Over the Counter Product Updateelearning.pharmacist.com/portal/Files/Learning...Bayer Products Migraine Advanced Aspirin (ASA) Headache Relief OTC Product Safety Concerns Energy Drinks

Over-the-Counter Product Update 2013 © 2013 American Pharmacists Association Self-Care Institute 1

Over‐the‐Counter Product Update 2013

Daniel L. Krinsky, BSPharm, MS

Associate Professor of Pharmacy Practice

Northeast Ohio Medical University

College of Pharmacy

Development and Support

2

This activity was developed by the American Pharmacists Association and brought to you by the APhA Self‐Care Institute which is supported by an independent education grant from McNeil Consumer Healthcare.

Accreditation Information

The American Pharmacists Association is accredited by theAccreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This activity, Over‐the‐Counter Product Update 2013, is approved for 2.0 hours of continuing pharmacy education credit (0.2 CEUs). The ACPE Universal Activity Number assigned by the accredited provider is: 0202‐0000‐13‐200‐L01‐P.

To obtain continuing pharmacy education credit for this activity, participants will be required to actively participate in the entire webinar and complete an online evaluation and CPE recording form located at www.pharmacist.com/education by August 29, 2013.

Initial Release Date: August 22, 2013

Target Audience: Pharmacists

ACPE Activity Type: Knowledge‐Based

Learning Level: 2

Fee: There is no fee for this activity


Disclosures

Daniel L. Krinsky, BSPharm, MS, has served as a consultant for Lexi‐Comp and received honoraria. He declares no other conflicts of interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria.

APhA’s editorial staff declares no conflicts of interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria. For complete staff disclosures, please see the Education and Accreditation Information section at www.pharmacist.com/education.

The American Pharmacists Association is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

Learning Objectives

Evaluate medications that entered the over‐the‐counter (OTC) marketplace during 2012 and 2013, and identify products in the OTC pipeline due to hit the market by the end of 2014

Assess recent research regarding the active ingredients, recommended use, or availability of existing OTC products

List recent legal and regulatory activities designed to minimize the misuse and abuse of nonprescription products

Discuss the proposed OTC plus category (NSURE) and how this may impact pharmacy practice

OTC Product Changes and

New Products


ZzzQuil Active ingredient: Diphenhydramine

Another brand extension

Indicated for individuals 12 years and older

Dosing: 50 mg/dose from either formulation

Caps: 2 of the 25 mg caps at bedtime if needed or as directed by prescriber

Liquid: 30 mL (25 mg/15 mL) or 2 tablespoons In the Drug Facts information, manufacturer states to “use dose cup or tablespoon”

Multiple product sizes: Liquids and LiquiCaps

http://www.zzzquil.com

First once‐daily topical gel

Promoted to reduce the appearance of scars caused by injury, acne, surgery, or burns

Primary ingredient:

Cepalin, a proprietary botanical extract derived from onions that is used in all Mederma scar products and stretch‐marks therapy

http://www.mederma.com

Mederma Advanced Scar Gel

LidoPatch

OTC pain relief patch

Contains 3.99% lidocaine

Works for up to 24 hours

Use to relieve minor pain associated with strains, sprains, arthritis, simple backache, bursitis, tendonitis

Note: Patches can be cut to fit a specific area

http://www.lidopatch.com


Rapid‐melt acetaminophen tablet

Available strengths:

80 mg (2–6 years)

160 mg (6–11 years)

2 Flavors: Bubblegum and grape

Gluten‐free and sugar‐free

Bilingual drug facts messaging on the package

http://www.rapimeds.com

Children’s RapiMed

High‐potency probiotic medical food

Indicated in children for dietary management of irritable bowel syndrome and ulcerative colitis

Available behind‐the‐counter because it is classified as a medical food requiring medical supervision

The term medical food, as defined in section 5(b) of the Orphan Drug Act (21 U.S.C. 360ee (b) (3)) is “a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.”

http://www.fda.gov; http://www.vsl3.com

VSL#3 Junior

Contains 8 proprietary bacteria strains

4 formulations that contain 112.5 billion to 900 billion live bacteria/dose

Requires refrigeration

All‐natural, gluten‐free, kosher‐ and halal‐certified, non‐dairy product

Watermelon flavored

Can be mixed with various cold beverages (e.g., juice, water) or foods (e.g., ice cream, applesauce)

http://www.vsl3.com

VSL#3 Junior


Background

Primatene Mist removed from the market Dec 31, 2011 Ozone‐depleting chlorofluorocarbons (CFC)

No reformulation (manufacturer planned to submit New Drug Application for CFC‐free product 1st quarter 2013, but nothing yet)

Amphastar Pharmaceuticals Inc. had 1 million units to distribute

Solicited assistance from Congress; H.R. 6190 introduced (Asthma Inhalers Relief Act of 2012) Goal was to allow marketing of remaining units (with profits to charity)

Resolution failed in the House Dec 12, 2012

The Tan Sheet, December 17, 2012:9.

