continuing education for pharmacists Volume XXXII, No. 8 : Treatment Guidelines and Update on Use of Belviq and Qsymia

Mona T. Thompson, R.Ph., PharmD

Dr. Mona T. Thompson has no relevant public health crisis in the United when compared to women with financial relationships to disclose. States. Most recent data indicate lower income or less education. No that 69 percent of adults are either significant relationship between Goal. The goal of this lesson is to or obese. Approximate- obesity and education among men provide a disease state overview ly half of these adults are obese, has been established. Obesity of obesity and summary of newly along with 17 percent of youths. prevalence also varies across states released treatment recommenda- This correlates with approximately and regions. tions. Two newly approved weight 78 million adults over the age of Higher rates of adult obesity loss medications, Belviq® (lorcar- 20 years and 12.5 million children were self-reported in 2012 for the serin) and Qsymia® (phentermine and adolescents. While the preva- Midwest (29.5 percent) and South and topiramate), as well as orlistat lence remains high, analysis from (29.4 percent) regions of the United (alli®, Xenical®) will be discussed in the 2011-2012 National Health States, including Ohio at 30.1 the role of chronic weight manage- and Nutrition Examination Sur- percent. ment with the inclusion of unique vey (NHANES) indicates that the In addition to ethnicity, race, Ohio law requirements for pre- increase has slowly stabilized or and socioeconomic status, other scribing these medications. leveled off since 2003-2004 data. risk factors may contribute to In June 2013, the American Medi- obesity. These include genetics, Objectives. At the completion of cal Association officially recognized family lifestyle, physical inactivity, this activity, the participant will be obesity as a disease. unhealthy and eating habits, able to: Obesity affects some groups quitting smoking, lack of sleep, 1. recognize the , more than others. Non-Hispanic certain medications, age, and preg- etiology, risk factors, diagnostic blacks have the highest age-adjust- nancy. Genetic and environmental criteria and associated long-term ed rates of obesity (47.8 percent) factors appear to be intertwined. health consequences of obesity; followed by Hispanics at (42.5 In addition to genetics, obesity 2. demonstrate an understand- percent), non-Hispanic whites (32.6 that runs in families is also due to ing of the role that anti-obesity percent) and non-Hispanic Asians their similar eating, lifestyle, and medications play in and (10.8 percent). Additionally, obe- activity habits. Reduced physical when they are appropriate; sity is higher among middle-aged activity may currently be the most 3. demonstrate an understand- adults, 40- to 59-years-old (39.5 important factor in the recent rise ing of the pharmacology, FDA- percent), than among younger in obesity. In the United States, approved indications and key pre- adults, age 20 to 39 (30.3 percent), less than half of all adults meet scribing points for the weight loss or adults age 60 or above (35.4 the Federal 2008 Physical Activity medications, Belviq and Qsymia; percent). Guidelines, and fewer than three and Differences in prevalence are in 10 high school students get at 4. identify the State Medical also observed among socioeco- least 60 minutes of physical activ- Board of Ohio Rules for prescribing nomic groups. Among non-Hispanic ity every day. Medications that are controlled substances for weight black and Mexican-American men, associated with include reduction. those with higher incomes are some antidepressants, anti-epilep- more likely to be obese than those tics, anti-glycemics, antipsychotics, Background with low income. Women with a steroids, and beta-blockers. Hence, Obesity, a state of excess storage higher income or those with college the etiology of obesity is much more of body fat, is a serious and costly degrees are less likely to be obese complex than a simple imbalance major contributors to chronic While not discussed in this review, Table 1 disease in the U.S., and present the issues are: 1) appropriate- Obesity terminology a major public health challenge. ness of the current BMI and waist Obesity raises the risk of morbidity circumference cut points used to Definitions* from , dyslipidemia, determine risk in overweight and Grade 1 overweight (overweight): type 2 mellitus, coronary obese adults across diverse popu- BMI of 25 to 29.9 kg/m2 heart disease, stroke, gallbladder lations; 2) impact of weight loss disease, , , on risk factors for cardiovascular Grade 2 overweight (obesity): BMI of respiratory problems, and some disease (CVD) and , 30 to 39.9 kg/m2 cancers. For a person with a BMI as well as CVD morbidity and mor- of 25 to 28.9 kg/m2, the relative tality; 3) optimal behavior, dietary Grade 3 overweight (severe or 2 risk for coronary heart disease is