Bremelanotide, sold as Vyleesi and often called PT-141, is an FDA-approved injection. Its label covers premenopausal women with acquired, generalized hypoactive sexual desire disorder [1]. The side-effect record comes from two 24-week phase 3 trials in 1,247 women, plus a 52-week open-label extension.
The short version: nausea is common and mostly early. Flushing and headache are common. Blood pressure rises briefly after each dose. Skin darkening is rare on the labeled schedule and common on daily dosing. For the wider goal, see the sexual health goal page.
Nausea
In the pooled phase 3 trials, nausea was reported by 40.0% on bremelanotide and 1.3% on placebo [1]. It usually began within an hour of the dose and lasted about two hours.
It was highest after the first dose, at 21%, and fell to about 3% after later doses. About 13% of treated women took an anti-nausea medicine. Nausea led 8% to leave the trials early, against none on placebo. Nausea also leads the side-effect list for the GLP-1 weight drugs, though through a different receptor.
The label also reports a test of pre-treatment. In 228 healthy women, oral ondansetron 30 minutes before a dose did not reduce nausea. The label does not recommend it for that use.
Blood pressure and heart rate
Each dose raises blood pressure for a few hours. In clinical studies the peak rise was 6 mmHg systolic and 3 mmHg diastolic, 2 to 4 hours after the dose [1]. Heart rate fell by up to 5 beats per minute. Both usually returned to baseline within 12 hours.
Because of this, the label bars use in uncontrolled high blood pressure or known heart disease. It advises no more than one dose in 24 hours. A safety review of the whole program described the rises as small and transient but statistically significant [4].
Skin darkening
The label explains why. Bremelanotide activates the MC1R receptor on pigment cells, and that leads to more melanin. In the phase 3 trials, focal darkening of the face, gums or breasts was reported in 1% of women on up to 8 doses a month [1]. No one on placebo reported it.
The schedule matters a great deal. In a separate study, 38% developed focal darkening after 8 consecutive daily doses. Of those who kept going for 8 more days, another 14% developed new changes. Women with darker skin were more likely to be affected. Resolution was not confirmed in all of them after stopping.
Flushing, headache and the rest
In the label’s table, flushing was reported by 20.3% against 0.3% on placebo. Headache was 11.3% against 1.9%, and vomiting 4.8% against 0.2%. Injection site reactions, a broad pooled term, were 13.2% against 8.4%.
Most events were mild (31%) or moderate (40%) and short-lived. Serious adverse reactions were reported in 1.1% on bremelanotide and 0.5% on placebo. Side effects led 18% of treated women to stop, against 2% on placebo.
One case of acute hepatitis occurred in the open-label extension, after 10 doses in a year. Liver tests returned to normal four months after stopping. The label says the drug’s role could not be definitively excluded, and no wider liver signal was seen.
Over a longer period
Of 856 women eligible after the core trials, 684 entered the 52-week open-label extension and 272 completed it [3]. Drug-related nausea was reported by 40.4%, flushing by 20.6% and headache by 12.0%. The authors report no new safety signals. The extension had no placebo group, and its analyses were descriptive.
Interactions to know about
The label says bremelanotide may slow stomach emptying, which can delay oral medicines [1]. It advises avoiding it with oral naltrexone products used for alcohol or opioid addiction, because it can sharply lower naltrexone levels.
How much benefit sits against these effects is a separate question. In the phase 3 trials the desire score rose 0.35 points more than placebo, pooled [2]. How the evidence compares for other peptides is in what are peptides, and the regulatory side is in are peptides legal.