Asthmanefrin

New racemic epinephrine product available as an OTC option for temporary relief of bronchial asthma

Dosing 4 years of age and older: 1–3 inhalations every 3 hours up to a

maximum of 12 inhalations in 24 hours

Available as 2.25% solution in 0.5 mL vials in foil pouches

Manufacturer offers 2 packages Starter kit includes EZ Breathe Atomizer and 10 vials of medication

Refill package includes 30 vials of medication

http://www.asthmanefrin.com

Asthmanefrin

Manual for EZ Breathe Atomizer available on manufacturer’s website

Review of this document reveals a fairly complicated process

Identifying the components (there are 7)

Assembly (6 steps)

Filling the medication cup (5 steps)

Operating the device (5 steps)

Cleaning the device (5 steps)

Asthmanefrin is a different type of device/delivery system and requires attention to detail, and ideally, counseling from a pharmacist or other health care provider


Asthmanefrin


Take‐home messages/clinical considerations

A new racemic epinephrine product—available as an OTC option for temporary relief of certain asthma symptoms

Drug delivery is a complicated process that may be challenging for many consumers

While this product may be an option for symptom management for certain individuals, ideally all individuals with asthma are managed by a health care provider who oversees all medication use, including OTC products

Encourage dialogue with your patients who may be interested in using the product to determine potential benefits and risks


Asthmanefrin

A new pseudoephedrine product: Nexafed

Manufactured to deter conversion to methamphetamine

Produced using the manufacturer’s Impede technology

Includes a “unique polymer matrix” of safe inactive ingredients that inhibits the extraction and conversion of the active ingredient to methamphetamine

Data submitted to FDA on file with manufacturer

Available in 30 mg tablets

From manufacturer website:

http://www.nexafed.com

Tamper‐Resistant Pseudoephedrine Product Now Available

Data from National Association for Continence

>30 million Americans experience incontinence

Women > men

CONTROL study

15‐week, open‐label observational study

Designed to evaluate behaviors of individuals most likely to use Oxytrol (oxybutynin) transdermal system

Enrollees in charge of product purchase, patch use, and recording information in diaries

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/NonprescriptionDrugsAdvisoryCommittee/UCM327162.pdf

Oxytrol: Approved January 25, 2013


Primary endpoint: Rate of incorrect use based on % who did not stop when any of the following occurred:

New symptom that did not fit use criteria

Worsening symptoms

New symptom where physician call was indicated

Results

85.6% of patients correctly used based on criteria for OTC use

Final evaluation: 3.4% of users did not stop when they should have stopped use

Other criteria for appropriate use and when to discontinue also were met

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/NonprescriptionDrugsAdvisoryCommittee/UCM327162.pdf

Oxytrol: CONTROL Study

Approved to treat overactive bladder (OAB) in women

Contains oxybutynin in a transdermal delivery system

Delivers 3.9 mg/day

New patch applied every 4 days

Potential issues

Accurate diagnosis: OAB symptoms resemble other, more serious diagnoses (especially in men—benign prostatic hypertrophy) and the possibility of delaying another diagnosis with similar symptoms

Adverse events (primarily anticholinergic)

Available fall 2013

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm336815.htm

Oxytrol

History and where we are now Center for Reproductive Rights filed a lawsuit against the FDA and

Sebelius seeking expanded access to emergency contraception

American Academy of Pediatrics recommended increased access to emergency contraception for teenagers independent of age; they also said more insurance companies should cover the cost of this therapy

April 5, 2013: Federal judge ruled FDA overstepped its bounds by limiting age

April 30, 2013: FDA lowers age limit to age 15 years for OTC purchase

May 14, 2013: Federal judge maintains that ruling stands

June 20, 2013: FDA drops plans for lawsuit and approves use for all women of child‐bearing age

Available for sale in multiple retail outlets

Plan B One‐Step (levonorgestrel)

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm358082


Other OTC Product Changes and New Products

X‐PEL anti‐lice shampoo and conditioner

Pepto‐Bismol To‐Go

Dramamine Motion Sickness Relief for Kids

St. Joseph cough/cold/flu and infants’ gas relief products

Bayer Products

Migraine

Advanced Aspirin (ASA)

Headache Relief

OTC Product Safety ConcernsEnergy Drinks

Over 90 reports of adverse events, including 13 deaths, reported with 5‐Hour Energy products

Legislators concerned about energy drinks, caffeinated beverages, and stimulant products

FDA Commissioner met with a group and stated the FDA is exploring ways to “protect vulnerable populations against high levels of caffeine in energy drinks”

Concern about possibly deceptive ads—discussing this with the Federal Trade Commission

FDA Adverse Event Reports Related to Energy Drinks: November 2012


Adverse events could be the trigger issue leading to more general review of Dietary Supplement Health and Education Act

Monster: Announced plans to change labeling from “supplements” to “conventional foods”

Not subject to supplement good manufacturing practices (GMPs) or reporting of serious adverse effects (AEs)

Will disclose caffeine content in all products

American Beverage Association recommends all energy drinks should identify caffeine content on product labels