intervention strategies, and other morbid obesity): BMI >40 kg/m 1.72, with a risk that progressively lifestyle treatment approaches for Equations increases with increasing BMI. In- weight loss and weight loss main- dividuals with BMIs greater than tenance; and 4) benefits and risks 2 BMI = weight(kg)/height(m2) 33 kg/m have a relative risk of of various bariatric surgical proce- 3.44. Overall, obesity is estimated dures. Body fat percentage = 1.2(BMI) + to increase the cardiovascular mor- Critical questions that the Ex- 0.23(age in years) – 10.8(sex**) – 5.4 tality rate four-fold and the cancer- pert Panel did not examine include related mortality rate two-fold. consideration of genetics in obesity, *According to the World Health Organization Additionally, data indicate that binge-eating disorders, pharmaco- **Sex = 1 for males and 0 for females pre- maternal obesity ap- therapy, and cost effectiveness of pears to be a major risk factor for interventions to manage obesity. between energy intake and energy stillbirth. While drug therapy was not a focus output. The annual cost of managing of the 2013 update, the Expert Various indices are used to obesity in the United States alone Panel did include the consideration measure obesity, such as body fat amounts to approximately $190 of anti-obesity medication in the percentage, skin thickness, waist billion per year, or 20.6 percent of treatment algorithm. or hip circumference, waist-hip national health expenditures. A The result of the Panel’s work ratio, and (BMI). 2005 study conducted by Cawley includes a treatment algorithm The BMI typically correlates close- and Meyerhoefer found that when which strongly recommends coun- ly with body fat (except at lower compared with a non-obese per- seling overweight and obese adults BMIs). According to the 1998 Clini- son, an obese person incurs $2,741 regarding CV risk and lifestyle cal Guidelines on the Identifica- more in annual medical costs. changes that can produce meaning- tion, Evaluation, and Treatment of Additionally, a study conducted by ful health benefits; prescribing a Overweight and Obesity in Adults Finkelstein et al. concluded that weight loss diet; and participating Evidence Report, overweight is de- the cost of obesity among U.S. full- in a comprehensive lifestyle pro- fined as a BMI of 25 to 29.9 kg/m2 time employees is estimated to be gram with trained interventionists. and obesity as a BMI of >30 kg/m2. $73 million including the cost of If the patient has been unable to Severe or morbid obesity is reserved medical care, lost productivity, and lose weight or sustain weight loss for patients with a BMI >40 kg/m2. absenteeism. Almost $121 billion with comprehensive lifestyle inter- Other experts define obesity based is spent annually on weight-loss vention and he/she has a BMI 2 2 on the percentage of body fat pres- products and services. >30 kg/m or >27 kg/m with comor- ent. bidity, adjunctive therapies may Healthy men have a body fat Overview of Treatment be considered. Based on expert percentage of 15 to 20 percent, Guidelines for Obesity opinion, the panelists recommend while healthy women have ap- In 2013, updated guidelines for the that for individuals with BMI >30 2 proximately 25 to 30 percent. For treatment of obesity were released or BMI >27 kg/m with at least one men, body fat greater than 25 by the American Heart Associa- obesity-associated comorbid con- percent definesobesity , with 21 to tion (AHA), American College of dition who are motivated to lose 25 percent considered borderline. Cardiology (ACC) and The Obesity weight, pharmacotherapy can be For women, over 33 percent de- Society (TOS) urging physicians to considered as an adjunct to com- finesobesity , with 31 to 33 percent consider obesity as a disease and prehensive lifestyle intervention to termed borderline. Table 1 contains actively treat patients for weight help achieve targeted weight loss the World Health Organization’s loss. The new guidelines were de- and health goals. Furthermore, the accepted definitions of obesity, as signed to address critical issues on potential risks of medication should well as the equations to determine overweight and obesity evaluation be considered against the potential BMI and body fat. and treatment that are encoun- benefits of successful weight loss. Overweight and obesity are tered in the primary care setting. The rationale for medication use is to help patients adhere to with variations in degree and a lower calorie diet more consis- duration of overweight, age, and Table 2 tently in order to achieve sufficient associated comorbidities so that it Select Evidence weight loss and health benefits, translates to a true representation Statements (ES) from the when combined with increased and meaningful results. Agents 2013 AHA/ACC/TOS physical activity. Medications work must also possess an acceptable Guideline for the to reinforce lifestyle change and safety profile. Management