Arthritis & Drug Safety and Risk Management

Advisory Committee Briefing Package

February 16, 17, and 18, 2005

  Table of Contents

Tab A Executive Summary [ htm ] [ pdf ] [ Word ]

  DAY 1

Tab B Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Package Insert Labeling Template [ htm ] [ pdf ] [ Word ]

VIOXX (refocoxib) NDA 21-042

Tab C Vioxx Timeline [ htm ] [ pdf ] [ Word ]

Tab D Original NDA Executive Summary

•  Osteoarthritis ( Dr. Villalba ) [htm] [pdf] [Word]
•  Cardio-Renal ( Dr. Pelayo ) [pdf]

Tab E VIGOR, Supplemental New Drug Application, S-007, dated April 2001, Studies 085 and 090

•  VIGOR Review Executive Summary ( Dr. Villalba ) [htm] [pdf] [Word]
•  Web address: FDA Briefing Package for February 2001, Arthritis Advisory Committee Meeting  http://www.fda.gov/ohrms/dockets/ac/01/briefing/3677b2.htm

•  See Clinical Review ( Dr. Villalba ) [Word] [pdf]
•  See Cardio-Renal Review ( Dr. Targum ) [Word] [pdf]

Tab F FDA Complete Responses to April 2001 Approvable Review [htm] [pdf] [Word

•  Safety in rheumatoid arthritis efficacy studies

•  Follow-up of patients from the original NDA

•  New studies
•  Completed

•  Ongoing (Alzheimer's studies)

•  Memo to File - Cardiovascular Data in Alzheimer's studies [htm] [pdf] [Word]

Tab G Alzheimer's studies: Supplemental New Drug Application, S-030, dated March 2004: Update of cardiovascular thrombolic events (CVTE)

•  Preliminary review of S-030 ( Dr. Villalba ) [htm] [pdf] [Word]

Tab H Placebo-controlled trials (Protocol 203 - APPROVe, CIVTOR, and Prostate Cancer) for evaluation of CV outcomes w/Vioxx

•  Protocol 203 Division of Anti-Inflammatory, Analgesic, and Ophthalmologic Drug Products (DAAODP) Advice Letter dated December 2002 [pdf]
•  APPROVe Data Presentation by Merck [pdf]

Tab I Approved Labels

•  Original Vioxx Label, dated May 1999 [htm] [pdf] [Word]
•  VIGOR Label, dated April 2002 [htm] [pdf] [Word]

CELEBREX (celecoxib) NDA 20-998

Tab J Celebrex Timeline [htm] [pdf] [Word]

Tab K Original NDA Review

•  Osteoarthritis and Rheumatoid Arthritis ( Dr. Witter ) [htm] [pdf] [Word]
•  Cardio-Renal Review ( Dr. Throckmorton ) [pdf]
Note: Pages 12 through 80 of this document are not provided

Tab L CLASS Supplemental New Drug Application, S-009: dated June 2000

•  Clinical Review Executive Summary ( Dr. Witter ) [htm] [pdf] [Word]
•  Web address: FDA Briefing Package for February 2001, Arthritis Advisory Committee Meeting  http://www.fda.gov/ohrms/dockets/ac/01/briefing/3677b1.htm

•  See Clinical Review ( Dr. Witter ) [Word] [pdf]
•  See Cardio-Renal Review ( Dr. Throckmorton ) [ pdf ]

Tab M Approved Labels

•  Original Celebrex Label, dated January 1999 [pdf]
•  CLASS Label, dated June 2002 [pdf]
Note: This document begins with Page 3

BEXTRA (valdecoxib oral) NDA 21-341

Tab N Bextra Timeline [htm] [pdf] [Word]

Tab O Original NDA Review

•  Executive Summary ( Dr. Johnson ) [htm] [pdf] [Word]

Tab P Approved Labels

•  Original Bextra Label, dated November 2001 [pdf]
•  Updated label to include postmarketing information on serious skin reactions and cardiovascular events, dated November 2002 [pdf]
•  Updated label to include Black box warning on serious skin reactions, dated November 2004 [pdf]

BEXTRA (parecoxib IV) NDA 21-294 (pending)

Tab Q Original NDA Review

•  Executive Summary ( Dr. Witter ) [htm] [pdf] [Word]

NAPROSYN (naproxen) NDA 17-581

Tab R Approved Label [pdf]

  DAY 2

Tab S Publications - Epidemiological Studies:

•  Graham , David J. , Memorandum dated September 30, 2004 . Note: An error occurs when printing this document; Page 16 prints blank. [pdf]

•  Fries JF, Murtagh KN, Bennett M, Zatarain E, Lingala B, Bruce B. The rise and decline of nonsteroidal anti-inflammatory drug-associated gastropathy in rheumatoid arthritis. Arth Rheum 2004;50(8):2433-40.
•  Rodriguez LAG, Varas-Lorenzo C, Maguire A , Gonzalez-Perez A. Nonsteroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population. Circ 2004;109:3000-6.
•  Ray WA, Stein CM, Hall K, Daugherty JR, Griffin MR. Non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease: an observational cohort study. The Lancet 2002;359:118-223.
•  Schneeweiss S , Glynn RJ, Tsai EH, Avorn J , Solomon DH. Adjusting for unmeasured confounders in pharmacoepidemiologic claims data using external information: the example of COX2 inhibitors and myocardial infarction. Epid 2005:16(1):17-24.
•  Ray WA, Stein CM, Daugherty JR, Hall K, Arbogast PG, Griffin MR. COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease. The Lancet 2002;360:1071-3.
•  Kimmel SE, Berlin JA, Reilly M, Jaskowiak J, Kishel L, Chittam J, Strom BL. Patients exposed to rofecoxib and celecoxib have different odds of nonfatal myocardial infarction. Ann Intern Med 2005;142.
•  Blackwell T. Alternative to vioxx is connected to 14 deaths: company argues health Canada is not definitive. Nation Post 2004; Nov 4:A1.

ARCOXIA (etoricoxib) NDA 21-389 (pending)

Tab T Original NDA Review

•  Safety Review of Safety and GI ( Dr. Schiffenbauer ) [htm] [pdf] [Word]

PREXIGE (lumiracoxib) NDA 21-521 (pending)

Tab U Original NDA Review

Tab V TARGET Summary Publications:

•  Hawkey C, Farkouh M, Gitton X, Eshrsam E, Huels J, Richardson P. Therapeutic Arthritis Research and Gastrointestinal Event Trial of lumiracoxib study design and patient demographics. Aliment Pharmacol Ther 2004; 20:50-63.
•  Schnitzer T , Burnester G , Mysler E , Hochberg M , Doherty M, Ehrsam E , Gitton X , Krammer G , Mellein B , Matchaba P , Gimona A , Hawkey C. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complication: randomized controlled trial. The Lancet 2004; 364:665-74.
•  Farkouh M , Kirshner H, Harrington R, Ruland S, Freek W , et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomized controlled trial. The Lancet 2004; 364:675-84.