FDA Adverse Event Reports Related to Energy Drinks: November 2012

OTC Products on the Horizon

Pending New Products and Possible Rx‐to‐OTC Switches

Nexium (esomeprazole)

Pfizer now has the rights to an OTC version

Currently: only considering 20 mg

No plans to require review by an FDA Advisory Committee (since Prilosec was initially approved for OTC sale, no others have required committee review)

Good chance this will be approved

Target market will be loyal users of prescription Nexium


● OTC contraception

American Congress of Obstetricians and Gynecologists

Statement in Nov 2012 supporting increased access—saying the risks and public health costs of unintended pregnancy were greater than the safety issues

Many factors need to be considered

Process to achieve the switch

Which products

How available

Coverage—will insurance cover once OTC?

Pending New Products and Possible Rx‐to‐OTC Switches

Emerging Research for Existing OTC Products

Purpose

Determine the impact of long‐term daily ASA use on cancer mortality

Population Characteristics

100,139 men and women with no history of cancer (Cancer Prevention Study II Nutrition Cohort) from 1997–2008

Predominately white

24% reported using ASA daily

46%: low‐dose ASA

54%: adult‐strength ASA

Jacobs EJ et al. J Natl Cancer Inst. 2012;104:1208–17.

New Research on ASA: Study #1Impact on Cancer Mortality


Results 5,138 patients died from cancer (1997–2008)

Daily ASA use (at baseline vs. no use): slight ↓ cancer mortality

<5 years of use: relative risk (RR) = 0.92; 95% confidence interval (CI), 0.85–1.01

≥5 years of use: RR = 0.92; 95% CI, 0.83–1.02

Associa on between recent daily ASA use and ↓ cancer mortality?

Limitations Differences in characteristics between groups

Mix of baby ASA and full‐strength ASA

Risk of adverse effects outweigh small benefit?

Jacobs EJ et al. J Natl Cancer Inst. 2012;104:1208–17.

New Research on ASA: Study #1Impact on Cancer Mortality

New Research on ASA: Study #2

Enteric coating and ASA absorption: Is there an association between coating and response?

Unknowns

What is the incidence of ASA resistance?

What is the mechanism of ASA resistance?

Researchers set out to identify possible mechanism for ASA resistance

Grosser T et al. Circulation. 2013;127:377–85.

New Research on ASA: Study #2 Methods and Results

400 subjects: 325 mg ASA—enteric coating (EC) or immediate‐release (IR) formulation

Measured COX‐1 activity to evaluate response

If NO response, retested with other formulation

If still NO response, retested with ASA 81 mg + clopidogrel 75 mg daily x 1 week

Approximately 50% taking 325 mg EC ASA appeared to have ASA resistance vs. no resistance with IR product

Subsequent analysis Issue was not resistance but was related to type of ASA used and timing of

administration



New Research on ASA: Study #2

Data suggest IR is better to ensure absorption, and ultimately for therapeutic benefit of antiplatelet activity

What have we learned?

For patients taking only ASA for secondary prevention, IR may be the best formulation to better ensure desired response

Many patients taking ASA through OTC purchases

Initiate dialogue with patients who you think might be using ASA


New Research on ASA: Study #3Are women who should be taking ASA as a preventive measure actually taking ASA?

Survey results:

41% of women who met criteria for primary prevention

48% of women who met criteria for secondary prevention

2004 to 2009:

Significant increase in use for primary prevention

No change in use for secondary prevention

Rivera CM et al. J Women’s Health. 2012; 21:379–387.

Risk of NSAID Use Following MI: Danish Study

Danish researchers investigated potential CV risk with NSAID use in patients post initial myocardial infarction (MI)

Determined incidence rates of CV death or nonfatal recurrent MIs due to use of NSAIDs

Patients assessed annually for up to 5 years

99,187 patients evaluated

43,608 (44%) were prescribed NSAIDs after initial MI

Olsen A‐MS et al. Circulation. 2012;126:1955–63.


Risk of NSAID Use Following MI:Danish Study

Results:

36,747 deaths (out of the 99,187 followed)

28,693 of these were either:

Coronary deaths or nonfatal recurrent MIs during the 5 years of follow‐up

Association between increased risk of death and use of any NSAID in the years following MI:

Hazard ratio (HR) 1.59 (95% CI, 1.49–1.69) after 1 year

HR 1.63 (95% CI, 1.52–1.74) after 5 years

Also an increased risk of coronary death or nonfatal recurrent MI:

HR 1.30 (95% CI, 1.22–1.39) after 1 year

HR 1.41 (95% CI, 1.28–1.55) after 5 years


Risk of NSAID Use Following MI:Danish Study

● Conclusions

There is an increased coronary risk with NSAID use post‐MI, regardless of the timeframe after the initial event

● How can we apply these data?

Counsel patients who are post‐MI to avoid NSAIDs


NSAIDs + Antihypertensive = Risk of Acute Renal Damage?

