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A Continuing Education Activity The Pharmacist’s Role in Obesity Management: A Long-term Commitment to Improving Overall Health Revised edition Jointly sponsored by Postgraduate Institute for Medicine and CME Incite A CPE activity approved for 2.0 hours (0.20 CEUs). Release date: October 20, 2013 Expiration date: October 20, 2015 CE grading online at www.powerpak.com This activity is sponsored by an educational grant from Vivus, Inc. A CME activity approved for 2.00 AMA PRA Category 1 Credit(s)™. Release date: October 20, 2013 Expiration date: October 20, 2015 This activity is sponsored by an educational grant from Vivus, Inc. Target Audience This continuing pharmacy education (CPE)-certified activity has been designed to meet the educational needs of pharmacists and clinicians who manage overweight or obese patients. Statement of Need/Program Overview The community pharmacist is an essential resource for overweight and obese patients who are attempting to manage their weight. Among all health professionals, pharmacists are perhaps most often asked about weight-loss agents, as they dispense prescription and nonprescription therapies for weight management. In addition, pharmacists may monitor patients’ medication profiles to detect prescription agents that may cause weight gain, and they can provide information about proper weight-loss programs. Pharmacists are also in a position to encourage patients to utilize long-term weight-management goals rather than “quick-fix” over-the-counter (OTC) products. They should stress to patients that even moderate weight loss (5% to 10% of body weight) is extremely beneficial—especially for patients with comorbid conditions, as well as the fact that losing weight requires a long-term commitment. Now that clinicians and patients have 2 newly approved pharmacologic treatment options for weight management, there is a greater-than-ever need for pharmacistspecific education. Clinical information on the safety, efficacy, and mechanism of action (MOA) of these 2 agents is necessary for pharmacists to process, understand, and deliver accurate counseling to patients, especially during the time when patients drop off and pick up prescriptions. Educational Objectives After completing this activity, the participant should be better able to: • Recognize the benefits of treating overweight and obese patients including the positive impact weight loss has on comorbid conditions • Compare the efficacy, MOA, and benefits versus risks of phentermine/ topiramate ER and lorcaserin • Counsel patients on adverse events they may experience while using pharmacotherapy as an adjunct to their obesity management • Assess patients’ medications to reduce unhealthy weight gain and decrease the incidence of obesity and associated comorbidities • Emphasize the importance of long-term weight-management goals with their patients • Provide accurate and appropriate counsel as part of the treatment team Faculty Robert Kushner, MD Professor of Medicine Northwestern University Feinberg School of Medicine Chicago, Illinois Credit Designation Postgraduate Institute for Medicine designates this continuing education activity for 1.0 contact hour(s) (0.1 CEUs) of the Accreditation Council for Pharmacy Education. (Universal Activity Number 0809-9999-13-314-H01-P) Type of Activity Knowledge Disclosure of Conflicts of Interest Postgraduate Institute for Medicine (PIM) requires instructors, planners, managers and other individuals who are in a position to control the content of this activity to disclose any real or apparent conflict of interest (COI) they may have as related to the content of this activity. All identified COI are thoroughly vetted and resolved according to PIM policy. PIM is committed to providing its learners with high quality CME activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of a commercial interest. The faculty reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME activity: Name of Faculty or Presenter Reported Financial Relationship Robert Kushner, MD Consulting Fees: Novo Nordisk, Retrofit, VIVUS, Zafgen Contracted Research: Aspire Bariatrics, Weight Watchers Jennifer Costello, PharmD, BCPS, BC-ADM Dr Costello has nothing to disclose. The planners and managers reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this CME activity: The following PIM planners and managers, Laura Excell, ND, NP, MS, MA, LPC, NCC, Trace Hutchison, PharmD, Samantha Mattiucci, PharmD, CCMEP, and Jan Schultz, RN, MSN, CCMEP, hereby state that they or their spouse/life partner do not have any financial relationships or relationships to products or devices with any commercial interest related to the content of this activity of any amount during the past 12 months. Priya Wanchoo, MBBS has nothing to disclose. Method of Participation and Request for Credit There are no fees for participating and receiving CME credit for this activity. During the period October 20, 2013, through October 20, 2015, participants must read the learning objectives and faculty disclosures and study the educational activity. This will need to be included with PowerPak’s Method of Participation: Jennifer Costello, PharmD, BCPS, BC-ADM Ambulatory Care Clinical Pharmacist Internal Medicine Faculty Practice Saint Barnabas Medical Center Livingston, New Jersey For pharmacists, transcript information will be available at www.mycpemonitor. net immediately. Accreditation Statement This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Postgraduate Institute for Medicine and CME Incite. The Postgraduate Institute for Medicine is accredited by the ACCME to provide continuing medical education for physicians. Disclosure of Unlabeled Use This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications. Media Monograph Credit Designation The Postgraduate Institute for Medicine designates this enduring material for a maximum of 2.0 AMA PRA Category 1 Credit(s)tm. