CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`205395Orig1s000
`
`
`OTHER REVIEW(S)
`
`

`

`REGULATORY PROJECT MANAGER
`PHYSICIAN’S LABELING RULE (PLR) FORMAT REVIEW
`OF THE PRESCRIBING INFORMATION
`
`Complete for all new NDAs, BLAs, Efficacy Supplements, and PLR Conversion Labeling Supplements
`
`Application: NDA 205395
`
`Application Type: New NDA
`
`Name of Drug/Dosage Form: darunavir/cobicistat (TRADENAME under review)/Tablet
`
`Applicant: Janssen Products, LP
`
`Receipt Date: March 31, 2014
`
`Goal Date: January 31, 2015
`
`1. Regulatory History and Applicant’s Main Proposals
`
`Janssen has submitted an original NDA containing a fixed dose combination (FDC) tablet of
`darunavir (DRV) 800 mg, and cobicistat (COBI) 150 mg for treatment of HIV infection in adults.
`The sponsor has developed the formulation in collaboration with Gilead Sciences Inc. (Gilead).
`DRV (PREZISTA®) is an approved HIV-1 protease inhibitor, while COBI is a CYP3A inhibitor
`indicated to increase the systemic exposures of certain protease inhibitors (also known as a
`pharmacokinetic enhancer) currently under FDA review.
`
`Janssen is requesting 3 years of market exclusivity for the FDC.
`
`In the pediatric population, Janssen is requesting a partial waiver for HIV infected subjects from
`birth to less than 3 years of age, as well as subjects weighing less than 15 kg. In addition, they are
`requesting deferral of studies in pediatric subjects weighing greater than 15 kg.
`
`2. Review of the Prescribing Information
`
`This review is based on the applicant’s submitted Word format of the prescribing information (PI).
`The applicant’s proposed PI was reviewed in accordance with the labeling format requirements listed
`in the “Selected Requirements for Prescribing Information (SRPI)” checklist (see the Appendix).
`
`3. Conclusions/Recommendations
`
`SRPI format deficiencies were identified in the review of this PI. For a list of these deficiencies see
`the Appendix.
`
`In addition, the following labeling issues were identified:
`
`I.
`
`i.
`ii.
`
`HIGHLIGHTS OF PRESCIRIBNG INFORMATION
`Remove
` in the title of the HIGHLIGHTS section
`Space required between Limitation Statement and Product Title
`
`Reference ID: 3692998
`
`(b)
`(4)
`
`

