According to the Centers for Disease Control and Prevention, a third of adults in the United States are overweight and another third are obese. A new drug has now been approved to help promote weight loss. Lorcaserin (Belviq) works by activating the serotonin 5-HT2C receptor in the brain, which causes a person to feel full after eating smaller amounts and therefore eat less. The drug is approved for adults who are obese (a body mass index [BMI] of 30 or higher) and adults who are overweight (a BMI of 27 or higher) and have at least one weight-related health problem, such as hypertension, type 2 diabetes, or dyslipidemia. Lorcaserin should be used in conjunction with weight-reduction strategies based on diet and exercise.
Clinical trials lasting between 52 and 104 weeks evaluated the safety and effectiveness of lorcaserin in adults with and without type 2 diabetes. About twice as many patients receiving lorcaserin reduced their weight by at least 5% as did patients receiving placebo: those without type 2 diabetes, 47% versus 23%, respectively; with type 2 diabetes, 38% versus 16%, respectively.
Two earlier weight-loss drugs, fenfluramine and dexfenfluramine, targeted serotonin 5-HT2B receptors. Activation of these receptors is believed to have been responsible for the development of heart valve damage. Fenfluramine and dexfenfluramine were removed from the market in 1997, after their connection to heart valve damage was demonstrated. Clinical trials of lorcaserin assessed heart valve function through echocardiography, and no clinically significant differences in the development of heart valve damage were found between those receiving medication and those receiving a placebo. This may be because the prescribed dosage, 10 mg twice daily, doesn't stimulate serotonin 5-HT2B receptors. Still, lorcaserin carries a warning that it may cause valvular heart disease. Patients with congestive heart failure appear to have an increased number of serotonin 5-HT2B receptors and may have a greater risk of heart damage; even though lorcaserin is relatively selective for serotonin 5-HT2C receptors, it may stimulate other serotonin receptors, including type 5-HT2B. The drug's safety as it pertains to other cardiac conditions hasn't yet been established; the manufacturer will complete six clinical trials to determine the associated risks of cardiac events such as myocardial infarction and stroke. Lorcaserin is a pregnancy category X drug and is contraindicated in pregnant women.
Lorcaserin carries several other warnings and precautions for use. Because the drug blocks some serotonin receptors, circulating serotonin levels are increased. Consequently, coadministration with other drugs that increase serotonin levels, such as selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), triptans, bupropion, dextromethorphan, and St. John's wort, may lead to serotonin syndrome or even neuroleptic malignant syndrome–like reaction, which can be life threatening. In both of these conditions the central nervous system is overactive. Patients experience adverse effects such as changes in mental status (agitation, irritability, hypomania, dysphoria, or anxiety), changes in the level of consciousness (confusion, delirium, or coma), changes in behavior (restlessness or agitation), autonomic nervous system changes (diaphoresis, fever, tachycardia, labile blood pressure, shivering, tachypnea, mydriasis), or neurologic problems (tremor, muscle spasms, muscle rigidity, hyperreflexia, or ataxia), as well as gastrointestinal problems (nausea, vomiting, and diarrhea). At its extreme, serotonin syndrome can mimic neuroleptic malignant syndrome (and is called neuroleptic malignant syndrome–like reaction), a rare complication of antipsychotics. The symptoms include muscle rigidity (which may also include akinesia, dyskinesia, or cogwheeling), hyperpyrexia (higher than 100.4°F [38°C]), changes in the level of consciousness (stupor, coma, delirium, or catatonia), and autonomic instability (tachycardia, alterations in blood pressure, respiratory distress; the vital signs may fluctuate rapidly).
Other labeled warnings and precautions include elevated risks of a disturbance in memory or attention, euphoria and dissociation, depression and suicidal thoughts, hypoglycemia (in patients with type 2 diabetes), and priapism (a persistent and often painful erection that can last more than six hours and cause serious, permanent damage).
In the clinical trials, adverse effects of lorcaserin differed slightly depending on whether the patient had type 2 diabetes. In those with diabetes, the most common adverse effects (occurring in more than 5% of patients) were hypoglycemia, headache, back pain, cough, and fatigue. In those without diabetes, the most common adverse effects were headache, dizziness, fatigue, nausea, dry mouth, and constipation. Lorcaserin was also noted in clinical trials to decrease the pulse rate, decrease white blood cell counts, and elevate prolactin levels.
Prior to initiating treatment and periodically throughout treatment, a thorough drug history should be taken to confirm that the patient isn't currently receiving any drugs that increase the risk of serotonin syndrome or neuroleptic malignant syndrome–like reaction, such as SSRIs, SNRIs, MAOIs, antipsychotics, St John's wort, or dopamine antagonists. Patient education should stress the importance of avoiding over-the-counter medications that can increase serotonin or monoamine oxidase levels, such as many cough and cold preparations; following a weight-loss diet; and continuing an exercise regimen while taking lorcaserin. NPs who prescribe lorcaserin to treat overweight and obese patients should monitor them for weight loss. If a patient hasn't lost 5% of her or his weight after 12 weeks of drug use, the drug should be discontinued because it's unlikely to produce a therapeutic effect. Nurses should assess patients receiving lorcaserin for indications of valvular heart disease (dyspnea, dependent edema, congestive heart failure, or a new cardiac murmur) and if they're present, consult with the prescriber because the patient needs to be evaluated and the drug likely discontinued. Special precautions should be taken if the patient has congestive heart failure. Patients should be instructed to avoid the use of hazardous machinery or driving until the effects of the drug on the patient are known. Other patient instructions include seeking immediate medical attention if depression, suicidal thoughts, or unusual mood or behavior changes occur while they're taking lorcaserin; using birth control to prevent pregnancy and avoiding breastfeeding; seeking medical attention if they experience an erection lasting longer than four hours, and taking only the prescribed dosage, never increasing it on their own.
For complete labeling information, see http://1.usa.gov/LLy4uP.