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  • CLASSES

    Centrally-Acting Antiobesity Products

    DEA CLASS

    Rx, schedule IV

    DESCRIPTION

    Serotonin 2C (HT2C) receptor agonist for weight loss
    Decreases food consumption and promotes satiety centrally; precise mechanism unknown
    Used for the treatment of obesity in adults as an adjunct to a reduced-calorie diet and physical activity; for patients with a BMI 30 kg/m2 or more (obese) or those with BMI 27 kg/m2 or more (overweight) who also have at least 1 weight related comorbid condition
    Safety and efficacy have not been established in conjunction with other weight loss medications or dietary supplements

    COMMON BRAND NAMES

    Belviq, Belviq XR

    HOW SUPPLIED

    Belviq XR/Lorcaserin/Lorcaserin hydrochloride Oral Tab ER: 20mg
    Belviq/Lorcaserin/Lorcaserin hydrochloride Oral Tab: 10mg

    DOSAGE & INDICATIONS

    For the treatment of obesity as an adjunct to a reduced-calorie diet and increased physical activity.
    Oral dosage (immediate-release tablets; i.e., Belviq)
    Adults

    10 mg PO twice daily. Do not exceed recommended dose. Response to therapy should be evaluated by week 12. If a patient has not lost at least 5% of baseline body weight, discontinue locaserin, as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment. Locaserin is indicated for chronic weight management in adult patients with an initial body mass index (BMI) of at least 30 kg/m2 or at least 27 kg/m2 in the presence of at least 1 weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes). The formula for BMI is weight in kilograms divided by height in meters squared. Safety and efficacy have not been established for coadministration of lorcaserin with other products intended for weight loss, including prescription drugs (e.g., phentermine), over-the-counter drugs, and dietary supplements/herbal preparations.

    Oral dosage (extended-release tablets; i.e., Belviq XR)
    Adults

    20 mg PO once daily. Do not exceed this dosage. Response to therapy should be evaluated by week 12. If a patient has not lost at least 5% of baseline body weight by Week 12, lorcaserin should be discontinued since it is unlikely that a clinically meaningful weight loss will be achieved and sustained with continued treatment. Locaserin is indicated for chronic weight management in adult patients with an initial body mass index (BMI) of at least 30 kg/m2 or at least 27 kg/m2 in the presence of at least 1 weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes). The formula for BMI is weight in kilograms divided by height in meters squared. Safety and efficacy have not been established for coadministration of lorcaserin with other products intended for weight loss, including prescription drugs (e.g., phentermine), over-the-counter drugs, and dietary supplements or herbal preparations.

    MAXIMUM DOSAGE

    Adults

    20 mg/day PO.

    Geriatric

    20 mg/day PO.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Mild to moderate hepatic impairment (Child Pugh Class A or B): No dose adjustment required.
    Severe hepatic impairment (Child Pugh Class C): Not evaluated; use with caution.

    Renal Impairment

    CrCl more than 50 mL/min: No dose adjustment required.
    CrCl 30 to 50 mL/min: Use with caution in moderate renal impairment.
    CrCl less than 30 mL/min: Not recommended in severe renal impairment or end stage renal disease.
     
    Intermittent hemodialysis
    Not recommended.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Immediate-release tablets (i.e., Belviq): May be administered with or without food.
    Extended-release tablets (i.e., Belviq XR): May be administered with or without food. Swallow tablets whole; do not chew, crush, or divide.

    STORAGE

    Belviq:
    - Protect from extreme heat
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Belviq XR:
    - Avoid exposure to heat
    - Protect from freezing
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Heart failure, valvular heart disease

    Regurgitant valvular heart disease, primarily affecting the mitral and/or aortic valves, has been reported in patients who took serotonergic drugs with 5-HT2B receptor agonist activity. The etiology of the regurgitant valvular disease is thought to be activation of 5-HT2B receptors on cardiac interstitial cells. At therapeutic concentrations, lorcaserin is selective for serotonin 5-HT2C receptors as compared to 5-HT2B receptors. In clinical trials, non-symptomatic valvular regurgitation was observed in lorcaserin treated patients. Lorcaserin has not been studied in patients with congestive heart failure or hemodynamically significant valvular heart disease. Preliminary data suggest that 5-HT2B receptors may be overexpressed in congestive heart failure. Therefore, lorcaserin should be used with caution in patients with congestive heart failure. Lorcaserin should not be used in combination with serotonergic and dopaminergic drugs that are potent 5-HT2B receptor agonists and are known to increase the risk for cardiac valvulopathy. Patients who develop signs or symptoms of valvular heart disease, including dyspnea, dependent edema, congestive heart failure, or a new cardiac murmur while being treated with lorcaserin should be evaluated and discontinuation of treatment should be considered. The effect of lorcaserin on cardiovascular morbidity and mortality has not been established.

