What Is Vyleesi?

1. What is Vyleesi, and how does it work?

Bremelanotide is a synthetic, ring-shaped peptide of seven amino acids. The Vyleesi label describes it as a melanocortin receptor agonist that activates several receptor subtypes, most potently MC1R, then MC4R, MC3R, MC5R and MC2R. At the approved dose, MC1R and MC4R matter most.

• MC4R sits on neurons throughout the central nervous system. It is the receptor linked to desire, and also to appetite.
• MC1R sits on the pigment cells of the skin. Activating it increases melanin, which explains the skin darkening some users see.

The label is direct about the limits of what is known: “The mechanism by which VYLEESI improves HSDD in women is unknown.” That distinguishes it from drugs for erectile dysfunction, which act on blood flow, and from hormone therapy. Vyleesi is meant to act on desire, not on physical arousal.

The label also lists pharmacokinetic basics. After a 1.75 mg injection, levels peak in about 1 hour, bioavailability is about 100%, and the half-life is about 2.7 hours (range 1.9 to 4.0). The peptide half-life explainer covers what those numbers do and do not say about how long an effect lasts.

2. Who is Vyleesi approved for?

The indication is narrow. Vyleesi is for premenopausal women with HSDD that is:

• Acquired: it developed in someone who previously had no problem with desire.
• Generalized: it occurs regardless of the type of stimulation, situation or partner.
• Distressing: the low desire causes marked distress or interpersonal difficulty.
• Not explained by something else: not due to a coexisting medical or psychiatric condition, problems in the relationship, or the effects of a medication or drug.

The label’s limitations of use exclude postmenopausal women and men, and state that Vyleesi is not indicated to enhance sexual performance. HSDD is a clinical diagnosis, so the decision about whether it applies belongs with a clinician who can rule out the other causes on that list, including medications. Because the label excludes low desire caused by a medication or drug, desire problems that started with a new prescription fall outside the approved use.

3. What is the Vyleesi dose?

The label’s regimen, for reference only:

The limits come from the risks. A second dose within 24 hours could add to the blood pressure effect, and few trial participants used more than 8 doses a month. More frequent use raises the chance of skin darkening and lengthens the time each month during which blood pressure is elevated. In the trials, most women used Vyleesi two to three times a month and no more than once a week.

4. What did the RECONNECT trials show?

Vyleesi’s approval rested on two identical phase 3 trials, Study 301 and Study 302, known as RECONNECT and published by Kingsberg and colleagues in 2019. They randomized 1,267 premenopausal women with HSDD to Vyleesi 1.75 mg or placebo, used as needed for 24 weeks. The women averaged 39 years old, had been in a monogamous relationship for a mean of 12 years and had HSDD for about 4 years; 96.6% were at US sites.

The two co-primary endpoints were questionnaires:

• FSFI desire domain, from the Female Sexual Function Index: two questions on how often and how strongly desire was felt over the past 4 weeks, scored 1.2 to 6.
• FSDS-DAO item 13, from the Female Sexual Distress Scale: how often the woman felt bothered by low desire, scored 0 (never) to 4 (always).

Both co-primary endpoints were statistically significant in both trials. The paper’s placebo-adjusted differences were 0.30 and 0.42 points for desire and -0.37 and -0.29 points for distress. The number of satisfying sexual events, a secondary endpoint, did not differ from placebo (P = 0.76 and P = 0.70).

FDA’s approval announcement translated those scores into responders. About 25% on Vyleesi versus about 17% on placebo had a desire increase of 1.2 points or more, and about 35% versus 31% had a distress decrease of 1 point or more. Those thresholds came from responder analyses first developed in the phase 2b dose-ranging study.

Dropout is part of the picture. The label notes that more women on Vyleesi than on placebo left the 24-week phase early: 40% versus 13% in Study 1 and 39% versus 25% in Study 2. Overall, 18% stopped Vyleesi because of side effects, against 2% on placebo.

After 24 weeks

Of 856 eligible women who completed the core phase, 684 entered a 52-week open-label extension and 272 finished it, according to Simon and colleagues. Those who stayed reported sustained improvement, but an open-label extension has no placebo group and keeps mostly the people who tolerate and like the drug, so it cannot show how much of the effect is the drug.

The critics

The trials were funded by Palatin Technologies and AMAG Pharmaceuticals. An independent reanalysis by Spielmans and Ellefson argued that the questionnaire endpoints have weak validity evidence in women with HSDD, that 8 of 11 efficacy outcomes registered on ClinicalTrials.gov had not been published, and that effect sizes on those outcomes ranged from nil to small. Their conclusion: bremelanotide’s benefits are “statistically modest” and limited to outcomes with scant validity evidence. That is a critique of how much the measured effect means, not evidence of harm.

