PT-141 (BREMELANOTIDE)

Peptide Data Sheet for Pharmacists and Compounding Professionals

BASIC INFORMATION

Name: PT-141 (Bremelanotide)
Class: Melanocortin receptor agonist
Structure: Cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone (α-MSH)
Molecular Weight: 1025.2 g/mol
Sequence: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH
Brand Name: Vyleesi®

Available Forms:

  • FDA-approved injectable solution (Vyleesi®)
  • Compounded formulations (subject to regulatory requirements)
  • Research peptide

REGULATORY STATUS

FDA Status

  • Vyleesi®: Approved in June 2019 for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women.
  • Not approved for men or postmenopausal women.
  • Available only by prescription.

Legal Considerations

  • Prescription-only medication.
  • Not approved for use to improve sexual performance outside of its approved indication.
  • Compounding pharmacies may prepare custom formulations under appropriate prescribing and in compliance with regulations.

MECHANISM OF ACTION

PT-141 (Bremelanotide) is a synthetic analog of α-MSH that:

  • Acts as a non-selective agonist of melanocortin receptors (primarily MC3R and MC4R) in the central nervous system.
  • Activation of these receptors is thought to modulate pathways involved in sexual desire and arousal.
  • Unlike PDE5 inhibitors (e.g., sildenafil), PT-141 does not directly affect peripheral blood flow to the genitals.
  • Its effects are centrally mediated, influencing sexual desire and function through neural pathways.
Mechanism of Action

PHARMACOKINETICS

| Parameter | Value | Notes | |———–|——-|——-| | Absorption | Rapid after subcutaneous administration | Peak plasma concentration: ~1 hour | | Distribution | Volume of distribution: ~2.7 L | Plasma protein binding: ~21% | | Metabolism | Extensively metabolized by hydrolysis | Specific pathways not fully elucidated | | Elimination | Half-life: ~2.7 hours (range 1.9-4.0 hours) | Primarily excreted in urine (64.8%) and feces (22.8%) |

CLINICAL APPLICATIONS

FDA-Approved Indications

  • Treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women.
  • Should only be used in women who have low sexual desire that is troubling to them and is not caused by:
    • Co-existing medical or psychiatric conditions
    • Problems within the relationship
    • Effects of medications or other drug substances

Off-Label/Investigational Uses

  • Male erectile dysfunction (some studies have shown efficacy)
  • Sexual arousal disorder in women (broader than HSDD)

DOSING GUIDELINES

FDA-Approved Dosing (Vyleesi®)

| Indication | Dose | Administration | |————|——|—————-| | HSDD in premenopausal women | 1.75 mg | Subcutaneously, as needed, at least 45 minutes before anticipated sexual activity |

Important Dosing Considerations:

  • Maximum one dose within a 24-hour period.
  • Maximum 8 doses per month.
  • If no improvement in HSDD after 8 weeks, discontinue treatment.

ADMINISTRATION

Subcutaneous Injection

  • Administer in the abdomen or thigh.
  • Rotate injection sites.
  • Supplied as a single-dose prefilled autoinjector.
  • Store at room temperature (20°C to 25°C; 68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
  • Do not freeze.

SAFETY PROFILE

Contraindications

  • Uncontrolled hypertension
  • Known cardiovascular disease
  • Hypersensitivity to bremelanotide or any excipients

Warnings and Precautions

  • Transient Increase in Blood Pressure and Decrease in Heart Rate: Occurs after each dose, usually resolves within 12 hours. Monitor blood pressure and heart rate in patients at risk.
  • Nausea: Common, especially with the first dose. May require antiemetic medication.
  • Focal Hyperpigmentation: Darkening of the skin (face, gums, breasts) may occur, particularly in patients with darker skin. More common with daily use (not the approved dosing regimen).
  • Risk of Serious Adverse Reactions with Naltrexone: Concomitant use with naltrexone (oral) may lead to a failure of naltrexone treatment.

