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Lorcaserin

Pronunciation

(lor KA ser in)

Index Terms

  • Lorcaserin HCl
  • Lorcaserin Hydrochloride

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]

Brand Names: U.S.

  • Belviq
  • Belviq XR

Pharmacologic Category

  • Anorexiant
  • Serotonin 5-HT2C Receptor Agonist

Pharmacology

Lorcaserin is believed to activate serotonin 5-HT2C 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-HT2C receptors compared to other 5-HT receptor subtypes (including 5-HT2A and 5-HT2B), the 5-HT receptor transporter, and 5-HT reuptake sites (Hurren, 2011).

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

Special Populations: Renal Function Impairment

Immediate-release:

Impaired renal function decreased Cmax 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 Cmax 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: Cmax was approximately 18% lower and Tmax 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/m2 or 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

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.

Dosing: Renal Impairment

Mild impairment (CrCl >50 mL/minute): No dosage adjustment necessary.

Moderate impairment (CrCl 30 to 50 mL/minute): There are no dosage adjustments provided in the manufacturer’s labeling; use with caution; serum concentrations and half-life of major metabolites are increased.

Severe impairment (CrCl <30 mL/minute): Use is not recommended.

ESRD: Use is not recommended; hemodialysis does not remove lorcaserin or M1 metabolite

Dosing: Hepatic Impairment

Mild to moderate impairment (Child-Pugh class A and B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer’s labeling; use with caution (has not been studied); undergoes extensive hepatic metabolism.

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

Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Anti-Parkinson Agents (Monoamine Oxidase Inhibitor): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity if selegiline, rasagiline, or safinamide is combined with a serotonin modulator. Use of transdermal selegiline with serotonin modulators is contraindicated. Consider therapy modification

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. 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: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Monitor therapy

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination

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

Linezolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely. Consider therapy modification

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Monitor therapy

Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Monitor therapy

Metoprolol: CYP2D6 Inhibitors may increase the serum concentration of Metoprolol. Management: Consider an alternative for one of the interacting drugs in order to avoid metoprolol toxicity. If the combination must be used, monitor response to metoprolol closely. Metoprolol dose reductions may be necessary. Consider therapy modification

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

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

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy

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

Tedizolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

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

TraMADol: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Monitor therapy

TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. 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 (PPH): Has been reported in patients receiving other centrally acting, serotonergic weight loss agents. 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 for suicidal thoughts or behaviors; 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-HT2B agonist activity (eg, cabergoline, fenfluramine [not currently on the US market], dexfenfluramine [not currently on the US market]). Cardiac valvular disease is believed to result from activation of 5-HT2B receptors in interstitial cardiac cells. Lorcaserin has greater affinity for 5-HT2C receptors compared to 5-HT2B receptors (at therapeutic doses). However, a slight increase in incidence of regurgitant cardiac valve disease (mitral and/or aortic) has been observed with lorcaserin compared to placebo in some clinical trials (pooled RR: 1.16; 95% CI: 0.81 to 1.67). The incidence observed in both groups 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 5HT2B 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]). Effect of lorcaserin on cardiovascular morbidity and mortality has not been established.

• 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 Risk Factor

X

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. Due to the fact that weight loss during pregnancy offers no clinical benefit, lorcaserin is contraindicated in pregnancy. Obese and overweight women should be encouraged to participate in weight reduction programs prior to attempting pregnancy; weight gain during pregnancy should be determined by their prepregnancy BMI and current guidelines (ADA 2009; IOM 2009).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, dry mouth, constipation, diarrhea, cough, back pain, common cold symptoms, pharyngitis, or rhinitis. Have patient report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating), signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of neuroleptic malignant syndrome (fever, muscle cramps or stiffness, dizziness, severe headache, confusion, change in thinking, tachycardia, abnormal heartbeat, or sweating a lot), signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea), hallucinations, difficulty breathing, swelling of arms or legs, abnormal heartbeat, bradycardia, tachycardia, severe dizziness, fatigue, persistent weakness, difficulty focusing, passing out, confusion, severe loss of strength and energy, memory impairment, painful urination, polyuria, severe headache, vision changes, nipple discharge, enlarged breasts (males), or priapism (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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