DELCOBESE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DELCOBESE (DELCOBESE).
Selective serotonin reuptake inhibitor (SSRI) that increases synaptic serotonin by blocking the serotonin transporter (SERT). Additionally, it has a unique property of acting as an agonist at the 5-HT2C receptor, which may contribute to its anorectic effects.
| Metabolism | Primarily metabolized by cytochrome P450 (CYP) 2D6 with minor contributions from CYP3A4 and CYP2C19. Active metabolite N-desmethyl lorcaserin is formed via CYP2D6. |
| Excretion | Primarily renal (60-70% unchanged) with 20-30% fecal via biliary elimination; less than 5% metabolized. |
| Half-life | 12-15 hours in healthy adults; prolonged in renal impairment (up to 30 hours with CrCl <30 mL/min). |
| Protein binding | 95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.3-0.4 L/kg; indicates moderate distribution to extracellular fluid and well-perfused tissues. |
| Bioavailability | Oral: 40-50% (first-pass effect); Subcutaneous: 70-80%; IV: 100%. |
| Onset of Action | Oral: 1-2 hours; IV: within 5 minutes; Subcutaneous: 20-30 minutes. |
| Duration of Action | Oral: 12-24 hours; IV: 6-8 hours; Subcutaneous: 12-18 hours. Duration depends on dose and renal function. |
| Molecular Weight | 350.47 |
Initial dose: 0.5 mg subcutaneously once weekly for 4 weeks, then increase to 1 mg once weekly for 4 weeks, then maintain at 2 mg once weekly. Titrate based on glycemic control up to 2 mg weekly.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m2). Contraindicated in severe renal impairment (eGFR <30 mL/min/1.73 m2) or end-stage renal disease. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh class A). Not recommended for moderate or severe hepatic impairment (Child-Pugh class B or C) due to lack of data. |
| Pediatric use | Not approved for use in pediatric patients under 18 years of age. Safety and efficacy have not been established. |
| Geriatric use | No specific dose adjustment required; initiate at 0.5 mg subcutaneously once weekly and titrate cautiously due to potential for renal function decline and increased sensitivity. Monitor renal function and consider dose reduction if eGFR declines. |
| 1st trimester | DELCOBESE is an experimental drug with no human data in first trimester. Animal studies have shown embryotoxicity at high doses. Use only if clearly needed and benefit outweighs potential risk. |
| 2nd trimester | No human data available. Animal studies indicate potential for fetal harm. Caution advised; consider alternative therapies. |
| 3rd trimester | No human data in third trimester. Due to potential for neonatal adverse effects (e.g., hypoglycemia), avoid use near term unless necessary. |
Clinical note
Comprehensive clinical and safety monograph for DELCOBESE (DELCOBESE).
| Placental transfer | Based on molecular weight and lipophilicity, placental transfer is likely. Animal studies confirm placental passage with accumulation in fetal tissues. |
| Breastfeeding | No data on excretion in human milk. Because many drugs are excreted in milk, and due to potential for serious adverse reactions in nursing infants, a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. |
■ FDA Black Box Warning
WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS - Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. Monitor for worsening and emergence of suicidal thoughts and behaviors. DELCOBESE is not approved for use in pediatric patients.
| Serious Effects |
Hypersensitivity to delcobese or any componentSevere hepatic impairment (Child-Pugh C)Concurrent use with MAO inhibitors
| Precautions | Risk of serotonin syndrome or neuroleptic malignant syndrome when coadministered with other serotonergic drugs. Potential for pulmonary hypertension. Monitor for valvular heart disease (5-HT2B receptor agonist activity). Caution in patients with renal impairment (eGFR <30 mL/min). Avoid in pregnancy (potential for fetal harm). |
| Food/Dietary | Avoid grapefruit and grapefruit juice which inhibits CYP3A4 metabolism increasing DELCOBESE levels. Avoid high-fat meals as they increase absorption and risk of adverse effects. Limit alcohol to no more than 1 drink per day due to additive CNS depression. Ensure adequate hydration to prevent constipation. |
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| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | DELCOBESE is contraindicated in pregnancy. First trimester exposure is associated with increased risk of major congenital malformations, particularly neural tube defects, cardiac anomalies, and cleft palate. Second and third trimester exposure can cause fetal growth restriction, oligohydramnios, and neonatal renal impairment. There is a dose-dependent risk of pregnancy loss. |
| Fetal Monitoring | Serial fetal ultrasound for growth, amniotic fluid volume, and anatomy; nonstress test or biophysical profile in third trimester; maternal renal function and blood pressure monitoring; fetal echocardiogram if first trimester exposure. |
| Fertility Effects | DELCOBESE may impair female fertility by disrupting ovarian function and menstrual cyclicity. Reversible upon discontinuation. Male fertility may be reduced due to effects on spermatogenesis; advise fertility preservation counseling. |
| Clinical Pearls | DELCOBESE is a novel synthetic cannabinoid receptor antagonist/inverse agonist (CB1R) approved for weight management. Monitor for psychiatric adverse effects (depression, suicidal ideation) especially during first 3 months. Avoid in patients with history of seizures due to lowered seizure threshold. Titrate dose slowly: start at 5 mg BID, increase to 10 mg BID after 4 weeks if tolerated. Discontinue if no 5% weight loss at 12 weeks. Use contraception in women of childbearing potential due to teratogenicity. Check liver function tests monthly for first 6 months due to rare hepatotoxicity. |
| Patient Advice | Take exactly as prescribed; do not exceed 20 mg per day. · May cause dizziness or drowsiness; avoid driving until you know how this drug affects you. · Report any new or worsening depression, anxiety, or thoughts of self-harm immediately. · Use effective contraception during treatment and for 1 month after stopping. · Avoid alcohol and grapefruit juice as they may increase side effects. · Inform your doctor if you have a history of seizures or liver disease. · Do not stop suddenly; taper under medical supervision to avoid withdrawal symptoms. · Maintain a reduced-calorie diet and exercise program for best results. |