Bremelanotide is an injectable agonist of melanocortin receptors that is administered subcutaneously. It is specifically indicated for the treatment of Hypoactive Sexual Desire Disorder (HSDD) in premenopausal females, or low sexual desire, by activating brain pathways involved in normal sexual responses. To qualify for treatment, patients must have HSDD that causes significant distress or interpersonal difficulty and is not related to any co-existing medical or psychiatric condition, problems within the relationship, or the effects of a medication or other drug substance. Bremelanotide is not intended for the treatment of HSDD in postmenopausal women, males, or to improve sexual performance. Clinical trials have shown that about 25% of patients treated with bremelanotide had an increase of 1.2 or more in their sexual desire score (scored on a range of 1.2 to 6, with higher scores indicating greater sexual desire) compared to approximately 17% of those who received a placebo. Bremelanotide is used “as needed” before anticipated sexual activity, and it does not need to be taken on a daily basis.

Bremelanotide is a melanocortin receptor (MCR) agonist that activates several receptor subtypes in a nonselective manner, with varying potency: MC1R, MC4R, MC3R, MC5R, and MC2R. At therapeutic doses, the binding to MC1R and MC4R is most significant. The central nervous system (CNS) contains neurons that express MC4R in many regions. The precise mechanism by which bremelanotide improves HSDD in women is not fully understood, but it is believed that the drug’s unique mechanism of action activates specific brain pathways involved in normal sexual responses.

The average terminal half-life of bremelanotide is approximately 2.7 hours when given subcutaneously (with a range of 1.9 to 4 hours) following a single subcutaneous dose. The mean clearance (CL/F), with a standard deviation of +/- 1 L/hour, is 6.5 L/hour.

In Hepatic Impairment: In patients with mild (Child-Pugh A; score of 5 to 6) hepatic impairment, a single subcutaneous dose of bremelanotide resulted in a 1.2-fold increase in bremelanotide exposure (AUC). In patients with moderate (Child-Pugh B; score of 7 to 9) hepatic impairment, the increase was 1.7-fold. However, the effect of severe hepatic impairment on the pharmacokinetics of bremelanotide has not been studied.

In Renal Impairment: After a single subcutaneous dose of bremelanotide, patients with mild (eGFR, 60 to 89 mL/minute/1.73 m²) renal impairment showed a 1.2-fold increase in bremelanotide exposure (AUC). Patients with moderate (eGFR, 30 to 59 mL/minute/1.73 m²) renal impairment showed a 1.5-fold increase, while those with severe (eGFR, less than 30 mL/minute/1.73 m²) renal impairment showed a 2-fold increase.

Do not use Bremelanotide if you have:
high blood pressure that is not controlled (uncontrolled hypertension)
known heart (cardiovascular) disease
Before using Bremelanotide, tell your healthcare provider about all of your medical conditions, including if you:
have high blood pressure.
have heart problems.
have kidney problems.
have liver problems.

are pregnant or plan to become pregnant. It is not known if Bremelanotide will harm your unborn baby.
Women who can become pregnant should use effective birth control during treatment with Vyleesi.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Bremelanotide may affect the way other medicines work, and other medicines may affect the way Bremelanotide works.
Bremelanotide is not intended to treat HSDD in men or postmenopausal women or to enhance sexual performance. The drug is contraindicated in patients with uncontrolled hypertension or known cardiac disease and is not recommended for patients at high risk for cardiac disease. Before starting treatment with bremelanotide, and periodically during treatment, assess the patient’s cardiovascular risk and ensure blood pressure is well-controlled. Bremelanotide causes a transient increase in blood pressure and decrease in heart rate after each dose. In clinical trials, systolic blood pressure (SBP) increased by a maximum of 6 mmHg, and diastolic blood pressure (DBP) increased by a maximum of 3 mmHg. The peak effect occurred 2 to 4 hours after administration, and blood pressure and heart rate returned to baseline within 12 hours post-dose. To minimize the risk of more significant blood pressure effects, advise patients not to take more than one bremelanotide dose within 24 hours, and administering more than 8 doses per month is not recommended. Nausea and vomiting are common side effects of bremelanotide, with nausea occurring in 40% of patients and vomiting occurring in 4.8% of patients. Anti-emetic therapy may be necessary for some patients. Bremelanotide can cause focal skin hyperpigmentation, particularly in patients with darker skin or daily dosing. Skin discoloration occurred in 1% of female patients in clinical trials, and resolution did not occur in all patients despite drug discontinuation. The recommended maximum dosing frequency is eight doses per month, and the drug should be discontinued if skin hyperpigmentation develops.

