1 INDICATIONS AND USAGE BELVIQ is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of: 30 kg/m2 or greater (obese), or 27 kg/m2 or greater (overweight) in the presence of at least one weight related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes) [see Dosage and Administration (2)] Limitations of Use: The safety and efficacy of coadministration of BELVIQ with other products intended for weight loss including prescription drugs (e.g., phentermine), over-the-counter drugs, and herbal preparations have not been established The effect of BELVIQ on cardiovascular morbidity and mortality has not been established BELVIQ is a serotonin 2C receptor agonist indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of: 30 kg/m2 or greater (obese) (1) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition, (e.g., hypertension, dyslipidemia, type 2 diabetes) (1) Limitations of Use: The safety and efficacy of coadministration with other products for weight loss have not been established (1) The effect of BELVIQ on cardiovascular morbidity and mortality has not been established (1)
3 DOSAGE FORMS AND STRENGTHS BELVIQ is provided as blue, film-coated, 10 mg tablets. The tablets are round, biconvex, debossed with "A" on one side and "10" on the other side. 10 mg film-coated tablets (3)
4 CONTRAINDICATIONS Pregnancy [see Use in Specific Populations (8.1)] Pregnancy (4)
5 WARNINGS AND PRECAUTIONS Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions: The safety of coadministration with other serotonergic or antidopaminergic agents has not been established. Manage with immediate BELVIQ discontinuation and provide supportive treatment. (5.1) Valvular heart disease: If signs or symptoms develop consider BELVIQ discontinuation and evaluate the patient for possible valvulopathy. (5.2) Cognitive Impairment: May cause disturbances in attention or memory. Caution with use of hazardous machinery when starting BELVIQ treatment. (5.3) Psychiatric Disorders, including euphoria and dissociation: Do not exceed recommended dose of 10 mg twice daily. (5.4) Monitor for depression or suicidal thoughts. Discontinue if symptoms develop. (5.4) Use of Antidiabetic Medications: weight loss may cause hypoglycemia. Monitor blood glucose. BELVIQ has not been studied in patients taking insulin. (5.5) Priapism: Patients should seek emergency treatment if an erection lasts >4 hours. Use BELVIQ with caution in patients predisposed to priapism. (5.6) 5.1 Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions BELVIQ is a serotonergic drug. The development of a potentially life-threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported during use of serotonergic drugs, including, but not limited to, selective serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), bupropion, triptans, dietary supplements such as St. John's Wort and tryptophan, drugs that impair metabolism of serotonin (including monoamine oxidase inhibitors [MAOIs]), dextromethorphan, lithium, tramadol, antipsychotics or other dopamine antagonists, particularly when used in combination [see Drug Interactions (7.1)]. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS-like signs and symptoms. The safety of BELVIQ when coadministered with other serotonergic or antidopaminergic agents, including antipsychotics, or drugs that impair metabolism of serotonin, including MAOIs, has not been systematically evaluated and has not been established. If concomitant administration of BELVIQ with an agent that affects the serotonergic neurotransmitter system is clinically warranted, extreme caution and careful observation of the patient is advised, particularly during treatment initiation and dose increases. Treatment with BELVIQ and any concomitant serotonergic or antidopaminergic agents, including antipsychotics, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated [see Adverse Reactions (6.1) and Drug Interactions (7.1)]. 