DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Silver Spring MD 20993 NDA 205649/S-005 SUPPLEMENT APPROVAL AstraZeneca Pharmaceuticals LP US Agent for AstraZeneca AB Attention: Ian Wogan Director, Regulatory Affairs One MedImmune Way Gaithersburg, MD 20878 Dear Mr. Wogan: Please refer to your supplemental New Drug Application (sNDA) dated and received July 28 2016, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Xigduo XR (dapagliflozin and metformin HCl extended-release) tablets. We also refer to our letter dated July 8, 2016, notifying you, under Section 505(o)(4) of the FDCA, of new safety information that we believe should be included in the labeling for sodiumglucose cotransporter-2 (SGLT-2) inhibitors. This information pertains to the risk of fatal ketoacidosis. This supplemental new drug application provides for revisions to the labeling for Xigduo XR consistent with our July 8, 2016, letter. APPROVAL & LABELING We have completed our review of this supplemental application. It is approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling text and with the minor editorial revision listed below and indicated in the enclosed labeling. • The revision dates listed for the Prescribing Information (including Recent Major Changes, Warnings and Precautions) were updated to reflect the date of approval of this supplement. WAIVER OF HIGHLIGHTS SECTION 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. Reference ID: 3973633 NDA 205649/S-005 Page 2 CONTENT OF LABELING 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 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content of labeling must be identical to the enclosed labeling (text for the package insert, 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 titled “SPL Standard for Content of Labeling Technical Qs and As at http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U CM072392.pdf 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 MS Word format, that includes the changes approved in this supplemental application, as well as annual reportable changes and annotate each change. To facilitate review of your submission, provide a highlighted or markedup 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, 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(s) 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. Reference ID: 3973633 NDA 205649/S-005 Page 3 PROMOTIONAL MATERIALS You may request advisory comments on proposed introductory advertising and promotional labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory comments, (2) the proposed materials in draft or mock-up form with annotated references, and (3) the package insert(s) to: OPDP Regulatory Project Manager Food and Drug Administration Center for Drug Evaluation and Research Office of Prescription Drug Promotion (OPDP) 5901-B Ammendale Road Beltsville, MD 20705-1266 Alternatively, you may submit a request for advisory comments electronically in eCTD format. For more information about submitting promotional materials in eCTD format, see the draft Guidance for Industry (available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U CM443702.pdf ). You must submit final promotional materials and package insert(s), 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 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf. Information and Instructions for completing the form can be found at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For more information about submission of promotional materials to the Office of Prescription Drug Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm. 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 package labeling. Within 7 days of receipt of this letter, submit your statement of intent to comply with 21 CFR 314.70(a)(4) to the address above, by fax to 301-847-8444, or electronically in eCTD format. For more information about submitting promotional materials in eCTD format, see the draft Guidance for Industry (available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U CM443702.pdf ). REPORTING REQUIREMENTS We remind you that you must comply with reporting requirements for an approved NDA (21 CFR 314.80 and 314.81). Reference ID: 3973633 NDA 205649/S-005 Page 4 If you have any questions, call Abolade (Bola) Adeolu, Regulatory Project Manager, at (301) 796-4264. Sincerely, {See appended electronic signature page} Jennifer Rodriguez Pippins, M.D., M.P.H. Deputy Director for Safety Division of Metabolism and Endocrinology Products Office of Drug Evaluation II Center for Drug Evaluation and Research ENCLOSURE: Content of Labeling Reference ID: 3973633 --------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------/s/ ---------------------------------------------------JENNIFER R PIPPINS 08/17/2016 Reference ID: 3973633