    AV block, bradycardia, bundle-branch block, sick sinus syndrome

    In clinical trials, lorcaserin use was associated with a small incidence of mild bradycardia. Cautious use of lorcaserin is therefore warranted in patients with preexisting bradycardia or a history of AV block (greater than first degree), bundle-branch block, or sick sinus syndrome. The effect of lorcaserin on cardiovascular morbidity and mortality has not been established.

    Pulmonary hypertension

    Certain centrally-acting weight loss agents that act on the serotonin system have been associated with pulmonary hypertension, a rare but lethal disease. Because of the low incidence of this disease, the clinical trial experience with lorcaserin is inadequate to determine if lorcaserin increases the risk for pulmonary hypertension. Cautious monitoring is warranted.

    Hyperprolactinemia

    Lorcaserin moderately elevates prolactin levels which can lead to hyperprolactinemia. In clinical trials, elevations of prolactin, greater than the upper limit of normal occurred in some patients. Therefore, clinicians should measure prolactin levels when signs and symptoms of hyperprolactinemia are suspected (e.g., galactorrhea, gynecomastia, menstrual changes, infertility).

    Anemia, hematological disease, leukopenia, neutropenia

    Lorcaserin should be used with caution in patients with hematological disease, such as anemia or leukopenia. In clinical trials, adverse reactions of decreases in white blood cell count (including leukopenia, lymphopenia, neutropenia, and decreased white cell count) were reported in 0.4% of patients receiving lorcaserin (compared to 0.2% receiving placebo). Decreases in red blood cell count (including anemia and decreases in hemoglobin and hematocrit) were also reported at rates only slightly higher than placebo. Clinicians should consider periodic monitoring of complete blood count during treatment with lorcaserin.

    Leukemia, multiple myeloma, Peyronie's disease, sickle cell disease

    Lorcaserin is a serotonin 5-HT2C receptor agonist, and priapism is a potential effect of 5-HT2C receptor agonism. Therefore, lorcaserin should be used with caution in men who have conditions that might predispose them to priapism (e.g., sickle cell disease, multiple myeloma, or leukemia), or in men with anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, or Peyronie's disease). There is limited experience of the use of lorcaserin in men taking medications for erectile dysfunction. Men who have an erection lasting greater than 4 hours, whether painful or not, should immediately discontinue the drug and seek emergency medical attention.

    Diabetes mellitus, hypoglycemia

    In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Lorcaserin has not been studied in combination with insulin.

    Depression, suicidal ideation

    Use lorcaserin with particular caution in patients with a medical history of depression or psychiatric disorders with emotional lability. Lorcaserin is believed to decrease food consumption and promote satiety centrally by activating serotonin 5-HT2C receptors on anorexigenic neurons located in the hypothalamus; the exact mechanism of action is not known. Further, some weight-loss drugs that target the central nervous system have been associated with depression or suicidal ideation. Patients treated with lorcaserin should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue use in patients who experience suicidal thoughts or behaviors.

    Driving or operating machinery

    In clinical trials, lorcaserin use was associated with confusion, fatigue, impairments in attention and memory, and somnolence in some patients. Since lorcaserin has the potential to impair cognitive function, patients should be cautioned about driving or operating machinery or performing other potentially hazardous tasks, until they are aware of how this medication affects them.

    Dialysis, renal failure, renal impairment

    During pharmacokinetic analysis of lorcaserin, accumulation of metabolites was observed in patients with severe renal impairment. Therefore, lorcaserin use in patients with renal failure or end stage renal disease on dialysis is not recommended. Administration of lorcaserin in patients with moderate renal impairment warrants caution; no dosage adjustments are required in patients with mild renal impairment.

    Hepatic disease

    The effect of severe hepatic impairment on lorcaserin has not been not evaluated. Use lorcaserin with caution in patients with severe hepatic disease. Dose adjustment is not required for patients with mild to moderate hepatic impairment.

    MAOI therapy

    Lorcaserin is a serotonergic drug. The development of a potentially life-threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported during use of serotonergic drugs. The safety of lorcaserin when combined with MAOI therapy or other serotonergic or antidopaminergic agents, including antipsychotics or drugs that impair the metabolism of serotonin has not been systematically evaluated and has not been established.

