PT-141 (Bremelanotide)
Also known as: Bremelanotide, Vyleesi, PT-141
Overview
Clinical Summary
Bremelanotide (PT-141) is a synthetic melanocortin receptor agonist approved by the FDA in 2019 under the brand name Vyleesi for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women. It is a cyclic heptapeptide that activates melanocortin-4 receptors (MC4R) in the central nervous system to modulate sexual desire. It is the first and only FDA-approved on-demand treatment for HSDD.
Plain Language Summary
Bremelanotide (brand name Vyleesi) is an FDA-approved medication for low sexual desire in premenopausal women. It works on receptors in the brain that are involved in sexual arousal and desire. It is given as a self-injection before anticipated sexual activity. It was originally discovered during research into tanning peptides (melanotan) when researchers noticed it increased sexual arousal as a side effect.
Mechanism of Action
Bremelanotide is a cyclic heptapeptide (Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH) that acts as a non-selective agonist at melanocortin receptors, with primary therapeutic activity attributed to MC4R activation. MC4R is expressed in hypothalamic and limbic brain regions involved in sexual function. Activation of MC4R is proposed to increase sexual desire through dopaminergic pathway facilitation in the medial preoptic area and other brain regions involved in sexual motivation. Unlike PDE5 inhibitors, bremelanotide acts centrally on desire rather than peripherally on arousal/erection.
Evidence Summary
FDA approval was based on two Phase 3 RCTs (RECONNECT) enrolling over 1,200 premenopausal women with HSDD. Both trials met their co-primary endpoints: statistically significant increase in sexual desire (measured by FSDS-DAO desire domain) and increase in satisfying sexual events compared to placebo. The effect size was modest but statistically significant. Post-hoc analyses showed improvement across multiple dimensions of sexual function. Studies in men for erectile dysfunction showed some efficacy but were not pursued to approval due to nausea and blood pressure effects.
Safety Profile
The most common adverse event is nausea (40% of patients), which is often the dose-limiting factor. Transient blood pressure elevation and facial flushing have been observed. The FDA label includes a boxed warning regarding focal hyperpigmentation (darkening of skin, gums, or breast) that may not fully resolve. Use is limited to no more than one dose per 24 hours and no more than 8 doses per month. Bremelanotide is contraindicated in uncontrolled hypertension.
Contraindications
- Uncontrolled hypertension or cardiovascular disease
- Known hypersensitivity to bremelanotide
- Concomitant use with naltrexone (blocks efficacy)
- Pregnancy (Category X: may cause fetal harm based on animal data)
Adverse Events
- Nausea (40%, most common)
- Flushing (20%)
- Injection site reactions
- Headache
- Transient hypertension
- Focal hyperpigmentation (boxed warning: may not fully resolve)
- Vomiting
Interactions
- Naltrexone: significantly reduces bremelanotide efficacy (contraindicated)
- Caution with oral medications due to potential delayed GI absorption
- May affect blood pressure; use caution with antihypertensives
Active Safety Signals
The FDA label for Vyleesi (bremelanotide) includes a boxed warning regarding focal hyperpigmentation (darkening of the face, gingiva, and breasts). This effect may not fully resolve after discontinuation. Patients should be counseled about this risk before initiating therapy.
Regulatory Notes
Bremelanotide (Vyleesi) was approved by the FDA on June 21, 2019, for HSDD in premenopausal women. It is marketed by Palatin Technologies / AMAG Pharmaceuticals. It is available by prescription only through a specialty pharmacy network. It is available as a 1.75 mg single-dose autoinjector for subcutaneous use. Grey-market versions of PT-141 (often in multi-dose vials) circulate widely; these are not pharmaceutical-grade.
Monitoring Considerations
Label-directed monitoring: blood pressure assessment before starting treatment and periodically during use. Monitor for focal hyperpigmentation. Assess for nausea and tolerability. No more than 8 doses per month. Evaluate treatment response (sexual desire, satisfying sexual events) at follow-up.
These are general considerations for clinical awareness and do not constitute prescriptive monitoring recommendations for any individual patient.
Stability and Handling Notes
Per FDA label: Vyleesi autoinjector should be stored at 20-25C (68-77F). Protect from light. Do not freeze. Use immediately after removing from carton.
References
- 1RCT
Bremelanotide for Female Sexual Dysfunctions in Premenopausal Women: RECONNECT Phase 3 Trial
Kingsberg SA, Clayton AH, Portman D, et al. (2019). Obstetrics & Gynecology
Key findings: Two Phase 3 RCTs (n=1,247) demonstrated statistically significant improvement in sexual desire and reduction in distress compared to placebo in premenopausal women with HSDD.
Limitations: Modest effect sizes. High nausea rate (40%). 24-week duration.
View source - 2FDA label
VYLEESI (bremelanotide injection) Prescribing Information
AMAG Pharmaceuticals (2019). FDA
Key findings: Full prescribing information including boxed warning for hyperpigmentation, indication, dosing, contraindications.
Limitations: Label information; not primary research.
View source - 3review
Melanocortin Receptor Agonists in the Treatment of Sexual Dysfunction
Clayton AH, Kingsberg SA. (2020). Expert Opinion on Investigational Drugs
Key findings: Review of melanocortin agonists for sexual dysfunction, including the path from melanotan discovery to bremelanotide approval.
Limitations: Narrative review.
Last reviewed: 2024-12-15 | Version: 1 | Status: Published
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