`

`Selected Requirements of Prescribing Information
`
`iii.
`iv.
`v.
`
`vi.
`vii.
`viii.
`
`ix.
`
`There should be no space between Product Title and Initial US Approval
`Initial US approval date should follow the format outlined in
`Product title should be changed to: TRADENAME (darunavir and cobicistat) tablet,
` for oral use
`The pharmacologic class for cobicistat is not accurate. See Stribild labeling.
`In CONTRAINDICATIONS section remove
`Please reformat the HIGHLIGHTS and FULL PRESCRIBING INFORMATION
`CONTENTS* so that the HIGHLIGHTS is no more than half page in length.
`Add a period at end of the sentence “See 17 PATIENT COUNSELING
`INFORMATION…….”
`
`II.
`
`III.
`
`IV.
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`i. The black horizontal line should appear on the TOC page, not the FPI page.
`ii. Remove the word
`iii. Remove brackets from statement at end of CONTENTS* section.
`
`In FULL PRESCRIBING INFORMATION (FPI): DOSAGE AND ADMINISTRATION
`section:
`i. Do not include information between section 2 and subsection 2.1. Incorporate that
`information into the subsections.
`ii. Under subsection 2.4, cobicistat is misspelled.
`
`i.
`ii.
`
`In FPI: ADVERSE REACTIONS section:
`Information should not appear between section 6 and 6.1. A subsection heading is needed.
`Include the following statement preceding the adverse reactions from clinical trials:
`“Because clinical trials are conducted under widely varying conditions, adverse reaction rates
`observed in the clinical trials of a drug cannot be directly compared to rates in the clinical
`trials of another drug and may not reflect the rates observed in clinical practice”.
`
`V.
`
`In FPI: USE IN SPECIFIC POPULATIONS section:
`i. The text following the title “Darunavir” should be in the same format as “Cobicistat: Studies
`in animals …….”
`
`VI.
`
`In FPI: DESCRIPTION section:
`i. The following correction is needed
`
`VII.
`
`In FPI: Patient Counseling Information
`i. Numbered sub-sections are not recommended since they may be redundant with other
`subsection titles in the labeling.
`
`All SRPI format deficiencies of the PI and other labeling issues identified above will be conveyed to
`the applicant in the 74-day letter. The applicant will be asked to correct these deficiencies and
`resubmit the PI in Word format by July 8, 2014). The resubmitted PI will be used for further labeling
`review.
`
`SRPI version 3: October 2013
`
`Reference ID: 3692998
`
`Page 2 of 11
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`Selected Requirements of Prescribing Information
`
`Appendix
`
`The Selected Requirement of Prescribing Information (SRPI) is a 42-item, drop-down checklist of
`important format elements of the prescribing information (PI) based on labeling regulations (21 CFR
`201.56 and 201.57) and guidances.
`
`Highlights
`See Appendix A for a sample tool illustrating the format for the Highlights.
`
`HIGHLIGHTS GENERAL FORMAT and HORIZONTAL LINES IN THE PI
`
`YES
`
`YES
`
`YES
`
`YES
`
`NO
`
`1. Highlights (HL) must be in a minimum of 8-point font and should be in two-column format, with
`½ inch margins on all sides and between columns.
`Comment:
`2. The length of HL must be one-half page or less (the HL Boxed Warning does not count against
`the one-half page requirement) unless a waiver has been granted in a previous submission (e.g.,
`the application being reviewed is an efficacy supplement).
`Instructions to complete this item: If the length of the HL is one-half page or less, then select
`“YES” in the drop-down menu because this item meets the requirement. However, if HL is
`longer than one-half page:
`(cid:4) For the Filing Period:
`! For efficacy supplements: If a waiver was previously granted, select “YES” in the drop-
`down menu because this item meets the requirement.
`! For NDAs/BLAs and PLR conversions: Select “NO” because this item does not meet the
`requirement (deficiency). The RPM notifies the Cross-Discipline Team Leader (CDTL) of
`the excessive HL length and the CDTL determines if this deficiency is included in the 74-
`day or advice letter to the applicant.
`(cid:4) For the End-of-Cycle Period:
`! Select “YES” in the drop down menu if a waiver has been previously (or will be) granted
`by the review division in the approval letter and document that waiver was (or will be)
`granted.
`Comment:
`3. A horizontal line must separate HL from the Table of Contents (TOC). A horizontal line must
`separate the TOC from the FPI.
`Comment: The horizontal line above TOC should appear on page one
`4. All headings in HL must be bolded and presented in the center of a horizontal line (each
`horizontal line should extend over the entire width of the column as shown in Appendix A). The
`headings should be in UPPER CASE letters.
`Comment:
`5. White space should be present before each major heading in HL. There must be no white space
`between the HL Heading and HL Limitation Statement. There must be no white space between
`
`SRPI version 3: October 2013
`
`Reference ID: 3692998
`
`Page 3 of 11
`
`

