Lorcaserin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Belviq: 10 mg [contains fd&c blue #2 aluminum lake]

Tablet Extended Release 24 Hour, Oral, as hydrochloride:

Belviq XR: 20 mg [contains fd&c yellow #6 aluminum lake]

Pharmacology

Mechanism of Action

Lorcaserin is believed to activate serotonin 5-HT_2C receptors, which stimulate pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus, leading to increased alpha-melanocortin stimulating hormone release at melanocortin-4 receptors and resulting in satiety and decreased food intake. At recommended doses, lorcaserin has greater affinity for 5-HT_2C receptors compared to other 5-HT receptor subtypes (including 5-HT_2A and 5-HT_2B), the 5-HT receptor transporter, and 5-HT reuptake sites (Hurren 2011).

Pharmacokinetics/Pharmacodynamics

Distribution

Distributes to the CNS and cerebrospinal fluid

Metabolism

Extensive hepatic metabolism, via multiple enzymatic pathways, producing two major metabolites (inactive), lorcaserin sulfamate (M1) and N-carbamoyl glucuronide lorcaserin (M5), as well as minor metabolites (glucuronide and sulfate conjugates)

Excretion

Urine (92%, as metabolites); feces (2%, as metabolites)

Time to Peak

1.5 to 2 hours (immediate release); 10 hours (extended release)

Half-Life Elimination

~11 hours (immediate-release); ~12 hours (extended-release)

Protein Binding

~70% to plasma proteins

Use in Specific Populations

Special Populations: Renal Function Impairment

Immediate-release:

Impaired renal function decreased C_max of lorcaserin.

Exposure of lorcaserin sulfamate metabolite (M1) and N-carbamoyl-glucuronide metabolite (M5) increased approximately 1.7-fold and 1.5-fold, respectively, in mild (creatinine clearance [CrCl] 50 to 80 mL/min), 2.3-fold and 2.5-fold, respectively, in moderate (CrCl 30 to 50 mL/min), and 10.5-fold and 5.1-fold, respectively, in severe renal impairment (CrCl less than 30 mL/min).

The terminal half-life of M1 is prolonged by 26%, 96%, and 508% in mild, moderate, and severe renal impairment, respectively. The terminal half-life of M5 is prolonged by 0%, 26%, and 22% in mild, moderate, and severe renal impairment, respectively. The metabolites M1 and M5 accumulate in patients with severely impaired renal function.

Special Populations: Hepatic Function Impairment

Immediate-release: Lorcaserin C_max was 7.8% and 14.3% lower in subjects with mild (Child-Pugh score 5 to 6) and moderate (Child-Pugh score 7 to 9) hepatic impairment, respectively. The half-life of lorcaserin is prolonged by 59% to 19 hours moderate hepatic impairment. Lorcaserin exposure (AUC) is approximately 22% and 30% higher in mild and moderate hepatic impairment, respectively.

Special Populations: Elderly

Immediate-release: C_max was approximately 18% lower and T_max was increased from 2 to 2.5 hours.

Use: Labeled Indications

Weight management: Chronic weight management, as an adjunct to a reduced-calorie diet and increased physical activity, in adults with either an initial body mass index (BMI) of ≥30 kg/m²or an initial BMI of ≥27 kg/m² and at least one weight-related comorbid condition (eg, hypertension, dyslipidemia, type 2 diabetes).

Contraindications

Hypersensitivity to lorcaserin or any component of the formulation; pregnancy

Dosage and Administration

Dosing: Adult

Weight management: Oral: Note: Evaluate response by week 12; if patient has not lost ≥5% of baseline body weight, discontinue therapy

Extended release: 20 mg once daily (maximum: 20 mg/day).

Immediate release: 10 mg twice daily (maximum: 20 mg/day).

Dosing: Geriatric

Refer to adult dosing.

