Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) Joint Meeting of the Drug Safety and Risk Management Advisory Committee, Nonprescription Drugs Advisory Committee, and the Anesthetic and Life Support Drugs Advisory Committee June 29-30, 2009 Questions to the Committee For each question, the relevant Option from the background package's Options Paper is presented in a text box. Although the order of presentation has been changed, these options are numbered as they appear in the Options Paper. A set of General Considerations for you to take into account in your discussion and decisions of all questions is provided on Page 9. In addition, other factors that you should take into account are listed and you may identify other factors that you find relevant. 1 Nonprescription Products FROM OPTIONS PAPER: "OPTION 1a" Reduce the current dosage strengths of acetaminophen in nonprescription products. This could include the maximum adult daily dose, maximum single adult dose, and maximum dosage strength. In addition to the General Considerations, consider the following: o Efficacy provided by the higher single and daily doses o Availability of different doses for various clinical indications o Additional safety concerns posed by the availability of higher strength acetaminophen products compared to lower strength products o Balance of efficacy benefit with safety concerns o How the "best" dosage should be determined o FDA will consider responses to Questions 1 and 2 when determining whether to reduce the current dosage strengths of acetaminophen in prescription products. Question 1 (Vote) Do you recommend that the maximum total daily dose (4 grams/day) of acetaminophen in nonprescription single ingredient and combination products be lowered? A - Yes, I recommend this change and consider it a high priority B - Yes, I recommend this change C - No, I do not recommend this change Question 2 (Vote) Do you recommend that the maximum nonprescription single adult dose be limited to 650 mg? A - Yes, I recommend this change and consider it a high priority B - Yes, I recommend this change C - No, I do not recommend this change 2 FROM OPTIONS PAPER: "OPTION 1b" If OTC dose were reduced, switch of current higher dosage to prescription status. This could be 500 mg per tablet, 1000 mg per maximum dose and/or 4 grams as the maximum daily dose. In addition to the General Considerations, consider the following: o Patient population(s) under healthcare providers' care who may require the current maximum strength of acetaminophen Question 3 (Vote) If the current doses of nonprescription products are lowered, do you recommend that the current maximum dosage of acetaminophen (i.e., 2 x 500 mg) be switched to prescription status? A - Yes, I recommend this change and consider it a high priority B - Yes, I recommend this change C - No, I do not recommend this change 3 FROM OPTIONS PAPER: "OPTION 2" Establish pack size limits for OTC acetaminophen products. In addition to General Considerations, consider the following: o The impact of the U.K. experience with mandated pack size restriction and no mandated sales restriction o Relevance of the U.K. experience to the U.S. marketplace o How FDA should determine an appropriate OTC pack size o Public health and safety consequences of the potential for increased use of other analgesics Question 4 (Vote) Do you recommend that pack size limits be implemented for nonprescription acetaminophen products? A - Yes, I recommend this change and consider it a high priority B - Yes, I recommend this change C - No, I do not recommend this change FROM OPTIONS PAPER: "OPTION 5a" Eliminate nonprescription acetaminophen combination products. In addition to the General Considerations, consider the following: o Role of combination products in duplicate dosing of acetaminophen o Consumer knowledge about presence of acetaminophen in OTC combination products Question 5 (Vote) Do you recommend eliminating