of Overweight should be prescribed as an adjunct Several agents were previ- to lifestyle interventions. Bariatric ously approved and used for weight and Obesity in Adults surgery is also listed as an option loss, but have since been removed 1. In overweight and obese adults for adjunctive therapy. from the market in the U.S. due at risk for type 2 diabetes, average The guidelines also provide to safety issues. A combination of weight loss of 2.5 to 5.5 kg at >2 evidence statements (ES) serving the amphetamine analogs fenflura- years, achieved with lifestyle inter- as a basis for treatment recom- mine and phentermine, commonly ventions (with or without orlistat) mendations to be used by clinicians referred to as Fen-Phen, was very reduces the risk of developing type 2 evaluating and treating patients effective and popular in the 1990s. diabetes by 30 to 60 percent. with obesity. All health care profes- Fenfluramine (Pondimin) and its sionals can appreciate the level of relative compound, dexfenflura- 2. In overweight and obese adults evidence indicating that weight mine (Redux), were withdrawn with type 2 diabetes, those who achieve greater weight loss at 1 year loss is associated with a positive from the U.S. market secondary with lifestyle intervention (with impact on the risk of diabetes, hy- to pulmonary hypertension and or without orlistat) have greater perlipidemia, and hypertension — valvular heart disease. Phenter- improvements in HbA1c. Weight loss disease states which are predomi- mine (Adipex) remains available of 5 to 10 percent is associated with nantly treated with medications. for short term use (defined as 12 HbA1c reductions of 0.6 to 1.0 per- Table 2 lists select evidence state- weeks). When used alone, it rarely cent and reduced need for diabetes ments extracted from the guideline. causes valvular disease. medications. These statements support the drive Phenylpropanolamine was to treat obesity and improve the widely used for many years as a 3. In overweight and obese adults with type 2 diabetes, orlistat com- health of the U.S. population. nasal decongestant in over-the- pared to placebo, both with lifestyle Both the Full Panel Report counter (OTC) and prescription interventions, results in 2 to 3 kg (http://www.nhlbi.nih.gov/guide- drug products, as well as OTC greater weight loss at 1 and 2 years. lines/obesity/ser/) and Guide- for weight control. In 2000, FDA The addition of orlistat is associated line (http://circ.ahajournals.org/ issued a public health advisory con- with greater reductions in fasting content/early/2013/11/11/01. cerning phenylpropanolamine sec- blood glucose averaging 11 and 4 mg/ cir.0000437739.71477.ee.full.pdf) ondary to a study indicating that dL at 1 and 2 years, respectively, as are accessible online and are free of its use was associated with an in- well as an average greater reduction charge. creased risk of hemorrhagic stroke. in HbA1c of 0.4 percent at 1 year. Consumers were advised to avoid 4. In overweight and obese adults Anti-Obesity Medication any products containing phenylpro- with or without elevated CVD risk, Therapy panolamine. FDA requested that there is a dose-response relationship The goal of anti-obesity medica- all drug companies discontinue the between the amount of weight loss tion is to utilize a safe and effective marketing of any product contain- achieved by lifestyle intervention and agent in combination with diet and ing phenylpropanolamine. the improvement in lipid profile. to achieve a meaningful Finally, sibutramine (Meridia) and substantial reduction in body was shown to pose unnecessary 5. In overweight and obese adults weight. In order for medications to cardiovascular risk in a post-mar- with elevated CVD risk (including type 2 diabetes and hypertension), achieve FDA approval, the differ- keting trial and was voluntarily there is a dose-response relationship ence in mean weight loss between withdrawn in 2010, 13 years after between the amount of weight loss the drug and the placebo groups is its initial approval in 1997. achieved at up to 3 years by lifestyle at least 5 percent for at least one Due to stringent criteria, only intervention (alone or combined with year and statistically significant. In three agents are currently ap- orlistat) and the lowering of BP. addition, the proportion of sub- proved by FDA as adjunctive thera- jects who lose at least 5 percent of py for chronic : further in the next section of this baseline body weight in the active orlistat (alli, Xenical), approved in lesson. Table 3 summarizes key product group is at least 35 per- 1999; lorcaserin (Belviq), approved prescribing points for these agents. cent, and is approximately double in 2012; and phentermine/topira- Short-term sympathomimetic the proportion in the placebo-treat- mate extended-release formulation amines and medications used off- ed group. Finally, the studied obese (Qsymia), approved in 2012. These label