5. What are Vyleesi’s side effects?

From the pooled placebo-controlled trials on the label (627 women on Vyleesi, 620 on placebo):

Nausea usually started within an hour of the dose and lasted about two hours. It was most common after the first dose (21%) and fell to about 3% with later doses. 13% needed an anti-nausea medicine, and 8% left the trials because of it. In a separate study of 228 healthy women, taking oral ondansetron 30 minutes beforehand did not reduce nausea, and the label says that pre-treatment is not recommended.

Blood pressure and heart rate. Each dose raised blood pressure by up to 6 mmHg systolic and 3 mmHg diastolic, peaking 2 to 4 hours after the dose, while heart rate fell by up to 5 beats per minute. Values usually returned to baseline within 12 hours. This is why Vyleesi is contraindicated with uncontrolled hypertension or known cardiovascular disease and not recommended for people at high cardiovascular risk.

Skin darkening. Focal hyperpigmentation, including the face, gums and breasts, occurred in 1% of trial patients using up to 8 doses a month, and in none on placebo. In another study, 38% developed it after 8 days of daily dosing, and another 14% after 8 more days. It was more likely in people with darker skin, and FDA’s announcement said it did not go away in about half of affected patients after stopping.

Liver. One case of acute hepatitis occurred in the open-label extension in a woman who had taken 10 doses over a year; liver tests normalized 4 months after stopping. The label says Vyleesi’s role could not be excluded, and no broader liver signal was seen in the program.

6. What drug interactions and pregnancy guidance does the label give?

Vyleesi may slow stomach emptying, and so may reduce how fast and how much of some oral medicines is absorbed. The label tells patients to avoid Vyleesi with oral drugs that depend on reaching a threshold level to work, giving antibiotics as the example, and to consider stopping it if a drug that needs a quick onset, such as the pain reliever indomethacin, seems delayed. It also says Vyleesi may significantly lower blood levels of oral naltrexone, so it should not be used with oral naltrexone products for alcohol or opioid addiction.

Animal studies in dogs and mice showed fetal harm at exposures 16 or more times the human level, and human pregnancy data are too few to judge. The label advises effective contraception during use and stopping Vyleesi if pregnancy is suspected; there is a pregnancy exposure registry.

On October 22, 2026, FDA approved a label update based on a required lactation study (NCT06867835). The updated label reports that in 10 lactating women given a single 1.75 mg dose, the relative infant dose was 0.132% of the weight-adjusted maternal dose, and no bremelanotide was measurable in milk at 24 hours. Effects on breastfed infants were not studied, and there are no data on milk production. At the time of writing, the DailyMed version still showed the earlier label.

7. How does Vyleesi relate to GLP-1 drugs?

There is no published study of Vyleesi in people taking a GLP-1 drug for diabetes or weight, so the points below are overlaps worth knowing rather than proven interactions.

• Nausea on top of nausea. GLP-1 drugs like semaglutide and tirzepatide cause nausea, especially during dose increases. Vyleesi’s nausea rate was 40% in its trials. Whether the two add up has not been measured.
• Slower stomach emptying. Both Vyleesi and GLP-1 drugs can slow gastric emptying and delay oral medicines. The Vyleesi label already flags antibiotics and quick-onset painkillers.
• Blood pressure. Vyleesi raises blood pressure for several hours after each dose. Its contraindications for uncontrolled hypertension and known cardiovascular disease apply whatever else a person takes, and many people on GLP-1 drugs have those conditions.
• Appetite. MC4R is one of the brain’s main satiety switches. That link led Palatin to test bremelanotide for weight. In its BMT-801 study, announced March 31, 2025, 96 adults with obesity took tirzepatide 2.5 mg weekly for 4 weeks, then were randomized for 4 more weeks; the group adding daily bremelanotide 1.25 mg lost 4.4% of body weight over the 8 weeks versus 1.6% on placebo. Daily dosing is far outside Vyleesi’s label, and it is the setting in which the label reports pigmentation in 38%.

Vyleesi is not a weight-loss drug. The melanocortin drug approved for weight is Imcivree (setmelanotide), and only for specific rare genetic and hypothalamic forms of obesity.