Administration

Administer with or without food. Swallow extended-release tablets whole; do not chew, crushed, or divide.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Ajmaline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Ajmaline. Monitor therapy

Amphetamines: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amphetamines. Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

Brexpiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: If brexpiprazole is to be used together with both a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor, the brexpiprazole dose should be reduced to 25% of the usual dose. Monitor therapy

BuPROPion: May enhance the serotonergic effect of Lorcaserin. This could result in serotonin syndrome. Management: Seek alternatives to this combination when possible. Consider therapy modification

CloZAPine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Monitor therapy

Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Monitor therapy

CYP2D6 Substrates (High risk with Inhibitors): CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Exceptions: Tamoxifen. Monitor therapy

DOXOrubicin (Conventional): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP2D6 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

Eliglustat: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor. Consider therapy modification

Ergot Derivatives: Lorcaserin may enhance the adverse/toxic effect of Ergot Derivatives. Specifically, use of these drugs together may increase the risk of developing valvular heart disease. Lorcaserin may enhance the serotonergic effect of Ergot Derivatives. This could result in serotonin syndrome. Avoid combination

Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Monitor therapy

Indoramin: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Indoramin. Monitor therapy

Metoprolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Metoprolol. Monitor therapy

Monoamine Oxidase Inhibitors (Type B): May enhance the serotonergic effect of Serotonergic Agents (Moderate Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Monitor therapy

Perhexiline: CYP2D6 Inhibitors may increase the serum concentration of Perhexiline. Management: Consider alternatives to this combination if possible. If combined, monitor for increased perhexiline serum concentrations and toxicities (eg, hypoglycemia, neuropathy, liver dysfunction). Perhexiline dose reductions will likely be required. Consider therapy modification

Phosphodiesterase 5 Inhibitors: Lorcaserin may enhance the adverse/toxic effect of Phosphodiesterase 5 Inhibitors. Specifically, the risk of developing priapism may be increased. Monitor therapy

Pitolisant: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Pitolisant. Monitor therapy

Propafenone: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Serotonergic Agents (High Risk): Lorcaserin may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: Amitriptyline; Amoxapine; ClomiPRAMINE; Desipramine; Dothiepin; Doxepin (Systemic); Doxepin (Topical); Imipramine; Lofepramine; Melitracen [INT]; Nortriptyline; Protriptyline; Sibutramine; Trimipramine. Monitor therapy

Serotonergic Agents (Moderate Risk, Miscellaneous): Lorcaserin may enhance the serotonergic effect of Serotonergic Agents (Moderate Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: Lorcaserin. Monitor therapy

Sibutramine: May enhance the adverse/toxic effect of Lorcaserin. Sibutramine may enhance the serotonergic effect of Lorcaserin. This could result in serotonin syndrome. Avoid combination

Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Consider alternatives with less of an inhibitory effect on CYP2D6 activity when possible. Consider therapy modification

Tamsulosin: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Monitor therapy

Thioridazine: CYP2D6 Inhibitors may increase the serum concentration of Thioridazine. Avoid combination

Tricyclic Antidepressants: Lorcaserin may enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Lorcaserin may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations and effects if these agents are combined. Monitor therapy

Adverse Reactions

>10%:

Central nervous system: Headache (15% to 17%)

Endocrine & metabolic: Hypoglycemia (diabetic patients 29%; symptomatic 7%; severe: 2%)

Hematologic: Abnormal lymphocytes (below lower limit of normal after ≥1 year, 12%)

Neuromuscular & skeletal: Back pain (6% to 12%)

Respiratory: Upper respiratory tract infection (14%), nasopharyngitis (11% to 13%)

1% to 10%:

Cardiovascular: Hypertension (5%), peripheral edema (5%), decreased heart rate (less than 50 bpm: 4% to 5%), acquired valvular heart disease (3%)

Central nervous system: Dizziness (7% to 9%), fatigue (7%), anxiety (4%), insomnia (4%), depression (3%), stress (3%), cognitive dysfunction (2%), psychiatric disturbance (2%)

Endocrine & metabolic: Increased serum prolactin (7%; 2 x ULN: 2%; 5 x ULN: <1%), exacerbation of diabetes mellitus (3%)

Gastrointestinal: Nausea (8% to 9%), diarrhea (7%), constipation (6%), xerostomia (5%), vomiting (4%), gastroenteritis (3%), toothache (3%), decreased appetite (2%)