for the treatment of obesity population must be heterogeneous three agents will be discussed will not be discussed in this lesson. that it is unlikely Table 3 to provide better Medications approved for chronic weight management results. A Cochrane Medication Dosage Usual Common ADRs Key Points Collaboration Form Daily Dose review examin- ing the long-term Orlistat 120 mg 120 mg TID oily spotting, flatus •take with pharmacotherapy (Xenical) capsule with discharge, multivitamin at bedtime for obesity and fecal urgency, •non-controlled fatty/oily stool, •total daily diet should overweight in- fecal incontinence include approximately 30 cluded 16 double- percent calories from fat blind, randomized, Orlistat 60 mg 60 mg TID placebo-controlled (alli) capsule trials of one to four years Lorcaserin 10 mg 10 mg BID Non diabetic: •Discontinue use if 5 percent in duration of (Belviq) tablet headache, dizziness, weight loss not achieved at orlistat use. The fatigue, nausea, dry 12 weeks review concluded mouth, and consti- •Cognitive impairment, pation psychiatric disorders, or that orlistat was Diabetic: hypoglyce- valvular heart disease may associated with mia, headache, back occur modest efficacy pain, cough, and •Caution with other sero- (<5 kg weight fatigue tonergic drugs loss) and reduced the number of Phentermine/ 3.75 mg/23 mg 7.5 mg/46 mg paresthesia, dizziness, •Discontinue use if 5 per- high-risk patients Topiramate 7.5 mg/46 mg to 15 mg/ dysgeusia, insomnia, cent weight loss not who developed (Qsymia) 11.25 mg/69 mg 92 mg once constipation, dry achieved at 12 weeks on diabetes. 15 mg/92 mg daily mouth max dose extended- •Monitor heart rate The most com- release •Monitor for sleep or mood mon adverse reac- capsules disorder tions of orlistat •Cognitive impairment (>5 percent and may occur at least double •REMS program to reduce that of placebo) fetal risk include oily spot- ting, flatus with discharge, fecal Orlistat cal is prescribed as 120 mg three urgency, fatty/oily stool, oily evacu- Orlistat is not a stimulant or times a day, with each main meal ation, increased defecation and controlled substance, rather a containing fat (during or up to one fecal incontinence. Gastrointestinal gastrointestinal lipase inhibitor. It hour after the meal). Patients are events may increase when Xeni- was approved by FDA in 1999 as advised to intake a nutritionally cal is taken with a diet high in fat Xenical, and then again in 2007 in balanced, reduced-calorie diet that (>30 percent total daily calories an OTC reduced-dose formulation contains approximately 30 percent from fat). In 2010, FDA approved marketed as alli. Orlistat remains of calories from fat. Alternatively, a revised label for Xenical and alli the only anti-obesity drug approved alli is dosed at 60 mg three times to include safety information about by the European Medicines Agency a day with meals containing 15 cases of severe liver injury that had (EMA). This unique agent works grams of fat. been rarely reported with the use by binding and inhibiting lipases In order to ensure adequate of this medication. At the time of that are produced by the pancreas absorption of fat soluble vitamins the drug safety communication in and stomach which act in the small (A, D, E, K, and beta-carotene), 2010, only 13 cases of severe liver intestine to break down dietary tri- individuals taking orlistat should injury had been reported among glycerides into free fatty acids. The be advised to take a multivitamin an estimated 40 million people fatty acids are then absorbed via once a day at bedtime. The product who had used the medication fatty acid transporters. Hence, or- labels suggest distributing the dai- worldwide. Therefore, a definite listat’s inhibition of lipases reduces ly intake of fat, carbohydrate, and cause and effect relationship has systemic fat absorption. Orlistat is protein over three main meals. It not been established. However, it indicated for chronic obesity man- is recommended that no more than is important to be aware of post- agement when used in conjunction three capsules be taken each day, marketing reports and to inform with a reduced-calorie diet. Xeni- as higher dosage studies indicate patients to report any symptoms of hepatic dysfunction such as anorex- impairment; psychiatric disorders 23 mg XR once daily in the morn- ia, pruritus, jaundice, dark urine, including euphoria and dissocia- ing for 14 days, followed by 7.5 light colored stools, or right up- tion; hypoglycemia associated with mg/46 mg daily. The dosage may per quadrant pain. Other risks of weight loss; and priapism. be escalated if 3 percent weight therapy include acute pancreatitis, Approval of lorcaserin was loss is not achieved after 12 weeks acute renal failure, and precancer- based on three randomized double- on 7.5 mg/46 mg dose in 14-day ous colon lesions. Due to orlistat’s blind trials, at least 52 weeks in increments to a maximum dose of non-scheduled