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Accreditation Statement Postgraduate Institute for Medicine is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings. Disclaimer Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/ or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. CE grading online at www.powerpak.com Pharmacist Intervention: A Golden Opportunity At the end of this activity, pharmacists and clinicians should be better able to: Among all health care professionals, pharmacists are perhaps most often asked about weight-loss agents, as they dispense prescription drugs and advise patients about taking nonprescription therapies for weight management on a day-to-day basis. While prescription drugs require rigorous clinical trial data to obtain FDA approval, over-the-counter (OTC) products are often under-studied for efficacy and patient safety. Pharmacists are in a unique position to encourage patients to establish realistic weight loss goals and utilize safe, long-term weight-management strategies. • Recognize the benefits of treating overweight and obese patients including the positive impact of weight loss on comorbid conditions • Assess patients’ medications to reduce unhealthy weight gain and decrease the incidence of obesity and associated comorbidities • Emphasize the importance of long-term weightmanagement goals with their patients • Compare the efficacy, mechanism of action, and benefits versus risks of phentermine/topiramate extended-release and lorcaserin • Counsel patients on adverse events they may experience while using pharmacotherapy as an adjunct to their obesity management Pharmacists should stress to patients that even moderate weight loss (5% to 10% of body weight) is extremely beneficial—especially for patients with comorbid conditions. Patients who have not been successful in losing 5% to 10% body weight with lifestyle modifications alone now have 2 newly approved pharmacologic treatment options for weight management: lorcaserin and phentermine/topiramate extended-release (PHEN/TPM ER). These medications (reviewed below) are to be used as adjuncts to lifestyle intervention and may be considered for patients with a BMI of 27.0 to 29.9 kg/m2 with at least 1 weight-related comorbidity or a BMI ≥30.0 kg/m2 with or without comorbidities. Obesity: A Heavy Burden Across The United States Obesity is a complex, chronic condition that is defined by excess body fat. Body-mass index (BMI), as calculated by kilograms of weight divided by patient height in meters squared (ie, kg/m2), is an abbreviated measure of total body fat that can easily be calculated in everyday practice. A classification of “overweight” occurs in any individual whose BMI is calculated to be between 25.0 and 29.9 kg/m2, whereas obesity is defined by a calculated BMI of ≥30 kg/m2, with the severity of obesity further divided into classes I through III. The rise in obesity class from I to III (severe/extreme obesity) corresponds with increased morbidity from obesity-related diseases along with an increased mortality risk.1,2 Obesity—particularly visceral adiposity—has been linked to development of many other cardiovascular risk factors, such as hypertension, insulin resistance/type 2 diabetes, and dyslipidemia.3 Excess weight also plays a major role in sleep apnea, increased incidence of certain types of cancer, osteoarthritis, and even mental health illnesses such as depression. The American Medical Association (AMA) and the American Association of Clinical Endocrinologists (AACE) recognize obesity as a disease, and it is the responsibility of all health care professionals, including pharmacists, to encourage and support patients to achieve a healthy weight. As of June 2013, the American Medical Association recognized obesity as a disease, recommending a range of medical interventions to advance obesity treatment. Summary of Key Responsibilities for Pharmacists • Perform a review of current medications •M onitor patients’ medication profiles to detect prescription agents that may cause weight gain (See Table 1.) •P roactively inform patients about possible adverse events to ensure they are aware of potential side effects, allowing them to make informed decisions about continuing therapy •P rovide information about evidence-based weight-loss programs •A nswer frequently asked questions regarding nonpharmacologic/ pharmacologic agents used to manage weight (eg, warnings/ contraindications, drug interactions, etc) Table 1. Medications That May Cause Weight Gain.4 Atypical Antipsychotics Mirtazapine Chlorpromazine Paroxetine Insulin/sulfonylureas Prednisone (for long periods) Lithium Sodium valproate Medroxyprogesterone Tricyclic antidepressants (such as amitriptyline, imipramine, and doxepin) The Pharmacist’s Role in Obesity Management: A Long-term Commitment to Improving Overall Health 3 Recently Approved Treatments For Obesity: Prescriptions For Change Prior to the recent approvals of lorcaserin (June 2012) and PHEN/ TPM ER (July 2012), the only pharmacotherapeutic agent approved for long-term use was orlistat (approved in 1999). Orlistat is currently available by prescription or OTC. Phentermine has been available for many years as a short-term (~12 weeks) adjunct to a well-balanced weight-management regimen.5,6 (See Table 2.) After more than 10 years without a new long-term treatment option for weight management, patients now have PHEN/TPM ER and lorcaserin to assist them with weight reduction and maintenance. Both drugs need to be used as adjuncts to lifestyle modification and are not intended for short-term, stand-alone care.7-10 (See Table 3.) Table 2. Previously Available Pharmacotherapies for Weight Management.5,6 Phentermine 37.5 mg Daily Agent MOA Central Noradrenergic Orlistat 120 mg TID 60 mg TID (OTC) Peripheral Pancreatic lipase inhibitor Approval Short-term use DEA Schedule IV Chronic Not scheduled Also available OTC Common adverse effects • Restlessness • Insomnia • Increase in pulse • Increase in BP •G I symptoms including oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, and others less frequently • I ncrease in urinary oxalate Abbreviations: BP, blood pressure; GI, gastrointestinal; MOA, mechanism of action; OTC, over the counter; TID, three times daily Table 3. Recently Approved Pharmacotherapies for Weight Management.7-10 Agent Approval status Phentermine/topiramate Extended-Release (PHEN/TPM ER) Lorcaserin Approved July 2012 Approved June 2012 September 2012 June 2013 MOA Phentermine stimulates norepinephrine release from hypothalamic neurons. Topiramate is an anticonvulsant, and its MOA is thought to be mediated through modulation of GABA receptors, inhibition of carbonic anhydrase, and antagonism of glutamate. Selectively targets the 5-HT2C receptor Common adverse events • Dry Mouth • Paraesthesia • Constipation • Dysgeusia • Insomnia • Dizziness • Headache •U pper Respiratory Infection • Nasopharyngitis • Dizziness • Nausea Contraindications • Pregnancy (Category X) • Glaucoma • Hyperthyroidism • During or within 14 days following MAOI therapy • Pregnancy (Category X) Availability Abbreviations: GABA, gamma-aminobutyric acid; MAOI, monoamine oxidase inhibitor; MOA, mechanism of action 4 The Pharmacist’s Role in Obesity Management: A Long-term Commitment to Improving Overall Health With these approvals comes the responsibility of health care professionals to identify and monitor patients who could most benefit from a weight-management program that includes changes in diet, exercise, and, potentially, a pharmacologic agent. PHEN/ TPM ER and lorcaserin are approved for patients with clinically defined obesity (BMI of ≥30 kg/m2) or for patients with a BMI of ≥27 kg/m2 and at least 1 comorbidity including hypertension, high cholesterol, or type 2 diabetes mellitus.9,10 In addition to potential adverse events, pharmacists should be aware of the drug-drug and drug-herb interactions with PHEN/TPM ER and lorcaserin. (See Table 4.) Pharmacists are in a unique position to encourage patients to establish realistic weight-loss goals and utilize long-term weight-management strategies. Table 4. Potential Drug-Drug and Drug-Herb Interactions With Weight-Loss Agents.9,10 Phentermine/topiramate Extended-Release (PHEN/TPM ER) Lorcaserin PHEN/TPM ER should not be used in combination with a MAOI or in patients who have taken MAOIs within the prior 14 days. Development of potentially life-threatening serotonin syndrome or neuroleptic malignant syndrome-like reactions can occur in patients taking the following drugs or supplements in combination with lorcaserin: • SNRIs • SSRIs • TCAs • Bupropion • Triptans • St. John’s Wort • Tryptophan • Dextromethorphan • Lithium • Tramadol • Antipsychotics • Other dopamine antagonists Patients should be educated on the s/sx of serotonin syndrome (such as agitation, hallucinations, coma, tachycardia, labile blood pressure, hyperthermia, hyperreflexia, incoordination, nausea, vomiting, diarrhea, and muscle rigidity, etc). Treatment with lorcaserin and any concomitant serotonergic or antidopaminergic agents, including antipsychotics, should be discontinued immediately if s/sx develop, and patients should be advised to seek symptomatic treatment. Concomitant use of topiramate with any other carbonic anhydrase inhibitor (eg, zonisamide, acetazolamide, or dichlorphenamide) may increase the incidence or severity of metabolic acidosis and may also increase the risk of kidney stone formation. Patients who have a predisposing condition for metabolic acidosis who are given PHEN/TPM ER concomitant with another carbonic anhydrase inhibitor, should be monitored for the appearance or worsening of metabolic acidosis. Serotonergic and dopaminergic agents that are potent 5-HT2B receptor agonists have been shown to increase the risk for cardiac valvulopathy. Patients should be advised not to take lorcaserin in combination with these agents (eg, cabergoline). Non–potassium-sparing diuretics may potentiate the potassiumwasting action of these diuretics. Concomitant administration of hydrochlorothiazide alone with topiramate alone has been shown to increase the Cmax and AUC of topiramate by 27% and 29%, respectively. Patients should be monitored for hypokalemia when PHEN/TPM ER is taken together with non–potassium-sparing medicinal products. Lorcaserin can increase the risk of priapism, and only limited experience exists for its use in combination with medications indicated for erectile dysfunction (eg, phosphodiesterase type 5 inhibitors). Patients should be advised to use caution when taking these medications together. Abbreviations: AUC, area under the curve; Cmax, maximum concentration; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; s/sx, signs and symptoms; TCA, tricyclic antidepressant The Pharmacist’s Role in Obesity Management: A Long-term Commitment to Improving Overall Health 5 Clinical Pearl: Staying On-Label Phentermine is a sympathomimetic amine appetite suppressant, which was a component of the 1990s “fen-phen” (fenfluraminephentermine) combination therapy. However, the valvulopathy issues associated with this combination appetite suppressant, which ultimately led to its discontinued use, were caused by off-target effects on the 5-HT2B receptors in the heart from the fenfluramine/ dexfenfluramine component, not the phentermine component (which has no serotonergic effects).11 Phentermine was and continues to be indicated and used as a monotherapy for short-term weight reduction. It should be noted that even the highest dose of PHEN/TPM ER (15/92 mg) contains doses of phentermine that are lower than previously approved for the individual 37.5-mg formulation. Topiramate, a carbonic anhydrase inhibitor, increases satiety (feeling of fullness). Topiramate immediate-release (IR) is a FDA-approved drug in monotherapy formulations for epilepsy at 200 to 400 mg and migraine prevention at 100 mg daily. Topiramate in the PHEN/TPM ER combination uses a lower dose than the monotherapy option. The immediate-release