Patients with HTN often use NSAIDs for certain conditions

Certain antihypertensives have hemodynamic effects on the kidney

Angiotensin converting enzyme (ACE) inhibitors, angiotensinII receptor antagonists (ARB), diuretics

Retrospective analysis in the U.K. evaluated risk of NSAIDs + antihypertensives on acute kidney damage

490,000 users of antihypertensive drugs included

Mean follow‐up 5.9 years

Lapi F et al. BMJ. 2013;346:e8525.



Results

● >2,200 cases of kidney injury were identified

● Double therapy (NSAID + either diuretic, ACE inhibitor, or ARB) = no increased risk of kidney damage compared with antihypertensive alone

● Triple therapy (NSAID + diuretic + ACE inhibitor or ARB) = increased risk of kidney damage compared with antihypertensive without an NSAID (RR = 1.3)

● Greatest risk observed during the first 30 days of triple therapy

Lapi F et al. BMJ. 2013;346:e8525.


● Combining the following effects likely results in

increased risk for kidney injury

Diuretics cause volume contraction

ACE inhibitors and ARBs cause renal efferent arteriole dilatation

NSAIDs cause renal afferent arteriole constriction

How to apply these data?

Counsel patients taking combination antihypertensive therapy to avoid NSAIDs

If using NSAID, should be under physician supervision

Lapi F et al. BMJ. 2013;346:e8525.

No Coughee, No Sneezy, But Accidental Pee Pee

Antihistamines and urinary incontinence (UI)

Examined incidence of urinary incontinence in men and women using various classes of medications

OTC products evaluated included: Second‐generation antihistamines (fexofenadine and loratadine)

NSAIDs (ibuprofen and ASA)

Various GI medications (H2RA and PPIs)

Overall incidence of UI

Women: 9%; Men: 4.6%

Average age in patients with UI higher (women: 53.3 vs. 48.1; men: 52.2 vs. 46.3; P <0.01 for both)

Hall SA et al. J Urol. 2012;188:183–9.


Comorbid conditions in each study group

Women with UI had statistically higher incidence of:

DM, elevated cholesterol, HTN, asthma, arthritis, depression, obesity, larger waist circumference, at least 1 child delivered vaginally, taking prescription drugs

Men with UI had statistically higher incidence of:

Depression



UI prevalence statistically higher in women using the following classes of OTC medications:

Antihistamines: 28.4% (fexofenadine and loratadine included in group that also included cyproheptadine and desloratadine)

NSAIDs:

15.8% (ASA)

7.8% (carboxyl‐propionic NSAIDs such as ibuprofen)

H2RA: 13.9%

PPIs: 20.5%



Proposed mechanism

H1 activation in the urethra results in contraction bladder outlet relaxation increased chances of stress incontinence when patient coughs or sneezes BINGO

However…just the act of coughing or sneezing can increase abdominal pressure which, in itself, could cause the same effect

Be wary of patients purchasing OTC antihistamines and the new Oxytrol (oxybutynin) patch!




Background

Millions of people use multivitamins (MV) with the hope that MV will make them healthier

Why are people taking MV?

Supplement lack of proper nutrition

Estimated >30% of American adults use MV regularly

Observational studies have suggested possible association between MV use and CV benefits

Sesso HD et al. JAMA. 2012;308:1751–60.

Multivitamins: Physicians’ Health Study II—CV Arm

Physician’s Health Study (PHS) II was a large trial to evaluate possible benefits of MV supplementation in preventing the development of cardiovascular disease (CVD)

MV used: Centrum Silver

Population: Male physicians aged 50 years and older

Study design: Randomized, double‐blind, placebo‐controlled

Median follow‐up: 11.2 years

Primary endpoint: Major CV events, including non‐fatal MI, non‐fatal stroke, CVD mortality

Secondary endpoints: Total stroke and total MI


Multivitamins: Physicians’ Health Study II—CV Arm

Baseline characteristics of patients

Average age: 64 years

Similar numbers of individuals in treatment and placebo groups for the following:

HTN (~42%)

Rates of routine exercise (~62%)

% Cigarette smokers (~3.6%)

Incidence of DM (~6%)

Self‐reported CVD (~5%)

Incidence of dyslipidemia (~36%)

Current ASA use (~77%; probably carryover from PHS I study)

Food intake (servings of fruits, vegetables, grains, and red meat daily)


Multivitamins: Physician’s Health Study II—CV Arm


Results

No benefit in those taking MV regarding:

Major CV events: HR 1.01; 95% CI, 0.91–1.10

CVD mortality: HR 0.95; 95% CI, 0.83–1.09

Similar data regarding secondary outcomes, except:

Lower incidence of MI deaths in patients taking MV

HR 0.61; 95% CI, 0.38–0.995; P = 0.048

Authors attribute this to chance with no further comment

No significant differences in adverse events



What did we learn?