status and safety length, in obese and overweight 15 mg/92 mg. Qsymia should be profile, it is exempt from the Ohio adults. The BLOSSOM and discontinued if 5 percent weight Medical Board rules discussed later BLOOM trial reported at least 5 loss is not achieved after 12 weeks in this lesson. percent weight loss by 47.2 percent on the maximum dose. Discontinu- and 47.5 percent of the participants ation should occur gradually, as Belviq in the locaserin 10 mg twice daily abrupt withdrawal of topiramate Lorcaserin hydrochloride (Belviq), group, compared to 25 percent and can cause seizures, even in pa- a schedule IV controlled substance, 20.3 percent in the placebo groups, tients with no history of epilepsy. was approved in 2012 as an ad- respectively. The BLOOM-DM Patients with moderate or severe junct to a reduced-calorie diet and study differed in that it enrolled renal impairment or patients with increased physical activity for patients with a diagnosis of type 2 moderate hepatic impairment chronic weight management in diabetes treated only with either should not exceed 7.5 mg/46 mg adults with an initial BMI of >30 metformin and/or a sulfonylurea. daily dose. kg/m2, or >27 kg/m2 in the pres- The proportion of patients achiev- Qsymia is contraindicated in ence of at least one weight-related ing at least a 5 percent weight loss pregnancy, patients with glaucoma comorbid condition (hypertension, was 38 percent in the lorcaserin or hyperthyroidism, during or with- dyslipidemia, type 2 diabetes). The 10 mg twice daily group, compared in 14 days of taking monoamine dosage is 10 mg twice daily, with to 16 percent in the placebo group. oxidase inhibitors, or known hyper- the caveat that use should be dis- The average weight loss in clini- sensitivity or idiosyncrasy to sym- continued if 5 percent weight loss cal trials was 5.5 kg. The effect of pathomimetic amines. The most is not achieved by week 12. These locaserin on cardiovascular morbid- common adverse reactions (greater patients are unlikely to achieve ity and mortality has not yet been than and at least 1.5 times placebo) clinically meaningful weight loss determined. are paraesthesia, dizziness, dys- with continued treatment. geusia, insomnia, constipation, and

Lorcaserin is a selective 5-HT2c Qsymia dry mouth. Other warnings and receptor agonist promoting anorex- Phentermine and topiramate precautions in the product label in- igenic effects and satiety through extended-release (Qsymia) was clude: monitoring heart rates in all the serotonin receptor activation. approved in 2012, and is a schedule patients; acute myopia and second- Lorcaserin exhibits preferential IV controlled substance approved ary angle closure glaucoma, mood affinity to 5-HT2c in comparison to for adjunct treatment of obesity or sleep disorders, cognitive im- other 5-HT receptor subtypes. This under the same circumstances as pairment, elevated creatinine, and selective activation limits the risk Belviq. Phentermine is a sympa- weight loss may cause hypoglyce- of hallucinations due to 5-HT2a ac- thomimetic amine that has been mia with anti-diabetic medications. tivation and the risk of cardiovas- available in the U.S. since 1959 for Because topiramate is a carbonic cular side effects including valvulo- short-term . anhydrase inhibitor, metabolic pathy and pulmonary hypertension Its mechanism of action is believed acidosis and kidney stones can oc- through 5-HT2b receptors. to be dependent on modulation cur. Antiepileptic drugs, including The most common adverse of catecholamines in the satiety topiramate, have been reported to events in non-diabetic patients centers of the hypothalamus, thus increase the risk of suicide ideation include headache, dizziness, reducing appetite. Topiramate, pre- and behavior. Qsymia is available fatigue, nausea, dry mouth, and viously approved by FDA and pri- through a limited program under constipation. In diabetic patients, marily used to treat seizure disor- a Risk Evaluation and Mitigation hypoglycemia, headache, back ders and migraines, was observed Strategy (REMS). pain, cough, and fatigue are re- to produce weight loss. The exact Qsymia was approved based on ported. Potential life-threatening mechanism by which topiramate two 56-week trials in which pa- serotonin syndrome or neuroleptic regulates appetite and induces tients were randomized to placebo malignant syndrome-like reactions weight loss is unknown. However, or to one of two doses of phenter- may occur when taken with other significant clinical evidence exists mine/topiramate. Results for the serotonergic or antidopaminergic to support its use as an anti-obesity EQUIP trial at one year are as agents. Other warnings or precau- drug. follows: 44.9 percent of patients tions in the product label include The recommended initial dose taking the 3.75 mg/23 mg dose valvular heart disease; cognitive is phentermine 3.75 mg/topiramate achieved at least 5 percent weight