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Healthy Weight: Pharmacist-Focused Strategies for

Optimizing Management of Obese Patients

Jennifer Costello, PharmD, BCPS, BC-ADM Ambulatory Care Clinical Pharmacist Internal Medicine Faculty Practice

Saint Barnabas Medical Center Livingston, NJ

Faculty Information Presenter:

Jennifer Costello, PharmD, BCPS, BC-ADM Ambulatory Care Clinical Pharmacist Internal Medicine Faculty Practice Saint Barnabas Medical Center Livingston, New Jersey Moderator:

Elena Beyzarov, PharmD Director of Scientific Affairs Pharmacy Times Office of Continuing Professional Education Plainsboro, New Jersey

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Disclosures

Jennifer Costello, PharmD, BCPS, BC-ADM, has no financial relationships with commercial interests to disclose.

Pharmacy Times Office of Continuing Professional Education

Planning Staff—Judy V. Lum, MPA, Elena Beyzarov, PharmD, and Donna W. Fausak—have no financial relationships with commercial interests to disclose.

The contents of this webinar may include information regarding the use of products that may be inconsistent with or outside the approved labeling for these products in the United States. Pharmacists should note that the use of these products outside current approved labeling is considered experimental and are advised to consult prescribing information for these products.

Objectives

Describe epidemiology, pathophysiology and medical consequences relating to obesity

Explore current pharmacologic therapy used in the management of obesity

Discuss comprehensive strategies linking weight reduction to specific clinical outcomes

Formulate patient counseling strategies incorporating lifestyle modifications and pharmacologic treatment for obese patients

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Healthy Weight: Pharmacist-Focused Strategies for

Optimizing Management of Obese Patients

Jennifer Costello, PharmD, BCPS, BC-ADM Ambulatory Care Clinical Pharmacist Internal Medicine Faculty Practice

Saint Barnabas Medical Center Livingston, NJ

State of Obesity: History of Prevalence

Prevalence of obesity

among U.S. adults.

Accessed 4/8/2013 at

facts

http://www.cdc.gov/obesit

y/data/adult.html

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Epidemiology of Obesity

In 2010, more than one-third of U.S. adults (35.7%) and approximately 17% (or 12.5 million) of children and adolescents considered obese

Obesity prevalence did not differ between men and women

World Health Organization (WHO) projecting worldwide disease burden of 2.5 billion overweight adults and 700 million obese adults by 2015

Centers for Disease Control and Prevention

World Health Organization. Obesity and overweight fact sheet. 2006. http://www.who.int/mediacentre/factsheets/fs311/en/index.html.

Medical Costs

In 2008, medical costs associated with obesity estimated at $147 billion – Medical costs for people who are obese were $1,429

(roughly 42%) higher than those of normal weight

– Medical burden of obesity has increased from 6.5% to 9.1% of annual medical spending

Centers for Disease Control and Prevention

World Health Organization. Obesity and overweight fact sheet. 2006. http://www.who.int/mediacentre/factsheets/fs311/en/index.html.

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Physical Conditions

The following physical conditions and factors contribute to obesity: – Nutritional habits

– Sedentary lifestyle

– Genetic predetermination

– Polycystic ovary syndrome

– Hypothyroidism

– Cushing's syndrome

– Prader-Willi syndrome

NHLBI Obesity Education Initiative. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. NHLBI

Obesity Education Initiative Expert Panel on the Identification, Evaluation, and Treatment of Obesity in Adults (US).Bethesda (MD): National Heart Lung,

and Blood Institute; September 1998

Medical Consequences of Obesity

Cardiovascular disease (CVD)

Type 2 diabetes (T2DM)

Hypertension (HTN)

Dyslipidemias

Stroke

Cancers (endometrial, breast, and colon)

Liver and Gallbladder disease

Sleep apnea and respiratory problems

Osteoarthritis

Gynecological problems (abnormal menses, infertility)

NHLBI Obesity Education Initiative. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. NHLBI

Obesity Education Initiative Expert Panel on the Identification, Evaluation, and Treatment of Obesity in Adults (US).Bethesda (MD): National Heart

Lung, and Blood Institute; September 1998

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Morbidity and Mortality with Obesity

Multiple studies have shown harmful effect of obesity and excess adiposity on cardiovascular health

Obesity associated with – Increased overall mortality (OR range 1.9–2.42)

– Increased mortality after cardiovascular events (OR range 1.07–1.94).