phentermine component in PHEN/TPM ER provides therapeutic effects to reduce appetite early in the day and is combined with topiramate ER that provides persistent therapeutic effects throughout the whole day.12 Substituting PHEN/TPM ER with phentermine and topiramate is not an equivalent therapy with regards to dosing or drug release and it is not AB-rated for substitutions; furthermore, the generic components are not approved by the FDA for the chronic management of weight loss and weight maintenance. The low-dose combination product also appears to be more effective than either drug used as monotherapy for long-term weight loss.13 Pharmacists should explain this difference to patients if they ask for the generic drugs, and they should not dispense anything other than the FDA-approved on-label PHEN/TPM ER formulation for weight management. Table 5. C omparing Weight-Loss Efficacy of PHEN/TPM ER and Lorcaserin at 1 Year.7,8,15-17 Drug, Study, Treatment Lorcaserin Mean Change in Body Weight (kg) BLOOM8/BLOSSOM15 studies combined 10 mg BID Placebo BLOOM-DM study Mean Change in Body Weight (%) Patients Losing ≥5% of Body Weight (%) -5.8 -5.8 47 -2.6 -2.5 23 -4.7 -4.5 38 -1.6 -1.5 16 -12.6 -10.9 67 -1.9 -1.6 17 -8.1 -7.8 62 -10.2 -9.8 70 -1.4 -1.2 21 16 10 mg BID Placebo PHEN/TPM ER EQUIP17 study 15 mg/92 mg Placebo CONQUER study 7 7.5 mg/46 mg 15 mg/92 mg Placebo Abbreviation: BID, twice daily 6 The Pharmacist’s Role in Obesity Management: A Long-term Commitment to Improving Overall Health Efficacy Substituting PHEN/TPM ER with phentermine and topiramate is not an equivalent therapy with regards to dosing or drug release; furthermore, the generic components are not AB-rated, and cannot be legally substituted. PHEN/TPM ER, the combination of the sympathomimetic amine appetite suppressant phentermine, and the carbonic anhydrase inhibitor topiramate, is available in various dosages: 3.75/23 mg, 7.5/46 mg, 11.25/69 mg, and 15/92 mg. When used in conjunction with diet and exercise, PHEN/TPM ER 7.5/46 mg and 15/92 mg produced an average weight loss of 8% to 11% of original body weight in clinical trials.14 Lorcaserin is a first-in-class selective 5-HT2C receptor agonist that suppresses appetite to regulate food intake. When used in conjunction with diet and exercise, lorcaserin at 10-mg twice daily (BID) produced an average weight loss of 5% to 6% of original body weight in clinical trials.14 (See Table 5.) Both agents are now included in the recently published 2013 AACE Comprehensive Diabetes Management Algorithm. (See Figure 1.) Figure 1. 2013 AACE Obesity Treatment Algorithm.18 ST EP 1 E V A L U AT I O N F O R C O M P L I C AT I O N S A N D S TA G I N G CARDIOMETABOLIC DISEASE BIOMECHANICAL COMPLICATIONS NO COMPLICATIONS BMI ≥ 27 WITH COMPLICATIONS BMI 25–26.9, or BMI ≥ 27 Stage Severity of Complications STEP 2 LOW MD/RD counseling; web/remote program; structured multidisciplinary program Medical Therapy: phentermine; orlistat; lorcaserin; phentermine/topiramate ER Surgical Therapy (BMI ≥ 35): ST EP 3 HIGH (i) Therapeutic targets for improvement in complications, (ii) Treatment modality and (iii) Treatment intensity for weight loss based on staging S E L E C T: Lifestyle Modification: MEDIUM Lap band; gastric sleeve; gastric bypass If therapeutic targets for improvements in complications not met, intensify lifestyle and/or medical and/or surgical treatment modalities for greater weight loss Reprinted with permission from American Association of Clinical Endocrinologists. Garber AJ, Abrahamson MJ, Barzilay JI, et al. AACE Comprehensive Diabetes Management Algorithm. Endocr Pract. 2013;19:327-336. The Pharmacist’s Role in Obesity Management: A Long-term Commitment to Improving Overall Health 7 PHEN/TPM ER Prescribing And Administration 9 PHEN/TPM ER is available at certified retail pharmacies as well as via mail order through the Qsymia Home Delivery Network. There are several considerations that should be taken into account when initiating treatment with PHEN/TPM ER, particularly in women of reproductive potential in whom a pregnancy test is recommended prior to initiation of therapy. Patients may come to the pharmacy with 2 individual prescriptions: 1 for PHEN/TPM ER 3.75/23 mg (titration dose for 14 days) and 1 for PHEN/TPM ER 7.5/46 mg. While both prescriptions may be filled at once, patients should be instructed to take PHEN/TPM ER 3.75/23 mg once daily in the morning for 14 days. After the 2-week period with the titration dose, patients should begin taking PHEN/TPM ER 7.5/46 mg once daily in the morning. Patients can take PHEN/TPM ER with or without food and should be counseled not to combine the capsules or take more than directed. Patients will be monitored for weight loss benefit and tolerability at the discretion of the prescribing clinician, and it is recommended that women of child-bearing potential take monthly pregnancy tests (which may be performed at home). (See Figure 2.) Following 12 weeks of treatment with PHEN/TPM ER 7.5/46 mg, patients are evaluated by the prescribing clinician for weight loss. • For patients who experience ≥3% loss of baseline body weight, PHEN/TPM ER 7.5/46 mg therapy can be continued long term with regular monitoring by the prescribing clinician. • For patients who experience <3% loss of baseline body weight, PHEN/TPM ER therapy should be either discontinued or the therapy dose escalated. - Dose escalation: Patients should be instructed to take PHEN/ TPM ER 11.25/69 mg (titration dose for 14 days) once daily in the morning. After the 2-week period with the titration dose, patients should begin taking PHEN/TPM ER 15/92 mg once daily in the morning. For patients who have undergone dose escalation to PHEN/TPM ER 15/92 mg, evaluation of weight loss will occur after 12 weeks by the prescribing clinician. • For patients who experience ≥5% loss of baseline body weight, PHEN/TPM ER 15/92 mg therapy can be continued long term with regular monitoring by the prescribing clinician. • For patients who experience <5% loss of baseline body weight at this stage, PHEN/TPM ER therapy should be discontinued, as it is unlikely that the patient will achieve and maintain clinically meaningful weight loss with continued treatment. Dose Modification Considerations: • Patients who have moderate liver impairment (Child-Pugh score 7 to 9) should not exceed 7.5/46 mg once daily. 