5.2 Valvular Heart Disease Regurgitant cardiac valvular disease, primarily affecting the mitral and/or aortic valves, has been reported in patients who took serotonergic drugs with 5-HT2B receptor agonist activity. The etiology of the regurgitant valvular disease is thought to be activation of 5-HT2B receptors on cardiac interstitial cells. At therapeutic concentrations, BELVIQ is selective for 5-HT2C receptors as compared to 5-HT2B receptors. In clinical trials of 1-year duration, 2.4% of patients receiving BELVIQ and 2.0% of patients receiving placebo developed echocardiographic criteria for valvular regurgitation at one year (mild or greater aortic regurgitation and/or moderate or greater mitral regurgitation): none of these patients was symptomatic [see Adverse Reactions (6.1) see Clinical Pharmacology (12.1)]. BELVIQ has not been studied in patients with congestive heart failure or hemodynamically-significant valvular heart disease. Preliminary data suggest that 5HT2B receptors may be overexpressed in congestive heart failure, Therefore, BELVIQ should be used with caution in patients with congestive heart failure. BELVIQ should not be used in combination with serotonergic and dopaminergic drugs that are potent 5-HT2B receptor agonists and are known to increase the risk for cardiac valvulopathy (e.g., cabergoline). Patients who develop signs or symptoms of valvular heart disease, including dyspnea, dependent edema, congestive heart failure, or a new cardiac murmur while being treated with BELVIQ should be evaluated and discontinuation of BELVIQ should be considered. 5.3 Cognitive Impairment In clinical trials of at least one year in duration, impairments in attention and memory were reported adverse reactions associated with 1.9% of patients treated with BELVIQ and 0.5% of patients treated with placebo, and led to discontinuation in 0.3% and 0.1% of these patients, respectively. Other reported adverse reactions associated with BELVIQ in clinical trials included confusion, somnolence, and fatigue [see Adverse Reactions (6.1)]. Since BELVIQ has the potential to impair cognitive function, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that BELVIQ therapy does not affect them adversely [see Patient Counseling Information (17)]. 5.4 Psychiatric Disorders Events of euphoria, hallucination, and dissociation were seen with BELVIQ at supratherapeutic doses in short-term studies [see Adverse Reactions (6.1), Drug Abuse and Dependence (9.2), and Overdosage (10)]. In clinical trials of at least 1-year in duration, 6 patients (0.2%) treated with BELVIQ developed euphoria, as compared with 1 patient (<0.1%) treated with placebo. Doses of BELVIQ should not exceed 10 mg twice a day. Some drugs that target the central nervous system have been associated with depression or suicidal ideation. Patients treated with BELVIQ should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue BELVIQ in patients who experience suicidal thoughts or behaviors [see Adverse Reactions (6.1)]. 5.5 Potential Risk of Hypoglycemia in Patients with Type 2 Diabetes Mellitus on Anti-diabetic Therapy Weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with insulin and/or insulin secretagogues (e.g., sulfonylureas); hypoglycemia was observed in clinical trials with BELVIQ. BELVIQ has not been studied in combination with insulin. Measurement of blood glucose levels prior to starting BELVIQ and during BELVIQ treatment is recommended in patients with type 2 diabetes. Decreases in medication doses for anti-diabetic medications which are non-glucose-dependent should be considered to mitigate the risk of hypoglycemia. If a patient develops hypoglycemia after starting BELVIQ, appropriate changes should be made to the anti-diabetic drug regimen [see Adverse Reactions (6.1)]. 5.6 Priapism Priapism (painful erections greater than 6 hours in duration) is a potential effect of 5-HT2C receptor agonism. If not treated promptly, priapism can result in irreversible damage to the erectile tissue. Men who have an erection lasting greater than 4 hours, whether painful or not, should immediately discontinue the drug and seek emergency medical attention. BELVIQ should be used with caution in men who have conditions that might predispose them to priapism (e.g., sickle cell anemia, multiple myeloma, or leukemia), or in men with anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, or Peyronie's disease). There is limited experience with the combination of BELVIQ and medication indicated for erectile dysfunction (e.g., phosphodiesterase type 5 inhibitors). Therefore, the combination of BELVIQ and these medications should be used with caution. 