– Increased morbidity and mortality with BMI >30 kg/m2

Data from the Prospective Studies Collaboration – Analyzed 900,000 adults

– Shown 30% increase in all-cause mortality for every increase of 5 units in BMI above BMI of 25 kg/m2

Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, Qizilbash N, Collins R, Peto R. Body-mass index and cause-

specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373:1083–1096.

Baik I, Ascherio A, Rimm EB, Giovannucci E, Spiegelman D, Stampfer MJ, Willett WC. Adiposity and mortality in men. Am J Epidemiol.

2000;152:264 –271.

Assessment of Obesity

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Classification of Obesity

Calculate a BMI

– BMI is primary tool for assessment of body fatness because of:

Global acceptance

Ease of calculation

– Limitations of BMI

Does not distinguish between lean and fat mass

Adults

Underweight BMI <18.5 kg/m2

Normal BMI 18.5 – 24.9 kg/m2

Overweight BMI 25 – 29.9 kg/m2

Obese BMI >30 kg/m2

Class 1 (Mild) BMI 30 – 34.9 kg/m2

Class 2 (Moderate) BMI 35 – 39.9 kg/m2

Class 3 (Severe) BMI >40 kg/m2

Adapted from Poirier P, Alpert MA, Fleisher LA, etal. Cardiovascular evaluation and management of severely obese

patients undergoing surgery: a science advisory from the American Heart Association. Circulation. 2009;120:86 –95.

Waist Circumference

Waist circumference (WC) has been shown to be simple, inexpensive and effective way to assess for central obesity – Should be measured, along with BMI assessment

WC has high association with CVD risk and mortality – As a result, definitions of metabolic syndrome have adapted WC

as surrogate marker of abdominal or central obesity

Measurement of WC not recommended for individuals with BMIs ≥35 – Measurement may lose predictive power if BMI extremely

elevated

U.S. Department of Health and Human Services, NIH-NHLBI. The practical guide: Identification, evaluation, and treatment of overweight and

obesity in adults. NIH publication no. 00-4084. Bethesda, MD: National Institutes of Health, 2000

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Determining High Risk Patients

Patients at high absolute risk for obesity-related disorders are those who present with 3 or more of the following risk factors: – Cigarette smoking

– Hypertension

– Elevated low-density lipoprotein (LDL) cholesterol

– Decreased high-density lipoprotein (HDL) cholesterol (<35 mg/dL),

– Impaired fasting glucose (glucose between 100-125 mg/dL),

– Family history of premature CHD

The presence of high absolute risk requires intensive cholesterol and blood-pressure management

U.S. Department of Health and Human Services, NIH-NHLBI. The practical guide: Identification, evaluation,

and treatment of overweight and obesity in adults. NIH publication no. 00-4084. Bethesda, MD: National

Institutes of Health, 2000

Assessing Adiposity

Assessing total body fat mass, distribution of body fat, and body composition (percent body fat)

Adiposopathy ('sick fat') describes pathogenic adipose tissue dysfunction that may be promoted and/or exacerbated by fat accumulation (adiposity)

Adipocyte and adipose tissue changes created by positive caloric balance and sedentary lifestyle in genetically and environmentally susceptible patients – Pathophysiologically, these abnormalities may lead to adverse

adipose endocrine and immune responses that contribute to metabolic disease

Bays, H, Blonde, L ad Rosenson, R. Adiposopathy: how do diet, exercise and weight loss drug therapies improve

metabolic disease in overweight patients. Expert review of cardiovascular therapy. November 2006, Vol. 4, No. 6, Pages

871-895

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Body Shape Matters

Complications of obesity (eg, insulin resistance, dyslipidemia, T2DM, CVD) more closely related to distribution of body fat than to absolute degree of fat

“Gynoid” obesity – Low risk for adiposity – More frequently found in women

“Android” obesity – High-risk form of obesity – More frequently found in men – Central obesity, 'beer-gut' obesity

