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Consumer Alert: What You Should Know About OTC and Prescription Drug
Marketing
Gerald DeVries, Ph.D.
November 8, 2013
Course Goal
• These presentations are intended to provide additional insight into the effects of various OTC and prescription drugs and how they are marketed to consumers.
• They are not intended to provide medical advice or disease diagnosis.
Course Outline
• Week 1
Basic principles of drug actions
Common OTC drugs for heartburn, pain, allergy & flu
FDA regulation of OTC drugs
• Week 2
Direct to consumer advertising
Classes of drugs most frequently advertised
Drug type and FDA regulation
Requirements of Effective OTC Drug Use
• Self-diagnosis of a condition.
• Self-selection of treatment.
• Self-management of therapy.
• Failure at any step may lead to unsafe and/or ineffective use of a drug.
Heartburn, GERD
Absorption, Efficacy
Product Al(OH) Mg(OH) CaCO3 Maalox 0 0 600 Mylanta 400 400 0 Rolaids 0 80 412 Tums EX 0 0 750 Maalox TC 600 300 0 Mylanta 400 400 0 Milk of 0 400 0 Magnesia
H2 Receptor Antagonists
• Tagamet: cimetidine
• Zantac: ranitidine
• Pepcid: famotidine
• Axid: nizatidine
Drug Interactions with H2 Antagonists
• Tagamet: inhibits liver metabolic enzymes, can increase levels of other drugs.
• Zantac: also inhibits liver enzymes but at much reduced levels.
• Pepcid & Axid: even safer in this regard
Goodman & Gilman, 2011
Pain, Analgesics
Duration of action, toxicity
Aspirin
• Pain/fever relief: 325-650 mg every 4-6 hours.
• Irreversible inhibition of COX.
• Anti-platelet activity: repeated dosing of 80 mg/day.
• Takes 8-10 days to reverse effect.
NSAID Toxicity
• Most common side effects are GI: nausea, abdominal pain, diarrhea, gastric or intestinal ulcers.
• Ulcers estimated to occur in 15-30% of regular users.
• Age generally correlated with increased probability of serious adverse reactions.
Poisons Associated with largest number of fatalities
• Sedatives/hypnotics/antipsychotics
• Acetaminophen
• Opiods
• Antidepressants
• Cardiovascular drugs
• Stimulants and street drugs
• Alcohols
Bronstein et al., 2008
Flu, Allergy
Drug Distribution in the Body
Anti-Histamines: 1st Generation Benadryl diphenhydramine Chlor-Trimeton chlorpheniramine Tavist clemastine fumarate Adverse effects: Sedation, dry mouth & respiratory tract, urinary retention
Anti-Histamines: 2nd Generation Claritin loratadine Zyrtec cetirizine Allegra fexofenadine Adverse effects: no sedation, no anti-cholinergic effects. Drugs of choice for common allergic disorders.
Combination OTC Therapies
Nasal Decongestants
• Pseudoephedrine (Sudafed): decreases volume of the nasal mucosa (blood vessel constriction).
• Loss of effect, rebound hyperemia, damage to nasal mucosa.
• Avoid in pts. with hypertension, ischemic heart disease, men with BPH.
Acetaminophen 250 mg Aspirin 250 mg Caffeine 65 mg
Famotidine 10 mg CaCO3 800 mg Mg(OH) 165 mg
Acetaminophen 650 mg Dextromethorphan 30 mg Doxylamine 12.5 mg
FDA Regulation of OTC Drugs
• Currently, >300,000 marketed nonprescription drug products. (U.S. FDA, 2012)
• Many drugs have “switched” from prescription to nonprescription.
• Increased the range of nonprescription drugs, e.g. antihistamines, nasal decongestants, analgesics, acid reducers.
Background for New FDA Initiative on OTC Drugs
• Undertreatment of common diseases contributes to critical gaps in public health.
• Lack of regular access to medical and pharmacological care.
• Poor medical adherence to therapy
- 20% to 30% of prescriptions not filled
- 50% of medications not taken as prescribed.
FDA Initiative on OTC Drugs (cont.)
• FDA exploring a regulatory expansion of the nonprescription drug class.
• Nonprescription Safe Use Regulatory Expansion (NSURE)
• Public meeting March, 2012
Pharmacists, Physicians, Pharma Industry, Nurse Practioners, Academics, Patient Support Groups
FDA Initiative (cont.)
• Drugs that may become available OTC without a prescription include cholesterol, asthma, migraine and blood-pressure medications.
Requirements of Effective OTC Drug Use
• Self-diagnosis of a condition.
• Self-selection of treatment.