5.7 Heart Rate Decreases In clinical trials of at least 1-year in duration, the mean change in heart rate (HR) was -1.2 beats per minute (bpm) in BELVIQ and -0.4 bpm in placebo-treated patients without diabetes and -2.0 beats per minute (bpm) in BELVIQ and -0.4 bpm in placebo-treated patients with type 2 diabetes. The incidence of HR less than 50 bpm was 5.3% in BELVIQ and 3.2% in placebo-treated patients without diabetes and 3.6% in BELVIQ and 2.0% in placebo-treated patients with type 2 diabetes. In the combined population, adverse reactions of bradycardia occurred in 0.3% of BELVIQ and 0.1% of placebo-treated patients. Use with caution in patients with bradycardia or a history of heart block greater than first degree. 5.8 Hematological Changes In clinical trials of at least one year in duration, adverse reactions of decreases in white blood cell count (including leukopenia, lymphopenia, neutropenia, and decreased white cell count) were reported in 0.4% of patients treated with BELVIQ as compared to 0.2% of patients treated with placebo. Adverse reactions of decreases in red blood cell count (including anemia and decreases in hemoglobin and hematocrit) were reported by 1.3% of patients treated with BELVIQ as compared to 1.2% treated with placebo [see Adverse Reactions (6.1)]. Consider periodic monitoring of complete blood count during treatment with BELVIQ. 5.9 Prolactin Elevation Lorcaserin moderately elevates prolactin levels. In a subset of placebo-controlled clinical trials of at least one year in duration, elevations of prolactin greater than the upper limit of normal, two times the upper limit of normal, and five times the upper limit of normal, measured both before and 2 hours after dosing, occurred in 6.7%, 1.7%, and 0.1% of BELVIQ-treated patients and 4.8%, 0.8%, and 0.0% of placebo-treated patients, respectively [see Adverse Reactions (6.1)]. Prolactin should be measured when symptoms and signs of prolactin excess are suspected (e.g., galactorrhea, gynecomastia). There was one patient treated with BELVIQ who developed a prolactinoma during the trial. The relationship of BELVIQ to the prolactinoma in this patient is unknown. 5.10 Pulmonary Hypertension Certain centrally-acting weight loss agents that act on the serotonin system have been associated with pulmonary hypertension, a rare but lethal disease. Because of the low incidence of this disease, the clinical trial experience with BELVIQ is inadequate to determine if BELVIQ increases the risk for pulmonary hypertension.
6 ADVERSE REACTIONS The following important adverse reactions are described below and elsewhere in labeling: Serotonin Syndrome or NMS-like Reactions [see Warnings and Precautions (5.1)] Valvular Heart Disease [see Warnings and Precautions (5.2)] Cognitive Impairment [see Warnings and Precautions (5.3)] Psychiatric Disorders [see Warnings and Precautions (5.4)] Hypoglycemia [see Warnings and Precautions (5.5)] Heart Rate Decreases [see Warnings and Precautions (5.7)] Hematological Changes [see Warnings and Precautions (5.8)] Prolactin Elevation [see Warnings and Precautions (5.9)] Most common adverse reactions (greater than 5%) in non-diabetic patients are headache, dizziness, fatigue, nausea, dry mouth, and constipation, and in diabetic patients are hypoglycemia, headache, back pain, cough, and fatigue. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Eisai Inc. at 1-888-274-2378 or FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch . 6.1 Clinical Trials Experience In the BELVIQ placebo-controlled clinical database of trials of at least one year in duration, of 6888 patients (3451 BELVIQ vs. 3437 placebo; age range 18-66 years, 79.3% women, 66.6% Caucasians, 19.2% Blacks, 11.8% Hispanics, 2.4% other, 7.4% type 2 diabetics), a total of 1969 patients were exposed to BELVIQ 10 mg twice daily for 1 year and 426 patients were exposed for 2 years. In clinical trials of at least one year in duration, 8.6% of patients treated with BELVIQ prematurely discontinued treatment due to adverse reactions, compared with 6.7% of placebo-treated patients. The most common adverse reactions leading to discontinuation more often among BELVIQ treated patients than placebo were headache (1.3% vs. 0.8%), depression (0.9% vs. 0.5%) and dizziness (0.7% vs. 0.2%). Most Common Adverse Reactions Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions for non-diabetic patients (greater than 5% and more commonly than placebo) treated with BELVIQ compared to placebo were headache, dizziness, fatigue, nausea, dry mouth, and constipation. The most common adverse reactions for diabetic patients were hypoglycemia, headache, back pain, cough, and fatigue. Adverse reactions that were reported by greater than or equal to 2% of patients and were more frequently reported by patients taking BELVIQ compared to placebo are summarized in Table 2 (non-diabetic subjects) and Table 3 (subjects with type 2 diabetes mellitus). Table 2. Adverse Reactions Reported by Greater Than or Equal to 2% of BELVIQ Patients and More Commonly than with Placebo in Patients without Diabetes Mellitus Adverse Reaction Number of patients (%) BELVIQ 10 mg BID N=3195 Placebo N=3185 Gastrointestinal Disorders Nausea 264 (8.3) 170 (5.3) Diarrhea 207 (6.5) 179 (5.6) Constipation 186 (5.8) 125 (3.9) Dry mouth 169 (5.3) 74 (2.3) Vomiting 122 (3.8) 83 (2.6) General Disorders And Administration Site Conditions Fatigue 229 (7.2) 114 (3.6) Infections And Infestations Upper respiratory tract infection 439 (13.7) 391 (12.3) Nasopharyngitis 414 (13.0) 381 (12.0) Urinary tract infection 207 (6.5) 171 (5.4) Musculoskeletal And Connective Tissue Disorders Back pain 201 (6.3) 178 (5.6) Musculoskeletal pain 65 (2.0) 43 (1.4) Nervous System Disorders Headache 537 (16.8) 321 (10.1) Dizziness 270 (8.5) 122 (3.8) Respiratory, Thoracic And Mediastinal Disorders Cough 136 (4.3) 109 (3.4) Oropharyngeal pain 111 (3.5) 80 (2.5) Sinus congestion 93 (2.9) 78 (2.4) Skin And Subcutaneous Tissue Disorders Rash 67 (2.1) 58 (1.8) Table 3. Adverse Reactions Reported by Greater Than or Equal to 2% of BELVIQ Patients and More Commonly than with Placebo in Patients with Type 2 Diabetes Mellitus Number of patients (%) Adverse Reaction BELVIQ 10 mg BID N=256 Placebo N=252 Gastrointestinal Disorders Nausea 24 (9.4) 20 (7.9) Toothache 7 (2.7) 0 General Disorders And Administration Site Conditions Fatigue 19 (7.4) 10 (4.0) Peripheral edema 12 (4.7) 6 (2.4) Immune System Disorders Seasonal allergy 8 (3.1) 2 (0.8) Infections And Infestations Nasopharyngitis 29 (11.3) 25 (9.9) Urinary tract infection 23 (9.0) 15 (6.0) Gastroenteritis 8 (3.1) 5 (2.0) Metabolism And Nutrition Disorders Hypoglycemia 75 (29.3) 53 (21.0) Worsening of diabetes mellitus 7 (2.7) 2 (0.8) Decreased appetite 6 (2.3) 1 (0.4) Musculoskeletal And Connective Tissue Disorders Back pain 30 (11.7) 20 (7.9) Muscle spasms 12 (4.7) 9 (3.6) Nervous System Disorders Headache 37 (14.5) 18 (7.1) Dizziness 18 (7.0) 16 (6.3) Psychiatric Disorders Anxiety 9 (3.5) 8 (3.2) Insomnia 9 (3.5) 6 (2.4) Stress 7 (2.7) 3 (1.2) Depression 6 (2.3) 5 (2.0) Respiratory, Thoracic And Mediastinal Disorders Cough 21 (8.2) 11 (4.4) Vascular Disorders Hypertension 13 (5.1) 8 (3.2) Other Adverse Reactions Serotonin-associated Adverse Reactions SSRIs, SNRIs, bupropion, tricyclic antidepressants, and MAOIs were excluded from the BELVIQ trials. Triptans and dextromethorphan were permitted: 2% and 15%, respectively, of patients without diabetes and 1% and 12%, respectively, of patients with type 2 diabetes experienced concomitant use at some point during the trials. Two patients treated with BELVIQ in the clinical program experienced a constellation of symptoms and signs consistent with serotonergic excess, including one patient on concomitant dextromethorphan who reported an event of serotonin syndrome. Some symptoms of possible serotonergic etiology that are included in the criteria for serotonin syndrome were reported by patients treated with BELVIQ and placebo during clinical trials of at least 1 year in duration. In both groups, chills were the most frequent of these events (1.0% vs. 0.2%, respectively), followed by tremor (0.3% vs. 0.2%), confusional state (0.2% vs. less than 0.1%), disorientation (0.1% vs. 0.1%) and hyperhidrosis (0.1% vs. 0.2%). Because serotonin syndrome has a very low incidence, an association between BELVIQ and serotonin syndrome cannot be excluded on the basis of clinical trial results [see Warnings and Precautions (5.1)]. Hypoglycemia in Patients with Type 2 Diabetes In a clinical trial of patients with type 2 diabetes mellitus, hypoglycemia requiring the assistance of another person