"U.S. Marshals, acting on behalf of the U.S. Food and Drug Administration, today seized tainted dietary supplements from Globe All Wellness, LLC (Globe All), in Hollywood, Fla. The products may be unsafe because they contain an undisclosed active "...
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].
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 and DRUG INTERACTIONS].
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 see CLINICAL PHARMACOLOGY].
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.
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].
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 INFORMATION].
Events of euphoria, hallucination, and dissociation were seen with BELVIQ at supratherapeutic doses in short-term studies [see ADVERSE REACTIONS, Drug Abuse and Dependence, and OVERDOSAGE]. 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].
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-glucosedependent 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].
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.
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.
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]. Consider periodic monitoring of complete blood count during treatment with BELVIQ.
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]. 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.
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.
Patient Counseling Information
See FDA-approved patient labeling (PATIENT INFORMATION).
- BELVIQ is indicated for chronic weight management only in conjunction with a reduced-calorie diet and increased physical activity.
- Patients should be instructed to discontinue use of BELVIQ if they have not achieved 5% weight loss by 12 weeks of treatment.
- Patients should be informed of the possibility of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions with the combined use of BELVIQ with other serotonergic drugs, including selective serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs), triptans, drugs that impair metabolism of serotonin (including monoamine oxidase inhibitors [MAOIs]), dietary supplements such as St. John's Wort and tryptophan, tramadol, or antipsychotics or other dopamine antagonists.
- Patients who develop signs or symptoms of valvular heart disease, including dyspnea or dependent edema should seek medical attention.
- Patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that BELVIQ therapy does not affect them adversely.
- Patients should be instructed to seek medical attention in the event of emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
- Patients should be cautioned not to increase their dose of BELVIQ.
- Men who have an erection lasting greater than 4 hours, whether painful or not, should immediately discontinue the drug and seek emergency medical attention.
- Patients should be instructed to avoid pregnancy or breastfeeding while undergoing BELVIQ therapy and to talk to their prescribing physician should they get pregnant or decide to breastfeed.
- Patients should tell their healthcare provider about all the medications, nutritional supplements and vitamins (including any weight loss products) that they may take while taking BELVIQ.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Lorcaserin hydrochloride was not mutagenic in an in vitro bacterial mutation assay (Ames test), was not clastogenic in an in vitro chromosome aberration assay in Chinese hamster ovary cells, and was not genotoxic in an in vivo micronucleus assay in rat bone marrow.
The carcinogenic potential of lorcaserin hydrochloride was assessed in two-year carcinogenicity studies in mice and rats. CD-1 mice received doses of 5, 25 and 50 mg/kg. There were no treatmentrelated increases in the incidence of any tumor in mice at doses that produced plasma exposure in males and females of 8 and 4-times the daily human clinical dose, respectively.
In the rat carcinogenicity study, male and female Sprague-Dawley rats received 10, 30, and 100 mg/kg lorcaserin hydrochloride. In females, mammary adenocarcinoma increased at 100 mg/kg, which was associated with plasma exposures that were 87-times the daily human clinical dose. The incidence of mammary fibroadenoma was increased in female rats at all doses with no safety margin to the clinical dose. The increases in adenocarcinomas and fibroadenomas may be associated with lorcaserin hydrochloride-induced changes in prolactin homeostasis in rats. The relevance of the increased incidence of mammary adenocarcinomas and fibroadenomas in rats to humans is unknown.
In male rats, treatment-related neoplastic changes were observed in the subcutis (fibroadenoma, Schwannoma), the skin (squamous cell carcinoma), mammary gland (adenocarcinoma and fibroadenoma), and the brain (astrocytoma) at greater than or equal to 30 mg/kg (plasma exposure 17-times human clinical dose). At higher exposure, liver adenoma and thyroid follicular cell adenoma were increased but were considered secondary to liver enzyme induction in rats and are not considered relevant to humans. Human brain exposure (AUC24h,ss ) to lorcaserin at the clinical dose is estimated to be 70-fold lower than brain exposure in rats at the dose at which no increased incidence of astrocytoma was observed. Excluding the liver and thyroid tumors, these neoplastic findings in male rats are of unknown relevance to humans.
Impairment of Fertility
Potential effects on fertility were assessed in Sprague-Dawley rats in which males were dosed with lorcaserin hydrochloride for 4 weeks prior to and through the mating period, and females were dosed for 2 weeks prior to mating and through gestation day 7. Lorcaserin hydrochloride had no effects on fertility in rats at exposures up to 29 times the human clinical dose.
Use In Specific Populations
Pregnancy Category X.
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.
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.
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.
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.
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.
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 and CLINICAL PHARMACOLOGY]. Elderly patients with normal renal function should require no dose adjustment.
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].
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].This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 3/3/2015
Additional Belviq Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.