loss, compared to 66.7 percent tak- ments for prescribing controlled months. The date the patient filled ing 15 mg/92 mg and 17.3 percent substances for weight loss through the last prescription is day 1 of the in the placebo group. The same pri- a physical examination and a thor- six-month period during which the mary endpoint was utilized in the ough medical and social history. physician may not initiate a course CONQUER trial which reported 62 The physician must also evaluate of treatment using a controlled percent in the 7.5 mg/46 mg group and document that the patient has substance for weight loss. versus 70 percent in the 15 mg/92 no signs of drug or alcohol abuse, The Ohio Medical Board also mg group, and finally 21 percent or contraindications to the medica- provides guidance on how Qsymia in the placebo group. The data tion. prescriptions, in regard to dosing indicate that Qsymia may be more If the physician decides to be- titrations, should be written. Es- effective than lorcaserin, but may gin treatment, the physician must sentially, each time a titration is to cause more troublesome adverse meet with the patient face-to-face occur in 14 days, it is recommended effects. at least every 30 days to con- that the patient return to the of- tinually reassess and re-evaluate fice for a new prescription for the Ohio Rules for response to treatment. At every increased dose. There is no explicit Prescribing and visit, the physician must document prohibition of refills on Qsymia or Dispensing Qsymia and that the patient is demonstrating Belviq in the rule; however, it is Belviq continual efforts to lose weight, strongly discouraged as this will Qsymia and Belviq are FDA- dedicated to the treatment pro- deter patients from meeting face- approved schedule IV medica- gram and showing progress. The to-face with their physician every tions designed for chronic weight presence or absence of contraindi- 30 days. A refill on such a prescrip- management in adults, and have cations, adverse effects, and indica- tion would be appropriate as long potential for abuse or dependence. tors of possible substance abuse as the day supply does not exceed These agents have different restric- must also be documented at these 30 days. For instance, a prescrip- tions regarding their prescribing visits. A physician may only utilize tion for Qsymia 7.5 mg/46 mg, #15, for weight reduction in comparison a schedule III or IV controlled sub- with one refill is acceptable. Physi- to short-term weight reduction stance for purposes of weight re- cians are discouraged from writing products like phentermine. The duction if it has an FDA-approved multiple prescriptions with the laws and rules regarding the use indication for this purpose. notation, “Do not fill before ___,” as of controlled substances for weight The 12-week treatment limita- this will deter the visit and manda- reduction are found in the State tion enforced for short-term weight tory evaluation as well. There is Medical Board of Ohio section of loss agents (i.e., phentermine) does no limit on the amount of time a the Ohio Administrative Code. not apply to Qsymia and Belviq as patient can be on Qsymia or Belviq, Medical Board Rule 4631-11-04, they carry FDA-approval for chron- as long as the physician is comply- Ohio Administrative Code (OAC), ic weight management. Patients ing with required monitoring and Controlled substances: Utiliza- may be switched to one of these documentation. tion for weight reduction, governs two new drugs after completing 12 The physician shall discontinue the use of schedules III and IV weeks on phentermine (or ear- utilizing these therapies if he/she controlled substances to assist in lier), as long as there has been no ascertains or has reason to believe weight loss. The rules can be found interruption in treatment (defined that the patient has a history or at http://codes.ohio.gov/oac/4731- as <7 days). Or, the patient may shows propensity for alcohol or 11. These rules, as well as posted be switched to one of the two new drug abuse; has made any false or Q&A attachment to the rule, will drugs if treatment is interrupted misleading statements regarding be summarized in the next section for more than seven days due to such use; the patient fails to lose of this lesson. Pharmacists are en- one of the reasons outlined in OAC weight while under treatment; or couraged to access these documents 4731-11-4(C)(3). If treatment was the patient fails to comply with for full prescribing guidance set interrupted for over seven days treatment recommendations. forth by the Medical Board. for any other reason than listed, Schedule III or IV controlled sub- In general, before the decision the patient may not begin treat- stances for weight reduction are to utilize weight loss medications, ment with one of these agents until prohibited during pregnancy. the physician must determine that six months after the last date the the patient has made