    Geriatric

    Clinical studies of lorcaserin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects, but greater sensitivity of geriatric patients to lorcaserin cannot be ruled out. Since older adult patients have a higher incidence of renal impairment, lorcaserin use in the elderly should be made on the basis of renal function. Geriatric patients with normal renal function require no dose adjustment.

    Labor, obstetric delivery, pregnancy

    Lorcaserin is contraindicated during pregnancy, because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm. Maternal exposure to lorcaserin in late pregnancy in animal studies revealed no evidence of teratogenicity, but treatment at highest doses (44 times the human exposure) resulted in stillborns and reduced viability of pups. All doses increased risk of lower birth weight in viable offspring and lowered body weight which persisted to adulthood. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard of maternal weight loss to the fetus. There is no accepted use of this drug during labor or obstetric delivery.

    Breast-feeding

    It is not known whether lorcaserin is excreted in human milk. Therefore, the manufacturer recommends a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Children

    The safety and effectiveness of lorcaserin in pediatric patients below the age of 18 have not been established. Therefore, use of lorcaserin is not recommended in children or adolescents.

    ADVERSE REACTIONS

    Severe

    cardiac valvulopathy / Delayed / 0-2.4
    suicidal ideation / Delayed / 0.6-0.6
    bradycardia / Rapid / 0.3-0.3
    serotonin syndrome / Delayed / Incidence not known
    neuroleptic malignant syndrome-like symptoms / Delayed / Incidence not known
    visual impairment / Early / Incidence not known

    Moderate

    hypoglycemia / Early / 0-29.3
    hyperprolactinemia / Delayed / 0.1-6.7
    blurred vision / Early / 0-6.3
    constipation / Delayed / 5.8-5.8
    hypertension / Early / 0-5.1
    peripheral edema / Delayed / 0-4.7
    impaired cognition / Early / 2.3-2.3
    depression / Delayed / 2.3-2.3
    lymphopenia / Delayed / 0-0.4
    leukopenia / Delayed / 0-0.4
    neutropenia / Delayed / 0-0.4
    confusion / Early / 0.2-0.2
    euphoria / Early / 0.2-0.2
    memory impairment / Delayed / Incidence not known
    conjunctivitis / Delayed / Incidence not known

    Mild

    headache / Early / 14.5-16.8
    infection / Delayed / 0-13.7
    back pain / Delayed / 0-11.7
    nausea / Early / 8.3-9.4
    dizziness / Early / 7.0-8.5
    cough / Delayed / 0-8.2
    fatigue / Early / 7.2-7.4
    diarrhea / Early / 6.5-6.5
    xerophthalmia / Early / 0-6.3
    xerostomia / Early / 5.3-5.3
    muscle cramps / Delayed / 0-4.7
    vomiting / Early / 3.8-3.8
    anxiety / Delayed / 3.5-3.5
    insomnia / Early / 3.5-3.5
    dental pain / Delayed / 2.7-2.7
    rash (unspecified) / Early / 0-2.1
    musculoskeletal pain / Early / 0-2.0
    chills / Rapid / 1.0-1.0
    tremor / Early / 0.3-0.3
    hyperhidrosis / Delayed / 0.1-0.1
    drowsiness / Early / Incidence not known

