Vyleesi (Bremelanotide) Safety in Adults 30, 49: What the Clinical Data Show

What the safety data cover

The label's safety database is two identical, 24-week, randomized, double-blind, placebo-controlled trials in premenopausal women with acquired, generalized hypoactive sexual desire disorder: 1,247 women in the safety population, 627 on Vyleesi and 620 on placebo [1]. Participants ranged from 19 to 56 years old, with a mean age of 39; 86% were White and 12% Black [1]. A 52-week open-label, uncontrolled extension then enrolled 684 patients [1][3].

The figures below describe the whole trial population, which includes women in their thirties and forties [1].

Dosing rules feed directly into the safety picture: 1.75 mg subcutaneously in the abdomen or thigh, 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 [1]. The label also says to stop after 8 weeks if there has been no improvement in symptoms [1]. How long the effect of a single dose lasts is unknown [1]. Most patients in the trials used Vyleesi two to three times a month and no more than once a week [1].

Nausea: how common, how long, and what did not work

Nausea is the most common adverse reaction by a wide margin: 40.0% on Vyleesi versus 1.3% on placebo [1]. Thirteen percent of treated patients received an anti-nausea medicine, and 8% stopped the trials because of nausea [1].

The label describes the pattern: median onset within one hour after a dose, lasting about two hours [1]. Nausea was most frequent after the first dose, reported by 21% of patients, then fell to about 3% with later doses [1]. For nausea that persists or is severe, the label says to consider discontinuing Vyleesi, or starting anti-nausea treatment for patients who are bothered by it and want to continue [1].

Pre-treating with ondansetron did not help in the one study that tested it. In a phase 4, single-dose, placebo-controlled study, 228 healthy women were randomized 1:1 to 8 mg oral ondansetron or placebo 30 minutes before a 1.75 mg subcutaneous dose, and there was no significant difference in the incidence of nausea [1]. The label states that ondansetron given 30 minutes before Vyleesi does not reduce nausea and is not recommended [1]. Ondansetron given after Vyleesi, or after nausea has started, has not been formally studied [1].

Blood pressure and heart rate

The 6 mmHg systolic and 3 mmHg diastolic figures are maximal increases, not averages. They peak between 2 and 4 hours after a dose, heart rate falls by up to 5 beats per minute at the same time, and both usually return to baseline within 12 hours [1]. Repeat daily dosing 24 hours apart for up to 16 days produced no additive effect on blood pressure or heart rate [1].

A separate open-label ambulatory monitoring study of 127 premenopausal women dosed once daily for 8 days measured the average effect: mean daytime blood pressure rose 1.9 mmHg systolic (95% CI 1.0 to 2.7) and 1.7 mmHg diastolic (95% CI 0.9 to 2.4), with a mean heart rate decrease of 0.5 beats per minute (95% CI -1.6 to -0.7) [1]. The mean peak effect was 2.8 mmHg systolic between 4 and 8 hours after dosing and 2.7 mmHg diastolic between 0 and 4 hours, and readings 12 to 24 hours after a dose were similar to pre-dose values [1].

The label lists uncontrolled hypertension or known cardiovascular disease as contraindications and does not recommend Vyleesi for patients at high risk of cardiovascular disease [1]. It says to consider the patient's cardiovascular risk and make sure blood pressure is well controlled before starting and periodically during treatment, and to avoid more than one dose in 24 hours to limit the blood pressure effect [1].

Focal hyperpigmentation

With up to 8 doses a month in the placebo-controlled trials, focal hyperpigmentation — darkening of the face, gums or breasts — was reported by 1% of Vyleesi patients and no placebo patients [1]. Frequency depends heavily on dosing schedule: in another study, 38% of patients developed focal hyperpigmentation after daily dosing for 8 days, and an additional 14% developed new pigmentary changes after 8 more consecutive days [1]. Patients with dark skin were more likely to develop it, resolution was not confirmed in all patients after stopping the drug, and more than 8 monthly doses is not recommended [1].

The label explains the pigment change this way: bremelanotide activates MC1R as well as MC4R at therapeutic doses, and MC1R is expressed on melanocytes, where binding leads to melanin expression and increased pigmentation [1]. The label says to consider discontinuing Vyleesi if hyperpigmentation develops [1].

Other adverse reactions

In the pooled phase 3 trials, Vyleesi versus placebo: flushing 20.3% vs 0.3%, injection site reactions 13.2% vs 8.4%, headache 11.3% vs 1.9%, vomiting 4.8% vs 0.2%, cough 3.3% vs 1.3%, fatigue 3.2% vs 0.5%, hot flush 2.7% vs 0.2%, paresthesia 2.6% vs 0.0%, dizziness 2.2% vs 0.5% and nasal congestion 2.1% vs 0.5% [1]. The label says the majority of events were mild (31%) to moderate (40%) in intensity and transient [1].