Based on these data, this particular MV provided no CV benefit in this population

Should not try to apply these data to other populations

Nutritional status and medication regimen could have (and probably) contributed to results

This study continually gets lots of press—educate patients

Patients must understand potential benefits and risks, and what their $$$ will provide when purchasing and using MV



Evaluated role of MV consumption and cancer risk reduction potential

Same patient population

Second arm of the study

Results Men taking MV had a significantly lower overall incidence of cancer (8%)

HR 0.92; 95% CI, 0.86–0.998; P = 0.04

Men with family history of cancer did not benefit

HR 1.05, 95% CI; 0.94–1.17; P = 0.37

Men with no family history showed benefit

HR 0.86, 95% CI; 0.76–0.98; P = 0.02

Multivitamins: Physician’s Health Study II—Cancer Arm

Gaziano JM et al. JAMA. 2012;308:1871–80.


No difference in any of the following:

Incidence of specific types of cancer, such as prostate, colorectal, or other site‐specific cancers

Incidence of mortality from cancer

HR 0.88; 95% CI, 0.77–1.01; P = 0.07

Authors point out that a majority of cancers identified were prostate (low‐grade, high‐survival type), and during study period there was increased use of PSA screening



What did we learn and what questions still need to be answered?

MV may provide benefit in overall development of cancer

Is this benefit due to a particular ingredient or combination of ingredients?

Were these patients generally healthy initially, and if so, how does that affect the data?

Not all MVs are the same!

Educate patients

Do not rely solely on MV for cancer prevention; multifactorial, complex issue involving many aspects, including lifestyle, genetics, etc.



Omega‐3 Fatty Acids: #1

● Background

A few professional societies recommend certain patients take omega‐3 fatty acids (FA)

American Heart Association Nutrition Committee and European Society of Cardiology

FDA: Only approved use is for lowering triglycerides (TGs) in patients with overt hypertriglyceridemia (TG >500 mg/dL)

Prescription products: Lovaza and Vascepa

Proposed benefit: Decrease TGs, reduce platelet aggregation, lower BP, prevent arrhythmias

Rizos EC et al. JAMA. 2012;308:1024–33.



Review and analysis designed to determine association between use of omega‐3 FA and certain CV outcomes

20 trials included; total 68,680 patients

Excluded studies where patients used product <1 year

18/20: Supplements

2/20: From diet

Average duration of use: 2 years



5 outcomes reviewed:

Cardiac mortality

Sudden death

MI

Stroke

All‐cause mortality



Results: No statistically significant benefit from omega‐3 FA for any of the 5 outcomes:

Cardiac mortality (n = 13): RR = 0.91; 95% CI, 0.85–0.98

Sudden death (n = 7): RR = 0.87; 95% CI, 0.75–1.01

MI (n = 13): RR = 0.89; 95% CI, 0.76–1.04

Stroke (n = 9): RR = 1.05; 95% CI, 0.93–1.18

All‐cause mortality (n = 17): RR = 0.96; 95% CI, 0.91–1.02



Omega‐3 Fatty Acids: #1 What have we learned?

Omega‐3 FA did not provide any statistically significant benefit for the 5 outcomes evaluated

Data consistent with other similar reviews and analyses

Patients will most likely continue to use these products based on manufacturer and media claims (and neighbor testimonial!)

Studying effect of each FA ingredient (EPA, DHA) may shed more light on this topic

Certain patients are candidates for the prescription version



Goal

Evaluate possible benefit of n‐3 FA in preventing CV events in patients with DM

Enrolled 12,536 patients

All had DM, impaired glucose tolerance (GT) or elevated fasting blood glucose (BG)

All at risk for CV event

Randomized to receive 1 g daily of n‐3 FA supplement or placebo (1 g olive oil)

ORIGIN Trial Investigators. N Engl J Med. 2012;367:309–18.

Omega‐3 Fatty Acids: #2 Evaluated patients more frequently earlier in the study, then every 4 months

Dietary recommendations not made but evaluated using food frequency questionnaire

Each group had similar percentage of patients based on CV history, use of tobacco, age, incidence of HTN

Median dietary intake of EPA or DHA was 210 mg daily




Results

Median follow‐up: 6.2 years

No significant difference in total deaths from any CV cause

Patients using omega‐3 FA: 9.1%

Patients using placebo: 9.3%

HR 0.98; 95% CI, 0.87–1.10; P = 0.72



No effect on major CV events

16.5% vs. 16.3%

HR 1.01; 95% CI, 0.93–1.10; P = 0.81

Omega 3 FA reduced TG average of 14.5 mg/dL

No difference in adverse events

Excellent adherence rates

Average 88% at end of the trial


Omega‐3 Fatty Acids: #2 What have we learned?

Dose was 25% of prescription dose: Would a higher dose have made a difference?

In this study more patients were using CV medications

ACEs, ARBs, antiplatelets, beta‐blockers, statins: Would this affect results?

Data similar to JAMA study

Could patients who start omega‐3 FA sooner after a CV event see more benefit?

Are patients with DM different?

Still little quality research to support recommending OTC omega‐3 FA to prevent CV events



Cranberry: Not Just Any Old Berry?

