Usage
- Medical Conditions: Lorcaserin was prescribed for chronic weight management in adults with an initial Body Mass Index (BMI) of 30 kg/m² or greater (obese), or 27 kg/m² or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes). It was used as an adjunct to a reduced-calorie diet and increased physical activity. Note: Lorcaserin is no longer available in the US due to an increased risk of cancer observed in clinical trials.
- Pharmacological Classification: Serotonin 5-HT2C receptor agonist.
- Mechanism of Action: Lorcaserin selectively activates 5-HT2C receptors in the hypothalamus, a region of the brain that regulates appetite. This activation leads to decreased food intake and increased satiety.
Alternate Names
- International/Regional Variations: No significant variations.
- Brand Names: Belviq®, Belviq XR® (withdrawn from the market).
How It Works
- Pharmacodynamics: Lorcaserin primarily exerts its weight-loss effects by selectively activating 5-HT2C receptors in the hypothalamus, leading to decreased appetite and increased satiety. It has minimal activity at 5-HT2A and 5-HT2B receptors, mitigating the risk of valvular heart disease.
- Pharmacokinetics:
- Absorption: Lorcaserin is rapidly absorbed after oral administration, reaching peak plasma concentrations (Tmax) in 1.5-2 hours.
- Metabolism: Extensively metabolized in the liver, primarily through glucuronidation and sulfation. The primary metabolites are inactive on serotonin receptors.
- Elimination: Mainly excreted in the urine (approximately 92%) with a small amount in feces (approximately 2%). The elimination half-life (t1/2) is around 11 hours.
- Mode of Action: Binds to and activates 5-HT2C receptors on anorexigenic pro-opiomelanocortin (POMC) neurons located in the arcuate nucleus of the hypothalamus. The activation of POMC neurons promotes the release of α-melanocyte-stimulating hormone (α-MSH), leading to appetite suppression.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Lorcaserin acts as a selective agonist at 5-HT2C receptors. It is also an inhibitor of CYP2D6.
- Elimination Pathways: Primarily renal excretion of metabolites.
Dosage
Lorcaserin is no longer available, thus the following information is for historical purposes only.
Standard Dosage
Adults:
- 10 mg orally twice daily.
- Maximum dose: 20 mg/day.
Children:
- Use is not recommended. Safety and efficacy not established.
Special Cases:
- Elderly Patients: No dose adjustment necessary for those with normal renal function. Dosage adjustments should be based on renal function.
- Patients with Renal Impairment:
- Mild (CrCl > 50 mL/min): No adjustment required.
- Moderate (CrCl 30-50 mL/min): Use with caution.
- Severe (CrCl < 30 mL/min) or ESRD: Not recommended.
- Patients with Hepatic Dysfunction:
- Mild to Moderate (Child-Pugh score 5-9): No adjustment required.
- Severe (Child-Pugh score > 9): Use with caution. Data regarding severe hepatic impairment is limited.
- Patients with Comorbid Conditions: Use with caution in patients with diabetes, as it may cause hypoglycemia. Monitor blood glucose closely. Use with caution in patients with a history of depression or other mental health conditions, as lorcaserin may worsen symptoms.
Clinical Use Cases
Lorcaserin is not indicated for use in these settings:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations
Dosage Adjustments
- Discontinue lorcaserin if a patient has not lost at least 5% of baseline body weight by week 12 of therapy.
Side Effects
Common Side Effects:
- Headache
- Dizziness
- Fatigue
- Nausea
- Dry mouth
- Constipation
- Upper respiratory tract infection
Rare but Serious Side Effects:
- Serotonin syndrome
- Neuroleptic malignant syndrome-like reactions
- Valvular heart disease (though less common than with other serotonergic drugs)
- Priapism
- Hypoglycemia (especially in patients with diabetes)
- Worsening of depression or suicidal thoughts
- Psychiatric symptoms (e.g., euphoria, hallucination, dissociation) at higher-than-recommended doses
Long-Term Effects: The long-term effects are not fully characterized, as studies beyond two years are lacking. Increased incidence of cancer observed in clinical trials.
