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Estudos

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LORCASERINA
Controle do apetite com menos efeitos colaterais

DESCRIÇÃO
A Lorcaserina é um sal (cloridrato), agonista do receptor da serotonina 2C, indicado para o controle crônico do peso
como adjuvante à dieta e ao exercício.

MECANISMO DE AÇÃO
A Lorcaserina reduz o apetite por sua ligação seletiva ao receptor central de serotonina 5HT-2C em neurônios
anorexigênicos pró-opiomelanocortina (POMC) no hipotálamo. Os agonistas serotoninérgicos não seletivos também
promovem perda de peso, mas aumentam o risco de doença valvar cardíaca associada à serotonina, potencialmente
mediada pelo receptor 5HT-2B, efeito este não apresentado pelo uso da Lorcaserina, devido ao seu agonismo seletivo
pelo receptor 2C da serotonina.

INDICAÇÕES
 Controle ponderal
 Redução do apetite

DOSE USUAL
Recomendação oral de 20mg de Lorcaserina ao dia.

SUGESTÕES DE FÓRMULAS

Lorcaserina....................................................... 10 mg Lorcaserina slow release.................................. 20 mg

Modo de uso: 1 dose, 2 vezes ao dia. Modo de uso: 1 dose ao dia.


Indicação: redução do apetite e controle do peso. Indicação: redução do apetite e controle do peso.

PRINCIPAIS REFERÊNCIAS

CHRISTOPHER, R. et al. Single- and Multiple-dose Pharmacokinetics of a Lorcaserin Extended-release Tablet. Clin Ther. v. 38, n. 10, p. 2227-
2238. 2016. Disponivel em:< https://www.ncbi.nlm.nih.gov/pubmed/27692638>. Acesso em: 22/12/2016, às 16:51.

SHUKLA, A. P.; KUMAR, R. B.; ARONNE, L. J. Lorcaserin Hcl for the treatment of obesity. Expert Opin Pharmacother. v. 16, n. 16, p. 2531-8.
2015. Disponivel em:< https://www.ncbi.nlm.nih.gov/pubmed/26472579>. Acesso em: 22/12/2016, às 17:00.

http://aformulabr.com.br/qrcode/actigymafv01.pdf
LORCASERINA
ESTUDOS CLÍNICOS

Effectiveness, tolerability and practical application of the newer generation anti-obesity medications.

OBJECTIVE: Comparison of the efficacy and tolerability of five newer anti-obesity medications to guide clinical decision
making, examining bupropion-naltrexone combination, liraglutide, lorcaserin, orlistat, and phentermine-topiramate
combination. METHODS: A brief literature review and internet search for high-powered, randomized and placebo-
controlled drug trials was conducted. Drug trial information was established for five currently approved anti-obesity
medications. Secondarily, a statistical comparison of medications through Number Needed to Treat (NNT) and Number
Needed to Harm (NNH) analyses were attempted as a way to provide a clinical analysis across these varied medications.
Finally, a commentary about clinical application is issued for each agent accounting for typical side-effects, serious side-
effects, mechanism of action and ease of use. RESULTS: All five agents are currently approved oral medications to
lower weight. The NNT range was 3-12, and NNH range was 4-17. The agent with the best NNT is phentermine-
topiramate combination (NNT=3) and the agent with the best NNH is bupropion-naltrexone combination (NNH=17).
CONCLUSION: When considering each patient's clinical presentation, knowledge of each drug's mechanism of action,
side-effect profile, efficacy, and NNT and NNH values can help in selecting an anti-obesity medication to augment his
or her weight loss efforts.

Impact of lorcaserin on glycemic control in overweight and obese patients with type 2 diabetes: analysis of
week 52 responders and nonresponders.

OBJECTIVES: Treatment guidelines for type 2 diabetes mellitus (T2DM) suggest weight loss as a means to maintain
glycemic control. Lorcaserin has been approved for chronic weight management in the United States as an adjunct to
a reduced-calorie diet and exercise, and the previous phase 3 Behavioral Modification and Lorcaserin for Obesity and
Overweight Management in Diabetes Mellitus (BLOOM-DM) study has shown that, in addition to weight loss, lorcaserin
is associated with improvements in glycemic parameters. In this post hoc analysis of the BLOOM-DM trial, the
relationship between responder status (patients achieving ≥5% weight loss at Week 52) and glycemic and
cardiometabolic parameters is evaluated. METHODS: Data are presented for patients receiving lorcaserin 10 mg twice
daily or placebo for 52 weeks. RESULTS: More than twice as many patients receiving lorcaserin plus diet and exercise
counseling were classified as Week 52 responders compared to those receiving diet and exercise counseling alone
(37.5% vs. 16.1%, respectively; p < 0.001), and lorcaserin Week 52 responders had greater improvements vs. placebo
Week 52 responders in FPG (-38.1 mg/dL vs. -26.0 mg/dL) and HbA1c (-1.3% vs. -1.0%). Furthermore, more lorcaserin-
treated Week 52 responders decreased the number of concomitant oral antidiabetic medications (OADs) used, and
fewer increased the number of OADs used, compared to placebo. Unexpectedly, lorcaserin Week 52 nonresponders
also had substantial reductions in glycemic levels, despite very modest weight loss. CONCLUSIONS: These data
support lorcaserin use in overweight and obese patients with T2DM to promote weight loss and facilitate glycemic
control.