Genitourinary: Urinary tract infection (7% to 9%)

Hematologic: Decreased hemoglobin (10%), decreased neutrophils (6%)

Hypersensitivity: Seasonal allergy (3%)

Neuromuscular & skeletal: Muscle spasm (5%), musculoskeletal pain (2%)

Ocular: Eye disease (5% to 6%)

Respiratory: Cough (4% to 8%), oropharyngeal pain (4%), sinus congestion (3%)

<1%, postmarketing, and/or case reports: Hypersensitivity reaction, serotonin syndrome

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause confusion, somnolence, fatigue, and cognitive impairment (difficulty with concentration/attention/memory); patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Hematological effects: Leukopenia, lymphopenia, neutropenia, anemia, and/or decreases in hematocrit and hemoglobin have been observed. Consider monitoring CBC periodically during use.
• Hyperprolactinemia: May occur; in general, increases are moderate (≤2 x ULN), although prolactin elevations (5 x ULN) have been reported rarely. Obtain prolactin levels if signs or symptoms of hyperprolactinemia occur (eg, galactorrhea, gynecomastia).
• Priapism: May occur with use; men with erections >4 hours should immediately discontinue lorcaserin and seek emergency medical attention to avoid irreversible damage to erectile tissue. Use with caution in men with conditions that increase the risk for priapism (eg, sickle cell anemia, multiple myeloma, leukemia) or men with anatomical penis deformities (eg, angulation, cavernosal fibrosis, Peyronie disease).
• Primary pulmonary hypertension: Has been reported in patients receiving other centrally acting, serotonergic weight loss agents. Although the incidence of development or worsening of pulmonary hypertension appears low with lorcaserin (Bohula 2018), available data from clinical trials are inadequate to determine if lorcaserin increases the risk for pulmonary hypertension.
• Psychiatric disorders: Euphoria, hallucinations, and dissociation have been observed with lorcaserin at supratherapeutic doses. Monitor patients closely during use for emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior; discontinue lorcaserin in patients who experience suicidal thoughts or behaviors.
• Serotonin syndrome (SS)/neuroleptic malignant syndrome (NMS)-like reactions: SS and NMS-like reactions have occurred with serotonergic agents such as lorcaserin, particularly when used in combination with other serotonergic agents (eg, triptans, SNRIs, SSRIs, TCAs, bupropion, St John’s wort, tryptophan), agents that impair metabolism of serotonin (eg, MAO inhibitors, dextromethorphan, tramadol, lithium), or antidopaminergic agents (eg, antipsychotics). Identification and differentiation of SS (eg, tremor, myoclonus, agitation) and more severe NMS-like reactions (eg, hyperthermia, muscle rigidity, autonomic instability, mental status changes) may be complex; monitor patients closely for either syndrome. Discontinue treatment (and any concomitant serotonergic and/or antidopaminergic agents) immediately if signs/symptoms arise.
• Valvular heart disease: Cardiac valvular disease has been associated with the use of agents exhibiting potent 5-HT_2B agonist activity (eg, cabergoline, fenfluramine [not currently on the US market], dexfenfluramine [not currently on the US market]) (Fidler 2011; Smith 2010). Cardiac valvular disease is believed to result from activation of 5-HT_2B receptors in interstitial cardiac cells. Lorcaserin has greater affinity for 5-HT_2C receptors compared to 5-HT_2B receptors (at therapeutic doses). Clinical trials have shown a statistically nonsignificant increase in the incidence of new or worsening valvulopathy after 1 year, as determined by echocardiography (manufacturer's labeling; Bohula 2018); however, after a median follow up of 3.3 years an increased risk of symptomatic valvulopathy was not found (Bohula 2018). The incidence of valvulopathy observed in these trials was low, making it difficult to ascertain the risk of valvular disease with lorcaserin therapy based on available data. Evaluate patients if signs/symptoms of valvular heart disease (eg, dyspnea, dependent edema, heart failure, new onset cardiac murmur) arise during therapy; consider discontinuing therapy if present. Use has not been studied in patients with hemodynamically significant valvular heart disease.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with bradycardia or heart block (second or third degree); bradycardia has been observed rarely with use. Use with caution in patients with heart failure (has not been studied); data suggests that 5HT_2B receptors may be overexpressed in heart failure which could potentially increase the risk of valvular heart disease developing from use. In a scientific statement from the American Heart Association, lorcaserin has been determined to be an agent that may cause direct myocardial toxicity (magnitude: major) (AHA [Page 2016]). In a prospective placebo-controlled trial in patients with significant baseline cardiovascular risk, lorcaserin did not increase the risk of major cardiovascular outcomes (cardiovascular death, MI, stroke, HF, unstable angina, or coronary revascularization) (Bohula 2018).
• Diabetes: Use with caution in patients with type 2 diabetes mellitus; weight loss from therapy may result in decreased requirements of antidiabetic agents and an increased risk of hypoglycemia; monitor blood glucose. Hypoglycemia has been observed.
• Hepatic impairment: Use with caution in patients with severe hepatic impairment (has not been studied). Lorcaserin undergoes extensive hepatic metabolism.
• Renal impairment: Serum concentrations and principal metabolite (M1 and M5) half-lives are increased in renal impairment. Use is not recommended in patients with severe impairment or end stage renal disease. Use with caution in patients with moderate renal impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information