occurred in 4 (1.6%) of BELVIQ-treated patients and in 1 (0.4%) placebo-treated patient. Of these 4 BELVIQ-treated patients, all were concomitantly using a sulfonylurea (with or without metformin). BELVIQ has not been studied in patients taking insulin. Hypoglycemia defined as blood sugar less than or equal to 65 mg/dL and with symptoms occurred in 19 (7.4%) BELVIQ-treated patients and 16 (6.3%) placebo-treated patients. Cognitive Impairment In clinical trials of at least 1-year duration, adverse reactions related to cognitive impairment (e.g., difficulty with concentration/attention, difficulty with memory, and confusion) occurred in 2.3% of patients taking BELVIQ and 0.7% of patients taking placebo. Psychiatric Disorders Psychiatric disorders leading to hospitalization or drug withdrawal occurred more frequently in patients treated with BELVIQ (2.2%) as compared to placebo (1.1%) in non-diabetic patients. Euphoria. In short-term studies with healthy individuals, the incidence of euphoric mood following supratherapeutic doses of BELVIQ (40 and 60 mg) was increased as compared to placebo [see Drug Abuse and Dependence (9.2)]. In clinical trials of at least 1-year duration in obese patients, euphoria was observed in 0.17% of patients taking BELVIQ and 0.03% taking placebo. Depression and Suicidality. In trials of at least one year in duration, reports of depression/mood problems occurred in 2.6% BELVIQ-treated vs. 2.4% placebo-treated and suicidal ideation occurred in 0.6% BELVIQ-treated vs. 0.4% placebo-treated patients. 1.3% of BELVIQ patients vs. 0.6% of placebo patients discontinued drug due to depression-, mood-, or suicidal ideation-related events. Laboratory Abnormalities Lymphocyte and Neutrophil Counts. In clinical trials of at least 1-year duration, lymphocyte counts were below the lower limit of normal in 12.2% of patients taking BELVIQ and 9.0% taking placebo, and neutrophil counts were low in 5.6% and 4.3%, respectively. Hemoglobin. In clinical trials of at least 1-year duration, 10.4% of patients taking BELVIQ and 9.3% taking placebo had hemoglobin below the lower limit of normal at some point during the trials. Prolactin. In clinical trials, elevations of prolactin greater than the upper limit of normal, two times the upper limit of normal, and five times the upper limit of normal, occurred in 6.7%, 1.7%, and 0.1% of BELVIQ-treated patients and 4.8%, 0.8%, and 0.0% of placebo-treated patients, respectively. Eye disorders. More patients on BELVIQ reported an eye disorder than patients on placebo in clinical trials of patients without diabetes (4.5% vs. 3.0%) and with type 2 diabetes (6.3% vs. 1.6%). In the population without diabetes, events of blurred vision, dry eye, and visual impairment occurred in BELVIQ-treated patients at an incidence greater than that of placebo. In the population with type 2 diabetes, visual disorders, conjunctival infections, irritations, and inflammations, ocular sensation disorders, and cataract conditions occurred in BELVIQ-treated patients at an incidence greater than placebo. Echocardiographic Safety Assessments The possible occurrence of regurgitant cardiac valve disease was prospectively evaluated in 7794 patients in three clinical trials of at least one year in duration, 3451 of whom took BELVIQ 10 mg twice daily. The primary echocardiographic safety parameter was the proportion of patients who developed echocardiographic criteria of mild or greater aortic insufficiency and/or moderate or greater mitral insufficiency from baseline to 1 year. At 1 year, 2.4% of patients who received BELVIQ and 2.0% of patients who received placebo developed valvular regurgitation. The relative risk for valvulopathy with BELVIQ is summarized in Table 4. BELVIQ was not studied in patients with congestive heart failure or hemodynamically-significant valvular heart disease [see Warnings and Precautions (5.2)]. Table 4. Incidence of FDA-Defined Valvulopathy at Week 52 by Treatment Group1 1 Patients without valvulopathy at baseline who received study medication and had a post-baseline echocardiogram; ITT-intention-to-treat; LOCF-last observation carried forward Study 1 Study 2 Study 3 BELVIQ N=1278 Placebo N=1191 BELVIQ N=1208 Placebo N=1153 BELVIQ N=210 Placebo N=209 FDA-defined Valvulopathy, n (%) 34 (2.7) 28 (2.4) 24 (2.0) 23 (2.0) 6 (2.9) 1 (0.5) Relative Risk (95% CI) 1.13 (0.69, 1.85) 1.00 (0.57, 1.75) 5.97 (0.73, 49.17) Pooled RR (95% CI) 1.16 (0.81, 1.67)
