otc cold and cough products: use in children advisory committee meeting october 18, 2007
DESCRIPTION
OTC Cold and Cough Products: Use in Children Advisory Committee Meeting October 18, 2007. Joel Schiffenbauer, MD Deputy Division Director/DNCE Office of Nonprescription Products. Agenda. Introduction Monograph Petitioners Industry representatives FDA representatives Discussion - PowerPoint PPT PresentationTRANSCRIPT
Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
OTC Cold and Cough OTC Cold and Cough Products: Use in ChildrenProducts: Use in Children
Advisory Committee MeetingAdvisory Committee MeetingOctober 18, 2007October 18, 2007
Joel Schiffenbauer, MDDeputy Division Director/DNCE
Office of Nonprescription Products
2Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
AgendaAgenda
• Introduction• Monograph• Petitioners• Industry representatives• FDA representatives• Discussion• Open public session• Discussion and Questions
3Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
What is the issue?What is the issue?
• Are cough/cold products safe and effective in children?
4Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
Citizen PetitionCitizen Petition
• Children are frequently afflicted by the common cold
• A growing body of evidence demonstrates that these products are not effective in young children
• Although typically considered safe by parents and pediatricians misuse has led to significant adverse effects in children under 6
5Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
Citizen Petition: Actions Citizen Petition: Actions RequestedRequested
• Provide a statement to the public explaining that OTC antitussive, expectorant, nasal decongestant, antihistamine and combination cough and cold products have not been shown to be safe and effective for the treatment of cough and cold in children under six years of age
6Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
Citizen Petition: Actions Citizen Petition: Actions RequestedRequested
• Notify manufacturers of these products whose labeling uses such terms as “infant” or “baby” or display images of children under the age of 6 that: – such marketing is not supported by
scientific evidence and – manufacturers will be subject to
enforcement action at any time
7Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
Citizen Petition: Actions Citizen Petition: Actions RequestedRequested
• Amend 21CFR 341 to require that labeling for OTC antitussive, expectorant, nasal decongestant, antihistamine and combination cough and cold products state: – these products have not been found to be safe
or effective in children under 6 years of age for treatment of cough and cold and
– these products should not be used for treatment of cough and cold in children under 6 years of age
8Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
OTC MonographsOTC Monographs
• OTC Drug Review– Safety/Efficacy review of OTC
drugs marketed in US prior to 1975• >300,000 OTC drug products• 800 active ingredients in multiple
therapeutic categories
9Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use Products for Over-the-Counter Human Use
21 CFR 34121 CFR 341
• Therapeutic Categories– Antihistamine (21 CFR 341.12)– Antitussive (21 CFR 341.14)– Bronchodilator (21 CFR 341.16)– Expectorant (21 CFR 341.18)– Nasal Decongestant (21 CFR 341.20)
10Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use Products for Over-the-Counter Human Use
21 CFR 34121 CFR 341
• Provides the following information:– Permitted active ingredients– Permitted combinations– Labeling
• Statement of identity• Indications• Directions for use• Warnings
– Professional labeling
11Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
Examples of Combination Products Examples of Combination Products Permitted in MonographPermitted in Monograph
Decongestant and antihistamine
Decongestant and expectorant
Decongestant and analgesic
Antitussive and expectorant
Decongestant, antihistamine and antitussiveDecongestant, antihistamine, antitussive and analgesic
12Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
Sales Data: IMS Health, IMS National Sales Sales Data: IMS Health, IMS National Sales Perspectives™, Retail and Non-RetailPerspectives™, Retail and Non-Retail
– Provides in units the amount of drug products purchased by retail and non-retail settings of care
– Possible surrogate for use, assuming that facilities purchase drugs in quantities reflective of actual patient use
13Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
IMS Health, IMS National Sales Perspectives™, Years 2002 – 2006
14Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
IMS Health, IMS National Sales Perspectives™, Years 2002 – 2006
15Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
What is the issue?What is the issue?• Are cough/cold products safe and effective in
children? – Citizen petition
• What is the evidence for efficacy of these products in children?
• What is the safety profile of these products in children?
16Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
EfficacyEfficacy• Studies in children (limitations of study design)• Extrapolation of PK data
– E11 Guidance Document: Clinical investigations of medicinal products in the pediatric population (December 2000)
– Examples: chlorpheniramine, pseudoephedrine
• Example of development and dosing determinations for drugs for treatment of allergic rhinitis
17Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
SafetySafety
• Medication errors • Reports
– Case reports/series in literature – AERS reports/TESS– Maryland Poison Control 2004 - children under 5
• Approximately 1100 calls related to cold and cough products
• Approximately 1400 calls related to topical preparations products
• For cold and cough products: 5 cases were coded as having symptoms consistent with an outcome of “moderate effect” all had complete resolution with supportive care
• All 5 cases, except one, were acute accidental overdose (children inadvertently took medication)
18Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
Points to considerPoints to consider• Is the disease process (common cold) similar in adults and
children?
– If so, is extrapolation of efficacy data appropriate for these indications? What additional PK data is needed?
– If not, are clinical studies needed? consider difficulties with conducting studies in children
• What do the published studies contribute to our understanding of the efficacy of these products? Do they demonstrate that these products are not effective in children?
19Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
Points to considerPoints to consider
• Are there safety issues that can be identified even when these drugs are used at the correct doses?
• What contribution does unintentional overdosing make to the overall safety profile of these drugs?
– What factors might contribute to unintentional overdosing and are these cases preventable (dosing devices, varying concentrations, overlapping ingredients)?
20Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
Points to considerPoints to consider• Are there ages for which these products should
not be used (consider less than 2, 2 to less than 6, and 6-12)?
• If products are labeled “do not use” should this apply to consumers as well as to health care providers such that no one will use these products?
• How should we address the use of combination products and the potential for medication errors when products contain multiple ingredients?
21Joint NDAC/PAC meetingJoint NDAC/PAC meetingOctober 18, 2007October 18, 2007
DisclaimerDisclaimer
• The Agency has not reached any final decisions as to actions to be taken in response to the Citizen Petition. Any recommendations expressed by individual reviewers should not be considered final decisions by the Agency.