Bremelanotide

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Auto-injector, Subcutaneous, as acetate [preservative free]:

Vyleesi: 1.75 mg/0.3 mL (0.3 mL)

Pharmacology

Mechanism of Action

Nonselective melanocortin receptor agonist that activates several receptor subtypes, most notably MC4R (present throughout the CNS) and MC1R (expressed on melanocytes). Mechanism for improvement of hypoactive sexual desire disorder is unknown.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: 25 ± 5.8 L

Metabolism

Primarily amide hydrolysis of the cyclic peptide

Excretion

Urine (64.8%); feces (22.8%)

Time to Peak

~1 hour

Half-Life Elimination

Terminal: ~2.7 hours (range: 1.9 to 4 hours)

Protein Binding

21%

Use in Specific Populations

Special Populations: Renal Function Impairment

In patients with mild (eGFR 60 to 89 mL/minute/1.73 m²), moderate (eGFR 30 to 59 mL/minute/1.73 m²), and severe (eGFR <30 mL/minute/1.73 m²) renal impairment, AUC increased by 1.2-, 1.5-, and 2-fold, respectively.

Special Populations: Hepatic Function Impairment

In patients with mild (Child-Pugh class A) and moderate (Child-Pugh class B) hepatic impairment, AUC increased by 1.2- and 1.7-fold, respectively.

Use: Labeled Indications

Hypoactive sexual desire disorder: Treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is not due to a coexisting medical or psychiatric condition, problems with the relationship, or the effects of a medication or drug substance.

Limitations of use: Not indicated for the treatment of HSDD in postmenopausal women or in men or to enhance sexual performance.

Contraindications

Uncontrolled hypertension or known cardiovascular disease

Dosage and Administration

Dosing: Adult

Note: Discontinue use of bremelanotide if no improvement in symptoms after 8 weeks.

Hypoactive sexual desire disorder: SubQ: 1.75 mg as needed, ≥45 minutes before sexual activity (maximum: 1.75 mg/24 hours). No more than 8 doses per month are recommended.

Dosing: Geriatric

Refer to adult dosing.

Administration

SubQ: Administer SubQ in the abdomen or thigh.

Storage

Store at ≤25°C (77°F). Do not freeze. Protect from light.

Drug Interactions

Indomethacin: Bremelanotide may decrease the serum concentration of Indomethacin. Monitor therapy

Naltrexone: Bremelanotide may decrease the serum concentration of Naltrexone. Avoid combination

Adverse Reactions

>10%:

Cardiovascular: Flushing (20%)

Central nervous system: Headache (11%)

Dermatologic: Skin hyperpigmentation (1% to 38%)

Gastrointestinal: Nausea (40%)

Local: Injection site reaction (13%)

1% to 10%:

Cardiovascular: Increased blood pressure (<2%)

Central nervous system: Fatigue (3%), paresthesia (3%), dizziness (2%), pain (<2%), restless leg syndrome (<2%)

Endocrine & metabolic: Hot flash (3%)

Gastrointestinal: Vomiting (5%), diarrhea (<2%), upper abdominal pain (<2%)

Neuromuscular & skeletal: Arthralgia (<2%), increased creatine phosphokinase in blood specimen (<2%), limb pain (<2%), myalgia (<2%)

Respiratory: Cough (3%), nasal congestion (2%), rhinorrhea (<2%)

Frequency not defined:

Cardiovascular: Decreased heart rate

Central nervous system: Hypoesthesia

Dermatologic: Injection site pruritus

Respiratory: Flu-like symptoms

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular: A transient increase in blood pressure and reduction in heart rate may occur after each dose; peak effects occur 2 to 4 hours post-dose and typically return to baseline within 12 hours. Use is not recommended in patients at high risk for cardiovascular disease and is contraindicated in patients with uncontrolled hypertension or established cardiovascular disease.
• Focal hyperpigmentation: Focal hyperpigmentation, including involvement of the face, gingiva, and breasts, has been reported. May occur more frequently in patients with dark skin and with more frequent administration. Consider discontinuation if focal hyperpigmentation develops; may resolve in some patients.
• Gastrointestinal: Nausea, especially after the initial dose, has been reported. Onset usually occurs within 1 hour post-dose and may last approximately 2 hours. Incidence commonly decreases with subsequent doses. Use of an antiemetic may be effective; discontinuation of therapy may be considered for persistent or severe nausea.

Concurrent drug therapy issues:

• Delayed gastric emptying: May delay gastric emptying and reduce the rate and extent of absorption of concurrently administered oral drugs. Monitor for efficacy of concurrently administered oral drugs and consider discontinuation of bremelanotide if efficacy is affected. Additionally, concurrent use with oral drugs dependent on threshold concentrations for efficacy (eg, antibiotics) may need to be avoided.

Monitoring Parameters

Blood pressure and heart rate (if clinically indicated)

Pregnancy

Pregnancy Considerations

Outcome information following maternal use of bremelanotide during pregnancy is limited. Females of reproductive potential should use effective contraception during bremelanotide therapy; discontinue if pregnancy is suspected.

Data collection to monitor pregnancy and infant outcomes following exposure to bremelanotide is ongoing. Health care providers are encouraged to enroll females exposed to bremelanotide during pregnancy in the Vyleesi Pregnancy Registry (1-877-411-2510).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience nausea, flushing, injection site irritation, vomiting, stuffy nose, cough, tingling, fatigue, or weakness. Have patient report immediately to prescriber severe headache, severe dizziness, passing out, vision changes, or slow heartbeat (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.