Regulatory History of Aspirin

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Regulatory History of Aspirin

• Cardiovascular and Renal Drugs
• Advisory Committee Meeting
• Michelle M. Jackson, Ph.D.
• Division of Over-The-Counter Drug Products

Cardiovascular and Renal Drugs AC
Meeting December 8, 2003
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Content

• The OTC Drug Monograph Process
• Regulatory History of Aspirin
• 1989 1997 Advisory Committee Discussions
• Professional Labeling for Aspirin

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OTC Drug Monograph Process

• 1. Advisory Review Panels
• Panels submit reports to FDA
• 2. Advance Notice of Proposed Rulemaking (ANPR)
• Public comment period
• 3. Tentative Final Monograph (TFM)
• Public comment period
• 4. Final Monograph (FM)

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OTC Drug Review

• Citizen Petition (21 CFR 10.30)
• Right of citizens to petition the government
• Used to issue, amend, or revoke a regulation
• Used to take or refrain from taking certain
  actions

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OTC Drug Review (cont)

• OTC Drug Labeling
• OTC drug labeling provided for consumers
• - Consumers are able to safely self medicate
• Professional Drug Labeling
• OTC drug labeling provided for healthcare
  professionals (not for the general public)
• Advice of a healthcare professional is needed for
  the safe and effective use of the drug product

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Regulatory History of Aspirin

• July 21, 1972 Review of OTC internal
  analgesic ingredients
• Advisory Review Panel
• July 8, 1977 ANPR - Publication of OTC
  internal analgesic panel report
• Public Comment Period
• November 16, 1988 TFM - Public Comment Period
• May 8, 1989 Comment Sterling Drug Inc.
• Claim for aspirin for the prevention
  of primary heart attack
• October 6, 1989 Advisory Committee Meeting

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Regulatory History of Aspirin (cont)

• October 15, 1992 Aspirin Foundation (CP9)
• Claim for treating acute MI
• December 21, 1992 Aspirin Strategy Group (CP10)
• Claim for treating acute MI
• June 6, 1994 Aspirin Strategy Group (CP12)
• Claim for anyone at risk for MI
• and stroke
• June 13, 1996 Amendment to the TFM
• January 23, 1997 Advisory Committee Meeting
• October 23, 1998 Final Monograph Professional
  Labeling

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ANPR July 8, 1977 Panels
Report

• Anti-platelet effects of aspirin
• Increased bleeding time
• Warnings against use in people with GI or
  bleeding problems, or during pregnancy
• No mention of CV claims

9
TFM November 16, 1988

• Proposed professional labeling for use of
  aspirin
  
  
  
  
  - reducing the risk of recurrent TIAs
  or stroke in men
• - reducing the risk of death and/or
  nonfatal MI
• - rheumatologic diseases

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Comments to the TFM

• Professional Labeling for Aspirin
• Use for primary prevention of MI
• Reduce the dose for TIA and stroke from
• 1,300 mg to 300 mg a day
• Include labeling for both men and women

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1989 Advisory Committee Meeting (PHS Labeling
claim for primary prevention of MI)

• No effect on total cardiovascular mortality
• No data on routine use in men w/o risk factors
  and in women
• Concerns about use in healthy people or
  inappropriate patient populations

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Amendment to the TFM June 13, 1996

• In response to 2 CPs requesting
• an indication for use of aspirin in treating
  acute MI initial dose of 160 mg to 162.5 mg
  continued daily for at least 30 days

13
1997 Advisory Committee Meeting CP requested
an amendment to the professional labeling for
aspirin in secondary prevention of CV events in
patients

• undergoing coronary, cerebral, or peripheral
  arterial revascularization procedures
• with chronic non-valvular atrial fibrillation
• requiring hemodialysis access with fistula or
  shunt
• with elevated risk due to some form of vascular
  disease

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1997 Advisory Committee Meeting Recommendations

• Low-dose aspirin in patients with stable angina
• Low-dose aspirin in patients with arterial
  revascularization procedures
• Not indicated in patients with peripheral
  vascular disease

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1998 Final Monograph
FDAs Evaluation of the PHS Reasons why
the claim for primary prevention of MI was not
included in the FM

• Some subjects had prior MI
• 8 who suffered a nonfatal MI also had evidence
  of a previous MI
• No statistically significant effects of aspirin
  when fatal / nonfatal MI and stroke were combined

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1998 Final Monograph FDAs Evaluation of the
PHS (cont)

• Reduction in the incidence of fatal and non-fatal
  MI was accompanied by an increase in
• - hemorrhagic stroke
• - sudden death
• - other CV deaths
• BDT does not support the use of aspirin to
  prevent initial MI

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Professional Labeling

• Information does not appear on the OTC label
• Labeling is provided to healthcare professionals
  by manufacturers
• Prescribing information for
• vascular indications
• revascularization procedures
• rheumatologic diseases

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Professional Labeling (cont.)
Components of Professional Labeling

Contraindications
Adverse Reactions
Professional Labeling of Aspirin
Precautions
Warnings
Overdosage
Indications
Dosage Administration
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Professional Labeling (cont.)
Vascular Indications Vascular Indications
Indications Recommended Daily Dose (mg)
Ischemic Strokes / TIA 50 - 325 Suspected Acute MI 160 - 162.5 Prevention of Recurrent MI 75 - 325 Unstable Angina Pectoris 75 - 325 Chronic Stable Angina Pectoris 75 - 325 Ischemic Strokes / TIA 50 - 325 Suspected Acute MI 160 - 162.5 Prevention of Recurrent MI 75 - 325 Unstable Angina Pectoris 75 - 325 Chronic Stable Angina Pectoris 75 - 325

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Professional Labeling (cont.)
Revascularization Procedures Revascularization Procedures
Indications Recommended Daily Dose (mg)
Coronary Artery 325 Bypass Graft Percutaneous Transluminal Presurgery 325 Coronary Artery Postsurgery 160 - 325 Carotid Endarterectomy 80 - 650 Coronary Artery 325 Bypass Graft Percutaneous Transluminal Presurgery 325 Coronary Artery Postsurgery 160 - 325 Carotid Endarterectomy 80 - 650

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Bayer Healthcares Request

• Professional labeling for the use of aspirin
  regimen (75-325 mg) for primary prevention of MI
  in patients at risk for a CHD

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