Side Effects of Belviq (lorcaserin)

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

• headache,
• dizziness,
• fatigue,
• nausea,
• dry mouth,
• constipation, and
• low blood sugar (hypoglycemia).

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.

The most common side effects are:

• headache,
• dizziness,
• fatigue,
• nausea,
• dry mouth,
• constipation, and
• hypoglycemia (low blood sugar).

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.

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

• 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

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

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

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

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.

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.