Contraindications
- Severe hepatic impairment
- Severe renal impairment or end-stage renal disease
- Concomitant use of serotonergic drugs (e.g., SSRIs, SNRIs, MAOIs, triptans)
- Pregnancy and breastfeeding
Drug Interactions
- Serotonergic Drugs: SSRIs, SNRIs, MAOIs, triptans, tryptophan, St. John’s wort, and certain other antidepressants can increase the risk of serotonin syndrome.
- CYP2D6 Inhibitors: Concomitant use with strong CYP2D6 inhibitors may increase lorcaserin exposure.
- Drugs Metabolized by CYP2D6: Lorcaserin inhibits CYP2D6 and may increase levels of drugs metabolized by this enzyme (e.g., some antidepressants, antipsychotics, some beta-blockers).
- Cabergoline and Methylergonovine: Avoid concomitant use due to shared 5-HT2B receptor activity.
- Other Medications: Caution advised with other CNS depressants, antidiabetic medications.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated. Animal studies have shown adverse effects on fetal development.
- Fetal Risks: Potential for stillbirths and reduced pup viability at higher doses.
- Breastfeeding: Unknown if lorcaserin is excreted in breast milk. Discontinue breastfeeding or lorcaserin due to potential risk to neonates.
Drug Profile Summary
- Mechanism of Action: Selective 5-HT2C receptor agonist that decreases food intake and increases satiety.
- Side Effects: Common: Headache, dizziness, fatigue, nausea. Serious: Serotonin syndrome, valvular heart disease, priapism.
- Contraindications: Severe hepatic/renal impairment, concomitant serotonergic drug use, pregnancy.
- Drug Interactions: Serotonergic drugs, CYP2D6 inhibitors/substrates, cabergoline, methylergonovine.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 10 mg twice daily (historical).
- Monitoring Parameters: Body weight, blood glucose (in diabetics), mental status, cardiac function.
Popular Combinations
Lorcaserin is no longer available, thus combinations are not relevant.
Precautions
- Pre-screening for cardiac and mental health conditions.
- Monitor for serotonin syndrome, especially when combined with other serotonergic drugs.
- Monitor blood glucose in patients with diabetes.
- Evaluate for valvular heart disease.
- Advise patients about potential for priapism.
- Avoid in pregnancy and breastfeeding.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Lorcaserin?
A: Lorcaserin is no longer available. The historical recommended dosage was 10 mg twice daily for adults. Use was not recommended for children.
Q2: How does Lorcaserin work for weight loss?
A: It selectively activates 5-HT2C receptors in the hypothalamus, leading to decreased appetite and increased feelings of fullness.
Q3: What are the common side effects of Lorcaserin?
A: Common side effects include headache, dizziness, fatigue, nausea, dry mouth, and constipation.
Q4: Who should not take Lorcaserin?
A: Patients with severe liver or kidney disease, pregnant or breastfeeding women, and individuals taking certain serotonergic medications should not take lorcaserin.
Q5: Can Lorcaserin be used with other weight loss medications?
A: The safety and efficacy of combining lorcaserin with other weight loss medications have not been established.
Q6: Does Lorcaserin have any cardiovascular risks?
A: While the risk of valvular heart disease is lower than with some other weight-loss drugs, lorcaserin should be used with caution in patients with congestive heart failure.
Q7: What if I miss a dose of Lorcaserin?
A: If you missed a dose of lorcaserin (no longer available), you should take it as soon as you remember, unless it is close to the time for your next dose. Do not double up on doses.
Q8: Why was Lorcaserin withdrawn from the market?
A: Lorcaserin was withdrawn due to an increased occurrence of cancer observed in a clinical safety trial.
Q9: Are there any alternative medications for weight loss?
A: Yes, there are alternative medications available for weight loss. Consult a healthcare professional to discuss appropriate options.