• Self-management of therapy.
• Failure at any step may lead to unsafe and/or ineffective use of a drug.
Thank You
Consumer Alert: What You Should Know About OTC and Prescription Drug
Marketing
Gerald DeVries, Ph.D.
November 15, 2013
Course Outline
• Week 1
Basic principles of drug actions
Common OTC drugs for heartburn, pain, allergy & flu
FDA regulation of OTC drugs
• Week 2
Direct to consumer advertising
Classes of drugs most frequently advertised
Drug type and FDA regulation
Prescription Drugs
• Total sales in 2010 - $307 billion
• 12% of all health care spending
• Private health insurance - $117 billion (45%)
• Public programs - $93 billion (36%)
-Medicare
-Medicaid
• Consumers - $49 billion (19%)
History of DTC Marketing
• United States and New Zealand are the only developed countries that permit DTC advertising (DTCA) of prescription drugs.
• 1962 FDA granted authority to regulate presecription drug advertisement.
• 1981 Merck publishes first print ad in Reader’s Digest.
• 1983 Boots Pharm. first TV DTC ad.
History of DTCA (cont.)
• 1985 – 1997 Ads primarily focused in print media, because of “brief summary” req.
• 1997 FDA releases new guidelines: no longer mandated “brief summary”. Replaced with “adequate provision” clause. Only major risks and most common adverse events disclosed.
• 1996 DTCA $791 million
• 2005 DTCA $4.2 billion
Top Selling Drugs 2011
• Lipitor Pfizer $7.668 billion
• Plavix Bristol-Myers $6.771
• Nexium AstraZeneca $6.155
• Abilify Otsuka $5.194
• AdvairDiskus GSK $4.636
• Seroquel AstraZeneca $4.636
• Singulair Merk $4.592
• Crestor AstraZeneca $4.403
Top Selling Drugs 2011 (cont.)
• Cymbalta Lilly $3.666 billion
• Humira Abbott $3.531
• Enbrel Amgen $3.506
• Remicade Centocor $3.474
• Actos Takeda $3.437
• Neulasta Amgen $3.316
• Rituxan Genentech $3,004
• Zyprexa Lilly $2.964
Types of DTC Ads
• Product claim ad: names a drug and the indications
-risks must be included in “major statement” and “adequate provision for access to a brief summary” is required.
- telephone number, website, reference to print ad, ask health care provider.
Types of DTC Ads
• Reminder ad: names a drug, dosage form, but not its uses.
- no product claims are made, so fair balance does not apply
- mention of risks in “brief summary”, “major statement” or adequate provision is not required.
Types of DTC Ads
• Help-seeking ad: describes a disease or condition but does not mention a specific drug.
- no product is mentioned, nor are any claims made, so “fair balance” does not apply.
Content Analysis of DTCA
• Appeals:
- positive emotional 95%
- negative emotional 68%
• Lifestyle portrayals:
- Condition interferes with healthy activities 26%
- Product enables healthy activity 56%
Frosch et al., Annals Family Medicine, 2007
Content Analysis (what’s not there)
• Factual claims:
- Any factual information 82%
- Risk factors or cause of condition 25%
- Prevalence of condition 24%
• Lifestyle portrayals:
- lifestyle change as alternative 0%
- lifestyle change is insufficient 21%
DTC Target Audiences
On balance, do you think prescription drug advertising is mostly a good thing, or mostly
a bad thing?
Do you agree or disagree with this statement?
Prescription drug ads educate people about Available treatment and encourage them to
get help for medical conditions they might not have been aware of.
Effect of DCTA on Physician/Patient Interaction
• Encourages patients to contact a clinician.
• Promotes patient dialogue with clinicians.
• Encourages patient compliance.
• Manufactures disease and encourages drug over-utilization.
• Leads to inappropriate prescribing.
• Strains relationships with clinicians.
Ventola CL, P&T, 2011
Influence of Patients’ Requests for Advertised Antidepressants
• Study of physicians prescribing practices in major depression, or adjustment disorder.
• Major depression: rates of prescribing when pts. ask for brand names, 53%; general drugs, 76%; no requests, 31%.
• Adjustment disorder: brand name, 55%; general, 39%; no request, 10%.
Kravitz et al.; JAMA, 2005
Biologics vs Conventional Drugs
Biologics
• Drugs made in or isolated from living systems.
• Increasingly use recombinant DNA technology.
• First recombinant product for human use, human insulin (Humulin) approved in the US in 1982.
