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Center for Drug Evaluation and Research CENTER FOR DRUG EVALUATION AND RESEARCH Approval Package for: APPLICATION NUMBER: NDA 50-795/S-22 Trade Name: Doryx MPC Generic or Proper doxycycline hyclate delayed release, 60 mg and 120 mg Name: Tablets Sponsor: Mayne Pharma International Pty Ltd Approval Date: May 20, 2016 Indication: Rickettsial infections, Sexually transmitted infections, Respiratory tract infections, Specific bacterial infections, Ophthalmic infections, Anthrax, including inhalational anthrax (post-exposure), Alternative treatment for selected infections when penicillin is contraindicated, Adjunctive therapy in acute intestinal amebiasis and severe acne, Prophylaxis of malaria CENTER FOR DRUG EVALUATION AND RESEARCH NDA 50-795/S-022 CONTENTS Reviews / Information Included in this NDA Review. Approval Letter X Other Action Letters Labeling X REMS Summary Review X Officer/Employee List X Office Director Memo Cross Discipline Team Leader Review X Clinical Review X Product Quality Review X Environmental Assessment Non-Clinical Review Statistical Review Clinical Microbiology X Clinical Pharmacology and Biopharmaceutics Review X Other Reviews X Risk Assessment and Risk Mitigation Review(s) Proprietary Name Review X Administrative/Correspondence Document(s) CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: NDA 50-795/S-22 APPROVAL LETTER DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Silver Spring MD 20993 NDA 50-795/S-022 SUPPLEMENT APPROVAL Mayne Pharma International Pty Ltd c/o Metrics, Inc. Attention: Susan Canady Regulatory Affairs Specialist 1240 Sugg Parkway Greenville, NC 27834 Dear Ms. Canady: Please refer to your Supplemental New Drug Application (sNDA) dated July 13, 2015, received July 20, 2015, and your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Doryx MPC (doxycycline hyclate delayed-release) 60 mg and 120 mg Tablets. This Prior Approval supplemental new drug application provides for a modified formulation and two new product strengths (60 mg and 120 mg tablets). APPROVAL & LABELING We have completed our review of this supplemental application, as amended. It is approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling text. 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 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 Reference ID: 3934777 NDA 50-795/S-022 Page 2 The SPL will be accessible from publicly available labeling repositories. Also within 14 days, amend all pending supplemental applications that includes 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 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). CARTON AND IMMEDIATE CONTAINER LABELS We acknowledge your May 18, 2016 submission containing final printed carton and container labels. 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 Eva Zuffova, Regulatory Project Manager, at (301) 796- 0697. Sincerely, {See appended electronic signature page} Sumathi Nambiar, MD, MPH Director Division of Anti-Infective Products Office of Antimicrobial Products Center for Drug Evaluation and Research ENCLOSURES: Content of Labeling Carton and Container Labeling Reference ID: 3934777 --------------------------------------------------------------------------------------------------------- This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------- /s/ ---------------------------------------------------- SUMATHI NAMBIAR 05/20/2016 Reference ID: 3934777 CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: NDA 50-795/S-22 LABELING HIGHLIGHTS OF PRESCRIBING INFORMATION --------------DOSAGE FORM AND STRENGTHS------------ These highlights do not include all the information needed to Doryx MPC Delayed-Release Tablets: 60 mg, 120 mg (3) use DORYX MPC safely and effectively. See full prescribing information for DORYX MPC ----------------------CONTRAINDICATIONS------------------- Doxycycline is contraindicated in persons who have shown DORYX MPC (doxycycline hyclate delayed-release tablets), hypersensitivity to any of the tetracyclines. (4) for oral use. Initial U.S. Approval: 1967 --------------WARNINGS AND PRECAUTIONS------------- The use of drugs of the tetracycline-class during tooth -------------------RECENT MAJOR CHANGES--------------- development (last half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discoloration of -------------------INDICATIONS AND USAGE--------------- the teeth (yellow-gray-brown). (5.1) Doryx MPC is a tetracycline class drug indicated for: Clostridium difficile-associated diarrhea. Evaluate patients if Rickettsial infections (1.1) diarrhea occurs. (5.2) Sexually transmitted infections (1.2) Photosensitivity manifested by an exaggerated sunburn Respiratory tract infections(1.3) reaction has been observed in some individuals taking Specific bacterial infections (1.4) tetracyclines. Limit sun exposure. (5.3) Ophthalmic infections (1.5) Overgrowth of non-susceptible organisms, including fungi, Anthrax, including inhalational anthrax (post-exposure) (1.6) may occur. If such infections occur, discontinue use and Alternative treatment for selected infections when penicillin institute appropriate therapy. (5.4) is contraindicated (1.7) Adjunctive therapy in acute intestinal amebiasis and severe ---------------------ADVERSE RECTIONS----------------------- acne (1.8) Adverse reactions observed in patients receiving tetracyclines Prophylaxis of malaria (1.9) include anorexia, nausea, vomiting, diarrhea, rash, photosensitivity, urticaria, and hemolytic anemia. (6) To reduce the development of drug-resistant bacteria and maintain the effectiveness of doxycycline hyclate, Doryx MPC and other To report SUSPECTED ADVERSE REACTIONS, contact antibacterial drugs, Doryx MPC Tablets should be used only to Mayne Pharma at 1-844-825-8500 or FDA at 1-800-FDA- treat or prevent infections that are proven or strongly suspected to 1088 or www fda.gov/medwatch. be caused by bacteria. (1.10) -------------------DRUG INTERACTIONS------------------------ ------------DOSAGE AND ADMINISTRATION--------------- Patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage (7.1) Important Administration Instructions: Avoid co-administration of tetracyclines with penicillin o Doryx MPC is not substitutable on a mg per mg basis (7.2) with other oral doxycyclines. (2.1) Absorption of tetracyclines, including Doryx MPC is o Do not chew or crush tablets. (2.1) impaired by antacids containing aluminum, calcium, or Dosage in Adults magnesium, bismuth subsalicylate and iron-containing o The usual dosage of Doryx MPC is 240 mg on the first preparations (7.3) day of treatment (administered 120 mg every 12 hours) Concurrent use of tetracyclines, including Doryx MPC may followed by a maintenance dose of 120 mg daily.(2.3) render oral contraceptives less effective (7.4) Barbiturates, carbamazepine, and phenytoin decrease the o In the management of more severe infections half-life of doxycycline (7.5) (particularly chronic infections of the urinary tract), 120 mg every 12 hours is recommended. (2.3) -------------USE IN SPECIFIC POPULATIONS-------------- Dosage in Pediatric Patients Tetracycline-class drugs can cause fetal harm when o For all pediatric patients weighing less than 45 kg with administered to a pregnant woman, but data for doxycycline severe or life threatening infections (e.g., anthrax, Rocky are limited. (5.6, 8.1) Mountain spotted fever), the recommended dosage of Tetracyclines are excreted in human milk; however, the Doryx MPC is 2.6 mg per kg of body weight extent of absorption of doxycycline in the breastfed infant is administered every 12 hours. Pediatric patients weighing not known. Doryx MPC use during nursing should be 45 kg or more should receive the adult dose.(2.3) avoided if possible. (8.3) o For pediatric patients with less severe disease (greater See 17 for PATIENT COUNSELING INFORMATION than 8 years of age and weighing
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