Bremelanotide

Indications

Bremelanotide is used for: Indicated for treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) Characterized by low sexual desire that causes marked distress or interpersonal difficulty Not due to a coexisting medical or psychiatric condition, problems with the relationship, or effects of a medication or drug substance Acquired HSDD refers to HSDD that develops in a patient who previously had no problems with sexual desire Generalized HSDD refers to HSDD that occurs regardless of the type of stimulation, situation, or partner

Adult Dose

Hypoactive Sexual Desire Disorder 1.75 mg SC as needed, at least 45 minutes before anticipated sexual activity Do not administer >1 dose/24 hr >8 doses/month not recommended Duration of efficacy after each dose is unknown; optimal window for administration has not been fully characterized Efficacy of consecutive doses within 24 hr has not been established, and administering doses close together may increase the risk of additive effects on blood pressure Hepatic impairment Mild-to-moderate (Child-Pugh A and B; score 5-9): No dosage adjustment necessary Severe (Child-Pugh C; score 10-15): Not evaluated; use with caution; patients may have an increase in the incidence and severity of adverse reactions (eg, nausea, vomiting)

Child Dose

Renal Dose

Renal impairment Mild-to-moderate (eGFR 30-89 mL/min/1.73 m²): No dosage adjustment necessary Severe (eGFR 30-89 mL/min/1.73 m²): Use with caution; patients may have an increase in the incidence and severity of adverse reactions (eg, nausea, vomiting)

Administration

SC administration use only Administer in the abdomen or thigh, as needed, at least 45 minutes before anticipated sexual activity Optimal time for administration will be determined by the patient based on duration of effect and any adverse reactions such as nausea Do not administer more than 1 dose within 24 hr Administering more than 8 doses/month is not recommended; more frequent dosing increases the risk for focal hyperpigmentation and length of time per month when blood pressure is increased

Contra Indications

Uncontrolled hypertension Known cardiovascular disease

Precautions

Most commonly reported adverse reaction was nausea, which improves for most patients with the second dose; consider discontinuing treatment for persistent or severe nausea or initiating antiemetic therapy in patients who are bothered by nausea but are continuing treatment Focal hyperpigmentation Focal hyperpigmentation, including involvement of the face, gingiva, and breasts, was reported Patients with dark skin were more likely to develop focal hyperpigmentation Resolution of focal hyperpigmentation was not confirmed in all patients after discontinuation Consider discontinuing treatment if hyperpigmentation develops Increased blood pressure and heart rate reduction Transient increase in blood pressure and reduction in heart rate may occur after each dose Blood pressure and heart rate returned to baseline usually within 12 hr postdose No additive effects were seen for blood pressure or heart rate following repeat daily dosing 24-hours apart for up to 16 day Before initiating treatment, and periodically during treatment, consider patient’s cardiovascular risk and ensure blood pressure is well-controlled

Pregnancy-Lactation

Pregnancy Few pregnancies in women exposed to bremelanotide in clinical trials are insufficient for determining whether there is a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes Pregnancy exposure registry Pregnancy exposure registry monitors pregnancy outcomes in women exposed to bremelanotide during pregnancy Encourage women exposed to drug to register in the Vyleesi pregnancy exposure registry at (877) 411-2510 Animal data Based on findings in animal studies, use in pregnant women may be associated with potential for fetal harm In animal reproduction and development studies, daily SC administration of bremelanotide to pregnant dogs during organogenesis at exposures ?16 times the maximum recommended dose (based on AUC) produced fetal harm SC bremelanotide doses in mice during pregnancy and lactation produced developmental effects in offspring at ?125-times the maximum recommended dose (based on AUC) Lowest bremelanotide dose associated with fetal harm has not been identified for either species Contraception Not recommended during pregnancy Females of reproductive potential: Use effective contraception during treatment; discontinue treatment if pregnancy is suspected Lactation There is no information on presence of bremelanotide or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Interactions

Effect of bremelanotide on other drugs Administration may slow gastric emptying and thus potentially reducing the rate and extent of absorption of concomitantly administered oral medications Avoid use when taking concomitant oral drugs that are dependent on threshold concentrations for efficacy (eg, antibiotics) Consider discontinuing treatment if there is a delayed drug effect of concomitant oral medications when a quick onset of drug effect is desired (eg, drugs for pain relief such as indomethacin) Naltrexone Avoid use with an orally administered naltrexone-containing product that is intended to treat alcohol and opioid addiction, owing to the severe consequence of naltrexone treatment failure

Adverse Effects

Side effects of Bremelanotide : >10% Nausea (40%) Flushing (20%) Injection site reactions (13.2%) Headache (11.3%) 1-10% Vomiting (4.8%) Cough (3.3%) Fatigue (3.2%) Hot flush (2.7%) Paresthesia (2.6%) Dizziness (2.2%) Nasal congestion (2.1%) <2% Upper abdominal pain Diarrhea Myalgia Arthralgia Pain Restless leg syndrome Rhinorrhea Increased creatine phosphokinase Blood pressure increased Pain in extremity Focal skin hyperpigmentation Flushing

Mechanism of Action

Melanocortin receptor (MCR) agonist nonselectively activates several receptor sub types with the following order of potency: MC1R, MC4R, MC3R, MC5R, MC2R At therapeutic dose levels, binding 9 of 17 to MC1R and MC4R is most relevant Neurons expressing MC4R are present in many areas of the central nervous system Mechanism to improve HSDD in women is unknown MC1R is expressed on melanocytes; binding at this receptor leads to melanin expression and increased pigmentation