Safety and tolerability review of lorcaserin in clinical trials.

Lorcaserin is a novel selective serotonin 2C receptor agonist indicated by the US Food and Drug Administration for
chronic weight management in adults with obesity or overweight with ≥1 comorbidity. The safety and efficacy of
lorcaserin were established during two Phase III clinical trials in patients without diabetes (BLOOM and BLOSSOM) and
one Phase III clinical trial in patients with type 2 diabetes (BLOOM-DM). Headache was the most common adverse
event experienced by patients during all Phase III trials. Additional adverse events occurring in >5% of patients receiving
lorcaserin included dizziness, fatigue, nausea, dry mouth and constipation in patients without diabetes, and
hypoglycaemia, back pain, cough and fatigue in patients with diabetes. In a pooled analysis of echocardiographic data
collected during the three lorcaserin Phase III trials, the incidence of FDA-defined valvulopathy was similar in patients
taking lorcaserin and the placebo. Here, the safety profile of lorcaserin at the FDA-approved dose of 10 mg twice daily
is reviewed using data from the lorcaserin Phase III programme, with a focus on theoretical adverse events commonly
associated with agonists of the serotonin receptor family. Based on the lorcaserin Phase III clinical trial data, lorcaserin
is safe and well tolerated in the indicated patient populations.
Lorcaserin Administration Decreases Activation of Brain Centers in Response to Food Cues and These
Emotion- and Salience-Related Changes Correlate With Weight Loss Effects: A 4-Week-Long Randomized,
Placebo-Controlled, Double-Blind Clinical Trial.

Lorcaserin is a serotonin 5-hydroxytryptamine 2c receptor agonist effective in treating obesity. Studies in rodents have
shown that lorcaserin acts in the brain to exert its weight-reducing effects, but this has not yet been studied in humans.
We performed a randomized, placebo-controlled, double-blind trial with 48 obese participants and used functional MRI
to study the effects of lorcaserin on the brain. Subjects taking lorcaserin had decreased brain activations in the attention-
related parietal and visual cortices in response to highly palatable food cues at 1 week in the fasting state and in the
parietal cortex in response to any food cues at 4 weeks in the fed state. Decreases in emotion- and salience-related
limbic activity, including the insula and amygdala, were attenuated at 4 weeks. Decreases in caloric intake, weight, and
BMI correlated with activations in the amygdala, parietal, and visual cortices at baseline. These data suggest that
lorcaserin exerts its weight-reducing effects by decreasing attention-related brain activations to food cues (parietal and
visual cortices) and emotional and limbic activity (insula, amygdala). Results indicating that baseline activation of the
amygdala relates to increased efficacy suggest that lorcaserin would be of particular benefit to emotional eaters.

Efficacy and safety of lorcaserin in obese adults: a meta-analysis of 1-year randomized controlled trials (RCTs)
and narrative review on short-term RCTs.

Lorcaserin is a new anti-obesity drug recently approved by US Food and Drug Administration. We conducted a
systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the association of lorcaserin
therapy with weight loss and adverse events in obese adults (18-65 years old). Weight loss of 3.23 kg (95% confidence
interval [CI]: 2.70, 3.75) and body mass index reduction of 1.16 kg m⁻² (95% CI: 0.98, 1.34) was observed compared
with placebo in RCTs of 1 year duration. The use of lorcaserin for 8 and 12 weeks reduced weight of 1.60 kg (95% CI:
0.34, 2.86) and 2.9 kg (95% CI: 2.2, 3.5), respectively. In comparison to placebo, lorcaserin decreased waist
circumference, blood pressure, total cholesterol, low-density lipoprotein-cholesterol and triglycerides, however did not
statistically affect heart rate or high-density lipoprotein-cholesterol. Headache, nausea and dizziness were found to be
significantly higher in the patients receiving lorcaserin than patients receiving placebo, whereas diarrhoea is no more
likely than in patients receiving placebo. In conclusion, lorcaserin achieves modest weight loss and appears to be well
tolerated. Clinical and pharmacovigilance studies with longer study duration are needed to inform of the long-term
efficacy and safety of lorcaserin.

Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic
Review and Meta-analysis.