Background

Almost half of all women will have at least one urinary tract infection (UTI) in their lifetime

Recurrence fairly common

Cranberry has been used as a folk remedy for decades

Possible reason for benefit

Prevent bacterial adhesion to uroepithelial cells

Compound in cranberry, proanthocyanidins, inhibits E. colifrom binding to mucosa within urinary tract

Wang C‐H et al. Arch Intern Med. 2012;172:988–96.

Results

13 trials (total 1,616 patients) analyzed

9 used juice form

4 used capsules and tablets

Variable dosing: 0.4 to >190 grams daily

Most patients used for >6 months

Researchers used varying definitions for UTI (different cutoffs for bacteriuria, pyuria, symptoms)

Adherence with cranberry difficult to assess



Quantitative analysis: 10 trials, significant heterogeneity

When data limited to studies with lower heterogeneity:

Cranberry benefits: RR = 0.62; 95% CI, 0.49–0.80

Protective effects much more pronounced in non‐placebo trials

Greater benefit seen in:

Women with history of UTIs

Female patients

Children

Individuals using the juice formulation

Patients taking cranberry more than twice daily




Why is the juice more effective?

Fluid status better?

Additional ingredients that work synergistically?

Why greater benefit using more than twice daily?

Anti‐adhesion properties shown to last approximately 8 hours

Cautions: Glucose content of the juice increased GI upset



What have we learned?

Cranberry in whatever form may offer benefit in preventing UTIs

Formulation probably has an effect

Number of doses per day probably has an effect

Minimal risk except for patients with DM

Use juice with caution due to sugar content



PubMed search April 30, 2013:

5 references when searching for raspberry ketone (RK) andweight

4/5 are in vitro studies

Most recent publication: RK was one of many ingredients in a weight loss product

Structure of RK is similar to capsaicin and synephrine Shown to possess anti‐obesity actions and affect the lipid metabolism

Studies in rodents have demonstrated anti‐obesity actions as well as improved lipid parameters and a positive effect on hepatic cells

Raspberry Ketones and Weight Loss


Interesting finding…

Bulbophyllum apertum flower (Orchidaceae) releases RK in its fragrance, which attracts males of several fruit fly species belonging to the genus Bactrocera

If you see anyone with fruit flies buzzing around them, perhaps they are using raspberry ketones?!

Keng‐Hong T et al. J Chem Ecol. 2005;31:497–507.


Safety unknown

Similar structure to synephrine

Use with caution in patients with CVD

Instead of using raspberry ketones, follow other suggestions:

Eat a well‐balanced diet and exercise!


Previous studies have demonstrated a positive metabolic effect of chocolate

Improvement in BP, cholesterol

Observational study in 2006

Relationship between chocolate and lower CV and all‐cause mortality (based on metabolic syndrome factors)

Contains phytonutrients with antioxidant properties

Authors hypothesized benefits of chocolate could offset negatives and net result would be positive effect on body mass index (BMI)

Golomb BA et al. Arch Int Med. 2012;172:519–21.

Chocolate: Not Just a Topping for Your Sundae


1,017 individuals enrolled in evaluation

975 completed questionnaire regarding frequency of chocolate consumption/week

Each had BMI based on data provided during screening meeting

Other factors evaluated:

Intake of what are commonly considered “healthy” foods (e.g., fruits and vegetables)

Frequency of vigorous exercise

Subject’s mood using the Center for Epidemiologic Studies Depression scale (CES‐D)



Results

Average chocolate consumption: twice weekly

Average number of times exercising: 3.6 x/week

No relationship between chocolate consumption and intake of fruits and vegetables (P = 0.55)

Saturated fat intake related to chocolate consumption and higher BMI (P <0.001)

Frequency of chocolate consumption significantly related to:

Increased calorie intake, increased saturated fat intake, higher CES‐D scores (P< 0.01)

Lower BMI (P = 0.01)



No data on overall diet, although each subject completed a questionnaire about food frequency

Unable to determine other potential confounding factors

Medications, supplements, type of chocolate, serving size

What do these data mean?

We all need to consume chocolate at least twice a week?

Chocolate‐covered strawberries should become one of the major food groups?





Proton Pump Inhibitor Updates

Clopidogrel Interaction

Study design: Observational cohort study and self‐controlled case series

Objective: Determine the relationship between use of PPIs and harmful outcomes in patients using clopidogrel and ASA

Population: 24,471 patients (clopidogrel + ASA)

Primary outcome: Death or MI

Douglas IJ et al. BMJ. 2012;345:e4388.


Results

12,439 patients (50%) also were receiving PPI therapy

Primary outcome occurred in 1,419 (11%) patients while receiving PPI vs. 1,341 (8%) who did not receive PPI therapy

Similar trend seen for medications that are non‐CYP2C19 inhibitors



Limitations

PPI users were on average 2 years older

PPI users more commonly had DM (34% vs. 29%), peripheral vascular disease (PVD) (12% vs. 11%), and cancer (15% vs. 13%)

Difference due to population differences (PPI vs. non‐PPI users) rather than true difference?