a good-faith physician prescribed phentermine. Pharmacist Role in effort to lose weight through a Further, Rule 4731-11-04(C)(3) pro- Dispensing Controlled treatment program (caloric restric- vides that except for specified situ- Substances for Obesity tion, nutritional counseling, behav- ations, a physician may not initiate While the Medical Board has ior modification, and exercise) that treatment for weight loss with a imposed stringent rules upon has been unsuccessful. In addition, controlled substance if the patient physicians prescribing such thera- the physician must decide if the has received controlled substances pies, the pharmacist also has a patient meets the FDA require- for weight loss within the last six corresponding responsibility to ensure that these medications are calculate a six-month break if chronic weight management. When prescribed for a legitimate medical required, and establish if a gap these medications are prescribed, purpose. Pharmacists who have greater than seven days may have physicians and pharmacists togeth- concern, or question the legiti- occurred and requires justification. er have an obligation to not only macy of these prescriptions, should Pharmacists are not required ensure that patients are counseled contact the physician, discuss the to document that the patient is on the potential adverse effects, patient’s case with him/her, and losing weight or to calculate the but also that they are dispensed in document the conversation. If con- BMI. However, he/she should use accordance with Ohio rule. cern remains regarding legitimacy professional judgment in dispens- of medical purpose, the pharmacist ing the agent if it is apparent that may refuse to fill the prescription. the patient does not meet the BMI Acknowledgement for contributions to the Additionally, pharmacists cannot requirements. lesson: Maria Biasella, as an OSU PharmD accept a prescription written by Candidate Advanced Practice Nurses (APNs) Summary The author, the Ohio Pharmacists Founda- or Physician Assistants (PAs) as In conclusion, obesity is a serious tion and the Ohio Pharmacists Association they are not authorized to prescribe disease endangering the public disclaim any liability to you or your patients any of the controlled substances for health of the U.S. population and resulting from reliance solely upon the infor- weight reduction. resulting in serious morbidity and mation contained herein. Bibliography for additional reading and inquiry is available Pharmacists may also request mortality. Clinical trials suggest upon request. an Ohio Automated Rx Report- that even modest weight loss cor- ing System (OARRS) report on a relates with a reduction in the risk This lesson is a knowledge-based CE activity and is targeted to pharmacists in all practice settings. patient to determine if the pre- of developing diabetes, as well as scription is for a legitimate medical improved glucose control, blood Program 0129-0000-14-008-H01-P purpose. An OARRS report will pressure control, and lipid profile. Release date: 8-15-14 identify any other controlled sub- Anti-obesity therapy may be a Expiration date: 8-15-17 stances for weight reduction that suitable adjunct treatment to help CE Hours: 1.5 (0.15 CEU) a patient may have filled at any patients who are unable to reach other pharmacy. Such information weight loss goals. Qsymia and The Ohio Pharmacists Foundation Inc. is accredited by the Accreditation Council can be used to calculate duration Belviq are two agents, in addition for Pharmacy Education as a provider of of therapy for short-term agents, to orlistat, that may be used for continuing pharmacy education. Program 0129-0000-14-008-H01-P continuing education quiz Please print. 0.15 CEU Name______Obesity: Treatment Guidelines and Update on Use of Belviq and Qsymia Address______City, State, Zip______1. Which of the following groups has the highest age- adjusted rates of obesity? Email______a. Hispanics c. Non-Hispanic blacks b. Non-Hispanic whites d. Non-Hispanic Asians NABP e-Profile ID______Birthdate______(MMDD)

2. According to the 1998 Clinical Guidelines on the Iden- Return quiz and payment (check or money order) to Correspondence Course, OPA, tification, Evaluation, and Treatment of Overweight and 2674 Federated Blvd, Columbus, OH 43235-4990 Obesity in Adults, overweight is defined as a: a. BMI 25 to 29.9 kg/m2. c. BMI >40 kg/m2. b. BMI >30 kg/m2. 8. Common adverse reactions with lorcaserin include: a. insomnia. c. diarrhea. 3. Due to safety issues, all of the following products have b. fatigue. d. seizures. been withdrawn from the market EXCEPT: a. phentermine. c. dexfenfluramine. 9. The average weight loss in lorcaserin clinical trials was: b. fenfluramine. d. sibutramine. a. 5.5 kg. c. 10.0 kg. b. 8.3 kg. d. 12.2 kg. 4. Orlistat is a/an: a. carbonic anhydrase inhibitor. 10. Abrupt withdrawal of topiramate may cause: b. sympathomimetic amine. a. tachycardia. c. seizures.