Amytis Towfighi and Paul Poirier Klein, Benoit Lamarche, Francisco Lopez-Jimenez, Goutham Rao, Marie-Pierre St-Onge, Marc-Andre Cornier, Jean-

Pierre Després, Nichola Davis, Daurice A. Grossniklaus, Samuel. Assessing Adiposity : A Scientific Statement From the American Heart Association

Circulation. 2011;124:1996-2019

Pictures from uncyclopedia.wikia.com

Impact of weight loss on comorbidities

Initial treatment goal for obesity is 10% reduction in weight over 6 months – Weight loss should occur at approximately 1-2

pounds/week for period of 6 months – Individualized diet planned to create deficit of 500 to

1,000 kcal/day

– Patients may see 15% reduction in LDL, 30% reduction in triglycerides, 8% increase in HDL

– In patients with prediabetes, losing 7% of body weight can delay and possibly prevent diabetes

– Weight maintenance program priority after initial 6 months of weight-loss therapy

Clinical Guidelines on the Identification, Evaluation and Treatment of Overweight and Obesity in Adults: Evidence Report. Oves Res. 1998 Sep;6 Suppl 2:51S-209S. U.S. Department of Health and Human Services, NIH-NHLBI. The practical guide: Identification, evaluation, and treatment of overweight and obesity in adults. NIH publication no. 00-4084. Bethesda, MD: National Institutes of Health, 2000

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Exercise

More than 50% of U.S. adults do not get recommended levels of physical activity 60 – 90 minutes daily – Although 30 minutes of exercise/day associated with

cardiovascular and metabolic benefit, longer duration targets obesity prevention

Physical activity should be part of comprehensive weight loss therapy – Modestly contributes to weight loss in overweight and obese

adults

– May decrease abdominal fat

– Increases cardiorespiratory fitness

– May help with maintenance of weight loss

U.S. Department of Health and Human Services, NIH-NHLBI. The practical guide: Identification, evaluation, and treatment of overweight and obesity in adults. NIH publication no. 00-4084. Bethesda, MD: National Institutes of Health, 2000

Role of the Pharmacist

Pharmacists should stress to patients that even moderate weight loss may be beneficial.

Communicate impact of obesity on co-morbidities and correlation with cardio-metabolic diseases (T2DM, HTN, CVD)

Pharmacists can monitor patient medication profiles to detect prescribed agents that may have potential for weight gain

Pharmacists can encourage patients to utilize long-term weight-management strategies rather than quick-fix OTC products

Goldstein DJ. Beneficial health effects of modest weight loss. Int J Obes Relat Metab Disord. 1992;16:397–415

Brahim, A, Dowden, C, Norwood, R, Haines, S. Obesity Screening and diet counseling: A buisness venture for pharmacists. Drug Topics, May 15,2010

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Pharmacologic Therapy

Potential Strategies for Anti-Obesity Drug Action

Reducing food intake

– Amplify effects of signals/factors that inhibit food intake OR block signals/factors that augment food intake

Blocking nutrient absorption

– Especially fat or carbohydrates in intestine

Modulating fat metabolism/storage

– Regulate fat synthesis/breakdown by making appropriate adjustments to food intake or energy expenditure

Ioannides-Demos LL, Piccenna L, McNeil JJ. Pharmacotherapies for Obesity: Past, Current, and Future Therapies. 2011. Journal of Obesity

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History of Pharmacologic Therapy for Obesity

Aminorex, phenylpropanolamine, rimonabant withdrawn due to various adverse effects

Sibutramine recently voluntarily withdrawn due to risks of serious cardiovascular events

Dexfenfluramine, fenfluramine (part of “Fen-Phen”—fenfluramine/phentermine)

– Recalled in 1997 Increased prevalence of valvular heart disease

Possible association with primary pulmonary hypertension

Until recently, orlistat was the only available long-term

therapy for obesity in U.S. and Europe

Ioannides-Demos LL, Piccenna L, McNeil JJ. Pharmacotherapies for Obesity: Past, Current, and Future Therapies. 2011. Journal of Obesity