8 •P atients who have moderate (creatinine clearance [CrCl] ≥30 and <50 mL/min) or severe (CrCl <30 mL/min) renal impairment should not exceed 7.5/46 mg once daily. •P HEN/TPM ER discontinuation: Patients should be instructed to discontinue the top dose of PHEN/TPM ER 15/92 mg gradually by taking a dose every other day for at least 1 week prior to stopping treatment altogether, due to the potential of precipitating a seizure from rapidly changing topiramate concentrations. Risk Evaluation and Mitigation Strategy A Risk Evaluation and Mitigation Strategy (REMS) is an approach used to inform health care professionals and patients of known or potential serious risks associated with a medication. The purpose of the PHEN/TPM ER REMS is to inform health care professionals of the increased risk of congenital malformations, specifically orofacial clefts, in infants exposed to the topiramate component of PHEN/ TPM ER during the first trimester of pregnancy. Prescribing clinicians are encouraged to complete a voluntary training activity at QsymiaREMS.com. It reviews the importance of educating women of reproductive potential on pregnancy prevention such as a recommendation for negative pregnancy tests prior to initiating therapy and then monthly, use of appropriate contraception (see Table 6), and the need to discontinue PHEN/TPM ER immediately if pregnancy occurs.19,20 The QsymiaREMS.com Web site offers numerous resources to patients, clinicians, and pharmacists including patient medication guides, pregnancy prevention guidelines, dose-management checklists, and a pharmacy hotline that provides dispensing support at 1-855-302-6698.19 PHEN/TPM ER is provided through certified pharmacies which can be found online or on the mobile-enabled “FindQsymia.com” Web site. Lorcaserin Prescribing And Administration 10 Lorcaserin is available in 10-mg tablets and is dosed BID. Patients can take lorcaserin with or without food, preferably before morning and evening meals. Patients will be monitored for tolerability at the discretion of the prescribing clinician, and women of child-bearing potential should be discouraged from becoming pregnant or breastfeeding. Following 12 weeks of BID treatment with lorcaserin, patients are evaluated by the prescribing clinician for weight loss and tolerability. For those patients who experience ≥5% loss of baseline body weight, lorcaserin therapy at 10 mg BID can be continued long term with regular monitoring by the prescribing clinician. For those patients who experience <5% loss of baseline body weight, lorcaserin therapy should be discontinued, as it is unlikely that the patient will achieve and maintain clinically meaningful weight loss with treatment continuation. (See Figure 2.) The Pharmacist’s Role in Obesity Management: A Long-term Commitment to Improving Overall Health Figure 2. Dosing Algorithms for Lorcaserin and PHEN/TPM ER.9,10 Lorcaserin PHEN/TPM ER 10 mg twice daily for 12 weeks 3.75/23 mg for 14 days <5% weight loss ≥5% weight loss 7.5/46 mg for 12 weeks Discontinue Maintain 10 mg BID <3% weight loss Discontinue ≥3% weight loss Escalate Dose Maintain 7.5/46 mg 11.25/69 mg for 14 days 15/92 mg for 12 weeks <5% weight loss ≥5% weight loss Discontinue Maintain 15/92 mg Table 6. Contraception Counseling Chart.19 CONTRACEPTIVE METHODS TO REDUCE RISK OF PREGNANCY IN WOMEN UNDERGOING PHEN/TPM ER THERAPY OPTION 1 – Highly Effective Methods to Use Alone Intrauterine device (IUD) or intrauterine system (IUS) – Copper IUD – Levonorgestrel-releasing IUS Progestin implant Tubal sterilization Male partner’s vasectomy OPTION 2 – Acceptable Methods to Use Together Choose First Method Hormonal Contraception Estrogen and progestin – Oral (the pill) – Transdermal patch – Vaginal ring Progestin only – Oral – Injection Choose Second Method AND OPTION 3 – Acceptable Methods to Use Together Choose First Method Barrier Method – Diaphragm (with spermicide) – Cervical cap (with spermicide) Barrier Method – Diaphragm (with spermicide) – Cervical cap (with spermicide) –M ale condom (with or without spermicide) Choose Second Method AND Barrier Method – Male condom (with or without spermicide) The Pharmacist’s Role in Obesity Management: A Long-term Commitment to Improving Overall Health 9 Pharmacologic weight loss not recommended in pregnancy. Effective Counseling: Avoid Treatment Discontinuation It is extremely important to proactively tell patients about the common adverse events they may experience before they start taking these medications to decrease unnecessary treatment discontinuation. (See Tables 7 and 8.) Table 7. Most Common Adverse Events of PHEN/TPM ER.7,9 PHEN/TPM ER 7.5/46 (n=498) PHEN/TPM ER 15/92 (n=994) Placebo (n=993) 14 21 2 Constipation 15 17 6 Dysgeusia 7 10 1 Insomnia 6 10 5 Dizziness 7 10 3 Adverse Events (%) Dry Mouth Paraesthesia 13 21 2 Population includes all patients who received ≥1 dose of PHEN/TPM ER or placebo Table 8. Most Common Adverse Events of Lorcaserin.8,10 Lorcaserin 10 mg BID n=1593, Year 1 Lorcaserin 10 mg BID n=573, Years 1 and 2 Placebo n=1584, Year 1 14.8 14.5 11.9 Nasopharyngitis 13.4 16.4 12.0 8.2 1.7 3.8 Nausea 7.5 3.5 5.4 Adverse Events (%) Headache Upper Respiratory Infection Dizziness 18.0 7.2 Population includes all patients who received ≥1 dose of lorcaserin or placebo Abbreviation: BID, twice daily 10 The Pharmacist’s Role in Obesity Management: A Long-term Commitment to Improving Overall Health 11.0 Patients who are taking SSRIs, SNRIs, TCAs, dextromethorphan, triptans, or tryptophan should be educated about the risk of serotonin syndrome when taking lorcaserin. Pharmacist-To-Pharmacist