c. selective 5-HT2c receptor agonist. b. hypotension. d. fecal incontinence. d. gastrointestinal lipase inhibitor. 11. Qsymia is contraindicated in all of the following condi- 5. Individuals taking orlistat should be advised to: tions EXCEPT: a. monitor heart rate. a. pregnancy. c. hyperthyroidism. b. watch for cognitive impairment. b. glaucoma. d. hypertension. c. take a multivitamin once daily at bedtime. d. take with caution with other serotonergic drugs. 12. Which of the following active ingredients of Qsymia is associated with suicide ideation and behavior? 6. FDA revised the labeling of orlistat products to include a. Topiramate b. Phentermine safety information relating to: a. renal impairment. c. CNS impairment. 13. In order for a physician to prescribe controlled b. liver injury. d. cardiac function. substances for chronic weight loss, he/she must see the patient face-to-face every: 7. The dosage of lorcaserin is: a. 15 days. c. 60 days. a. 120 mg TID. c. 60 mg TID. b. 30 days. d. 90 days. b. 92 mg once daily. d. 10 mg BID. 14. If treatment with phentermine is interrupted for more than seven days, treatment with Belviq or Qsymia may Completely fill in the lettered box corresponding to not begin until how many months after the last date the your answer. physician prescribed phentermine? a. One month c. Six months 1. [a] [b] [c] [d] 6. [a] [b] [c] [d] 11. [a] [b] [c] [d] b. Three months d. 12 months 2. [a] [b] [c] 7. [a] [b] [c] [d] 12. [a] [b] 3. [a] [b] [c] [d] 8. [a] [b] [c] [d] 13. [a] [b] [c] [d] 15. All of the following statements are true for pharma- 4. [a] [b] [c] [d] 9. [a] [b] [c] [d] 14. [a] [b] [c] [d] cists dispensing controlled substances for obesity EX- 5. [a] [b] [c] [d] 10. [a] [b] [c] [d] 15. [a] [b] [c] [d] CEPT: a. the pharmacist should document conversations with  I am enclosing $5 for this month’s quiz made payable to: Ohio Pharmacists Association. the patient’s physician. b. the pharmacist may refuse to fill the prescription if 1. Rate this lesson: (Excellent) 5 4 3 2 1 (Poor) concerned about the legitimacy of medical purpose. 2. Did it meet each of its objectives?  yes  no c. an OARRS report will help the pharmacist determine If no, list any unmet______if the prescription is for a legitimate medical purpose. 3. Was the content balanced and without commercial bias? d. the pharmacist must document patient’s weight loss  yes  no during therapy. 4. Did the program meet your educational/practice needs?  yes  no 5. How long did it take you to read this lesson and complete the quiz? ______To receive CE credit, your quiz must be received no later than August 15, 2017. A passing grade of 80% must be attained. CE credit for 6. Comments/future topics welcome. successfully completed quizzes will be uploaded to the CPE Monitor. CE statements of credit will not be mailed, but can be printed from the CPE Monitor website. Send inquiries to [email protected]. august 2014