nonprescription acetaminophen combination products? A - Yes, I recommend this change and consider it a high priority B - Yes, I recommend this change C - No, I do not recommend this change 4 FROM OPTIONS PAPER: "OPTION 6" Limit formulations for OTC LIQUIDS. In addition to the General Considerations, consider the following: o The OTC monograph does not currently stipulate specific concentrations of acetaminophen liquid formulations o Dosage administration considerations for pediatric patients of various ages o Identifying the concentration of acetaminophen liquid that should be made available for children, if only one concentration is allowed Question 6 (Vote) Do you recommend that only one concentration of nonprescription acetaminophen liquid be available? A - Yes, I recommend this change and consider it a high priority B - Yes, I recommend this change C - No, I do not recommend this change 5 Prescription Products FROM OPTIONS PAPER: "OPTION 5b" Eliminate prescription acetaminophen combination products. In addition to the General Considerations, consider the following: o Currently, the combination products fall under Schedule III. Single ingredient opioid analgesics, by DEA regulation, are regulated as Schedule II and have different prescribing and dispensing requirements. o Potential safety concerns associated with the drugs that will be used as therapeutic replacements for the opioid-acetaminophen combinations (e.g., NSAIDs, Schedule II opioids.) Question 7 (Vote) Do you recommend eliminating the prescription acetaminophen combination products? A - Yes, I recommend this change and consider it a high priority B - Yes, I recommend this change C - No, I do not recommend this change 6 FROM OPTIONS PAPER: "OPTION 3" and "OPTION 4" If prescription acetaminophen combination products continue to be marketed, implement additional safety measures by requiring "unit-of-use" packaging and/or additional warning materials. With "unit-of-use" packaging, products would be packaged by the manufacturer or distributer for sale in a pharmacy, without the product needing to be repackaged. Packaging would display standardized information on the prescription package directed to patients (e.g., prominent display of 'ACETAMINOPHEN' as an active ingredient and a warning about potential liver damage.) and convey a Medication Guide to patients. A boxed warning could be implemented with or without "unit-of-use" packaging. In addition to the General Considerations, consider the following: o FDA recently issued new regulations for labeling OTC products containing acetaminophen to enhance warning information and prominence of identification of 'acetaminophen' as an active ingredient. o Current pharmacy practices do not require consistent nomenclature and warning information on pharmacy-packaged prescriptions. Question 8 (Vote) If prescription acetaminophen combination products continue to be marketed, do you recommend that "unit-of-use" packages be required? A - Yes, I recommend this change and consider it a high priority B - Yes, I recommend this change C - No, I do not recommend this change Question 9 (Vote) Do you recommend that FDA require a boxed warning for prescription acetaminophen combination products? A - Yes, I recommend this change and consider it a high priority B - Yes, I recommend this change C - No, I do not recommend this change 7 Question 10 (Vote) Overall Ranking of Options Options related to both Rx and OTC products containing acetaminophen have been discussed. You have already indicated whether you consider each individual option a high priority. To further clarify how FDA should focus its resources to decrease the public health burden of acetaminophen liver toxicity, indicate the single option, including both nonprescription and prescription options, which you recommend that FDA consider its highest priority. If you do not recommend that FDA implement any of the proposed options, please indicate this on the