`

`Selected Requirements of Prescribing Information
`
`the product title and Initial U.S. Approval. See Appendix A for a sample tool illustrating white
`space in HL.
`
`Comment: White space between product title and intial US approval.
`- 6. Each smnmarized statement or topic in HL must reference the section(s) or subsection(s) of the
`F1111 Prescribing Information G'PI) that contain more detailed information. The preferred format
`is the numerical identifier in parenthesis [e.g., (1.1)] at the end of each summarized statement or
`topic.
`
`Comment:
`
`- 7. Section headings must be presented in the following order in HL:
`min—m—
`
`
`
`Required (if no contraindications must state “None.”)
`
`* RMC only applies to the BOXED WARNING. INDICATIONS AND USAGE. DOSAGE AND
`ADMINISTRATION. CONTRAINDICATIONS. and WARNINGS AND PRECAUTIONS sections.
`
`Comment:
`
`HIGHLIGHTS DETAILS
`
`Highlights Heading
`
`- 8. At the beginning of HL, the following heading must be bolded and should appear in all UPPER
`CASE letters: “HIGHLIGHTS OF PRESCRIBING INFORMATION”.
`Comment:
`
`Highlights Limitation Statement
`
`- 9. The bolded HL Limitation Statement must include the following verbatim statement: “These
`highlights do not include all the information needed to use (insert name of drug product)
`
`safely and effectively. See full prescribing information for (insert name of drug product).”
`The name of drug product should appear in UPPER CASE letters.
`
`Comment:
`
`Product Title in Highlights
`- 10. Product title must be bolded.
`
`SRPI version 3: October 2013
`
`Reference ID: 3692998
`
`Page 4 0f 11
`
`

`

`Selected Requirements of Prescribing Information
`
`Comment:
`
`YES
`
`Initial U.S. Approval in Highlights
`11. Initial U.S. Approval in HL must be bolded, and include the verbatim statement “Initial U.S.
`Approval:” followed by the 4-digit year.
`Comment:
`
`Boxed Warning (BW) in Highlights
`12. All text in the BW must be bolded.
`Comment:
`13. The BW must have a heading in UPPER CASE, containing the word “WARNING” (even if
`more than one warning, the term, “WARNING” and not “WARNINGS” should be used) and
`other words to identify the subject of the warning (e.g., “WARNING: SERIOUS
`INFECTIONS and ACUTE HEPATIC FAILURE”). The BW heading should be centered.
`Comment:
`14. The BW must always have the verbatim statement “See full prescribing information for
`complete boxed warning.” This statement should be centered immediately beneath the heading
`and appear in italics.
`Comment:
`15. The BW must be limited in length to 20 lines (this includes white space but does not include the
`BW heading and the statement “See full prescribing information for complete boxed
`warning.”).
`Comment:
`
`Recent Major Changes (RMC) in Highlights
`16. RMC pertains to only the following five sections of the FPI: BOXED WARNING,
`INDICATIONS AND USAGE, DOSAGE AND ADMINISTRATION,
`CONTRAINDICATIONS, and WARNINGS AND PRECAUTIONS. RMC must be listed in
`the same order in HL as the modified text appears in FPI.
`Comment:
`17. The RMC must include the section heading(s) and, if appropriate, subsection heading(s) affected
`by the recent major change, together with each section’s identifying number and date
`(month/year format) on which the change was incorporated in the PI (supplement approval date).
`For example, “Warnings and Precautions, Acute Liver Failure (5.1) --- 9/2013”.
`Comment:
`18. The RMC must list changes for at least one year after the supplement is approved and must be
`removed at the first printing subsequent to one year (e.g., no listing should be one year older than
`revision date).
`Comment:
`
`Indications and Usage in Highlights
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`YES
`
`SRPI version 3: October 2013
`
`Reference ID: 3692998
`
`Page 5 of 11
`
`

`

`N/A
`
`NO
`
`YES
`
`YES
`
`Selected Requirements of Prescribing Information
`
`19. If a product belongs to an established pharmacologic class, the following statement is required
`under the Indications and Usage heading in HL: “(Product) is a (name of established
`pharmacologic class) indicated for (indication)”.
`Comment: The pharmacologic class for cobicistat is not accurate.
`
`Dosage Forms and Strengths in Highlights
`20. For a product that has several dosage forms (e.g., capsules, tablets, and injection), bulleted
`subheadings or tabular presentations of information should be used under the Dosage Forms and
`Strengths heading.
`Comment:
`
`Contraindications in Highlights
`21. All contraindications listed in the FPI must also be listed in HL or must include the statement
`“None” if no contraindications are known. Each contraindication should be bulleted when there
`is more than one contraindication.
`Comment:
`
`.
`
`Adverse Reactions in Highlights
`22. For drug products other than vaccines, the verbatim bolded statement must be present: “To
`report SUSPECTED ADVERSE REACTIONS, contact (insert name of manufacturer) at
`(insert manufacturer’s U.S. phone number) or FDA at 1-800-FDA-1088 or
`www.fda.gov/medwatch”.
`Comment:
`
`Patient Counseling Information Statement in Highlights
`23. The Patient Counseling Information statement must include one of the following three bolded
`verbatim statements that is most applicable:
`If a product does not have FDA-approved patient labeling:
`! “See 17 for PATIENT COUNSELING INFORMATION”
`If a product has FDA-approved patient labeling:
`! “See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling”
`! “See 17 for PATIENT COUNSELING INFORMATION and Medication Guide”
`Comment:
`
`YES
`
`Revision Date in Highlights
`24. The revision date must be at the end of HL, and should be bolded and right justified (e.g.,
`“Revised: 9/2013”).
`Comment:
`
`SRPI version 3: October 2013
`
`Reference ID: 3692998
`
`Page 6 of 11
`
`(b) (4)
`
`