    DRUG INTERACTIONS

    Acarbose: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Acetaminophen; Dextromethorphan: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Acetaminophen; Dextromethorphan; Doxylamine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Acetaminophen; Tramadol: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, tramadol. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome (NMS) like signs and symptoms.
    Acetohexamide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Albiglutide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Alogliptin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Alogliptin; Metformin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Alogliptin; Pioglitazone: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Alpha-glucosidase Inhibitors: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Amitriptyline: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, tricyclic antidepressants. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Amitriptyline; Chlordiazepoxide: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, tricyclic antidepressants. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Amphetamines: (Major) The safety and efficacy of coadministration of lorcaserin with other products intended for weight loss including prescription drugs (e.g., phentermine, fenfluramine, dexfenfluramine, orlistat, phendimetrazine, amphetamines), over-the-counter drugs (e.g., orlistat, phenylpropanolamine, ephedrine), and herbal preparations (ephedra, Ma huang) have not been established. Some of these agents (fenfluramine, dexfenfluramine) are known to increase the risk for cardiac valvulopathy and pulmonary hypertension. Co-use of sibutramine with other serotonergic medications is contraindicated due to the risk for serotonin-related adverse effects, such as serotonin syndrome.
    Atazanavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with lorcaserin as there is a potential for elevated cobicistat concentrations. Lorcaserin is a CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Theoretically, concurrent use of methylene blue and lorcaserin may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and lorcaserin increases central serotonin effects). Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Theoretically, concurrent use of methylene blue and lorcaserin may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and lorcaserin increases central serotonin effects). Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Bupropion: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, bupropion. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Bupropion; Naltrexone: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, bupropion. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Cabergoline: (Major) Lorcaserin should not be used in combination with serotonergic and dopaminergic drugs that are potent 5-HT2B receptor agonists and are known to increase the risk for cardiac valvulopathy (e.g., cabergoline, ergotamine, dihydroergotamine, and other ergot alkaloids).
    Canagliflozin; Metformin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Chlorpheniramine; Dextromethorphan: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Chlorpropamide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Citalopram: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, selective serotonin reuptake inhibitors (SSRIs). Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Clomipramine: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, tricyclic antidepressants. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with lorcaserin as there is a potential for elevated cobicistat concentrations. Lorcaserin is a CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with lorcaserin as there is a potential for elevated cobicistat concentrations. Lorcaserin is a CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with lorcaserin as there is a potential for elevated cobicistat concentrations. Lorcaserin is a CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6.
    Dapagliflozin; Metformin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Dapagliflozin; Saxagliptin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with lorcaserin as there is a potential for elevated cobicistat concentrations. Lorcaserin is a CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6.
    Desipramine: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, tricyclic antidepressants. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Dextromethorphan: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Dextromethorphan; Guaifenesin: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Dextromethorphan; Promethazine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Dextromethorphan; Quinidine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, dextromethorphan. In addition, lorcaserin inhibits CYP2D6-mediated metabolism of dextromethorphan. In a clinical trial in CYP2D6 extensive metabolizers (n=21), concomitant administration of lorcaserin (10 mg twice daily for 4 days) increased dextromethorphan Cmax by approximately 76% and AUC by approximately 2-fold. Increased exposure to dextromethorphan may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea/vomiting, and dysarthria (slurred speech). Because manufacturers are constantly revising the ingredients of cough and cold formulas on the market, the patient should carefully assess product labels for the presence of dextromethorphan as an ingredient prior to any such product use.
    Dipeptidyl Peptidase-4 Inhibitors: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Doxepin: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, tricyclic antidepressants. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Doxorubicin: (Major) Lorcaserin is a mild CYP2D6 inhibitor and doxorubicin is a major CYP2D6 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of locaserin and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Dulaglutide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Empagliflozin; Linagliptin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Empagliflozin; Metformin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Ergot alkaloids: (Major) Lorcaserin should not be used in combination with serotonergic and dopaminergic drugs that are potent 5-HT2B receptor agonists and are known to increase the risk for cardiac valvulopathy (e.g., cabergoline, ergotamine, dihydroergotamine, and other ergot alkaloids).
    Escitalopram: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, selective serotonin reuptake inhibitors (SSRIs). Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Exenatide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Fluoxetine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, selective serotonin reuptake inhibitors (SSRIs). Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Fluoxetine; Olanzapine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, selective serotonin reuptake inhibitors (SSRIs). Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Fluvoxamine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, selective serotonin reuptake inhibitors (SSRIs). Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Glimepiride: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Glimepiride; Pioglitazone: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Glimepiride; Rosiglitazone: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Glipizide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Glipizide; Metformin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Glyburide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Glyburide; Metformin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Guarana: (Major) Caffeine, an active constituent of guarana, is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Use of guarana should be avoided with amphetamine, dextroamphetamine, methylphenidate, modafinil, pemoline, pseudoephedrine, beta-agonists or other sympathomimetics. When combined with any of these medications, nervousness, irritability, insomnia, and/or cardiac arrhythmias may result.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Theoretically, concurrent use of methylene blue and lorcaserin may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and lorcaserin increases central serotonin effects). Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Imipramine: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, tricyclic antidepressants. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Incretin Mimetics: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Insulin Degludec; Liraglutide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Insulin Glargine; Lixisenatide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Insulins: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Linagliptin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Linagliptin; Metformin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Linezolid: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including linezolid, an antibiotic that is also a reversible, non-selective MAO inhibitor. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent clinical use of linezolid and medications that enhance central serotonergic activity.