Some Current Biologic Drugs
• Remicade: monoclonal antibody (rheumatoid arthritis; Crohn’s disease)
• Humira: monoclonal antibody (rheumatoid arthritis; psoriatic arthritis)
• Enbrel: fusion protein (rheumatoid arthritis)
• Erbitux: monoclonal antibody (cancer)
• Herceptin: monoclonal antibody (cancer)
Cost of Biologic Therapies
• Herceptin (breast cancer): $54 K/yr
• Kadcyla (breast cancer): $117 K/yr
• Lucentis (macular degeneration): $23 K/yr
• Humira (rheumatoid/Crohns): $50 K / yr
• Avastin (cancer): $100 K / yr
• Cerezyme ( Gaucher ) : $200 K / yr
Cost of Biologics (cont.)
• Often used for chronic, on-going conditions
• Top 6 biologics currently consume 43% of the drug budget for Medicare Part B
Sloan-Kettering Says No
• Zaltrap receives FDA approval for colorectal cancer August, 2012
• Sanofi sets price at $11K / month
• Sloan-Kettering refuses to use Zaltrap for cost reasons
• Sanofi announces reduction in cost by 50% in November, 2012
Biologics Growth
• Approximately 30% of pharmaceutical R&D pipeline composed of biologics.
• Anticipated by 2016 10 of the 20 top-selling drugs will be biologics.
• Seven of these (Humira, Avastin, Rituxan, Herceptin, Remicade, Prolia and Lucentis) are monoclonal antibodies.
• Global sales in 2009 were $93 billion.
Samsung Biologics
• Samsung and Biogen Idec announce joint venture
• “One of our goals is to help patients … by increasing accessibility to existing medicines.”
• “Making high quality biosimilars is critical to that goal”
• A number of biologics come off patent in the next decade.
Pathway for Small Molecule Generics
• Abbreviated New Drug Application process established by the 1984 Hatch-Waxman Amendments to the FDCA, creating a generic drug program for “small molecule” drugs.
• Act facilitated earlier, less costly market entry.
Requirements for Generic Drug Approval
• Same active ingredient
• Same route of administration
• Same strength
• Same intended use
• Same rate and extent of absorption into the body
• Do NOT need to provide independent evidence of safety and efficacy in clinical trials
Impact of Generics on Health Care Costs
• Retail price of generics on average is 75% lower than brand name drugs.
• Generics make up about 78% of drugs dispensed in retail settings.
• Estimated savings to US health care system through use of generics (1999 – 2010) is more than $1 trillion. [GAO Jan. 2012]
What is Bioequivalence?
“For simple chemical molecules, the mechanism to establish comparability is streamlined through the concept of “bioequivalence”1
For complex biological molecules, the concept of bioequivalence has yet to be established, because pharmacokinetic criteria are not relevant or measurable3
1. European Agency for the Evaluation of Medicinal Products (EMEA), Committee for Proprietary Medicinal products (CPMP) Note For Guidance on the Investigation of Bioavailability and Bioequivalence CPMP/EWP/QWP/1401/98
2. Food Drug administration (FDA). Guidance for Industry Statistical Approaches to Establishing Bioequivalence. Available at: http:// www.fda.gov/cder/guidance/3616fnl.htm. Accessed January 2003
3. Schellekens H and Ryff JC. Biogenerics: the off-patent biotech products. Trends Pharmacol Sci 2002;23:119 –121
Two medicinal products are bioequivalent if they have the same pharmacokinetics, i.e.,
Their time to maximal plasma concentration [Cmax], and area under the plasma concentration-time curve (AUC) falls in the same pre-specified confidence interval2
Regulation of Biologics
• Science-Based Regulatory Concept of “Comparability”
• Supported by industry, e.g. Pharmaceutical Research and Manufacturers of America
• In Europe, per 2003 EMA guideline, “comparable” extended to products from different sponsors.
Regulation of Biologics (cont.)
• In 2010, Biologics Price Competition and Innovation Act (BPCIA) allows FDA to approve biosimilars and to lead on the formal designation of interchangeability.
• However, it is not clear if the FDA will waive pre-clinical and clinical studies for biosimilars in the near future.
State Bills to Limit Biosimilars
• Amgen and Genentech are proposing bills to restrict pharmacists substituting generic biologics for brand name products.
• North Dakota: State Senator said “Genentech was the one that brought the bill to me.”
• Indiana: PH Comm. Chairman said bill had been brought to him by Genentech and supported by Eli Lilly.
State Bills (cont.)
• California bill SB 598 would have allowed biosimilars deemed “interchangeable” with brand name product by FDA to be substituted by pharmacists.
• However, pharmacists would have to notify patient’s doctor and patient.
• Gov. Jerry Brown vetoed the bill.
Thank You