Orlistat (Xenical®, Alli®)

Pancreatic lipase inhibitor blocks absorption of approximately 25-30% of ingested fat

Helps in management of obesity ONLY when used in conjunction with reduced-calorie; low-fat diet and increased physical activity

Indicated for obese patients – Initial body mass index (BMI) ≥30 kg/m2 or

– BMI ≥27 kg/m2 in presence of other risk factors (eg, DM, dyslipidemia, HTN)

Drew, B, Dixon, A, and Dixon, JB. Obesity management: Update on orlistatVasc Health Risk Manag. 2007 December; 3(6): 817–821

B. Mittendorfer, et al. Orlistat inhibits dietary cholesterol absorption. Obes Res. 2001 Oct;9(10):599-604.

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Orlistat: Efficacy Orlistat 120mg taken 3 times daily with meals

– Mean weight loss of 5 to 8.5 kg during first 6 months of therapy Orlistat + reduced-energy diet Weight plateau at approximately 6 months

– In studies extending to 48 months, mean 3 to 6 kg weight loss maintained

In addition to helping reduce weight, orlistat shown to:

– Lower plasma low-density lipoprotein (LDL) cholesterol levels

Associated with reduction in cholesterol absorption from 53% to 40%, representing 25% reduction in cholesterol absorption (P <0.05)

– Lower Hgb A1C levels in diabetic patients

Franz MJ, VanWormer, JJ, Crain Al, et al. Weight-loss outcomes: a systematic review and meta-analysis of weight-loss clinical trials with a minimum 1-year follow-up. J am Diet Assoc. 2007 Oct;107(10):1755-67.

Orlistat: Treatment Candidates

Among obese patients who meet criteria for anti-obesity drug therapy, orlistat is most likely to benefit those who:

– Do not feel hungry

– Are not preoccupied with food

– Eat out or order-in often

– Have increased CVD risk or multiple cardiovascular risk factors

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Orlistat: Adverse Effects

Because orlistat blocks intestinal absorption of fat, it may result in diarrhea and steatorrhea – Minimized by maintaining strict low-fat diet (<30% of

diet)

Loss of fat soluble vitamins, with potential for

malnutrition – Recommend daily multivitamin for all patients on

orlistat

Associated with cases of acute pancreatitis,

increased levels of urinary oxalate (cases of kidney stones), and severe liver injury

FDA Medwatch 2011

Phentermine/Extended-Release Topiramate (Qsymia®)

“PHEN/TPM”

Phentermine

– Centrally acting sympathomimetic amine structurally related to amphetamine,

– Increases norepinephrine release, and to lesser extent, dopamine release

– Causes appetite suppression, decreases food consumption – Increases heart rate secondary to increased catecholamines

Time-release topiramate

– Precise mechanism on weight unclear – May have CNS effects that increase satiety receptors that may reduce

compulsive or addictive food cravings – Topiramate’s activation of GABA receptors may also decrease night-

time and deprivation-induced feeding

Expert Rev. Cardiovasc. Ther. 8(12), 1777–1801 (2010); Khazaal Y, Zullino DF. Topiramate induced weight loss is possibly due to the blockade of conditioned and automatic processes. Eur. J. Clin. Pharmacol. 63(9),891–892 (2007); Turenius CI, Htut MM, Prodon DA et al. GABA(A) receptors in the lateral hypothalamus as mediators of satiety and body weight regulation. Brain Res. 1262, 16–24 (2009).

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PHEN/TPM Indicated for obese patients

– Initial BMI ≥30 kg/m2 or – BMI ≥27 kg/m2 in presence of other risk factors (eg, DM, dyslipidemia,

HTN)

Helps in management of obesity WHEN used in conjunction with reduced-calorie; low-fat diet and increased physical activity

Dosing – Initial: Phentermine 3.75 mg/topiramate 23 mg once daily for 14 days

– Increase dose to phentermine 7.5 mg/topiramate 46 mg once daily for 12 weeks, then evaluate weight loss

If 3% of baseline body weight has not been lost, discontinue use or increase dose to phentermine 11.25 mg/topiramate 69 mg once daily for 14 days, and then to phentermine 15 mg/topiramate 92 mg once daily