Other warnings/precautions:

• Abuse potential: Incidences of euphoria and hallucinations were low (<1%) in clinical trials of obese patients with durations up to 104 weeks; however, in abuse potential studies of recreational drug abusers and in short term studies of healthy patients using supratherapeutic doses, the incidences of hallucinations and euphoria were higher (>10%). May produce psychic dependence. Physical dependence or a withdrawal syndrome has not been observed.
• Appropriate use: Pharmacotherapy for weight loss should be used in conjunction with a comprehensive weight management program including diet and exercise. Discontinue if significant weight loss has not occurred (ie, <5% within the first 12 weeks of treatment). The safety and efficacy of coadministration with other products intended for weight loss have not been established.

Monitoring Parameters

Weight, waist circumference; CBC (periodically during use); blood glucose (in diabetics); prolactin levels (if galactorrhea, gynecomastia or other signs/symptoms of hyperprolactinemia arise); monitor for depression and/or suicidal thoughts/behavior; signs/symptoms of SS/NMS-like reaction; signs/symptoms of valvular heart disease (dyspnea, dependent edema)

Pregnancy

Pregnancy Risk Factor

X

Pregnancy Considerations

An increased risk of adverse maternal and fetal outcomes is associated with obesity. However, moderate weight gain based on prepregnancy BMI is required for positive fetal outcomes. Therefore, medications for weight loss therapy are not recommended at conception or during pregnancy (ACOG 156 2015; Stang 2016). Due to the lack of clinical benefit and potential for fetal harm, use of lorcaserin is contraindicated in pregnant females

Patient Education

What is this drug used for?

• It is used to help you lose weight.

Frequently reported side effects of this drug

• Nausea
• Dry mouth
• Constipation
• Diarrhea
• Cough
• Back pain
• Common cold symptoms
• Sore throat
• Stuffy nose

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating.
• Depression like thoughts of suicide, anxiety, emotional instability, or confusion.
• Neuroleptic malignant syndrome like fever, muscle cramps or stiffness, dizziness, severe headache, confusion, change in thinking, fast heartbeat, abnormal heartbeat, or sweating a lot.
• Serotonin syndrome like dizziness, severe headache, agitation, sensing things that seem real but are not, fast heartbeat, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea.
• Sensing things that seem real but are not
• Difficulty breathing
• Swelling of arms or legs
• Abnormal heartbeat
• Slow heartbeat
• Fast heartbeat
• Severe dizziness
• Fatigue
• Persistent weakness
• Difficulty focusing
• Passing out
• Confusion
• Severe loss of strength and energy
• Trouble with memory
• Painful urination
• Passing a lot of urine
• Severe headache
• Vision changes
• Nipple discharge
• Enlarged breasts (males)
• Erection that lasts more than 4 hours
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.