ballot provided. Nonprescription Products Option 1a - Reduce maximum dose of OTC acetaminophen Option 1b - Switch current maximum dose of OTC acetaminophen to prescription Note: Options 1a and 1b may be considered a single option or two separate options. Option 2 - Establish pack size limits for OTC products Option 5a - Eliminate OTC acetaminophen combination products. Option 6 - Limit OTC liquid formulations Prescription Products Option 5b - Eliminate prescription acetaminophen combination products Option 3 - Require unit of use packaging for prescription acetaminophen combination products Option 4 - Require a boxed warning for prescription acetaminophen combination products Question 11 (Discuss) What other options FDA should consider that have not been discussed in the options provided? 8 The 'General Considerations' apply to each of the questions. You may want to tear off this sheet and use it for reference when responding. General Considerations o o o o Potential for this change to decrease incidence of liver injury Effect on patients (e.g., convenience, monetary factors, education) Effect on healthcare practitioners Whether the regulatory steps, resources, and time needed to implement this change are merited by the potential impact of the change o Steps that manufacturers would need to take to support this change o Other potential consequences of this change that should be anticipated 9 Committee Vote Note: the following abbreviations are used: CR: Consumer Representative PR: Patient Representative 10 *Return to List of Questions FDA ACS Question 1 Vote Result Presented 37 Yes, High Priority Yes No 11 10 16 No-Voting 0 Vote Time: 2009-06-30 11:50:55 Name List Proposal Name: Question 1 Yes, High Priority ( Vote: 11 ) Chojkier Gellad Omogui (CR) Walker-Harding DeNisco Heckbert Shrank Wolfe (CR) Eichner (PR) Olsen Stergachis Day Griffin Lorenz Eisenach Kirsch Pollock Brull Kerns Levine Nelson (Chair) Todd Covington Krenzelok Markman Prough Vaida Yes ( Vote: 10 ) Cooper Farber Kramer Watts No ( Vote: 16 ) Benowitz Engle Landis Morrato Raja Zelterman No-Voting ( Total: 0 ) 7/1/2009 12:17:13 PM Page 1 of 1 *Return to List of Questions FDA ACS Question 2 Vote Result Presented 37 Yes, High Priority Yes No 12 12 13 No-Voting 0 Vote Time: 2009-06-30 11:53:30 Name List Proposal Name: Question 2 Yes, High Priority ( Vote: 12 ) DeNisco Farber Kramer Omogui (CR) Eichner (PR) Gellad Lorenz Stergachis Eisenach Heckbert Olsen Wolfe (CR) Chojkier Day Pollock Walker-Harding Cooper Griffin Raja Watts Engle Landis Morrato Todd Kerns Levine Nelson (Chair) Vaida Yes ( Vote: 12 ) Benowitz Covington Kirsch Shrank No ( Vote: 13 ) Brull Krenzelok Markman Prough Zelterman No-Voting ( Total: 0 ) 7/1/2009 12:19:20 PM Page 1 of 1 *Return to List of Questions FDA ACS Question 3 Vote Result Presented 37 Yes, High Priority Yes No 8 18 11 No-Voting 0 Vote Time: 2009-06-30 12:09:03 Name List Proposal Name: Question 3 Yes, High Priority ( Vote: 8 ) Benowitz Kramer Shrank DeNisco Lorenz Watts Heckbert Omogui (CR) Cooper Eichner (PR) Gellad Nelson (Chair) Raja Vaida Covington Eisenach Griffin Olsen Stergachis Walker-Harding Engle Krenzelok Markman Zelterman Kerns Landis Pollock Yes ( Vote: 18 ) Chojkier Day Farber Morrato Prough Todd No ( Vote: 11 ) Brull Kirsch Levine Wolfe (CR) No-Voting ( Total: 0 ) 7/1/2009 12:21:47 PM Page 1 of 1 *Return to List of Questions FDA ACS Question 4 Vote Result Presented 37 Yes, High Priority Yes No 2 15 20 No-Voting 0 Vote Time: 2009-06-30 13:33:11 Name List Proposal Name: Question 4 Yes, High Priority ( Vote: 2 ) Morrato Olsen Yes ( Vote: 15 ) Chojkier Eichner (PR) Landis Shrank Walker-Harding Day Eisenach Levine Stergachis Wolfe (CR) DeNisco Kramer Markman Vaida Zelterman Brull Engle Griffin Kirsch Nelson (Chair) Prough Watts Cooper Farber Heckbert Krenzelok Omogui (CR) Raja No ( Vote: 20 ) Benowitz Covington Gellad Kerns Lorenz Pollock Todd No-Voting ( Total: 0 ) 7/1/2009 12:22:36 PM Page 1 of 1 *Return to List of Questions FDA ACS Question 5 Vote Result Presented 37 Yes, High Priority Yes No 2 11 24 No-Voting 0 Vote Time: 2009-06-30 13:55:17 Name List Proposal Name: Question 5 Yes, High Priority ( Vote: 2 ) Farber Kramer Yes ( Vote: 11 ) Chojkier Eichner (PR) Morrato Walker-Harding Day Krenzelok Nelson (Chair) Wolfe (CR) DeNisco Levine Todd Brull Eisenach Griffin Kirsch Markman Pollock Shrank Watts Cooper Engle Heckbert Landis Olsen Prough Stergachis Zelterman No ( Vote: 24 ) Benowitz Covington Gellad Kerns Lorenz Omogui (CR) Raja Vaida No-Voting ( Total: 0 ) 7/1/2009 12:23:39 PM Page 1 of 1 *Return to List of Questions FDA ACS Question 6 Vote Result Presented 37 Yes, High Priority Yes No 19 17 1 No-Voting 0 Vote Time: 2009-06-30 14:17:38 Name List Proposal Name: Question 6 Yes, High Priority ( Vote: 19 ) Brull Eichner (PR) Heckbert Nelson (Chair) Prough Vaida Wolfe (CR) Cooper Eisenach Levine Olsen Shrank Walker-Harding DeNisco Griffin Lorenz Pollock Stergachis Watts Chojkier Engle Kerns Landis Omogui (CR) Zelterman Covington Farber Kirsch Markman Raja Yes ( Vote: 17 ) Benowitz Day Gellad Kramer Morrato Todd No ( Vote: 1 ) Krenzelok No-Voting ( Total: 0 ) 7/1/2009 12:24:49 PM Page 1 of 1 *Return to List of Questions FDA ACS Question 7 Vote Result Presented 37 Yes, High Priority Yes No 10 10 17 No-Voting 0 Vote Time: 2009-06-30 14:52:47 Name List Proposal Name: Question 7 Yes, High Priority ( Vote: 10 ) Chojkier Eisenach Levine Wolfe (CR) Cooper Farber Nelson (Chair) DeNisco Heckbert Vaida Covington Kirsch Stergachis Day Kramer Watts Engle Kerns Lorenz Olsen Prough Walker-Harding Gellad Krenzelok Markman Omogui (CR) Raja Yes ( Vote: 10 ) Benowitz Eichner (PR) Shrank Zelterman No ( Vote: 17 ) Brull Griffin Landis Morrato Pollock Todd No-Voting ( Total: 0 ) 7/1/2009 12:25:51 PM Page 1 of 1 *Return to List of Questions FDA ACS Question 8 Vote Result Presented 37 Yes, High Priority Yes No 5 22 10 No-Voting 0 Vote Time: 2009-06-30 15:38:35 Name List Proposal Name: Question 8 Yes, High Priority ( Vote: 5 ) Benowitz Markman Heckbert Prough Levine Chojkier Day Eisenach Kerns Morrato Pollock Todd Cooper DeNisco Farber Kramer Nelson (Chair) Raja Walker-Harding Gellad Lorenz Vaida Kirsch Omogui (CR) Watts Yes ( Vote: 22 ) Brull Covington Eichner (PR) Griffin Landis Olsen Stergachis Wolfe (CR) No ( Vote: 10 ) Engle Krenzelok Shrank Zelterman No-Voting ( Total: 0 ) 7/1/2009 12:26:36 PM Page 1 of 1 *Return to List of Questions FDA ACS Question 9 Vote Result Presented 37 Yes, High Priority Yes No 25 11 1 No-Voting 0 Vote Time: 2009-06-30 15:39:55 Name List Proposal Name: Question 9 Yes, High Priority ( Vote: 25 ) Benowitz Cooper Eichner (PR) Gellad Levine Olsen Raja Walker-Harding Zelterman Brull Day Eisenach Heckbert Markman Omogui (CR) Shrank Watts Chojkier DeNisco Engle Kramer Morrato Prough Stergachis Wolfe (CR) Farber Krenzelok Nelson (Chair) Vaida Kerns Landis Pollock Yes ( Vote: 11 ) Covington Kirsch Lorenz Todd No ( Vote: 1 ) Griffin No-Voting ( Total: 0 ) 7/1/2009 12:27:34 PM Page 1 of 1 Joint Meeting of the Drug Safety and Risk Management Advisory Committee with the Anesthetic and Life Support Drugs Advisory Committee and the Nonprescription Drugs Advisory Committee Question 10 Vote Record *Return to List of Questions NONPRESCRIPTION PRODUCTS 1b 1a 2 OPTION Sheet # 1 2 3 4 5 6 7 8 9 10 11 12 13 14 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 Name 1 Benowitz Brull Chojkier Cooper Covington Day DeNisco Eichner Eisenach Engle Farber Gellad Griffin Heckbert Kerns Kirsch Kramer Krenzelok Landis Levine Lorenz Markman Morrato Nelson, L (Chair) Olsen Omoigui Pollock Prough Raja Shrank Stergachis Todd Vaida Walker-Harding Watts Wolfe Zelterman 5a 6 PRESCRIPTION PRODUCTS 4 5b 3 Do Not Recommend that FDA implement any of the proposed options. X 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 TOTALS 9 3 1 0 2 7 7 1 7 0 OPTION 1 1a 1b 2 5a 6 5b 3 4 X Question 10 Committee Vote 7/1/2009 12:34 PM