    Liraglutide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Lithium: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, lithium. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Lixisenatide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Loperamide: (Moderate) The plasma concentration of loperamide, a CYP2D6 substrate, may be increased when administered concurrently with lorcaserin, a mild CYP2D6 inhibitor. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
    Loperamide; Simethicone: (Moderate) The plasma concentration of loperamide, a CYP2D6 substrate, may be increased when administered concurrently with lorcaserin, a mild CYP2D6 inhibitor. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
    Meglitinides: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Metformin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Metformin; Pioglitazone: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Metformin; Repaglinide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Metformin; Rosiglitazone: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Metformin; Saxagliptin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Metformin; Sitagliptin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Theoretically, concurrent use of methylene blue and lorcaserin may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and lorcaserin increases central serotonin effects). Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Methylene Blue: (Major) Theoretically, concurrent use of methylene blue and lorcaserin may increase the risk of serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and lorcaserin increases central serotonin effects). Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with intravenous methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Miglitol: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Monoamine oxidase inhibitors: (Major) Avoid use together if possible. The MAOIs are not recommended to be taken with serotonergic medications due to the risk for serotonin syndrome. Lorcaserin affects serotonergic neurotransmitter systems. Patients receiving this combination should be monitored for the emergence of serotonin syndrome.
    Nateglinide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with lorcaserin. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as lorcaserin, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
    Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with lorcaserin. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as lorcaserin, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
    Nortriptyline: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, tricyclic antidepressants. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Orlistat: (Moderate) The safety and efficacy of coadministration of lorcaserin with other products intended for weight loss including prescription drugs (e.g., phentermine, fenfluramine, dexfenfluramine, orlistat, phendimetrazine, amphetamines), over-the-counter drugs (e.g., orlistat, phenylpropanolamine, ephedrine), and herbal preparations (ephedra, Ma huang) have not been established. Some of these agents (fenfluramine, dexfenfluramine) are known to increase the risk for cardiac valvulopathy and pulmonary hypertension. Co-use of sibutramine with other serotonergic medications is contraindicated due to the risk for serotonin-related adverse effects, such as serotonin syndrome.
    Paroxetine: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, selective serotonin reuptake inhibitors (SSRIs). Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Perphenazine; Amitriptyline: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, tricyclic antidepressants. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Phendimetrazine: (Major) The safety and efficacy of coadministration of lorcaserin with other products intended for weight loss including prescription drugs (e.g., phentermine, fenfluramine, dexfenfluramine, orlistat, phendimetrazine, amphetamines), over-the-counter drugs (e.g., orlistat, phenylpropanolamine, ephedrine), and herbal preparations (ephedra, Ma huang) have not been established. Some of these agents (fenfluramine, dexfenfluramine) are known to increase the risk for cardiac valvulopathy and pulmonary hypertension. Co-use of sibutramine with other serotonergic medications is contraindicated due to the risk for serotonin-related adverse effects, such as serotonin syndrome.
    Phentermine: (Major) The safety and efficacy of coadministration of lorcaserin with other products intended for weight loss including prescription drugs (e.g., phentermine, fenfluramine, dexfenfluramine, orlistat, phendimetrazine, amphetamines), over-the-counter drugs (e.g., orlistat, phenylpropanolamine, ephedrine), and herbal preparations (ephedra, Ma huang) have not been established. Some of these agents (fenfluramine, dexfenfluramine) are known to increase the risk for cardiac valvulopathy and pulmonary hypertension. Coadministration of sibutramine with other serotonergic medications is contraindicated due to the risk for serotonin-related adverse effects, such as serotonin syndrome.
    Phentermine; Topiramate: (Major) The safety and efficacy of coadministration of lorcaserin with other products intended for weight loss including prescription drugs (e.g., phentermine, fenfluramine, dexfenfluramine, orlistat, phendimetrazine, amphetamines), over-the-counter drugs (e.g., orlistat, phenylpropanolamine, ephedrine), and herbal preparations (ephedra, Ma huang) have not been established. Some of these agents (fenfluramine, dexfenfluramine) are known to increase the risk for cardiac valvulopathy and pulmonary hypertension. Coadministration of sibutramine with other serotonergic medications is contraindicated due to the risk for serotonin-related adverse effects, such as serotonin syndrome.
    Phosphodiesterase inhibitors: (Major) Lorcaserin is a serotonin 2C receptor agonist, and priapism is a potential effect of 5-HT2C receptor agonism. Because there is little experience with the combination of lorcaserin and medications indicated for erectile dysfunction (e.g., phosphodiesterase inhibitors), combined use should be approached with caution.
    Pioglitazone: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Pramlintide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Protriptyline: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, tricyclic antidepressants. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Repaglinide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Rosiglitazone: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Saxagliptin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Selective serotonin reuptake inhibitors: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, selective serotonin reuptake inhibitors (SSRIs). Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Serotonin norepinephrine reuptake inhibitors: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, serotonin norepinephrine reuptake inhibitors. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Serotonin-Receptor Agonists: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, serotonin-receptor agonists. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Sertraline: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, selective serotonin reuptake inhibitors (SSRIs). Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Sibutramine: (Severe) Co-use of sibutramine with other serotonergic medications is contraindicated due to the risk for serotonin-related adverse effects, such as serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. The safety and efficacy of coadministration of lorcaserin with other products intended for weight loss have not been established.
    Simvastatin; Sitagliptin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Sitagliptin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    St. John's Wort, Hypericum perforatum: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, St. John's Wort. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Sulfonylureas: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Thiazolidinediones: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Tolazamide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Tolbutamide: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Tramadol: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, tramadol. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome (NMS) like signs and symptoms.
    Tricyclic antidepressants: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, tricyclic antidepressants. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
    Trimipramine: (Moderate) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, tricyclic antidepressants. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.