`

`Selected Requirements of Prescribing Information
`
`Contents: Table of Contents (TOC)
`See Appendix A for a sample tool illustrating the format for the Table of Contents.
`
`YES
`
`YES
`
`N/A
`
`YES
`
`YES
`
`NO
`
`YES
`
`25. The TOC should be in a two-column format.
`Comment:
`26. The following heading must appear at the beginning of the TOC: “FULL PRESCRIBING
`INFORMATION: CONTENTS”. This heading should be in all UPPER CASE letters and
`bolded.
`Comment:
`27. The same heading for the BW that appears in HL and the FPI must also appear at the beginning
`of the TOC in UPPER CASE letters and bolded.
`Comment: The sponsor included WARNING heading, but it needs to be removed.
`28. In the TOC, all section headings must be bolded and should be in UPPER CASE.
`Comment:
`29. In the TOC, all subsection headings must be indented and not bolded. The headings should be in
`title case [first letter of all words are capitalized except first letter of prepositions (through),
`articles (a, an, and the), or conjunctions (for, and)].
`Comment:
`30. The section and subsection headings in the TOC must match the section and subsection headings
`in the FPI.
`Comment: The subsection headings do not match the headings in the FPI. Lowercase lettering
`is used in the TOC and uppercase lettering is used in FPI. (see section 6 and 14)
`31. In the TOC, when a section or subsection is omitted, the numbering must not change. If a section
`or subsection from 201.56(d)(1) is omitted from the FPI and TOC, the heading “FULL
`PRESCRIBING INFORMATION: CONTENTS” must be followed by an asterisk and the
`following statement must appear at the end of TOC: “*Sections or subsections omitted from the
`full prescribing information are not listed.”
`Comment:
`
`SRPI version 3: October 2013
`
`Reference ID: 3692998
`
`Page 7 of 11
`
`

`

`Selected Requirements of Prescribing Information
`
`Full Prescribing Information (FPI)
`FULL PRESCRIBING INFORMATION: GENERAL FORMAT
`
`YES
`
`32. The bolded section and subsection headings in the FPI must be named and numbered in
`accordance with 21 CFR 201.56(d)(1) as noted below (section and subsection headings should
`be in UPPER CASE and title case, respectively). If a section/subsection required by regulation
`is omitted, the numbering must not change. Additional subsection headings (i.e., those not
`named by regulation) must also be bolded and numbered.
`
`BOXED WARNING
`1 INDICATIONS AND USAGE
`2 DOSAGE AND ADMINISTRATION
`3 DOSAGE FORMS AND STRENGTHS
`4 CONTRAINDICATIONS
`5 WARNINGS AND PRECAUTIONS
`6 ADVERSE REACTIONS
`7 DRUG INTERACTIONS
`8 USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`8.2 Labor and Delivery
`8.3 Nursing Mothers
`8.4 Pediatric Use
`8.5 Geriatric Use
`9 DRUG ABUSE AND DEPENDENCE
`9.1 Controlled Substance
`9.2 Abuse
`9.3 Dependence
`10 OVERDOSAGE
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`12.2 Pharmacodynamics
`12.3 Pharmacokinetics
`12.4 Microbiology (by guidance)
`12.5 Pharmacogenomics (by guidance)
`13 NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`13.2 Animal Toxicology and/or Pharmacology
`14 CLINICAL STUDIES
`15 REFERENCES
`16 HOW SUPPLIED/STORAGE AND HANDLING
`17 PATIENT COUNSELING INFORMATION
`Comment:
`33. The preferred presentation for cross-references in the FPI is the section (not subsection)
`heading followed by the numerical identifier. The entire cross-reference should be in italics and
`enclosed within brackets. For example, “[see Warnings and Precautions (5.2)]” or “[see
`Warnings and Precautions (5.2)]”.
`Comment:
`
`YES
`
`SRPI version 3: October 2013
`
`Reference ID: 3692998
`
`Page 8 of 11
`
`