Serious adverse reactions were reported in 1.1% of Vyleesi patients versus 0.5% on placebo, and 18% versus 2% stopped treatment because of adverse reactions; the leading reasons on Vyleesi were nausea 8%, headache 2%, vomiting 1%, flushing 1% and injection site reactions 1% [1]. One headache was serious, an intractable pain leading to hospitalization, and 1% of patients discontinued because of headache [1]. No flushing event was serious and few were severe (less than 1%) [1]. Reactions reported in less than 2% of patients and more often than on placebo included upper abdominal pain, diarrhea, myalgia, arthralgia, restless leg syndrome, rhinorrhea, increased creatine phosphokinase, increased blood pressure and focal skin hyperpigmentation [1].

The single liver case

One case of acute hepatitis occurred during the open-label extension, in a patient who had received 10 doses over one year [1]. She presented with serum transaminases above 40 times the upper limit of normal, total bilirubin 6 times the upper limit of normal, and alkaline phosphatase less than 2 times the upper limit of normal, and her liver tests returned to normal 4 months after the drug was stopped [1]. Because another cause was not identified, the label states the role of Vyleesi could not definitively be excluded; there was no imbalance between treatment groups in transaminase outliers or other hepatotoxicity signals across the development program [1].

Drug and alcohol interactions

The label warns against using Vyleesi with an orally administered naltrexone-containing product intended to treat alcohol or opioid addiction, because Vyleesi may significantly decrease the systemic exposure of oral naltrexone and treatment failure would have severe consequences [1]. It also says to avoid Vyleesi with oral medicines that depend on threshold blood concentrations for effectiveness, such as antibiotics [1].

Vyleesi may slow stomach emptying and reduce the rate and extent of absorption of oral medicines. The label says to consider discontinuing Vyleesi if an oral medicine such as indomethacin has a delayed effect when a quick effect is wanted [1]. In clinical pharmacology studies, only naltrexone and indomethacin were meaningfully affected [1].

Alcohol was tested in a crossover study of 24 healthy volunteers given 0.6 g/kg ethanol — the equivalent of three drinks in a 70 kg person — with a single intranasal dose of bremelanotide [1]. Alcohol had no effect on bremelanotide blood levels, and the incidence of abnormal orthostatic blood pressure reductions was comparable to alcohol alone [1]. Flushing was more common with the combination than with alcohol alone but similar to bremelanotide alone, and headache was more common than with bremelanotide alone but similar to alcohol alone [1]. That study used a 20 mg intranasal dose, which reaches a 2.5-fold higher mean peak concentration than the approved 1.75 mg injection [1].

Pregnancy and contraception

The label advises patients to stop Vyleesi if pregnancy is suspected and to use effective contraception while taking it [1]. In animals, daily subcutaneous bremelanotide in pregnant dogs during organogenesis caused fetal harm at exposures at least 16 times the maximum recommended human dose based on AUC, and developmental effects appeared in mouse offspring at exposures at least 125 times the human dose [1]. In humans, 7 pregnancies were reported across trials of more than 1,057 patients treated for up to 12 months: no major congenital anomalies, one miscarriage, five full-term live births and one unknown outcome [1]. FDA approved a labeling supplement on October 22, 2026 that updates Section 8 and the patient information; that text was not yet in the DailyMed label as of October 28, 2026 [4].

Long-term use

In the 52-week open-label extension, 684 of 856 eligible women enrolled and 272 completed it [3]. The most common treatment-emergent events considered related to the drug were nausea 40.4%, flushing 20.6% and headache 12.0%, and the only severe event experienced by more than one participant across both studies was nausea [3]. These are descriptive results with no placebo group, so they describe what happened over a year of as-needed use rather than a comparison [3].

Who the label says should not use it

The label says Vyleesi is not indicated for HSDD in postmenopausal women or in men, and not to enhance sexual performance [1].

Compounded PT-141 is not Vyleesi

Vyleesi is the FDA-approved bremelanotide product [1][2]. PT-141 products sold as compounded or research-use peptides are not Vyleesi and are not FDA-approved drugs, and compounded drugs are not reviewed by FDA for safety, effectiveness or quality before marketing [5]. Bremelanotide does not appear on FDA's list of bulk drug substances that may present significant safety risks when compounded, a list current as of April 22, 2026 [6]. Vyleesi trial results do not establish the safety of products sold as PT-141 [1][5].