    PREGNANCY AND LACTATION

    Pregnancy

    It is not known whether lorcaserin is excreted in human milk. Therefore, the manufacturer recommends a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Lorcaserin is believed to decrease food consumption and promote satiety by selectively activating 5-HT2C receptors on anorexigenic pro-opiomelanocortin neurons located in the hypothalamus. The exact mechanism of action is not known. Lorcaserin at the recommended daily dose selectivity interacts with 5-HT2C receptors as compared to 5-HT2A and 5-HT2B receptors, other 5-HT receptor subtypes, the 5-HT receptor transporter, and 5-HT reuptake sites.

    PHARMACOKINETICS

    Lorcaserin is administered orally. Following administration, it distributes to the cerebrospinal fluid and central nervous system. It is approximately 70% bound to human plasma proteins. Metabolism occurs predominantly in the liver via multiple enzymatic pathways. Lorcaserin sulfamate (M1) represents a major circulating metabolite with a plasma Cmax that exceeds lorcaserin Cmax by 1- to 5-fold. The principal metabolites exert no pharmacological activity at serotonin receptors. The plasma half-life of immediate-release lorcaserin is approximately 11 hours and the half-life of extended-release lorcaserin is 12 hours. Parent drug and metabolites are excreted in the urine. In studies, 94.5% of radiolabeled material was recovered, with 92.3% and 2.2% recovered from urine and feces, respectively. The N-carbamoyl glucuronide lorcaserin (M5) is the major metabolite in urine; M1 is a minor metabolite in urine, representing approximately 3% of dose. Other minor metabolites excreted in urine were identified as glucuronide or sulfate conjugates of oxidative metabolites.
     
    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2D6
    Lorcaserin is extensively metabolized in the liver by multiple enzymatic pathways. Lorcaserin can decrease the metabolism of CYP2D6 substrates.. In one small trial of CYP2D6 extensive metabolizers, lorcaserin increased dextromethorphan peak concentrations by approximately 76% and AUC by about 2-fold.

    Oral Route

    The absolute bioavailability of lorcaserin has not been determined. Immediate-release lorcaserin reaches steady-state within 3 days after twice daily dosing, and accumulation is estimated to be about 70%. Following oral administration under steady-state conditions, peak plasma concentrations of immediate-release lorcaserin occur at 1.5hours compared to 10 hours for extended-release lorcaserin. Single dose administration of extended-release lorcaserin 20 mg results in a comparable total plasma exposure to 2 doses of immediate-release lorcaserin 10 mg administered 12 hours apart, and an approximate 25% lower peak exposure relative to the immediate-release tablets. However, at steady state, the Cmax and AUC of both formulations is bioequivalent under fasted conditions. Administration of immediate-release lorcaserin under fed conditions increased Cmax by approximately 9% and exposure (AUC) by approximately 5%; Tmax was delayed approximately 1 hour. Intake of high fat, high calorie breakfast before a single 20 mg oral dose of the extended-release formulation resulted in approximately 46% increase in Cmax and 17% increase in AUC but no change in Tmax. At steady state, however, there was no significant food effect on the rate or extent of absorption. Therefore, both immediate-release and extended-release lorcaserin may be administered without regard to meals.