Included as part of the PRECAUTIONS section.
Serotonin Syndrome Or Neuroleptic Malignant Syndrome
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
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.,
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
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
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
- 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
- Men who have an erection lasting greater than 4 hours, whether
painful or not, should immediately discontinue the drug and seek emergency
- 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
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
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].