`

`Selected Requirements of Prescribing Information
`
`N/A
`
`34. If RMCs are listed in HL, the corresponding new or modified text in the FPI sections or
`subsections must be marked with a vertical line on the left edge.
`Comment:
`
`FULL PRESCRIBING INFORMATION DETAILS
`
`FPI Heading
`35. The following heading must be bolded and appear at the beginning of the FPI: “FULL
`PRESCRIBING INFORMATION”. This heading should be in UPPER CASE.
`Comment:
`
`BOXED WARNING Section in the FPI
`36. In the BW, all text should be bolded.
`Comment:
`37. The BW must have a heading in UPPER CASE, containing the word “WARNING” (even if
`more than one Warning, the term, “WARNING” and not “WARNINGS” should be used) and
`other words to identify the subject of the Warning (e.g., “WARNING: SERIOUS
`INFECTIONS and ACUTE HEPATIC FAILURE”).
`Comment:
`CONTRAINDICATIONS Section in the FPI
`38. If no Contraindications are known, this section must state “None.”
`Comment:
`ADVERSE REACTIONS Section in the FPI
`39. When clinical trials adverse reactions data are included (typically in the “Clinical Trials
`Experience” subsection of ADVERSE REACTIONS), the following verbatim statement or
`appropriate modification should precede the presentation of adverse reactions:
`“Because clinical trials are conducted under widely varying conditions, adverse reaction rates
`observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials
`of another drug and may not reflect the rates observed in practice.”
`Comment:
`40. When postmarketing adverse reaction data are included (typically in the “Postmarketing
`Experience” subsection of ADVERSE REACTIONS), the following verbatim statement or
`appropriate modification should precede the presentation of adverse reactions:
`
`“The following adverse reactions have been identified during post-approval use of (insert drug
`name). Because these reactions are reported voluntarily from a population of uncertain size, it is
`not always possible to reliably estimate their frequency or establish a causal relationship to drug
`exposure.”
`Comment:
`PATIENT COUNSELING INFORMATION Section in the FPI
`41. Must reference any FDA-approved patient labeling in Section 17 (PATIENT COUNSELING
`INFORMATION section). The reference should appear at the beginning of Section 17 and
`
`YES
`
`N/A
`
`N/A
`
`N/A
`
`NO
`
`YES
`
`YES
`
`SRPI version 3: October 2013
`
`Reference ID: 3692998
`
`Page 9 of 11
`
`

`

`Selected Requirements of Prescribing Information
`
`YES
`
`include the type(s) of FDA-approved patient labeling (e.g., Patient Information, Medication
`Guide, Instructions for Use).
`Comment:
`42. FDA-approved patient labeling (e.g., Medication Guide, Patient Information, or Instructions for
`Use) must not be included as a subsection under section 17 (PATIENT COUNSELING
`INFORMATION). All FDA-approved patient labeling must appear at the end of the PI upon
`approval.
`Comment:
`
`SRPI version 3: October 2013
`
`Reference ID: 3692998
`
`Page 10 of 11
`
`

`

`Selected Requirements of Prescribing Information
`
`Appendix A: Format of the Highlights and Table of Contents
`
`SRPI version 3: October 2013 Page 11 of 11
`
`Reference ID: 3692998
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`NINA MANI
`01/27/2015
`
`KAREN D WINESTOCK
`01/28/2015
`This review was drafted on June 5, 2014.
`
`Reference ID: 3692998
`
`

