Imcivree (setmelanotide acetate)

Dosage of setmelanotide acetate is expressed in terms of setmelanotide.

Setmelanotide is administered by subcutaneous injection. Do not administer IV or by IM injection.

Setmelanotide is commercially available as a 10 mg/mL, clear to slightly opalescent, colorless to slightly yellow solution for subcutaneous use in a 1 mL multiple-dose vial.

Store unopened setmelanotide vials in the refrigerator at 2-8oC in the original carton. After removal from the refrigerator, vials may be kept at temperatures ranging from refrigerated to room temperature (2-25oC) for up to 30 days with brief excursions up to 30oC. After the vial is punctured (opened), discard after 30 days.

Train the patient and/or their caregivers on proper subcutaneous injection technique; instruct patients to use a 1 mL syringe with a 28- or 29-gauge needle for administration.

Remove setmelanotide from the refrigerator approximately 15 minutes prior to administration. Alternatively, warm setmelanotide prior to administration by rolling the vial gently between the palms of the hands for 60 seconds.

Inject subcutaneously into the abdomen, thigh, or arm, rotating to a different site each day.

Administer setmelanotide once daily, at the beginning of the day, without regard to meals. If a dose is missed, resume the once daily regimen as prescribed with the next scheduled dose.

No dosing information is available for this tab.

No clinical studies evaluating the drug interaction potential of setmelanotide have been conducted. Setmelanotide has low potential for pharmacokinetic drug-drug interactions related to cytochrome P-450 (CYP) isoenzymes, transporters, and plasma protein binding.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Prior serious hypersensitivity reaction, including anaphylaxis, to setmelanotide or any of its excipients.

• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Pregnancy

• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Depression
• Suicidal ideation

• Hypernatremia
• Hyponatremia
• Hypothalamic-pituitary insufficiency
• Kidney disease with likely reduction in glomerular filtration rate (GFr)
• Progression of nevus

The most common adverse reactions (incidence >=20%) include skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.

Less Frequent

• Aggressive behavior
• Priapism
• Suicidal ideation

Rare or Very Rare

• Anaphylaxis
• Hypersensitivity drug reaction

More Frequent

• Accidental fall
• Acquired melanocytic nevus
• Acute abdominal pain
• Back pain
• Cough
• Depression
• Diarrhea
• Dry skin
• Fatigue
• Fever
• Headache disorder
• Injection site sequelae
• Nausea
• Pharyngitis
• Skin pigmentation enhancement
• Spontaneous penile erection
• Upper respiratory infection
• Vomiting

Less Frequent

• Acute adrenocortical insufficiency
• Alopecia
• Arthralgia
• Chills
• Constipation
• Dizziness
• Flu-like symptoms
• General weakness
• Hypernatremia
• Hyponatremia
• Increased pigmentation of skin pigmentary lesion
• Insomnia
• Libido changes
• Muscle spasm
• Pain in extremities
• Skin rash
• Skin striae
• Vertigo
• Vulvodynia
• Xerostomia

No enhanced messaging available.

The safety and effectiveness of setmelanotide have been established to decrease body weight and maintain weight reduction long term in pediatric patients >=2 years of age with obesity due to Bardet-Biedl syndrome or POMC, proprotein convertase subtilisin/kexin type 1 (PCSK1), or LEPR deficiency with variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance.

Use of setmelanotide for these indications is supported by evidence from two 1-year open-label studies that included 9 pediatric patients (6 to 17 years of age) with POMC, PCSK1, or LEPR deficiency, one 66-week study, which included a 14-week randomized, double-blind, placebo-controlled period and enrolled 22 pediatric patients (6 to 17 years of age) with Bardet-Biedl syndrome, and a single, 1-year, open-label study of 12 pediatric patients (2 to <6 years of age) with POMC or LEPR deficiency or Bardet-Biedl syndrome.

The efficacy and safety of setmelanotide have not been established in pediatric patients <2 years of age.

Setmelanotide is not approved for use in neonates or infants. Serious adverse reactions, including fatal reactions and the ''gasping syndrome,'' occurred in premature neonates and low birth weight infants in the neonatal intensive care unit who received drugs containing benzyl alcohol as a preservative. In these cases, benzyl alcohol dosages of 99-234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine. Additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Preterm, low birth weight infants may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known (setmelanotide contains 10 mg of benzyl alcohol per mL).

Discontinue setmelanotide when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

Setmelanotide contains the preservative benzyl alcohol. Because benzyl alcohol is rapidly metabolized by a pregnant woman, benzyl alcohol exposure in the fetus is unlikely. However, adverse reactions have occurred in premature neonates and low birth weight infants who received IV benzyl alcohol-containing drugs.

There are no available data with setmelanotide use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, setmelanotide administered subcutaneously to pregnant rats from before mating to the end of organogenesis was not teratogenic at doses 11 times the maximum recommended human dose (MRHD) of 3 mg. Setmelanotide administered subcutaneously to pregnant rabbits during the period of organogenesis was not teratogenic at clinical doses. Setmelanotide administered subcutaneously to pregnant rats during organogenesis through lactation did not result in adverse developmental effects at doses 7 times the MRHD.

For the general US population, weight loss offers no potential benefit to a pregnant woman and may result in fetal harm. Maternal obesity increases the risk for congenital malformations, including neural tube defects, cardiac malformations, oral clefts, and limb reduction defects. However, weight loss during pregnancy may result in fetal harm including increased risk of small for gestational age. Appropriate weight gain based on pre-pregnancy weight is currently recommended for all pregnant women, including those who are already overweight or obese, due to the obligatory weight gain that occurs in maternal tissues during pregnancy.

There is no information on the presence of setmelanotide or its metabolites in human milk, the effects on the breast-fed infant, or the effects on milk production. However, setmelanotide is present in the milk of rats. When a drug is present in rat milk, it is likely that the drug will be present in human milk.

Multiple-dose vials of setmelanotide contain the preservative benzyl alcohol. Because benzyl alcohol is rapidly metabolized by a lactating woman, benzyl alcohol exposure in the breast-fed infant is unlikely. However, adverse reactions have occurred in premature neonates and low birth weight infants who received IV benzyl alcohol-containing drugs.

Treatment with setmelanotide is not recommended while breastfeeding.

The manufacturer makes no specific dosage recommendations for geriatric patients.

Clinical studies of setmelanotide did not include patients >=65 years of age. It is not known whether geriatric patients would respond differently than younger adult patients.