Evaluate weight loss after 12 weeks on phentermine 15 mg/topiramate 92 mg

if 5% of baseline body weight has not been lost at dose of phentermine 15 mg/topiramate 92 mg gradually discontinue therapy (eg, 1 dose every other day for at least 1 week)

QSYMIA® [package insert]. Winchester, KY: VIVUS Inc.; 2012

PHEN/TPM: Efficacy

Three Phase 3 trials (EQUIP, CONQUER, SEQUEL)

– Treatment with PHEN/TPM consistently demonstrated statistically significant weight loss compared with placebo

After 56 weeks of treatment, percent weight loss achieved with PHEN/TPM was 10.6%, 8.4%, and 5.1% with 15/92 mg, 7.5/46 mg, and 3.75/23 mg, respectively (p < 0.0001)

52-week extension study (SEQUEL) showed maintained weight loss over 2 years with 9.3% and 10.5% weight loss from baseline for 7.5/46 mg and 15/92 mg PHEN/TPM, respectively (p < 0.0001)

– Reductions in WC, fasting triglycerides, fasting glucose also attributable to PHEN/TPM

Smith SM, Meyer, M and Trinkley KE. Phentermine/Topiramate for the Treatment of Obesity. Ann Pharmacotherpay 2013 March 12. Epub ahead of print

•

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PHEN/TPM: Adverse Effects

Contraindicated in patients with glaucoma or hyperthyroidism

In general, well tolerated in phase three clinical trials – Most reported adverse effects included dry mouth, dizziness,

constipation, insomnia, and paraesthesia (topiramate)

Topiramate and phentermine adverse effects are dose-related

Rates of discontinuation due to adverse events were greatest with high-dose PHEN/TPM (17.4%) – Compared to mid-dose (11.6%), low-dose (11.6%), or

placebo (8.4%) – Most common reasons for discontinuation were blurred

vision, headache, and irritability

QSYMIA® [package insert]. Winchester, KY: VIVUS Inc.; 2012

PHEN/TPM: Adverse Effects (cont.) Counseling points for pharmacists REMS GUIDE

– Increased heart rate Patients should be monitored when starting or increasing

dosage

Phentermine component of high-dose PHEN/TPM increased resting HR by 1.2 bpm in EQUIP study (P=0.0830), compared to placebo and by 1.7 bpm in CONQUER (p<0.0001) and SEQUEL studies

Clinical significance of increased HR is unknown

Counseling point: patients should have regular measurements of resting HR during treatment

with PHEN/TPM

QSYMIA® [package insert]. Winchester, KY: VIVUS Inc.; 2012

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PHEN/TPM: Adverse Effects (cont.)

REMS Guide – Teratogenicity

Category X = increased risk of birth defects in first trimester, causing cleft lip/cleft palate

Have negative pregnancy test before taking PHEN/TPM and every month while taking PHEN/TPM

In each phase three trial, two forms of birth control required for women of childbearing age.

– Even with strict study protocol, 17 pregnancies reported: 3 spontaneous abortions, 3 elective abortions, 9 healthy live births. Congenital malformations were not observed

Counseling point: Counsel on birth control use, pregnancy test requirements, and where to

report pregnancy if it occurs QSYMIA® [package insert]. Winchester, KY: VIVUS Inc.; 2012

PHEN/TPM: Adverse Effects (cont.)

Topiramate causes reduced serum concentrations of bicarbonate and potassium – Increases risk of hypokalemia & nephrolithiasis

In CONQUER trial, three serious adverse reports of nephrolithiasis occurred in participants treated with high-dose PHEN/TPM, likely due to topiramate

Counseling point: Patients should be monitored for hypokalemia. Baseline metabolic panel (BMP)

should be collected at baseline before initiating PHEN/TPM and periodically thereafter

QSYMIA® [package insert]. Winchester, KY: VIVUS Inc.; 2012

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Lorcaserin (Belviq®)

Lorcaserin (Belviq®)