`

`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Medical Policy
`
`PATIENT LABELING REVIEW
`
`Date:
`
`To:
`
`Through:
`
`From:
`
`Subject:
`
`Drug Name
`(established name)
`
`January 5, 2015
`
`Debra Birnkrant, MD
`Director
`Division of Antiviral Products (DAVP)
`
`LaShawn Griffiths, MSHS-PH, BSN, RN
`Associate Director for Patient Labeling
`Division of Medical Policy Programs (DMPP)
`
`Barbara Fuller, RN, MSN, CWOCN
`Team Leader, Patient Labeling
`Division of Medical Policy Programs (DMPP)
`
`Morgan Walker, PharmD, MBA
`Labeling Reviewer
`Division of Medical Policy Programs (DMPP)
`Jessica Fox, PharmD, RAC
`Regulatory Review Officer
`Office of Prescription Drug Promotion (OPDP)
`Review of Patient Labeling: Patient Package Insert (PPI)
`
`PREZCOBIX (darunavir and cobicistat)
`
`Dosage Form and Route:
`Application
`Type/Number:
`Applicant:
`
`Tablets, for oral use
`NDA 205395
`
`Janssen Products, LP
`
`Reference ID: 3682480
`
`

`

`1
`
`INTRODUCTION
`On March 31, 2014, Janssen Products, LP submitted for the Agency’s review a New
`Drug Application (NDA) 205395 for PREZCOBIX (darunavir and cobicistat)
`tablets, with the proposed indication for the treatment of HIV-1 infection in adult
`patients.
`This collaborative review is written by the Division of Medical Policy Programs
`(DMPP) and the Office of Prescription Drug Promotion (OPDP) in response to a
`request by the Division of Antiviral Products (DAVP) on April 3, 2014, for DMPP
`and OPDP to review the Applicant’s proposed Patient Package Insert (PPI) for
`PREZCOBIX (darunavir and cobicistat) tablets.
`
`2 MATERIAL REVIEWED
`(cid:120) Draft PREZCOBIX (darunavir and cobicistat) tablets PPI received on March 31,
`2014, and received by DMPP and OPDP on April 3, 2014.
`(cid:120) Draft PREZCOBIX (darunavir and cobicistat) tablets Prescribing Information
`(PI) received on March 31, 2014, revised by the Review Division throughout the
`review cycle, and received by DMPP and OPDP on December 18, 2014.
`(cid:120) Approved PREZISTA (darunavir) tablet comparator labeling dated April 7, 2014
`and TYBOST (cobicistat) tablet comparator labeling dated September 24, 2014.
`
`3 REVIEW METHODS
`To enhance patient comprehension, materials should be written at a 6th to 8th grade
`reading level, and have a reading ease score of at least 60%. A reading ease score of
`60% corresponds to an 8th grade reading level. In our review of the PPI the target
`reading level is at or below an 8th grade level.
`Additionally, in 2008 the American Society of Consultant Pharmacists Foundation
`(ASCP) in collaboration with the American Foundation for the Blind (AFB)
`published Guidelines for Prescription Labeling and Consumer Medication
`Information for People with Vision Loss. The ASCP and AFB recommended using
`fonts such as Verdana, Arial or APHont to make medical information more
`accessible for patients with vision loss. We have reformatted the PPI document
`using the Verdana font, size 11.
`In our collaborative review of the PPI we have:
`simplified wording and clarified concepts where possible
`(cid:120)
`ensured that the PPI is consistent with the Prescribing Information (PI)
`(cid:120)
`removed unnecessary or redundant information
`(cid:120)
`ensured that the PPI is free of promotional language or suggested revisions to
`(cid:120)
`ensure that it is free of promotional language
`
`Reference ID: 3682480
`
`

