Lorcaserin Disease Interactions

Regurgitant cardiac valvular 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 is thought to involve activation of 5-HT2B receptors on cardiac interstitial cells. At therapeutic concentrations, lorcaserin is selective for 5-HT2C receptors relative to 5-HT2B receptors, thus it is not known if lorcaserin can cause valvulopathy. In clinical trials of one year duration, 2.4% of patients receiving lorcaserin and 2.0% of patients receiving placebo developed echocardiographic criteria for valvular regurgitation at one year (mild or greater aortic regurgitation and/or moderate or greater mitral regurgitation). None of these patients was symptomatic. 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. Therapy with lorcaserin should be administered cautiously in patients with congestive heart failure or preexisting valvulopathy. Patients who develop signs and symptoms of valvular heart disease such as dizziness, fatigue, weakness, dyspnea, edema, or arrhythmia during treatment with lorcaserin should seek prompt medical attention. Discontinuation of lorcaserin should be considered.

Lorcaserin may decrease heart rate. In clinical trials of at least one year duration, the mean decrease in heart rate was 1.2 beats per minute (bpm) in lorcaserin-treated and 0.4 bpm in placebo-treated patients without diabetes, and 2.0 bpm in lorcaserin-treated and 0.4 bpm in placebo-treated patients with type 2 diabetes. The incidence of heart rate less than 50 bpm was 5.3% in lorcaserin-treated and 3.2% in placebo-treated patients without diabetes, and 3.6% in lorcaserin-treated and 2.0% in placebo-treated patients with type 2 diabetes. In the combined population, adverse reactions of bradycardia occurred in 0.3% of lorcaserin-treated and 0.1% of placebo-treated patients. Therapy with lorcaserin should be administered cautiously in patients with bradycardia or a history of heart block greater than first degree.

Lorcaserin can cause elevations in prolactin. In clinical trials of at least one year duration, elevations of prolactin greater than the upper limit of normal, two times the upper limit of normal, and five times the upper limit of normal occurred in 6.7%, 1.7%, and 0.1% of lorcaserin-treated patients, compared to 4.8%, 0.8%, and 0.0% of placebo-treated patients, respectively. One patient treated with lorcaserin developed a prolactinoma. Based on in vitro data, approximately one-third of human breast cancers are thought to be prolactin-dependent. The clinical significance of this observation with respect to long-term lorcaserin therapy is unknown. Chronic administration of other prolactin-stimulating drugs (e.g., neuroleptics, phenothiazines) has been associated with mammary tumorigenesis in rodent studies but not in human clinical or epidemiologic studies. Until further data are available, therapy with lorcaserin should be administered cautiously in patients with a previously detected breast cancer.

Drugs like lorcaserin that target the central nervous system have been associated with depression and suicidal ideation. Psychiatric events of euphoria, hallucination, and dissociation were observed with lorcaserin at supratherapeutic dosages in short-term studies. In clinical trials of at least one year duration, 0.2% of patients treated with lorcaserin developed euphoria, compared to <0.1% treated with placebo. Therapy with lorcaserin should be administered cautiously in patients with preexisting depression or psychiatric illnesses. Lorcaserin dosage should not exceed 10 mg twice a day, and patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Lorcaserin should be discontinued in patients who experience suicidal thoughts or behavior.

Hematological changes, including decreases in hemoglobin and hematocrit counts, have been reported with the use of lorcaserin. Caution should be exercised when treating patients who have ongoing or a history of significant hematologic abnormalities. It is recommended to consider periodic monitoring of complete blood count during treatment.

Lorcaserin is extensively metabolized in the liver by multiple enzymatic pathways. In study subjects with varying degrees of hepatic function, lorcaserin peak plasma concentration (Cmax) was reduced by 7.8% and 14.3% in subjects with mild (Child-Pugh score 5 to 6) and moderate (Child-Pugh score 7 to 9) hepatic impairment, respectively, compared to subjects with normal hepatic function. Lorcaserin exposure (AUC) increased by approximately 22% and 30% in patients with mild and moderate hepatic impairment, respectively, and the half-life was prolonged by 59% to 19 hours in patients with moderate hepatic impairment. No dosage adjustment of lorcaserin is required in patients with mild to moderate hepatic impairment. The effect of severe hepatic impairment on the pharmacokinetics of lorcaserin was not evaluated. Therapy with lorcaserin should be administered cautiously in patients with severe hepatic impairment.

Lorcaserin may cause priapism due to 5-HT2C receptor agonism. The condition is characterized by prolonged, often painful erections lasting longer than 4 hours. If not treated promptly, priapism can cause irreversible damage to the erectile tissue. Therapy with lorcaserin should be administered cautiously in patients with a history of priapism, conditions that may predispose them to priapism (e.g., sickle cell anemia, multiple myeloma, leukemia, thalassemia), or anatomical deformations of the penis (e.g., angulation, cavernosal fibrosis, Peyronie's disease). Patients who experience an erection lasting longer than 4 hours, whether painful or not, should immediately discontinue the drug and seek emergency medical attention.

Lorcaserin is believed to promote satiety by selectively activating serotonin 2C receptors on anorexigenic pro-opiomelanocortin neurons located in the hypothalamus. Certain centrally-acting weight loss agents that act on the serotonin system have been associated with pulmonary hypertension, a rare but lethal disease. Care should be taken when prescribing this drug to patients at risk or with pulmonary hypertension.

Lorcaserin is extensively metabolized in the liver by multiple enzymatic pathways, and the metabolites are primarily eliminated by the kidney. In patients with varying degrees of renal function, lorcaserin systemic exposure (AUC) was not significantly different, but AUC of the sulfamate metabolite (M1) was increased by approximately 1.7-fold in mild (CrCl 50 to 80 mL/min), 2.3-fold in moderate (CrCl 30 to 50 mL/min), and 10.5-fold in severe renal impairment (CrCl <30 mL/min) compared to normal renal function (CrCl >80 mL/min), while AUC of the N-carbamoyl-glucuronide metabolite (M5) was increased by approximately 1.5-, 2.5-, and 5.1-fold, respectively. No dosage adjustment of lorcaserin is required in patients with mild renal impairment, but caution is advised when used in patients with moderate renal impairment. Use in patients with severe renal impairment or end stage renal disease is not recommended.

Obese, type 2 diabetic patients who achieve weight loss may demonstrate improved metabolic control of their disease as a result of their reduced weight. Therefore, patients with type 2 diabetes mellitus should be monitored during weight-reduction therapy (or therapy that may be expected to induce significant weight loss as a secondary effect) for hypoglycemia and reduced need for oral hypoglycemic medication or insulin, and the dosages of these agents adjusted accordingly. Patients should be apprised of the risk of hypoglycemia and be alert to potential signs and symptoms such as headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, and palpitation.