IMPORTANCE: Five medications have been approved for the management of obesity, but data on comparative
effectiveness are limited. OBJECTIVE: To compare weight loss and adverse events among drug treatments for obesity
using a systematic review and network meta-analysis. DATA SOURCES: MEDLINE, EMBASE, Web of Science,
Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries. STUDY SELECTION:
Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug
Administration-approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-
topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo. DATA EXTRACTION AND
SYNTHESIS: Two investigators identified studies and independently abstracted data using a predefined protocol. A
Bayesian network meta-analysis was performed and relative ranking of agents was assessed using surface under the
cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria. MAIN OUTCOMES
AND MEASURES: Proportions of patients with at least 5% weight loss and at least 10% weight loss, magnitude of
decrease in weight, and discontinuation of therapy because of adverse events at 1 year. RESULTS: Twenty-eight
randomized clinical trials with 29 018 patients (median age, 46 years; 74% women; median baseline body weight, 100.5
kg; median baseline body mass index, 36.1) were included. A median 23% of placebo participants had at least 5%
weight loss vs 75% of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95% credible interval [CrI],
6.63-12.85; SUCRA, 0.95), 63% of participants taking liraglutide
(OR, 5.54; 95% CrI, 4.16-7.78; SUCRA, 0.83), 55% taking naltrexone-bupropion (OR, 3.96; 95% CrI, 3.03-5.11; SUCRA,
0.60), 49% taking lorcaserin (OR, 3.10; 95% CrI, 2.38-4.05; SUCRA, 0.39), and 44% taking orlistat (OR, 2.70; 95% CrI,
2.34-3.09; SUCRA, 0.22). All active agents were associated with significant excess weight loss compared with placebo
at 1 year-phentermine-topiramate, 8.8 kg (95% CrI, -10.20 to -7.42 kg); liraglutide, 5.3 kg (95% CrI, -6.06 to -4.52 kg);
naltrexone-bupropion, 5.0 kg (95% CrI, -5.94 to -3.96 kg); lorcaserin, 3.2 kg (95% CrI, -3.97 to -2.46 kg); and orlistat,
2.6 kg (95% CrI, -3.04 to -2.16 kg). Compared with placebo, liraglutide (OR, 2.95; 95% CrI, 2.11-4.23) and naltrexone-
bupropion (OR, 2.64; 95% CrI, 2.10-3.35) were associated with the highest odds of adverse event-related treatment
discontinuation. High attrition rates (30%-45% in all trials) were associated with lower confidence in estimates.
CONCLUSIONS AND RELEVANCE: Among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion,
phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5%
weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving at
least 5% weight loss.

Single- and Multiple-dose Pharmacokinetics of a Lorcaserin Extended-release Tablet.

PURPOSE: Lorcaserin is a serotonin 2C receptor agonist indicated for chronic weight management as an adjunct to
diet and exercise. The initial approved formulation is a 10-mg, immediate-release (IR) tablet for administration BID.
These studies investigated the single- and multiple-dose pharmacokinetic properties of a new, recently US Food and
Drug Administration-approved, extended-release, 20-mg once-daily formulation. METHODS: We performed 2 separate
2-period, 2-sequence crossover studies in 36 healthy adults: a study comparing the IR formulation to the extended-
release formulation under fasting conditions and a study comparing the extended-release formulation under fed and
fasted conditions. FINDINGS: Compared with lorcaserin IR, the Tmax after a single dose of lorcaserin extended-release
was greater (median, 12 vs 3 hours), and the Cmax was 26% lower (38.8 vs 52.3 ng/mL). AUC data were bioequivalent
for the 2 formulations in both single- and multiple-dose regimens, confirming no formulation effect on lorcaserin
bioavailability. In fasted and fed conditions, Tmax after a single dose was identical (median, 12 hours), but Cmax was
approximately 45% higher in the fed state (mean, 38.5 ng/mL fasted vs 56.1 ng/mL fed). However, at steady state,
Cmax and AUC were determined to be bioequivalent between the fasted and fed states, indicating no clinically relevant
food effect on the pharmacokinetic properties of lorcaserin extended-release. The safety profile was consistent between
the 2 formulations. IMPLICATIONS: Overall, the results indicate that lorcaserin extended-release is a suitable once-
daily alternative to the approved IR BID formulation.

Obesity: Current and potential pharmacotherapeutics and targets.

Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type
2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed.
Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms
underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal
circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity
signals that modulate neural activity and regulate eating behavior. Dysregulation of one or more of these homeostatic
components results in obesity. Coincident with obesity, reward mechanisms that regulate hedonic aspects of food intake
override the homeostatic regulation of eating. In addition to functional interactions between homeostatic and reward
systems in the regulation of food intake, homeostatic signals have the ability to alter vulnerability to drug abuse.
Regarding the treatment of obesity, pharmacological monotherapies primarily focus on a single protein target. FDA-
approved monotherapy options include phentermine (Adipex-P®), orlistat (Xenical®), lorcaserin (Belviq®) and liraglutide
(Saxenda®). However, monotherapies have limited efficacy, in part due to the recruitment of alternate and counter-
regulatory pathways. Consequently, a multi-target approach may provide greater benefit. Recently, two combination
products have been approved by the FDA to treat obesity, including phentermine/topiramate (Qsymia®) and
naltrexone/bupropion (Contrave®). The current review provides an overview of homeostatic and reward mechanisms
that regulate energy balance, potential therapeutic targets for obesity and current treatment options, including some
candidate therapeutics in clinical development. Finally, challenges in anti-obesity drug development are discussed.
Lorcaserin Hcl for the treatment of obesity.

INTRODUCTION: Obesity is a major health priority necessitating safe and effective strategies to address the obesity
epidemic. Lorcaserin is a serotonergic agonist specific to the 5HT- 2C receptor approved for chronic management of
obesity in patients with a BMI ≥ 30 kg/m(2) or a BMI ≥ 27 kg/m(2) with comorbidities related to obesity. AREAS
COVERED: In this paper, the pharmacodynamic and pharmacokinetic properties of lorcaserin are reviewed followed by
a discussion of efficacy and safety data from major clinical trials. EXPERT OPINION: Lorcaserin is a unique highly
selective serotonergic agonist designed to mitigate the risks associated with previous agents in this class. At therapeutic
doses, it is well tolerated and produces modest but clinically meaningful weight loss with significant improvement in
cardiometabolic parameters. Therapeutic efficacy should be assessed at 12 weeks (≥ 5% weight loss) to identify
responders who will derive maximum weight loss and metabolic benefit from long-term therapy. The results of the
ongoing cardiovascular outcomes trial (CAMELLIA TIMI 61) will determine the role of lorcaserin in primary prevention
of diabetes in overweight/obese individuals and its use in the high-risk population of patients with established
cardiovascular disease or multiple cardiovascular risk factors.

Efficacy comparison of medications approved for chronic weight management.

For the first time, patients who are obese are able to benefit from 5 different FDA approved pharmacologic agents for
chronic weight management. Although weight loss from all of these medications was limited to 5% to 10% of total body
weight loss in the Phase III clinical trials, patients are capable of losing more weight when a cumulative approach of
diet, exercise, and multiple medications are used. A pilot study of adding phentermine to lorcaserin yielded double the
weight loss than lorcaserin alone. A higher percentage of total body weight is lost with use of combination
phentermine/topiramate compared to orlistat, lorcaserin, and bupropion/naltrexone but there are more contraindications
to its use and potential cardiovascular adverse effects due to adrenergic agonism. Lorcaserin and bupropion/naltrexone
yielded similar weight loss but carry different adverse effect profiles and interactions with other psychiatric medications
may preclude use of one over the other. When choosing a medication for obesity, several factors need to be considered,
such as comorbidities, medication interactions, and risk of potential adverse effects.

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review on short-term RCTs. Obes Rev. v. 14, n. 5, p. 383-92. 2013. Disponivel em:< https://www.ncbi.nlm.nih.gov/pubmed/23331711>. Acesso em:
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CHRISTOPHER, R. et al. Single- and Multiple-dose Pharmacokinetics of a Lorcaserin Extended-release Tablet. Clin Ther. v. 38, n. 10, p. 2227-
2238. 2016. Disponivel em:< https://www.ncbi.nlm.nih.gov/pubmed/27692638>. Acesso em: 22/12/2016, às 16:51.
FARR, O. M. et al. Lorcaserin Administration Decreases Activation of Brain Centers in Response to Food Cues and These Emotion- and Salience-
Related Changes Correlate With Weight Loss Effects: A 4-Week-Long Randomized, Placebo-Controlled, Double-Blind Clinical Trial. Diabetes. v.
65, n. 10, p. 2943-53. 2016. Disponivel em:< https://www.ncbi.nlm.nih.gov/pubmed/27385157>. Acesso em: 23/12/2016, às 11:36.
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KUMAR, R. B.; ARONNE, L. J. Efficacy comparison of medications approved for chronic weight management. Obesity (Silver Spring). v. 23, n. 1,
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PI-SUNYER, X. et al. Impact of lorcaserin on glycemic control in overweight and obese patients with type 2 diabetes: analysis of week 52
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Acesso em: 23/12/2016, às 12:10.
SHUKLA, A. P.; KUMAR, R. B.; ARONNE, L. J. Lorcaserin Hcl for the treatment of obesity. Expert Opin Pharmacother. v. 16, n. 16, p. 2531-8.
2015. Disponivel em:< https://www.ncbi.nlm.nih.gov/pubmed/26472579>. Acesso em: 22/12/2016, às 17:00.