The serotonin (5-HT) pathway

– Long been implicated in weight control

– Activation (or agonism) of 5-HT receptors thought to promote decreased food intake, weight loss, loss of adiposity, and improved metabolic parameters associated with adipose tissue dysfunction

Agents that affect serotonin (5-HT) pathway

– Past nonselective serotonergic agonists (eg, fenfluramine, dexfenfluramine), which validated serotonin receptors as pharmacologic targets for weight loss

– These agents increased risk of serotonin-associated valvulopathy, which occurs through agonism of 5-HT2B receptors expressed on cardiac valvular interstitial cells

– Lorcaserin selectively activates central 5-HT2C receptors, which may be associated with weight loss without effects on heart valves

Smith RS, Weissman NJ, Anderson CM, et al. Multicenter, Placebo-Controlled Trial of Lorcaserin for Weight Management. N Engl J Med. 2010;

363:245-256

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Lorcaserin

Believed to decrease food consumption and promote satiety by selectively activating 5-HT2C receptors on anorexigenic pro-opiomelanocortin neurons in hypothalamus

Approved for people who are obese – BMI of ≥30

Or

– BMI of ≥27 or above and at least one weight-related health condition such as T2DM, HTN or hyperlipidemia

Lorcaserin (cont.)

Helps in the management of obesity WHEN used in conjunction with reduced-calorie, low-fat diet and increased physical activity

Dose: 10 mg orally twice daily with or without food

– Response to therapy should be assessed by week 12

– Therapy should be discontinued in patients not achieving ≥5% weight loss within 12 weeks because continued use is unlikely to produce and maintain clinically relevant weight loss

– Lorcaserin not recommended in patients with severe renal impairment or end-stage renal disease

– Caution advised in patients with severe hepatic impairment

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Lorcaserin: Efficacy

Three randomized clinical trials, durations ranging from 52 to 104 weeks

– Lorcaserin compared with placebo, along with weight management (including reduced caloric intake and increased physical activity)

– Two trials in adults without T2DM

Over 7,000 patients enrolled

– One study in adults with T2DM

604 patient enrolled

Belviq [package insert]. Zofingen, Switzerland: Arena Pharmaceuticals GmbH; 2012

Lorcaserin: Efficacy (cont.) Blossom and Bloom Trials

– Lorcaserin resulted in statistically significant average patient weight loss of 5.8% (12.7lbs), compared to 2.2% (4.7lbs) in placebo groups

– 47.5% of lorcaserin-treated patients lost at least 5% of baseline body weight, compared with 20.3% of placebo-treated patients.

– U.S. Food and Drug Administration-defined echocardiographic valvulopathy occurred in 2% of placebo-treated patients and 2% of lorcaserin-treated patients (at 10 mg BID)

– Lorcaserin administered in conjunction with a lifestyle modification program associated with modest weight loss; significantly greater than with placebo

Fidler MC, et al A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab. 2011 Oct;96(10):3067-77 Smith SR, Weissman NJ, Anderson CM, et al; Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) Study Group. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363(3):245-256 Chan EW, He, Y, Chui, CS et al. Efficacy and safety of lorcaserin in obese adults: a meta-analysis of 1-year randomized controlled trials (RCTs) and narrative review on short-term RCTs. Obes Rev. 2013 Jan 21

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Lorcaserin: Efficacy in Diabetes

Statistically significant mean reduction in body weight from baseline to 1 year – 4.5% treated with lorcaserin twice daily, 5% treated with

lorcaserin once daily, compared to 1.5% treated with placebo

Statistically significant BMI reduction – 1.6 kg/m2 with lorcaserin twice daily and 1.7 kg/m2 with

lorcaserin once daily, compared with a 0.6 kg/m2 reduction with placebo

Statistically significant improvement in glycemic control – HbA1c was reduced 0.9% with lorcaserin twice daily and 1%

with lorcaserin once daily, compared with a 0.4% reduction with placebo

Blood pressure or lipid parameters not reduced in either lorcaserin group, compared with placebo

O'Neil PM, Smith SR, Weissman NJ, et al. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study. Obesity. 2012;20(7):1426-1436

Lorcaserin: Adverse Effects

Most common adverse effects reported with lorcaserin – Non-diabetic patients

Headache, dizziness, fatigue, nausea, dry mouth, and constipation

– Diabetic patients

Hypoglycemia, headache, back pain, cough, and fatigue

Cardiovascular – Combined data from 3 large 1-year studies reported to

sufficiently rule out increase in risk of valvulopathy

– Use in caution with patients with bradycardia

Bradycardia reported in 0.3% of patients treated with lorcaserin, compared to 0.1% with placebo

Belviq [package insert]. Zofingen, Switzerland: Arena Pharmaceuticals GmbH; 2012

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Lorcaserin: Adverse Effects (cont.)