Limitation of database recording of events

Conclusion from authors

“…the drug interaction…does not result in clinical harm”



Safety label change

Approved by FDA CDER

Oct 2012—esomeprazole, omeprazole, and naproxen/ esomeprazole

Nov 2012—added omeprazole/sodium bicarbonate

Update to Warnings and Precautions section

“Avoid concomitant use of esomeprazole/omeprazole” with clopidogrel

Update to Drug Interactions section

“Concomitant use…results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition”

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm327922.htm



Feb 2012—FDA safety communication

PPIs may be associated with increased risk of Clostridium difficile–associated diarrhea (CDAD)

C. difficile diagnosis should be explored if patient on PPI has unresolved diarrhea

FDA also evaluating H2 blockers

Adverse Event Reporting System

Most common in elderly; had underlying conditions or were taking broad‐spectrum antibiotics

Review of observational studies

Majority showed higher risk of C. difficile with PPI exposure

Strength of association varied

Limited data on dose and duration relationships

http://www.fda.gov/Drugs/DrugSafety/ucm290510.htm

Clostridium difficile–Associated Diarrhea

Safety label change: Approved by FDA CDER

Update to Warnings and Precautions section

“Published observational studies suggest that PPI therapy may be associated with an increased risk of CDAD, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (6.x)].”

“Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.”

http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm335421.htm

Clostridium difficile–Associated Diarrhea

Smoking Cessation Updates


CDC: Cigarette Smoking Among Adults in 2011

Tobacco use remains the leading cause of preventable death/disease in United States

443,000 U.S. adult deaths from smoking‐related illnesses per year

$96 billion in direct medical expenses; $97 billion in lost productivity

Prevalence remained steady from 2010–2011 (19.3% vs. 19.0%)

Prevalence highest among: American Indian/Alaskan natives (32%)

Individuals who did not graduate from high school (26%)

Living below the poverty level (29%)

Healthy People 2020 target is 12%

CDC. MMWR Morb Mortal Wkly Rep. 2012;61:889–94.

Mobile Phone Interventions Objective

Assess effectiveness of mobile phone–based interventions for smoking cessation

Study inclusion

Randomized or quasi‐randomized trials

Smokers of any age interested in quitting

Any type of mobile phone–based intervention

Results

5 studies with ≥6 month cessation outcomes (>9,000 participants)

3/5 = texting only

1/5 = text messaging vs. Internet application

1/5 = video messaging

Pooled result: RR = 1.71; 95% CI 1.47–1.99

Whittaker R et al. Cochrane Database Syst Rev. 2012;11:CD006611.

Impact on Life Span Population: U.K. women (1.2 million)

Objective: Determine effects of smoking (and cessation) on mortality

Methods: Recruitment (1996–2001) with follow‐up surveys approximately 3 and 8 years later

Followed via national mortality records

Survey obtained information at baseline about smoking status, number of cigarettes, etc.

Pirie K et al. Lancet. 2013;381;133–41.


Impact on Life Span

Results 20% at baseline were current smokers, 28% ex‐smokers, 52% non‐

smokers

Smokers at baseline had a mortality rate ratio of 2.76 (95% CI, 2.71–2.81) vs. non‐smokers although 44% of baseline smokers quit by 8‐year follow‐up survey

Ex‐smokers who quit at ages 25–34 years or 35–44 years had RR = 1.05 and RR = 1.20 for all‐cause mortality, respectively

When combined with 2010 U.K. national death rates, mortality rates tripled

53% of smokers dying before age 80

22% of non‐smokers dying before age 80

11‐year life span difference

Pirie K et al. Lancet. 2013;381;133–41.

Impact on Life Span

Population: Japanese adults (27,311 men and 40,662 women) smoking status obtained between 1963–1992

Objective: Determine impact of smoking on mortality and life expectancy

Determined mortality from 1 year after first obtaining smoking status until January 1, 2008

Main outcome: Mortality for any cause in current, former, and never smokers

Sakata R et al. BMJ. 2012;345:e7093.

Impact on Life Span

Results Older smokers tended to smoke more and started earlier

Born between 1920–1945

Mortality almost double for men and women (rate ratio of 1.89 and 1.81, respectively) vs. never smokers

Regardless of period of birth and sex, mortality rate ratios were highest among those starting before age 20

Earlier the cessation, the higher the benefit

Life expectancy ↓ by 8 years for men and 10 years for women

Sakata R et al. BMJ. 2012;345:e7093.


Impact on Weight Gain

Design: Meta‐analysis

Objective: Evaluate weight gain in smokers who achieve cessation for up to 12 months

Results

62 studies

“Untreated quitters”

2.5 lb, 5 lb, 6.3 lb, 9.3 lb, and 10.3 lb mean weight gain at 1, 2, 3, 6, and 12 months after quitting

At 12 months, 16% lost weight, 37% gained <11 lb, 34% gained <11–22 lb and 13% gained >22 lb

Weight gain estimates similar for those using medications to quit

Most weight gain occurred within 3–6 months of cessation

Aubin HJ et al. BMJ. 2012;345:e4439.