Take-Home Points Proactive Involvement These new anti-obesity drugs are adjuncts to weight-loss regimens; nonobese patients hoping to lose “a few pounds” are not the indicated population. Patients on PHEN/TPM ER or lorcaserin have true obesity-related health concerns and will rely on pharmacists to answer multiple questions about the risks and potential benefits of their treatments. In addition to partnering with physicians, pharmacists should encourage lifestyle modifications, which include reduced-calorie diets, increased physical activity, and the importance of setting moderate and achievable weight-loss goals of 5% to 10%. Patients on these medications will want to know when the drug will work, what side effects they may expect, how to manage side effects, and what risks might be specific to them or their drug therapy. With training, pharmacists can educate patients about weight loss, communicate crucial safety recommendations, and monitor for drug interactions or adverse events. Specific observations and questions on suicidal thoughts or changing psychiatric symptoms, pregnancy prevention, and new-onset cardiac symptoms can identify patients with increased safety risk before a serious event occurs. Patient Resources for Weight Loss Along with active intervention, pharmacists should emphasize the Weight-control Information Network (WIN) from the National Institutes of Health (NIH) and related resources that help patients with behavior change and managing their expectations and goals for weight loss. WIN NIH hosts a Facebook page for patient interaction and updated tools, and the Centers for Disease Control and Prevention (CDC) provides interactive BMI calculators and diet/exercise trackers for patients. Programs for healthy weight loss are available from the National Heart, Lung, and Blood Institute (NHLBI; LEARN module), the American Diabetic Association, the Mayo Clinic, and local YMCA diabetes prevention programs. (See Fast Links Resources below.) Conclusion The approval of these 2 new effective weight-loss therapies provides additional options for clinicians to address excess weight, when used as an adjunct to lifestyle modification. For obese individuals or those with a BMI of 27 kg/m2 or greater who struggle to lose weight with diet and exercise alone and who have or are developing obesity-related comorbidities, these agents can offer 5% to 10% weight loss that can be maintained over time with treatment. When used as part of a balanced approach to better health, lorcaserin and PHEN/TPM ER are filling an unmet need in obesity treatment, such that they may lead to a successful reduction in excess weight and subsequent reduction in the onset and progression of several cardiometabolic comorbidities. Postmarket reports could expand the therapeutic potential of these drugs, confirm their safe application, and give health care professionals added clarity on how best to incorporate these 2 new important drug options into clinical practice for the treatment of obesity. The Pharmacist’s Role in Obesity Management: A Long-term Commitment to Improving Overall Health 11 References 1. National Institutes of Health. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. The evidence report. 1998. http://www.nhlbi.nih.gov/guidelines/obesity/ob_gdlns.pdf. Accessed November 8, 2013. 2. Weight-Control Information Network of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Overweight and obesity statistics. Oct 2012. http://www.win.niddk.nih.gov/statistics/. Accessed November 8, 2013. 3. K aplan NM. The deadly quartet: upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med. 1989;149(7):1514-1520. 4. Leslie WE, Hankey CR, Lean ME. Weight gain as an adverse effect of some commonly prescribed drugs: a systematic review. QJM. 2007;100(7):395-404. 5. A dipex-P [package insert]. Sellersville, PA: Teva Pharmaceuticals Co; 2012. http://www.accessdata.fda.gov/drugsatfda_docs/ label/2012/085128s065lbl.pdf. Accessed November 8, 2013. 6. Xenical [package insert]. South San Francisco, CA: Genetech USA Inc; 2012. http://www.accessdata.fda.gov/drugsatfda_docs/ label/2012/020766s029lbl.pdf. Accessed November 8, 2013. 7. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341-1352. 8. Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363(3):245-256. 9. Qsymia [package insert]. Mountain View, CA: VIVUS, Inc; 2012. http://www.accessdata.fda.gov/drugsatfda_docs/ label/2012/022580s000lbl.pdf. Accessed November 8, 2013. 10. B elviq [package insert]. Zofingen, Switzerland: Arena Pharmaceuticals GmbH; 2012. http://www.accessdata.fda.gov/ drugsatfda_docs/label/2012/022529lbl.pdf. Accessed November 8, 2013. 11. J ick H, Vasilakis C, Weinrauch LA, et al. A population-based study of appetite-suppressant drugs and the risk of cardiac-valve regurgitation. N Engl J Med. 1998;339(11):719-724. 12. B ays H. Phentermine, topiramate and their combination for the treatment of adiposopathy (‘sick fat’) and metabolic disease. N Engl J Med. 1998;339:719-724. 13. A ronne LJ, Wadden TA, Peterson C, et al. Evaluation of Phentermine and Topiramate versus Phentermine/Topiramate Extended-Release in Obese Adults. Obesity. 2013;21(11):2163-2171. 14. Colman E, Golden J, Roberts M, Egan A, Weaver J, Rosebraugh C. The FDA’s assessment of two drugs for chronic weight management. N Engl J Med. 2012;367(17):1577-1579. 15. F idler MC, Sanchez M, Raether B, et al; BLOSSOM Clinical Trial Group. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab. 2011;96(10):3067-3077. 16. 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 (Silver Spring). 2012;20(7):1426-1436. 17. A llison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring). 2012;20(2):330-342. 18. G arber AJ, Abrahamson MJ, Barzilay JI, et al. AACE comprehensive diabetes management algorithm. Endocr Pract. 2013;19(2):327-336. 19. V IVUS, Inc. Qsymia risk evaluation and mitigation strategy (REMS). http://QsymiaREMS.com. Accessed November 8, 2013. 