FDA Presentations for the April 24-25, 2018 Joint Meeting of the Arthritis Advisory Committee and

168 Pages·2017·2.18 MB·English

Regulatory History of the
Interaction Between Aspirin and
Other Nonprescription NSAIDs
April 24, 2016
Jenny Kelty, MD
Medical Officer
Division of Nonprescription Drug Products
Office of Drug Evaluation IV
CDER, FDA
Agenda
• Over-the-counter (OTC) regulatory pathways
• OTC NSAIDS
• OTC NSAID cardiovascular labeling history
• OTC labeling of aspirin (ASA) and non-aspirin
NSAID interaction
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OTC Regulatory Pathways
New Drug Application Monograph
Similar to prescription drugs Notice and comment rulemaking
Product-specific Ingredient- and
category-specific regulation
Application submitted for No FDA application or
pre-marketing approval pre-approval
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Currently Marketed OTC NSAIDs
Drug Class Regulatory Pathway
Aspirin (acetylated salicylate) Salicylates TFM IAAA
Magnesium salicylate NDA
Choline salicylate ANDA
Sodium salicylate
Ibuprofen Propionic acid NDA
derivative ANDA
Naproxen Propionic acid NDA
Naproxen sodium derivative ANDA
TFM IAAA = Tentative Final Monograph for Internal Analgesic, Antipyretic, and Antirheumatic Drug
Products; FR = Federal Register; NDA = New Drug Application; ANDA = Abbreviated New Drug Application
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Aspirin
• Available in several dosage forms and strengths
ranging from 81 mg to 500 mg
• Indication
– Temporary relief of minor aches and pains
– Reduction of fever
• OTC dosing available for adults and children 2 years
of age and older

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Aspirin Cardiovascular Professional
Labeling (21 CFR 343.80)
• Vascular Indications: ischemic stroke, transient
ischemic attack, acute myocardial infarction (MI),
prevention of recurrent MI, unstable angina
pectoris, and chronic stable angina pectoris
• Revascularization Procedures: coronary artery
bypass graft (CABG), percutaneous transluminal
coronary angioplasty (PTCA), and carotid
endarterectomy
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OTC Ibuprofen
• 1974 – Approved for prescription use under NDA for arthritic
conditions
• 1978 – Approved for prescription use under NDA in for
moderate pain
• 1984 – Approved for OTC use under NDA for minor pain relief
and fever reduction
• Available in a variety of strengths and formulations for children
and adults as single-ingredient and combination drug products
• OTC dosing available down to 6 months of age

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OTC Naproxen Sodium
• 1976 – Naproxen approved for prescription use under NDA
• 1980 – Naproxen sodium approved for prescription use under NDA
• 1994 – Naproxen sodium approved for OTC use under NDA for minor
pain relief and fever reduction
• Available OTC as tablet or capsule containing 220 mg naproxen sodium
• OTC dosing in adults and children ≥12 years of age:
– 220-440 mg every 8-12 hours
– Max dose: 660 mg in 24 hours
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OTC NSAID Cardiovascular
Thromboembolic Risk Labeling History
• 2005 Joint meeting of FDA’s Arthritis and Drug
Safety & Risk Management Advisory
Committees
• 2014 Joint meeting of FDA’s Arthritis and Drug
Safety & Risk Management Advisory
Committees
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2005 Joint Meeting of FDA’s Arthritis and
Drug Safety & Risk Management ACs
• Do not use
– right before or after heart surgery
• When using this product the risk of heart attack
or stroke may increase if you use more than
directed or for longer than directed.
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