setmelanotide

Action and Spectrum

Actions and Spectrum: 

The action of setmelanotide is to increase energy expenditure and reduce food intake, which can lead to weight loss in individuals with obesity caused by genetic mutations in the MC4R receptor. This medication is currently in development for the treatment of obesity and related disorders, such as Prader-Willi syndrome. 

The spectrum of setmelanotide includes its potential use in treating a variety of metabolic disorders, such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease. It may also be useful in treating conditions related to appetite regulation, such as binge eating disorder and night eating syndrome. Additionally, setmelanotide may be used in combination with other medications to achieve greater weight loss and improve overall health outcomes in individuals with obesity. 

Drug Interaction

Adverse Reaction

Frequency defined  

>10%  

Skin hyperpigmentation (78%)  

Injection site reaction (96%)  

Nausea (56%)  

Abdominal pain (33%)  

Diarrhea (37%)  

Back pain (33%)  

Vomiting (30%)  

Fatigue (30%)  

Depression (26%)  

Spontaneous penile erections (23%)  

Upper respiratory tract infection (26%)  

Arthralgia (19%)  

Dizziness (15%)  

Asthenia (19%)  

Black Box Warning

Black Box Warning 

The black box warning for setmelanotide states that the drug may cause increased pigmentation (darkening) of the skin, eyes, and mucous membranes. This pigmentation may be permanent and may occur in areas of the body not exposed to sunlight. 

Contraindication / Caution

Contraindication/Caution: 

setmelanotide is contraindicated in patients with a history of melanoma or other pigmented skin lesions, as it may increase the risk of developing or progressing melanoma. It should also be used with caution in patients with a history of cardiovascular disease or hypertension, as it may increase blood pressure.

Additionally, it should be used with caution in patients with a history of depression or other mental health conditions, as it may worsen these conditions. It is also important to monitor blood glucose levels in patients with diabetes, as setmelanotide may decrease insulin sensitivity. 

Pregnancy / Lactation

Pregnancy warnings:     

US FDA pregnancy category: Not assigned 

Lactation:   

Excreted into human milk is unknown  

Pregnancy Categories:         

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.    

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.     

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.     

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.     

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology:  

setmelanotide is a melanocortin-4 receptor agonist, which means it binds to and activates the melanocortin-4 receptor in the body. This receptor is found in the hypothalamus and other areas of the brain, as well as in adipose tissue and the gastrointestinal tract. 

Pharmacodynamics: 

The primary mechanism of action of setmelanotide is to stimulate the melanocortin-4 receptor, which leads to an increase in appetite suppression and energy expenditure. This results in weight loss and improved glucose metabolism in individuals with genetic disorders of obesity, such as pro-opiomelanocortin (POMC) deficiency or leptin receptor (LEPR) mutations. 

Pharmacokinetics:  

Absorption   

The absorption of the drug has a peak plasma time of 8 hours and a peak plasma concentration of 37.9 ng/mL after a 3-mg dose. The area under the curve (AUC) is 495 hr⋅ng/mL, and the trough plasma concentration is 6.77 ng/mL. The drug reaches a steady state within 2 days  

Distribution   

In terms of distribution, the drug is 79.1% protein bound and has a volume of distribution (Vd) of 48.7 L  

Metabolism   

The drug is thought to be metabolized into small peptides by catabolic pathways 

Elimination and excretion   

The elimination of the drug has a half-life of approximately 11 hours, a total clearance of 4.86 L/hr, and is excreted mainly in the urine (39% unchanged)  

Adminstartion

Administration:  

SC Administration  

setmelanotide is a medication that is administered subcutaneously (under the skin) as a self-injectable daily dose. The dosage and frequency may vary depending on the individual’s condition and response to treatment. It is important to follow the instructions provided by a healthcare professional and to use a properly calibrated injection device. It should be stored in a refrigerator and protected from light. It should not be mixed with any other medication or solution and should be discarded if it appears cloudy or discolored.

Patient Information Leaflet

Patient information leaflet 

Generic Name: setmelanotide  

Why do we use setmelanotide? 

setmelanotide is a medication used to treat rare genetic disorders that cause obesity, including pro-opiomelanocortin (POMC) deficiency obesity, LEPR deficiency obesity, and Bardet-Biedl syndrome (BBS). These disorders are caused by mutations in genes that regulate the body’s melanocortin system, which is involved in regulating appetite and energy expenditure. setmelanotide works by mimicking the activity of the melanocortin-4 receptor (MC4R), which is a key component of this system. By activating the MC4R, setmelanotide helps to reduce appetite and increase energy expenditure, leading to weight loss and improvement in overall health.