Common Adverse Effects

| System | Adverse Effects | Approximate Incidence | |——–|—————-|————————| | Gastrointestinal | Nausea | ~40% | | | Vomiting | ~13% | | Nervous System | Headache | ~11% | | | Flushing | ~20% | | | Dizziness | ~5% | | General | Injection site reactions | ~13% | | | Fatigue | ~4% |

Drug Interactions

  • Naltrexone: May interfere with the efficacy of naltrexone. Avoid concomitant use.
  • Indomethacin: May increase bremelanotide exposure. Use with caution.
  • Rosuvastatin: May increase bremelanotide exposure. Use with caution.
  • Drugs that affect GI motility: May alter absorption of bremelanotide, but clinical significance is unknown.

SPECIAL POPULATIONS

Renal Impairment

  • Mild to moderate: No dose adjustment needed.
  • Severe (eGFR <30 mL/min/1.73m²): Use with caution, may increase exposure.
  • End-stage renal disease: Not recommended.

Hepatic Impairment

  • Mild to moderate: No dose adjustment needed.
  • Severe: Not studied, use with caution.

Geriatric Patients

  • Not indicated for postmenopausal women.
  • Safety and efficacy not established in geriatric populations.

Pregnancy and Lactation

  • Pregnancy: May cause fetal harm. Advise premenopausal women to use effective contraception during treatment. Discontinue if pregnancy occurs.
  • Lactation: Unknown if excreted in human milk. Advise women not to breastfeed during treatment.

PHARMACIST GUIDANCE

Compounding Considerations

  • Vyleesi® is available as an FDA-approved product.
  • Compounding may be considered if specific patient needs cannot be met by the commercial product (e.g., different dosage form, allergen removal), but must comply with all relevant regulations (USP <795>, <797>, state laws).
  • Stability and compatibility data for compounded formulations may be limited.
  • Requires aseptic technique for sterile preparations.

Storage and Handling

  • Vyleesi® Autoinjector: Store at room temperature (20°C to 25°C; 68°F to 77°F).
  • Compounded Preparations: Follow specific stability data and USP guidelines. Typically refrigerated for lyophilized powder and reconstituted solutions.

Patient Counseling Points

  1. Administration Technique
    • Proper subcutaneous injection technique for autoinjector.
    • Importance of injection site rotation (abdomen or thigh).
    • Administer at least 45 minutes before sexual activity.
  2. Dosing Limitations
    • No more than one dose in 24 hours.
    • No more than 8 doses per month.
  3. Common Side Effects
    • Nausea is common, especially with the first dose; may take antiemetic if prescribed.
    • Flushing, headache, and injection site reactions may occur.
    • Report persistent or severe side effects.
  4. Blood Pressure and Heart Rate
    • May cause a temporary increase in blood pressure and decrease in heart rate.
    • Patients with cardiovascular risk factors should be monitored.
  5. Skin Hyperpigmentation
    • Potential for darkening of skin, especially with more frequent use than approved.
    • Report any unusual skin changes.
  6. Pregnancy and Contraception
    • Advise use of effective contraception.
    • Discontinue if pregnancy is suspected or confirmed.
  7. When to Discontinue
    • If HSDD does not improve after 8 weeks.

MAXIMIZING THERAPEUTIC OUTCOMES

Optimizing Efficacy

  • Ensure proper diagnosis of acquired, generalized HSDD.
  • Rule out other causes of low sexual desire.
  • Counsel on realistic expectations and proper use.
  • Administer as needed, at least 45 minutes before sexual activity.

Managing Common Challenges

  • Nausea: Consider prophylactic antiemetic if severe or persistent.
  • Injection Site Reactions: Proper technique, site rotation.
  • Cost and Access: Discuss insurance coverage and patient assistance programs if available.

REFERENCES

  1. FDA. Vyleesi (bremelanotide) Prescribing Information. June 2019.
  2. Kingsberg SA, et al. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstet Gynecol. 2019;134(5):899-908.
  3. Simon JA, et al. Efficacy and Safety of Bremelanotide for Hypoactive Sexual Desire Disorder in Premenopausal Women: Results from Two Phase 3 Randomized Double-Blind Placebo-Controlled Trials. J Sex Med. 2019;16(11):1784-1796.
  4. Molinoff PB, et al. Bremelanotide: a novel melanocortin agonist for the treatment of hypoactive sexual desire disorder in premenopausal women. Womens Health (Lond). 2010;6(5):641-50.