Belviq XR

Name: Belviq XR

What is the most important information I should know about Belviq XR (lorcaserin)?

Do not use lorcaserin if you are pregnant. Weight loss during pregnancy can harm an unborn baby.

Serious drug interactions can occur when certain medicines are used together with lorcaserin. Tell each of your healthcare providers about all medicines you use now, and any medicine you start or stop using.

What do I need to tell my doctor BEFORE I take Belviq XR?

  • If you have an allergy to lorcaserin or any other part of Belviq XR (lorcaserin extended-release tablets).
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have kidney disease.
  • If you are taking cabergoline.
  • If you are pregnant or may be pregnant. Do not take this medicine if you are pregnant.
  • If you are breast-feeding. Do not breast-feed while you take Belviq XR.
  • If the patient is a child. Do not give this medicine to a child.

This is not a list of all drugs or health problems that interact with Belviq XR.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Contraindications

● Pregnancy: Weight loss in a pregnant woman offers no benefit and may result in fetal harm [see Use in Specific Populations (8.1)]

● Hypersensitivity: Belviq XR is contraindicated in patients with prior hypersensitivity reactions to lorcaserin or to any of the product components. Hypersensitivity reactions have been reported [see Adverse Reactions (6.2)]. 

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)]

6.1       Clinical Trials Experience

In the lorcaserin placebo-controlled clinical database of trials of at least one year in duration, of 6888 patients (3451 lorcaserin 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 immediate-release lorcaserin hydrochloride 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 lorcaserin 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 lorcaserin-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 lorcaserin 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 lorcaserin 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 Lorcaserin Patients and More Commonly than with Placebo in Patients without Diabetes Mellitus


Adverse Reaction
Number of patients (%)
Lorcaserin*
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)
* Immediate-release lorcaserin hydrochloride, 10 mg twice daily
Table 3.       Adverse Reactions Reported by Greater Than or Equal to 2% of Lorcaserin Patients and More Commonly than with Placebo in Patients with Type 2 Diabetes Mellitus
Number of patients (%)
Adverse Reaction Lorcaserin*
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)
* Immediate-release lorcaserin hydrochloride, 10 mg twice daily

Other Adverse Reactions

Serotonin-associated Adverse Reactions  

SSRIs, SNRIs, bupropion, tricyclic antidepressants, and MAOIs were excluded from the lorcaserin 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 lorcaserin 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 lorcaserin 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 XR 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, severe hypoglycemia (requiring the assistance of another person, requiring intravenous glucose, or hospitalization) occurred in 4 (1.6%) of lorcaserin-treated patients and in 1 (0.4%) placebo-treated patient. Of these 4 lorcaserin-treated patients, all were concomitantly using a sulfonylurea (with or without metformin). Lorcaserin 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%) lorcaserin-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 lorcaserin and 0.7% of patients taking placebo.

Psychiatric Disorders

Psychiatric disorders leading to hospitalization or drug withdrawal occurred more frequently in patients treated with lorcaserin (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 lorcaserin (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 lorcaserin 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% lorcaserin-treated vs. 2.4% placebo-treated and suicidal ideation occurred in 0.6% lorcaserin-treated vs. 0.4% placebo-treated patients. 1.3% of lorcaserin 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 lorcaserin 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 lorcaserin 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 lorcaserin-treated patients and 4.8%, 0.8%, and 0.0% of placebo-treated patients, respectively.  

Eye disorders  

More patients on lorcaserin 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 (5.9% vs. 1.6%). In the population without diabetes, events of blurred vision, dry eye, and visual impairment occurred in lorcaserin-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 lorcaserin-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 immediate-release lorcaserin hydrochloride 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 lorcaserin and 2.0% of patients who received placebo developed valvular regurgitation. The relative risk for valvulopathy with lorcaserin is summarized in Table 4. Lorcaserin 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  
Study 1 Study 2 Study 3
Lorcaserin*
N=1278
Placebo
N=1191
Lorcaserin*
N=1208
Placebo
N=1153
Lorcaserin*
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)
  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
    * Immediate-release lorcaserin hydrochloride, 10 mg twice daily

6.2       Post-Marketing Experience

The following adverse reactions have been identified during post approval use of lorcaserin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: drug hypersensitivity

Nonclinical toxicology

13.1       Carcinogenesis, Mutagenesis, Impairment of Fertility

            Mutagenesis

Lorcaserin 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.

            Carcinogenesis

The carcinogenic potential of lorcaserin 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 treatment-related 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-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 had no effects on fertility in rats at exposures up to 29 times the human clinical dose.

For the Consumer

Applies to lorcaserin: oral tablet, oral tablet extended release

Along with its needed effects, lorcaserin (the active ingredient contained in Belviq XR) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking lorcaserin:

More common
  • Anxiety
  • bladder pain
  • bloody or cloudy urine
  • blurred vision
  • body aches or pain
  • chills
  • cold sweats
  • coma
  • confusion
  • cool, pale skin
  • cough
  • depression
  • difficult, burning, or painful urination
  • difficulty with breathing
  • dizziness
  • ear congestion
  • fast heartbeat
  • fever
  • frequent urge to urinate
  • headache
  • increased hunger
  • loss of voice
  • lower back or side pain
  • nasal congestion
  • nausea
  • nightmares
  • pounding in the ears
  • runny nose
  • seizures
  • shakiness
  • slow or fast heartbeat
  • slurred speech
  • sneezing
  • sore throat
  • swelling of the breasts or breast soreness in both females and males
  • unexpected or excess milk flow from the breasts
  • unusual tiredness or weakness
Less common
  • Bloating or swelling of the face, arms, hands, lower legs, or feet
  • decreased ability to exercise
  • dry mouth
  • flushed, dry skin
  • fruit-like breath odor
  • increased hunger
  • increased sensitivity to sunlight
  • increased thirst
  • increased urination
  • itching, pain, redness, or swelling of the eye or eyelid
  • joint pain
  • loss of consciousness
  • rapid weight gain
  • severe skin rash or hives
  • stomachache
  • sweating
  • swollen glands
  • tingling of the hands or feet
  • trouble with breathing
  • trouble with sleeping
  • unexplained weight loss
  • unusual weight gain or loss
  • vomiting
  • watering of the eyes
Rare
  • Black, tarry, stools
  • chest pain
  • cough or hoarseness
  • pale skin
  • sores, ulcers, or white spots on the lips or in the mouth
  • swollen glands
  • unusual bleeding or bruising
Incidence not known
  • Agitation
  • confusion
  • convulsions
  • diarrhea
  • high fever
  • increased sweating
  • loss of bladder control
  • overactive reflexes
  • painful or prolonged erection of the penis
  • poor coordination
  • restlessness
  • severe muscle stiffness
  • shivering
  • talking or acting with excitement you cannot control
  • trembling or shaking
  • twitching
  • unusually pale skin

Get emergency help immediately if any of the following symptoms of overdose occur while taking lorcaserin:

Symptoms of overdose
  • Abdominal or stomach discomfort
  • false or unusual sense of well-being
  • seeing, hearing, or feeling things that are not there

Some side effects of lorcaserin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Back pain
  • difficulty having a bowel movement (stool)
  • muscle aches
Less common
  • Decreased appetite
  • difficulty with concentration
  • dry eyes
  • muscle spasms
  • muscle, joint, or bone pain
  • problems with memory
  • rash
  • sleeplessness
  • stress
  • toothache
  • trouble seeing

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