7 DRUG INTERACTIONS Serotonergic drugs (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), triptans, bupropion, dextromethorphan, St. John's Wort): use with extreme caution due to the risk of serotonin syndrome. (7.1) 7.1 Use with Other Agents that Affect Serotonin Pathways Based on the mechanism of action of BELVIQ and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, but not limited to, triptans, monoamine oxidase inhibitors (MAOIs, including linezolid, an antibiotic which is a reversible non-selective MAOI), selective serotonin reuptake inhibitors (SSRIs), selective serotonin-norepinephrine reuptake inhibitors (SNRIs), dextromethorphan, tricyclic antidepressants (TCAs), bupropion, lithium, tramadol, tryptophan, and St. John's Wort [see Warnings and Precautions (5.1)]. 7.2 Cytochrome P450 (2D6) substrates Use caution when administering BELVIQ together with drugs that are CYP 2D6 substrates, as BELVIQ can increase exposure of these drugs [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS Nursing Mothers: Discontinue drug or nursing. (8.3) Pediatric Use: Safety and effectiveness not established and use not recommended. (8.4) 8.1 Pregnancy Pregnancy Category X. Risk Summary BELVIQ is contraindicated during pregnancy, because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm. Maternal exposure to lorcaserin in late pregnancy in rats resulted in lower body weight in offspring which persisted to adulthood. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard of maternal weight loss to the fetus. Clinical Considerations A minimum weight gain, and no weight loss, is currently recommended for all pregnant women, including those who are already overweight or obese, due to the obligatory weight gain that occurs in maternal tissues during pregnancy. Animal Data Reproduction studies were performed in pregnant rats and rabbits that were administered lorcaserin during the period of embryofetal organogenesis. Plasma exposures up to 44 and 19 times human exposure in rats and rabbits, respectively, did not reveal evidence of teratogenicity or embryolethality with lorcaserin hydrochloride. In a pre- and postnatal development study, maternal rats were dosed from gestation through post-natal day 21 at 5, 15, and 50mg/kg lorcaserin; pups were indirectly exposed in utero and throughout lactation. The highest dose (~44 times human exposure) resulted in stillborns and lower pup viability. All doses lowered pup body weight similarly at birth which persisted to adulthood; however, no developmental abnormalities were observed and reproductive performance was not affected at any dose. 8.3 Nursing Mothers It is not known whether BELVIQ is excreted in human milk. Because many drugs are excreted in human milk, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use The safety and effectiveness of BELVIQ in pediatric patients below the age of 18 have not been established and the use of BELVIQ is not recommended in pediatric patients. 8.5 Geriatric Use In the BELVIQ clinical trials, a total of 135 (2.5%) of the patients were 65 years of age and older. Clinical studies of BELVIQ did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects, but greater sensitivity of some older individuals cannot be ruled out. Since elderly patients have a higher incidence of renal impairment, use of BELVIQ in the elderly should be made on the basis of renal function [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)]. Elderly patients with normal renal function should require no dose adjustment. 8.6 Renal Impairment No dose adjustment of BELVIQ is required in patients with mild renal impairment. Use BELVIQ with caution in patients with moderate renal impairment. Use of BELVIQ in patients with severe renal impairment or end stage renal disease is not recommended [see Clinical Pharmacology (12.3)]. 8.7 Hepatic Impairment Dose adjustment is not required for patients with mild hepatic impairment (Child-Pugh score 5-6) to moderate hepatic impairment (Child-Pugh score 7-9). The effect of severe hepatic impairment on lorcaserin was not evaluated. Use lorcaserin with caution in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].