8. Who makes Vyleesi, and what is its history?

Palatin’s December 2023 filing also mentions earlier licenses to Fosun in China and Kwangdong in South Korea. Kwang Dong ran a 193-person phase 3 bridging trial in South Korea (NCT04943068), listed as completed. Drugs@FDA listed Vyleesi as an active prescription product under Cosette in November 2026, and no shortage or discontinuation record turned up in openFDA.

9. How does Vyleesi compare with Addyi and with gray-market PT-141?

The Addyi label, first approved in 2015, now covers women under 65 rather than only premenopausal women, so its population is broader than Vyleesi’s. The two drugs work by different mechanisms and have not been compared head to head in a trial found for this page.

Gray-market products sold as PT-141 for men, for tanning or for general libido sit outside any approved use. The trials above tested one sterile 1.75 mg injection in a defined group of women; they cannot vouch for a vial of unknown content or a nasal spray at a different dose. The PT-141 page covers the research in men and the nasal-spray history.

10. What is worth tracking on Vyleesi?

The label itself suggests what to record: the date and time of each dose relative to sexual activity, whether a dose fell within 24 hours of the last one, the monthly dose count against the 8-dose limit, nausea and how long it lasted, any new skin darkening, and blood pressure if it is being monitored. The 8-week mark matters too, because the label says to stop if there has been no improvement by then. Keeping desire and distress notes week by week makes that conversation with a prescriber concrete. A peptide log can hold those entries next to any GLP-1 doses, which makes overlapping nausea easier to see.

11. Vyleesi FAQ

• What is Vyleesi used for?

  Vyleesi is approved for premenopausal women with acquired, generalized hypoactive sexual desire disorder: low sexual desire that causes marked distress or relationship difficulty, developed after a period of normal desire, occurs regardless of partner or situation, and is not explained by another medical or psychiatric condition, relationship problems, or a medication. It is not approved for men, postmenopausal women or to enhance sexual performance.

• Is Vyleesi the same as PT-141?

  PT-141 is the development code for bremelanotide, the active ingredient in Vyleesi. Vyleesi is the FDA-approved product: a sterile 1.75 mg dose in a single-use autoinjector made under FDA-reviewed manufacturing. Gray-market vials and nasal sprays sold as PT-141 are not Vyleesi, and the label's safety data do not transfer to them.

• How do you take Vyleesi?

  Per the label, 1.75 mg is injected under the skin of the abdomen or thigh with the autoinjector, as needed, at least 45 minutes before anticipated sexual activity. No more than one dose in 24 hours, and more than 8 doses a month is not recommended. The label says the duration of effect after each dose is unknown.

• How well does Vyleesi work?

  Modestly. In the RECONNECT trials, desire scores rose about 0.3 to 0.4 points more than on placebo on a 1.2-to-6 scale, and distress about low desire fell about 0.3 points more on a 0-to-4 scale. FDA's summary said about 25% on Vyleesi versus 17% on placebo had a desire increase of 1.2 points or more. The number of satisfying sexual events did not differ from placebo.

• What are the side effects of Vyleesi?

  In the placebo-controlled trials: nausea 40.0% versus 1.3%, flushing 20.3% versus 0.3%, injection-site reactions 13.2% versus 8.4%, headache 11.3% versus 1.9%, and vomiting 4.8% versus 0.2%. Nausea was most common after the first dose (21%) and fell to about 3% with later doses. Blood pressure rises briefly after each dose, and focal skin darkening can occur.

• Can you take Vyleesi with a GLP-1 drug like Ozempic or Zepbound?

  No study of that combination in the HSDD setting was found. Both cause nausea, and the Vyleesi label says it may slow stomach emptying and reduce absorption of some oral drugs, an effect GLP-1 drugs share. A small Palatin obesity study gave daily bremelanotide with low-dose tirzepatide, but that used doses outside Vyleesi's label. Whether to combine them is a question for the prescriber.

• Can you use Vyleesi while breastfeeding?

  An October 22, 2026 label update reports a study in 10 lactating women: after a single 1.75 mg dose, the relative infant dose was 0.132% of the weight-adjusted maternal dose, and no bremelanotide was measurable in milk at 24 hours. Effects on infants were not evaluated. The label also advises effective contraception during use and stopping if pregnancy is suspected.

• How is Vyleesi different from Addyi?

  Addyi (flibanserin) is a daily tablet taken at bedtime, with a boxed warning about low blood pressure and fainting with alcohol and certain drug interactions. Its current label covers women under 65 with acquired, generalized HSDD. Vyleesi is an as-needed injection limited to premenopausal women, with nausea and transient blood pressure rises as its main issues.

12. Sources