20. F DA REMS Approval: Qsymia (phentermine and topiramate extended-release) capsules (4/2013). http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ UCM312598.pdf. Accessed November 8, 2013. 12 The Pharmacist’s Role in Obesity Management: A Long-term Commitment to Improving Overall Health Fast Links Resources for Health Care Professionals Adverse event reporting to the FDA: www.MedWatch.com or at 1-800-FDA-1088 AHA’s Answers by Heart patient fact sheets: http://www.heart.org/HEARTORG/Conditions/More/ToolsForYourHeartHealth/ Answers-by-Heart-Fact-Sheets_UCM_300330_Article.jsp Lorcaserin (Belviq) safety information: http://www.belviq.com/ BMI calculator for patients and health care professionals at NHLBI: http://www.nhlbi.nih.gov/guidelines/obesity/BMI/bmicalc.htm Qsymia REMS resources, voluntary health care provider training program, pharmacy training and pharmacy certification information, and certified pharmacy-locator tool: www.Qsymia.com Qsymia support: www.VIVUS.com (adverse event reporting at [email protected] or 1-888-998-4887) Your Weighting Room: A Physician Resource Center: http://www.yourweightingroom.com/Default.aspx Fast Links Resources for Patients LEARN: http://medicalcenter.osu.edu/patientcare/healthcare_services/center_for_wellness_ prevention/comprehensive_weight_management/weight_management/LEARN/Pages/ index.aspx) WIN: http://win.niddk.nih.gov/ WIN on Facebook: https://www.facebook.com/win.niddk.nih.gov The Pharmacist’s Role in Obesity Management: A Long-term Commitment to Improving Overall Health 13 Notes 14 The Pharmacist’s Role in Obesity Management: A Long-term Commitment to Improving Overall Health ✁ 4 Fast Facts New Pharmacotherapies for Weight Management Fact 1 Phentermine/topiramate extended-release (PHEN/TPM ER) and lorcaserin are approved for patients with clinically defined obesity. • Patients with clinically defined obesity have a BMI of ≥30 kg/m2 or ≥27 kg/m2 and at least 1 weight-related comorbidity including hypertension, high cholesterol, or type 2 diabetes mellitus. • These new pharmacotherapies are to be used as adjuncts to lifestyle intervention. Fact 2 PHEN/TPM ER cannot be substituted with generic alternatives. • Substituting PHEN/TPM ER with phentermine and topiramate is not an equivalent therapy with regard to dosing or drug release, and it is not AB-rated for substitutions. • The generic components are not approved by the FDA for chronic management of weight loss and weight maintenance. Fact 3 Treatment with lorcaserin and any concomitant serotonergic or antidopaminergic agents, including antipsychotics, should be discontinued immediately if signs and symptoms of serotonin syndrome develop. • Patients should be educated about the signs and symptoms of serotonin syndrome when starting treatment with lorcaserin. Fact 4 Pharmacologic weight loss is not recommended during pregnancy. • Women of childbearing potential are eligible to take PHEN/TPM ER, but need to be informed and aware of the risk information and recommendations for use of effective contraception and monthly pregnancy testing, as well as the need to discontinue PHEN/TPM ER if they become pregnant. Quick Reference Guide Dosing Algorithms for Lorcaserin and PHEN/TPM ER Lorcaserin PHEN/TPM ER 10 mg twice daily for 12 weeks 3.75/23 mg for 14 days <5% weight loss ≥5% weight loss 7.5/46 mg for 12 weeks Discontinue Maintain 10 mg BID <3% weight loss ≥3% weight loss Escalate Dose Discontinue Maintain 7.5/46 mg 11.25/69 mg for 14 days 15/92 mg for 12 weeks <5% weight loss ≥5% weight loss Discontinue Maintain 15/92 mg Common Adverse Events and Contraindications Agent Phentermine/topiramate Extended-Release (PHEN/TPM ER) Lorcaserin Common adverse events • Dry mouth • Paraesthesia • Constipation • Dysgeusia • Insomnia • Dizziness • Headache • Upper respiratory infection • Nasopharyngitis • Dizziness • Nausea Contraindications • Pregnancy (Category X) • Glaucoma • Hyperthyroidism • During or within 14 days following MAOI therapy • Pregnancy (Category X) MAOI, monoamine oxidase inhibitor. ✁ New Pharmacotherapies for Weight Management The Pharmacist's Role in Obesity Management: A Long-term Commitment to Improving Overall Health POSTTEST QUESTIONS 1. Medications that can potentially cause weight gain include: A. Atypical antipsychotics D. A and B B. Lithium E. A, B, and C C. Liraglutide 4. Which of the following pharmacotherapies for chronic weight management received FDA approval in 2012? A. Liraglutide B. Phentermine C. Liraglutide and phentermine/topiramate ER D. Lorcaserin and phentermine/topiramate ER 2. A visibly obese adult who takes medication to control their high blood pressure, high cholesterol, and type 2 diabetes requests a consultation with you regarding what steps to take to improve their health. The best counseling advice for this patient is to: A. Explain they would need to decrease their BMI to 25 in order to see any major health benefits B. Explain they would need to decrease their BMI to 27 in order to see any major health benefits C. Explain the benefits of a 5% to 10% reduction in weight on their health conditions and suggest ways they could get started with making lifestyle changes D. Explain the benefits of a 20% to 30% reduction in weight on their health conditions and suggest ways they could get started with making lifestyle changes 5. Weight-loss medications: A. Are contraindicated during pregnancy (as is weight loss in general) B. Should not be used while taking any medication for depression C. Can be useful as stand-alone therapies D. Are indicated for anyone with a BMI >25 6. What is a realistic percent weight-loss outcome at 6 months following nonsurgical weight-loss treatment? A. <1% B. 3% to 5% C. 5% to 10% D. 15% to 20% 3. An obese (BMi ≥30) person with hypertension has been unsuccessful in his/her weight loss goals (5% reduction) after 6 months of lifestyle modification. Which of the following strategies is the best to consider next for weight loss? A. Continue current lifestyle modification for another 6 months B. Continue current exercise activities C. Consider treatment with a pharmacotherapeutic agent for weight loss D. Bariatric surgery 7. The American Medical Association recognizes obesity as a: A. Disease B. Choice that is made by some patients C. Side effect that cannot be prevented D. Condition that cannot be improved once it has occurred EVALUATION FORM Please complete the following evaluation questions to receive your certificate. 