 022063).
`
`We also refer to our letter dated December 14, 2021, notifying you, under Section
`505(o)(4) of the FDCA, of new safety information pertaining to the association between
`the use of amphetamines and intestinal ischemia, that we believe should be included in
`the labeling for all amphetamines.
`
`These supplemental new drug applications provide for revisions to the labeling for
`Vyvanse, Adderall XR and Mydayis consistent with our December 14, 2021, safety
`labeling change notification letter.
`
`APPROVAL & LABELING
`
`We have completed our review of this application, as amended. It is approved, effective
`on the date of this letter, for use as recommended in the enclosed agreed-upon
`labeling.
`
`WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
`
`Please note that we have previously granted a waiver of the requirements of 21 CFR
`201.57(d)(8) regarding the length of Highlights of Prescribing Information.
`
`CONTENT OF LABELING
`
`Reference ID: 4943991
`
`
`
`NDA 021977 S-048
`NDA 208510 S-005
`NDA 021303 S-036
`NDA 022063 S-003
`
`Page 2
`
`
`
`As soon as possible, but no later than 14 days from the date of this letter, submit the
`content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using
`the FDA automated drug registration and listing system (eLIST), as described at
`FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
`Prescribing Information and Medication Guide), with the addition of any labeling
`changes in pending “Changes Being Effected” (CBE) supplements, as well as annual
`reportable changes not included in the enclosed labeling.
`
`Information on submitting SPL files using eList may be found in the guidance for
`industry SPL Standard for Content of Labeling Technical Qs and As.2
`
`The SPL will be accessible from publicly available labeling repositories.
`
`Also within 14 days, amend all pending supplemental applications that include labeling
`changes for this NDA, including CBE supplements for which FDA has not yet issued an
`action letter, with the content of labeling [21 CFR 314.50(l)(1)(i)] in Microsoft Word
`format, that includes the changes approved in this supplemental application, as well as
`annual reportable changes. To facilitate review of your submission(s), provide a
`highlighted or marked-up copy that shows all changes, as well as a clean Microsoft
`Word version. The marked-up copy should provide appropriate annotations, including
`supplement number(s) and annual report date(s).
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
`new active ingredients (which includes new salts and new fixed combinations), new
`indications, new dosage forms, new dosing regimens, or new routes of administration
`are required to contain an assessment of the safety and effectiveness of the product for
`the claimed indication in pediatric patients unless this requirement is waived, deferred,
`or inapplicable.
`
`Because none of these criteria apply to your application, you are exempt from this
`requirement.
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and
`promotional labeling. For information about submitting promotional materials, see the
`
`1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
`Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4943991
`
`
`
`NDA 021977 S-048
`NDA 208510 S-005
`NDA 021303 S-036
`NDA 022063 S-003
`
`Page 3
`
`
`final guidance for industry Providing Regulatory Submissions in Electronic and Non-
`Electronic Format-Promotional Labeling and Advertising Materials for Human
`Prescription Drugs.3
`
`You must submit final promotional materials and Prescribing Information, accompanied
`by a Form FDA 2253, at the time of initial dissemination or publication
`[21 CFR 314.81(b)(3)(i)]. Form FDA 2253 is available at FDA.gov.4 Information and
`Instructions for completing the form can be found at FDA.gov.5
`
`All promotional materials that include representations about your drug product must be
`promptly revised to be consistent with the labeling changes approved in this
`supplement, including any new safety information [21 CFR 314.70(a)(4)]. The revisions
`in your promotional materials should include prominent disclosure of the important new
`safety information that appears in the revised labeling. Within 7 days of receipt of this
`letter, submit your statement of intent to comply with 21 CFR 314.70(a)(4).
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`If you have any questions, call Ermias Zerislassie, Safety Regulatory Project Manager,
`at 301-796-2770.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Tiffany R. Farchione, MD
`Director
`Division of Psychiatry
`Office of Neuroscience Center for Drug
`Evaluation and Research
`
`
`ENCLOSURE(S):
`• Content of Labeling
`o Prescribing Information
`o Medication Guides
`
`3 For the most recent version of a guidance, check the FDA guidance web page at
`https://www.fda.gov/media/128163/download.
`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`U.S. Food and Drug Administration
`Silver Spring, MD 20993
`www.fda.gov
`
`Reference ID: 4943991
`
`
`
`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`TIFFANY R FARCHIONE
`02/25/2022 07:16:07 PM
`
`Reference ID: 4943991
`
`