Miscellaneous OTC News

Safe Use Initiative: Acetaminophen Concern: Liver injury from acetaminophen overuse or overdosing

Cause: Overuse of single ingredient product or overuse by using multiple products with acetaminophen

White paper titled NCPDP Recommendations for Improved Prescription Container Labels for Medicines Containing Acetaminophen by the National Council for Prescription Drug Programs

Goals: Make it easier for patients to:

Identify their prescription contains acetaminophen

Compare active ingredients on prescription and OTC products

Take steps to avoid taking two medications containing acetaminophen

http://www.ncpdp.org/pdf/NCPDPacetaminophenWPfinal02Aug2011.pdf


Safe Use Initiative:Acetaminophen Toxicity

● Key Recommendations1. Full spelling of acetaminophen and all active ingredients on

pharmacy labels

2. Concomitant use and liver warning labels

Develop standard concomitant use and liver warning label

Adopt a hierarchy for key messages on warning label

Remove warning labels with similar messages

3. Prioritize standard warning label to increase chance it will be applied to containers

4. Icons can be used on warning labels if they improve patient understanding

5. General health literacy and plain language principles should be used on labels

http://www.ncpdp.org/pdf/NCPDPacetaminophenWPfinal02Aug2011.pdf

Potential New Nonprescription Paradigm

Paradigm will have “conditions of safe use”

FDA is considering a significant paradigm shift by making more medications to manage chronic diseases available through “new” channels

Large number of individuals with certain chronic diseases do not, for whatever reason, have access to medications

Has implications for potential future switches

http://www.gpo.gov/fdsys/pkg/FR‐2012‐02‐28/pdf/2012‐4597.pdf

Conditions being considered

Some kinds of high blood pressure

DM

Asthma

High cholesterol

Migraine headaches

Insomnia

http://www.gpo.gov/fdsys/pkg/FR‐2012‐02‐28/pdf/2012‐4597.pdfThe Tan Sheet. January 7, 2013;1:4–5.



Key issues

Does offering certain medications in a new paradigm provide an opportunity to improve outcomes?

Access

What does this mean for the practice of pharmacy, medicine, or other providers? Relationships among all?

Who has authority to make various decisions?

What to do about generics?

What is the role of technology?

Use technology to determine candidates (device + drug)



Other key issues

Is pharmacy prepared for this?

If not, what would it take to become prepared?

Where else might these products be made available?

What qualifications are necessary to be a “player”?

What will the expectations be for all the players?

What business models are possible?

What legislative issues need to be addressed?



Is pharmacy prepared for this?

Certain organizations believe pharmacists need to play a critical role (APhA, NACDS)

Some large chains have stated importance of pharmacists (Walmart, CVS)

Expressed some concerns mentioned previously and others, including: Pharmacist training and time

Space in the store, resources to provide patient education, counseling

Payment

The Tan Sheet. June 18, 2012; article #05120611008.



Update: January 7, 2013 “The Tan Sheet”

New paradigm has a name: NSURE

Nonprescription Safe Use Regulatory ExpansionFDA noted: This is not an initiative to create a third class of drugs

The Tan Sheet. January 7, 2013;1:4–5.


Stay tuned and follow this issue closely

Potential significance is huge

APhA is monitoring Check the website www.pharmacist.com periodically for updates

http://www.gpo.gov/fdsys/pkg/FR‐2012‐02‐28/pdf/2012‐4597.pdf


Do Our Patients Listen to Us When We Make an OTC Recommendation? Recent evaluation of a follow‐up program for OTC

consults in community pharmacy

2 pharmacies—pharmacist and student recommendations for OTC products

During interaction, patients received:

Detailed counseling (staff tracked this on a form)

Point‐of‐care survey

An offer for a follow‐up call

Follow‐up survey

Bosse N et al. J Am Pharm Assoc. 2012;52:535–40.


Authors measured the following:

Patient surveys evaluating perceived benefit of recommendation

Documentation of possible drug therapy problems

Follow‐up surveys regarding response, adherence, and satisfaction

Do Our Patients Listen to Us When We Make an OTC Recommendation?


Results 83/207 patients agreed to a follow‐up call

1 call made to 54/83 patients

9/83 patients received 2 calls

82.6% of patients who received 1 call and completely adhered to regimen had “great symptom relief”

>75% stated they felt follow‐up was “very helpful,” resulted in improved symptom relief, and suggested this service be offered routinely

So maybe people do listen!

Do Our Patients Listen to Us When We Make an OTC Recommendation?


Key Points

We are being inundated with new products and research related to OTC medications (e.g., ASA, NSAIDs, PPIs) and must take an active role to evaluate the literature to be able to field patient questions and make appropriate recommendations

Several patient safety concerns and recalls took place in 2012: Are you getting this news?

There is emerging news regarding safety concerns related to PPIs


Key Points

Smoking cessation news from the CDC gives us further tools to educate our patients

The new nonprescription paradigm with “conditions of safe use” is emerging—stay tuned!

Questions?

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Documents

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