`

`(cid:120)
`
`(cid:120)
`
`ensured that the PPI meets the criteria as specified in FDA’s Guidance for
`Useful Written Consumer Medication Information (published July 2006)
`ensured that the PPI is consistent with the approved comparator labeling where
`applicable
`
`4 CONCLUSIONS
`The PPI is acceptable with our recommended changes.
`
`5 RECOMMENDATIONS
`(cid:120) Please send these comments to the Applicant and copy DMPP and OPDP on the
`correspondence.
`(cid:120) Our collaborative review of the PPI is appended to this memorandum. Consult
`DMPP and OPDP regarding any additional revisions made to the PI to determine
`if corresponding revisions need to be made to the PPI.
`Please let us know if you have any questions.
`
`Reference ID: 3682480
`
`12 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately
`following this page
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`MORGAN A WALKER
`01/05/2015
`
`JESSICA M FOX
`01/05/2015
`
`BARBARA A FULLER
`01/05/2015
`
`LASHAWN M GRIFFITHS
`01/05/2015
`
`Reference ID: 3682480
`
`

`

`MEMORANDUM
`REVIEW OF REVISED LABEL AND LABELING
`Division of Medication Error Prevention and Analysis (DMEPA)
`Office of Medication Error Prevention and Risk Management (OMEPRM)
`Office of Surveillance and Epidemiology (OSE)
`Center for Drug Evaluation and Research (CDER)
`
`Date of This Memorandum:
`December 23, 2014
`Requesting Office or Division:
`Division of Antiviral Products (DAVP)
`Application Type and Number: NDA 205395
`Product Name and Strength:
`Prezcobix (darunavir, cobicistat) Tablets, 800 mg/150 mg
`Submission Date:
`December 22, 2014
`Applicant/Sponsor Name:
`Janssen Research and Development, L.L.C.
`OSE RCM #:
`2014-719-2
`DMEPA Primary Reviewer:
`Mónica Calderón, PharmD, BCPS
`DMEPA Associate Director:
`Lubna Merchant, MS, PharmD
`
`PURPOSE OF MEMO
`1
`Janssen has submitted the revised container label (Appendix A) for Prezcobix in response to the
`recommendations we made during a previous label and labeling Memo. 1 Thus, the Division of
`Antiviral Products (DAVP) requested that we review the revised label to determine if it is
`acceptable from a medication error perspective.
`
`CONCLUSIONS
`2
`The revised container label is acceptable from a medication error perspective.
`
`
`1 Calderon M. Label and Labeling Review for Prezcobix (NDA 205395). Silver Spring (MD): Food and Drug
`Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Division of
`Medication Error Prevention and Analysis (US); 2014 Dec 19. 32 p. OSE RCM No.: 2014-719-1.
`
`Reference ID: 3678351
`
`1
`
`1 Page(s) of Draft Labeling have been Withheld in Full as b4
`(CCI/TS) immediately following this page
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`MONICA M CALDERON
`12/24/2014
`
`LUBNA A MERCHANT
`12/24/2014
`
`Reference ID: 3678351
`
`

`

`MEMORANDUM
`REVIEW OF REVISED LABEL AND LABELING
`Division of Medication Error Prevention and Analysis (DMEPA)
`Office of Medication Error Prevention and Risk Management (OMEPRM)
`Office of Surveillance and Epidemiology (OSE)
`Center for Drug Evaluation and Research (CDER)
`
`Date of This Memorandum:
`December 19, 2014
`Requesting Office or Division:
`Division of Antiviral Products (DAVP)
`Application Type and Number: NDA 205395
`Product Name and Strength:
`Prezcobix (darunavir, cobicistat) Tablets, 800 mg/150 mg
`Submission Date:
`November 24, 2014
`Applicant/Sponsor Name:
`Janssen Research and Development, L.L.C.
`OSE RCM #:
`2014-719-1
`DMEPA Primary Reviewer:
`Mónica Calderón, PharmD, BCPS
`DMEPA Team Leader:
`Vicky Borders-Hemphill, PharmD
`
`PURPOSE OF MEMO
`1
`Janssen Research and Development, L.L.C has submitted the revised container label (Appendix
`A) for Prezcobix in response to recommendations that we made during a previous label and
`labeling review.1 Thus, the Division of Antiviral Products (DAVP) requested that we review the
`revised container label to determine if it is acceptable from a medication error perspective.
`
`Janssen has agreed with all of our recommendations with one exception, they wish to maintain
`the two statements “Alert: Find out about medicines…” on the side panel of the container label
`and “Each tablet contains…” on the principal display panel (PDP) so as to align with other
`Janssen HIV product labels that currently have similar text on the side panel and PDP panel,
`respectively. They further state the text, “Alert: Find out about medicines…” is highlighted to
`call the attention of the patient.
`
`
`1Calderon M. Label and Labeling Review for Prezcobix (NDA 205395). Silver Spring (MD): Food and Drug
`Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Division of
`Medication Error Prevention and Analysis (US); 2014 Nov 06. 32 p. OSE RCM No.: 2014-719.
`
`Reference ID: 3675943
`
`1
`
`