Bremelanotide is not recommended for use during pregnancy due to the potential for fetal harm, based on findings from animal studies. If pregnancy is suspected, bremelanotide should be discontinued. Females of child-bearing potential should use appropriate contraception while on therapy. Pregnant women exposed to bremelanotide and healthcare providers are encouraged to contact the Bremelanotide Pregnancy Exposure Registry at (877) 411-2510. Animal studies have shown that daily subcutaneous administration of bremelanotide to pregnant dogs during organogenesis at exposures greater than or equal to 16 times the maximum recommended dose (based on area under the concentration-time curve or AUC) produced fetal harm. Similarly, developmental effects were observed in the offspring of mice subcutaneously dosed with bremelanotide during pregnancy and lactation at greater than or equal to 125-times the maximum recommended dose (based on AUC). However, the lowest bremelanotide dose associated with fetal harm has not been identified for either species.

Currently, there is no data available on whether bremelanotide or its metabolites are present in human milk, and the potential effects on breastfed infants or milk production are unknown. Therefore, before deciding whether to breastfeed while taking bremelanotide, consider both the potential benefits of breast-feeding and the potential risks of drug exposure to the infant, as well as the potential risks of not treating or inadequately treating the maternal condition.

Bremelanotide, a melanocortin receptor agonist, transiently increases blood pressure and decreases heart rate after each dose, making it contraindicated in patients with uncontrolled hypertension. Before and during treatment, assess the patient’s cardiovascular risk and ensure blood pressure is well-controlled. To minimize the risk of pronounced blood pressure effects, advise patients not to take more than one dose of bremelanotide within 24 hours. In clinical studies, bremelanotide increased systolic blood pressure (SBP) by a maximum of 6 mmHg and diastolic blood pressure (DBP) by 3 mmHg, with a corresponding reduction in heart rate up to 5 beats per minute, usually returning to baseline within 12 hours post-dose. Less than 1% of patients discontinued bremelanotide therapy due to hypertension. Focal skin hyperpigmentation is a possible adverse reaction, particularly in patients with dark skin, and occurs more frequently with chronic daily use. Discontinuation of bremelanotide is recommended if skin hyperpigmentation develops. Nausea is the most commonly reported gastrointestinal adverse reaction, occurring in 40% of patients and requiring anti-emetic therapy in 13% of bremelanotide-treated patients. Vomiting was reported in 4.8% of patients. Injection site reactions are also possible.

Currently, there is no data available on whether bremelanotide or its metabolites are present in human milk, and the potential effects on breastfed infants or milk production are unknown. Therefore, before deciding whether to breastfeed while taking bremelanotide, consider both the potential benefits of breast-feeding and the potential risks of drug exposure to the infant, as well as the potential risks of not treating or inadequately treating the maternal condition.

Gummies: The medication should be kept between 68°F and 77°F (20°C to 25°C), away from heat, moisture, and light. It’s important to store all medicine out of reach of children, and any unused medication should be discarded after the beyond-use date. It’s crucial not to flush unused medications or pour them down a sink or drain.

Nasal Spray: Refrigerate between 36-46°F (2°C to 7°C)

Vyleesi (bremelanotide) injection package insert. Waltham, MA: AMAG Pharmaceuticals, Inc.; 2020 Oct.

Diamond, L., Earle, D., Rosen, R. et al. Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction. Int J Impot Res 16, 51–59 (2004). https://doi.org/10.1038/sj.ijir.3901139