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Side Effects of Belviq (lorcaserin): Interactions & Warnings

Does Belviq (lorcaserin) cause side effects?

Belviq (lorcaserin) is a serotonin 2C (5-HT2C) receptor agonist that promotes weight loss when  used with diet and exercise in overweight adults with a weight-related medical problem or obese adults to lose weight and keep it off. 

Although the exact mechanism of action is not known, Belviq is thought to selectively stimulate 5-HT2C receptors in the hypothalamus, the area of the brain known to play a major role in regulating hunger and food intake. By activating these receptors, Belviq may decrease food consumption by decreasing appetite and making a person feel full even after eating less food than usual.

Common side effects of Belviq include

Serious side effects of Belviq include

  • heart valve problems,
  • changes in attention or memory,
  • mental problems,
  • depression or thoughts of suicide,
  • painful erections,
  • slow heartbeat,
  • a drop in blood cell count, and
  • an increase in the hormone, prolactin.

Drug interactions of Belviq include triptans, linezolid, tryptophan, lithium, tramadol, St. John's wort, dextromethorphan (a common over-the-counter medicine for treating colds and coughs), and various classes of commonly used antidepressants including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MOAIs), due to the potential risk for serotonin syndrome, a rare but serious disorder caused by abnormally high levels of serotonin. 

Belviq may increase blood levels of drugs broken down by CYP 2D6 liver enzymes. Caution must be used if Belviq is used with drugs that are extensively metabolized via this pathway. 

Weight loss offers no potential benefit during pregnancy and may harm a fetus. Use of Belviq during pregnancy is not recommended. 

It is unknown if Belviq is excreted in breast milk. Many drugs are excreted in breast milk and have the potential of causing harm to the nursing infant. A decision should be made to either discontinue breastfeeding or taking the drug.

What are the important side effects of Belviq (lorcaserin)?

The most common side effects are:

Other less common but serious side effects associated with lorcaserin include:

  • heart valve problems,
  • changes in attention or memory,
  • mental problems,
  • depression or thoughts of suicide,
  • painful erections,
  • slow heartbeat,
  • a drop in blood cell count, and
  • an increase in the hormone, prolactin.

Belviq (lorcaserin) side effects list for healthcare professionals

The following important adverse reactions are described
below and elsewhere in labeling:

  • Serotonin Syndrome or NMS-like Reactions
  • Valvular Heart Disease
  • Cognitive Impairment
  • Psychiatric Disorders
  • Hypoglycemia
  • Heart Rate Decreases
  • Hematological Changes
  • Prolactin Elevation

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

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

The most common adverse reactions for diabetic patients were

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

Adverse Reaction
Number of patients (%)

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.
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. 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.

Table 4: Incidence of FDA-Defined Valvulopathy at Week
52 by Treatment Group1

 
Stutuy 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)

1Patients without valvulopathy at baseline who
received study medication and had a post-baseline echocardiogram;
ITT-intention-to-treat; LOCF-last observation carried forward

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

What drugs interact with Belviq (lorcaserin)?

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.

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.

Does Belviq (lorcaserin) cause addiction or withdrawal symptoms?

Drug Abuse And Dependence

Controlled Substance
  • Belviq is listed in Schedule IV of the Controlled Substances
    Act.
Abuse
  • In a human abuse potential study in recreational drug
    abusers, supratherapeutic oral doses of lorcaserin (40 and 60 mg) produced up
    to two- to six-fold increases on measures of “High”, “Good Drug Effects”,
    Hallucinations” and “Sedation” compared to placebo.
  • These responses were
    similar to those produced by oral administration of the positive control drugs,
    zolpidem (15 and 30 mg) and ketamine (100 mg). In this study, the incidence of
    the adverse reaction of euphoria following lorcaserin administration (40 and 60
    mg; 19%) is similar to the incidence following zolpidem administration (13- 16%),
    but less than the incidence following ketamine administration (50%).
  • The
    duration of euphoria following lorcaserin administration persisted longer ( >
    9 hours) than that following zolpidem (1.5 hours) or ketamine (2.5 hours)
    administration.
  • Overall, in short-term studies with healthy individuals,
    the rate of euphoria following oral administration of lorcaserin was 16%
    following 40 mg (n = 11 of 70) and 19% following 60 mg (n = 6 of 31).
  • However,
    in clinical studies with obese patients with durations of 4 weeks to 2 years,
    the incidence of euphoria and hallucinations following oral doses of lorcaserin
    up to 40 mg was low ( < 1.0%).
Dependence
  • There are no data from well-conducted animal or human
    studies that evaluate whether lorcaserin can induce physical dependence, as
    evidenced by a withdrawal syndrome.
  • However, the ability of lorcaserin to
    produce hallucinations, euphoria, and positive subjective responses at
    supratherapeutic doses suggests that lorcaserin may produce psychic dependence.

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