1. What degree best describes you? ❒ MD/DO ❒ PA/PA-C ❒ PharmD/RPh ❒ PhD ❒ NP ❒ RN ❒ Other, please specify: ________________________________________ ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– 2. What is your area of specialization? ❒ Family Medicine ❒ General Practice ❒ Internal Medicine ❒ Endocrinology, Metabolism ❒ OB/GYN & Women’s Health ❒ Cardiology, General ❒ Pharmacy ❒ Other, please specify:_________________ ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– 3. Which of the following best describes your primary practice setting? ❒ Solo Practice ❒ Group Practice ❒ Government ❒ University/teaching system ❒ Community Hospital ❒ HMO/managed care ❒ Non-profit/community ❒ I do not actively practice ❒ Other, please specify: ________________________________________ ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– 4. How long have you been practicing medicine? ❒ More than 20 years ❒ 11-20 years ❒ 5-10 years ❒ 1-5 years ❒ Less than 1 year ❒ I do not directly provide care 5. Approximately how many patients do you see each week? ❒ Less than 50 ❒ 50-99 ❒ 100-149 ❒ 150-199 ❒ 200+ ❒ I do not directly provide care 6. How many patients do you currently see each week that are overweight or obese? ❒ Fewer than 5 ❒ 6-15 ❒ 16-25 ❒ 36-45 ❒ 46-55 ❒ 56 or more 15 ❒ 26-35 ❒ I do not directly provide care 7. rate how well the activity supported your achievement of these learning objectives: A. Recognize the benefits of treating overweight and obese patients including the positive impact weight loss has on comorbid conditions B. Assess patients’ medications to reduce unhealthy weight gain and decrease the incidence of obesity and associated comorbidities C. Emphasize the importance of long-term weight-management goals with their patients D. Compare the efficacy, MOA, and benefits versus risks of phentermine/topiramate ER and lorcaserin E. Counsel patients on adverse events they may experience while using pharmacotherapy as an adjunct to their obesity management F. Provide accurate and appropriate counsel as part of the treatment team 8. rate how well the activity achieved the following: A. The faculty were effective in presenting the material B. The content was evidence based C. The educational material provided useful information for my practice D. The activity enhanced my current knowledge base E. The activity provided appropriate and effective opportunities for active learning (eg, case studies, discussion, Q&A, etc.) F. The opportunities provided to assess my own learning were appropriate (eg, questions before, during or after the activity) Strongly Agree Agree Strongly Neutral Disagree Disagree 5432 1 5432 1 5432 1 5432 1 5432 1 5432 1 Strongly Agree Agree Strongly Neutral Disagree Disagree 5432 1 5432 1 5432 1 5432 1 5432 1 5432 1 9. Based upon your participation in this activity, do you intend to change your practice behavior? (choose only one of the following options) ❒ I do plan to implement changes in my practice based on the information presented ❒ My current practice has been reinforced by the information presented ❒ I need more information before I will change my practice 10. Thinking about how your participation in this activity will influence your patient care, how many of your patients are likely to benefit? Please use a number (eg, 250): ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– –––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– 11. if you plan to change your practice behavior, what type of changes do you plan to implement? (check all that apply) ❒ Apply latest guidelines ❒ Change in diagnostic testing ❒Change in differential diagnosis ❒ Change in pharmaceutical therapy ❒Choice of treatment/management approach ❒Other, please specify: –––––––––––––– ❒ Change in non-pharmaceutical therapy ❒Change in current practice for referral –––––––––––––––––––––––––––––––––– 12. How confident are you that you will be able to make your intended changes? ❒ Very confident ❒Somewhat confident ❒Unsure ❒Not very confident 13. Which of the following do you anticipate will be the primary barrier to implementing these changes? ❒ Formulary restrictions ❒ Patient adherence/compliance ❒ Treatment related adverse events ❒ Time constraints ❒ Insurance/financial issues ❒ Other, please specify: –––––––––––––– ❒ System constraints ❒ Lack of multidisciplinary support –––––––––––––––––––––––––––––––––– 14. Was the content of this activity fair, balanced, objective, and free of bias? ❒ Yes ❒ No, please explain: –––––––––– ––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– 15. Please list any clinical issues/problems within your scope of practice you would like to see addressed in future educational activities: request for Credit (*required fields) Would you be willing to participate in a post-activity follow-up survey? ❒Yes ❒No Name*––––––––––––––––––––––––––––––––––––––––––––––––––––––––– Degree*––––––––––––––––––––––––––––––––––––––––– Organization ––––––––––––––––––––––––––––––––––––––––––––––––––– Specialty*––––––––––––––––––––––––––––––––––––––– Address* ––––––––––––––––––––––––––––––––––––––––– City––––––––––––––––––––––––––– State–––––– ZIP*––––––––––––––– Telephone ––––––––––––––––––––––––––––– Fax ––––––––––––––––––––– Email*––––––––––––––––––––––––––––––––––––––––– For Physicians only ❒ I participated in the entire activity and claim 2.0 credits. ❒ I participated in only part of the activity and claim _____ credits. For Pharmacists only (please print legibly) NABP ePID (maximum of 10 digits) ___ ___ ___ ___ ___ ___ ___ ___ ___ ___ Date of birth (MMDD) ___ ___ ___ ___ 16 Notes