Pregnancy category X – Weight loss in pregnancy offers no potential benefit

and may result in fetal harm

– Teratogenicity was not observed in animal models

Priapism – Potential effect of 5-HT2C receptor stimulation

Caution advised if lorcaserin administered in combination with medications used for treatment of erectile dysfunction

Lorcaserin DEA Evaluation

DEA currently evaluating lorcaserin as controlled substance; scheduling category being determined – Proposed to be a Schedule IV of the Controlled

Substances Act

– In abuse studies, lorcaserin increased measures of “high,” “good drug effects” and “hallucinations and sedation” in recreational drug abusers, compared with placebo

– These responses were similar to those observed with agents such as zolpidem and ketamine

Shram MJ, Schoedel KA, Bartlett C, Shazer RL, Anderson CM, Sellers EM. Evaluation of the abuse potential of lorcaserin, a serotonin 2C (5-HT2C) receptor agonist, in recreational polydrug users. Clin Pharmacol Ther. 2011;89(5):683-92

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Medications in the pipeline

Exenatide as off-label use for obesity

Several combination drug therapies in research and development

– Bupropion-naltrexone

– Bupropion-zonisamide

Buproprion works as appetite suppressant with unknown mechanism

Ioannides-Demos LL, Piccenna L, McNeil JJ. Pharmacotherapies for Obesity: Past, Current, and Future Therapies. 2011. Journal of Obesity Halpern B. Oliveira ESL. Faria AM, et al. Combinations of Drugs in the Treatment of Obesity. Pharmaceuticals 2010, 3, 2398-2415

Herbal Supplements

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Herbal Supplements/OTC Products

Aggressively marketed to consumers with dramatic claims made regarding weight loss effects

– Lack sufficient scientific evidence

– Patients should be aware that none of these products regulated by FDA

– No assurance of efficacy or adherence to current good manufacturing practices (cGMPs)

Brahim, A, Dowden, C, Norwood, R, Haines, S. Obesity Screening and diet counseling: A buisness venture for pharmacists. Drug Topics, May

15,2010

Pittler MH, Schmidt K, Ernst E. Adverse events of herbal food supplements for body weight reduction: systematic review. Obes Rev. 2005

May;6(2):93-111

Herbal Supplements/OTC Products: Adverse Effects

Bitter orange – Stimulant effects – Cases of reported cardiotoxicity

St. John's Wort – Potent CYP450 inducer – May cause drug interactions if patients taking other medications

metabolized via CYP450 pathway

5-HTP (5-Hydroxytryptophan) – Reports of eosinophilia-myalgia syndrome (EMS) – Unclear whether caused by 5-HTP or contaminants (adulteration) in

products

Ephedra and ephedrine-containing supplements – Increased risk of psychiatric, autonomic or gastrointestinal adverse

events – Heart palpitations reported

Brahim, A, Dowden, C, Norwood, R, Haines, S. Obesity Screening and diet counseling: A business venture for pharmacists. Drug Topics, May 15,2010; Pittler

MH, Schmidt K, Ernst E. Adverse events of herbal food supplements for body weight reduction: systematic review. Obes Rev. 2005 May;6(2):93-111

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Lifestyle Modification is the cornerstone to weight, blood pressure and hyperlipidemia

reduction!