`

`Of note, DAVP recommended Janssen remove
`
`
`
`CONCLUSIONS
`2
`In light of the DAVP’s recommendations to remove
`
`
`
`
`
`We recommend the Applicant remove
`container label.
`
` statement from the
`
`2.1 RECOMMENDATIONS TO JANSSEN
`A. Container Label
`1. Remove the following statement from the PDP,
`DAVP’s recommendation to remove the statement from the FPI.
`
`to align with
`
`Reference ID: 3675943
`
`2
`
`1 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS)
`immediately following this page
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`MONICA M CALDERON
`12/19/2014
`
`BRENDA V BORDERS-HEMPHILL
`12/19/2014
`
`Reference ID: 3675943
`
`

`

`Consultative Review
`DPP Consult #11499
`
`Consultant Reviewer:
`
`
`
`Cara Alfaro, Pharm.D.
`Clinical Analyst
`Division of Psychiatry Products/OND/CDER
`
`Consultation Requester:
`
`Kofi A. Kumi, Ph.D.
`Clinical Pharmacology Reviewer
`DCPI/Office of Clinical Pharmacology
`
`Sarita Boyd
`Senior Clinical Analyst
`Division of Anti-Viral Products (DAVP)
`
`Subject of Request:
`
`Product labeling for boosted protease inhibitors when co-
`administered with lurasidone (Latuda)
`
`Date of Request:
`
`11/21/2014
`
`Requested Completion Date: 12/12/2014
`
`Background
`The Division of Anti-Viral Products (DAVP) has consulted the Division of Psychiatry Products
`(DPP) and the Office of Clinical Pharmacology (OCP) for labeling recommendations regarding
`the potential concomitant use of lurasidone and boosted protease inhibitors. DAVP has been
`discussing how to label the predicted drug-drug interaction between lurasidone, an atypical
`antipsychotic and CYP3A4 substrate, and HIV protease inhibitors that are co-administered with
`either ritonavir or cobicistat to increase systemic exposure of the protease inhibitor. Examples of
`these medications, referred to as “boosted protease inhibitors” include darunavir/ritonavir,
`darunavir/cobicistat, atazanavir/ritonavir and atazanavir/cobicistat. DAVP notes that although
`ritonavir and cobicistat are strong CYP3A inhibitors, these drugs are always combined with an
`HIV protease inhibitor in clinical practice and are never used alone. The net effect of boosted
`protease inhibitors (e.g. darunavir/cobicistat) are predicted to be borderline moderate-to-strong
`CYP3A inhibitors based on drug-drug interaction data with maraviroc (Selzentry). DAVP is
`currently reviewing the NDA for darunavir/cobicistat (Prezcobix) (IND 113198, NDA 205395)
`
`DPP (Alfaro) and OCP (Kumi) attended a labeling meeting on 12/2/2014 to briefly discuss
`labeling recommendations regarding this issue. This consult serves as the final recommendation
`from DPP and OCP and is consistent with advice shared at the labeling meeting.
`
`Latuda (lurasidone)
`Latuda (lurasidone) is an atypical antipsychotic approved for the treatment of schizophrenia and
`the treatment of depressive episodes associated with bipolar I disorder. The recommended dose
`range for the treatment of schizophrenia is 40 to 160 mg/day and the reco