IMCIVREE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IMCIVREE (IMCIVREE).
Setmelanotide (IMCIVREE) is a melanocortin 4 receptor (MC4R) agonist that activates the MC4R, a key regulator of energy homeostasis, appetite, and body weight. It reduces hunger and promotes weight loss by increasing pro-opiomelanocortin (POMC) signaling.
| Metabolism | Primarily metabolized by hydrolysis via peptidases and cathepsins into small peptides and amino acids; not significantly metabolized by CYP450 enzymes. |
| Excretion | Primarily metabolized via catabolism to small peptides and amino acids; renal excretion of inactive metabolites accounts for <5% of the dose as unchanged drug. |
| Half-life | Terminal elimination half-life is approximately 22 hours (range 15–29 hours) following subcutaneous administration, supporting once-daily dosing. |
| Protein binding | Approximately 79% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 2.2 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Subcutaneous: Absolute bioavailability is approximately 100% after subcutaneous injection. |
| Onset of Action | Subcutaneous: Reduction in hunger scores observed within 2 weeks; clinically meaningful weight loss typically seen by 4 weeks. |
| Duration of Action | Duration of action is approximately 24 hours, consistent with once-daily dosing; sustained weight loss requires continuous administration. |
3 mg subcutaneously once daily initially; titrate upward in 1 mg increments every 2 weeks based on tolerability to a maximum of 6 mg once daily.
| Dosage form | SOLUTION |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Insufficient data for severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease; use with caution. |
| Liver impairment | Contraindicated in Child-Pugh class C (severe hepatic impairment). No adjustment recommended for Child-Pugh class A or B; use with caution. |
| Pediatric use | Approved for patients aged ≥6 years: initial dose 0.6 mg subcutaneously once daily for 2 weeks, then 1.2 mg once daily for 2 weeks, then 2.4 mg once daily for 2 weeks, then titrate to 3.6 mg once daily; maximum 4.2 mg once daily. Dose based on tolerability and response. |
| Geriatric use | No specific geriatric dose adjustments. Consider age-related renal function decline and monitor for adverse events. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for IMCIVREE (IMCIVREE).
| Breastfeeding | It is unknown whether setmelanotide is excreted into human milk. No human data on M/P ratio available. In lactating rats, setmelanotide was excreted in milk at concentrations similar to or lower than maternal plasma. Because of the potential for adverse reactions in breastfed infants, women should not breastfeed during treatment and for at least 1 week after the final dose. |
| Teratogenic Risk | Setmelanotide (IMCIVREE) is a melanocortin 4 receptor agonist. No adequate human data on fetal risk exist. In animal studies, no teratogenicity was observed at exposures up to 40 times the human exposure. However, because of the mechanism of action (increased melanocortin signaling) and potential effects on fetal appetite regulation pathways, caution is warranted. Use during pregnancy only if potential benefit justifies potential fetal risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concomitant use with other weight loss products (e.g., phentermine, bupropion/naltrexone, liraglutide, semaglutide).","Prior serious hypersensitivity reaction to setmelanotide or any excipient.","Pregnancy: no adequate data; consider risk to fetus."]
| Precautions | ["Disturbance in sexual arousal: spontaneous penile erections in males and sexual adverse reactions in females have been reported; instruct patients to discontinue if persistent or painful erections occur (>4 hours).","Depression and suicidal ideation: monitor for emergence or worsening of depression, suicidal thoughts, or mood changes.","Hypersensitivity reactions: angioedema, urticaria, rash; discontinue if severe.","Risk of gallbladder disease: gallbladder sludge and cholecystitis reported; monitor for symptoms.","Hypoglycemia in patients with type 2 diabetes: may increase risk when used with insulin or insulin secretagogues; monitor blood glucose.","Heart rate increase: mean increase of 2-3 bpm observed; assess cardiovascular status.","Concomitant use with other weight loss agents: safety and efficacy not established; avoid combination."] |
Loading safety data…
| Fetal Monitoring | Monitor pregnancy outcomes if exposure occurs. No specific fetal monitoring required beyond routine prenatal care. Consider monitoring for maternal adverse effects such as hypertension, headache, nausea, and diarrhea. |
| Fertility Effects | No human fertility data available. In animal studies, setmelanotide had no adverse effects on fertility in male or female rats at exposures up to 40 times the human exposure. However, because melanocortin signaling can influence reproductive hormone release, theoretical effects on fertility cannot be excluded. |