Choose MyPlate.Gov

MyPlate is part of larger communications initiative based on 2010 Dietary Guidelines for Americans to help consumers make better food choices

MyPlate is designed to remind

Americans to eat healthfully • Not intended to change

consumer behavior alone

www.choosemyplate.gov

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Reading Nutritional Labels

Start: Note size of single serving

and how many servings in package

Check total calories per serving: Look at serving size and

how many servings you’re really consuming

Limit these nutrients: Limit total fat to no more than 56–78 grams/day - No more than 16 grams of

saturated fat - Less than two grams of trans- saturated fat - Less than 300 mg cholesterol (for 2,000 calorie diet)

www.theheart.org

How many calories is too much?

As you think about amount of calories in food/serving, remember that for 2,000-calorie diet:

– 40 calories/serving is considered low

– 100 calories/serving is considered moderate

– ≥200 calories/serving is considered high

For Diabetics

– Focus is on total carbohydrate reduction

– Limit diet to less than 250 or 200 grams of carbohydrates/day

www.theheart.org

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If a food Claims to be… It means that one serving of the product contains…

Calorie free Less than 5 calories

Sugar free Less than 0.5 grams of sugar

Fat

Fat free Less than 0.5 grams of fat

Low Fat 3 grams of fat or less

Reduced fat or less fat At least 25 percent less fat than the regular product

Light (lite) At least 1/3 fewer calories or no more than 1/2 the fat of the regular product

Sodium

Low sodium 140 milligrams or less of sodium

Reduced or less sodium At least 25 percent less sodium than the regular product

www.theheart.org

Information for patients

Nutrition.gov – Links to United States Department of Agriculture (USDA)

National Nutrient Database for Standard Reference – Allows patients and providers to research nutritional content of

food items – Hyperlink connects to NHLBI's "Guide to Reducing Your Blood

Pressure," which educates patients about sodium intake and healthy eating

America On the Move Foundation (http://www.americaonthemove.org/) – Provides tools to track daily activity and energy intake – Group classification available to encourage peer motivation in

tracking progress toward achieving goals – Online tool allows patients to convert daily activities (eg,

gardening) into steps for inclusion in daily step totals

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Information for patients (cont.)

THE CDC (http://www.cdc.gov)

– Provides patient and caregivers with following info:

Weight-loss resources that include education on energy requirements

Choosing nutritious foods, and recommendations for physical activity and exercise

Barriers to Pharmacists Counseling on Obesity

Mail survey conducted

139 community pharmacists responded

Indicated they rarely-to-sometimes counseled obese patients

Responded they were somewhat comfortable with counseling about obesity management

– Perceived obesity management strategies to be somewhat effective in weight loss, but were neutral regarding their confidence in achieving positive outcomes with counseling

O’ ’Donnell DC, Brown CM, Dastani HB. Barriers to counseling patients with obesity: a study of Texas community pharmacists. J Am Pharm Assoc. 2006 Jul-Aug;46(4):465-71

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Barriers to Pharmacists Counseling on Obesity (cont.)

Top barriers to counseling included

Lack of time (76.8%)

Lack of patient demand or expectations (55.8%)

Lack of reimbursement/compensation (49.3%)

Creating awareness among patients regarding pharmacists’ ability to counsel perceived as most important in overcoming barriers

O’ ’Donnell DC, Brown CM, Dastani HB. Barriers to counseling patients with obesity: a study of Texas community pharmacists. J Am Pharm Assoc. 2006 Jul-Aug;46(4):465-71

Pharmacists Counseling Points

When pharmacotherapy indicated, pharmacists can help! – Pharmacists can identify interactions with medications

or identify contraindications with other concomitant disease states

– Reinforcement of lifestyle modifications and providing encouragement to patients on monthly basis

– Increased frequency of patient contact may improve success of weight loss and maintenance efforts

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Pharmacists Counseling (cont.)

– Identifying and monitoring patients using nonprescription or herbal weight-loss preparations also important aspect of ensuring patient safety

– Pharmacists in unique position to identify patients utilizing herbal preparations for weight loss and minimize potential adverse effects and drug interactions associated with these products

Conclusion

Medication modalities utilized need to be combined with diet modification and an exercise program to be the most effective

New medications on the market to treat obesity have potential side effects and REMS programs that pharmacists should be aware of

Pharmacists can have a large role in counseling obese patients and improving outcomes

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Disclaimer

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